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  • 2000-2004  (595)
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  • 1
    ISSN: 1530-0358
    Keywords: Abdominoperineal resection ; Laparoscopy ; Colorectal carcinoma ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Although laparoscopic colorectal surgery is attracting ever more attention, its use for curative treatment of colorectal carcinoma in particular continues to be controversial. The present study was an attempt to analyze the results of the perioperative course, oncologic quality, and preliminary long-term results. METHOD: The data considered here were collected within the framework of a prospective, observational study initiated on August 1, 1995, and involving a total of 18 institutions in Germany and Austria. At the end of three years, the results are now being presented selectively,i.e., focusing only on abdominoperineal resection. RESULTS: A total of 116 patients underwent laparoscopic abdominoperineal resections, 98 (84.5 percent) of which were performed with curative intent. The mean operating time was 226 (confidence interval, 140–365) minutes. Seven patients (6 percent) experienced an intraoperative complication, which in more than one-half of the cases was a vascular injury involving the presacral venous plexus; the conversion rate was 3.4 percent. Postoperatively, 40 patients developed 97 complications—including those of a very minor nature—giving an overall morbidity rate of 34.4 percent. Reoperation in six patients (5.2 percent) had to be performed for an afterbleed in one-half of the cases and ileus in the other one-half. Postoperative mortality was a low 1.7 percent. In most of the curative resections, an oncologically radical operation with high transection of the inferior mesenteric artery and a complete dissection of the pelvis down to the floor was performed. The median number of lymph nodes investigated was 11.5, and there was wide fluctuation in the numbers among the individual institutions. Tumor cell dissemination occurred intraoperatively in five patients. In the meantime, 79 patients (81 percent) underwent at least one follow-up examination, the mean follow-up period being 491 days. Seven patients developed a local recurrence, and a further six patients developed distant metastases. For recurrence-free survival rate, the Kaplan-Meier estimation calculated a probability of 71 percent. CONCLUSION: Not all of the reservations about laparoscopic abdominoperineal resection, in particular with regard to resection with curative intent, have yet been eliminated. The present study does, however, show that a laparoscopic approach can in principle meet oncologic requirements of radicality and, with regard to the postoperative course, is associated with considerable benefits to the patient.
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  • 2
    ISSN: 1530-0358
    Keywords: Fistula-in-ano ; Surgery ; Imaging ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Magnetic resonance imaging of fistula-in-ano has been shown to predict surgical anatomy accurately and identify complex features. In addition, fistula complexity has been correlated with poor outcome after surgical intervention. We investigated whether preoperative magnetic resonance imaging could predict clinical outcome after surgery for fistulous disease better than clinical examination under anesthetic. METHODS: Seventy patients with clinically suspected fistula-in-ano underwent preoperative dynamic contrast-enhanced magnetic resonance imaging before surgical exploration. Outcome was assessed at a minimum of one year after surgical exploration and correlated in a blinded fashion with the surgical and magnetic resonance grading of the severity of the fistulous disease. RESULTS: Of 70 patients, 12 were not operated on and 6 were lost to follow-up, making 52 patients eligible for analysis. Assessment by dynamic contrast-enhanced magnetic resonance imaging more accurately predicted outcome than the findings at initial surgical exploration. Dynamic contrast-enhanced magnetic resonance imaging had a sensitivity of 81 percent, specificity of 73 percent, and positive predictive value of 75 percent; surgery had a sensitivity of 77 percent, specificity of 46 percent, and positive predictive value of 59 percent. Surgical assessment of apparent disease severity bore no relation to final outcome. Dynamic contrast-enhanced magnetic resonance imaging could accurately predict whether patients were likely to have a satisfactory or unsatisfactory outcome after surgery. CONCLUSION: Dynamic contrast-enhanced magnetic resonance imaging better predicts clinical outcome of patients with fistula-in-ano than initial surgical exploration.
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  • 3
    ISSN: 1534-4681
    Keywords: Rectal cancer ; Intensive follow-up ; Local recurrence ; Reoperation ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Because more than 90% of local recurrences after curative surgery for rectal cancer appear within the first 36 months after surgery, an intensive and strict follow-up program during this period could improve early diagnosis and, thus, prognosis of patients. Methods: Of the 216 patients who underwent surgery for rectal cancer, 127 entered an intensive follow-up program (median follow-up: 42 months); the clinical outcome of the remaining 89 patients was reconstructed with the help of their general practitioners. Results: Fifty eight (26.8%) of the 216 patients who were treated with curative surgery alone developed a local recurrence; pelvic recurrences were prevalent. Eleven (30.5%) of the 36 patients who had recurrence during follow-up, and 6 of the 22 who had not undergone follow-up, had a reoperation with curative intent; the median survival was 19 months vs. 8 months, respectively (P 5 ns). Four (44.4%) curative reoperations were performed on the 9 asymptomatic patients and in 13 (26.5%) of the 49 cases with symptomatic local recurrences. Median survival was 15 months vs. 14 months, respectively (P 5 n.s). All patients except one (living after 42 months from reoperation) died within 48 months. Conclusions: In our study, adherence to a strict follow-up program unfortunately proved to be ineffective for improving long-term survival for patients who underwent reoperation with curative intent.
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  • 4
    ISSN: 1534-4681
    Keywords: Gastric cancer ; Prognosis ; Pepsinogen C ; Pepsinogen A
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: In this study we evaluated the expression and clinical significance of pepsinogen C, an aspartic proteinase involved in the digestion of proteins in the stomach, in patients with gastric cancer. Methods: Pepsinogen C expression was examined by immunohistochemical methods in a series of 95 gastric carcinomas. The prognostic value of pepsinogen C was retrospectively evaluated by multivariate analysis taking into account conventional prognostic parameters. Follow-up period of patients was 21.4 months. Results: A total of 25 (26.3%) gastric carcinomas stained positively for pepsinogen C. The percentage of pepsinogen C-positive tumors was higher in well-differentiated (50%) than in moderately differentiated (19.5%) and poorly differentiated (21.9%) tumors (P 〈 .05). Similarly, significant differences in pepsinogen C immunostaining were found between node-negative and node-positive tumors (47.1% vs. 14.7%; P 〈 .001). In addition, statistical analysis revealed that pepsinogen C expression was associated with clinical outcome in gastric cancer patients. Low pepsinogen C levels predicted short overall survival periods in the overall group of patients with gastric cancer (P 〈 .001), and in 71 patients with resectable carcinomas (P 〈 .005). Multivariate analysis according to Cox’s model indicated that pepsinogen C immunostaining was an independent predictor of outcome for both overall and resectable gastric cancer patients (P 〈 .05, for both). Conclusions: The expression of pepsinogen C in gastric cancer may represent a useful biological marker able to identify subgroups of patients with different clinical outcomes.
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  • 5
    ISSN: 1534-4681
    Keywords: Stomach ; Cancer ; Gastric cancer ; Lymph node metastasis ; Prognosis ; Survival rate ; Multivariate analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: In gastric cancer, the level and number of lymph node metastases is useful for predicting survival, and there are several staging systems for lymph node metastasis. The aim of this study was to compare the several lymph node classifications and to clarify the most important lymph node information associated with prognosis using multivariate analysis. Methods: A total of 106 patients with histologically node-positive gastric cancer treated by radical gastrectomy and extended lymph node dissection (D2, D3) were studied. The level of lymph node metastasis was categorized simply as Level I nodes (perigastric, No.1–6), Level II nodes (intermediate, No.7–9), and Level III nodes (distant, No.10–16), irrespective of the tumor location. The Level II nodes included lymph nodes along the left gastric artery, common hepatic artery, and celiac trunk. Results: Overall 5-year survival rate was 51%. Univariate analysis showed that 5-year survival rate was significantly influenced by the level of positive nodes (P 〈 .01), total number of positive nodes (P 〈 .01), number of positive Level I nodes (P 〈 .01), and number of positive Level II nodes (P 〈 .01), in addition to the tumor location (P 〈 .05), tumor size (P 〈 .05), gross type (P 〈 .01), and depth of wall invasion (P 〈 .01). Of these, independent prognostic factors associated with 5-year survival rate were the number of positive Level II nodes (0–1 vs. ≥2) (62% vs. 19%, P 〈 .01) and the depth of wall invasion (within vs. beyond muscularis) (79% vs. 43%, P 〈 .01). Conclusions: Among several staging systems for lymph node metastases, the number of positive Level II nodes provided the most powerful prognostic information in patients with node-positive gastric cancer. When there were two or more metastases in the Level II nodes, prognosis was poor even after D2 or D3 gastrectomy.
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  • 6
    ISSN: 1530-0358
    Keywords: Microscopic peritoneal dissemination ; Colon-cancer ; Gastric cancer ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: We evaluated the incidence and prognostic relevance of microscopic intraperitoneal tumor cell dissemination of colon cancer in comparison with dissemination of gastric cancer as a rational for additive intraperitoneal therapy. METHODS: Peritoneal washouts of 90 patients with colon and 111 patients with gastric cancer were investigated prospectively. Sixty patients with benign diseases and 8 patients with histologically proven gross visible peritoneal carcinomatosis served as controls. Intraoperatively, 100 ml of warm NaCl 0.9 percent were instilled and 20 ml were reaspirated. In all patients hematoxylin and eosin staining (conventional cytology) was performed. Additionally, in 36 patients with colon cancer and 47 patients with gastric cancer, immunostaining with the HEA-125 antibody (immunocytology) was prepared. The results of cytology were assessed for an association with TNM category and cancer grade, based on all patients, and with patient survival, among the R0 resected patients. RESULTS: In conventional cytology 35.5 percent (32/90) of patients with colon cancer and 42.3 percent (47/111) of patients with gastric cancer had a positive cytology. In immunocytology 47.2 percent (17/36) of patients with colon cancer and 46.8 percent (22/47) of patients with gastric cancer were positive. In colon cancer, positive conventional cytology was associated with pT and M category (P=0.044 andP=0.0002), whereas immunocytology was only associated with M category (P=0.007). No association was found between nodal status and immunocytology in colon cancer and with the grading. There was a statistically significant correlation between pT M category and conventional and immunocytology in gastric cancer (P〈0.0015/P=0.007 andP〈0.001/P=0.009, respectively). Positive immunocytology was additionally associated with pN category (P=0.05). In a univariate analysis of R0 resected patients (no residual tumor), positive immunocytology was significantly related to an unfavorable prognosis in patients with gastric cancer only (n=30). Mean survival time was significantly increased in patients with gastric cancer with negative cytology compared with positive cytology (1,205 (standard error of the mean, 91)vs. 771 (standard error of the mean, 147) days;P=0.007) but not in patients with colon cancer (1,215 (standard error of the mean, 95)vs. 1,346 (standard error of the mean, 106) days;P=0.55). CONCLUSIONS: Because microscopic peritoneal dissemination influences survival time after R0 resections only in patients with gastric but not with colon cancer, our results may provide a basis for a decision on additive, prophylactic (intraperitoneal) therapy in gastric but not colon cancer.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Diseases of the colon & rectum 43 (2000), S. 1222-1226 
    ISSN: 1530-0358
    Keywords: Colorectal neoplasms ; Young age ; Case-control study ; Pathology ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Colorectal adenocarcinoma before the age of 40 is uncommon, and its prognosis is controversial, with many studies reporting a worse prognosis than in older patients and others showing no difference. The current study compared two groups of patients who had surgical resection for colorectal adenocarcinoma. METHODS: The case group was composed of 34 patients younger than 40 (34 ± 4) years. Detailed pathologic prognosis factors, tumor cell proliferation measured by proliferating cell nuclear antigen, survival, family history, and predisposing conditions were analyzed. Results were compared with a control group constituted of 34 patients older than 65 (75 ± 6) years matched by gender, cancer site, and Dukes stage. RESULTS: Tumor differentiation, presence of vascular and perineural neoplastic invasion, tumor growth pattern, tumor cell proliferation measured by proliferating cell nuclear antigen count, and survival according to the Kaplan-Meier method were not significantly different between younger and older patients. The only difference between the two groups was a higher prevalence of family history and predisposing conditions for colorectal cancer in younger patients (23vs. 3 percent;P=0.03). CONCLUSION: This case-control study documents that pathologic features and prognosis of colorectal adenocarcinoma are comparable in patients younger than 40 years compared with older patients for identical stages. The higher prevalence of positive family history in younger patients suggests a different genetic background compared with older patients.
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  • 8
    ISSN: 1534-4681
    Keywords: Gastric cancer ; Younger patients ; Elderly patients ; Comparative study ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Gastric cancer is one of the most common gastrointestinal malignancies worldwide. Some studies have suggested that it has a worse prognosis in young than in elderly patients. Methods: All young and elderly patients treated for gastric adenocarcinoma during the period 1988 to 1994 in a tertiary referral center in Mexico City were included. Demographic, clinical, and pathologic features of young patients (less than 40 years of age) with gastric cancer were compared with those of elderly patients (70 years of age or older) with the same diagnosis. Overall survival was the main outcome measure. Results: There were 38 patients in each group. The mean age of the young and elderly groups was 33 and 77 years, respectively. Family history of gastric cancer was reported by 6 patients of the younger group and by 1 patient in the older group (P 〈 .05). Most patients in both groups were symptomatic and had an advanced stage of the disease. With a mean follow-up of 17 months, the overall median survival for all patients was 12 months. By group, the median survival was 13 and 12 months for the young and elderly patients, respectively (P = .38). Variables with significant impact on survival were the stage of the disease, possibility of surgical resection, location of the tumor, and a family history of gastric cancer. Conclusions: Young patients represent a significant proportion of patients with gastric cancer in Hispanic populations. There were no significant differences in clinicopathological characteristics and outcome of gastric adenocarcinoma between young and elderly patients. Survival was determined by the stage of the tumor and the possibility of complete surgical resection.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Annals of surgical oncology 7 (2000), S. 520-525 
    ISSN: 1534-4681
    Keywords: Proximal gastric third ; Adenocarcinoma ; Total gastrectomy ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The incidence of proximal gastric third carcinoma (PGC) has been rising in recent years. Classification and surgical therapy remain controversial. Methods: Between May 1986 and October 1997, 532 patients were operated for primary gastric carcinoma. All patient data were analyzed retrospectively comparing findings in patients with PGC and those with distal gastric carcinoma (DGC). Results: Two hundred fifty patients had a PGC, and 282 patients had a DGC. The rate of R0 resections was 79.3% for PGC and 81.6% for DGC. In 93.9% of the patients with PGC total gastrectomy was performed; for DGC total gastrectomy was done in 74.5% of patients. Postoperative morbidity and mortality were 29.2% for PGC and 23.8% for DGC, and 3.2% for PGC and 3.5% for DGC, respectively. Patients with advanced tumor stages (stage III and IV) were more common in the PGC group (73.3% vs. 53.6% in DGC). After R0 resection, the 5-year survival rate was 33.2% for PGC and 59.7% for DGC. Conclusions: There was no significant difference between the rates of R0 resections for PGC and DGC. Total gastrectomy can be performed with low postoperative morbidity and mortality. PGC and DGC represent the same tumor entity, and prognosis is similar, but due to more advanced tumor stages, the long-term survival is worse for patients with PGC than for those with DGC. Left retroperitoneal lymphadenectomy may be indicated for PGC.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Diseases of the colon & rectum 43 (2000), S. 1227-1236 
    ISSN: 1530-0358
    Keywords: Rectal cancer ; Apoptosis ; p53 ; bcl-2 ; Prognosis ; Recurrence ; Survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: The aim of this study was to evaluate the prognostic value of the apoptotic index for recurrence and disease-free survival after curative surgery for rectal cancer, particularly in relation to clinicopathologic variables, p53− and bcl-2 expression. METHODS: Formalin-fixed, paraffin-embedded tissue samples of rectal carcinomas resected curatively within a five-year period were used (N=160). Apoptotic cells with fragmented DNA were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphatase-biotin nick-end-labeling method. The ratio of apoptotic tumor cells (in percent) was classified into low apoptotic index (less than 10 percent) and high apoptotic index (10 percent or more). Immunohistochemical analysis was performed using monoclonal antibodies (DO-1 for p53 and clone 124 for bcl-2). Statistics included univariate and multivariate analysis, and survival was calculated using the Kaplan-Meier method. RESULTS: Seventy-five percent of tumors showed a low apoptotic index, and 25 percent had a high apoptotic index. No correlation was found between apoptotic index and International Union Against Cancer stage (P〉0.05). However, significant correlations were documented with histologic differentiation (mean apoptotic index, 5.74 percent in moderatelyvs. 3.98 percent in poorly differentiated carcinomas; P=0.0173), lymph node involvement (mean apoptotic index, 6.11 percent in pN1vs. 3.72 percent in pN2; P=0.0074), p53 status (mean apoptotic index, 6.26 percent in p53−vs. 4.42 percent in p53+; P=0.0085), and bcl-2 expression (mean apoptotic index, 5.13 percent in bcl-2−vs. 6.51 percent in bcl-2+; P=0.0418). Tumors of the lower rectum had a lower apoptotic index than those of the upper rectum (P=0.0277). Neither univariate nor multivariate analysis assessed apoptotic index as predictor of prognosis: Recurrence rates did not differ between tumors related to apoptotic index (22 percent with low apoptotic indexvs. 15 percent with high apoptotic index; P〉0.05), and no significant differences were found regarding survival (P〉0.05). On multivariate analysis, International Union Against Cancer stage (P=0.0002), p53 (P=0.0002), gender (P=0.0136), and bcl-2 (P=0.0243) were independent predictors of recurrence. These variables, except for bcl-2, were also independently related to disease-free survival. CONCLUSIONS: Reflecting tumor biology, apoptotic index as single variable showed no prognostic significance, whereas p53 was an independent predictor for both recurrence and survival, and bcl-2 was independently related to recurrence, but not to survival. Clinically, International Union Against Cancer stage and gender were independent prognostic factors after curative surgery for rectal cancer.
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  • 11
    ISSN: 1534-4681
    Keywords: Colorectal hepatic metastases ; Liver neoplasm ; Liver resection ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Hepatic resection is potentially curative in selected patients with colorectal metastases. It is a widely held practice that multiple colorectal hepatic metastases are not resected, although outcome after removal of four or more metastases is not well defined. Methods: Patients with four or more colorectal hepatic metastases who submitted to resection were identified from a prospective database. Number of metastases was determined by serial sectioning of the gross specimen at the time of resection. Demographic data, tumor characteristics, complications, and survival were analyzed. Results: From August 1985 to September 1998, 155 patients with four or more metastatic tumors (range 4–20) underwent potentially curative resection by extended hepatectomy (39%), lobectomy (42%), or multiple segmental resections (19%). Operative morbidity and mortality were 26% and 1%, respectively. Actuarial 5-year survival was 23% for the entire group (median 5 32 months) and there were 12 actual 5-year survivors. On multivariate analysis, only number of hepatic tumors (P = .005) and the presence of a positive margin (P = .003) were independent predictors of poor survival. Conclusions: Hepatic resection in patients with four or more colorectal metastases can achieve long-term survival although the results are less favorable as the number of tumors increases. Number of hepatic metastases alone should not be used as a sole contraindication to resection, but it is clear that the majority of patients will not be cured after resection of multiple lesions.
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  • 12
    ISSN: 1436-3305
    Keywords: Key words EGC ; Prognosis ; Treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Background. During the 1970s, a special type of Gastric Cancer with excellent prognosis (early gastric cancer; EGC) was identified by the Japanese Research Society for Gastric Cancer. EGC has been defined as a tumor which invades the mucosa and/or submucosa, regardless of the lymph node status. Using this definition, we identified an initial phase of tumor development which could be treated both endoscopically and surgically. Methods. We examined 412 EGC patients, recruited between 1976 and 1999, with an average follow-up of 9 years. All tumors were classified according to the macroscopic and microscopic criteria proposed by the Japanese Society of Gastroenterological Endoscopy (JSGE) and Lauren, respectively. The infiltrative growth pattern was evaluated according to Kodama's classification. Only tumor-related death was considered as an end-point of interest for the survival analysis. Results. Submucosal tumors (P = 0.008), Pen A (see definition below) type disease (P = 0.0001), and lymph node-positive cancers (P = 0.0002) were significant prognostic factors on univariate analysis. Moreover, bivariate analysis showed that the worst prognosis, in terms of survival, was for patients with nodal involvment, submucosal invasion, and node-positive and Pen-A type cancer. The abbreviation Pen, penetrating, indicates a lesion with a diameter of less than 4 cm, which invades the submucosa diffusely. Pen A type EGC represents a subgroup of tumors which infiltrates the submucosa extensively, with nodular masses, causing the complete destruction of the muscularis mucosae. Conclusion. In our series, Pen A type was an important prognostic factor (hazard ratio; HR, 8.32; 95% confidence interval [CI], 3.49–19.86. For this reason, we believe it is important to evaluate the infiltration into the wall in all patients with EGC, paying particular attention to the growth pattern of the neoplasm. Moreover, submucosal Pen A type tumors had a considerably worse prognosis and this finding was reinforced when lymph node metastases coexisted. We suggest, therefore, that surgical treatment with at least a D2 lymphadenectomy is performed in all these patients, as the lesions must be considered to be advanced, no longer being EGC.
