Rectal cancer: the Basingstoke experience of total mesorectal excision, 1978-1997.

OBJECTIVE: To examine the role of total mesorectal excision in the management of rectal cancer. DESIGN: A prospective consecutive case series. SETTING: A district hospital and referral center in Basingstoke, England. PATIENTS: Five hundred nineteen surgical patients with adenocarcinoma of the rectum treated for cure or palliation. INTERVENTIONS: Anterior resections (n = 465) with low stapled anastomoses (407 total mesorectal excisions), abdominoperineal resections (n = 37), Hartmann resections (n = 10), local excisions (n = 4), and laparotomy only (n = 3). Preoperative radiotherapy was used in 49 patients (7 with abdominoperineal resections, 38 with anterior resections, 3 with Hartmann resections, and 1 with laparotomy). MAIN OUTCOME MEASURES: Local recurrence and cancer-specific survival. RESULTS: Cancer-specific survival of all surgically treated patients was 68% at 5 years and 66% at 10 years. The local recurrence rate was 6% (95% confidence interval, 2%-10%) at 5 years and 8% (95% confidence interval, 2%-14%) at 10 years. In 405 "curative" resections, the local recurrence rate was 3% (95% confidence interval, 0%-5%) at 5 years and 4% (95% confidence interval, 0%-8%) at 10 years. Disease-free survival in this group was 80% at 5 years and 78% at 10 years. An analysis of histopathological risk factors for recurrence indicates only the Dukes stage, extramural vascular invasion, and tumor differentiation as variables in these results. CONCLUSIONS: Rectal cancer can be cured by surgical therapy alone in 2 of 3 patients undergoing surgical excision in all stages and in 4 of 5 patients having curative resections. In future clinical trials of adjuvant chemotherapy and radiotherapy, strategies should incorporate total mesorectal excision as the surgical procedure of choice.

Mesorectal excision for rectal cancer.

Concern about world wide local recurrence rates for rectal cancer of 20-45%, together with anxiety at the recent proliferation of adjuvant therapies, led us to review the efficacy of total mesorectal excision (TME) with which no adjuvant therapy had been combined. Precise, sharp dissection is undertaken around the integral mesentery of the hind gut, which envelopes the entire mid rectum. This procedure adds to operative time and complications but has been claimed to eliminate virtually all locally recurrent disease after "curative" surgery. Independent analysis (J. K. M.) of prospective follow-up data extended over a 13-year interval (1978-91; mean 7.5 years). The actuarial local recurrence rate after curative anterior resection at 5 years is 4% (95% Cl 0-7.5%) and the overall recurrence rate is 18% (10-25%). 10-year figures are 4% (0-11%) and 19% (7-32%). In view of the high-risk classification used for the North Central Cancer Treatment Group (NCCTG), which has led to a trend to chemoradiotherapy, a similar group of high-risk Basingstoke cases was constructed for comparison purposes. This group included 135 consecutive Dukes' B (B2) and Dukes' C cancer operations, both anterior resection and abdominal-perineal excision, for tumours below 12 cm from the anal verge. Results from TME alone are substantially superior to the best reported (NCCTG) from conventional surgery plus radiotherapy or combination chemoradiotherapy: 5% local recurrence at 5 years compared with 25% and 13.5%, respectively; and 22% overall recurrence compared with 62.7% and 41.5%, respectively (Dukes' B cases [B2], 15%; Dukes' C cases, 32%). Meticulous TME, which encompasses the whole field of tumour spread, can improve cure rates and reduce the variability of outcomes between surgeons. Far more genuine "cures" of rectal cancer are possible by surgery alone than have generally been believed or are currently accepted. Better surgical results are an essential background for the more selective use of adjuvant therapy in the future.

Successful pregnancy following tailor-made intracavitary radiotherapy for microinvasive adenocarcinoma of the endocervix.

We report a case of microinvasive adenocarcinoma of the endocervix in a lady anxious for a family. Intracavitary radiotherapy using a specially designed 125-I bearing applicator allowed radical treatment of the endocervix whilst sparing the endometrium and ovaries and preserving fertility. The patient remains well and disease free following a successful pregnancy.

Involved field radiotherapy or chemotherapy in the management of stage I nodal intermediate grade non-Hodgkin's lymphoma.

Early stage intermediate grade non-Hodgkin's lymphoma (NHL) is frequently treated with chemotherapy alone or in conjunction with radiotherapy. We have managed clinical Stage I nodal, intermediate grade NHL with involved field radiotherapy alone for non-bulky (less than 5 cm post-surgery) disease or combination chemotherapy alone for more bulky disease. Forty-three patients were treated between 1978 and 1989. Of the 30 patients with non-bulky disease treated with radiotherapy, 29 (97%) achieved complete remission (CR). Thirteen (42%) patients relapsed after radiotherapy and ten of these achieved a further CR (durable in eight) following salvage chemotherapy. Eleven patients with bulky disease received combination chemotherapy with nine (82%) attaining CR (durable in eight). Two patients with bulky disease received radiotherapy-both achieved CR, but have relapsed and died of lymphoma. Overall actuarial 5 year survival for the total group is 77% with a median follow-up of 30 months (range 3-119 months). The 5 year actuarial survival for the 30 patients with non-bulky disease treated with radiotherapy is 86% at a median follow-up of 39 months (range 8-119 months). The 4 year actuarial survival of the 11 patients treated with chemotherapy is 60% with a median follow-up of 25 months (range 3-55 months). We conclude that involved field radiotherapy alone is efficacious for clinical stage I patients with non-bulky nodal intermediate grade NHL and that patients relapsing after radiotherapy are adequately salvaged by chemotherapy. Patients with bulky disease have an inferior survival and should receive combination chemotherapy.

