NFkappaB prevents apoptosis and liver dysfunction during liver regeneration.

Although NFkappaB binding activity is induced during liver regeneration after partial hepatectomy, the physiological consequence of this induction is unknown. We have assessed the role of NFkappaB during liver regeneration by delivering to the liver a superrepressor of NFkappaB activity using an adenoviral vector expressing a mutated form of IkappaBalpha. This adenovirus (Ad5IkappaB) was almost exclusively expressed in the liver and inhibited NFkappaB DNA binding activity and transcriptional activity in cultured cells as well as in the liver in vivo. After partial hepatectomy, infection with Ad5IkappaB, but not a control adenovirus (Ad5LacZ), resulted in the induction of massive apoptosis and hepatocytes as demonstrated by histological staining and TUNEL analysis. In addition, infection with Ad5IkappaB but not Ad5LacZ decreased the mitotic index after partial hepatectomy. These two phenomena, increased apoptosis and failure to progress through the cell cycle, were associated with liver dysfunction in animals infected with the Ad5IkappaB but not Ad5LacZ, as demonstrated by elevated serum bilirubin and ammonia levels. Thus, the induction of NFkappaB during liver regeneration after partial hepatectomy appears to be a required event to prevent apoptosis and to allow for normal cell cycle progression.

Sirtuin 1 suppresses mitochondrial dysfunction of ischemic mouse livers in a mitofusin 2-dependent manner.

Ischemia/reperfusion (I/R) injury is a major cause of morbidity and mortality after liver surgery. The role of Sirtuin 1 (SIRT1) in hepatic I/R injury remains elusive. Using human and mouse livers, we investigated the effects of I/R on hepatocellular SIRT1. SIRT1 expression was significantly decreased after I/R. Genetic overexpression or pharmacological activation of SIRT1 markedly suppressed defective autophagy, onset of the mitochondrial permeability transition, and hepatocyte death after I/R, whereas SIRT1-null hepatocytes exhibited increased sensitivity to I/R injury. Biochemical approaches revealed that SIRT1 interacts with mitofusin-2 (MFN2). Furthermore, MFN2, but not MFN1, was deacetylated by SIRT1. Moreover, SIRT1 overexpression substantially increased autophagy in wild-type cells, but not in MFN2-deficient cells. Thus, our results demonstrate that the loss of SIRT1 causes a sequential chain of defective autophagy, mitochondrial dysfunction, and hepatocyte death after I/R.

Surgical management of hepatic hydatid disease.

The use of conservative or radical surgical procedures in the management of hepatic echinococcosis is controversial. A review of data on 23 patients with hydatid cysts of the liver that were diagnosed between 1935 and 1990 at our institution was undertaken to determine the safety and efficacy of various surgical procedures. In eight patients (group 1), the cysts were treated conservatively by instillation of a scolicidal agent followed by evacuation of the cyst, drainage, or omentoplasty of the residual cyst cavity. Thirteen patients (group 2) underwent radical excision of the cyst by either pericystectomy or hepatic resection. In addition, two patients were treated by combined techniques. Scolicidal agents were used in 18 patients (78%) and apparently resulted in caustic biliary injury and death in 2 patients. Group 1 and group 2 patients had similar complication rates (62% and 54%, respectively) and mean hospital stay (24 and 23 days, respectively). Recurrent cysts, however, were detected in three of six patients who underwent a conservative surgical procedure and participated in follow-up, whereas no patients treated by a radical procedure had a recurrence. Because pericystectomy and hepatic resection resulted in a low rate of recurrence and eliminated the need for use of potentially toxic scolicidal agents, these procedures may be the preferred method for the surgical management of hepatic hydatid disease.

Pancreatic pseudocysts complicated by splenic parenchymal involvement: results of operative and percutaneous management.