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  • 13
    ISSN: 1436-3305
    Keywords: Key words Tumor marker ; CEA ; CA19-9 ; Gastric cancer ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Background. This clinicopathological study evaluated the utility of serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 as predictors of locoregional recurrence and long-term disease-free survival in patients with gastric cancer. Methods. During the period January 1989 to December 1994, 485 patients with primary gastric cancer were evaluated. Gastrectomies were performed in 434 patients. Prognostic factors were analyzed by the Kaplan-Meier method and multivariate analysis, using Cox regression. Results. Elevated serum CEA and CA19-9 levels were observed in 92 of the 485 patients (19.0%), and in 95 of the 435 patients (21.8%), respectively, and both markers were elevated in 29 of these 435 patients (6.7%). Elevated serum CEA and CA19-9 levels correlated well with lymph node metastasis, lymphatic invasion, vessel invasion, stage grouping, depth of invasion, and curability. Patients with elevated serum CEA levels were at significantly higher risk of having all recurrence factors than were those with normal serum CEA levels. Patients with elevated serum CA19-9 levels were at significantly higher risk of having peritoneal metastases and distant metastases than were those with normal serum CA19-9 levels. A significant difference in the cumulative survival curves of patients was demonstrated between those with elevated and those with normal serum CEA or CA19-9 levels, even for patients at the same disease stage (stage III). Patients with elevated levels of both markers had a significantly worse prognosis than patients in whom the levels of both markers were normal. In patients who underwent gastrectomy, elevated serum CEA levels either preoperatively or within 3 weeks after gastrectomy were associated with significantly worse prognosis than were normal levels. When the cutoff level of serum CEA was increased to 10 ng/ml, serum CEA, age, lymph node metastasis, and surgical stage grouping were selected as independent prognostic factors by multivariate analysis of 14 prognostic factors, using Cox regression. Conclusion. Serum CEA and CA19-9 levels provide additional prognostic information in patients with primary gastric cancer. In particular, an elevated serum CEA level provides additional prognostic information and is a useful indicator of curability in patients who undergo gastrectomy. Serum CEA level is an independent prognostic factor in patients with primary gastric cancer.
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Trauma und Berufskrankheit 2 (2000), S. S154 
    ISSN: 1436-6274
    Keywords: Schlüsselwörter ; Hinteres Kreuzband ; Isolierte Ruptur ; Therapie ; Prognose ; Key words ; Posterior cruciate ligament ; Isolated tears ; Treatment ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract The treatment of injuries to the PCL is still controversial. There are still no answers to many questions on the biomechanics of PCL, the natural history of PCL injury, the surgical technique of PCL reconstruction and the biology of PCL healing. It is well established that primary repair of bony avulsions of the PCL provides good static and functional results. PCL tears should also be treated surgically in combined knee ligament injuries. For isolated midsubstance tears of the PCL, however, no prospective randomised long-term studies are available to date demonstrating that surgical treatment with current techniques leads to better results than nonoperative, functional treatment. Nonoperative management is advocated because the knee instability following isolated PCL midsubstance tear is only moderate, the natural history has been seen to end in acceptable functional stability, knee proprioception is preserved, and the incidence of late osteoarthritis is low.
    Notes: Zusammenfassung Die Behandlung von Rupturen des hinteren Kreuzbands wird international noch immer kontrovers diskutiert. Zahlreiche Fragen zur funktionellen Anatomie, zum Spontanverlauf nach Ruptur, zur chirurgischen Technik sowie zum Heilungsverlauf sind unbeantwortet. Gesichert ist, daß die primäre operative Versorgung von knöchernen Ausrissen des hinteren Kreuzbands zu guten Ergebnissen führt. Bei kombinierten Knieinstabilitäten sollte das verletzte hintere Kreuzband auch operativ versorgt werden. Für die isolierte, interligamentäre Ruptur des hinteren Kreuzbands konnte bisher jedoch mit keiner prospektiven, randomisierten Langzeitstudie bewiesen werden, daß die heutigen Operationsverfahren reproduzierbar zu besseren Ergebnissen führen als die konservativ-funktionelle Behandlung. Für die konservative Therapie sprechen die nur mäßige Instabilität nach isolierter Ruptur des hinteren Kreuzbands, der günstige Spontanverlauf und der Erhalt der Propriozeption des Kniegelenks sowie die im Verlauf nur geringe Arthroserate.
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  • 15
    ISSN: 1436-2813
    Keywords: Key Words Adenosquamous carcinoma ; Remnant stomach ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report herein the case of a 59-year-old man found to have adenosquamous carcinoma of the remnant stomach which demonstrated rapid progression. The patient was admitted to our hospital to undergo surgery for a papillary tumor of the remnant stomach. Total resection of the remnant stomach with lymph node dissection was performed, and pathological examination confirmed a diagnosis of adenosquamous carcinoma with invasion into the muscularis propria and lymph node metastasis around the perigastric areas. Multiple liver metastases were found 6 months after the operation, for which a right hepatectomy was performed with curative intent; however, he died 2 months later due to lymphangitis carcinomatosa of the lung.
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  • 16
    ISSN: 1436-2813
    Keywords: Key Words: genetic changes ; prognostic factor ; breast cancer ; amplification ; loss of heterozygosity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: ERBB2 , INT2, and MYC genes, in 131 patients with breast carcinoma, 49 of whom had lymph node involvement, but none of whom had distant metastases. Among the several chromosome arms tested, LOH at 17q was correlated with lymph node metastasis. Amplification of the ERBB2, MYC, and INT2 genes was found more frequently in tumors from patients with lymph node metastases than in tumors from those without lymph node metastases. Univariate analysis demonstrated that LOH at 17q and INT2 amplification were factors influencing disease-free survival (DFS). A multivariate analysis was performed on 89 tumors that were able to be evaluated for both LOH at 17q and INT2 amplification, and the results showed that patients who had tumors with these genetic changes were more likely to have a poor prognosis. The findings of this study suggest that investigating genetic changes, in addition to conventional clinicopathologic factors, may contribute to defining groups of breast cancer patients with differences in prognosis.
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  • 17
    ISSN: 1436-3305
    Keywords: Key words Hypergastrinemia ; Carcinoid tumor ; Prognosis ; Autoimmune gastritis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Gastric carcinoid tumors associated with chronic atrophic gastritis type A have been reported to show good prognosis, because invasion and metastasis are rare. We report a case of gastric carcinoid tumor associated with hypergastrinemia that showed no malignant changes for 12 years. A 15-year-old man with abdominal discomfort underwent endoscopic examination. A polypoid lesion was detected on the atrophic mucosa of the fundus, and was diagnosed as a carcinoid tumor. Serological examination revealed a high level of anti-parietal-cell antibody, suggesting that the patient had chronic atrophic gastritis type A. The tumor was treated by endoscopic mucosal resection. Follow-up examinations were performed for 12 years, but showed no recurrence. This case confirms that gastric carcinoid tumors associated with chronic atrophic gastritis type A may have a good prognosis.
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  • 18
    ISSN: 1436-3305
    Keywords: Key words Stomach ; Cancer ; Gastric cancer ; Lymph node metastasis ; Prognosis ; Survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Background. Although many authors have investigated the prognostic factors of gastric cancer, there are few comprehensive studies on the prognosis of patients with extensive lymph node metastasis. The aim of this study was to clarify the prognostic factors of gastric cancer with extragastric lymph node metastasis, using multivariate analysis. Methods. The study population consisted of 121 patients who had undergone radical gastrectomy and extended lymph node dissection (D2, D3) for gastric cancer with extragastric lymph node metastasis. We examined 18 clinicopathologic factors, including the type of gastrectomy, tumor size, depth of wall invasion, status of lymph node metastasis, and stage of disease. Survival rates were analyzed by the Kaplan-Meier and Mantel-Cox methods, and multivariate analysis was done using the Cox proportional hazards model. Results. The overall 5-year survival rate was 32%, and the 5-year survival rate after curative gastrectomy was 37%. Overall survival rate was associated with the type of gastrectomy, stage of disease, operative curability, tumor size, depth of wall invasion, and anatomical distribution of positive nodes, whereas the survival rate after curative gastrectomy was correlated with the type of gastrectomy, stage of disease, tumor size, gross type, and depth of wall invasion. Independent prognostic factors were operative curability and depth of wall invasion, and survival after curative gastrectomy was influenced only by the depth of wall invasion (mucosa and submucosa [T1], muscularis and subserosa [T2] vs serosa [T3]). Conclusion. In patients with gastric cancer with extragastric lymph node metastasis, independent prognostic factors after gastrectomy were operative curability and depth of wall invasion. Long-term survival can be achieved when the patients have no serosal invasion (T1, T2) and are treated by curative gastrectomy.
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  • 19
    ISSN: 1432-2307
    Keywords: Keywords AgNORs ; Standardised AgNOR analysis ; Parathyroid tumour ; Proliferation ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Prediction of evolution of secondary hyperplasia and tumours of the parathyroid glands is still a problem in histopathology. To assess whether the quantity of silver-stained nucleolar organiser region (AgNOR) proteins might be used as a prognostic tool in parathyroid pathology, a standardised AgNOR analysis has been performed on 19 cases of parathyroid hyperplasia caused by secondary hyperparathyroidism (PH), 8 cases of adenoma (PA) and 10 cases of carcinoma (PC). Clinico-pathological data and follow-up information were available. On formalin-fixed and paraffin-embedded sections, the visualisation and quantification of AgNORs were achieved according to the 1995 guidelines of the Committee on AgNOR Quantification. Then, the mean area (square micrometres) of AgNORs per nucleus (NORA) was evaluated by means of an image analyser and specific softwares. After testing the normal distribution of NORA values, statistical parametric tests were utilised; Kaplan-Meier and Cox multivariate analyses were also performed. In parathyroid lesions, a progressive increase of mean NORA values was observed from PH (2.895 µm2; SE 0.171) through PA (3.638 µm2; SE 0.125) to PC (4.701 µm2; SE 0.179); these differences were highly significant (P〈0.001), although some degree of overlap was found among single NORA values. A significantly higher mean NORA value was revealed in PC with distant metastases than was noted in cases with no current clinical evidence of disease progression. Furthermore, a significantly (P〈0.001) higher mean NORA value was encountered in the group of PH with recurrences (3.600 µm2; SE 0.106) than in nonrecurrent PH (2.261 µm2; SE 0.087). Multivariate analyses indicated that the NORA value was an independent prognostic parameter determining the risk of recurrence in PH. We suggest that AgNOR quantity may be a promising additional tool for predicting the biological behaviour of parathyroid lesions.
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  • 20
    ISSN: 1569-8041
    Keywords: BRCA1 ; breast cancer ; p53 ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:The association between BRCA1 germ-linemutations and breast cancer prognosis is controversial. A historical cohortstudy was designed to determine the prognosis for women with axillary lymphnode negative hereditary breast cancer. Patients and methods:We tested pathology blocks from 118Ashkenazi Jewish women with axillary lymph node negative breast cancer for thepresence of the two common BRCA1 founder mutations, 185delAG and5382insC. Patients were followed up for a median of 76 months. SomaticTP53mutations were screened for by immunohistochemistry, and directsequencing was performed in the BRCA1-positive tumours. Results:Sixteen breast cancer blocks (13.6%) carried aBRCA1 mutation. Young age of onset, high nuclear grade, negativeestrogen receptor status and over-expression of p53 were highly associatedwith BRCA1-positive status (P-values all 〈0.01).BRCA1 mutation carriers had a higher mortality than non-carriers(five-year overall survival, 50% and 89.6%, respectively,P = 0.0001). Young age of onset, estrogen receptor negative status,nuclear grade 3, and over-expression of p53 also predicted a poor outcome. Coxmultivariate analyses showed that only germ-line BRCA1 mutationstatus was an independent prognostic factor for overall survival (P= 0.01). Among nuclear grade 3 tumours, the BRCA1 mutation carrierstatus was a significant prognostic factor of death (risk ratio 5.8,95% confidence interval: 1.5–22, P = 0.009). Sequencingof BRCA1-related breast cancers revealed one TP53missensemutation not previously reported in breast cancer. Conclusions:Using a historical cohort approach, we haveidentified BRCA1 mutation status as an independent prognostic factorfor node negative breast cancer among the Ashkenazi Jewish women. Thosemanaging women carrying a BRCA1 mutation may need take these findingsinto consideration. Additionally, our preliminary results, taken together withthe work of others suggest a different carcinogenic pathway inBRCA1-related breast cancer, compared to non-hereditary cases.
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  • 21
    ISSN: 1569-8041
    Keywords: BCL-2 ; breast cancer ; HER-2 ; p53 ; predictive factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:The selection of therapies for breast cancer is todaybased on prognostic features (chemotherapy, radiotherapy), hormone receptorstatus (hormonal therapy) and HER-2 status (trastuzumab therapy). HER-2,p53and BCL-2are tumour-related proteins that have thepotential to further improve individualisation of patient management, bypredicting response to chemotherapy, hormonal therapy and radiotherapy. Materials and methods:This paper reviews the rationale for theuse of these proteins as predictive factors, as well as the publishedliterature addressing the use of each one to predict response to hormonaltherapy, chemotherapy and radiotherapy. Results:HER-2, p53and BCL-2remaininadequately assessed as predictive factors in breast cancer. HER-2 evaluationis required for the selection of patients for trastuzumab (Herceptin®)therapy, as trials of this therapy have been limited to HER-2 overexpressors.HER-2 overexpression may be predictive of resistance to hormonal therapy.Anthracyclines are effective therapy for breast cancer regardless of HER-2status, but patients whose tumours overexpress HER-2 appear to receive thegreatest relative benefit from this therapy. Studies of HER-2 as a predictorof response to CMF and to radiotherapy are inconclusive at this time. No datayet exist to support the use of p53or BCL-2as predictivefactors in the therapy of breast cancer. Conclusions:At this point in time, there is inadequate evidenceto support the use of HER-2, p53or BCL-2to guide theselection of hormonal therapy, chemotherapy or radiotherapy for breast cancer.
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  • 22
    ISSN: 1569-8041
    Keywords: breast cancer ; camptothecins ; colorectal cancer ; GI147211 ; non-small-cell lung cancer ; topoisomerase I
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:GI147211 is a water-soluble synthetic analogue ofcamptothecin showing promising in vivoand in vitroantitumor activity and an acceptable toxicity profile. Patients and methods:Between April 1995 and November 1996, 67eligible patients with pretreated breast cancer (25 patients) andchemo-naïve colorectal (19 patients) and non-small-cell lung cancer (23patients) were entered into three multicentric, non-randomized phase IItrials. Treatment schedule consisted of intravenous GI147211 administered ata dose of 1.2 mg/m2/day for five consecutive days every threeweeks. Results:Hematological toxicity was common with grade 3–4neutropenia in 54% of patients and neutropenic fever together or notassociated with infection in 14.5% of patients. Grade 3–4thrombocytopenia and grade 2–4 anemia were observed in 20% andin 68% of patients, respectively. Non-hematological toxicity wasgenerally mild to moderate and consisted mainly of gastrointestinal toxicity,asthenia and alopecia. A dose-escalation to 1.5 mg/m2/d wasfeasible in 17 (25%) patients. The antitumor activity of GI147211 wasmoderate in breast cancer patients (3 partial responses (PRs), response rate(RR) 13%) and minimal in non-small cell lung cancer patients (2 PRs,RR 9%). No objective responses were obtained in colorectal patients. Conclusions:GI147211, at the dose and schedule employed in thisstudy, showed an acceptable safety profile but a modest antitumor activity inthe examined tumor types.
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  • 23
    Electronic Resource
    Electronic Resource
    Springer
    Biomedical microdevices 2 (2000), S. 305-316 
    ISSN: 1572-8781
    Keywords: membranes ; breast cancer ; oncology ; cell column regulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract Using microfabrication technology, we have developed a new experimental apparatus and technique which allow isolation of individual cells and which facilitate the study of kinetic volume changes and membrane permeability. The key component of the apparatus is a microdiffusion chamber which was constructed using silicon microfabrication technology and standard photolithography. The central unit of the chamber is a 1 μ m thick silicon nitride membrane with a center hole on the order of 2–3 μ m in diameter. The device is novel in its analysis of a single cell, instead of the traditional array of cells, and its avoidance of the damage artifacts and computational difficulties which are inherent in other, commonly used methods of cellular analysis. The device is used in conjunction with a predictive computer model which simulates the response of the entire membrane or a portion of the membrane to various permeant and impermeant concentrations. This study introduces the apparatus and the model, and illustrates the effectiveness of the new procedure by determining several membrane permeability coefficients for HBL-100 (healthy human breast line). The empirical data and theoretical data were combined to yield a water permability (L p) of 1.1 ± 0.5μ m/(min-atm) (mean ± 1 standard deviation) (N= 5) during the uncoupled transport of water at 22 ±C. In the presence of 6 M glycerol, the water permeability (L p), permeability coefficient (P S), and the reflection coefficient (σS) were determined to be 2.0 ± 0.63 μ m/(min-atm), 2.7E-5 ± 6.1E-6 cm-sec-1, and 0.76 ± 0.5 (N = 6). No previous values of these coefficients could be found for HBL-100 cells.
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  • 24
    ISSN: 1569-8041
    Keywords: biological/pathological characteristics ; breast cancer ; prognosis ; progression ; symptomatic/asymptomatic patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:It is well known that mammographic screening reducesbreast cancer mortality. One possible explanation for this effect is thatscreening makes it possible to detect smaller breast cancers with fewerinvolved nodes, but another hypothesis is that some screening-detected tumorsare in a pathologically and biologically different phase of evolution fromthose that are detected clinically. The aim of the present study was tocompare the biological, pathological and clinical characteristics ofsymptomatic vs. asymptomatic breast cancers. Patients and methods:The study considers a series of 1916consecutive patients who underwent surgery for stage I and II infiltratingbreast cancer at Verona hospitals after having undergone ultrasound andmammography (at least one of which was positive). They were divided into twogroups on the basis of why they decided to undergo the imaging examinations:group A refers to the 1247 patients with a palpable lump, and group B to the616 who were asymptomatic. Results:The patients in group A were older, and had larger tumorsand a higher percentage of positive nodes than those in group B; they also hadsignificantly higher grade tumors, higher Ki-67 levels, and a higherpercentage of ER and PgR negative and c-erbB-2 positive tumors (allof the P-values were significant). A logistic regression analysisadjusted for tumor diameter and age showed a reduction in the significance ofeach of the considered variables, but all of them remained significantlyassociated with the modality of diagnosis except ER, PgR andc-erbB-2. Conclusions:Our results suggest that asymptomatic tumors arebiologically different from their clinically presenting counterparts, thusconfirming the hypothesis that progression towards greater malignancy mayoccur during the natural history of breast cancer.
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  • 25
    ISSN: 1569-8041
    Keywords: 4-OH-IF ; breast cancer ; drug combination ; human cell lines ; primary cultures ; VNB
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Vinorelbine and ifosfamide are active drugs againstbreast cancer, but the best treatment schedule has yet to be defined bypreclinical or clinical studies. The antitumor activity of4-hydroxy-ifosfamide (4-OH-IF), the active form of ifosfamide, and vinorelbine(VNB) and their interaction were investigated in two established breast cancercell lines (MCF-7 and BRC-230) and in 10 primary breast cancer cultures. Materials and methods:Cytotoxic activity was evaluated by ahighly efficient clonogenic assay (HECA). The median-effect principle wasapplied to evaluate synergistic and antagonistic interactions and thecorresponding combination index values were calculated. Cell cycleperturbations were analysed by flow cytometry. Results:In MCF-7 and BRC-230 cell lines the sequence VNB for 4hours followed by 4-OH-IF for 24 hours produced an antagonistic effect.Conversely, the inverse sequential scheme, 4-OH-IF → VNB providedsynergistic effects on both cell lines. The synergism was associated with astrong block in the G2-M phase. Synergistic activity of 4-OH-IF → VNBsequence was confirmed in 7 of 10 primary breast cancercultures. Conclusions:In conclusion, the sequence 4-OH-IF → VNBappeared to be the most effective scheme both in established cell lines andin primary breast cancer cultures.
