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Biomedical subjects

R K Phillips

Publications and source records attributed to R K Phillips.

At least 181 records · Page 10Linked to original sources

Cancer and the Peutz-Jeghers syndrome.

Among 72 patients with the Peutz-Jeghers syndrome malignant tumours have developed in 16 (22%) of whom all but one have died. There were nine gastrointestinal and seven nongastrointestinal tumours. The relative risks of death from gastrointestinal cancer and all cancers were 13 (95% CI 2.7-38.1) and 9 (95% CI 4.2-17.3) respectively. The chance of dying of cancer by the age of 57 was 48%. There is evidence for a hamartoma/carcinoma sequence in the Peutz-Jeghers syndrome, suggesting that the gene locus involved is relevant to the development of malignancy in general.

Adult↗

Proctocolectomy and ileostomy for ulcerative colitis: the longer term story.

Elective surgery for ulcerative colitis usually involves the removal of the entire large bowel with either a conventional ileostomy or the formation of an ileoanal pouch anastomosis. Seventy patients undergoing a one stage elective total proctocolectomy and ileostomy between 1976 (the first year an ileoanal pouch was carried out in this hospital) and 1986 have been studied. We have confirmed that proctocolectomy and ileostomy for ulcerative colitis is not the trouble free operation many presume it to be when considering the alternative of an ileoanal pouch.

Adult↗

Prediction of outcome after curative resection for large bowel cancer.

Prospectively collected information on 2524 patients who had undergone "curative" resection for colorectal cancer was analysed to establish the rank-order of importance of both clinical and pathological factors affecting outcome. The patients were divided into two groups. In the first, a statistical weighting was established for each prognostic factor and those that influenced long-term survival were, in order of importance, lymph node status, tumour mobility, number of lymph nodes positive for tumour, presence of bowel obstruction, and depth of primary tumour penetration. Factors that influenced in-hospital mortality were cardiopulmonary complications, intraabdominal sepsis (without anastomotic leak), presence of bowel obstruction, and age. In the second group these mathematical weightings were applied, and the predicted and observed outcomes were in close agreement. Statistical techniques of this kind will be of value in prognosis and in analysis of the results of new treatment regimens.

Adult↗

Influence of tumour site on presentation, management and subsequent outcome in large bowel cancer.

To demonstrate any difference in outcome between patients with carcinoma at various sites within the large bowel, analysis of a large number of patients is necessary. From the Large Bowel Cancer Project, 4292 patients have been evaluated to compare mode of presentation, surgical management, pathological findings and outcome. Carcinoma at the splenic flexure was associated with the highest risk of obstruction (49 per cent); postoperative cardiopulmonary complications (36 per cent); in-hospital mortality (18 per cent); and the lowest age-adjusted 5-year survival (28 per cent), even after curative resection (38 per cent). This survival disadvantage was seen even in those without obstruction. Further, it was not accounted for by differences in age, sex, Dukes' stage or tumour differentiation between the various sites as stratification by these variables failed to alter significance (log rank chi 2 = 11.1; d.f. = 4; P less than 0.05). Compared with carcinoma of the left colon and rectum, tumours in the right colon were more likely to be poorly differentiated and locally advanced (in terms of fixation and penetration of the bowel wall) but were not associated with a higher risk of either distant spread at presentation or local recurrence. Age-adjusted 5-year survival following curative surgery was higher for the right colon (65 per cent) than the left (59 per cent).

Adult↗

Effect of steel wire sutures on the incidence of chemically induced rodent colonic tumours.

An experiment is presented which shows that colonic primary tumours cluster around a previously constructed anastomosis and that the choice of suture materials (but not the technique of their insertion) can influence this. In a rodent model where dimethylhydrazine was administered 2 months after surgery, anastomotic tumours were most often seen when wire sutures--as used in the staples of anastomotic stapling guns--had been employed (10 out of 16 large bowel tumours were anastomotic as compared with 2 of 12 in a silk sutured group, P = 0.019). An explanation may be that wire sutures persist much longer than silk (in the experiment, 10 months after insertion, 4 per cent of silk sutures were still present, 15 per cent of wire, P less than 0.01). This was translated into a greater degree of scarring at the anastomosis, being most severe in the presence of persisting sutures. Of the 12 anastomotic tumours found in both groups, 7 (58 per cent) were in the minority (17-26 per cent) who had persisting sutures and the remaining 5 in the 47 who had none. Techniques of suturing (needle always passed from the serosa in; needle from mucosa out--the latter in such a way that mucosal cells could be displaced into the bowel wall where it was supposed that they might be more susceptible to subsequent carcinogenesis) did not affect tumour yield. We suggest that non-absorbable sutures, and especially stainless steel wire, should not be used when constructing an anastomosis after large bowel cancer surgery.

1,2-Dimethylhydrazine↗

Malignant large bowel obstruction.

Of 4583 patients in the Large Bowel Cancer Project, 713 (16 per cent) were obstructed. The site of greatest risk was the splenic flexure (49 per cent). Advanced stage was neither the full reason why some patients obstructed nor for their subsequent poor prospects (age-adjusted 5-year survival: not obstructed, 45 per cent; obstructed, 25 per cent). Also, there was no greater risk of vascular invasion, no heavier lymph node burden and no worse tumour differentiation in patients with obstruction. In-hospital mortality was high (23 per cent), was not reduced by either a policy of primary or staged resection and was not influenced by the site of obstruction. There was no survival advantage for either policy, but hospital stay after primary resection was half that of staged. Immediate anastomosis in the obstructed left colon had a high clinical leak rate (18 per cent versus 6 per cent elective; P less than 0.001). Both registrars and consultants had similar mortality rates for elective primary resection and for the management of obstruction itself (as evidenced by results after the first stage of a staged resection). Selection probably accounts for the very much better results achieved by consultants for primary resection in the presence of obstruction (in-hospital mortality: consultants, 13 per cent; registrars, 24 per cent).

