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Various approaches to portal vein (PV) reconstruction have been described; however, there is still scope to improve the safety and efficiency of how PV anastomosis is performed in infants.We analyzed, retrospectively, the predictive factors for PV reanastomosis during living donor liver transplantation (LDLT) in 117 infants ( 1 year old) with biliary atresia (BA).Twenty-six infants required PV reanastomosis because of intraoperative PV thrombosis in 21 and insufficient PV flow in 5. Univariate analysis identified multiple previous laparotomies and a prolonged anhepatic phase (AHP) as significant risk factors for repeated PV anastomosis. The AHP cutoff value for identifying patients requiring PV reanastomosis was 134 min. Multivariate analysis revealed prolonged AHP 134 min (odds ratio, 15.98; 95% confidence interval, 5.05-50.6; P 0.001) as an independent risk factor for repeated PV anastomosis. The plasma D-dimer and fibrinogen degradation product concentration just after reperfusion were significantly higher in patients requiring PV reanastomosis (P 0.001). Patients requiring reanastomosis of the PV had a higher incidence of PV complications after LDLT than those who did not need PV reanastomosis (P = 0.01).Attempting to minimize the AHP is indispensable for successful LDLT in infants with BA.

Anaplastic large cell lymphoma (ALCL) accounts for 10-15% of childhood non-Hodgkin lymphoma cases; it is generally chemo-sensitive and is one of the most curable pediatric cancers. We report here a case of pediatric ALCL complicated with acute liver failure due to the aggravation of pre-existing biliary hepatopathy by lymphoma-associated hemophagocytic lymphohistiocytosis (HLH). Although the initial treatment response against ALCL was very good, poor and irreversible liver function due to biliary cirrhosis worsening by lymphoma-associated HLH prevented the patient from receiving further consolidation chemotherapies. To make matters worse, his condition was accompanied with intrahepatic fungal pseudoaneurysm and invasive fungal infection. Thus, we decided to perform an urgent living-donor liver transplantation from his father to correct the patient's liver function and make it possible to proceed with further ALCL therapy. After the living-donor liver transplantation, the patient successfully received consolidation therapy with brentuximab vedotin. To our knowledge, this may be an early reported case of a pediatric patient undergoing liver transplantation during treatment for ALCL. In most patients with HLH-associated ALCL, liver function improves when ALCL is controlled. However, acute liver failure is occasionally observed in HLH cases with pre-existing liver dysfunction. In such cases, liver transplantation should be considered to correct liver dysfunctions if the disease control of HLH is satisfactory.

For patients who have chronic myeloid leukemia (CML), one of the primary treatment options is administration of nilotinib 300 mg twice daily (BID). In previous studies which compared outcomes associated with nilotinib or imatinib treatment, nilotinib achieved a higher rate of deep molecular response (MR). We conducted a phase II, open‐label, multicenter study to investigate an intrapatient nilotinib dose‐escalation strategy for patients with newly diagnosed chronic‐phase (CP) CML based on early MR4.5 achievement. The primary study endpoint was achievement of MR4.5 by 24 months following the initiation of nilotinib 300 mg BID. Fifty‐three patients were enrolled, 51 received nilotinib, and 37 completed the treatment. An increase in the nilotinib dose (to 400 mg BID) was allowed when patients satisfied our criteria for no optimal response at any time point. The median (range) dose intensity was 600 (207‐736) mg/day. Of 46 evaluable patients, 18 achieved an optimal response and 28 did not. Of the latter, nine patients underwent dose escalation to 400 mg BID, and none achieved MR4.5. The remaining 19 patients could not undergo dose escalation, 12 (63%) because of adverse events (AEs), and 7 (37%) for non‐AE related reasons. Four of these patients achieved MR4.5. The MR4.5 rate by 24 months was 45.7%. The progression‐free, overall and event‐free survival were each 97.6%. No new safety concerns were observed. Our findings support the use of continuous nilotinib at a dose of 300 mg BID for newly diagnosed patients with CML‐CP., The N‐Road study aimed to determine the optimal treatment strategy for nilotinib use in patients with newly diagnosed CML‐CP based on early achievement of deep molecular response. Most patients received nilotinib at a dose of 300 mg BID and were able to achieve an early deep molecular response. Together with the finding that none of the patients whose dose was escalated to 400 mg BID achieved MR4.5, we consider that continuous nilotinib at a dose of 300 mg BID may be the optimal treatment strategy for newly diagnosed patients with CML‐CP.

Background The native liver of patients with maple syrup urine disease (MSUD) (1st recipients) can be used as a graft for non-MSUD patients with end-stage liver disease (2nd recipients). This study aimed to demonstrate the optimal operational procedures and the long-term outcomes of 2nd recipients. Methods Six 2nd recipients of living donor domino liver transplantation (LD-DLT) (age: 42.5 [22-169] months at DLT) received a native liver as a graft from an MSUD patient at our hospital between June 2014 and April 2020. We reviewed the operational procedures and outcomes of 2nd recipients after LD-DLT. Results The 2nd recipients' original diseases included biliary atresia, congenital hepatic fibrosis, congenital protein C deficiency, familial hypercholesterolemia, hepatoblastoma, and mitochondrial hepatopathy. Five of the six recipients had a whole liver and one had a right lobe graft. The site at which the vessels of the MSUD liver were dissected prioritized the safety of the 1st recipient. At the end of follow-up, all recipients were doing well without surgical complications. The mean serum amino acid values of the 2nd recipients did not exceed the upper limit of the reference values during the long-term observation period. All patients showed normal growth while maintaining the same z-score of height and weight after LD-DLT as the preoperative level. Conclusion The liver of patients with MSUD can be used safely without concern regarding long-term complications or de novo MSUD development. LD-DLT using the MSUD liver can expand the donor pool as an alternative graft in pediatric LT.

Background LT is an elective treatment choice for children diagnosed with GSD1b that can improve their quality of life and stabilize their glucose intolerance. However, careful attention should be paid to immunosuppression after LT due to the susceptibility to infection because of neutropenia and neutrophil dysfunction in GSD1b patients. This study revealed the immunological features and complications in the early post-LT period. Methods We compared findings between 11 (1.9%) children with GSD1b and 273 children with BA. Analyses using the PSM were performed to overcome selection bias. Results Despite persistent low tacrolimus trough levels in GSD1b patients, none of these children developed TCMR within 1 month after LDLT (GSD1b: 0/11 [0%] vs. BA: 86/273 [31.5%], p = .038). This result was also confirmed in PSM. The incidence of bloodstream infections was higher in GSD1b patients than in BA patients in the early phase of the post-transplant period (GSD1b: 4/11 [36.4%] vs. BA: 33/273 [12.1%], p = .041), but not reach statistical significance in PSM. In a phenotypic analysis, the ratio of CD8+ T cells in GSD1b recipients' peripheral blood mononuclear cell samples was lower than in recipients with BA through the first month after LDLT. Conclusions We found that GSD1b recipients were more likely to develop postoperative bloodstream infection than recipients with BA but did not experience TCMR despite low tacrolimus levels in the early post-LDLT period. A tailored immunosuppression protocol should be prepared for GSD1b recipients after LDLT.

