Multidisciplinary approach for the treatment of gastric cancer.

Gastric cancer is a global phenomenon and is the second leading cause of cancer-related deaths worldwide. The highest rates of gastric cancer are seen in Asia and parts of Eastern Europe. In Western countries, the incidence of gastric cancer has declined over the last several decades. At the same time, the distribution of gastric tumors has shifted towards more proximal location in Western patients compared to their Asian counterparts. The most common risk factors include dietary factors, smoking, acid hyposecretory conditions, and H. pylori infection. Clinical diagnosis is made by obtaining a good history and physical exam, complemented by endoscopy and imaging studies. Patients often have advanced disease at time of diagnosis. In the absence of metastases, and provided that the patient is medically fit, surgery is the mainstay of treatment. The extent of gastric resection, including the extent of lymph node dissection, varies by region, with more extensive operations being done in Asia, particularly Japan. Because of the propensity of gastric cancer to recur both locally and distantly, additional therapies including chemotherapy and radiation therapy are recommended along with surgery. These can be administered pre-, peri-, or postoperatively based on institutional practices. As with surgical technique, how and when these additional treatments are offered depends largely on regional practice. In the setting of unresectable, or metastatic disease, palliative options including endoscopic and surgical interventions, radiotherapy, and chemotherapy are available.

Recurrent germline mutation in MSH2 arises frequently de novo.

INTRODUCTION: An intronic germline mutation in the MSH2 gene, A-->T at nt942+3, interferes with the exon 5 donor splicing mechanism leading to a mRNA lacking exon 5. This mutation causes typical hereditary non-polyposis colorectal cancer (HNPCC) and has been observed in numerous probands and families world wide. Recurrent mutations either arise repeatedly de novo or emanate from ancestral founding mutational events. The A-->T mutation had previously been shown to be enriched in the population of Newfoundland where most families shared a founder mutation. In contrast, in England, haplotypes failed to suggest a founder effect. If the absence of a founder effect could be proven world wide, the frequent de novo occurrence of the mutation would constitute an unexplored predisposition. METHODS: We studied 10 families from England, Italy, Hong Kong, and Japan with a battery of intragenic and flanking polymorphic single nucleotide and microsatellite markers. RESULTS: Haplotype sharing was not apparent, even within the European and Asian kindreds. Our marker panel was sufficient to detect a major mutation arising within the past several thousand generations. DISCUSSION: As a more ancient founder is implausible, we conclude that the A-->T mutation at nt942+3 of MSH2 occurs de novo with a relatively high frequency. We hypothesise that it arises as a consequence of misalignment at replication or recombination caused by a repeat of 26 adenines, of which the mutated A is the first. It is by far the most common recurrent de novo germline mutation yet to be detected in a human mismatch repair gene, accounting for 11% of all known pathogenic MSH2 mutations.

Serum pancreastatin levels predict response to hepatic artery chemoembolization and somatostatin analogue therapy in metastatic neuroendocrine tumors.

INTRODUCTION: Neuroendocrine tumors often metastasize to the liver and present with disabling hormonal symptoms. Hepatic artery chemoembolization (HACE) combined with somatostatin therapy, pre-embolization, peri-embolization and post-embolization, at doses to control symptoms, is an aggressive approach that can relieve hormonal symptoms with minimal morbidity and mortality. METHODS: Chemoembolization was performed using 30 mg of adriamycin, 50 mg of mitomycin, 12 ml of hexabrix, 10 ml of ethiodol, and 360-500-microm particles. Pancreastatin, a split product of chromogranin A, was measured pre-HACE and post-HACE in all patients. RESULTS: Forty-three chemoebolization procedures were performed in 34 symptomatic patients from December 1995 to August 1999. Seventeen patients had intestinal primaries (50%), seven had pancreatic primaries (20%), five had bronchial primaries (15%), and five had unknown primaries (15%). Systemic pancreastatin levels were improved or stable in 31 patients (78%). Symptoms were improved in these 31 patients (78%). Systemic serotonin levels were improved or stable in 24 patients (60%). Radiographic improvement or stability was seen in 18 patients (45%). Procedural related morbidity included pain, fevers, nausea, vomiting, and transient elevations of liver function studies in 75-100% of patients. There was one procedural related mortality (2%). Less than 20% improvement in pancreastatin levels from baseline was associated with death in five of five patients (100%). This was not observed with serotonin levels. CONCLUSION: Measurement of serum pancreastatin levels is an easy and useful method to predict success in patients who undergo HACE plus somatostatin therapy for metastatic neuroendocrine tumors to the liver. This therapeutic approach is effective in relieving symptoms in 78% of patients, with minimal major morbidity or mortality.

