Splanchnic and pancreatic tissue perfusion in experimental acute pancreatitis.

BACKGROUND: Gut hypoperfusion has a major role in the pathogenesis of multiple organ failure, which is the main cause of death in severe acute pancreatitis. The effects of experimental acute pancreatitis on splanchnic and pancreatic perfusion and oxygenation were studied to find out whether gut hypoperfusion occurs already at the same time as changes in pancreatic perfusion. METHODS: Twenty-four domestic pigs weighing 21-27 kg were randomized to severe or mild acute pancreatitis or control groups. Eight anaesthetized and mechanically ventilated pigs were intraductally infused with taurocholic acid to induce severe acute pancreatitis and eight received intraductal saline to induce mild acute pancreatitis. Eight pigs served as controls. RESULTS: Intraductally infused taurocholic acid rapidly induced severe necrotizing acute pancreatitis as assessed macroscopically and histologically. Histological changes of mild acute pancreatitis were seen in animals after intraductal saline infusion. After the induction, pancreatic tissue oxygen tension decreased promptly in severe acute pancreatitis and increased in mild acute pancreatitis. Laser-Doppler red cell flux decreased in severe acute pancreatitis. Gut pH gap and pCO2 gap decreased in 2 h after the induction of severe acute pancreatitis. Central haemodynamics were fairly stable throughout the study period in all groups. CONCLUSION: In experimental severe acute pancreatitis, splanchnic malperfusion seems to begin with pancreatic hypoperfusion before disturbances in gut microcirculation.

Pancreatic tissue perfusion in experimental acute pancreatitis.

OBJECTIVE: To investigate pancreatic tissue perfusion and oxygenation in severe and mild experimental acute pancreatitis in pigs. DESIGN: Randomised controlled experiment. SETTING: Animal laboratory, Finland. ANIMALS: 24 domestic pigs weighing 21-27 kg. INTERVENTIONS: 24 pigs were randomised into severe acute pancreatitis, mild acute pancreatitis and control groups (n = 8 in each). The pancreatic duct of eight anaesthetised and mechanically ventilated pigs was cannulated and taurocholic acid was infused into the pancreatic duct to induce severe acute pancreatitis. Eight animals received intraductally infused saline and developed mild acute pancreatitis. Eight pigs had their ducts cannulated alone, and served as controls. MAIN OUTCOME MEASURES: Pancreatic tissue oxygenation, laser Doppler red cell flux, central haemodynamics. RESULTS: Intraductally infused taurocholic acid rapidly induced macroscopically and histologically proven severe necrotising acute pancreatitis. Histological changes characterising mild acute pancreatitis were seen in animals after intraductal saline infusion. Pancreatic tissue oxygen tension decreased in the severe group and increased in the mild group during the six-hour study period. Laser Doppler red cell flux decreased in the severe group. Central haemodynamics, arterial blood gases, and acid base balances were stable throughout the study period in all groups. CONCLUSION: The present model of severe acute pancreatitis significantly impairs pancreatic oxygenation in the early phase. In mild acute pancreatitis, pancreatic oxygenation increases.

Human vascular adhesion protein-1 in smooth muscle cells.

Human vascular adhesion protein-1 (VAP-1) is a dual-function molecule with adhesive and enzymatic properties. In addition to synthesis in endothelial cells, where it mediates lymphocyte binding, VAP-1 is expressed in smooth muscle cells. Here we studied the expression, biochemical structure, and function of VAP-1 in muscle cells and compared it to those in endothelial cells. VAP-1 is expressed on the plasma membrane of all types of smooth muscle cells, but it is completely absent from cardiac and skeletal muscle cells. In tumors, VAP-1 is retained on all leiomyoma cells, whereas it is lost in half of leiomyosarcoma samples. In smooth muscle VAP-1 predominantly exists as a approximately 165-kd homodimeric glycoprotein, but a trimeric (approximately 250 kd) form of VAP-1 is also found. It contains N-linked oligosaccharide side chains and abundant sialic acid decorations. In comparison, in endothelial cells dimeric VAP-1 is larger, no trimeric forms are found, and VAP-1 does not have N-glycanase-sensitive oligosaccharides. Unlike endothelial VAP-1, VAP-1 localized on smooth muscle cells does not support binding of lymphocytes. Instead, it deaminates exogenous and endogenous primary amines. In conclusion, VAP-1 in smooth muscle cells is structurally and functionally distinct from VAP-1 present on endothelial cells.

