[Tuberculosis of the large intestine--a differential diagnosis of inflammatory and neoplastic colon tumors]. / Dickdarmtuberkulose--eine Differentialdiagnose inflammatorischer und neoplastischer Colontumoren.

We report on a case of ileocoecal tuberculosis. The clinical, radiological, endoscopic and pathologic findings are considered. The differential diagnosis between tuberculosis, chronic inflammatory bowel diseases and carcinoma of the colon are described.

Closure of acute bronchial stump insufficiency with a musculus latissimus dorsi flap.

We describe a successful closure of an acute bronchial stump insufficiency after pneumonectomy by intrathoracic transposition of the pedunculated latissimus dorsi muscle: A 56-year-old patient with a necrotizing bronchial carcinoma developed a stump insufficiency after right pneumonectomy. Repeated resection and renewed closure of the completely dehiscent stump was not possible, as the stem bronchus had been separated close to the tracheal bifurcation in the preceding operation. Therefore we transposed the pedunculated musculus latissimus dorsi into the thoracic cavity. The closure of the bronchial stump insufficiency was achieved by fixation of the muscle on to the open stump and surrounding tissue of the mediastinal pleura with fibrin glue. The postoperative course was without complications, no further insufficiency or empyema developed.

[Stomach and duodenal cancers in familial adenomatosis coli]. / Magen- und Duodenalkarzinome bei familiärer Adenomatosis coli.

In the last years the number of patients with familial adenomatosis coli and metachrone carcinoma of the upper gastrointestinal tract is increasing. We describe two patients who, 9 and 15 years after colectomy for adenomatosis coli, developed a duodenal carcinoma. Each patient was treated with a partial duodeno-pancreatectomy. Another patient was resected prophylactically because of a diffuse adenomatosis of the duodenum three years after colectomy. We suggest that each patient with a history of colectomy for adenomatosis coli should have regular follow-ups including endoscopy of the upper gastrointestinal tract.

Intraabdominal infections: classification, mortality, scoring and pathophysiology.

Studies on intraabdominal infections have been difficult to compare in the past due to a missing system of classification for peritonitis. According to a recently developed classification system, secondary peritonitis, including spontaneous acute peritonitis, postoperative peritonitis and posttraumatic peritonitis, is the most common complication of severe intraabdominal infections. In several studies the mortality rate of postoperative peritonitis was still between 60% and 79%. Scoring systems were developed, some of them with the idea to predict mortality in peritonitis. Although the APACHE II score cannot predict the outcome of peritonitis in an individual patient, it is a reliable, valid and objective system for risk stratification in intraabdominal infections. Local trauma or bacterial contamination is responsible for an acute phase reaction, which involves the release of certain cytokines such as TNF-alpha, interleukin-1 (IL-1) and interleukin-6 (IL-6). The IL-6 seems to play an important role in the mechanism of the acute phase reaction, acting on hepatocytes to release acute phase proteins (e.g. CRP). Preliminary results of investigations of IL-6 levels in peritonitis indicate a possible role for IL-6 as a predictor of the outcome of peritonitis.

A randomized controlled trial of adjuvant immunotherapy (murine monoclonal antibody 494/32) in resectable pancreatic cancer.

In a prospective randomized multicentric trial, 61 patients from six hospitals with resectable pancreatic cancer were recruited between 1987 and 1989. All patients underwent a Whipple resection. Two weeks after surgery, the patients were randomized to be given either intravenous (IV) treatment with 370 mg (100 mg loading dose, 9 x 30 mg continuing within 10 days) of monoclonal antibody (MoAb) 494/32 (Behringwerke AG, Marsburg, Germany) or no additional anti-cancer treatment. This murine immunoglobulin (Ig) G1 antibody has been shown to strongly bind to human pancreatic cancer cells and to induce an antibody-dependent cellular cytotoxicity (ADCC). Both study groups were well matched with respect to age, sex, tumor staging, and grading. Six patients suffered from minor toxicity (vomiting and abdominal pain) after immunotherapy. Ten months after the end of the recruitment period, 65% and 53% of the patients in the treatment and control groups, respectively, had died. Of the living patients, 60% and 53% are alive with recurrent or progressive cancer disease. Median survival time was 428 days (range, 248 to 510 days) and 386 days (range, 296 to 509 days) in the treatment and control groups, respectively. The authors concluded that repeated IV treatment with the antibody 494/32 is not helpful in resectable pancreatic cancer. This study provides the first controlled data on passive immunotherapy in solid cancer.

