Posttransplantation lymphoproliferative disorder in liver recipients: characteristics, management, and outcome.

Posttransplantation lymphoproliferative disorder (PTLD) is a well-recognized complication of organ transplantation. The aim of this study, performed over 9 years, was to examine the histopathological findings, clinical course, and outcome of patients who, having undergone orthotopic liver transplantation (OLT), developed PTLD. The sample included 7 adult liver allograft recipients (1.7%), 4 men and 3 women, with a mean age of 53 years (range, 40 to 61 years) who developed PTLD 1 to 36 months post-OLT (mean, 6 months). Four patients received either antithymocyte globulin as primary immunosuppression or OKT3 for steroid-resistant cellular rejection. Four patients had localized hepatic tumor with or without regional lymph node involvement, 2 patients had extralymphoreticular disease (head of pancreas and chest wall), and 1 patient had spleen and lymph node involvement. All tumors were B-cell lymphomas; three polymorphic and four monomorphic. Clonality was assessed by immunostaining for kappa and lambda and gene rearrangement. Monoclonality was found in 4 patients and polyclonality in 2 (1 of whom progressed to monoclonality); in 2 patients, clonality could not be determined. Immunohistochemistry findings for the presence of the Epstein-Barr virus (EBV)-determined nuclear antigen and the latent membrane protein 1 were noted in lymphoma tissue in 6 patients. Immunosuppressive therapy was decreased in all patients. Polyclonal tumors were treated with acyclovir (1 patient is in complete remission and 1 patient died), and monoclonal tumors with systemic chemotherapy (2 patients are in complete remission and 2 patients died). One patient was treated with monoclonal antibodies (CD20) but failed to respond, and 1 patient was treated with excision and is in complete remission. The mortality rate was 43%; for the remainder, median survival is 21 months (range, 10 to 42 months). We conclude that PTLD may re-present early after OLT. EBV has a special role in the pathogenesis, combined with immunosuppressive therapy. The outcome is poor, and new therapeutic approaches are needed.     

Early posttransplant lymphoproliferative disease in pediatric liver transplant recipients

Among 23 pediatric patients who underwent orthotopic liver transplant (OLT), we report two (11 and 26 months old) with posttransplant lymphoproliferative disease (PTLD) that occurred in the early posttransplantation period. They were Epstein-Barr Virus (EBV)-negative and received graft from EBV-positive donors. The surveillance for EBV viremia using serial EBV polymerase chain reaction determinations in the peripheral blood was positive at 10 and 90 days after OLT concomitant with symptoms of primary infection, both patients were treated with gancyclovir. The patients should progression to a Burkitt's and a non-Hodgkin's lymphoma that appeared 3 months posttransplantation. They were treated by withdrawal of immunosuppression and six courses of cyclophosphamide as well as anti-CD20 monoclonal antibody (Rituximab) every 21 days. One patient experienced acute graft rejection, which resolved with steroids and low doses of tacrolimus, she is free of disease at 24 months after the end of treatment. The other patient relapsed with a cerebral lymphoma, receiving aggressive chemotherapy, but died due to sepsis. In conclusion, PTLD occurred among in 2/23 patients who underwent OLT and appeared in the first quarter post OLT. The risk factors associated with early PTLD were primary EBV infection after OLT, young age, and EBV-negative recipient receiving a transplant from an EBV-positive donor. Antiviral treatment alone was inefficient; withdrawal of immunosuppression and courses of Rituximab and cyclophosphamide were well tolerated and controlled PTLD. The risk of graft rejection was increased by withdrawal of immunosuppression. One patient died.     

