The effect of FK506 on canine bile flow.

While the primary immunosuppressive agents utilized in solid-organ transplantation are steroids and cyclosporine, the more recently introduced agent FK506 is assuming a progressively more important role as an immunosuppressant, particularly in liver transplantation. While the effect of cyclosporine on rat and canine bile flow has been well evaluated, no information is available regarding the effect of FK506 on bile flow. Dogs with chronic biliary fistulas were utilized, enabling unanesthetized animals to be studied. FK506 was administered intravenously in varying doses, and bile volume, bile salts, and bile electrolytes were measured. FK506 produced dose-related increases in bile volume and bile chloride concentration and output, with 8 micrograms/kg-1hr-1 being the maximal dose. To ascertain that the response was not osmotic in association with FK506 secretion in bile, 500 micrograms/kg-1hr-1 FK506 was administered, which did not produce a choleresis significantly greater than 8 micrograms/kg-1hr-1. FK506 was subsequently administered orally in daily dose of 0.15 mg/kg-1 for two weeks. Oral FK506 did not consistently increase bile flow, as evaluated by a bile salt dose-response curve (9, 18, 36 mumol/min sodium taurocholate) but did significantly increase bile chloride secretion. Two weeks of oral administration of FK506 in therapeutic doses did not significantly alter serum bile salt concentrations. The results of this study indicate that intravenous FK506 produces a chloride-rich choleresis in dogs.

The effect of vagotomy on the canine enterogastrone mechanism.

The effect of truncal vagotomy on the enterogastrone mechanism was evaluated in dogs with Heidenhain pouches and gastric and pancreatic fistulas. During continuous infusion of pentagastrin, 8 microg-Kg.-hr., HCl was infused into the duodenum in doses of 12, 18, and 24 mEq. per hour before and one month following transthoracic vagotomy. The effect of vagotomy on the inhibition of pentagastrin-stimulated Heidenhain pouch hydrogen ion output produced by the endogenous release of duodenal hormones was evaluated. The results indicate that there was no difference in the degree of inhibition produced by 12 and 18 mEq. intraduodenal HCl before and after vagotomy. When 24 mEq. per hour HCl was infused, the percent inhibition was significantly greater after vagotomy compared to values before vagotomy. The D50 of intraduodenal acid for inhibition of Heidenhain pouch hydrogen ion output was not altered by vagotomy, whereas the calculated maximal response (inhibition) was increased after vagotomy. Pancreatic volume was greater after vagotomy when compared to values before vagotomy, when 24 mEq. of HCl per hour was infused into the duodenum. These data suggest that vagotomy does not impair the effectiveness of the enterogastrone mechanism and at high doses of intraduodenal acid may augment it.

Significance of the in-training examination in a surgical residency program.

The exact role that the American Board of Surgery In-Training Examination plays in resident evaluation remains poorly defined. We have required that all residents take the In-Training Examination annually. An analysis was performed of the results of the In-Training Examination and the Qualifying Examination of the American Board of Surgery for 16 residents who completed their residencies between July 1976 and July 1981. Twelve graduates passed their initial Qualifying Examinations with a mean +/- 1 SEM score of 81 +/- 2. Four graduates failed with a score of 70 +/- 0.3. Corresponding scores on their final In-Training Examinations were 42 +/- 9 and 11 +/- 6 (p less than 0.001). Each year the In-Training Examination Scores obtained by the residents who passed the Qualifying Examination were significantly higher than were those scores obtained by the graduates who failed. Linear regression analysis identified a significant correlation between the graduates' initial (r = 0.676) and final (r = 0.760) In-Training Examination scores and the Qualifying Examination score. In our resident training program, In-Training Examination results correlated well with Qualifying Examination results and may be used as an objective determinant for remedial measures and resident retentions. These data should be developed on a national level. While Board certification was or likely will be accomplished by all our residents, our goal is to strengthen the academic characteristics of the training program to produce uniform success on the initial Qualifying Examination.

Comparative evaluation of synthetic meshes used for abdominal wall replacement.

