Surgical and nonsurgical management of primary and metastatic liver tumors.

The medical records of 267 patients who had liver tumors, primary and metastatic, from 1988 to 1995 were retrospectively reviewed. Two hundred thirteen patients (80%) had metastatic disease, and 54 patients (20%) had primary liver disease. Their clinical manifestations and laboratory values were evaluated as factors predictive of diagnosis and survival. There was a significant increase in the occurrence of upper abdominal pain, weight loss, extrahepatic symptoms due to the metastatic origin, and hepatomegaly. Metastases from colorectal primary lesions were synchronous in 34 patients and metachronous in 31 patients. Stomach, lung, and pancreatic primaries were more commonly synchronous. Breast metastases were more commonly metachronous. Elevated serum glutamic-oxaloecetic transaminase and alkaline phosphatase and decreased albumin were the most common liver test abnormalities at diagnosis. Carcinoembryonic antigen values were elevated in the majority of colon cancer patients. Eighty-one percent of patients with primary liver cancer had elevated levels of alpha-fetoprotein, 40 per cent were seropositive for hepatitis B, and 23 per cent were seropositive for hepatitis C. Seventy-nine patients (30%) underwent surgery for their cancer, 37 (47%) had resections, 38 (48%) were unresectable, and 4 (5%) underwent liver transplantation. The patients who underwent surgery had a 32 per cent 5-year survival rate compared to a 0 per cent 5-year survival in the patients who did not have surgery (p = 0.0001). The patients who had resections had a better survival rate than those deemed unresectable at surgery (62% versus 0% at 5-years with p = 0.0008). The perioperative morbidity rate was 16 per cent, with lobectomies having the best rate and trisegmentectomies having the worst. Perioperative mortality rate was zero for all liver resections. Hepatic resection and, in selected patients, liver transplantation are the only two available therapeutic modalities that produce long-term survival with a possible cure in patients with primary and metastatic liver tumor.

Suspected biliary complications after laparoscopic and open cholecystectomy leading to endoscopic cholangiography: a retrospective comparison.

To study how suspected postoperative biliary complications are influenced by surgical technique, we compared clinical profiles of 63 patients referred for ERCP after open (OC) and laparoscopic cholecystectomy (LC) over a four-year period. ERCP was not performed for postoperative pain alone and only six (9.5%) studies were normal. Referrals after LC were younger (mean 39.1 vs 53.6 years, P < 0.001) and ERCP was requested earlier (mean 71.6 vs 2360 days, P < 0.001) in the postoperative course. Choledocholithiasis (CDL) alone, the most common finding, was successfully managed with a single ERCP in 97.2% of cases. CDL after LC occurred in younger patients (35.5 vs 58.9 years, P < 0.01) who presented earlier (mean 98.6 days vs 5.1 years, P < 0.01), without biliary ductal dilatation (P < 0.01). Although CDL after LC was associated with higher ALT and bilirubin levels than after OC, the difference was not statistically significant. Cystic duct leaks (LC: six patients, OC: four patients) were typically associated with CDL after OC and 90% resolved with endoscopic therapy. Biliary ligation (four cases) was managed successfully with choledochojejunostomy. We conclude that findings at ERCP for suspected biliary obstruction or injury after OC or LC are similar and usually can be endoscopically managed. After LC, referrals currently are younger, present much earlier, and retained stones are less likely to be associated with ductal dilatation than after OC.

Chronic hepatitis C with normal aminotransferase levels: a clinical histologic study.

