Detection of metachronous breast carcinoma: the role of follow-up?

Second primary (metachronous) breast carcinoma occurs at a rate of approximately 1% per year. Early detection of metachronous carcinomas will optimise the chances of curative treatment. The aim of this study was to identify the method of detection of metachronous carcinomas, so that efforts to detect these tumours can be made more focused. Thirteen patients presented twice to a surgical department in a 7-year period with second primary breast carcinomas. The means of detection of the second primary carcinoma was identified in each case. Eleven of the patients presented with new symptoms which they had noticed themselves. The remaining two carcinomas were detected mammographically, and their presence was confirmed on clinical examination. In no case was the second primary carcinoma detected by clinical examination alone. Metachronous carcinoma is unlikely to be detected by routine clinical examination, but rapid assessment of new symptoms should be facilitated. Follow-up mammography at regular intervals should also improve early detection of metachronous breast carcinoma.

Autologous predonation, haemodilution and intraoperative blood salvage in elective abdominal aortic aneurysm repair.

The feasibility of predonated autologous blood transfusion and intraoperative blood salvage in elective abdominal aortic aneurysm repair was studied. Twenty consecutive patients were evaluated, of whom five were excluded according to protocol criteria. Patients each donated 1 unit blood 14 and 7 days before operation. A third unit was withdrawn in the anaesthetic room and replaced with Hartmann's solution, producing a haemodiluted state. Intraoperative losses were minimized using the Haemonetics Cell Saver III Plus autotransfusion system. Predonated blood from two patients passed its expiry date owing to repeated operation postponements, leaving 13 patients for study. The mean(s.d.) intraoperative blood loss was 700(300) ml with a mean(s.d.) intraoperative salvage of 420(300) ml. Two patients were transfused intraoperative salvage of 420(300) ml. Two patients were transfused according to clinical need. Thus nine patients safely avoided homologous transfusion. With autologous predonation, haemodilution and intraoperative blood salvage, elective aortic aneurysm repair can be performed safely with minimal need for homologous blood.

Surgical discharge summaries: improving the record.

The problem area of communication between hospital and general practitioners may potentially be improved by the advent of new information technology. The introduction of a regional computer database for general surgery allows the rapid automated production of discharge summaries and has provided us with the opportunity for auditing the quality of old and new styles of discharge communication. A total of 118 general practitioners were sent a postal questionnaire to establish their views on the relative importance of various aspects of patient information and management after discharge. A high response rate (97%) indicated the interest of general practitioners in this topic. The majority (73%) believed that summaries should be delayed no more than 3 days. The structured and shortened new format was preferred to the older style of discharge summary. The older format rarely arrived within an appropriate time and its content was often felt to be either inadequate (35%) or excessive (7%) compared with the new format (8% and 1%, respectively). The diagnosis, information given to the patient, clinic date, list of medications and investigations were considered the more important details in the summary. Improvements in the discharge information were suggested and have subsequently been incorporated in our discharge policy. The use of new information technology, intended to facilitate clinical audit, has improved our ability to generate prompt, well-structured discharge summaries which are accepted by the general practitioners.

Inhibition of intestinal carcinogenesis by dietary supplementation with calcium.

Dietary supplementation with calcium reduces colonic crypt cell production rates in both normal and hyperplastic mucosa. Calcium can bind intraluminally with bile salts and fatty acids thus reducing their mitogenic effect. The protective role of oral calcium on intestinal carcinogenesis (induced by azoxymethane) was tested in 60 male Sprague-Dawley rats submitted to either 80 per cent mid jejuno-ileal resection (n = 30) or jejunal transection (n = 30). Half the rats in each group received calcium lactate 24 g/l added to their drinking water. Rats were killed 25-27 weeks postoperatively. Enterectomy increased colonic tumour yield by 60-106 per cent (P = 0.002-0.005) and duodenal tumour yield by 70-86 per cent. Calcium abolished this effect at both sites, halving intestinal tumour yields in rats with both transection and resection (P less than 0.05). Doubling the dietary intake of calcium inhibits experimental carcinogenesis.

Elevated plasma enteroglucagon alone fails to alter distal colonic carcinogenesis in rats.

