Wilhelm Gaus

Role of octreotide in the prevention of postoperative complications following pancreatic resection

Though morbidity and mortality rates following pancreatic resection have improved in recent years, they are still around 35% and 5%, respectively. Typical complications, such as pancreatic fistula, abscess, and subsequent sepsis, are chiefly associated with exocrine pancreatic secretion. In order to clarify whether the perioperative inhibition of exocrine pancreatic secretion prevents complications, we assessed the efficacy of octreotide, a long-acting somatostatin analogue. We conducted a randomized, double-blind, placebo-controlled, multicenter trial in 246 patients undergoing major elective pancreatic surgery. Patients were stratified into a high-risk stratum (limited to patients with pancreatic and periampullary tumors) or low-risk stratum (patients with chronic pancreatitis). Patients received octreotide (3 x 100 micrograms) or placebo subcutaneously for 7 days perioperatively. Eleven complications were defined: death, leakage of anastomosis, pancreatic fistula, abscess, fluid collection, shock, sepsis, bleeding, pulmonary insufficiency, renal insufficiency, and postoperative pancreatitis. Two hundred patients underwent pancreatic head resection, 31 patients underwent left resection, and 15 patients had other procedures. The overall mortality rate within 90 days was 4.5%, with 3.2% in the octreotide group and 5.8% in the placebo group. The complication rate was 32% in the patients receiving octreotide (40 of 125 patients) and 55% in patients receiving placebo (67 of 121 patients) (p less than 0.005). In the patients in the high-risk stratum, complications were observed in 26 of the 68 (38%) patients treated with octreotide and in 46 of 71 (65%) patients given placebo (p less than 0.01). Whereas in patients in the low-risk stratum, the complication rate was 25% (14 of 57 patients) in those treated with octreotide and 42% (21 of 50 patients) in patients given placebo (p = NS). The perioperative application of octreotide reduces the occurrence of typical postoperative complications after pancreatic resection, particularly in patients with tumors.

Gabexate mesilate in human acute pancreatitis

Abstract Background: A multicenter controlled study was performed to evaluate the effect of high doses of the low molecular weight protease inhibitor gabexate mesilate on mortality and complications associated with moderate and severe acute pancreatitis. Methods: Two hundred twenty-three patients from 29 hospitals were entered in the randomized, double-blind trial. Admission to the study was based on strict criteria excluding mild acute pancreatitis. The patients received placebo or 4 g gabexate mesilate per day intravenously for 7 days. All patients were followed up for 90 days after randomization. The analysis was based on 14 complications, including death. Results: There was no statistical difference in either mortality or complications associated with acute pancreatitis between the placeboand gabexate mesilate groups. Conclusions: The results show that gabexate mesilate was not effective in preventing complications and mortality in acute pancreatitis.

Riluzole in Huntington's disease: a 3‐year, randomized controlled study

We conducted a randomized double‐blind trial of riluzole in Huntingtons disease to investigate the efficacy of this antiexcitotoxic drug in slowing disease progression.

Haemodialysis-membrane biocompatibility and mortality of patients with dialysis-dependent acute renal failure : A prospective randomised multicentre trial

BACKGROUNDnThere is controversy as to whether haemodialysis-membrane biocompatibility (ie, the potential to activate complement and neutrophils) influences mortality of patients with acute renal failure. We did a prospective randomised multicentre trial in patients with dialysis-dependent acute renal failure treated with two different types of low-flux membrane.nnnMETHODSn180 patients with acute renal failure were randomly assigned bioincompatible Cuprophan (n=90) or polymethyl-methacrylate (n=90) membranes. The main outcome was survival 14 days after the end of therapy (treatment success). Odds ratios for survival were calculated and the two groups were compared by Fishers exact test. Analyses were based on patients treated according to protocol (76 Cuprophan, 84 polymethyl methacrylate).nnnFINDINGSnAt the start of dialysis, the groups did not differ significantly in age, sex, severity of illness (as calculated by APACHE II scores), prevalence of oliguria, or biochemical measures of acute renal failure. 44 patients (58% [95% CI 46-69]) assigned Cuprophan membranes and 50 patients (60% [48-70]) assigned polymethyl-methacrylate membranes survived. The odds ratio for treatment failure on Cuprophan compared with polymethyl-methacrylate membranes was 1.07 (0.54-2.11; p=0.87). No difference between Cuprophan and polymethyl-methacrylate membranes was detected when the analysis was adjusted for age and APACHE II score. 18 patients in the Cuprophan group and 20 in the polymethyl-methacrylate group had clinical complications of therapy (mainly hypotension).nnnINTERPRETATIONnThere were no differences in outcome for patients with dialysis-dependent acute renal failure between those treated with Cuprophan membranes and those treated with polymethyl-methacrylate membranes.

Risk Factors for Alveolar Echinococcosis in Humans

A case-control study of alveolar echinococcosis cases in Germany identifies several risk factors for the disease.

