Cytoreductive surgery for ovarian carcinoma.
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Biomedical subjects
Publications and source records attributed to P F Schofield.
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A prospective study of prognostic factors has been carried out in a group of 186 patients with tethered rectal carcinomas. Of these, 97 were randomized to surgery alone and 89 to receive preoperative radiotherapy (20 Gy in four fractions). DNA ploidy was determined by flow cytometry. DNA aneuploidy was detected in 60 patients (62 per cent) in the surgery only group, but in only 33 patients (37 per cent) after radiotherapy (P less than 0.01). There was a significant reduction in local recurrence in irradiated patients (P less than 0.0001). DNA diploid tumours were less likely to recur locally. This was more marked in the radiotherapy group (P = 0.01) than in the surgery only group (P = 0.06). After radiotherapy, only the surgeons' assessments of a 'curative' resection and DNA ploidy were independent predictors of local recurrence in multivariate regression analysis, whilst Dukes' classification was not. In conclusion, DNA ploidy may indicate response to radiotherapy and is an important predictor of subsequent local tumour progression.
DNA extracted from 31 primary colorectal carcinomas was analyzed for the presence of ras gene amplification and mutations. Nine carcinomas had Ha-ras amplification and seven Ki-ras amplification. Nine carcinomas had codon 12 Ki-ras mutations. Immunohistochemical staining for ras proteins revealed a normal membrane association in normal mucosa and benign polyps but an abnormal cytoplasmic distribution in carcinomas. Amplification, mutations, and immunohistochemical staining were independent of histologic differentiation, Dukes' stage, or DNA ploidy status. This study demonstrates that abnormalities of ras genes are a common finding in colorectal carcinomas. They are potentially important biologic changes associated with malignancy, although they do not appear to be related to clinical behavior.
Discrepancies in morbidity and local recurrence rates in published clinical trials of pelvic XRT for colorectal cancer are caused by a variety of complex factors. It is, however, clear that XRT is able to cure early rectal carcinomas and is particularly useful in alleviating the symptoms of advanced or recurrent disease. The selection of appropriate cases for combinations of XRT and surgery can be made on the basis of digital examination under anaesthetic. One aim of these combinations is to reduce the number of patients with mobile tumours of the lower two-thirds of the rectum who require a permanent colostomy. In the absence of effective chemotherapy for metastatic disease, liver XRT may have a place in controlling the growth rate of occult liver metastases in selected patients.
Gastrointestinal lymphoma (GIL) is rare but may be cured by surgery and chemotherapy. Because symptoms frequently mimic common abdominal conditions, presentation is often to a surgeon. Fifty-five patients with GIL were treated between 1975 and 1984: all underwent operations before the correct diagnosis was made, 22 (40%) as emergencies. Misdiagnosis in 23 (42%) led to a delay in correct treatment of greater than or equal to 6 months from the start of symptoms: in 17 (31%) the delay was greater than or equal to one year. Endoscopy and radiology were inaccurate and suggested peptic ulceration, Crohn's disease or irritable bowel syndrome. The site of disease was usually stomach and duodenum (26, 47%) or ileum and jejunum (29, 53%). The extent of surgical resection was associated with survival at greater than or equal to 3 years-in 16 (29%) who underwent 'complete resection' 14 survived, but only one of 28 survived when the operation was limited to diagnostic biopsy (P less than 0.0001). Most deaths occurred within one year of operation, commonly from perforation or haematemesis from residual mural disease during chemotherapy. In 5 of 11 patients who had biopsy only, CT scans suggested localized disease, and 'complete resection' was achieved at a second laparotomy. Complete resection should be attempted wherever possible before chemotherapy. The place for surgeons with experience is clearly central to the management of this disease.
A total of 14 patients had operations for massive colonic haemorrhage. Of the seven who had a right hemicolectomy, four had the bleeding site localised, and three had only 'equivocal' indications of a right-sided source. One of these rebled 11 months later, but all survived and are well. Of the remaining patients, two had left-sided resection, one requiring an immediate second operation for rebleeding, and five, subtotal colectomy, of whom two died. A literature review confirms the suggestion that if the bleeding site has not been identified but, nevertheless, there are clues suggesting it to be right-sided, the best results will be obtained by right hemicolectomy. Left-sided resection should be used only when there is proof of left-sided bleeding, otherwise there will be an unacceptably high mortality. No clues, 'equivocal' indications of a left-sided source, or the presence of bilateral disease, should lead the operator to perform subtotal colectomy.
Fifty consecutive patients with early Hodgkin's disease underwent staging laparotomy. There were no deaths and most complications were minor. As a consequence, 17 (34%) patients were upstaged from clinical stage I or II to pathological stage III or IV. Subdiaphragmatic disease was found in five out of 22 patients with nodular sclerosing, seven out of ten with lymphocyte predominant and four out of 13 patients with mixed cellularity histological type. The age, sex, preoperative clinical stage and mediastinal involvement did not correlate with the presence of intra-abdominal disease. Among 15 patients with a normal preoperative computed tomography (CT) scan, nine had intra-abdominal disease at laparotomy and all three patients with suggested subdiaphragmatic involvement by the CT scan examination were clear. The surgeon's ability to diagnose early involvement at laparotomy was also limited. There seems to be a continued need for staging laparotomy to ensure adequate treatment of one-third of patients with early Hodgkin's disease.
