The effects of liver denervation on the regulation of hepatic biliary secretion.

Effects of liver denervation on bile formation were studied in eight dogs prepared with chronic biliary fistulas. The animals were studied in the basal state, after feeding, and during infusion of glucagon 50 ng/kg/min, secretin 2 U/kg/hr, or somatostatin 200 ng/kg/min. After this first set of experiments the animals underwent a total hepatic denervation that consisted of section of the hepatic ligaments and a careful dissection of the portal vein, hepatic artery, and common duct with stripping of all the surrounding connective tissue and topical application of phenol. The above experiments were then repeated. Denervation did not modify bile flow, or bile salts, cholesterol, or phospholipid concentration or output. Biliary response to glucagon and secretin was similar before and after denervation. Somatostatin had an anticholerectic effect in both intact and denervated animals, but significantly reduced bile salt output only in the intact dogs. Feeding had a choleretic effect pre- and postdenervation, and the infusion of somatostatin following feeding decreased bile flow to the same degree before and after denervation. In the intact animals the output of all three biliary lipids was reduced by somatostatin after feeding but they were unaffected by somatostatin after denervation. Moreover, cholesterol and phospholipid outputs were stable after feeding in intact animals, but significantly decreased after denervation. 14C-erythritol clearance studies indicated no change in the canalicular component of bile flow with denervation, except again during somatostatin suppression of feeding. These data indicate that basal bile flow is normal after denervation but that innervation may play an important role in the modulation of responses to somatostatin and more complex stimuli such as feeding.

The role of resection in the management of melanoma metastatic to the adrenal gland.

Melanoma metastatic to the adrenal gland diagnosed before death was exceedingly rare before the development of computed tomographic (CT) scanning. The records of 28 patients with melanoma metastatic to the adrenal gland seen since 1975 were reviewed. Eighteen patients were men and 10 were women. Twenty-three patients had unilateral disease. Four patients were diagnosed only at autopsy, leaving 24 for analysis of treatment and survival. Twenty-one patients had received specific active immunotherapy, four had received chemotherapy (dacarbazine, lomustin, bleomycin, and vincristine), and three had received both before the diagnosis of their adrenal disease. Adrenal metastases were diagnosed by CT scanning in 14 patients with symptoms, 10 (91%) of whom had pain. Ten patients were diagnosed by CT before entry into a chemotherapy protocol. Of eight patients who underwent resection of all known disease, five underwent unilateral adrenalectomy, two underwent unilateral adrenalectomy and bowel resection, and one underwent bilateral adrenalectomy. Two patients underwent partial resection of large unilateral tumors. Fourteen patients with adrenal metastases and disease elsewhere were initiated or continued with chemotherapy or were treated symptomatically. Mean survival in the group that underwent resection for cure was 59 months (3 to 112 months), whereas survival in the group with unresectable tumors was 15 months (1.5 to 132 months). Four of eight patients who underwent resection for cure lived more than 5 years after detection of adrenal metastasis, whereas in only one of 14 patients with unresectable tumors was the same true. Patients with metastatic melanoma localized to one or both adrenal glands may benefit from early detection and surgical intervention.

Subtotal colectomy for familial polyposis. A clinical series and review of the literature.

Familial polyposis is an inherited syndrome in which untreated persons have virtually a 100% incidence of developing colon cancer. Much controversy exists over whether subtotal colectomy with ileoproctostomy is the appropriate procedure in these patients owing to the risk of subsequent cancer in the retained portion of the rectum. At Duke University Medical Center, Durham, NC, a group of 25 patients chose to undergo the subtotal colectomy and ileoproctostomy instead of the definitive total proctocolectomy. Of the 25 patients in this series, invasive adenocarcinoma has developed in the rectal segment in only 1 patient. This patient, the oldest in our series, had carcinoma in situ in her initial operative specimen and has done well following an abdominal perineal resection and 13 years of follow-up. Six other patients have subsequently undergone definitive resections of the rectum because of intractable benign polyps. These results compare favorably with those reported in the literature. We conclude that subtotal colectomy with ileoproctostomy is still a useful and successful mode of treatment for select patients with familial polyposis if they are followed up frequently and aggressively and if the surgeon maintains a low threshold for recommending completion proctectomy.

Indications for and the technique of local resection of tumors of the papilla of Vater.

