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At least 1,333 records · Page 74Linked to original sources
PubMed1998

Tumour susceptibility and spontaneous mutation in mice deficient in Mlh1, Pms1 and Pms2 DNA mismatch repair.

Germline mutations in the human MSH2, MLH1, PMS2 and PMS1 DNA mismatch repair (MMR) gene homologues appear to be responsible for most cases of hereditary non-polyposis colorectal cancer (HNPCC; refs 1-5). An important role for DNA replication errors in colorectal tumorigenesis has been suggested by the finding of frequent alterations in the length of specific mononucleotide tracts within genes controlling cell growth, including TGF-beta receptor type II (ref. 6), BAX (ref. 7) and APC (ref. 8). A broader role for MMR deficiency in human tumorigenesis is implicated by microsatellite instability in a fraction of sporadic tumours, including gastric, endometrial and colorectal malignancies. To better define the role of individual MMR genes in cancer susceptibility and MMR functions, we have generated mice deficient for the murine homologues of the human genes MLH1, PMS1 and PMS2. Surprisingly, we find that these mice show different tumour susceptibilities, most notably, to intestinal adenomas and adenocarcinomas, and different mutational spectra. Our results suggest that a general increase in replication errors may not be sufficient for intestinal tumour formation and that these genes share overlapping, but not identical functions.

Adaptor Proteins, Signal Transducing↗
PubMed1989

A case-control study of large bowel cancer and hormone exposure in women.

Several lines of evidence indicate a potential role for hormonal or reproductive factors in the subsequent development of large bowel cancer in women. To evaluate the relationship between hormone exposure and large bowel cancer a case-control study was carried out in 18 Illinois hospitals. Female cases, ages 45-74 (n = 90), and controls (n = 208) were identified from an ongoing large bowel cancer study. Data were obtained from medical records, personal interviews, and a subsequent mail survey with a questionnaire specific to hormone usage. Menopausal estrogen use was found to be protective with respect to the subsequent development of large bowel cancer with an odds ratio of 0.6 (95% CI, 0.33-0.99). This effect remained after controlling individually for age at diagnosis, ever pregnant (yes/no), parity, age at first birth, hysterectomy with documented oophorectomy, cholecystectomy, and appendectomy. Simultaneous adjustment, using logistic regression, for age at diagnosis, parity, hysterectomy, and cholecystectomy resulted in an adjusted odds ratio for menopausal estrogen use and large bowel cancer of 0.5 (95% CI, 0.27-0.90). Subsite analysis revealed the protective effect to be strongest for the rectal cancer cases. These data support the hypothesis that exogenous hormones may alter the risk of large bowel cancer in women.

Adenocarcinoma↗
PubMed1986

Immunodeficiency secondary to structural intestinal defects. Malrotation of the small bowel and cavernous hemangioma of the jejunum.

Two patients with gastrointestinal tract abnormalities were discovered to have significant defects in both humoral and cellular immunity. Patient 1, a 4-year-old girl with suspected food allergy, failure to thrive, and chronic diarrhea, exhibited a decreased serum IgG immunoglobulin level, decreased numbers of peripheral blood T lymphocytes (erythrocyte rosettes), decreased numbers of T-lymphocyte subpopulations (T3+, T4+), decreased responses of lymphocytes to common mitogens, and absent in vivo responses to delayed hypersensitivity skin test antigens. Patient 2, a 3-year-old girl with chronic anemia, presented with immunological abnormalities similar to those of patient 1. On investigation, both patients were found to have significant structural abnormalities of the gastrointestinal tract. Patient 1 had a malrotation of the small bowel, while patient 2 had a cavernous hemangioma of the mid-jejunum. Following surgical correction of the gastrointestinal abnormalities, there was improvement in all immunologic values. By ten to 18 months after surgery, both patients demonstrated normal immunological function. Thus, anatomic lesions of the gastrointestinal tract that mimic more common childhood disorders, such as food allergy and anemia, may produce serious states of secondary immunodeficiency.

B-Lymphocytes↗
PubMed2000

Experience with endoluminal colonic wall stents for the management of large bowel obstruction for benign and malignant disease.

HYPOTHESIS: To assess the applicability and efficacy of endoluminal colonic wall stents (ECWSs) in the management of large bowel obstruction (LBO). DESIGN: Inception cohort study. SETTING: University-based tertiary medical center. PATIENTS: Eleven consecutive patients with LBO in the absence of peritonitis. INTERVENTION: Placement of ECWS under endoscopic and fluoroscopic guidance. MAIN OUTCOME MEASURES: The success rate in ECWS placement, the efficacy in decompressing the obstruction, and the patency rate of the ECWS. RESULTS: Successful placement of ECWSs was obtainable in 10 of 11 patients. Once placed, all 10 patients achieved immediate decompression of their LBO. Eight patients had malignant obstructions associated with distant spread of disease; 3 patients had diverticular disease. Among those with malignant obstruction, 6 patients had successful and lasting palliation without colostomy, 1 patient underwent 1-stage resection 1 month later with no evidence of obstruction, and 1 patient could not be stented so diversion was done. None of the patients with diverticular disease required diversion: 2 had complete bowel preparation followed by resection with primary anastomosis, whereas the third declined surgery. Four of the 10 patients required overlapping ECWSs to bridge the stricture. One patient required a second ECWS secondary to recurrence of obstruction after stent migration and has continued palliation of his stage 4 rectal cancer for the last 11 months. No other complications were encountered. CONCLUSIONS: Urgent surgery with colostomy for LBO was avoided in 10 of 11 patients because of successful placement of ECWSs. We believe that endoscopic colonic stenting is safe, effective, and lasting, and should be considered as initial nonoperative management in all patients seen with LBO in the absence of peritonitis.