Successful outcome of orthotopic liver transplantation in patients with preexisting malignant states

Preexisting malignancy is considered a relative contraindication to orthotopic liver transplantation (OLT) because of the risk of tumor recurrence. The purpose of this study is to assess the outcome of OLT in patients with a preexistent malignant state. Of 1,097 OLTs performed between 1989 and 1999 at King's College Hospital (London, UK), 18 patients had a pretransplantation malignant state, including 6 cases of myeloproliferative disorder (MPD) presenting as Budd-Chiari syndrome. Those patients with solid-organ malignancies had their tumor detected at an early stage and underwent curative treatment before or during OLT. Patients were followed up for a median of 71 months (range, 1 to 119 months) post-OLT, and the rates of rejection and malignancy were compared with those of transplant recipients without preexisting malignancy during the same period. One patient had a recurrence of his primary malignancy (non-Hodgkin's lymphoma) after 27 months, whereas another patient developed a de novo posttransplant lymphoproliferative disorder after 57 months. One patient with MPD developed acute leukemia 72 months after OLT. In comparison, of 1,079 OLTs performed in patients without preexisting malignancy during the same period, there were 34 cases of de novo malignancies. The rate of rejection in patients with and without preexisting malignancy was similar. Successful medium-term outcome after OLT can be achieved in carefully selected patients with preexisting malignancy providing the malignancy is amenable to curative treatment before or at OLT. Primary MPDs responsible for Budd-Chiari syndrome should not be considered a contraindication to OLT. (Liver Transpl 2001;7:11-15.)     

Post-transplant lymphoproliferative disorders after lung transplantation: first-line treatment with rituximab may induce complete remission

BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are potentially lethal complications of solid organ transplantation. We, here, report on our experience with rituximab, an anti-CD20 monoclonal antibody, as first-line treatment for PTLD in six lung transplant recipients. PATIENTS AND METHODS: Two of the patients developed PTLD during the first year after transplantation, while four developed late-onset PTLD. One patient presented with PTLD localized to the graft, one had unilateral cervical lymph nodes, and the others presented with multi-organ involvement. All patients had diffuse large B-cell lymphoma. Immunosuppressive therapy was reduced and rituximab was administered at a dose of 375 mg/m(2)/wk for 4 wk. RESULTS: One patient did not respond to the first two courses of rituximab, received conventional chemotherapy, and achieved complete remission; four patients achieved complete remission after four courses with a median relapse-free survival of 34 months (range: 14-55); and one patient did not respond and died. The diagnosis of complete remission was established by conventional imaging techniques combined to whole-body positron emission tomography scan. CONCLUSIONS: We conclude that reduction in immunosuppression combined to first-line treatment with rituximab may induce long-term complete remission in lung transplant recipients presenting PTLD.     

Liver transplantation for primary biliary cirrhosis: influence of primary immunosuppression on survival

INTRODUCTION: Liver transplantation is the only established curative therapy for end-stage primary biliary cirrhosis (PBC). However, the influence of primary immunosuppression on long-term patient and graft survival is still controversial. PATIENTS AND METHODS: Among 1372 patients who underwent liver transplantation from April 1989 to January 2001, 95 (6.9%) suffered from PBC. The primary immunosuppression consisted of cyclosporine (CyA; n = 56) and tacrolimus (FK; n = 39). RESULTS: The median survival of all PBC patients at 5 years was 92% and at 10 years, 90%. There was no difference between the two primary immunosuppression agents. Seven patients died, including five in the cyclosporine group (median = 25 months) and two in the tacrolimus cohort (median = 37 months). One CyA patient group died due to PBC recurrence. Seven patients underwent retransplantation without any difference in primary immunosuppression (CyA 7%; FK 10%). Fifty patients developed an acute rejection episode (CyA 57%; FK 46%); 2 patients, chronic rejection (CyA 2%; FK 4%). Fifty-five patients developed AMA titers after liver transplantation (CyA 66%; FK 46%). Patients presented cyclosporine-based regimens showed significantly (P = .001) more side effects. CONCLUSION: Long-term follow-up after liver transplantation for PBC shows excellent organ and patient survival. The choice of the primary immunsuppressant had no significant influence on patient survival, PBC-related graft loss, or development of acute or chronic rejection episodes.     

