Steve Goldschmid

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.

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

Summary.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.

Dieulafoy's Cirsoid Aneurysm of the Duodenum

Dieulafoys 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 Dieulafoys 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. Dieulafoys 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.

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.

Cancer and age related colonic crypt deficiencies in cytochrome c oxidase I.

AIM To investigate whether deficiency of expression of cytochrome c oxidase I (CcOI) in colonic crypts is associated with colon cancer. METHODS The pattern and level of expression of CcOI in non-neoplastic colonic crypts, and in dysplastic tissues, was assessed using standard immunohistochemical methods. Biopsies were obtained from individuals undergoing colonoscopies for screening purposes or for a medically indicated reason. Tissue samples were also obtained from surgical colonic resections. Samples from resections were taken from colonic mucosa 1 and 10 cm from tumors and from the tumors themselves. Samples were evaluated for frequency of crypts with reduced or absent expression of CcOI. In most crypts the loss was apparent throughout the entire crypt, while in a small minority the loss was segmental. The strong immunoreactivity using this monoclonal antibody makes the scoring unambiguous. The percent of crypts with reduced or absent expression of CcOI or (infrequent) segmented loss of expression was then calculated. Data analyses were performed using SPSS statistical package 17.0. RESULTS The average frequency of CcOI deficient crypts (CcOI-DC) is low in individuals between 20 and 39 years of age, with 0.48% ± 0.40% CcOI-DC for women and 1.80% ± 0.35% for men. CcOI-DC increases after age 40 years, so that between the ages of 40 and 44 years the average frequency of CcOI-DC goes up to 5.89% ± 0.84% in women and 2.15% ± 1.27% in men. By 80-84 years of age, the average frequency of CcOI-DC goes up in women to 15.77% ± 0.97% and in men to 22.6% ± 0.65%. The increases in CcOI-DC from ages 40-44 years compared to 80-84 years in women and men are significantly different with P < 0.01. For women over age 60 years, deficiency of CcOI expression is greater in those women who have had a cancer in their colon. The frequency of CcOI-DC, measured in men, increased in tissues adjacent to colon cancer, being 4.03% ± 0.27% in individuals free of neoplasia in the age range 55-64 years and 14.13% ± 0.35% in resected histologically normal tissue of men with cancer in the same age range, P < 0.001. Similar significant differences were noted in older age ranges. The frequency of CcOI-DC crypts in the cecum and sigmoid colon of an individual are significantly correlated, with an R(2) = 0.414 for women and R(2) = 0.528 for men, P < 0.001. This suggests that the factors determining the level of CcOI deficiency act throughout the colon. Most defective crypts are in clusters of two or more, a likely consequence of crypt fission. In the non-neoplastic margins of cancers, crypts are frequently deficient for CcOI, and such crypts may appear in large clusters, some containing more than 100 deficient crypts. CcOI deficiency is also apparent in colon cancers and sometimes involves a large section of the tumor. Overall, CcOI deficient cells can be visualized in segments of crypts, in whole crypts that increase in frequency with age, in crypts undergoing fission, in clusters of crypts where the clusters increase in size with age, in increased frequency near tumors, in large clusters in the intimate margins of tumors, and in the tumors themselves. There is no clear dividing line between early stages that can be considered aspects of aging and later stages that can be considered aspects of the progression to cancer. This ambiguity may reflect a rather general situation leading to adult cancer where the early stages of cellular change appear to be relatively innocuous features of the aging process but over decades may evolve into malignancy. CONCLUSION CcOI deficient crypts increase in frequency with age, and clusters of deficient crypts are associated with, and may give rise to, colon cancer.

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.

Magnetic resonance enterography in Crohn's disease: techniques, interpretation, and utilization for clinical management.

Crohns disease treatment has improved significantly with the development of immunosuppressive and immunomodulatory agents, while surgery remains an important option in selected patients. However, a relative lag in diagnostics has become apparent with a growing need for the capacity to noninvasively and safely evaluate the tissue changes of Crohns disease within the bowel wall and deeper tissues. We have noted marked technical improvements in magnetic resonance enterography (MRE) and in our understanding of the different facets of Crohns disease that can be elucidated by optimized MRE, in contrast to other diagnostics. This review will provide an integrated understanding of MRE related to other available tests and recommendations for the optimal use of MRE for the clinical management of Crohns disease. We will review the relative strengths and limitations of MRE as applied to clinical evaluation and therapeutic decisions, including the use of the unique capacity to delineate active inflammation and fibrosis in the submucosal and deeper enteric tissues, which is beyond the diagnostic reach of endoscopy and biopsy.

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.