Involvement of the central nervous system by non-Hodgkin's lymphoma in adults. A review of 36 cases.

Thirty-six (10.1 per cent) of a total of 355 adult patients with non-Hodgkin's lymphoma seen over a seven and a half year period developed compression or infiltration of the central nervous system (CNS). In nine patients (2.5 per cent) extradural tumour masses compressed the spinal cord or brain. Five of these patients, all previously untreated, responded well to treatment, with excellent recovery of CNS function and survival in the long term. The prognosis for the four patients with advancing drug-resistant systemic disease at the time of CNS compression was poor. In 27 patients (7.6 per cent) a clinical or cytological diagnosis of meningeal infiltration was made (on cerebrospinal fluid). Meningeal disease was seen most frequently in patients with high-grade lymphoma, either at presentation or during subsequent progression of systemic disease. All of these patients have died of systemic and/or CNS disease less than 20 (median 3) months from diagnosis of meningeal disease. Meningeal infiltration represents a significant clinical problem for which new approaches to prophylaxis and treatment are required.

Recurrence and survival after total mesorectal excision for rectal cancer.

A 7 1/2-year consecutive series is presented from a district hospital with a policy of referring all rectal carcinomas to one surgical firm. The performance of lower anterior resections has limited the rate of abdominoperineal excision with permanent colostomy to 11%. Of 115 patients in whom curative resection was attempted, 69 had anastomoses below 5 cm and 39 had mural resection margins of less than 2.5 cm. Surgical priority, however, was given to complete excision of the visceral rectal mesentery or mesorectum. At an average of 4.2 years postoperatively, three pelvic recurrences have developed but there have been no staple-line recurrences in patients who had "curative" surgery. The corrected cumulative probability of survival at 5 years is 87% and the tumour-free survival by Dukes stage is A 94%, B 87%, and C 58%. Patients with low tumours did no less well than those with high tumours, when treated by anterior resection. On this evidence, it is often safe to limit mural clearance and thus preserve the anal sphincters, provided that the mesorectum is excised intact with the cancer.

A report on a prospective trial of no initial therapy in patients with initial therapy in patients with asymptomatic favourable prognosis non-Hodgkin's lymphoma.

Thirty-one (58 per cent) of a group of fifty-three unselected patients with stage II-IV favourable prognosis non-Hodgkin's lymphoma were regarded as being eligible for a prospective study of no initial therapy. Seventeen of these patients (55 per cent) have required no treatment for periods from 6 + -47 + months, (median 18 months) and fourteen patients have been treated with chemotherapy for progressive disease after a period varying from 3-40 months (median 9.5 months). Selected asymptomatic patients with non-bulky disease may be suitable for no initial therapy. Randomized prospective trials will be needed to test whether survival is affected by delaying therapy.

Poor prognosis non-Hodgkin's lymphoma in the elderly: clinical presentation and management.

Thirty-eight patients age 65 years and older with a diagnosis of non-Hodgkin's lymphoma of poor prognostic type were seen over a five and a half year period. These patients represented 19 per cent of our total new patient non-Hodgkin's lymphoma population during this time. Advanced age, coexisting medical illness, widespread lymphoma and poor treatment compliance were common problems. Despite this we were able to render 26 per cent of patients disease-free for periods from 12 to over 48 months. Age should not be considered a bar to staging and effective therapy. Palliative management was unsuccessful, and we believe that treatment should be given with the intention of cure. Features suggesting that a patient was more likely to achieve a lasting complete remission included early stage (I-IIA), a lack of systemic ('B') symptoms, an absence of bone marrow or bulky gastrointestinal tract disease and no pre-existing serious medical condition.

The mesorectum in rectal cancer surgery--the clue to pelvic recurrence?

Five cases are described where minute foci of adenocarcinoma have been demonstrated in the mesorectum several centimetres distal to the apparent lower edge of a rectal cancer. In 2 of these there was no other evidence of lymphatic spread of the tumour. In orthodox anterior resection much of this tissue remains in the pelvis, and its is suggested that these foci might lead to suture-line or pelvic recurrence. Total excision of the mesorectum has, therefore, been carried out as a part of over 100 consecutive anterior resections. Fifty of these, which were classified as 'curative' or 'conceivably curative' operations, have now been followed for over 2 years with no pelvic or staple-line recurrence.

Combination of radiotherapy and razoxane (ICRF 159) for chondrosarcoma.

Eight patients with 12 chondrosarcomas were treated with radiation and razoxane (ICRF 159). Two tumors in 1 patient progressed unequivocally, 3 tumors in 3 patients showed no change, and 7 tumors in 5 patients had complete or partial (more than 50%) regressions. At least 2 complete regressions have responded for more than 2 1/2 years at the present time.

Comparison of radiotherapy with and without razoxane (ICRF 159) in the treatment of soft tissue sarcomas.

Comparison of the recurrence rates of soft tissue sarcomas treated by radiotherapy (14 patients) or radiotherapy and synchronous administration of razoxane (19 patients) has shown a statistically significant benefit for those patients treated by the combination. No increase in tissue reactions or adverse side-effects (apart from a readily reversible leukopenia) was observed. The implication is that razoxane acts as a well tolerated adjuvant for radiotherapy.

CCNU in brain tumours.

CCNU, a nitrosourea compound, has been found effective in the management of both primary and secondary tumours of the brain. It is proposed to carry out an investigation comparing radiotherapy alone with radiotherapy and CCNU combined, in cerebral gliomata.