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Biomedical subjects

R K Phillips

Publications and source records attributed to R K Phillips.

At least 73 records · Page 4Linked to original sources
PubMed1996

Tissue prostaglandin levels in familial adenomatous polyposis patients treated with sulindac.

BACKGROUND: Recent work has demonstrated a correlation between frequency of aspirin ingestion and colorectal cancer prevention. Sulindac, another nonsteroidal anti-inflammatory drug (NSAID), has been shown to cause polyp regression and a fall in cell proliferation in patients with familial adenomatous polyposis, who are destined to develop colorectal cancer unless the colon is removed. However, the mode of action of NSAIDs in colorectal carcinogenesis prevention remains to be determined, although a prostaglandin-mediated mechanism seems likely. METHODS: Rectal or duodenal biopsies from 20 patients with familial adenomatous polyposis, who had been randomized to sulindac or placebo, were analyzed for prostaglandin (PG) E2 and F2 alpha levels before and after treatment. RESULTS: A significant fall in prostaglandin E2 and F2 alpha levels was seen in patients who were on sulindac; this correlated with a visual improvement in number and size of polyps in the same patients (P = 0.0096; PGE2, P = 0.036; PGF2 alpha, Spearman's rank correlation). CONCLUSIONS: Nonsteroidal anti-inflammatory drugs may prevent colorectal cancer by their inhibition of prostaglandin synthesis. Prostaglandins may be implicated in carcinogenesis through an increase in cell proliferation, through immunosuppression, by increasing neovascularization, or via a mutagenic effect.

Adenomatous Polyposis Coli↗
PubMed1996

Colorectal polyp counts and cancer risk in familial adenomatous polyposis.

BACKGROUND & AIMS: In familial adenomatous polyposis, colorectal cancer prevention is by prophylactic colectomy, but dietary or chemopreventative strategies have been recently proposed in low-risk individuals. The aim of this study was to define predictive risk factors for colorectal cancer in familial adenomatous polyposis. METHODS: Between 1918 and 1993, 317 patients underwent colectomy. A multivariate analysis was performed to assess the relationship between colorectal cancer risk and polyp count, sex, and age at colectomy. RESULTS: The median polyp count was 842 (range, 78-7500), and cancer was found in 22% of patients. Polyp count and age, but not sex, predicted cancer risk. Patients with >1000 polyps had 2.3 times greater risk of cancer than those with <1000 polyps (P=0.006). Synchronous cancers increased with poly count (P<0.05). Each 10-year age group had a 2.4-fold difference in cancer risk (95% confidence interval, 1.9-3.2; P<0.001). Four cases of cancer occurred in patients at low risk (younger than 30 years of age, <1000 polyps; 3.3%). CONCLUSIONS: More adenomas and older age are associated with a higher risk of colorectal cancer. However, cancer does occur in low-risk individuals and may be missed by surveillance, making alternatives to prophylactic surgery inadvisable.

Adenomatous Polyposis Coli↗
PubMed1996

Differences in the levels and pattern of DNA-adduct labelling in human cell lines MCL-5 and CCRF, proficient or deficient in carcinogen-metabolism, treated in vitro with bile from familial adenomatous polyposis patients and from unaffected controls.

In patients with familial adenomatous polyposis (FAP), duodenal adenomas cluster around the ampulla and their distribution closely resembles mucosal exposure to bile, suggesting a role for bile in their development. Previous studies using 32P-postlabeling to detect DNA adducts, have provided evidence to support this hypothesis. We have now investigated the role of metabolic activation in influencing the levels and patterns of adduct formation by incubating precolectomy gallbladder bile from FAP patients and bile from unaffected controls with human lymphoblastoid cell lines that are metabolically proficient (MCL-5), or deficient (CCRF). 32P-Postlabeling assays showed that MCL-5 cells (genetically engineered to express five human cytochromes P450 and microsomal epoxide hydrolase) formed characteristic adduct spots with benz[a]pyrene, benzo[g]chrysene, 7,12-dimethylbenz[a]anthracene, benzidine, sterigmatocystin and 3-methylcholanthrene, whereas CCRF cells did not. Accordingly, we assayed the ability of bile from FAP patients and controls to form DNA adducts in MCl-5 and in CCRF cells. Relative adduct labelling (RAL) in MCL-5 cells treated with FAP bile (12 patients, median 10, range 1-74) was significantly higher than in cells treated with control bile (12 patients, median 4, range 0-9; P = 0.0007) as was RAL for the two major adduct spots. These two major adduct spots were not observed when bile was incubated with CCRF cells. The adduct spots in CCRF DNA appeared in positions similar to some of the minor adduct spots produced by bile in MCL-5 DNA and to some of the adduct spots seen previously when bile was incubated with salmon sperm DNA in vitro. RAL for CCRF cells incubated with FAP bile (seven patients, median 23.0, range 0-49) was significantly higher than in cells treated with control bile (seven patients, median 2.0, range 0-26; P = 0.0034). These results indicate that the bile obtained from FAP and control patients contains adduct-forming substances, some of which are direct acting and some of which require metabolic activation. In both cell lines, FAP bile produced significantly higher adduct labelling than control bile, adding to the evidence that bile can induce DNA damage in vitro and plays a role in neoplastic development in the FAP foregut.

