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Notes: The primary aim of this study was to investigate whether the naturally occurring beta-carbolines norharman and harman differed between alcohol-dependent patients who developed alcohol withdrawal syndrome (AWS) and those who did not. The secondary aim was to determine whether different treatment regimens influenced the levels of the beta-carbolines. Thirty chronic alcoholics with carcinoma of the upper digestive tract were included in this study. They were prophylactically treated by two different medical regimens: flunitrazepam and clonidine (FNZ regimen) and gamma-hydroxybutyrate and clonidine (GHB regimen). Patients exceeding the Revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar) score of 20 were assigned to the AWS therapy group and received haloperidol in addition to their prevous prophylactic treatment. Patients without AWS remained in the prophylactic group. From days 1–4 of the intensive care unit (ICU) stay norharman, but not harman, was increased in the AWS therapy group. In the FNZ regimen, six of 16 patients (38%) and in the GHB regimen, nine of 14 patients (64%) developed AWS (p= 0.14). Norharman levels did not differ between the two regimens. However, harman levels were increased in the GHB treated regimen on days 1, 2 and 4 following admission to the ICU and correlated with the severity of alcohol withdrawal syndrome. As norharman was elevated in the therapeutically treated ICU patients, this marker appears to be involved in the pathogenesis of AWS. As harman was elevated before and during hallucinations on the GHB regimen, it seems reasonable to carry out further investigations into the potential role of harman as a hallucinatory substance.

Notes: Hintergrund: Die Prognose der Patienten mit Pankreaskarzinom ist unverändert schlecht. Ein kurativer Ansatz besteht nur in Frühstadien bei radikal chirurgischem Vorgehen. Der Wert der kombinierten Radiochemotherapie wird sowohl postoperativ adjuvant als auch palliativ bei Inoperabilität trotz nachgewiesener Wirksamkeit wegen der kurzen medianen Überlebenszeiten zwischen acht und 15 Monaten kontrovers beurteilt. Sowohl im adjuvanten als auch im neoadjuvanten multimodalen Therapiekonzept haben sich in den letzten Jahren erhebliche, klinisch relevante Entwicklungen ergeben. Auch die Integration der intraoperativen Strahlentherapie (IORT) wird kontrovers diskutiert. Material und Methode: Seit den Ergebnissen der GITSG-Studie gilt die postoperative adjuvante Radiochemotherapie mit 5-FU in den USA als Standard. Nachfolgestudien der EORTC und der ESPAC rekrutieren derzeit Patienten oder sind abgeschlossen, die Ergebnisse sind noch nicht publiziert. Neoadjuvante Therapiekonzepte (präoperative Radiochemotherapie) sind in den letzten drei Jahren in unterschiedlichen Ansätzen zumeist bei primärer Operabilität, aber auch bei Inoperabilität untersucht worden. Unter Einsatz der 3-D-Bestrahlungsplanung