Local resection of tumors of the papilla of Vater was performed in six cases (three benign adenomas and three adenocarcinomas). Pathology was suggested in all cases by endoscopic biopsy and confirmed by operative excision. A method of excision of the tumor and reconstruction of the pancreaticobiliary apparatus was used that eliminated all gross and microscopic disease. Only one of the patients with benign disease (familial polyposis) suffered from local recurrence. All three patients with malignant tumors developed local recurrences within 2 years of resection. Local resection seems to be a viable alternative to Whipple's resection in patients with benign tumors. In malignant cases, local resection should be considered only a palliative procedure and confined to elderly patients with severe concomitant disease and patients in whom a more radical procedure would incur an undue surgical risk.

Surgical management of pancreatic lymphoma.

The clinical and pathologic records of 12 patients with pancreatic lymphoma were reviewed retrospectively to determine distinguishing clinical features. Radiologically, all patients had large abdominal masses in the region of the pancreas. Preoperative percutaneous cytologic biopsy specimens failed to make the diagnosis, and two specimens were interpreted incorrectly as poorly differentiated adenocarcinoma. The diagnosis was difficult to make in two cases, even at laparotomy. Four patients underwent a biliary bypass, and two underwent a concomitant gastric or duodenal bypass. Two patients died postoperatively. Four patients responded well to chemotherapy and/or radiation therapy, and two did not have any recurrences at 3 and 7 years postoperatively. Although rare, lymphoma should be considered in patients with undiagnosed pancreatic masses. The diagnosis may only be made with appropriate preoperative or intraoperative suspicion, and treatment may be rewarding, particularly in comparison with pancreatic adenocarcinoma.

Management of pancreatic pseudocysts.

BACKGROUND: Operative internal drainage has been standard treatment for chronic unresolved pancreatic pseudocysts (PPs). Recently, percutaneous external drainage (PED) has become the primary mode of treatment at many medical centers. STUDY DESIGN: A retrospective chart review was performed of 96 patients with PPs who were managed between 1987 and 1996. Longterm followup information was obtained by telephone and mail questionnaire. RESULTS: Twenty-seven patients underwent computed tomographic (CT)-guided PED. PP resolution occurred in 17 patients. Clinical deterioration or secondary infection mandated urgent pancreatic debridement in 7 (26%) patients and cystgastrostomy in 2 (7%) patients. There was one hospital death in this group. Thirty-two patients underwent cystgastrostomy or cystjejunostomy (n = 21), distal pancreatectomy (n = 8), pancreatic debridement and external drainage (n = 2), or cystectomy (n = 1). Two (6%) patients required postoperative pancreatic debridement for failure of resolution and peritonitis and two patients underwent PED of abscess. There was one hospital death in the expectantly managed group of 37 patients. Median followup of 3 years (range, 0.5-9.3 years) in 66 patients revealed that 6, 3, and 4 patients of PED, surgery, and expectantly managed groups, respectively, had radiologic evidence of recurrent PPs. CONCLUSIONS: Operative management for PPs appears to be superior to CT-guided PED. Although the later was often successful, it required major salvage procedures in one third of the patients. An expectant management protocol may be suitable for selected patients.

Laparoscopic fundoplication for dysphagia and peptic esophageal stricture.

Peptic esophageal stricture with dysphagia is a late manifestation of severe gastroesophageal reflux disease (GERD). Although laparoscopic fundoplication is an effective antireflux operation, its efficacy for persons with peptic esophageal stricture and dysphagia has not been well defined. The aim of this study was to evaluate outcomes after fundoplication in this subgroup of GERD patients. Forty GERD patients with moderate, severe, or incapacitating dysphagia and peptic esophageal stricture were compared to a control group of 121 GERD patients without significant dysphagia or stricture. Reflux symptom severity was scored by each patient preoperatively and at most recent follow-up postoperatively (mean 1.5 years) using a scale ranging from 0 to 4 (0 = symptoms absent; 4 = symptoms incapacitating). Symptom scores were compared by the Wilcoxon rank-sum test. Postoperative redilation and fundoplication failure rates were also determined. At a mean follow-up of 1.5 years after fundoplication, the median dysphagia score had improved from 3 to 0 (P <0.001) in stricture patients and remained low (score 0) in the control group. The median heartburn score also improved from 3 to 0 (P <0.001) in stricture patients, with an identical response in the control group (P <0.001). Among dysphagia/stricture patients, 35 (87.5%) reported overall satisfaction and have not required secondary medical treatment or esophageal dilation. Four patients (10%) have required endoscopic redilation for residual dysphagia and one (2.5%) had reoperation for fundoplication herniation shortly after operation. Laparoscopic fundoplication is an effective therapy for patients with dysphagia and peptic esophageal stricture.

