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At least 451 records · Page 25Linked to original sources
PubMed1997

In vivo activation of mitogen-activated protein kinases in rat intestinal neoplasia.

BACKGROUND & AIMS: To investigate whether mitogen-activated protein kinase (MAPK) cascades might play a role in the progression of colon cancer, c-Jun N-terminal kinase (JNK) and extracellular signal regulating kinase (ERK) activity during colonic tumorigenesis were examined. METHODS: The 1,2-dimethylhydrazine (DMH)-induced colon carcinoma model was used to study the activation of these kinases during intestinal carcinogenesis. Male Sprague-Dawley rats were injected with DMH for 24 weeks. Normal-appearing intestinal mucosa from control and treated animals and DMH-induced intestinal tumors were assayed for JNK and ERK activity using solid phase in vitro kinase assays. Tumors were typed for mutations in the K-ras gene. RESULTS: There was little or no difference in JNK and ERK activity in hyperproliferative mucosa from DMH-treated animals compared with normal mucosa from control animals. However, in 16 colonic neoplasms, an average of 23-fold and 29-fold increases in JNK and ERK activities were observed, respectively, over control levels. In addition, activating protein-1 binding was strongly induced in the colonic tumors. Activation did not correlate with the presence of mutations in K-ras. CONCLUSIONS: Both the JNK and ERK MAPKs are highly activated during late progression of colorectal carcinoma. This change is dependent on the tumorigenic state rather than changes in proliferation.

1,2-Dimethylhydrazine↗
PubMed2001

Paraneoplastic hypercalcemia in a patient with adenosquamous cancer of the colon.

Hypercalcemia is a well-known manifestation of paraneoplastic syndromes associated with a variety of malignancies. However, colon cancer has only rarely been associated with hypercalcemia of malignancy. We present the case of a patient with recurrent adenosquamous carcinoma of the ascending colon found to have hypercalcemia. The patient is a 76-year-old white woman who initially presented with colon cancer in the cecum and underwent a right hemicolectomy. All lymph nodes and surgical margins were free of tumor. Pathological examination at that time revealed adenosquamous carcinoma of the colon. Eight months later she complained of dizziness, anorexia, and constipation and was found to have a calcium level of 13.6 mg/dL. CT scan revealed a mass measuring 10.5 to 12.7 cm in the right hepatic lobe, and a bone scan was normal. Her intact parathyroid hormone (PTH) level was 6 pg/mL (normal 12-72) and her PTH-related protein (PTHrP) level was 25.7 pmol/L (normal <1.3). She then underwent a hepatic resection. The serum PTH, calcium, and PTHrP levels normalized after resection. Hypercalcemia of malignancy in colon cancer is rare and has an association with adenosquamous histology. The hypercalcemia is attributed to PTHrP, and here we demonstrate this in the serum and tumor specimens. The effects of PTHrP are shown to be short-lived postoperatively. We find only 14 other cases in the literature of hypercalcemia related to a colonic neoplasm, and this is the only patient reported to be surviving. The diagnosis of a paraneoplastic syndrome mediated via PTHrP should be considered when hypercalcemia is encountered in the setting of metastatic colon carcinoma.

Aged↗
PubMed1977

Association of Streptococcus bovis with carcinoma of the colon.

Two patients with colonic adenocarcinoma and Streptococcus bovis endocarditis suggested a possible association between the two. Non-enterococcal Group D streptococci were isolated from fecal cultures of 11 of 105 controls, 35 of 63 patients with carcinoma of the colon, seven of 25 with inflammatory bowel disease, four of 21 with non-colonic neoplasms and five of 37 with other gastrointestinal disorders. All such streptococci examined for lactose fermentation were S. bovis. The prevalence of S. bovis in fecal cultures from patients with carcinoma of the colon was significantly increased (P less than 0.001) as compared to that in controls, and also to all other groups (P less than 0.001). No other group had results significantly different from those of controls (P less than 0.05) although patients with inflammatory bowel disease were more frequently carriers. The carrier state was unrelated to age, hospitalization status, colonic stasis, gastrointestinal bleeding or recent barium-enema examination. The implications of this association are unknown.

