Liver transplantation for patients with alcoholic liver disease: An open question

End-stage alcoholic liver disease is a recognised indication for liver transplantation but some questions on the matter remain open. It is difficult to quantify alcohol consumption, and a single definition of post-transplant relapse is lacking. Moreover, there are no internationally accepted criteria for the selection of candidates for liver transplantation and the eligibility parameters for these patients are controversial. Additional clinical and psychological evaluations are necessary in this setting, especially to establish the risk of alcohol relapse. Nevertheless, patient and graft survival rates after liver transplantation in alcoholic liver disease are comparable to those after transplant for other aetiologies, alcohol consumption relapse being one of the most important problems in the post-transplant phase.In conclusion, alcohol-related liver disease is a good indication for liver transplantation. The main future goals are to formulate a well-defined pre-transplant approach and a single definition of alcohol relapse and to improve prevention strategies.     

Gastrointestinal complications after kidney transplantation

Gastrointestinal complications are common after renal transplantation, and they have a wide clinical spectrum, varying from diarrhoea to post-transplant inflammatory bowel disease(IBD). Chronic immunosuppression may increase the risk of post-transplant infection and medication-related injury and may also be responsible for IBD in kidney transplant re-cipients despite immunosuppression. Differentiating the various forms of post-transplant colitis is challenging, since most have similar clinical and histological features. Drug-related colitis are the most frequently encountered colitis after kidney transplantation, particularly those related to the chronic use of mycophenolate mofetil, while de novo IBDs are quite rare. This review will explore colitis after kidney transplantation, with a particular focus on different clinical and histological features, attempting to clearly identify the right treatment, thereby improving the final outcome of patients.     

Bridge to lung transplantation and rescue post-transplant: the expanding role of extracorporeal membrane oxygenation

Over the last several decades, the growth of lung transplantation has been hindered by a much higher demand for donor lungs than can be supplied, leading to considerable waiting time and mortality among patients waiting for transplant. This has led to the search for an alternative bridging strategy in patients with end-stage lung disease. The use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation as well as a rescue strategy post-transplant for primary graft dysfunction (PGD) has been studied previously, however due to initially poor outcomes, its use was not heavily instituted. In recent years, with significant improvement in technologies, several single and multi-center studies have shown promising outcomes related to the use of ECMO as a bridging strategy as well as a therapy for patients suffering from PGD post-transplant. These results have challenged our current notion on ECMO use and hence forced us to reexamine the utility, efficacy and safety of ECMO in conjunction with lung transplantation. Through this review, we will address the various aspects related to ECMO use as a bridge to lung transplantation as well as a rescue post-transplant in the treatment of PGD. We will emphasize newer technologies related to ECMO use, examine recent observational studies and randomized trials of ECMO use before and after lung transplantation, and reflect upon our own institutional experience with the use of ECMO in these difficult clinical situations.     

UCSF criteria by pre-transplant radiologic study can not assure similar post-transplant results of hepatocellular carcinoma within Milan criteria

The recurrence of hepatocellular carcinoma (HCC) after transplantation is the main limitation of liver transplantation. Therefore, several selection criteria for liver transplantation in HCC patients have been established. The objective of this study was to verify the clinical validity of selection criteria evaluated by pre-transplant radiologic imaging study. Sixty-nine participants were enrolled for this study between September 2005 and May 2007. We analyzed the post-transplant survival and recurrence rate using radiologic selection criteria and other clinical factors. Grouping by pretransplant criteria for liver transplantation, 16 recipients (23.2%) were above Milan criteria and 7 recipients (10.1%) were above UCSF criteria. Nine recipients (13.0%) were grouped as above Milan/below UCSF. The recipients who met Milan showed 85.8% 1-year survival rates, which was comparable to that of non-HCC (91.6%) (p = 0.767). During the post-transplant follow-up period (1-52 months, 14.81 +/- 12.0 months), 16 recurrences (23.2%) were diagnosed. The 1-year recurrence-free survival rate of recipients who met the Milan criteria was 78.6%, and those that did not meet these criteria was 22.7% (p < 0.0001). With regard to UCSF criteria, these percentages were 72.0% and 14.2%, respectively (p < 0.0001). According to a combined grouping, the 1-year recurrence-free survival rate was 25.4% in the above Milan/below UCSF group. There were significant differences among each of the groups (overall p < 0.0001). The application of UCSF criteria that are defined by pre-transplant radiologic findings as patient selection criteria for liver transplantation is limited.     

