Production of immunogenic human papillomavirus-16 major capsid protein derived virus like particles.

Background & objective: Recombinant DNA technology allows expression of the human papillomavirus (HPV) major capsid protein (L1) in heterologous expression systems and the recombinant protein self assembles to virus-like particles (VLP). We took up this study to produce recombinant HPV-16 L1 in yeast, establish the process of recombinant L1 derived VLP preparation and develop an ELISA using VLP as the antigen for serological evaluation of anti HPV-16 L1 antibody status. Methods: Complete HPV-16 L1 was amplified from genomic DNA of an esophageal cancer biopsy, cloned and the protein was expressed in a galactose-inducible Saccharomyces cerevisiae expression system. Self assembled VLP was purified by a two-step density gradient centrifugation process and the VLP preparation used to test its suitability in developing an ELISA. Results: The recombinant protein was predominantly a ~55 KD species with distinct immunoreactivity and formed VLP as confirmed by electron microscopy. An ELISA using the VLP showed its efficacy in appropriate immunoreactivity to serum/plasma IgG. Interpretation & conclusions: Recombinant HPV-16 capsid protein derived VLP was produced and the VLP antigen based ELISA can be used to probe serological association of HPV with different clinical conditions. The VLP technology can be improved further and harnessed for future vaccine development efforts in the country.

Infusion chemotherapy with cisplatinum and fluorouracil in the treatment of locally-advanced and metastatic gallbladder cancer.

BACKGROUND: Gallbladder cancer (GBC) has a poor prognosis. Chemotherapy is traditionally considered to be ineffective. The goal of the current study was to evaluate the efficacy of infusional 5-fluorouracil (5-FU) and cisplatinum (CDDP) in patients with inoperable GBC. MATERIALS AND METHODS: A total of 65 patients with inoperable GBC received palliative chemotherapy with CDDP and 5-FU. All the patients had clinically measurable disease as well as adequate bone marrow, hepatic, and renal function. Response was assessed after three cycles of chemotherapy. RESULTS: A total of 19 patients had locally advanced unresectable cancer and 46 patients had metastatic cancer. There were 39 females and 26 males, with a median age of 50 years. A total of 212 chemotherapy cycles were administered to the patients. Response evaluation after three cycles of chemotherapy revealed complete response in five patients [7.69%; 95% confidence interval (95% CI): 2.87-16.22], partial response in 17 patients (26.15%; 95% CI: 16.57-37.81), stabilization of disease in 9 patients (13.85%; 95% CI: 6.96-23.88), and progression in 21 patients (32.30%; 95% CI: 21.80-44.35). At 6 months 44.6% patients were alive and 18.5% patients were alive at 12 months. The median overall survival was 5.7 months and the median time to disease progression was 3.1 months. This chemotherapy combination was well tolerated. There were no chemotherapy-related deaths. CONCLUSIONS: Infusion chemotherapy with CDDP and 5-FU appears to have a fair amount of activity in patients of inoperable GBC, with acceptable toxicity. Tumor shrinkage following treatment with this regimen enabled surgical resection in two patients. We believe that this promising combination must be tested against gemcitabine-based combinations in patients with inoperable GBC.

Cholecystectomy for asymptomatic gallstones can reduce gall bladder cancer mortality in northern Indian women.

Gall bladder cancer (GBC) is a leading cause of cancer-related mortality in the northern parts of the Indian subcontinent. A majority of patients with GBC are middle-aged women, who normally would have substantial family responsibilities. Most patients are diagnosed with advanced cancer and are suitable for palliative care only. There is a strong association between long-standing gallstone disease and the development of GBC. Although randomized trials are lacking, prospective population-based data from low-risk and high-risk regions reveal that cholecystectomy reduces the mortality from GBC. Prophylactic cholecystectomy is recommended in populations with high incidence of GBC. The morbidity and mortality of laparoscopic cholecystectomy in uncomplicated gallstone disease is very low in India. Because of these reasons we argue that prophylactic cholecystectomy should be offered to young healthy women from high-risk regions of India whenever they are diagnosed to have asymptomatic gallstones. Simultaneously, population-based observational studies could be undertaken to generate more evidence.

