Inducible cyclooxygenase (Cox-2), also known as prostaglandin H synthase 2 (PGH-2) is a key enzyme in the formation of prostaglandins and thromboxanes. Cox-2 is the product of an immediate-early gene that is expressed in response to growth factors, tumor promoters, or cytokines. Overexpression of Cox-2 is associated with both human colon cancers and suppression of apoptosis in cultured epithelia] cells, an activity that is reversed by the nonsteroidal anti-inflammatory drug, sulindac sulfide. To address the relationship between Cox-2, apoptosis, and tumor development in vivo, we studied C57BL/6J-Min/+(Min) mice, a strain containing a fully penetrant dominant mutation in the Apc gene, leading to the development of gastrointestinal adenomas by 110 days of age. Min mice were fed AIN-76A chow diet and given sulindac (0.5 +/- 0.1 mg/day) in drinking water. Control Min mice and homozygous C57BL/6J-+/+ normal littermates lacking the Apc mutation (+/+) were fed AIN-76A diet and given tap water to drink. At 110 days of age, all mice were sacrificed, and their intestinal tracts were examined. Control Min mice had 11.9 +/- 7.8 tumors per mouse compared to 0.1 +/- 0.1 tumors for sulindac-treated Min mice. As expected, +/+ littermates had no macroscopic tumors. Examination of histologically normal-appearing small bowel from Min animals revealed increased amounts of Cox-2 and prostaglandin E(2) compared to +/+ littermates. Using two different in situ techniques, terminal transferase-mediated dUTP nick end labeling and a direct immunoperoxidase method, Min animals also demonstrated a 27-47% decrease in enterocyte apoptosis compared to +/+ animals. Treatment with sulindac not only inhibited tumor formation but decreased small bowel Cox-2 and prostaglandin E(2) to baseline and restored normal levels of apoptosis. These data suggest that overexpression of Cox-2 is associated with tumorigenesis in the gastrointestinal epithelium, and that both are inhibited by sulindac administration.

Adenomatous Polyposis Coli↗

PubMed1996

Laparoscopic colon resection for cancer--an unfavorable view.

Explore the source record for details and available documents.

Adenoma↗

PubMed1995

Laparoscopic colectomy for cancer.

Explore the source record for details and available documents.

Colectomy↗

PubMed1995

Disorders of the rectus abdominis muscle and sheath: a 22-year experience.

OBJECTIVES: To determine the spectrum of diseases that can involve the rectus abdominis muscle and sheath (RMS) and to describe the clinical features of these conditions. METHOD: A retrospective medical record review of RMS disorders seen at The New York Hospital-Cornell Medical Center from 1971 to 1992. RESULTS: A total of 40 patients with diseases of the RMS were identified. Thirty patients had primary diseases of the RMS, most commonly desmoid tumor and hematoma. Secondary disorders of the RMS included abscesses from diverticulitis, a perforated sigmoid carcinoma, gallbladder empyema, and disseminated actinomycosis. Eleven of 18 patients with desmoid tumors had familial adenomatous polyposis (FAP). The desmoid tumors in patients with FAP resulted in greater morbidity and mortality than those in patients without FAP. All patients with hematomas were on anticoagulation or had a history of trauma, vigorous coughing, or physical exertion. CONCLUSIONS: 1) RMS disease should be suspected in patients with a palpable abdominal mass and a history of familial adenomatous polyposis, trauma, anticoagulation, or vigorous coughing or exercise. 2) The most common non-neoplastic condition of the RMS is a hematoma. 3) The desmoid tumor is the most common neoplasm of the RMS. 4) Abdominal ultrasonography and CT readily distinguish RMS disease from intraabdominal pathology.

Abscess↗

PubMed1995

Surgical prophylaxis of familial colon cancer: prevention of death from familial colorectal cancer.

Patients at risk for inherited colorectal cancer constitute a heterogeneous population. A total colectomy is minimal treatment for those patients with invasive cancer or those with established risk factors. For others at risk, predictive genetic markers, correlated with clinical and pathologic determinants, will establish the basis for policies of surveillance and preventive surgery.

