Terminology of liver anatomy and liver resections: coming to grips with hepatic Babel.
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Biomedical subjects
Publications and source records attributed to S M Strasberg.
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BACKGROUND: Open laparotomy has traditionally been required to stage hepatobiliary and pancreatic (HBP) cancers accurately. For unresectable patients, costs and morbidity have been high. Today, laparoscopy alone or combined with laparoscopic ultrasonography (LUS) is being examined for its value in defining the extent of malignancy. STUDY DESIGN: We have analyzed the effect of routine implementation of this new staging technique in our HBP center. Staging laparoscopy (SL) with LUS was performed in 50 consecutive patients with HBP malignancies. All patients were considered to have resectable tumors as determined by traditional preoperative staging modalities. Primary tumors were located in the liver (n = 7), biliary tract (n = 11), or pancreas (n = 32). An average of 2.7 preoperative studies per patient were performed prior to SL-LUS. RESULTS: Staging laparoscopy with laparoscopic ultrasonography predicted resectable tumors in 28 patients (56%). At laparotomy, 26 of 28 were actually resectable: the false-negative rate was 4%. Staging laparoscopy with laparoscopic ultrasonography indicated unresectability in 22 patients (44%). Staging laparoscopy alone demonstrated previously unrecognized occult metastases in 11 patients (22%). In 11 other patients (22%) in whom SL alone was negative, LUS established unresectability from vascular invasion (n = 5), lymph node metastases (n = 5), or intraparenchymal hepatic tumor (n = 1). All cases of unresectability due to vascular invasion were validated by laparotomy. Five of six lymph node or hepatic metastases were proved histologically by LUS-guided needle biopsy rather than laparotomy. CONCLUSIONS: Unnecessary laparotomy can be safely avoided by SL-LUS in many patients with HPB malignancies, reducing costs and morbidity.
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We have previously shown that part of the injury sustained by cold-preserved livers on reperfusion is the consequence of platelet adhesion to sinusoidal endothelium. The purpose of the present study was to determine whether prostaglandin E1 (PGE1) can reduce the injury and if so, how to maximize this beneficial effect. Rat livers were cold-preserved in University of Wisconsin solution for 30 hours then subjected to 1-hour warm ischemia after which they were reperfused at 37 degrees C with oxygenated Krebs-Henseleit solution with or without isolated platelets. PGE1 was used to treat the donor liver during harvesting, cold preservation, and reperfusion. In some studies, PGE1 was used to pretreat platelets before exposing them to the liver, and in other studies, both liver and platelets were treated. Pretreatment of platelets with paraformaldehyde, which inactivates them, or ADP, which activates them, was also studied. Treatment of livers with PGE1 significantly decreased preservation injury when livers were reperfused in the absence of platelets. However, when platelets were added to the perfusate, prior treatment of the liver with PGE1 had relatively minor beneficial effects. Pretreatment of platelets alone with PGE1 was also beneficial, but again the effect was small. However, when both liver and platelets were treated with PGE1 there was a highly significant decrease in the extent of liver injury and platelet adhesion. Perfusate transaminase levels were lower, bile flow was improved, and histologically, livers appeared less injured. Pretreatment of platelets with paraformaldehyde produced similar results to pretreatment with PGE1. When platelets were preactivated with adenosine diphosphate, extensive hepatic injury occurred upon reperfusion despite PGE1 treatment of the liver. PGE1 can lessen preservation-reperfusion injury impressively when administered to both liver and platelets but has little effect when platelets have been preactivated.
Liver core temperature during organ procurement, storage, and rewarming has not been reported in human orthotopic liver transplantations (OLT). We have shown in the rat that optimal temperature for liver storage is not 4 degrees C but 0 degree C to 1 degree C. Therefore, a study was undertaken in humans and in pigs to determine the pattern of temperature change during OLT. The porcine studies were performed, because it was not possible to follow human grafts during the period that they were sterilely packaged. Temperature depression in humans was rapid during organ perfusion, remained stable during organ dissection, and decreased again slightly, when after excision, the organ was perfused again. Temperature depression during the period of perfusion with University of Wisconsin (UW) solution was curvilinear with the initial rapid temperature depression followed by a period of slower temperature depression. Volume perfused versus time was linear during these periods and the relationship between temperature depression and volume infused was curvilinear. At the time of packaging, 65 +/- 12 minutes after start of cold perfusion, the liver core temperature was 5.7 degrees C +/- 1.3 degrees C. Studies in the pig showed that it took 75 to 100 minutes for liver core temperature to decrease below 5 degrees C, and core temperature reached a plateau at 1 degree C at 195 +/- 75 minutes after packaging. During the rewarming period in humans, while vascular anastomoses were being constructed, there was a rapid linear increase in temperature from 0.8 degree C, when the graft was removed from the cold, to 17.2 degrees C +/- 3.1 degrees C at 45.5 +/- 4.4 minutes later, just before portal reperfusion commenced. These studies show that it takes only a short time to cool livers down to 10 degrees C, but after flushing is stopped, temperature depression is markedly reduced, and ideal temperatures are not reached before packaging. Rewarming of livers during performance of vascular anastomoses is rapid and reaches temperatures at which substantial hepatic metabolism is occurring.