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  • 26
    ISSN: 1569-8041
    Keywords: adjuvant treatment ; breast cancer ; tamoxifen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aim:Immediate adjuvant tamoxifen reduces disease recurrence andimproves survival in patients with early breast cancer. However, is it toolate to administer tamoxifen to patients who have already undergone treatment,but were unable to benefit from this adjuvant therapy? The French NationalCancer Centers (FNCLCC) have investigated the efficacy of delayed tamoxifenadministration in a randomized controlled trial. Patients and methods:From September 1986 to October 1989, womenwith primary breast cancer, who had undergone surgery, radiotherapy, and/orreceived adjuvant chemotherapy but not hormone therapy more than two yearsearlier, were randomized to receive either 30 mg/day tamoxifen or notreatment. The 10-year disease-free and overall survival rates of the twogroups of patients and of various subgroups were determined according to theKaplan–Meyer method and compared by the log-rank test. Results:This intention-to-treat analysis comprised 250 women inthe tamoxifen group and 244 in the control group. Patient characteristics(age, T stage, number of positive nodes, receptor status, and interval sincetumor treatment) were comparable in both groups. Delayed adjuvant tamoxifensignificantly improved overall survival only in node-positive patients and inpatients with estrogen receptor-positive (ER+) or progesteronereceptor-positive (PR+) tumors. Disease-free survival, however, wassignificantly improved in the global population and in several patientsubgroups (node-positive, ER+, PR+). Patients in whom the interval betweenprimary treatment and delayed adjuvant tamoxifen was greater than five yearsalso had significantly improved disease-free survival. Conclusions:Overall and disease-free survival results indicatethat delayed adjuvant tamoxifen administration (30 mg/day) is justified inwomen with early breast cancer, even if this treatment is initiated two ormore years after primary treatment.
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  • 27
    Electronic Resource
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    Springer
    Annals of oncology 11 (2000), S. 1349-1351 
    ISSN: 1569-8041
    Keywords: breast cancer ; radiotherapy ; tumor lysis syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tumor lysis syndrome (TLS) is a rare serious acute complication of cancertherapy, reported mainly following chemotherapy in patients with large tumorload and chemosensitive disease. These are mainly patients with non-Hodgkin'slymphoma, leukemia and rarely in solid tumors. It is less frequently describedafter radiotherapy for lymphoid and hematological malignancies. TLS followingradiotherapy for solid tumors is a very rare complication. In thisreport/review we describe a seventy-three-year-old male patient withprogressive metastatic carcinoma of the breast to the lungs, liver and bone.He was referred for radiotherapy because of generalized bony pains. Thepatient was planned for sequential hemi-body irradiation starting with themore symptomatic upper half body. After premedication, he was given 8.5 Gy tothe mid point at the maximum chest separation with anterior lung attenuatorlimiting uncorrected lung dose to 6.15 Gy. A further 3.5 Gy electron boost tothe fungating breast tumor was given to the 100%. Forty-eight hours after irradiation he developed hyperkalemia,hyperphosphatemia, hyperuricemia, hypocalcemia and renal failure. Theseclinical and biochemical changes are typical of tumor lysis syndrome (TLS).Despite hydration, and treating the hyperuricemia, the patient developed comaand died eight days after irradiation. The prophylaxis and management of TLS and in high-risk patients aredescribed to avoid this frequently fatal complication.
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  • 28
    ISSN: 1569-8041
    Keywords: breast cancer ; erbB2 ; HER-2/neu ; tamoxifen ; therapy resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aim:We aimed to study the importance of erbB2 status in earlystage postmenopausal breast cancer for patients who participated in a trialof five vs. two years of adjuvant tamoxifen. Patients and methods:We analysed the erbB2 status of the tumoursfrom 577 patients participating in the trial, either by a DNA amplificationassay (n = 181) or by measurement of the protein level with flowcytometry (n = 396). Results:ErbB2 was overexpressed or gene amplified in 102 of thepatients (18%). Overall, erbB2-positive patients had a significantlylower recurrence-free probability than others, 62% at five years ascompared to 83%, and showed a significantly decreased breast cancersurvival rate (P = 0.0007). ErbB2 status was significantlyassociated with recurrence and death in Cox multivariate analysis, adjustingfor nodal status, tumour size and estrogen receptor status. The relative riskof recurrence (RR) for five vs. two years of tamoxifen was analysed inrelation to erbB2 status for patients still disease-free two years aftersurgery. Whereas erbB2-negative patients showed significant benefit fromprolonged treatment (RR = 0.62, 95% confidence interval (95%CI): 0.42–0.93), no benefit was evident for erbB2-positive patients (RR= 1.1, 95% CI: 0.41–3.2). When the same analysis was restrictedto ER-positive patients a similar difference in relative hazard was obtainedbut the difference was not strictly significant (P = 0.065). Conclusions:For early stage breast cancer patients treated withadjuvant tamoxifen, overexpression of erbB2 is an independent marker of poorprognosis. The results suggest that overexpression decreases the benefit fromprolonged tamoxifen treatment.
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  • 29
    ISSN: 1569-8041
    Keywords: breast cancer ; cyclophosphamide ; elderly ; idarubicin ; oral chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 30
    ISSN: 1569-8041
    Keywords: adjuvant therapy ; breast cancer ; docetaxel ; feasibility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background and purpose:Docetaxel is an active agent in thetreatment of metastatic breast cancer. We evaluated the feasibility ofdocetaxel-based sequential and combination regimens as adjuvant therapies forpatients with node-positive breast cancer. Patients and methods:Three consecutive groups of patients withnode-positive breast cancer or locally-advanced disease, aged ≤70 years,received one of the following regimens: a) sequential A → T → CMF:doxorubicin 75 mg/m2 q 3 weeks × 3, followed by docetaxel 100mg/m2 q 3 weeks × 3, followed by i.v. CMF days 1 + 8 q 4weeks × 3; b) sequential accelerated A → T → CMF: A and T wereadministered at the same doses q 2 weeks; c) combination therapy: doxorubicin50 mg/m2 + docetaxel 75 mg/m2 q 3 weeks × 4,followed by CMF × 4. When indicated, radiotherapy was administeredduring or after CMF, and tamoxifen started after the end of CMF. Results:Seventy-nine patients have been treated. Median age was48 years. A 30% rate of early treatment discontinuation was observedin patients receiving the sequential accelerated therapy (23% duringA → T), due principally to severe skin toxicity. Median relativedose-intensity was 100% in the three treatment arms. The incidence ofG3–G4 major toxicities by treated patients, was as follows: skintoxicity a: 5%; b: 27%; c: 0%; stomatitis a: 20%;b: 20%; c: 3%. The incidence of neutropenic fever was a:30%; b: 13%; c: 48%. After a median follow-up of 18months, no late toxicity has been reported. Conclusions:The accelerated sequential A → T → CMFtreatment is not feasible due to an excess of skin toxicity. The sequentialnon accelerated and the combination regimens are feasible and under evaluationin a phase III trial of adjuvant therapy.
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  • 31
    ISSN: 1432-1335
    Keywords: Key words erbB-3 ; Colorectal carcinoma ; Survival ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background/aims: The family of erbB receptors includes four transmembrane glycoproteins with tyrosine kinase activity. These receptors are widely expressed in normal tissues, but they also have been implicated in the development of several human adenocarcinomas. c-erbB-3/HER-3 has been detected to a greater or lesser extent in many tissues from the digestive, urinary, reproductive and respiratory tracts. The overexpression of c-erbB-3/HER-3 protein has also been shown in 53%–88% of colorectal adenocarcinomas. In this study we investigated the expression of the c-erbB-3/HER-3 gene product in colorectal tumour samples, and compared the results obtained with several clinicopathological parameters, including the survival of patients. Methods: Paraffin-embedded tissue sections were analysed immunohistochemically, using monoclonal antibody RTJ1 to human erbB-3 protein. Antibody RTJ1 specificity was confirmed by immunoprecipitation followed by Western blotting analysis. Amplification of the erbB-3 oncogene was tested by dot-blot hybridization. Results: Adenocarcinomas of the colon were positive for erbB-3 protein in 78% of samples examined. Dot-blot analysis showed no amplification of the erbB-3 gene in colon adenocarcinomas. Statistical analysis showed that patients with tumours that could not be stained for erbB-3 protein survived significantly longer (P 〈 0.05) than patients with tumours staining positive for the erbB-3 protein. A Cox proportional-hazards model with stepwise variable selection identified age, sex and erbB-3 expression as important prognostic factors. Conclusion: These findings demonstrate that erbB-3 protein expression could serve as a prognostic factor in colorectal malignancies.
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  • 32
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    Journal of cancer research and clinical oncology 126 (2000), S. 48-52 
    ISSN: 1432-1335
    Keywords: Key words Enzyme-linked immunosorbent assay ; p53 protein ; WAF1 protein ; Lung cancer ; Prognosis ; AbbreviationsNSCLC non-small-cell lung cancer ; RR relative risk
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: p21WAF1, a cyclin-dependent kinase inhibitor, is an important mediator of the cell-cycle arrest and tumor suppression induced by the protein p53. Although alterations of the p53 gene and its overexpression are frequent in most malignancies, including non-small-cell lung cancer (NSCLC), and may be associated with poor patient prognosis, the clinical utility of p21WAF1 expression in NSCLC has not been established. Methods: We have used a commercial enzyme-linked immunosorbent assay (ELISA) kit for p21WAF1 to test soluble extracts of 54 NSCLC specimens with known clinicopathological properties. Results: There was no correlation between p21WAF1 and p53 concentrations, the latter being determined by a time-resolved immunofluorometric assay developed in-house. Furthermore, p21WAF1 levels were not associated with patient age, tumor/node/metastasis (TNM) stage, lymph node metastasis, histological grade or type, or smoking history, in Mann-Whitney analysis. χ2-tests, based on cutoffs equal to the 25th, 50th, or 75th percentiles of the p21WAF1 distribution, similarly did not reveal any statistically significant associations between p21WAF1 and other clinicopathological variables. Because of the small number of patients and the median follow-up of only 18 months, a meaningful survival analysis could not be performed. Conclusion: In summary, this preliminary study suggests that ELISA-quantified p21WAF1 levels in NSCLC extracts are weaker than p53 in terms of prognostic value and do not contribute to the further subclassification of patients.
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  • 33
    Electronic Resource
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    Der Ophthalmologe 97 (2000), S. 121-125 
    ISSN: 1433-0423
    Keywords: Schlüsselwörter Postoperative Endophthalmitis ; Prognose ; Visus ; Bakterien-Kultur ; Verlaufsform ; Key words Postoperative endophthalmitis ; Prognosis ; Visual acuity ; Microbiology culture ; Onset of endophthalmitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Background: The outcome of 20 patients is summarized in a retrospective study to identify clinical findings that influence the long-term prognosis of postoperative endophthalmitis. Patients: Between 1991 and 1997 a total of 20 patients with postoperative endophthalmitis were admitted. Median age was 80 years (range: 9–95), 11 patients were male, 9 female. Sixteen pars-plana vitrectomies, 2 anterior vitrectomies and 2 rinsings of the anterior chamber without vitrectomy were performed. Furthermore, all patients received intraocular and systemic antibiotic treatment. For microbiological investigation, specimens from vitreous, anterior chamber and conjunctiva were sent in. Long-term outcome was controlled for an average of 14 months after treatment of the endophthalmitis (range: 4–36 months). Results: At the end of treatment, 40% of patients had a visual acuity of 0.4 or better, 80% had 1/20 or better. Patients with a preoperative visual acuity of at least hand movement had a better postoperative visual outcome than patients with only light perception. Visual acuity was better in patients with chronic endophthalmitis than in patients with acute or subacute endophthalmitis. In patients with chronic or subacute endophthalmitis, improvement of visual acuity was found some months after the operation more often than in patients with acute endophthalmitis. However, in 40% of cases with an acute onset, no improvement or even worsening of the visual acuity was documented. Best postoperative results were found after infection with Staphylococcus epidermidis and Propionibacterium acnes. Conclusion: Important prognostic factors of postoperative endophthalmitis are visual acuity, the onset of the endophthalmitis (acute, subacute or chronic) and the microbiological findings. At the time of surgery and antibiotic treatment, visual acuity should be at least hand motion to expect an improvement in the visual outcome.
    Notes: Zusammenfassung Fragestellung: Im Rahmen einer retrospektiven Studie sollte das Patientengut mit postoperativer Endophthalmitis bezüglich prognostischer Gesichtspunkte ausgewertet werden. Patienten und Methode: 20 Patienten (9 weiblich, 11 männlich), im Alter von 9–95 Jahren (Median 80 Jahre) mit postoperativer Endophthalmitis wurden im Zeitraum von 1991 bis 1997 in unserer Klinik behandelt. 16mal wurde eine Pars-plana-Vitrektomie (PpV) durchgeführt, weiterhin 2 vordere Vitrektomien und 2 Vorderkammerspülungen ohne Vitrektomie. Alle Patienten erhielten intraokular und systemisch Antibiotika. Der postoperative Beobachtungszeitraum betrug 4 bis 36 Monate (im Durchschnitt 14,0). Die mikrobiologische Untersuchung umfaßte Kulturen von Glaskörper, Vorderkammer und Bindehaut. Ergebnisse: Bei 80% der Patienten war der letzte Visus 1/20 und besser, bei 40% mindestens 0,4. Bei einem präoperativen Visus von mindestens Handbewegung (HB) war der postoperative Visus besser als bei einem schlechteren Ausgangsvisus (Lichtschein). Die chronischen Endophthalmitiden hatten ein besseres Visusergebnis als die akuten und subakuten Endophthalmitiden. Bei den chronischen und subakuten Verläufen war häufiger als bei den akuten Verläufen noch ein Visusanstieg in den ersten Monaten nach der Operation möglich. Bei 40% der akuten Verläufe stagnierte der Visusanstieg, oder der Visus wurde schlechter. Der postoperative Visus war bei Staphylococcus epidermidis- und Propionibacterium acnes-Infektionen am besten. Schlußfolgerung: Prognostische Faktoren der postoperativen Endophthalmitis sind der Visus, das Kulturergebnis und die Verlaufsform (akut, subakut, chronisch). Zum Zeitpunkt der Operation und der intravitrealen Antibiotikagabe sollte der Visus nicht schlechter als Handbewegungen sein, um postoperativ einen besseren Visus zu erreichen.
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  • 34
    ISSN: 1433-0458
    Keywords: Schlüsselwörter Plattenepithelkarzinom ; Kopf-Hals-Bereich ; CGH ; Prognose ; Cox-Regression ; Key words Squamous cell carcinoma ; Head and neck region ; CGH ; Prognosis ; Cox regression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract In individual patients with head and neck squamous cell carcinomas (HNSCC), established prognostic factors do not satisfactorily predict clinical outcome. For the first time we investigated a total of 100 HNSCC by Comparative Genomic Hybridization (CGH) to define chromosomal alterations that are associated with the patients prognosis. Patients were followed for at latest 4 but at least 2 years after surgery or until death. During this observation period twenty-nine of them died because of cancer disease. The Kaplan-Meier method was used plotting survival curves for every single chromosomal alteration as well as every clinico-pathological parameter. The curves were tested for significance by the log rank as well as the Breslow test. Significance of particular prognostic parameters was then evaluated by the Cox regression model. The overall survival time as well as the recurrence free survival time were significantly lower in patients who's tumors showed amplifications of the chromosomal region 11q13 (p=0.0008 for LR and p=0.0024 for B). The survival time of the patients was also lower if the carcinomas carried overrepresentations of chromosome 3q (p=0.0299 for LR and p=0.0546 for B). Multivariate analysis (Cox's proportional hazards model) revealed both alterations as most important independent prognostic factors in HNSCC. None of the conventional clinico-pathological parameters (pT-, pN-status, UICC stage, grading) achieved statistical significance in the multivariate model. These results suggest that in HNSCC the occurence of 11q13 amplification and 3q overrepresentation are highly significant independent prognostic markers and of better value than the established TNM and grading criteria.
    Notes: Zusammenfassung Die Prognose von Patienten mit Kopf-Hals-Karzinomen lässt sich anhand der etablierten Stagingparameter oft nur sehr ungenügend einschätzen. Auf der Suche nach neuen Markern, die den Tumorphänotyp genauer charakterisieren, wurden in der vorliegenden Studie 100 primäre Plattenepithelkarzinome des Kopf-Hals-Bereichs mit Hilfe der Comparativen Genomischen Hybridisierung (CGH) molekularzytogenetisch untersucht. Die detektierten genetischen Veränderungen (Deletionen oder DNA-Überrepräsentierungen bzw. Amplifikationen) wurden für jeden Chromosomarm aufgeschlüsselt und statistisch zusammen mit den klinisch-pathologischen Daten uni- und multivariat hinsichtlich ihrer prognostischen Aussagefähigkeit überprüft. Alle Patienten dieser Studie wurden primär operiert und in Abhängigkeit vom Tumorstadium adjuvant nachbestrahlt. In dem längstens 4-jährigen Beobachtungszeitraum waren von den 100 Patienten 29 am Tumorleiden verstorben. Die kumulierten Überlebensraten nach der Kaplan-Meier-Methode zeigten, dass sowohl die rezidiv- und metastasenfreie als auch die Gesamtüberlebenszeit signifikant kürzer ist bei Patienten, deren Tumoren eine Amplifikation der chromosomalen Region 11q13 und/oder eine DNA-Überrepräsentierung des Chromsomarms 3q aufweisen (p=0,0008 bzw. p=0,0299 im Log-Rank-Test und p=0,0024 bzw. p=0,0546 im Breslow-Test). Die Cox-Regression wurde für das rezidiv- und metastasenfreie Überleben und für das Gesamtüberleben jeweils mit den klinisch-pathologischen Parametern pT-, pN-Status, UICC-Stadium, Grading und den genetischen Markern 11q13-Amplifikation sowie 3q-Überrepräsentierung durchgeführt. Die Analyse ergab die genetischen Veränderungen im Bereich von 11q13 und 3q als die wichtigsten Marker für die Einschätzung des Überlebens, während die klinisch-pathologische Tumorklassifikation ohne prognostischen Einfluss war (bei Signifikanzniveau p〈0,05). Das Ergebnis unserer Studie eröffnet die Möglichkeit eines “genetischen Tumorgradings”, das als Zusatzinformation einer verbesserten Prognoseeinschätzung bei Kopf-Hals-Karzinomen dient.
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  • 35
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    Der Nervenarzt 71 (2000), S. 822-828 
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Alkoholdelir ; Prognose ; Alkoholfolgekrankheiten ; CCT ; Liquor ; Keywords Alcohol withdrawal ; Delirium tremens ; Prognosis ; CT-scan ; Cerebrospinal fluid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract A severe course of alcohol withdrawal has been observed in 28% of patients in a neurological intensive care unit due to complicating central nerve system (CNS) diseases. In any atypical alcoholic delirium, especially with focal neurological signs, partial seizures, or decreased level of consciousness, CNS diseases like meningoencephalitis, intracranial hemorrhage, or central pontine myelinolysis must be diagnosed by computed tomography (CT) scan and cerebral spinal fluid (CSF) tap. The diagnostic and prognostic value of CT scan and CSF analysis was examined in 32 persons with alcohol withdrawal syndrome or delirium tremens. Neurological complications and cerebral convulsions at the beginning of delirium tremens appear to predispose the patient to a protracted clinical course and necessary mechanical ventilation. Blood-CSF barrier permeability is increased in 70% of alcohol withdrawal patients and that also seems to be a marker of a prolonged clinical course. Cerebral atrophy as shown in CT scan does not play a role in predicting clinical course. In our experience, CT examination or lumbar puncture is not necessarily recommended if clinical signs are typical for alcohol delirium.
    Notes: Zusammenfassung Der Verlauf intensivmedizinisch behandelter Alkoholdelirien ist in 28% der Fälle durch eine begleitende ZNS-Erkrankung erschwert. Durch das Delir mitigierte neurologische Begleiterkrankungen, wie Meningoenzephalitiden, intrakranielle Hämatome oder eine zentrale pontine Myelinolyse können bei Vorliegen einer atypischen deliranten Symptomatik durch eine neurologische Zusatzdiagnostik mit Hilfe von CCT/MRT und Liquoranalyse ausreichend diagnostiziert werden. Der diagnostische und prognostische Wert dieser Zusatzdiagnostik wurde an 32 neurologisch-intensivmedizinisch behandelten Alkoholikern im Delir untersucht. Das Auftreten zerebraler Komplikationen korreliert dabei ebenso wie ein initialer Grand-mal-Anfall mit einem protahierten Verlauf und Beatmungspflichtigkeit. Eine Blut-Liquor-Schrankenstörung ließ sich bei 70% nachweisen. Es finden sich Hinweise für einen verlängerten Krankheitsverlauf dieser Patienten. Dem alleinigen Nachweis einer zerebralen Atrophie im CCT/MRT kommt dagegen kein prognostischer Wert hinsichtlich des Delirverlaufes zu. Ein Alkoholdelir mit jedoch typischem klinischem Bild erfordert nach unseren Ergebnissen keine bildgebende oder liquoranalytische Untersuchung.
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  • 36
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Paraneoplastische zerebelläre Degeneration ; Opsoklonus-Myoklonus-Syndrom ; Limbische Enzephalitis ; Therapie ; Prognose ; Key words Paraneoplastic cerebellar degeneration ; Opsoclonus-myoclonus syndrome ; Limbic encephalitis ; Therapy ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Paraneoplastic neurological syndromes are rare diseases that occur in relation to cancer. Supporting the hypothesis of an autoimmune mechanism, specific antineuronal antibodies have sometimes been detected. The current possibilities for treatment are limited. A female patient, aged 57, suffering from a breast cancer, developed a severe paraneoplastic cerebellar syndrome and limbic encephalitis within a few weeks. It is possible that the impressive partial remission that occurred during the ensuing 6 months was not due to therapy. Although the patient was still bound to a wheelchair, discharge from hospital was possible because she was still able to perform daily tasks by herself. A recurrence of the cerebellar symptoms with mild alterations of mental status occurred 2 months later but again showed a good remission.