Adenomatous Polyposis Coli↗
PubMed1996

A modifying locus for familial adenomatous polyposis may be present on chromosome 1p35-p36.

Mutations of the APC gene cause familial adenomatous polyposis (FAP) in humans and multiple intestinal neoplasia (Min) in laboratory mouse strains. A dominant modifying gene (Mom1), which partially suppresses the min phenotype, has been mapped to mouse chromosome 4. This region is syntenic with human chromosome 1p35-p36. The phospholipase A2 (Pla2s) locus is an excellent candidate for Mom1 and the equivalent human locus PLA2G2A is found on chromosome 1p35. It does not necessarily follow, however, than any modifier of mouse polyposis also influences human disease. In order to test whether a locus on 1p modifies FAP, subjects from 28 FAP families have been typed at microsatellite loci on this chromosome arm. The severity of their duodenal polyposis has also been assessed by endoscopy. Pedigree (lod score) linkage analysis found no evidence of a simple, dominant modifying gene, comparable with the action of Mom1 in inbred mouse strains. Given the more complex genetic and environmental interactions likely to exist in outbred human populations, it is probably more appropriate to use tests which do not specify a mode of inheritance. Using these methods of analysis, the data suggest that a locus on chromosome 1p35-p36 may influence the severity of duodenal FAP.

Adenomatous Polyposis Coli↗
PubMed1996

[Hemorrhoidectomy: current status].

The many treatments for haemorrhoids highlight a lack of consensus. Differences in patients' and surgeons' priority make objective evaluation of haemorrhoid treatment difficult; different types of haemorrhoids are being treated in patients from different socio-economic backgrounds by surgeons of varying expertise from within different cultural settings. In this article we have reviewed the results of common treatments for haemorrhoids and give an outline of our operative technique when performing haemorrhoidectomy.

Hemorrhoids↗
PubMed1996

Overexpression of p53 in duodenal tumours in patients with familial adenomatous polyposis.

Duodenal polyps and tumours of different histology from patients with familial adenomatous polyposis (FAP) were examined for p53 overexpression to determine the genetic events in duodenal tumorigenesis. Samples from endoscopic biopsy specimens of 152 duodenal adenomatous polyps (taken from 79 patients) and from 13 surgically resected adenomatous polyps or cancers (taken from nine patients) were studied by routine histological examination and immunohistochemistry. p53 was overexpressed in: 0 per cent of normal mucosa samples (none of 29), 25 per cent of tubular adenomas (28 of 111), 72 per cent of tubulovillous and villous adenomas (13 of 18) and 100 per cent of duodenal cancers (seven of seven); and in 28 per cent of mildly dysplastic polyps (32 of 113), 56 per cent of moderately or severely dysplastic polyps (nine of 16) and 100 per cent of cancers (seven of seven). Overexpression of p53 increased with passage down the adenoma-carcinoma pathway and might therefore be a valuable additional marker of risk for duodenal malignancy in patients with FAP.

Adenomatous Polyposis Coli↗
PubMed1996

Transperineal repair of symptomatic rectocele with Marlex mesh: a clinical, physiological and radiologic assessment of treatment.

BACKGROUND: The aim of this study was to evaluate the operative repair of rectoceles in a defined group of women by a technique designed to deal with the cause (failure of the rectovaginal septum) rather than the effect (rectal and vaginal wall bulging). STUDY DESIGN: Only women whose defecation was aided by vaginal digitation and who had large rectoceles on proctography were included. Any other clinical symptoms in the absence of vaginal digitation, even when proctography demonstrated a rectocele, were not taken as indicators for surgery in this study. There were nine women, median age 50 years (range, 32 to 61). The rectovaginal septum was repaired with Marlex mesh through a perineal approach by one surgeon. The median follow-up period was 29 months. RESULTS: Eight of the nine women achieved successful evacuation after surgery without the need for vaginal digitation. Rectocele size, depth, and the percent of barium trapped in the rectocele on proctography were all improved. Anorectal physiology measurements were unchanged by surgery. CONCLUSIONS: Operative repair of the rectovaginal septum removes the need for vaginal digitation in most women with large rectoceles on proctography. Further studies in well-defined groups of women are needed to establish how well rectocele repair aids women with a variety of other pelvic and perineal symtoms.