Central haemodynamics in experimental acute pancreatitis.

OBJECTIVE: To investigate central haemodynamics in severe and mild acute pancreatitis in pigs. DESIGN: Randomised controlled experiment. SETTING: Animal laboratory, Finland. SUBJECTS: 24 domestic pigs weighing 21-27 kg. INTERVENTIONS: In 8 anaesthetised and mechanically ventilated pigs the pancreatic duct was cannulated and taurocholic acid was infused to induce severe acute pancreatitis. Eight animals received intraductal saline infusion and developed mild acute pancreatitis. Eight pigs were cannulated alone and served as controls. MAIN OUTCOME MEASURES: Cardiac index, heart rate, mean arterial pressure, central venous pressure, mean pulmonary arterial pressure, pulmonary arterial occlusion pressure, haemoglobin, arterial blood gases and acid base balance. RESULTS: Intraductally infused taurocholic acid rapidly induced severe necrotising acute pancreatitis as assessed both macroscopically and histologically. Histological changes of mild acute pancreatitis were seen in animals after intraductal saline infusion. Central haemodynamics, arterial blood gases, and acid base balances were stable throughout the study period in all groups. The main finding was haemoconcentration as indicated by the increase in arterial haemoglobin concentration in pigs with mild and severe acute pancreatitis. CONCLUSION: Haemoconcentration precedes central haemodynamic alterations in experimental acute pancreatitis.

Simo Antero Brofeldt--hospital leader, university teacher and military surgeon.

Simo Antero Brofeldt, Professor of surgery at the University of Helsinki from 1933 to 1942, was active in the planning and building of the Finnish Red Cross Hospital. He was the first chief surgeon of the hospital from 1932 to 1942, and consulting surgeon to the Finnish army High Command during the Second World War. He contributed to the development of trauma surgery, was acknowledged as a superb organizer and served the defence forces with honour.

Aspoxicillin versus piperacillin in severe abdominal infections--a comparative phase III study.

We compared aspoxicillin, a new broad-spectrum penicillin derivative, with piperacillin in severe abdominal infection. Aspoxicillin 4 g administered tds (n = 52) or piperacillin 4 g qds (n = 53) usually as monotherapy were randomly given to patients suffering from perforated appendicitis, acute cholecystitis, ulcer or colon perforation, or intra-abdominal abscess. Blood, tissue and exudate cultures were obtained when applicable for pathogen identification and susceptibility testing. The efficacy rates were similar in the two study groups. Of the 50 evaluable aspoxicillin patients 45 (90%) were considered as treatment responders compared with 48 patients out of 53 (91%) in the piperacillin group (NS). The 95% confidence interval for the efficacy difference was -12% to +11% thus showing no difference between the two drugs. Both drugs were generally well tolerated and no serious drug-related adverse events were noted. However, five patients died because of their illness and one patient had a fatal myocardial infarction. In conclusion, aspoxicillin 4 g tds was shown to be equal to piperacillin 4 g qds in severe abdominal infections.

What happens to the Valtrac anastomosis of the colon? A follow-up study.

Late results after colonic anastomoses performed with the biofragmentable anastomosis ring (BAR; Valtrac; Davis & Geck, Wayne, NJ) were evaluated in 30 patients who had undergone a left-sided colonic or rectosigmoid anastomosis a mean of 24.5 (range, 12-38) months earlier. Patients were asked about their late postoperative recovery and their bowel habits. A barium enema was performed, and then a flexible endoscopy was done, during which the anastomotic area was evaluated both in macroscopic terms and histologically. One of the patients had died, and three refused to participate in the investigation. Of the remaining 26 patients, one had been reoperated on 22 months after the primary sigmoid resection. The reason for reoperation was an anastomotic stricture. One of the patients was admitted to the hospital during the study and was operated on for reasons not related to the anastomosis. Twenty-four patients underwent the study scheme. All had recovered uneventfully. Sixteen anastomoses could not be identified radiologically and seven not even during endoscopy. Histologically, there was mild-to-moderate fibrosis and scarring in 17 anastomoses, and, in the seven that could not be identified, only normal colonic mucosa was found. The late results of BAR anastomoses are satisfying, and the rate of complications is acceptable.

Piperacillin/tazobactam versus imipenem/cilastatin in the treatment of intra-abdominal infections.