Adult↗

PubMed1994

Evidence for adenoma-carcinoma sequence in the duodenum of patients with familial adenomatous polyposis. The Leeds Castle Polyposis Group (Upper Gastrointestinal Committee).

AIMS: To explore the association between duodenal adenoma and carcinoma in patients with familial adenomatous polyposis (FAP). METHODS: A multicentre survey of 1262 patients with FAP yielded 47 cases of duodenal cancer. The association between adenoma and cancer was assessed in these cases. RESULTS: Adenomatous tissue was found within duodenal cancer in 29 of 44 (66%) patients with FAP and in mucosa adjacent to duodenal cancer in 31 of 42 (73%) such patients. Adenomas were found as a component of, or adjacent to, duodenal cancer in 38 of 45 (84%) patients. CONCLUSIONS: These observations support the existence of the adenomacarcinoma sequence in the duodenum of patients with FAP. Factors associated with malignant change included villous histology, moderate or severe dysplasia, and the presence of stage IV duodenal polyposis.

Adenoma↗

PubMed1993

Colonic mucosal pH in humans.

Mucosal pH was measured at specific anatomic segments within the colon using a flexible pH probe in patients prepared for colonoscopy. The data revealed similar pH measurements along the length of the colon, irrespective of the presence or absence of colorectal neoplasia. Patients exhibited a relatively acidic right colon; a more alkaline transverse, left, and sigmoid colon; and a relatively acidic rectum. There were no apparent gender- or age-related effects on colonic mucosal pH.

Colon↗

PubMed1993

Gender and colorectal cancer.

Studies of gender differences in colorectal cancer have shown temporal shifts in incidence and site distribution which can be attributed, in part, to environmental and behavioural factors. In high-risk populations, rectal cancer and left-sided colon cancer have been more frequent in older men, whereas right-sided colon cancer has been more commonly found in older women. Among known associations with reduced colorectal cancer risk, women appear to ingest more dietary fibre, seem to benefit more from physical activity and body mass, and consume less alcohol. Although these differences may contribute to the risk differential, hormonal events during reproductive years also appear to affect women's risk at older age. The interactions of sex hormone metabolism and nutrition, including dietary fibre, in colorectal carcinogenesis provide a rewarding field for investigation.

Colonic Neoplasms↗

PubMed1992

Treatment options for the patient with colorectal cancer.

Treatment decisions for patients with colorectal cancer depend on the site and extent of the cancer. Medical factors rarely preclude appropriate treatment. For colonic and upper rectal cancer, curative treatment is almost entirely operative. Even patients with disseminated colon cancer merit a limited palliative resection to abort bleeding and prevent obstruction. When surgery is elective, colostomy is rarely necessary, although it may be required in patients who have obstructed or perforated colon cancer. For distal rectal cancer, various treatment options, including radiation therapy, have reduced the need for a colostomy, although maintaining comparable cure rates. Currently, only about one in seven patients with rectal cancer requires a permanent colostomy.

Colorectal Neoplasms↗

PubMed1992

Loss of colonic HLA antigens in familial adenomatous polyposis.

The loss of HLA antigens by neoplastic cells is considered important for tumor growth and metastasis, since it may allow tumors to escape immune surveillance. We studied the expression of HLA class I and II antigens in the colons of 10 patients with familial adenomatous polyposis (FAP), a condition which leads inevitably to colorectal cancer. Expression of HLA class antigens was studied by immunohistochemistry in (a) adenomas from patients with FAP, (b) histologically normal mucosa distant from the adenomas, and (c) histologically normal colonic mucosa from normal subjects. The expression of HLA class I and II antigens was decreased in histologically normal mucosa from FAP patients compared to normal controls. Adenomas showed a similar but quantitatively more pronounced reduction (or loss) of HLA antigen expression. The reduction of HLA expression in adenomas was comparable to that observed in sporadic colon carcinomas. This generalized suppression of HLA gene expression in the colon of FAP patients, which precedes the onset of overt histological manifestations of neoplasia, may be an important early event in colon carcinogenesis.

Adenomatous Polyposis Coli↗

PubMed1992

Clostridial septicemia in an urban hospital.