肝移植治疗原发性胆汁性肝硬化的疗效分析

目的 观察原发性胆汁性肝硬化(PBC)患者和移植肝的实际生存时间,肝移植后死亡的原因及肝移植后的复发率。 方法 根据QLTS的数据库中的随访资料,回顾性分析52例共接受54次肝移植的PBC患者。52例PBC肝移植患者中,平均年龄(5 3.2±6.7)岁,平均随访时间是(5 5.4±11.3)个月。分析术前的临床特征、移植后生存情况和死亡原因,采用欧洲模式计算未接受肝移植患者和接受肝移植的患者的生存率。 结果 PBC肝移植患者的1、5、1 0年的实际生存率分别为8 8.4％、80.1％和76.9％,未接受肝移植患者实际生存率分别为80.9％、6 5.4％和19.8％。PBC患者移植后的生存率比未接受肝移植的患者(欧洲模型)预期生存率高。有6例患者经肝活检后证实PBC复发,平均复发时间(34.1±10.2)个月。肝移植术后死亡的原因是多器官功能衰竭、腹腔内出血、肾功能衰竭、败血症及心血管疾病。 结论 肝移植可提高P B C患者的生存率,延长其生存时间。     

Setting the standard in T-cell-depleted haploidentical transplantation and beyond

Much progress has been made in the clinical, biological and technical aspects of the T-cell-depleted haploidentical hematopoietic stem cell transplantation (HSCT). Our experience demonstrates that infusing a megadose of extensively T-cell-depleted hematopoietic peripheral blood stem cells after an immuno-myeloablative conditioning regimen in acute leukemia patients ensures sustained engraftment with minimal GvHD without the need of any post-transplant immunosuppressive treatment. Since our first successful pilot study, our efforts have concentrated on developing new conditioning regimens, optimizing the graft processing and improving the post-transplant immunological recovery. The results we have so far achieved in high risk acute leukemia patients show that haploidentical transplantation is now a clinical reality. The present challenge is to reduce post-transplant infectious mortality and several strategies are being tested.     

Benefits of PEGylation in the early post-transplant period of intraportal islet transplantation as assessed by magnetic resonance imaging of labeled islets

While a few studies have demonstrated the benefit of PEGylation in islet transplantation, most have employed renal subcapsular models and none have performed direct comparisons of islet mass in intraportal islet transplantation using islet magnetic resonance imaging (MRI). In this study, our aim was to demonstrate the benefit of PEGylation in the early post-transplant period of intraportal islet transplantation with a novel algorithm for islet MRI. Islets were PEGylated after ferucarbotran labeling in a rat syngeneic intraportal islet transplantation model followed by comparisons of post-transplant glycemic levels in recipient rats infused with PEGylated (n = 12) and non-PEGylated (n = 13) islets. The total area of hypointense spots and the number of hypointense spots larger than 1.758 mm² of PEGylated and non-PEGylated islets were quantitatively compared. The total area of hypointense spots (P < 0.05) and the number of hypointense spots larger than 1.758 mm² (P < 0.05) were higher in the PEGylated islet group 7 and 14 days post translation (DPT). These results translated into better post-transplant outcomes in the PEGylated islet group 28 DPT. In validation experiments, MRI parameters obtained 1, 7, and 14 DPT predicted normoglycemia 4 wk post-transplantation. We directly demonstrated the benefit of islet PEGylation in protection against nonspecific islet destruction in the early post-transplant period of intraportal islet transplantation using a novel algorithm for islet MRI. This novel algorithm could serve as a useful tool to demonstrate such benefit in future clinical trials of islet transplantation using PEGylated islets.     

Benefits of PEGylation in the early post-transplant period of intraportal islet transplantation as assessed by magnetic resonance imaging of labeled islets

While a few studies have demonstrated the benefit of PEGylation in islet transplantation, most have employed renal subcapsular models and none have performed direct comparisons of islet mass in intraportal islet transplantation using islet magnetic resonance imaging (MRI). In this study, our aim was to demonstrate the benefit of PEGylation in the early post-transplant period of intraportal islet transplantation with a novel algorithm for islet MRI. Islets were PEGylated after ferucarbotran labeling in a rat syngeneic intraportal islet transplantation model followed by comparisons of post-transplant glycemic levels in recipient rats infused with PEGylated (n = 12) and non-PEGylated (n = 13) islets. The total area of hypointense spots and the number of hypointense spots larger than 1.758 mm² of PEGylated and non-PEGylated islets were quantitatively compared. The total area of hypointense spots (P < 0.05) and the number of hypointense spots larger than 1.758 mm² (P < 0.05) were higher in the PEGylated islet group 7 and 14 days post translation (DPT). These results translated into better post-transplant outcomes in the PEGylated islet group 28 DPT. In validation experiments, MRI parameters obtained 1, 7, and 14 DPT predicted normoglycemia 4 wk post-transplantation. We directly demonstrated the benefit of islet PEGylation in protection against nonspecific islet destruction in the early post-transplant period of intraportal islet transplantation using a novel algorithm for islet MRI. This novel algorithm could serve as a useful tool to demonstrate such benefit in future clinical trials of islet transplantation using PEGylated islets.     