Adenocarcinoma↗
PubMed1998

[Streptococcus bovis endocarditis. Clinical and microbiological observations and review of the literature].

Fourteen patients (11 men and 3 women) with Streptococcus bovis infective endocarditis have been observed by the Infectious Disease Section of our Department of Clinical Medicine between the years 1988-1998. The mean age was 63.2 years (range 35-85 years); 5 patients previously suffered valvular disease or had a valvular prosthesis, the infection involved the mitral valve in 6 patients, the aortic in 8, the prosthetic valve in 1. No patient developed cardiac failure or died during hospitalization; only 1 episode of major embolism (spleen) was observed. No patient required cardiac surgery. All patients became afebrile after starting antibiotic treatment; no cases of Streptococcus bovis relapse have been observed, during a six-month follow-up after antibiotics discontinuation, in 13 patients fully evaluated. The remaining patient was lost to follow-up. An underlying asymptomatic colonic neoplasm was diagnosed at colonoscopy in 7 of 11 evaluated patients. This study confirms that Streptococcus bovis infective endocarditis is relatively benign, but it stresses the frequency and potential severity of the associated colonic lesions, requiring colonoscopy and making the treatment of high risk lesion mandatory.

Adult↗
PubMed1997

Importance of adenomas 5 mm or less in diameter that are detected by sigmoidoscopy.

BACKGROUND: The need for colonoscopy in patients with adenomas 5 mm or less in diameter that are detected by sigmoidoscopy is controversial. METHODS: We prospectively determined the prevalence of proximal colonic neoplasms in asymptomatic patients at average risk for colorectal cancer, each of whose index lesion on screening fiberoptic sigmoidoscopy was a benign adenoma. Polyps found on sigmoidoscopy underwent biopsy, and colonoscopy was recommended to all patients with neoplastic polyps. Rectosigmoid adenomas were classified as diminutive (< or = 5 mm in diameter), small (6 to 10 mm in diameter), or large (> or = 11 mm in diameter). RESULTS: Of 3496 consecutive patients referred for sigmoidoscopy, 311 had neoplastic rectosigmoid polyps; 108 of these patients were excluded from the analysis because of a history of colonic neoplasia, symptoms, prior colonic evaluation, or incomplete follow-up data. The remaining 203 patients made up the study group, and all underwent colonoscopy. Neoplasms were found in the proximal colon in 40 of 137 patients (29 percent) with diminutive index polyps, 15 of 52 patients (29 percent) with small index polyps, and 8 of 14 patients (57 percent) with large index polyps. Advanced neoplasms (adenomas > or = 10 mm in diameter, adenomas with a villous component or moderate-to-severe dysplasia, carcinoma in situ, or frank carcinoma) were found in 8 patients (6 percent), 5 patients (10 percent), and 4 patients (29 percent), respectively. Two patients with diminutive index polyps had proximal carcinoma in situ, and two had proximal stage I carcinomas; one patient with a large index polyp had proximal stage III carcinoma. CONCLUSIONS: The substantial prevalence of proximal colonic neoplasms, including advanced lesions, in asymptomatic average-risk patients with rectosigmoid adenomas < or = 5 mm in diameter warrants colonoscopy in these patients.

Adenoma↗
PubMed1990

Colon-cancer screening in dialysis patients.

The usefulness of colon-cancer screening using stool-guaiac testing has been established in large control populations, but not in dialysis patients. In 72 asymptomatic dialysis patients [51 treated with hemodialysis (HD), and 21 with peritoneal dialysis (PD)] who underwent outpatient stool occult blood testing, the test result was positive in 11 (15%) patients (8 HD and 3 PD). Eight of the 11 were investigated further by colonoscopy and, when deemed necessary by the treating physician, esophagogastroduodenoscopy and/or barium enema were also performed. A site of active bleeding was identified in three of the eight patients (hemorrhoids, telangiectasia, ulcerative colitis). In each of the five other patients, potentially bleeding lesions were identified: colonic polyps (two malignant and two benign) in four patients. Barrett's esophagus in one, diverticulosis in two, and colonic vascular deformities in two. These results were compared with those of a large ongoing fecal occult blood screening program in which the prevalence of positive stool occult blood tests is 5% and in which 42% of the positive patients have colonic neoplasms. Thus, although the baseline incidence of positive guaiac tests may be higher in dialysis patients than in nonuremic controls, our results suggest that stool guaiac testing of dialysis patients may not only be useful in detecting colonic polyps, but may also identify other previously unsuspected causes of gastrointestinal bleeding.