Complications of laparoscopic paraesophageal hernia repair.

The complications of laparoscopic paraesophageal hernia repair at two institutions were reviewed to determine the rate and type of complications. A total of 76 patients underwent laparoscopic paraesophageal hernia repair between December 1992 and April 1996. Seventy-one of them had fundoplication (6 required a Collis-Nissen procedure). Five patients underwent hernia reduction and gastropexy only. There was one conversion to laparotomy. Traumatic visceral injury occurred in eight patients (11%) (gastric lacerations in 3, esophageal lacerations in 2, and bougie dilator perforations in 3). All lacerations were repaired intraoperatively except for one that was not recognized until postoperative day 2. Vagus nerve injuries occurred in at least three patients. Three delayed perforations occurred in the postoperative period (4%) (2 gastric and 1 esophageal). Two patients had pulmonary complications, two had gastroparesis, and one had fever of unknown origin. Seven patients required reoperation for gastroparesis (n = 2), dysphagia after mesh hiatal closure of the hiatus (n = 1), or recurrent herniation (n = 4). There were two deaths (3%): one from septic complications and one from myocardial infarction. Paraesophageal hernia repair took significantly longer (3.7 hours) than standard fundoplication (2.5 hours) in a concurrent series (P <0.05). Laparoscopic paraesophageal hernia repair is feasible but challenging. The overall complication rate, although significant, is lower than that for nonsurgically managed paraesophageal hernia.

A model for biliary and vascular access in the unanesthetized, unrestrained rat.

Conventional methods for vascular access and bile collection in the rat, such as the isolated perfused liver, study under anesthesia, and animal restraint, do not allow study of a physiologically intact rat. A simple technique for vascular access and monitoring of biliary secretions in the intact, unrestrained, unanesthetized rat for extended periods of time is described. Sample experiments demonstrated a 20% complication rate and an 85% 24-hour survival. This model may prove useful in studies requiring chronic vascular and visceral catheterization in the awake rat.

Role of surgical intervention in the management of intestinal metastases from malignant melanoma.

Malignant melanoma is the most common metastatic lesion of the intestine. Surgical consultation is often sought when bowel metastases become symptomatic. To determine the role of surgical intervention in such cases, a database of 6,000 melanoma patients was examined, and a subset of 102 patients with small intestinal or colonic metastases were identified premortem. Common presenting features included abdominal pain with or without acute symptoms (29% of patients), obstruction or intussusception (27%), and bleeding (26%). The presence of metastatic lesions was confirmed by surgical exploration in 80% of patients, endoscopic procedures in 11%, and percutaneous biopsy in 5%. Cure was achieved in 36 patients by resection, which resulted in the removal of all demonstrable disease. The subsequent mean length of survival in this group was 31 +/- 5.2 months. Forty-two patients underwent palliative enteric bypass or debulking procedures, and 24 patients received either chemotherapy alone or symptomatic treatment. The average length of survival in these latter groups was 9.6 +/- 15.9 and 9.6 +/- 3.6 months, respectively, both of which were significantly less than the duration of survival in the complete resection group (p less than 0.05). Small or large bowel resection for bleeding or obstruction and enteric bypass for obstruction provided symptomatic relief in 92% of patients thus treated. There was no operative mortality in the series. An aggressive search for resectable disease in patients with symptoms secondary to intestinal metastases from malignant melanoma should be performed. Surgical intervention may then allow the palliation of pain, obstruction, and bleeding. Survival can be significantly prolonged if it is possible to remove all demonstrable disease.

Effect of cyclosporine on bile secretion in rats.

Short-term effects of cyclosporine were studied in the isolated perfused rat liver model. Bile flow was inhibited by cyclosporine in 2 mg/kg and 20 mg/kg doses but not by a 0.2 mg/kg dose. Cholestasis was accompanied by a decrease in bile acid secretion, indicating an inhibitory effect on the bile acid-dependent fraction of bile flow. Perfusate bilirubin levels increased threefold in rat livers given 20 mg/kg of cyclosporine, but did not change in control animals. Alkaline phosphatase and transaminase levels did not differ from those of control animals. The isolated perfused rat liver was able to excrete cyclosporine, as demonstrated by a continual decrease in perfusate cyclosporine levels. No light microscopic evidence of cholestasis or hepatocellular damage was demonstrated on histologic staining. Our model appears to be a good one for the study of altered hepatic physiologic characteristics caused by administration of cyclosporine.

