Clinical significance of heat shock protein 90α expression as a biomarker of prognosis in patients with gastric cancer.

BACKGROUND: Heat shock protein 90 (HSP90) possesses two major isoforms - HSP90α and HSP90ß. They have essential roles in the protection against stressful conditions. They are also important for the re-establishment of cellular homeostasis. We investigated the clinical significance of HSP90α and HSP90ß expression in patients with gastric cancer (GC). METHODS: HSP90α and HSP90ß expression levels were examined immunohistochemically in surgical specimens obtained from 186 GC patients. The correlations between their expression levels and clinicopathological parameters including patient survival were analyzed. RESULTS: The frequencies of larger tumor size (maximum diameter ≥4 cm) and more prominent tumor invasion (≥pT3) in the high intensity HSP90α expression group were 73.4% and 68.8% higher, respectively, than those in the low intensity group (both P = 0.001). High HSP90α expression level was also significantly associated with lymphatic invasion, lymph node metastasis, and advanced stage (TNM stage ≥III) disease (P = 0.047, P = 0.046, and P = 0.004, respectively). Patients with high HSP90α expression levels demonstrated significantly worse survival than those with low HSP90α expression levels (P = 0.047). In contrast, survival did not differ significantly according to the intensity of HSP90ß expression. CONCLUSIONS: Our results showed that HSP90α overexpression might be associated with disease progression and poorer survival in patients with GC. Therefore, HSP90α could be used as possible biomarker for the prognosis of GC.

Capecitabine plus oxaliplatin versus gemcitabine plus oxaliplatin as first-line therapy for advanced biliary tract cancers: a multicenter, open-label, randomized, phase III, noninferiority trial.

BACKGROUND: Capecitabine plus oxaliplatin (XELOX) has shown modest activity and tolerable toxicity in a phase II trial for biliary tract cancers (BTCs). Meanwhile, gemcitabine plus oxaliplatin (GEMOX) has been the reference arm in recent phase II and III trials for BTCs. We aimed to investigate the efficacy of XELOX versus GEMOX as first-line therapy for advanced BCTs. PATIENTS AND METHODS: In this open-label, randomized, phase III, noninferiority trial, we randomly selected patients with metastatic BCTs to receive GEMOX (gemcitabine 1000 mg/m2 on days 1 and 8, and oxaliplatin 100 mg/m2 on day 1) or XELOX (capecitabine 1000 mg/m2, twice daily, on days 1-14 and oxaliplatin 130 mg/m2 on day 1) as first-line treatment, given every 3 weeks, totaling eight cycles. The primary end point was to prove the noninferiority of XELOX to GEMOX in terms of 6-month progression-free survival (PFS) rate. RESULTS: In total, 114 patients randomly received GEMOX and 108 randomly received XELOX. The median PFS was 5.3 months for the GEMOX group and 5.8 months for the XELOX group. The 6-month PFS rate was 44.5% for the GEMOX group and 46.7% for the XELOX group. The 95% confidence interval of the 6-month PFS rate difference between both groups was -12% to 16%, meeting the criteria for noninferiority of XELOX to GEMOX. There was no difference in objective response (P=0.171) and median overall survival (P=0.131) between both groups. The most common grade three to four adverse events were neutropenia and thrombocytopenia. No patient died of treatment-related causes. The XELOX group had significantly lower frequencies of hospital visits than the GEMOX group (P<0.001). CONCLUSION: XELOX showed significant noninferiority to GEMOX in terms of 6-month PFS rate. Thus, XELOX could be an alternative first-line treatment of BCTs. TRIAL REGISTRATION: This study was registered in ClinicalTrials.gov (number NCT01470443).

Importance of Timed and Detailed Evaluation of Kidney Transplantation Candidates.