wurde die Dosis von 40 Gy auf 45 bis 50 Gy gesteigert. In einzelnen spezialisierten Institutionen werden diese Konzepte mit einer IORT kombiniert. Neuere Chemotherapeutika wie Gemcitabin und die Taxane werden in Phase-II-Studien als kombinierte Radiochemotherapie bei primär inoperablem Pankreaskarzinom getestet. Ergebnisse: Sowohl durch die postoperative adjuvante als auch durch die neoadjuvante Radiochemotherapie mit anschließender Pankreatikoduodenektomie können mediane Überlebensraten von 15 bis 25 Monaten erreicht werden. Durch die neoadjuvante Radiochemotherapie bei primär resektablem Pankreaskarzinom scheint die Rate positiver postoperativer Schnittränder sowie die Anzahl der Patienten mit Lymphknotenmetastasen reduziert zu werden. Obwohl eine Überlebensverlängerung oder eine höhere lokale Tumorkontrolle (ca. 80% bei beiden Therapieformen) durch die neoadjuvante Radiochemotherapie gegenüber der adjuvanten Radiochemotherapie bisher nicht bewiesen werden konnte, erhalten mehr als 25% der Patienten nach radikaler Operation aufgrund der Morbidität keine adjuvante Radiochemotherapie. Wegen der nur mäßigen Verlängerung der medianen Überlebenszeit um ca. fünf bis zehn Monate ist die adjuvante Radiochemotherapie in Europa nicht allgemein akzeptiert. Mit der kombinierten Radiochemotherapie bei lokaler Inoperabilität kann die Überlebenszeit verdoppelt werden. Die wirksamste Kombination scheint mit 5-FU als Dauerinfusion über fünf Tage mit einer Dosis von etwa 250 mg/m2 vorzuliegen. In der Hand des Erfahrenen bietet die IORT eine nebenwirkungsarme, effektive Ergänzung der Therapie, die zu einer Erhöhung der lokalen Tumorkontrolle und einer anhaltenden Schmerzkontrolle führt. Neuere Substanzen wie Gemcitabin und die Taxane scheinen in vitro wirksame Strahlensensitizer zu sein. In ersten Ergebnissen in Phase-I- und Phase-II-Studien wurde die MTD noch nicht gefunden. Während die Toxizität bei Einzelfraktionen von 1,8 bis 2 Gy tolerabel scheint, ist Vorsicht bei höheren Einzeldosen geboten. Schlussfolgerungen: Vor dem Hintergrund der unverändert schlechten Prognose des Pankreaskarzinoms werden zur Zeit unterschiedliche Konzepte der adjuvanten und neoadjuvanten kombinierten Radiochemotherapie, teils auch mit neueren Substanzen, geprüft. Dies betrifft sowohl resektable als auch nicht resektable Pankreaskarzinome. Aus allgemein onkologischer und radioonkologischer Sicht erscheint das neoadjuvante Konzept derzeit überzeugend, obwohl der Beweis der besseren Wirksamkeit aussteht. Hierfür sind randomisierte Studien notwendig. Die Integration der IORT in diese Therapiekonzepte ist zur Erhöhung der lokalen Tumorkontrolle sinnvoll. Diese aggressiven Strategien sind jedoch nur bei einem kleinen Teil der Patienten indiziert. Im Falle der Inoperabilität ist die kombinierte Radiochemotherapie bei lokoregionär begrenztem inoperablen Pankreaskarzinom bei entsprechendem Allgemeinzustand derzeit die Therapie der Wahl.