[Acute stress-induced cholecystitis]. / Die akute Stresscholezystitis.

Acute posttraumatic and postoperative cholecystitis is a serious and life-threatening complication with mortality rates ranging from 10 to 50%. The pathogenesis is multifactorial: possible reasons are blood transfusions, dehydration, narcotics, shock and positive end-expiratory pressure (PEEP). Between 1980 and 1990 12 patients underwent surgery for acute cholecystitis. Six of them suffered from a so-called acute acalculous cholecystitis. Two patients died postoperatively. The symptoms are that of a "common" cholecystitis with leukocytosis, fever, abdominal distension and upper right abdominal pain. Sonography is a good method to establish the diagnosis and helps in the decision for cholecystectomy. Clinicians must remember the possibility of an acute cholecystitis in any surgical patient developing abdominal pain or unexplained fever.

Percolation and binding of MAB BW 494 to pancreatic carcinoma tissues during high dose immunotherapy and consequences for future therapy modalities.

The distribution of the monoclonal antibody (MAb) BW494 in human pancreatic carcinoma biopsies during high dose i.v. immunotherapy was investigated. Using immunohistochemical techniques combined with anti-idiotypic, endothelial cell specific and bispecific MAbs it was shown that 3 days after onset of immunotherapy, MAb BW494 was bivalently bound to tumor cells in some highly vascualized areas near capillaries. No binding was observed in other highly vascularized tumor cell areas although the epitope detected by MAb BW494 was present. In contrast to our expectation the majority of the tumor cells was not yet saturated by the antibody, probably due to diffusion barriers in the solid tumor tissue.

Fluorescence studies on lung tumors.

Illumination of unstained 9 microns cryosections of lung tissue with 365 nm results in visible fluorescence light with a maximum intensity at about 460 nm. These fluorescence tomographical studies can be used for detecting carcinoma of the lung. The fluorescence pattern obtained can be matched nicely with histological findings. Since it takes less than 5 min for getting the fluorescence images, the fluorescence tomographical technique might be used in addition to established methods for determining the histology of a biopsy sample.

Studies of pancreatic cancer utilizing monoclonal antibodies.

Since 1985, 150 patients with pancreatic ductal adenocarcinoma have been treated with the monoclonal antibody BW 494 in four different multicentric trials in Germany. The antibody recognizes a human pancreatic cancer associated antigen and mediates an antibody dependent cellular cytotoxicity (ADCC) in vitro, when human mononuclear cells are coincubated as effector cells. In patients with at advanced unresectable pancreatic cancer there where two phase-I-studies finished in 1987 and 1989, respectively, and one uncontrolled phase-II-study finished in 1988. In 1987, we started a controlled randomized trial in patients with resectable (Whipple) pancreatic cancer, which will be finished in 1990. There were no major side effects if the intravenous antibody application was restricted to a 10-d treatment protocol (up to 370 mg given in 10 different dosages). Human anti-mouse-antibodies could be demonstrated in all patients investigated for within 4 wk after immunotherapy. In patients with advanced pancreatic cancer (n = 87), monoclonal antibody treatment did not induce significant response rates. There was stable disease in 1/3 to 1/2 of the patients lasting three months or longer. Therapeutic success may be expected in patients with minor tumor burden.

Percolation and binding of monoclonal antibody BW494 to pancreatic carcinoma tissues during high dose immunotherapy and consequences for future therapy modalities.

