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Value of fiberoptic gastrointestinal endoscopy in infants and children.

Fiberoptic gastrointestinal endoscopy was performed on 52 patients between the ages of 2 months and 16 years. The procedures were safely and easily done with premedications consisting of meperidine, promethazine, and chlorpromazine, and atropine, with diazepam given at the time of the procedure. Fiberoptic endoscopy was particularly helpful in localizing the site of upper gastrointestinal hemorrhage, in retrieving foreign objects, and in removing colonic polyps. In contrast, endoscopy added little to the clinical history and roentgenographic studies in children with recurrent abdominal pain or vomiting, in whom we believe fiberoptic endoscopy is not indicated unless the symptoms or history appear inconsistent with the diagnosis of functional bowel disease.

Abdomen↗

Colonoscopic follow-up of adenomas and colorectal cancer.

Increasing experience with colonoscopy has altered recommendations for the frequency of follow-up surveillance examinations for adenomatous polyps and colorectal cancer. Current recommendations include a follow-up colonoscopy at 1 year for patients with more than two adenomatous or highly suggestive polyps and after curative surgery for colorectal cancer. Other patients can safely receive a follow-up colonoscopy at longer intervals of 3 years. Published data and a review of the Ochsner Clinic experience are presented to support these recommendations.

Adenoma↗

Human acquired naevi are clonal.

Naevi are nearly universal in humans, yet their cellular origin remains obscure. Understanding the cellular and molecular mechanisms involved in naevus development may be important in understanding the pathogenesis of malignant melanoma. This study aimed to discover whether human acquired naevi are premalignant by examining whether they are clonal. To determine clonality naevi were removed and separated into epithelial and naevus cell fractions and the DNA prepared and digested by a methylase-sensitive restriction enzyme. The highly polymorphic X-linked human androgen receptor (HUMARA) gene was then amplified by a polymerase chain reaction and examined by gel electrophoresis and autoradiography. In polyclonal cell populations both alleles are usually seen as two distinct bands, whilst clonal populations yield a single band. Using these techniques 35 junctional naevi, 11 compound naevi and one congenital naevus from 40 women were examined. Of these, 81% (37 out of 47) of the naevi were clonal, while all of the epithelial cell controls were polyclonal. These data are novel and have great importance for understanding the development of human acquired naevi and cutaneous malignant melanoma. Because monoclonality is a marker of neoplasia, or preneoplasia, our data support the hypothesis that common acquired naevi should be considered to be premalignant lesions, similar to colonic polyps. Such lesions may have undergone the first molecular step(s) in the development of cutaneous malignant melanoma. Understanding the events involved may lead to new methods of prevention and treatment.

Clone Cells↗

Intervention studies on cancer.

This paper (and an extensive supplementary report) considers how far cancer/risk factor associations based on epidemiology have been confirmed by evidence from 226 studies involving interventions other than smoking. Many are small, uncontrolled, of unrepresentative populations, concern cancer markers not cancer, and may involve combinations of agents. Many agents suspected of causing cancer are untested by intervention trials. For seven of 16 agents tested (fibre, folic acid, low-fat diet, riboflavin, zinc, vitamin Bs, and vitamin D), the evidence is clearly inadequate to confirm or deny the epidemiology, while the evidence relating to calcium only concerns biomarkers. For other agents, the evidence relating to cancer itself is weak. In studies where cancer is the endpoint, only three effects have been replicated: (a) selenium supplementation and decreased liver cancer incidence, (b) treatment by the retinoid etretinate and reduced bladder tumours in susceptible individuals, and (c) beta-carotene supplementation and increased lung cancer incidence. Studies involving pre-cancerous conditions as the endpoint, which have a number of practical advantages, more frequently report benefits of intervention. Thus, oral pre-cancerous lesions can certainly be reduced by beta-carotene, vitamin A, and other retinoids, and possibly by vitamin E. It also seems that retinoids can reduce pre-cancerous cervix, skin and lung lesions, that vitamin C and the NSAID sulindac can reduce colonic polyps, and that sunscreens can reduce solar keratoses. Our findings clearly show that the great majority of causal relationships suggested by epidemiology have not been validated by intervention trials. This may be partly due to lack of suitable studies of adequate size or duration, or to using single dietary compounds as agents that are by themselves not responsible for the epidemiologically-observed associations between diet and cancer. However, this lack of validation must cause concern in view of the markedly conflicting evidence on beta-carotene and lung cancer between epidemiological and intervention studies. More intervention studies are needed, but in their absence, caution in interpreting epidemiological findings is warranted.