Kidney transplant recipients are at increased risk of cardiovascular morbidity and malignant neoplasm, and meticulous evaluation of potential recipients is needed to minimize risks of complications after transplantation. The purpose of this study was to analyze the results of preoperative assessments and document the importance of timed and detailed examinations. METHODS: Medical records of patients evaluated as kidney transplant candidates from January 2015 to September 2017 were retrospectively collected and analyzed. RESULTS: Of the 216 patients evaluated during the study period, 135 (62.5%) were male, 112 (51.9%) had diabetes mellitus, 163 (75.5%) had hypertension, 31 (14.4%) had a cardiovascular event history, and 7 (3.2%) had previous history of malignant neoplasms. Mean (SD) patient age was 50.7 (10.8) years. All 216 recipient candidates underwent echocardiography. Mean (SD) ejection fraction was 57.8% (5.9%), and 48 candidates (22.2%) showed regional wall motional abnormality. Coronary angiography was performed on 81 candidates, and in 57 (70.4%) of these, coronary artery disease was detected. Malignant neoplasms were detected in 10 (4.6%) candidates. Kidney transplantation was performed on 55 candidates. One recipient died of Pneumocystis jirovecii pneumonia at 15 months after kidney transplant, but there was no death-censored graft failure, newly detected malignant neoplasm, or cardiovascular event over a mean (SD) follow-up duration of 15.5 (8.6) months. CONCLUSION: Evaluation of kidney transplant candidates resulted in diagnoses of malignant neoplasms in 4.6% of patients and coronary artery disease in 26.4% of patients. The results of this study demonstrate candidates for kidney transplant should undergo detailed preoperative evaluation.

Evolution and persistence of resistance-associated substitutions of hepatitis C virus after direct-acting antiviral treatment failures.

Daclatasvir plus asunaprevir (DCV+ASV) treatment is an all-oral direct-acting antiviral (DAA) therapy for the genotype 1b HCV-infected patients. In this study, we investigated how resistance-associated substitutions (RASs) evolved after treatment failures and assessed the effect of those substitutions on viral fitness. Sequencing of NS5A and NS3 revealed typical RASs after treatment failures. Interestingly, the RASs of NS3 reverted to the wild-type amino acid within 1 year after treatment failures. However, the RASs of NS5A were stable and did not change. The effect of NS5A and NS3 RASs on viral RNA replication was assessed after mutagenic substitution in the genotype 1b HCV RNA. Among single substitutions, the effect of D168V was more substantial than the others and the effect of the triple mutant combination (D168V+L31V+Y93H) was the most severe. The RAS at NS5A Y93 affected both viral RNA replication and virus production. Finally, the effect of trans-complementation of NS5A was demonstrated in our co-transfection experiments and these results suggest that such a trans-complementation effect of NS5A may help maintain the NS5A RASs for a long time even after cessation of the DAA treatment. In conclusion, the results from this investigation would help understand the emergence and persistence of RASs.

Impact of controlled attenuation parameter on detecting fibrosis using liver stiffness measurement.

BACKGROUND: Liver fibrosis is often accompanied by steatosis, particularly in patients with non-alcoholic fatty liver disease (NAFLD), and its non-invasive characterisation is of utmost importance. Vibration-controlled transient elastography is the non-invasive method of choice; however, recent research suggests that steatosis may influence its diagnostic performance. Controlled Attenuation Parameter (CAP) added to transient elastography enables simultaneous assessment of steatosis and fibrosis. AIM: To determine how to use CAP in interpreting liver stiffness measurements. METHODS: This is a secondary analysis of data from an individual patient data meta-analysis on CAP. The main exclusion criteria for the current analysis were unknown aetiology, unreliable elastography measurement and data already used for the same research question. Aetiology-specific liver stiffness measurement cut-offs were determined and used to estimate positive and negative predictive values (PPV/NPV) with logistic regression as functions of CAP. RESULTS: Two thousand and fifty eight patients fulfilled the inclusion criteria (37% women, 18% NAFLD/NASH, 42% HBV, 40% HCV, 51% significant fibrosis ≥ F2). Youden optimised cut-offs were only sufficient for ruling out cirrhosis (NPV of 98%). With sensitivity and specificity-optimised cut-offs, NPV for ruling out significant fibrosis was moderate (70%) and could be improved slightly through consideration of CAP. PPV for significant fibrosis and cirrhosis were 68% and 55% respectively, despite specificity-optimised cut-offs for cirrhosis. CONCLUSIONS: Liver stiffness measurement values below aetiology-specific cut-offs are very useful for ruling out cirrhosis, and to a lesser extent for ruling out significant fibrosis. In the case of the latter, Controlled Attenuation Parameter can improve interpretation slightly. Even if cut-offs are very high, liver stiffness measurements are not very reliable for ruling in fibrosis or cirrhosis.

Survival benefit of liver resection for Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma.