Effect of L-glutamine supplementation on impaired glucose regulation during intravenous lipid administration.

In contrast to L-glutamine, lipid emulsions are routinely administered to patients receiving nutritional support. The provision of fat during intravenous feeding is essential, but the potentially toxic byproducts of fatty acid oxidation may have adverse metabolic consequences. In the present study, we have examined the effect of L-glutamine, an inhibitor of fatty acid oxidation, on the development of defective blood glucose regulation caused by a 48-hour infusion of 10% intralipid in rats. Male Sprague-Dawley rats (200-290 g) were anesthetized with sodium pentobarbital, the right femoral vein cannulated, and baseline blood samples were taken. Each rat was placed in a metabolic cage with access to water, in the presence or absence of rodent chow. Two hours after waking, the rats were infused with 10% intralipid with either saline (control), 2% L-glutamine, or 2% L-alanine. After 48 hours, all animals were sacrificed and blood samples were again obtained. The mean +/- SEM plasma glucose levels before and after lipid infusion at the rate of 1 mL/hr in control rats fed ad libitum, were 125 +/- 13 and 170 +/- 5 mg/dL (p < 0.01, n = 7). Similarly, plasma free fatty acids (FFA) in these animals rose from 0.74 +/- 0.11 to 1.34 +/- 0.32 mmol/L (p < 0.05). Plasma insulin levels also increased from 337 +/- 44 to 1278 +/- 88 pg/mL (p < 0.01). Reduction of intralipid dose infusion did not prevent insulin resistance characterized by hyperglycemia and hyperinsulinemia. However, addition of L-glutamine to the high-dose lipid infusion with chow feeding prevented changes in plasma glucose, insulin levels, and FFA but not triglyceride levels. Also, glutamine but not alanine supplementation in intralipid infused rats without chow feeding prevented changes in plasma glucose, insulin, and malondialdehyde levels. In conclusion, these data show that glutamine supplementation during intravenous lipid administration in rats prevents the development of impaired glucose regulation associated with hyperlipidemia.

Outcomes of laparoscopic fundoplication for gastroesophageal reflux disease and paraesophageal hernia.

BACKGROUND: Laparoscopic fundoplication has become the standard for operative treatment of gastroesophageal reflux disease (GERD). METHODS: We reviewed our experience with 1,000 consecutive patients receiving laparoscopic fundoplication for GERD (n = 882) or paraesophageal hernia (n = 118) between October 1991 and July 1999. Patients with achalasia and failed fundoplication were excluded from analysis. All the patients were evaluated preoperatively by upper endoscopy, esophageal manometry, and barium swallow. After 1994, 24-h pH monitoring was performed selectively in patients with extraesophageal symptoms and/or those without erosive esophagitis. There were 490 men 510 women in this review. Their mean age was 49 years. Procedures performed were 360 degrees floppy fundoplication (n = 879), 360 degrees fundoplication without fundus mobilization (Rossetti) (n = 22), 270 degrees posterior fundoplication (n = 96), and anterior fundoplication (n = 2). Esophageal lengthening procedure (Collis gastroplasty) was performed in combination with fundoplication in 15 patients. In seven patients the treatment was converted to open fundoplication. OUTCOMES: The average length of hospitalization was 2.2 days, and 136 patients stayed longer than 2 days. Major complications occurred in 21 patients: esophageal perforation (n= 10), acute paraesophageal herniation (n = 4), splenic bleeding (n = 2), cardiac arrest (n = 1), pneumonia (n = 3), and testicular abscess (n = 1). Additional operations were required to manage the complications in 14 patients (70%): Four of these procedures were performed emergently, and 10 patients underwent reoperation between 6 h and 10 days. There were three deaths, all of which involved elderly patients with paraesophageal hernia. There were 35 late failures requiring reoperation for recurrence of GERD or development of new symptoms: The treatment of 32 patients was revised laparoscopically, and 4 patients required laparotomy. Beyond 1 year (median follow-up period, 27 months), 94% of the reviewed patients were satisfied with their surgical outcome.

Are the favorable outcomes of splenectomy predictable inpatients with idiopathic thrombocytopenic purpura (ITP)?

