Early post-transplant hyperbilirubinemia is a possible predictive factor for developing neurological complications in pediatric living donor liver transplant patients receiving tacrolimus.

The cause of post-transplant CNI-NCs is multifactorial and not ascribed solely to CNI toxicity. A total of 90 children (aged <20 years) who underwent LDLT were evaluated to investigate the predictive factors associated with CNI-NCs. Twelve patients (13.3%) developed CNI-NCs after LDLT (age range, 2-15 years). The symptoms of CNI-NCs were seizures, VD, and stupor. The median onset of CNI-NCs was 10 days (range, 5-30 days) post-transplant. In the univariate analysis, higher recipient age at LDLT, donor age and recipient's BW, lower actual GV/SLV and TAC dosage/BW, and higher mean T-Bil and sodium level for 7 days after transplantation were independently significantly associated with TAC-NCs. Multivariate analysis showed that the T-Bil level in the first week after LDLT was the only significant independent predictive factor for TAC-NCs (HR, 1.588; 95% CI, 1.042-2.358; P=.031). In conclusion, CNI-NCs occurred most frequently in children over 5 years and were associated with hyperbilirubinemia for 7 days post-transplant, regardless of TAC levels. The transplant team should refer to a neurologist to define the diagnosis and to collaborate to resolve the neurological problems.

Long-term survival with growth hormone replacement after liver transplantation of pediatric nonalcoholic steatohepatitis complicating acquired hypopituitarism.

Nonalcoholic steatohepatitis (NASH) is the most severe form of nonalcoholic fatty liver disease (NAFLD). In adult patients, liver transplantation (LT) is the treatment of choice for end-stage liver disease secondary to NASH. However, little information is available regarding outcomes of LT in pediatric patients with NASH. We describe here a pediatric patient with NASH associated with hypopituitarism who underwent living donor liver transplantation (LDLT). An 11-year-old boy was diagnosed with a pituitary tumor, which was removed by trans-interhemispheric approach following bifrontal craniotomy. Histopathological examination revealed a mature teratoma. Eighteen months later, magnetic resonance imaging showed recurrence of the pituitary tumor, which was found to be a germinoma. He underwent 3 months of chemoradiotherapy, with a complete response. He gradually became obese, with elevated transaminase levels. At age 15 years, he developed fatigue and dyspnea and was found to have liver cirrhosis secondary to NASH with severe hepatopulmonary syndrome. He underwent LDLT using a right liver graft from his mother. Twelve months later, abdominal computed tomography showed recurrence of NAFLD. Five years after the LDLT, transaminases were slightly elevated. Growth hormone replacement therapy was started, reducing transaminase levels to their normal ranges. Ten years after LDLT, fatty liver remains stable, although his body mass index has not been reduced. Growth hormone replacement therapy may be effective in graft maintenance. This is the first case report of a patient with maintained stable liver function 10 years after LDLT for pediatric NASH.

Strangulated Small Bowel Obstruction After Renal Transplant With No History of Laparotomy: Case Report.

Strangulated small bowel obstruction is a complication after abdominal surgery, which is rare in renal transplant patients. A 61-year-old man with a strangulated small bowel obstruction underwent renal transplant surgery 7 years before the current admission. He was admitted to our hospital for abdominal pain, nausea, and abdominal distention. An abdominal computed tomography and an ultrasound examination showed intestinal expansion and fluid collection without ascites. His disease was diagnosed as a small bowel obstruction and conservative treatment was begun. However, because of increasing abdominal pain and the collection of ascites, he underwent an emergency laparotomy and was diagnosed as having a strangulated small bowel obstruction. A fibrous cord had formed between the peritoneum (beside the transplanted kidney) and the root of the sigmoid mesocolon, strangulating the looped ileum and causing bleeding necrosis and hemorrhagic ascites collection. The cord and the necrotic ileum were resected, followed by an end-to-end anastomosis. He was discharged 17 days after the surgery in good condition. This is the first reported case of a person having a strangulated small bowel obstruction by a fibrous cord, who did not have a history of laparotomy after renal transplant. A strangulated small bowel obstruction after a renal transplant in a patient with no history of a laparotomy is a rare, but possible postoperative complications should be considered when making a differential diagnosis.

Epstein-Barr virus--associated posttransplantation lymphoproliferative disorder with tacrolimus metabolism deterioration in infants after living-donor liver transplantation.