BACKGROUND: Although transarterial chemoembolization is recommended as the standard treatment for Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma (BCLC-B HCC), other treatments including liver resection have been used. This study aimed to determine the survival benefit of treatment strategies including resection for BCLC-B HCC compared with non-surgical treatments. METHODS: The nationwide multicentre database of the Korean Liver Cancer Association was reviewed. Patients with BCLC-B HCC who underwent liver resection as a first or second treatment within 2 years of diagnosis and patients who received non-surgical treatment were selected randomly. Survival outcomes of propensity score-matched groups were compared. RESULTS: Among 887 randomly selected patients with BCLC-B HCC, 83 underwent liver resection as first or second treatment and 597 had non-surgical treatment. After propensity score matching, the two groups were well balanced (80 patients in each group). Overall median survival in the resection group was better than that for patients receiving non-surgical treatment (50·9 versus 22·1 months respectively; P < 0·001). The 1-, 2-, 3- and 5-year overall survival rates in the resection group were 90, 88, 75 and 63 per cent, compared with 79, 48, 35 and 22 per cent in the no-surgery group (P < 0·001). In multivariable analysis, non-surgical treatment only (hazard ratio (HR) 3·35, 95 per cent c.i. 2·16 to 5·19; P < 0·001), albumin level below 3·5 g/dl (HR 1·96, 1·22 to 3·15; P = 0·005) and largest tumour size greater than 5·0 cm (HR 1·81, 1·20 to 2·75; P = 0·005) were independent predictors of worse overall survival. CONCLUSION: Treatment strategies that include liver resection offer a survival benefit compared with non-surgical treatments for potentially resectable BCLC-B HCC.

Silencing of translation initiation factor eIF3b promotes apoptosis in osteosarcoma cells.

OBJECTIVES: Eukaryotic translation initiation factor 3 (eIF3) is a multi-subunit complex that plays a critical role in translation initiation. Expression levels of eIF3 subunits are elevated or decreased in various cancers, suggesting a role for eIF3 in tumorigenesis. Recent studies have shown that the expression of the eIF3b subunit is elevated in bladder and prostate cancer, and eIF3b silencing inhibited glioblastoma growth and induced cellular apoptosis. In this study, we investigated the role of eIF3b in the survival of osteosarcoma cells. METHODS: To investigate the effect of eIF3b on cell viability and apoptosis in osteosarcoma cells, we first examined the silencing effect of eIF3b in U2OS cells. Cell viability and apoptosis were examined by the Cell Counting Kit-8 (CCK-8) assay and Western blot, respectively. We also performed gene profiling to identify genes affected by eIF3b silencing. Finally, the effect of eIF3b on cell viability and apoptosis was confirmed in multiple osteosarcoma cell lines. RESULTS: eIF3b silencing decreased cell viability and induced apoptosis in U2OS cells, and by using gene profiling we discovered that eIF3b silencing also resulted in the upregulation of tumour necrosis factor receptor superfamily member 21 (TNFRSF21). We found that TNFRSF21 overexpression induced cell death in U2OS cells, and we confirmed that eIF3b silencing completely suppressed cell growth in multiple osteosarcoma cell lines. However, eIF3b silencing failed to suppress cell growth completely in normal fibroblast cells. CONCLUSION: Our data led us to conclude that eIF3b may be required for osteosarcoma cell proliferation by regulating TNFRSF21 expression.Cite this article: Y. J. Choi, Y. S. Lee, H. W. Lee, D. M. Shim, S. W. Seo. Silencing of translation initiation factor eIF3b promotes apoptosis in osteosarcoma cells. Bone Joint Res 2017;6:186-193. DOI: 10.1302/2046-3758.63.BJR-2016-0151.R2.

Early complications after percutaneous radiofrequency ablation for hepatocellular carcinoma: an analysis of 1,843 ablations in 1,211 patients in a single centre: experience over 10 years.