The effect of physiologic increases of plasma enteroglucagon, induced by massive bypass or resection of small bowel, on large bowel cell turnover and carcinogenesis was studied in rats in which the distal colon was isolated as a mucous fistula. After injections of azoxymethane, either 85% end-to-side jejunoileal bypass, 85% jejunoileal resection, or sham bypass was performed. Controls underwent colonic transection and resuture, azoxymethane treatment, and then sham bypass. Thirty weeks later the plasma enteroglucagon level had almost trebled after jejunoileal bypass (p less than 0.001) and almost doubled after jejunoileal resection (p less than 0.002) when compared with sham bypass; sham values did not differ from controls. The median number of tumors per rat in the distal (defunctioned) colon fell from 2 to 0 (p less than 0.05). Segmental weight fell by 45% (p less than 0.001) and crypt cell production rate by 75% (p less than 0.001). Neither tumor yield nor adaptation was affected by jejunoileal bypass or jejunoileal resection. Plasma enteroglucagon has no effect on colonic cell turnover or carcinogenesis in the absence of luminal content.

Proximal enterectomy provides a stronger systemic stimulus to intestinal adaptation than distal enterectomy.

Enteroglucagon has been implicated as a tropic hormone in the control of intestinal adaptation. Because cells producing enteroglucagon are located mainly in the distal small bowel (and colon), ileal resection might be expected to produce less adaptive change than a jejunal resection of equivalent length. This hypothesis was tested in male Sprague-Dawley rats (n = 40) weighing 184.0 +/- 7.3 g and receiving a Thiry-Vella fistula (TVF) of the mid-60% of the small intestine. One group had concomitant resection of the jejunum proximal to the TVF (n = 12), another had resection of the ileum distal to the TVF (n = 13), while controls had a TVF alone (n = 15). When killed 10 days postoperatively rats with ileal resection weighed only 81% of controls (p less than 0.001) and 85% of those with jejunal resection (p less than 0.01). Jejunal resection produced an 81% increase in crypt cell production rate (measured by a stathmokinetic technique) over control values (28.5 +/- 4.2 v 15.8 +/- 2.3 cells/crypt/h: p = 0.025), whereas ileal resection had no demonstrable effect (17.5 +/- 2.3 cells/crypt/h). Adaptive hyperplasia in isolated small bowel is modulated by factors localised to the distal small intestine, enteroglucagon being a plausible candidate.

Increased dietary calcium and small bowel resection have opposite effects on colonic cell turnover.

Oral supplements of calcium reduce the mitogenic effects of fatty acids and bile acids on large bowel mucosa. The cytokinetic effects of intraluminal calcium were tested in normal and adapting colonic epithelium. Male Sprague-Dawley rats (n = 60) weighting 356.7 +/- 24.9 g were submitted to either an 80 per cent jejuno-ileal resection or simple transection and resuture of the jejunum. Within each group, half the animals had 24 g/l calcium lactate added to the drinking water. Seven weeks postoperatively crypt cell production rate (CCPR) was determined in the lower descending colon. Among controls with transection CCPR was 4.49 cells crypt-1 h-1; calcium supplements reduced this figure by 26 per cent (P less than 0.05). As expected jejuno-ileal resection increased CCPR (by 51-61 per cent), but again calcium reduced this response by 31 per cent (P less than 0.02). Increased dietary levels of calcium thus inhibit colonic cell turnover and blunt the adaptive response to massive enterectomy, conceivably by binding tropic factors such as bile acids.

Sugar, fat, and the risk of colorectal cancer.

The habitual diet of 50 patients with large bowel cancer, as assessed by a dietary history method, was compared with that of 50 closely matched controls. Patients were included only if their symptoms were unlikely to have changed previous eating habits. The mean daily intakes of all major nutrient classes and of dietary fibre were estimated. Patients with large bowel cancer consumed 16% more energy than controls (mean (SEM) daily intake 9.92 (0.41) v 8.56 (0.32) MJ (2370 (98) v 2046 (76) kcal), respectively; p less than 0.0001), mainly in the form of carbohydrate (21% more; 282.6 (13.7) v 233.4 (10.5) g; p less than 0.0001) and fat (14% more; 100.8 (4.3) v 88.4 (3.2) g; p less than 0.001). The extra carbohydrate was largely in the form of sugars depleted in fibre and the extra fat as combinations of fat and such sugars. As the selection criteria used make it unlikely that this eating pattern was caused by the disease the data suggest that a high intake of sugars depleted in fibre and fat predisposes to the development of large bowel cancer.

Crypt cell production rate in ulcerative proctocolitis: differential increments in remission and relapse.