UNLABELLED: Pancreatic pseudocysts are a common finding in acute and chronic pancreatitis, but most are small and uncomplicated, and do not require treatment. Pseudocysts with splenic parenchymal involvement are uncommon but have the potential for massive hemorrhage. Data on the clinical presentation and optimal treatment of this unusual complication of pseudocysts are lacking. The purpose of this review was to identify the clinical features of pancreatic pseudocysts complicated by splenic parenchymal involvement and to determine the outcome with nonoperative and operative therapy. METHODS: A retrospective review of the medical records of all patients with pancreatic pseudocysts from December 1984 to January 1999 revealed 238 patients, of whom 14 (6%) had splenic parenchymal involvement. These medical records were reviewed in detail and all pertinent radiographs were reviewed by the authors to confirm splenic parenchymal involvement by a pancreatic pseudocyst. RESULTS: Initial treatment included observation (n = 2), percutaneous drainage (n = 8), and surgery (n = 4). Of the eight patients treated by percutaneous drainage, one died, three required repeated percutaneous drainage, and three required surgical intervention. None of the patients treated primarily by surgery required additional therapy for the pseudocyst. Overall, 11 patients had complications of the primary therapy, and 25% of patients treated by surgery had significant hemorrhage. Complications included infection (n = 5), pseudocyst persistence (n = 4), bleeding (n = 2), multisystem organ failure (n = 2), gastric outlet obstruction (n = 1), and splenic rupture (n = 2). CONCLUSIONS: Pancreatic pseudocysts complicated by splenic parenchymal involvement may have life-threatening clinical presentations and respond poorly to percutaneous drainage. Distal pancreatectomy and splenectomy are effective, but the complication rate is high.

Pancreatic lymphoma: is it a surgical disease?

Primary pancreatic lymphoma is a rare neoplasm that reportedly regresses promptly with aggressive chemotherapy. Recently, the role of surgical management has been relegated to biopsy alone. The aim of this study was to review our experience with primary pancreatic lymphoma and to determine the outcome of patients managed by radiation therapy and/or chemotherapy. From 1952 to 1991, 107 patients with non-Hodgkin's lymphoma involving the pancreas were identified. Twelve patients (11%) had primary pancreatic lymphoma. The presenting symptoms and signs were nonspecific: abdominal pain (83%), weight loss (50%), and a palpable mass (58%). Six of the 12 patients (50%) undergoing celiotomy had a preoperative diagnosis of pancreatic carcinoma. These lymphomas were large (x = 8 +/- 2 cm) and deemed unresectable because of size, alleged mesenteric vessel encroachment, regional lymph node metastasis, or because of an intraoperative diagnosis of lymphoma. Biopsy alone was performed in 50% of patients and biliary bypass and/or gastroenterostomy was performed in 25% of patients. A single resection (pancreatoduodenectomy) was performed 1 year after a full course of chemotherapy had failed. Ten patients, all of whom died of progressive lymphoma, received primary postoperative radiation therapy and/or chemotherapy, and no patient was disease-free at follow-up. Mean survival was 13 months for patients who received chemotherapy alone (n = 2), 22 months for those treated with radiation therapy only (n = 5), and 26 months for those receiving combined radiation therapy and chemotherapy (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Prospective randomized trial of early initiation and hospital discharge on a liquid diet following elective intestinal surgery.

Length of hospital stay after elective intestinal surgery may be related to patient tolerance of a diet. We hypothesized that early initiation and discharge home on a clear liquid diet would decrease the length of hospital stay without increasing morbidity. The aim of this study was to determine if early initiation and discharge on a clear liquid diet decreases the length of hospital stay and is safe. Forty-four patients were randomly assigned to either a standard diet or a clear liquid diet. A standard diet (n = 17) was begun after the passage of flatus or stool, and consisted of clear liquids to a volume of approximately 750 ml, then three solid meals, and discharge thereafter. Patients randomized to a clear liquid diet (n = 27) received 30 ml/hr of clear liquids on postoperative day 2, unlimited clear liquids on postoperative day 3, and were dismissed on a clear liquid diet on postoperative day 4. All patients were followed by a daily telephone call and clinic visit. The primary outcome variable was length of hospital stay. The incidence of postoperative intestinal-related sequelae, complications, and readmission rates did not differ between groups. Postdischarge intestinal symptoms were common in both groups but tended to resolve faster in the patients on a standard diet. The length of hospital stay was decreased in the patients on a clear liquid diet compared to those on a standard diet (6.1 +/- 1.1 days vs. 4.4 +/- 0.2 days; P = 0.09), but total hospital costs did not differ. Early initiation and hospital discharge on a clear liquid diet after elective intestinal surgery decreases the length of hospital stay and is safe.

Hepatic steatosis as a potential risk factor for major hepatic resection.