AIM: To evaluate the incidence of adverse events and associated factors after radiofrequency ablation (RFA) in patients with hepatocellular carcinoma within 30 days. MATERIALS AND METHODS: The early complications that occurred within 30 days after RFA at a single institution from January 2000 to July 2010 were reviewed in order to evaluate the morbidity, mortality, and risk factors associated with the complications. In total, 1,211 patients (845 men, 70.5%) with a mean age of 68 years (range, 27-88 years) underwent 1,843 RFA procedures. RESULTS: The overall incidence rate of complications was 6.8% (125 cases). Major complications (n=36, 2%) included liver abscess (n=15, 0.8%), intraperitoneal bleeding (n=8, 0.4%), liver failure (n=5, 0.3%), variceal bleeding (n=3, 0.2%), haemothorax (n=2, 0.1%), cholecystitis (n=2, 0.1%), and bowel perforation (n=1, 0.1%). Among the minor complications (n=89, 4.8%), the most common was the post RFA syndrome accompanied by pain and fever (n=75, 4.1%). Other minor complications included significant pleural effusion (n=7, 0.4%), skin wound infection (n=4, 0.2%), and thermal injuries to the skin (n=3, 0.2%). Procedural infections significantly increased with tumour size (OR=1.379; 95% confidence interval [CI], 1.191-1.579; p<0.001), and multiple overlapping ablations (OR=1.118; 95% CI, 1.019-1.227, p=0.018). Thrombocytopenia (<50,000/µl), prothrombin time, and serum albumin level were significantly associated with post-RFA bleeding episodes (p=0.041, p=0.021, and p=0.003, respectively). The overall mortality rate was 0.3% (three cases of hepatic failure, two case of sepsis, and one case of renal failure). CONCLUSIONS: RFA is a safe and effective local treatment for hepatocellular carcinoma. Careful selection of patients and appropriate RFA planning could decrease procedural mortality and morbidity.

Reactivation of Tert in the medial prefrontal cortex and hippocampus rescues aggression and depression of Tert(-/-) mice.

The role of telomerase reverse transcriptase (TERT) has been extensively investigated in the contexts of aging and cancer. Interestingly, Tert(-/-) mice exhibit additional but unexpected aggressive and depressive behaviors, implying the potential involvement of TERT function in mood control. Our conditional rescue experiments revealed that the depressive and aggressive behaviors of Tert(-/-) mice originate from Tert deficiency in two distinct brain structures. Reactivation of Tert in the hippocampus was sufficient to normalize the depressive but not the aggressive behaviors of Tert(-/-) mice. Conversely, re-expression of Tert in the medial prefrontal cortex (mPFC) reversed the aggressive but not the depressive behavior of Tert(-/-) mice. Mechanistically, decreased serotonergic signaling and increased nitric oxide (NO) transmission in the hippocampus transduced Tert deficiency into depression as evidenced by our observation that the infusion of a pharmacological agonist for serotonin receptor 1a (5-HTR1A) and a selective antagonist for neuronal NO synthase into the hippocampus successfully normalized the depressive behavior of Tert(-/-) mice. In addition, increased serotonergic transmission by the 5-HTR1A agonist in the mPFC was sufficient to rescue the aggressive behavior of Tert(-/-) mice. Thus, our studies revealed a novel function of TERT in the pathology of depression and aggression in a brain structure-specific manner, providing direct evidence for the contribution of TERT to emotional control.

Impaired RBC deformability is associated with diabetic retinopathy in patients with type 2 diabetes.

AIM: Red blood cell (RBC) deformability, the ability of RBCs to change shape under stress, is known to be decreased in type 2 diabetes (T2D). However, as yet little is known of the association between RBC deformability and diabetic complications in T2D. For this reason, this study has investigated the association between RBC deformability and diabetic complications. METHODS: In this cross-sectional study, 452 T2D patients were initially enrolled. RBC deformability was measured using a microfluidic ektacytometer and expressed as an elongation index at 3Pa (EI@3Pa, %). RESULTS: A final total of 373 patients (mean age: 60.04±11.93 years; males: 201) were included in the study. When categorized into quartiles of RBC deformability, the lower EI@3Pa groups had higher glycated haemoglobin (HbA1c), triglycerides and prevalence of diabetic retinopathy compared with the higher quartiles (P<0.05 for trend). In particular, the EI@3Pa was significantly lower in patients with retinopathy than in those without retinopathy (30.53±1.95 vs 31.20±1.53, P=0.001). Between the lowest EI@3Pa quartile (Q1) to the highest (Q4, reference), the odds ratio (OR) for Q1 was 2.81 (95% CI: 1.21-6.49, P=0.004 for trend), after adjusting for age, gender, presence of hypertension and smoking, duration of diabetes, HbA1c, glomerular filtration rate and triglycerides. CONCLUSION: In terms of diabetic complications, the lowest EI@3Pa group was closely associated with only the risk of diabetic retinopathy in our study. These results suggest that RBC deformability might be contributory to the development of the microvascular complication.

