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PubMed2002

Oncological complications of excess GH in acromegaly.

Around fifteen percent of the deaths reported in acromegaly are attributable to malignancy (SM Melmed, J Clin Endocrinol Metab 2001;86:2929-2934; A Mestrón, SM Webb, In: Endocrine Society, San Francisco, June 2002 (abstract)), uncontrolled disease is associated with a growth advantage for concurrent neoplasms, which are more likely to be aggressive; however, there is no clear evidence of de novo cancer initiation in acromegaly and no proven causal relationship of acromegaly with malignant disease. Overall and cancer mortality in acromegaly have been shown to correlate with the degree of GH control; if post therapy GH is controlled, both the overall and cancer mortality do not appear to differ from that of the normal population (SM Orme et al., J Clin Endocrinol Metab 1998;83:2730-2734; JD Nabarro, Clin Endocrinol 1987;26:481-512). However, no long-term prospective evaluation of cancer prevalence or its relation to biochemical or clinical disease activity is available. IGF-1 appears to exert a permissive effect on tumorigenesis; there is no clear evidence that tumor initiation is triggered by IGF-1 in acromegaly; nevertheless, since IGF-1 may be higher in neoplasms, aggressive treatment aimed at controlling the disease activity will theoretically be advantageous for acromegalic patients with cancer. The prevalence of colon polyps and colon cancer appear to be incresed in acromegaly as is mortality for colon cancer (Orme et al., 1998), so regular colonoscopy screening and polypectomy would seem advisable, especially in older patients with active acromegaly. Surveillance for prostate cancer in elderly males with high IGF-1, especially if also receiving testosterone replacement therapy, is recommendable, by measurement of serum PSA, rectal examination and/or prostatic ultrasound. In women, mammography should be offered, especially after the age of 50 years, as in the normal population. Neither prostate nor breast cancer have been consistently shown to have an increased prevalence in acromegaly, but larger prospective epidemiological studies are required to study this further.

Acromegaly↗
PubMed2001

Cyclooxygenase-2 and antagonists in pain management.

Non-steroidal anti-inflammatory drugs are widely used for the treatment of pain and inflammation by inhibiting the formation of prostaglandins. However, their use is limited by their side-effects, including gastrointestinal, renal function, cardiovascular and platelet function. Cyclooxygenase activity is the principal target for the action of non-steroidal anti-inflammatory drugs. Two isoforms of cyclooxygenase have been characterized: (i) cyclooxygenase-1, which is found in many tissues and is generally constitutively expressed and synthesizes prostanoids that mediate homeostatic functions; and (ii) cyclooxygenase-2, the inducible isoform, which is mainly expressed at sites of injury or inflammation and synthesizes prostanoids that mediate inflammation, pain and fever. These findings led to the development of selective cyclooxygenase-2 inhibitors, with comparable anti-inflammatory and analgesic properties to traditional non-steroidal anti-inflammatory drugs, but with significantly fewer side-effects. However, these new selective cyclooxygenase-2 inhibitors are not risk free, and care should be taken when using these drugs, especially with elderly patients with multiple medical problems. Finally, the future is bright for the broader usage of these agents in the treatment of diseases other than inflammation and pain, such as Alzheimer's disease, colonic polyp and colon cancer, just to name a few.

Journal Article↗
PubMed1996

Bacteriocolonic pathway for ethanol oxidation: characteristics and implications.

Alcohol ingested orally is transported to the colon by blood circulation, and after the distribution phase, intracolonic ethanol levels are equal to those in the blood. Recent studies in our laboratory suggest that in the large bowel ethanol is oxidized by a bacteriocolonic pathway. In this pathway intracolonic ethanol is at first oxidized by bacterial alcohol dehydrogenase to acetaldehyde. Then acetaldehyde is oxidized either by colonic mucosal or bacterial aldehyde dehydrogenase to acetate. Part of intracolonic acetaldehyde may also be absorbed to portal vein and be metabolized in the liver. The bacteriocolonic pathway offers a new explanation for the disappearance of a part of ethanol calories. Due to the low aldehyde dehydrogenase activity of colonic mucosa, acetaldehyde accumulates in the colon. Accordingly during ethanol oxidation highest acetaldehyde levels of the body are found in the colon and not in the liver. High intracolonic acetaldehyde may contribute to the pathogenesis of alcohol-induced diarrhoea. Because acetaldehyde is a carcinogen in experimental animals, it may also contribute to the increased risk of colon polyps and colon cancer, which have been found to be associated with heavy alcohol consumption. Intracolonic acetaldehyde may also be an important determinant of the blood acetaldehyde level and a possible hepatotoxin. In addition to acetaldehyde, gut-derived endotoxin is another potential candidate in the pathogenesis of alcohol-related liver injury. Experimental alcoholic liver injury has recently been prevented by antibiotics, and this effect was related to the prevention of endotoxin-induced activation of Kupffer's cells.

Aldehyde Dehydrogenase↗
PubMed2003

Small interfering RNAs directed against beta-catenin inhibit the in vitro and in vivo growth of colon cancer cells.

