Induction Immunosuppressive Therapy for Kidney Transplant in Elderly Recipients: A Single-Center Experience.

OBJECTIVES: The number of elderly kidney transplant recipients is increasing, and age-tailored induction immunosuppression regimens are needed. We compared safety and efficacy of basiliximab versus thymoglobulin at various dosages. MATERIALS AND METHODS: Of 590 kidney transplants at our center from 2012 to 2019, 119 (20.1%) were for recipients over 65 years of age; 118 patients received deceased donor kidneys, and 1 received a related living donor kidney. We retrospectively reviewed medical records for demographics, baseline characteristics, donor characteristics, induction regimens, infectious complications, graft function, and patient survival. RESULTS: Patients were subdivided into the following 4 induction immunosuppression groups: basiliximab (n = 15, 12.6%), 3 mg/kg thymoglobulin (n = 8, 6.7%), 4.5 mg/kg thymoglobulin (n = 67, 56.3%), and 6 mg/kg thymoglobulin (n = 29, 24.4%). All patients received pulse doses of methylprednisolone followed by a prednisone taper. Other maintenance immunosuppression agents included tacrolimus and mycophenolic acid. Recipients in the basiliximab and 3 mg/kg thymoglobulin groups were older (median age ⟩70 years; P ⟨ .001). The 4.5 and 6 mg/kg thymoglobulin groups had higher proportions of African American patients and patients with calculated panel reactive antibody over 20%. There were significantly fewer infectious complications in the basiliximab and 3 mg/kg thymoglobulin groups. Despite differences in biopsy-proven acute rejection rates, estimated glomerular filtration rate and graft and patient survival rates at 1 year were similar across groups. All patients with biopsy-proven acute rejection were African American patients. CONCLUSIONS: Kidney transplant in patients ≥65 years is safe and feasible. Changes in this unique population's immune system warrant age-tailored regimens. We found that patients at low immunologic risk would benefit from basiliximab orthymoglobulin at 3 mg/kg. Regardless of calculated panel reactive antibodies, African American patients should be considered as high immunologic risk group forrejection, and higher thymoglobulin dosing should be considered.

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 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.

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.

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.

Pediatric liver transplantation for primary malignant liver tumors with a focus on hepatic epithelioid hemangioendothelioma: the UNOS experience.

Treatment for HEH does not follow a standardized algorithm. From clinical experience, it is assumed that pediatric patients with HEH will fare as well as other common pediatric liver tumors post-OLT. The UNOS dataset was examined for patients with pediatric OLT between 1987 and 2007. Patients were grouped into non-tumors, HB, HCC, HEH, and rare liver tumors. COD analysis was calculated using Fisher's exact test. Patient, allograft, and recurrence-free survival were compared using Kaplan-Meier curves and log-rank tests. A total of 366 patients with pediatric OLT were identified with primary liver tumors (HB - 237, HCC - 58, HEH - 35, other - 36). HEH patient survival (five yr: 60.6%) was poorer than non-tumor OLTpatient survival (five yr: 84.4%). Survival was worse when compared to HB (five yr: 72%) and rare liver tumors (five yr: 78.9%), but better than HCC (five yr: 53.5%). Allograft survival in HEH (five yr: 50.1%) lies between HB (five yr: 63.6%) and HCC (five yr: 42.8%). COD analysis demonstrates recurrence as a major cause in HB and HCC, but not for HEH or other liver tumors. The data suggest that patient survival may not be as high as previously believed and further investigation is warranted.

Sequencing the full-length of the phosphatase and tensin homolog (PTEN) gene in hepatocellular carcinoma (HCC) using the 454 GS20 and Illumina GA DNA sequencing platforms.

BACKGROUND: Phosphatase and tensin homolog (PTEN) is a tumor-suppressor gene that is mutated in cancer of the liver, pancreas, endometrium, and prostate. PTEN-dependent pathways are involved in mediating cell growth and invasion. To sequence the whole gene (including introns and exons), we have taken advantage of new technologies that allow for rapid, inexpensive sequencing to great depth. METHODS: DNA from 15 HCC specimens were pooled, and long-range PCR was performed by using the GeneAmp XL PCR kit. Primer parameters included: length of 20-30 base pairs (bp), melting temperature of -68 degrees C, and G/C content of 50-60%. PCR products were then column-purified and pooled, and DNA libraries were prepared for "shotgun sequencing" on both the 454 GS and Illumina GA sequencing platforms. RESULTS: We successfully amplified approximately 98.9% of the PTEN gene by using one long-range PCR protocol applied to 24 primer sets, resulting in 20 amplicons approximately 6.5 kilobases (kb) in length, 2 amplicons approximately 10 kb in length, and 2 amplicons approximately 2.5 kb in length. Sequencing of fragmented PCR products on both sequencing platforms identified six high-frequency SNPs that were catalogued in dbSNP as known variants. CONCLUSIONS: Shotgun sequencing based on a single long-range PCR protocol in pooled samples is an efficient and relatively inexpensive way to sequence an entire gene.