PPARγ neddylation essential for adipogenesis is a potential target for treating obesity.

The preadipocyte-to-adipocyte differentiation (adipogenesis) is a key process in fat mass increase and thus it is regarded as a compelling target for preventing or treating obesity. Of adipogenic hormone receptors, peroxisome proliferator-activated receptor gamma (PPARγ) has crucial roles in adipogenesis and lipid accumulation within adipocytes. Here we demonstrate that the NEDD8 (neuronal precursor cell expressed, developmentally downregulated 8)-based post-translation modification (neddylation) of PPARγ is essential for adipogenesis. During adipogenesis, NEDD8 is robustly induced in preadipocytes and conjugates with PPARγ, leading to PPARγ stabilization. When the neddylation process was blocked by NEDD8-targeting siRNAs (or viral vectors) or an inhibitor MLN4924, adipocyte differentiation and fat tissue development were substantially impaired. We also demonstrate that MLN4924 effectively prevents the high-fat diet-induced obesity and glucose intolerance in mice. This study provides a better understanding of how the PPARγ signaling pathway starts and lasts during adipogenesis and a potential anti-obesity strategy that targets the neddylation of PPARγ.

Prognostic value of negative interim 2-[¹8F]-fluoro-2-deoxy-d-glucose PET/CT in diffuse large B-cell lymphoma.

AIM: To assess the prognostic value of negative interim combined 2-[(18)F]-fluoro-2-deoxy-d-glucose ((18)F-FDG) positron-emission tomography/computed tomography (PET/CT) in patients with diffuse large B-cell lymphoma (DLBCL). MATERIALS AND METHODS: Ninety-two patients with histologically proven DLBCL were enrolled. All of the patients underwent (18)F-FDG PET/CT at diagnosis, and interim PET/CT after the second cycle of chemotherapy with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone (R-CHOP). Negative interim PET/CT was defined as the disappearance of all abnormal (18)F-FDG uptake compared to the pretreatment PET/CT image, as determined by visual assessment. The clinical outcome of patients was estimated as progression-free survival (PFS), and the prognostic significance of clinicopathological and imaging parameters were assessed using the Cox proportional hazards model. RESULTS: Thirty-six patients (39.1%) showed lymphoma progression within a median follow-up of 30.8 months. According to univariate analysis, Ann Arbor stage, serum lactate dehydrogenase level, Eastern Cooperative Oncology Group scale, International Prognostic Index (IPI) score, and maximum standardised uptake values on initial PET/CT were significant prognostic factors for PFS (all p<0.05). Among these parameters, only the IPI score was an independent predictor for PFS (p=0.044). Survival of patients with a high IPI score (≥3) was poorer than those with a low IPI score (0-2; p<0.001). CONCLUSION: Despite a negative interim (18)F-FDG PET/CT, approximately 39% of DLBCL patients showed progression during follow-up. Although the negative PET/CT was obtained during chemotherapy, it is important to closely follow-up patients, especially those with a high IPI score.

CHIP-mediated degradation of transglutaminase 2 negatively regulates tumor growth and angiogenesis in renal cancer.

The multifunctional enzyme transglutaminase 2 (TG2) primarily catalyzes cross-linking reactions of proteins via (γ-glutamyl) lysine bonds. Several recent findings indicate that altered regulation of intracellular TG2 levels affects renal cancer. Elevated TG2 expression is observed in renal cancer. However, the molecular mechanism underlying TG2 degradation is not completely understood. Carboxyl-terminus of Hsp70-interacting protein (CHIP) functions as an ubiquitin E3 ligase. Previous studies reveal that CHIP deficiency mice displayed a reduced life span with accelerated aging in kidney tissues. Here we show that CHIP promotes polyubiquitination of TG2 and its subsequent proteasomal degradation. In addition, TG2 upregulation contributes to enhanced kidney tumorigenesis. Furthermore, CHIP-mediated TG2 downregulation is critical for the suppression of kidney tumor growth and angiogenesis. Notably, our findings are further supported by decreased CHIP expression in human renal cancer tissues and renal cancer cells. The present work reveals that CHIP-mediated TG2 ubiquitination and proteasomal degradation represent a novel regulatory mechanism that controls intracellular TG2 levels. Alterations in this pathway result in TG2 hyperexpression and consequently contribute to renal cancer.

