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Objective: We undertook a prospective randomized clinical trial comparing TIPS to peritoneovenous (PV) shunts in the treatment of medically intractable ascites to establish relative efficacy and morbidity, and thereby superiority, between these shunts., Methods: Thirty-two patients were prospectively randomized to undergo TIPS or peritoneovenous (Denver) shunts. All patients had failed medical therapy., Results: After TIPS versus peritoneovenous shunts, median (mean +/- SD) duration of shunt patency was similar: 4.4 months (6 +/- 6.6 months) versus 4.0 months (5 +/- 4.6 months). Assisted shunt patency was longer after TIPS: 31.1 months (41 +/- 25.9 months) versus 13.1 months (19 +/- 17.3 months) (P < 0.01, Wilcoxon test). Ultimately, after TIPS 19% of patients had irreversible shunt occlusion versus 38% of patients after peritoneovenous shunts. Survival after TIPS was 28.7 months (41 +/- 28.7 months) versus 16.1 months (28 +/- 29.7 months) after peritoneovenous shunts. Control of ascites was achieved sooner after peritoneovenous shunts than after TIPS (73% vs. 46% after 1 month), but longer-term efficacy favored TIPS (eg, 85% vs. 40% at 3 years)., Conclusion: TIPS and peritoneovenous shunts treat medically intractable ascites. Absence of ascites after either is uncommon. PV shunts control ascites sooner, although TIPS provides better long-term efficacy. After either shunt, numerous interventions are required to assist patency. Assisted shunt patency is better after TIPS. Treating medically refractory ascites with TIPS risks early shunt-related mortality for prospects of longer survival with ascites control. This study promotes the application of TIPS for medically intractable ascites if patients undergoing TIPS have prospects beyond short-term survival.

Objective: To determine if cross-tolerance to septic shock could be induced by a previous insult with sublethal hemorrhage (SLH) and to characterize the mechanisms involved in this induced protective response., Background Data: It is possible to condition animals by prior SLH such that they tolerate an otherwise lethal hemorrhage. It is also possible to condition animals with low doses of lipopolysaccharide (LPS) so that they survive a "lethal" septic insult. However, a paucity of information exists on cross-tolerance between hemorrhage and sepsis., Methods: Rats were made tolerant by conditioning SLH or sham operation. Twenty-four hours later, tolerant and sham rats were exposed to a lethal dose of LPS. To explore the mechanism of tolerance induction, rats were given the macrophage (Mphi) inhibitor CNI-1493 or saline carrier before SLH. Survival and pulmonary vascular injury were determined after LPS. Serum tumor necrosis factor (TNF) levels and splenic Mphi TNF gene expression were measured at several time points., Results: Prior SLH indeed made rats tolerant and imparted a significant survival benefit and reduction in pulmonary vascular injury after LPS. The tolerance induced by SLH was reversed by Mphi inhibition. Tolerant animals had low serum TNF levels immediately after SLH and reduced circulating TNF levels after LPS. SLH, however, did not inhibit the augmentation of TNF gene expression after LPS., Conclusions: Sublethal hemorrhage bestows protection against a lethal LPS challenge. Inhibition of the Mphi attenuated the benefit of the tolerance induced by SLH. Circulating TNF but not TNF gene after LPS is lessened by SLH. This implicates changes in Mphi intracellular signaling in induction of the tolerant state.