Subjective global assessment: a simple and reliable screening tool for malnutrition among Indians.

BACKGROUND AND AIMS: Subjective global assessment (SGA) is a simple and reliable malnutrition-screening tool. The SGA has not been evaluated in India or in populations where chronic energy deficiency (CED) is rampant. We evaluated the value of preoperative nutrition, determined using the SGA, in predicting postoperative adverse outcomes in cancer patients. METHODS: Two hundred and ninety-four cancer patients undergoing elective surgery were screened for malnutrition using a modified version of the SGA, and 266 patients (aged 14-73 years [median 50]; 165 male) were eligible. All patients were followed up till discharge, and number of days on antibiotics, length of postoperative stay, occurrence of major adverse events, and death within 30 days were recorded. The association of preoperative SGA scores (A, B, or C) and BMI groups (< 18.5, 18.5-20 or> 20 Kg/m2) and four outcome variables were tested for statistical significance. RESULTS: The cancer sites included head and neck region in 112, gastrointestinal tract in 53, thoracic organs in 28, and other sites in 73 patients. The SGA scores were A in 152, B in 98, and C in 16 patients. The BMI was < 18.5 in 110 (41.8%) patients. The length of postoperative stay and the number of antibiotic days revealed a significant trend from SGA-A to SGA-C (p=0.000). Pre-defined adverse events occurred in 7.9%, 17.3% and 25% of SGA groups A, B, and C, respectively (p=0.025). The risk for adverse events was significantly higher in SGA-C group (OR 5.27, 95% CI 1.35-20.51, p< 0.016) compared to SGA-A group. Three patients in SGA-B group and one in SGA-C group died within 30 days (p=0.04). No significant association was detected between the three BMI groups and duration of antibiotic use, length of postoperative stay, adverse events or mortality. CONCLUSION: SGA is a simple and inexpensive way to identify clinically relevant malnutrition in Indian patients undergoing cancer surgery. Low BMI was not associated with postoperative adverse outcomes, and its use for nutritional screening is likely to overestimate severe malnutrition in Indian patients.

Impact of intra-operative ultrasonography in liver surgery.

BACKGROUND/OBJECTIVE: Intra-operative ultra-sonography (IOUS) during surgery for primary and metastatic hepatic tumors identifies additional lesions and helps in determining the most optimal surgical strategy. We assessed the impact of IOUS in liver surgery at our hospital, a tertiary-care cancer center. METHODS: Patients with potentially resectable hepatic tumors underwent surgical exploration. The relationship of the tumor with regard to the intrahepatic vasculature was determined by IOUS. A search was also made for additional lesions not detected by pre-operative imaging modalities. In appropriate cases, IOUS was also used to assist resection and radiofrequency ablation/ethanol injection. RESULTS: Between January 2003 and January 2005, 52 patients underwent surgery for primary or secondary hepatic tumors. IOUS was performed in 48 of these patients. It detected additional hepatic lesions in 14 patients (29.2%). IOUS contributed to changing the operative plan in 21 patients (43.8%). It was directly responsible for avoiding resection or ablation in 7 patients (14.6%), 5 of whom had multiple bilobar lesions, 1 had IOUS-guided biopsy that revealed caseating granuloma on frozen section, and 1 patient had no lesion on IOUS. Three patients had extent of resection changed based on IOUS findings. IOUS also guided radiofrequency ablation in 8 patients and ethanol injection in one patient. CONCLUSION: IOUS is an essential tool in surgery for hepatic tumors. In addition to accurate staging, it also aids in safe resection and radiofrequency ablation in appropriate cases.

Gastric carcinoids--a changing trend.

