Boonchoo Sirichindakul

Living-donor kidney transplantation across ABO barriers: the first case in Thailand

Background: Transplantation among ABO blood group incompatibility was considered an absolute contraindication until recent development of successful protocols. A living-donor across ABO barriers may provide another option for end-stage kidney disease patients. Objective: To report the first case of ABO-incompatible living-donor kidney transplantation (ABOi-LKT) in Thailand. Patients and method: The kidney transplantation across ABO barriers was performed following the Japanese recommended protocol. The kidney recipient was a thirty-four years old woman with blood group-O, whereas the kidney donor was her brother with blood group A. To reduce anti-donor (anti-blood group-A antibody) blood levels, the patient underwent double filtration plasmapheresis and received an intravenous anti-CD20 monoclonal antibody. A maintenance immunosuppressive regimen was similar to the one of ABO-compatible setting. Results: The kidney allograft had immediate good function. The transplantation was uneventful, and the patient went home within two weeks. Kidney allograft biopsies were performed on a protocol-driven basis at time-zero, the first and sixth month post-transplantation. Histologic studies showed unremarkable findings. The patient is now twelve months after transplantation and has achieved excellent kidney function. Conclusion: ABOi-LKT provides an alternative treatment for end-stage kidney disease patients. A multi-center study of ABOi-LKT in Thailand is ongoing, and this may change the national policy of organ donation in the near future.

The Cytochrome P450 3A5 Non-Expressor Kidney Allograft as a Risk Factor for Calcineurin Inhibitor Nephrotoxicity

Background: Tacrolimus is mainly metabolized by cytochrome P450 3A5 (CYP3A5), which is expressed in the liver. However, CYP3A5 is also expressed in the kidney tissue and may contribute to local tacrolimus clearance in the kidney allograft. We aimed to evaluate the association between the allograft CYP3A5 genotype and transplant outcomes. Methods: We conducted a retrospective cohort study at the King Chulalongkorn Memorial Hospital, Thailand, comparing 2 groups of donor and recipient CYP3A5 genotypes, the expressor (*1/*1 and *1/*3) and the non-expressor (*3/*3). The primary outcomes were allograft complications including calcineurin inhibitor (CNI) nephrotoxicity and acute rejection episode. Results: Of the 50 enrolled patients, 21 donors were expressors and 29 donors were the non-expressors. Tacrolimus trough concentrations were similar between the 2 genotypes. The incidence of CNI nephrotoxicity was higher in recipients with non-expressor donor genotype compared with the expressor donor genotype (72.4 vs. 33.3%, p = 0.006). CNI nephrotoxicity incidence was not different when recipient’s genotypes were compared. Multivariate analysis from Cox-regression showed a hazard ratio of 3.18 (p = 0.026) for CNI nephrotoxicity in the non-expressor compared with the expressor donor. The recipient CYP3A5 genotypes did not significantly contribute to CNI nephrotoxicity. Kaplan-Meier analysis demonstrated the lowest CNI nephrotoxicity-free survival in recipients with the expressor genotype who received allograft from the non-expressor donors (p = 0.005). Conclusion: In conclusion, our results suggest that donor CYP3A5 non-expressor genotype (*3/*3) is a risk for CNI nephrotoxicity.

A benign liver tumor mimics hepatic metastasis from colon cancer.

Abstract Background: Liver is the most common distant metastasized organ in advanced colon cancer. Surgical resection of metastatic lesions would offer the best chance of a long-term survival. An accurate diagnosis and evaluation of extent of disease is crucial in the management of liver metastasis. Objective: Report a benign hepatic condition mimicking liver metastasis in a colon cancer patient. Case presentation: A 53-year-old male with an early stage sigmoid colon cancer was treated with sigmoidectomy followed by adjuvant chemotherapy consisting of 5-FU, leucovorin, and oxaliplatin for six months. Annual computerized tomography of abdomen at two years after the surgery revealed three hypervascular nodules in the liver. Investigations including MRI of the liver and whole body FDG-F18 PET/CT demonstrated evidence consistent with non-metastatic liver nodules. Liver biopsy of one of the lesions led to the diagnosis of “focal nodular hyperplasia”. Conclusion: The possible etiology, diagnosis, and further management of this benign liver tumor, the focal nodular hyperplasia became clear.

Treatment outcome of hepatocellular carcinoma patients with high-risk vascular invasion: a retrospective analysis

Abstract Background: Invasion of major hepatic vessels in hepatocellular carcinoma (HCC) generally prohibits the surgical treatment. Objective: Analyze outcomes of non-surgical approaches in this group of HCC. Methods: Retrospective review of medical records of 648 HCC admitted to King Chulalongkorn Memorial Hospital between January 2003 and December 2005 was carried out to select only patients who had unresectable HCC with vascular invasion and hepatic functions-Child-Pugh class-A. Vascular invasion was defined as involvement of portal vein, inferior vena cava (IVC), or their branches identified by imaging techniques. Non-surgical treatments were either transarterial chemoembolization (TACE) or systemic chemotherapy (SCT) in addition to general supportive care. Treatment outcomes of the patients were analyzed. Results: Out of 71 unresectable HCC patients enrolled, 57patients were treated with TACE, while 14 received SCT. In the TACE group, 39 (68%), 7 (12%) and 11 (19%) patients had portal vein, IVC, and both vessels invasion, respectively. In the SCT group; 11 (78%), 1 (7%) and 2 (14%) had invasion of portal vein, IVC, and both vessels, respectively. Median overall survival in both groups was 158 days. Univariate analysis demonstrated that AFP level <1000 ng/mL, tumor size <10 cm, and SCT treatment significantly influenced survival. Additional multivariate analysis confirmed that diameters of tumor, and SCT were independent prognostic factors for good survival. A survival analysis showed longer survival in the SCT group than that of TACE (210 vs. 149 days, p=0.03) group. Conclusion: Survival of HCC patients with major vessels invasion was better when treated with SCT compared to TACE. Future prospective study in larger populations to test the hypothesis is warranted.