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Objective. The purpose of this study was to report the authors' experience with hepatic resection for cystic lesions of the liver. Summary Background Data. Past experience with aspiration, sclerosing therapy, internal drainage, fenestration, and marsupialization are of limited value. Hepatic resection has evolved into a safe operation over the last two decades. Methods. A retrospective study of 44 patients with various cystic lesions of the liver (polycystic disease, 2; solitary or multiple congenital cysts, 19; biliary cystadenoma, 6; cystadenocarcinoma, 3; squamous cell carcinoma, 3; Caroli's disease, 5; and hydatid cyst, 6) was performed. Results. After 7 trisegmentectomies, 24 lobectomies, 6 left lateral segmentectomies, and 7 nonanatomical hepatic resections, only 1 operative death occurred in a Jehovah's Witness. Symptomatic relief was complete and permanent in all of the patients with benign congenital or parasitic hepatic cysts, except for the two patients with polycystic disease of the liver. One of the 3 patients with adenocarcinoma and 3 patients with squamous cell carcinoma of the cyst wall died of tumor recurrence between 3 and 14 months after hepatic resection. Conclusions. Hepatic resection is safe and effective for cystic lesions of the liver. Symptomatic relief is complete and permanent after hepatic resection, except in cases of diffuse polycystic disease of the liver. Liver transplantation should be considered for diffuse polycystic disease of the liver when the symptoms are extremely severe.

Experience with liver transplantation over a period of 11 years at the University of Pittsburgh is presented. The application of liver transplantation to cases of hepatocellular carcinoma has changed considerably over this 11-year period with the sequential introduction of adjuvant and, more recently, neoadjuvant chemotherapy. Results with the combination of chemotherapy plus surgery appear to be better than results with either agent alone. Moreover, the early results with neoadjuvant therapy appear to be better than those achieved with adjuvant therapy. As a result of this experience, conceptual changes in the approach to the problem of hepatic cancer and the role of both chemotherapy and liver transplantation in its management have changed at the University of Pittsburgh. These changes are identified and discussed.

Twenty‐six adult patients with preformed IgG donor lymphocytotoxic antibodies received primary liver allografts under FK 506 immunosuppression. The effect of the crossmatch‐positive state on early graft function and on the immunopathological and histopathological findings was compared with that of 52 crossmatch‐negative control recipients. The presensitized (crossmatch‐positive) patients had prolongation of early graft dysfunction, underwent more clinically indicated biopsies and had a higher incidence of cellular rejection, both overall (p < 0.05) and within 10 days of transplantation (p < 0.01). They also had a higher incidence of graft failure in the first 180 days (p < 0.01). Hyperacute rejection with necrotizing or neutrophilic arteritis was not seen in the crossmatchpositive grafts. However, histological findings associated with presensitization included platelet margination in central veins and sinusoids in biopsy specimens 60 to 90 min after graft revascularization. Later biopsy specimens had neutrophilic portal venulitis followed by cholangiolar proliferation, acute cholangiolitis and centrilobular hepatocyte swelling that mimicked preservation injury, endothelial activation of arteries with medial changes and relapsing episodes of acute cellular rejection. These clinicopathological observations suggest that lymphocytotoxic antibodies can have a deleterious effect on liver allograft function and survival, even if they do not precipitate immediate or hyperacute rejection. (HEPATOLOGY 1992;16:671–681.) Copyright © 1992 American Association for the Study of Liver Diseases

The incidence of portal vein thrombosis was examined in 885 patients who received orthotopic liver transplantations for various end‐stage liver diseases between 1989 and 1990. The thrombosis was classified into four grades. Grade 1 was thrombosis of intrahepatic portal vein branches, grade 2 was thrombosis of the right or left portal branch or at the bifurcation, grade 3 was partial obstruction of the portal vein trunk, and grade 4 was complete obstruction of the portal vein trunk. Among the 849 patients without previous portosystemic shunt, 14 patients (1.6%) had grade 1, 27 patients (3.2%) had grade 2, 27 patients (3.2%) had grade 3 and 49 patients (5.8%) had grade 4 portal vein thrombosis. The incidence of portal vein thrombosis was highest (34.8%) in the patients with hepatic malignancy in the cirrhotic liver, followed by those with Budd‐Chiari syndrome (22.2%) and postnecrotic cirrhosis of various causes (15.7%). The patients with encephalopathy, ascites, variceal bleeding, previous splenectomy and small liver had significantly higher incidences of portal vein thrombosis than the others. The total incidence of portal vein thrombosis among the 36 patients with previous portosystemic shunt was 38.9%, which was significantly higher than that (13.8%) of those without shunt. (HEPATOLOGY 1992;16;1195–1198.) Copyright © 1992 American Association for the Study of Liver Diseases

