Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with gastric cancer.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with gastric cancer (GC), published in late 2022 and the updated ESMO Gastric Cancer Living Guideline published in July 2023, were adapted in August 2023, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with GC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with GC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), coordinated by ESMO and the Japanese Society of Medical Oncology (JSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian regions represented by the 10 oncological societies. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with GC across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling and age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different regions of Asia.

Margetuximab with retifanlimab as first-line therapy in HER2+/PD-L1+ unresectable or metastatic gastroesophageal adenocarcinoma: MAHOGANY cohort A.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric and gastroesophageal adenocarcinoma (GEA) is globally treated with chemotherapy plus trastuzumab. Novel therapeutic strategies strive to not only optimize efficacy, but also limit toxicities. In MAHOGANY cohort A, margetuximab, an Fc-engineered, anti-HER2 monoclonal antibody (mAb) was combined with retifanlimab, an anti-programmed cell death protein 1 mAb, in the first-line HER2-positive/programmed death-ligand 1 (PD-L1)-positive GEA. PATIENTS AND METHODS: MAHOGANY cohort A part 1 is a single-arm trial to evaluate margetuximab plus retifanlimab in patients with HER2 immunohistochemistry 3+, PD-L1-positive (combined positive score ≥1%), and non-microsatellite instability-high tumors. Primary objectives for cohort A were safety/tolerability and the confirmed objective response rate (ORR). RESULTS: As of 3 August 2021, 43 patients were enrolled and received margetuximab/retifanlimab. Nine grade 3 treatment-related adverse events (TRAEs) were reported in eight (18.6%) patients and eight serious TRAEs in seven (16.3%) patients. There were no grade 4/5 TRAEs. Three patients discontinued margetuximab/retifanlimab because of immune-related adverse events. The ORR by independent assessment was 53% [21/40 (95% confidence interval (CI) 36.1-68.5)], with a median duration of response of 10.3 months (95% CI 4.6-not evaluable); disease control rate was 73% [29/40 (95% CI 56.1-85.4)]. The study sponsor discontinued the study in advance of the planned enrollment when it became apparent that the study design would no longer meet the requirements for drug approval because of recent advances in the treatment of GEA. CONCLUSIONS: The chemotherapy-free regimen of combined margetuximab/retifanlimab as first-line treatment in double biomarker-selected patients demonstrated a favorable toxicity profile compared with historical outcomes using chemotherapy plus trastuzumab. The ORR observed in this study compares favorably versus ORR observed with other chemotherapy-free approaches.

De Novo Hepatitis B Virus Infection After Liver Transplantation in Hepatitis B Core-positive Recipients Using Hepatitis B Core-negative Grafts.

BACKGROUND: Hepatitis B core antibody-positive (HBcAb+) graft is known as a risk for de novo hepatitis B virus (HBV) infection in recipients after liver transplantation (LT). However, little is known about the possibility or incidence of de novo HBV infections after LT in hepatitis B surface antigen-negative (HBsAg-)/HBcAb+ recipients using HBsAg-/HBcAb- grafts. The study aimed to evaluate the prevalence of de novo HBV infection in HBsAg-/HBcAb+ recipients using HBsAg-/HBcAb- grafts. A retrospective review was performed with the records of 1129 adult patients who underwent primary LT at a single institution in an HBV endemic area between January 2000 and December 2013. A total of 78 patients (6.9%) were reviewed for de novo HBV infection after LT. De novo HBV infection was developed in 1 patient (1.28%). The patient was a 65-year-old woman who underwent LT due to alcoholic liver cirrhosis. De novo HBV was not related to graft loss or death and well treated with tenofovir. In conclusion, de novo HBV infections may occur in HBsAg-/HBcAb+ recipients using HBsAg-/HBcAb- grafts, and caution is needed in these patients.

Isolation of internal and external sphincter progenitor cells from the human anal sphincter with or without radiotherapy.