Adult↗
PubMed1975

Carcinoembryonic antigen in human ovarian neoplasms.

The presence and location of carcinoembryonic antigen (CEA) was examined in tissue sections of 14 mucinous and 13 serous cystadenomas and cystadenocarcinomas of the ovary. CEA was demonstrated in the mucinous tumors but was not present in the serous tumors. In the mucinous tumors, CEA was located in the glycocalyx and apical portions of the absorptive-type epithelium, with only trace quantities in goblet cells, a pattern identical to that seen in colonic neoplasms. Endocervical-type epithelium in the mucinous tumors contained little or no CEA.

Carcinoembryonic Antigen↗
PubMed1979

Colonic adenomas--a colonoscopy survey.

A colonoscopy survey of 620 patients with 1049 colon adenomas showed a predominantly left-sided distribution (77%). Of these lesions 97% were amenable to endoscopic removal or ablation. Sixty per cent of patients presented with rectal bleeding as their major symptom. There was agreement between radiology and colonoscopy in only 62% of patients, as many of the studies were single contrast barium enemas, performed before referral. Forty-eight per cent of adenomas in our series were less than 1.0 cm in diameter. Of the larger adenomas (greater than 2.0 cm in diameter) 66% were situated in the sigmoid colon, and of those containing invasive carcinoma (4.8% of the total) an even higher percentage (94%) were in the sigmoid and low descending colon. With increasing polyp size, there was a greater predominance of villous elements and this was associated with a higher risk of malignant change than the more frequent and generally smaller tubular adenoma. Local colonoscopic excision alone is sufficient treatment for adenomas with malignant change unless they are poorly differentiated histologically and providing adequate resection is demonstrated. Twenty-eight patients treated in this way are alive without recurrence at periods from six to 62 months. Although 65% of patients had only one adenoma, and 90% three or less, there is a risk of developing other benign and malignant colon neoplasms and careful follow-up is required.

Adenoma↗
PubMed1990

Carcinogenicity tests of fecapentaene-12 in mice and rats.

Fecapentaenes, a class of direct-acting bacterial mutagens, have been isolated from the feces and intestinal tract of humans on a Western meat-containing diet. Two bioassays to test pure fecapentaene-12 (FP-12) for carcinogenicity were performed. FP-12 in dimethylsulfoxide (DMSO) solution was injected i.p. into newborn ICR/MA mice on days 1, 3, 7, 10, 14 and 21. The mice killed after 21 months had neoplasms in liver, lung, glandular stomach and subcutaneous fibrosarcoma. Intrarectal (i.r.) infusion of FP-12 in an aqueous vehicle into male F344 rats for 71 weeks, and killing the rats after 21 weeks more, displayed no evidence of neoplasia associated with FP-12 exposure. The positive control, N-nitrosomethylurea (NMU), given i.r. as 4 2-mg doses in 2 weeks, as expected, yielded multiple colonic neoplasms in less than 11 months. Fecapentaene may exert its effect in bacteria and in newborn mice through the generation of hydroxy radicals. However, adult rodent and human colon may have adequate biochemical defense mechanisms against low level, even continuous exposures to chemicals like FP-12, and thus be at low risk of neoplasia, as was found.

Adenoma↗
PubMed2006

Cytoreductive surgery combined with intraperitoneal chemohyperthermia for the treatment of advanced colon cancer.

