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Gastrointestinal malignancies in Crohn's disease. A 20-year experience.

The relationship between gastrointestinal neoplasms and Crohn's disease is poorly defined. The purpose of this study was to characterize the features of gastrointestinal malignancies that developed in Crohn's patients. In this retrospective review the authors identified six patients with Crohn's disease who developed such lesions over a 20-year period: four patients had colorectal cancers and two had ileal malignant neoplasms. Patients averaged 52.7 years of age (range, 21 to 61 years). Three patients were men and three women. Five of the six patients had endured Crohn's disease for more than 20 years. Only two lesions were diagnosed before surgery. The colorectal lesions were predominantly right-sided and all occurred in bowel segments with active Crohn's disease. The lesions demonstrated aggressive histologic features: three of six tumors were poorly differentiated, one of the five adenocarcinomas was mucinous, and three of the colorectal cancers were Dukes' B or C lesions. Four of six patients survived five or more years. There was a single malignant carcinoid, which represents the seventh case report of a carcinoid tumor occurring in a patient with Crohn's disease. This study indicates that patients with Crohn's disease develop a wide variety of small bowel and colorectal cancers. Furthermore, it suggests that Crohn's patients with colonic disease should periodically undergo surveillance colonoscopy.

Adenocarcinoma↗

[Clinical evaluation of the efficacy of the combined determination of serum markers CEA, CA 19.9, CA 72.4 as indexes of gastro-intestinal tract neoplasms].

The aim of our study was to evaluate the usefulness of the tumor markers CA 72.4, CEA and CA 19.9 in the monitoring of gastrointestinal carcinomas. Our experience demonstrated the usefulness of the determination of CA 72.4 in the follow up of patients with gastrointestinal neoplasms.

Antigens, Tumor-Associated, Carbohydrate↗

Small bowel tumours: a diagnostic challenge.

In a 20-year retrospective study of 43 patients having surgery for small bowel neoplasia in a district general hospital, the commonest pathologies were lymphoma (12), carcinoid (12) and adenocarcinoma (11). Malignant neoplasms occurred in 38 patients presenting on average at 68 years of age. In 4 patients a synchronous gastrointestinal neoplasm was found. The average duration of symptoms was 11 weeks for operated patients. In 31 patients the presentation was as a surgical emergency. Only 10 had imaging investigations prior to emergency presentation from which diagnostic information was obtained in 1 patient and helpful information in a further 4. The 5-year survival figures of patients with small bowel neoplasia were carcinoid (50%), lymphoma (27%) and adenocarcinoma (15%), reflecting the poor prognosis of these patients even after 'curative resection'. Patients with carcinoid tumours were the exception, as long-term survival was not unusual even without complete resection of all macroscopic disease.

Adenocarcinoma↗

Selective IgA deficiency and neoplasia.

From the Immunodeficiency Cancer Registry, it has appeared that there is an increasing frequency of neoplasia in individuals who have a selective absence of serum IgA. Approaching this question from another point of view, we have found that of 4,120 sera drawn in this cancer-oriented hospital, 12 sera had a total absence of IgA and 3 additional sera had less than 10 mg/dl. The incidence of IgA deficiency in a cancer hospital is thus 1 : 342 or 1 : 273, which is statistically similar to that previously found for other patient groups studied in the USA (average of two studies, 1 : 418), but it is substatistically increased over the incidence of IgA deficiency found in normal blood donors (average of five studies 1 : 1,677). Analysis of these sera by diagnostic categories showed that of 1,517 sera of patients with lymphoproliferative disorders, 6 were IgA deficient (frequency 1 : 253), and of 249 sera of patients with gastrointestinal neoplasm, 2 were IgA deficient (frequency 1 : 125). We conclude that, in the absence of IgA, certain organ systems, the gastrointestinal and lymphoid tissue may be at increased risk for malignant change and that the protective, anti-neoplastic role of IgA requires investigation.

Adult↗

Intestinal intraepithelial lymphocytes and lymphoepithelial interactions in the human gastrointestinal mucosa.