Adult↗
PubMed2002

Primary cancers of the small bowel: analysis of prognostic factors and results of surgical management.

HYPOTHESIS: This study was done to review the clinical presentation, surgical management, pathologic features, and prognostic factors for primary small-bowel cancers. DESIGN: Retrospective case series. SETTING: Tertiary care, university hospital. PATIENTS: One hundred twenty-nine patients were surgically treated between January 1, 1977, and December 31, 2000. There were 73 men and 56 women, with a median age of 55 years (age range, 19-82 years). Median follow-up was 36 months. MAIN OUTCOME MEASURES: Presenting symptoms and signs, operations performed, and surgical pathologic features were analyzed and survival curves were generated. RESULTS: Clinical findings included abdominal pain (63%), vomiting (48%), weight loss (44%), and gastrointestinal tract bleeding (23%). The distribution of tumors by histological features was as follows: adenocarcinoma (33%), carcinoid tumor (29%), lymphoma (19%), and sarcoma (19%). Cumulative 5-year survival rate was 37% in the adenocarcinoma group, 64% in the carcinoid tumor group, 29% in the lymphoma group, and 22% in the sarcoma group. Significant prognostic predictors of overall survival for the entire cohort and for each tumor subtype included complete resection and American Joint Committee on Cancer tumor stage (P<.05). Patient age, tumor location, histological grade, and use of chemotherapy and radiation therapy did not significantly influence survival. Curative resections were accomplished in 83 patients (64%) with a median survival of 37 months compared with 46 patients undergoing incomplete or palliative resections with a median survival of 10 months (P<.05). Adjacent organ resection was required in 18 (22%) of the 83 patients undergoing potentially curative resections. The median time to recurrence was 16 months. Twenty-one patients (16%) developed associated primary cancers. CONCLUSIONS: Aggressive surgical resection in an attempt to achieve complete tumor removal seems warranted. Despite complete resections, patients with high-stage tumors remain at risk for recurrence.

Actuarial Analysis↗
PubMed1975

Malignant lymphoma of the jejunum in a patient with Wiskott-Aldrich syndrome. Surgical treatment.

An 8-year-old boy with Wiskott-Aldrich syndrome underwent laparotomy and resection of a stage 1E malignant lymphoma of the jejunum. Although preoperative platelet counts were less than 10,000/cu mm, intraoperative bleeding was minimal, and postoperative bleeding from the wound was easily controlled with platelet infusions and local application of epinephrine. Six weeks later, he underwent reoperation for small intestinal obstruction and no residual tumor could be identified. The patient died 4 1/2 months following the initial surgery from an intracerebral hemorrhage. Postmortem examiniation did not reveal residual lymphoma.

Blood Platelets↗
PubMed1977

Adenocarcinoma in regional enteritis of the small intestine.

An increased risk for regional enteritis patients of small bowel adenocarcinoma to develop has been suspected but unproved. We have analyzed 49 cases reported since 1957 and two additional ones of our own. These have been compared with a current group of small bowel adenocarcinomas not associated with regional enteritis. The Crohn-associated cancers differed from adenocarcinomas not associated with Crohn disease in that (1) mean age at cancer discovery was less (46 vs 64 years), (2) more cancers arose in the ileum (76% vs 27%), (3) diagnosis and cure were less successful, and (4) they occurred more frequently. The 32 cases reported in the past five years were compared with the expected 0.1 to 5 cases. Regional enteritis patients were found to have an increased risk for the development not only of small bowel adenocarcinoma, but one that is more occult and lethal than that in individuals wihtout Crohn disease.

Adenocarcinoma↗
PubMed1977

Multiple lipomas of the ileum with volvulus.

We describe a patient with symptomatic multiple lipomas with volvulus. He complained of gradually increased abdominal pain and distention. Preoperative roentgenograms showed many rounded filling defects of the small intestine. Operation was performed to reduce intestinal obstruction and ileal resection was performed. The dilated ileum was rotated 720 degree clockwise and it contained 115 submucosal and 26 subserosal lipomas. Histologically, the lipomas were benign and consisted of well-developed fat tissue. The patient's postoperative course was satisfactory, and neither residual lipoma nor recurrence were found at barium enema examination two years after operation.

Adult↗