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In vitro generation of tumour-specific lymphocyte reactivity to colonic carcinoma cells. Comparison with normal colonic mucosa cells.

Purified tumour cells and normal mucosa cells from fresh human colorectal cancer resection specimens, and T-cell-enriched autologous peripheral blood lymphocytes, were mixed in short-term (6 day) mixed lymphocyte-tumour cell (MLTC) microcultures. Lymphocyte stimulation was measured by 3H-thymidine uptake, and a stimulation index (SI = [lymphocytes vs tumour cells (cpm)-tumour cells (cpm)]/[lymphocytes (cpm)] greater than 3 was regarded as significant. Significant lymphocyte reactivity was found in 10/15 patients with colon carcinoma. However, 1 patient with autologous tumour reactivity, also showed significant stimulation against autologous normal mucosa cells, suggesting tumour-associated reactivity. Maximum stimulation occurred most frequently at a lymphocyte:tumour cell ratio of 2:1 and with nylon wool-passaged lymphocytes.

Adenocarcinoma↗

Investigation of colonic prostaglandins in carcinogenesis in the rat colon.

Large bowel carcinoma was induced in rats by injecting MNNG intrarectally, and changes in the large bowel mucosa prostaglandin (PG) with time were determined. The PGE2 levels of the colonic mucosa in a control group were 20.9 +/- 9.7 (pg/mg total protein) at 5 weeks, 25.5 +/- 9.7 at 10 weeks, 26.5 +/- 18.1 at 20 weeks, and 34.8 +/- 12.7 at 40 weeks. The PGE2 levels in the MNNG-treated group were 44.7 +/- 6.2 at 5 weeks, 43.1 +/- 14.9 at 10 weeks, 70.1 +/- 23.4 at 20 weeks, and 79.7 +/- 54.1 at 40 weeks. The intrinsic PGE2 levels of the noncancerous mucosa were thus significantly higher for the MNNG group than for the control group at all weeks. At 40 weeks, the PGE2 levels of cancer lesions were significantly high compared with those of the noncancerous area. In the cancerous lesions, 6-keto-PGF1 alpha and PGF2 alpha decreased and TXB2 increased significantly at 40 weeks. The observations demonstrated that PGE2 was implicated as a promoter in the development and proliferation of carcinoma in MNNG-induced large bowel carcinogenesis in rats.

Animals↗

Comparison of the rigid sigmoidoscope and the flexible sigmoidoscope in conjunction with colon x-ray for detection of lesions of the colon and rectum.

A series of 1007 patients was randomly divided into two groups, one a group of 499 patients who underwent rigid sigmoidoscopy and the other a group of 508 patients who had flexible sigmoidoscopy. Contrast barium enema studies were subsequently performed in all patients. Eighteen per cent of the patients had a neoplasm. We concluded that, given the amount of colon surveyed by rigid and flexible sigmoidoscopy in conjunction with contrast barium enema, there was no difference in the rate of detection between the two endoscopic techniques.

Barium Sulfate↗

[Colon cancer: a rare complication in a colonic esophageal segment after coloesophagoplasty].

We report the case of a 65-year-old woman who presented to the Hermanos Ameijeiras Hospital in Cuba due to dysphagia for the previous 5 months. Forty years previously, she had undergone esophagocoloplasty for caustic esophagitis. Adenocarcinoma was diagnosed in the colonic interposition. The tumor was resected with oncologic margins and food transit was successfully restored.

Adenocarcinoma, Papillary↗

Prospective determination of distal colon findings in average-risk patients with proximal colon cancer.