Adenocarcinoma↗

Local recurrence following 'curative' surgery for large bowel cancer: I. The overall picture.

The Large Bowel Cancer Project is a collaborative prospective study of 4228 patients with a histologically proven adenocarcinoma, of whom 2336 (55 per cent) survived a 'curative' resection. Follow-up information is available on 2220 patients (95 per cent). Subsequently, 309 (14 per cent) have developed a local recurrence confirmed by: biopsy (127; 41 per cent), clinical examination (77; 25 per cent), X-ray (15; 5 per cent), a raised CEA (2; 1 per cent), or some other method - e.g. CT scan or a confident unbiopsied laparotomy finding (88; 29 per cent). Statistically significant factors (chi2 test, P less than 0.05) associated with local recurrence are: Dukes' classification: A 4 per cent; B 13 per cent; C 18 per cent Tumour differentiation: Well 11 per cent; Moderate 14 per cent; Poor 21 per cent Obstruction: Absent 13 per cent; Present 21 per cent Perforation: Absent 13 per cent; Present 28 per cent Tumour mobility: Freely mobile 11 per cent; Others 21 per cent Operation performed (rectal and rectosigmoid tumours): Abdomino-perineal 12 per cent; Anterior resection 18 per cent; Surgeon (Consultant only): Range less than 5 per cent to greater than 20 per cent. Stratification of the above variables altered only the statistical significance pertaining to tumour differentiation (P less than 0.1, d.f. = 2). In particular, the differences between Consultant surgeons remained.

Adenocarcinoma↗

Local recurrence following 'curative' surgery for large bowel cancer: II. The rectum and rectosigmoid.

1988 patients with an adenocarcinoma of the rectum (1292; 65 per cent) or rectosigmoid (696; 35 per cent) have been studied. A resection (1700 patients) or polypectomy (124 patients) was performed in 1824 (92 per cent) and, of the former, 1376 patients either underwent abdominoperineal (AP) excision of the rectum (788 patients) or an anterior resection (598 patients). The in-hospital mortality was 63 patients (8 per cent) for AP and 44 (7 per cent) for anterior resection, and a curative resection had been performed in 504 (71 per cent) of those undergoing an AP, and 393 (71 per cent) of those undergoing an anterior resection. Follow-up information is available for 478 patients (95 per cent) who underwent an AP and 370 (94 per cent) who underwent an anterior resection. More patients have developed a local recurrence after an anterior resection (67; 18 per cent) than after AP (57; 12 per cent) (Logrank chi2 = 6.6, d.f. = 1, P less than 0.02) (stratified for sex and Dukes' stage). This difference is not accounted for by a lesser margin of distal clearance after an anterior resection; firstly because the margin of clearance was not different in those who did and those who did not develop a local recurrence (AP: whole group = 4.4 cm, local recurrence = 4.5 cm; anterior resection: whole group = 3.0 cm, local recurrence = 3.1 cm) and secondly because for each centimetre of distal clearance there was a consistently greater probability of recurrence for anterior resection (Logrank chi2 = 9.1, d.f. = 1, P less than 0.01) (stratified for sex, Dukes' stage and distal clearance margin).

Adenocarcinoma↗

The effect of tetracycline lavage and trauma on visceral and parietal peritoneal ultrastructure and adhesion formation.

The clinical efficacy of tetracycline lavage (1 mg/ml) in the management of abdominal sepsis has led to advocacy of its use in potentially contaminated cases. Yet at higher concentrations (6 mg/ml), tetracycline is a pleural sclerosant. The possibility of early ultrastructural peritoneal damage and later adhesion formation has been examined in syngeneic female Wag rats. At high concentration (10 mg/ml), tetracycline caused adhesions in the absence of peritoneal trauma and there was an associated loss of serosal microvilli. Lavage with low concentration tetracycline (1 mg/ml) or saline after clean abdominal surgery led to more adhesions than if no lavage was employed. There was an unexplained paradoxically low incidence of adhesions if prior mild contamination of the peritoneal cavity with 1 ml 10(5) E. coli had been performed.

Animals↗

Large bowel cancer: surgical pathology and its relationship to survival.

Modifications of Dukes' (1932) classification of rectal tumours have led to confusion. From the data of 2518 patients who had undergone curative colorectal surgery the interrelationships between tumour penetration, grade, vascular invasion and pattern of lymph node involvement have been examined and their individual relevance to survival determined. Subdivision of Dukes' A cases into those confined to the muscularis mucosae (A) and those penetrating into, but not through, the bowel wall (B1) should be abandoned. Despite interrelationships between lymph node status, grade of tumour and vascular invasion, they all contribute prognostic information independent of each other. Apical lymph node involvement, more than four lymph nodes involved and extensive primary tumours with nodal involvement all carry a bad prognosis. Although interrelated each variable is individually relevant. However, subgroups of patients with Dukes' C tumours have an observed survival significantly better than expected. When few lymph nodes are involved or the primary tumour is confined to the bowel wall but lymph nodes are involved, the expectation of life is equivalent to Dukes' B.

Adenocarcinoma↗

Experimental colon neoplasia enhanced by extract of sperm (protamine).

An experimental study of colorectal tumorigenesis in inbred rats given the potent carcinogen dimethylhydrazine has shown that protamine, given before any tumours had developed, significantly enhanced the development of large bowel tumours (100% incidence). Those animals having no adjuvant therapy or who received either heparin or 5-fluorouracil (alone or in combination) had an approximate 50% incidence of such tumours.

Adenocarcinoma↗