Should a lower quality organ go to the least sick patient? Model for end-stage liver disease score and donor risk index as predictors of early allograft dysfunction.

BACKGROUND: There is a global tendency to justify transplanting extended criteria organs (ECD; Donor Risk Index [DRI] ≥ 1.7) into recipients with a lower Model for End-Stage Liver Disease (MELD) score and to transplant standard criteria organs (DRI < 1.7) into recipients with a higher MELD scores. There is a lack of evidence in the current literature to justify this assumption. METHODS: A review of our prospectively entered database for donation after brain death (DBD) liver transplantation (n = 310) between January 1, 2006, and September 30, 2010, was performed. DRI was dichotomized as <1.7 and ≥ 1.7. Recipients were divided into 3 strata, those with high (≥ 27), moderate (15-26), and low MELD (<15) scores. The recently validated definition of early allograft dysfunction (EAD) was used. We analyzed EAD and its relation with donor DRI and recipient MELD scores. RESULTS: The overall incidence of EAD was 24.5%. Mortality in the first 6 months in recipients with EAD was 20% compared with 3.4% for those without EAD (relative risk [RR], 5.56, 95% confidence interval [CI], 1.96-15.73; P < .001). Graft failure rate in the first 6 months in those with EAD was 27% compared with 5.8% for those without EAD (RR, 4.63; 95% CI, 2.02-10.6; P < .001). In patients with low MELD scores, a significantly increased rate of EAD (25%) was seen in patients transplanted with a high DRI liver compared with those transplanted with a low DRI liver (6.25%; P = .012). In moderate and high MELD recipients, there was no significant difference in the rate of EAD in patients transplanted with a high DRI liver (62%) compared with those transplanted with a low DRI liver (59%). CONCLUSION: These results suggest that contrary to common belief it is not justified to preferentially allocate organs with higher DRI to recipients with lower MELD scores.

Survival after liver transplantation for hepatocellular carcinoma.

BACKGROUND: Selection criteria for patients with hepatocellular carcinoma (HCC) suitable for liver transplantation (LT) include tumor size and number and vascular invasion. There has been a recent trend to expand the transplant criteria for HCC. We reviewed our experience to determine survival following LT based on tumor characteristics. METHODS: A retrospective analysis was performed on 72 patients with HCC who underwent LT between 1985 and July 2002. The Milan criteria were applied for LT candidacy for HCCs that were deemed unresectable from anatomical considerations and/or the severity of underlying cirrhosis. Patients were divided into four groups: group 1: patients with known HCC who satisfied the selection criteria (n = 22); group 2: patients with known HCC that exceeded the criteria (n = 17); group 3: patients with incidental HCC found at pathological examination of the explant (n = 33); group 4: contemporary LT recipients without HCC (n = 935). RESULTS: In the known HCC group, the interval between listing as status 2 and transplantation was 72.2 +/- 133.6 days (median 23 days). Three-year patient survival was 80.2% in group 1, 35.8% in group 2, 63.2% in group 3, and 81.5% in group 4. In group 2 patients, the tumors were significantly larger, had more nodules, and were more often bilobar. In group 3, five (15%) exceeded the criteria mainly because of tumor size and four patients died within 3 years post-LT (three from tumor recurrence). CONCLUSION: Liver transplantation for HCC yields acceptable survival in early-stage tumors, particularly if transplanted soon after listing. Long-term survival was inferior in patients with multiple tumors and tumors that were greater than 5 cm in diameter.

Management of biliary problems after liver transplantation.

1. Biliary complications of some type occur in approximately one of every eight liver transplant recipients. Although they are uncommon causes of mortality, they are significant sources of morbidity. 2. Leaks and strictures that occur early after transplantation have technical causes. Late strictures and obstruction are more likely to be complex and have multiple causes, including hepatic artery occlusion, preservation injury, rejection, and recurrent disease. 3. Diagnosis relies on abdominal imaging and cholangiographic studies. Patency of the hepatic artery must be proven when a complication of the donor biliary tree occurs. 4. Management of late complications is largely influenced by the nature and extent of strictures. Percutaneous and endoscopic treatment of anastomotic strictures offers a significant prospect of successful long-term management. 5. Nonsurgical management of more complex hilar and intrahepatic strictures is less successful, and surgical revision or retransplantation may be required for definitive treatment.

Surgery and transplantation for hepatocellular cancer.

1. Curative treatment of hepatocellular carcinoma (HCC) depends on early diagnosis. 2. The cure rate for operable HCC occurring in the absence of cirrhosis is only 10% to 25%. 3. Features of HCC in patients with cirrhosis that are associated with a 5-year survival rate of 75% after liver transplantation include (1) solitary tumor less than 5 cm; (2) 3 or fewer tumors, each less than 3 cm; and (3) absence of vascular invasion. 4. Advanced cirrhosis limits the widespread application of partial hepatectomy to patients with HCC. 5. Neoadjuvant therapy has not yet been proven to improve patient outcome for early-stage HCC that is promptly treated by transplantation.