Crypt cell production rate (CCPR) has been measured by a stathmokinetic technique in the relapse and remission phases of ulcerative proctocolitis. Rectal biopsies were obtained from eight patients with colitis in relapse, 14 patients with colitis in remission, and 14 patients with histologically normal mucosa. Biopsies were maintained in organ culture for 16 hours and were then exposed to vincristine for one to three hours. Crypt cell production rate was determined from the rate of accumulation of arrested metaphases. Mean CCPR in the relapse group (14.2 cells/crypt/hour) was 45% faster than in the remission group (9.8 cells/crypt/hour; p less than 0.001), which was in turn 14% faster than in normal mucosa (8.6 cells/crypt/hour; p less than 0.04). More rapid turnover of the rectal epithelium in quiescent as well as active colitis may help to explain the enhanced risk of carcinogenesis in this disease.

Goblet cell changes during intestinal adaptation to azoxymethane and enteric bypass in the rat.

Numbers of intestinal goblet cells containing specific acid mucins were determined in male Sprague-Dawley rats receiving azoxymethane (total dose 90 mg kg-1) with or without jejunoileal bypass (JIB). Controls had injections of vehicle and sham bypass. Thirty weeks postoperatively colorectal length and crypt depth were increased by azoxymethane and further increased by JIB. JIB doubled the yield of intestinal tumours (P less than 0.01). Goblet cells containing sulphomucins normally predominated throughout the intestinal tract. Contents of sulphomucins and especially sialomucins were consistently higher in the small bowel and colon of rats receiving azoxymethane alone, but again the highest values were observed in animals with azoxymethane plus JIB. Both small-bowel bypass and azoxymethane stimulate adaptive growth of the colon and small bowel remaining in circuit. Goblet-cell hyperplasia is a feature of this response, and sialomucins are preferentially secreted by the adapting epithelium.

Survival of 727 patients with single carcinomas of the large bowel.

The outcome of 727 patients presenting with solitary colorectal carcinoma over a seven-year period is reviewed. Of the patients, 52 per cent were females 45 per cent were over 70 years and 31 per cent had an emergency admission. Of the tumors, 43 per cent occurred in the rectum and 40 per cent were stage D (not treated curatively). Predisposing causes included inflammatory bowel disease (n = 12) and abdominal irradiation (n = 6); associated adenomatous polyps were present in 22 per cent of resection specimens. Hospital mortality rates (20 per cent overall) were adversely affected by emergency admission (36 per cent), age greater than 70 years (29 per cent) and advanced, stage D disease (31 per cent). Corrected overall five-year survival rate was 32 per cent and, after curative resection, 59 per cent. Of patients in whom curative resection included contiguous organs, 47 per cent survived five years. Survival was reduced in patients over 70 years (26 per cent), in emergency admissions (24 per cent), in poorly differentiated tumors (18 per cent), and if tumor fixity was present (14 per cent). Factors contributing to a favorable outlook included a long history (greater than one year) and a tumor situated in the left colon. Recurrence developed in 47 per cent of patients surviving curative resection and was seldom diagnosed at a curable stage.

Adaptation to jejunoileal bypass promotes experimental colorectal carcinogenesis.

The co-carcinogenic potential of 85 per cent jejunoileal bypass (JIB) was tested in male Sprague-Dawley rats (n = 81) given 6 preliminary injections of the selective intestinal carcinogen azoxymethane (total dose 90 mg/kg). Controls had sham JIB. Colorectal adaptation was studied 30 weeks postoperatively in rats given injections of vehicle alone. JIB caused 17-33 per cent increments in colonic length, weight and crypt depth; crypt cell production rate was more than doubled (P less than 0.01). Despite lowering body weight by 27 per cent, JIB increased the median number of colorectal tumours per rat from 3 to 8 (P less than 0.01). The findings suggest that evidence of hyperplasia and dysplasia should be sought in patients receiving subtotal jejunoileal bypass for obesity.

Large bowel growth.

Developmental events in the large bowel have been studied pre- and post-natally and indicate that by birth, crypt organisation and kinetic activity are organised along adult lines. The period from birth to maturity is marked by an increase in crypt size and a massive increase in their number, with new crypts developing by a process of longitudinal fission from the base of existing ones. We know little of the fate of crypt size and number thereafter. Adaptive responses to resection or bypass of intestine are much less marked in large bowel when compared to small bowel, but in general postoperative responses have not been as extensively examined. Of the factors maintaining mass and cell turnover in large bowel mucosa simple luminal bulk seems to be most important, although a role exists for endocrine and neurovascular influences. Knowledge of growth, kinetic activity and adaptive responses in human large bowel is scanty and represents a large area for further study.