OBJECTIVE: To define chronic hepatitis C virus (HCV) infection among patients with persistently normal aminotransferase levels (PNAL). DESIGN: Retrospective chart review of all patients encountered during 1-yr with positive hepatitis C antibody (anti-C100-3 ELISA), no alternative cause for their liver disease and PNAL for 6 or more consecutive months prebiopsy. Blinded review of liver histology. SETTING: Outpatient hepatology clinics of two academic centers. PATIENTS: Fifty patients with PNAL among 303 with hepatitis C. MEASUREMENTS: Epidemiologic profiles, reasons for seroscreening and confirmatory analyses were tabulated. Histology was reviewed and grading of inflammatory activity and stage of fibrosis was determined by protocol. RESULTS: Among 50 patients with PNAL, 35 (70%) were female, 34 (68%) had parenterally acquired HCV, 44 (88%) abstained (> 2 yr) from ethanol, all were HIV-negative and none pharmacologically immunosuppressed. HCV infection was uniformly confirmed by RIBA II or HCV-RNA assay. The mean level of HCV-RNA by quantitative PCR was 3.79 x 10(5) copies/ml (range, 500 to 1.8 x 10(6) copies/ ml) and by B-DNA, 53 x 10(5) copies/ml (range, 3.5-230 x 10(5) copies/ml). Traditional histoevaluation yielded chronic hepatitis ("active", n = 15; "persistent", n = 25), cirrhosis (n = 7), and normal histology (n = 3). Blinded protocol review of histology (inflammatory grade/fibrotic stage) revealed 0/0 (n = 4), 1/0 (n = 6), 2/0 (n = 17), 2/1 (n = 3), 2/4 (n = 1), 3/0 (n = 2), 3/1 (n = 6), 3/2 (n = 2), and 3/3 (n = 9). CONCLUSIONS: In chronic HCV infection, active inflammation, fibrosis, and variable circulating HCV-RNA levels may coexist with PNAL, particularly among female nondrinkers. Asymptomatic carriers with normal histology comprise 6 to 8% of chronic hepatitis C with PNAL. Management guidelines for this group of patients need to be developed.

Diagnostic considerations in evaluation of patients presenting with melena and nondiagnostic esophagogastroduodenoscopy.

Proper evaluation of patients with melena and nondiagnostic esophagogastroduodenoscopy is comparatively undefined. We sought to determine the percentage of patients with melena and nondiagnostic upper endoscopy and assess the yield of further evaluation. Of 209 patients presenting with melena, 180 underwent esophagogastroduodenoscopy as the initial study, which was nondiagnostic in 43 cases (24%). Further evaluation was pursued in 30. A presumed source of melena was found in 11 patients (37%), identified by colonoscopy in seven, bleeding scan in three, and barium enema plus flexible sigmoidoscopy in one. Nearly all such defined cases originated from the right colon. Small bowel contrast studies, flexible sigmoidoscopy of barium enema alone, and angiography failed to reveal a source. Our findings suggest that many (24%) patients presenting with melena will have nondiagnostic upper endoscopy; further evaluation reveals a potential source in 37% of this group, with the right colon being the most likely location of pathology; and colonoscopy is the test of choice in this cohort.

A critical review of the Couinaud technique of hepatic resection.

The Couinaud technique of left hepatic lobectomy involves the isolation and division of portal vein, hepatic artery, and biliary tributaries as a unit within the liver parenchyma. It saves time and minimizes blood loss by virtue of the common investment of the portal structures in a thick connective tissue sheath. Right hepatic lobectomy can be performed in a similar manner based on the same assumption that the biliary and vascular tributaries maintain a constant anatomic relationship with one another. We describe a patient who underwent right hepatic lobectomy by the Couinaud technique who (in retrospect) had congenital absence of a left hepatic duct. Because small bile ducts from the left lobe drained into the right hepatic duct deep to the sight of resection, obstructive jaundice resulted postoperatively, necessitating orthotopic liver transplantation. Presently, the patient is doing well 1 year after transplantation. When the Couinaud technique is used in the setting of a biliary anatomic variant, the results can be disastrous. This case illustrates that the Couinaud technique is unsafe unless biliary anatomic variants are excluded prior to hepatic lobectomy.

Liver transplantation. When is it indicated and what can be expected afterwards?

