Rationale for, and design of, a clinical trial targeting polyamine metabolism for colon cancer chemoprevention.

Polyamine metabolic genes are downstream targets of several genes commonly mutated in colon adenomas and cancers. Inhibitors of ornithine decarboxylase, such as difluoromethylornithine (DFMO), and agents that stimulate polyamine acetylation and export, such as non-steroidal anti-inflammatory drugs (NSAIDS), act at least additively to arrest growth in human cell models and suppress intestinal carcinogenesis in mice. These preclinical studies provided the rationale for colon cancer prevention trials in humans. A Phase IIb clinical study comparing the combination of DFMO and the NSAID sulindac versus placebo was conducted. Endpoints were colorectal tissue polyamine and prostaglandin E2 contents and overall toxicity to participants. Participants in the Phase IIb study served as a vanguard for a randomized, placebo-controlled prospective Phase III trial of the combination of DFMO and sulindac with the primary study endpoint the prevention of colon polyps. Seventy percent of participants will have completed the three years of treatment in December 2006.

Does fluoroscopic guidance for Maloney esophageal dilation impact on the clinical endpoint of therapy: relief of dysphagia and achievement of luminal patency.

BACKGROUND: Use of fluoroscopy for Maloney esophageal dilation is controversial. We designed this prospective, randomized, single-blinded study to determine whether fluoroscopic guidance has an impact on relief of dysphagia and achievement of luminal patency. METHODS: Patients with benign esophageal strictures were randomized to undergo Maloney dilation with or without fluoroscopic guidance. Strictures were dilated to size 48F. Dysphagia scores were obtained before and 1 week after dilation. RESULTS: Eighty-three patients underwent 100 dilation sessions with fluoroscopic guidance being used for 50 sessions (156 dilations) and blinded technique for 50 (161 dilations). A 12.5 mm barium pill passed after dilation following 62.0% of the fluoroscopic dilation sessions and 42.0% of the blinded dilations (p = 0.045). Dysphagia was improved in 93.0% of patients receiving fluoroscopic dilations and 69.0% of patients receiving blinded dilations (p = 0.006). The mean improvement in dysphagia score was -2.10 points for the fluoroscopic group versus -1.50 points for the blinded group (p = 0.057). Differences in these parameters between techniques were even greater in 12 patients re-randomized to both techniques at different sessions. CONCLUSIONS: The use of fluoroscopic guidance impacts favorably on the efficacy of Maloney dilation, resulting in greater relief of dysphagia and increased luminal patency compared to the blinded technique. Based on these results, use of fluoroscopy is recommended when Maloney esophageal dilation is performed.

Endoscopic diagnosis and treatment of esophageal cancer.

Esophageal carcinoma is one of the deadliest malignant tumors. This article reviews its epidemiology, etiology, and clinical and endoscopic presentation, as well as methods for proper staging to identify the patients who will not benefit from surgery and require palliative therapy. The various treatment options are discussed in detail with an emphasis on the latest endoscopic palliative measures.

Approaches to the management of cholelithiasis for the medical consultant.

Gallstones constitute a major medical problem in the United States. Patients who are asymptomatic require no therapy. Subsequent symptoms develop in a minority of patients, and the need for cholecystectomy is low. Symptomatic patients with reversible risk factors for gallstones, those who refuse surgery, and those who are poor surgical candidates should be considered for medical therapy. Our approach is outlined in Figure 2. Practical options include oral dissolution agents, contact dissolution agents, and shock-wave lithotripsy. Unfortunately, these therapies are successful in very select patients, and only a small percentage of patients with symptomatic gallstones will be candidates for any combination of these. If successful, the recurrence rate is high. Cholecystectomy is a safe, effective procedure that definitively treats symptomatic cholelithiasis. Patients with frequent symptoms of biliary colic, those with severe symptoms, and those who are young and do not have reversible risk factors for gallstones should be considered for cholecystectomy. If surgical expertise is available, the patient requiring an elective cholecystectomy should be educated regarding the laparoscopic approach that offers a better cosmetic result, shorter hospital stay, and faster return to normal activities. The medical consult must be aware of all the options available for managing patients with cholelithiasis. This will afford greater versatility in medical care or perioperative management.

Role of laparoscopy in the evaluation of patients with suspected hepatic or peritoneal malignancy.

The purpose of this study was to determine the role of laparoscopy in patients with suspected hepatic or peritoneal malignancy and a normal computerized tomograph (CT). Twenty-five consecutive patients with a normal liver and no peritoneal lesions on CT were evaluated. Patients with a documented primary neoplasm or a positive ascitic fluid cytology were excluded. At laparoscopy, malignancy was documented by biopsy in 12 patients for an incidence of 48%. Of the patients with exudative ascites, 75% had peritoneal metastases. In addition seven patients had benign liver disease documented by laparoscopic biopsy. Liver enzymes were not helpful in distinguishing benign and malignant disease in this group of patients. This study indicates that a negative CT does not exclude liver or peritoneal malignancy. Laparoscopy has a significant yield in patients with a negative CT suspected of having hepatic or peritoneal malignancy and is the procedure of choice in evaluating these patients.

Pseudoinvasion with high-grade dysplasia in a colonic adenoma. Distinction from adenocarcinoma.

High-grade dysplasia was found to extend to an area of pseudoinvasion in the submucosa of a colonic adenoma mimicking invasive carcinoma. The presence of both benign and cytologically malignant epithelium and residual foci of lamina propria among the submucosal glands distinguishes this entity from adenocarcinoma arising in an adenomatous polyp.