Objective: The purpose of this study was to evaluate the ability to transfect a murine pancreas with a human cytokine regulatory gene (interleukin-10 [IL-10]) and examine the duration of transgene expression, its effect on the normal pancreas, and its antiinflammatory effect during acute pancreatitis., Summary Background Data: Interleukin-1beta and tumor necrosis factor-alpha are known detrimental mediators during the progression of acute pancreatitis, and blockade of either cytokine results in decreased severity of pancreatitis and improved survival. Although gene therapy has been proposed as a method to deliver protein-based therapy during a number of conditions, no means of effectively transfecting the pancreas without inducing injury has been developed., Methods: A plasmid-human IL-10 construct (pMP6-hIL-10) complexed with cationic liposomes was administered by single intraperitoneal injection to healthy mice. Effective transfection (reverse transcriptase-polymerase chain reaction for hIL-10 mRNA), transfected cell type (in situ polymerase chain reaction for hIL-10 DNA), and the effect on the normal pancreas were determined. Additional animals were transfected to determine the effects of this regulatory gene on the severity of pancreatitis., Results: Nearly 80% of all pancreatic cells expressed human DNA that was subsequently transcribed into mRNA through day 14. The transfection event had no effect on amylase, lipase, or pancreatic histologic appearance. Successful transfection could attenuate subsequently induced pancreatitis (all parameters p < 0.05)., Conclusions: Transient transfection of a human IL-10 gene can be accomplished into all cell types of murine pancreata using a plasmid/ liposome vector. The DNA is effectively transcribed into intact mRNA and does not cause inflammation or acinar cell damage. Transfer of this cytokine regulatory gene decreases the severity of pancreatitis, demonstrating a benefit of gene therapy during this acute inflammatory process.

Objective: This study determined the ability of interleukin-1 receptor antagonist (IL-1ra) to decrease the mortality of experimental acute pancreatitis. The response of the inflammatory cytokine cascade and its subsequent effects on pancreatic morphology were measured to determine the role of these peptides in mediating pancreatic injury., Summary Background Data: Previous studies have shown that proinflammatory cytokines are produced in large amounts during acute pancreatitis and that blockade at the level of the IL-1 receptor significantly decreases intrinsic pancreatic damage. The subsequent effect on survival is not known., Methods: A lethal form of acute hemorrhagic necrotizing pancreatitis was induced in young female mice by feeding a choline-deficient, ethionine supplemented (CDE) diet for 72 hours. For determination of mortality, the animals were divided into 3 groups of 45 animals each: control subjects received 100/microL normal saline intraperitoneally every 6 hours for 5 days; IL-1ra early mice received recombinant interleukin-1 receptor antagonist 15 mg/kg intraperitoneally every 6 hours for 5 days beginning at time 0; IL-1ra late mice received IL-1ra 15 mg/kg intraperitoneally every 6 hours for 3.5 days beginning 1.5 days after introduction of the CDE diet. A parallel experiment was conducted simultaneously with a minimum of 29 animals per group, which were sacrificed daily for comparisons of serum amylase, lipase, IL-1, IL-6, tumor necrosis factor-alpha, IL-1ra, pancreatic wet weight, and blind histopathologic grading., Results: The 10-day mortality in the untreated control group was 73%. Early and late IL-1ra administration resulted in decreases of mortality to 44% and 51%, respectively (both p < 0.001). Interleukin-1 antagonism also was associated with a significant attenuation in the rise in pancreatic wet weight and serum amylase and lipase in both early and late IL-1ra groups (all p < 0.05). All control animals developed a rapid elevation of the inflammatory cytokines, with maximal levels reached on day 3. The IL-1ra-treated animals, however, demonstrated a blunted rise of these mediators (all p < 0.05). Blind histologic grading revealed an overall decrease in the severity of pancreatitis in those animals receiving the antagonist., Conclusions: Early or late blockade of the cytokine cascade at the level of the IL-1 receptor significantly decreases the mortality of severe acute pancreatitis. The mechanism by which this is accomplished appears to include attenuation of systemic inflammatory cytokines and decreased pancreatic destruction.