BACKGROUND: Recent guidelines indicate that colonoscopy and sigmoidoscopy are both acceptable options for screening average-risk patients for colorectal cancer. Retrospective studies have found that a majority of patients with cancer proximal to the splenic flexure have a normal screening flexible sigmoidoscopy. METHODS: This was a multicenter, prospective description of colonoscopic findings and family history in consecutive patients with proximal colon cancer. RESULTS: Among 116 prospectively identified average-risk patients with cancer proximal to the splenic flexure, 40 (34.5%) had neoplasia distal to the splenic flexure. The prevalence of patients with adenomas greater than or equal to 1 cm, with only one tubular adenoma less than 1 cm, and with only hyperplastic polyps were 16.4%, 8.6%, and 6.9%, respectively. CONCLUSIONS: Most average-risk patients with cancer proximal to the splenic flexure will have a normal screening flexible sigmoidoscopy. These patients have an unexpectedly high prevalence of large distal adenomas, but the prevalence of both single small tubular adenomas and hyperplastic polyps alone is similar to that expected during screening of the general population. Clinicians and payers should continue to seek methods to improve the cost-effectiveness and availability of screening colonoscopy in average-risk persons.

Adenocarcinoma↗

Effects of cyclic-nucleotide derivatives on the growth of human colonic carcinoma xenografts and on cell production in the rat colonic crypt epithelium.

Previous studies have shown that various amine hormones are able to influence the growth rate of human colorectal carcinomas propagated as xenografts in immune-deprived mice, and it is now well known that the effects of many amine and other hormones are mediated by cyclic nucleotides, acting as second messengers within cells. In the present study the influence of various derivatives of cyclic adenosine monophosphate and cyclic guanosine monophosphate on the growth of two different lines of colorectal cancer growing in immune-deprived mice, and on the cell production rate in the colonic crypt epithelium of the rat, was assessed. Growth of each tumour line, as well as crypt-cell production, was suppressed by treatment wit N6O2' dibutyryl and N6 monobutyryl derivatives of cyclic adenosine monophosphate. Dibutyryl cyclic guanosine monophosphate, on the other hand, was found to promote the growth of Tumour HXK4 and to promote crypt cell production, but to have no significant effect on Tumour HXM2.

Adenocarcinoma↗

Aorto-colonic fistula as a late complication of colon interposition for oesophageal atresia.

A 22-year-old man developed severe haematemesis 21 years after colon interposition for long-gap oesophageal atresia. A fistula, from an anastomotic ulcer to the descending thoracic aorta, was discovered and treated successfully by surgical resection. This previously unreported complication highlights the need for the prevention of peptic complications following oesophageal replacement in children.

Adult↗

Adjuvant chemotherapy in the treatment of colon cancer: randomized multicenter trial of the Italian National Intergroup of Adjuvant Chemotherapy in Colon Cancer (INTACC).

BACKGROUND: To determine whether the addition of leucovorin to the combination 5-fluorouracil plus levamisole prolongs disease-free survival and overall survival in patients with radically resected colon cancer (Dukes' B(2-3) and C). PATIENTS AND METHODS: Patients (1703) were accrued between March 1992 and February 1995 in a large-scale clinical trial within five Italian cooperative groups. After stratification for center, patients were randomized as follows: arm A, 5-fluorouracil [450 mg/m(2) intravenous (i.v.) bolus on days 1-5] and levamisole (150 mg orally for 3 days, every 14 days for 6 months) versus arm B, 6-S-leucovorin (100 mg/m(2) i.v. bolus on days 1-5) followed by 5-fluorouracil (370 mg/m(2) i.v. bolus on days 1-5), plus levamisole (as arm A), every 4 weeks for six cycles. RESULTS: After a median follow-up of 6.4 years no significant difference was seen for either disease-free survival (58% versus 60%, not significant) or 5-year overall survival (68% versus 71%, not significant), respectively. Gastrointestinal toxicity (World Health Organization grade 3/4) was more frequent in arm B (8% versus 18%, not significant). CONCLUSIONS: In this trial the schedules used showed no statistically significant differences in terms of disease-free survival or overall survival in the treatment of colorectal cancer.

Adult↗

Prolonged ambulatory small intestinal and colonic motility monitoring: potential in irritable bowel syndrome--first report of prolonged ambulatory oesophageal, small intestinal and colonic motility in the same patient.