Activation of nuclear PTEN by inhibition of Notch signaling induces G2/M cell cycle arrest in gastric cancer.

Mutation in PTEN has not yet been detected, but its function as a tumor suppressor is inactivated in many cancers. In this study we determined that, activated Notch signaling disables PTEN by phosphorylation and thereby contributes to gastric tumorigenesis. Notch inhibition by small interfering RNA or γ-secretase inhibitor (GSI) induced mitotic arrest and apoptosis in gastric cancer cells. Notch inhibition induced dephosphorylation in the C-terminal domain of PTEN, which led to PTEN nuclear localization. Overexpression of activated Notch1-induced phosphorylation of PTEN and reversed GSI-induced mitotic arrest. Dephosphorylated nuclear PTEN caused prometaphase arrest by interaction with the cyclin B1-CDK1 complex, resulting in their accumulation in the nucleus and subsequent apoptosis. We found a correlation between high expression levels of Notch1 and low survival rates and, similarly, between reduced nuclear PTEN expression and increasing the TNM classification of malignant tumours stages in malignant tissues from gastric cancer patients. The growth of Notch1-depleted gastric tumors was significantly retarded in xenografted mice, and in addition, PTEN deletion restored growth similar to control tumors. We also demonstrated that combination treatment with GSI and chemotherapeutic agents significantly reduced the orthotopically transplanted gastric tumors in mice without noticeable toxicity. Overall, our findings suggest that inhibition of Notch signaling can be employed as a PTEN activator, making it a potential target for gastric cancer therapy.

Overexpression of HSP47 in esophageal squamous cell carcinoma: clinical implications and functional analysis.

Several biomarkers of esophageal squamous cell carcinoma (ESCC) have been explored to improve the prognosis of this disease. One of these, the 47-kDa heat shock protein (HSP47), has been screened as a potential biomarker by genomic profiling and is known to be overexpressed in some malignant diseases. In this study, we explored the role and evaluated the prognostic value of HSP47 expression in ESCC. The function of this protein was analyzed by assaying proliferation, wound healing, and colony formation in an HSP47-knockdown ESCC line. The prognostic implication of HSP47 expression was analyzed by immunohistochemical staining in 157 surgical specimens. HSP47 expression level and other clinical variables were analyzed using multivariate Cox proportional hazards models. Silencing of the HSP47 gene in the ESCC cell line inhibited cell proliferation and colony formation. HSP47 was highly expressed in ESCC tissue samples, compared with normal esophageal tissues. The level of immunohistochemical staining of HSP47 and pathologic stage were significantly correlated with overall and recurrence-free survival, as shown by multivariate analysis (P = 0.014 and 0.044, respectively). We found that overexpression of HSP47 is associated with poor prognosis in patients with ESCC and that this is consistent with the function of HSP47 in terms of increased cell proliferation and colony formation. These results suggest that HSP47 is a potential prognostic biomarker for ESCC and merits further research for novel diagnostic and therapeutic applications.

Outcome and technical aspects of liver retransplantation: analysis of 25-year experience in a single major center.

BACKGROUND: The need for liver retransplantation (re-LT) has been increasing. Here we describe the outcome and technical aspects of re-LT during 25 years in a single major center. METHODS: We retrospectively reviewed patients who underwent LT from March 1988 to February 2013. Among 1,312 LTs during 25 years, 38 (2.9%) were re-LTs, including 28 adults (mean age 52.0 y) and 10 children (mean age 5.7 y). RESULTS: The most common indication was primary nonfunction in early re-LT and biliary complication in late re-LT. Preoperative major comorbidity was very common (81.6%). Among them, infection was the most frequent (52.6%). Living-donor re-LT constituted 21.1%. In operative technique, nonconventional methods were substantially performed, including high hilar dissection for hepatectomy (>50%), arterial anastomosis with the use of right gastroepiploic or jump graft (23.7%), and hepaticoenterostomy (60.5%). Several reanastomoses were needed in 10.5% for artery and 5.3% for duct. In adults and children, mean estimated blood losses were 9,541 mL and 977 mL, respectively. Mean operative times for adults and children were 508 and 432 minutes, respectively. In-hospital mortality was 35.7% in adults and 40.0% in children. The main cause of death was sepsis for both adults and children. Survival rates at 1 month and 1, 3, and 5 years were, respectively, 89.4%, 56.5%, 50.3%, and 50.3% in adults, and 70.0%, 60.0%, 60.0%, and 60.0% in children. CONCLUSIONS: Outcome of re-LT is poorer than primary LT regardless of the cause of graft failure. Therefore, more technical concerns need to be considered. We also need more efforts to control perioperative infections to improve survival after re-LT.