AIM: We aimed to isolate and propagate internal and external anal sphincter progenitor cells from the human anal sphincter, with or without radiotherapy, for tailored cell therapy of faecal incontinence. METHODS: Sphincter progenitor cells were isolated from normal internal and external anal sphincters collected from 10 patients with rectal cancer who had undergone abdominoperineal resection with (n = 6) or without (n = 4) preoperative chemoradiotherapy. The isolated cells and differentiated muscle fibres were identified using immunofluorescence assay, western blotting and reverse transcription polymerase chain reaction (RT-PCR). The proliferation of progenitor cells with and without radiotherapy was compared by quantitative 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RESULTS: The immunofluorescence assay before differentiation confirmed that the internal anal sphincter progenitor cells expressed CD34 and neural-glial antigen 2 (NG2), whereas the external anal sphincter progenitor cells expressed CD34 and PAX7. After differentiation, the internal anal sphincter progenitor cells expressed desmin, calponin and α-smooth muscle actin, whereas the external anal sphincter progenitor cells expressed desmin, myogenic factor 4 and myosin heavy chain. The differential expression profiles of both cell types were confirmed by western blotting and RT-PCR. MTT assays showed that the viability of internal and external anal sphincter progenitor cells was significantly lower in the radiotherapy group than that in the nonradiotherapy group. CONCLUSIONS: This study describes the differential harvest internal and external sphincter muscle progenitor cells from human anal sphincters. We confirm that radiotherapy decreases the viability of internal and external anal sphincter progenitor cells.

Safety and efficacy of nivolumab in combination with S-1/capecitabine plus oxaliplatin in patients with previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: interim results of a randomized, phase II trial (ATTRACTION-4).

BACKGROUND: Nivolumab is approved as an option for third- or later-line treatment of advanced gastric/gastroesophageal junction (G/GEJ) cancer in several countries after ATTRACTION-2. To further improve the therapeutic efficacy of first-line therapy, exploration of a nivolumab-chemotherapy combination is warranted. In part 1 (phase II) of ATTRACTION-4, the safety and efficacy of nivolumab combined with S-1 plus oxaliplatin (SOX) or capecitabine plus oxaliplatin (CapeOX) as first-line therapy for unresectable advanced or recurrent human epidermal growth factor receptor 2 (HER2)-negative G/GEJ cancer were evaluated. PATIENTS AND METHODS: Patients were randomized (1 : 1) to receive nivolumab (360 mg intravenously every 3 weeks) plus SOX (S-1, 40 mg/m2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m2 intravenously on day 1 every 3 weeks) or CapeOX (capecitabine, 1000 mg/m2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m2 intravenously on day 1 every 3 weeks) until disease progression, unacceptable toxicity, or consent withdrawal. RESULTS: Of 40 randomized patients, 39 (nivolumab plus SOX, 21; nivolumab plus CapeOX, 18) and 38 (21 and 17, respectively) comprised the safety and efficacy populations, respectively. Most frequent (>10%) grade 3/4 treatment-related adverse events were neutropenia (14.3%) in the nivolumab plus SOX group, and neutropenia (16.7%), anemia, peripheral sensory neuropathy, decreased appetite, type 1 diabetes mellitus, and nausea (11.1% each) in the nivolumab plus CapeOX group. No treatment-related death occurred. Objective response rate was 57.1% (95% confidence interval 34.0-78.2) with nivolumab plus SOX and 76.5% (50.1-93.2) with nivolumab plus CapeOX. Median overall survival was not reached (NR) in both groups. Median progression-free survival was 9.7 months (5.8-NR) and 10.6 months (5.6-12.5), respectively. CONCLUSION: Nivolumab combined with SOX/CapeOX was well tolerated and demonstrated encouraging efficacy for unresectable advanced or recurrent HER2-negative G/GEJ cancer. ATTRACTION-4 has proceeded to part 2 (phase III) to compare nivolumab plus SOX/CapeOX versus placebo plus SOX/CapeOX. CLINICALTRIALS.GOV ID: NCT02746796.

Urinary Neutrophil Gelatinase-Associated Lipocalin as a Biomarker for Renal Injury in Liver Transplant Recipients Using Calcineurin Inhibitors.

