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Genetic and environmental factors in colorectal carcinogenesis

Zimbalist, E H; Plumer, A R
The molecular genetic mechanisms of colorectal cancer are among the best understood of any common cancer. Recent research has identified mutated tumor suppressor genes and oncogenes as normal tissue progresses from benign to malignant, and the novel mismatch repair genes involved in a specific form of hereditary colorectal cancer as well as a significant percentage of sporadic cases. This information has led to a better understanding of the inheritance of large bowel cancer, as well as a model of tumorigenesis which proposes a multistep process as colonic epithelial cells progress from their normal state through successive stages of adenoma to malignancy. Exogenous factors such as fiber and fat are important modifiers of inherited risk. Dietary factors may influence the carcinogenic process by modifying intestinal transit time, altering the flow and recycling of bile, or changing the intestinal bacterial flora composition. A number of studies have also suggested the modulation of risk in both hereditary syndromes and sporadic cases with certain micronutrients or medications like nonsteroidal anti-inflammatories.
PMID: 8590523
ISSN: 0257-2753
CID: 1893932

Paromomycin-associated pancreatitis in HIV-related cryptosporidiosis [Case Report]

Tan, W W; Chapnick, E K; Abter, E I; Haddad, S; Zimbalist, E H; Lutwick, L I
OBJECTIVE: To report a case of pancreatitis related to paromomycin administration. CASE SUMMARY: A 39-year-old man with AIDS developed pancreatitis concurrent with successful treatment of intestinal cryptosporidiosis with paromomycin. The hyperamylasemia resolved with discontinuation of the agent and recurred when paromomycin treatment was reinstituted. DISCUSSION: To our knowledge, this is the first reported case of pancreatitis believed to be induced by paromomycin. Although pancreatitis in HIV-infected patients has multiple causes, the nature of this case suggests the involvement of paromomycin. The mechanism of action is unclear. CONCLUSIONS: Pancreatitis should be considered in the differential diagnosis of abdominal pain in patients who are treated with paromomycin.
PMID: 7711341
ISSN: 1060-0280
CID: 1893942

Expansion of the epithelial cell proliferative compartment and frequency of adenomatous polyps in the colon correlate with the strength of family history of colorectal cancer

Gerdes H; Gillin JS; Zimbalist E; Urmacher C; Lipkin M; Winawer SJ
Expansion of the proliferative compartment of epithelial cells in colonic crypts and colonic adenomas have been described as phenotypic precursors to colon cancer in individuals affected with hereditary or sporadic colon cancer. This study measured the size of the proliferative compartment in colonic crypts and the frequency of adenomas in asymptomatic members of families having sporadic colorectal cancer. The subjects were divided into 2 groups according to the frequency of colorectal cancer in their families. A shift of the compartment of proliferating epithelial cells toward the lumenal surface of colonic crypts was seen in the group of subjects with a stronger family history of colorectal cancer, with significant differences in the numbers of proliferative cells in the upper and the lower crypt compartments (P < 0.05) and in the fraction of proliferative cells at the highest compartment at the lumenal surface of the crypts (P < 0.05). Cell proliferation patterns in normal-appearing mucosa of the 2 groups revealed no difference in whole crypt [3H]thymidine labeling index. Colonoscopic examination of the 56 subjects revealed an overall prevalence of adenomas of 21%; when stratified by frequency of colorectal cancer in their families, 3 of 22 subjects (14%) with a weaker family history had adenomas, while 9 of 34 (26%) with a stronger family history had adenomas. Thus, parallel abnormalities of colonic epithelial cell proliferation and neoplasia were seen in individuals with a family history of colorectal cancer, both of which were more pronounced with increasing strength of family history. This observation provides further evidence of relationships among these factors in the etiology of 'sporadic' colorectal cancer
PMID: 8417821
ISSN: 0008-5472
CID: 36490

Decreased intrinsic factor secretion in AIDS: relation to parietal cell acid secretory capacity and vitamin B12 malabsorption