Adult↗
PubMed1996

[The effect of the physico-chemical properties of suture materials and the surface structure on adherence of tumor cells].

Local recurrence following curative resection for colorectal cancer may be caused by the seeding of free malignant cells at the anastigmatic site. This study investigated the influence of suture material on in vitro tumor cell adherence. Radiolabeled rat colonic cancer cells (RCC5) were incubated with a variety of suture materials, and the relative contribution of chemical composition and physical configuration to cell adherence was assessed. Nonadherent cells were washed free, and the cell adherence was determined by radioactive counting. Marked differences in adherence were observed, with cells preferentially adhering to protein-based and multifilament sutures. These observations were confirmed using scanning electron microscopy. These findings indicate that both chemical composition and physical configuration influence the adherence of tumor cells to sutures and suggest that the use of protein-based and multifilament sutures be carefully considered in situations where free malignant cells may be present following colorectal surgery.

Animals↗
PubMed1995

Juvenile polyposis.

Juvenile polyposis is an uncommon condition characterized by the development of multiple juvenile polyps, predominantly in the colon but also in the rest of the gastrointestinal tract. The condition usually presents in childhood; only 15 per cent of patients present as adults. The rarer and often fatal form, namely, juvenile polyposis of infancy, is typified by diarrhoea, protein-losing enteropathy, bleeding and rectal prolapse. The more common form of juvenile polyposis (affecting the colon, stomach and small bowel) occurs in the first or second decade with rectal bleeding and anaemia. A family history of the condition is found in 20-50 per cent of patients with apparently an autosomal dominant trait. The gene for juvenile polyposis has not yet been identified. Epithelial dysplasia is common and the cumulative risk of colorectal cancer is > 50 per cent. Various extracolonic abnormalities may also occur. Most patients are treated surgically for colonic polyps, although endoscopic polypectomy is also an option. The rest of the gastrointestinal tract should be screened as should asymptomatic first-degree relatives.

Adenomatous Polyposis Coli↗
PubMed1995

Persistence of idiopathic anal fistula may be related to epithelialization.

Anal fistulas may fail to heal because of continuing disease within the intersphincteric anal glands. Histological studies of the intersphincteric component of 18 consecutive idiopathic anal fistulas show that fistula persistence may be caused by epithelialization of the fistula track from internal or external openings. Some fistulas are lined by epithelium similar to that of anal gland ducts, but this may also represent epithelium derived from the transitional zone of the anal canal. Persistence may be related more to non-specific epithelialization of the track than to a chronically infected anal gland.

Anal Canal↗
PubMed1995

Polyposis: the Peutz-Jeghers syndrome.

The classical pigmentation of Peutz-Jeghers syndrome distinguishes it immediately from the other polyposis syndromes. Less widely appreciated than this most obvious manifestation are the pitfalls in management presented by the risk of cancer and by the performance of multiple laparotomies that also characterize this condition. An outline of these risks and an approach that minimizes them is presented.

Diagnosis, Differential↗
PubMed1995

Intraoperative measurement of colonic anatomy and attachments with relevance to colonoscopy.

This study examined the variations in colonic length and mesenteric attachments in 118 patients undergoing laparotomy. Measurements were taken according to a set protocol with the bowel pulled medially, or towards the pubic symphysis or the xiphisternum, mimicking the possible displacements that may occur during colonoscopy. A free sigmoid loop was not present in 20 patients (17 percent) because of adhesions. A descending mesocolon of 10 cm or more in length was recorded in ten patients (8 percent) and an ascending mesocolon 10 cm or greater in 11 (9 percent). Some 24 patients (20 percent) had mobile splenic flexures and in 34 (29 percent) the mid-transverse colon reached the symphysis pubis or lower when pulled downwards. Mean (range) total colonic length was 114.1 (68-159) cm. This study helps define anatomical variations that may affect the facility, or otherwise, of colonoscopy.

Adult↗
PubMed1995

Non-inflammatory rectovaginal fistula.

The results of surgical repair of straightforward rectovaginal fistula in 26 women (obstetric, 13; infection, nine; trauma, one; unknown but not radiation-induced or related to inflammatory bowel disease, three) were ultimately excellent; 23 patients were cured. However, this result obscures a high early failure rate in five of 12 patients having a transanal advancement flap and in one of eight having perineoproctotomy (lay open and repair). A temporary stoma was used in 11 patients (five of eight with a perineoproctotomy, three of 12 with an advancement flap and in three having another local procedure.

Adult↗