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  • 1
    ISSN: 1530-0358
    Keywords: Beta-catenin ; Immunohistochemistry ; Metastasis ; Predictive value ; Prognosis ; Rectal cancer ; Tumor marker
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Adenomatous polyposis coli protein, glycogen synthetase kinase-3-beta, T cell transcription factor/lymphoid enhancer-binding factor, and beta-catenin modulate cell differentiation and proliferation via the expression of effector genes. It has recently been postulated that betacatenin is a potent oncogene of sporadic colorectal carcinogenesis and a prognostic tumor marker. Our aim was to investigate whether the nuclear overexpression of betacatenin, possibly caused by mutations in exon 3 of betacatenin (CTNNB1), is correlated with distant metastatic spread or disease-free survival in rectal carcinoma. METHODS: Immunohistochemical analysis was performed with an anti-beta-catenin-monoclonal antibody on paraffin sections of two groups of patients (n=2 × 77) with rectal carcinoma curatively treated by surgery alone. The patients selected were all free of local disease, to exclude surgical influence. Patient groups were matched for age, gender, International Union Against Cancer stage, and year of operation (1982 to 1991) and differed only in subsequent metachronous distant metastatic spread. Follow-up was prospective (median, 9.6 years). Three staining patterns were defined: membranous (normal), diffuse cytoplasmic (pathologic), and intense nuclear staining (pathologic). When intense nuclear staining was defined, the specimen was microdissected. Then, DNA was isolated, polymerase chain reaction-amplified, and sequenced to detect mutations in exon 3. RESULTS: Nuclear overexpression of beta-catenin correlated neither with distant metastatic spread (chisquared, 0.37;P=0.79) nor with disease-free survival (log-rank with trend,P=0.62). No mutations were found in the area of the serine/threonine-kinase glycogen synthetase kinase-3-beta-phosphorylation site in exon 3 (CTNNB1) of beta-catenin. CONCLUSION: Although beta-catenin seems to play an important role in early colorectal carcinogenesis, its value as a prognostic marker is questionable. It must be assumed that metastatic ability is determined by other factors than the disturbance of the beta-catenin T cell transcription factor/lymphoid enhancer-binding factor cascade and that other mechanisms might cause the observed nuclear translocation of beta-catenin.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Der Chirurg 68 (1997), S. 215-224 
    ISSN: 1433-0385
    Keywords: Key words: Laparoscopic colorectal surgery ; Port site metastases ; Pitfalls of laparoscopy. ; Schlüsselwörter: Laparoskopische colorectale Chirurgie ; Port-site-Metastasen ; Onkologische Fehler bei der Laparoskopie.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung. Die onkologischen Probleme bei laparoskopisch colorectalen Eingriffen in kurativer Intention bestehen im Auftreten von Port-site-Metastasen, in einer inadäquaten Radikalität, einer Tumorzellverschleppung durch ungeschützte Präparatebergung und unzureichende Operationstechnik sowie Nichtbeachtung technisch-onkologischer Grenzen bei bestimmten Tumorlokalisationen. Die bisher vorliegenden Untersuchungen ergeben eine mehr mechanische Pathogenese der Port-site-Metastasen durch Verschleppung von Tumorzellen in die Trokareinstichstellen über Instrumente, Trokare und Resektionspräparate. Durch entsprechende Vorsichtsmaßnahmen scheint somit eine Vermeidung möglich. Das CO2-Pneumoperitoneum spielt anscheinend eine untergeordnete Rolle bei der Entstehung der Port-site-Metastasen. Die onkologische Radikalität laparoskopischer Eingriffe beim colorectalen Carcinom kann bei fehlenden Langzeitdaten zur Zeit nicht beurteilt werden. Es liegen lediglich vereinzelte Untersuchungen zur Zahl der bei den Eingriffen mitentfernten Lymphknoten vor. Die Anzahl scheint nicht die bei vergleichbaren offenen Resektionen zu erreichen, eine genauere Analyse müßte jedoch die selektionierten Indikationen nach Tumorgröße und -lokalisation berücksichtigen. Die Vielzahl der möglichen Fehler und Gefahren der onkologischen laparoskopischen Chirurgie führt zu der klaren Forderung, daß die Eingriffe nur innerhalb von prospektiven klinischen Studien mit selektionierten Indikationen erfolgen sollten. Eine prospektiv randomisierte Studie für alle Tumorstadien und -lokalisationen ist vor diesem Hintergrund kritisch zu werten.
