Philip F Schofield

Adjuvant preoperative radiotherapy for locally advanced rectal carcinoma. Results of a prospective, randomized trial.

PURPOSE: A prospective, randomized clinical trial was conducted by the Northwest Rectal Cancer Group to study the effects of preoperative radiotherapy given one week before surgery in locally advanced (tethered or fixed) rectal carcinoma. METHODS: A total of 284 patients were entered into the trial between 1982 and 1986; 141 were allocated to receive surgical treatment alone, and 143 were allocated to receive preoperative radiotherapy. A 10 × 10 × 10 cm volume in the posterior pelvis, centered on the tumor, was irradiated at a dose of 20 Gy, divided into four daily fractions of 5 Gy each. RESULTS: No differences were observed in any of the clinicopathologic variables in the two arms of the trial; there were no striking down-staging effects in the irradiated tumors. After a minimum follow-up period of 96 months, the overall and cancer-related mortality rates were similar in both arms of the study (P =0.21 andP =0.09, respectively). There was a highly significant reduction in local recurrences in the irradiated group (12.8 percent x-ray therapyvs. 36.5 percent surgery;P =0.0001). The majority of local recurrences after preoperative radiotherapy occurred inside the radiotherapy field (10 cases; 7 percent), with only six cases (5 percent) outside the field. No significant difference was observed in the rates of distant metastasis between the two treatment groups (P =0.73). CONCLUSIONS: Although there is no statistically significant survival benefit in the whole series, there is a survival benefit for the subset of patients considered by the surgeon to have undergone a curative operation. We recommend that this form of adjuvant therapy should be offered to all patients with locally advanced rectal cancer who are to undergo radical surgery.

Microvascular studies in human radiation bowel disease.

The microvasculature was investigated in the normal bowel (n = 43 patients) and in radiation bowel disease (n = 18 patients). Tissue samples obtained from postoperative colectomy specimens in which the intramural vessels had been perfused with barium sulphate suspension were examined. Microradiography was used to study vascular pattern which was abnormal in radiation bowel disease. A recently described radiograph fluorescence system was used to estimate barium concentration, and hence microvascular volume. The radiation group showed a highly significant reduction in barium concentration (p less than 0.001), when compared with the normal group. This reduction was diffuse in samples from 15 patients who had received combined intracavity and external radiotherapy, but localised in two patients who had received intracavity treatment only. It is concluded that microvascular compromise is an important factor in the natural history of radiation bowel disease.

An assessment of the reliability and reproducibility of measurement of potential doubling times (Tpot) in human colorectal cancers

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.

Role of autologous lymphocyte cytotoxicity in colonic neoplasia.

The T-lymphocyte mediated killing of autologous carcinoma colon cells was investigated. There was no change in the incidence of activity with advanced disease, age, or nutritional status of the patient and no difference could be demonstrated in lymphocytes extracted from blood, draining lymph nodes, or the tumour itself. Nevertheless. T-lymphocyte activity did appear to be specific for the patientss own tumour, as it was rarely observed with allogeneic tumours. There was also no correlation with lymphocyte natural killer activity. The in vitro studies demonstrated patient specific T-lymphocyte activity in 23 of 47 patients with carcinoma of the colon, but the results do not correlate with clinical and pathological findings.

Familial spontaneous rupture of the colon: report of two cases.

SPONTANEOUS RUPTURE Of the colon is a very rare condition. I t was first reported in 1919, z but in reviewing the worlds literature in 1965, Duffield and VanBuren could discover only 34 cases, s Almost all of the recorded cases have been ruptures of the sigmoid colon or rectosigmoid. Both patients presented in this paper had ruptures in an extremely unusual site. They constitute the first reported instance of familial spontaneous rupture of the colon.

Proceedings: Leucocytotoxicity in malignant and non-malignant colonic diseases.

Recent theories of the aetiology of HD have postulated immune reactivity to viral or thymic antigens as fundamental to the disease process (Kaplan, Hodqkins Disease, Harvard University Press, 1972). HD spleen tissue in short-term culture produces high levels of immunoglobulin G in comparison with control spleen cultures. Preliminary results suggest that this immuno-globulin binds to peripheral blood lympho-cytes. In addition, supernatants from HD lymph node and spleen cultures inhibited the migration of guinea-pig peritoneal macro-phages in vitro in 11 of 15 cases. Control supernatants from carcinomatosis and re-active lymph nodes and normal spleens inhibited significantly in only 1 of 16 cases. The biological properties of this inhibitor parallel those described for lymphocyte derived Migration Inhibition Factor: MIF (David and David, 1972). Lymphokine production in vitro is compatible with elevated levels of immune reactivity in HD tissue. There is a need for tissue culture lines of human tumours for in vitro studies. Attempts have been made to establish such lines from 220 tumour specimens. Ninety-six specimens from breast carcinoma patients have been cultured. These comprised 64 tumour specimens and 32 pleural effusions from patients with advanced disease. No cell lines have been obtained from the tumour specimens although epithelial cells proliferated for at least one month in 19 of the 64; 24/32 pleural effusions proliferated and 13 of these yielded cell lines. The nature of the cell is in doubt because mesothelial cells grow very well under the culture conditions used. Seven of 29 colonic carcinomata specimens and 7/8 ascitic fluids from patients with colon carcinoma have also grown for at least one month. Three cell lines have been obtained from ascitic fluids; however, the cells are considered to be mainly mesothelial in origin. Good growth has been obtained from 12/24 melanomata cultured and two cell lines have been established. Although numerous supplements have been added to the basic McCoys 5A medium, enhanced growth was obtained only after the addition of insulin and galactose.