BACKGROUND & AIMS: Most cholesterol gallstones have a pigmented center, but it is unclear whether its presence is primary or secondary. This study was performed to determine if bilirubin would accumulate in a gallstone model consisting of cholesterol pellets. METHODS: Cholesterol was compressed into pellets at 2500 psi, producing a pellet that behaved like human cholesterol gallstones in regard to penetration of solutes into the stone. Pellets were implanted into gallbladders of pigs and harvested after 4 weeks. Bilirubin species were measured by high-performance liquid chromatography. RESULTS: The proportions of bilirubin species in bile were not changed by the presence of pellets, i.e., diconjugates (mean +/- SD, 1.9% +/- 1.0% vs. 0.7% +/- 0.8%), monoconjugates (83.8% +/- 5.5% vs. 87.8% +/- 6.6%), and unconjugated bilirubin (14.2% +/- 5.3% vs. 11.5% +/- 5.6%) were similar at the time of implantation and removal. The cut surfaces of the pellets were pigmented. Pellets contained 5.46 +/- 1.38 micrograms bilirubin/g sample at harvesting, and 98.6% +/- 2.3% of bilirubin in pellets was unconjugated. In in vitro studies, there was a large increase in unconjugated bilirubin in the bile. Pellets also became pigmented in vitro, but there was considerable variability in the bilirubin species present in the pellets. CONCLUSIONS: Unconjugated bilirubin accumulates in cholesterol pellets and pigments them. This provides a mechanism by which cholesterol gallstones could become secondarily pigmented.
With the growth of laparoscopic general surgery, both minor and major complications are being encountered. This article discusses complications related to operative laparoscopy, including those associated with access techniques and the pneumoperitoneum. Complications specific to certain procedures, including laparoscopic cholecystectomy, appendectomy, colon resection, anti-reflux surgery, and herniorrhaphy, are also discussed in detail.
From 1990 through 1993, we treated 36 patients with recurrent typical biliary colic but who showed no ultrasonic evidence of cholelithiasis by laparoscopic cholecystectomy. Associated symptoms included nausea (75%), bloating (56%), fatty-food intolerance (53%), vomiting (17%), weight loss (31%), bowel irregularity (28%), reflux or dyspepsia (25%), and fever (17%). Diagnostic evaluation included ultrasound (100%), upper gastrointestinal series (36%), oral cholecystogram (14%), computed tomographic scan (39%), endoscopic retrograde cholangiopancreatography (17%), upper gastrointestinal endoscopy (14%), and hepatobiliary scan (92%). Quantitative hepatobiliary scans in 33 patients revealed a low gallbladder ejection fraction (EF) of less than 35% in 29 patients (88%; mean EF = 9%), and 13 patients experienced reproducible pain after cholecystokinin provocation. All patients underwent attempted laparoscopic cholecystectomy; one case of unsuspected acute acalculous cholecystitis was converted to open laparotomy because of unclear anatomy. Gross and histological examination of the gallbladders revealed chronic inflammation (83%), cholesterolosis (31%), cholesterol crystals or small stones (17%), acute inflammation (8%), polyps (6%), and normal histology (6%); however, blind retrospective scoring of gallbladders revealed significant chronic inflammation in only 38%. In the 2 to 40 months (mean, 14 months) since operation, there have been no deaths (97% follow-up). Laparoscopic cholecystectomy relieved pain in 93% of patients with a low preoperative EF compared with 75% of patients with a normal EF (nonsignificant p value). Persistent abdominal or gastrointestinal complaints included flatulence (31%), loose stools or fecal urgency (29%), belching (29%), indigestion (20%), nausea (11%), and "typical" gallbladder pain (9%). We conclude that many patients with symptoms of biliary colic and scintigraphic evidence of biliary dyskinesia have histologic findings of chronic cholecystitis. Although laparoscopic cholecystectomy usually eliminates biliary colic, persistent nonbiliary complaints are frequent.
Laparoscopic surgery of the bile ducts is evolving rapidly. Laparoscopic bile duct exploration is reaching wide application and is competitive with postoperative ERCP for treatment of choledocholithiasis. Staging laparoscopy is an important laparoscopic advance that is increasing resectability rates for pancreatic and hepatic tumors through laparoscopic detection of unresectable tumors. Bile duct injury is an important problem in laparoscopic cholecystectomy. Classification, avoidance, and management are discussed.