    Notes: Summary. Oncological problems associated with laparoscopic colorectal surgery with curative intent include port site metastases, inadequate radicality, seeding of tumour cells through unprotected recovery of the surgical specimen, faulty surgical technique, and failure to observe the technical and/or oncological limitations applicable to certain tumour sites. Investigations so far reported reveal a preponderance of mechanical pathogenesis of port site metastases caused by the contamination of trocar entry ports by tumour cells borne on instruments, trocars and resected material. This suggests that appropriate precautionary measures could resolve the problem. It appears that the CO2 pneumoperitoneum plays only a minor role in the development of port site metastases. Owing to a lack of long-term data, the oncological radicality of laparosopic resections for colorectal carcinoma cannot be assessed; merely a few reports on the number of lymph nodes removed during such operations have been published. Nevertheless, it would appear that fewer lymph nodes were removed than with comparable conventional surgery. However, a more accurate analysis needs to take account of the fact that the indication for laparoscopic surgery is determined by the size and location of the tumour. The many potential pitfalls and hazards of oncological laparoscopic surgery make it mandatory that such interventions should be done only within the framework of prospective clinical studies covering limited indications. Randomized prospective studies to cover all tumour stages and sites cannot be recommended.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 128 (1999), S. 123-133 
    ISSN: 1432-1106
    Keywords: Key words Precision grip ; Context-dependency ; Force ; Finger representation ; Motor cortex ; Premotor cortex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In three monkeys trained to finely grade grip force in a visuomotor step-tracking task, the effect of the context on neuronal force correlates was quantitatively assessed. Three trial types, which differed in force range, number, and direction of the force steps, were presented pseudo-randomly and cued with the color of the cursor serving as feedback of the exerted force. Quantitative analyses were made on 85 neurons with similar discharge patterns in the three trial types and significant linear positive (54 cells) or negative (31 cells) correlation coefficients between firing rate and force. An analysis of covariance (ANCOVA) showed that the population slopes for 2-step were steeper than for 3-step trials. Another ANCOVA at the population level, computed on the differences in firing rate and force between force steps, persistently disclosed a significant effect of trial type. For the first two force steps, the differences in firing rate were significantly larger in the 2-step than in the 3-step increase trials. Further analyses revealed that neither the force range nor the number of steps was a unique factor. A small group of neurons was tested in an additional trial series with a uniform cue for all three trials, leading to either a loss of context-dependency or to unexpected changes in firing rate. This demonstrates that the cue color was an important instruction for task performance and neuronal activity. The most important findings are that the context-dependent changes were occurring ”on-line”, and that neurons displaying context-dependency were found in all three lateral premotor cortex hand regions and in the primary motor cortex. Finger muscle activity did not show any context dependency. The context-dependent effect leads to a normalization of the cortical activity. The advantage of normalization is discussed and mechanisms for the gain regulation are proposed.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Surgical endoscopy and other interventional techniques 11 (1997), S. 902 -906 
    ISSN: 1432-2218
    Keywords: Key words: Neoplasms, staging — Laparoscopy, adverse effects — Pancreatic neoplasms, surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Laparoscopic resection for cancer is controversial and port-site metastases are not infrequent. The mechanisms of occurrence of port-site metastases remain unclear. Animal experiments have suggested a role for carbon dioxide (CO2), but port-site metastases also occur after thoracoscopy, where no CO2 is used. The aim of this study was to define the role of CO2 in the seeding of tumor cells in the human patient. Methods: CO2, instruments, trocars, suction device, and peritoneal washing were examined during 12 staging laparoscopies for pancreatic cancer. The presence, viability, and biological significance of cells were investigated using conventional cytology, polymerase chain reaction (PCR), and restriction fragment length polymorphisms (RFLPs) to detect the presence of a mutant k-ras gene as a genetic marker of cancer cells. Results: Cytology exam of peritoneal washing, instruments, the suction device, and trocars revealed many cells. Tumor cells were detected in 6/12 peritoneal, in 4/12 trocars and 4/11 instruments washings, but not in 12 CO2 samples. The DNA content of CO2 was very low—as assessed by PCR. Mutant DNA was detected by RFLP in four out of 12 aerosols. Six aerosols did not contain any DNA. Two aerosols were borderline. Conclusions: During staging laparoscopy for pancreatic cancer in humans, CO2 contains only very low levels of free-floating tumor cells, even in the presence of massive peritoneal contamination. These results suggest that the incidence of port-site metastases might be reduced if mechanical contamination of the port sites with instruments or with the specimen can be avoided.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2218
