Role of C-erbB2 expression in gallbladder cancer.

Background: Gallbladder cancer (GBC) is a lethal malignancy presenting at an advanced stage. The pathogenesis is not well categorized, and surgery is the only treatment available at the early stage of the disease. There have been few reports on role of growth factor receptors in GBC. C-erbB2 is one such receptor whose over-expression is being explored in GBC as one of the factors involved in carcinogenesis and possible target for therapy. Materials and Methods: One hundred and four consecutive cases of GBC were retrospectively studied with regard to clinical features, histological type, grade and stage of tumor. Immunohistochemistry for C-erbB2 was done and expression was correlated with different clinic-pathological parameters and survival. Results: C-erbB2 overexpression was seen in 9.4% cases with complete staining and both complete and incomplete staining (2+ and 3+) was seen in 13.4% cases. Eighty percent of the C-erbB2 over-expressed cases were well differentiated and in stage II to stage IV disease. Dysplasia adjacent to carcinoma did not show any expression. No correlation was found with tumor grade, stage, gall stones, and patient survival. Xanthogranulomatous inflammation was inversely correlated with C-erbB2 over-expression. Median survival was 30 months in C-erbB2 over-expressed cases, and 12 months in C-erbB2 negative cases. Conclusion: We found complete membranous staining of C-erbB2 in 9.4% of GBC which was frequent in well differentiated and stage II to stage IV tumors. C-erbB2 tumors had longer median survival than C-erbB2 negative tumors. C-erbB2 is not involved early in the carcinogenetic process as none of the dysplasia showed expression. C-erbB2 over-expression may be considered as target for therapy in advanced stage of GBC.

Natural toxins and their therapeutic potential.

Plants have been extensively investigated for exploring their therapeutic potentials, but there are comparatively scanty reports on drugs derived from animal kingdom, except for hormones. During last decade, the toxins that are used for defense by the animals, have been isolated and found useful tools for physiological and pharmacological studies, besides giving valuable leads to drug development. Toxins with interesting results have been isolated from the venoms of snakes, scorpions, spiders, snails, lizards, frogs and fish. The present review describe about some toxins as drugs and their biological activities. Some fungal, bacterial and marine toxins have also been covered in this article.

Degradation kinetics of Metronidazole and its Mutual Prodrug with Ciprofloxacin : a Calorimetric Analysis

Calorimetric technique has aroused considerable interest as a versatile tool in pharmaceutical industry and academia to provide useful information about thermodynamic and kinetic aspects of drug molecules. The present paper utilizes this technique to monitor the hydrolytic degradation of metronidazole and its prodrug with ciprofloxacin; i.e. 2-(2-methyl-5-nitroimidazol-1-yl)ethyl-1-cyclopropyl-6-fluoro-1;4-dihydro-4-oxo-7-(1-piperazinyl)-quinoline-3-carboxylate. The synthesis of the present mutual prodrug was envisaged to combine the antiprotozoal and anaerobic antibacterial effects of metronidazole with antibacterial effects of ciprofloxacin. Heat flux microcalorimeter was used to determine the rate of heat evolved during the degradation of the drug and prodrug as a function of concentration; pH and temperature. In terms of enthalpy of hydrolysis the response is exothermic both for drug and prodrug. However; the absolute value of the enthalpy of reaction (?rH0) is low for the prodrug. The degradation followed pseudo first order kinetics; showed marked stability at pH 3-7 followed by accelerated hydrolysis at higher pH; characteristic of general acid-base catalysis. The catalytic rate constant for hydrogen ion (kH) and hydroxyl ion (kOH) were found to be 0.413 and 526.1 M-1h-1; respectively; at 318.15 K. The hydrolysis of the prodrug was found to be approximately 50-60 times faster than that of the drug. This may be attributed to the fact that hydrolysis of ester group in prodrug is assisted by keto group on the ciprofloxacin. However; there is no effect of protonation of nitrogen in piperazine ring in ciprofloxacin on the hydrolysis due to the distance from the ester moiety

Cholecystectomy in patients with asymptomatic gallstones to prevent gall bladder cancer--the case against.

Gallstones (GS) are common in northern India. GS are the most important risk factor for gall bladder cancer (GBC). Data from the West, however, indicate that the risk of GBC in persons with asymptomatic GS is very small and does not warrant prophylactic cholecystectomy. Can these recommendations be applied to northern India where incidence rates of GBC are one of the highest in the world? Not all persons with asymptomatic GS require cholecystectomy. There may, however, be a case for offering cholecystectomy to a young woman in northern India with a large GS or a gall bladder packed with GS, though there is no evidence to support this recommendation. Type of stone, tumor markers and genetic markers need to be investigated to identify those with asymptomatic GS who are at the highest risk of developing GBC so that they can selectively be offered pre-emptive cholecystectomy to prevent GBC.

Gallbladder cancer: an 'Indian' disease.

The prevalence of gallbladder cancer, the commonest biliary malignancy, shows geographical and racial variations. It is reported to be rare in India. However, the incidence of gallbladder cancer in north and central India is very high--it is the commonest gastrointestinal cancer in women. Even Indian migrants to different countries have a higher risk of having gallbladder cancer as compared to the respective native populations. The incidence of gallbladder cancer parallels the prevalence of gall stone disease; large and long-standing gall stones being associated with a higher risk of gallbladder cancer. Gall stone disease is common in north India and occurs at a younger age than in the western populations. Moreover, patients with gall stone disease present for treatment a long time after the onset of symptoms. Both these factors result in prolonged exposure of the gallbladder to stones. Besides gall stone disease, various other factors may also play a role in the causation of gallbladder cancer which is an (north) Indian disease.

