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Routine use of adjuvant chemotherapy (AC) following hepatectomy for colorectal liver metastases (CRLM) is not universally practiced because of the lack of supporting evidence. Therefore, we investigated the efficacy of AC following curative CRLM resection.Among the 742 patients who underwent their first hepatectomy for CRLM at our institution, 335 were stratified into surgery alone (SA; n=162) and AC (n=173) groups. Poor prognostic factors for SA were identified using multivariate logistic regression analysis. Propensity score matching was used to compare the clinical outcomes between SA and AC groups according to the number of prognostic factors.Multivariate analysis showed that preoperative carcinoembryonic antigen (CEA) levels (≥10 ng/ml; p=0.01), primary lymph node metastases (≥1; p=0.0001), and the number (n≥4; p=0.01) and maximum diameter (≥5 cm; p=0.00001) of CRLM tumours were independent poor prognostic factors for overall survival (OS) in the SA group. Patients with ≥3 risk factors were categorized as being high risk. After propensity score matching, the 5-year OS rate was significantly higher in the AC group (n=13) than that in the SA group (n=15; 47.9% vs. 7.3%; p=0.03) among high-risk patients.Adjuvant chemotherapy after curative CRLM resection may improve the prognosis of patients with three or more risk factors including preoperative CEA levels ≥10 g/ml, primary lymph node metastases ≥1, number (≥4) and maximum diameter (≥5 cm) of CRLM tumours.

The liver is the most common metastatic site of colorectal cancer. Hepatectomy is the mainstay of treatment for patients with colorectal liver metastases (CRLMs). However, there are cases of early recurrence after upfront hepatectomy alone. In selected high-risk patients, neoadjuvant chemotherapy (NAC) may improve long-term survival.To determine the efficacy of NAC for initially resectable CRLMs.Among 644 patients who underwent their first hepatectomy for CRLMs at our institution, 297 resectable cases were stratified into an upfront hepatectomy group (238 patients) and a NAC group (59 patients). Poor prognostic factors for upfront hepatectomy were identified using multivariate logistic regression analysis. Propensity score matching was used to compare clinical outcomes between the upfront hepatectomy and NAC groups, according to the number of poor prognostic factors. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test.Preoperative carcinoembryonic antigen levels (≥ 10 ng/mL) (NAC may improve the prognosis of high-risk patients with resectable CRLMs who have two or more risk factors.

This study aimed to retrospectively analyse adverse predictors to identify patients with huge hepatocellular carcinoma who were not appropriate candidates for hepatic resection.From 551 patients with hepatocellular carcinoma who underwent hepatectomy between 1992 and 2019, 92 were diagnosed with huge hepatocellular carcinoma (diameter10 cm) and 115 were diagnosed with large hepatocellular carcinoma (diameter=5-10 cm). Clinical features and overall and disease-free survival rates were compared between the two groups.Cumulative overall survival was significantly worse in the huge group than in the large group (p=0.035). In the huge group, multivariate analyses revealed that liver cirrhosis, multiple intrahepatic metastases (≥4), poor histological grade, and macroscopic portal vein invasion were significantly associated with poor prognosis.We identified four adverse predictors of survival and determined that patients with two or more predictors are not appropriate candidates for straightforward hepatic resection.