Liver transplantation in childhood with more than 10 years of follow-up: analysis of a single-center experience

We pioneered pediatric liver transplantation (OLT) in Spain (June 1985). The aim of this study was to evaluate the current status of our OLT recipients with more than 10 years follow-up. MATERIALS AND METHODS: The 50 patients with >10 years follow-up had a mean age at OLT of 5.6 years with 60% showing a main indication of biliary atresia. All but one (tacrolimus) received cyclosporine. RESULTS: No patient loss occurred among these patients. Eighteen patients had follow-up >15 years and 12 >20 years. The incidence of acute rejection was 56%; chronic rejection, 16%; and lymphoproliferative disorders, 12%. Seven (14%) required retransplantation at a mean of 4.2 years after the first OLT due in four instances to chronic rejection. After 10 years of follow-up, one patient developed portal vein thrombosis and three biliary strictures. All patients remain on immunosuppression. In 64% cyclosporine was switched to tacrolimus or another agent. One patient developed acute rejection at 19.2 years. In 14% of patients the liver function test is abnormal with serum creatinine is >1.5 mg/dL in 10%; one requires insulin and three, antihypertensive drugs. Noncompliance with medications was detected in 10%. Three recipients had offspring. CONCLUSIONS: OLT was an effective treatment with a good quality of life also on long-term follow-up.     

Anthracycline-based chemotherapy as first-line treatment in adults with malignant posttransplant lymphoproliferative disorder after solid organ transplantation

BACKGROUND: Recommended first-line treatment for posttransplant lymphoproliferative disorder (PTLD) is reduction in immunosuppressive therapy, irrespective of histopathological type. Second-line treatment with chemotherapy is generally reserved for tumors that fail to respond to reduced immunosuppression. In view of the similarities between monomorphic PTLD and non-Hodgkin's lymphoma in the general population, our policy is to treat monomorphic PTLD with anthracycline-based chemotherapy as first-line treatment. METHODS: A retrospective single-center analysis of 18 adults who developed PTLD following liver or kidney transplantation was undertaken, with particular emphasis on tumor histology, treatment received, and clinical outcome. RESULTS: Of the 18 patients with PTLD, 13 had high-grade malignant lymphoma on diagnostic biopsy and received anthracycline-based chemotherapy and reduction in immunosuppression as first-line therapy. Nine (69%) of the 13 patients achieved complete remission and eight (62%) remained in complete remission five years after diagnosis. There was no graft loss from rejection or drug toxicity. Four (22%) patients had polymorphic PTLD on diagnostic biopsy (of which two were re-classified as monomorphic) and one had a low-grade malignant lymphoma. All five patients were treated by reduction in immunosuppression without chemotherapy and were in complete remission at a median of two years after diagnosis. Overall, complete remission was seen in 14 out of 18 patients (78%) at one year following diagnosis. CONCLUSION: The use of anthracycline-based chemotherapy and reduction of immunosuppression as first-line treatment in adults with monomorphic PTLD is well tolerated and achieves sustained complete remission in around 70% of patients with a low risk of graft loss.     

Successful treatment of posttransplant lymphoproliferative disease with prolonged rituximab treatment in intestinal transplant recipients

BACKGROUND: Posttransplant Epstein-Barr virus-associated B-cell lymphoproliferative disease (PTLD) has a higher incidence after intestinal transplantation than after transplantation of other solid organs and is associated with a high mortality. A new anti-CD20 monoclonal antibody, rituximab, has shown efficiency in the treatment of B-cell lymphoma, including PTLD, but its use has not yet been reported in intestinal transplant recipients. METHODS: We retrospectively reviewed five patients who were diagnosed with PTLD from March 1999 to August 2001, after intestinal transplantation. These patients were primarily managed with rituximab, associated with reduction or interruption of immunosuppression and antiviral therapy with ganciclovir and cytomegalovirus immune globulin. Rituximab was administered at weekly doses of 375 mg/m until full remission was ascertained, and the interval between doses was then increased. No patient received chemotherapy. RESULTS: One patient had nonmalignant lymphoproliferation, and four had malignant PTLD, as assessed by histopathology and monoclonality of the tumor. Two pediatric patients had severe generalized disease. All patients had received OKT3 as treatment of rejection before developing PTLD. All tumors showed proliferation of CD20 cells and were positive for Epstein-Barr virus by in situ hybridization. All patients responded to rituximab therapy and have achieved full remission with a follow-up of 3 to 30 (median, 8) months. CONCLUSION: Prolonged rituximab treatment, in association with reduction of immunosuppression and antiviral therapy, is highly efficient as part of the first-line treatment of CD20 B-cell PTLD after intestinal transplantation.     

