John R. McGregor

Plasma gastrin concentrations are normal in patients with colorectal neoplasia and unaltered following tumor resection

BACKGROUND/AIMS Previous studies have found that colorectal cancer patients have hypergastrinemia, but most have been inadequately controlled. Preoperative fasting and meal-stimulated gastrin levels were measured in patients with colorectal tumors (n = 42) and in carefully matched controls (n = 34). Helicobacter pylori status was assessed because it causes significant hypergastrinemia. METHODS Plasma gastrin levels were measured by radioimmunoassay. Helicobacter status was assessed using the [14C]urea breath test and serology (immunoglobulin G). RESULTS Preoperatively, fasting plasma gastrin levels were similar in patients with tumors (median, 55 ng/L; interquartile range, 45-82.5) and controls (77.5 ng/L; 53.7-137.5; P = 0.10). Similarly, peak gastrin levels were not significantly different in tumor patients (200 ng/L; 137.5-312.5) and controls (247.5 ng/L; 147.5-375; P = 0.21). The prevalence of H. pylori infection in patients with tumors (60%) and controls (53%) was similar in both groups. Five (20%) tumor patients who were H. pylori-positive preoperatively were negative postoperatively, and their median peak plasma gastrin level decreased from 200 ng/L to 140 ng/L. After these patients were excluded, fasting and peak plasma gastrin concentrations were similar preoperatively and postoperatively. CONCLUSIONS When confounding factors are controlled for, plasma gastrin levels are not increased in colorectal cancer and do not decrease after curative resection. Previously noted decreases in gastrin levels after tumor resection may be attributable to loss of H. pylori infection in some patients, as noted here.

EFFECT OF THE SURGEON'S SPECIALITY INTEREST ON THE TYPE OF RESECTION PERFORMED FOR COLORECTAL CANCER

PURPOSE: The aim of this study was to examine the type of resection performed for colorectal cancer by surgeons with a colorectal interest and compare this with the type of resection performed by surgeons with other specialty interests. METHODS: One hundred sixteen patients had curative surgery performed for primary colorectal cancer over a one-year period by ten surgeons with four different specialty interests. RESULTS: Surgeons with an interest in colorectal cancer resected twice as much colon (280 mmvs.130 mm;P>0.0001, Mann-WhitneyUtest) and were more likely to remove adjacent clinically involved organs (15 percentvs.0 percent) for left-sided colon and rectal cancers compared with surgeons with vascular or transplant interests. Surgeons with an interest in gastroenterology performed a resection that was intermediate between the colorectal and other specialty groups for left-sided cancers. Distal resection margins were significantly greater (55 mmvs.20 mm;P>0.001) for sigmoid cancers in the colorectal group, but were similar in all groups for rectal cancer. Resection lengths and margins for right-sided cancers were similar in all groups, although the number of lymph nodes retrieved from the mesentry was greater in the colorectal group (13vs.7.5;P=0.08). CONCLUSION: This study shows a wide variability in the type of resection performed for colorectal cancer and illustrates the need for clinical trials to evaluate the effect of such variability on patient outcome.

Omeprazole inhibits colorectal carcinogenesis induced by azoxymethane in rats.

Numerous clinical and experimental studies suggest that gastrin plays an important part in the development of colorectal cancer in humans. This study was done to assess the influence of omeprazole induced hypergastrinaemia on the development of colorectal tumours in an experimental animal model. Forty female Sprague-Dawley rats received either omeprazole (40 mumol/kg) or vehicle (0.25% methylcellulose) by once daily oral gavage throughout the experiment. All animals received 12 consecutive weekly subcutaneous injections of azoxymethane (10 mg/kg/week) beginning at week 6. Serum gastrin concentrations were measured during weeks 1 and 5 and at death (week 27). Chronic omeprazole treatment resulted in appreciable hypergastrinaemia during the study, mean gastrin concentrations in omeprazole treated rats being raised by up to nine to 10 fold, compared with vehicle treated control rats (p < 0.001). Despite this, tumour incidence in the omeprazole group was significantly lower at 63%, compared with 95% in the vehicle only group (p < 0.02). The median number of tumours in the omeprazole group (1) compared with the vehicle group (3) was also significantly lower (p = 0.02). Average tumour size, site distribution, and the comparative frequencies of adenomas and adenocarcinomas were similar in the two groups. This study shows that omeprazole protects against colorectal carcinogenesis in this model despite causing appreciable hypergastrinaemia. The mechanism by which this occurs is unclear and merits further investigation. Because of the compounding protective effects of omeprazole, this model is not a suitable one for studying the longterm trophic effects of gastrin on the colon.