Outpatient care of the cystic fibrosis patient after lung transplantation

Lung transplantation has become an accepted treatment for respiratory failure due to cystic fibrosis (CF). Effective means of patient selection, surgical technique, immunosuppression, and post-transplant management permit survival as good as that of transplant patients with other diseases. The new lungs do not acquire the CF ion transport abnormalities but are subject to the usual post-transplant complications. CF problems in other organ systems persist and may be worsened by some of the immunosuppressive regimens. Prolonged survival increases the risk of age-related CF and other complications. Effective medical management requires expert knowledge of CF and lung transplantation and of how their problems interact, and good communications among the participating care teams.     

Recurrent Epstein–Barr virus associated disease in a cardiac transplant patient: evolution from plasmacytic hyperplasia to diffuse large cell lymphoma

Abstract: An Epstein–Barr virus (EBV)-seronegative 31-year-old male underwent cardiac transplantation in 1991 for congenital cardiomyopathy. He presented with a protracted course of waxing and waning lymphadenopathy beginning four years after transplantation with eventual progression to a fulminant EBV-positive large cell lymphoma eight years after transplantation. Risk factors for the development of post-transplant lymphoproliferative disease in this patient, the importance of a standardized approach to pathology in assessing therapeutic options, and the management strategies used are discussed.     

A problem-oriented approach to intestinal and liver disease after marrow transplantation

Bone marrow transplantation has become an accepted treatment for malignancy (particularly leukemia and lymphoma), aplastic anemia, and certain inborn errors of metabolism. Patients require intensive care because of chemoradiation therapy toxicity, a prolonged period of immunosuppression and thrombocytopenia, graft-versus-host disease (GVHD), and the need for parenteral nutrition. Gastrointestinal and hepatic diseases are frequent post-transplant problems. They present with intractable nausea and vomiting, intestinal bleeding, diarrhea, esophageal complaints, abdominal pain, and hepatobiliary symptoms. Our clinical approach to complex transplant patients depends on the timing of signs and symptoms after marrow grafting and on the likelihood that specific disease processes are present. Each of these major problems is covered in this review.     

Role of liver transplantation in acute liver failure

Orthotopic liver transplantation is employed as salvage therapy for individuals who are unable to recover from acute liver failure. Prognostic models are helpful but not entirely accurate in predicting those who will eventually require liver transplantation. There are specific criteria for United Network for Organ Sharing category 1a (urgent) listing of these patients. Unfortunately, clinical deterioration develops rapidly and many require removal from the waiting list prior to transplantation. With advances in critical care management and surgical technique, 1-year post-transplant survival rates have improved to 60 to 80%. Alternatives to conventional orthotopic liver transplantation include living donor liver transplantation, ABO-incompatible grafts, and auxiliary liver transplantation. There are many ethical and psychosocial issues inherent to transplanting these sick patients due to the urgent nature of acute liver failure. Fortunately, the long-term survival and quality of life in these transplant recipients is good.     

An unusual case of groin discomfort.

Groin complications after cardiac catheterizations are common. With the increasing use of mechanical hemostatic devices, cardiologists must be alert to a wide array of potential problems. We report an unusual complication after the use of a closure device.     

Cardiac and cardiovascular consequences after haematopoietic stem cell transplantation

Haematopoietic stem cell transplantation (HCT) is the treatment of choice for defined malignant and non-malignant haematological disorders. The main drawbacks of HCT are early transplant-related mortality and late complications, which interfere with patient outcome, health status and quality of life. In comparison with other post-transplant complications, cardiac or cardiovascular consequences seem to occur at a much lower frequency. Early complications are usually associated with patient history before transplantation, primary diagnosis, age of the patient and associated comorbidities, and the type of transplantation and conditioning used. Late cardiac and cardiovascular events may occur years and even decades after HCT, and are related to cardiotoxic chemotherapy, mediastinal radiation therapy, gender, age at transplantation, cardiovascular risk factors and graft-versus-host disease in allogeneic HCT. As has been observed in long-term survivors of Hodgkin lymphoma, where the incidence of cardiovascular complications emerged as a significant problem with increasing follow-up, it is anticipated that the incidence of these complications after HCT will also increase significantly with increasing follow-up of the survivors. This review presents the available data on early and late cardiac and cardiovascular consequences after HCT, and presents recommendations for cardiac assessment and management of these complications.     

UK guidelines for referral and assessment of adults for heart transplantation

Patients with advanced heart failure have a dismal prognosis and poor quality of life. Heart transplantation provides an effective treatment for a subset of these patients. This article provides cardiologists with up-to-date information about referral for transplantation, the role of left ventricular assist devices prior to transplant, patient selection, waiting-list management and donor heart availability. Timing is of central importance; patients should be referred before complications (eg, cardiorenal syndrome or secondary pulmonary hypertension) have developed that will increase the risk of, or potentially contraindicate, transplantation. Issues related to heart failure aetiology, comorbidity and adherence to medical treatment are reviewed. Finally, the positive role that cardiologists can play in promoting and facilitating organ donation is discussed.     