The utility of the Hartmann procedure.

BACKGROUND: In 1923 the French surgeon Henri Hartmann described an operation for rectosigmoid cancer as an alternative to abdomino-perineal resection for high-risk patients. In the subsequent years, the indications for performing the Hartmann procedure have broadened to include complicated diverticulitis, ischemic bowel, iatrogenic perforations, volvulus, and colitis. METHODS: We have retrospectively reviewed our experience in 185 patients who underwent the Hartmann procedure from January 1981 to December 1995. Charts were reviewed for indications, morbidity, and mortality and to determine the outcome of patients who underwent the Hartmann procedure. RESULTS: The main indications for performing the Hartmann procedure were complicated diverticulitis (including perforation, obstruction, and abscesses) in 108 patients, rectosigmoid cancer in 31 patients, and other indications in 46 patients. There were a total of 27 deaths for an in-hospital mortality of 14%. All complications occurred at a rate of less than 9%. Of the 158 surviving patients, 90 (57%) eventually underwent the second stage of the operation to restore bowel continuity. The average length of time between initial resection and reanastomosis was 149 days. There were no deaths associated with the second stage of the procedure and complications occurred at a rate less than 4%. CONCLUSIONS: This is the largest reviewed series of the Hartmann procedure. Mortality is lower than in other reported series, and morbidity is low. Our data demonstrate that the second stage of the procedure, in properly selected individuals, is a procedure that can be performed with minimal morbidity and no mortality. This is different from other published reports. We conclude that the Hartmann procedure is a safe and efficacious option for the surgeon confronted with the complex pathology of the rectosigmoid area, with acceptable morbidity and mortality.

Combination chemotherapy and radiation for palliation of hepatocellular carcinoma.

Twenty seven patients with hepatocellular carcinoma were treated by sequential methotrexate (75 mg/m2) and 5-fluorouracil (5-FU) (750 mg/m2) on day 1 followed on days 8-36 by external beam radiotherapy (total dose 30 cGy). The response was assessed by liver size on clinical examination. One patient had complete response, and six patients had partial response. The overall response to the treatment was 25.9%. More than a 50% reduction in serum alfa-fetoprotein level was noted in 66.6% patients. Seventy-one percent of patients had palliation of pain following therapy. The median survival of responders was 11 months and of nonresponders, 2 months. Radiation was discontinued in two patients who developed radiation hepatitis. Additional trials with different dosages and schedules are needed to fully evaluate this form of therapy.

Brachial plexus injury due to compression: an alternate mechanism of injury: case report and review of the literature.

We present a case of a brachial plexus injury due to compression of the nerves from a traumatic hematoma, with no associated bone or vascular injury. The paralysis in this case was not evident for 48 hours after the initial injury, implying that the brachial plexus was not damaged directly. Electromyograms documenting brachial plexopathy were obtained. The mechanism of injury in this case is different from the usual mechanisms of injury in brachial plexus trauma. The majority of brachial plexus injuries are associated with multisystem trauma. The mechanism of injury to the brachial plexus is either from extreme traction on the nerves or direct impact. Downward traction generally results in lesions in the upper cervical nerve roots, whereas upward traction results in lesions of the lower cervical nerve roots, C8 and T1. The usual symptoms of brachial plexus injuries include paralysis of the shoulder, arm, and/or hand with parasthesias and altered sensation. Temperature and color of the limb may be altered because of damage to the autonomic nervous system. The treatment of brachial plexus injuries varies depending on the mechanism and the time the injury is discovered in relation to the inciting trauma. Current treatment includes assessing function with physical examination, preoperative electromyogram, and then repair of viable nerve roots and associated vascular injuries.