Aim Mitochondrial respiratory chain disorder (MRCD) can cause acute liver failure (ALF), which may necessitate liver transplantation (LT). However, MRCD is often difficult to diagnose before LT and the indications of LT are controversial due to the likelihood of progressive neurological disease. The present study further characterized the patient population and described the outcomes. Methods Thirteen patients who underwent LT for MRCD from November 2005 to May 2020 were enrolled in this study. Results Six of 13 MRCD patients were diagnosed with a mitochondrial inner membrane protein 17-related mitochondrial DNA depletion syndrome (MTDPS). Overall, nine survived with a median follow-up of 1.8 years (IQR, 1.3-5.1 years); four died within 2 years. In the long-term, seven survivors showed no progression of hypotonia after LT and attended a normal kindergarten or primary school. Neurological abnormalities were observed in two survivors, including vison loss related to Leber's hereditary optic neuropathy in one patient and psychomotor retardation related to Leigh syndrome in the other. Three non-survivors after LT were diagnosed with MTDPS and died of severe pulmonary hypertension, which had developed at 8, 9, and 18 months after LT (n=1 each). The remaining patient died of postoperative respiratory infection with respiratory syncytial virus. Conclusion The long-term results support the performance of LT in patients with MRCD, although a genetic diagnosis is preferable for determining the accurate indications for LT in these patients. Furthermore, care should be taken to avoid complications due to mitochondrial dysfunction during the long-term follow-up.

Excessive alcohol consumption has a negative impact on graft survival after liver transplantation (LT). However, it is difficult to predict alcohol relapse before LT. This study surveyed the alcohol consumption of LT recipients to identify the risk factors for harmful drinking. We surveyed the alcohol consumption of LT recipients by using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C). AUDIT-C scores ≥ 5 points in men and ≥ 4 points in women indicated a high risk for harmful and hazardous drinking. Excessive alcohol consumption was considered to be20 g per day. Ninety-nine LT recipients completely filled out the questionnaire. Alcohol consumption after LT was detected in 26 recipients (26.5%); 4 of them had alcoholic liver disease before transplantation and 22 did not have alcoholic liver disease. The amount of alcohol consumption per day significantly decreased after LT (alcohol consumption per day: 49.6 g before LT vs 8.1 g after LT, P .05). Fourteen recipients (14.1%) consumed alcohol excessively after LT. The AUDIT-C score before LT and smoking were risk factors for excessive alcohol consumption in the multivariate analysis. To properly manage post-transplant recipients, assessing the risk of excessive alcohol consumption by using the AUDIT-C is necessary.

Refractory ascites after liver transplant commonly occurs in living donor liver transplant (LDLT). Refractory ascites is associated with postoperative complications and poor prognosis. This study sought to determine the risk factors of refractory ascites and discuss their perioperative management.A retrospective study of 122 living donor liver transplant recipients between 2008 and 2017 was performed to analyze the risk factors, incidence, and characteristics of refractory ascites. Refractory ascites post LDLT was defined as the production of ascites fluid1000 mL/d on postoperative day 14 or required repeated drainage.A total of 24 patients (19.6%) developed refractory ascites. The 1-year survival rate was significantly worse in the refractory ascites group compared with the nonrefractory ascites group (P .001). In a univariate analysis, patients with refractory ascites had a higher Model for End-Stage Liver Disease (MELD) score, donor age, presence of left lobe graft, ascites at laparotomy, portal venous pressure just after surgery, cold ischemia time, and absence of hepatocellular carcinoma compared with patients without refractory ascites. Multivariate proportional regression analyses revealed that MELD score ≥20, left lobe graft, donor age 50 years or older, and ascites at laparotomy ≥350 mL were independently associated with refractory ascites. Postoperative complications, such as bleeding (P .001), sepsis (P .001), and bloodstream infection within 30 days after LDLT (P .00), were significantly higher in the refractory ascites group.Refractory ascites is associated with reduced 1-year survival and increased postoperative complications. Four factors including MELD score ≥20, donor age 50 years or older, presence of left graft, and ascites at laparotomy ≥350 mL were independent predictors for refractory ascites.

BACKGROUND Fragility fractures caused by osteoporosis are common complications seen in recipients of organ transplantation who survive long term. Although many risk factors have been identified for osteoporosis after organ transplantation, none of them have been recognized as the main cause of development of the condition. Several studies have examined vitamin D receptor (VDR) gene single-nucleotide polymorphisms (SNPs) for their influence on bone mineral density (BMD) and fracture risk, but with variable results. We aimed to elucidate the risk factors that affect incidence of osteoporosis and fragility fractures in liver transplant recipients. MATERIAL AND METHODS In this study, we monitored incidence of fragility fracture and osteoporosis in 45 patients who had been evaluated with dual-energy X-ray absorptiometry (DXA) after liver transplantation. We also analyzed the association between VDR SNPs such as BsmI, ApaI, FokI, and TaqI with osteoporosis and fracture incidence in 27 patients in our cohort in whom SNPs were evaluated and DXA performed after liver transplantation. RESULTS Osteoporosis was diagnosed in 17 of 45 patients in whom BMD was measured after liver transplantation. Of the patients with osteoporosis, 15 (88.2%) subsequently had fragility fractures. The incidence of postoperative osteoporosis was significantly higher in the recipients who had alcoholic liver cirrhosis as their primary disease. Interestingly, there were significantly more patients with a homozygous BsmI GG genotype in the group diagnosed with osteoporosis. CONCLUSIONS Our study suggests that patients who undergo liver transplantation and have alcoholic liver cirrhosis or the BsmI GG genotype may be at increased risk for osteoporosis. Further research is necessary to confirm these findings.

Background EBV-associated HLH driven by EBV-infected CD8+ T cells is a rare complication after pediatric solid organ transplantation. The etiology and disease spectrum of post-transplant EBV-HLH are poorly understood, and making a precise diagnosis and providing optimal treatment remain a challenge. Methods/case description/results We report a 2-year-old multivisceral transplant recipient who developed fever and cytopenia with a persistent high EBV-load state. Repeated tissue examinations and CT scans could not identify a localized mass, which is the key to the diagnosis of PTLD as per the WHO classification. Hence, EBV-HLH was diagnosed by clinical manifestations as well as characterization of EBV-infected cells, pathological examination on cell block of pleural effusion and clonality analysis. This EBV-HLH did not respond to intensive chemotherapy, resulted in the recipient's death, acting similarly to hematological malignancy. Conclusions Characterization of EBV-infected cells in peripheral blood should be considered when persistent high EBV loads develop with symptoms consistent with PTLD, but no evidence of localized mass, and the tissue diagnosis is unavailable after pediatric solid organ transplantation.

While sarcopenia is an important predictor of LT outcomes in adults, few studies have examined the association of sarcopenia with LT outcomes in pediatric patients. We investigated the clinical influence of sarcopenia on the post-transplant outcomes in infants with BA. To define sarcopenia in infants, the cross-sectional area of the tPMA in 93 healthy control infants was measured by computed tomography. Sarcopenia was defined as a tPMA lower than two standard deviations below the mean of healthy control infants. Eighty-nine infants with BA with a median age at LT of 7.6 months old were enrolled. The clinical characteristics and outcomes of LT were verified in the sarcopenia group (n = 21) and non-sarcopenia group (n = 68). The sarcopenia group had a significantly longer operation time and greater blood loss during LT than the non-sarcopenia group (P = .03 and 0.02). The incidence of portal vein stenosis and post-operative bloodstream infection was also significantly higher in the sarcopenia group than in the non-sarcopenia group (23.8% vs 4.4%, P = .02 and 28.6% vs 10.3%, P = .04, respectively). The total length of hospital stay did not differ significantly. The 1-year patient and graft survival rates tended to be lower in the sarcopenia group than in the non-sarcopenia group (90.5% vs 98.5%, P = .07 and 85.7% vs 97.1%, P = .05, respectively). Sarcopenia in infants with BA may be associated with the patient survival and serve as an effective marker for post-operative outcomes of LT.

