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Background/aim: Few studies have established a definite conclusion regarding the limitation of surgical treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage B and C hepatocellular carcinoma (HCC)., Patients and Methods: A retrospective analysis was performed on 717 consecutive patients who underwent initial hepatectomy for HCC., Results: Reductive hepatectomy was performed in 103 patients, with a median survival time (MST) of 18.0 months. Total bilirubin and albumin levels were identified as independent prognostic factors. The predictive score of these factors ranged from 0 to 2. Subsequent local treatment was performed in 91.0, 75.0, and 25.0% of patients who scored 0, 1, and 2, respectively. The MST for patients with a score of 0, 1, and 2 was 20.1, 14.8, and 2.7 months, respectively, with a significant difference., Conclusion: Patients with BCLC stage B and C could be properly treated with reductive hepatectomy and subsequent local treatments., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The present study aimed to assess the clinical features of patients who received lenvatinib treatment for unresectable hepatocellular carcinoma (HCC)., Methods: The clinical characteristics, adverse events, and radiological responses were evaluated for 51 consecutive patients., Results: Of the study subjects, 37 patients had Child-Pugh class A (CPA) liver function, and 14 patients had Child-Pugh class B (CPB) liver function. The overall response rates in the CPA and CPB groups were 42.9% and 25.0%, respectively, and disease control rates were 82.9% and 83.3%, respectively, without significant difference (p = 0.2621 and 0.9697). There was no significant difference between CPA and CPB groups regarding the incidence of adverse events, except for hepatic coma. No significant difference was observed in the relative dose intensity between the CPA and CPB groups, for the first month, 1-2 months, or 2-3 months (p = 0.2368, 0.9368, and 0.9293)., Conclusion: The comparable outcomes between the CPA and CPB groups suggest the acceptability of lenvatinib treatment in patients with impaired liver function, at least in the acute phase. With careful follow-up, the dose can be relatively intensified, even in patients with impaired liver function and this may contribute to offering comparable treatment., (Copyright © 2020 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Although total tumour volume (TTV) may have prognostic value for hepatic resection in certain solid cancers, its importance in colorectal liver metastases (CRLM) remains unexplored. This study investigated its prognostic value in patients with resectable CRLM., Method: This was a retrospective review of patients who underwent hepatic resection for CRLM between 2008 and 2017 in a single institution. TTV was measured from CT images using three-dimensional construction software; cut-off values were determined using receiver operating characteristic (ROC) curve analyses. Potential prognostic factors, overall survival (OS) and recurrence-free survival (RFS) were determined using multivariable and Kaplan-Meier analyses., Results: Some 94 patients were included. TTV cut-off values for OS and RFS were 100 and 10 ml respectively. Right colonic primary tumours, primary lymph node metastasis and bilobar liver metastasis were included in the multivariable analysis of OS; a TTV of 100 ml or above was independently associated with poorer OS (hazard ratio (HR) 6·34, 95 per cent c.i. 2·08 to 17·90; P = 0·002). Right colonic primary tumours and primary lymph node metastasis were included in the RFS analysis; a TTV of 10 ml or more independently predicted poorer RFS (HR 1·90, 1·12 to 3·57; P = 0·017). The 5-year OS rate for a TTV of 100 ml or more was 41 per cent, compared with 67 per cent for a TTV below 100 ml (P = 0·006). Corresponding RFS rates with TTV of 10 ml or more, or less than 10 ml, were 14 and 58 per cent respectively (P = 0·009). A TTV of at least 100 ml conferred a higher rate of unresectable initial recurrences (12 of 15, 80 per cent) after initial hepatic resection., Conclusion: TTV was associated with RFS and OS after initial hepatic resection for CRLM; TTV of 100 ml or above was associated with a higher rate of unresectable recurrence., (© 2020 The Authors. BJS Open published by John Wiley & Sons Ltd on behalf of British Journal of Surgery Society.)

Background: The albumin-bilirubin (ALBI) grade, stratified from the ALBI score, may have prognostic value in patients with hepatocellular carcinoma. We aim to evaluate the prognostic abilities of the ALBI score/grade among living-donor liver transplantation patients., Methods: We retrospectively collected data of 81 patients who underwent living-donor liver transplant at Kobe University Hospital between June 2000 and October 2018. The efficacy of the ALBI score/grade as a prognostic factor was assessed and compared with that of the well-established Model for End-Stage Liver Disease (MELD) score., Main Findings: Multivariate analysis indicated that recipient age (P = .003), donor age (P = .003), ALBI score ≥ -1.28 (P = .002), and ALBI grade III (P = .004) were independently associated with post-transplant survival. A high MELD score was not associated with post-transplant survival in univariate or multivariate analyses. Although there was no significant difference in the overall survival rate relative to recipient and donor age, ALBI score/grade was significantly associated with the 1- and 5-year survival rates (P = .023, P = .005). ALBI scores specifically detected fatal complications of post-transplant graft dysfunction (P = .031) and infection (P = .020)., Conclusion: ALBI score/grade predicted patient survival more precisely than the MELD score did, suggesting that it is a more useful prognostic factor compared to the MELD score in living-donor liver transplantation cases., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: This study evaluated the prognosis of hepatocellular carcinoma (HCC) patients with extrahepatic metastases who can undergo hepatectomy., Methods: A total of 32 patients who underwent hepatectomy for HCC with extrahepatic metastases, including lymph node and/or distant metastases were recruited for this study., Results: Fourteen patients had lymph node metastasis only, 16 had distant metastasis only, and 2 had both metastasis types during preoperative diagnosis. The 3-year overall survival (OS) rate of all patients was 17.9%, and the median survival time (MST) was 11.8 months. Univariate analysis revealed that intrahepatic maximal tumor size, intrahepatic tumor number, and intrahepatic tumor control after hepatectomy were significant factors influencing OS (p < 0.05). Multivariate analysis revealed that independent risk factors for OS were intrahepatic maximal tumor size and intrahepatic tumor number (p < 0.05). The MST and 3-year OS rate of patients with maximal tumor size <100 mm and intrahepatic tumor number ≤2 were 39.0 months and 51.9%, respectively., Conclusions: Hepatectomy is not recommended for HCC patients with extrahepatic metastasis with ≥3 intrahepatic tumors, even when all intrahepatic tumors can be eliminated via hepatectomy. Aggressive surgery may be justified for HCC patients with ≤2 intrahepatic tumors and maximal tumor size <100 mm, irrespective of vascular invasion., (© 2020 S. Karger AG, Basel.)