Paget's disease of the male breast.

A histopathologically proven case of Paget's disease of the breast in a 47-year-old male induced a review of the 32 cases in the world's literature. Paget's disease usually presents in the 5th and 6th decades of life without any obvious racial predilections. The most frequent presenting signs include ulceration, eczema, nipple discharge, bleeding, and crust formation. At the time of presentation, 50 per cent of the patients have a palpable breast mass, positive lymph nodes, or both. When entertaining the diagnosis of Paget's disease of the breast using morphologic characteristics of the cells, the diagnosis of malignant melanoma and Bowen's disease (intraepithelial squamous cell carcinoma) must be included in the differential diagnosis. Certain differences will be seen between these three entities based on specific cell staining and the uptake of certain tumor markers. There is no evidence that this disease behaves differently in males versus females, but the 5-year survival for males is worse: 20 to 30 per cent in males versus 30 to 50 per cent in females. The treatment of this disease must focus on the pathology of the underlying tumor. Current treatment involves modified radical mastectomy or radical mastectomy for Stage I and II tumors. Adjuvant chemotherapy, radiation, and tamoxifen are also used depending on the nodal and receptor status of the tumor.

Duodenal diversion of percutaneous biliary drain through a percutaneous endoscopic gastrostomy: report of a case.

Occasionally, percutaneous biliary drainage is the only possible form of treatment in a patient with a malignant obstruction at the porta hepatis. We report on a case of gallbladder carcinoma with a complete block at the porta hepatis, which was palliated with a percutaneous biliary drain. Enteral reinfusion of bile was accomplished through a duodenal tube placed through a percutaneous endoscopic gastrostomy.

Percutaneous endoscopic gastrostomy for long term enteral nutrition.

BACKGROUND: Percutaneous endoscopic gastrostomy for long term enteral nutrition is often indicated in patients with head, neck and oesophageal cancer but despite its growing popularity elsewhere, it is not widely used in India. METHODS: Between March 1990 and July 1991, we performed percutaneous endoscopic gastrostomy in 54 patients. The primary sites of tumour were the hypopharynx (11), oral cavity (7), tongue (7), cricopharynx (7), oesophagus (16) and other sites (6). The indications were difficulty in swallowing following treatment (22), preoperative nutritional support (7) and terminal care (21). In 49 patients, it was performed by the 'pull' technique in the endoscopy room under local anaesthesia and mild sedation. Indigenously prepared tubes and blenderised foods were used. Fifteen patients underwent dilatation of the tumour prior to the gastrostomy. RESULTS: The procedure was successful in 50 (93%) patients. Three failures were caused by obstructing tumours and one by a previous gastric resection. Feeding was started 18 to 24 hours after the procedure in 48 patients. No major complications occurred but minor complications were seen in 11 (22%) patients. Fourteen patients had their gastrostomy tube removed after 2 to 6 months of use while 15 patients undergoing therapy or with persistent dysphagia were on gastrostomy feeds for 1 to 6 months. Of the 21 terminally ill patients, 8 died, 6 were lost to follow up and 7 were on feeds for 1 to 6 months. CONCLUSIONS: Percutaneous endoscopic gastrostomy is a simple, safe and effective method for long term enteral feeding. Indigenous tubes and home made blenderised foods are adequate substitutes for the more expensive commercial kits and enteral formulations.

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.

Dilatation of radiation-induced esophageal strictures under sublingual buprenorphine analgesia: a pilot study.

BACKGROUND: Pain during dilatation of radiation strictures is a troublesome complaint. There is little information on sedation and analgesia during this procedure. We performed a pilot study to compare the analgesic efficacy of sublingual buprenorphine and intravenous pentazocine during dilatation of radiation-induced esophageal strictures. METHODS: Thirty-one patients with esophageal cancer who had radiation-induced strictures were randomized to receive either buprenorphine 0.2 mg sublingually two hours before dilatation (n = 17) or pentazocine 30 mg intravenously five minutes before dilatation (n = 14). Dilatation was considered successful if it could be performed to 12 mm diameter or more. Pain experienced during dilatation was graded as mild, moderate or severe. RESULTS: Sixteen patients in the buprenorphine group and 12 in the pentazocine group were dilated to > 12 mm size (p = ns). Twelve and nine patients respectively in the two groups experienced mild or no pain; ten and six patients had minor side-effects (p = ns). CONCLUSION: Buprenorphine is useful for sedoanalgesia during dilatation of radiation-induced strictures of the esophagus.