Sufficient PV flow is necessary to achieve successful PV reconstruction in pediatric LDLT. IOCP can be used to assess the severity of PV stenosis and to identify potential portosystemic collateral pathways. The present study reviewed the utility of IOCP and the outcomes of patients who underwent assessment with an IOCP. Consecutive primary LDLTs were performed in 488 pediatric recipients between November 2005 and October 2019. IOCP was used in patients who were unable to achieve sufficient PV flow after the ligation of collaterals. In total, 11 patients underwent IOCP to assess potential portosystemic collateral pathways. The median age and body weight was 8 months (IQR, 6-11 months) and 6.6 kg (IQR, 5.7-8.9 kg), respectively. The reasons for using the IOCP were recurrent PV thrombus in seven patients and insufficient PV flow in four patients. IOCP revealed remaining collaterals in six patients and residual hypoplastic PV in eight patients. Two patients required additional interruption of the potential collaterals under IOCP, which were unable to be recognized as a dominant portosystemic collateral pathway on preoperative imaging. All eight patients with residual hypoplastic PV required vein graft interposition for the complete removal of the hypoplastic PV. All the patients are currently doing well with a median follow-up period of 4.9 years (IQR, 2.2-5.6 years). IOCP can be an effective tool for precisely detecting occult portosystemic collateral pathways and for assessing the patency of the PV anastomosis in pediatric LDLT.

OBJECTIVES Central perivenulitis can occur in association with T-cell-mediated rejection and can sometimes require strong immunosuppressant therapy as refractory rejection. Furthermore, patients with central perivenulitis are more likely to have subsequent episodes of T-cell-mediated rejection and develop chronic rejection than those without central perivenulitis. We retrospectively analyzed clinical data of pediatric patients with episodes of T-cell-mediated rejection according to severity of central perivenulitis and monitored HLA-DR-positive CD8-positive T cells and recent thymic emigrants during treatment for T-cell-mediated rejection. MATERIALS AND METHODS We identified biopsy-proven T-cell-mediated rejection in 50 liver transplant recipients (45 with living-related donors, 5 with deceased donors) between September 2014 and August 2018. Lymphocyte subsets in peripheral blood samples were analyzed. RESULTS Of 50 pediatric patients, 30 were boys and 20 were girls (median age at transplant of 1.1 y; interquartile range, 0.6-6.2 y). Central perivenulitis was found in 46 patients (92%), which was mild in 13, moderate in 16, and severe in 17. Antithymocyte globulin was more frequently administered to patients with severe central perivenulitis than others (P < .05). Patients with antithymocyte globulin treatment were less likely to have subsequent episodes of T-cell-mediated rejection than those without this treatment (P < .05). The absolute number of CD8-positive HLA-DR-positive T cells in patients during treatment was significantly higher than in control patients (P < .05). The absolute number of recent thymic emigrants in patients with active infection was significantly lower than in patients without infection (P < .05). CONCLUSIONS Our results suggest the efficacy and safety of antithymocyte globulin for treating T-cell-mediated rejection with severe central perivenulitis in pediatric liver transplant recipients and suggest that antithymocyte globulin can prevent subsequent episodes of T-cell-mediated rejection. Analyzing lymphocyte subsets during treatment for rejection may help highlight viable therapeutic strategies for achieving a good outcome.

Background Because immunosuppression is necessary for kidney transplant recipients, malignant tumorigenesis of recipient organs is a concern; however, few studies have discussed the malignant alteration of transplanted grafts that have been functional for a long time. In addition, a urothelial carcinoma (UC) in transplanted kidney graft is a rare disease. Case report A 62-year-old man had end-stage renal failure 31 years ago and received a kidney transplant from his father. Acute renal failure due to obstruction of the transplanted ureter was diagnosed. Ultrasound, ureterogram, and non-enhanced computed tomography scans revealed no obvious evidence of any neoplastic lesion. We treated the obstruction and hydronephrosis with transplant ureter stenting. However, the regional lymph nodes enlarged, and it became necessary to change the ureteral stent frequently because of stent stenosis; therefore, he underwent lower transplant ureteral resection and reconstruction. Histopathology confirmed a UC with a flat and infiltrative growth pattern. The patient then underwent graftectomy including right external iliac vein resection and reconstruction; however, because of numerous metastatic nodules, radical surgery could not be performed. The patient subsequently died because of septic shock after the second surgery. Conclusion We report a case of an invasive UC with a flat and infiltrative growth pattern derived from a transplant kidney graft that occurred 31 years after a living-donor transplant that could not be treated immediately and was difficult to diagnose.

Background Bile leakage is a major cause of morbidity after hepatectomy. This study aimed to identify the predictive factors for bile leakage after hepatectomy. Materials and methods Between January 2011 and December 2016, 556 patients underwent a liver resection for hepatocellular carcinoma with curative intent, and were enrolled to participate in this study. The incidence of postoperative bile leakage (POBL) was determined and the predictive factors for POBL were identified using univariate and multivariate analysis. Results POBLs occurred in 28 patients (5.0%). The multivariate analysis identified a history of stereotactic body radiotherapy, a body mass index Conclusion We determined that POBL was associated with operative mortality and identified five independent predictive factors associated with POBL. Risk stratification using these predictive factors may be useful for identifying patients at a high risk of POBL.

In deceased donor liver transplantation, a donor liver with moderate (>30%) macrosteatosis used to be considered inappropriate for grafting. We examined the outcomes of children who underwent living donor liver transplantation (LDLT) at the National Center for Child Health and Development whose donor livers had moderate-to-severe macrosteatosis. Twelve children were enrolled who had received a moderate-to-severe macrosteatotic liver graft and underwent liver biopsy soon after LDLT. The primary diseases were biliary atresia in 7 patients, acute liver failure in 3 patients, glycogen storage disease type 1 in 1 patient, and primary sclerosing cholangitis in 1 patient. Median age was 11 months. There were 4 recipients who received grafts from their fathers, and 8 received grafts from their mothers. Median donor age was 35.5 years. We compared the degree of donor liver steatosis with the results of graft liver biopsies that were collected 4-105 days after LDLT. The levels of donor liver macrovesicular steatosis were moderate (34%-66%) in 9 patients and severe (>66%) in 3 patients. The nonalcoholic fatty liver disease activity score was 3 in 7 patients and 4 in 5 patients. Shortly after LDLT, 11 of 12 patients showed improvement in steatosis compared with the donor livers. One biopsy specimen taken 22 days after LDLT showed 60% macrosteatosis, which was the same as that in the donor liver. However, this patient was alive and well 6 years after LDLT. One patient died after LDLT because of infection and respiratory failure. The levels of steatosis of the donor liver grafts improved soon after LDLT in children, and the outcomes of children receiving a moderate-to-severe macrosteatotic liver from their parents were excellent.