BACKGROUND: Posttransplantation lymphoproliferative disorder (PTLD) in infants after liver transplantation is strongly associated with tacrolimus (Tac) administration and primary Epstein-Barr virus (EBV) transmission. METHODS: From 1991 to 2012, 32 survivors younger than 2 years who had undergone living-donor liver transplantation using Tac for primary immunosuppression were retrospectively investigated for changes in Tac trough levels before and at the onset of posttransplantation viral infection episodes. RESULTS: Twenty-one recipients experienced 33 viral infection episodes associated with EBV-related PTLD (n = 5), symptomatic EBV infection without development of PTLD (n = 8), and other viral infections (n = 20). Although the average Tac trough levels during the 2 months before the onset of viral infection episodes were similar among the 33 episodes (9.0 ± 2.8 ng/mL), the Tac trough levels at the onset were significantly higher in the episodes with PTLD than in those with EBV infection without the development of PTLD and with other viral infections (19.2 ± 9.0 ng/mL vs. 9.3 ± 5.2 ng/mL and 10.6 ± 5.1 ng/mL, respectively) (P<0.05). Tacrolimus trough levels at the onset of PTLD were significantly higher during the 2 months before the onset (median, 1.83 times higher than average) compared with EBV infection (1.14 times higher) and other viral infections (1.06 times higher) (P<0.05). The Tac blood concentration-to-dose ratio at the onset of PTLD was more than twice as high as the average value during the 2 months before the onset. CONCLUSION: Deteriorated Tac metabolism accompanied by a positive change in the blood EBV DNA load may enable us to predict the development of PTLD in liver-transplanted infants with viral infection.

Renal function status in liver transplant patients in the first month post-transplant is associated with progressive chronic kidney disease.

AIM: Renal dysfunction is a common complication of liver transplantation (LT), related to hepatorenal syndrome with end-stage liver disease or calcineurin-inhibitor nephrotoxicity. Chronic kidney disease (CKD) is also a common problem in long-term survivors post-LT. This study was done to investigate the association between renal functional status soon after LT and the development of CKD. METHODS: We retrospectively evaluated 63 patients who were aged 18 years or older, and underwent LT at Tohoku University Hospital. The estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease study equation for Japan. RESULTS: Before transplantation, 25 patients (39.7%) were diagnosed with CKD (eGFR, <60 mL/min per 1.73 m(2) ). The incidence of CKD was 22.4% (13/58) at 2 years, 23.2% (13/56) at 3 years and 22.7% (12/54) at 5 years. The patients with CKD at 2 years post-transplant were more likely to have a history of glomerulonephritis, and were significantly older at the time of LT, compared to those without CKD. Levels of eGFR of less than 60 mL/min per 1.73 m(2) in the first month post-transplant and a volume of intraoperative blood loss of more than 300 mL/kg were predictive factors for the development of CKD at 2 years post-transplant and thereafter. CONCLUSION: We have shown that there is an improvement of renal function in the majority of patients after LT. Regardless of the presence of pre-existing CKD, both renal function status at the first month post-transplant and a volume of intraoperative blood loss were predictive factors for the development of CKD at 2 years post-transplant and thereafter.

Hepatic venous reconstruction using the superficial femoral vein in a right-lobe living donor liver transplant patient with interrupted inferior vena cava.

Anatomical abnormalities in patients with BA often include polysplenia, preduodenal portal vein, interrupted retrohepatic IVC, cardiac abnormalities, and situs inversus. In LDLT patients who had congenital vascular anomalies, additional surgical modifications for the reconstruction of hepatic venous branches are sometimes necessary to prevent venous parenchymal congestion. We report a 12-yr-old female with post-Kasai BA with interrupted retrohepatic IVC who underwent right-lobe LDLT because the left liver graft volume was insufficient. The donor right liver graft had three major hepatic branches, including the RHV, IRHV, and MHV tributary (V8). We performed hepatic venous reconstruction by creating a large, wide triple orifice consisting of the RHV and two SFVs, which were anastomosed to the V8 and IRHV using the donor's SFV as an interposition graft. In conclusion, the reconstruction of venous orifices for right-lobe LDLT patients with the absent retrohepatic IVC is can be carried out using an SFV graft derived from the living donor or the recipient.

[Effects of psychological distress due to the Great East Japan Earthquake, tsunami, Fukushima Nuclear Power Plant disasters on psychiatric symptoms in patients with mental disorders: observational studies in Tochigi].

BACKGROUND: The Great East Japan Earthquake and subsequent tsunami of March 11, 2011 severely damaged a widespread region of northeastern Japan. Consequently, the Fukushima Nuclear Power Plant experienced a level seven 3 reactors melted down, which released a large amount of radioactive materials into the air. Due to the structural damage and radiation leaks, the victims are facing prolonged psychological distress. METHODS: Eighty-two subjects with mental disorders who made their initial visit during the first 4 months after the earthquake and one hundred and ninety-four subjects with mental disorders who had been admitted during the first one year after the earthquake to the Jichi Medical University Hospital, which is located at the edge of the disaster-stricken region, were recruited for this study. Enrolled participants were assessed according to ICD-10. A questionnaire survey was employed to evaluate the severity of psychological distress and total amount of damage. RESULTS: The conditions of 22% of the outpatients had been worsened by the psychological distress related to the earthquake. Seven percent of the patients who had been hospitalized showed marked exacerbations due to the psychological distress associated with the disaster. COMMENTS: It is of note that the exacerbation of psychiatric symptoms due to the disaster was evident among patients with mental disorders who lived even at the edge of the disaster area (i. e., subject to an earthquake intensity of 5 upper and 150 km from the Fukushima Nuclear Power Plant). The results suggest that the close follow-up of disaster victims with mental disorders is of critical importance.