Few studies have reported the impact of chemoradiotherapy (CRT) on the objective response of patients with locally advanced unresectable esophageal squamous cell carcinoma (ESCC). We evaluated the factors predicting therapeutic effectiveness and the short- and long-term outcomes in patients with T4b ESCC treated with CRT.We included 155 patients with T4b ESCC who underwent CRT at the Department of Surgery, Gastroenterological Center, Yokohama City University, between January 2000 and December 2018. Responders were defined as patients who demonstrated a complete response (CR) or partial response (PR). Multivariate analysis for objective response was performed using a logistic regression model, and prognostic factors were evaluated by univariate and multivariate analyses.Among the 155 patients included, 20 and 84 patients demonstrated a CR and PR, respectively, resulting in a response rate of 67.1%. The median overall survival (OS) was 15.2 months, and the 3-year survival rate was 32.1%. High Glasgow prognostic score (GPS) and advanced N-category independently predicted the objective response to CRT. GPS and objective response were independent prognostic factors for OS. There was no significant difference in the long-term survival of responders who received subsequent chemotherapy or salvage surgery.High GPS and advanced N-category predicted a poor objective response to CRT in patients with T4b ESCC. Therefore, chemotherapeutic regimens with a higher efficacy are required. The indications for salvage surgery for responders should be carefully considered, with care taken to avoid complications. To confirm this, prospective randomized controlled studies are necessary.

Los mapas y los censos poblacionales o padrones constituyeron dos instrumentos cruciales en el proceso de configuración territorial de las misiones guaraníes. Ambas tecnologías, incorporadas por los jesuitas para el gobierno de la población y el territorio, no solamente sirvieron para representar o describir la situación de las misiones en distintos momentos, sino que fueron dispositivos fundamentales para delimitar el espacio misionero. A su vez, sirvieron como herramientas de la administración misionera apropiadas por la población indígena en la definición de su pertenencia identitaria. De manera similar y complementaria a la escritura narrativa, los mapas y padrones funcionaron como soportes eficaces de la memoria territorial. La primera parte del artículo explora las características de los cacicazgos guaraníes en las misiones y su rol en la organización del territorio. La segunda y tercera partes se adentran en los usos de la cartografía misionera como instrumento de construcción territorial en manos de los religiosos y de las autoridades indígenas de las misiones. La cuarta parte estudia las relaciones entre algunos mapas poco conocidos hasta el momento y los padrones o censos poblacionales como dispositivos complementarios de organización del espacio y la memoria.

Surgery in elderly patients with esophageal cancer is challenging due to high mortality and limited survival. This study aimed to evaluate the safety and effectiveness of curative esophagectomy in elderly patients with esophageal cancer. This study included 77 and 112 patients with esophageal cancer aged ≥ 70 and 40–64 years, respectively, who underwent R0 esophagectomy between January 1998 and December 2016. Patient characteristics, intraoperative outcomes, postoperative complications, and long-term survival were compared. The proportions of comorbid diseases (85.7% vs. 57.1%; P

No studies have reported the effect of solitary living on adjuvant chemotherapy continuation in patients with gastric cancer. This study aimed to investigate the influence of solitary living on the efficacy of adjuvant chemotherapy after curative gastrectomy.We enrolled 155 patients with pathological stage II/III gastric cancer who underwent gastrectomy and adjuvant chemotherapy between January 2013 and March 2020. The patients were divided into two groups according to their living conditions, the solitary group (n = 34) versus the non-solitary group (n = 121). Clinicopathological features, predictive factors for the continuation of adjuvant chemotherapy, and long-term survival were compared between the two groups.The median body weight loss (BWL) at one month after surgery (8.9% vs. 7.0%, p = 0.01), and the rates of failure to continue six courses of chemotherapy were higher in the solitary group (41.2% vs. 14.9%, p = 0.002) than in the non-solitary group. Multivariate analysis revealed that solitary living was an independent predictive factor for discontinuing adjuvant chemotherapy (odds ratio 3.36, 95% confidence interval [CI; 1.32-8.58], p = 0.01) as well as 10% BWL at one month after surgery (odds ratio 3.99, 95% CI [1.57-10.2], p = 0.004). The relapse-free survival was significantly worse in the solitary group (p = 0.03).Solitary living may be an independent risk factor for discontinuation of adjuvant chemotherapy in patients with gastric cancer. It is necessary to examine whether social and medical support organized by medical institutes and the government improves the continuation of adjuvant chemotherapy in patients living alone.