Congenital hepatic fibrosis (CHF) often accompanies autosomal recessive polycystic kidney disease (ARPKD), which stems from a PKHD1 gene mutation. The aim of this study was to clarify the prognosis of children with CHF who received living donor liver transplantation (LDLT) from donors who might be heterozygous carriers of a hepatorenal fibrocystic disease. Fourteen children with CHF who underwent LDLT at our center were enrolled. Eight and two patients had ARPKD and nephronophthisis, respectively. Eight of the donors were the recipients' fathers, and six donors were their mothers. We examined the histological and radiological findings of the donor livers and complications in the recipients following the liver transplantation. Seven of the donor livers presented morphological abnormalities of the bile ducts. Abdominal computed tomography revealed liver cysts in eight donors. One recipient underwent re-LT for graft failure due to rejection. Three patients presented with rejection, and one presented with sepsis. The overall survival rate was 100% and the original graft survival rate was 93%. In conclusion, the prognosis of recipients who received a LDLT from their parents for CHF was excellent. However, the morphology of half the donor livers was abnormal. Careful follow-up is needed to ensure long-term graft survival.

Although poor long-term graft survival in LT in AYA is recognized, detailed epidemiological data are still lacking. L-TCMR may have poor outcomes. This study aimed to provide a detailed, epidemiological assessment of the association between AYA age and rejection. L-TCMR was defined in this study as TCMR with central vein or perivenular inflammation occurring later than 3 months after LT. A total of 342 patients who survived for at least 3 months after LT between 2005 and 2015 were enrolled. The AYA group (10-24 years) was compared with the C group (less than 10 years), and the incidence and outcomes of L-TCMR were analyzed. In total, 342 patients had LT; 38 of these were AYA with the mean follow-up period of 6.7 years. A total of 304 patients in C group had a mean follow-up period of 6.3 years (P = .28). The incidence of L-TCMR in AYA group was significantly higher than in C group (15.8% vs 4.6%, P = .006). The time to L-TCMR after LT was significantly shorter in AYA group (P = .01). Neither patient survival nor the incidence of non-adherence differed significantly between the groups (P = .18 and P = .89). The number of additional immunosuppressants after L-TCMR was significantly higher in the AYA group (P = .04). A high incidence of L-TCMR was observed in AYA group irrespective of non-adherence. AYA patients with L-TCMR should be followed carefully due to the poor results of post-treatment biopsy and the need for intensive immunosuppressive therapy.

Living donor liver transplantation (LDLT) has become a major life-saving procedure for children with end-stage liver disease in Japan, whereas deceased donor liver transplantation (DDLT) has achieved only limited success. The annual number of pediatric liver transplantations is approximately 100-120, with a patient 20-year survival rate of 81.0%. In 2005, the liver transplantation program at the National Center for Child Health and Development in Tokyo, Japan, was initiated, with an overall number of 560 pediatric patients with end-stage liver disease to date. In July 2010, our center was qualified as a pediatric DDLT center; a total of 132 patients were listed for DDLT up until February 2019. The indications for DDLT included acute liver failure (n = 46, 34.8%), metabolic liver disease (n = 26, 19.7%), graft failure after LDLT (n = 17, 12.9%), biliary atresia (n = 16, 12.1%), and primary sclerosing cholangitis (n = 10, 7.6%). Overall, 25.8% of the patients on the waiting list received a DDLT and 52.3% were transplanted from a living donor. The 5-year patient and graft survivals were 90.5% and 88.8%, respectively, with an overall waiting list mortality of 3.0%. LDLT provides a better survival compared with DDLT among the recipients on the DDLT waiting list. LDLT is nevertheless of great importance in Japan; however, it cannot save all pediatric recipients. As the mortality of children on the waiting list has not yet been reduced to zero, both LDLT and DDLT should be implemented in pediatric liver transplantation programs.

Several technical modifications in portal vein (PV) reconstruction have shown excellent outcomes in pediatric liver transplantation (LT); however, which procedure is the best for PV reconstruction of the hypoplastic PV in pediatric LT remains unclear.One hundred sixteen pediatric patients aged 1 or younger with biliary atresia (BA) undergoing living donor LT (LDLT) at our center were enrolled in the present study to investigate the outcomes of the different types of PV reconstruction. We compared the results between patients with and without vein graft (VG) interposition (VG group, n = 33; non-VG group, n = 83) to analyze the risk factors for PV complications (PVCs). The median follow-up period was 4.7 years.PVCs occurred in 10 cases (7.2%), including 5 cases in the non-VG group and 5 in the VG group. Stenosis and thrombosis occurred in 10 and 3 cases, respectively, and 3 cases suffered from both. Three patients were surgically treated for PVCs, and 2 underwent stent insertion to treat short-term recurrence after the initial treatment. The incidence of PVCs in the 2 groups did not differ to a statistically significant extent. Although retrograde PV flow was 1 of the significant risk factors in a univariate analysis, a multivariate analysis revealed that early transplant era was the only independent risk factor for PVCs.VG interposition for PV reconstruction in LDLT appears to be a feasible alternative option with acceptable outcomes for patients with BA. Achieving sufficient PV flow is essential to preventing PVCs after LDLT.

Background Intrapulmonary shunt (IPS) is recognized in 10% of chronic liver disease patients. Liver transplantation (LT) is associated with a high risk of morbidity and mortality in patients with IPS. Patients and methods Of 519 pediatric LT cases between November 2005 and October 2018, 50 patients with IPS were enrolled in this study. The patients were divided into 3 groups, according to the shunt ratio, calculated by scintigraphy: mild (15%-20%, n = 26), moderate (20%–40%, n = 19), and severe (> 40%, n = 5). We compared the patients’ characteristics before LT and the outcomes of LT between these groups. Results The major original disease resulting in LT in the mild and moderate groups was biliary atresia (73.1% and 52.6%, respectively), while that in the severe group was congenital portosystemic shunt (60%). The median ages at LT were 7.5, 6.1, and 8.3 years in the mild, moderate, and severe groups, respectively. All of the mild and moderate IPS patients lived; however, 3 patients with severe IPS (60.0%) died within 3 months. The shunt ratios of the mild and moderate IPS patients normalized within 2 years after LT, while the 2 surviving severe IPS patients showed a slight improvement. The autopsy findings of the lung in 1 deceased severe IPS patient showed medial hypertrophy and proliferation of intimal cells of the pulmonary arteries, suggesting a diagnosis of portopulmonary hypertension. Conclusions LT can be safely performed for mild and moderate IPS patients; however, LT for severe IPS patients should be carefully indicated because concomitant portopulmonary hypertension may be masked by IPS.

In liver transplantation (LT) for biliary atresia (BA) with situs inversus (SI), the surgical procedure is technically challenging due to multiple anatomical variations. We evaluated the surgical procedures and the outcomes in our patients and in the previously reported patients undergoing LT for BA with SI. Between November 2005 and October 2018, 235 children underwent LT with an overall 10-year graft survival of 94.7%. Of these, 6 (2.6%) patients received LT for BA with SI. Living donor liver transplantation (LDLT) was applied in all patients. Vascular anomalies at our center included the absence of the inferior vena cava (IVC; n = 5), a preduodenal portal vein (PV; n = 4), and an aberrant hepatic artery (HA; n = 1). Hepatic vein (HV) outflow obstruction occurred in 1 patient with an absent IVC and necessitated repositioning of the graft immediately after LDLT. PV stenosis occurred in 1 patient with a preduodenal PV at 5 months after LDLT. The overall survival of our patients was 80.0% at 3 years. In the literature, 49 patients with LT for BA with SI were reviewed. The survival rate was 91.8%, and the vascular complications included HV outflow obstruction (2.0%), PV complications (10.2%), and HA thrombosis (4.1%). All PV complications occurred in LDLT patients with a preduodenal PV (5/23; 21.7%). In conclusion, the detailed assessment of the surgical procedures and the systematic literature review demonstrated excellent outcomes after LT for BA with SI. Liver recipients with a preduodenal PV are exposed to a higher risk for vascular complications after a very challenging LT procedure with overall good outcomes.