Irritable bowel syndrome (IBS), which affects up to 25% of the population in western countries and accounts for up to 50% of referrals to gastroenterologist, remains mainly a diagnosis of exclusion. We have studied, for the first time, prolonged ambulatory motility recordings from the oesophagus, small intestine and colon of a patient who was referred to us with a 12-year history of abdominal pain and a presumptive diagnosis of IBS. The results indicated that the diagnosis was pseudo-obstruction syndrome rather than IBS. Wider clinical use of the new techniques of prolonged ambulatory intestinal motility monitoring in IBS would offer considerable potential not only in achieving a greater understanding of its pathophysiology but also in providing a more precise definition of clinical and therapeutic subgroups.

Colon↗

Calcium and vitamin D modulate mouse colon epithelial proliferation and growth characteristics of a human colon tumor cell line.

The role of calcium and vitamin D in the prevention of colorectal cancer is only now being investigated at the organismal, cellular, and molecular biologic levels. Recent epidemiologic studies have supported the hypothesis that dietary calcium and vitamin D may be related to a reduced risk for colon cancer. The evidence from laboratory investigations in animals and in cell culture also indicate a possible preventative effect. Addition of calcium and vitamin D to the roster of developmental cancer chemopreventative agents for further research is warranted.

Animals↗

Expression of gelatinase-A (MMP-2) in human colon cancer and normal colon mucosa.

Proteolytic enzymes, such as type IV collagenases (MMP-2 gelatinase A, 72-kD type IV collagenase and MMP-9 gelatinase B, 92-kD type IV collagenase) play an important role in tumor invasion and metastasis. In the present study the levels of MMP-2 antigenic concentration and immunohistochemical staining were compared in paired colorectal tumor (n = 64) and background colon tissue of the same patients with clinical and pathological staging. The antigenic concentrations were found to be statistically significantly higher in cancer tissue (mean 11.29 ng/mg protein) than in corresponding normal mucosa (10.23 ng/mg protein) (p = 0.008). There was also a positive correlation between MMP-2 antigenic concentration and clinicopathologic parameters such as grade (p < 0.001) and Dukes' stage (p = 0.001), but not with lymph node involvement. Immunohistological localization of MMP-2 was observed in tumor as well as in stromal cells. Staining intensity increased from adenoma to adenocarcinoma. The degree of staining was associated with grade (p < 0.001), Dukes' stage (p < 0.001) and lymph node involvement (p < 0.001).

Adenocarcinoma↗

Histological and histochemical changes in the colon mucosa after ureterosigmoidostomy or colonic conduit.

A study was made of 22 patients previously subjected to urinary diversion, 12 with ureterosigmoidostomy and 10 with colon conduit. The histological and histochemical examination of biopsies of intestinal mucosa near to and far from the ureteral orifices showed transformations with considerable inflammatory infiltration, variations in the composition of the acid mucins with a prevalence of sialomucins, lengthening and branching of the glandular crypts, and sometimes dysplasias of the epithelium. These structural modifications are typical of transitional mucosa. Transitional mucosa might reflect an aspecific reaction of the intestinal mucosa or alternatively it might signify a precancerous condition. Its presence in intestinal diversions suggests the advisability of careful follow-up in all patients subjected to this operation.

Aged↗

Demonstration of altered cellular DNA content distribution in long-term colon epithelial cell lines with colon cancer genotypes.

During prolonged culture (7-40 passages assayed) DNA distribution was constant in IVT-negative lines with FPC genotype and in IVT-negative lines without any known colon cancer genotype, whereas the DNA histograms of the IVT-positive lines with HNPCC genotype showed a marked change. The DNA index (DI) of greater than 1 increased sixfold in the HNPCC-A (affected) line and threefold in the HNPCC-AR (at-risk) line due to an equal increase in DI of 2 and DI of greater than 2. It is proposed that there is a possible association between the HNPCC genotype, the presence of IVT, and the marked increase in both DI of 2 and DI of greater than 2 in DNA histograms, since neither the lines with normal nor those with FPC genotypes showed these changes. The biological significance of IVT might be due to its influence on the constancy of the distribution of cellular DNA content, leading to aneuploidy, which has been known to precede in vitro tumorigenic phenotypes.