Auxiliary partial orthotopic liver transplantation as a treatment for hemophilia a: a case report.

A 37-year-old man with moderately severe hemophilia A (factor VIII of 1.2%), who had a normal liver without liver cirrhosis or hepatocellular carcinoma, was referred to our liver transplantation (LT) team. LT was planned for sufficient coagulation factor level maintenance and prophylaxis against future hemorrhagic complications. The donor was the patient's 35-year-old wife, who was nonhemophilic. We performed an auxiliary partial orthotopic liver transplantation (APOLT) with the approval of the Institutional Ethics Committee. A left partial liver graft taken from the donor was orthotopically transplanted to the recipient after resection of the native left hemiliver while preserving the native right lobe. After surgery, the patient tolerated the procedure, and tacrolimus was used to maintained immunosuppression. In this recipient, factor VIII activity significantly increased soon after the APOLT, and has been maintained at >20% without any further bleeding episodes for the past 74 months since the procedure. This finding suggests that APOLT may be an effective alternative treatment for patients with hemophilia A.

The effects of a 6-month Tai Chi Qigong training program on temporomandibular, cervical, and shoulder joint mobility and sleep problems in nasopharyngeal cancer survivors.

INTRODUCTION: Nasopharyngeal cancer (NPC) survivors often sustain head-neck-shoulder impairments from conventional treatments, which could disturb sleep. This novel study aimed to examine the efficacy of Tai Chi (TC) Qigong in optimizing temporomandibular joint (TMJ), cervical, and shoulder joint mobility and reducing sleep problems in NPC survivors. METHODS: Fifty-two NPC survivors participated in the study. The experimental group (n = 25) received 6 months of TC Qigong training (1.5 h/session; 4 sessions/wk including self-practice) while the control group (n = 27) received no training. Cervical side flexion and rotation, shoulder flexion and horizontal flexion range of motion (ROM), mouth opening capacity (interincisor distance), and sleep problems (Medical Outcomes Study Sleep Scale) were assessed at baseline, mid-intervention (3 months), immediately after TC Qigong training, and at 6-month follow-up. RESULTS: Intention-to-treat analysis revealed improvement in cervical side flexion ROM only (P < .008) and unchanged shoulder and TMJ mobility (P > .008) after the TC Qigong training. Deterioration was observed in shoulder flexion ROM and mouth opening capacity in the no-training controls over time (P < .008). Sleep problems also decreased in the TC Qigong group (P < .008), and this effect was most profound during the follow-up period. In addition, improvement in cervical side flexion ROM was associated with a reduction in sleep problems in the experimental group after TC Qigong training (P < .05). CONCLUSIONS: The 6-month TC Qigong intervention improved neck mobility, maintained TMJ and shoulder joint mobility, and reduced sleep problems for NPC survivors. TC Qigong could be an effective nonpharmacological intervention for managing progressive trismus, chronic neck and shoulder hypomobility, and reducing sleep problems among NPC survivors.

Meralgia paresthetica-like symptoms following epidural analgesia after total knee arthroplasty.

Meralgia paresthetica (MP) is generally caused by entrapment of the lateral femoral cutaneous nerve (LFCN), and presents with pain and paresthesia in the anterolateral thigh. This paper describes a patient who had MP-like symptoms as a result of continuous epidural analgesia after total knee arthroplasty. The patient with pre-existing left foraminal stenosis at L3-L4 and disc herniations at L4-5 did not complain of paresthesia or pain during the combined spinal-epidural anesthetic procedure. However, during epidural analgesia on the second post-operative day, he complained of paresthesia and pain in the anterolateral thigh of the contralateral leg. Electromyography showed a neurogenic lesion at the level of L3. Although an ultrasound-guided diagnostic block of the LFCN was performed twice post-operatively, the patient's symptoms persisted. The symptoms gradually resolved 12 months after the surgery. In our case, we suggest that the continuous epidural infusate caused neural ischemia of the L3 nerve root by a compressive effect.