Background Refractory ascites is one of the major complications of liver transplant (LT) and is associated with increased morbidity and mortality. The aim of this study was to analyze the efficacy and safety of novel cell-free and concentrated ascites reinfusion therapy (KM-CART) for the treatment of refractory ascites during preoperative living donor liver transplant. Methods Forty KM-CART procedures were performed on 8 liver transplant candidates. We investigated the safety and efficacy of KM-CART in terms of the processed ascites, adverse events, laboratory data, and patient condition. Results By using KM-CART, an average of 12.5 L (range, 2.6–26.1 L) of ascites was filtered and concentrated to 0.5 L (range, 0.1–1.6 L) in 62 minutes (range, 8-187 minutes). Final products contained 21.5 g (range, 2.5–65.6 g) of albumin and 13.5 g (range, 1.5–61.8 g) of globulin. No endotoxin contamination was detected in the ascites. Although the incidence of adverse events was 35.0% (including fever, hypotension, bleeding, leg cramps, and nausea), all of these could be treated conservatively. Body weight and oral intake were significantly improved after KM-CART. Furthermore, the use of fresh frozen plasma for the LT recipients with KM-CART was significantly lower than that for patients without KM-CART. In addition, no patients lost their opportunity for LT because of adverse events due to KM-CART. Conclusions Our findings show that KM-CART could be a promising option for the treatment of refractory ascites during the preoperative period of LT. This study provides the foundation for further large-scale prospective studies.

Abdominal aortic calcification (AAC) is known as a risk factor of coronary artery disease, stroke, hyperphosphatemia, chronic inflammation, diabetes, and decreased estimated glomerular filtration rate. However, the clinical implications of incidental AAC findings in liver transplantation (LT) have not been evaluated in terms of posttransplantation survival and complications. Therefore, we analyzed the relationships between the AAC level and the outcomes following LT. A total of 156 consecutive patients who underwent LT between January 2007 and December 2014 were divided into 2 groups according to their AAC level (

Background We report a case of acute rejection of a liver graft, together with the occurrence of de novo donor-specific antibodies (DSAs), in a 53-year-old Japanese man who had undergone deceased-donor liver transplantation. Methods The graft rejection was triggered by low cyclosporine levels and pegylated interferon treatment for the recurrence of hepatitis C virus (HCV) infection 18 months after transplantation. Although the graft was ABO-compatible, pre-formed DSA B51 was detected; therefore, total plasma exchange was performed and intravenous rituximab (500 mg/body) was administered before transplantation. Results DSA was absent 6 months after transplantation. HCV recurrence was treated with pegylated interferon-α-2a. Renal function deteriorated with this anti-HCV therapy, with serum cyclosporine levels decreasing to 50 ng/mL. A rapid virologic response was achieved, but liver function deteriorated after 3 months of anti-HCV therapy, with histologic evidence of acute cellular rejection and formation of de novo DSAs. Anti-thymocyte globulin was administered for 5 days, which led to immediate improvement in liver function. However, renal function declined, warranting hemodialysis. The patient recovered 2 months after acute rejection, although de novo DSAs persisted. Conclusions Careful immunologic monitoring may be required for patients receiving interferon therapy for HCV infection to maintain sufficient blood levels of immunosuppressive agents and to prevent acute liver graft rejection.

We investigated the impact of polymorphisms in host innate immunoregulatory genes on the development of infectious complications after kidney transplantation (KT). The single-nucleotide polymorphisms (SNPs) of C1QA [276 A/G], FCGR2A [131 H/R], and FCGR3A [158 F/V], genes encoding the Fc gamma receptor (FcγR), were analyzed in 81 KT recipients in relation to the occurrences of postoperative infectious complications within 30 days after KT. Consistent with a lower affinity of the isoform encoded by the FCGR3A [158 F] to both IgG1 and IgG3, a significantly higher incidence of urinary tract infections (UTIs) was observed in the FCGR3A [158 F/V or F/F] individuals (65.5%) than in the FCGR3A [158 V/V] individuals (34.5%) following KT. The combination of FCGR2A and FCGR3A SNPs further stratified the incidence of UTIs, regardless of C1QA SNP following KT. No differences were observed in the incidence of fungal or cytomegalovirus infections with respect to the 3 gene polymorphisms. In conclusion, our findings indicate that FcγR SNPs are predisposing factors for UTIs after KT. This study provides a foundation for further prospective studies on a larger scale.

Background The role and phenotypic alterations of intrahepatic natural killer (NK) cells in liver disease were investigated. Although intrahepatic NK cells reportedly functionally deteriorate in the fibrotic liver, it remains unclear how the clinical severity of liver disease affects intrahepatic NK cells in patients with advanced liver failure. Methods We analyzed the phenotypic properties of intrahepatic NK cells by using mononuclear cells extracted from ex vivo liver perfusate effluents from patients who underwent liver transplantation. The relationship between the clinical severity of liver disease and the phenotype of intrahepatic NK cells in these patients was also evaluated. To estimate the immunological responsiveness of intrahepatic NK cells, phenotypic enhancement after interleukin-2 stimulation was analyzed. Results Intrahepatic NK cells from patients with advanced liver failure exhibited down-regulated monomodal expression of NKp46, a major activating molecule. Notably, the expression level of NKp46 decreased depending on the severity of liver disease, Model for End-Stage Liver Disease score, and Child-Pugh score rather than the etiology. After in vitro recombinant interleukin-2 stimulation, the enhancement of expression of cytotoxic molecules, NKp44, and tumor necrosis factor–related apoptosis-inducing ligand was significantly impaired in intrahepatic NK cells from patients with liver failure, concurrently with decreased expression of CD122 and interleukin-2 receptor beta. Conclusions Our results suggest that terminal deterioration of liver environments by chronic liver disease impairs the potential of local NK cells, depending on the severity of the deterioration. These influences of advanced liver failure on intrahepatic NK cells may be attributed to multicentric carcinogenesis in patients with liver failure.

We herein report a case of heterotopic gastric mucosa in the hilar bile duct. An asymptomatic 58-year-old male was noted to have mild liver dysfunction in March 2009 during the follow-up for angina pectoris. Abdominal-enhanced CT revealed wall thickening from the upper common hepatic bile duct to the left hepatic bile duct. Endoscopic retrograde cholangiopancreatography (ERCP) showed stenosis at the junction of the left hepatic bile duct. Although the patient's serum tumor markers were all within the normal ranges, the possibility of malignant disease of the biliary tree could not be ruled out. Left hepatectomy with the caudate lobe and resection of the extrahepatic bile duct were performed. Histopathologically, the resected specimen showed a polypoid lesion measuring 2 × 2 cm in size that projected into the lumen of the left hepatic bile duct. Microscopic examination revealed this polypoid lesion to be composed of mucous glands resembling gastric fundic glands, with parietal and chief cells. We also review eight other reports of heterotopic gastric mucosa in the biliary tree previously published in the English literature.

The correlation between imatinib (IM) trough plasma concentration (Cmin) and clinical response was assessed in patients with chronic-phase chronic myeloid leukemia. The Cmin correlated with neither the achievement of complete cytogenetic response (977 vs. 993 ng/ml, P = 0.48) nor a major molecular response (1,044 vs. 818 ng/ml, P = 0.17). Although this was significantly higher in patients with complete molecular response (CMR) than in those without (1,430 vs. 859 ng/ml, P = 0.04), the difference was not significant in the sub-population treated with a standard dose of IM (400 mg/day). Finally, multivariate analysis showed that the IM standard dose, but not Cmin, was predictive of the achievement of CMR. We thus suggest that, in practical clinics at least, adherence to the standard dose is the most important factor for the achievement of CMR.