The beta-catenin and APC genes are key components of the Wnt signaling pathway. Mutation of these genes results in increased levels of the beta-catenin protein, which is associated with enhanced cellular proliferation and the development of both colon polyps and colon cancer. Recently, a technique known as RNA interference has been successfully adapted to mammalian cells so that it is now possible to specifically decrease the expression of cellular genes after transfection of annealed small interfering 21-mer RNAs. In the current study, we used small interfering RNA (siRNA) directed against beta-catenin to determine the effects of decreasing the high constitutive levels of this protein in colon cancer cell lines with mutations in either beta-catenin or APC. Our studies demonstrate that siRNA directed against beta-catenin markedly decreased beta-catenin-dependent gene expression and inhibited cellular proliferation as reflected in the reduced growth of these colon cancer cells both in soft agar and in nude mice. These results indicate that siRNA can target specific factors whose expression is altered in malignancy and may have the potential as a therapeutic modality to treat human cancer.

Adenomatous Polyposis Coli Protein↗
PubMedDate not supplied

[Gardner syndrome: clinical and epidemiologic up to date].

In 1950 EJ Gardner first described a new syndrome characterized by (1) familial colonic polyposis, (2) multiple osteomas, (3) soft tissues cysts and (4) fibrous lesions. Thereafter, in 1975 Watne and coll. have demonstrated the occurence, in patients affected by Gardner syndrome, of the early onset of osteomas and dental inclusions in maxillary bones. Gardner syndrome is actually considered a severe life treathening condition due to the poor quality of life and the evolutive pattern of colonic polyps to colon cancer in 100% of cases. The aim of this paper is the review of the pathophysiologic and clinical aspects of Gardner syndrome, with report of institutional clinical data about epidemiology and clinical presentation of such condition, attempting to elaborate a clinical protocol for early detection of that.

Adenomatous Polyposis Coli↗
PubMed2002

Selenoprotein levels in patients with colorectal adenomas and cancer.

OBJECTIVES: Selenium is a trace mineral that, as a constituent of certain selenoproteins, acts as an antioxidant. Results of studies addressing a cancer protective effect of selenium have been controversial. The present study measured selenoprotein-P, extracellular glutathione peroxidase, and plasma selenium in patients with colon cancer and adenomatous colon polyps to determine whether patients who develop colorectal adenomas or cancer are selenium deficient. METHODS: Patients who presented to an endoscopy center for colonoscopy or who were referred to our institution with a newly diagnosed colorectal cancer were offered enrollment in the trial. Each patient underwent phlebotomy, usually immediately after colonoscopy. In all, 103 patients were enrolled in the study. Of these, 33 patients were found to have colorectal cancer, 35 adenomatous colon polyps, and 17 normal examinations. A total of 18 patients had other diagnoses and were not included in the study group. RESULTS: The mean age for the colorectal cancer group was 69 yr, for the adenomatous colon polyp group 62 yr, and for the normal group was 56 yr. The adenomatous colon polyp and normal groups were predominantly female. Based on one way analysis of variance tests, there was no significant difference in selenoprotein-P or plasma selenium levels or extracellular glutathione peroxidase activity among the three groups (p = 0.28, 0.098, and 0.35 respectively). CONCLUSIONS: The present data suggest that patients with adenomatous colon polyps and those with colorectal cancer are not selenium deficient.

Adenoma↗
PubMed2002

Colchicine effect in a colonic hyperplastic polyp. A lesion mimicking serrated adenoma.

Colchicine effect has been described recently in gastrointestinal biopsies, where it can result in accumulation of metaphase mitoses and epithelial disorganization. We describe the case of a colonic hyperplastic polyp with colchicine effect from a 52-year-old woman who was receiving colchicine for primary biliary cirrhosis. Biopsy of the polyp revealed prominent metaphase mitoses and focal loss of nuclear polarity in the surface epithelium, features that mimicked a serrated adenoma. Distinguishing between hyperplastic polyp and serrated adenoma is important because of the different management implications and the increased potential for neoplastic progression in the latter.

Adenoma↗
PubMed1988

Common inheritance of susceptibility to colonic adenomatous polyps and associated colorectal cancers.

We studied 670 persons in 34 kindreds by flexible proctosigmoidoscopic examination (60 cm) to determine how frequently colorectal adenomas and cancers result from an inherited susceptibility. Kindreds were selected through either a single person with an adenomatous polyp or a cluster of relatives with colonic cancer. The kindreds all had common colorectal cancers, not the rare inherited conditions familial polyposis coli and nonpolyposis inherited colorectal cancer. Likelihood analysis strongly supported the dominant inheritance of a susceptibility to colorectal adenomas and cancers, with a gene frequency of 19 percent. According to the most likely genetic model, adenomatous polyps and colorectal cancers occur only in genetically susceptible persons; however, the 95 percent confidence interval for this proportion was 53 to 100 percent. These results suggest that an inherited susceptibility to colonic adenomatous polyps and colorectal cancer is common and that it is responsible for the majority of colonic neoplasms observed clinically. The results also reinforce suggestions that first-degree relatives of patients with colorectal cancer should be screened for colonic tumors. This evidence of an inherited susceptibility to a cancer with well-recognized environmental risk factors supports the hypothesis that genetic and environmental factors interact in the formation and transformation of polyps.