Orthotopic liver transplantation is an established form of therapy for selected patients who have chronic parenchymal liver disease with cirrhosis, a chronic cholestatic syndrome, fulminant hepatic failure, or unresectable hepatic malignant disease. In most centers with experienced staff, 5-year survival rates exceed 70%. For a good outcome, it is essential that the patient be referred to a transplant center early, before overt clinical deterioration occurs. Following transplantation, lifelong immunosuppression is required to prevent allograft rejection, and extensive follow-up is necessary for early reversal of complications. The primary care physician plays a critical role in identifying organ donors.

Chronic abdominal pain as the initial manifestation of pancreatic injury due to remote blunt trauma of the abdomen.

Three patients were admitted with severe abdominal pain that began after an asymptomatic latent period following blunt trauma to the abdomen. During initial medical evaluation 3 months to 1 year after the trauma, serum amylase levels were normal or minimally elevated, and computed tomography scanning revealed edema and/or pseudocyst formation in the tail of the pancreas. Pancreatography showed ductal stenosis or obstruction in the midbody of the pancreas in each patient. At surgery, chronic pancreatitis in the tail was clearly demarcated from the normal head of the gland. Distal pancreatectomy was curative. Blunt traumatic pancreatic ductal injury may occur without typical immediate posttraumatic acute pancreatitis. Chronic distal pancreatitis following an asymptomatic latent period may culminate in delayed admission months to years after the initial injury. Endoscopic retrograde cholangiopancreatography should be considered for evaluation of patients with chronic abdominal pain and prior blunt trauma to the abdomen.

Traumatic pancreatitis in a patient with pancreas divisum: clinical and radiographic features.

A previously healthy patient with chronic hyperamylasemia and epigastric pain following blunt abdominal trauma complicated by retroperitoneal hematoma is reported. Endoscopic retrograde cholangiopancreatographic and computerized tomographic examinations revealed pancreatographic characteristics of pancreas divisum with traumatic disruption of the duct of Santorini and adjacent pseudocyst formation. Distal pancreatectomy with cystjejunostomy resulted in total recovery. This represents the first documented case of traumatic pancreatitis in a patient with pancreas divisum.

Closure of a controlled biliary fistula complicating partial cholecystectomy with endoscopic biliary stenting.

An elderly woman presented 2 months after partial cholecystectomy performed for gangrenous cholecystitis with choledocholithiasis and a controlled biliary fistula. Despite ductal clearance of stones via endoscopic retrograde sphincterotomy and stone extraction, bilious drainage via the fistulous tract persisted. Endoscopic insertion of a 10F Amsterdam endoprosthesis resulted in complete closure of the fistula within 6 wk. This case represents the first example of closure of a biliary fistula after partial cholecystectomy.

A pilot clinical trial of the cholecystokinin receptor antagonist MK-329 in patients with advanced pancreatic cancer.

MK-329 is a nonpeptidal, highly specific cholecystokinin (CCK) receptor antagonist, with affinity for pancreatic and gallbladder CCK receptors similar to CCK itself. MK-329 and its progenitor, asperlicin, can inhibit the growth of CCK receptor-positive human pancreatic cancer in athymic mice. Based on these activities and the ability of MK-329 to transiently increase food intake and enhance morphine analgesia in murine models, we conducted an open trial of MK-329 in 18 patients with advanced pancreatic cancer in whom the CCK receptor status of the tumors was unknown. Tumor response, pain control, and nutritional parameters (hunger rating, caloric intake, body weight, and anthropometrics) were serially assessed. The results of the study failed to demonstrate any impact of MK-329 on tumor progression, pain, or nutrition. Toxicity was mild and limited to nausea, vomiting, diarrhea, and abdominal cramps, with 17 of 18 patients able to tolerate treatment. While a role for MK-329 in the management of patients with advanced pancreatic cancer cannot be supported by the results of this trial, additional studies of this agent in patients with known CCK receptor-positive tumors, at escalated doses, and possibly in conjunction with other growth antagonists, appear warranted.

Obstructive jaundice. Nonsurgical options for 'surgical' jaundice.