Clinical Trials as Topic↗

Analysis of episodes of care in a perfluorooctanesulfonyl fluoride production facility.

The observed to expected episodes of care experience of 652 employees at a fluorochemical (perfluorooctanesulfonyl fluoride) production facility was compared with 659 film plant (nonfluorochemical) employees at the same site (Decatur, AL). Episodes of care were defined by a hierarchical analysis of health claims data from 1993 through 1998. The age- and sex-adjusted expected number of episodes of care was calculated from the company's U.S. manufacturing workforce. For a priori interests, the observed to expected episodes of care ratios were comparable for fluorochemical and film plant employees for liver tumors or diseases, bladder cancer, thyroid and lipid metabolism disorders, and reproductive, pregnancy, and perinatal disorders and higher for biliary tract disorders and cystitis recurrence. Non-a priori associations among the fluorochemical plant workers included benign colon polyps, malignant colorectal tumors, and malignant melanoma.

Adult↗

Current status of nonsteroidal anti-inflammatory drugs in physiatry: balancing risks and benefits in pain management.

The gastropathy associated with the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) for musculoskeletal pain disorders has contributed to significant morbidity and mortality. The distinction between the cyclooxygenase 1 and 2 enzymatic properties lead to the development of selective cyclooxygenase-2 inhibitory NSAIDs with the prospect of reducing NSAID-related gastropathy while maintaining anti-inflammatory properties. Initial studies of the efficacy and safety of the selective cyclooxygenase-2 inhibitors seemed promising. Larger clinical trials were carried out to reinforce the efficacy and safety of the cyclooxygenase-2 anti-inflammatory medications (coxibs). Further analysis of these trials raised concern with regard to both the efficacy and safety of this class of drugs. The most recent clinical trials of the coxibs have demonstrated significant cardiovascular thrombogenic potential, particularly at higher doses. Clinical investigators and regulatory agencies have questioned whether these findings mitigate the efficacy of coxibs and NSAIDs in general in the prophylaxis of colonic polyps, Alzheimer's disease, and more saliently, musculoskeletal pain disorders. This article addresses the current controversy of the efficacy and safety of the coxibs and NSAIDs in general based on recent clinical trials and review by healthcare consortiums. This article also provides guidelines regarding the use of NSAIDs, including the diminishing armamentarium of the coxibs, and the alternative therapeutic options available to the physiatrist in managing musculoskeletal pain disorders.

Anti-Inflammatory Agents, Non-Steroidal↗

Screening preferences for colorectal cancer: a patient demographic study.

BACKGROUND: Colorectal cancer is a leading cause of cancer-related death. Screening for colorectal cancer is a rational and cost-effective strategy for reducing the incidence of colorectal cancer and related mortality. Despite endorsement by academic and health care organizations, patient awareness and compliance with screening is low, partly because of patient-related barriers to screening. METHODS: A convenience sample of adults attending the internal medicine and family practice clinics of a community teaching hospital was studied. A description of fecal occult blood testing (FOBT), sigmoidoscopy, and colonoscopy procedures was given in a packet along with a questionnaire. The questionnaire focused on screening procedures followed in our hospital (i.e., yearly FOBT and sigmoidoscopy every 5 years or colonoscopy every 10 years for average-risk individuals). RESULTS: Of the 193 patients who responded, 55% preferred sigmoidoscopy and FOBT, 29% chose colonoscopy, and 16% wanted no screening. Those with knowledge of someone with colon cancer or colon polyps reported a significantly higher preference for screening than those without such knowledge. Catholics were most likely to prefer no screening compared with non-Catholics. Ex-smokers (compared with all others) were more likely to want screening. Catholics were least likely to want colonoscopy. Patients with previous experience of colorectal screening preferred future screening. Those preferring no screening were significantly younger than those who expressed a preference for screening. CONCLUSION: The results of this study demonstrate diversity in patient choices for colorectal cancer screening. A focus on people's preferences rather than on the test itself may help develop and target appropriate intervention for prevention of colorectal cancer.

Adult↗

A new path planning algorithm for maximizing visibility in computed tomography colonography.

