There is marked advancement in transplant therapy. In particular, progress in immunosuppressants has especially improved graft success dramatically. However, the rate of malignant tumor generation and morbidity in regard to postrenal transplants are notably increasing. Compared to the mechanism whereby malignant tumors are generated in healthy adults, exposure to immunosuppressants and viral infections are involved in the generation of malignant tumors postrenal transplant and thus has a different aspect. Compared to the West, digestive organ cancers were the malignant tumors commonly generated in Japan. However, recent reports from various countries state that the rates at which skin cancer and posttransplant lymphoproliferative disorders are generated have increased at the same level as they have in the West. The appearance of mTOR inhibitors is expected hereafter to produce change in the rate of malignant tumor generation. However, restraint of excessive immune suppression, viral infection control, and postoperative control by screening tests have at least improved treatment results of malignant tumors. Moreover, this is linked to improvement in long-term results in renal transplants.
Liver transplant (LT) recipients have a higher overall risk of developing de novo malignancy than the general population dose with a standardized incidence ratio (SIR) of 1.95, which was calculated from the incidence of de novo malignancies in major centers and national registries of various countries. It is also elucidated that major risk factors for de novo malignancy after LT include patient ages, excessive immunosuppression, history of alcoholic liver disease, primary sclerosing cholangitis, sun exposure, smoking, and certain oncogenic viral infections. Despite de novo malignancy being a leading cause of mortality and morbidity after LT, no guideline has been defined to reduce its occurrence. All LT recipients are recommended to receive counseling on smoking cessation, limitation of alcohol use, and sun protection, as well as annual checkups for cancer screening. Further studies to develop effective screening methods for de novo malignancy, alternative immunosuppressive protocols, and multidisciplinary care pathways are required.
A nationwide survey on the incidence of variable malignancy after heart transplantation has been undertaken in Japan. This study included 83 patients (60 men, 23 women) who underwent heart transplantation in the 10-year period from January 2001 to December 2010 at heart transplantation centers in Japan. Patients were a mean age of 37 years at transplantation. Of these, 5 developed malignancy at the mean follow-up period of 5 years and 9 months (range: from 1 year and 6 months to 8 years and 9 months). Diagnoses of malignancy included malignant lymphoma in 3, colon cancer in 1, and urinary bladder cancer in 1. Some of the symptoms that triggered diagnoses were lymphadenopathy, fever, and lumbago. Incidental diagnoses of urinary bladder cancer were made during radiological examinations for gynecological disease. All 5 patients had been kept on triple immunosuppressant therapy and had experienced either no rejection or a single episode of one. A patient with malignant lymphoma deceased two years after the diagnosis, whereas the remaining 4 patients have survived as of the date of survey. This study carries considerable limitation that the number of heart recipients during the study period consisted of nearly half of the total heart transplant cases by the year 2014. Further studies are warranted to enhance the establishment of a guideline for optimal management of long-term survivors after heart transplant patients in view of prevention and an early diagnosis of malignancy.
【Background】Long-term immunosuppression is associated with an increased risk of cancer. Especially in pancreas transplantations, more intensive immunosuppression is used than in other organ transplantations because of strong immunogenicity. The aim of this studywas to analyze the incidence of de novo malignancies after pancreas transplantations in Japan. 【Methods】Posttransplant patients with de novo malignancies were surveyed and characterized. 【Results】Among 107 cases receiving a pancreas transplantation in Japan from 2001 to 2010, de novo malignancy developed in 9 cases; posttransplant lymphoproliferative disorder (PTLD) in 6, malignant brain tumor in 1, renal cell carcinoma in 1, and colon cancer in 1. 【Conclusions】We clarified the incidence of de novo malignancies after pancreas transplantation in Japan.
【Objective】Immunosuppressive drugs could be crucial factors for a poor outcome after islet allotransplantation. Unlike rapamycin, the effects of tacrolimus, the current standard immunosuppressant used in islet transplantation, on graft revascularization remain unclear. We examined the effects of tacrolimus on islet revascularization using a highly sensitive imaging system, and analyzed the gene expression in transplanted islets by introducing laser microdissection techniques. 【Methods】Islets isolated from C57BL/6-Tg (CAG-EGFP) mice were transplanted into the nonmetallic dorsal skinfold chamber on the recipients. Balb/c athymic mice were used as recipients and divided into two groups, including a control group (n=9) and tacrolimus-treated group (n=7). Changes in the newly-formed vessels surrounding the islet grafts were imaged and semi-quantified using multi-photon laser-scanning microscopy and a Volocity system. Gene expression in transplanted islets was analyzed by the BioMark dynamic system. 【Results】The revascularization process was completed within 14 days after pancreatic islet transplantation at subcutaneous sites. The newly-formed vascular volume surrounding the transplanted islets in the tacrolimus-treated group was significantly less than that in the control group (p＜0.05). Although the expression of Vegfa (p＜0.05) and Ccnd1 (p＜0.05) was significantly upregulated in the tacrolimus-treated group compared with that of the control group, no differences were observed between the groups in terms of other types of gene expression. 【Conclusion】The present study demonstrates that tacrolimus inhibits the revascularization of isolated pancreatic islets without affecting the characteristics of the transplanted grafts. Further refinements of this immunosuppressive regimen, especially regarding the revascularization of islet grafts, could improve the outcome of islet allotransplantation. *This article is a secondary publication in Japanese of "Tacrolimus inhibits the revascularization of isolated pancreatic islets" published by Nishimura R, Nishioka S, Fujisawa I, et al. PLoS One.2013 Apr 17; 8. DOI: 10.1371/journal.pone.56799
On March 11, 2011, our hospital was severely damaged by the Great East Japan Earthquake. We report the rare case of a 5-month-old patient with hepatic artery thrombosis (HAT) after a living-donor liver transplantation (LDLT). The patient survived the earthquake, which occurred 3 days after the reoperation, even though we were without abilities to perform blood tests or computed tomography (CT) for 4 days after. This female infant with biliary atresia underwent LDLT 5 months after birth and developed peritonitis resulting from perforation of the small intestine 7 days later. Her blood pressure decreased and she developed HAT. We performed emergency reconstruction of the hepatic artery and repair of the small intestine; 3 days later, the Great East Japan Earthquake occurred. We could not perform blood tests or CT scan because the water supply was damaged. Gas supply lines were also damaged, and sterilization was not possible; surgical tools were limited. However, emergency power was available, so we performed ultrasonography every 6 hours and predicted liver function from intrahepatic blood flow, also monitoring for Glisson's capsule edema. The blood examination system recovered 14 days after LDLT, and we confirmed improvement of the liver function. The patient was extubated 37 days after LDLT and discharged on postoperative day 67. *This article is a secondary publication in Japanese of "A patient with hepatic artery thrombosis after living-donor liver transplantation survived the great East Japan Earthquake 3 days after reoperation; a case report." published by Miyagi S, Kawagishi N, Satoh K, et al. Transplant Proc 2013; 45: 2066-2068.