Fatal sclerosing peritonitis associated with primary effusion lymphoma after liver transplantation: a case report

Sclerosing peritonitis (SP) after liver transplantation has been described in 10 cases in the literature. The etiology is still unknown; however, SP is considered a consequence of chronic irritation and inflammation. It can be classified as primary (idiopathic) or secondary form. Although pathologically benign, it has a negative course, resulting in unrelenting abdominal pain, small bowel obstruction, malnutrition, and death. Posttransplantation lymphoproliferative disease (PTLD) is one of the leading causes of late death. Its development is related to complex interactions between immunosuppressive drugs and environmental agents. Primary effusion lymphoma (PEL) as an onset presentation of PTLD is relatively uncommon. Most examples of effusion-based PTLD have been secondary to widespread solid organ involvement and associated with Human herpes virus 8 (HHV-8) recurrence. Here in, we report a case of a 55-year-old man who rapidly developed refractory ascites and bacterial peritonitis at 1-year after orthotopic liver transplantation (OLT) with a fatal clinical course at the beginning of the second follow-up year after an uncomplicated liver transplantation due to cryptogenic cirrhosis. The diagnosis of HHV-8-positive lymphoma was established by postmortem examination with multiple solid localizations and massive dense fibrotic adhesions encompassing the small intestine, colon, liver, and porta hepatis without any involvement of body cavities.     

Liver replacement after massive hepatic trauma

Two patients sustained massive hepatic injuries from blunt trauma in motor vehicle accidents. At the time of operation, nonreconstructable injuries to the porta hepatis were found in addition to destruction of the right lobe. Life-threatening hemorrhage was controlled, but both patients were left with nonfunctional or inadequate hepatic remnants. Liver transplantation was performed. Both patients recovered after liver replacement. One died 7 weeks later of cytomegalovirus infection. The other recipient is well 16 months later. Liver transplantation is a reasonable option in patients with lethal hepatic injuries or unreconstructable injuries to the porta hepatis.     

Tolerance: is it worth the risk?

BACKGROUND: The success of orthotopic liver transplantation (OLT) has been limited by the adverse effects of immunosuppression. The purpose of this study was to determine the safety and feasibility of withdrawing immunosuppression in OLT recipients to achieve tolerance. METHODS: Eighteen adult OLT recipients in our steroid-free protocol without rejection were selected for this protocol. All patients chosen for this trial were on tacrolimus monotherapy with normal liver function tests (LFTs). Tacrolimus was weaned as long as LFTs remained stable. Weaning was halted for elevations of liver enzymes and tacrolimus was increased to the last dosage at which the patients had normal LFTs. Rejection was treated by increasing tacrolimus to levels of 10-15 ng/ml. Mycophenolate mofetil (MMF) or sirolimus was added if there was severe rejection by biopsy. Steroids were used if there was no improvement. RESULTS: One patient has been weaned off immunosuppression. Three additional patients were weaned completely off but had tacrolimus resumed because of mild elevations in LFTs. Eleven of 18 (61%) patients had rejection. Two patients required steroid therapy and one required rabbit antithymocyte globulin in addition to MMF and steroids. One of the patients with rejection developed diabetes and one patient had renal failure, which subsequently resolved. One patient died following a stroke. CONCLUSIONS: Clinical tolerance can be achieved in a minority of patients, even when being maintained on minimum immunosuppression. The potential benefit of achieving tolerance must be weighed against the risks of rejection therapy in patients doing well on low-dose immunosuppression.     

Orthotopic liver transplantation for incurable alveolar echinococcosis: report of five cases from west China

Alveolar echinococcosis of the liver, caused by the larval stage of Echinococcus multilocularis, has the characteristics of a slow-growing liver cancer. The aim of the present work was to report a series of patients who received orthotopic liver transplantation (OLT) for life-threatening disease. Our article summarizes the medical history, diagnosis, treatment, and prognosis of five patients who received OLT between 2001 and 2002. Most patients had a long history of symptomatic disease (iterative cholangitis, obstructive jaundice) and repeated abdominal surgery. One patient died during the hospitalization mostly related to bacterial infection and multiple organ failure. Another accidental death happened 3 months later from heart failure. Three patients are alive in good condition verifying that OLT is a feasible option for these end-stage cases. In general, combination therapy-chemotherapy, interventional therapy, radical surgery or/and OLT at an early stage-is proposed in advanced cases of which OLT has clearly played a vital role. Despite major technical difficulties, OLT for incurable disease is feasible. Specific management is needed to improve the results: earlier decision for OLT in symptomatic disease, routine pre- and post-transplant therapy, reduced immunosuppression, and regular follow-up.     

