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The effects of piroxicam on postoperative changes of collagen--measured as hydroxyproline--concentrations were measured around intestinal anastomoses in rats. Piroxicam, in a dose of 2 mg/kg/day, significantly reduced the decrease of hydroxyproline concentrations around colonic anastomoses during the first 3 days after the operation but also reduced the increase of hydroxyproline concentrations observed at day 7 around ileal anastomoses in the control group. 10 mg piroxicam/kg/day resulted in a 100% lethal peritonitis after the 5th postoperative day. We suggest that piroxicam affects collagen metabolism by inhibiting granulocyte functions.

Crohn's disease has a tendency to form fistulae and abscesses, which may lead directly to urological complications. Three patients were seen who had entero-vesical fistulae; only one of these could be demonstrated radiologically. There were also seven patients with Crohn's disease who had ureteric obstruction.

Since 1971, 151 nonpalpable breast cancers (100 invasive carcinomas, 39 in situ ductal carcinomas, and twelve lobular carcinomas in situ) have been diagnosed and treated at the St. Radboud University Hospital. Of the 100 clinically occult invasive carcinomas, 53 had pathologic diameters of more than 10 mm, 29 were of sizes between 6 and 10 mm, and 18 were tumors of 5 mm or less. Residual tumor outside the "excisional" biopsy cavity was encountered in 76 of the 118 mastectomy specimens (64.4%) fully capable of evaluation. Invasive residual tumor would have been left behind in 34 of 86 mastectomy specimens (39.5%). Of 27 axillas studied, no patient with in situ carcinoma had evidence of axillary lymph node metastases. Invasive carcinoma, however, showed axillary lymph node involvement in 7.7% of mastectomy specimens when the size of the primary tumor was not more than 5 mm, in 12.5% when the size was between 6 and 10 mm, and in 29.5% when the primary tumor was more than 10 mm in diameter. The 10-year recurrence-free survival (RFS) of patients with clinically occult invasive carcinomas greater than 10 mm in size was 71.9% and differed significantly from the 90.9% for patients with the invasive tumors less than or equal to 5 mm, as well as from the 100% RFS of patients with invasive tumors of between 6 and 10 mm and noninvasive tumors. Although the 10-year RFS was 92.6% for the patients with negative axillary nodes and 80.0% for the patients with positive axillary nodes, this difference did not reach statistical significance. However, the disease-specific overall survival after 10 years was significantly different between node-negative patients (96.4%) and node-positive patients (78.8%). Multivariate analysis disclosed that the relationship between size of the primary tumor and RFS was independent of the presence of axillary lymph node metastases. In conclusion, the validity of the concept of minimal breast cancer has been re-enforced. However, the results of this study suggest that the upper limit of the original definition of minimal breast cancer is too narrow and should be extended, so that, apart from the noninvasive tumors--regardless of their size--all invasive tumors having a maximum diameter less than or equal to 10 mm should be regarded as minimal breast cancers.

From the non-B-cell tumors of the pancreas the gastrinoma (Zollinger-Ellison-syndrome) is the best known. The glucagonoma and the vipoma are less known and less common. The diagnosis of these syndroms, produced by overproduction of hormones, is a clinical one. The radiodiagnost has to localize the primary tumor and to exclude metastases. The x-ray findings of the glucagonoma in 3 patients and of the vipoma in 1 patient are described.

During a 9 year period, 300 consecutive women underwent breast biopsies solely because of nonpalpable, mammographically suspicous findings. One hundred clinically occult breast carcinomas were found, 65 of which were invasive and 35 noninvasive. Eighty-three mastectomy specimens were evaluable for evidence of multifocal carcinoma in another quadrant of the breast or at a distance of 5 cm and residual cancer outside the excisional biopsy cavity. Multicentricity was present in 47 percent and residual tumor in 60 percent of the whole group. When only clinically occult invasive carcinomas were considered, other foci of invasive carcinoma were demonstrated in 26 percent of the patients and residual invasive cancer in 35 percent. The rate of bilaterality was 14 percent, occurring synchronously in 11 percent of the patients. Any therapeutic procedure for nonpalpable breast carcinoma, whether invasive or noninvasive ductal carcinoma, should be directed to the whole breast. Mammography of the contralateral side should be an integral part of the preoperative work-up of patients with palpable lesions ipsilaterally.