Notes: Abstract Hidradenitis suppurativa (HS) is a chronic fistula- and abscess-forming disease of the cutis and subcutis of unknown etiology. Disease recurrence is frequent and may cause severe complications. We analyzed patients with HS who underwent surgery between 1976 and 1997. The operative procedures were divided into drainage procedures (n=6), limited regional (n=14), and radical wide excisions (n=11). The extent of surgery was examined in terms of the clinical course and late postoperative sequelae of HS. At a mean follow-up of 72 months, we found developed locoregional recurrent HS in 45% of patients. There was 100% recurrence after drainage, 42.8% after limited, and 27% after radical excision (P〈0.05). HS recurred after a median interval of 3 months for drainage, 11 months for limited excision, and 20 months for radical excision (P〈0.05). The disease-free interval continued up to 35 months. Long-term sequelae included penile amputation and a case of fatal squamous cell carcinoma. Although radical wide excision of the HS-affected cutis is associated with the lowest recurrence rate, it is still considerable and warrants long-term follow-up.

Notes: Abstract Background: The fate of patients with multiple endocrine neoplasia of type II A (MEN II A) is determined by medullary thyroid carcinoma, which occurs in all cases. This has led to the therapeutic concept of prophylactic thyroidectomy in affected family members with the goal of removing the thyroid before the manifestation of carcinoma. We investigated a prophylactically thyroidectomized MEN II A population to determine whether the highly specific and sensitive tumor marker calcitonin correlates with tumor spread. Patients and methods: Fifteen patients with MEN II A (aged 4 – 24 years) who had undergone prophylactic thyroidectomy since 1990 were included in the study. Baseline and pentagastrin-stimulated calcitonin levels were preoperatively determined in all cases. The indication for surgery was established on the basis of pathologic calcitonin levels in the first seven patients and on the basis of detected RET proto-oncogene mutation in the other eight patients. Bilateral central lymphadenectomy was performed in all patients in addition to thyroidectomy. Results: Histology demonstrated C-cell hyperplasia in five patients (aged 4 – 13 years), unilateral medullary microcarcinoma in six (aged 9 – 17 years) and a bilateral medullary microcarcinoma in three cases (aged 17 – 24 years). One 9-year-old boy with bilateral microcarcinoma already had a lymph node metastasis. The mean baseline calcitonin level correlated with the histologic findings (r = 0.71, P = 0.003) but there was no correlation between pentagastrin-stimulated calcitonin levels and histology (r = 0.21, P = 0.47). Conclusion: In MEN II A patients undergoing prophylactic thyroidectomy, baseline but not stimulated calcitonin levels already correlate with the histologic tumor stage at the stage of clinically occult C-cell hyperplasia or medullary microcarcinoma. However, biochemical screening cannot reliably discriminate the transition from C-cell hyperplasia to invasive microcarcinoma. Individuals with MEN II A should therefore undergo early prophylactic thyroidectomy once the diagnosis is confirmed by molecular genetic testing.

Notes: Abstract Translocation of enteric microorganisms from the intestinal tract to extraintestinal sites has been proposed as an early step in the development of gram-negative sepsis. This study examined the role of altered bowel transit in influencing intestinal bacteriostasis and bacterial translocation using morphine as a pharmacologic inhibitor of such transit. In the first experiment, either normal saline (N=8) or morphine sulfate (20 mg/kg;N=8) was injected subcutaneously. Two hours later, morphine (7.5 mg/kg) was infused subcutaneously for an additional 22 hr; control animals received saline alone. After completion of this regimen, a volume of 0.2 ml of 2.5 mM FITC dextrans (10,000 daltons) were injected intraduodenally in each group. The bowel was removed 25 min later, divided into 5-cm segments, and the content of dextrans measured. Small bowel propulsion was expressed as the geometric center of the distribution of dextrans throughout the intestine (in percentage length of small bowel). Gut propulsion was significantly reduced after morphine treatment as compared to controls (32.8±8.2% vs 55.8±4.0%;P〈0.01). In 16 additional rats, saline or morphine was again administered as described. After 24 hr, samples were obtained from the mesenteric lymph node (MLN) complex, blood, spleen, liver, duodenum, jejunum, ileum, and cecum for standard bacteriology. The bacterial counts increased significantly in each intestinal segment following morphine treatment. Microorganisms translocated to the MLN complex in 5, and to distant sites in four of eight morphine-treated animals, respectively. Translocation to the MLN complex occurred in only one of eight controls (P〈0.05); no translocation to distant sites occurred in control animals. We conclude that the morphine-induced prolongation in bowel transit promotes bacterial translocation secondary to an overgrowth of enteric bacteria in the intestinal lumen.

Notes: Abstract This study tested the hypothesis that hypovolemic shock elicits or promotes the development of infection during acute pancreatitis. Pancreatitis was induced in rats by ligation of the common biliopancreatic duct; nonlaparotomized animals served as controls. After 24 hr, the animals were subjected to either sham-shock (instrumented only) or to shock by withdrawal of blood through a femoral artery line by maintaining the mean arterial blood pressure at 30 mm Hg for 1 or 2 hr. After completion of the shock period, the shed blood was returned to the animal. All animals were sacrificed 24 hr later and specimens obtained from portal and systemic blood, liver, spleen, pancreas, and mesenteric lymph nodes for bacteriologic culture using standard techniques. The pancreas was also analyzed by morphometric techniques. The histologic changes of pancreatitis induced by biliopancreatic obstruction were characterized by marked edema with accompanying mild inflammation, hemorrhage, and necrosis. Concomitant with these morphologic findings was an associated translocation of enteric organisms to the mesenteric lymph nodes without spread to distant organs. Shock by itself induced only a mild edema in the pancreas and did not cause bacterial translocation. Furthermore, shock failed to aggravate the morphologic alterations of acute pancreatitis and did not promote bacterial spread to mesenteric nodes over that observed with pancreatitis alone. Thus, we conclude that periods of severe shock lasting up to 2 hr do not play a major role in the pathogenesis of infection in our model of pancreatitis.