Current techniques for pediatric liver transplantation.

PURPOSE OF REVIEW: Orthotopic liver transplantation in the pediatric population is a technically challenging undertaking, requiring highly specialized surgical techniques unique to this group. This review describes the most current method of transplantation for these patients. RECENT FINDINGS: Pediatric liver transplantation employs multiple modifications of standard transplant technique, including alternative methods of vascular and biliary anastomoses as well as technical variant grafts. We herein describe how these methods are employed in procurement, back-table preparation, hepatectomy, and allograft implantation. SUMMARY: This review provides concise direction of surgical technique for pediatric liver transplant recipients.

Liver transplant fellowship and resident training is not a part of the "July effect".

BACKGROUND: The influx of new resident physicians has been shown to cause increased complications in academic institutions, named the "July effect." This study investigated if this effect is associated with liver transplants and if it affects patient or allograft outcomes after orthotopic liver transplantation (OLT). MATERIALS AND METHODS: The United Network of Organ Sharing or Organ Procurement and Transplantation Network database was queried. Cases were separated and coded by the month of transplant. The survival analysis was calculated by log-rank and Kaplan-Meier tests in SPSS version 15.0 (IBM Corporation, Chicago, IL). RESULTS: A total of 108,666 OLTs were analyzed through March 31, 2011. The mean short-term patient survivals at 30 d and 1 y were 94.3% and 85.2%, respectively. The mean long-term survivals at 3, 5, and 10 y were 77.6%, 72.1%, and 58.8%, respectively. The mean short-term allograft survivals at 30 d and 1 y were 90.6% and 79.4%, respectively. The mean long-term allograft survivals at 3, 5, and 10 y were 71.0%, 65.0%, and 51.5%, respectively. OLTs in the month of April had significantly improved patient and allograft survivals compared with those in the months of January, October, and December; OLTs in the month of December had significantly decreased patient and allograft survivals compared with those in the months of July and August. CONCLUSIONS: OLTs in the month of April had significantly improved outcomes, and OLTs in the month of December had significantly decreased outcomes. These months do not correlate with the beginning of new trainees; therefore, there is no July effect observed in liver transplant fellowship and resident training.

Liver transplantation in cystic fibrosis: a report from Baylor College of Medicine and the Texas Children's Hospital.

CF affects one of 2000 Caucasians, and approximately 25% are found to have CFLD for which OLT may be indicated. Timing of transplantation, contraindications, and survival are still widely debated. We report the outcomes of OLT for pediatric patients with CFLD from the largest children's hospital in the United States. Our records since September 1998 were analyzed for all patients undergoing OLT for CFLD. Nine patients were then compared to similar patients in the UNOS/OPTN database (n = 155). Survivals were calculated with the Kaplan-Meier method and compared using the log-rank test. All statistics were performed in SPSS 15.0. We performed OLT on nine pediatric patients with CFLD, with age ranging from nine to 17 yr at the time of transplant. Mean survival was 69.2 months; patient and allograft survivals at one and five yr were 88.9%, with one death at day 21 due to Aspergillus fumigatus sepsis. Two patients underwent concurrent multi-organ transplantation. One patient required double lung transplantation four yr after isolated OLT. Comparison to the UNOS/OPTN database revealed a trend toward improved survival. Patients with CF can achieve favorable outcomes after OLT, as we report excellent survivals for pediatric patients with CFLD.

Transplanting whole livers from donors less than 6 kilograms--is it prudent?

INTRODUCTION: Experience suggests transplanting whole liver allografts (WL) from donors weighing <6 kg portends a worse prognosis. Patient and allograft survivals of infants who underwent transplantation with livers from donors ≥6 kg, <6 kg, or technical variant allografts from deceased donors (TV) and those from living donors (LD) were compared. METHODS: The United Network of Organ Sharing database was queried for infant orthotopic liver transplantation (≤2 y). Of 5976 orthotopic liver transplantations, 860 patients received TV from deceased donors, 534 received LD split allografts, 509 patients had WL from donors weighing <6 kg, and 4073 remaining patients had WL from donors weighing ≥6 kg. Kaplan-Meier method and log-rank tests were employed. RESULTS: Patients who received WL from donors weighing <6 kg had survival mean of 13.9 y ± 177 d. Overall patient survivals were 76.7%, 71.4%, 68.4%, and 65.9% at 1, 3, 5, and 10 y. This is significantly worse compared with all other groups, both in patient and allograft survival (P ≤ 0.001). In patients whose donors ≥6 kg, overall patient survivals were 82.1%, 78.7%, 77.3%, and 75.4% at 1, 3, 5, and 10 y. Infants who received TV had patient survival of 87.8%, 84.7%, 82.7%, and 80.6% at 1, 3, 5, and 10 y. Infants who received LD allografts had patient survival of 92.4%, 90.7%, 89.6%, and 88.5% at 1, 3, 5, and 10 y. CONCLUSIONS: Smaller weight of the donor influences the infant patient outcome. Patients with allografts from donors weighing <6 kg have a worse prognosis compared with those who received TV and LD allografts and those whose donors weigh ≥6 kg. Patients who receive LD allografts had the best survival.