Posttransplant lymphoproliferative disorder in pediatric renal transplantation

Of 84 renal transplants performed in our center since 1986, six recipients (7.1%) developed posttransplant lymphoproliferative disorder (PTLD). All received quadruple immunosuppression with Minnesota anti-lymphoblastic globulin or anti-thymocyte globulin, methylprednisolone, cyclosporine, and azathioprine or mycophenolate mofetil. Five were seronegative for Epstein-Barr virus (EBV) when they received their renal transplant. All patients received prophylactic acyclovir treatment postrenal transplant and none developed a cytomegalovirus (CMV) infection. All patients were positive for EBV by serology and polymerase chain reaction at the time of diagnosis of PTLD. Clinical features at presentation included fever (6/6), adenopathy (4/6), hypertrophied adenoids (4/6), liver involvement (2/6), and allograft involvement (2/6), 2–78 months (4/6<6 months) postrenal transplant. Histopathology of PTLD tissue revealed T cell rich/ Hodgkin disease-like B cell PTLD in one patient, polymorphic PTLD in four, and monomorphic (large B cell lymphoma) PTLD in one. Immunophenotyping of the PTLD biopsy specimen revealed predominant T cells in three, mixed B and T cells in two patients, and B cell in one. No aneuploid populations were identified by flow cytometric DNA ploidy assay. DNA from the PTLD tissue revealed weak to moderate IgH gene rearrangement in four of six patients but no T cell receptor β-chain or c-myc gene rearrangement on Southern blot analysis. The child with monomorphic (large B cell lymphoma) PTLD was clonal with λ light chain restriction on immunophenotyping. Treatment consisted of reduced immunosuppression and ganciclovir/ acyclovir in all patients. CMV hyperimmune globulin was used as an adjunctive therapy in two patients. Chemotherapy was needed in only one patient. A single rejection episode occurred in two children following reduction in immunosuppression, which reversed following intravenous methylprednisolone therapy. PTLD resolved in all patients and at present all patients are alive with functional grafts 2–54 months post diagnosis. Our experience suggests that reduced immunosuppression and anti-viral treatment is adequate in most cases of PTLD, but chemotherapy and hyperimmune globulin therapy may be beneficial in cases resistant to first-line therapy. Since all but one of our patients were EBV seronegative at the time of transplant, vigilance is especially important for early detection of PTLD in this group of the pediatric renal transplant population. Received: 17 November 1998 / Revised: 4 February 1999 / Accepted: 4 February 1999     

Successful outcome with a "quintuple approach" of posttransplant lymphoproliferative disorder

BACKGROUND: The treatment of posttransplant lymphoproliferative disorder (PTLD) remains empirical. We review our treatment of seven cases of PTLD consisting of five interventions: 1) reduction of immunosuppression; 2) antiviral drugs; 3) interferon-alpha; 4) gamma-globulins; and 5) anti-CD19 monoclonal antibodies. METHODS AND RESULTS; Seven consecutive patients who had undergone a simultaneous pancreas-kidney, liver, heart, or kidney transplantation were treated. One patient acquired a primary EBV infection with an oligoclonal immunoblastic lymphoma early after pancreas-kidney transplantation; all others developed a monoclonal polymorphic or immunoblastic lymphoma 2 to 123 months after transplantation. In all patients extranodal sites were involved, in three the graft was also involved. Five patients received the full quintuple approach and all rapidly obtained a complete remission (CR) with a median follow-up of 31 months (7-74 months). Of the two patients who did not receive interferon-alpha for fear of graft rejection one responded slowly with a CR after 7 months, and the other obtained a rapid CR followed by a relapse at 4 months. All three patients with a liver or heart transplant could keep their graft. All patients are still alive with a median follow-up of 31 months (7-74 months). CONCLUSION: This combined approach resulted in a favorable outcome in patients with high risk monoclonal PTLD after solid organ transplantation.     

