African Americans with genotype 1 treated with interferon for chronic hepatitis C have a lower end of treatment response than Caucasians.

African Americans as a group have a higher incidence of chronic hepatitis C (CHC) than Caucasians but are often under-represented in clinical trials used to define response rates to interferon therapy. The aim of this study was to compare African Americans with Caucasians with respect to end-of-treatment response to interferon. This retrospective study had 61 African Americans and 49 Caucasians with CHC. All patients were treated for at least 12 weeks with interferon-alpha2b (Intron A) thrice weekly. End-of-treatment response was defined as three consecutive nondetectable HCV RNA measurements at least 1 month apart. Sustained response was defined as a negative serum HCV RNA 6 months after end of treatment. Of the 110 patients, 19 achieved an end-of-treatment response (17%) but only four achieved a sustained response (4/110=4%). Of the patients achieving a sustained response, one was genotype 1 (male Caucasian), three were genotype 2/3 with four patients having no follow-up information. The end-of-treatment response was 7% for patients with genotype 1 and 71% for genotype non-1 (P < 0.005 for genotype non-1). The end-of-treatment response was significantly higher in Caucasians (14/49=31%) compared with African Americans (5/61=8%; P < 0.05). A lower response rate in African Americans with genotype 1 in contrast to Caucasians was the primary reason for the difference in end-of-treatment response (1/45=2% vs. 5/33=15%, P < 0.05). Hence, interferon treatment resulted in a poor sustained response rate in the group of patients representative of the urban populations with the highest prevalence of hepatitis C. A genotype other than type 1 was the strongest predictor of end-of-treatment response in patients treated but over 86% of patients in this urban clinic were genotype 1. Caucasians were more likely to respond than African Americans, especially in patients with genotype 1.

Zollinger-Ellison syndrome, acromegaly, and colorectal neoplasia.

Zollinger-Ellison syndrome (ZES) and acromegaly are two hypersecretory states in which colorectal neoplasia has been described, but the incidence in the former condition may not be increased. We describe four patients with colorectal neoplasia associated with the ZES and review other published cases. Tissue ELISA with Adnab-9 antibody, a putative colorectal cancer risk marker, from a patient with ZES and from seven patients with acromegaly was compared to 13 controls at average risk for colorectal neoplasia. The patient with ZES without detectable colonic neoplasia and seven patients with acromegaly had increased binding of Adnab-9 in the colonic mucosa by ELISA. The difference was significant for the acromegaly patients compared to the controls (p < 0.05). The accumulated 34 instances of colorectal neoplasia in ZES patients suggests that this association may not be rare. Adnab-9 expression, detectable in both ZES and acromegaly, may reflect predisposition to colorectal neoplasia in both hyper-secretory states. Therefore, while a basis for association of colorectal neoplasia and hypergastrinemia exists, the clinical data are not compelling enough to warrant surveillance of patients with ZES. To resolve this problem, more definitive case control studies should be conducted.

Chemoradiotherapy of esophageal carcinoma.

BACKGROUND: Chemoradiotherapy has demonstrated efficacy in esophageal cancer but rarely is curative. To improve local control and decrease metastases, a 7-month regimen was used with standard-dose radiotherapy (RT), cisplatin (DDP), and continuous infusion (CI) 5-fluorouracil (5-FU) in patients with locoregional squamous/adenocarcinoma of the esophagus. METHODS: Initial treatment consisted of RT to the esophagus (4000-5000 cGy) for 5-6 weeks, CI 5-FU (300 mg/m2/day) concurrent with RT, and DDP (25 mg/m2/day x 3) for Days 1-3 and 21-23. Two monthly cycles of DDP (75 mg/m2 Day 1) and 5-FU (300 mg/m2 x 21 days) followed. Patients were restaged with endoscopy and computed tomography scan. Patients without evidence of residual disease received three more cycles of chemotherapy (CT); those with persistent tumor underwent esophagectomy or additional CT/RT, and those with disease progression were offered alternative CT. RESULTS: From December 1987 to September 1991, 18 men and 8 women, including 2 with adenocarcinoma, were eligible for inclusion in the study. All were evaluable for toxicity and response. The median age was 61.5 years (range, 50-80 years), the median pretreatment weight loss was 9 lbs, and the median serum albumin level was 4.3 mg%. Therapy was toxic; 19 patients were hospitalized for treatment-related esophagitis, thrombosis, or infection. Grade III and IV leucopenia were seen in 12 patients and 1 patient, respectively. One patient had Grade IV thrombocytopenia. Of 26 patients, 17 (65%) had no tumor on restaging. Five patients had recurrences in the esophagus (1), liver (3), and lung (2). Three patients had second neoplasms. The median survival was 24 months. CONCLUSION: This treatment regimen provides high frequency of local tumor resolution, but with significant toxicity.