BACKGROUND: Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is an early biomarker of renal injury. We examined the feasibility of using uNGAL as an early predictor of renal impairment in patients under calcineurin inhibitors in liver transplant recipients. METHODS: From urine samples obtained from liver transplant recipients, the glomerular filtration rate (GFR) at the time of urine sampling was compared with that at 5 to 7 months later. Patients were divided into 3 groups according to initial GFR and then divided into 2 groups according to the uNGAL level of 25 ng/mL. Progression of renal injury (PRI) was defined as a decrease in the GFR of more than 5 mL/min/1.73 m2 in the mild or moderate groups, or if a normal group patient shifted to the mild or moderate group. RESULTS: Fifty-one patients were enrolled. The mean uNGAL level was higher in the moderate group than in the normal and mild groups (18.38 ± 14.31 vs 7.74 ± 8.13; P < .01). A proportion of uNGAL-high was also higher in the moderate group than in the mild group (40% vs 5%; P = .03). uNGAL-high was a risk factor for 6-month PRI (odds ratio, 60.375; 95% confidence interval, 1.283-4088.25; P = .037) and 1-year PRI (odds ratio, 21.311; % confidence interval, 0.947-479.578; P = .054). CONCLUSIONS: A uNGAL of >25 ng/mg can be a marker for moderate renal impairment (GFR of 30-59 mL/min/1.73 m2) and a predictor of PRI at 6 months in patients using calcineurin inhibitors. Renal protection strategies should be considered in liver transplant recipients with a uNGAL of >25 ng/mg in spot urine sampling.

Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300.

Background: There currently are no internationally recognised treatment guidelines for patients with advanced gastric cancer/gastro-oesophageal junction cancer (GC/GEJC) in whom two prior lines of therapy have failed. The randomised, phase III JAVELIN Gastric 300 trial compared avelumab versus physician's choice of chemotherapy as third-line therapy in patients with advanced GC/GEJC. Patients and methods: Patients with unresectable, recurrent, locally advanced, or metastatic GC/GEJC were recruited at 147 sites globally. All patients were randomised to receive either avelumab 10 mg/kg by intravenous infusion every 2 weeks or physician's choice of chemotherapy (paclitaxel 80 mg/m2 on days 1, 8, and 15 or irinotecan 150 mg/m2 on days 1 and 15, each of a 4-week treatment cycle); patients ineligible for chemotherapy received best supportive care. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. Results: A total of 371 patients were randomised. The trial did not meet its primary end point of improving OS {median, 4.6 versus 5.0 months; hazard ratio (HR)=1.1 [95% confidence interval (CI) 0.9-1.4]; P = 0.81} or the secondary end points of PFS [median, 1.4 versus 2.7 months; HR=1.73 (95% CI 1.4-2.2); P > 0.99] or ORR (2.2% versus 4.3%) in the avelumab versus chemotherapy arms, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 90 patients (48.9%) and 131 patients (74.0%) in the avelumab and chemotherapy arms, respectively. Grade ≥3 TRAEs occurred in 17 patients (9.2%) in the avelumab arm and in 56 patients (31.6%) in the chemotherapy arm. Conclusions: Treatment of patients with GC/GEJC with single-agent avelumab in the third-line setting did not result in an improvement in OS or PFS compared with chemotherapy. Avelumab showed a more manageable safety profile than chemotherapy. Trial registration: ClinicalTrials.gov: NCT02625623.

Evaluation of bee venom as a novel feed additive in fast-growing broilers.

1. The present study was designed to evaluate purified bee venom (BV) as an alternative to antibiotics in broiler chickens. The experimental treatment diets were formulated by adding BV into a maize-soybean meal-based diet to give 0, 10, 50, 100, and 500 µg BV per kg of diet. 2. Dietary BV quadratically improved (P < 0.05) feed conversion ratio and increased body weight gain at 1-21 d as level in diet increased. Higher BV levels lowered relative weight of spleen (linear and quadratic, P < 0.05), bursa of Fabricius (quadratic, P < 0.05), and liver (linear and quadratic, P < 0.05) at 21 d of age. Relative breast meat yields were increased quadratically at 21 d and linearly at 35 d with supplementation levels. Dietary BV increased (linear and quadratic, P < 0.05) lightness (L*) value for meat at 21 d, decreased (linear, P < 0.05) ileal villus height and narrowed (quadratic, P < 0.05) width. 3. Dietary BV inclusion linearly increased the concentration of secretory immunoglobulin A (sIgA) on ileal mucosa at 21 d and decreased (quadratic, P < 0.05) nitric oxide contents in serum samples at 21 d and 35 d. Total short-chain fatty acids (SCFA) in caecal digesta were reduced with increasing venom in diets at 21 d of age. None of the serum parameters except for creatinine was affected by dietary BV. 4. It was concluded that dietary BV exhibited wide range of in vivo biological properties in broiler chickens and could be incorporated into feed to promote growth and animal health.