The lack of adequate fascia for closure of large hernias and traumatic abdominal wall defects has led to a search for suitable fascial substitutes. In this study closure of rabbit abdominal wall defects with knitted polypropylene, knitted polytetrafluoroethylene (PTFE), and molded polyglactin mesh was evaluated for bursting strength, fibrous tissue incorporation, and inflammatory reaction. Full-thickness, inch-square defects in the abdominal walls of rabbits were closed with use of the synthetic meshes, and similar defects in the contralateral abdominal walls were closed with a vascularized flap of external oblique fascia (control flaps). The animals were sacrificed at 3 and 12 weeks, the abdominal walls were removed, and the bursting strength of the grafts and control flaps was determined with a tissue tensometer. Polypropylene and PTFE meshes were similar in bursting strength and not greatly different from controls at 3 and 12 weeks. At 3 weeks polyglactin mesh had a bursting strength comparable to that of control flaps but at 12 weeks was significantly weaker. Fibrous tissue incorporation within the mesh fibers was better with PTFE mesh than with polypropylene mesh. Adequate fibrous tissue incorporation into polyglactin mesh before hydrolysis did not occur, making it an unsatisfactory material for use for permanent abdominal wall replacement.

The effects of reversal of jejunoileal bypass operations on hepatic triglyceride content and hepatic morphology.

Obesity is associated with significant hepatic steatosis, inflammation, and cirrhosis. These changes may be accentuated by jejunoileal bypass operations. This study is intended to determine if reconstruction of jejunoileal bypass operations alters hepatic triglyceride content and hepatic morphology. Eighty-eight +/- 27 months after jejunoileal bypass, 26 patients underwent reconstruction for a variety of complications of the operation, including five patients with cirrhosis. At the time of reconstruction, hepatic triglyceride content was 132 +/- 13 mg/100 mg protein. After reconstruction, hepatic triglyceride content increased to 205 +/- 32 mg/100 mg protein in patients whose body weight increased and decreased to 84 +/- 6 mg/100 mg protein in patients whose body weight decreased. After reconstruction, hepatic inflammation decreased in 20 patients and hepatic fibrosis decreased in 17. These changes were not related to body weight changes. In five patients with cirrhosis at the time of reconstruction, one died of liver failure and hepatic morphologic findings improved in four after reconstruction of jejunoileal bypass operations. The results of this study suggest that reconstruction of jejunoileal bypass operations with weight loss or maintenance of body weight after reconstruction is associated with decreased fat in the liver. Approximately 65% of the patients will have improvement in hepatic morphologic parameters after reconstruction. Inflammation will be more greatly benefited than will fibrosis. In some patients, hepatic histologic abnormalities are unchanged or will progress despite reconstruction of jejunoileal bypass operations.

The role of prostaglandins in feline experimental cholecystitis.

The arachidonic acid metabolites are recognized as important biochemical mediators of inflammation in a wide variety of disease processes. Also the ability to change prostaglandin formation by inhibition of prostaglandin synthetase activity with aspirin and other nonsteroidal anti-inflammatory agents is important in the treatment of many diseases with an inflammatory component. Although gallbladder disease is primarily related to the development of cholesterol stones, inflammation is an important contributor to the subsequent symptoms and accompanying illness. This research evaluates the formation of prostaglandins E and F by gallbladder tissue. Gallbladder mucosal cells and muscle tissue were maintained in tissue culture medium. Production of prostaglandins E and F was determined by quantitation by radioimmunoassay of these substances in culture media and mucosal cell and muscle tissue homogenates. Prostaglandin production by normal gallbladder tissue in a variety of species including man was consistently demonstrated in the nanogram per milligram mucosal cell or muscle tissue protein range. In cats, inflammation was produced by placing a 4% carrageenan-soaked sponge in the gallbladder, and prostaglandin synthetase inhibition was produced by indomethacin administration. The feline gallbladder increased prostaglandin F production in inflamed gallbladder mucosal cells and E production by inflamed gallbladder muscle tissue, and indomethacin inhibited these increases. A positive, significant correlation existed between the increased prostaglandin E and prostaglandin F production by inflamed gallbladder tissue and the amount of inflammation present as determined by a histologic score. The histologic score of the amount of gallbladder inflammation present was decreased significantly by indomethacin when compared with inflamed gallbladders from cats not receiving indomethacin. Prostaglandins may play a role in the inflammatory processes occurring in acute cholecystitis.

The effect of cholecystokinin-receptor antagonists on cholecystokinin-stimulated bile flow in dogs.