    Notes: Zusammenfassung Paraneoplastische neurologische Syndrome sind seltene Erkrankungen in Assoziation mit einem Tumor, die bei vermutetem Autoimmunmechanismus mit antineuronalen Antikörpern einhergehen können und deren Verlauf therapeutisch nur bedingt beeinflussbar ist. Berichtet wird von einer 57-jährigen Patientin mit Mammakarzinom, die in engem zeitlichen Rahmen sowohl eine schwere paraneoplastische Zerebellopathie als auch eine limbische Enzephalitis entwickelte. In unklarem Zusammenhang zur Therapie kam es innerhalb von 6 Monaten zu einer vergleichsweisen guten Rückbildung beider Syndrome, so dass zwar noch eine partielle Rollstuhlpflichtigkeit bestand, bei weitgehender Selbständigkeit aber eine Entlassung nach Hause möglich war. Ein Rezidiv 2 Monate später mit im Vordergrund stehender zerebellärer Symptomatik verlief ebenfalls günstig.
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  • 37
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Kryptogene Temporallappenepilepsie ; MR-Spektroskopie ; Prognose ; Epilepsiechirurgie ; Key words Cryptogenic temporal lobe epilepsy ; MR spectroscopy ; Prognosis ; Epilepsy surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The preoperative localization of pharmaco-resistent focal epilepsies before surgery and the prognosis concerning seizure outcome are both of importance. In addition to conventional MRI diagnostics for the detection of small epileptogenic lesions, proton magnetic resonance spectroscopic imaging (HMR spectroscopy) can be useful for assessing the bilaterality of pathological changes in cryptogenic temporal lobe epilepsies. The technique and findings of HMR spectroscopy are reported in patients with cryptogenic temporal lobe epilepsies. The findings indicate that chemical shift imaging (CSI) investigations of the ipsilateral and contralateral hemispheres provide important information for the prediction of seizure outcome after epilepsy surgery.
    Notes: Zusammenfassung Bei der epilepsiechirurgischen Behandlung kryptogener Temporallappenepilepsien kommt neben der Lokalisation des epileptischen Fokus der Beurteilung der Prognose hinsichtlich der postoperativen Anfallskontrolle Bedeutung zu. Hierbei kann die Protonen-MR-Spektroskopie (1 HMR-Spekroskopie oder Chemical Shift Imaging CSI) nützliche Informationen liefern. Technik und Befunde des CSI im Vergleich zu einem Normkollektiv werden bei Patienten mit kryptogenen Temporallapenepilepsien dargestellt. Hierbei werden Ergebnisse der 1HMR-Spekroskopie (NAA/Cholin) und der T2-Relaxometrie mit der postoperativen Anfallskontrolle verglichen. Die Ergebnisse zeigen, dass die 1HMR-Spekroskopie mit NAA/Cholin wichtige Informationen für die Prädiktion hinsichtlich der postoperativen Anfallskontrolle liefert.
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  • 38
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    Trauma und Berufskrankheit 2 (2000), S. S57 
    ISSN: 1436-6274
    Keywords: Schlüsselwörter ; Proximale Ulnafraktur ; Olekranonfraktur ; Osteosynthese ; Prognose ; Key words ; Fracture of the proximal ulna ; Fracture of the olecranon ; Internal fixation ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract The pathogenesis, diagnosis, treatment and prognosis of fractures of the ulna and olecranon are described. It appears that both the potential benefits of using internal fixation techniques in the proximal ulna and the olecranon and the risks involved are heavily influenced by concomitant injuries, which means that the diagnosis and appropriate treatment of these are of decisive importance for the outcome.
    Notes: Zusammenfassung Pathogenese, Diagnostik, Therapie und Prognose von Ulna- und Olekranonfrakturen werden beschrieben. Dabei zeigt sich, daß die Chancen und Gefahren bei Osteosynthesen der proximalen Ulna und des Olekranons wesentlich von den Begleitverletzungen beeinflußt werden, deren Diagnose und adäquate Behandlung demzufolge für das Outcome entscheidende Bedeutung besitzt.
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  • 39
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    International journal of clinical oncology 5 (2000), S. 217-228 
    ISSN: 1437-7772
    Keywords: Key words Colorectal carcinoma ; Cytokines ; IL-6 ; IL-10 ; Prognosis ; Survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Host-tumor interactions are primarily controlled by paracrine interactions between adjacent normal host cells and malignant cells. Recent evidence from experimental and clinical neoplasms indicates that neoplasms, or their products, produce levels of circulating pro- and anti-inflammatory cytokines that modulate these local paracrine interactions in such a way that promotes tumor growth. This brief review focuses on several cytokines (interleukin-6, interleukin-10, transforming growth factor-beta, and vascular endothelial growth factor) that have systemic effects in experimental models and are associated with prognosis in patients with colorectal carcinoma. The primary focus of this review is on colorectal carcinoma, but implications for other malignancies are also considered. Colorectal and similar carcinomas may exert systemic control over neoplastic progression by modulating circulating levels of cytokines that then influence the growth of distant metastasis by affecting local paracrine interactions.
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  • 40
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    International journal of clinical oncology 5 (2000), S. 121-125 
    ISSN: 1437-7772
    Keywords: Key words Splenic metastasis ; Colorectal cancer ; Splenectomy ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. The value of splenectomy for secondary splenic tumors remains unclear. The aim of this study was to disclose the clinical significance of splenectomy for colorectal cancer metastases to the spleen by reviewing our two patients and the 24 other patients reported thus far. Methods. We report two patients with splenic metastasis from colonic cancer. A review of 26 cases, including ours, was conducted. Results. One of our patients had isolated splenic metastasis and is alive with no evidence of disease 14 months after splenectomy, while the other had non-isolated splenic metastasis and died of disseminated disease 17 months after splenectomy. In the 26 patients overall, the outcome of those with isolated splenic metastasis (n = 20) was significantly better than that for those with non-isolated splenic metastasis (n = 6; P = 0.05). There were three long-term (more than 3 years) survivors; all three were patients with isolated splenic metastasis, with the longest survival being 110 months. Patients with mucinous carcinoma showed a better survival rate than patients with other histological types (P = 0.08). In patients with isolated metastasis, metastases after splenectomy occurred in the peritoneum (n = 3), liver (n = 1), and lung (n = 1) within 2 years. Conclusions. Splenectomy may provide long-term survival for patients with isolated colorectal cancer metastasis to the spleen. The mucinous variant may be a favorable prognostic factor after splenectomy. Recurrence after splenectomy is likely to occur within 2 years, mainly in the peritoneum.
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  • 41
    ISSN: 1437-9813
    Keywords: Key words Biliary atresia ; Bile lake ; α-glutathione-s-transferase (GST) ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Early identification of patients likely to deteriorate post-hepatic portoenterostomy for biliary atresia (BA) would be beneficial. α-Glutathione-s-transferase (α-GST) is a serologic marker of reactive hepatocellular damage because of its low molecular weight, uniform hepatic distribution, high cytosol concentration, and short half-life. We evaluated whether serum α-GST in post-surgical BA patients correlates with liver function (LF) and investigated its potential as a medium- to long-term marker of prognosis. Postoperative BA patients (n = 30; mean age: 11.8 ± 3.7 years) were divided into three groups based on average LF over the 3 months prior to this study. Group I (n = 8) were jaundice-free and had normal LF. Group II (n = 12) had moderate liver dysfunction, and group III (n = 10) had severe liver dysfunction. Serum α-GST was determined using a specific ELISA. Tissue α-GST was determined immunohistochemically, using liver needle-biopsy specimens. Bile lakes were found in 5 group II patients and 5 group III patients. Serum α-GST was significantly higher in group II (20.7 ± 8.4 ng/ml) than in groups I (4.7 ± 1.3 ng/ml) and III (8.0 ± 1.2 ng/ml) (P 〈 0.0001) and was highest in group II subjects with bile lakes. In control liver specimens α-GST distribution was weak but uniform throughout normal liver lobule hepatocytes. In group II there was strong staining in centrilobular hepatocytes, and in group III α-GST was only found in regenerative nodules. We conclude that α-GST may be a more sensitive indicator of hepatocellular damage in BA because its distribution is correlated to the proportion of functioning liver tissue present. This is the first report of this relationship, which has great implications for group II subjects because a sudden shift in concentration of α-GST may be a better predictor of impending hepatic dysfunction than conventional LF tests.
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  • 42
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    Pediatric surgery international 16 (2000), S. 351-355 
    ISSN: 1437-9813
    Keywords: Key words Extrahepatic biliary atresia ; Hepatoportoenterostomy ; Prognosis ; Long-term results
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Clinical and histologic findings from 206 patients operated upon for extrahepatic biliary atresia (EHBA) are analyzed in order to define the prognosis of patients with EHBA. The prospective study took into consideration both initial fibrosis of the liver and the morphology of the porta hepatis (PH) at surgery. Kaplan-Meier survival estimates and statistical calculations demonstrated a relationship between long-term survival and histologic findings in the liver and porta hepatis. The efficacy of HPE is significantly influenced by the morphology of the PH and to a lesser extent by the initial liver fibrosis. Surgery should thus achieve pattern 1 morphology of the PH, but this is problematic because of the close relationship of the vascular and biliary structures in its two lateral zones.
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  • 43
    ISSN: 1437-7772
    Keywords: Key words c-erb B-2 ; Prognosis ; Breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. The prognostic significance of c-erb B-2 in breast cancer remains controversial. The aim of this study was to determine the practical prognostic significance of c-erb B-2 protein status in breast cancer extracts, using an enzyme immunoassay. Methods. An enzyme immunoassay was used to measure levels of c-erb B-2 protein prospectively in 360 patients with breast cancer, using cytosol fractions prepared for steroid receptor assay. The status of c-erb B-2 protein was assessed using a cut-off value for positivity of 18 ng/mg protein. Univariate and multivariate analyses were performed. To evaluate the prognostic significance of c-erb B-2 protein status. Results. Levels of c-erb B-2 protein in tumor tissue extract ranged from 0 to 213.0 ng/mg protein (mean, 15.5 ng/mg protein). In 52 tumors (14.4 %) more than 18.0 ng/mg protein was detected, and these tumors were regarded as c-erb B-2 protein-positive. Correlations were found between c-erb B-2 protein positivity and large tumor size (〉3 cm; P = 0.0095), higher histological grade (P 〈 0.0001), estrogen receptor negativity (P 〈 0.0001), and progesterone receptor negativity (P 〈 0.0001). There was also a marginally significant correlation between c-erb B-2 protein positivity and lymph node positivity. Multivariate analysis showed that c-erb B-2 protein status was a significant independent prognostic factor for disease-free survival, being strongly significant in patients with positive lymph nodes. Conclusion. c-erb B-2-positive breast cancers are biologically more aggressive and c-erb B-2 protein status could be a candidate as a prognostic factor for patients with breast cancer, being particularly valuable in patients with positive lymph nodes.
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  • 44
    ISSN: 1437-7772
    Keywords: Key words Breast cancer ; Breast-conserving therapy ; Local recurrence ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. In patients with early stage breast cancer who have breast-conserving therapy (BCT), the impact of local recurrence on the risk of distant metastasis is still controversial. Local recurrence after BCT is an uncommon event, so it is impossible to determine a standard treatment method by a clinical trial because not enough patients can be enrolled. Methods. Between February 1988 and December 1997, 399 patients with clinical stage I and II breast cancer underwent BCT in our department. Of these 399 patients, 22 developed local recurrence during this period. To assess the relationship between their clinical characteristics and prognosis, we performed a retrospective review of these 22 patients. Results. The 5-year overall survival rate after local recurrence was 66.7%. All four patients who had cutaneous or inflammatory type recurrence developed distant metasta-sis after salvage treatment. Of three patients with multiple recurrence, two developed disseminated disease after salvage treatment. Two of four patients treated by repeat lumpectomy developed further local recurrence after salvage lumpectomy. Conclusion. To improve prognosis in patients with multiple, cutaneous, or inflammatory recurrence, aggressive adjuvant systemic therapy may be required after salvage surgery.
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  • 45
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    International journal of clinical oncology 5 (2000), S. 36-40 
    ISSN: 1437-7772
    Keywords: Key words Renal cell carcinoma ; Contralateral adrenal metastasis ; Clinicopathological characteristics ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Metachronous solitary metastasis of renal cell carcinoma (RCC) to the contralateral adrenal gland is very rare. We assessed the clinocopathological findings of such patients who received adrenalectomy. Methods. We retrospectively reviewed the records of all 495 patients who underwent nephrectomy for RCC; excluding those in stage IV, between 1980 and 1993. Of these patients, 5 who showed metachronous solitary metastasis to the contralateral adrenal gland, and also received adrenalectomy were the subjects of this study. Results. The adrenal metastasis was found between 14 and 132 months (median, 81 months) after nephrectomy. After the solitary adrenalectomy, patient survival ranged from 450 to 2160 days (median, 660 days); 2 patients were alive with no evidence of disease at 660 and 1830 days, respectively, and 3 patients died of this disease, at 450, 480, and 2160 days, respectively, after adrenalectomy. The overall survival rate was 100% at 5 years, 80% at 6 years, 60% at 7 years, and 40% thereafter. The 2 patients with no evidence of disease did not receive steroid supplementation, because they had not received ipsilateral adrenalectomy. No significant difference was observed between survivors and non-survivors in terms of clinicopathological factors such as affected side, location of the tumor, tumor size of primary/metastatic lesion, and stage or grade of primary/metastatic lesion. From the viewpoint of outcome, patients with early recurrence tended to show an unfavorable prognosis compared with prognosis in those with late recurrence. Conclusion. The prediction of outcome in patients with RCC who undergo, adrenalectomy for metachronous solitary metastasis to the contralateral adrenal gland is difficult. Although the factors that affect prognosis are uncertain, long-term observation for unusual metachronous metastasis to the contralateral adrenal gland is mandatory in patients with RCC.
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  • 46
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    International journal of clinical oncology 5 (2000), S. 164-170 
    ISSN: 1437-7772
    Keywords: Key words P-glycoprotein ; Osteosarcoma ; Soft-tissue sarcoma ; Prognosis ; Immunohistochemistry ; RT-PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. The purpose of this study was to investigate the correlation between P-glycoprotein status and outcome in adult patients with high-grade osteosarcomas and soft-tissue sarcomas. Methods. P-glycoprotein status was determined im-munohistochemically in specimens from 28 patients with osteosarcoma and 34 patients with soft-tissue sarcoma. The polyclonal antibody mdr(Ab-1) was used for either decalcified or undecalcified tissue samples which were formalin-fixed and paraffin-embedded. The expression of P-glycoprotein mRNA was also determined by the polymerase chain reaction in 23 fresh sarcoma specimens. P-glycoprotein status was analyzed in relation to the duration of event-free survival. Results. Positivity for P-glycoprotein was found in 29% of the osteosarcomas and 34% of the soft-tissue sarcomas. Consistent results were obtained at both the immunohistochemical and reverse transcriptase-polymerase chain reaction (RT-PCR) levels in 19 of 23 sarcomas (83%). In patients with osteosarcoma, the presence of increased levels of P-glycoprotein was significantly associated with a decreased probability of event-free survival after diagnosis (P = 0.022). In contrast, in patients with soft-tissue sarcoma there was no correlation between the level of P-glycoprotein and prognosis. Conclusions. In patients with high-grade osteosarcomas, the presence of increased levels of P-glycoprotein detected by polyclonal antibody mdr(Ab-1) was associated with a significantly increased risk of adverse events. This association was not found in patients with soft-tissue sarcomas.
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  • 47
    ISSN: 1434-0879
    Keywords: Key words Superficial bladder cancer ; p21WAF1/CIP1 ; Prognosis ; Cyclin D1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immunoreactivity of p21WAF1/CIP1 and cyclin D1 proteins was assessed in a cohort of 207 patients with superficial (pTa-pT1) bladder cancer followed up for a mean of 4.9 years. The results of the immunostainings were compared with T category, WHO grade, tumor cell proliferation rate (MIB-1 score), the expressions of p53 and bcl-2 as well as survival. Sixty-eight percent and 75% of the tumors were p21WAF1/CIP1 positive (≥5% of cells positive) and cyclin D1 positive (≥10% of cells positive), respectively. The p21WAF1/CIP1 expression was related to cyclin D1 immunolabelling (P 〈 0.001) but not to the other variables studied. The expression of cyclin D1 was inversely associated with T category (P=0.001), WHO grade (P=0.006), MIB-1 score (P=0.014), p53 expression (P=0.001), and bcl-2 (P=0.011) immunoreactivity. In univariate analysis, T category (P=0.0001), WHO grade (P 〈 0.0001), MIB-1 score (P 〈 0.0001), bcl-2 (P=0.0092), p53 (P=0.0016) and p21WAF1/CIP1 (P=0.009) expressions were significant prognostic factors with regard to tumor progression, whereas cyclin D1 was without any prognostic significance (P=0.1). Out of 123 p21 positive tumors 21 progressed, whereas only 2 out of 58 p21 negative tumors progressed. In multivariate analysis, the MIB-1 score was the only independent predictor of cancer-specific survival (P=0.03), whereas tumor grade (P=0.002) and cyclin D1 expression (P=0.04) were independent predictors of tumor recurrence. Only the WHO grade (P=0.04) retained its prognostic value indicating the risk of progression. We suggest that in superficial bladder cancer p21WAF1/CIP1 and cyclin D1 immunohistochemistry provide no additional prognostic information compared with already established prognostic factors for predicting the risk of progressive disease.
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  • 48
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    Annals of hematology 79 (2000), S. 455-458 
    ISSN: 1432-0584
    Keywords: Key words Anterior chamber ; Hypopyon ; Leukemia ; Extramedullary ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We encountered a patient with acute myelogenous leukemia (AML) who developed leukemic hypopyon. Leukemia initially spread into the pharynx, gingiva, lymphnode, and bone marrow. He achieved complete remission after chemotherapy but developed blurred vision and hypopyon. Anterior chamber paracentesis disclosed leukemic infiltration of the anterior chamber. Infiltration of the central nervous system also occurred. He received systemic chemotherapy, intrathecal chemotherapy, and local chemotherapy. However, he did not achieve prolonged remission. These findings suggest that these chemotherapy treatments have an inadequate effect for AML with anterior chamber infiltration. This rare complication is associated with extramedullary infiltration of leukemia.
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  • 49
    ISSN: 1279-8509
    Keywords: Acute myeloid leukemia ; Chemotherapy ; Allogenic transplantation ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to assess the place of HLA-identical allogeneic bone marrow transplantation (BMT) and to compare it to other post-induction therapies, we analyzed patient outcome in intention-to-treat based on the presence or not of an HLA-identical familial donor in young adults with de novo acute myeloid leukemia (AML) in first complete remission (CR). Between 1985 and 1998, 152 consecutive AML patients aged less than 41 years old, seen in our institution, were treated according to 3 different successive protocols (LYLAM85, LAM90, AML10). 144/152 patients entered our prospective study in which they were registered at time of diagnosis for presence or absence of HLA-identical donor and analyzed in intention-to-treat. In this study, 52 patients (36%), who had at least one identical sibling donor (group 1), were offered allogeneic BMT after CR achievement. The 92 patients without donor were allocated to group 2 and were assigned to receive chemotherapy or autologous transplantation as post-remission according to the protocol they were initially included in. Patients from both groups had similar disease characteristics at diagnosis. Karyotypes at diagnosis were defined as low risk (t(8;21) or t(15;17) or chromosome 16 abnormalities(, intermediate risk (normal karyotypes), or high risk (other abnormalities). Overall, 114/152 patients (75%) achieved a CR. Of the 144 eligible patients, 46/52 (88%) with a donor and 68/92 (74%) without a donor achieved a CR. The median follow-up duration of the 144 patients was 21.2 months. The relapse rate was higher in group 2 (56%) than in group 1 (31%). However, the overall survival was not different between patients with and without donor (median survival respectively at 16.7 months and 26.6 months with estimated survival at 5 years respectively at 32% and 34%). Thirty-four patients from group 1 (65%) were actually transplanted in first CR. The probability of 5-year survival for patients receiving effectively allogeneic BMT was 44% and was not significantly better than that of patients who did not. In univariate as in multivariate analysis, karyotypic status was the main prognostic factor for CR achievement (p = 0.002), CR duration (p 〈 0.0001), and overall survival (p 〈 0.0001). There were no significant differences between group 1 and group 2 when survivals were compared with adjustment for karyotypes. We conclude that the availability of an HLA-identical sibling donor did not confer any prognostic advantage in terms of outcome for young adults with AML in first CR. These results make allogeneic BMT process questionable as systemic post-remission therapy in patients with an HLA-identical familial donor.