The records of 56 patients at an urban hospital who had positive blood cultures for clostridia were reviewed. Each patient was classified as immunologically normal or immunosuppressed. Data were collected on clinical history, type of clostridial bacteremia, physical and laboratory determinants of infection, therapeutic intervention, clinical course and outcome. Of the 56 patients, 22 were determined to be immunosuppressed. Among all 56 patients, 28 had a malignancy, usually gastrointestinal or hematologic in origin. Fever, leukocytosis and abdominal pain were common in both groups. Clostridial bacteremia almost always heralded clostridial septicemia. A gastrointestinal source of infection, particularly carcinoma of the colon or rectum or enterocolitis, was evident or presumed in 43 of the 56 patients. Clostridium perfringens was the most frequently isolated microorganism, but C. septicum was associated with more complications and a higher mortality rate. Septic complications and mortality were higher among the patients with immunosuppression.

Adolescent↗

PubMed1992

Multivariate analysis of morbidity and mortality from the initial surgical management of obstructing carcinoma of the colon.

Eighty consecutive patients presenting with complete large intestinal obstruction from primary carcinoma were evaluated. A multivariate analysis was performed to evaluate perioperative morbidity and mortality. There were five deaths in the immediate postoperative period (30 days). Extensive and lesser complications occurred in eight and 11 patients, respectively. There were 25 lesions of the right colon, whereas in 55 patients, the lesion was located distal to the left branch of the middle colic artery. Females were more likely to present with obstructed carcinomas of the left colon than males. Patients with an obstruction of the left colon more frequently presented with dehydration than those with a tumor of the right colon (p less than 0.05). Most carcinomas of the right colon were resected, whereas lesions of the left colon were managed with diverting colostomy in 33 patients and by primary resection in 22. Thirteen patients with carcinomas of the left colon had an immediate anastomosis without mortality. Preoperative severe cardiopulmonary disease, Acute Physiology and Chronic Health Evaluation score and advanced carcinoma (Dukes' C or D) were statistically related to early hospital morbidity and mortality, while individual physiologic parameters, site of lesion or operation performed were not. Primary resection may be performed safely in selected patients. Multivariate assessment and clinical staging may allow for appropriate patient selection and improve immediate outcome.

Aged↗

PubMed1991

Ploidy in invasive colorectal cancer. Implications for metastatic disease.

A retrospective study was performed to determine the ploidy of superficial (above muscularis propria) and deep (below muscularis propria) biopsy specimens from the primary colorectal cancer of 88 patients with Dukes Stage C2 and D colorectal tumors. The ploidy of lymph node and liver metastases was compared with that of the superficial and deep specimen from the corresponding primary tumor. Among the tumors studied, 78% exhibited nondiploid stemlines. In 19% of the tumors, the ploidy of the superficial biopsy differed from that of the deep biopsy. Among these discordant tumors, all of the deep biopsy specimens corresponded in ploidy to the liver metastases, whereas most of the superficial specimens were similar in ploidy to the lymph node metastases. Our observations suggest that measurement of a single site may not be sufficient to detect nondiploid stemlines within a tumor. They also suggest that measurement of deeper parts of invasive tumors may be more reflective of the phenotype of distant metastases than measurement of superficial specimens.

Colorectal Neoplasms↗

PubMed1991

Familial polyposis coli: the spectrum of ocular and other extracolonic manifestations.

Familial polyposis coli (FPC) is hereditary condition that conveys a virtual 100% risk for the development of colon cancer in the untreated patient. A total of 56 patients with FPC underwent complete ophthalmic examination. Highly pleomorphic pigmented retinal lesions were identified bilaterally in 52% (n = 29) and unilaterally in 14% (n = 8) of our subjects. In all, 33 patients had one or more extracolonic expressions associated with FPC, including desmoids, osteomas, epidermoid cysts, lipomas, fibromas, and upper gastrointestinal tract polyps. In 15 patients, pigmented fundus lesions were the only extracolonic manifestations. No significant association between eye findings and other extracolonic manifestations could be established. The presence or absence of pigmented fundus lesions was found to cluster within families. Pigmented fundus lesions are probably a variably penetrant expression of the polyposis gene and do not appear to be specifically associated with subgroups of inherited polyposis syndromes such as Gardner's syndrome.

Adenomatous Polyposis Coli↗