A consecutive series of 123 colorectal cancers, prospectively followed for 3 years, was studied to determine if the prognostic significance of DNA ploidy related to: (a) thresholds used to define DNA aneuploidy, or (b) aneuploid sub-groups defined by DNA index (DI) and peak size. Aneuploidy was defined using 3 methods depending on the minimum proportion of nuclei considered to constitute an aneuploid peak; type 1, 5%; type 2, 10%; type 3, 10% if DI is 1.1-1.8, but 15% if DI is 1.9-2.1. DNA aneuploidy rates were type 1, 75%; type 2, 67%; type 3, 58%. The significance of clinical and pathological correlations varied with the use of different methods. All were associated with a significant DNA diploid survival advantage which was strongest for type 3 (p = 0.006). DI was unrelated to survival irrespective of the presence or absence of an associated S/G2; 33% with a DI of 1.1-1.8 and 35% with a DI of 1.9-2.1 survived. Prognosis was inversely proportional to aneuploid peak size, 48% with small peaks (less than 20%), 30% with intermediate peaks (greater than 20% less than 40%), but none with large peaks (greater than 40%) survived (p = 0.03). We conclude that: (a) thresholds used to define DNA aneuploidy affect the prognostic significance of DNA ploidy; (b) survival is independent of the DI of aneuploid peaks; and (c) measurement of aneuploid peak size refines the prognostic value of DNA ploidy.
A prospective study of prognostic factors has been carried out in a group of 123 consecutive patients with colorectal cancer. The fate of all patients is known at 3 years after operation. Clinical and pathological data were recorded at the time of presentation and operation, and the patients have been subject to regular postoperative review. DNA ploidy status was determined by flow cytometry. In all, 39 (33 per cent) patients had DNA diploid tumours and 80 (67 per cent) patients had DNA aneuploid tumours. In four cases, tumour material was not obtained. The patients with DNA aneuploid tumours had a worse prognosis than those with DNA diploid tumours, but this was only seen in those patients classified as Dukes' B. In a Cox's regression analysis, the surgeon's assessment of operability was the strongest predictor of survival, followed by the pathological classification and the patient's age. After these factors had been considered, the DNA ploidy status conferred no independent survival value.
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In a series of 20 patients undergoing elective colorectal surgery, 10 received an infusion of metronidazole 500 mg and 10 an infusion of 1500 mg commencing at the induction of anaesthesia. The concentrations of metronidazole in the plasma, rectus muscle and colon of the two groups during the course of the operation were compared. In those patients who received 1500 mg, the plasma and tissue concentrations were all well above the minimum inhibitory concentration (MIC) of metronidazole against Bacteroides fragilis. In those patients who received 500 mg, serum and tissue concentrations were at or only just above the MIC. It may be that 1500 mg would be a more effective dose of metronidazole for prophylactic use in colorectal surgery.
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Colovesical fistula often presents with recurrent or persistent urinary tract infection, especially in men. The commonest cause is diverticular disease. Other causes include carcinoma of the colon, Crohn's disease, radiotherapy and trauma. Barium enema may suggest the pathology but cystoscopy is the best investigation to confirm the presence of a fistula. One-stage resection and anastomosis is suitable for most patients with diverticular disease.
The light and electron microscopic features of rectal biopsies from 10 symptomatic patients treated with irradiation for pelvic malignancies are detailed. They are divided into two groups. Group I: biopsies taken during or shortly after the course of irradiation (six patients). Group II: biopsies taken 4 months or more after course completion (four patients). The distinguishing light microscopic features in the first group are epithelial meganucleosis, lack of mitotic activity, and patchy fibroblastic proliferation in the lamina propria. The blood vessels appear normal. In the second group, there are severe vascular changes characterized by narrowing of the arterioles by subintimal fibrosis, telangiectasia of capillaries and post-capillary venules, endothelial degeneration, and platelet thrombi formation. These vascular changes are always associated with severe fibrosis of the lamina propria and crypt distortion. The ultrastructural and light microscopic findings indicate that the cellular epithelial reaction and fibroblastic proliferation antedate the vascular injury, and the latter has no role in the acute phase reaction.
The clinical presentation and management of 24 patients treated for colovesical fistula were reviewed. It is concluded that an aggressive investigative approach in the management of patients with suspected colovesical fistula is rewarding. Cystoscopy and barium enema appear to be the most useful investigative tools. Once found the fistulae should be managed surgically. Radical excision of the sigmoid colon with primary anastomosis is the treatment of choice and is accompanied by no mortality and a very low complication rate.
Expression of c-myc was studied immunohistochemically in 100 colorectal carcinomas, using a monoclonal antibody, Myc 1-6E10, which is purported to recognize the oncoprotein (p62c-myc) in paraffin-embedded material. In normal epithelium, maturing crypt cells and terminally differentiated surface cells were positive, and proliferating basal crypt cells negative. All carcinomas stained positively, but intensity was independent of histological differentiation, Dukes' stage, DNA ploidy and survival. Staining was predominantly cytoplasmic despite the suspected nuclear location of p62c-myc and there was considerable staining of fibroblasts. When staining was compared in frozen and paraffin-embedded sections fixed in different ways, different patterns were observed. Acetone-fixed frozen sections exhibited weak nuclear and cytoplasmic staining or were negative. In formol-saline fixed frozen sections, there was stronger predominantly nuclear staining. In paraffin-embedded sections staining was predominantly cytoplasmic. This study suggests that c-myc expression is enhanced in the majority of colorectal carcinomas and although independent of clinical behaviour, may be a common event in malignant transformation. However, since staining is affected by fixation and processing, data obtained using Myc 1-6E10 on routinely processed specimens should be interpreted with caution.