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  • 50
    ISSN: 1248-9204
    Keywords: Hernia ; Strangulation ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It is believed that direct hernias are less likely to strangulate because, in contrast to an indirect inguinal hernia, the neck of the direct hernia is wide. For this reason, some surgeons do not repair direct hernias in I elderly patients. We analyzed all incarcerated hernias repaired on an emergency basis during a 3-year period in order to discover the extent of incarcerated direct hernias in our practice. A total of 293 patients with incarcerated hernia were evaluated; of these, 222 were inguinal (193 indirect −86.9%- and 29 direct −13.1%-). The strangulation rate for inguinal hernias was found to be 29.7%. There was a significant difference between indirect and direct inguinal hernias in respect to strangulation rate (32.6% vs 10.3% p = 0.014). However, we did not find any difference between bowel resection rates in incarcerated-strangulated indirect and direct hernias (14/193 −7.3%- vs 2/29 −6.9%-, p = 0.95). Hospitalization time was significantly longer for the patients who developed strangulation than those who did not. The side of direct hernia had no effect on strangulation (10.5% for right-sided vs 10.0% for left-sided, p = 0.97). The only prognostic factor for strangulation and resection in regression analysis was the age-group of the patients (〈 60 vs. 60 or older). At operation the average diameter of the defect in the transversalis fascia was 23.8 mm. The diameter of the defect had no effect on strangulation.
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  • 51
    ISSN: 1279-8517
    Keywords: Gastric carcinomas ; Cardiac carcinomas ; TNM-classification ; Prognosis ; Lesser and greater omenta
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The problem of T classification of proximal gastric carcinomas is becoming increasingly important due to a rise in the incidence of these tumors. The aim of this study was to examine the gastric insertion of the lesser and greater omenta and its role in the T classification of gastric carcinomas. The stomach and greater and lesser omenta were removed from 76 fixed cadavers and 12 measurements each were done in defined localizations. The lesser omentum extended to the gastric wall in 98% of the cases. This junction as well as the omental thickness and thus the retroperitoneal part are especially pronounced in the cardiac region. According to the current UICC classification, even advanced tumors extending into the gastric wall can be classified T2 as long as they do not penetrate the visceral peritoneum. This results in « understaging » and a seemingly poorer prognosis for cardiac carcinomas. Our study results support the recommendation of Hermanek and Wittekind [5] to subdivide the T2 stage of gastric carcinomas on the basis of infiltration depth.
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  • 52
    ISSN: 1432-0851
    Keywords: Key wordsαvβ3 ; Integrins ; Melanoma ; Blood vessels ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The αvβ3 integrin has emerged as a key mediator in angiogenesis. Its role in tumor-induced angiogenesis is supported by its up-regulation in vivo in the vasculature of a number of different types of carcinoma. The potential clinical significance of αvβ3 expression on blood vessels in carcinomas is suggested by its association with tumor progression. Currently no information is available about the clinical significance of αvβ3 expression on the vasculature of lesions of melanocytic origin. Since we have previously found that αvβ3 expression on melanoma cells in primary lesions is associated with a poor prognosis, in the present study we have compared αvβ3 expression on blood vessels and on cells of melanocytic origin in nevi and in malignant melanoma lesions. In addition we have examined the lesions for expression of the αv subunit to gain information on the regulation of αvβ3 expression on endothelial cells and on cells of the melanocyte lineage. αvβ3 expression on endothelial cells and on melanocytic cells was a relatively sensitive and specific marker for malignant lesions. However, αvβ3 expression on endothelial cells in primary melanoma lesions was not associated with the prognosis of the disease. The αv subunit and the αvβ3 complex were differentially expressed on endothelial cells and on melanocytic cells, implying that different regulatory pathways control their expression. This finding may account for the differential clinical significance of αvβ3 expression on tumor vasculature and on melanoma cells we observed in our patient cohort. Lastly, αvβ3 may be a useful target for immunotherapeutic approaches in melanoma because of its high expression on the vasculature of all metastatic lesions tested and its restricted distribution in normal tissues.
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  • 53
    ISSN: 1432-1238
    Keywords: Key words Mortality ; Oliguria ; Multiple organ failure ; Severity-of-illness ; Prognosis ; Scoring systems
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives: To describe risk factors for the development of acute renal failure (ARF) in a population of intensive care unit (ICU) patients, and the association of ARF with multiple organ failure (MOF) and outcome using the sequential organ failure assessment (SOFA) score. Design: Prospective, multicenter, observational cohort analysis. Setting: Forty ICUs in 16 countries. Patients: All patients admitted to one of the participating ICUs in May 1995, except those who stayed in the ICU for less than 48 h after uncomplicated surgery, were included. After the exclusion of 38 patients with a history of chronic renal failure requiring renal replacement therapy, a total of 1411 patients were studied. Measurements and results: Of the patients, 348 (24.7 %) developed ARF, as diagnosed by a serum creatinine of 300 μmol/l (3.5 mg/dl) or more and/or a urine output of less than 500 ml/day. The most important risk factors for the development of ARF present on admission were acute circulatory or respiratory failure; age more than 65 years, presence of infection, past history of chronic heart failure (CHF), lymphoma or leukemia, or cirrhosis. ARF patients developed MOF earlier than non-ARF patients (median 24 vs 48 h after ICU admission, p 〈 0.05). ARF patients older than 65 years with a past history of CHF or with any organ failure on admission were most likely to develop MOF. ICU mortality was 3 times higher in ARF than in other patients (42.8 % vs 14.0 %, p 〈 0.01). Oliguric ARF was an independent risk factor for overall mortality as determined by a multivariate regression analysis (OR = 1.59 [CI 95 %: 1.23–2.06], p 〈 0.01). Infection increased the risk of death associated with all factors. Factors that increased the ICU mortality of ARF patients were a past history of hematologic malignancy, age more than 65 years, the number of failing organs on admission and the presence of acute cardiovascular failure. Conclusion: In ICU patients, the most important risk factors for ARF or mortality from ARF are often present on admission. During the ICU stay, other organ failures (especially cardiovascular) are important risk factors. Oliguric ARF was an independent risk factor for ICU mortality, and infection increased the contribution to mortality by other factors. The severity of circulatory shock was the most important factor influencing outcome in ARF patients.
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  • 54
    ISSN: 1432-1238
    Keywords: Key words Acute renal failure ; 80 years old ; Etiology ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To determine the epidemiological trends, spectrum of etiologies, morbidity and mortality of acute renal failure (ARF) in patients over 80 years old.¶Design: Historical cohort analysis.¶Setting: Intensive care unit (ICU) of nephrology, Tenon Hospital, Paris.¶Patients and participants: The criteria of inclusion was ARF, defined on the basis of a creatinine value over 120 μmol/l, in patients over 80 years of age admitted between October 1971 and September 1996. When moderate chronic nephropathy was pre-existing, ARF was defined by the increase of at least 50 % over the basal creatininemia.¶Measurements and results: Three hundred and eighty-one patients over 80 years of age were included. The etiology and mechanism of ARF are detailed. 29 % of the patients received dialysis. Global mortality at the hospital was 40 %. Factors significantly associated with a poor prognosis are identified. Mean survival after hospitalization was 19 months.¶Conclusion: The frequency of admission to ICUs for ARF in patients older than 80 years seems to be on the increase. Mortality is less severe than expected. These patients could benefit from the renal replacement therapy of modern intensive care medicine.
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  • 55
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    Intensive care medicine 26 (2000), S. S064 
    ISSN: 1432-1238
    Keywords: Key words Bacteraemia ; Sepsis ; Septic shock ; Epidemiology ; Prognosis ; Risk factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To examine the incidence, risk factors, aetiologies and outcome of the various forms of the septic syndromes (the systemic inflammatory response syndrome [SIRS] sepsis, severe sepsis, and septic shock) and their relationships with infection.¶Design: Review of published cohort studies examining the epidemiology of the septic syndromes, with emphasis on intensive care unit (ICU) patients.¶Results: The prevalence of SIRS is very high, affecting one-third of all in-hospital patients, and 〉 50 % of all ICU patients; in surgical ICU patients, SIRS occurs in 〉 80 % patients. Trauma patients are at particularly high risk of SIRS, and most these patients do not have infection documented. The prevalence of infection and bacteraemia increases with the number of SIRS criteria met, and with increasing severity of the septic syndromes. About one-third of patients with SIRS have or evolve to sepsis. Sepsis may occur in approximately 25 % of ICU patients, and bacteraemic sepsis in 10 %. In such patients, sepsis evolves to severe sepsis in 〉 50 % of cases, whereas evolution to severe sepsis in non-ICU patients is about 25 %. Severe sepsis and septic shock occur in 2 %–3 % of ward patients and 10 %–15 % or more ICU patients, depending on the case-mix; 25 % of patients with severe sepsis have shock. There is a graded severity from SIRS to sepsis, severe sepsis and septic shock, with an associated 28-d mortality of approximately 10 %, 20 %, 20 %–40 %, and 40 %–60 %, respectively. Mortality rates are similar within each stage, whether infection is documented or not, and microbiological characteristics of infection do not substantially influence outcome, although the source of infection does. While about three of four deaths occur during the first months after sepsis, the septic syndromes significantly impact on long-term outcome, with an estimated 50 % reduction of life expectancy over the following five years. The major determinants of outcome, both short-term and long-term, of patients with sepsis are the severity of underlying diseases and comorbidities, the presence of shock and organ failures at onset of sepsis or evolving thereafter. It has been estimated that two-thirds of the overall mortality can be attributed to sepsis.¶Conclusions: The prevalence of sepsis in ICU patients is very high, and most patients have clinically or microbiologically documented infection, except in specific subset of patients. The prognosis of septic syndromes is related to underlying diseases and the severity of the inflammatory response and its sequelae, reflected in shock and organ dysfunction/failures.
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  • 56
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    Journal of cancer research and clinical oncology 126 (2000), S. 280-284 
    ISSN: 1432-1335
    Keywords: Key words Thymoma ; Prognostic factors ; Prognosis ; DNA cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Purpose: The aim of this work was to evaluate the prognostic significance of DNA image cytometry in thymoma. Patients and methods: Image cytometric studies with an automatic video-based analysis system (LEYTAS) were carried out on 47 archival specimens from 36 patients with thymomas who underwent operation at a single institution from 1954 to 1992. The significance of aneuploidy DNA-content (5c-exceeding events), and nuclear size on stage and survival were evaluated. The median follow-up was 52.7 (6–164) months. Results: Masaoka's stage was predictive of aneuploidy (P 〈 0.01) and disease-free survival (P 〈 0.015). In stage I 18% of the tumors were aneuploid, in stage II 78%, in stage III 85% and in stage IV 100%. The occurrence of 5c-exceeding events was associated with both decreased disease-free survival (P 〈 0.01) and overall survival (P = 0.013). Nuclear size was not significantly correlated to stage. Under multivariate analysis, aneuploidy and DNA content failed to attain independent significance for stage, performance status, and histology. Conclusion: DNA image cytometry may provide additional information about the prognosis of resected thymoma.
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  • 57
    ISSN: 1432-1238
    Keywords: Key words Cardiopulmonary bypass ; Coronary artery bypass graft ; Valve surgery ; Thoracic aortic surgery ; Prognosis ; Hypotension ; Systemic inflammatory response syndrome (SIRS) ; Procalcitonin ; Endotoxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To investigate procalcitonin (PCT) levels in patients undergoing cardiopulmonary bypass (CPB) in order to assess the prevalence and prognostic capacity of elevated PCT levels following CPB in open heart surgery.¶Design: prospective observational study in consecutive patients.¶Setting: Twenty-four-bed ICU, department of thoracic and cardiovascular surgery, university hospital.¶Patients: Seven hundred and twenty two patients, 691 of whom underwent CPB, i. e., 476 had coronary bypass surgery (CABG), 130 valve replacement, 34 combined CABG and valve replacement, and 23 thoracic aortic surgery.¶Interventions: Standard perfusion techniques were used with cardioplegic arrest and mild hypothermia (28–32 °C). With the exception of thoracic aortic procedures, full–flow perfusion was performed.¶Measurements and results: PCT was measured prior to surgery and daily thereafter until ICU discharge or death. PCT significantly increased at day 1 postoperatively compared to baseline values (0.25 ± 1.65 vs 6.49 ± 22.0 ng/ml, p 〈 0.005). However, in 55.1 % of patients PCT was below 1.0 ng/ml. In 12.8 % of CABG patients PCT was increased to 〉 5.0 ng/ml, compared to 39 % in valve patients and 35 % of patients with aortic surgery. An elevated PCT level 〉 1.0–5.0 ng/ml at day 1 was highly predictive of mortality (P 〈 0.03, vs 〈 1.0 ng/ml), with an additional accuracy when levels 〉 5.0 ng/ml were measured (P 〈 0.002 vs 〈 1.0 ng/ml).¶Conclusions: These results provide evidence that PCT might serve as an early prognostic marker in patients undergoing CPB in open heart surgery. It may be worth considering immunomodulating approaches in patients presenting elevated PCT levels in the early phase after CPB.
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  • 58
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Gastrointestinaltrakt ; Karzinoid ; Neuroendokrine Tumoren ; DNA-Zytophotometrie ; Prognose ; Key words Gastrointestinal tract ; Carcinoid ; Neuroendocrine tumors ; DNA cytophotometry ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary A total of 123 manifestations (97 primary tumours and 26 metastases) of neuroendocrine tumours of the gastrointestinal tract observed in 95 patients was investigated for the prognostic value of clinical, histological and DNA cytophotometric parameters. Metastases almost exclusively occurred among ileal carcinoids, which also were responsible for all 14 cases of lethal outcome observed during the follow-up period of mean 42 months. Aneuploid DNA values could be determined significantly more frequently among ileal than in non-ileal carcinoids and showed – upon analysis of the total group of gastrointestinal neuroendocrine tumours – a significant correlation to lethal course of disease. In addition, among 18 cases with primary and secondary carcinoid manifestations available for DNA cytophotometry, an association between the DNA content of metastatic neuroendocrine tumours and prognosis came to light. When applicated to the group of ileal neoplasms, however, the parameter DNA content did not allow a better prognostic assessment.
    Notes: Zusammenfassung Untersucht wurden 123 Manifestationen (97 Primärtumoren und 26 Metastasen) von bei 95 Patienten beobachteten neuroendokrinen (NE-)Tumoren des Gastrointestinaltrakts auf die prognostische Bedeutung verschiedener klinischer, histologischer und DNA-zytophotometrischer Parameter. Metastasen traten fast ausschließlich bei ilealen Karzinoiden auf, denen auch sämtliche 14 während der durchschnittlichen Nachbeobachtungszeit von 42 Monaten aufgetretenen letalen Erkrankungsverläufe zuzuordnen waren. Aneuploide DNA-Verteilungsmuster wurden signifikant häufiger bei ilealen als bei nichtilealen Karzinoiden angetroffen und waren – bezogen auf die Gesamtgruppe – signifikant mit tödlichem Krankheitsausgang korreliert. Darüber hinaus zeigte sich bei 18 Fällen mit DNA-zytophotometrisch auswertbaren primären und sekundären Karzinoidmanifestationen eine Assoziation zwischen dem DNA-Histogrammtyp metastatischer Karzinoide und der Prognose. Innerhalb der Gruppe der Ileumtumoren erlaubte der Parameter DNA-Gehalt aber keine Verbesserung der Prognoseabschätzung.
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  • 59
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Apoptose ; Proliferation ; Hämatopoetischer Zellumsatz ; Topoisomerase II α ; PCNA ; Chronische myeloproliferative Erkrankungen ; Prognose ; Reaktive Läsionen ; Key words Apoptosis ; Proliferation ; Hematopoietic turnover index ; Topoisomerase II α ; PCNA ; Chronic myeloproliferative disorders ; Prognosis ; Reactive lesions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Apoptosis and proliferation are important regulators of normal development and homeostasis in the bone marrow. Therefore, dynamics of hematopoiesis is mainly defined by these two parameters. However, since only few data are available from previous studies, we performed a retrospective analysis to elucidate some aspects of this complex pathomechanism. A total of 400 patients with chronic myeloproliferative disorders (CMPDs) and corresponding reactive bone marrow lesions were enrolled into this study. Apoptosis was detected in bone marrow tissue by the ISEL-technique and topoisomerase II α expression was demonstrated by the monoclonal antibody Ki-S1. Furthermore, by determination of the proliferating-cell nuclear antigen labeling (PCNA) index, we were able to calculate the proportion of cells in the G2/M phase, because both nuclear antigens are expressed in different phases of the cell cycle. Patients with IMF, PV, and ET revealed a normal range of apoptosis, whereas in chronic myeloid leukemia (CML) a significant increase could be observed. On the other hand, IMF and PV were characterized by a raised proliferative activity. Dynamics of hematopoiesis was assessed by calculation of the so called hematopoietic turnover index. In CML and reactive lesions no alterations of this parameter were detectable, but IMF and PV showed a significant increase. Survival analysis disclosed a relevant worsening of life expectancy for patients with reduced apoptosis and proliferation. In conclusion, our in-situ results confirm and extend previous experimental data on hematopoietic cell kinetics. In this context, a greater regenerative capacity of hematopoiesis may be reflected by an increased rate of apoptosis and/or proliferation and therefore is associated with a more favorable outcome.
    Notes: Zusammenfassung Apoptose und Proliferation stellen im Rahmen einer funktionsgerechten Regelung der Hämatopoese einen integralen Bestandteil für die Aufrechterhaltung des zellulären Gleichgewichts im Knochenmark dar. Insofern ist die Dynamik des hämatopoetischen Zellumsatzes durch diese beiden Parameter gekennzeichnet. Da weiterführende Untersuchungen in dieser Hinsicht lediglich vereinzelt am Knochenmark durchgeführt worden sind, haben wir im Rahmen einer retrospektiven Analyse versucht, einige Aspekte dieses komplexen Mechanismus zu beleuchten. Insgesamt wurden 400 Patienten mit chronischen myeloproliferativen Erkrankungen (CMPE) sowie korrespondierenden reaktiven Veränderungen in die Untersuchung aufgenommen. Neben dem direkten Nachweis der Apoptose im Knochenmark durch die ISEL-Technik haben wir die Topoisomerase II α Expression mittels des monoklonalen Antikörpers Ki-S1 gemessen. Zusätzlich konnten wir durch die Bestimmung der PCNA-Markierung aufgrund der Zellzyklus-spezifischen Färbereaktion beider nukleärer Antigene den Anteil der in G2-/M-Phase befindlichen Zellen ermitteln. Während die IMF, die PV sowie die ET eine im Normbereich liegende Apoptoserate erkennen ließen, war dieser Wert bei der CML signifikant erhöht. Auf der anderen Seite wiesen IMF und PV eine deutlich gesteigerte proliferative Aktivität im Knochenmark auf. Bei der Berechnung eines hämatopoetischen Zellumsatz Index (HZI) zeigten diese beiden CMPE-Subtypen einen signifikanten Anstieg, wohingegen bei der CML sowie den reaktiven Läsionen keine relevante Verschiebung dieses Parameters festzustellen war. Im Rahmen prognostischer Analysen hatten IMF und PV Patienten mit reduzierter Proliferation und Apoptoserate jeweils eine signifikant kürzere Überlebenszeit. Unsere in-situ Ergebnisse erweitern und bestätigen vorausgegangene experimentelle Studien zur hämatopoetischen Zellkinetik. Darüber hinaus lassen sich aus unseren Daten prognostische Überlegungen ableiten, da insbesondere bei der PV und IMF Apoptose und Proliferation signifikanten Einfluß auf das Überleben der Patienten hatten. In diesem Zusammenhang spiegelt eine vermehrte Apoptose- und Proliferationsrate im Knochenmark offenbar eine größere regenerative Kapazität der Hämatopoese wieder und könnte daher für einen günstigeren Verlauf verantwortlich gemacht werden.
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  • 60
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    Der Pathologe 21 (2000), S. 456-459 
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Undifferenziertes kleinzelliges Hepatoblastom ; Immunhistochemie ; Keywords Undifferentiated small-cell hepatoblastoma ; Immunohistochemistry ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Undifferentiated small-cell hepatoblastoma (HB) is a rare malignant tumor of childhood. The cell of origin is supposed to be a pluripotential, probably entodermal, stem-cell. Differential diagnosis of this type of HB is difficult among the group of small round and blue cell malignant tumors of children. The immunohistochemically determined coexpression of cytokeratin 8, 18, and 19 and of vimentin and actin, regularly in the absence of α-fetoprotein expression may be diagnostically helpful. We present the case of an undifferentiated small-cell HB of a 15-month-old girl with agenesis of the right kidney. As morphological peculiarity the tumor presented disseminated histiocytic giant cells.