The current multicenter study was conducted at five sites using 86 patients to evaluate the safety and efficacy of piperacillin/tazobactam (4 grams per 500 milligrams every eight hours) compared with imipenem/cilastatin (1 gram every eight hours) in the treatment of patients who were hospitalized with a clinically or bacteriologically confirmed diagnosis of intra-abdominal infection. Forty-seven patients received piperacillin/tazobactam and 39 received imipenem/cilastatin. The favorable response among patients who were clinically evaluable with a valid response in the group treated with piperacillin/tazobactam was 87 percent. In the group treated with imipenem/cilastatin it was 77 percent. Bacteriologic eradication rate among bacteriologically evaluable patients with a valid response in the group treated with piperacillin/tazobactam was 100 percent. In the group treated with imipenem/cilastatin it was 89 percent. The eradication rate of pathogens isolated from patients who were evaluable by biologic factors in the group treated with piperacillin/tazobactam was 100 percent and in the group treated with imipenem/cilastatin treatment, 96 percent. In the group treated with piperacillin/tazobactam the incidence and type of adverse reactions were similar to those seen with piperacillin alone. It is concluded that piperacillin/tazobactam is safe and efficacious in the treatment of patients hospitalized with intraabdominal infections and that tazobactam extends the spectrum of piperacillin.

Selective endothelial binding of interleukin-2-dependent human T-cell lines derived from different tissues.

The ability of lymphocytes to recognize and bind to high endothelial venules (HEVs) is essential for lymphocyte migration from the blood into lymphoid tissues and into sites of inflammation. Endothelial cell binding capacity also critically determines the clinical usefulness of T-cell lines and clones in immunotherapy. In the present study, interleukin-2-dependent T-cell lines were derived from the blood, lamina propria of the gut, inflamed synovium, synovial fluid, and peripheral lymph nodes. After 3-8 weeks of culture, the expression of homing-associated molecules and binding to mucosal, synovial, and peripheral lymph node HEVs were analyzed. Cell lines derived from the blood and mucosal sites bound significantly better to mucosal and synovial HEVs than to peripheral lymph node HEVs. Three out of seven synovial T-cell lines showed preferential binding to synovial HEVs, whereas the rest bound almost equally well to synovial and mucosal HEVs. T-cell lines from peripheral lymph nodes bound preferentially to lymph node HEVs despite the lack of L-selectin (the peripheral lymph node homing receptor). Expression of the known homing-associated molecules did not predict the HEV-binding specificity of these lines. Importantly, two cell lines bound well to synovial venules, but poorly, if at all, to mucosal or peripheral lymph node HEVs, supporting the concept that synovial-specific HEV recognition mechanisms exist. In conclusion, the tissue origin of T-cell lines critically determines their selectivity for endothelial cell recognition, and besides the known "homing receptors," other molecules may also mediate tissue-specific HEV-binding of interleukin-2-activated T cells.

Small bowel anastomosis with the biofragmentable anastomosis ring and manual suture: a prospective, randomized study.

A total of 170 patients undergoing upper gastrointestinal surgery requiring a jejuno-jejunal enteroanastomosis were randomized into two groups according to the method to be employed at the enteroanastomosis. The most common procedures were partial gastrectomy for benign disease (84 patients), partial or total gastrectomy for malignant disease (35 patients), and bilioenteral bypass (31 patients, 25 for malignant disease). The enteroanastomosis was created by manual suture (3-0 Dexon, two layers) in 89 patients and with the Biofragmentable Anastomosis Ring (Valtrac-BAR) in 81 patients. Both end-to-side (101 patients) and side-to-side (69 patients) reconstructions were done. No ruptures or obstructions of the jejuno-jejunal anastomosis occurred. The postoperative recovery of the gastrointestinal tract was similar in the two groups in duration of nasogastric drainage, intravenous fluid therapy, and intestinal paralysis. Nor was there any difference between the groups in the duration of the postoperative hospital stay. Ten patients, 7 in suture-group and 3 in BAR-group, died postoperatively of causes unrelated to the enteroanastomosis. Thus the mortality rate was 7.9% in the suture group and 3.7% in the BAR group. The biofragmentable ring offers a safe alternative to manual sutures for small bowel anastomoses.

Colonic anastomosis using the biofragmentable anastomotic ring and manual suture: a prospective, randomized study.