Caroli disease patients have excellent survival after liver transplant.

BACKGROUND: Caroli disease (CD) is characterized by dilation of the intrahepatic biliary tree, which may result in malignancy. Treatments include management of symptoms and hepatic resection to decrease disease burden. In patients with CD not amenable to these treatments, orthotopic liver transplantation (OLT) has been used. This study examines if OLT is a reasonable treatment for patients with CD. MATERIALS AND METHODS: The United Network of Organ Sharing/Organ Procurement and Transplantation Network database between September 30, 1987 and March 31, 2011 was queried. Cases without patient or allograft survival time or without a diagnosis were excluded from analysis. Patients with CD were compared to patients with primary biliary cirrhosis (PBC), secondary biliary cirrhosis (BC), primary sclerosing cholangitis (PSC), and all indications for OLT. Survival analysis was performed by log-rank test and Kaplan-Meier. RESULTS: One hundred forty patients with CD were compared to 4797 patients with PBC, 489 patients with secondary BC, 6033 patients with PSC, and 92,210 patients post-OLT. Patient and allograft survivals of CD patients at 1, 3, 5, and 10 y are, respectively, 88.5%, 83.4%, 80.9%, and 77.8%; and 81.2%, 74.8%, 70.6%, and 67.9%. CD patients have significantly improved patient and allograft survivals after OLT compared to patients with secondary BC (P = 0.003, P = 0.015) and all other patients undergoing OLT (P = 0.003, P = 0.026). There is a trend towards long-term improved patient and allograft survival in transplanted patients with CD compared to patients with PBC and PSC. CONCLUSIONS: These results suggest that OLT should be considered an effective treatment modality for patients with CD resulting in excellent long-term outcomes.

Liver transplantation with donation after cardiac death donors: a comprehensive update.

BACKGROUND: Use of donation after cardiac death (DCD) donors has been proposed as an effective way to expand the availability of hepatic allografts used in orthotopic liver transplantation (OLT); yet, there remains no consensus in the medical literature as to how to choose optimal recipients and donors based on available information. METHODS: We queried the United Network of Organ Sharing/Organ Procurement and Transplantation Network database for hepatic DCD allografts used in OLT. As of March 31, 2011, 85,148 patients received hepatic allografts from donation-after-brain-death (DBD) donors, and 2351 patients received hepatic allografts from DCD donors. We performed survival analysis using log-rank and Kaplan-Meier tests. We performed univariate and multivariate analyses using the Cox proportional hazards model. All statistics were performed with SPSS 15.0. RESULTS: Patients receiving hepatic DCD allografts had significantly worse survival compared with patients receiving hepatic DBD allografts. Pediatric patients who received a hepatic DCD allograft had similar survival to those who received a hepatic DBD allograft. The optimal recipient-related characteristics were age <50 y, International Normalized Ratio <2.0, albumin >3.5 gm/dL, and cold ischemia time <8 h; optimal donor-related characteristics included age <50 y and donor warm ischemia time <20 min. CONCLUSIONS: By identifying certain characteristics, the transplant clinician's decision-making process can be assisted so that similar survival outcomes after OLT can be achieved with the use of hepatic DCD allografts.

Biliary adenofibroma with carcinoma in situ: a rare case report.

This case report exhibits a rare biliary tumor within the liver of a 53-year-old Caucasian woman. This exophytic, multicystic, 6.5 × 5.0 cm mass was composed of complex tubulocystic structures lined by nonmucin-secreting, biliary epithelium embedded in fibrous stroma, consistent with biliary adenofibroma. This is the seventh case described in the literature. Multiple foci of high-grade dysplasia/carcinoma in situ were found with a microscopic focus of invasive carcinoma in review of the pathology, making this only the second case reporting malignant transformation. It is presented to illustrate the premalignant potential in a biliary epithelial tumor currently categorized as benign.

Acute liver failure.

PURPOSE OF REVIEW: Clinical investigations in acute liver failure (ALF) continue to advance our understanding and capacity to diagnose and treat afflicted children and adults. The purpose of this review is to summarize the advances in clinical research in ALF during 2009-2010 that are pertinent to hepatologists and transplant surgeons caring for these critically ill patients. RECENT FINDINGS: Principal advances occurred in the characterization of cause and epidemiology, genetic susceptibility, assessment of prognosis for survival with medical therapy, clarification of long-term outcomes of transplantation for ALF, and publication of the final results of large randomized, placebo-controlled therapeutic trials. SUMMARY: Despite advances in our understanding, ALF remains a cause of significant mortality in children and adults because of the absence of curative medical therapy. Hence, only emergency liver transplantation is reliably life-saving. There is an urgent need for better understanding of the pathogenesis of ALF caused by different causes, of genetic susceptibility, development of validated prognostic indicators and application of this knowledge to devise new therapeutic strategies for testing in appropriately powered, randomized controlled trials.