Although representing a major immunological apparatus, it is not known how the immune system of the intestinal mucosa differentiates between dietary antigens (resulting in systemic tolerance) and potential pathogens. It is thought that intraepithelial T lymphocytes (IEL) may play a central role in local intestinal immunity and are likely to be important in immunity to gastrointestinal neoplasms and rejection responses to gut allografts. However, the biology of IEL and their unusual immunological microenvironments in the gastrointestinal mucosa are little understood. IEL are predominantly CD8+ TcR alpha beta+ CD3+ T cells which differ from lamina propria and peripheral T cells in many respects. IEL show low expression of CD5, CD6, LFA-1 (CD11a/CD18) and VLA-4, and high expression of HML-1. TcR gamma delta + IEL, although a minority population, are also phenotypically distinct, insofar as they are 50% CD8+, mainly V delta 1+ V gamma 9- and CD4- CD5-. IEL show poor proliferative responses to PHA, anti-CD3 and phorbol ester/calcium ionophore in vitro and have no clear functional role: they neither provide helper nor suppressor functions for Ig synthesis by B cells and do not mediate spontaneous cytotoxicity. However, there is evidence that IEL show preferential activation in response to sheep erythrocytes, presumably signalling via CD2. As normal and inflamed intestinal epithelia do not express ICAM-1, it seems unlikely that the LFA-1/ICAM-1 interaction is of importance to IEL activation. Rather, the CD2 (LFA-2) interaction with LFA-3 expressed by enterocytes may serve both to anchor IEL and to provide an accessory stimulus for activation. Nevertheless, the questions of antigenic specificity and immunological role remain unanswered.

Antigen-Presenting Cells↗

A modified inflammatory bowel disease questionnaire and the Vaizey Incontinence questionnaire are more sensitive measures of acute gastrointestinal toxicity during pelvic radiotherapy than RTOG grading.

PURPOSE: Simple scales with greater sensitivity than Radiation Therapy Oncology Group (RTOG) grading to detect acute gastrointestinal toxicity during pelvic radiotherapy, could be clinically useful. METHODS AND MATERIALS: Do questionnaires used in benign gastrointestinal diseases detect toxicity in patients undergoing radiotherapy? The patient-completed Inflammatory Bowel Disease (IBDQ) and Vaizey Incontinence questionnaires were compared prospectively at baseline and at Week 5 to physician-completed RTOG grading. RESULTS: A total of 107 patients, median age 63 years, were recruited. After 5 weeks of treatment, patients with gynecologic and gastrointestinal cancer were more symptomatic than urologic patients (p = 0.012; p = 0.014). Overall, 94% had altered bowel habits, 80% loose stool, 74% frequency, 65% difficult gas, 60% pain, >48% distress, 44% tenesmus, >40% restrictions in daily activity, 39% urgency, 37% fecal incontinence, and 40% required antidiarrheal medication. The median RTOG score was 1 (range, 0-2), median IBDQ score 204.5 (range, 74-224), and median Vaizey score 5 (range, 0-20). Chemotherapy preceding radiotherapy increased fecal incontinence (p = 0.002). RTOG scores stabilized after 3 weeks, IBDQ scores peaked at Week 4, and Vaizey scores worsened throughout treatment. IBDQ and Vaizey scores distinguished between groups with different RTOG scores. CONCLUSION: The IBDQ and Vaizey questionnaires are reliable and sensitive, offering greater insight into the severity and range of symptoms compared with RTOG grading.

Adult↗

From gene mutations to tumours--stem cells in gastrointestinal carcinogenesis.

Stem cells share many properties with malignant cells, such as the ability to self-renew and proliferate. Cancer is believed to be a disease of stem cells. The gastrointestinal tract has high cancer prevalence partly because of rapid epithelial cell turnover and exposure to dietary toxins. The molecular pathways of carcinogenesis differ according to the tissue. Work on hereditary cancer syndromes including familial adenomatous polyposis (FAP) has led to advances in our understanding of the events that occur in tumour development from a gastrointestinal stem cell. The initial mutation involved in the adenoma-carcinoma sequence is in the 'gatekeeper' tumour-suppressor gene adenomatous polyposis coli (APC). Somatic hits in this gene are non-random in FAP, with the type of mutation selected for by the position of the germline mutation. In the stomach, a metaplasia-dysplasia sequence occurs and is often related to Helicobacter pylori infection. Clonal expansion of mutated cells occurs by niche succession. Further expansion of the aberrant clone then occurs by the longitudinal division of crypts into two daughter units--crypt fission. Two theories seek to explain the early development of adenomas--the 'top down' and 'bottom up' hypotheses. Initial studies suggested that colorectal tumours were monoclonal; however, later work on chimeric mice and a sex chromosome mixoploid patient with FAP suggested that up to 76% of early adenomas were polyclonal. Introduction of a homozygous resistance allele has reduced tumour multiplicity in the mouse and has been used to rule out random collision of polyps as the cause of these observations. It is likely that short-range interaction between adjacent initiated crypts is responsible for polyclonality.