One hundred and fifty consecutive patients undergoing colonic surgery were randomized into two groups: 71 underwent hand-suture with a two-layer anastomosis of resorbable suture material (3/0 Dexon) and 79 were fitted with the biofragmentable anastomotic ring (Valtrac-BAR). Five patients, two treated using the BAR and three by suturing, developed anastomotic leakage which required a Hartmann-type reoperation. This was successful in four; one patient in the suture group died after reoperation. One patient who underwent suture had an early anastomotic stricture with fatal sequelae. Three other patients (one in the BAR group and two in the suture group) died after operation from other causes. Thus the mortality rate was 6 per cent in the suture group and 1 per cent in the BAR group. During follow-up, one patient in each group underwent reoperation for anastomotic stricture. Recovery of the gastrointestinal tract was similar in the two groups regarding duration of nasogastric drainage, intravenous fluid therapy and ileus. There was no difference between the groups in duration of hospital stay. The BAR seems to be a safe and reliable alternative to conventional suture anastomosis in colonic surgery.

Laparoscopic cholecystectomy. Experience of the first 150 patients.

Between April 1991 and May 1992, 150 patients were treated by laparoscopic cholecystectomy. Eleven patients (7.3%) required conversion to open laparotomy and five (3.3%) patients were operated on for postoperative complications. There were two (1.3%) patients with a hepatic duct lesion, one of which was treated with a T-tube alone but the other required a bilioenteral reconstruction. The average operation time was 72 minutes (range 30-240 minutes). The mean hospital stay of all patients was 2.1 days (range 1-28 days) and the mean time to return to work was 11.5 days (range 6-60 days).

Cholecystoenteral anastomosis with the biofragmentable ring and manual suture--a prospective, randomized study.

20 patients treated by cholecystojejunostomy for obstructive icterus were randomized to be treated either with a biofragmentable intraluminal ring (Valtrac) (10 patients) or suture of the cholecystointestinal anastomosis (10 patients). Postoperatively one patient in each group died of advanced malignancy. There were no surgical complications in either group. The relief of icterus, recovery of the gastrointestinal tract and the mean hospital stay were similar in both groups. The biofragmentable anastomosis ring (BAR) is a safe method for cholecystoenteral anastomoses.

Gastrointestinal viscerosynthesis with biofragmentable anastomosis ring.

The biofragmentable anastomosis ring (BAR) has been in clinical use since 1987. It yields a standardized intestinal viscerosynthesis leaving no foreign body in the tissues. Several multicentre and single studies have shown its safety and efficacy in elective colonic surgery. Our studies have shown it to be safe and reliable also in small bowel surgery and bilio-digestive anastomosis. Our long-term results in colonic surgery are very promising. A review of anastomosis technique and current literature is given.

Surgery of acute peptic ulcer haemorrhage.

During the years 1973-1985, 145 patients with acute peptic ulcer haemorrhage were treated surgically at the Department of Surgery, Turku University Central Hospital. The bleeding site was gastric ulcer in 76 patients; 58 of these were treated by gastric resection and 17 by ulcer excision combined with vagotomy and pyloroplasty. Forty-two out of 69 patients with bleeding duodenal ulcer were treated with partial gastrectomy, the remaining with transfixion and vagotomy and pyloroplasty. The rebleeding rate was 2% and reoperation rate 9% among the patients who had a resection. In contrast 19% of the transfixed and 12% of ulcer excision cases rebled. The primary overall mortality was 12%; 44% of the patients with recurrent bleeding died. Because rebleeding was the most important cause of mortality, partial gastrectomy in bleeding gastric as well as duodenal ulcer may be preferable.

Diagnostic factors for postoperative candidosis in abdominal surgery.

Abdominal surgery patients with postoperative septicaemia and a deep septic focus were analyzed in an attempt to identify characteristics typical of postoperative candidosis. There were 36 patients, 10 with candidosis and 26 with bacterial septicaemia. Typical for candidosis when the septic signs appeared was a history of prolonged antibiotic treatment before the operation (10/10), long courses of antibiotics (7/10), and therapy with combinations containing aminoglycoside (7/10). Operations on the small intestine were characteristic of candidosis patients (4/10). A poor clinical condition (9/10) on admission to the hospital, late onset of septicaemic symptoms postoperatively (7/10), long hospitalization (9/10), parenteral nutrition (10/10) and reoperations (9/10) were also features associated with the development of candidosis. Patients with postoperative candidosis have several characteristics on the basis of which the developing serious infection can be suspected and empirical therapy started. It may be appropriate to initiate antifungal prophylaxis in connection with operations when necrotic intestine is resected. Avoiding long courses of postoperative antibiotics could also be a measure to diminish the incidence of postoperative candidosis.