The distribution of the monoclonal antibody (MAb) BW494 in human pancreatic carcinoma biopsies during high dose intravenous immunotherapy was investigated. Using immunohistochemical techniques combined with anti-idiotypic, endothelial cell-specific and bispecific MAbs, it was shown that 3 days after onset of immunotherapy, MAb BW494 was bivalently bound to tumour cells in some highly vascularised areas near capillaries. No binding was observed in other highly vascularised tumour cell areas although the epitope detected by MAb BW494 was present. In contrast to our expectation the majority of the tumour cells were not yet saturated by the antibody, probably due to diffusion barriers in the solid tumour tissue.

[Value of sono- and computerized tomography as a localization procedure in primary hyperparathyroidism]. / Der Aussagewert der Sono- und Computertomographie als Lokalisationsdiagnostika beim primären Hyperparathyreoidismus.

A total of 56 patients underwent preoperative high-resolution sonography (4 MHz); 33 had additional computed tomography (4 mm slices, contrast material as drip infusion) to localize abnormal parathyroid tissue in primary hyperparathyroidism. The sensitivity of sonography was 48% compared to 38% for computed tomography. The efficiency of both techniques was mostly dependent on size and location of the parathyroid. Computed tomography was superior in detecting ectopic parathyroids. Because of its low sensitivity sonography is only of facultative importance as a localization procedure for primary hyperparathyroidism. Computed tomography is indicated only for localizing ectopic parathyroid tissue after initial operation has failed.

[Therapy concepts in colorectal liver metastases. What is proven, what is open to discussion?]. / Therapiekonzepte bei kolorektalen Lebermetastasen. Was ist gesichert, was ist offen?

Isolated liver metastases of colorectal carcinomas principally can be treated by surgical intervention or cytostatic chemotherapy. Unquestionable indications for resection therapy are either solitary metastases or metastases limited to one liver lobe, since resection provides the best long-time results. In multilocular metastases or non-resectable liver metastases systemic monochemotherapy with 5-Fluorouracil (5-FU) presents respondance rates of about 20 percent with remissions lasting 3 to 6 months. Thereby a prolongation of life could not be proven statistically. Initial studies with a combination therapy of 5-FU/Folinic acid promise higher remission rates due to an increased cytotoxicity caused by a synergistic effect. Because of the mainly arterial supply of liver metastases the different procedures of regional chemotherapy-intraarterial infusion, isolated liver perfusion, chemoembolisation-provide the tumor with high drug concentrations without provoking systemic side effects. This advantage of a regional application of cytostatic drugs is reduced by the high percentage (2 to 87 percent) of extrahepatic tumor manifestations occurring after an average of 6 to 8 months.

[Monoclonal antibodies in the therapy of non-resectable pancreatic cancers. Initial experiences]. / Monoklonale Antikörper in der Therapie nicht-resektabler Pankreascarcinome. Erste Erfahrungen.

In this study 34 patients with pancreatic cancer were treated postoperatively with monoclonal antibodies (MABs). The antibody BW 494/32 is directed against a membrane antigen of differentiated adenocarcinomas of the pancreas and mediates cellular cytotoxicity. The patients suffered from non resectable tumors, mostly with lymph-node or liver metastases. The patients received repeated doses of MABs over a time period from 5 to 14 days. The highest single dose was 100 mg, the highest cumulative dose 490 mg. At the moment 16 out of 34 patients are eligible for evaluation of tumor response. There was no complete or partial remission (reduction more than 50% of tumor volume). However, two patients responded with minor tumor regression up to 32 weeks documented by reduction of liver metastases and primary tumor in cat scan. Five additional patients presented with a long period of stable disease after immunotherapy (up to 40 weeks). 9 patients had progressive tumor disease in spite of MAB-treatment. Two to three weeks after antibody infusion most patients produce human anti-murine-antibodies, so that severe allergic reactions may occur, if the application is repeated.

Immunotherapy of pancreatic cancer with monoclonal antibody BW 494.