Adenomatous Polyposis Coli↗
PubMed1981

Endoscopic polypectomy in the gastrointestinal tract.

The results of 160 consecutive fibre-optic endoscopic polypectomies in the gastrointestinal tract are reviewed. Of 22 polyps snared in the upper digestive tract, 16 could be retrieved. One gastric polyp showed early intramucosal carcinoma. Biopsies from a pedunculated duodenal polyp, which was lost after snaring, revealed adenoma with moderate atypia. Of 138 resected colonic polyps, 132 were retrieved. Of these, 104 (79%) were adenomas. Of 49 colonic adenomas smaller than 10 mm, 4 (8%) showed severe atypia (carcinoma in situ) but not invasive carcinoma. Of 36 adenomas sized 10--19 mm 8 (22%) showed severe atypia and one (3%) invasive carcinoma. Of 19 adenomas larger than 60 mm, 6 (32%) showed severe atypia and one (5%) invasive carcinoma. Of the colonic polyp patients, 87% had only one or two polyps. Synchronous adenomas and non-neoplastic polyps were found in 6 of 11 cases with 3 or more colonic polyps. It is concluded that endoscopic polypectomy, carefully and properly performed, is a valuable and promising procedure in the diagnosis and treatment of polyps in the gastrointestinal tract, especially in the large bowel.

Adenoma↗
PubMed2000

Gastrin and gastrin receptor activation: an early event in the adenoma-carcinoma sequence.

BACKGROUND AND AIMS: Gastrin and the cholecystokinin type B/gastrin receptor (CCKBR) have been shown to be expressed in colorectal adenocarcinoma. Both exogenous and autocrine gastrin have been demonstrated to stimulate growth of colorectal cancer but it is not known if gastrin affects the growth of colonic polyps. The purpose of this study was to determine if gastrin and CCKBR are expressed in human colonic polyps and to determine at which stage of progression this occurs. METHODS: A range of human colonic polyps was assessed for gastrin and CCKBR gene and protein expression. RESULTS: Normal colonic mucosa did not express gastrin or CCKBR. Gastrin and CCKBR reverse transcription-polymerase chain reaction products were detected and verified by specific hybridisation with an oligo probe on Southern blots. Gastrin and CCKBR were expressed in 78% and 81% of polyps, respectively. Both genes were coexpressed in 97% of cases. Immunohistochemistry identified progastrin in 91%, glycine extended gastrin 17 in 80%, and amidated gastrin 17 in only 47% of polyps. CCKBR was present in 96% of polyps. Expression of gastrin and CCKBR was seen in all histological types and sizes of polyps. CONCLUSIONS: This study is the first to show widespread expression of both gastrin and its receptor in colorectal polyps. Their activation occurs early in the adenoma-carcinoma sequence. Gastrin may promote progression through the adenoma-carcinoma sequence.

Adenoma↗
PubMed1991

Histological classification of schistosomal egg induced polyps of colon and their clinical significance. An analysis of 272 cases.

272 cases of schistosomal egg induced polyps collected from mass-screening for colorectal carcinoma in Jiashan County were divided into 3 types: fibrous type (FT), mixed type (MT) and epithelial proliferative type (ET). The ET was characterized by crypt elongation, hypertrophy, variation in size, disorderly arrangement, as well as the high percentage of atypical hyperplasia (64.9%). The coexistence and transition between inflammatory reactive hyperplastic and neoplastic crypts were noticed. By HID/AB staining, sialomucins were increased in ET, CEA and PNA receptors detected by the ABC method were present in 18/20 and 6/18 of ET respectively. The mucin expression of ET was similar to that of adenomas. It is likely that a spectrum of ET, atypical hyperplasia and adenoma may exist. We suggest that the patients with ET, especially those with atypical hyperplasia, should be regarded as "risk group", and close follow-up is needed.

Adenoma↗
PubMed1991

[The morphogenesis of polyps of the large intestine].

The proportion of so-called hyperplastic polyps among other colon epithelial tumours remains unclear. Colon polyps are studied in 400 patients: hyperplastic polyps are found in 107, a combination of hyperplastic polyp with tubular adenoma in 143, tubular adenoma in 72, villous adenoma in 41 and tubulovillous adenoma in 37 cases. Hyperplastic structures and formation of adenomatous structures were, as a rule, observed in a polyp tip, this corresponding to the increase of nuclei volume and DNA amount in the tip colonocytes. The determination of karyometric coefficient (the ratio of the colonocyte nuclei volume in the polyp tip to colonocytes in the intact mucosa) is proposed as a quantitative criterion of proliferative and dysplastic processes.

Colon↗
PubMed1989

Follow-up of a sessile juvenile polyp of the colon: a case report.

The aim of this case report is to underline some unusual features of a colonic juvenile polyp found in a young adult: lack of symptoms, site, sessile morphology and increase in site (greater than 50% in 2 years). The usefulness of the radiological survey to indicate endoscopic polypectomy is emphasized.

Adolescent↗