Effects of fumonisin B1 and mycotoxin binders on growth performance, tibia characteristics, gut physiology, and stress indicators in broiler chickens raised in different stocking densities.

The present study was carried out to investigate the effects of stocking density, fumonisin B1 (FB), and mycotoxin binder (TB) on growth performance, bone quality, physiological stress indicators, and gut health in broiler chickens. Day-old Ross 308 male broiler chicks (n = 1,440/experiment) were randomly allocated to 72 floor pens in a 3 × 2 × 2 factorial arrangement, using 3 stocking densities (12.5 birds/m2 [HSD], 10 birds/m2 [MSD], or 7.5 birds/m2 [LSD]), 2 levels of purified FB (0 or 10 ppm), and 2 levels of TB (0 or 0.2%). Each treatment had 6 replicates (n = 6/treatment) and experiments lasted 34 days. All data were analyzed using 3-way ANOVA with stocking density level, FB, and TB as main factors. Body weight gain and feed intake were lower (P < 0.05) in broilers kept at HSD and MSD compared to LSD-housed counterparts. Birds fed an FB-contaminated diet exhibited a higher feed-to-gain ratio compared with those fed an FB-free diet (P < 0.05). None of the treatments affected intestinal morphology or ileal secretory immunoglobulin A levels. Stocking density affected tibia breaking strength (P < 0.05), which was lower in chickens housed at HSD compared with LSD-housed chickens. The heterophil/lymphocyte ratio (H/L ratio) was elevated (P < 0.05) in HSD and MSD groups compared with the LSD group. Serum nitric oxide (NO) levels were elevated (P < 0.05) in chickens fed the FB-contaminated diet compared with the control diet-fed counterparts. Significant interaction (P < 0.05) between FB and TB on serum NO levels was noted. In summary, increasing stocking density lowered growth performance and bone quality, but increased the H/L ratio. Dietary TB did not affect FB-induced increases in the feed-to-gain ratio. No interaction was observed between stocking density and FB for the measured variables.

Efficacy and Safety of Generic Mycophenolate Mofetil (My-rept) 500-Milligram Tablets in Primary Liver Transplant Recipients.

BACKGROUND: Generic immunosuppressants may be cost-effective if clinical outcomes are equivalent to the brand-name medications. Mycophenolate mofetil in the form of My-rept may be cost-effective being a generic immunosuppressant, which is available as a 500-mg tablet as well as a 250-mg capsule (Chong Kun Dang Pharmaceutical Corporation, Seoul, Korea). OBJECTIVE: This study aimed to evaluate the efficacy, safety, cost-effectiveness, and convenience of My-rept 500-mg tablets in liver transplant recipients. SETTING: The setting was an outpatient liver transplantation clinic of a tertiary hospital in Korea. METHOD: A phase 4, single-center, open-label, noncomparative study was undertaken. A total of 50 patients were recruited. Acute transplant rejection, changes in blood chemistry, white blood cell count, assessments of renal function, occurrence of adverse drug reactions, and other characteristics of the patients were recorded for 24 weeks. After study termination, a satisfaction survey was conducted. RESULTS: All enrolled patients and their liver grafts had survived for 24 weeks post-transplantation. No episodes of acute rejection were reported. Nine patients (18.8%) presented with adverse drug reactions that had been commonly reported with the use of other mycophenolate mofetil products, and no serious adverse drug reactions were reported. CONCLUSION: In conclusion, the My-rept 500-mg tablet appears to be feasible and convenient for administration to recipients of a liver transplant.

Primary Living-donor Liver Transplantation Is Not the Optimal Treatment Choice in Patients With Early Hepatocellular Carcinoma With Poor Tumor Biology.