Cholecystokinin is a choleretic in dogs. Some of the effects of cholecystokinin in stimulating bile flow in dogs are produced by cholecystokinin stimulating the release of other choleretic hormones such as insulin and glucagon. The purpose of this study was to determine the effects of cholecystokinin receptor antagonists on canine hepatic bile flow and insulin and glucagon release from the pancreas. Cholecystokinin octapeptide (CCK-8) and intraduodenal fat were administered to dogs that had undergone cholecystectomy with chronic biliary fistulas with and without the administration of cholecystokinin receptor antagonists. Bile secretion and systemic venous insulin, glucagon, and cholecystokinin levels were measured. The cholecystokinin receptor antagonists benzotript and CR 1409 had no effect on bile flow or hormone levels when administered without cholecystokinin, whereas proglumide produced a large increase in bile flow without altering hormone levels. The response produced by proglumide may be the result of an osmotic effect produced by the substance being secreted in bile and its stimulating bile salt secretion in bile. CCK-8 and intraduodenal fat increased bile flow, bile chloride secretion, and cholecystokinin, insulin, and glucagon concentrations in venous blood. The cholecystokinin receptor antagonists benzotript and CR 1409 significantly decreased the bile flow and insulin and glucagon changes produced by exogenous CCK-8. The effect of intraduodenal fat on bile flow was not inhibited by the cholecystokinin receptor antagonists, whereas the increased insulin and glucagon levels were decreased significantly. Intraduodenal fat may release other choleretic hormones not affected by cholecystokinin receptor antagonists. The choleresis produced by exogenous CCK-8 is inhibited by cholecystokinin receptor antagonists, perhaps by inhibiting the release of the choleretic hormones insulin and glucagon.

The effect of electrical vagal stimulation on canine pancreatic exocrine function.

The effect of electrical vagal stimulation on canine pancreatic exocrine function was studied in conscious dogs by stimulating intact thoracic vagus nerves, the distal ends of cut vagus nerves in animals with intact gastric denervation, and the distal ends of cut vagus nerves in dogs whose stomachs had been previously selectively denervated. The effectiveness of the stimulus was confirmed by monitoring gastric hydrogen ion output. The results indicate that stimulation of intact nerves produced minimal alteration in pancreatic output and bicarbonate and protein secretion while significantly increasing gastric fistula hydrogen ion output. Stimulation of the distal ends (efferent fibers) of cut vagus nerves in dogs with intact gastric innervation significantly increased the volume and protein output of the pancreas and the acid output of the stomach. Stimulation of the distal ends of cut right and both vagus nerves in dogs whose stomach had been denervated previously, again, significantly increased the volume and protein output of the pancreas without stimulation of stomach hydrogen ion output. The data presented in this study suggest that the canine pancreas is innervated directly by vagal fibers, which when stimulated produce an increase in protein (enzyme) output and volume of secretion. Maintenance of the pancreatic response following denervation of the stomach suggests that the response is primarily the result of direct vagal innervation and is not produced by gastrin released from the antrum.

Evaluations of surgery resident performance correlate with success in board examinations.

BACKGROUND: American Board of Surgery (ABS) In-Training Examination (ABSITE) scores correlate with future examination scores, but faculty evaluations of resident skill have not been shown to predict future performance. METHODS: Objective and subjective evaluations during the past 15 years in our columnar university surgical residency were reviewed to assess their ability to predict success on the qualifying (written) and oral (certifying) examinations offered by the ABS. RESULTS: The ABSITE scores correlated with success on the qualifying examination (multiple R2 = 0.473). Subjective assessments of resident knowledge at any level did not correlate with ABSITE or qualifying scores, but above average scores did predict success on the certifying examination (chi 2, p < 0.005). Chief-year ABSITE total percentile score and score of first qualifying examination also predicted success on the certifying examination. The attrition rate in our nonpyramidal program was 23%, of which more than one half were voluntary. One of 11 residents leaving the program has subsequently attained ABS certification. CONCLUSIONS: This study shows that faculty's subjective evaluations predicted resident success on the ABS certifying examination and also endorses the ABS oral examination as an effective measure of the candidate's ability to communicate surgical knowledge.

Comparison of minimally invasive methods of parietal cell vagotomy in a porcine model.