Animals↗

Gastric cancer and pernicious anemia appearing as pseudoachalasia.

An elderly black man was admitted to our institution with macrocytic anemia, dysphagia, and significant weight loss. Results of an esophagogram were suggestive of achalasia. Gastric adenocarcinoma infiltrating the gastric cardia was seen on gastroscopy. The mode of presentation of gastric cancer in this case has not been previously reported in association with pernicious anemia. Patients with pernicious anemia are at higher risk of having gastrointestinal neoplasms than is the general population. We review the current literature and address the controversy concerning the need to subject patients with pernicious anemia to surveillance with upper gastrointestinal endoscopy.

Adenocarcinoma↗

Gastrointestinal stromal tumors (GIST).

BACKGROUND/AIMS: Gastrointestinal stromal tumors (GIST) are the most frequent non-epithelial tumors of the alimentary tract. The interstitial cells of Cajal or more primitive progenitor mesenchymal cells are suggested as their cells of origin. GIST's occur throughout the gastrointestinal tract but are generally located in the stomach and the intestine. About 70% of GIST's are immunohistochemically positive for CD34 and more than 90% for c-kit protein (CD117). About two thirds of GIST's are malignant. The tumor size, mitotic rate, cellularity and nuclear pleomorphism are the most important parameters characterizing the biological behavior of tumors. The diagnostic procedures are similar to those of other gastrointestinal neoplasms but only a half of the patients will have correct preoperative histological diagnosis. GIST's can be cured only by surgery. The procedure of choice, if possible, is resection without extended lymphadenectomy. Radiation and chemotherapy are generally ineffective. METHODOLOGY: 22 patients were operated on for GISTs in our department between 1996 and 2003. RESULTS: All but one proved to be benign. The patients were all asymptomatic after the operation except the malignant case. In his case an irresectable local recurrence developed later. CONCLUSIONS: GIST is a rare neoplasm of the GI tract. The only possibility for treatment of GISTs is surgical removal.

Adult↗

Non-life-threatening sepsis: report of two cases.

Streptococcus bovis is one of the nonenterococcal species included among the streptococci group D. It is part of the normal bowel flora in humans and animals, but it is also responsible for infectious diseases (10-15% of all cases of bacterial endocarditis). Many cases of bacteremia and metastatic abscesses (spleen, liver, soft tissues, bone, meninges, endocardium) caused by S. bovis were reported as associated with digestive tract diseases, mainly colonic disease, and, in particular colonic neoplasms, or chronic liver diseases. A role in carcinogenesis has been suggested for this microorganism. The authors report two cases of S. bovis sepsis, one associated with colonic neoplasm and the other with liver cirrhosis and gastric carcinoma. Discussion is focused on probable mechanisms that favor gastric colonization and systemic diffusion of S. bovis from the gut in patients with gastrointestinal neoplasms or chronic liver disease and provides clinical recommendations for patients with S. bovis infections.

Adenocarcinoma↗

A case report of a spontaneous gastrointestinal stromal tumor (GIST) occurring in a F344 rat.

We report a case of gastrointestinal stromal tumor (GIST) that developed in a male F344 rat at week 101 of an experiment in a carcinogenicity study. Macroscopically, the primary tumor, which measured 1 cm in diameter, involved the submucosal tissue of the forestomach at the lesser curvature extending to the glandular stomach and esophagus. Histopathologically, the tumor was composed of neoplastic cells with small- to medium-sized spindle-shaped single nuclei and fibrillary cytoplasm lacking distinct cell borders. It invaded extensively into the tunica muscularis and subserosa, further extending to the lamina propria mucosa and serosal surface. A few densely proliferating portions showed a tendency to storiform pattern. Metastatic tumor nodules were found in the liver, spleen, and femur bone marrow, with multiple nodules, up to 1 cm in diameter, apparent in the liver. Immunohistochemically, diffuse, but weak cytoplasmic immunoreactivity for KIT was evident, and most neoplastic cells also exhibited strong immunoreactivity for a -smooth muscle actin and vimentin. Sparse nuclear S-100-immunoreactive cells were further observed, but none of neoplastic cells were immunoreactive for CD34, caldesmon, desmin, cytokeratin, or synaptophysin. Collectively, these features meet the criteria for a GIST, with limited potential for differentiation to smooth muscle and neural cells.

Actins↗

Small bowel tumors: diagnosis, therapy and prognostic factors.