Long-term survival in children with primary hepatic malignancies can not be expected without complete tumor resection. In the last ten years we have treated 21 children with hepatocellular carcinoma (HCC) and 21 children with hepatoblastoma (HEP), with tumor extirpation our surgical goal. Operative treatment included partial hepatectomy ([PH] 20), either primary (10) or delayed (following chemotherapy) (10), total hepatectomy and orthotopic liver transplantation ([OLT] 13), or upper abdominal exenteration and multiple organ transplantation (2). Two patients had both PH and subsequent total hepatectomy and OLT. Overall survival was 48% ( 20 42), with 9 patients dying of progressive disease prior to removal of their tumor. HEP patient survival was 67% ( 14 21), including 2 of 6 who underwent primary PH, 7 of 8 who had delayed PH, and 5 of 6 who underwent OLT. Survival for the children with HCC was 29% ( 6 21), including 1 of 4 after primary PH, 1 of 2 following delayed PH, 3 of 7 following OLT, and 1 of 2 after exenteration and multiple organ transplantation. Preoperative chemotherapy facilitated removal of 10 initially unresectable tumors (8 HEP, 2 HCC) at a second-look procedure. Total hepatectomy and OLT markedly improved survival in patients with disease unresectable by standard methods. Partial hepatectomy, either primary or delayed, should be attempted in all children with hepatic malignancies. Total hepatectomy and OLT appears to be a viable adjunct in the treatment of childhood malignancies, and should be used for otherwise unresectable tumors as part of a carefully planned protocol. © 1992.

Extensive hepatocellular adenomatosis (HA) and focal nodular hyperplasia (FNH) represent a proliferation of hepatic cells that occurs most frequently in women. These lesions are uncommon in the pediatric age group, accounting for 2% of pediatric hepatic tumors, and are extremely rare in males. The etiology of HA and FNH has been correlated with the use of oral contraceptives. We report to the best of our knowledge the first series of patients treated with OLTx for HA and FNH (five cases). All these patients had lesions involving at least 90% of the hepatic parenchyma and all underwent major hepatic surgery before OLTx because of life threatening complications. One patient died in the immediate postoperative period following retransplantation for primary non-function of the first OLTx. Four out of five patients are currently alive from 4.1 to 9.6 years after OLTx. Our results justify the use of OLTx for symptomatic patients with HA and FNH who cannot be treated with conventional hepatic resections.

During fiscal year 1986, 40 out of 196 patients (21%) developed hyperamylasemia following orthotopic liver transplantation. The placement of a retropancreatic aortohepatic arterial interposition graft was associated with hyperamylasemia (p < 0.025). Eight patients (20%) developed clinically significant acute pancreatitis and its sequelae; abscesses and pseudocysts each in 2. Pancreatitis was attributable to the retropancreatic arterial graft in 4, viral infection in 2 and obstruction of the pancreatic duct in 1 patient. All 4 patients with arterial graft-related pancreatitis exhibited poor graft function immediately postoperatively, of whom 2 required retransplantation - both of which failed to function. Five patients died (63%); 2 from primary graft non-function, 2 due to sepsis and 1 from systemic cytomegalovirus infection. We conclude that acute pancreatitis after liver transplantation is a life-threatening complication which is often associated with graft non-function.

Seventy-four consecutive pediatric liver transplant recipients were reviewed to assess the effect of the monoclonal anti-T-lymphocyte antibody OKT3 on subsequent viral infection (9 patients were excluded due to postoperative demise during the 1st week). Twenty-two patients received OKT3 in addition to standard cyclosporine-prednisone immunosuppression for either steroid-resistant acute rejection (18) or to facilitate reduction of cyclosporine due to severe renal impairment (4). Invasive infections were diagnosed by histology or culture in tissue biopsies or bronchoalveolar lavage specimens. The overall incidence of viral infection was 58%, half of which was due to cytomegalovirus (CMV). Invasive viral disease was associated with increased mortality (37% vs. 3% p = 0.001). Viral-related deaths were due to CMV (5), disseminated adenovirus (3), disseminated enterovirus (1) and respiratory syncytial viral pneumonia (1). The use of OKT3 was associated with increased viral disease (59% vs. 33% p = 0.04) and invasive primary CMV disease (58% vs. 19% p = 0.04). Trends were observed toward increased overall viral infection (73% vs. 51% p = 0.08), primary CMV infection (58% vs. 25% p = 0.08) and overall mortality (27% vs. 9% p = 0.08) following OKT3 therapy. We conclude that pediatric liver transplant recipients who require OKT3 therapy may be at increased risk for invasive viral disease and especially invasive primary CMV disease.