Prospectives on the treatment of chronic hepatitis B and chronic hepatitis C with thymic peptides and antiviral agents.

At the present time, interferon is considered the only effective therapeutic approach in the treatment of both chronic hepatitis B and chronic hepatitis C. It is clear that the disappointing response rates in both chronic hepatitis B and C place added emphasis on efforts to identify alternative forms of therapy. In addition to the development of other antiviral agents including the nucleoside analogs which might prove more effective and have fewer associated side-effects, other agents currently under investigation include thymic peptides such as thymosin alpha 1. In the future, the therapeutic approach to the treatment of chronic hepatitis B and C may consist of combination therapy using perhaps an immune modulator and an antiviral agent or, several antiviral drugs. Alternatively, there is indication that cellular targeting systems with delivery of the toxic material to the specific cell containing the virus may be more effective, while minimizing side-effects. Finally, there are agents such as ursodeoxycholic acid which perhaps, makes bile less toxic and can be used as adjunctive therapy with improvement in liver chemistry values. The treatment of chronic hepatitis B and chronic hepatitis C has shifted in emphasis form the concept of treating liver disease towards that of treating viral infections which happen to effect primarily the liver.

Taurine deficiency after intensive chemotherapy and/or radiation.

Taurine, a nonessential amino acid (AA), is the most abundant free AA in the intracellular space. We measured plasma AA concentrations in 36 patients 7-28 d after intensive chemotherapy and/or radiation. Plasma taurine concentrations were uniformly low in all patients (20.0 +/- 6.4 mumol/L, mean +/- SD). Plasma taurine in 11 healthy volunteer control subjects was 45.0 +/- 20.3 mumol/L (P less than 0.001). Other AA concentrations, specifically those of precursor AAs methionine and cystine, were normal. We prospectively measured plasma AA concentrations in 12 patients before starting and 6-10 d after completing intensive cytotoxic treatment. Values before treatment were 37.2 +/- 11.6, 109.6 +/- 30.7, and 18.5 +/- 4.8 for taurine, cystine, and methionine, respectively, and were 24.3 +/- 6.0, 111.2 +/- 23.8, and 24.0 +/- 14.5 after treatment. Pretreatment plasma taurine correlated directly with the magnitude of decrease in plasma taurine during cytotoxic treatment (n = 12, r = 0.85, P less than 0.01). Intensive cytotoxic chemotherapy and/or radiation leads to a reduction in plasma taurine concentrations without any change in its precursor AAs, methionine and cystine. The clinical relevance of plasma taurine depletion will need further study.

Clinical features, evaluation, and detection of colorectal cancer.

The most common presentation of colorectal carcinoma is in the symptomatic patient, most often with complaints of rectal bleeding, abdominal pain, or change in bowel habits. Symptomatic patients often have advanced disease and, because surgical resection is the only effective therapy at present, their chance for cure is poor. Until effective treatment is available, therefore, we must identify patients at high risk for lifelong screening. In addition, more effective means of surveillance of the general population need to be developed in order to diagnose patients at risk for sporadic colorectal cancer, given that this represents the majority of patients with disease. Tumor markers also would be useful to find residual disease while it is still resectable in patients who have undergone surgery for curative resection.

Screening and surveillance for colorectal cancer.

Pathologic reviews and clinical studies demonstrate that groups with increased cancer risk can be identified. It is estimated that about 3.5 per cent of colorectal cancers in this country are the result of known heritable cancer syndromes, such as familial polyposis. Much effort is currently being devoted to evaluation of biologic markers, such as cell surface antigens and their antibodies, ornithine decarboxylase, errors in DNA repair, abnormalities in metabolism of polyadenosine diphosphate, and application of molecular genetic techniques to identify patients with genetic cancer susceptibility.

Management of the malignant polyp.

Colonoscopy and endoscopic polypectomy are being utilized more frequently these days with the increased emphasis on the prevention, early detection, and treatment of colon cancer. Consequently, the problem of managing the malignant polyp is likely to be more frequently encountered. Many attempts have been made to clarify the management principles involved. Although the studies conducted have been imperfect in their design, the variety of information obtained from these studies is making the picture clearer. A more conservative approach is evolving. Many malignant polyps may be managed by endoscopic polypectomy alone. The criteria for which patients are to be managed in this fashion seem to be relatively simple ones, though technical problems with polypectomy performance and histologic evaluation are still frequently encountered. More carefully designed long-term studies are needed to create firm guidelines for the management of malignant polyps. Should screening and surveillance result in the discovery of earlier and more readily treatable forms of invasive colon cancer, endoscopic polypectomy will most certainly be a cornerstone of their treatment.