Caspofungin-resistant Aspergillus flavus after heart transplantation and mechanical circulatory support: a case report

Abstract: Invasive aspergillosis (IA) is a severe complication in the post-transplant period in recipients of solid organs. Therefore, early diagnosis and specific therapy of fungal infections in these patients are indispensable. We report the case of a 49-year-old patient, who suffered from IA after cardiac transplantation, which was complicated by post-transplant right heart failure requiring mechanical circulatory support using veno-arterial extracorporeal membrane oxygenation and a right ventricular assist device. Despite antifungal treatment, the patient died 3 weeks after transplantation because of multi-organ failure secondary to IA. The isolated Aspergillus strains exhibited in vitro resistance to caspofungin.     

Mesenchymal stem cell therapy in patients with small bowel transplantation: Single center experience

AIM: To study the effects of mesenchymal stem cell (MSC) therapy on the prevention of acute rejection and graft vs host disease following small bowel transplantation.METHODS: In our transplantation center, 6 isolated intestinal transplants have been performed with MSC therapy since 2009. The primary reasons for transplants were short gut syndrome caused by surgical intestine resection for superior mesenteric artery thrombosis (n = 4), Crohn’s disease (n = 1) and intestinal aganglionosis (n = 1). Two of the patients were children. At the time of reperfusion, the first dose of MSCs cultured from the patient’s bone marrow was passed into the transplanted intestinal artery at a dose of 1000000 cells/kg. The second and third doses of MSCs were given directly into the mesenteric artery through the arterial anastomosis using an angiography catheter on day 15 and 30 post-transplant.RESULTS: The median follow-up for these patients was 10.6 mo (min: 2 mo-max: 30 mo). Three of the patients developed severe acute rejection. One of these patients did not respond to bolus steroid therapy. Although the other two patients did respond to anti-rejection treatment, they developed severe fungal and bacterial infections. All of these patients died in the 2^nd and 3^rd months post-transplant due to sepsis. The remaining patients who did not have acute rejection had good quality of life with no complications observed during the follow-up period. In addition, their intestinal grafts were functioning properly in the 13^th, 25^th and 30^th month post-transplant. The patients who survived did not encounter any problems related to MSC transplantation.CONCLUSION: Although this is a small case series and not a randomized study, it is our opinion that small bowel transplantation is an effective treatment for intestinal failure, and MSC therapy may help to prevent acute rejection and graft vs host disease following intestinal transplantation.     

Successful treatment of JMML relapsed after unrelated allogeneic transplant with cytoreduction followed by DLI and interferon-alpha: evidence for a graft-versus-leukemia effect in non-monosomy-7 JMML

Relapse is the major cause of treatment failure after allogeneic transplantation of children with juvenile myelomonocytic leukemia (JMML), and the role of post-transplant immunomodulation is poorly understood. We report a 12-month-old child with JMML relapsed after unrelated marrow transplantation who received cytoreduction followed by donor lymphocyte infusion (DLI) with improvement, and after addition of interferon-alpha (IFN) achieved complete donor chimerism. He was weaned from IFN and has maintained complete remission for 19 months. This is the first published report of a patient with non-monosomy-7 JMML responding to post-transplant immunomodulation and suggests a role for DLI plus IFN in these patients.     

Rapid immune reconstitution following autologous hematopoietic stem cell transplantation in children: a single institution experience

In this retrospective study, we review the immune reconstitution of children undergoing autologous hematopoietic stem cell transplantation. A total of 125 patients underwent autologous transplantation between 1992 and 2000. The report includes data on 58 patients. Data were not available on the remaining patients who either died before testing or data were not obtained. The parameters evaluated include: (a) immunophenotype by flow cytometry to quantify lymphocyte subpopulations (b) mitogen stimulation assays, and (c) quantitative immunoglobulins. The analysis reveals that CD3+ cells did not reach the normal range during the first year post-transplant. The median percentage of CD4+ cells was below normal up to 6 months post-transplant, while the absolute number remain low throughout the first year. The CD8+ percentage and absolute numbers remain normal at all times post-transplant. The CD19+ cells were also normal post-transplantation. The mitogen lymphocyte stimulation was normal in 27 out of 31 patients tested after 6 months post-transplant. Our analysis of immune reconstitution shows a similar pattern to previous studies with a faster recovery of the CD4/CD8 ratio, especially in those patients who did not receive TBI. In conclusion, the observed deficiencies are transient and have very little clinical significance because, historically, the rate of serious infections is low despite prolonged immune suppression. The recovery post-autologous transplant is fast.