During the 10-year period (1980 to 1989), 76 patients with hepatocellular carcinoma (HCC) were treated by subtotal hepatic resection (HX) and 105 patients by orthotopic liver transplantation (TX) under cyclosporine-steroid therapy. Overall 1- to 5-year survival rates of the HX group were 71.1%, 55.0%, 47.2%, 37.2%, and 32.9%, respectively, and those of the TX group were 65.7%, 49.0%, 39.2%, 35.6%, and 35.6%, respectively. The survival rates after HX and after TX correlated well with pTNM stages and were similar in each stage between the two groups. However, when HCC was associated with cirrhosis of the liver, the survival rates after TX were significantly better than those after HX at each stage of pTNM classification. The tumor-recurrence rate was high both after HX (50%) and TX (43%), particularly in advanced stages of pTNM classification (60% or more). Twelve patients after HX and 13 patients after TX lived more than 5 years during this 10-year period. Fibrolamellar HCC and early stages of HCC were highly represented among the long-term survivors. Further improvement in survival rates depends on nonsurgical anti-cancer therapy before and/or after surgical removal of HCC.

From 1976 to 1988, 63 patients received radiation therapy for primary cancers of the extrahepatic biliary system (eight gallbladder and 55 extrahepatic biliary duct). Twelve patients underwent orthotopic liver transplantation. Chemotherapy was administered to 13 patients. Three patients underwent intraluminal brachytherapy alone (range, 28 to 55 Gy). Sixty patients received megavoltage external-beam radiation therapy (range, 5.4 to 61.6 Gy; median, 45 Gy), of whom nine received additional intraluminal brachytherapy (range, 14 to 45 Gy; median, 30 Gy). The median survival of all patients was 7 months. Sixty patients died, all within 39 months of radiation therapy. One patient is alive 11 months after irradiation without surgical resection, and two are alive 50 months after liver transplantation and irradiation. Symptomatic duodenal ulcers developed after radiation therapy in seven patients but were not significantly related to any clinical variable tested. Extrahepatic biliary duct cancers, the absence of metastases, increasing calendar year of treatment, and liver transplantation with postoperative radiation therapy were factors significantly associated with improved survival.

In closing, it is important to note that the indications for liver transplantation are not static but rather are remarkably dynamic and capable of change over time. Thus yesterday's major indications can become relative contraindications, while yesterday's absolute contraindications have become today's nuisances. The goal for physicians who care for individuals with problems such as alcoholic liver disease, viral hepatitis, and hepatic cancer should be to develop new strategies of care that will ultimately eliminate these diseases as problems, rather than eliminating individuals with such health problems from currently available health options. In other words, physicians who accept the responsibility for a patient's life should be searching for the best form of therapy available for their patient rather than examining the reasons that exist for limiting one's choice in health care.

The growth rates of recurrent hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLTX) were estimated by calculating the tumor doubling time (TDT) in 20 patients. The mean TDT, calculated by multiple measurement of tumor size, was 44.3 ± 11.3 days (mean ± standard error) in 12 patients with pulmonary metastasis (range, 10 to 161 days) and 37.6 ± 8.9 days (range, 7 to 65 days) in 5 patients with liver allograft recurrence. The TDT as estimated by serum alpha‐fetoprotein (AFP) levels in 6 patients was 37.3 ± 10.0 days (range, 12 to 84 days). The mean TDT obtained from 5 control subjects with HCC who were treated with liver resection (without immunosuppression) was 273.8 ± 79.1 days (range, 82 to 560 days). The disease‐free period and survival time after OLTX both correlated well with the TDT (r = 0.546 and r = 0.701, respectively). The patients with fibrolamellar HCC had a greater TDT and a longer survival time than those with nonfibrolamellar HCC. Despite a wide range of TDT in patients who received transplants, their recurrent HCC tumors grew significantly faster than those of patients with the same disease who did not receive transplants. The factors involved in this accelerated growth rate may include the use of immunosuppressive drugs and the consequent suppression of host immunity against the growth of micrometastasis. Cancer 68:2095–2100. Copyright © 1991 American Cancer Society

We evaluated the efficacy of reconstruction of the hepatic artery for intraoperative or postoperative thrombosis in orthotopic liver transplantation. Of 37 grafts with artery thrombosis, 13 (35.1%, 6 intraoperative and 7 postoperative) underwent reconstruction of the hepatic artery. The arterial flow was reestablished and maintained in 5 (38.5%) of the 13. Recurrent thrombosis in the other 8 grafts developed 2 to 24 days (mean, 13.8 days) after transplantation. Reconstruction was successful in 50% (4/8) of the adults, compared with only 20% (1/5) of the children. Satisfactory results were obtained when a definitive cause of thrombosis could be identified. We conclude that early recognition and correction of the cause of hepatic artery thrombosis during or after orthotopic liver transplantation, especially in adults, is often a graft-saving and lifesaving procedure worthy of consideration. © 1990, American Medical Association. All rights reserved.