In a phase I trial 34 patients with pancreatic cancer were treated with the murine monoclonal antibody (MAb) BW 494 (BI 51.011) directed against a glycoprotein antigen. The patients received repeated doses of MAb over a time period from 5 to 14 days (highest single dose 100 mg, highest cumulative dose 490 mg). During this treatment serum levels of murine IgG increased to 43.4 micrograms/ml. The serum half life of murine IgG ranged from 2 to 3 days. Repeated injections of MAb BW 494 were normally well-tolerated when given within the first 15 days. Two patients presented with fatigue and a neuritis-like syndrome 2 weeks after the last IgG infusion which had resolved spontaneously by the next day. Severe allergic reactions were observed in 3 patients after repeated injections of the MAb. These 3 patients had high levels of human anti-murine antibodies (HAMA). Four weeks after the first application of MAb BW 494, 17/18 patients presented with HAMA (IgG). It could be demonstrated that the anti-murine response was in part anti-idiotypic. At the moment 16/34 patients are eligible for evaluation of tumor response. There was no complete or partial remission; however, 2 patients responded with minor tumor regression up to 32 weeks documented by reduction of liver metastases and primary tumor in CAT scan. Five additional patients presented with a long period of stable disease after immunotherapy (up to 40 weeks). Nine patients had progressive tumor disease in spite of MAb treatment.

[Parenteral use of a fat emulsion in the early postoperative period]. / Uber den parenteralen Einsatz einer Fettemulsion in der frühen postoperativen Phase.

Parenteral application of fat emulsions has been established as useful in long term artificial nutrition especially during weaning off the ventilator. In order to ascertain whether these advantages can also be proved in nonventilated patients in the immediate postoperative phase, alternatively carbohydrates versus a new fat emulsion were investigated. 30 patients were randomly allocated to three different nutrition regimens. The caloric and nitrogen supplementation was identical for all groups, while the carbohydrate and fat content was different. Group I: only carbohydrates (as caloric source), group II: high fat load (3 g/kg/day), group III: medium fat dosage (1.5 g/kg/day). Routine laboratory parameters as well as acid-base-status and fat metabolism were evaluated. While most of the routine parameters were not significantly different between the groups, triglyceride levels in serum were highest in group II but never exceeding 280 mg/dl (-x). Nitrogen balance as well as protein metabolism were significantly improved using regimen III, thus documenting the beneficial effect of a medium fat dosage in the immediate postoperative phase. Parenteral nutrition combining amino acids, carbohydrates and a fat emulsion seems to be the optimal postoperative regimen even in patients without ventilatory support.

Short-term and long-term monitoring of the serum level of TPA after radical resection of gastrointestinal or lung cancer.

Radically operated tumour patients (gastrointestinal cancer, n = 10; lung cancer, n = 10) were subjected to continuous prospective monitoring of the serum level of tissue polypeptide antigen (TPA) prior to surgical treatment as well as during the subsequent year. The following observations were made: Immediately after radical surgery the serum level of TPA fell temporarily. During the first 2 weeks following this initial decrease, the serum level of TPA rose. In view of the radical surgical treatment the patients had undergone, this finding is interpreted as being not caused directly by the tumour but by tissue repair or proliferation. It is concluded that the first postoperative control of the serum concentration of TPA should be performed not earlier than 4 weeks after tumour resection. If the level of TPA increased after these 4 weeks, the suspicion of a tumour relapse or metastasization was raised. In single cases, a transient rise of serum TPA may not be due directly to the tumour but to other events, e.g. intercurrent infection. In general, the course of the serum level of TPA did not exhibit a marked difference between patients with gastrointestinal and lung cancer.

[Serum endotoxin level in the course of open peritonitis treatment]. / Serum-Endotoxin-Spiegel während des Verlaufs der offenen Peritonitis-Behandlung.

In 27 patients with severe diffuse purulent or fecal peritonitis planned relaparotomies with peritoneal lavage or continuous dorsoventral lavage with open abdomen were performed after surgical treatment of the primary infection. During the course of the lavage treatment serum endotoxin was measured daily. The endotoxin-induced liberation of lysosomal proteases was studied by determining the elastase from polymorphonuclear leucocytes. 16 surviving patients showed decreasing endotoxin levels and decreasing elastase concentrations during the course of abdominal lavages. Planned peritoneal lavage and continuous dorso-ventral lavage seem to have the same potency in eliminating endotoxin from the infected peritoneal cavity. In letal courses endotoxinemia either persisted at high levels or even progressed inspite of lavage treatment.