Roux-en-Y reconstruction for severe postoperative duodenogastric reflux disease.

Thirty-two patients underwent Roux-en-Y diversion because of symptomatic postoperative duodenogastric reflux. Operative mortality was nil, but eight patients had transiently delayed gastric emptying postoperatively. At follow-up 45 months (range 9-89 months) after the Roux-en-Y operation 28 (88%) patients were in good clinical state; four patients were classified as poor. The main cause for a poor clinical outcome was a stomal ulcer in three patients. Atrophic gastritis was seen in the operative specimens of 22 patients. Severity of gastritis evaluated by gastroscopic biopsies at follow-up was less marked in 16 patients as compared to the histology of the samples from the original operation (P less than 0.001). Intestinal metaplasia had regressed in nine cases and proceeded in three cases (NS). Severe postoperative duodenogastric reflux can be treated by the Roux-en-Y reconstruction with good subjective relief of symptoms and beneficial histologic changes in the gastric stump mucosa.

Natural killer cell activity after immediate postoperative enteral and parenteral nutrition.

Effects of immediate postoperative enteral and parenteral nutrition on natural killer (NK) cell activity were compared after major abdominal surgery. Eleven patients were fed enterally (2,000 kcal/12.4 g N) and eleven parenterally (1,940 kcal/12.4 g N) for three days after operation. NK cell activity against K562 target cells, determined in the 51Cr release assay, was similar in patients of both groups preoperatively. Postoperatively the patients showed a decrease in NK cell activity (p less than 0.01) but without differences between the groups. The percentages of NK cells did not change between or within the two groups. The results suggest that immediate postoperative enteral nutrition had no superiority over parenteral nutrition on NK cell function in surgical patients.

Second follow-up study of mucosal changes in the gastric remnant after resection for peptic ulcer disease.

Second follow-up 36-37, 26-27 and 15-18 years after gastric resection for peptic ulcer disease was performed for 72 patients who in the first screening five years earlier had severe atrophic gastritis and/or intestinal metaplasia in the gastric remnant mucosa. Of the 72 patients 60 were still alive. The death certificates revealed no gastric stump carcinomas among the 12 deceased patients. Neither were any cases of gastric stump carcinoma found among the 38 endoscopically screened patients. Severe atrophic gastritis, which was present in 37 patients in 1982-83, had regressed in 14 cases (p less than 0.01) and proceeded in one case. The extent of intestinal metaplasia had increased in 11 cases and decreased in five cases (p = 0.149, NS). Dysplasia, which was not seen five years ago, was now detected in four cases (10.5%). There was an association between dysplasia and incomplete intestinal metaplasia in three cases. Although these mucosal changes may be premalignant it is not possible to be categorical about the prognosis. Thus, endoscopic screening of all patients whose stomach has been resected for peptic ulcer disease cannot be recommended. Endoscopy, however, is always indicated when gastric symptoms appear in a patient with history of gastric resection.

Surgical treatment of high bleeding gastric ulcer.

In the surgical treatment of 68 consecutive patients with benign, high, bleeding gastric ulcer between 1966 and 1981, the following operative procedures were used; high gastric resection in 31 (45.5%) cases, local ulcer excision with truncal vagotomy and pyloroplasty in 23 (33.8%), local ulcer excision with low gastric resection in 11 (16.2%) and a local procedure alone in three (4.5%) cases. Of these 68 operations, 40 (59%) were early elective operations and 28 (31%) acute or emergency operations. Altogether, six (8.9%) patients died postoperatively, all but one after acute or emergency operation. High gastric resection was the most risky operation and five of the six deaths were in this operative group. Nonfatal complications developed in 18 (26.4%) cases but without correlation to the timing or to the type of operation. Early rebleeding during the hospital stay necessitating reoperation occurred in three (4.4%) patients, two of these among the three cases operated on using a local procedure and without a definitive operation. During the follow-up five (7.3%) recurrent ulcers developed, four after local ulcer excision with truncal vagotomy and pyloroplasty and one after high gastric resection. It seems to us that in the treatment of patients with high gastric ulcer, local operation alone is never acceptable. High gastric resection is often technically hazardous with a high postoperative mortality rate. The best methods seemed to be local ulcer excision combinated with truncal vagotomy and pyloroplasty or, perhaps preferably, with low gastric resection.