Surgical management of complicated hydatid cysts of the liver.

AIMS: To review the clinical presentation and surgical management of complicated hydatid cysts of the liver. METHODS: Forty-three patients with hydatid disease of the liver were managed surgically between 1991 and 1998. There were 14 men and 29 women with a median age of 34 years. An abdominal ultrasound, computed tomography and serology established diagnosis. Preoperative endoscopic retrograde cholangiography was performed in patients with associated jaundice and high suspicion of intrabiliary rupture. Eleven (26%) patients had complicated cysts and formed the basis for our study. RESULTS: Infection (n = 5, 11%) and intrabiliary rupture (n = 4, 9%) were the common complications. Intrathoracic rupture and intraperitoneal rupture were encountered in one patient each. All patients with infected cysts presented with pain and fever (n = 5, 100%) while those with intrabiliary rupture had jaundice (n = 4, 100%), pain and fever (n = 3, 75%). Surgical procedures performed in complicated cysts were-infection: omentoplasty (n = 2) and external drainage (n = 3); intrabiliary rupture: omentoplasty (n = 2) and internal drainage (n = 2). Patient with intrathoracic and intraperitoneal rupture underwent external drainage. There was no mortality. Postoperative morbidity was encountered in 14 patients and was more in complicated cysts (n = 6/11; 55%) compared to uncomplicated cysts (n = 8/32; 25%). CONCLUSION: Hydatid disease in not an uncommon problem. Around a fourth of patients, present with complications such as infection or intrabiliary rupture. The site, size, number of cysts and presence of complications govern the choice of surgical procedure. Complicated cysts can be successfully managed surgically with good long-term results.

Gastroenterology and the Internet.

BACKGROUND: The Internet has come to play a significant role in health care across the world. Simple specific how-to-use information about the Internet for Gastroenterologists is lacking in the literature. AIM: To explain the origin, functions, use and impact of the Internet and to provide a list of important web site addresses related to Gastroenterology. METHODS: We undertook a detailed scan of the Internet and identified a large number of web sites pertaining to Gastroenterology. The sites were then thoroughly searched to evaluate their potential usefulness to Gastroenterology clinicians and researchers. A list of web site addresses were then compiled according to specific sub-areas of Gastroenterology. CONCLUSION: This overview of Internet and compliation of important web site addresses is expected to stimulate and instruct Gastroenterologists in the use of the Net in health care delivery and research. The list of web sites according to subspecialities provided in this article is expected to facilitate their search.

Malignant gastroparesis and outlet obstruction in carcinoma gall bladder.

INTRODUCTION: Malignant gastroparesis and mechanical gastric outlet obstruction are two major accompaniments of advanced upper abdominal malignancies. The incidence of such problems has not been well documented in patients of carcinoma gall bladder. The aim of this study was to determine the incidence of gastric outlet problems in patients of carcinoma gall bladder and correlate them with clinical presentation. The role of prophylactic gastrojejunostomy (GJ) and its postoperative outcome was also evaluated. PATIENTS AND METHODS: Thirty seven patients of carcinoma gall bladder were prospectively studied. Twenty five patients underwent radio labelled solid meal gastric emptying study and eleven of these underwent prophylactic GJ and followup gastric emptying study in early postoperative period. RESULTS: Mechanical gastric outlet obstruction was seen in 10 (27%) patients. Delayed gastric emptying on scintigraphic study was found in 10 (40%) of remaining patients (n = 25). Only 6 (60%) of these patients were actually symptomatic. All patients who had delayed gastric emptying also had an advanced disease. No correlation was found between delayed gastric emptying and presence of jaundice and/or serum levels of bilirubin. Prophylactic GJ had 18% postoperative morbidity as compared to 28.5% for therapeutic GJ done during the same period. Oral feed were started latest by 11th postoperative day. Prophylactic GJ did not affect gastric emptying patterns in early postoperative period. CONCLUSION: Mechanical gastric outlet obstruction was present in 27% patients. Delayed gastric emptying was seen in 40% of remaining patients with carcinoma gall bladder. Delayed gastric emptying correlated well with symptoms of gastric stasis and the stage of disease. Functioning of gastrojejunostomy was not fully dependent on presence or absence of malignant gastroparesis.

Technical complications of feeding jejunostomy: a critical analysis.

INTRODUCTION: A retrospective review of patients undergoing feeding jejunostomy (FJ) was undertaken in order to evaluate procedure related complications and their impact on final outcome. PATIENTS AND METHODS: Ninety six patients had FJ at the department of Surgical Gastroenterology, SGPGIMS from January 1989 to December 1995. RESULTS: FJ as an adjunct was performed in 89 patients with predominantly oesophageal (n = 62) and pancreatic surgery (n = 17). Seven patients had FJ as the only procedure. Fifteen patients (15.2%) had complications related to FJ. Minor complications (7.2%) included dislodgement (n = 3), blockage of the tube (n = 2) and pericatheter leak (n = 2). Major complications (8.3%) which needed surgical intervention were, detachment of the jejunostomy from the abdominal wall (n = 3), leak into the peritoneal cavity (n = 3), jejunal perforation by the tip of the catheter (n = 1) and peritonitis after removal of the tube (n = 1). Procedure related mortality was 3.2%. CONCLUSIONS: FJ should not be treated as a minor procedure and due attention to the technical details is required in its performance, otherwise it may well become the cause of a poor result following a very successful major operation.