Background: The predictive factors for discontinuation of S-1 administration and prognostic factors in elderly patients with pStage II/III gastric cancer receiving S-1 adjuvant chemotherapy remain unclear. Methods: Between January 2004 and December 2016, 80 elderly gastric cancer patients (≥70 years) undergoing curative D2 gastrectomy were enrolled in this study. Predictive factors for completion of S-1 administration over 1 year, adverse events due to S-1 administration, and prognostic factors for overall survival (OS) and relapse-free survival (RFS) were evaluated. Results: Twenty-eight patients (35%) completed 8 courses of S-1. The median relative dose intensity was 82.1% (IQR 31.1–100%). The incidence rates of hematological and nonhematological adverse events were acceptable. Distal gastrectomy was an independent predictive factor for completion of S-1 administration (odds ratio [OR] 0.364; 95% confidence interval [CI] 0.141–0.939; p = 0.037). Higher postoperative neutrophil count/lymphocyte count (N/L) ratio and more advanced stage adversely influenced OS. Multivariate analysis revealed that a higher postoperative N/L ratio and more advanced stage adversely affected RFS. Conclusion: To complete adjuvant S-1 administration to elderly patients with pStage II/III gastric cancer, total gastrectomy should be avoided if possible. A new regimen for elderly gastric cancer patients with higher postoperative N/L ratios and more advanced stage should be established.

A duct-to-duct-biliary-anastomosis is the preferred biliary reconstruction technique in liver transplantation; biliary complications remain the major concerns for the technique. We examined the significance of the intramural vascular network of the extrahepatic bile duct (EBD) and its relevant vessels. We microscopically examined the axial sections of the EBD with 5 mm intervals of 10 formalin-fixed deceased livers. The luminal-areas of the 3 and 9 o'clock arteries correlated significantly and positively with the distance from the bifurcation of the right and left hepatic ducts (the 3 o'clock artery

A 60-year-old woman was not accompanied by any symptom. She had a gallstone which was identified 20 years prior. Ultrasonography performed by a local doctor revealed that the gallbladder was filled with small stones, and the patient was referred to our department for further examination and treatment for gallbladder stone. Tumor markers are elevated. Contrast- enhanced CT revealed gallbladder stones and thickening in the gallbladder body. PET-CT showed abnormal accumulation of FDG-PET with SUVmax 3.6 in the body of the gallbladder. With a diagnosis of gallbladder cancer, extended cholecystectomy and gallbladder bed resection with regional lymph node dissection were performed. The tumor was diagnosed histologically as small cell type neuroendocrine carcinoma of the gallbladder(pT2a[SS], pN0, pStage ⅡA; Japanese society of hepato-biliary-pancreatic surgery, the 7th edition). The postoperative course was uneventful. This patient has been followed up for 8 years without obvious signs of recurrence. R0 resection and lack of lymph node metastasis can allow long- term survival.

Background/aim Prophylactic splenectomy has shown no inferiority for tumors not invading the greater curvature side. Despite this, the clinical impact of prophylactic splenectomy for proximal advanced gastric cancer is not clear. This review aimed to clarify the impact of splenectomy for advanced gastric cancer in the upper third of the stomach. Materials and methods A systematic review and meta-analysis were conducted based on PubMed and EMBASE databases. The following search terms were used: "gastric cancer" OR "splenectomy" OR upper third of the stomach" OR preservation of the spleen. Results Out of 765 articles, 18 studies (combined n=6,341) were included in the analysis. Four randomized controlled trials (RCT) and eight retrospective studies suggested the benefits of spleen-preserving gastrectomy. Six retrospective studies showed no significant benefit of spleen-preserving gastrectomy. Prophylactic splenectomy showed a close association with a higher incidence of postoperative morbidity (pancreatic fistula and anastomotic leakage) with no concomitant improvement in overall survival. Prophylactic splenectomy should not be routinely performed and RCTs are necessary to confirm the impact of splenectomy for cN(+) at the splenic hilum tumors and tumors invading the greater curvature.