We have identified a novel fusion partner of MLL, namely the mastermind like 2 (MAML2 gene), in secondary acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) with inv(11)(q21q23). RT-PCR and sequencing revealed that exon 7 of MLL was fused to exon 2 of MAML2 in the AML and MDS cells. The inv(11)(q21q23) results in the creation of a chimeric RNA encoding a putative fusion protein containing 1,408 amino acids from the NH2-terminal part of MLL and 952 amino acids from the COOH-terminal part of MAML2. The NH2-terminal part of MAML2, a basic domain including a binding site of the intracellular domain of NOTCH, was deleted in MLL-MAML2. MLL-MAML2 in secondary AML/MDS and MECT1-MAML2 in mucoepithelioid carcinoma, benign Wartin's tumor, and clear cell hidradenoma consist of the same COOH-terminal part of MAML2. A luciferase assay revealed that MLL-MAML2 suppressed HES1 promoter activation by the NOTCH1 intracellular domain. MAML2 involving a chimeric gene might contribute to carcinogenesis in multiple neoplasms by the disruption of NOTCH signaling.

We investigated the impact of polymorphisms in host innate immunoregulatory genes on the development of infectious complications after liver transplantation (LT). The single-nucleotide polymorphisms (SNPs) of C1QA [276A/G], FCGR2A [131H/R], and FCGR3A [158F/V], genes encoding the Fc gamma receptor (FcγR), were analyzed in 89 living donor LT recipients in relation to the occurrences of postoperative infectious complications within 30 days after LT. Consistent with a lower affinity of the isoform encoded by FCGR3A [158F] to both IgG1 and IgG3, a significantly higher incidence of bloodstream infections (BSI) was observed in the FCGR3A [158F/V or F/F] than in the FCGR3A [158V/V] individuals. The combination of FCGR2A and FCGR3A SNPs further stratified the incidence of BSI, regardless of C1QA SNP. The predominant causative pathogen of BSI in the FCGR3A [158F/F or F/V] patients was gram-positive cocci (73.3%), of which one third was methicillin-resistant Staphylococcus aureus. No differences were observed in the incidence of fungal infections or in cytomegalovirus infections with respect to the three gene polymorphisms. Our findings indicate that FcγR SNPs are predisposing factors for BSI and can predict mortality after LT. This study provides a foundation for further prospective studies on a larger scale.

A 65-year-old male with rapidly progressive Lennert's lymphoma terminating in fulminant hepatic failure is presented. Staging radiological studies revealed that he had cervical and mediastinal lymph node swellings and multiple nodular lesions in the spleen. Lymph node biopsy specimens showed the proliferation of epithelioid cells interspersed with large blastic lymphocytes. These lymphocytes were CD3+, CD45RO (UCHL-1) +, CD4-, CD8+, CD56-, CD30-, CD15-, T-cell intracellular antigen-1+, granzyme B+ and perforin+, suggestive of the cytotoxic T-cell lineage. Under the diagnosis of Lennert's lymphoma, he was treated with standard CHOP chemotherapy. After two courses of the chemotherapy, despite the decreased size of cervical lymph nodes, high-grade fever and constitutional symptoms appeared. As multiple low-density nodules were observed in the liver by computed tomography, needle biopsy was performed. The biopsy specimens showed the proliferation of CD3+, CD4- and CD8+ lymphoma cells. Thereafter, the liver function deteriorated rapidly, and disseminated intravascular coagulation emerged. He died of rapidly progressive hepatic failure. This case is another example demonstrating that at least some of the Lennert's lymphomas phenotypically correspond with cytotoxic T-cell lymphomas, as was previously suggested by us [Am. J. Surg. Pathol. 24 (2000) 1627]. It should be also emphasized that Lennert's lymphomas containing cytotoxic proteins may have a fulminant clinical course, which cannot be rescued by the conventional chemotherapy.

The effects of crude polyphenol extracted from immature apples on the enzymatic and biological activities of a cholera toxin (CT) were investigated. When the apple polyphenol extract (APE) was examined for properties to inhibit CT-catalyzed ADP-ribosylation of agmatine, it was found that APE inhibited it in a dose-dependent manner. The concentration of APE to inhibit 50% of the enzymatic activity of CT (15 microg/ml) was approximately 8.7 microg/ml. The APE also diminished CT-induced fluid accumulation in two diarrhea models for in vivo mice. In the ligated ileum loops, 25 microg of APE significantly inhibited fluid accumulation induced by 500 ng of CT. In a sealed mouse model, even when APE was administered orally 10 min after a toxin injection, fluid accumulation was significantly inhibited at a comparable dosage. Lineweaver-Burk analysis demonstrated that APE had negative allosteric effects on CT-catalyzed NAD: agmatine ADP-ribosyltransferase. We fractionated the APE into four fractions using LH-20 Sephadex resin. One of the fractions, FAP (fraction from apple polyphenol) 1, which contains non-catechin polyphenols, did not significantly inhibit the CT-catalyzed ADP-ribosylation of agmatine. FAP2, which contains compounds with monomeric, dimeric, and trimeric catechins, inhibited the ADP-ribosylation only partially, but significantly. FAP3 and FAP4, which consist of highly polymerized catechin compounds, strongly inhibited the ADP-ribosylation, indicating that the polymerized structure of catechin is responsible for the inhibitory effect that resides in APE. The results suggest that polymerized catechin compounds in APE inhibit the biological and enzymatic activities of CT and can be used in a precautionary and therapeutic manner in the treatment of cholera patients.

A 66-year-old Japanese man developed severe anemia and erythroid hypoplasia in bone marrow without any significant underlying disease. The results of an antiglobulin test were strongly positive, and serum erythropoietin (Epo) was high. The patient was diagnosed as having acquired pure red cell aplasia (PRCA) and was treated with steroids. Anemia was subsided by reticulocyte production in parallel with a decrease in the titer of antiglobulin test and the level of Epo. We studied the immunological mechanism directed against erythroid cells in vitro by using the patient's serum. In vitro analysis indicated the presence of an inhibitor of erythroid precursors at onset, and its disappearance at remission, suggesting the presence of inhibitor against erythroid precursors.

Aims: To explore the biomarker for predicting the occurrence of adverse events in myeloma patients treated by intravenous bortezomib, we measured proteasome activity in peripheral blood mononuclear cells. Methods: Samples were obtained from 34 bortezomib-naïve patients. Proteasome activity was measured at pre- and postchemotherapy phase by using a synthetic substrate. Results: Bortezomib injection resulted in a dramatic decrease in proteasome activity, reaching 32.4 ± 18.79% (mean ± SD) of the pretreatment level at 1 h, but it generally recovered at the end of the first course. In total, 6 patients manifested with severe bortezomib-induced peripheral neuropathy (sBIPN) in the second-third course. There was a nonsignificant trend for these patients to have lower levels of the relative proteasome activity at the end of the first course than those without sBIPN (median: 74.03 vs. 103.2%, p = 0.052). Moreover, in all of them, proteasome activity did not recover to the pretreatment level, whereas no patients with complete recovery manifested with sBIPN. Analysis with Fisher's exact test demonstrated that incomplete recovery of proteasome activity is a significant risk factor for sBIPN (p = 0.014). Conclusion: Patients with incomplete recovery of proteasome activity are at high risk for developing sBIPN, and the susceptible patients can be indicated by monitoring proteasome activity.