Building a comprehensive genomic program for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer, causing approximately 660,000 deaths worldwide annually. The preferred treatment of HCC is surgical resection or orthotopic liver transplantation (OLT) for patients meeting specific criteria. For patients outside these criteria, options are limited and include medical therapy, radiofrequency ablation, chemoembolization, or palliative measures, and these result in poor outcomes. Various centers at Baylor are elucidating the genomics of HCC to improve treatment options, with a focus on three etiologies: hepatitis C virus, hepatitis B virus, and non-viral. METHODS: Through collaborative efforts, we have established an effective specimen biobanking protocol, and we are using several techniques to analyze HCC, including whole genome sequencing, whole exome sequencing, gene-specific analysis, gene expression, and epigenetic analysis. RESULTS: We have completed whole genome sequencing on two patient samples, whole exome sequencing on 47 patient samples, gene-specific analysis on 94 patient samples, gene expression on 4 patient samples, and epigenetic analysis on 1 patient sample. CONCLUSIONS: We hope to use these results to define novel genetic therapeutic strategies that may work in conjunction with surgical approaches to improve long-term patient and graft survival rates in patients with HCC. We also aim to provide a functional framework of a comprehensive program for genomic analysis that may be imitated by other institutions and for other tumors in the global quest toward personalized genomic medicine.

A primer on a hepatocellular carcinoma bioresource bank using the cancer genome atlas guidelines: practical issues and pitfalls.

BACKGROUND: Since the advent of the human genome, the era of personalized genomic medicine is indisputably in progress. METHODS: In an effort to contribute to the evolving knowledge of genomic medicine, we have aimed directly at building a bioresource bank for hepatocellular carcinoma. This tumor bank is based on the rigorous guidelines set forth by the National Cancer Institute, and it offers analytes to help elucidate the mechanisms of progression from cirrhosis to malignancy, risk factors for recurrence, and applicability of current treatment options to a diverse group of people. CONCLUSIONS: Surgeons have a privileged position between patients (and their cancer) and the benches of basic science. Thus, we offer a primer based on our own experiences, from which surgeons may take elements to build their own bioresource bank for use in collaboration with others. We highlight some practicalities and pitfalls that could be overlooked, as well as a discussion of possible solutions.

Homozygous familial hypercholesterolemia: case series and review of the literature.

Introduction. Familial hypercholesterolemia (FH) is caused by nonfunctioning low-density lipoprotein (LDL) receptors, resulting in high serum cholesterol. Two types of FH are described: the heterozygous form is diagnosed in adults and responds well to medical therapy; the homozygous form is rare, diagnosed in children, and often requires multiple treatments to prevent complications. Cholesterol accumulation in tissues produces common clinical manifestations including cutaneous xanthomas, coronary artery disease, and aortic stenosis. Treatment options consist of lifestyle modifications, lipid-lowering medications, LDL aphaeresis, and orthotopic liver transplantation (OLT). Case Presentation. Two patients with FH presented at young ages due to characteristic cutaneous xanthomas. The patients underwent cardiac testing that revealed atherosclerotic changes. The patients received maximal medical therapy, but only experienced a small decrease in serum cholesterol and LDL levels. After several years of medical treatment without improvement of symptoms, the patients were listed for OLT. The transplantations were successful, and only one patient had a postoperative complication of acute rejection, treated successfully. Currently, both patients are doing well with regression of the cutaneous xanthomas and atherosclerotic changes. Conclusion. OLT is a safe and effective option for patients with homozygous FH refractory to maximal medical therapy and may represent the optimal treatment for these patients.

Neuroendocrine Liver Metastases and Orthotopic Liver Transplantation: The US Experience.

Liver transplantation remains a controversial therapy for Neuroendocrine liver metastases (NLM), with coflicting suvival data reported. The aim was to assess the evolution of outcomes for patients transplanted for NLM in the US, both before and after the introduction of the MELD scoring system in 2002. The UNOS/OPTN database was reviewed to identify patients diagnosed with NLM who subsequently underwent a liver transplantation from 1988 to March 2011 (n = 184); Patient survival was determined using Kaplan-Meier methods and log-rank tests, and cox regression analysis was performed, using SPSS 15.0 (SPSS, Inc, Chicago, IL). The overall NLM patient survivals in the pre-MELD era were 79.5%, 61.4%, and 49.2% at 1, 3, and 5 years, respectively. After the introduction of the MELD score, NET/NLM patients had improved overall patient survivals at 1, 3, and 5 years of 84.7%, 65%, and 57.8%. Patients transplanted after 2002 had an improved survival outcome. Notably, the overall patient survival for NET is not significantly different when compared to the outcomes of patients transplanted for HCC, in the current era. This progress acknowleges the significant improvement in outcomes for NLM patients after liver transplantation and the potential for further gain in the survival of otherwise nonsurgical, terminal patients.