Purpose: To assess the utility of measurement of the computed tomography (CT) attenuation value (CTav) in predicting tumor necrosis in hepatocellular carcinoma (HCC) patients who achieve a complete response (CR), defined using modified Response Evaluation Criteria in Solid Tumors (mRECIST), after lenvatinib treatment. Method: We compared CTav in arterial phase CT images with postoperative histopathology in four patients who underwent HCC resection after lenvatinib treatment, to determine CTav thresholds indicative of histological necrosis (N-CTav). Next, we confirmed the accuracy of the determined N-CTav in 15 cases with histopathologically proven necrosis in surgical specimens. Furthermore, the percentage of the tumor with N-CTav, i.e. the N-CTav occupancy rate, assessed using Image J software in 30 tumors in 12 patients with CR out of 571 HCC patients treated with lenvatinib, and its correlation with local recurrence following CR were examined. Results: Receiver operating characteristic (ROC) curve analysis revealed an optimal cut-off value of CTav of 30.2 HU, with 90.0% specificity and 65.0% sensitivity in discriminating between pathologically identified necrosis and degeneration, with a CTav of less than 30.2 HU indicating necrosis after lenvatinib treatment (N30-CTav). Furthermore, the optimal cut-off value of 30.6% for the N30-CTav occupancy rate by ROC analysis was a significant indicator of local recurrence following CR with 76.9% specificity and sensitivity (area under the ROC curve; 0.939), with the CR group with high N30-CTav occupancy (>30.6%) after lenvatinib treatment showing significantly lower local recurrence (8.3% at 1 year) compared with the low (30.6% might be a predictor of maintenance of CR. Use of these indicators have the potential to impact systemic chemotherapy for HCC.

Introduction: The benefits of surgery in older patients with gastric cancer are controversial. This single-institution retrospective study in Japan aimed to evaluate the impact of gastrectomy in older patients with gastric cancer. Methods: A series of 234 patients aged ≥80 years with histologically confirmed gastric cancer had indications for surgical treatment at the Gastroenterological Center, Yokohama City University Medical Center, between April 2002 and December 2018. Patients who were lost to follow-up (n = 27), had tumors not eligible for surgery (n = 14), and could not achieve R0 resection (n = 7) were excluded from this retrospective study. The remaining 186 patients were included. Patient characteristics, intraoperative outcomes, postoperative complications, and long-term survival were evaluated. Results: The incidence of postoperative complications with Clavien–Dindo grade ≥ II was observed in 61 patients (32.8%). The 5-year relapse-free survival and overall survival (OS) rates were 84.2% and 63.4%, respectively. Multivariate analysis showed that geriatric nutritional risk index (p = 0.047), neutrophil/lymphocyte ratio (>2.36) (odds ratio, 1.94; 95% confidence interval, 1.02–3.67; p = 0.043), and total gastrectomy (TG) (odds ratio, 1.97; p = 0.042) significantly predicted postoperative complications. Moreover, TG (hazard ratio, 1.91; p = 0.036) was an independent prognostic factor of OS. Conclusions: Poor immunonutritional status and TG led to worse short-term outcomes. Moreover, TG was an independent prognostic factor of OS in older patients with gastric cancer. It is necessary to provide effective perioperative care, including nutritional support, to clarify whether short-term outcomes would be improved.

