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Biomedical subjects

R K Phillips

Publications and source records attributed to R K Phillips.

At least 127 records · Page 7Linked to original sources

Randomized controlled trial of the effect of sulindac on duodenal and rectal polyposis and cell proliferation in patients with familial adenomatous polyposis.

Twenty-four patients with familial adenomatous polyposis who had previously undergone prophylactic colectomy and had advanced duodenal polyposis were entered into a randomized trial to assess the effect of the non-steroidal anti-inflammatory drug sulindac on duodenal and rectal polyps. Polyp size and number were assessed by videotaped duodenoscopy (and rectoscopy in 14 patients) at entry and after 6 months of treatment; the tapes were compared by two assessors who were unaware of the randomization and the shuffled chronological order of the recordings. Mucosal cell proliferation was measured by in vitro incorporation of 5-bromo-2'-deoxyuridine. Sulindac therapy was associated with a reduction in epithelial cell proliferation in the duodenum (median labelling index (LI) 15.8 versus 14.4 per cent, P = 0.003) and a trend towards duodenal polyp regression (P = 0.12). In the rectum, cell proliferation showed a marked reduction (median LI 8.5 versus 7.4 per cent, P = 0.018), and significant (P = 0.01) polyp regression was seen. Rectal polyposis was less severe than that in the duodenum and responded more dramatically. Sulindac is a possible treatment for patients in whom rectal polyps have failed to show significant regression after ileorectal anastomosis and who are unsuitable for pouch surgery; it may be useful in early duodenal polyposis or as an adjunct after duodenal clearance.

Adenomatous Polyposis Coli↗

Life expectancy after colectomy and ileorectal anastomosis for familial adenomatous polyposis.

PURPOSE: Despite the introduction of screening, surveillance, and prophylactic colectomy surgery, patients with familial adenomatous polyposis (FAP) are at risk of dying from other malignancies. METHODS: In order to quantify this risk and identify the causes of mortality, a retrospective life table analysis was performed on 222 patients with familial adenomatous polyposis who had undergone a total colectomy and ileorectal anastomosis between 1948 and 1990. These FAP patients were compared with an age- and sex-matched group of the general population and a relative risk of dying was calculated. RESULTS: Of 222 patients, 53 have died. In a matched group of the general population the expected number of deaths would be 15.8. The relative risk of dying is therefore 3.35. There has been no significant improvement with time and the relative risk is greatest for female patients. CONCLUSION: The three main causes of mortality are upper gastrointestinal malignancy, desmoid disease, and perioperative complications. Further research should therefore be aimed at prevention and improved treatment of these in order to improve survival.

Adenomatous Polyposis Coli↗

Influence of suture physicochemical and surface topographic structure on tumor cell adherence.

Local recurrence following curative resection for colorectal cancer may be caused by the seeding of free malignant cells at the anastomotic 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↗

Cellular proliferation at sutured and sutureless colonic anastomoses.

Elevated cellular proliferation in the vicinity of an anastomosis may explain the enhanced susceptibility to carcinogens. The aim of this study was to determine whether anastomotic cellular proliferation was altered by different suture materials and whether a rise in cell turnover also occurred after a "sutureless" closure. A transverse descending colon enterotomy was repaired with interrupted sutures of 5/0 silk (n = 20), stainless steel (n = 20), or Vicryl (Ethicon, Inc., Somerville, NJ) (n = 20) or by a sutureless technique (n = 20). Using a stathmokinetic technique, crypt cell production rates (CCPR) were calculated at the anastomosis and in the adjacent colon at varying intervals between one week and six months after treatment. Overall colonic cellular proliferation appeared to be elevated at a sutured colotomy for at least three months (P < 0.05). In contrast, no significant elevation in cellular proliferation was observed at sutureless anastomoses. The duration of elevated proliferative response varied among the sutures.

Anastomosis, Surgical↗

Colectomy with ileorectal anastomosis lowers rectal mucosal cell proliferation in familial adenomatous polyposis.