The reciprocal translocation t(1;3)(p36;q21) is associated with myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML) characterized by trilineage dysplasia, in particular dysmegakaryocytopoiesis, and a poor prognosis. As yet no molecular genetic analyses of the t(1;3) have been reported. In four patients with t(1;3), all of whom had AML-M4, which evolved from MDS, the breakpoints at 3q21 clustered within a 60-kb region centromeric to the breakpoint of the inv(3)(q21q26), whereas the breakpoints at 1p36 clustered within a 90-kb region at 1p36.3. The presence of novel clusters in both the 3q21 and 1p36 breakpoints (BCRs) suggests a common, underlying molecular mechanism for the development of t(1;3)-positive MDS/AML. The Ribophorin I (RPN1) gene close to the BCR at 3q21 was highly expressed without gross structural changes, whereas the GR6 gene located within the BCR at 3q21 was not expressed. No other highly expressed genes were isolated in a 150-kb region at 3q21. Thus, it is likely that a gene at 1p36.3 is activated by the translocation of the 3q21 region or a gene important for transformation lies on 3q21, outside the 150-kb region. Further characterization of the BCRs at 1p36.3 and 3q21 should provide important insights into the molecular genetic mechanisms involved in the genesis of t(1;3)-positive MDS/AML. Genes Chromosomes Cancer 27:229-238, 2000.

We hypothesized that bone acquisition was affected by the timing of meal intake after resistance exercise training. This was based on the following previous results: 1) Nutrient intake right after exercise resulted in an increase in muscle mass and a decrease in abdominal fat mass as well as muscle protein synthesis when compared to the intake of a meal later after the exercise; and 2) body composition has been proposed to be a good predictor of bone mass. To substantiate our hypothesis, 20 male rats were assigned to either a group fed a meal right after squat exercise (R) or a group fed a meal 4 h after the exercise (L). The 10-wk training program consisted of approximately 70% of one repetition maximum for each animal, 15 repetitions per set, 10 sets per day, 3 d per week. As a result, hindlimb muscle mass in the R group was greater (p

The purpose of this study was to investigate the effect of glucose administered with amino acids before and during exercise on hepatic ureagenesis. Eight mongrel dogs subjected to treadmill running for 150 minutes at 10 km/h on a 12% incline were intravenously infused with either a mixture of amino acids and glucose (AAG) or amino acids alone (AA). The infusion was started 60 minutes before exercise and continued until the end of exercise. The rate of urinary urea excretion increased after infusion of both AAG and AA. However, the rate of urinary urea excretion was significantly lower in the AAG group versus the AA group during the first 1.5 hours of the recovery period ([R0 to R90] 514+/-24 v 637+/-24 mg/h, mean+/-SE, P < .05). Moreover, hepatic urea output was decreased during AAG versus AA infusion (229+/-62 v 367+/-55 microg/kg/min, P < .05). Hepatic glucose production during exercise was also significantly lower in AAG versus AA infusion (354+/-54 v 589+/-56 mg/kg, P < .05). On the other hand, no difference was observed in hepatic total amino acid uptake between the groups. Thus, these results indicate that AAG administered before and during exercise appears to reduce hepatic ureagenesis due to reduced hepatic gluconeogenesis as compared with administration of AA alone. These findings also suggest that nitrogen retention is enhanced by glucose administered during exercise.

Campylobacter fetus subspecies fetus rarely causes celluitis associated with bacteremia in debilitated hosts. We have identified this infection in two patients with systemic lupus erythematosus and in one with liver cirrhosis. All three patients had eaten raw beef, liver, or improperly cooked pork before the manifestations of the illness. C. fetus subspecies fetus was recovered from blood and feces from the three patients. This organism was also isolated from a subcutaneous aspirate of the cellulitis lesion in one patient. DNA macrorestriction endonuclease profiles analyzed by pulsed field gel electrophoresis differed for the isolates from the three patients but were identical for the blood and fecal isolates or the aspirate and fecal isolates from each patient. These findings suggest that cellulitis associated with bacteremia arises from ingestion of C. fetus subspecies fetus organisms and that clinicians and microbiologists should be aware of this infection in debilitated hosts.

Maintaining hepatic inflow and appropriate venous drainage is important for maximizing the capacity of the retrieved graft in liver transplantation. Here, we report a successful case of multiple hepatic vein (HV) reconstruction using an all-in-one sleeve patch graft of the autologous great saphenous vein to ensure adequate blood flow through the HV. A patient with hepatocellular carcinoma caused by hepatitis C virus–induced cirrhosis underwent living donor liver transplantation using a right lobe graft. A preoperative dynamic computed tomography scan and intraoperative findings revealed that the graft had three middle HV tributaries, a superficial vein, segment VIII HV (V8), and segment V HV (V5). The openings of the superficial vein and V8 were located very close to that of the right hepatic vein (RHV) in the cutting surface. Each HV had significant diameter and drainage territory requiring reconstruction. An autologous great saphenous vein was used to create a sleeve patch to incorporate the close-packed HV openings. The autologous sleeve patch graft was sutured to the openings of the RHV and the superficial vein and the hole created on the sleeve patch graft was anastomosed to the openings of V8 directly on the back table to create an all-in-one sleeve patch. For the V5 reconstruction, the recipient's intrahepatic portal vein graft was used to create an interpositional conduit from the recipient's V5 to the inferior vena cava. The postoperative course was uneventful and postoperative studies revealed good graft function with excellent blood flow in the HV.

Congenital cystic adenomatoid malformation (CCAM) in adolescents or adults is extremely rare. In this case study, a 17-year-old boy was admitted to our clinic for the treatment of a giant bulla in the lower lobe of the right lung. Preoperative imaging studies led to the diagnosis of cystic lung disease. The patient underwent wedge resection of the right lower lobe with VATS, and histological examination confirmed the presentation of type 1 CCAM. A thoracoscopic lobectomy was performed after the second surgery because of postoperative air leakage.Herein, we report a case of CCAM in an adolescent. VATS was a suitable procedure for the operation. Between the parenchyma-saving resection and lobectomy for CCAM, we believe that the lobectomy is the better treatment option when the extent of the disease cannot be determined clearly or it is extremely large. Therefore, strategies for deciding between parenchyma-saving resection and lobectomy for the treatment of CCAM should be developed.

A 76-year-old male was referred for the treatment of liver tumors detected by abdominal computed tomography (CT). Dynamic CT revealed a low-density tumor with an irregularly enhanced rim in the left lateral sector, and a highly enhanced, well-circumscribed tumor in the caudate lobe, accompanied by dilation of the intrahepatic biliary ducts in the left lobe. Preoperative imaging studies led to the diagnosis of double cancers consisting of intrahepatic cholangiocarcinoma and hepatocellular carcinoma (HCC). Left hemihepatectomy with caudate lobectomy was performed. The postoperative course was uneventful. Microscopic evaluation revealed that the tumor in the left lateral sector was adenosquamous carcinoma (ASC), whereas that in the caudate lobe was HCC. This report presents the first case describing the resection of synchronous double cancers of primary hepatic ASC and HCC.