OBJECTIVE: Liver resection (LR) and living-donor liver transplantation (LDLT) are considered the two potentially curative treatments for hepatocellular carcinoma (HCC). The aim of this study was to investigate whether there is a difference in the oncologic outcomes between LR and LDLT according to tumor biology. METHODS: Patients (137 LDLTs and 199 LRs) were stratified into four groups by tumor biology according to the number of risk factors for recurrence (preoperative alpha-fetoprotein >200 ng/mL, Edmonson grade 3 or 4, tumor size >3 cm, and presence of microvascular invasion). RESULTS: In the favorable tumor biology patients (groups I and II), there was a significantly worse recurrence-free survival rate in those patients who underwent LR compared to those who underwent LDLT (group I, P = .002; group II, P = .001). The overall survival rates in the LR and LDLT groups were not different (group I, P = .798; group II, P = .981). In the poor tumor biology patients (groups III and IV), there was no significant difference between the two groups in terms of recurrence-free survival rate (group III, P = .342; group IV, P = .616). The LDLT group showed a significantly lower overall survival rate (group III, P = .001; group IV, P = .025). CONCLUSIONS: Primary LDLT should not be recommended in early stage HCC patients with poor tumor biology because of lower survival rates and a high chance of HCC recurrence.

Usefulness of PIVKA-II After Living-donor Liver Transplantation for Hepatocellular Carcinoma.

OBJECTIVE: Prothrombin induced by the absence of vitamin K or antagonist-II (PIVKA-II) is a useful tumor marker for hepatocellular carcinoma (HCC). However, the usefulness of post-transplantation surveillance with PIVKA-II is not clear. We evaluated the clinical value of PIVKA-II in monitoring HCC recurrence after living-donor liver transplantation (LDLT). METHODS: One hundred twenty patients who had undergone LDLT for HCC from February 1999 to December 2010 and whose serum alpha-fetoprotein (AFP) and PIVKA-II had been measured sequentially before and after LDLT were included in this study. Patients were classified into four groups according to the preoperative level of AFP and PIVKA-II (group I, normal AFP and PIVKA-II; group II, elevated AFP; group III, elevated PIVKA-II; and group IV, elevated both AFP and PIVKA-II). RESULTS: Preoperative PIVKA-II level tended to increase with increasing tumor size, number of nodules, presence of microvascular invasion, and poor differentiation. In 27 patients developing recurrent HCC after LDLT, the sensitivity of AFP and PIVKA-II was 59.2% and 88.8%, respectively. When the two markers were combined, the sensitivity increased to 92.5%. Especially, the sensitivity for PIVKA-II was high at groups I and III (100.0% for both, respectively). In patients in groups I, III, and IV, an elevated PIVKA-II level was the most common first sign of HCC recurrence after LDLT. An elevated PIVKA-II level was the most common first sign of recurrence, regardless of recurrence site. CONCLUSIONS: PIVKA-II might be a useful tumor marker in the monitoring of recurrence after LDLT, complementary to AFP.

Surgical Techniques of Allogeneic Liver Transplantation in a Nonhuman Primate Model.

Herein, we report our experience of performing allogeneic orthotopic liver transplantation (LT) in nonhuman primates. We designed an allogeneic ABO-compatible orthotopic LT model in monkeys in a manner similar to that used in humans. We applied almost the same surgical procedures used for human conventional deceased donor LT. A total of 6 monkeys underwent allogeneic LT. One cynomolgus monkey aged 45 months (3.4 kg) and 5 rhesus macaque monkeys aged 50.2 ± 14.8 months (5.40 ± 0.33 kg) were used as recipients. In the donor surgery, the liver was perfused in situ through the aorta using cold histidine-tryptophan-ketoglutarate solution. The portal vein (diameter, 5-10 mm), supra- and infra-hepatic inferior vena cava (IVC) (diameter, 12-15 mm), and common bile duct (diameter, 1.5-3.0 mm) were dissected out. The hepatic artery was kept in continuity with the celiac trunk and abdominal aorta up to the iliac bifurcation (diameter, 5-6 mm). The mean graft weight was 102.0 g (94.8-111.0 g). Recipient surgery was conducted in parallel. After recipient hepatectomy, the graft was implanted. The suprahepatic IVC and portal vein were anastomosed to those of the graft. After reperfusion, the infrahepatic IVC was anastomosed. The aorta conduit of the graft was anastomosed to the infrarenal aorta of the recipient in a retrocolic end-to-side manner. Biliary reconstruction was performed in a duct-to-duct anastomosis with cholecystectomy. Mean operative time was 107.0 minutes for donor and 198.2 minutes for recipient. There was one operative death due to unknown cause. In conclusion, for allogeneic orthotopic LT in nonhuman primate model, we can apply almost the same procedure used for human conventional deceased donor LT in a similar manner.