Postransplant lymphoproliferative disorder localized near the allograft in renal transplantation

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD), a complication of immunosuppression, develops in approximately 1% of renal allograft recipients. Typically, PTLD is a proliferation of B-cells associated with Epstein-Barr virus (EBV) infection; it is said to be most often a systemic disease. Involvement occasionally is localized near the allograft. METHODS: This is a retrospective analysis of all cases of PTLD in recipients of 1474 renal transplants performed at University of Alabama at Birmingham between 1993 and 1997. RESULTS: Of 14 patients developing PTLD, 10 had disease localized near the allograft. The mean interval from transplantation to diagnosis was 221 +/- 70 days. All patients presented with renal dysfunction; an ultrasound examination revealed a hilar mass, with hydronephrosis in five and stenosis of renal vessels in eight. No patient had lymphadenopathy, according to computerized tomographic or magnetic resonance imaging findings. After reduction of immunosuppressive therapy, seven required a nephrectomy because of rejection, progressive dysfunction, or mass enlargement. Tissue recovered in four patients was consistent with PTLD; the tumors in the remaining three patients were unresectable and regressed. One patient died 1 month after a nephrectomy, and another died 4 years after surgery; neither had evidence of PTLD when they died. Three patients retain functional grafts without clinical or radiographical evidence of progression. All patients with disseminated disease died. CONCLUSIONS: In a large cohort of renal allograft recipients, PTLD affected 1%. Disease localized near the allograft was the most common variant. For most patients with localized disease, the outcome was graft loss, and the mortality was low. Localized PTLD should be considered in the differential diagnosis of allograft dysfunction in the 1st posttransplant year.     

肝中央区肝肿瘤的手术切除

目的 探讨位于肝中央区肝肿瘤手术切除的安全性和可行性。方法 回顾性分析近6年经手术切除位于肝中央区的肝肿瘤36例的临床资料,其中肝癌26例,良性肿瘤10例。肿瘤累及第一肝门者13例,第二肝门10例,第三肝门5例,同时累及第一和第三肝门3例,第二和第三肝门5例。结果 全组术中并发大出血4例(11．1％),术后发生并发症11例(30．5％),包括肝衰竭1例(2．7％),胆瘘2例(5．5％),胸腔积液6例(16．7％),膈下感染1例(2．7％),腹壁切口疝1例(2．7％);除1例因急性肝衰竭术后死亡外,余均恢复出院。结论 此类手术难度大、风险大．只要术前重视适应证的选择,术中妥善处理,仍可成功切除肿瘤,减少并发症的发生。     

Orthotopic liver transplantation in human immunodeficiency virus (HIV)-positive patients: outcome of 7 patients from the Bonn cohort.

The outcome and clinical features of 7 HIV-positive patients who were liver transplanted at Bonn University in the era of highly active antiretroviral therapy (HAART) between 1997 and 2004, analyzed by retrospective chart review, are reported. Reasons for orthotopic liver transplantation (OLT) were end-stage liver disease due to chronic hepatitis C (n = 4) or hepatitis B (n = 1) or acute liver failure due to fulminant hepatitis B (n = 2). Immunosuppression was based on cyclosporine A and prednisone. HAART was reinitiated 1 month after transplantation, and immunosuppression was carefully adapted to account for drug-drug interactions between cyclosporine A and protease inihibitors. Prednisone was withdrawn 5 months (median) after OLT when immunosuppression had been reliably established in the presence of HAART. One patient died 95 days after OLT due intrathoracic hemorrhage, whereas 6 patients were alive at a median of 24 months. A single episode of acute rejection was observed. The spectrum of postoperative complications was no different from HIV-negative patients apart from Kaposi's sarcoma and multicentric Castleman's disease in a single patient. Recurrent hepatitis B infection was efficiently prevented, whereas hepatitis C reinfection occurred in all 4 patients who had preexisting hepatitis C. Earlier reports on fatal courses of recurrent hepatitis C infection, high rates of organ rejection, and HAART-related liver toxicity were not observed in our patients. In conclusion, even though preliminary, our data suggest that outcomes after liver transplantation of HIV-infected patients can be improved.     