Hepatic steatosis is a recognized risk factor for primary nonfunction of hepatic allografts, but the effect of steatosis on postoperative recovery after major liver resection is unknown. Our aim was to determine if hepatic steatosis is associated with increased perioperative morbidity and mortality in patients undergoing major resection. A retrospective review of medical records of 135 patients who had undergone major hepatic resection from 1990 to 1993 was performed. Histopathology of the hepatic parenchyma at the resection margin was reviewed for the presence of macro- or microvesicular steatosis. The extent of steatosis was graded as none (group 1), mild with less than 30% hepatocytes involved (group 2), or moderate-to-severe with 30% or more hepatocytes involved (group 3). Outcome of patients was correlated with extent of steatosis. Patients with moderate-to-severe steatosis were obese (body mass index = 25.8 +/- 0.5 vs. 26.5 +/- 1.0 vs. 33.4 +/- 2.9; P< 0.05 groups 1, 2, and 3, respectively) and had an increased serum bilirubin concentration preoperatively. Hepatectomy required a longer operative time for group 3 (290 +/- 9 minutes vs. 287 +/- 13 minutes vs. 355 +/- 24 minutes; P

Complete fundoplication is not associated with increased dysphagia in patients with abnormal esophageal motility.

Abnormal esophageal motility is a relative contraindication to complete (360-degree) fundoplication because of a purported risk of postoperative dysphagia. Partial fundoplication, however, may be associated with increased postoperative esophageal acid exposure. Our aim was to determine if complete fundoplication is associated with increased postoperative dysphagia in patients with abnormal esophageal motor function. Medical records of 140 patients (79 females; mean age 48 +/- 1.1 years) who underwent fundoplication for gastroesophageal reflux disease (GERD) were reviewed retrospectively to document demographic data, symptoms, and diagnostic test results. Of the 126 patients who underwent complete fundoplication, 25 met manometric criteria for abnormal esophageal motility (#30 mm Hg mean distal esophageal body pressure or #80% peristalsis), 68 had normal esophageal function, and 33 had incomplete manometric data and were therefore excluded from analysis. Of the 11 patients who underwent partial fundoplication, eight met criteria for abnormal esophageal motility, two had normal esophageal function, and one had incomplete data and was therefore excluded. After a median follow-up of 2 years (range 0.5 to 5 years), patients were asked to report heartburn, difficulty swallowing, and overall satisfaction using a standardized scoring scale. Complete responses were obtained in 72%. Sixty-five patients who underwent complete fundoplication and had manometric data available responded (46 normal manometry; 19 abnormal manometry). Outcomes were compared using the Mann-Whitney U test. After complete fundoplication, similar postoperative heartburn, swallowing, and overall satisfaction were reported by patients with normal and abnormal esophageal motility. Likewise, similar outcomes were reported after partial fundoplication. This retrospective study found equally low dysphagia rates regardless of baseline esophageal motility; therefore a randomized trial comparing complete versus partial fundoplication in patients with abnormal esophageal motility is warranted.

Extended lymph node dissection for gastric cancer. Is it of value?

The value of extended lymph node dissection for gastric cancer has not been clearly defined. The incidence, staging, and, possibly, the biology of gastric carcinoma in Japanese and Western confound the evaluations of radical lymph node dissection. Surgeons and pathologists must be familiar with the unified international gastric cancer staging system, and careful attention should be given to accurate identification and rigorous examination of regional lymph nodal groups.

Secondary causes of intestinal obstruction: rigorous preoperative evaluation is required.

The clinical presentation, management and outcome of patients with small intestinal and large bowel obstruction unrelated to adhesive or primary colonic neoplastic disease is not well described. The aim of this study was to determine the clinical presentation, evaluation, operative management, and outcome in patients with secondary causes of intestinal obstruction. The medical records of 200 patients who underwent an operation for intestinal obstruction from January 1995 through December 1997 were reviewed. Seventy-three patients (37%) had secondary causes of intestinal obstruction, and these records were reviewed in detail. The cohort included 37 men and 36 women with a mean age of 52 +/- 2 years. The etiology of intestinal obstruction was metastatic neoplastic obstruction (19%), colonic volvulus (18%), Crohn's disease (14%), herniae (11%), diverticular disease (7%), and miscellaneous causes (31%). Six patients (8%) had intestinal motor disorders and a misdiagnosis of intestinal obstruction. The clinical presentation of patients with secondary causes of obstruction was similar to typical patients with adhesive small bowel obstruction. Preoperative evaluation included frequent use of CT (42%), but intestinal contrast studies were used in 13 (18%) patients only. Two-thirds of the patients required an intestinal resection, and 50 per cent of the patients with a misdiagnosis had a nontherapeutic celiotomy. Operative mortality and morbidity were 3 per cent and 48 per cent, respectively, and 15 per cent of patients required reoperation. Suspected intestinal obstruction from secondary causes requires rigorous preoperative evaluation with liberal use of intestinal contrast examinations to avoid misdiagnosis, operative complications, and reoperations.