Increased risk for posttransplant lymphoproliferative disease in recipients of liver transplants with hepatitis C.

Posttransplant lymphoproliferative disease (PTLD) is associated with immunosuppression and lymphotrophic viral infections. Hepatitis C virus (HCV) has been identified as a risk factor for non-Hodgkin's lymphoma, but no association between HCV and PTLD has been shown. To investigate this possibility, we identified patients with HCV who received their first orthotopic liver transplant at our unit between January 1, 1992, and December 31, 1996, and compared them with contemporary liver transplant recipients without HCV for incidence and risk factors for PTLD and survival. Fifty-seven patients with HCV and 127 patients without HCV were compared. There was no age difference (52 v 53 years; P =.85), but there were more men in the HCV group (man-woman ratio, 2.1:1 v 0.9:1; P =.006). No difference was observed in the follow-up period, graft survival, rejection episodes, or use of different immunosuppressive regimes (P >.05 for all). Four patients with HCV (7%) developed PTLD compared with 1 patient without HCV (0.8%; P =.02). The relative odds for developing PTLD in patients with HCV were 9.5. All patients who developed PTLD were administered OKT3 induction therapy. These data suggest that PTLD may be more prevalent in patients undergoing liver transplantation for HCV-related liver disease who also receive OKT3, and that HCV infection may be a risk factor for developing PTLD.

Periodic acid-Schiff staining abnormality in microvillous atrophy: photometric and ultrastructural studies.

BACKGROUND: The accumulation of periodic acid Schiff (PAS)-positive material in the epithelium in microvillous atrophy (MVA) is diagnostic but unexplained. It occurs earlier in the epithelial life cycle than the formation of microvillous inclusions and warrants further investigation. METHODS: Scanning photometry was used to assess the distribution of the PAS-positive material within epithelial cells and to assess how this changed with position on the crypt-villus axis. Thiery staining was applied to test the PAS positivity of the secretory granules, and quantitative ultrastructural morphometry was used to study secretory granule distribution in the epithelium. RESULTS: The PAS abnormality arose in upper crypt epithelium in congenital and late-onset MVA and continued up the villus. Thiery staining demonstrated that the secretory granules were PAS positive. Quantitative morphometry showed that secretory granules in congenital MVA were predominantly present in upper crypt and declined in the low villus. In late-onset MVA, secretory granules arose in the upper crypt but predominated in the low villus region. No evidence of secretory granule coalescence with the apical membrane was seen, although evidence of crinophagy was observed. Secretory granule profiles were seen, indicating that they formed part of a membrane-bound vesicular network within the cell, rather than existing simply as discrete bodies. The Golgi complex appeared normal. CONCLUSIONS: The secretory granules are responsible for the PAS-positive staining in upper crypt and low villus regions in MVA. They appear to form an intracytoplasmic vesicular network, undergo crinophagy, and decline in prominence in the low to midvillous region. The absence of evidence of coalescence with the apical membrane indicates that the secretory granules arise from a post-Golgi block in exocytosis rather than from endocytosis of gut luminal contents. Periodic acid-Schiff positivity in upper villous regions arises from microvillous inclusions and lysosomal bodies.

From here to infinity.

There are many abused words in the English language. Sometimes this is deliberate, for instance the slang use of 'wicked' to mean good, rather than bad or evil. At other times, it happens through a process of evolution, for example 'fabulous', which has changed from legendary and incredible to something very good. And then there are the words that are just misunderstood--like disinterested and infinite.

Liver transplantation for hepatic and biliary malignancy.

The treatment of liver cancer by transplantation has evolved into a process of selecting early stage tumors that have a high likelihood of cure. Carefully selected cirrhotic patients with early hepatocellular cancer (< or = 5 cm. diameter and single; < or = 3 cm. diameter if multiple and 3 or fewer lesions; no vascular invasion) have 5-year actuarial survival rates of approximately 75% after transplantation. Preoperative imaging should be as extensive as necessary to accurately define the characteristics of tumor size, location, and number and exclude signs of extrahepatic involvement. Adjuvant and neoadjuvant chemotherapy became part of treatment protocols in many centers at the same time that more stringent criteria for transplant candidacy were applied to patients with cancer, making it difficult to attribute improved results to the chemotherapy. Nevertheless, neoadjuvant chemoembolization for hepatocellular cancer is logical for patients who may wait long periods before receiving transplants. The fibrolamellar variant of hepatoma is a less aggressive tumor and patients can do well after transplantation, but late recurrences are common. Hepatoblastoma in children can respond very favorably to chemotherapy combined with transplantation. Cholangiocarcinoma remains a dreadful malignancy. The rare cases of insitu cholangiocarcioma in patients who receive transplants for sclerosing cholangitis can be cured, but known cholangiocarcinoma has an exceedingly high rate of recurrence after transplantation alone. Recent work combining chemotherapy and radiation with transplantation has not had dramatic success at improving cure rates. Patients with metastatic neuroendocrine tumors of the liver can receive good palliation by transplantation, but the majority of patients eventually develop recurrent cancer.