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OBJECTIVE: The purpose of this prospective study was to compare the accuracies of laparoscopic sonography and laparoscopic videofluoroscopic cholangiography in detecting common bile duct stones and in identifying ductal anomalies during laparoscopic cholecystectomy. SUBJECTS AND METHODS: Ninety-five patients who underwent laparoscopic videofluoroscopic cholecystectomy were prospectively studied with laparoscopic sonography and laparoscopic videofluoroscopic cholangiography. The number of successful studies, the time required to complete the study, and complications resulting from the study were recorded. The biliary system was evaluated for complete visualization of the common bile duct, visualization of the cystic duct, ductal anomalies, maximum diameter of the common bile duct, and common bile duct stones and/or debris. Also determined was whether laparoscopic sonographic findings altered operative management. RESULTS: Laparoscopic sonography was successfully performed in 93 of 95 patients, and laparoscopic videofluoroscopic cholangiography was successfully performed in 90 of 95 patients. The time required to complete laparoscopic sonography ranged from 3 to 18 min (mean +/- SD, 8 +/- 3 min), and that required to complete laparoscopic cholangiography ranged from 5 to 28 min (mean +/- SD, 14 +/- 6 min). Laparoscopic sonography visualized the complete common bile duct in 84 of 93 patients, and laparoscopic cholangiography did so in 86 of 90 patients. Laparoscopic sonography showed the cystic duct in 87 of 93 patients, and laparoscopic cholangiography did so in 80 of 90 patients. Laparoscopic sonography showed no ductal anomalies in any of the 93 patients. Laparoscopic cholangiography showed ductal variants in 13 of 90 patients; however, 11 of the variants were proximal to the sonographic scan plane. Laparoscopic sonography showed common bile duct stones in 12 of 93 patients, and laparoscopic cholangiography did so in five of 90 patients. Laparoscopic sonography altered operative management in two of 93 patients. CONCLUSION: Our results show that laparoscopic sonography is as accurate as laparoscopic videofluoroscopic cholangiography in visualizing the common bile duct and cystic duct and in detecting common bile duct stones. However, the data are too limited to determine whether laparoscopic sonography is as accurate as laparoscopic cholangiography in detecting ductal anomalies.
Preservation injury to bile ducts is a serious problem in liver transplantation, especially when preservation exceeds 12 hours. The authors hypothesized that the injury was caused by contact of bile ducts with bile salts during cold preservation and might be preventable by infusion of more hydrophilic bile salts. Swine livers were harvested after intraportal infusions of saline (control), of the hydrophobic bile salt taurodeoxycholate, or of the hydrophilic bile salts tauroursodeoxycholate or dehydrocholate. The effect of infusing a combination of hydrophilic and hydrophobic bile acids was also studied. Bile samples were taken before and during the infusions. Then livers were perfused with UW solution, ducts were flushed retrograde with UW, and livers were stored at 0 to 1 degree C for 20 hours. Bile ducts were harvested after preservation, and coded microscopic slides of the specimens were examined by light microscopy. There was large variability in baseline bile salt concentration. Injury after preservation consisted of sloughing and pyknosis of surface and glandular epithelium. The histologic injury score determined after preservation was directly related to bile salt concentration in bile ducts at the time of flushing. During bile salt infusions, the infused bile salt replaced most or all of the other bile salts present in bile. Severe postpreservation injury of intrahepatic ducts occurred after taurodeoxycholate infusions, but injury was minimal when either of the two hydrophilic bile salts was infused. The mixture of bile acids produced intermediate results. Retrograde flushing with UW does not prevent injury to intrahepatic ducts. The authors conclude that the injury is caused by contact with bile salts, is dependent on bile salt concentration and composition, and is preventable.
Because an increase in biliary deoxycholate levels seems to be a risk factor for cholesterol gallstone formation, we determined the relationship between deoxycholate levels and levels of the pronucleating protein, immunoglobulin G (Ig) in human gallbladder bile. Patients with cholesterol gallstones had a higher concentration of biliary IgG compared with a pigmented stone group and control patients. This was associated with the simultaneous presence of two conditions in the cholesterol stone group, supersaturated bile and a high deoxycholate/cholate ratio. The other patient groups met only one of the two conditions. Next, animal studies were performed to determine if model biles mimicking the two conditions could affect IgG secretion by the gallbladder. Gallbladders were exposed in vivo and then in an Ussing chamber to model biles. The voltage clamp technique was used to monitor functional integrity of the preparation. Three different model biles were tested: (1) taurodeoxycholate (TDC), 80%; taurocholate (TC), 20%; and cholesterol saturation index (CSI), 1.2; (2) TDC, 20%; TC, 80%; and CSI, 1.2; and (3) TDC, 80%; TC, 20%; and CSI, 0.6. IgG concentrations became significantly higher in group 1 than in the other two groups. The concentration of mucous glycoprotein was also significantly greater in group 1 when compared with group 2. Plasma cells were increased in number in mucosal and submucosal layers in group 1. We conclude that cholesterol supersaturated model bile with high content of TDC induces gallbladder epithelial alterations, which increase the luminal concentration of IgG and mucous glycoprotein.