Primary peritoneal mesothelioma.

A patient with primary peritoneal mesothelioma who had occupational exposure to asbestos 30 years ago is reported. The disease was progressive and the patient died 12 months after the diagnosis.

Familial polyposis coli with villous adenoma of ampulla of Vater.

Adenoma of the ampulla of Vater is one of the extracolonic manifestations of familial polyposis coli (FPC). We report three patients with FPC in whom villous adenoma of the ampulla was detected. An adenoma carcinoma sequence has been suggested in such lesions.

Percutaneous endoscopic gastrostomy for enteral feeding.

Percutaneous endoscopic gastrostomy was performed for enteral feeding in a patient with orocutaneous fistula. The method of construction of the gastrostomy tube from locally available material is described.

Double primary neoplasms of the stomach and kidney.

We report a case of synchronous double primary neoplasms of the stomach and kidney. Immunohistochemistry confirmed the two primaries to be of different origin based on antigen expression.

Rectal lymphogranuloma venereum in association with rectal adenocarcinoma.

Rectal involvement in lymphogranuloma venereum (LGV) is more common in women. Inguinal bubo is often absent and the patient seeks medical attention only at a late stage when rectal stricture has developed. LGV rectal stricture resembles and is known to predispose to rectal cancer. Hence it is necessary to rule out rectal malignancy in patients with LGV stricture. We report a case of rectal LGV associated with rectal adenocarcinoma.

Out-patient esophageal dilation: an experience in 130 patients using Savary-Gilliard dilators.

Experience of outpatient esophageal dilation using Savary-Gilliard dilators in 130 patients during a 17 month period is reported. The strictures were radiation induced (48), tumoral stenoses (40), anastomotic (16) and due to other causes (26). Both fluoroscopy and endoscopy were used in 58%, endoscopy alone in 23% and fluoroscopy alone in 19% of patients for placement of the guide wire. One hundred and twenty six stricture dilations (97%) were technically successful. Eighty one (62%) patients could be dilated to 14 mm or more. One hundred and nineteen (94%) patients were dilated in one or two sessions. Among the 109 patients who followed up, dilation was successful in providing adequate dysphagia relief in 97 patients and facilitated the performance of other therapies in 9 patients. Major complications included severe continuous chest pain (1 case), hematemesis (2), fever (4) and transient stridor (2). The patient with persistent pain and 9 patients undergoing other therapies required hospitalization. There were no perforations or death. We conclude that esophageal dilation with Savary-Gilliard dilators is safe and effective even in tumors and post-radiation strictures. It can be performed on an outpatient basis in a majority of patients.

Association of esophageal cancer and esophageal varices.

Of the 312 cases of esophageal cancer seen over 2 years, four patients had associated varices. Three patients gave history of alcohol abuse. All had malnutrition and splenomegaly. Endoscopic biopsies were safe in the presence of varices. External radiation did not have any untoward effect on the varices. Prophylactic sclerotherapy was not required in these patients. The association between esophageal carcinoma and varices could be secondary to alcohol consumption or merely coincidental.

Medication induced esophageal injury.

Five patients of medication-induced esophageal injury are reported. A history of ingestion of medications preceding the onset of dysphagia was obtained in all patients. Endoscopy revealed localised mucosal ulceration with surrounding edematous mucosa at the level of the aortic arch in four, and in the retro-cardiac esophagus in one patient. The medications involved were sustained release potassium chloride, doxycycline, ibuprofen, and an unidentified antibiotic and antihypertensive (one each). Healing of the esophageal ulcers was confirmed in all the patients by endoscopy.

Gastric metastases from esophageal cancer.

Gastric metastases from esophageal cancer are seldom diagnosed antemortem. Two patients who had endoscopically detected gastric metastases from esophageal cancer are reported. One patient had a metastasis developing 6 months after radiation therapy; the other developed metastasis after surgical resection of the primary tumor.