Three methods of excising nonpalpable breast lesions have been evaluated: (1) "blind" method, using mammographic coordinates; (2) preoperative localization with the Frank needle; and (3) Frank needle localization aided by a multiperforated compression plate. Successful removal at first attempt occurred in about 80% with any method. The size of the biopsy specimens did not differ significantly among the three groups and is most probably a function of the breast volume. The failure rate was seven (2.1%) of 332 biopsies. Since three of the six repeated biopsies yielded specimens with malignancy, the persistence of a radiographically suspicious lesion on follow-up mammogram of the operated-on breast is an urgent indication for reoperation.

The changes in collagen, measured as hydroxyproline, concentration around both ileal and colonic anastomoses in germ-free and control rats have been investigated and compared with each other. The germ-free rats were raised, operated on and maintained under completely pyrogen-free conditions. Animals were killed 2, 3 or 7 days after operation. There was a significant reduction in the lowering of hydroxyproline concentrations around the colonic anastomosis of germ-free rats compared with control rats both in the anastomosis at days 2 and 3 (P = 0.04 and P = 0.006 respectively) and in the proximal segment at day 3 (P = 0.03). In ileal anastomoses, significant differences between control and germ-free rats were only found at 7 days. Here, the increase in hydroxyproline concentration observed in control rats was significantly reduced in germ-free rats. These data are taken to support the hypothesis that bacteria affect colonic anastomotic healing by contributing to postoperative collagen degradation.

During a period of ten years, 118 (32.9 per cent) instances of carcinoma were found in 359 specimens taken at biopsy for nonpalpable mammographic lesions. In recent years, the positive predictive value has increased from 68 per cent due to the development of magnification mammography and the use of a mammographic grid. Correlating mammographic and histopathologic data, the rate of malignant disease was 12.7 per cent for instances of a circumscribed or nodular mass, 32.4 per cent for clustered microcalcifications as the only suspect finding, 28.6 per cent when a mass with microcalcifications was present and 66.7 per cent when a stellate-shaped mass was found. Of 188 instances of carcinoma, 40 were noninvasive: 32 instances of ductal carcinoma (27.1 per cent) and eight of lobular carcinoma in situ (6.8 per cent). The possibility of frozen section diagnosis was studied retrospectively by comparison with the paraffin section reports. A correct diagnosis, whether benign or malignant, was achieved in 68 per cent. No frozen section examination was done in 17.3 per cent and the diagnosis was deferred to results of paraffin section in 12.2 per cent. False-negative results were encountered in seven patients (1.9 per cent) and false-positive results in two (0.6 per cent). Both of these patients had florid sclerosing adenosis. Although frozen section diagnosis is feasible in nonpalpable lesions of the breast, it is recommended that this method not be used in instances of pure microcalcifications and tiny solid masses of 5 millimeters or less.

The intra-abdominal implantation of a gelatin capsule containing human fecal material introduces peritonitis in the rabbit. The severity of the disease and the length of survival depend on the volume of the inoculum. A 7-day survival chance varies between 45 and 92%, depending on fecal loading. All rabbits develop intra-abdominal abscesses and in the surviving animals infection persists for at least a week, allowing further study of several aspects of peritonitis.

Interstitial collagen is a major constituent of the tumor matrix. The quantity of this protein may influence the prognosis. The collagen content of 54 colorectal tumors, measured as the hydroxyproline concentration in relation to clinicopathologic stage and histologic grade, was investigated and no support for either a negative or positive influence on the prognosis.

Two patients developed pseudogout attacks during treatment for hyperparathyroidism, the first shortly after surgery and the second during medical treatment of her hypercalcaemia. From our observations in these patients and from data in the literature, we conclude that pseudogout attacks following parathyroidectomy in patients with chondrocalcinosis are caused by the decrease in the serum calcium levels and not by the major surgical procedure itself.

The influence of the pressure during the flushing procedure on the results of the subsequent transplantation was investigated in a model of heterotopic functional small bowel transplantation in the outbred Wistar rat. In this model insufficient small bowel preservation will result in a lethal shock, soon after revascularization. If the size of the small bowel graft was reduced to a 15-cm segment of the proximal jejunum, improper preservation did not lead to lethal shock, but to histological changes of the graft. The influence of high flushing pressure (80 cm), medium flushing pressure (50 cm), low flushing pressure (35 cm), and no flushing procedure at all, was investigated in different groups of rats. Flushing was performed by gravity using chilled Ringer's lactate solution (4 degrees C), buffered with NaHCO3 at a pH of 7.4. The results were evaluated histologically as well as clinically. Results indicated flushing of the graft to be superior to a nonflushing procedure. A flushing pressure of 80 cm and even 50 cm proved to be harmful to the jejunal graft. Flushing pressure of 35 cm resulted in successful segmental (jejunal) and subtotal (minus 5- to 7-cm distal ileum) small bowel transplantation. However, survival of a total small bowel graft could not be achieved with the optimal flushing procedure indicating that the functional integrity of a small bowel graft also depends on conditions other than the method of short-term preservation.