Herzlich, B C; Schiano, T D; Moussa, Z; Zimbalist, E; Panagopoulos, G; Ast, A; Nawabi, I
AIDS-associated gastric secretory failure has been characterized by decreased secretion of acid, pepsin, and gastric juice volume. To determine whether decreased intrinsic factor secretion and vitamin B12 malabsorption occur in this entity, we performed prospective measurements of maximal acid output, intrinsic factor output, vitamin B12 absorption, serum vitamin B12, and holotranscobalamin II in 10 consecutive AIDS patients. Four of 10 patients had low maximal acid output, i.e., < or = 1.5 mEq/h (control = 12.8 +/- 9.0, range 2.5-25 mEq/h). Four patients had low intrinsic factor output, i.e., < or = 1.1 microgram/h (control = 8.2 +/- 6.9, range 3.1-19.4 micrograms/h). One patient with low intrinsic factor output had low serum vitamin B12 and a Schilling test consistent with pernicious anemia. A second patient with very low intrinsic factor output (0.16 micrograms/h) had low parts I and II Schilling tests; malabsorption most likely resulted from both low intrinsic factor secretion and ileal disease. One of three vitamin B12 malabsorbing patients, with normal serum vitamin B12, had low holotranscobalamin II, 25 pg/ml (control holotranscobalamin II = 76 +/- 44, range 44-152 pg/ml). Maximal acid output and intrinsic factor output did not correlate in AIDS (r = 0.36, p = 0.30) in contrast to the expected correlation in controls (r = 0.91, p = 0.03). We conclude that low intrinsic factor secretion is common in AIDS and contributes to vitamin B12 malabsorption. Decreased parietal cell secretion of intrinsic factor and acid may occur independently in human immunodeficiency virus-associated gastric secretory failure. Low holotranscobalamin II, an early manifestation of vitamin B12 malabsorption, results in decreased delivery to vitamin B12-dependent tissues prior to depletion of serum vitamin B12. Regular supplementation with vitamin B12 may therefore be warranted in patients with advanced HIV infection.
PMID: 1449141
ISSN: 0002-9270
CID: 1893922

Is trimethoprim-sulfamethoxazole helpful in Crohn's disease? [Letter]

Gradon, J D; Zimbalist, E H
PMID: 1977794
ISSN: 0192-0790
CID: 1893952

Chronic pancreatitis and pseudocyst formation secondary to carcinoid tumor of the pancreas [Case Report]

Gettenberg, G; Zimbalist, E; Marini, C
The incidence of chronic pancreatitis has been increasing in the western world. Although chronic alcohol abuse accounts for 90% of adult cases, the physician must be aware of the multiplicity of causes for chronic pancreatitis. We present a case of obstruction of the pancreatic duct and chronic pancreatitis caused by a primary carcinoid tumor.
PMID: 3350292
ISSN: 0016-5085
CID: 1893962

Ileocolonic schistosomiasis presenting as lymphoma [Case Report]

Zimbalist, E; Gettenberg, G; Brejt, H
The blood flukes of the genus Schistosome have a wide geographic distribution. Schistosoma japonicum is found in the Far East while Schistosoma mansoni is found in Africa, South America, the Middle East, and the Carribean. There are numerous other species of Schistosome; however, japonicum, mansoni, and hematobium account for the majority of human disease. Infection of the gastrointestinal tract is not uncommon in the United States. Recognition of this disease is important for appropriate medical therapy and avoidance of unnecessary surgery. A case of schistosomiasis simulating small bowel lymphoma is presented and salient features of this infection are reviewed.
PMID: 3107371
ISSN: 0002-9270
CID: 1893972

Outpatient management of esophageal cancer with endoscopic Nd:YAG laser

Lightdale, C J; Zimbalist, E; Winawer, S J
In 50 inoperable patients with advanced malignant obstruction of the esophagus, endoscopic Nd:YAG laser treatment was used for palliation of dysphagia. In 30 of these patients, treatment was carried out entirely in an outpatient setting, providing more time at home and saving costs of hospitalization. Most patients had received prior radiation and chemotherapy. All were unable to swallow solid food; 16 had difficulty with liquids. Palliation was achieved in 69% allowing patients to eat a nearly normal diet. Therapy was least successful in cancers involving the cervical esophagus, in cancers more than 8 cm in length, and in cancers that were primarily infiltrating or extraluminal. Epidermoid carcinomas and adenocarcinomas were effectively treated, except for adenocarcinomas of the gastric cardia, which tended to be infiltrating. There were two serious but nonfatal complications, one perforation and one episode of bleeding, directly attributable to Nd:YAG laser therapy. An esophageal dilation prior to endoscopic Nd:YAG laser treatment facilitated outpatient management.
PMID: 2432776
ISSN: 0002-9270
CID: 1893982