Adolescent↗

Persistence of gene expression changes in noninflamed and inflamed colonic mucosa in ulcerative colitis and their presence in colonic carcinoma.

AIM: A few studies have applied genomic-wide gene expression analysis in inflamed colon tissue sample in ulcerative colitis (UC). We reported the first study of non-inflamed mucosal gene expression in UC and explored its clinical implication. METHODS: Non-inflamed mucosa was obtained from 6 UC patients who received total colectomy. The gene expression of UC in noninflamed mucosa was monitored with a microarray. For a selected gene, RT-PCR was performed to verify array results and to further examine expression pattern in inflamed mucosa of UC, colorectal cancer tissue and normal mucosa using additional matched pairs. RESULTS: Two genes showing 2.5-fold decreased expression with significance set at in UC samples were homeo box a4 (HOXa4) and mads box transcription enhancer factor 2, polypeptide B (MEF2b). RT-PCR showed that MEF2b expression in non-inflamed mucosa was significantly downregulated, whereas the expression of MEF2b increased in accordance with the severity of mucosal inflammation. HOXa4 expression both in inflamed and non-inflamed mucosa in UC was consistently downregulated, and the downregulation of HOXa4 was also found in colorectal carcinoma. CONCLUSION: It is suggested that the MEF2b expression in UC which increase in accordance with inflammation may be induced by the inflammatory mediator. In contrast the downregulation of HOXa4 may be partly involved in the pathogenesis of disease including UC and UC-related carcinogenesis.

Adult↗

Acute colon diverticulitis in multiple myeloma patient: an unusual presentation of a colonic perforation. Case report.

This case report describes an acute colonic diverticular perforation occurred to a multiple myeloma patient, taking corticosteroid and morphine therapy, revealed by a subcutaneous emphysema of upper chest and right abdomen as initial presentation. Sigmoid diverticulitis with perforation and generalized peritonitis is a severe complication of the diverticular disease and it is due to diverticular microperforation. This condition occurs more frequently in patients with widespread diverticolosis and usually after 50 years of age, and the frequency of related complications increases with age (and with the use of corticosteroids). Extraperitoneal air from the sigmoid-rectum perforation can escape diffusing superiorly though paravertebral retroperitoneal tissues and via the diaphragmatic iatus into the mediastinum, producing pneumomediastinum and it diffuses to yield superior thoracic emphysema. This report suggests that the diagnosis of retroperitoneal perforation is usually difficult because of the lack of signs of peritoneal irritation and the paucity of symptoms, particularly in patients treated with corticosteroids.

Acute Disease↗

[Spastic colon (irritable colon)].

Spastic colon is a pathological entity whose clinical symptoms are for the most part abdominal pain, constipation and episodes of diarrhea without loss of weight. In all probability, it is merely a particularly striking presentation of a GI tract that is irritable throughout its entirety. The pathophysiological basis is a disordered propulsive bowel motoricity. Etiologically, psychological factors in the presence of an appropriate genetic or acquired disposition are conceivable. Possible mediators are considered to be noradrenalin, beta-endorphin and the corticotropin-releasing factor. The diagnosis can be established with a high degree of probability on the basis of the characteristic clinical picture. A definitive diagnosis, however, requires the very careful exclusion of other possible diagnoses. Therapy includes talks with the patient, physical and dietetic measures and the use of drugs to ameliorate diarrhea or, in the case of prokinetic agents, to re-establish normal propulsive bowel activity.

Acetylcholine↗

Redundant colon and carcinoma of the right colon.

The combination of redundant colon, multiple villose, adenomas, and a colloid adenocarcinoma arising in one villous adenoma in a black man is rare. The authors report such a case.

Adenocarcinoma, Mucinous↗