Rectal polyp regression has been observed in familial adenomatous polyposis (FAP) after colectomy and ileorectal anastomosis (IRA). In view of the association between risk of neoplasia and epithelial cell turnover rates, a study was conducted to determine the effect of colectomy and IRA on rectal mucosal proliferation in FAP. Endoscopic biopsies of flat rectal mucosa were taken from 12 FAP patients with an established IRA and 10 FAP patients prior to colectomy. Mucosal proliferation was assessed by flash-labeling S-phase cells with bromodeoxyuridine. Labeled cells were visualized on paraffin sections with an immunohistochemical stain using a monoclonal antibody to bromodeoxyuridine. Twenty crypt columns were analyzed. The mean labeling index (percent labeled cells/crypt) of the FAP patients with established IRAs (7.0 +/- 1.4 percent) was significantly less than that of the precolectomy patients (12.8 +/- 3.0 percent) (Mann-Whitney U test, P = 0.0004). Comparison of labeled distribution curves shows a contraction of the crypt proliferative zone in the IRA group. Colectomy with IRA in FAP is associated with a significant reduction in rectal mucosal cell proliferation. These findings support the claim of reduced risk of rectal cancer following this procedure in FAP and are of relevance to the study of environmental vs. genetic control of cell proliferation.

Adenomatous Polyposis Coli↗

Solitary juvenile polyps: not a marker for subsequent malignancy.

BACKGROUND: Solitary juvenile polyps are considered benign. In contrast, juvenile polyposis is associated with malignancy and poor long-term outcome. Recent reports suggest that solitary juvenile polyps may also undergo both adenomatous and malignant change. The long-term outcome of patients with solitary juvenile polyps is unknown. Patients are treated conservatively and discharged from follow-up. The present study was designed to examine the incidence of cancer and mortality of these patients, comparing their life expectancy with that of the general population. METHODS: The outcome of 82 patients with a solitary juvenile polyp between 1958 and 1982 was examined by life table analysis. Patients were traced through the Office of Population Censuses and Surveys for death and cancer registration. Patients were compared with an age- and sex-matched group of the general population. RESULTS: The relative risk of dying for patients who have previously had a solitary juvenile polyp in comparison with the general population was found to be 0.66 (95% confidence interval, 0.34-1.14). There was only one case of colorectal cancer. CONCLUSIONS: Patients with a solitary juvenile polyp are not at increased risk of dying of or developing colorectal cancer and do not require further follow-up or investigations.

Adenocarcinoma↗

DNA adducts, detected by 32P-postlabelling, in DNA treated in vitro with bile from patients with familial adenomatous polyposis and from unaffected controls.

Patients with familial adenomatous polyposis (FAP) have a high risk of developing duodenal adenomas and carcinomas. The distribution of these neoplasms resembles mucosal exposure to bile, suggesting that bile may play a role in adenoma development. Our previous results, using DNA adducts detected by 32P-postlabelling as an index of genotoxicity, have supported this hypothesis. We found significantly higher adduct labelling in the duodenum of FAP patients than in the duodenum of control patients and significantly higher labelling in the small bowel of rats gavaged with FAP bile than in rats given control bile. We have now investigated the ability of human bile to form adducts with DNA in vitro. Bile obtained from the gallbladder of 18 FAP patients immediately before colectomy, and from 18 control patients, was incubated with salmon sperm DNA in solution at 37 degrees C for 1 h, after which the purified DNA was analysed for DNA adducts, using the nuclease P1 method of 32P-postlabelling. Relative adduct labelling values (RAL, adducts per 10(9) nucleotides) produced by FAP bile samples were significantly higher than RAL values produced by control bile samples (medians 197 versus 86, P = 0.0016, Mann-Whitney test). We found a consistent pattern of adduct labelling, varying in intensity between samples. Adduct spots were eluted from TLC plates and analyzed by reverse-phase HPLC. Each major spot gave several peaks that were consistent between bile samples from different patients and were similar in FAP and control bile. These results indicate that bile from FAP and control patients contains similar, directly acting genotoxic compounds but that levels are higher in FAP than in control patients. This suggests that bile from FAP patients is more genotoxic than bile from control patients. Incubation of bile with free-radical scavengers and deconjugating enzymes failed to influence adduct labelling in this system.

Adenomatous Polyposis Coli↗

An inexpensive method of quality assessment in anastomosis workshops.