    Keywords: Key words: Multicenter study — Open colorectal surgery — Laparoscopic surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Prospective randomized multicenter studies comparing laparoscopic with open colorectal surgery are not yet available. Reliable data from prospective multicenter studies involving consecutive patients are also lacking. On the basis of the personal caseloads of specialized surgeons or of retrospective analyses, it is difficult to judge the true effectiveness of this new technique. This study aims to investigate the results of laparoscopic colorectal surgery in consecutive patients operated on by unselected surgeons. Methods: This observational study was begun August 1, 1995, in the German-speaking part of Europe (Germany and Austria) and 43 centers initially agreed to participate. All consecutive cases were documented. All data were rendered anonymous. Analysis was performed on an intention-to-treat basis. The study committee was blinded to the participating center. Results: By the end of the 1st year, 500 patients (M:F ratio 0.83, mean age 62.9 years) had been treated by 18 centers; 269 operations were performed for benign indications and 231 for cancer (palliative and curative). Most operations were done on the distal colon or rectum. An anastomosis was performed in 84%, with an overall leakage rate of 5.3% (colon 3.6% and rectum 11.8%), which required surgical reintervention in 1.7%. The mean operating time was 176 min and showed a decreasing tendency over the period under study. The conversion rate was 7.0% and the overall complication rate 21.4%. The reoperation rate was 6.6%; the most common cause was bleeding. There was one ureteral lesion (0.2%), but urinary tract infections were fairly common (4.8%). A postoperative pneumonia was diagnosed in 1.6% of the cases. No thromboembolic complications were reported. The 30-day mortality rate was 1.4% and overall hospital mortality 1.8%. Conclusions: Laparoscopic colorectal operations are still rare (about 1% of all colorectal operations in Germany). Laparoscopic procedures are more common on the left colon and rectum than on the right colon. The surgical complication rate is acceptable, comparable with rates reported by others for open surgery. Cardiopulmonary and thromboembolic complications were rarely seen. Mortality and surgical morbidity rates do not differ significantly among participating centers. A learning curve, reflected by a shortening of the operating time and a somewhat lower conversion rate, was observed over the observation period.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2218
    Keywords: Key words: Laparoscopic colorectal surgery — Multicenter study — Sigmoid diverticulitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: In the large bowel, resection of the sigmoid colon is the most commonly performed laparoscopic intervention because large bowel lesions often are located in this part of the bowel and the procedure technically is the most favorable one. A number of publications involving case series or the results of highly experienced individual surgeons already have confirmed the feasibility of laparoscopic resection in cases of diverticulitis. The aim of the present prospective multicentric investigation was to check the results obtained by a large number of surgeons performing laparoscopic resection of the sigmoid colon for diverticulitis in various stages of severity. Results: Between January 8, 1995 and January 1, 1998, the Laparoscopic Colorectal Surgery Study Group recruited 1,118 patients to the prospective multicenter study. Diverticulitis of the sigmoid colon, which accounted for 304 cases, was the most common indication for laparoscopic intervention. In most of these patients undergoing laparoscopic surgery (81.9%), the diverticulitis manifested as acute phlegmonous peridiverticulitis, recurrent attacks of inflammation, or stenosis. Complicated forms of diverticulitis in Hinchey stages I to IV and late complications of chronic diverticular disease with fistula formation and bleeding accounted for only 18.1% of the cases. For the overall group, the conversion rate was 7.2%. Patients with less severe diverticulitis (i.e., those presenting with peridiverticulitis, stenosis, or recurrent attacks of inflammation) had a conversion rate of 4.8% and the rate for complicated cases was 18.2%. Regarding laparoscopically completed interventions, 3 of 282 patients died (1.1%). In the group of patients with peridiverticulitis, stenosis, or recurrent attacks of inflammation the overall complication rate was 14.8%. The group with perforated diverticulitis in Hinchey stages I to IV or those with fistula and bleeding, the corresponding rate was 28.9%, and after conversion it was 31.8%. Conclusions: Laparoscopic colorectal interventions in sigmoid diverticulitis are, for the most part, carried out as elective procedures for peridiverticulitis, stenosis, or recurrent attacks of inflammation. The conversion, complication, and mortality rates associated with these interventions are acceptable. Laparoscopic procedures in Hinchey stages I to IV sigmoid diverticulitis and in the presence of fistula and bleeding are more likely to be associated with complications, and should be carried out only by highly experienced laparoscopic surgeons.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-2218
    Keywords: Key words: Anastomotic leakage — Laparoscopic colorectal surgery — Multicenter study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: We report on a prospective observational multicenter study of more than 1,000 consecutive patients undergoing laparoscopic colorectal procedures. The aim of the current study was to investigate the safety of laparoscopic colorectal surgery as reflected by the anastomotic insufficiency rates in the various sections of the bowel, and to compare these rates with those of open colorectal surgery. Methods: The study was begun on August 1, 1995. Twenty-four centers in Germany, Austria, and Switzerland participated in this prospective multicenter study. All patients undergoing laparoscopic colorectal surgery were included in the study. No selection criteria were applied, which means that every operation begun as a laparoscopic procedure was included. Data on patient demographics, surgical indications, surgical course, and patient outcome were recorded prospectively in a computer database. All data were rendered anonymous. Results: Between August 1995 and February 1998, the 24 participating centers treated 1,143 patients (male/female ratio, 1:1.36; mean age, 60.7 years). In all, 626 operations were performed for benign indications and 517 for cancer. Most procedures involved the sigmoid colon and rectum (80.9%). An anastomosis was performed in 83% of the operations. Most of the anastomoses were laparoscopically assisted using the stapling technique. We observed an overall leakage rate of 4.25% (colon 2.9%; rectum 12.7%), and surgical reintervention was required in 1% of the cases. The rate of conversion to open surgery was 5.6%. Intraoperative complications occurred in 5.9%, and reoperation was necessary in 4.1% of the cases. The overall morbidity rate was 22.3%, and the 30-day mortality rate was 1.57%. Conclusions: The feasibility and safety of the laparoscopic colorectal approach is demonstrated clearly. The current study shows that the laparoscopic or laparoscopically assisted approach to colorectal surgery is not associated with a higher risk of anastomotic leaks. Morbidity and mortality rates with this method approximate those seen with conventional colorectal surgery.
    Type of Medium: Electronic Resource
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