With the recent advances in imaging techniques, increased numbers of hepatic lesions are found today, and surgeons are asked frequently for the best course of management. Benign hepatic tumors sometimes cause life-threatening complications and more often trigger disabling or annoying symptoms in otherwise healthy individuals. Although various imaging techniques are quite accurate in identifying cysts and hemangiomas, other benign hepatic lesions, such as adenomas, focal nodular hyperplasia and other benign solid tumors, cannot be differentiated from malignant lesions with a high degree of confidence.

Seventeen female patients who underwent orthotopic liver transplantation between June 1973 and June 1987 became pregnant 5 months to 11 years after transplantation. Immunosuppression was maintained with combinations of prednisone, cyclosporine, and azathioprine prior to and during pregnancy. One patient discontinued immunosuppression after knowledge of pregnancy, taking only azathioprine sporadically. Mean age at time of delivery was 26 years. Twelve patients had no alteration in liver function studies; 7 patients demonstrated mild or moderate enzyme elevations prior to delivery, with one case of rejection confirmed by percutaneous liver biopsy. Major problems related to pregnancy were hypertension, anemia, and hyperbilirubinemia. Twenty live births occurred (2 patients had 2 separate pregnancies, one patient had a set of twins); 13 were by caesarian section, 7 by vaginal delivery. Eleven of the 13 caesarian births were premature by gestational age. All vaginal births were term. Toxemia of pregnancy and early rupture of membranes were the principal indications for caesarean section. There were no congenital abnormalities or birth defects and all the children are surviving well. Fifteen of 16 children older than one year all have normal physical and mental development, with one child manifesting immature speech development. Four children are under one year, all with normal milestones thus far. Sixteen of the 17 mothers are alive from 2—18 years after transplantation; the only death was from a lymphoma, almost 4 years after transplantation and 2½ years after delivery. This experience suggests that women undergoing liver transplantation can safely bear children despite an increased risk of premature caesarian births. The effect of chronic immunosuppression of female pediatric patients on their reproductive potential later in adulthood remains to be fully evaluated but the results so far are favorable. © 1990 by Williams & Wilkins.

One hundred and fifteen patients underwent orthotopic liver transplantation (OLT) for primary liver malignancy. Overall survivals of these patients were significantly lower than those of patients with non-malignant diseases (5-year survival rates 37% and 65%, respectively). Hepatocellular carcinoma (HCC) was the most common malignancy among our patients (n = 80). Fibrolamellar HCC (n = 9) was associated with better survival than non-fibrolamellar HCC (N = 71) among the lesions ≥5 cm in diameter. More frequent recurrence was noted in patients with large tumors (≥5 cm), multiple tumors, and gross vascular involvement. A significant lower survival rate was observed in patients with bile duct cancer (n = 19) than in those with HCC or epithelioid hemangioendothelioma (n = 8). Careful patient selection and effective adjuvant anticancer therapy are needed to improve the results of OLT for primary liver malignancy.

The results of 397 consecutive orthotopic hepatic transplantations in 333 recipients were reviewed. One or more surgical complications developed in 172 of 323 patients (55 per cent), excluding ten intraoperative deaths. The six month mortality rate among the patients with surgical complications (55 of 172; 32 per cent) was statistically higher than that among patients without such complications (16 of 151; 11 per cent) (p < 0.001; chi-square, 58.36). Surgical complications including exploratory laparotomy for bleeding or infection in 74 (22 per cent), reconstruction of the bile duct for biliary obstruction or leakage in 55 (17 per cent), external biliary drainage for biliary leakage in four (1 per cent), tracheostomy in 80 (24 per cent), thoracotomy in 12 (4 per cent) and splenectomy in seven (2 per cent). The incidence of biliary obstruction (16 per cent mortality rate) and leakage (48 per cent mortality rate) was 18 per cent (34 of 193) and 2 per cent (four of 193) each after choledochocholedochostomy, which was 3 per cent (five of 187) and 9 per cent (17 of 187) each choledochojejunostomy. Biliary obstruction (16 per cent mortality rate) was more common after choledochocholedochostomy (p < 0.005; chi-square, 23.01), whereas the incidence of more serious biliary leakage (48 per cent mortality rate) was higher after choledochojejunostomy (p < 0.005; chi-square, 8.97). It is concluded that orthotopic hepatic transplantation remains an unforgiving extensive surgical procedure, in which choledochocholedochostomy remains the first-choice reconstruction of the biliary tract because of its lower mortality.