BACKGROUND: Parietal cell vagotomy (PCV) is an accepted therapy for peptic ulcer disease. Traditional operative PCV results may be obtained laparoscopically or endoscopically. The purpose of this study was to quantitatively evaluate newer methods of PCV. METHODS: Variations in PCV, gastroscopic chemoneurolysis and laparoscopic photoneurolysis, were evaluated in 20 to 25 kg pigs. Traditional operative PCV was performed by laparotomy and served as the operative control. With a posterior truncal vagotomy, a PCV was performed laparoscopically by an anterior seromyotomy with either operative division of the neurovascular bundles with titanium clips or with a defocused CO2 laser. Transesophageal gastroscopic PCV was performed by transmucosal injections of the chemoneurolytic agents, 0.75% cobaltous chloride or 0.1% benzalkonium chloride. Adequacy of PCV at the time of operation was assessed by endoscopic Congo red testing. Two weeks later, repeat Congo red testing was performed by open gastrotomy. Quantitation of completeness of PCV and statistical comparison was determined by photographing the pentagastrin-stimulated gastric mucosa 5 minutes after Congo red application and subsequent comparison of innervated area versus total gastric mucosal area by a computer-driven digitized area-calculation program. RESULTS: All PCV techniques studied produced significant acid-secretory reduction, and both laparoscopic and gastroscopic PCV denervated the parietal cells in a manner comparable with operative PCV. Laser photoneurolysis could only be accomplished by producing full-thickness necrosis of the gastric wall. Submucosal injection of cobaltous chloride produced granulomatous nodules with foreign body crystals. Unlike operative and laparoscopic PCV, transmucosal gastroscopic benzalkonium PCV did not produce gross gastroparesis. CONCLUSIONS: All evaluated laparoscopic and endoscopic PCV techniques effectively denervated the parietal cells of the porcine stomach when evaluated at 2 weeks after treatment. Gastroscopic submucosal injection of benzalkonium chloride produced effective denervation with no evident histologic tissue changes and suggestive evidence of normal gastric emptying. Further evaluation with more extended periods of observation of these new techniques of performing PCV appear warranted.

Evaluation of intragastric pH in acutely ill patients.

The effect of various modalities on maintaining a high intragastric pH in acutely ill patients was evaluated. Twelve patients with one or more organ system failures had the effect of nasogastric suction, intragastric antacid instillation, and intravenous cimetidine administration on intragastric pH determined by an indwelling, intragastric pH probe. Each therapeutic modality was administered for 12 hours and the order of performance randomized. Nasogastric suction was associated with a constant intragastric pH of less than 2.0. Mean intragastric pH with cimetidine administration was significantly higher than with antacid administration and consistently greater than 5.0. If low intragastric pH represents susceptibility to acute mucosal lesions, cimetidine therapy was more effective than antacids in the doses and frequency of administration used in this study in maintaining a high intragastric pH, and it may be effective in preventing stress ulcer formation.

Segmental hepatic resection utilizing the ultrasonic dissector.

Hepatic resection continues to become a more widely accepted therapeutic modality, with increased use as improved imaging modalities more precisely define the nature and extent of various liver abnormalities. The surgical anatomy of the liver indicates that there are eight segments with single or multiple segmental resections able to be performed. The use of the ultrasonic dissector facilitates the performance of transparenchymatous segmental resection without obtaining vascular inflow or outflow control. This report describes the segmental anatomy of the liver and the use of the ultrasonic dissector. Thirteen patients have undergone segmental hepatic resection with the ultrasonic dissector. Five patients had cirrhosis. Mean +/- 1 SD operative time required for segmental resection was 128 +/- 57 minutes, and blood loss was 830 +/- 623 mL. Utilization of the ultrasonic dissector to perform segmental hepatic resection may increase our versatility in the management of various hepatic and biliary tract diseases.

Comparative evaluation of educational methods in surgical resident education.

