Large bowel biopsies in colitis: a clinicopathological collaboration.
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Biomedical subjects
Publications and source records attributed to P F Schofield.
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This study has assessed the feasibility and reliability of cytology smears taken from patients with known rectal carcinomas without the use of any special instruments. In a pilot study of 23 patients who all had proved rectal cancer, 19 patients had satisfactory smears, one of which produced a false negative result. The remaining 18 displayed varying degrees of dysplasia (10) or frank malignancy (8). One of the patients with a smear containing severely dysplastic cells had a negative biopsy but had clear clinical and radiological evidence of a rectal tumour. Subsequently, a blind controlled study was undertaken on 29 patients with either carcinoma, proctitis or a normal rectum. All 29 sets of smears were of diagnostic quality and were correctly diagnosed as benign or malignant by the cytologist who had no knowledge of the clinical diagnosis. This is a rapid and simple diagnostic test which, if positive for malignancy, allows treatment to be planned at the first consultation. In combination with a forceps biopsy, the rate of positive diagnosis may be increased. A dysplastic smear adds to the level of clinical suspicion and confirms the need for biopsy of a lesion.
An assessment has been made of the reproducibility of measuring tumour proliferation using in vivo iododeoxyuridine (IUdR) labelling and flow cytometry. The variation that occurs between different institutions (Paterson Institute for Cancer Research, Manchester and the Gray Laboratory, Northwood), different observers and different runs on the same flow cytometer have been measured on 139 samples from 53 patients with colorectal cancer. The results demonstrate that the IUdR technique for measuring tumour proliferation is reproducible. Correlations were seen between measurements of Tpot obtained by different individuals and on separate machines. However, direct comparisons of the measured parameters showed that there were highly significant differences in the values obtained between institutes and observers (P < 0.001). Despite these variations, there were still significant detectable differences in Tpot measurements between individual tumours (P < 0.001). Analysis of the results obtained by running the same samples on two separate occasions on the same machine showed that the technique was highly reproducible and that the staining procedure was stable. Eighty per cent of the samples were similarly assigned to either above or below the median Tpot value, regardless which observer/laboratory combination was utilised. These data suggest that large clinical trials using Tpot should employ a single centre and a single individual to prepare, run and analyse samples.
Intra-tumoural heterogeneity of proliferation has been assessed by taking multiple biopsies from 30 colorectal cancers. Following in vivo IUDR labelling, dual parameter flow cytometry was used to measure tumour DNA index (DI) and labelling index (LI) and to derive DNA synthesis time (Ts) and potential doubling time (Tpot). Heterogeneity was seen for all parameters under investigation. Overall coefficients of variation (CV) and logarithmic transformation of Ts and Tpot (due to their non-gaussian distributions) indicate that LI (CV 25%) was the most variable parameter. Intra-tumoral heterogeneity in Tpot (lnTpot CV = 22%) was less than inter-individual variation (CV = 63%), suggesting that this variation should not be a limitation to the possible usefulness of this technique as an independent prognostic indicator. Correlations of Tpot values were examined between the shortest, the median and the value for a pooled homogenate sample from a single tumour. Using an homogenate, it was possible to accurately predict classification of tumour Tpot values as being below the median ('fast tumours') in 15 of 19 cases (79%). The data suggest that assaying an homogenate may allow a more rapid analysis of a multiply sampled tumour.
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Explore the source record for details and available documents.
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Twenty-four patients in whom trephine stoma formation was performed over a 4-year period are described. This procedure permits the formation of an end ileostomy or colostomy without laparotomy. It is simple, rapid, safe and allows speedy recovery. It is widely applicable and previous abdominal surgery is no contraindication. The procedure was impossible in two patients who required laparotomy and in a third in whom a loop colostomy was created. Operation time was shorter and postoperative opiate requirements less than when laparotomy was undertaken for stoma formation. Follow-up (median 1 year) of 17 patients confirmed a low incidence of complications (two prolapses, one parastomal hernia) after trephine stoma formation. This procedure is recommended as the preferred method of ileostomy or colostomy formation when laparotomy is not otherwise indicated.
Neutropenic colitis is recognized as a rare complication of chemotherapy in haematological malignancies. By contrast, the complication is less well known in relationship to chemotherapy for solid malignancies. There are very few examples reported and this paper adds three further cases and reviews the literature. We emphasize that although some cases of neutropenic colitis may be managed medically, full thickness involvement of the bowel wall may lead to perforation and require surgery. The pathogenesis of this progression is discussed and it is concluded that clinical awareness is important in the diagnosis. The signs of peritonitis or septicaemia are indications for excisional surgery with the formation of a temporary ileostomy.
Colorectal adenomas and carcinomas from familial adenomatous polyposis (FAP) patients were screened for the presence of K-ras gene mutations at codon 12 using an in vitro amplification step (polymerase chain reaction) followed by dot blot analysis using oligonucleotide probes specific for different mutations at codon 12. We examined 28 colorectal adenomas and two colorectal carcinomas from 12 FAP patients and observed a mutation at codon 12 in seven adenomas and in both carcinomas. The frequency of K-ras gene mutations in colorectal tumours from FAP patients is similar to those in cases of sporadic adenomas and sporadic colorectal carcinomas indicating that the mechanisms involved in their development may be similar.