A method of comparing the quality of intestinal anastomoses performed in craft workshops is described. The equipment is readily available in any hospital, inexpensive and requires no technical construction. The apparatus accurately measures the intraluminal pressure at the first sign of anastomotic leak and a method of deriving the wall tension is explained. Calculation of wall tension at the point of failure allows comparison of anastomoses of different size. An instructor can therefore monitor the improvement of an individual trainee or rank a class according to the quality of their anastomoses.

Anastomosis, Surgical↗

32P-postlabelling studies of target tissues and bile from patients with familial adenomatous polyposis and from unaffected controls.

Patients with the inherited form of colon cancer, familial adenomatous polyposis (FAP), are at high risk of developing duodenal adenomas and carcinomas. The periampullary clustering of these neoplasms suggests that bile plays a role in their development. We investigated this theory using 32P-postlabelling to detect DNA adducts. We found significantly higher adduct levels in duodenum of FAP patients than in unaffected controls, and higher levels in duodenum than stomach. Levels of adducts were significantly higher in the small bowel of rats gavaged with FAP gallbladder bile than in the small bowel of those that received control gallbladder bile. We found that bile from FAP gallbladder produced significantly more DNA adducts than control gallbladder bile when incubated with salmon sperm DNA in vitro. These results support the hypothesis that the bile of FAP patients may be involved in the development of duodenal adenomas in these patients.

Adenomatous Polyposis Coli↗

Repair of rectocoele using Marlex mesh.

A new operation for rectocoele which places Marlex mesh in the rectovaginal septum is described in four women, of whom three have normal defaecation and one is improved but still needs occasionally to use digital perineal pressure. The aetiology of rectocoele is discussed.

Adult↗

Magnetic resonance imaging of anal fistulae.

Success of surgery for an anal fistula depends on accurate assessment of the fistula; however, such assessment is technically difficult. We have done a prospective study that determined the accuracy of magnetic resonance imaging (MRI) in demonstrating the course of fistulae, by comparing MRI scan interpretations with subsequent operative findings. 16 patients (mean [range] age 42 [24-66] years) had MRI followed by surgery within a mean of 22 (1-101) days. MRI scan interpretations agreed precisely with independently documented operative findings in 14 of 16 patients. MRI is an accurate method of delineating anal fistulae, and should be considered for patients with difficult fistulae that recur despite skilled attention because it demonstrates abnormalities that might otherwise be missed.

Adult↗

Bacteriology of anal fistulae.

Anal fistulae are said to arise from cryptoglandular infection of the anal glands, which lie within the intersphincteric space. The type and virulence of the micro-organism responsible may determine whether an anal fistula develops. The microbiology of chronic anal fistulae has not been reported previously. Twenty-five consecutive anal fistulae were studied prospectively (eight intersphincteric fistulae, 12 trans-sphincteric fistulae, two suprasphincteric fistulae, one extrasphincteric fistula, one superficial fistula, one anovaginal fistula). There were 18 men and seven women, with a median age of 42 (range 22-71) years. Patients with Crohn's disease or acute anorectal suppuration were excluded. In 18 patients, 0.1 ml granulation tissue from the track of the fistula was obtained and processed within 4 h using standard microbiological techniques. Sixty-nine isolates representing at least 17 species were obtained. The predominant organisms were Escherichia coli (22 per cent), Enterococcus spp. (16 per cent) and Bacteroides fragilis (20 per cent). The majority of the growths were obtained only from enrichment. Bacteria from only one patient grew at a dilution of 10(3). Granulation tissue from 25 patients was processed for mycobacterial culture, and Mycobacterium tuberculosis was grown from one patient. No other mycobacterium was isolated. The chronic inflammation in anal fistulae does not seem to be maintained by either excessive numbers of organisms or organisms of an unusual type.

Adult↗

Anatomy and function of the anal longitudinal muscle.

The longitudinal muscle in the intersphincteric space has received little attention despite an explosion of interest in anorectal physiology in the past decade. Its anatomy is contested and its function unknown. Speculation, however, gives it a role as a skeleton supporting and binding the rest of the internal and external sphincter complex together, as an aid during defaecation by everting the anus, as a support to the haemorrhoidal cushions, and as a determining factor in the ramification of sepsis.

Anal Canal↗