OBJECTIVE: To determine the influence of study methods on American Board of Surgery (ABS) examination performance. DESIGN: Performance on ABS examinations by and faculty evaluations of 54 categorical surgical residents from 1976 to 1992 were correlated with the residents' use of commonly available educational methods (textbooks, Selected Readings in General Surgery, grand rounds, preceptor guidance, clinical surgery review courses, surgical science review courses, Surgical Education and Self-Assessment Program [SESAP], and continuing medical education lectures) in early, late, and after residency. SETTING: An average-sized midwestern US university surgical residency. RESULTS: Residents who consistently scored above the 33rd percentile on ABS examinations had used texts early, Selected Readings later, and SESAP after residency more frequently than those with ABS In-Training Examination scores in the lower one third. Selected Readings and clinical review courses were associated with significant increases in ABS percentile scores when used in late or after residency and, along with SESAP, were used when residents improved their low ABS In-Training Examination scores. CONCLUSIONS: Independent study methods are the most effective pathway to successful ABS examination performance. Formal surgical review courses may help improve the ABS examination scores of residents at a higher risk of failure.

Preoperative angiographic diagnosis of small bowel leiomyomas.

Two patients with gastrointestinal (GI) tract bleeding underwent preoperative selective visceral arteriography that demonstrated small-bowel tumors compatible with leiomyoma. A review of the material indicates that 42% of patients with small-bowel leiomyomas also have GI tract bleeding. Arteriography is valuable in obtaining a preoperative diagnosis.

Evaluation of prostacyclin production by human gallbladder.

The prostanoids have been demonstrated to be involved in gallbladder physiology and disease. In previous reports, prostaglandin E (PGE) compounds were found to be increased in inflamed human gallbladders. Prostaglandin synthetase inhibition decreased PGE formation by human gallbladders; however, the relief of symptoms of cholecystitis did not correlate well with the decrease in PGE formation. This suggested that other prostanoids may be involved in cholecystitis. The purpose of this study was to evaluate the production of the proinflammatory arachidonic acid metabolite prostacyclin by gallbladders from patients with calculous cholecystitis. The formation of PGE and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), the stable metabolite of prostacyclin, in normal human gallbladder mucosal cells and muscle tissue was compared with that produced by diseased mucosal cells and muscle tissue. Normal human gallbladders produced small amounts of 6-keto-PGF1 alpha, and no differences in formation rates were evident when muscle tissue was compared with mucosal cells. Diseased gallbladders produced significantly greater amounts of 6-keto-PGF1 alpha than did normal gallbladders, and diseased gallbladder muscle produced approximately four times greater amounts of 6-keto-PGF1 alpha than did diseased gallbladder mucosa. Prostacyclin formation is increased in diseased human gallbladders and may be an important mediator of the inflammatory changes of cholecystitis.

Pancreatitis after biliary tract surgery.

Pancreatitis associated with biliary tract operations continues to be an important clinical problem. The results of biliary tract operations performed on 1256 patients were carefully scrutinized for the presence of postoperative hyperamylasemia and pancreatitis persisting after 48 hours. Patients were evaluated in the context of the presence or absence of preoperative pancreatic dysfunction. Similarly, various operative risk factors were evaluated, including cholangiography, choledocholithiasis, common duct exploration, choledochoscopy, choledochoduodenostomy, and sphincteroplasty. Operative cholangiography did not induce postoperative pancreatitis. The incidence of postoperative pancreatitis following cholecystectomy was 0.6%, which was significantly greater than the incidence following common duct exploration (8.4%). Pancreatitis following biliary tract surgery seemed to be not directly related to the performance of choledochoscopy, sphincteroplasty, or choledochoduodenostomy, as it developed with similar frequency in patients undergoing common duct exploration alone. The timing of operative therapy in patients with biliary tract pancreatitis did not significantly alter the frequency with which pancreatitis persisted in the postoperative period. In 970 patients undergoing cholecystectomy, one patient who had preoperative pancreatitis died of postoperative pancreatitis. Of 286 patients undergoing common duct exploration, seven patients died with pancreatitis. In three of these patients there was no active preoperative pancreatitis, and in one of these patients pancreatitis was the cause of death. Four patients with preoperative pancreatitis eventually died of pancreatitis in the postoperative period. Pancreatitis is an important complication of biliary tract disease and operations, and all efforts should be extended to suppress its occurrence and development.

Management and outcome of patients with combined bile duct and hepatic artery injuries.