The development of nonoperative methods of biliary drainage has altered traditional concepts regarding management of medical and surgical jaundice. Patients with newly diagnosed obstructive jaundice typically are elderly and have an unresectable neoplasm. Because surgical cure is often impossible and operation is usually risky in such patients, decompression of the biliary tree by endoscopic retrograde cholangiopancreatography and endoscopically inserted biliary stents has become an increasingly popular means of palliation. Percutaneous transhepatic cholangiography and surgical bilidigestive bypass remain important alternatives. Selection of optimal management for the individual patient requires an in-depth evaluation by a skilled team consisting of the primary care physician, endoscopist, interventional radiologist, and surgeon.

Endoscopic retrograde sphincterotomy in swine.

Endoscopic retrograde sphincterotomy was performed on four sedated pigs, ages 3-4 months, using a standard human duodenoscope and papillotome. Sphincterotomies, 1 cm in length, were well-tolerated, and all animals recovered promptly, spontaneously regained gastrointestinal function, and gained weight. The first three animals were sacrificed after one week, and autopsy revealed no complications. The fourth animal was sacrificed immediately following the procedure, and no evidence of perforation was found. These observations demonstrate that the pig is a valid experimental model for endoscopic sphincterotomy. Its use in training is limited by technical and anatomic differences from humans. Potential uses of this technique in research are discussed.

Hepatologic considerations in patients with parenchymal liver disease undergoing surgery.

Patients with liver disease requiring surgical procedures are at increased perioperative risk. In addition, the deleterious effect of anesthesia on hepatocellular function, altered drug pharmacokinetics, aberrant hemostasis, postoperative encephalopathy and infection, with multiorgan failure, all contribute to perioperative morbidity and mortality. Although limited by the lack of widely accepted quantitative liver function tests, preoperative evaluation and risk assessment is imperative. Acute viral hepatitis, alcoholic hepatitis, refractory coagulopathy, Child's class C cirrhosis, and emergent surgery are major risk factors predictive of a poor outcome. In addition, elective abdominal surgical procedures should be avoided in potential candidates for orthotopic liver transplantation. Identification and correction of reversible risk factors via meticulous preoperative definition of the etiology, chronicity, and severity of the patient's liver disease within the confines of surgical urgency is the goal of the preoperative hepatology consultation.

Cell surface expression of hepatitis B surface and core antigens in transfected rat fibroblast cell lines.

Hepatocellular necrosis during hepatitis B virus infection is hypothesized to result from host immune responses against either hepatitis B surface antigen or hepatitis B core antigen expressed on the surface membrane of infected hepatocytes. To study the capacity of hepatitis B deoxyribonucleic acid to induce membrane expression of either hepatitis B surface antigen or hepatitis B core antigen in vitro, we assessed transfected rat fibroblast cell lines by indirect immunofluorescence. Rat fibroblasts were transfected with plasmid vectors containing the natural promoters, native enhancer, and uninterrupted sequences of either the Pre S/S gene or core gene. Resulting cell lines produced hepatitis B surface antigen and hepatitis B core antigen/hepatitis B e antigen, respectively. Immunofluorescence microscopy or flow cytometry showed that hepatitis B surface antigen and hepatitis B core antigen were expressed in a granular pattern in the surface membrane of transfected cells. We conclude that surface membrane expression of both hepatitis B surface antigen and hepatitis B core antigen is an intrinsic consequence of expression of either the Pre S/S or core gene.

Steroid-responsive chronic hepatic graft-versus-host disease without extrahepatic graft-versus-host disease.

A 29-yr-old woman developed severe, progressive cholestasis 5 months after allogeneic bone marrow transplantation. Extrahepatic graft-versus-host disease (GVHD) was absent. Skin biopsy was equivocal 2 months after transplant, rash was absent during the period of cholestasis, and cholangiographic abnormalities were absent. Liver biopsy 7.5 months posttransplant revealed chronic hepatic GVHD. Cholestasis dramatically resolved with high dose corticosteroid therapy. Chronic hepatic GVHD occurs in the absence of overt extraintestinal GVHD and respond promptly to therapy. This underscores the importance of aggressive diagnostic evaluation of posttransplant cholestasis.