OBJECTIVE: Gastric carcinoids (GC) are rare tumors. Recent studies have reported a higher frequency of GC, with these constituting 10%-30% of all carcinoid tumors. We have observed GC more frequently at our institute in recent years than in the past. METHODS: Endoscopy reports from January 1997 to June 2003 were reviewed to identify patients with GC. For these patients, biopsy specimens were reviewed and details of clinical features were extracted from case records. RESULTS: Seventeen patients with GC (aged 27 to 76 years; 11 men) were identified; in comparison, there had been only 8 cases in the previous 16 years. Of these, 14 patients had multiple tumors; these were located in the fundus (n = 6), fundus and proximal body (4), and body (4) of the stomach. Three patients had solitary tumors in the antrum. The tumor size ranged from pinhead to 4 cm. Etiologically, 13 patients had type 1 GC (associated with chronic atrophic gastritis type A), one had type 2 GC (associated with Zollinger-Ellison syndrome; multiple endocrine neoplasia 1) and three had type 3 GC (sporadic). Treatment included total gastrectomy (2), distal gastrectomy (2), tumor excision (1), endoscopic polypectomy (3), and vitamin B12 supplementation with surveillance (9). CONCLUSION: Our data show an increase in diagnosis of GC, similar to reports from Western countries. The rise is in the proportion of GC associated with atrophic gastritis. Whether this reflects a higher frequency of detection due to more endoscopic biopsy sampling or due to some other reason needs investigation.

Total parenteral nutrition.

Parenteral nutrition is a form of therapy in which elemental nutrients (sugars, lipids, amino acids, vitamins and minerals) are given as an intravenous infusion. It is complementary and not competitive to enteral nutrition. While a vast majority of patients can be managed by enteral nutrition, a few patients need parenteral nutrition for survival. Very few patients may need both enteral and parenteral nutrition for short periods. The indications, delivery methods and formulations of parenteral nutrition have been refined in the past 30 years. It is now possible to give parenteral nutrition for prolonged periods at home. Three-in-one parenteral nutrition mixture bags are presently available in India. This article discusses the practical aspects of using parenteral nutrition in everyday practice.

Bile cultures and sensitivity patterns in malignant obstructive jaundice.

BACKGROUND: Bactibilia is one of the important factors in the development of postoperative septic complications. We undertook this retrospective analysis to identify the organisms present in bile and their antibiotic susceptibility patterns in patients with malignant obstructive jaundice. METHODS: Bile specimens were obtained during endoscopic cholangiography (ERC; n=65), by flushing biliary stents (n=15), intra-operatively before incising the common bile duct (n=7) or during percutaneous transhepatic biliary drainage (PTBD; n=1). Eighty-eight samples from 65 consecutive patients were analyzed for their bacterial spectrum and sensitivity to antibiotics. Concomitant septic complications such as wound infection and cholangitis were also assessed. RESULTS: Of 65 patients (hilar block 39, distal block 26), 17 (26.1%) had bactibilia at initial ERCP; in addition, 3 of 7 bile specimens obtained during surgery, one collected during PTBD, and 13 of 15 stent flushings grew bacterial organisms. Cholangitis developed in 15 patients (12 with hilar block, 3 with distal block). Blood cultures were positive in 3 cases, and initial bile culture was positive in four patients with cholangitis. The most commonly found organisms were Escherichia coli (36.6%), Klebsiella pneumonia (18.3%), Pseudomonas aeruginosa (8.3%), Proteus vulgaris (8.3%) and coagulase-negative staphylococci (8.3%). The organisms found on ERC were similar to those found at wound cultures in 3 of the 4 cases who developed wound infection. Amikacin, gentamicin, cefotaxime, ceftazidime, and cefoperazone-sulbactam combination showed good activity against E. coli and K. pneumonia. CONCLUSION: Approximately one-fourth of patients with malignant obstructive jaundice have positive bile cultures at initial ERC. Post-ERC cholangitis is common in hilar blocks.

Enteral nutrition by tube feeding in adults.

Patients who cannot eat enough require alternatives to oral feeding. Tube feeding is one such method for patients with a functioning gut. The techniques for the placement of feeding tubes and diets for tube feeding have improved during the past 20 years. Comfortable thin-bore polyurethane tubes are replacing the thicker vinyl tubes. Long term access routes such as gastrostomy and jejunostomy are being done by endoscopic or radiological techniques. Pre-defined formula feeds have reduced the effort and labour involved in the preparation, storage and administration of blenderized tube feeds. However, the use of soft feeding tubes and commercial formulae will increase the cost of nutrition therapy in India. The ultimate cost-effectiveness of tube feeding will depend on whether it is used appropriately during an illness with adequate delivery of feeds, and whether attention is given to small details by a dedicated nutritional support team. A strong commitment to the scientific use of nutritional support is necessary for getting the best results from tube feeding in everyday practice.