AIMS Early tumor recurrence (ETR) after hepatic resection is a crucial predictor of poor prognosis in patients with hepatocellular carcinoma (HCC). The aim of this study was to identify clinically significant serum microRNAs (miRNAs) involved in the ETR of HCC. METHODS We compared expression profiles of circulating miRNAs from serum samples between five HCC patients with ETR (recurrence within 12 months after hepatectomy) and five HCC patients without recurrence using microarray analysis of miRNA. The identified miRNA associated with ETR was further verified in 121 HCC patients, 73 liver disease patients, and 15 health controls by real-time quantitative reverse transcription-polymerase chain reaction (PCR). RESULTS Of the approximately 2000 miRNAs analyzed, we identified 15 miRNAs for which expression levels correlated significantly with ETR. Of these miRNAs, we further investigated expression of miRNA-1246 (miR-1246). Quantitative PCR confirmed that miR-1246 was upregulated in HCC with ETR, compared to the level in HCC without ETR (P

Background The significance of the dimensional factors (tumor diameter, area and volume) as the prognostic factor has not been precisely evaluated in pT1 gastric cancer. Objectives This study aimed to identify the clinical impact and to confirm the clinical feasibility of the dimensional factors as prognostic factors in pT1 gastric cancer. Methods We analyzed prognostic factors for disease-specific survival (DSS), overall survival (OS) using clinicopathological factors by univariate and multivariate analyses and the pattern of recurrence in 2011 pT1 gastric cancer (mucosal and submucosal cancers) undergoing R0 gastrectomy. The cut-off values of each dimensional factor was decided by the ROC curve. Results Cox proportional hazard regression model showed that older age (≥75) and more advanced pN stage were adverse independent prognostic factors for DSS, and revealed that older age (≥75), greater preoperative co-morbid diseases, proximal and total gastrectomy, operative method and Clavien-Dindo classification (≥grade III) were independent adverse factors for OS. Any dimensional factors were not independent prognostic factors for any survival. Conclusions The dimensional factors do not influence both OS and DSS in pT1 gastric cancer patients and so it is difficult to apply these dimensional factors for conducting therapeutic strategies.

BACKGROUND Converse Ω anastomosis is a recently developed technique of delta-shaped anastomosis for intracorporeal gastroduodenostomy to simplify the anastomotic procedures and reduce their potential risks. This study aimed to evaluate the safety and effectiveness of converse Ω anastomosis, comparing it with conventional extracorporeal Billroth-I anastomosis after laparoscopic distal gastrectomy (LDG) for gastric cancer. PATIENTS AND METHODS Among 169 gastric cancer patients who underwent LDG with Billroth-I anastomosis anastomosis between April 2013 and March 2018, we selected 100 patients by propensity score matching (50 in the converse Ω anastomosis group and 50 in the extracorporeal anastomosis group). Patients' characteristics, intraoperative outcomes, postoperative complications, and survival time were compared between the 2 groups. RESULTS Median anastomosis time was significantly longer in the converse Ω group than in the extracorporeal group (40.0 vs. 30.5 min, P=0.005). However, the total procedure time did not differ significantly between the groups. Intraoperative blood loss volume was significantly lower in the converse Ω group than in the extracorporeal anastomosis group (40 vs. 120 mL, P

Background Although endoscopic interventions for chronic pancreatitis are highly developed, surgery for severe complicated cases such as the coexistence of bile duct, duodenum, and portal vein stenosis is a challenging issue for surgeons. In such instances, pancreaticoduodenectomy could lead to massive intraoperative bleeding due to severe collateral veins. A surgical drainage procedure, instead of pancreatic resection, may be a reasonable and safer option in such cases, but the literature on a surgical drainage technique to resolve all obstructions of the pancreatic duct, bile duct, and duodenum at once is limited. We devised a new surgical drainage method for such cases with consideration for a possible future second surgery for newly developed pancreatic cancer because chronic pancreatitis is a well-known high-risk factor for pancreatic cancer in the long term. Here, we report this surgical procedure. Case presentation A 55-year-old man was diagnosed with alcoholic chronic pancreatitis 15 years ago. Before surgery, he underwent regular endoscopic pancreatic stenting for pancreatic ductal stenosis for 3 years. Three months before surgery, his duodenal stenosis worsened, and he was referred to our department for surgery. Preoperative imaging revealed pancreatic and bile duct stenosis, duodenal stenosis, and portal vein stenosis. To avoid intraoperative bleeding caused by the development of collateral veins, we performed a triple drainage procedure: longitudinal pancreaticojejunostomy with coring-out of the pancreatic head, hepaticojejunostomy, and gastrojejunostomy. The patient did not develop postoperative complications, and he was discharged from the hospital on postoperative day 14. For 5 years after surgery, no abdominal pain or recurrent pancreatitis was observed. Conclusion Our triple drainage procedure seems effective and minimally invasive for patients complicated with bile duct stenosis, duodenal stenosis, and portal vein stenosis.