    Notes: Zusammenfassung Undifferenzierte kleinzellige Hepatoblastome (HB) zählen zu den seltenen malignen Tumoren der Leber im Kindesalter. Da der Tumor in der Regel kein α-Fetoprotein exprimiert, ist der Nachweis von Zytokeratin 8, 18 und 19 sowie Vimentin und Aktin diagnostisch wegweisend. Als Ausgangszelle wird eine pluripotente, wohl entodermale Stammzelle vermutet. In der Gruppe der klein-, rund- und blauzelligen malignen Tumoren des Kindesalters bietet diese Variante des HB differenzialdiagnostische Schwierigkeiten. Wir berichten über ein undifferenziertes kleinzelliges HB eines 15 Monate alten weiblichen Kleinkindes mit Agenesie der rechten Niere. Als morphologische Besonderheit des Tumors werden disseminierte histiozytäre Riesenzellen beschrieben.
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  • 61
    ISSN: 1432-1084
    Keywords: Key words: MR imaging ; Non-small cell lung cancer ; Therapeutic effect ; Prognosis ; Survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. The aim of this study was to evaluate the therapeutic effect more accurately and predict the prognosis of treated non-small cell lung cancer by using contrast-enhanced magnetic resonance imaging (CE-MRI). Contrast-enhanced computed tomography (CE-CT) and CE-MRI were examined 90 non-small cell lung cancer patients treated with conservative therapies. Enhancement patterns of CE-MRI were classified into three types: peripheral; mottled; and homogeneous. Reduction ratio of tumor size (RRT) based on the World Health Organization response criteria and a new response rate; reduction ratio of viable tumor size (RRVT) which evaluates not only the reduction of tumor size but also changes in necrosis and/or cavity size, were evaluated. Changes of enhancement pattern were compared and correlated with pathological diagnosis. The RRTs, RRVTs, and interobserver agreements evaluated by all modalities were compared. The RRTs and RRVTs in each subgroup were correlated and compared with prognoses. Change of enhancement pattern depended on therapy had no tendency (p = 0.06). Enhancement pattern had significant correlation with pathological diagnosis (p 〈 0.0001). Partial response (PR) case of RRVT had significant difference between imaging techniques (p = 0.04). The RRVT of other cases and RRT had no significant difference. Interobserver agreements of RRT and RRVT were almost perfect (ϰ≥ 0.93). Prognosis had better correlation with RRVT than with RRT. Differences of relapse-free survival and survival between patients considered as having no change (NC) by RRT and PR by RRVT (NC-PR) and patients considered as having NC by RRT and RRVT were significant (p = 0.03, p = 0.01). There were no significant differences of relapse-free survival and survival between NC-PR patients and patients considered as having PR by RRT and RRVT. The CE-MRI technique could accurately evaluate the therapeutic effect and predict the prognosis of treated non-small cell lung cancer.
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  • 62
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    European journal of orthopaedic surgery & traumatology 10 (2000), S. 199-202 
    ISSN: 1432-1068
    Keywords: Abscess ; Prognosis ; Spinal epidural abscess
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Five patients suffering from spinal epidural abscess associated with neurologic deficit are reported. Four patients underwent a decompressive procedure for abscess drainage, and one patient was medically treated. One of the patients showed a neurologic deterioration at the early postoperative period. The long-term follow-up showed a good outcome in all patients. It is concluded that epidural abscess associated with progressive neurologic deficit requires immediate decompression and administration of antibiotic. Postoperative neurological deterioration may be seen despite proper and immediate decompression and in such a case neurologic improvement is observed in the late postoperative period.
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  • 63
    ISSN: 1432-0851
    Keywords: Key words IL-2 serum levels ; NSCLC ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Interleukin(IL)-2 is a T helper (Th) 1 type cytokine that has been shown to play an important role in antitumour immune responses. In this study, the prognostic significance of serum IL-2 levels was investigated in 60 advanced non-small-cell lung cancer (NSCLC) patients. IL-2 serum levels were determined before chemotherapy, at the end of chemotherapy and during follow-up, using a commercially available enzyme-linked immunoadsorbent assay kit. The results were analysed according to the response to therapy and were used to generate a model predicting overall survival and time to treatment failure. All 60 patients were shown to have higher IL-2 serum levels than controls (P 〈 0.0001). Stage IV patients had significantly lower IL-2 levels than stage III patients (P 〈 0.0001), although they were still significantly higher than controls (P 〈 0.0001). It is interesting that, when patients were divided into responders and non-responders according to the response to therapy, the former were shown to have significantly higher pre-chemotherapy levels than the latter (P 〈 0.0001). Moreover, a further significant increase in IL-2 serum levels (P=0.004) and a significant decrease (P 〈 0.0001) were shown in responders and non-responders, respectively at the end of the therapy. Using univariate and multivariate analyses, both overall survival and time to treatment failure were shown to be affected by the mean pathological levels of IL-2. Furthermore, the prognostic significance of the serum level of IL-2 was confirmed by the stepwise regression analysis. In conclusion, determination of pre-treatment IL-2 serum levels was shown to be of independent prognostic utility in patients with advanced NSCLC; therefore, its possible use for prediction of outcome is proposed.
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  • 64
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    Journal of neurology 247 (2000), S. 943-948 
    ISSN: 1432-1459
    Keywords: Key words Transverse myelitis ; Motor evoked potentials ; Somatosensory evoked potentials ; Electromyography ; Prognosis ; Magnetic resonance imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A systematic evaluation of anterior horn cell, motor and sensory pathways is possible by electromyography (EMG), motor (MEPs) and somatosensory (SEPs) evoked potentials, respectively, which may provide valuable information on acute transverse myelitis (ATM). In a prospective hospital-based study, EMG, MEP and SEP studies were carried out on admission and after 3 months in 39 patients with ATM. All the patients also underwent detailed clinical evaluation, and spinal magnetic resonance imaging (MRI) was performed in 28. Outcome was defined at the end of 3 months as poor, partial or complete recovery on the basis of functional status. Spinal MRI revealed hyperintense signal changes in T2 extending for two segments to the entire spinal cord. Central motor conduction time to tibialis anterior (CMCT-TA) was more frequently abnormal (90%), followed by tibial SEP (77%). CMCT to abductor digiti minimi (ADM) was abnormal in 30% and median SEP in 15% of patients. Evidence of denervation on EMG was present in 51% of patients. The CMCT-TA improved in 48% patients and tibial SEP in 32%. Median SEP improved in all patients, and CMCT-ADM remained prolonged in two. At 3 months 2 patients had died, and 18 had poor, 10 partial and 9 complete recovery. CMCT was correlated with miscle power, tone, reflec and MRI changes. Patients' outcome of was correlated with CMCT, SEP and EMG. These results are consistent with pronounced involvement of dorsal region of spinal cord in ATM. MEP is more frequently abnormal than SEP.
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  • 65
    ISSN: 1432-1459
    Keywords: Key words Sarcoidosis ; Spinal cord ; Magnetic resonance imaging ; Corticosteroid therapy ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Spinal cord sarcoidosis is a rare disorder whose natural history and therapeutic outcome are not fully known. We examined four patients with spinal cord sarcoidosis both clinically and radiologically, particularly in relation to corticosteroid treatment. The initial manifestation was cervical myelopathy in three and uveitis in one. All four patients progressed slowly until corticosteroid therapy was initiated. The cervial spine was involved in all patients. Magnetic resonance imaging (MRI) showed spinal cord swelling with T2-weighted high intensity and linear leptomeningeal and patchy or diffuse intramedullary enhancement with gadolinium diethylene triaminepentaacetic acid. With corticosteroid therapy, dramatic improvement was seen on MRI, including disappearance or marked reduction of swelling and enhancement. Plasma levels of angiotensin-converting enzyme (ACE) were also markedly improved. In contrast, the clinical symptoms were little improved in one patient, unchanged in two, and rather worsened in one patient. Recurrence was seen on MRI at the maintenance dose in all four patients, without any dramatic change in clinical manifestation. MRI findings and plasma ACE are well correlated with active leasion of the spinal cord sarcoidosis, providing a useful marker for recurrence, but do not parallel the clinical manifestations.
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  • 66
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    Archives of gynecology and obstetrics 264 (2000), S. 13-19 
    ISSN: 1432-0711
    Keywords: Key words Fallopian tube cancer ; Radiotherapy ; Chemotherapy ; Lymph node metastasis ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objective: To contribute toward the understanding of the therapeutic management of fallopian tube cancer. Methods: Recent studies related to the treatment of fallopian tube cancer were reviewed. Results: Current evidence indicates that even patients in early stages have nodal disease, and often experience relapses in distant sites. In advanced stages, survival prolongation by the use of platinum-based chemotherapy has been demonstrated. Aggressive cytoreductive surgery followed by chemotherapy and negative second-look laparotomy offer the possibility of long-term survival. However, a significant fraction of patients eventually relapses after negative second-look laparotomy, and a poor survival rate after positive second-look laparotomy has been observed. Conclusions: This series suggests the need for thorough evaluation of lymph nodes at the time of surgery. The use of platinum-based chemotherapy is probably the best adjuvant therapy for both early stages and advanced stages. The clinical value of second-look laparotomy will remain limited until effective salvage therapy is developed. The potential benefits of neoadjuvant chemotherapy and the use of paclitaxel will be increasingly important.
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  • 67
    ISSN: 1432-1335
    Keywords: Key words Blood group antigen ; ABH isoantigens ; Colorectal carcinoma ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The deletion of blood group ABH isoantigens on tumor tissues has been reported to be an adverse prognostic marker for patients with various solid tumors. In the present study, we evaluated the prognostic value of altered expression of ABH isoantigens in colorectal carcinomas. Using monoclonal antibodies, the expression of A, B, and H antigens was assessed by immunohistochemistry on paraffin-embedded carcinoma samples from 82 patients who had undergone surgery for colorectal cancer. ABH isoantigens were found to be deleted in 36 carcinomas (43.9%) and expressed in 46 (56.1%). Univariate and multivariate analysis using a logistic regression model revealed that N factor (lymph node metastasis) and blood group type were independently related to the expression of ABH isoantigens. In contrast to previous reports on other cancers, patients whose colorectal carcinomas express ABH isoantigens had a poorer prognosis than those whose carcinomas showed deletion of ABH isoantigens (P = 0.0008). The expression of ABH isoantigens was an independent prognostic variable, in addition to T (depth of tumor invasion), N, and M (distant metastasis) factors, as shown by means of Cox regression analysis. In conclusion, the expression of ABH isoantigens in carcinoma tissue is an important poor prognostic factor in patients with colorectal cancer. This variable needs to be considered in the design of future trials of therapy.
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  • 68
    ISSN: 1433-0350
    Keywords: Keywords Intracranial cyst ; Prenatal ; Fetus ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This review evaluates the contribution of prenatal diagnosis to the understanding of intracranial cysts. We describe the outcome of 54 fetuses in which prenatal investigations indicated the presence of such lesions. The cysts were diagnosed between 20 and 30 weeks of gestation. Most (63%) were supratentorial and interhemispheric. There was only a single sylvian cyst. In the infratentorial compartment, median retrocerebellar cysts were predominant. Incisural cysts accounted for 14.8% of the series. Nine pregnancies were interrupted because of the presence of associated brain disorders. Forty-five children are alive. Thirty-four had neuropsychological tests. Cysts rarely progressed, most frequently stabilized and often regressed postnatally. Hydrocephalus was rare. In two cases delivery was precipitated at 36 weeks to allow urgent treatment of rapidly evolving cysts. Thirteen children (28.2%) were treated postnatally, in general for developing cysts. The median follow-up for the whole series exceeds 4 years. Behavior, neurological development, and intelligence are normal in 88% of the cases, and 91% have a normal neurological status. Prognosis at the time of the prenatal consultation was correct in 89% of the cases. We emphasize the value of prenatal magnetic resonance imaging and karyotype studies to limit risks of incorrect prognosis.
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  • 69
    ISSN: 1432-2307
    Keywords: Key words Endometrium ; Endometrial carcinoma ; Lectins ; Con A ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Lectins are proteins and glycoproteins of non-immune origin which bind specifically to carbohydrate residues, agglutinate cells and/or precipitate complex carbohydrates. Lectin-binding patterns in normal, hyperplastic and neoplastic endometria were studied using four biotinylated lectins (Con A, LCA, e-PHA, l-PHA) and the avidin-biotin-peroxidase technique. Canavalia ensiformis agglutinin (ConA) and Lens culinaris agglutinin (LCA) reacted strongly with the luminal borders and the cytoplasm of epithelial cells but, whilst in normal and benign endometrial tissues the cytoplasmic staining was confined to the apical and the basal aspect of the cells, in endometrial carcinomas and in some atypical hyperplasias lectin binding also occurred in the lateral cytoplasm (Con-A-lat), although in differing proportions of cells. Interestingly, extensive Con-A-lat in the tumour cells was much more frequent in non-endometrioid carcinomas (P〈0.05) and was significantly associated with poor histological differentiation (P〈0.0001), low oestrogen and progesterone receptor content (P〈0.01 and P=0.0001, respectively) and an unfavourable long-term survival (P〈0.05). With Phaseolus vulgaris erythroagglutinin (e-PHA) and leucoagglutinin (l-PHA) a linear, rather inconsistent, staining at the level of the basement membranes was observed in the glands: this, also noted with LCA, appeared intact in normal and hyperplastic glands without cytological atypia, and fragmented or absent in malignant glandular structures and in most hyperplastic glands showing cytological atypia. It is concluded that changes in the distribution of lectin-binding molecules in the endometrial cells are associated with the malignant state, whilst the extent of Con-A-lat reflects the biological behaviour of the tumours.
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  • 70
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    Virchows Archiv 436 (2000), S. 102-108 
    ISSN: 1432-2307
    Keywords: Key words Oral ; Squamous cell carcinoma ; Proliferation ; Apoptosis ; Tumour suppressor gene ; Oncogene ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Tumour progression is characterised by an imbalance between cell proliferation and apoptosis. The aim of our study was to estimate the importance of proliferation and apoptosis associated parameters in primary squamous cell carcinomas (SCCs) of the oral cavity and oropharynx. For determination of apoptosis, the enzymatic labelling of DNA fragmentation with a terminal transferase reaction was used in 156 tissue samples of 107 patients, including corresponding lymph-node metastases in nine cases. P53, bcl-2, and Ki-67 were determined immunohistologically. P53 was detectable in 50.5% of the cases. Positive staining was associated significantly with decreased apoptosis (P〈0.003). Bcl-2 was upregulated in 31.8% of the cases depending on the tumour grading (P〈0.001) and correlated negatively with apoptosis (P〈0.001). Proliferation (P〈0.006) and apoptosis (P〈0.03) were enhanced in larger tumours, though a direct correlation between these two parameters was not proven. Nevertheless, in contrast to the conventional tumour staging and grading, neither the expression of p53 or bcl-2 nor the apoptosis or Ki-67 measurements were able to predict survival or recurrence-free survival of the patients suffering from a SCC in the oral cavity or oropharynx. Our observations suggest that the function of wild-type p53 to induce apoptosis is lost in at least half of the SCCs under study and that the physiological function of bcl-2 as potent inhibitor of apoptosis is widely preserved in oral SCC.
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  • 71
    ISSN: 1432-2307
    Keywords: Key words CD44 ; Adhesion molecules ; Prognosis ; Soft tissue sarcoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Recent studies have shown that expression of alternatively splicing variants of CD44 is correlated with prognosis for several kinds of malignant tumors. However, little is known about the expression of CD44 standard and variant isoforms in soft tissue sarcomas. In this study 47 cases of soft tissue sarcoma [18 malignant fibrous histiocytomas (MFHs), 13 synovial sarcomas (SSs), 7 malignant schwannomas (MSs), and 9 liposarcomas (LSs)] were examined immunohistochemically. The monoclonal antibodies to the standard form of CD44 (CD44H) and variant exons of CD44v3, 4, 5, 6, 7, 9, and v10 were used. We analyzed the membranous expression pattern of CD44H and CD44 variant exons and assessed the relation between expression of CD44s and metastasis-free survival rates (MFSR) of patients with soft tissue sarcoma. A few sarcomas expressed CD44v3 (2/47) and v7 (2/47), but none of the sarcomas expressed CD44v10. CD44v4 (5/47), v5 (4/47), v6 (10/47), and v9 (9/47) are relatively common types of variant isoforms in soft tissue sarcomas. Expression of CD44v6 is more frequently detected in high-grade than in low-grade tumors. CD44v6 or CD44v9 expression was correlated with metastasis-free survival of patients with soft tissue sarcomas.
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  • 72
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    Child's nervous system 16 (2000), S. 21-24 
    ISSN: 1433-0350
    Keywords: Key words Children ; Glasgow Coma Scale ; Glasgow Outcome Scale ; Prognosis ; Traumatic brain stem lesions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Glasgow Coma Scale (GCS) scores on admission may be predictors of outcome in patients with brain injuries. This study correlated the outcomes of children with traumatic brain stem lesions with their initial GCS scores and morphological patterns of injury as shown on computed tomography (CT) or magnetic resonance (MR) imaging. During the last 16 years, we have treated 1,108 children with brain injuries. The entire series included only 21 (1.9%) children who had clinical signs of brain stem lesions with morphological correlates on CT or MR imaging. Clinical findings were assessed according to the GCS and compared with scores on the Glasgow Outcome Scale (GOS). Of these 21 children, 16 (76%) had morphological lesions seen on CT scans. In 5 (24%) of the children only the MR images revealed brain stem lesions and their CT scans were negative. Generalized severe brain swelling was present in 6 cases (28%). There was a significant difference in GOS scores between patients with initial GCS scores of 3 and 4 and those with GCS scores between 5 and 7 (P〈0.02). Children with intracranial pressure higher than 40 mmHg had poorer outcomes than patients whose intracranial pressure was lower, but the differences were not significant. Outcome did not correlate significantly with morphological patterns of injury or the presence of extracranial injuries. The GCS is a reliable indicator of severity of injury and of outcome in children with brain stem injuries. MR imaging was more sensitive than CT in detecting brain stem lesions.
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  • 73
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    Child's nervous system 16 (2000), S. 760-764 
    ISSN: 1433-0350
    Keywords: Keywords Children ; Brain-injury ; Network ; Prognosis ; Visuo-spatial neglect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A care network has been created in the Paris area according to two criteria – the continuity and the specificity of the care, with a single place to manage pediatric neurosurgical emergencies. This network makes possible research about brain-injured children. Until recently, the ”Kennard principle”, that is, the assumption that recovery after similar lesions is greater in children than in adults has been supposed to be always true. In fact, if the lesions are diffuse, recovery is not greater in children compared with adults, or in younger children compared with older ones: the prognosis depends on the remaining ability to learn new practices. Normal IQ does not mean absence of sequelae. The cognitive deficits are very similar to those found in adults at the acute phase. For instance, visuo-spatial neglect appears as rather frequent when systematically looked for. The final assessment of outcome after childhood traumatic brain-injury should be done only after several years.
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  • 74
    ISSN: 1569-8041
    Keywords: breast cancer ; combination therapy ; paclitaxel ; vinorelbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose:To evaluate the anti-tumour activity and tolerance of thecombination of paclitaxel plus vinorelbine in metastatic breast cancer (MBC)patients previously treated with anthracyclines. Patients and methods:Fifty-six MBC patients who have had at leastone previous anthracycline-containing chemotherapy regimen were enrolled inthis phase II trial. Patients received paclitaxel (135 mg/m2 overone-hour infusion) and vinorelbine (30 mg/m2) both on day 1 of eachthree-week course of therapy (maximum eight courses or until diseaseprogression was evident). Results:Six complete and nineteen partial responses were observedamong the fifty-four assessable patients (response rate of 46%,95% CI: 33%–60%). Responses were observed in alldisease sites and in all subsets of patients. The response rates whenpaclitaxel plus vinorelbine were used as first, second and third-linechemotherapy for metastases were 67%, 41% and 35%,respectively. The response rate among anthracycline-refractory patients was46% (6 of 13). Median time to progression in the overall patient groupwas 28 weeks. The main toxicities (CTC grade 2 or more) were alopecia,myelosuppression and peripheral neuropathy (85%, 46% and19% of patients, respectively). Nine patients (17%) hadneutropenic fever in fifteen of the three hundred twenty-eight coursesadministered (5%). Conclusions:The combination of paclitaxel and vinorelbine on day1 every three weeks is active in MBC patients with prior anthracyclineexposure. The regimen is safe, well tolerated and convenient for the patients.