BACKGROUND: Historically, splenectomy has been an accepted procedure in the management of immune thrombocytopenic purpura (ITP). However, it is also true that the response to splenectomy in patients with ITP seems to be unpredictable. Therefore, the purpose of this study was to identify clinical variables that might predict a favorable response to splenectomy in patients with ITP. METHODS: Data were collected retrospectively for 40 adult patients with ITP who underwent laparoscopic (LS) and open (OS) splenectomy at Emory University Hospital between 1992 and 1999. Demographics and outcomes were recorded. Age, sex, disease duration, comorbidities (ASA > 2), previous response to steroids and/or other medications, and preoperative platelet count were analyzed by univariate (t-test, Fisher's exact test) and multivariate statistical methods. RESULTS: Of the 20 patients in each group, improved platelet counts were noted in 18 patients (90%) in the LS group and 20 patients (100%) in the OS group. Follow-up (16 +/- 3 months) was obtained in 19 LS patients (95%) and 16 OS patients (80%), with 84% and 87.5% sustained response rates, respectively. After univariate analysis, two variables (age and disease duration) were found to be significantly related to the outcome of splenectomy (p

Heartburn is more likely to recur after Toupet fundoplication than Nissen fundoplication.

Toupet (270 degrees) fundoplication is commonly recommended for patients with gastroesophageal reflux (GER) and esophageal dysmotility. However, Toupet fundoplication may be less effective at protecting against reflux than Nissen (360 degrees) fundoplication. We therefore compared the effectiveness and durability of both types of fundoplication as a function of preoperative esophageal motility. From January 1992 through January 1998, 669 patients with GER underwent laparoscopic fundoplication (78 Toupet, 591 Nissen). Patients scored heartburn, regurgitation, and dysphagia preoperatively, and at 6 weeks and 1 year postoperatively, using a 0 ("none") to 3 ("severe") scale. We compared symptom scores (Wilcoxon rank sum test) and redo fundoplication rates (Fisher exact test) in Toupet and Nissen patients. We also performed subgroup analyses on 81 patients with impaired esophageal motility (mean peristaltic amplitude, <30 mm Hg or peristalsis <70% of wet swallows) and 588 patients with normal esophageal motility. Toupet and Nissen patients reported similar preoperative heartburn, regurgitation, and dysphagia. At 6 weeks after operation, heartburn and regurgitation were similarly improved in both groups, but dysphagia was more prevalent among Nissen patients. After 1 year, heartburn and regurgitation were re-emerging in Toupet patients, and dysphagia was again similar between groups. Patients with impaired motility who have Nissen fundoplication are no more likely to suffer persistent dysphagia than their counterparts who have Toupet fundoplication. In addition, patients with normal motility are more likely to develop symptom recurrence after Toupet fundoplication than Nissen fundoplication, with no distinction in dysphagia rates. We conclude that since Toupet patients suffer more heartburn recurrence than Nissen patients, with similar dysphagia, selective use of Toupet fundoplication requires further study.

Current management of perianal intraepithelial neoplasia.

The surgical management of intraepithelial perianal neoplasms is straightforward. The goal is complete locoregional control of the disease. Success is determined at the time of operation by frozen section analysis and reexcision if necessary. Procedures that will interfere with sphincter function should be delayed in favor of alternative treatment with radiotherapy or chemoradiotherapy. Close long-term follow-up is necessary to ensure the best possible outcome should a lesion recur.

The feasibility of the detection and quantitation of beta-adrenergic blockers by solid-phase extraction and subsequent derivatization with methaneboronic acid.

Urine specimens containing 11 common beta blockers were processed using solid-phase extraction technology to extract the drugs from the urine matrix, then converted to their cyclic methaneboronates by treatment with methaneboronic acid in ethyl acetate. The compounds tested included acebutolol, atenolol, alprenolol, bisoprolol, betaxolol, carteolol, penbutolol, propranolol, pindolol, timolol, nadolol, sotalol, labetolol, metoprolol, and oxprenolol. The extraction efficiencies were greater than 90% for all drugs tested. The cyclic methaneboronates formed by this procedure generally possessed good chromatographic properties. The mass spectral behavior of the methaneboronates was excellent, with all compounds containing several high mass fragments and every tested compound possessing a unique mass spectrum.

Clinical features and mechanisms of major laparoscopic biliary injury.

Laparoscopic cholecystectomy has quickly become the gold standard for the treatment of symptomatic cholelithiasis. With the introduction of this new technique has come a learning curve, with a higher than expected initial rate of complications. The most significant complication, as with open cholecystectomy, is injury to the bile duct. This article reviews the clinical features and mechanisms of major biliary injury in laparoscopic cholecystectomy.