Although vascular invasion is an important factor in the progression and treatment of hepatocellular carcinoma (HCC), it remains difficult to determine, on the basis of preoperative imaging alone, whether vascular invasion, especially microvascular invasion, has occurred. The current retrospective study enrolled 292 patients who, between 2004 and 2014, underwent curative hepatectomy as an initial treatment for HCC. The patients were divided between those with (n=70) and those without (n=222) microvascular invasion. Whether tumor-marker-based prediction of microvascular invasion was possible was assessed by comparing the preoperative serum α-fetoprotein (AFP) and prothrombin induced by vitamin K absence or antagonist-II concentrations between two groups of patients. The AFP concentration was significantly higher in patients with microvascular invasion compared with patients without microvascular invasion (P=0.0019). Stepwise logistic regression analysis demonstrated the AFP concentration and the logarithmic conversion ratio of the AFP gradient (log AFP grad) to be useful (P=0.0019; 0.0424) for predicting microvascular invasion. The serum AFP concentration and log AFP grad appear to be clinically useful in predicting microvascular invasion in patients with HCC.

Long-term repetitive movements, such as opening and closing scissors, increase strain on muscles and joints. Amplitude probability distribution function (APDF) analysis of surface electromyogram (sEMG) data was used to quantify the burden of muscle activity. We aimed to test the hypothesis that scissors with a power-support device assist repetitive thumb movements to reduce potential myoelectric activity. Twenty female university students who met the eligibility criteria performed a cutting experiment, with and without power-support device scissors. The primary outcome was a change in muscle load due to sEMG data that were analyzed using APDF, and the secondary outcomes investigated the occurrence of muscle fatigue and pain. The adductor pollicis muscle showed a significant decrease in muscle activity with power assistance. In addition, it was also found that fatigue and pain of the thumb and on the radial side of the forearm were significantly lower under the power-assisted conditions. The results of this study suggest that the assistive action of scissors with a power-support device compensate for muscle load on the thenar eminence. This may be used as a reference value to prevent the occurrence of hand disorders for hairdressers.

This article explores the vertical aspects of the Jesuit confraternity system in the thirty community towns under Span­ish rule (1609−1767) designated as “Missions” or “Reductions” in the Río de la Plata region of South America. The principal docu­ments analyzed are the cartas anuas, the annual reports of the Jesuits. The chronological analysis is carried out with a view to tracing the process of integrating the Guaraní Indians into the Spanish colonial regime by means of the religious congregation founded in each Mission town. As a supplementary issue, we deal with the significance of the Spanish word policía (civility) used as a criterion to ascertain the level of culture attained by the Amer­indians. Normally the Jesuits considered members of indigenous confraternities to be endowed with policía, so they used confrater­nities to transplant Christian civility among the Guaraní Indians in the Spanish overseas colony.