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  • 75
    ISSN: 1569-8041
    Keywords: breast cancer ; cyclophosphamide ; fluorouracil ; mitoxantrone ; radiation therapy ; secondary leukemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:The topoisomerase II-targeted drugs,epipodophyllotoxins and anthracyclines, have been shown to inducetherapy-related AML (t-AML) characterized by a short latency period afterchemotherapy, the absence of prior myelodysplastic syndrome and stereotypedchromosome aberrations. Few reports have been published on patients treatedwith the anthracenedione mitoxantrone which also targets topoisomerase II. Weobserved 10 cases of such t-AML over a 7-year-period in breast cancer patientstreated with mitoxantrone combined with fluorouracil, cyclophosphamide andregional radiotherapy, and in three cases with vindesine. Patients and methods:We retrospectively analyzed patientsreferred to our hospital for AML with a past history of polychemotherapy forbreast cancer, including mitoxantrone, either as adjuvant (8patients)/neoadjuvant (1 patient) therapy or for metastatic disease (1patient). We studied the probability of developing t-AML in a prospectiveseries of 350 patients treated with an adjuvant FNC regimen (mitoxantrone,fluorouracil, cyclophosphamide) and radiation therapy. Results:The median age was 45 years (range 35–67). t-AMLdeveloped 13–36 months (median 16) after beginning chemotherapy forbreast cancer, and 4–28 months (median 10.5) after ending treatment. Asdescribed in t-AML following treatment with epipodophyllotoxins oranthracyclines, we found a majority of FAB M4, M5 and M3 phenotypes (7 of 10),and characteristic karyotype abnormalities that also can be found in denovoAML: breakpoint on chromosome 11q23 (3 patients), inv(16)(p13q22)(2 patients), t(15;17)(q22;q11) (1 patient), t(8;21)(q22;q22) (1 patient) anddel(20q)(q11) (1 patient). The prognosis was poor. All patients died of AMLshortly after diagnosis. Since two patients had been enrolled in a prospectivetrial for the treatment of breast cancer which included 350 patients, theprobability of developing t-AML was calculated to be 0.7% from25–40 months, using the Kaplan–Meier method (95% confidenceinterval (95% CI): 0.1–4.5). Conclusions:The combination of mitoxantrone withcyclophosphamide, fluorouracil, and radiation therapy can induce t-AML, aswith other topoisomerase II-targeted drugs. Despite a low incidence, theprognosis appears to be poor.
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  • 76
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    Annals of oncology 11 (2000), S. 1255-1262 
    ISSN: 1569-8041
    Keywords: age ≤35 years ; breast cancer ; single institution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Early-onset breast cancer may differ with respect toetiology, clinical features and outcome compared with breast cancer in olderwomen. To gain further insight, we retrospectively reviewed the clinicalfeatures and outcome of women ≤35 years with primary breast cancer seen atour institution over a 30-year period. Patients and methods:Charts were reviewed for women with operablebreast cancer diagnosed ≤35 years of age seen at the Princess MargaretHospital (PMH), Toronto from 1965–1994. Results:One thousand eighty-six women with non-metastaticinvasive breast cancer, aged 18.3–35.6 years (median 32.1 years) werereferred to PMH. Symptoms at presentation included: self-detected breast lump(83%), other breast symptom (10%), physician diagnosis(4%) and unknown (3%). Tumor size was known in 936 (〉2 cm in61%) and nodal status in 888 (lymph node positive in 52%).Modified radical mastectomy was performed in 568 (57%) andbreast-conservation surgery (BCS) in 422 (42%). Five hundred sixteen(51%) patients received adjuvant radiotherapy and five hundredthirty-four (53%) adjuvant systemic therapy. Two hundred ninety-three(29%) patients had a family history of breast cancer (FH).Contralateral breast cancer (CBC) occurred more frequently in women with FH(Prange 0.042–0.008). Local recurrence (LR) was 37% and73% at 10 years in those treated by BCS with and without radiotherapy,respectively. At 10 years, disease-free survival (DFS) was 30% andoverall patient survival 48%. Conclusions:In this cohort, breast cancer was usuallyself-diagnosed and tumors were 〉2 cm at presentation in approximatelytwo-thirds of cases, suggesting the possibilities of a delay in diagnosis,more aggressive tumors or both. Our results are compatible with the knownassociation of breast cancer FH with increased CBC. Our data also corroboratesthe suggestion that positive genetic testing in this age group should lead toconsideration of more aggressive ipsilateral and contralateral breastmanagement. In those receiving adjuvant irradiation after BCS, the LR rate washigh, but did not impact on overall survival.
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  • 77
    ISSN: 1569-8041
    Keywords: breast cancer ; carboplatinum ; chemotherapy ; continuous 5-fluorouracil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We performed a trial using the combination of epirubicin 50mg/m2/day 1, carboplatinum AUC 5/day 1 and continuous5-fluorouracil (5-FU) 200 mg/m2/day (every 4 weeks for6 months) to confirm the efficacy and low toxicity profile of thisregimen in breast cancer. In 51 patients with metastatic(n = 33) or locally advanced (n = 18)breast cancer the overall response rate was 86% (95% confidenceinterval (95% CI): 73%–94%): 94% in locallyadvanced and 81% metastatic disease. Grade 3–4 toxicity was low:4% of patients presented with febrile neutropenia, 16% withsevere palmar-plantar syndrome, 10% with Port-a-cath thrombosis. This study confirms the high efficacy of infusional 5-FU-based regimens andjustifies further research into novel promising oral 5-FU derivatives.
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  • 78
    ISSN: 1569-8041
    Keywords: adjuvant chemotherapy ; breast cancer ; doxorubicin ; elderly patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:The purpose of this study was to evaluate the clinicaloutcome of doxorubicin-based adjuvant chemotherapy in elderly breast cancerpatients and to compare results in elderly patients with those in youngerpatients. Patients and methods:We retrospectively reviewed the records ofall patients aged 50 years or older treated in trials of doxorubicin-basedadjuvant chemotherapy between 1974 and 1988. Old age was not an exclusioncriterion for these trials. Patient characteristics, hematologic andnonhematologic side effects, patterns of recurrence, and causes of death weredetermined for patients aged 50–64 years and for patients aged 65 yearsor older, and results were compared between these two groups.Kaplan–Meier survival curves were plotted, and tested by the generalizedWilcoxon test. Results:A total of 390 patients aged 50 years or older weretreated with doxorubicin-based adjuvant chemotherapy during the study period.Of these, 325 were aged 50–64 years (group 1), and 65 were aged 65 yearsor older (group 2). The median follow-up period for group 1 was 185 months(range 29–272+ months), and the median follow-up period for group 2 was169 months (range 128–240+ months). There were no statisticallysignificant differences between the two groups with respect to performancestatus, hormone receptor profile, tumor size, nodal status, or type oflocoregional therapy. There also were no statistically significant differencesbetween the two groups in recurrence patterns, disease-free survival, oroverall survival. The granulocyte and platelet nadirs of cycles 1, 3, and 6were similar between the two groups. No cumulative hematologic side effectswere seen in either group. The occurrence of second malignancies was extremelylow in both groups. In both groups, the majority of deaths were due toprogression of disease. Conclusions:Adjuvant doxorubicin-based chemotherapy is welltolerated in elderly breast cancer patients who have good performance statusand normal cardiac ejection fraction. Adjuvant doxorubicin-based chemotherapyin these patients results in disease-free and overall survival rates similarto those seen in younger patients.
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  • 79
    ISSN: 1569-8041
    Keywords: breast cancer ; hot flashes ; paroxetine ; serotonin uptake inhibitors ; survivors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Many breast cancer survivors suffer debilitating hotflashes. Estrogen, the drug of choice in perimenopausal women, is generallynot recommenced to breast cancer survivors. Nonhormonal treatments are mostlydisappointing. Anecdotal reports in our institution suggested that theselective serotonin-reuptake inhibitor, paroxetine hydrochloride, might beefficacious in alleviating hot flashes. Patients and methods:Thirty women with prior breast cancer whowere suffering at least two hot flashes a day entered a single institutionpilot trial to evaluate paroxetine's efficacy in reducing the frequency andseverity of hot flashes. After completing daily diaries for one week on notherapy, the women received open-label paroxetine, 10 mg daily for one week,followed by four weeks of paroxetine, 20 mg daily. The women completedhot-flash daily diaries throughout the study period, and a health-relatedsymptom-assessment questionnaire and a quality-of-life rating scale in thefirst and sixth week of the study. Results:Twenty-seven women completed the six-week study period.The mean reduction of hot flash frequency was 67% (95%confidence interval (95% CI): 56%–79%). The meanreduction in hot flash severity score was 75% (95% CI:66%–85%). There was a statistically significantimprovement in depression, sleep, anxiety, and quality of life scores.Furthermore, 25 (83%) of the study participants chose to continueparoxetine therapy at the end of study. The most common adverse effect wassomnolence, resulting in drug discontinuation in two women, and dose reductionin two women. One woman discontinued drug due to anxiety. Conclusions:Paroxetine hydrochloride is a promising new treatmentfor hot flashes in breast cancer survivors, and warrants further evaluationin a double-blind randomized placebo-controlled trial.
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  • 80
    ISSN: 1569-8041
    Keywords: breast cancer ; socio-economic status ; stage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:This study describes and compares the pathologicalprognostic factors and surgeon assessment of stage of breast cancer of womenliving in affluent and deprived areas to assess whether clinical stage atpresentation may explain the known poorer survival outcomes for deprivedwomen. Patients and methods:A population-based review of the caserecords of 417 women with breast cancer was carried out. Results:No difference in pathological criteria was found betweenthe 88% of women living in affluent and deprived areas for whom suchdata were available. Clinical assessment of the remaining 50 cases showed thatwomen living in deprived areas were more likely to present with locallyadvanced or metastatic disease. Conclusion:The poorer survival of women from deprived areas withbreast cancer may be explained by more deprived women presenting with advancedcancers.
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  • 81
    ISSN: 1569-8041
    Keywords: breast cancer ; choice ; decision-making process ; patient–physician relationship
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Shared decision-making is increasingly advocated asan ideal model. However, very few studies have tested the feasibility ofgiving patients the opportunity to participate in the choice of treatment. Patients and methods:Women, with non-metastatic breast cancer,eligible for non-intensified adjuvant chemotherapy attending our hospital wereproposed two administrations of chemotherapy and radiotherapy: a sequentialand a concomitant one. Two patient-questionnaires were used to elicitmotivations for their choice and their degree of comfort with the process ofdecision-making and one questionnaire to test physicians' ability to predictpatients' choice. Results:Participation rate in the study was 75.3%(n = 64). Majority (64%) of patients chose the concomitanttreatment. Multivariate analysis revealed that patients with a lower level ofeducation, who discussed the choice with social circle, and who most fearedside-effects were more likely to choose the sequential treatment. Physicianswere able to predict patients' choice in 66% of cases. 89% ofpatients declared that they were "fully satisfied" with having participatedin the choice of treatment and 79% supported shared decision-making. Conclusions:Results are in favour of promoting activeparticipation of cancer-patients in medical decision-making. The adequatedegree of such participation remains however to be elicited and tested fortherapeutic choices implying more difficult trade-offs between quantity andquality of life.
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  • 82
    ISSN: 1569-8041
    Keywords: adjuvant therapy ; breast cancer ; second cancer ; tamoxifen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Women treated with tamoxifen for breast cancer are atincreased risk of endometrial cancer. We conducted a retrospective cohortstudy to evaluate the risk of second primary cancers after adjuvant tamoxifentherapy for breast cancer in Japan. Patients and methods:The subjects of the study were 6148 womenwho had been diagnosed with stage I, II, or IIIA unilateral primary breastcancer and had received surgical treatment during the period from January 1982through December 1990 at nine institutions in Japan. The information on eachpatient was obtained from medical records or a prospectively compiled computerdatabase at each institution. Results:Of the 6148 women, 3588 (58.4%) were administeredtamoxifen as an adjuvant treatment and 2560 (41.6%) were notadministered. Median follow-up periods were 7.64 years for tamoxifen-treatedpatients and 8.10 years for non-tamoxifen-treated patients, respectively. Theduration of tamoxifen treatment was mostly two years or less (80.7%),and few patients received tamoxifen for more than five years. The cumulativeincidence rates of all second cancers at 10 years were 4.61% and4.09% among tamoxifen-treated and non-tamoxifen-treated patients(P = 0.62), respectively, and the incidence rate ratio (IRR) forall second cancers was 1.06 (95% confidence interval (CI):0.77–1.47) after adjustment of several covariates. The numbers ofendometrial cancers was 9 and 3 among tamoxifen-treated andnon-tamoxifen-treated patients, respectively, and the IRR was 2.37 (95%CI: 0.64–8.77, P = 0.20). Of the 12 patients who developedendometrial cancer, 4 died of cancer (for 3 of them, the cause of death wasbreast cancer), and the other 8 patients were alive as of March 1996. Stomachcancer was the most frequent second cancer and the IRR was 1.34 (95%CI: 0.76–2.38, P = 0.31). There was no substantialincrease in any other type of gastrointestinal cancer such as colorectal andliver cancers among tamoxifen-treated patients. Conclusions:The incidence and risk of second primary cancersassociated with tamoxifen therapy is low. The potential benefit of adjuvanttamoxifen therapy in breast cancer patients outweighs the risk of secondprimary cancers for Japanese breast cancer patients.
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  • 83
    ISSN: 1569-8041
    Keywords: breast cancer ; docetaxel ; epirubicin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose:In a previous phase I trial we evaluated the toxicity anddetermined the maximum tolerated doses of the docetaxel (D)–epirubicin(Epi) combination. We conducted a multicenter phase II study to evaluate theefficacy and tolerability of this regimen as front-line treatment in womenwith advanced breast cancer (ABC). Patients and methods:Fifty-four women with ABC stage IIIB (4patients) or IV (50 patients) received front-line treatment with Epi 70mg/m2 on day 1 and D 90 mg/m2 on day 2. The median agewas 55 years, performance status (WHO) was 0–1 in 49 patients andvisceral disease was present in 45 (83%). Results:All patients were evaluable for toxicity and 50 forresponse. In an intent-to-treat analysis complete remission was observed in5(9%) patients, partial remission in 31 (57%) (overall responserate 66%, 95% confidence interval: 54%–79%),stable disease in 9 (17%) and disease progression in 9 (17%).After a median follow-up of 11.5 months, the median duration of responses was8 months, the median time to disease progression 11.5 months and the mediansurvival has not yet been reached. The probability of one-year survival was65%. Three hundred six cycles of treatment were administered (median6 cycles per patient). Grade 3 and 4 neutropenia was observed in 8(15%) and 31 (57%) patients, respectively, and febrileneutropenia in 19 (35%). Prophylactic rh-G-CSF was used in 45(83%) patients or 226 (74%) cycles. Other hematologic ornon-hematologic toxicities were usually mild. In five (9%) patients theleft ventricular ejection fraction (LVEF) was decreased by more than10% with the treatment. Two patients died during the treatment ofrespiratory failure without associated neutropenia. Conclusions:The combination of docetaxel–epirubicin is aneffective and well tolerated front-line treatment in patients with ABC.
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  • 84
    ISSN: 1569-8041
    Keywords: breast cancer ; p53 ; prognostic factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:There is heterogeneity of methods and conflictingresults concerning the prognostic value of p53 in node-negativebreast cancer. The clinical value of a quantitative method for measuringtumoral p53 content still needs to be evaluated. Patients and methods: A long-term retrospective study wasconducted on 297 node-negative patients with a median follow-up greater than10 years (11 years, 101–172 months). Classic prognostic factors wereconsidered including age, tumor size, histoprognostic grade and estradiol (ER)and progesterone receptors (PR). In addition, the value of p53 determination (immunoluminometric assay in tumor cytosol) was assessed forthis long follow-up period. Results: p53 concentrations were significantly linked tothe histological grade (P = 0.001), to tumor size (P = 0.02)and ER status (P = 0.01). Higher p53 tumoral concentrationswere found in tumors with large size, pejorative histological grade andnegative ER status. In contrast, p53 tumoral concentrations were notinfluenced by menopausal or PR status. Multivariate Cox analysis demonstratesthat tumor size was the only significant predictor of disease-free survival(P = 0.049) with a risk factor at 1.38. As regards specific survival,univariate Cox analysis indicates that p53 taken as a continuousvariable is a significant predictor (P = 0.024) together withhistological grade, tumor size and ER status. In a multivariate Cox analysisthere were two significant and independent variables for predicting overallsurvival: tumor size (P = 0.031) and ER status (P = 0.015)with the highest risk factor (RR = 2.14). Conclusions:The present investigation points out that theprognostic power of p53 tumor determination evaluated at more than10 years median survival is not higher than the well-recognized classicprognostic factors in node-negative breast cancer. The present data highlightthe need to assess the prognostic value of potentially new biological factorsin node-negative breast cancer on cohorts of patients followed over periodsin excess of 10 years.
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  • 85
    ISSN: 1569-8041
    Keywords: breast cancer ; genetic counselling ; risk assessment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:With the identification of genes predisposing tohereditary breast cancer, the accurate and consistent estimation of a woman'srisk of developing breast cancer based on her family history is of paramountimportance if national service guidelines are to be developed. Patients and methods:The residual lifetime risk of developingbreast cancer was estimated for 200 women attending a breast cancer geneticassessment clinic by three different methods currently in use in the UK. Riskswere computed on the basis of the Cancer and Steroid Hormone (CASH) study dataand were classified as ‘low/moderate’ (〈20%) or ‘high’(〉20%). These risk categories are representative of those currentlyused to allocate surveillance and genetic testing. Risks were then comparedto estimates derived by other methods used in current clinical practice,including those of Houlston and Murday. Results:The CASH data-based method ascribed 27% to thehigh risk category, as compared to 53% for the combined Houlston andMurday methods. A method based on the number of affected relatives aloneascribed only 14% to the high risk category. Overall, 108 (54%)women were placed in the same risk category by all three methods. Conclusions:This study demonstrates that there is a significantdegree of variability between methods currently used to estimate breast cancerrisk which has serious implications for individual patient management, serviceprovision and multicentre studies evaluating the benefits of genetic testingfor breast cancer susceptibility.
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  • 86
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    Annals of oncology 11 (2000), S. 495-496 
    ISSN: 1569-8041
    Keywords: breast cancer ; gemcitabine ; metastases ; vinorelbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose:Gemcitabine (GEM) and vinorelbine (VNR) are both activeagainst advanced breast cancer (ABC), being able to induce a median ORR of25% and 40%, respectively. Because of their different mechanismof action and good tolerability, the combination of GEM and VNR has beentested in ABC. Patients and methods:Twenty-nine ABC patients pretreated withanthracycline-taxane were treated with GEM 1000 mg/m2 on day 1, 8,15, and VNR 25 mg/m2 on day 1 and 8 every twenty-eight days.Analysis of toxicity pattern, response rate, TTP and OS were carried out. Results:Twenty-nine patients were enrolled into the trial. TheORR was 48% (95% CI: 29–67): a CR was observed in threepatients (10%; 95% CI: 2–27), while eleven patients(38%; 95 CI: 21–58) achieved PR, eight (28%) had a SD, andseven (24%) progressed. Toxicity was mainly hematological and included:grade 3 leukopenia in 48% of cases without episodes of neutropenicfever, grade 3–4 thrombocytopenia in 10%, and grade 2 anemia in7%. Non-hematological toxicities were mild and rather infrequent. Conclusions:The GEM–VNR combination seems to be active inpretreated ABC with an acceptable toxicity pattern, and may well reppresentan interesting therapeutic choice after anthracycline/taxane regimens.
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  • 87
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    Annals of oncology 11 (2000), S. 469-474 
    ISSN: 1569-8041
    Keywords: breast cancer ; Prognostic factors ; psychosocial factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Research interest in psychosocial predictors of theonset and course of cancer has been active since the 1950s. Recently wereported associations between psychological factors and survival in patientswith metastatic melanoma. We now report a replication of this study in asample of women with metastatic breast cancer. Patients and methods:Ninety-nine patients with metastatic breastcancer completed questionnaires measuring cognitive appraisal of threat,coping, psychological adjustment, perceived aim of treatment, social supportand quality of life, approximately four months after diagnosis. Survival wasmeasured from date of study entry to date of death or censored at the date oflast follow-up for surviving patients. Results:In a multivariate analysis, four factors independentlypredicted outcome. Patients with metastases in the liver, lung or pleurasurvived for a shorter duration (P 〈 0.001); older patients(P 〈 0.001) and those with a better appetite (P 〈0.05) also lived for a shorter time. Patients who minimised the impact ofcancer survived longer (a median of 29.1 vs. 23.9 months after study entry,P 〈 0.01). Conclusions:Minimisation was also significantly associated withoutcome in patients with metastatic melanoma who participated in anidentically designed study, reported elsewhere. This suggests thatminimisation may have a general impact on cancer progression and deservescloser scrutiny in other cancers.
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  • 88
    ISSN: 1569-8041
    Keywords: 5-FU ; breast cancer ; metastatic ; navelbine ; protracted continuous infusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:The protracted continuous infusion (PCI) of5-fluorouracil (5-FU) has proven in several studies an active and welltolerated treatment for advanced, pretreated breast cancer. Navelbine has alsoactivity in this setting. Patients and methods:Heavily pretreated patients with metastaticbreast carcinoma were eligible for the study. Treatment consisted of 5-FU 250mg/m2 given as a PCI by an elastomeric pump and navelbine 20mg/m2 on days 1 and 8, every four weeks. Eighty-three patients(median age 54 years; range 32–82 years) entered the study. The mediannumber of metastatic tumour sites was 2, with visceral involvement in 56patients. Apart from five patients with contraindications, all patients hadbeen pretreated with anthracyclines. Thirty-one patients had received taxanesand seventy-four bolus 5-FU. Results:A median of 5 cycles (range 1–14) per patient wasadministered. The median duration of 5-FU infusion was 17 weeks (range, 4-90).In the 80 evaluable patients (3 not yet evaluable) 12 complete remissions and24 partial remissions occurred (response rate, 45%). Median durationof response was 9 months. Toxicity was mild. Median survival was 20 months. Conclusions:PCI–5-FU combined with navelbine offers areasonable chance of tumour regression with modest side effects in patientswith heavily pretreated breast cancer.