In virtual colonoscopy, minimizing the blind areas is important for accurate diagnosis of colonic polyps. Although useful for describing the shape of an object, the centerline is not always the optimal camera path for observing the object. Hence, conventional methods in which the centerline is directly used as a path produce considerable blind areas, especially in areas of high curvature. Our proposed algorithm first approximates the surface of the object by estimating the overall shape and cross-sectional thicknesses. View positions and their corresponding view directions are then jointly determined to enable us to maximally observe the approximated surface. Moreover, by adopting bidirectional navigations, we may reduce the blind area blocked by haustral folds. For comfortable navigation, we carefully smoothen the obtained path and minimize the amount of rotation between consecutive rendered images. For the evaluation, we quantified the overall observable area on the basis of the temporal visibility that reflects the minimum interpretation time of a human observer. The experimental results show that our algorithm improves visibility coverage and also significantly reduces the number of blind areas that have a clinically meaningful size. A sequence of rendered images shows that our algorithm can provide a sequence of centered and comfortable views of colonography.

Algorithms↗

Insertion/deletion polymorphism and other restriction fragment length polymorphisms in the MCC gene.

The MCC gene is a candidate as a tumor suppressor gene for colorectal neoplasms. Further, MCC is tightly linked to the familial adenomatous polyposis (FAP) locus by linkage and physical analysis. Hence, restriction fragment length polymorphisms (RFLPs) of this gene might be very useful for presymptomatic diagnosis of individuals in families segregating mutant alleles of the APC gene. Here we report the identification of five polymorphic systems in MCC gene (both cDNA and genomic), one of which is an insertion/deletion polymorphism that is detectable by a polymerase chain reaction method. These five RFLP systems should be useful for linkage studies in FAP and for examining loss of heterozygosity at this locus in colonic polyps and tumors.

Adenomatous Polyposis Coli↗

Serum antibody against unfused recombinant E7 protein of human papillomavirus type 16 in cervical cancer patients.

Sera were examined for the presence of antibody against E7 protein of human papillomavirus type 16 (HPV-16) by Western blot analysis using the bacterially derived unfused protein. The occurrence rates of anti-E7 antibody against HPV-16 were 14.1% (10/71) in cervical cancer patients, 0% (0/48) in cervical intraepithelial neoplasia patients, and 0% (0/41) in female non-malignant patients. Three patients (one with endometrial cancer, one with breast cancer, and one male patient with colon polyp) out of 115 patients with tumors in organs other than the cervix, had antibody against E7 protein of HPV-16. The serum antibody, once positive, could be detected for a long time after surgical removal of the cancers in all cases that could be followed up. HPV-16 DNA could be detected in 50% (13/26) of cervical cancer patients. Sixty-nine percent (9/13) of patients with HPV-16 DNA in cancers had the antibody and all the patients with stages II, III, and IV cervical cancer (8/8) harboring HPV-16 DNA showed the presence of the antibody against E7 protein of HPV-16. In contrast, only 20% (1/5) of cervical cancer patients with stage Ia or Ib harboring HPV-16 DNA showed positive for the anti-E7 antibody in sera. These findings suggest that the presence of anti-E7 antibody in serum depends on the staging of cervical cancer and extent of HPV infection.

Adult↗

Management of the malignant colorectal polyp: the importance of clinicopathological correlation.

The results of management of colorectal adenomas removed endoscopically and found to contain invasive cancer seen in a single institution over a 10 year period are presented. Clinical data were obtained retrospectively from patient case notes and all specimens were reviewed by one pathologist. Fifty-four patients with malignant polyps were studied after exclusion of others with polypoid carcinomas, epithelial misplacement and cases managed by primary segmental resection. Of the various considered predictors of adverse outcome, only histologically incomplete excision proved significant. However, when excision was considered macroscopically complete there was no significant association between incomplete histological excision and adverse outcome. Consideration should be given to conservative management of such cases.

Adenocarcinoma↗

Birt-Hogg-Dubé syndrome and Hornstein-Knickenberg syndrome are the same. Different sectioning technique as the cause of different histology.

The autosomal dominant inherited syndromes of Hornstein and Knickenberg (HKS), and Birt, Hogg and Dube (BHDS) are both characterized clinically by the overall spread of multiple flesh coloured papules of the skin. However, it is a matter of debate if colonic neoplasms (adenomas as well as adenocarcinomas) are associated findings in the HKS or rather in the BHDS. Furthermore, histological differences are said to exist between the skin lesions in the two syndromes: whereas perifollicular fibromas were described in the HKS, fibrofolliculomas and trichodiscomas were found in the BHDS. In the present study, we report on a father and his daughter in whom we initially diagnosed a BHDS. We then examined a greater number of the papular lesions in histologic sections cut vertically as well as horizontally to the epidermis. Our results indicate that the histologic differences between the skin lesions in the two syndromes are artificial ones, caused by interpretation of different sectioning planes, and that consequently HKS and BHDS are the same. Therefore, it is necessary to look for colonic polyps in the syndrome in question, regardless if one prefers the name HKS or BHDS for it.