BACKGROUND: Tumors of the small bowel are rare, accounting for about 3-6% of all gastrointestinal neoplasms. However, diagnosis and treatment are difficult and an ongoing challenge. METHODS: We retrospectively reviewed the medical records of 54 patients with tumors of the small intestine over a period of 10 years to elucidate important factors for diagnosis, therapy and prognosis. RESULTS: 42 patients had malignant (36 primary, 6 secondary) and 12 had benign tumors. Histologically, adenocarcinoma (33%), leiomyosarcoma (17%) and carcinoid (17%) were the most frequent malignancies found. All 12 benign lesions were either leiomyomas or adenomas. Initial symptoms were nonspecific: abdominal pain in 67% and 50%, anemia in 38% and 58% and weight loss in 38% and 42% in patients with malignant and benign tumors, respectively. Upper gastrointestinal series, endoscopy, computed tomography scan and selective angiography were the most useful diagnostic tools. Resectability rate for malignant tumors was 98%; curative resection was achieved in 51%. Survival for malignant tumors has been poor: median postoperative survival was 26.9 months, the 1- and 5-year survival rates were 42.9% and 20.8%, respectively. CONCLUSIONS: These results document the need for an aggressive diagnostic work-up in these rare tumors with non-specific symptoms, as early diagnosis and radical operative therapy are important prognostic factors.

Abdominal Pain↗

Serum alpha-fetoprotein in patients with neoplasms of the gastrointestinal tract.

Serum alpha-fetoprotein levels were measured by a sensitive double-antibody radioimmunoassay in 580 patients with a variety of malignant and nonmalignant gastrointestinal diseases to determine the incidence of levels elevated above 40 ng/ml. Over 200 normal control subjects have all had levels below 40 ng/ml. Fifteen % of 95 patients with gastric carcinoma, 3 percent of 191 patients with colorectal carcinoma, 24 percent of 45 patients with pancreatic carcinoma, 25 percent of 8 patients with biliary tract carcinoma, and 70 percent of 73 patients with hepatocellular carcinoma had elevated serum alpha-fetoprotein. None of 14 patients with esophageal or small bowel carcinoma had elevated levels. In contrast, 1 percent of 154 patients with nonmalignant, nonhepatic gastrointestinal disease had elevations of serum alpha-fetoprotein. Alpha-Fetoprotein appears to be a potential marker for tumor activity in some patients with certain gastrointestinal cancers.

Adult↗

Gastrointestinal stromal tumours: etiology, pathology and clinical management.

Investigation of the regulation of cell growth, differentiation and death by signalling pathways has led to a greater understanding of how alterations in these pathways play a critical role in the development of some cancers, and has opened new opportunities for their treatment. In the present review, results with the prototype drug of this class, imatinib (Gleevec, Glivec [formerly STI571]; Novartis, Switzerland), in metastatic gastrointestinal stromal tumours are presented. The present review originated from a conference of the authors held in Montreal, Quebec in June 2003, under the sponsorship of Novartis.

Antineoplastic Agents↗

Fruit and vegetables, and human cancer.

A large body of evidence indicates that high intakes of fruit and vegetables are associated with a reduced risk of cancer at several sites. The association is generally most marked for epithelial cancers, apparently stronger for those of the digestive and respiratory tracts, and somewhat weaker for hormone-related cancers. The relationship between frequency of consumption of vegetables and fruit and cancer risk was analysed using data from a series of case-control studies conducted in northern Italy since 1983. The relative risks (RRs) for most common neoplasms ranged from 0.2 to 0.5 for the highest compared with the lowest tertile of vegetable intake. Protective effects were highest for epithelial neoplasms, but were also observed for hormone-related neoplasms. Fruit was related to reduced RRs for cancers of the oral cavity and pharynx, oesophagus, stomach, larynx, as well as of the urinary tract. There was a specific and consistent pattern of protection by tomatoes, a typical Mediterranean food, with RRs between 0.4 and 0.7, most notably for gastrointestinal neoplasms. No significant association was observed between fruit and vegetable consumption and non-epithelial lymphoid neoplasms. For digestive tract cancer, population attributable risks for low intake of fresh vegetables and fruit ranged from 15 to 40% of all cases in this Mediterranean population. Combined with tobacco and alcohol, the population attributable risks exceeded 85% for men and 55% for women for upper digestive and respiratory tract neoplasms. Thus, from a public health viewpoint, epidemiological evidence indicates that a substantial reduction in epithelial cancer risk can be obtained by increasing fruit and vegetable consumption.

Alcohol Drinking↗