Biomedical subjects
Publications and source records attributed to R K Phillips.
The association of ischaemic colitis with a distal obstructing carcinoma is described in two patients. When a segment of colonic ischaemia is demonstrated on barium enema, it is important to consider an association with a distal tumour.
Intra-abdominal desmoid tumours represent a major cause of morbidity and mortality in patients with familial adenomatous polyposis (FAP), and such patients are also liable to develop musculoskeletal desmoids. We have reviewed the CT appearances of 44 desmoid lesions (28 intra-abdominal and 16 musculoskeletal) in 20 patients with FAP. We found a considerable heterogeneity in the CT appearance of musculoskeletal and intraabdominal desmoids, with respect to their density, definition and change in size or density on follow-up, not only between different patients but also in patients with multiple lesions, who rarely showed identical appearances of all lesions. In some cases, mesenteric tumours may initially present as ill-defined soft tissue infiltration of mesenteric fat, becoming larger and more mass-like with time. On medical treatment, shrinkage was seen infrequently in musculoskeletal desmoids, and not at all with mesenteric lesions. CT evidence of bowel involvement by intra-abdominal lesions was frequent, most commonly appearing as 'tethering' or encasement of bowel loops. The presence of a large mesenteric mass (> 10 cm diam.), multiple mesenteric masses, extensive small bowel involvement and/or bilateral hydronephrosis were associated with ultimate death.
The aim of this study was to document the appearances of fistula-in-ano on magnetic resonance imaging (MRI) and to prospectively evaluate the accuracy of MRI in the pre-operative assessment of anal fistulae. Patients with a clinical diagnosis of fistula-in-ano and awaiting surgery (n = 35) were examined with MRI. The fistulous tracks with their secondary extensions and abscesses are readily seen as low signal on T1-weighted images and high signal areas on STIR images. In order to determine the accuracy of the MRI interpretations, an experienced coloproctologist operated on all 35 patients without the knowledge of the scan interpretations and the findings at surgery were compared with the MRI scan interpretations. Concordance rates between MRI and operative findings were 86% for presence and course of the primary track, 91% for the presence and site of secondary extensions or abscesses and 97% for the presence of horse-shoeing. Although operative findings by an experienced coloproctologist were taken as the gold standard, we have shown that in 9% of our study group, failure of healing was related to pathology missed at surgery which had been documented on pre-operative MRI. It is probable, therefore, that the accuracy of MRI is higher than the figures quoted above. MRI is advocated as the imaging method of choice in the assessment of anal fistulae and its use may lead to a reduction in the recurrence rate due to inaccurate surgical assessment.
The phenotypic expression in familial adenomatous polyposis (FAP) is variable. This study compares the phenotype of 27 patients with an identical 5 base pair (bp) deletion at codon 1309 with a group of 61 matched patients with FAP where knowledge of specific mutations is not available and with seven other different mutations in 24 subjects. Patients with the codon 1309 deletion have significantly more colorectal polyps at the time of colectomy than age and sex matched FAP controls (p = 0.0001). The median number of polyps in colectomy specimens of patients with the deletion at codon 1309 was 4000 (interquartile (IQ) range 3000-4875), compared with 600 (IQ range 488-1400) in the matched controls. Mutations at codon 1323, 1407, and 233 were also associated with large numbers of polyps. Desmoid disease and extracolonic cancers were more common with the mutation at codon 1309 (p = 0.003). In conclusion, there may be a correlation between a specific germline mutation and the number of large bowel polyps. There is residual heterogeneity in phenotypic expression, however, and this may result from the influence of other genes, specific environmental factors or chance.