Optimal salvage chemotherapy has not been established for lymphoid malignancy, which is refractory to the conventional cyclophosphamide, doxorubicin, vincristine, and prednisone regimen. To explore an effective regimen, we conducted a phase I pilot study of combination chemotherapy with methotrexate, ifosfamide, l-asparaginase and dexamethasone (MILD), which are unaffected by MDR1-encoded P-glycoprotein. A total of 18 patients with lethal lymphoid malignancy were enrolled over a 2-yr period. The median age was 63 yr. Eleven patients had T/NK-cell malignancies, six had B-cell malignancies, and one was diagnosed with a blastic plasmacytoid dendritic cell neoplasm. Patients aged >/=60 and

More than 40 genes have been reported as translocation partners of the mixed lineage leukemia gene (MLL) in hematologic malignancies. AF17 was identified earlier than most other MLL translocation partners. On the other hand, there is only 1 report of an MLL-AF17 fusion transcript in acute myeloid leukemia (AML). Here we describe a 40-year-old man with a diagnosis of AML involving t(11;17)(q23;q21). We identified a chromosomal breakpoint for t(11;17)(q23;q21) at MLL intron 6 and AF17 intron 8. Although the previously reported form of the MLL-AF17 fusion transcript was not detected by reverse transcriptase-polymerase chain reaction (PCR) analysis, a novel form of an MLL-AF17 fusion transcript joining MLL exon 6 to AF17 exon 9 was detected by complementary DNA panhandle PCR. The fact that 2 forms of MLL-AF17 retain the leucine zipper domain of AF17 suggests that the dimerization domain of AF17 is critical for leukemogenesis by the MLL-AF17 fusion gene.

A 24-yr-old man was referred for fever, right cheek swelling, subcutaneous tumor and liver dysfunction. Physical examination showed an elastic hard subcutaneous tumor on the right cheek, left axillary lymph node swelling and multiple small subcutaneous tumors in the trunk. Laboratory examinations showed elevated levels of transaminase, soluble interleukin-2 receptor and ferritin. Biopsy of the subcutaneous tumor showed proliferation of medium-sized cells with abundant clear cytoplasm and hyperchromatic nuclei among the subcutaneous fat tissues. These cells showed CD3+, CD4-, CD8+, CD56- and CD20- phenotype and possessed cytotoxic molecules such as granzyme B and T-cell intracellular antigen-1. Bone marrow aspiration showed proliferation of small numbers of abnormal lymphocytes with severe hemophagocytosis. He was thus diagnosed as having subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and treated with dose-escalated CHOP regimen. After three courses of the chemotherapy, he was further treated with high-dose chemotherapy and total body irradiation (TBI) with autologous peripheral blood stem cell rescue. Thereafter, he has been in remission for more than 2 yr. We consider that SPTCL with hemophagocytosis is an extremely aggressive disease, and high-dose chemotherapy and TBI should be included for the choice of the treatment.

The case of a 49-year-old man with peripheral T-cell lymphoma arising in Behcet disease (BD) is reported. A diagnosis of incomplete BD was made, and the patient was treated with immunosuppressive agents for 9 months. A left perirenal mass emerged, and a computed tomography-guided needle biopsy of the tumor revealed the infiltration of small- and medium-sized lymphoma cells. The cells were positive for CD3, CD8, CD45RO, CD43, granzyme B, and T-cell intracellular antigen-1. A diagnosis of non-Hodgkin's lymphoma (diffuse medium, T-cell) was made. A left orbital mass also appeared. Standard combination chemotherapy diminished the perirenal and orbital lesions. Lymphoma cell infiltration in the esophagus was detected after chemotherapy, and the patient died of massive bleeding from the gastrointestinal tract. Non-Hodgkin's lymphoma is rarely associated with BD, and only 7 cases have been reported in the literature. We have summarized the published case reports of malignant lymphoma arising in BD. To our knowledge, this case report is the first to describe cytotoxic T-cell lymphoma arising in Behçet disease.

We describe the case of a 40-year-old man whose disease was initially diagnosed as acute myelocytic leukemia. The patient achieved remission with chemotherapy, but relapsed shortly afterwards with an acute T-cell lymphoblastic leukemia. He died of intracranial bleeding. Karyotyping analysis showed a del(9p?) as a common abnormality in the leukemic cells at onset and relapse. Fluorescence in situ hybridization analysis demonstrated allelic loss of the CDKN2A gene in cells from both stages of the disease. At relapse the leukemia cells had additional abnormalities such as add(1)(p36) and del(12)(p11). We postulate that the loss of CDKN2A is involved in leukemogenesis but does not determine the lineage of the leukemic cells. Instead, abnormalities of genes at 1p36, 12p11, or both may be involved in driving a lymphoid phenotype.

A 75-yr-old male simultaneously having lymphoplasmacytic lymphoma (LPL) and diffuse large B-cell lymphoma (DLBCL) is presented. He had manifested with lumbago, high-grade fever, and confusion. Physical examination on admission showed disorientation and severe back pain. There were neither lymphadenopathy nor hepatosplenomegaly. Routine laboratory tests showed moderate pancytopenia, hypercalcemia (serum calcium, 15.9 mg/dL), IgM lambda-type monoclonal gammopathy (IgG, 405 mg/dL; IgA, 42 mg/dL; and IgM, 2023 mg/dL), and lambda-type Bence-Jones protein in the urine (0.8 g/d). Bone marrow biopsy showed the clusters of surface lambda-positive small-sized mature-appearing lymphoplasmacytoid cells. Bone survey and computed tomographic scan showed multiple osteolytic lesions and a tumor involving the third lumbar spine (L3). An open biopsy of the L3 tumor showed diffuse proliferation of CD20- and lambda-positive large cells. We thus diagnosed the patient as simultaneously having LPL and DLBCL. Although the combination chemotherapy was at least partially effective, he died of bacteremia and organ failure after three courses of chemotherapy. To clarify the clonal relatedness between LPL and DLBCL, we analyzed the sequences of the complementarity-determining region 3 in immunoglobulin heavy-chain genes. The data showed that LPL and DLBCL in the present patient originated from two independent clones.

We conducted an epidemiological study to investigate the relation of food intake to Helicobacter pylori (H. pylori) infection in an area endemic for H. pylori. In this study, 365 subjects, 104 men and 261 women, were randomly selected from 7,389 adult (over age 20) inhabitants of town A, Japan. The prevalence of immunoglobulin G (IgG) class antibody to H. pylori (anti-H. pylori) was 83.7% and the prevalence of anti-H. pylori increased with age significantly (P < 0.05). Subjects with anamnesis of gastritis, gastroduodenal ulcer and gastric cancer tended to have a higher anti-H. pylori positive ratio (93.5%) than those without (81.0%). But there was no relationship between anti-H. pylori prevalence and sex, blood type, smoking or drinking habits. Daily intake of foods by food groups, nutrients and the concentrations of serum ingredients were compared between 37 anti-H. pylori-positive and 40 negative subjects selected from 365 inhabitants by matching up according to sex and age. The daily intake of cereals, potatoes and starches, and milks tended to be higher in positive than negative subjects, while the daily intake of algae and tea appeared to be a little higher in negative than in positive subjects. The daily zinc intake of antibody-positive subjects was significantly higher (P < 0.05) than in antibody negative subjects. On the other hand, the daily iron intake in negative subjects was significantly higher (P < 0.05) than in positive subjects. The serum concentrations of copper, zinc, and vitamin E tended to be higher in positive than negative subjects. But there were no significant differences in serum ingredients concentrations between antibody negative and positive subjects. Our findings suggest that iron and zinc intakes may effect on H. pylori infection.