BACKGROUND: Major bile duct injury is an important therapeutic problem that can be associated with simultaneous injury to the hepatic artery. Limited information exists regarding the course of patients who have combined bile duct and arterial injuries. OBJECTIVE: To compare the management and outcome of isolated bile duct injuries with bile duct and hepatic artery injuries. PATIENTS AND METHODS: Since 1991, 13 patients have undergone reconstruction of right and left hepatic confluence or proximal bile duct injuries. At the time of bile duct injury, 4 of these patients had simultaneous occlusion or extirpation of the right hepatic or common hepatic artery. All patients underwent reconstruction of the biliary tract with hepaticojejunostomies. The immediate and long-term outcomes of the patients with and without hepatic artery injury were compared. RESULTS: In the immediate postoperative period, 3 of 4 patients with combined injuries had hepatic necrosis and/or abscesses with 2 patients requiring transcutaneous or operative drainage. This problem was not diagnosed in patients with isolated bile duct injuries. None of the biliary anastomoses have failed in the patients with isolated bile duct injuries while 50% of the anastomoses in patients with combined injuries have caused recurrent problems following reconstruction. CONCLUSION: Patients with major bile duct injuries should be evaluated for concomitant hepatic arterial injury as management and outcome may be influenced by the absence of arterial blood flow to the injured bile ducts and to the liver.

Preoperative pulmonary function evaluation for laparoscopic cholecystectomy.

OBJECTIVE: Hypercarbia with respiratory acidosis is a recognized complication of laparoscopic cholecystectomy. This study was performed to identify preoperatively those patients who may develop hypercarbia and acidosis during the procedure. DESIGN: Retrospective analysis of preoperative variables. PATIENTS: Thirty-one consecutive patients underwent laparoscopic cholecystectomy at one institution who were receiving both preoperative pulmonary function tests and arterial blood gas analysis. RESULTS: More than 80 demographic, laboratory, and perioperative variables were entered into a univariate analysis to identify predictors of intraoperative acidosis (pH, < 7.35). Patient age, duration of the procedure, and preoperative blood gas values were not predictors of intraoperative acidosis. Several univariant predictors for patients experiencing carbon dioxide pneumoperitoneum-induced hypercarbia were identified; these included an elevated American Society of Anesthesiologists classification and significant decreases in forced expiratory flow at 25% of maximum, maximal forced expiratory flow, maximal voluntary ventilation, vital capacity, inspiratory capacity, and diffusing capacity of the lung for carbon monoxide. CONCLUSIONS: This study suggests that neither age nor preoperative arterial blood gas values are predictive of intraoperative hypercarbia and acidosis during periods of carbon dioxide pneumoperitoneum. However, preoperative pulmonary function measures of decreased flow, limited capacity, and compromised diffusion do correspond to the development of intraoperative acidosis. Preoperative evaluation with pulmonary function tests demonstrating forced expiratory volumes less than 70% of predicted values and diffusion defects less than 80% of predicted values can identify those patients who are at risk of developing hypercarbia and acidosis.

Splenopneumopexy to treat portal hypertension produced by venous occlusive disease.

Splenopneumopexy is intended to induce collateral circulation between the portal system and the pulmonary veins. It involves performing a parenchymatous anastomosis between the amputated superior pole of the spleen and the exposed pulmonary venous structures in the left lower lobe. This operative procedure was used to treat four patients with extended portal-splenic-mesenteric venous occlusion who did not respond satisfactorily to sclerotherapy. The patients underwent transfemoral embolization of their splenic arteries before splenopneumopexy. Following the operations, all patients have remained well, experiencing cessation of gastrointestinal bleeding for up to 48 months. Splenopneumopexy may be a therapeutic alternative in selected patients with portal hypertension, including those patients with widespread occlusion of the portal vein and its radicles.

Cystic duct cholangiography during laparoscopic cholecystectomy.

At present, there is no consensus regarding the routine use of intraoperative cholangiography during cholecystectomy. We describe a reliable technique for performing cystic duct cholangiography during laparoscopic cholecystectomy. Using this technique, we were able to cannulate the cystic duct in 97% of patients, completely visualize the biliary tree and duodenum in 93% of patients, and identify unsuspected choledocholithiasis in 3% of patients. Treatment options for the management of choledocholithiasis demonstrated by cholangiograms during laparoscopic cholecystectomy include conversion to an open cholecystectomy and common duct exploration, or endoscopic sphincterotomy and common duct stone extraction following laparoscopic cholecystectomy.