Cholangiocarcinoma represents the second most common primary liver tumor after hepatocellular carcinoma. Mahanine, a carbazole alkaloid derived from Murraya koenigii (Linn.) Spreng, has been used as folk medicine in Thailand, where the liver fluke-associated cholangiocarcinoma is common. The expression of microphthalmia-associated transcription factor (MITF) is maintained at immunohistochemically undetectable levels in hepatocytes and cholangiocytes. To explore the regulation of MITF expression in the liver, we immunohistochemically analyzed the MITF expression using hepatocellular carcinoma and cholangiocarcinoma specimens of the human liver cancer tissue array. MITF immunoreactivity was detected in subsets of hepatocellular carcinoma (6 out of 38 specimens; 16%) and cholangiocarcinoma (2/7 specimens; 29%). Moreover, immunoreactivity for glioma-associated oncogene 1 (GLI1), a transcription factor of the Hedgehog signaling pathway, was detected in 55% of hepatocellular carcinoma (21/38 specimens) and 86% of cholangiocarcinoma (6/7 specimens). Importantly, MITF was detectable only in the GLI1-positive hepatocellular carcinoma and cholangiocarcinoma, and MITF immunoreactivity is associated with poor prognosis in patients with hepatocellular carcinoma. Subsequently, the effect of mahanine was analyzed in HepG2 human hepatocellular carcinoma and HuCCT1 and KKU-100 human cholangiocarcinoma cells. Mahanine (25 µM) showed the potent cytotoxicity in these hepatic cancer cell lines, which was associated with increased expression levels of MITF, as judged by Western blot analysis. MITF is over-expressed in subsets of hepatocellular carcinoma and cholangiocarcinoma, and detectable MITF immunoreactivity is associated with poor prognosis in patients with hepatocellular carcinoma. MITF expression levels may be determined in hepatic cancer cells by the balance between the Hedgehog signaling and the cellular stress.

Regorafenib is an oral multikinase inhibitor affecting angiogenesis, oncogenesis, metastasis, and tumor immunity. As a systemic treatment, it has been shown to provide survival benefits in hepatocellular carcinoma (HCC) patients progressing on sorafenib treatment. We report herein a case of HCC with hepatic vein tumor thrombosis protruding into the inferior vena cava (IVC-HVTT) which was successfully treated by surgery following second-line chemotherapy with regorafenib. A 79-year-old man with chronic hepatitis was diagnosed with HCC. Computed tomography revealed a solitary tumor in segments 7 and 8 and an IVC-HVTT from the right hepatic vein. Since IVC-HVTT removal is a difficult procedure, the tumor was diagnosed as unresectable, and administration of sorafenib was started. Five weeks later, the lesion had increased in size by 15.3%; subsequently, regorafenib was given as second-line therapy for 12 months. After shrinkage of the IVC-HVTT, the patient was referred to our hospital for surgery. One month after the cessation of regorafenib, an extended resection of segment 8 and total removal of the IVC-HVTT was successfully performed without using total hepatic vascular exclusion. There were no serious postoperative complications. Additionally, there has been no recurrence for about 2 years since the initial therapy.

Long interspersed element-1 (LINE-1) is a mammalian transposable element, and its genomic insertion could cause neurological disorders in humans. Incidentally, LINE-1 is present in intron 3 of the microphthalmia-associated transcription factor (Mitf) gene of the black-eyed white mouse (Mitfmi-bw allele). Mice homozygous for the Mitfmi-bw allele show the white coat color with black eye and deafness. Here, we explored the functional consequences of the LINE-1 insertion in the Mitf gene using homozygous Mitfmi-bw mice on the C3H background (C3H-bw mice) or on the C57BL/6 background (bw mice). The open-field test showed that C3H-bw mice moved more irregularly in an unfamiliar environment during the 20-min period, compared to wild-type mice, suggesting the altered emotionality. Moreover, C3H-bw mice showed the lower serum creatinine levels, which may reflect the creatine deficiency. In fact, morphologically abnormal neurons and astrocytes were detected in the frontal cortex of bw mice. The immunohistochemical analysis of bw mouse tissues showed the lower intensity for expression of guanidinoacetate methyltransferase, a key enzyme in creatine synthesis, in neurons of the frontal cortex and in glomeruli and renal tubules. Thus, Mitf may ensure the elongation of axons and dendrites by maintaining creatine synthesis in the frontal cortex.