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Concanavalin A (Con A) affinity chromatography is the standard procedure to separate cholesterol nucleating biliary proteins from lipids and pigment. We observed that even after extensive washing following application of bile, lipid contaminants remain. We have determined the contribution of lipid contamination to cholesterol nucleation and assessed a modified procedure to remove lipids from the column. Human gallbladder bile was spiked with [3H]cholesterol and [14C]phospholipid and applied to two sets of Con A-Sepharose columns. One column was washed in the usual manner with Tris-HCl buffer and the other with buffer containing 10 mM taurocholate prior to eluting bound glycoproteins with alpha-D-methylmannopyranoside. Eluted proteins were added to heated abnormal bile at a final concentration of 250 micrograms/ml to study the effect on cholesterol nucleation. A separate aliquot (20 microliter) of the protein solutions was counted for radioactivity. Cholesterol nucleating activity was less in samples from columns washed with 10 mM taurocholate than in samples from columns not washed with the bile salt. Lipid radioactivity was associated with Con A-binding proteins prepared without taurocholate, but not in those prepared with taurocholate wash. Light microscopy revealed the presence of cholesterol microcrystals and vesicles in some Con A-binding protein preparations prepared without a taurocholate wash. However, pellets from ultracentrifuged Con A preparations prepared without a bile salt wash revealed cholesterol crystals in all samples (n = 6). Washing with taurocholate did not affect recovery of protein mass and appearance of bands on SDS-PAGE gel showed an identical pattern in the two groups. This modified procedure to prepare potential nucleating proteins from gallbladder bile should eliminate erroneous results that may arise due to lipid contamination.
Laparoscopic hepatobiliary surgery has advanced rapidly in the past few years. Laparoscopic cholecystectomy has been the most significant advance and its value will become even greater as the incidence of biliary injuries is decreased. LCBDE and staging laparoscopy are very promising procedures. Other hepatobiliary laparoscopic operations such as liver resections and biliary-enteric anastomoses are still in developmental stages and will require a longer period of assessment.
Initial poor function and primary nonfunction are important problems in clinical transplantation. The incidence of primary nonfunction is about 6% and that of initial poor function is about 15%. Grafts with initial poor function have a higher graft failure rate in the first 3 mo after transplantation. Severe steatosis and cold preservation in University of Wisconsin solution for over 30 hr will alone cause primary nonfunction. However, primary nonfunction is probably most often caused by the presence of multiple relative risk factors. The major donor-relative risk factors are moderate steatosis, cold preservation over 12 hr and donor age over 50 yr, whereas retransplantation, high (United Network of Organ Sharing class 4) medical status and kidney failure are recipient relative risk factors. The most important perioperative risk factor is warm ischemia time. Rates of primary nonfunction and initial poor function might be reduced by avoidance of combinations of risk factors. Several tests have been developed to predict primary nonfunction and initial poor function, but none is yet clinically efficient.
The optimal preservation temperature for liver allografts is unknown. We evaluated the effect of small differences in preservation temperature, 5 degrees C vs 0 degrees C, on outcome of prolonged preservation. Livers of Wistar rats were preserved at these temperatures in UW solution for 40 h. Function was studied during reperfusion on the isolated perfused rat liver system at 37 degrees C. To compare the effects of a small reduction in temperature with known beneficial strategies, the effects of including antiproteases and periodic flushing of the graft with UW solution during cold preservation at 5 degrees C were also studied. Aspartate transaminase (AST) and alanine transaminase release after 4 h of reperfusion were much higher in the livers stored at 5 than at 0 degrees C (P < 0.0005). Addition of antiproteases to the preservation solution or periodic flushing reduced AST release but neither treatment at 5 degrees C was as good as simple storage at 0 degrees C. Cumulative bile production after 4 h of reperfusion was significantly greater in the 0 degrees C preserved group than in liver at 5 degrees C or 5 degrees C with periodic flushing. The addition of antiproteases resulted in slightly increased bile production (not significant). Platelets and WBCs in the perfusate decreased during reperfusion. This effect was more pronounced in the 5 degrees C preserved livers than in those stored at 0 degrees C. Antiproteases in the preservation solution appeared to inhibit platelet and WBC loss. Perfusate flow was significantly higher in the 0 degrees C group. We conclude that small differences in preservation temperature even at these low temperatures are important in postreperfusion liver function.