BACKGROUND: Chemohyperthermic peritoneal perfusion (CHPP) after extensive cytoreductive surgery is a possible choice as a regional treatment for peritoneal carcinomatosis (PC). The multicentric France EVOCAPE 1 study demonstrated that the median overall survival of patients with colon peritoneal carcinomatosis subjected to conventional surgical and/or chemotherapeutic treatment was 5.2 months. Historically, mitomycin C is the drug of choice in the treatment of intraperitoneal carcinomatosis from colon cancer. METHODS: Twenty-five patients affected by stage IV colon cancer with only peritoneal involvement and a prior completion of at least a partial first cycle of systemic chemotherapeutic and/or surgical treatment (24 patients) were enrolled. Immediately following extensive cytoreductive surgery, early postoperative closed abdomen CHPP was performed. RESULTS: Complete surgical cytoreduction (CC0-CC1) was obtained in 22 patients. Postoperative mortality was 1 out of 25 (4%). Major postoperative morbidity was 6 out of 25 (24%). Median overall survival estimated by Kaplan-Meier curve was 30.3 months. Locoregional progression-free survival was 17.3 months. Of all the patients 64% and 40% were alive after 1 and 2 years respectively. CONCLUSIONS: In referral centers CHPP after optimal surgical debulking is a safe procedure for peritoneal carcinomatosis from colonic cancer. Locoregional control was obtained in the majority of the pretreated patients and 1-year survival was statistically improved. A closed abdomen CHPP procedure lasting 1 hour and standard mitomycin C at a dosage of 15 mg/m(2) is probably as efficacious as other hyperthermic procedures, using higher mitomycin C dosages, with a comparable or lower number of cases of side effects. These results, as in other published phase II studies, justify future randomized trials to assess definitively the role of CHPP in the treatment of locally advanced colon neoplasms in western countries.

Adult↗
PubMed1997

Colorectal epithelial cell proliferative kinetics and risk factors for colon cancer in sporadic adenoma patients.

Colorectal epithelial cell proliferative kinetics are altered in patients at increased risk for colon cancer: proliferation rates [labeling index (LI)] are higher and there is a shift of the proliferative zone from one confined to the lower 60% of the colonic crypt to one that includes the entire crypt (higher phi(h)). To assess factors associated with LI and phi(h), we performed a cross-sectional analysis using baseline rectal mucosal biopsies from sporadic adenoma patients participating in a chemoprevention trial. Biopsies (taken without preparatory cleansing) were taken 10 cm above the level of the anus, and proliferation was assessed by detection of endogenous S-phase-associated proliferating cell nuclear antigen by immunohistochemical methods. High-quality, scorable biopsies were obtained for 115 patients, and using analysis of covariance and multiple linear regression, the LI and phi(h) were evaluated in relation to diet and other lifestyle factors, demographics, anthropometrics, family history of colon cancer, and polyp history. Statistically significant findings included the following: (a) The LI for those in the upper versus the lowest tertile of vegetable and fruit consumption was, proportionately, 35% lower (3.4% versus 5.3%; P < 0.001); for vitamin supplement users versus nonusers, it was 36% lower (3.3 versus 5.2%; P < 0.001); for recurrent versus incident polyp patients, it was 36% higher (6.2 versus 4.0%; P < 0.001); and for those with rectal polyps only versus those with colon polyps only, it was 28% higher (6.0 versus 4.3%; P = 0.05); and (b) the phi(h) for those in the upper versus the lowest tertile of sucrose consumption was, proportionately, 48% higher (7.1% versus 3.7%; P = 0.01). These results indicate that (a) colorectal epithelial cell proliferation rates are higher in recurrent adenoma patients than in incident adenoma patients and in patients with rectal adenomas only versus those with colon adenomas only, but they are lower in patients with higher intakes of vegetables and fruit and in those who take vitamin/mineral supplements, and (b) the distribution of proliferating cells is shifted toward more inclusion of the upper 40% of the crypt in patients with higher intakes of sucrose. The pattern of positive, negative, and null associations of potential risk factors with cell proliferation is similar to that commonly found with colonic neoplasms.