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  • 89
    ISSN: 1569-8041
    Keywords: adjuvant chemotherapy ; attitudes ; breast cancer ; consensus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:A worldwide variation in policy is seen regardingadjuvant systemic treatment for node negative breast cancer (NNBC). After thefirst presentations of the 10-year EBCTCG results, a study was carried out inthe Netherlands to assess patterns of care and to obtain the views ofoncologists as to what constitutes a worthwhile benefit from treatment. Methods:A questionnaire regarding patterns of use of andpreferences for adjuvant chemotherapy in younger women was mailed to surgical,medical and radiation oncologists in the Netherlands. Results:Thirty-five percent stated that NNBC patients under 50in their hospital never received adjuvant chemotherapy. The majorityconsidered a 10-year survival gain of 6%–10% sufficientto warrant the use of chemotherapy in patients under 50. Surgical oncologistsrequired a larger benefit from treatment than radiotherapists and medicaloncologists. The more frequently oncologists treated patients in a researchcontext, the less benefit they required from treatment to make it worthwhile. Conclusions:Data such as these are valuable input into theprocess of guideline development, and may help discussion within theprofession as to what benefit offsets the burden of treatment.
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  • 90
    ISSN: 1569-8041
    Keywords: breast cancer ; clinical trial ; docetaxel ; hepatic metastases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Previous phase II studies of docetaxel have indicatedthat hepatic metastases from breast cancer respond well to first-linetreatment with docetaxel. The objective of this prospective, open label phaseII study therefore was specifically to evaluate the activity and safety ofdocetaxel in this indication. Patients and methods:The study recruited 47 women (mean age 50years, range 33–66 years) with hepatic metastases from breast cancer whofulfilled the eligibility criteria. After premedication with steroids,patients received a one-hour intravenous infusion of docetaxel 100mg/m2 at three-weekly intervals for up to eight cycles. Responseto treatment during medication was assessed after three, six and whereappropriate, eight cycles and every three month follow-up thereafter, untildisease progression or death. Results:The best overall response rate (ORR) for evaluablepatients was 64.3% (95% CI: 48.0%–78.5%).In terms of the primary efficacy parameters, the ORR at the sixth cycle oftreatment was 62% (95% CI: 45%–80%) with17% complete responses. The median duration of response was 139 days(95% CI: 111–216 days) and the median survival durationcalculated on an intent-to-treat basis was 335 days (227–568 days,95% CI). One (2%) toxic death was reported. Conclusions:Docetaxel is a highly effective cytotoxic agent inthe treatment of patients with liver metastases from breast cancer.
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  • 91
    ISSN: 1569-8041
    Keywords: breast cancer ; lymph nodes ; sentinel lymph node biopsy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Sentinel node biopsy (SNB) has been proposed as analternative to axillary lymph-node dissection (ALND) in breast cancer. Beforeimplementing SNB in our practice, we wished to test its validity by comparingit to the standard ALND, both in our hands and with other reported series. Patients and methods:One hundred thirty-two patients wereincluded prospectively. SNB and immediate ALND were performed. For SNB, atechnetium-colloid was used to produce preoperative lymphoscintigraphy andintraoperative gamma-probe search for the SN. Serial sectioning andimmunostains were used on the SN. A comprehensive review of the literature wasdone in order to run a meta-analysis of diagnostic tests using a summaryreceiver operating characteristic curve (SROC) to calculate the pooledparameters of sensitivity and associated 95% confidence interval(95% CI), including our own data. Results:Our technical success rate was 96%. Localsensitivity was 96%, with a 95% CI from85%–99%. Seven patients were upstaged by the SNB. Aliterature search identified 18 studies published from 1996–1999.Estimates of sensitivity ranged from 83%–100%. The pooleddata meta-analysis gave a global sensitivity of 91%, with a 95%CI from 89%–93%. The area under the global SROC curve was0.9967. Conclusions:The minimally invasive SNB was shown to be apractical alternative to ALND. We propose to use local as well as globalsensitivity and associated 95% CI to test the validity of SNB in theclinical setting. Due to limitations of ALND as the golden standard, SNB canin fact be considered a more accurate method for nodal staging.
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  • 92
    ISSN: 1569-8041
    Keywords: docetaxel + gemcitabine ; docetaxel + vinorelbine ; phase I ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose:The objective of this study was to determine thedocetaxel MTD when combined with gemcitabine or vinorelbine in advanced breastcancer patients who had received previous anthracycline-based chemotherapy foradvanced disease. Patients and methods:Advanced breast cancer patients aged between18 and 70 with ECOG PS 0–2 who had not responded to, or had relapsedafter, first-line anthracycline-based chemotherapy, were randomized to receiveeither gemcitabine 1000 mg/m2 or vinorelbine 25 mg/m2in combination with escalating doses of docetaxel (starting from 30mg/m2), all on days 1 and 8 every three weeks. Escalation wasstopped if 〉33% of patients treated at a given dose level showed DLTat the first cycle. Results:A total of 34 patients with locally advanced (8) ormetastatic disease (26) were treated, for a total of 94 cycles delivered.Nineteen patients received docetaxel in combination with gemcitabine and 15with vinorelbine. All patients had been pretreated with anthracyclines, and24 of 34 had also received weekly dose-dense paclitaxel. A docetaxel dose of40/m2 proved to be safe when combined on days 1 and 8 withgemcitabine, while a dose of 35 mg/m2 was tolerated in combinationwith vinorelbine. Overall, nine episodes of DLT, all of them neutropenia,occurred at the first cycle. Considering all 94 cyles, grades 3 or 4neutropenia and thrombocytopenia occurred in 15 (44%), and 7(20%) patients. Non-hematologic toxicity was mild, except for threecases of grade 2 peripheral neuropathy. All patients were assessed forresponse on an 'intent-to-treat' basis. Overall, five partial responses wererecorded (docetaxel + gemcitabine = 3 and docetaxel + vinorelbine = 2), fora 15% (95% CI: 5%–31%) overall responserate. Only 1 of 24 (4%) patients who had received weekly dose-densepaclitaxel responded to treatment. Conclusions:The weekly docetaxel administration in combinationwith either gemcitabine or vinorelbine is a well-tolerated treatment forheavily pretreated advanced breast cancer patients. This approach, althoughsometimes capable of achieving a major response, does not seem advisable inadvanced breast cancer patients refractory to both anthracyclines andpaclitaxel.
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  • 93
    ISSN: 1569-8041
    Keywords: breast cancer ; estrogen receptor ; progesterone receptor ; preoperative chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:We recently demonstrated that in premenopausalpatients with estrogen receptors (ER)-absent tumors, early initiation ofsystemic chemotherapy after primary surgery might improve outcome. These dataindicate a different responsiveness to chemotherapy for tumors not expressinghormone receptors. To test this hypothesis we evaluated the responsiveness topreoperative chemotherapy in patients with ER and progesterone receptors(PgR)-absent tumors. Patients and methods:Patients with biopsy-provenT2–T3, N0–2 breast cancertreated at a single institution from January 1995 to August 1999 withpreoperative chemotherapy were retrospectively evaluated. ER and PgR weredetermined immunohistochemically and classified for this purpose as absent(0% of the cells positive) or positive (≥1% of the cells). Results:On 117 evaluable patients 72 had an objective response(61%). A significant difference in response was observed for patientswith ER and PgR absent compared with those with ER and/or PgR-positive tumors(82% vs. 57%,P = 0.03 Fishers's exact test).Pathological complete remission rates were also significantly different in thetwo groups (23% vs. 7%, respectively; P = 0.04). Conclusions:The different degree of response according to hormonereceptors expression supports the hypothesis that tumors not expressing bothER and PgR might represent a different clinical entity in terms ofchemotherapy responsiveness.
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  • 94
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    Psychotherapeut 45 (2000), S. 108-115 
    ISSN: 0935-6185
    Keywords: Schlüsselwörter Therapeutische Orientierung ; Therapeutenvariable ; Erstuntersuchung ; Arbeitsbeziehung ; Prognose ; Key words Therapeutical orientation ; Therapist variable ; Diagnostic interview ; Working alliance ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Psychology , Medicine
    Description / Table of Contents: Summary The present study is aimed at investigating differences between therapists of different theoretical orientations regarding their perception of patients who applied for psychotherapy at a university outpatient department. It was based on the judgements of nine psychodynamically and four cognitive-behaviorally oriented therapists about 144 and 89 patients, respectively, who were assessed after having completed their diagnostic interviews. Cognitive-behaviorally oriented therapists perceived the quality of the working alliance to be better and their feelings of sympathy towards the patients they had interviewed to be stronger than did psychodynamically oriented therapists. Psychodynamic therapists saw higher distress in the early childhood, whereas behavior therapists rated patients’ present coping abilities higher. In addition, the latter judged patients’ motivation, a common understanding of the illness, several prognostical factors and the global prognosis more favourable. Regarding the frequencies of disorder categories and the severity of functional restriction due to the disorders no differences were found. The results are discussed from both a cognitiv-behavioral and a psychoanalytical point of view.
    Notes: Zusammenfassung Die vorliegende Arbeit hat das Ziel, Unterschiede in der Wahrnehmung des Patienten bei der psychotherapeutischen Erstuntersuchung je nach theoretischer Orientierung des Diagnostikers zu untersuchen. Sie basiert auf den Einschätzungen von neun tiefenpsychologisch/analytisch und vier kognitiv-verhaltenstherapeutisch orientierten Therapeuten, die 144 bzw. 89 Patienten einer universitären psychotherapeutischen Poliklinik nach dem Erstgespräch beurteilten. Kognitiv-verhaltenstherapeutisch orientierte Erstuntersucher nahmen die Qualität der therapeutischen Arbeitsbeziehung signifikant als besser und die Patienten, die sie untersuchten, als sympathischer wahr. Tiefenpsychologisch orientierte Diagnostiker sahen stärker ausgeprägte frühkindliche Belastungen, wohingegen Verhaltenstherapeuten die aktuelle Bewältigungskompetenz der Patienten höher bewerteten. Zudem schätzen sie die Motivation des Patienten, das gemeinsame Krankheitsverständnis, verschiedene prognostische Faktoren sowie die globale Prognose als günstiger ein. Hinsichtlich der Häufigkeit diagnostischer Kategorien und der Beurteilung der Beeinträchtigungsschwere fanden sich keine Unterschiede je nach therapeutischer Orientierung. Die festgestellten Unterschiede werden sowohl vor einem kognitiv-verhaltenstherapeutischen als auch vor einem psychoanalytischen Theoriehintergrund interpretiert.
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  • 95
    ISSN: 1615-2573
    Keywords: Key words Heart failure ; Doppler transmitral flow pattern ; Cardiac natriuretic peptide ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study was designed to determine whether the restrictive filling transmitral flow velocity pattern is associated with increased plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). It was also designed to evaluate the prognostic value of these parameters from patients with chronic congestive heart failure (CHF) admitted for episodes of acute decompensation. We performed Doppler echocardiography, measured plasma levels of ANP and BNP in 33 patients at the time of admission, and assessed the subsequent cardiac mortality for 3 months. Eleven patients (33%) had a restrictive filling pattern of deceleration time (DcT) 〈120 ms. Plasma ANP and BNP levels were markedly increased in all patients to 189 ± 145 pg/ml and 865 ± 559 pg/ml, respectively. Seventeen patients (52%) showed more than 700 pg/ml of plasma levels of BNP. There was a significant correlation of DcT with the plasma ANP level (r = −0.41, P = 0.017), and a better correlation of DcT with the plasma BNP level (r = −0.50, P = 0.003). The combined index of both shorter DcT (〈120 ms) and higher plasma BNP levels (〉700 pg/ml) was the best predictor of cardiac mortality by Cox univariate analysis (χ2 = 5.87, P = 0.015). Furthermore, the sensitivity and specificity of this index for the detection of cardiac mortality were 80% and 86%, respectively. In conclusion, the combined analysis of the Doppler transmitral flow velocity pattern and measurement of the plasma BNP level is noteworthy since it is noninvasive and convenient. Moreover, it is extremely useful in predicting the prognosis for patients with chronic CHF admitted for episodes of acute decompensation.
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  • 96
    ISSN: 1615-2573
    Keywords: Key words Diastolic function ; Prognosis ; Myocardial infarction ; Color M-mode Doppler echocardiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Color M-mode Doppler echocardiography (CMD) has been utilized in assessing left ventricular (LV) filling dynamics. We tested a novel CMD index, the depth of the spatiotemporal maximum of early diastolic inflow (D-maxV) in the left ventricle, to clarify its significance in assessing LV diastolic function. In 26 normal subjects and 32 patients with ischemic heart disease, D-maxV was determined with CMD as the distance from the mitral valve opening point to the center of the aliasing area in early diastole. Transmitral flow velocity was measured with pulsed Doppler. During routine catheterization, high-fidelity LV pressure measurements yielded diastolic variables in patients. D-maxV was significantly lower in the patients than the normals (13.0 ± 7.0 vs 23.4 ± 6.8 mm, P 〈 0.0001). D-maxV exhibited significant linear correlations with the minimal first derivative of LV pressure (r = 0.72, P 〈 0.01), the time constant of isovolumic relaxation (r = −0.67, P 〈 0.01), and LV minimal pressure (r = −0.53, P 〈 0.02) in the patients with wide ranges of peak early to late inflow velocity ratio (0.43–3.9) and deceleration time of early filling (79–293 ms). D-maxV showed an inverse correlation with LV end-diastolic pressure (r = −0.53, P 〈 0.02) and no significant correlation with mean pulmonary capillary wedge pressure. Moreover, Kaplan-Meier analysis focusing on the patients with myocardial infarction revealed that the group with D-maxV 〈 10.4 mm (n = 13) exhibited a lower cumulative cardiac event-free rate than that with D-maxV ≥ 10.4 mm (n = 14) (49.4% vs 92.9% at 5 years, P 〈 0.05). The depth of the spatiotemporal maximum of early diastolic LV inflow velocity reflects LV relaxation and is free of pseudonormalization. Evaluation of the LV relaxation separately from preload may have a prognostic value for myocardial infarction.
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  • 97
    ISSN: 1573-7276
    Keywords: bone sialoprotein ; osteopontin ; breast cancer ; metastasis ; bone metastases ; immunohistochemistry ; in situ hybridization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Bone sialoprotein (BSP) and osteopontin (OPN) are prominent, mineral-associated proteins in the extracellular matrix of bone that have been implicated in the metastatic activity of cancer cells. The expression of BSP, which is normally restricted to mineralizing tissues, has been observed in cancers with a high propensity for forming bone metastases. To investigate the relationship between BSP expression and the formation of bone metastases we have conducted an initial study of the expression of BSP in 10 intraductal breast carcinoma bone metastases using immunostaining and in situ hybridization, and compared the expression with OPN. The metastases were characterized by the infiltration of tumour cells into bone with extensive bone resorption evident. Moderate to strong staining for BSP was observed in all (100%) carcinomas, which also expressed BSP mRNA as determined by in situ hybridization. Variable staining for BSP was also observed in the mineralized bone and expression of BSP mRNA could be observed in osteoblastic cells on the bone surface and in some osteocytes at sites of bone remodelling. Contrary to a previous report, BSP expression could be demonstrated by PCR in three breast cancer cell lines, MCF-7, T47-D and MDA-MB-231. Moreover, in sub-cutaneous tumours formed by MDA-MB-231 breast cancer cells injected into athymic mice, higher immunostaining for BSP was seen in large ulcerating tumours in which mineral deposits were formed. In contrast to BSP, staining for OPN in bone metastases was generally restricted to the interface between tumor cells and bone surface of the carcinomas. While OPN staining was also observed in the cytoplasm of osteoclasts, which showed strong hybridization to a digoxygenin-labelled OPN cRNA probe, expression of OPN was not clearly detectable in the tumour cells. These studies provide the first demonstration of BSP expression by tumour cells in bone metastases and support the concept that BSP may have a role in targeting metastatic cells to bone. Expression of OPN in bone metastases appears to be related to increased bone resorptive activity by osteoclasts.
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  • 98
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    Clinical & experimental metastasis 18 (2000), S. 573-580 
    ISSN: 1573-7276
    Keywords: breast cancer ; cell motility ; KGF ; metastasis ; MCF-7 ; T-47D ; ZR-75-1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Endogenous growth factors and cytokines are known to have a major influence on the progression, motility and invasiveness of tumor cells. We have reported previously that conditioned media from mouse fibroblasts increases the motility of breast cancer cells. Further, we determined that keratinocyte growth factor (KGF) was an active factor from mouse fibroblasts responsible for most of the motility response in breast cancer cells. The present study examined the effect of human KGF on the motility of estrogen receptor (ER)-positive and ER-negative human breast cancer cell lines in culture using time-lapse videomicroscopy to quantify cell motility. In the present study we observed that recombinant human KGF enhanced several parameters of cellular motility in ER-positive cells but not in ER-negative cell lines. Further, we observed that the level of KGF receptor (KGFR) expression in ER-positive cells was much greater than in the ER-negative cell lines. The motility response to KGF was found to be both dose-and time-dependent. Of the three ER-positive breast cancer cell lines tested, MCF-7 cells were the most responsive to KGF stimulation. Finally, MCF-7 cells grown in estrogen-depleted media did not respond to KGF. These results suggest that KGF from stromal tissue surrounding a primary tumor mass can enhance tumor cell motility and may be an early signal in the progression of breast cancer cells to a more motile and metastatic phenotype. Thus, KGF, KGFR and/or the KGF signaling pathway may be important therapeutic targets for the treatment or prevention of breast cancer metastasis.
    Type of Medium: Electronic Resource
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  • 99
    ISSN: 1573-7276
    Keywords: breast cancer ; chromosome 11q13 ; gap junctions ; metastasis suppressor gene ; motility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Introduction of normal, neomycin-tagged human chromosome 11 (neo11) reduces the metastatic capacity of MDA-MB-435 human breast carcinoma cells by 70–90% without affecting tumorigenicity. Differential display comparing MDA-MB-435 and neo11/435 led to the discovery of a human breast carcinoma metastasis suppressor gene, BRMS1, which maps to chromosome 11q13.1–q13.2. Stable transfectants of MDA-MB-435 and MDA-MB-231 breast carcinoma cells with BRMS1 cDNA still form progressively growing, locally invasive tumors when injected in mammary fat pads of athymic mice but exhibit significantly lower metastatic potential (50–90% inhibition) to lungs and regional lymph nodes. To begin elucidating the mechanism(s) of action, we measured the ability of BRMS1 to perturb individual steps of the metastatic cascade modeled in vitro. Consistent differences were not observed for adhesion to extracellular matrix components (laminin, fibronectin, type IV collagen, type I collagen, Matrigel); growth rates in vitro or in vivo; expression of matrix metalloproteinases, heparanase, or invasion. Likewise, BRMS1 expression did not up regulate expression of other metastasis suppressors, such as NM23, Kai1, KiSS1 or E-cadherin. Motility of BRMS1 transfectants was modestly inhibited (30–60%) compared to parental and vector-only transfectants. Ability to grow in soft agar was also decreased in MDA-MB-435 cells by 80–89%, but the decrease for MDA-MB-231 was less (13–15% reduction). Also, transfection and re-expression of BRMS1 restored the ability of human breast carcinoma cells to form functional homotypic gap junctions. Collectively, these data suggest that BRMS1 suppresses metastasis of human breast carcinoma by complex, atypical mechanisms.
    Type of Medium: Electronic Resource
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  • 100
    ISSN: 1573-7373
    Keywords: choroidal metastasis ; leptomeningeal carcinomatosis ; breast cancer ; docetaxel ; mitoxantrone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Choroidal metastases from breast cancer represent an unusual metastatic presentation that has been traditionally treated with radiation therapy. Herein, we report a case of metastatic breast cancer presenting with pulmonary, cutaneous, lymph node and symptomatic choroidal metastases treated with systemic combination chemotherapy incorporating docetaxel and mitoxantrone without induction or consolidation radiation therapy to control visual symptoms from choroidal metastases. The patient experienced a durable complete remission in all metastatic sites that was maintained for 21 months since the initiation of chemotherapy, afterwhich she developed isolated leptomeningeal carcinomatosis managed successfully with intensive intrathecal methotrexate and whole brain irradiation leading to a new complete remission maintained until this report; 11 months after its presentation. This is the first case to our knowledge reporting complete regression of choroidal metastases with docetaxel-based chemotherapy as the only treatment modality and subsequent isolated leptomeningeal carcinomatosis recurrence.
    Type of Medium: Electronic Resource
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