Adult↗

Association of Streptococcus bovis bacteremia with bowel disease.

We reviewed the medical records of 19 patients who had Streptococcus bovis bacteremia. Eight patients had diverticulosis, four had benign adenomatous colonic polyps, and three had adenocarcinomas of the gastrointestinal tract. Laboratory workers and clinicians should be aware of the association of S. bovis bacteremia and gastrointestinal disease.

Gastrointestinal Diseases↗

Optimal timing of operation for bleeding peptic ulcer: prospective randomised trial.

From October 1980 to September 1983 all patients with upper gastrointestinal bleeding were admitted to a centralised unit and investigated by early endoscopy. A total of 142 patients with a proved duodenal or gastric ulcer were randomised after stratification for age and site of ulcer to early (aggressive) surgical management or a delayed (conservative) policy. Significantly more operations (n = 42; 60%) were performed in the early than in the delayed (n = 9; 20%) groups (p less than 0.01). There were no deaths among the 42 patients under 60. The overall mortality in the 100 patients aged over 60 was 10% and when analysed on an "intention to treat" basis there was no difference between early and delayed surgery. When, however, an unrelated death from a bleeding colonic polyp was excluded and the data analysed on "treatment received" the mortality was only 2% in the early group compared with 13% in the delayed group (p less than 0.05). When analysis was confined to gastric ulcer the difference between early (0%) and delayed (24%) treatment was even greater. The results of this trial indicate that for patients over 60 an aggressive surgical policy is associated with a significant reduction in mortality.

Adult↗

Disease severity and genetic pathways in attenuated familial adenomatous polyposis vary greatly but depend on the site of the germline mutation.

BACKGROUND: Attenuated familial adenomatous polyposis (AFAP) is associated with germline mutations in the 5', 3', and exon 9 of the adenomatous polyposis coli (APC) gene. These mutations probably encode a limited amount of functional APC protein. METHODS AND RESULTS: We found that colonic polyp number varied greatly among AFAP patients but members of the same family tended to have more similar disease severity. 5' Mutants generally had more polyps than other patients. We analysed somatic APC mutations/loss of heterozygosity (LOH) in 235 tumours from 35 patients (16 families) with a variety of AFAP associated germline mutations. In common with two previous studies of individual kindreds, we found biallelic changes ("third hits") in some polyps. We found that the "third hit" probably initiated tumorigenesis. Somatic mutation spectra were similar in 5' and 3' mutant patients, often resembling classical FAP. In exon 9 mutants, in contrast, "third hits" were more common. Most "third hits" left three 20 amino acid repeats (20AARs) on the germline mutant APC allele, with LOH (or proximal somatic mutation) of the wild-type allele; but some polyps had loss of the germline mutant with mutation leaving one 20AAR on the wild-type allele. CONCLUSIONS: We propose that mutations, such as nt4661insA, that leave three 20AARs are preferentially selected in cis with some AFAP mutations because the residual protein function is near optimal for tumorigenesis. Not all AFAP polyps appear to need "three hits" however. AFAP is phenotypically and genetically heterogeneous. In addition to effects of different germline mutations, modifier genes may be acting on the AFAP phenotype, perhaps influencing the quantity of functional protein produced by the germline mutant allele.

Adenomatous Polyposis Coli↗

Overview of screening and management of familial adenomatous polyposis.

The rarity of familial adenomatous polyposis (FAP) means that many clinicians may be unaware of the major advances that have taken place in screening for the condition over the past five years. This review is not only to document the current scene but also to give details of those involved in establishing registries throughout the country. FAP is a hereditary disorder which carries with it almost a 100% risk of colorectal cancer. The aim of screening is to detect gene carriers before they present with symptoms attributable to colonic polyps. In this way the incidence of colorectal cancer can be greatly reduced. The use of gene probes to identify patients with FAP is in its infancy but in selected pedigrees gene carriers can be identified using a venous blood sample. The recognition that congenital hypertrophy of the retinal pigment epithelium is an extracolonic manifestation of FAP in most pedigrees allows non-invasive ophthalmological screening of relatives at risk. The combination of these new screening methods with an effective regional registry for FAP can increase the number of patients detected by screening rather than by symptoms. This facilitates appropriate prophylactic surgery and reduces mortality related to colorectal cancer.

Adenomatous Polyposis Coli↗