Surveillance colonoscopy after resection for colon carcinoma.

Periodic surveillance colonoscopy was used to assess 207 asymptomatic patients with a previous history of colorectal carcinoma for 2 to 8 years. Thirty-five percent of the patients had a neoplastic lesion greater than or equal to 5 mm in diameter on initial colonoscopy. Synchronous or metachronous carcinomas were found in 11 patients; and of these second carcinomas, 82% were localized. The risk of a second carcinoma developing did not correlate with a finding of neoplastic polyps on the initial colonoscopy. Six recurrent carcinomas at the anastomosis were demonstrated. The stage of the recurrence correlated well with the stage of the primary carcinoma. Two negative colonoscopies at 1-year intervals were necessary to ensure that the colon had been cleared of neoplastic lesions. This study shows that surveillance colonoscopy in patients with a history of colorectal carcinoma has a high yield and is capable of detecting localized, asymptomatic carcinoma. After two annual colonoscopies fail to show neoplasms, surveillance colonoscopy may be scheduled at 3- to 5-year intervals.

A new objective measurement of esophageal lumen patency.

This study was performed to develop a system to measure dysphagia in an objective fashion, test its correlation with subjective estimates of dysphagia, and encourage the use of a standardized measure of esophageal stenosis. Thirty-five patients with mechanical dysphagia underwent subjective estimates of dysphagia using a dysphagia scale graded from 0 to 5, as well as a diet scale. Lumen diameter was measured endoscopically, using the open or closed biopsy forceps as a measuring guide. Patients were then given barium capsules or tablets of increasing diameter under fluoroscopy, in the upright position. Pills were given sequentially until a pill failed to traverse the esophagus in less than 20 s. The diameter of the pill failing to traverse the esophagus within 20 s correlated strongly with the endoscopically measured diameter by Spearmans rank correlation (Rs = 0.85). The weakest correlation was between endoscopically measured diameter and the dysphagia scale (Rs = 0.48). The diameter of the pill failing to traverse the esophagus within 20 s is an excellent estimate of esophageal lumen diameter. Pill size correlates much better with esophageal lumen diameter than dysphagia or diet scales. This new dysphagia assessment system should simplify standardization of the grading of dysphagia.

Trace element deficiencies in inflammatory bowel disease.

Since the institution of successful parenteral nutrition, much has been learned about malnutrition and the effects and complications of nutritional therapy. A variety of patient groups suffer from malnutrition, and clinicians accept the fact that an extremely high incidence of hospitalized medical and surgical patients are malnourished. Perhaps the group we most frequently see suffering from malnutrition are patients with inflammatory bowel disease (IBD). This is especially true in Crohn's disease, in which a variety of nutritional disturbances have been described.

Dieulafoy's cirsoid aneurysm of the duodenum.

Dieulafoy's lesion or cirsoid aneurysm is a rare cause of massive upper gastrointestinal hemorrhage. Historically cirsoid aneurysm most often occurs in the stomach, but has been reported to occur in the jejunum. In this paper, four cases are presented that are felt to represent the first documented cases of cirsoid aneurysm involving the duodenum. At endoscopy, the appearance of Dieulafoy's lesion may range from a pinpoint dot, clot, or tortuous vessel, to blood oozing or spurting from normal mucosa. A shallow defect may be present that can give the appearance of a partially healed peptic ulcer. Previous histologic studies have shown a wide-caliber-persistent artery with intimal thickening, sclerosis, and medial muscular hypertrophy. Once the diagnosis is made, surgical intervention utilizing simple ligation of the involved vessel results in cessation of recurrent hemorrhage. Dieulafoy's lesion is probably more common than the previous literature would suggest. The lesion needs to be considered in the clinical setting of the patient with massive upper gastrointestinal hemorrhage, a paucity of symptoms, and negative findings on barium studies, endoscopy, and exploratory laparotomy.

Treatment of pharyngoesophageal stenosis by polyvinyl prosthesis.

Many authors have objected to the use of esophageal stents in the palliative management of lesions obstructing the cervical esophagus, especially when the prosthesis must lie within 2 cm of the cricopharyngeus muscle (CPM). Ten patients with stenosis of the cervical esophagus by lesions within 2 cm of or involving the CPM were considered for prosthesis placement. The prosthesis was successfully placed in eight patients, five of whom had a tracheoesophageal fistula (TEF). A prosthesis could not be placed in two patients, and two patients complained of a minimal but tolerable foreign body sensation. Six prostheses were custom-made. The necessity to place a prosthesis within 2 cm of or even immediately proximal to the CPM should not be considered an absolute contraindication to esophageal prosthesis placement in selected patients. Foreign body sensation may be absent or minimal, and stent migration is common.

A comparison of biopsy techniques in suspected focal liver disease.

This prospective study was designed to determine the most accurate method of obtaining a tissue diagnosis in patients with suspected focal liver disease. Computed tomography (CT) was performed initially in all patients. Patients with extensive right lobe disease on CT had a blind, percutaneous liver biopsy. Those with focal lesions on CT were randomized to either a CT or laparoscopic directed biopsy. Patients with no lesions on CT had laparoscopy for further evaluation. The results indicate that blind percutaneous biopsy is sufficient if extensive right lobe disease is present. There is no significant difference in the sensitivity of laparoscopy and CT directed biopsy if focal lesions are detected by CT. However, a negative CT directed biopsy does not exclude malignancy. Laparoscopy has a significant yield in patients with a negative CT and is the procedure of choice in evaluating these patients.