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.

Comparing the immune responses of two genetically B-complex disparate Fayoumi chicken lines to Eimeria tenella.

The present study was conducted to compare the susceptibility of congenic Fayoumi lines to Eimeria tenella infection and to assess genetic differences in Eimeria egression. Chickens were orally inoculated with 5 × 10(4) sporulated E. tenella oocysts and challenged with 5 × 10(6) oocysts on the 10th day after the primary infection. The Fayoumi M5.1 line exhibited higher levels of body weight gain, less oocyst shedding and higher percentages of B and CD4(+)/CD8(+) T cells than the M15.2 chickens. These results demonstrate that M5.1 line is more resistant to E. tenella infection than M15.2 line. Furthermore, the percentage of sporozoite egress from peripheral blood mononuclear cells (PBMCs) was higher in the M5.1 line. The results of this study suggest that enhanced resistance of Fayoumi M5.1 to E. tenella infection may involve heightened cell-mediated and adaptive immunity, resulting in reduced intracellular development of Eimeria parasites.

Inexplicable Outcome of Early Appearance of Hepatocellular Carcinoma in the Allograft After Deceased Donor Liver Transplantation: A Case Report.

BACKGROUND: This case represents the earliest appearance of de novo HCC after liver transplantation (OLT) compared with cases of previously reported literatures. CASE REPORT: A 45-year-old man underwent deceased donor OLT owing to decompensated liver cirrhosis. He had YMDD viral mutation and hepatitis B (HBV) and C (HCV) coinfection but no tumor was found in the liver on MRI before OLT. The donor was a healthy young female donor who was HCV and HBV negative. There was no tumor in the explant liver. After OLT, HCV RNA and hepatitis B surface antigen became undetectable with DNA-positive HBV. Nine months after OLT, a computed tomography (CT) scan was performed owing to abdominal pain, detecting a mass occupying the right lobe that depicted enhanced characteristics typical of HCC. The chest CT demonstrated metastatic lung nodules in the right basal lower lobe. Fluorescence in situ hybridization showed tumor cells from the recipient. CONCLUSIONS: To the best of our knowledge, this is the first report of de novo hepatocellular carcinoma that has emerged within a short period of undergoing OLT.

Alteration by p11 of mGluR5 localization regulates depression-like behaviors.

Mood disorders and antidepressant therapy involve alterations of monoaminergic and glutamatergic transmission. The protein S100A10 (p11) was identified as a regulator of serotonin receptors, and it has been implicated in the etiology of depression and in mediating the antidepressant actions of selective serotonin reuptake inhibitors. Here we report that p11 can also regulate depression-like behaviors via regulation of a glutamatergic receptor in mice. p11 directly binds to the cytoplasmic tail of metabotropic glutamate receptor 5 (mGluR5). p11 and mGluR5 mutually facilitate their accumulation at the plasma membrane, and p11 increases cell surface availability of the receptor. Whereas p11 overexpression potentiates mGluR5 agonist-induced calcium responses, overexpression of mGluR5 mutant, which does not interact with p11, diminishes the calcium responses in cultured cells. Knockout of mGluR5 or p11 specifically in glutamatergic neurons in mice causes depression-like behaviors. Conversely, knockout of mGluR5 or p11 in GABAergic neurons causes antidepressant-like behaviors. Inhibition of mGluR5 with an antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP), induces antidepressant-like behaviors in a p11-dependent manner. Notably, the antidepressant-like action of MPEP is mediated by parvalbumin-positive GABAergic interneurons, resulting in a decrease of inhibitory neuronal firing with a resultant increase of excitatory neuronal firing. These results identify a molecular and cellular basis by which mGluR5 antagonism achieves its antidepressant-like activity.

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.