Resection of the colon in patients with familial adenomatous polyposis frequently results in the regression of polyps in the remaining rectum, suggesting a reduction of cellular proliferation. These patients remain at risk of developing rectal cancer but whether this risk increases with time is uncertain. Since ornithine decarboxylase activity is associated with cellular proliferation, mucosal ornithine decarboxylase was measured in rectal biopsy specimens from patients with familial adenomatous polyposis after ileorectal anastomosis (n = 36) and from normal controls (n = 30). The relationship between ornithine decarboxylase activity, age, and time from surgery was also examined. Median ornithine decarboxylase activity in familial adenomatous polyposis patients after ileorectal anastomosis (186, interquartile range (IQR) 107-534 pmol/mg protein/h) was not different from that in control subjects (227, IQR 123-374, p = 0.6). When patients were divided into three equal groups according to age, however, younger patients (< 25 years) had significantly higher activity than both older age groups (p < 0.02). Similarly, when patients were stratified according to the time elapsed since surgery, those who had had surgery less than six years previously had a significantly higher ornithine decarboxylase activity than those in whom a longer time interval had elapsed since surgery (p = 0.02). These results indicate that after colon resection, ornithine decarboxylase activity in patients with familial adenomatous polyposis is similar to that in normal controls but seems to fall over time. This may explain the regression of rectal polyps after colonic resection in this disorder.
AIMS: To explore the association between duodenal adenoma and carcinoma in patients with familial adenomatous polyposis (FAP). METHODS: A multicentre survey of 1262 patients with FAP yielded 47 cases of duodenal cancer. The association between adenoma and cancer was assessed in these cases. RESULTS: Adenomatous tissue was found within duodenal cancer in 29 of 44 (66%) patients with FAP and in mucosa adjacent to duodenal cancer in 31 of 42 (73%) such patients. Adenomas were found as a component of, or adjacent to, duodenal cancer in 38 of 45 (84%) patients. CONCLUSIONS: These observations support the existence of the adenomacarcinoma sequence in the duodenum of patients with FAP. Factors associated with malignant change included villous histology, moderate or severe dysplasia, and the presence of stage IV duodenal polyposis.
Familial adenomatous polyposis (FAP) is characterized by the presence of premalignant adenomas of the large and small bowel. Prophylactic colectomy deals with the risk for colon cancer, leaving duodenal cancer as the leading cause of death. Although most FAP patients have duodenal adenomas, only approximately 5% develop duodenal cancer. This study looks at progression of duodenal polyps with time. The outcome of endoscopic surveillance in the duodenum of 70 patients with familial adenomatous polyposis was determined. A mean of 40 months elapsed between endoscopies. Outcome was measured using video comparison and a staging system that includes histological assessment. Duodenal cancer developed in one patient, and was suspected in two others. The stage of duodenal polyposis worsened in another seven patients. When histology was ignored, comparison of video recordings in 52 patients showed a worsening in 21 (40%). In conclusion, further surveillance appears warranted so that patients at high risk for duodenal cancer might receive early treatment. Should slow progression of duodenal polyposis be shown to be associated with low risk, then most patients can be safely offered less frequent endoscopies than hitherto.
Patients with familial adenomatous polyposis (FAP) are at high risk for duodenal tumors, the distribution of which suggests that bile is important in their development. Studies of the bile of FAP patients suggest that it contains an excess of active carcinogens. Defective hepatic metabolism of carcinogens might account for these findings. The isozyme glutathione S-transferase mu (GST-mu) plays a major role in the hepatic metabolism of carcinogens. Peripheral blood GST-mu status reflects hepatic GST-mu status. The concentration of GST-mu was therefore measured by enzyme-linked immunosorbent assay of heparinized peripheral blood samples taken from 31 unrelated patients with FAP and from 38 unrelated control patients. FAP and control patients were matched for age, sex, diet, and smoking status. The median GST-mu concentration (micrograms per milliliter) was 0.5 (interquartile range, 0 to 11.6) in the FAP group and 8.85 (0.9 to 29.4, p = 0.0013) in the control group. Of the 31 FAP patients, ten had no detectable GST-mu activity compared with only one of the 38 controls (p = 0.002), while 71% of FAP patients had GST-mu concentrations less than a supplied positive control, compared with 50% of control patients (p = 0.064). Abnormal hepatic metabolism of carcinogens by GST-mu might contribute to the development of intestinal tumors in patients with FAP.