Adenoma↗
PubMed2001

Endometrial stromal sarcoma of the rectosigmoid colon arising in extragonadal endometriosis and revealed by portal vein thrombosis.

Malignant transformation is an infrequent complication of endometriosis. The ovary is the primary site in 76% of cases, and extragonadal sites are identified in 24%. Endometrioid carcinoma is the most common histologic type; sarcoma is very rare. We report a case of low-grade endometrial stromal sarcoma of the rectosigmoid colon presenting with epigastric pain due to portal vein thrombosis. This tumor arose from extragonadal endometriosis in a 61-year-old woman and was treated by surgical resection. The main differential diagnosis of this unusual colonic neoplasm includes primary mesenchymal tumors, such as gastrointestinal stromal tumors.

Cell Transformation, Neoplastic↗
PubMed1975

The association of carcinoembryonic antigen and peripheral lymphocytes.

A significant association between carcinoembryonic antigen (CEA) assay titers and peripheral lymphocyte counts was observed in 148 simultaneous determinations. The association was present in a high cancer risk study group of patients with myasthenia gravis and in a control group of patients with granulomatous disease of the bowel, ulcerative colitis, and colonic neoplasms. A highly significant difference in the percentage of positive CEA assays in relation to lymphocyte counts was noted both in the study and control groups. In the study group CEA was positive in seven of 41 patients (17 percent) with counts above 2,000 per cubic millimeter, and in 26 of 56 (43 percent) of those with lower counts (X2 = 9.06, p smaller than 0.005). The corresponding percentages in the control group were 20 and 61 percent (X2 = 5.60, p smaller than 0.025). A significant difference between the means of lymphocytes in groups with different CEA titers also was found (F = 6.77, p smaller than 0.05). The finding of lower peripheral lymphocytes and/or higher titers of CEA in groups with increased risk of cancer, i.e., severe myasthenia gravis, patients with thymomas and patients with long history of granulomatous disease of the bowel, suggests on association between the results of the two tests and cancer risk. The observations indicate that the yield of CEA assay in cancer detection may be higher in patients with lwo lymphocytes, and that these determinations used in conjunction may serve better as diagnostic and prognostic aids in patients with known neoplasms or in high cancer risk groups.

Adolescent↗
PubMed2002

Impaired antioxidant defense system of colonic tissue and cancer development in dextran sulfate sodium-induced colitis in mice.

BACKGROUND: The mechanisms underlying the frequent development of carcinomas associated with ulcerative colitis (UC) are not understood. Cellular antioxidants play a crucial role in protection against neoplastic disease. The purpose of this study is to investigate a critical balance between free radical activity and the antioxidant defense system in carcinogenesis associated with UC, using a model of experimental colitis induced in mice by dextran sulfate sodium (DSS) treatment. METHODS: Chronic colitis was induced by feeding the mice for 7 days with 4% DSS, followed by drinking water alone for the subsequent 14 days. Animals were sacrificed after one, two, three, or four cycles of DSS administration. Development of dysplastic epithelium and invasive carcinoma was histologically examined. Lipid peroxide level was estimated by measuring malondialdehyde (MDA) content. Alterations in MDA content and superoxide dismutase (SOD) activity in colonic tissues together with production of serum tumor necrosis factor (TNF)-alpha were determined. RESULTS: Colonic neoplasms including dysplastic epithelium and invasive carcinoma developed in 28.6 and 25.0% of the animals at the end of the third and fourth cycles, respectively. In accordance with elevation of serum TNF-alpha level, there was a substantial increase in MDA in the colonic mucosa, while tissue SOD activity tended to be suppressed during the DSS treatment periods. Dysplastic epithelium and invasive carcinoma revealed significantly lower SOD levels compared with colonic colitis, although MDA levels were not statistically different among these colonic diseases. CONCLUSIONS: The results obtained in this experimental model suggest that an impaired antioxidant defense system might be critical for cancer development associated with UC.

Animals↗
PubMed2005

Simultaneous laparoscopic treatment for diseases of the gallbladder, stomach, and colon.