Epidemiology of digestive tract cancers in India. VI. Projected burden in the new millennium and the need for primary prevention.

The incidence rates of most digestive cancers in India are moderate or low. The highest rates are recorded in the urban population of Mumbai and the lowest in the rural population of Barshi in Maharashtra state. The rates will rise as the life expectancy of Indians increases along with urbanization and, within the next few decades, may reach those recorded in Indians living abroad. Based on available population data, we estimate that in the year 2001 there will be approximately 145,000 new cases of digestive cancers in India. In men, the esophagus would be the commonest site (n = 24,925), followed by the stomach (23,100), rectum (10,462), liver (8812), colon (8004), pancreas (5757) and gall bladder (3967). In women, the esophagus would be the commonest site (n = 18,608), followed by the stomach (11,890), gall bladder (7360), rectum (6983), colon (6115), liver (4227) and pancreas (3435). The incidence of cancers of the esophagus and stomach is declining spontaneously in India. It may be possible to accelerate this by reducing the use of tobacco and improving the diet. At the same time the incidence of cancers of the colon, pancreas, liver and gall bladder is rising, largely due to urbanization that leads to major changes in the diet and personal habits. A preventive approach is needed by public health education. Indians should be encouraged to retain their traditional protective diets, eat more fruits and vegetables, do more physical activity, and abstain from tobacco. Gastroenterologists can also help in secondary prevention by screening high-risk individuals, e.g., patients with chronic liver disease for liver cancer and relatives of patients with familial bowel cancer.

Palliation of malignant colonic obstruction by self-expandable metal stent.

Advanced obstructive colorectal cancer is routinely treated by surgical colostomy. Self-expandable metal stents are a promising alternative. We report the use of an expandable metal stent to relieve colonic obstruction in an elderly lady with advanced colorectal malignancy.

Epidemiology of digestive tract cancers in India. V. Large and small bowel.

The large bowel is a leading site for cancers in developed countries whereas small bowel cancers are rare worldwide. The incidence rates of both large and small bowel cancer are low in India, and rectal cancer is more common than colon cancer. The incidence rates of colon cancer in eight population registries vary from 3.7 to 0.7/100,000 among men and 3 to 0.4/100,000 among women. For rectal cancer the incidence rates range from 5.5 to 1.6/100,000 among men and 2.8 to 0/100,000 among women. One intriguing observation is the occurrence of rectal cancer in young Indians. Rural incidence rates for large bowel cancers in India are approximately half of urban rates. Based on data from eight registries, we estimate that, in the year 2001, the incidence of large bowel cancer in India will be 18,427 in men and 13,092 in women. Immigrant studies reveal an increase in incidence as compared to the rates in native counterparts. Reliable time trends for India are available only from the Bombay registry. Significant increase in the incidence of colon cancer has been reported for both men and women over two decades, but the rates of rectal cancer are steady. The low incidence of large bowel cancers in Indians can be attributed to high intake of starch and the presence of natural antioxidants such as curcumin in Indian cooking. The role of hereditary factors has been evaluated in a few studies. Some studies have reported the occurrence of both FAP and HNPCC in India. There are no Indian studies on large bowel cancer prevention. The prevalence of adenomas is rare in elderly Indians undergoing colonoscopy, even in those with large bowel cancers. Small bowel cancers are extremely rare in India and no analytical studies have been published. Hospital-based data suggest that lymphomas of small bowel are more common than carcinomas. In conclusion, the incidence of large and small bowel adenomas and cancers is low in Indians. Increase in the incidence of large bowel cancers in immigrants and urban Indians compared to rural populations supports a role for environmental risk factors including diet. High rates of rectal cancers in young Indians could suggest a different etiopathogenesis, which is neither inherited nor traditional diet-related.