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After surgical excision of bowel, Crohn's disease is likely to recur around the anastomosis. It is suggested that this may indicate a biological effect of suture materials on gastrointestinal immunology. To investigate this, the influence of six suture materials on the function of macrophages obtained from the rat peritoneal cavity and human intestinal mucosa was assessed. All materials significantly impaired macrophage function.
Immunocytochemistry was used in parallel with conventional cytology to detect circulating malignant epithelial cells in 42 patients undergoing resection for colorectal cancer. Preoperative peripheral and peroperative mesenteric venous blood samples were taken. Tumour cells were isolated on a density gradient and cytospins prepared. Slides were stained by conventional cytology (May-Grünwald-Giemsa) and by an indirect immunoperoxidase technique with the anticytokeratin antibody KG8.13. Using conventional cytology, definite morphological evidence of malignancy was observed in three patients and suspicious features in a further seven. Immunocytochemistry confirmed these findings in all three of the malignant but in only one of the suspicious cases. Counts of immunostained cytospins showed the concentration of tumour cells in blood samples from these four patients to be in the range 0-954 cells/ml. This study supports the use of immunological markers to detect and enumerate malignant cells. This method provides a powerful tool to investigate one aspect of the metastatic process.
An intersphincteric approach has been developed that allows complete sphincter preservation in some patients with high fistulas. This operation in 13 patients (eight trans-sphincteric, five suprasphincteric tracks) has resulted in complete success in seven, partial success (ultimate sacrifice of the internal anal sphincter) in two and failure in four. When the operation is successful continence is better than after failed procedures.
Between January 1976 and June 1991, 161 women underwent restorative proctocolectomy. Seventeen (10.6 per cent) developed pouch-vaginal fistula. There was no difference in the incidence of inflammatory (15 of 141; 10.6 per cent) and non-inflammatory (two of 20; 10 per cent) disease, the severity of colitis or the number of stages in the operation. In 15 patients the fistula involved the ileoanal anastomosis; in two it had possibly occurred at the dentate line. There was no significant difference in the proportion of hand-sewn (ten of 120; 8.3 per cent) and stapled (seven of 41; 17 per cent) ileoanal anastomosis. Of the 17 women, six had pelvic sepsis in the immediate postoperative period and five had an anastomotic complication. There was no case of Crohn's disease. Three patients developed a pouch-vaginal fistula before closure of the ileostomy. The remaining 14 fistulas occurred a median of 7 (range 1-144) months after closure. Five further patients were referred from elsewhere to give a total of 22 for analysis of treatment and outcome. The fistula developed before ileostomy closure in five patients (group 1) and after closure in 17 (group 2). Following treatment, six fistulas had healed with five patients still undergoing treatment. In group 1, three of the five fistulas healed, whereas in group 2 only three of the 17 healed. Eight patients required excision of the pouch. The prognosis appears to be worse when pouch-vaginal fistula occurs after ileostomy closure. The optimal management is not yet established.
Between 1978 and 1988, 12 patients with familial adenomatous polyposis (FAP) and severe duodenal polyposis underwent duodenotomy and duodenal polypectomy. The patients were from two separate institutions; all were women, with a mean age of 45.6 (range 25-62) years at the time of duodenotomy. Recurrent duodenal polyposis was detected at endoscopy in all 12 patients, at a mean of 13.3 (range 5-36) months after duodenotomy. All patients had moderate to severe duodenal polyposis at the time of the last endoscopic examination. Local excision of duodenal adenomas is an unsatisfactory treatment option in those with FAP. The ideal management of patients with FAP who have severe duodenal polyposis remains uncertain.
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