Eighty-six colorectal cancer patients who entered the Radioimmunoguided Surgery (RIGS) protocol study were evaluated for 2-, 3-, 4-, and 5-year survival following second-look surgical procedures. Strict preoperative evaluation criteria eliminated patients with extra-abdominal tumor involvement. A saturated potassium iodide preparation was given before the intravenous administration of the B72.3 monoclonal antibody (1 mg) radiolabeled with 2 mCi of iodine-125 by the IODOGEN method. Precordial monitoring of the biologic clearance by the handheld, gamma-detecting probe (Neoprobe 1000 instrument) was conducted at weekly intervals until the average count was less than 20 counts in 2 seconds. Once the drug cleared from the blood, surgery was performed. The mean time interval between injection and operation was 24 days, with a range of 21 to 28 days and a median of 23 days. At surgery the abdomen was explored through the traditional methods of palpation and inspection, and the surgeon committed to a planned procedure. The abdomen was then re-explored with the handheld, gamma-detecting probe and the surgeon stated another intraoperative assessment. After using both traditional and RIGS detection methods, the surgeon stated whether his or her surgical plans changed because of the additional intraoperative information provided by the RIGS system. Fifty-three patients (62%) were deemed resectable by the traditional methods of palpation and inspection, but only 40 (47%) were specified as resectable by RIGS exploration. Two-, three-, four-, and five-year survival data could be gathered for each of the three groups: RIGS resectable (n = 40), traditional nonresectable (n = 33), and RIGS nonresectable (n = 13). At 2 years 95% of the resectable, 36% of the traditional nonresectable, and 53% of RIGS nonresectable patients survived. At 3 years 83%, 7%, and 30% of these patients survived, respectively. For the resectable patients, 74% survived at 4 years and 60% at 5 years, with no survivors from either nonresectable group. Use of the RIGS system increased accurate selection of resectable patients undergoing second-look surgery for recurrent colorectal cancer.

Laparoscopic cholecystectomy quickly emerged as an alternative to open cholecystectomy. However its safety, efficacy, and morbidity have yet to be fully evaluated. During the first 6 months of 1990, we performed 100 consecutive laparoscopic cholecystectomies with no deaths and a morbidity rate of 8% (8 of 100 patients; 4 major, 4 minor). There were 81 women and 19 men, with a mean age of 46.1 years (range, 17 to 84 years). All patients had a preoperative history consistent with symptomatic biliary tract disease, and most had proved gallstones by sonography. This included four patients with acute cholecystitis. Mean operating time improved significantly from month 1 to month 6 (122 +/- 45.4 minutes versus 78.5 +/- 30 minutes, respectively), indicating a rapid learning curve. Mean hospital stay was 27.6 hours, reflecting a policy of overnight stay. Postoperative narcotic requirements were limited to oral or no medications in more than 70% of patients. A regular diet was tolerated by 83% of the patients by the morning following the procedure. Median time of return to full activity was 12.8 +/- 6.8 days after operation. In addition analysis of the hospital costs of these 100 cases demonstrates a modest cost advantage over standard open cholecystectomy (n = 58) (mean, $3620.25 +/- $1005.00 versus $4251.76 +/- $988.00). There was one minor bile duct injury requiring laparotomy and t-tube insertion, two postoperative bile collections, and one clinical diagnosis of a retained stone that passed spontaneously. Four patients required conversion to open cholecystectomy because of technical difficulties with the dissection. Although there is a significant learning curve, laparoscopic cholecystectomy is a safe and effective procedure that can be performed with minimal risk. Laparoscopic cholecystectomy should be performed by surgeons who are trained in biliary surgery and knowledgeable in biliary anatomy, and, as with all operations, it should be performed with meticulous attention to technique.

A study was performed to quantitate the adrenal medullary and cortical response to hemorrhage in awake animals bled at different rates and to relate these responses to simultaneous changes in blood glucose and serum insulin. A series of awake pigs were bled either slowly or rapidly of 30% of their calculated blood volume. Infusions of exogenous epinephrine were performed in an additional series of unbled animals and infusions of epinephrine plus hydrocortisone were similarly performed in an additonal series. Increase in blood glucose and epinephrine secretion rate following hemorrhage were found to be significantly dependent upon the rate of initial hemorrhage. Cortisol secretion was found to rise significantly during and following hemorrhage in both rapidly and slowly bled animals. Serum insulin levels remained at baseline levels during shock, despite the presence of significant hyperglycemia. In unbled animals infused with epinephrine at rates comparable to those measured in shock, elevations in blood glucose were markedly lower, shifting to the right of the dose-response curve during hemorrhage. Simultaneous infusions of cortisol and epinephrine resulted in a dose-response curve which did not differ significantly from that following infusion of epinephrine alone.