Total pancreatectomy. An objective analysis of its use in pancreatic cancer.

When should total pancreatectomy be utilized in the treatment of adenocarcinoma of the pancreas? The rationale for total pancreatectomy comes from a tendency for pancreatic cancer to be multicentric (approximately 30% of patients), the absence of a pancreaticoenterostomy and its attendant morbidity, and the argument that total pancreatectomy is a better cancer procedure (more complete lymphadenectomy, wider soft tissue resection). In spite of these theoretical advantages, any impact on morbidity, mortality, or ultimately on survival has not been realized. Indeed, with the current operative mortality of pancreatic remnant-preserving resections being less than 5%, with the realization of the metabolic consequences of total pancreatectomy, and with the introduction of adjuvant chemo-radiation therapy, extended lymphadenectomy, and the concept of regional pancreatectomy, justification for total pancreatectomy for cancer of the head of the pancreas is questionable. The current data suggest that total pancreatectomy should be used only in selected individuals.

Diagnosis and management of gastric emptying disorders.

In summary, although gastric emptying disorders are relatively uncommon, they are potentially devastating conditions resulting from pathophysiologic motor disturbances. Rapid gastric emptying of liquids is the hallmark of the dumping syndrome and occurs after operations, including vagotomy. Vagal denervation abolishes receptive relaxation and accommodation in the proximal stomach (the storage site for ingested liquids) resulting in increased intragastric pressure which forces liquids through an ablated or bypassed pylorus. Dumping symptoms may occur in up to 50% of postgastrectomy patients, but most patients are treated satisfactorily by dietary manipulation or, in the rare incapacitated patient, by the long-acting somatostatin analogue octreotide. Reconstructive gastric surgery may rarely be indicated to slow gastric emptying and alleviate the dumping syndrome. Reoperative procedures include pyloric reconstruction after pyloroplasty, small intestinal pouches, interposed isoperistaltic and antiperistaltic jejunal segments, and a Roux-en-Y gastrojejunostomy. Interposed jejunal loops and the Roux-en-Y gastrojejunostomy provide the most satisfactory results. Delayed gastric emptying may occur in the acute postoperative period or be a late complication of gastric surgery. Loss of vagal input to the gastric antrum and resection of the antrum with vagotomy may produce an atonic stomach or atonic gastric remnant, respectively, which fails to grind and propel solids into the small intestine. Scintigraphic imaging of both the liquid and solid components of the meal is a valuable diagnostic adjunct. Gastric ileus occurring in the early postoperative period generally resolves within 6 weeks of operation, and the temptation to reoperate on a nonobstructed stomach should be avoided. Pharmacologic therapy of chronic gastric stasis with the benzamide prokinetic agents (metoclopramide, cisapride, renzapride), domperidone, and the motilin agonist erythromycin, may be effective initially, but long-term results are still undefined, and postvagotomy and postgastrectomy patients have not been studied adequately. Persistent postoperative gastric atony and the Roux stasis syndrome should be managed surgically by near-total gastrectomy which should result in symptomatic improvement in two thirds of patients.

Laparoscopic intussuscepting pancreaticojejunostomy.

Perhaps the greatest barrier to adoption of laparoscopic pancreaticoduodenectomy by experienced pancreatic surgeons is the technical challenge of constructing the pancreaticojejunostomy (PJ). The authors present a less demanding PJ technique they have developed that creates an end-to-end intussuscepting anastomosis using a running monofilament suture. This method reduces technical complexity and operative time while producing acceptably comparable outcomes.

Duodenal nutrients inhibit canine jejunal fasting motor patterns through a hormonal mechanism.