Effect of suture material on tumour cell adherence at sites of colonic injury

In an experimental animal model, radiolabelled viable intraperitoneal adenocarcinoma cells adhered in similar numbers to normal rat colon and that injured by a 1‐cm colotomy, with median cell counts of 7002 and 8602 respectively (P not significant). Repair of the colotomy with interrupted silk resulted in a significant increase in the median number of cells adhering to the injury site (21888; P = 0.0001 versus normal colon). Repair with Prolene had no effect on tumour cell adherence (a median of 7449 cells adhered; P not significant versus normal colon). Tumour cell adherence at sites of colonic injury is dependent on the suture material used and not on the injury itself in this model. This may be important when choosing suture type for anastomosis in patients undergoing surgery for colorectal cancer.

Anastomotic suture materials and experimental colorectal carcinogenesis

Local tumor recurrence following restorative surgery for colorectal cancer may occasionally result from the promotion of a neoplastic lesion in a zone of proliferative instability adjacent to the anastomosis. The aim of this study was to compare the influence of three anastomotic suture materials, including stainless steel (as a model of surgical stapling), on colorectal carcinogenesis in an experimental animal model. The transmural implantation of stainless steel sutures into the distal descending colon of albino Swiss rats during the postinitiation phase of tumor induction resulted in significantly fewer animals exhibiting perianastomotic tumors 12 weeks later (3 of 21 animals) when compared with either polyamide (Nurolon®; Ethicon, Edinburgh, United Kingdom) (14 of 20 animals;P<0.001) or polyglycolic acid (Dexon Plus®; Davis and Geck, Gosport, United Kingdom) sutures (17 of 21 animals;P <0.001). The findings were similar when the same materials were used to resuture a longitudinal colotomy. For both operative procedures, the type of suture material had no influence on the incidence of large bowel tumors distant from the anastomotic site. These results suggest that stainless steel staples may promote fewer perianastomotic large bowel tumors than certain more conventional suture materials and, therefore, may be safely employed in colorectal cancer surgery.

Bile carcinoembryonic antigen levels and occult hepatic metastases from colorectal cancer

PURPOSE: Up to 30 percent of patients will have occult hepatic metastases at the time of curative surgery for colorectal cancer. The ability to predict this group of patients would allow better targeting of appropriate therapy. It has been shown previously that patients with overt hepatic metastases have significantly high levels of carcinoembryonic antigen in gallbladder bile compared with serum levels. The aim of this study was to assess the accuracy of bile carcinoembryonic antigen levels taken at the time of operation in predicting patients with occult hepatic metastases. METHODS: Bile and serum carcinoembryonic antigen samples were collected from 37 patients undergoing surgery for colorectal cancer, 26 of whose procedures were deemed curative and who were followed up for a median of 63.5 months. RESULTS: Twelve patients were alive with no evidence of recurrent disease, and two had recurrent disease, whereas 12 died of disease. The median (interquartile range) serum carcinoembryonic antigen in the disease-free group was 2.8 (1.1–6.1) ng/ml, and in the recurrent group it was 6.35 (4.3–30) ng/ml (P=0.006), whereas bile carcinoembryonic antigen in the disease-free group was 7 (5–39) ng/ml as compared with 31 (5–383.7) ng/ml in the recurrent group (P=0.210). The accuracy of serum carcinoembryonic antigen in predicting occult hepatic metastases was 77 percent compared with 72 percent for bile carcinoembryonic antigen. CONCLUSION: Intraoperative bile carcinoembryonic antigen levels are no more accurate than serum carcinoembryonic antigen levels in predicting occult hepatic metastases in patients undergoing potentially curative colorectal cancer surgery.

Effect of fibrin sealant on perianastomotic tumor growth in an experimental model of colorectal cancer surgery

Viable intraluminal tumor cells can penetrate a clinically intact rodent colonic anastomosis and give rise to perianastomotic tumor growth. The aim of this study was to determine whether transanastomotic cell migration can be prevented by fibrin-based tissue sealant. Following distal colonic transection and reanastomosis with 5/0 silk sutures, Fischer F344 rats were randomly allocated to three experimental groups. In Group A, a circumferential ring of tissue sealant was placed around the serosal surface of the anastomosis; in Group B, sealant was limited to 50 percent of the anastomotic circumference; and, in Group C, no sealant was applied. All rats then had 105Mtln3carcinoma cells injected into the proximal colonic lumenviaa rectal catheter. The incidence of perianastomotic tumor at 21 days was significantly lower in Group A (3 of 14 animals) than in Group B (11 of 16 rats) (P =0.012; Fishers exact test) or Group C (10 of 14 rats;P=0.011). A further experiment demonstrated that sealant did not protect the anastomosis when tumor cells were instilled directly into the peritoneal cavity. A topical carcinocidal action therefore appears unlikely, but our results suggest that a circumferential anastomotic ring of fibrin sealant forms an effective mechanical barrier preventing intraluminal tumor cells from reaching the peritoneal cavity.