Use of antilymphocyte induction therapy in liver transplantation.

Polyclonal and monoclonal antilymphocyte agents (antilymphocyte globulin, antithymocyte globulin, OKT3, anti-interleukin-2 receptor antibody) are potent immunosuppressive agents that differ fundamentally in their mechanisms of action from cyclosporine- and tacrolimus-based induction therapy. Clinical trials and retrospective studies show low rates of acute rejection can be obtained when biological antilymphocyte agents are used for induction immunosuppression in liver transplant recipients. Infectious complications are similar to those of conventional induction regimens, and the incidence of posttransplant lymphoproliferative disease is acceptably low when excessive doses are not used. Published series of liver transplant recipients have so far not shown the clear superiority of antilymphocyte induction therapy, in terms of patient and graft survival, compared with standard therapy (cyclosporine or tacrolimus plus steroids and azathioprine). At present, there is no ideal induction regimen recommended for all patients.

Liver transplantation: past accomplishments and future challenges.

Liver transplantation has evolved from a rare and risky operation of questionable therapeutic value to the preferred treatment for an extensive list of end-stage liver diseases. Superior immunosuppression (cyclosporine), and improvements in surgery and anesthesia brought liver grafting to its current level of success. Nearly 60,000 liver transplants have been performed, and survival rates are very good; however liver grafting faces serious immediate and long term challenges, mainly due to the widening gap between donor supply and recipient demand. Increasing numbers of sick candidates, recurrent disease (especially hepatitis C) and recidivism rates after transplantation for alcoholic cirrhosis will force increasingly difficult decisions on candidate selection and priority listing of potential recipients. Although xenotransplantation may be the ultimate solution, it has its own specific set of biological and societal challenges - the full extent of which should be revealed in the next several years.

Liver transplant in adult Still's disease.

Adult Still's disease (ASD) is an uncommon form of polyarthritis associated with numerous systemic manifestations, including hepatic involvement. Rarely, liver involvement can be fatal. We describe the case of a young man with ASD with terminal liver failure who required a life saving liver transplant.

Key features distinguishing post-transplantation lymphoproliferative disorders and acute liver rejection.

Post-transplantation lymphoproliferative disorder (PTLD) and acute rejection are two serious complications of orthotopic liver transplantation that can have a similar histologic appearance. We undertook the present study to assess the best way to distinguish these two entities. We studied histologic features, immunophenotyping, and Epstein-Barr virus (EBV) status, as assessed by immunohistochemical stain and in situ hybridization (ISH), in three groups: Group I, 8 cases of PTLD post-orthotopic liver transplantation with liver involvement; Group II, 15 cases diagnosed with acute liver rejection (control group); and Group III, a subset of 6 biopsy specimens from 4 patients of Group I whose graft rejection was diagnosed within the 2 months preceding the diagnosis of PTLD. The mean proportion of plasma to plasmacytoid cells in most cases from Group I was more than 40%, whereas from Group II it was less than 25% (P = .0001). There was a higher number of B lymphocytes than T lymphocytes in Group I. The numbers of mitotic figures and immunoblasts were significantly different in the two groups (P < .0001 and P = .0005, respectively), being higher in the patients with PTLD. EBV immunostain was most specific for the diagnosis of PTLD (75% positive in Group I, negative in Group II). ISH for EBV-encoded RNA was positive in 87% of cases in Group I and only 6.6% of cases in Group II (P = .0005). In Group III, four of the six liver biopsy specimens had a low plasma cell count and were negative for EBV studies. The other two biopsy specimens in this group had 70 to 80% plasma cell infiltrate, in addition to positive EBV immunostain and ISH in one, for which tissue was available for study. We conclude that viral studies and assessment of the number of plasma cells and B lymphocytes can help to distinguish between acute rejection and early PTLD.

Biliary reconstruction without T tubes or stents in liver transplantation: report of 502 consecutive cases.

Although T tubes and stents are widely used as part of the routine biliary reconstruction in liver transplantation, they have inherent complications and there is no proof that they are beneficial to healing. We do not use T tubes or anastomotic stents, and we reviewed our experience with 502 consecutive, whole-size liver grafts to determine the incidence and nature of biliary complications. Duct-to-duct (D-D) and Roux-en-Y loop-to-duct (RY-D) anastomoses were performed in 321 and 176 cases, respectively. In 62% of cases, the donor gallbladder was transplanted and an external catheter cholecystostomy was fashioned to provide for postoperative cholangiography. In the remaining cases the gallbladder was removed. Biliary complications of all types occurred after 13.5% of the transplants. Anastomotic complications (stricture, obstruction, or leak) occurred in 8.2% of the cases, and they were least frequent (4.0%) with RY-D reconstructions. Gallbladder-related complications accounted for one quarter of all biliary complications, and they outweighed the advantage of convenient access to the biliary tree for cholangiography. Four patients (0.9%) died of biliary complications. We conclude that routine reconstruction of the biliary tract without T tubes or stents is a safe technique in liver transplantation. Retaining the donor gallbladder as a method of providing cholanglography is not necessary.