Precise localization of an intestinal arteriovenous malformation is essential for the complete resection of the lesion. Identification at operation can be difficult, and intraoperative angiography is not without complications. Blood flow within the small vessels of the bowel wall can be easily detected by Doppler ultrasonography, and arterial flow can be distinguished from venous flow. Intraoperative use of the Doppler ultrasound technique localized an AVM in the small intestine. Distinctive flow signals were present over the intestinal AVM which allowed it to be easily differentiated from adjacent normal intestine. Confirmation was secured by measuring the PO2 of blood aspirated from the vein draining the involved segment and comparing it to the PO2 from a vein draining an adjacent segment.

The high incidence of pulmonary embolism is well documented. At first suspicion of an embolism attack, adequate anticoagulant therapy was administered to 86% of the patients in this study. With failure of anticoagulants preoperatively, 30 patients received partial interruption of the IVC, 26 patients had their IVC ligated. Postoperatively, anticoagulants were administered to 64% of the patients who subsequently suffered recurrent attacks of embolism or new episodes of acute thrombophlebitis. These patients also had a substantial hazard of hemorrhage since 48% of the patients on heparin required transfusion. Postoperative mortality for the ligation group was associated with underlying conditions of the patients. These patients subjected to IVC plication had more deaths due to recurrence of pulmonary emboli and were demonstrated to have a substantially higher recurrence rate of pulmonary embolus. Reasons for this recurrence in both groups are discussed. Severe leg sequlae problems often associated with ligation were not encountered but were present in several patients subjected to plication.

A review of 42 patients with gastrinoma, who either survived five years or longer or who died during this period of evaluation, was carried out to define the surgical principles which might be combined with the recent trend toward cimetidine therapy. Thirty-four (80%) of the patients had total gastrectomy with an operative mortality rate of 2.3%, and eight patients (20%) had less than total gastrectomy. No tumor was found in six patients with hypergastrinemia and an abnormal secretin bolus whose five-year survival rate was 100%. Of the thirty-six patients having tissue proof of gastrinoma, twenty-two (61%) had complete resection of all gross tumor resulting in a 76% five-year survival rate. Fourteen patients had unresectable tumor or partial resection with a five-year survival rate of 21%. Complete gross tumor resection increased mean survival by six years (p < 0.01), but resulted in persistent eugastrinemia in only two patients. Long-term survival was possible with a combination of vagotomy, lesser gastric procedures, tumor resection, and cimetidine, seven of eight patients living more than five years. Surgical management of gastrinoma should be directed toward aggressive tumor resection and vagotomy, with reliance on cimetidine therapy postoperatively to control the gastric hypersecretion. Total gastrectomy should be reserved for cimetidine failures and those who do not wish to take cimetidine for the rest of their lives.

The accuracy of Doppler ultrasound in predicting the viability of ischemic intestine secondary to venous obstruction was assessed. Twenty loops of ischemic intestine were created in dogs by temporarily obstructing venous return from the bowel. Doppler arterial flow signals within the intestine quickly disappeared following venous occlusion. In ten segments, arterial signals promptly returned following release of venous occlusion. Nine of these ten segments were viable at reoperation 24 hours later. In ten segments, no arterial signals could be detected following release of venous occlusion, and only one segment proved to be viable. Doppler ultrasound findings were far more accurate in distinguishing between viable and nonviable intestine thatn were clinical guides to intestinal viability.