Gastrostomy is performed in patients with obstructive carcinoma of the esophagus. As in this operation the peritoneal cavity has to be opened we tried to find in experiments with 11 rabbits whether the percutaneous gastrostomy is a possible alternative.

The records of 146 consecutive multiply injured patients treated between 1976 and 1981 have been studied. Thirty-five patients underwent emergency laparotomy and in 24 patients the laparotomy was done 4 or more hours after admission. Eight of the 35 patients of the third group died, in 4 of whom the cause was head injury. The other 4 patients were extremely severely injured (Injury Severity Scores from 66 to 75). In the second group, 6 patients died, 5 from multi-organ failure due to sepsis and 1 patient from hypovolaemic shock. The more aggressive approach--to prevent multi-organ failure--is advised. The laparotomy, if indicated, must be done as an emergency procedure. During the same procedure fractures can be stabilized. In the postoperative period, mechanical ventilation should be instituted. Fresh blood should be given when more than 4000 ml stored blood is transfused, to prevent any tendency to bleed.

In the period 1977-1981 234 small bowel anastomoses were constructed in 143 patients. Eight anastomoses showed leakage (3.4%) and from nine anastomoses a fistula developed (3.8%): a total rate of disturbed healing of small bowel anastomoses (7.3%). In the presence of intra-abdominal infection this rate was 14.8%, in the absence of infection 0.8%. The results of treatment with oversewing and with resection and immediate anastomosis were disappointing. Better results were obtained by dismantling of the anastomosis, establishment of a split-enterostomy and reestablishment of continuity in a second stage. Mortality was 3/17 (18%). The literature is reviewed.

The effects of bile acid drainage on serum cholesterol levels have been investigated in Watanabe heritable hyperlipidemic rabbits, a unique model for homozygous familial hypercholesterolemia. Cholestyramine medication lowered serum cholesterol concentrations with 38%, while a 33% and a 50% small bowel bypass resulted in a decrease of 56 and 48%, respectively. Cholestyramine treatment after either bypass induced a minor additional fall in serum cholesterol. Ileal bypass and ileal resection were equally effective in reducing serum cholesterol. These results indicate the necessity for further investigation into the potential of bile acid drainage as a therapy in homozygous familial hypercholesterolemia.

A series of 67 patients treated by Hartmann's operation was studied, special attention being given to complications originating from the rectal stump. In 13 patients, complications--abscesses of the rectal stump and fistulas from the rectal stump to the small intestine--were seen. Eight of those occurred in patients with leakage at the anastomotic site after anterior resection and in patients with radionecrosis of the rectum. It is concluded that the risk of rectal stump complications is slight in patients with diverticulitis and with carcinoma, who made up the large majority of those in whom Hartmann's operation may be needed.

Peritoneal lavage is a sensitive method of detecting intra-abdominal injuries following closed abdominal injury. Our indications for peritoneal lavage are: severe head injury, severe thoracic injury, unexplained hypotension in a patient with possible blunt abdominal injury and patients on artificial ventilation. We present 40 patients with multiple injuries who underwent peritoneal lavage for suspected closed abdominal injury. Twenty-two lavages were positive and 19 laparotomies were performed, of which 18 revealed intra-abdominal injuries. Eighteen lavages were negative; no laparotomy was performed in this group. There was one false positive, but no false negative lavage.

Various histological parameters of wound repair have been studied in intestinal anastomoses in the rabbit in order to compare the healing processes in ileum and colon. The sequentional appearance of granulocytes, macrophages and fibroblasts has been studied from 3 h to 7 days after operation. Also, degree of necrosis, formation of capillaries and mucosal repair were analysed semi-quantitatively. Significant differences were observed between ileal and colonic anastomoses with respect to occurrence of granulocytes, necrosis and mucosal repair, particularly 7 days after operation. At that time, granulocytes and necrosis were virtually absent from ileal anastomoses, while mucosal integrity was restored in the majority of cases examined. In contrast, granulocytes and necrosis were still abundantly present in colonic anastomoses and mucosal repair was poor. These results support biochemical evidence that wounds in the ileum heal more rapidly than wounds in the colon. Possibly, the sustained presence of granulocytes, which are a potential source of collagenase activity, is important in this respect. Investigation of the same features of intestinal wound healing in rabbits with peritonitis induced by infection showed similar results and no differences were found between infected and non-infected animals.