Colonoscopic polypectomy.

Since the advent of fiberoptic endoscopy and the introduction of colonoscopic polypectomy, a simple and cost-effective procedure has been available to deal with an exceedingly common problem, the colonic polyp. Although polyps in the gastrointestinal tract have a varied natural history, there is strong evidence that adenomatous colonic polyps have a potential for malignant degeneration and that virtually all colorectal cancers arise from adenomatous polyps. This article will review some basic features of the endoscopic approaches and problems associated with polypectomy.

Life after colectomy.

Animal and epidemiologic studies have raised hopes that effective chemoprevention of colorectal cancer in very high-risk patients may be possible in the future, but at present, the only established effective way to prevent colorectal cancer in very high-risk patients is colectomy. Advances in surgical techniques, improvements in stomal appliances, and medical advances in dealing with complications of colorectal surgery (such as impotence) have contributed to substantial improvements in the quality of life of patients who have had prophylactic colectomies.

Strategies for the control of colorectal cancer.

An overview of this issue is presented, with a discussion of its application to control of colorectal cancer. A brief update on new findings in molecular and genetic aspects is also given. Finally, strategies for control of colorectal cancer are discussed.

Effect of cholera toxin on ileal water and solute transport after resection of the proximal small intestine in the rat.

Intestinal adaptation after extensive small bowel resection results in mucosal hypertrophy and an increased capacity of the remaining small intestine to absorb solutes and water. We tested the ability of the adapted rat ileum to respond to a secretory stimulus, cholera toxin. Six weeks after 50% jejunal resection (short gut) or sham operation water and solute transport were measured in a 16 cm segment of ileum before and after exposure to cholera toxin in a single pass in vivo perfusion system. During the control periods absorption of glucose, acetate and water per unit length of intestine was significantly greater in short gut animals (P less than 0.05 to 0.001). After exposure to cholera toxin absorption of glucose and acetate was significantly reduced in both groups (P less than 0.05 to 0.01). Sodium and chloride secretion and net change in water movement in response to cholera toxin were significantly greater (P less than 0.05 to 0.01) in short gut animals. Generally the differences between short gut and sham operation animals disappeared when the data were normalised for mucosal weight. Chloride secretion per gram mucosa was less in short gut animals (P less than 0.001). The data indicate that the adapted small bowel is not only capable of enhanced absorption but also of enhanced net secretion in response to cholera toxin. The changes reflect the increased number of enterocytes per unit length of intestine after intestinal adaptation.

[Intestinal protein assimilation and losses in man (author's transl)]. / Intestinale Eiweissassimilation und -verlust beim Menschen.

The total quantity of endogenous plus exogenous protein digested and absorbed in the normal gastrointestinal tract in man is in excess of 150 mg per day. Total fecal nitrogen indicates net losses of less than 10% per day in health. Malabsorption and maldigestion both contribute to a decrease in assimilation of exogenous and endogenous proteins. Abnormal serum protein losses across the gastrointestinal tract may be totally recovered if the leak is small and proximal in the intestine. Specific defects in amino acid absorption are often compensated by intact peptide absorption.

Decrease in net stool output in cholera during intestinal perfusion with glucose-containing solutions.

PIP: Glucose-electrolyte solutions were administered to cholera patients by intestinal tube and the effect of this treatment on net stool output was assessed; an ancillary concern was the comparison of the sugar used in the rehydration solution, comparing glucose, galactose, and fructose. All 8 patients studied were cholera victims who had been given intravenous rehydration upon presentation with severe shock; 25 controls were studied for comparison. Average net stool rate of the controls not given perfusions declined at an approximately linear rate throughout the course of diarrhea. However, in every case when glucose was added to perfusion solution, net stool output decreased compared with the decline seen in the total course of non-sugar-containing per fusion studies. In fact, the rate of intestinal fluid loss was decreased with the glucose solution within 12-32 hours of perfusion. Since intestinal sodium absorption was so enhanced by an actively transported sugar, fructose and galactose perfusion fluids were prepared, and it was found that fructose was less well absorbed than glucose or galactose: in general, the results with these sugars were consistent with the sodium-dependent active transport of galactose and the passive transport of fructose, unrelated to sodium transport.^ieng