The complication rate in jejunoileal bypass for morbid obesity is unacceptably high. Gastric bypass is technically difficult. In our series, 115 patients have undergone gastric partitioning for morbid obesity. The operation consists of stapling across the stomach below the gastroesophageal junction, leaving a gastric food reservoir of 50--60 cc. A 1 cm opening is left in the central portion of the staple line, allowing slow emptying into the distal stomach. The result is a reduced eating capacity and frequency which produce loss in weight. Three-quarters of the patients are women, and the age range is 17--62 years. Preoperative weights averaged 147 kg. Mean operative time was 48 minutes, and postoperative stay was 6.2 days. All patients were extensively evaluated preoperatively with upper GI series, cholecystogram, a number of blood chemistry tests, and endocrinologic and psychiatric consultations. All patients underwent a preoperative Minnesota Multiphasic Personality Inventory test. Cholecystectomy for cholelithiasis was performed on 18% of the patients at the time of operation. Of the seven patients operated on more than one year ago, five have lost an average of 31.6% of their preoperative weight. Of the 12 operated on less than one year but more than six months ago, eight have lost an average of 21% of their initial weight. The early failure rate of 33% has been reduced to 15% at present. One death occurred from pulmonary embolus 10 days following discharge, giving a mortality rate of .08%. The complication rate is 10%, comprising two pulmonary emboli, two psychoses, one wound dehiscence, one wound hernia, and ten wound infections, six of which were minor. There have been no complications of ulcer disease, reflux esophagitis, liver disease, renal disease, or metabolic disorders. Gastric partitioning is a safe, fast effective alternative for the surgical treatment of morbid obesity.

Since 1971, serial carcinoembryonic antigen (CEA) levels have been measured to monitor patients after primary resection of colorectal cancer. Based solely on a rise in CEA level above the baseline established after primary resection, 146 patients were readmitted to the hospital. Chest films, liver-spleen scan, colonoscopy, bone scan, abdominal and pelvic CAT scan, and hepatic arteriograms were performed, and elevated CEA levels were confirmed before reexploration was undertaken. In the 146 patients, 139 (95%) had recurrences, and 81 (58%) of these were resectable for potential cure. Two of the first 22 patients re-explored between 1971 and 1975 are still living 11 and 14 years after second look; of 45 patients reoperated upon from 1976 through 1979 and followed for at least 5 years, 14 (31%) are still living. A rise in CEA above the baseline established after primary resection proved to be a sensitive indicator of recurrence and prompted reexploration before symptoms developed. Early alternative therapy was begun in patients with unresectable recurrences.

Over a period of 21 years 39 patients with gastrinoma were surgically treated. Thirty-three patients had total gastrectomy with two postoperative deaths, and 6 patients had a lesser procedure. The postoperative fasting gastrin levels remained elevated and did not always indicate the extent of tumor involvement. Further mobilization of tumor gastrin by provocative infusion of calcium gluceptate, 15 mg/kg of body weight, should be carried out routinely. A hepatic angiogram should be considered when the gastrin levels exceed 1,000 picograms per ml. Chemotherapy consisting of Tubercidin, Streptozotocin and 5-Fluorouracil was given to 5 patients with extensive gastrinoma. All patients felt better and gained from three to 35 pounds in weight. Since 60% of the patients died or have definite evidence of tumor activity it is assumed that the tumor growth was not inhibited and that it is malignant. Approximately 40% of the patients seem to do well despite modest elevations in gastrin levels suggesting that the retained tumor could be considered benign.

This study demonstrates the unique clinical and histologic aspects of fibrolamellar hepatic carcinoma, a rare variant of hepatocellular carcinoma. Three cases are reviewed and an extensive study of immunologic and intracellular substances defining this tumor is presented. Length of survival was considerably longer than typical hepatoma. The cause of death generally is due to a lack of control of the primary tumor. Successful treatment appears to relate to the ability to perform a total excision of the primary hepatic tumor. Chemotherapy should be used only in the presence of metastatic disease. Surgical resection of metastatic disease, unlike the usual hepatocarcinoma, may have some beneficial use. Fibrinogen was found in all tumors. It is possible that this tumor produces fibrinogen to create its unique histologic appearance. Carcinoembryonic antigen is described for the first time in this tumor. Both deposits of alpha-1 antitrypsin and copper were found in most of the tissues studied. The presence and amounts of these substances differ markedly from the common type of hepatoma. This unique composition of intracellular components may both facilitate histologic diagnosis, particularly if the amount of tissue is limited, and give further insight into the etiology of this tumor.