In 60 patients a small bowel enterostomy was constructed as part of the treatment of various intra-abdominal infectious and obstructive conditions. Eleven patients (18 per cent) died in the immediate postoperative period from continuing sepsis. In one patient closure of the stoma was not considered because of disseminated malignancy. In the remaining 48 patients continuity of the gut was subsequently restored. In 22 patients (46 per cent) complications occurred, 12 (25 per cent) of which were intra-abdominal septic complications. The occurrence of intra-abdominal complications was found to be linked to premature (i.e. within 3 months) closure of the stoma. Reasons for premature closure were stomal difficulties and prerenal azotaemia. Stomal closure was attended by a 10 per cent mortality rate.

The effect of a combination of antineoplastic agents (bleomycin (2 mg/kg/d), 5-fluorouracil (10 mg/kg/d) and cisdiamminedichloroplatinum (0.35 mg/kg/d)), given intravenously, on the healing of colonic anastomoses was investigated in rats. Ninety-six male Wistar rats were divided into four groups. A control group of rats underwent surgery only. The remaining rats were operated either 2 days before, 2 days after or during the 5-day chemotherapy course. In all groups rats were killed after 3, 7 and 21 days. Wound healing of the anastomosis was assessed by measuring the bursting pressures and hydroxyproline contents. Operating in the middle of the 5-day chemotherapy course had the greatest effect on anastomotic healing. This was most apparent on the seventh day postoperatively. When surgery was performed on the second day after the chemotherapy course there was an early delay in wound healing as measured by hydroxyproline content. Seven days postoperatively concentrations were in the same range as those in the control group. Chemotherapy commencing 2 days after surgery did not affect anastomotic healing as compared to the control group. Bursting pressure and hydroxyproline content at the end of the experiment were more or less comparable in all groups.

The healing of both rabbit ileal and colonic infected anastomoses has been investigated. Infection was induced by implanting a capsule with human fecal material in the anastomotic area. Infection did result in lowered bursting pressures, which effect was most pronounced in ileum seven days postoperatively. In general, the average hydroxyproline levels in and around infected anastomoses were lower than the hydroxyproline concentrations measured around noninfected anastomoses. This difference was most significant in the segment proximal to the ileal anastomosis seven days after operation, in the segment distal to the colonic anastomosis three days after operation, and in the segment proximal to the colonic anastomosis seven days after operation. It is concluded that infection interferes with the early stages of the healing sequence in rabbit intestinal anastomoses, profoundly affecting collagen metabolism. Our work does not support recent publications that report an unchanged or even increased wound strength under infected conditions.

Microcalcifications constitute an important part of nonpalpable breast lesions and may be the first sign of a breast carcinoma. Between 1975 and 1984, 150 consecutive patients with clusters of at least five microcalcifications without palpable findings as the only indication for biopsy were treated. One hundred seventy-three groups of microcalcifications were excised and 51 malignancies were detected (29.5%). Most of the malignant lesions were noninfiltrating (56%). Axillary or distant metastases occurred in 11% of the fully evaluable cases. This warrants the expectation that these patients have a very favorable prognosis. Breast biopsy for nonpalpable-clustered microcalcifications is a feasible and valuable procedure. Close cooperation is required between the surgeon, radiologist, and pathologist.

Aim of the present study was to compare an alimentary and a hereditary rabbit model for hypercholesterolemia. Serum lipids, serum lipoproteins and distribution and prevention of atherosclerotic plaque formation were studied in (1%) cholesterol-fed NZW rabbits and both heterozygous and homozygous WHHL rabbits. Cholesterol-fed NZW rabbits showed a hypercholesterolemia without hypertriglyceridemia, caused by accumulation of a spectrum of cholesterol ester-rich beta-migrating lipoproteins with a relatively low density. The WHHL rabbits displayed both a hypercholesterolemia with an elevation of LDL, and a hypertriglyceridemia. The hypertriglyceridemia in the WHHL homozygotes was due to accumulation of VLDL remnants and in the heterozygotes to a slight rise in normal pre-beta VLDL. Despite the pronounced quantitative and qualitative differences in lipoproteins, the location and extent of atherosclerotic plaques which had developed after 13 weeks cholesterol-rich diet in NZW rabbits and in 10 months old homozygous WHHL rabbits, was quite similar. Partial ileal bypass surgery lowered serum cholesterol in all three groups and also prevented atherogenesis.