Initial clinical results of orthotopic liver transplantation for hepatic alveolar echinococcosis.

We analyzed the features of 7 patients who underwent orthotopic liver transplantation (OLT) from April 2001 to April 2006 for incurable hepatic alveolar echinococcosis (AE) in view of the technical features of the OLT, incidence, and type of complications, as well as patient survival. All 7 patients had biliary diseases that resulted from parasitic involvement of the hilum or a large parasitic lesion that invaded the lobes of the liver due to parasitic involvement of the hepatic veins, which are all typical syndromes of hepatic AE. Five patients had previously undergone surgery for hepatic AE and were at the end stage of liver functional disorder. Four patients' operations were performed under venovenous bypass. The mean duration of surgery was 9.1 hours. After transplantation, one patient experienced biliary leakage but was successfully treated with reoperation. One patient died 21 days later of septicemia caused by pneumonia and multiple organ failure, and another patient died 3 months after OLT from heart failure. The other 5 patients are alive and in good condition after transplantation. Although the transplantation procedure was more difficult than usual in these patients, most achieved prolonged survival and a good quality of life. This study suggests that OLT is feasible for incurable AE of the liver and that this procedure ensures a good clinical outcome.     

Post‐transplant lymphoproliferative disorder in adult liver transplant recipients: a South American multicenter experience

Post‐transplant lymphoproliferative disorder (PTLD) is a major and potentially life‐threatening complication after solid‐organ transplantation. The aim of this study was to describe the disease characteristics, clinical practices, and survival related to PTLD in adult orthotopic liver transplant (OLT) recipients in South America. We conducted a survey at four different transplant groups from Argentina, Brazil, and Chile. Among 1621 OLT recipients, 27 developed PTLD (1.7%); the mean age at diagnosis was 53.7 (±14) yr with a mean time of 39.7 (±35.2) months from OLT to PTLD diagnosis. Initial therapy included reduction in immunosuppression alone in 23.1% of the patients. Either rituximab or chemotherapy was employed as initial or second‐line therapy in 76.9% of the patients. PTLD location was frequently extranodal (80.7%) and mostly involving the transplanted liver (59.3%). The overall survival at one and five yr post‐PTLD diagnosis was 53.8% and 46.2%, respectively. Significant univariate risk factors for post‐PTLD mortality included lactate dehydrogenase ≥250 U/L (HR 9.66, p = 0.02), stage III/IV PTLD (HR 5.34, p = 0.004), and HCV infection (HR 7.68, p = 0.01). In conclusion, PTLD in OLT adult recipients is predominantly extranodal, and although mortality is high, long‐term survival is possible.     

Loss of speech after orthotopic liver transplantation

Alteration of speech is a rare but distressing complication of orthotopic liver transplantation (OLT). We describe a characteristic speech disorder identified in a large series of consecutive patients undergoing OLT. Between 1988 and 1993, 525 adults underwent OLT. For all recipients with neurologic complications, we reviewed clinical findings, imaging and electrophysiologic test results, and perioperative laboratory data. Five patients (ages 23–52; UNOS status 3–4) exhibited a characteristic pattern of stuttering dysarthria, leading to complete loss of speech production, occasionally with elements of aphasia. In four of the five patients, right-sided focal seizures were subsequently noted. All cases presented within the first 10 postoperative days and improved within 1 month of cessation of cyclosporin (CyA), although halting, monotonous speech was evident to some degree in all five for up to 1 year. There was no correlation between onset of symptoms and CyA levels. None of the patients had clinical or radiologic findings suggestive of central pontine myelinolysis or akinetic mutism. EEGs and Spect scan results were consistent with dysfunction in the left frontotemporoparietal regions of the brain. A characteristic speech disorder, which may be described as cortical dysarthria or speech apraxia, occurs in approximately 1% of adults undergoing OLT. Prompt recognition of this syndrome and temporary cessation of CyA therapy may favorably affect the course.