Ingestion of a meal converts the fasting motor pattern, the migrating motor complex (MMC), to a fed pattern of motility. The role of specific anatomic gut regions involved in these changing patterns of motility and the neurohormonal factors which mediate these changes, however, are unknown. Our aim was to determine the neurohormonal mechanisms by which nutrients within the duodenal lumen alter proximal jejunal motility. Fifteen dogs were prepared with a gastric cannula, duodenal infusion catheter, duodenal and proximal jejunal manometry catheters, and a totally diverting cannula in the most proximal portion of the jejunum. Ten of the dogs also underwent complete in situ neural isolation of the entire jejunoileum. Experiments were performed in the fasting state with no infusion (0 ml/min) and during a 5-hr duodenal infusion (3 ml/min) of either a nonnutrient electrolyte solution or a mixed nutrient solution while diverting distal duodenal chyme from the jejunum. During sham infusion (0 ml/min), the MMC was present in neurally intact dogs (group 1) and dogs with neurally isolated jejunoileum (group 2). Nonnutrient infusion did not inhibit or consistently alter the MMC in either group. Nutrient infusion limited to the duodenum inhibited the MMC in both duodenum and jejunum in dogs with neurally intact and neurally isolated jejunoileum. Latency of onset of the fed pattern in the duodenum and jejunum did not differ between groups. We conclude that postprandial inhibition of the MMC in the jejunum is mediated, in part, by a hormonal mechanism induced by duodenal lumenal nutrients.

Laparoscopic management of paraesophageal hernia: early results.

The objective was to review our early results with laparoscopic repair of paraesophageal hernias to determine the safety, technical feasibility, and short-term outcome of the operation. Twelve patients with a mean age of 75 +/- 1 years underwent laparoscopic repair of a paraesophageal hernia. Principles of open repair, including sac excision, primary crural repair, and pexy, were accomplished laparoscopically in 83%, 83%, and 100% of patients, respectively. In two patients the diaphragmatic defect was closed with mesh. Fundoplication was also performed in seven patients with symptoms of reflux disease. No laparoscopic procedure was converted to an open repair; however, one patient required a postoperative celiotomy to control hemorrhage. Short-term evaluation of all patients postoperatively detected gastroesophageal reflux disease (GERD) in five patients (42%), four of whom did not undergo fundoplication. Two major complications were esophageal perforation and bleeding. Minor complications included atrial fibrillation in two patients, meat impaction in one patient, and a small asymptomatic recurrence in a single patient. Overall patient satisfaction was high. Laparoscopic repair of paraesophageal hernias was safe and technically feasible and warrants further investigation. The incidence of postoperative esophageal reflux, however, is high if an antireflux procedure is not performed. Extensive preoperative evaluation for reflux should objectively identify patients requiring fundoplication and decrease the incidence of postoperative GERD.

Chronic bile diversion does not alter canine interdigestive myoelectric activity.

Previous studies have suggested that the cyclic entry of bile into the duodenum during fasting regulates interdigestive patterns of motility by releasing the putative regulatory hormone motilin. Our aim was to determine if cyclic secretion of bile into the duodenum regulates interdigestive myoelectric activity and plasma motilin concentrations. Six dogs were prepared with gastric and intestinal serosal electrodes. Myoelectric activity was measured during fasting and after a meal before and after reoperative translocation of the entrance of the bile duct to the mid-jejunum. The characteristics of the migrating myoelectric complex (MMC) and conversion to a postprandial pattern were similar before and after bile duct translocation. The period (112 +/- 5 vs 109 +/- 10 min; mean +/- SEM), migration velocity of phase III through the duodenum (8.9 +/- 1.2 vs 6.8 +/- 0.5 cm/min), and duration of individual phases of the MMC in the stomach, duodenum, and jejunum were not altered significantly (each P > 0.05) by chronic diversion of bile from the duodenum. Plasma motilin concentrations were similar before and after bile duct translocation (P > 0.05), continued to cycle temporally with the MMC, and peak concentrations occurred during phase III and were greater than during phases I and II (P < 0.01). We conclude that the presence of bile in the lumen of the duodenum does not regulate interdigestive myoelectric patterns of the canine upper gut or the cyclic release of motilin.

Type I choledochal cyst in association with familial adenomatous polyposis.

Choledochal cysts and familial adenomatous polyposis are infrequent disorders that are often manifest in childhood or in early adult life. The rarity and early presentation of these diseases suggests a genetic basis, which has been established for familial polyposis but not for choledochal cysts. We report a case of a 26-yr-old woman with both disorders and offer an alternative genetics-based etiology for the formation of choledochal cysts.