Solitary hepatic granuloma preoperatively diagnosed as intrahepatic cholangiocellular carcinoma: report of a case.

We herein report the case of a 67-year-old female with a solitary hepatic granuloma preoperatively diagnosed as a mass-forming type of intrahepatic cholangiocellular carcinoma. Magnetic resonance imaging using gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid as a contrast medium is expected to be useful for making a differential diagnosis between hepatic granuloma and other hypovascular liver tumors, such as the mass-forming type of intrahepatic cholangiocellular carcinoma and metastatic liver tumors.

Intestinal obstruction caused by colonic metastasis from intrahepatic cholangiocarcinoma 6 years after removal of the primary tumor: report of a case.

We report a case of intestinal obstruction caused by metastasis that manifested 6 years after surgery for intrahepatic cholangiocarcinoma (ICC). The patient, a 57-year-old man, had undergone resection of the hepatic left lobe, Spiegel lobe, and extrahepatic bile duct, following which histopathological examination had confirmed the diagnosis of ICC and that the resection margins were free from disease. There had been no signs of recurrence until an increase in the CA19-9 level was detected 6 years later. Colonoscopy revealed an ulcer-like lesion and stenosis at the level of the hepatic flexure. The patient was subsequently admitted to our hospital with abdominal pain and underwent right hemicolectomy with partial resection of hepatic segment V. Based on the immunohistological finding that the expression pattern of cytokeratins and mucins was consistent with ICC origin rather than colon cancer origin, we diagnosed colon metastasis from ICC.

Post-transplantation lymphoproliferative disorder in living-donor liver transplantation: a single-center experience.

BACKGROUND: Post-transplantation lymphoproliferative disorder (PTLD) is a group of life-threatening complications of organ transplantation, which occurs most frequently in pediatric patients. This retrospective study evaluates a single-institution experience of five cases of PTLD after living-donor liver transplantation (LDLT). PATIENTS AND METHOD: We reviewed the records of 78 pediatric patients (<18 years old) and 54 adult patients, who underwent LDLT between July 1991 and December 2009. RESULT: PTLD was diagnosed in five pediatric patients, yielding an overall incidence of 3.8%. There were no significant differences between the pediatric patients with and those without PTLD in terms of their age, sex, reason for transplantation, calcineurin inhibitor, Epstein-Barr virus (EBV) serostatus, ABO compatibility, lymphocyte cross-matching, or episodes of biopsy proven rejection. Two patients with abdominal lymphadenopathy and one with gastrointestinal PTLD responded to a reduction in immunosuppression. Treatment with rituximab was necessary for another gastrointestinal PTLD patient. Diffuse large-B-cell lymphoma was diagnosed in one patient with mediastinal and lung masses. This patient was treated with chemotherapy and rituximab, followed by surgical resection. All patients survived and no evidence of recurrence has been found since. CONCLUSION: Although PTLD is potentially life-threatening, it can be managed by appropriate and prompt treatment, with a good outcome.

Contralateral glissonian pedicle occlusion in a case of portal vein tumor thrombosis.

To dissect portal vein branches directly and encircle them separately is a common procedure that is performed to control back flow bleeding during operations for hepatocellular carcinoma with portal vein tumor thrombosis. However, this technique has an increased risk of injuring contralateral portal branches and disseminating thrombosis fragments to the remnant liver. We present an alternative technique using right-sided glissonian pedicle occlusion for hepatocellular carcinoma with left portal vein tumor thrombosis due to complex anatomical vasculatures of the hepatic pedicle. This technique would be very useful for liver resection of hepatocellular carcinoma with the major type of portal vein tumor thrombosis.

Unique histopathological features of graft biopsies with liver function abnormalities in living donor liver transplant patients receiving basiliximab induction therapy.