We describe a successful simultaneous laparoscopic treatment of a gallstone and gastric and colonic neoplasms. The patient was a 72-year-old man with epigastric discomfort. Abdominal ultrasound revealed a gallstone 2 cm in diameter. Gastroscopy revealed a 3-cm protruding submucosal tumor in the gastric fundus and colonoscopy revealed a 2-cm sessile lesion in the sigmoid colon. He underwent simultaneous laparoscopic treatment of the 3 organs because of the high risk of perforation or bleeding after gastric or colonic resection. This required the use of 5 ports, and a 3.5-cm incision was made in the left lower quadrant to access the 3 organs. The laparoscopic procedures consisted of cholecystectomy, partial stapled resection of the gastric fundus, and partial resection of the sigmoid colon. The histopathologic diagnoses were chronic cholecystitis, leiomyoma of the stomach, and tubulovillous adenoma with severe dysplasia of the colon. The operation took 183 minutes and blood loss was minimal. The patient started oral intake from the second postoperative day and was discharged uneventfully. He had from no postoperative complications or abdominal symptoms during a 15-month follow-up period. To our knowledge, this is a first successful clinical report of simultaneous laparoscopic treatment of 3 organ disorders.

Adenoma, Villous↗
PubMed1990

Piroxicam decreases postirradiation colonic neoplasia in the rat.

This study evaluated the effects of the nonsteroidal antiinflammatory agent piroxicam on chronic radiation proctitis in the rat. Forty female Wistar rats received a 2250-cGy dose of irradiation to the distal 2 cm of the colon. Twenty received piroxicam 8.0 mg/kg orally 30 minutes before exposure and 24 hours after exposure; 20 rats served as irradiated controls. All animals were evaluated by colonoscopy 1 and 3 weeks postexposure and every third week until death or killing at 1 year. At killing, colons were removed for light microscopic examination. One year postirradiation results showed no differences in mortality, vascular changes, acute inflammation, colitis cystica profunda, or rectal stricture between the control and piroxicam-treated groups. However, at 1 year postirradiation the control group demonstrated neoplasia in 15 of 19 animals compared with eight of 20 animals in the piroxicam-treated group. The first endoscopic appearance of colonic neoplasm occurred at 15 weeks postirradiation in one control irradiated rat whereas the first evidence of endoscopic neoplasm in the piroxicam-treated group did not occur until 36 weeks postirradiation. Histologic examination documented a tendency toward a greater presence of adenocarcinomas in the control group compared with the piroxicam-treated group. The authors conclude that piroxicam treatment significantly decreased the incidence of colonic neoplasia in general as well as delayed the endoscopic appearance of colonic neoplasia in rats after pelvic irradiation.

Adenocarcinoma↗
PubMed1995

Induction of nitric oxide synthase in colonic smooth muscle from patients with toxic megacolon.

BACKGROUND & AIMS: Colonic inflammation may lead to motility disturbances, including severe atony. Nitric oxide is released by inflamed tissue and induces smooth muscle relaxation. The aim of this study was to analyze NO generation pathways in colonic tissue from patients who had ulcerative colitis with or without toxic megacolon and in tumor-free samples from patients with colonic neoplasm. METHODS: Enzymatic activity was determined by transformation of [14C]arginine to [14C]citrulline in mucosa and muscular layer samples. Immunostaining of tissue sections with antibody against inducible NO synthase was investigated. The effects of endotoxin on NO synthase activity was tested in muscle strips from human colon. RESULTS: Ca(2+)-independent NO synthase was undetectable or very low in muscularis propria from tumor and colitis controls. In contrast, specimens from patients with toxic megacolon had high activity (P < 0.05). Positive immunostaining for inducible NO synthase was found in muscular layers from patients with megacolon but not in tumor and colitis controls. Finally, endotoxin induced Ca(2+)-independent NO synthase activity in colonic muscle. CONCLUSIONS: Toxic megacolon is associated with the appearance of inducible NO synthase in the colonic muscularis propria. Local generation of excessive amounts of NO may be responsible for the colonic dilatation that is the hallmark of this syndrome.

Adult↗