DNA extracted from 29 colorectal carcinomas and 40 sporadic adenomas was amplified by the polymerase chain reaction (PCR) and analysed for the presence of K-ras gene mutations at codon 12 using a panel of synthetic oligonucleotide probes specific for normal and mutated sequences. The presence of mutations was correlated with various histopathological and clinical data. Ten carcinomas (34.5%) and 14 sporadic adenomas (35%) showed K-ras mutations at codon 12. In the carcinoma group, no apparent correlation was found between the presence of mutant oncogenes and the degree of histological differentiation, Dukes' staging or the development of distant metastasis. In the adenoma group, the frequency of mutations increased with the size of the adenoma and the severity of the dysplastic changes. This study confirms that ras gene mutations are common and early events in colon carcinogenesis. They appear to give a selective growth advantage to those polyps with mutations which leads to their increase in size and thus possibly prepare the ground for malignant transformation.
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The prognosis of colorectal carcinoma relies heavily on pathological staging which includes the metastatic state of lymph nodes. Colorectal resectates from 47 patients (41 with colorectal carcinoma and six with non-malignant disease) were entered into a study to assess the best method for detecting metastases in lymph nodes. The maximum number of lymph nodes was harvested at an initial careful examination of the specimen. Subsequently, the pericolic and perirectal fat was dissected out, dehydrated in alcohol, cleared in xylene and further lymph nodes were recovered. Both sets of lymph nodes were examined by the standard histological method and subsequently stained immunohistochemically for cytokeratins (CK). The mean number of lymph nodes recovered at the initial dissection from all 47 cases was 6.7, this was raised to 58.2 after xylene clearance, ie an average of 51.5 lymph nodes were not recovered by traditional methods. At the initial dissection no epithelial cells were detected in any of the lymph nodes from the nonmalignant cases or 25 of the malignant cases. In the other 16 cases, epithelial cells were detected by H&E in 38 lymph nodes. Thus the initial staging was 3 Dukes A, 22 Dukes B and 16 Dukes C. After immunohistochemistry, eight additional cases (originally staged Dukes B) showed epithelial cells in the lymph nodes, these were chiefly occult invasion, raising the involved lymph nodes number to 70. After xylene clearance and applying the CK staining, an additional 135 lymph nodes were found to be involved, thus the overall number of involved lymph nodes was increased to 205. The combined technique changed the Dukes staging in 12 out of 41 cases of colorectal carcinoma, resulting finally in 3 Dukes A, 10 Dukes B and 28 Dukes C, ie 55% of Dukes B become Dukes C.
The clinicopathologic staging of colorectal cancer is the subject of recent debate. We studied morphologic variables in a series of tumors resected from 284 patients. Half had been prospectively, randomly allocated to receive a 4-day schedule of preoperative pelvic radiotherapy followed by immediate surgery. There was a significant (P less than 0.01) difference in the distribution of tumors of various histopathologic grades between irradiated (XS) and unirradiated (S) patients and borderline differences in the predictive values of venous spread, tumor grading, and local spread. However, these differences were less marked in 180 tumors examined by one review pathologist. They were thought to be due to misinterpretation of changes induced by radiotherapy. No differences were detected in the distribution of tumors of various sizes and Dukes' stage in the XS and S groups. The review pathologist recorded a borderline (P = 0.049) difference in the distribution of tumors of various CEA staining patterns between the XS and S groups. In a Cox regression model. Dukes' staging remained the most important predictive variable for survival and pelvic recurrence in the XS and S groups. Dukes' staging was apparently unchanged by this schedule of preoperative radiotherapy, but Broders' grading may be unreliable. Any new clinicopathologic staging system for colorectal cancer should record when preoperative radiotherapy is delivered. More studies of radiotherapy effects are required.
Complex perineal fistula and persistent perineal sinus are difficult to treat. We describe our experience with wide excision of the diseased perineum using a combined abdominoperineal approach. Ten patients were reconstructed by a rectus abdominis myocutaneous flap (n = 7), rectus abdominis muscle flap (n = 2), and omental graft (n = 1). Primary healing was achieved in all cases. A median follow-up of 18 months (range 6-54 months) has shown no recurrence of perineal disease or associated abdominal incisional hernia. There were no perioperative deaths. We propose that the rectus abdominis myocutaneous flap is indicated if large amounts of perineal skin has to be sacrificed. When less skin is removed a repair with greater omentum or rectus muscle alone is adequate. The abdominoperineal approach together with filling the residual pelvic cavity with well-vascularized tissue allows definitive treatment to be carried out in one stage.
A case of squamous cell carcinoma of the terminal ileum with no underlying duplication or inflammatory disorder is described. The neoplasm seemed to have originated from the surface epithelium, invading the wall and metastasising to the regional lymph nodes. The 65 year old patient was free of disease three years after having had the tumour removed. Previous reports of squamous carcinoma of the small intestine have been associated with intestinal duplication or metastatic disease from distant sites.
The relationship between in vitro radiation sensitivity and colony-forming efficiency has been examined for primary human tumors of the cervix, colorectum, and lymph gland. Tumors were cultured using the Courtenay-Mills soft agar clonogenic assay and radiosensitivity was assessed as surviving fraction at 2 Gy. There was no correlation between colony-forming efficiency and surviving fraction at 2 Gy, giving confidence to the use of surviving fraction at 2 Gy as a predictor of clinical outcome.