Induction with basiliximab (BXM) has been confirmed as an effective treatment regimen for prophylaxis of acute cellular rejection (ACR). From 1991 to 2008, 116 living donor liver transplantations (LDLTs) were performed. Among these, 50 were included in this study. We compared calcineurin inhibitor plus steroid treatment without BXM (n = 14, control group) and with BXM (n = 36, BXM group). Although the rates of biopsied patients with abnormal serum biochemical tests (SBTs) were similar in the control (10/14, 71.4%) and BXM (21/36, 58.3%) groups, ACR was diagnosed in 9/10 (90.0%) patients in the control group compared with 4/21 (19.0%) patients in the BXM group. In accordance with the histopathological diagnosis, there was a significant difference in the ratios of peripheral CD4(+) CD25(+) T cells at five wk after LDLT between patients with and without ACR in the BXM group. Next, we divided the 32 patients without ACR in the BXM group into two groups: biopsied patients with abnormal SBTs and non-biopsied patients. The donor age of the biopsied patients was significantly higher than that of the non-biopsied patients. Induction with BXM reduced the incidence of ACR, and unique pathological phenomena responsible for graft dysfunction after LDLT with an increased incidence of abnormal SBTs were observed.

Long-term outcome of living related renal transplantation in a patient with short bowel syndrome.

Short-bowel syndrome (SBS) is defined as the malabsorptive state that occurs after extensive resection of the small intestine. In patients with SBS, oral administration of drugs usually becomes difficult because of the severity of intestinal failure. We describe a successful living related renal transplantation (LRRTx) in an 18-year-old male with SBS. Shortly after birth, the patient developed necrotizing enterocolitis requiring massive resection of the small intestine, which resulted in SBS. At seven years of age, the patient developed proteinuria and was diagnosed as focal segmental glomerulosclerosis (FSGS). His kidney function was gradually deteriorated toward the end-stage renal failure. The patient received LRRTx at age of 18 years. To evaluate the absorption capacity of the patient, we investigated pharmacokinetics of calcineurine inhibitors (tacrolimus and cyclosporine). The drug concentration, which is sufficient to provide effective immunosuppression, was achieved with cyclosporine, but not with tacrolimus. The patient therefore received a triple immunosuppressive therapy with oral cyclosporine, methyl-prednisolone and mycophenolate mofetil. To prevent both recurrent FSGS and rejection, we repeatedly analyzed the trough level and the pharmacokinetics of cyclosporine after LRRTx. The patient was successfully treated with oral immunosuppression for over 5 years, without hemodialysis. To our knowledge, this is the first report showing the long-term outcome of LRRTx treated with oral cyclosporine in a patient with SBS.

Steroid-resistant late acute rejection after a living donor liver transplantation: case report and review of the literature.

The majority of acute cellular rejection occurs in the first few months after liver transplantation. It has been, however, reported that some recipients experience late acute rejection, which occurs more than 3 months after transplantation. We herein report a case of late acute rejection that occurred nearly 10 years after liver transplantation. The patient is a 27-year-old male who underwent a living donor liver transplantation when he was 17 years old. At 9 years 6 months after transplantation, the patient presented with the elevated serum levels of liver enzymes and total bilirubin. A liver biopsy showed acute cellular rejection. Steroid bolus therapy was not effective, but we successfully used deoxyspergualin as a rescue therapy. Late acute cellular rejection that occurs nearly 10 years after transplantation has so far been rarely reported. It is generally believed that late acute rejection may be more resistant to treatment and be associated with a higher rate of graft loss, as well being associated with the development of chronic ductopenic rejection. In this report, we have shown that deoxyspergualin is safe and effective for treatment of steroid-resistant late acute rejection, preventing from graft loss of chronic rejection.

Liver laceration associated with severe seizures after living donor liver transplantation.

Hemorrhagic complications commonly occur early after liver transplantation (LT), sometimes requiring emergent relaparotomy. However, active bleeding from the liver graft itself is a rare but life-threatening complication after living donor liver transplantation (LDLT). We report an unusual case of liver laceration with massive bleeding, associated with severe epileptic seizures as a result of tacrolimus-induced leukoencephalopathy, after LDLT. The patient was successfully rescued by conventional surgical management without a second transplantation. In conclusion, to our knowledge this is the first reported case of graft rupture due to immunosuppression-associated leukoencephalopathy after LT.

The safety of the donor operation in living-donor liver transplantation: an analysis of 45 donors.

We retrospectively assessed the safety of the donor operation, based on parameters such as blood loss, blood transfusion, operation time, duration of hospitalization, and complications. Forty-five pediatric and adult recipients underwent living-donor liver transplantation (LDLTx) in Tohoku University Hospital from July 1991 to October 2000. Donor operations were classified into three groups. In the LS group, the graft was the lateral segment ( n=20); in the LL group, the graft was the left lobe without the middle hepatic vein ( n=16); and in the LLM group, the graft was the left lobe with the middle hepatic vein ( n=9). No significant differences were observed among the three groups regarding postoperative liver function or duration of hospitalization. In the LS group, the operation time was shorter and the requirement of autologous blood transfusion was significantly lower than in the other two groups. Most complications following retrieval of the graft were minor. Safety is guaranteed when the left lobe or the left lateral segment is used for LDLTx, but meticulous management of the operation is required to prevent complications.