The post-operative mortality and morbidity rates associated with living-donor liver transplantation (LDLT) are still relatively high. Several papers have reported the risk factors associated with post-operative infectious complications, but few have analyzed the risk factors with respect to the severity of sepsis. The aim of this study was to clarify the risk factors that affect severe sepsis after LDLT.For 63 LDLT patients at our institute, we compared peri-operative characteristics in 29 patients who developed sepsis after surgery and 34 patients who did not. The sepsis group was further divided into severe sepsis (n = 16) and sepsis (n = 13) subgroups to identify significant peri-operative risk factors.Multivariate analysis identified 3 significant risk factors for post-operative sepsis after LDLT: ABO incompatibility (P = .015), low estimated glomerular filtration rates (90 mL/min/1.73 m(2); P = .074), and low peripheral lymphocyte counts (850/μL; P = .008). Multivariate analysis showed that the only significant risk factor for severe sepsis was a low pre-operative lymphocyte count (850/μL; P = .01). In the 2 sepsis subgroups, the 5- and 10-year survival rates for the severe sepsis subgroup (37.5% and 37.5%) were significantly lower than for the sepsis subgroup (83.3% and 62.5%; P = .05). The lung was the most common site of severe sepsis (n = 8; 50.0%).Patients who developed severe sepsis after LDLT had poor long-term survival, with pre-operative lymphocyte counts 850/μL being the significant risk factor. Pre-operative nutritional intervention and rehabilitation should be considered to improve LDLT outcomes.

A 52-year-old Japanese male underwent ABO-incompatible living donor liver transplantation for acute-on-chronic hepatitis B infection. Fifty-one months later, he became feverish and a cytomegalovirus (CMV) infection was diagnosed. A dramatically high CMV pp65 antigen (C10/C11) load (2,412) was measured, which did not respond to ganciclovir and immune globulin treatment, and increased further to 5,353. The next treatment strategy was the reduction of immunosuppressants, but to simply reduce immunosuppressants can lead to graft loss. Therefore, before using this strategy, responses to alloantigens were evaluated using a carboxyfluorescein-diacetate-succimidyl ester-labeled mixed lymphocyte reaction (CFSE-MLR). Only limited CD4(+) and CD8(+) T-cell proliferation was observed, suggesting the patient was hyporesponsive. After reducing tacrolimus levels from 3-4 ng/mL to

Microphthalmia-associated transcription factor (MITF) is a key regulator of differentiation of melanocytes and retinal pigment epithelial cells, but it also has functions in non-pigment cells. MITF consists of multiple isoforms, including widely expressed MITF-A and MITF-H. In the present study, we explored the potential role played by the Hedgehog signaling on MITF expression in two common types of primary liver cancer, using human cholangiocarcinoma cell lines, the KKU-100 and HuCCT1, along with the HepG2 human hepatocellular carcinoma cell line. Importantly, cholangiocarcinoma is characterized by the activated Hedgehog signaling. Here we show that MITF-A mRNA is predominantly expressed in all three human liver cancer cell lines examined. Moreover, cyclopamine, an inhibitor of the Hedgehog signalling, increased the expression levels of MITF proteins in HuCCT1 and HepG2 cells, but not in KKU-100 cells, suggesting that MITF expression may be down-regulated in some liver cancer cases.

Melanocytes develop from the vertebrate embryo-specific neural crest, migrate, and localize in various organs, including not only the skin but also several extracutaneous locations such as the heart, inner ear and choroid. Little is known about the functions of extracutaneous melanocytes except for cochlear melanocytes, which are essential for hearing ability. In this study, we focused on the structure of the choroid, in which melanocytes are abundant around the well-developed blood vascular system. By comparing structural differences in the choroid of wild-type and melanocyte-deficient Mitfmi-bw/Mitfmi-bw mutant mice, our observations suggest that choroidal melanocytes contribute to the morphogenesis and/or maintenance of the normal vasculature structure of that tissue.