Regional chemotherapy for hepatic metastases of colorectal carcinoma (continuous intraarterial versus continuous intraarterial/intravenous therapy): results of a controlled clinical trial

Sixty‐four patients with a biopsy diagnosis of colorectal cancer with liver metastases were treated with 5‐fluorodeoxyuridine (FUDR) infusions. In a pilot study, the first 20 patients were given hepatic artery infusions of FUDR by implanted pumps. The remaining 44 patients were then randomized prospectively to compare the effectiveness of continuous hepatic artery and intravenous infusion of FUDR (IA/IV group; 21 patients) with hepatic artery infusion alone (IA group; 23 patients). A continuous 14‐day infusion regimen of FUDR was applied each month. The dosage was 0.2 mg/kg/d of FUDR for the IA group and 0.3 mg/kg/d for the IA/IV group. The complete and partial response rates were each 50% in the pilot study and 52% and 48% in the IA and IA/IV randomized groups, respectively. Drug toxicities in the 64 patients included gastroenteritis (21%), chemical hepatitis (57%), and biliary sclerosis (25%). There was no difference in the toxicity of FUDR in the two randomized groups (P > 0.1). Extrahepatic spread of cancer during therapy was found in 61% (n = 14) of the IA group and 33% (n = 7) of the IA/IV group. There was no difference in survival between the randomized groups. The 64 patients were categorized into the following two groups according to their response to therapy: (1) responders (patients with complete or partial remission [n = 32]) or nonresponders (patients with stable disease or progression of metastases [n = 32]). The median survival time was 31 months for responders and 16 months for nonresponders (P < 0.0001). Intraarterial FUDR infusion provided control of liver metastases. The combination of intraarterial and intravenous therapy seemed to prevent extrahepatic spread during therapy in most of the patients, Survival appeared to be significantly prolonged in patients with a regression of metastases.

Double-blind, placebo-controlled study of intralesional interferon gamma for the treatment of localized scleroderma

BACKGROUNDnLocalized scleroderma is characterized by circumscribed fibrotic plaques and may progress to widespread skin involvement and fibrosis. Interferon gamma (IFN-gamma) has been shown to be a potent inhibitor of collagen synthesis and of the migration and proliferation of dermal fibroblasts.nnnOBJECTIVEnOur purpose was to determine whether IFN-gamma is effective in the treatment of localized scleroderma.nnnMETHODSnA double-blind, randomized, placebo-controlled, multicenter study was conducted. Twenty-four patients with progressive lesions received 100 micrograms of IFN-gamma or placebo subcutaneously on 5 consecutive days for 2 weeks followed by 100 micrograms of IFN-gamma or placebo once weekly for 4 weeks. Thereafter patients were observed for 18 weeks. To determine whether improvement could be related to an altered level of collagen messenger RNA (mRNA), biopsy specimens were taken from uninvolved and involved skin before and after therapy.nnnRESULTSnThe patients treated with IFN-gamma or placebo showed no significant difference in size or fibrosis of lesions or collagen type I mRNA synthesis. However, a reduction in the number of new lesions was observed in the IFN-gamma-treated group. The biopsy specimens obtained from involved skin showed a moderate increase of type I collagen and a significant decrease in the small proteoglycan decorin mRNA levels.nnnCONCLUSIONSnThe results indicate that IFN-gamma is ineffective in the treatment of localized scleroderma, but may inhibit the development of new lesions.

The efficacy and safety of Crataegus extract WS® 1442 in patients with heart failure: The SPICE trial

Crataegus preparations have been used for centuries especially in Europe. To date, no proper data on their efficacy and safety as an add‐on‐treatment are available. Therefore a large morbidity/mortality trial was performed.

Survival and prognosis: investigation of Crataegus extract WS 1442 in congestive heart failure (SPICE)--rationale, study design and study protocol.

SPICE is the first, international, randomized, placebo‐controlled, double‐blind study to investigate the influence of the herbal drug Crataegus Special Extract WS 1442 (hawthorn leaves with flowers) on mortality of patients suffering from congestive heart failure.

Ciprofloxacin and norfloxacin for selective decontamination in patients with severe granulocytopenia

SummaryIn a randomized multicenter study, ciprofloxacin and norfloxacin, each in two different dose regimens and in combination with non-absorbable antimycotics, were administered to 51 patients with acute leukaemia undergoing aggressive remission induction chemotherapy for infection prevention. Both drugs showed an effective elimination of gram-negative potential pathogens andStaphylococcus aureus not affecting the anaerobic flora of the gastrointestinal tract. A low incidence of side effects and a satisfactory patient compliance could be observed. A daily dosage of 1,000 mg ciprofloxacin or 800 mg norfloxacin is recommended for infection prevention in severely granulocytopenic patients.ZusammenfassungIn einer randomisierten multizentrischen Studie wurden 51 Patienten mit akuter Leukämie, die sich einer aggressiven Chemotherapie zur Remissionsinduktion unterzogen, mit Ciprofloxacin oder Norfloxacin, jeweils in zwei unterschiedlichen Dosierungen und in Kombination mit einem nicht resorbierbaren Antimykotikum, zur Infektionsprävention behandelt. Mit beiden Substanzen wurde eine effektive Elimination potentiell pathogener gram-negativer Bakterien undStaphylococcus aureus erreicht, während die anaerobe Darmflora nicht beeinflußt wurde. Es wurde nur eine geringe Inzidenz von Nebenwirkungen bei zufriedenstellender Patientencompliance beobachtet. Als Tagesdosis zur Infektionsprävention bei schwer granulozytopenischen Patienten sollten 1000 mg Ciprofloxacin oder 800 mg Norfloxacin verabreicht werden.