Background: This study aimed to evaluate the clinical relevance of hepatectomy for Barcelona Clinic Liver Cancer (BCLC) stages B and C advanced hepatocellular carcinoma (HCC)., Methods: A total of 314 patients (149 and 165 BCLC stages B and C, respectively) who underwent hepatectomy were included. Complete hepatectomy (without residual tumors after hepatectomy) and reductive hepatectomy (apparent residual tumors after hepatectomy) were performed for 212 and 102 patients, respectively. Short-term operative and postoperative outcomes, as well as long-term outcomes, were evaluated., Results: The median survival times of patients with stage B disease undergoing complete hepatectomy and reductive hepatectomy were 48.9 and 20.1 months, respectively (p = 0.0075), whereas those of patients with stage C disease were 19.5 and 17.6 months, respectively (p = 0.0140). The 3-year overall survival rates of patients with stage B disease undergoing reductive hepatectomy with and without subsequent local treatments after surgery were 47.5% and 0%, respectively, whereas those of patients with stage C diseases were 18.6% and 0%, respectively., Conclusions: Survival benefits are obvious for both BCLC stages B and C HCC when complete hepatectomy can be performed safely. Reductive hepatectomy is also acceptable for BCLC stages B and C when subsequent local treatment for remnant liver tumors can be performed safely after reductive hepatectomy. Without subsequent local treatment, reductive hepatectomy has little clinical relevance. Thus, a cautious approach to patient selection is required for this aggressive strategy.

Introduction: In-vivo fluorescence imaging techniques using indocyanine green (ICG) to identify liver tumours and hepatic segment boundaries have been recently developed. The purpose of this study is to evaluate the efficacy of fusion ICG-fluorescence imaging for navigation during hepatectomy., Methods and Analysis: This will be an exploratory single-arm clinical trial; patients with liver tumours will undergo hepatectomy using the ICG-fluorescence imaging system. In total, 110 patients with liver tumours scheduled for elective hepatectomy will be included in this study. Preoperatively, ICG will be intravenously injected at a dose of 0.5 mg/kg body weight within 2 days. To detect liver tumours intraoperatively, the hepatic surface will be initially observed using the ICG-fluorescence imaging system. After identifying and clamping the portal pedicle corresponding to the hepatic segments, including the liver tumours to be resected, additional ICG will be injected intravenously at a dose of 0.5 mg/kg body weight to identify the boundaries of the hepatic segments. The primary outcome measure will be the success or failure of the ICG-fluorescence imaging system in identifying hepatic segments. The secondary outcomes will be the success or failure in identifying liver tumours, liver function indicators, operative time, blood loss, rate of postoperative complications and recurrence-free survival. The findings obtained through this study are expected to help to establish the utility of ICG-fluorescence imaging systems, and therefore contribute to prognostic outcome improvements in patients undergoing hepatectomy for various causes., Ethics and Dissemination: The protocol has been approved by the Kobe University Clinical Research Ethical Committee. The findings of this study will be disseminated widely through peer-reviewed publications and conference presentations., Trial Registration Number: UMIN000031054 and jRCT1051180070., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Bile leak is still a major complication after liver resection to be improved. To intraoperatively detect this adverse complication, leak test is commonly performed after hepatic resection. However, by the conventional leak test, it is often difficult to know whether the test reagent reaches to intrahepatic bile duct near cut surface of liver with adequate volume and pressure to identify the existence of bile leak. Thus, in order to perform leak test more accurately, this study aims to evaluate the efficacy and safety of the leak test using contrast-enhanced intraoperative ultrasonic cholangiography (CE-IOUSC), which was reported by our group as a procedure for detection of bile duct., Methods and Analysis: The current study is a non-randomised, prospective, off-label, single-arm clinical trial for patients who undergo liver resection. A total of 100 patients will be enrolled. After completion of liver resection, the leak test is performed with CE-IOUSC using Sonazoid as a contrast agent to visualise dye injection into the intrahepatic bile duct. The primary endpoint is the success of the leak test, defined as clear visualisation of intrahepatic bile duct around cut surface by ultrasonography that indicates enough volume of dye injection. Secondary endpoints are postoperative bile leak and all adverse events related to CE-IOUSC. The findings obtained through this study will establish this procedure to assist surgeons for adequately performing the leak test, precisely detecting intraoperative biliary leak strictly and reducing postoperative bile leak., Ethics and Dissemination: The protocol is approved by Institutional Review Boards of Kobe University Hospital (No.290069). Our findings will be widely disseminated through conference presentations and peer-reviewed publications., Trial Registration Number: UMIN000031236 and jRCTs051180027., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

ADP-ribosylation factor-like 4c (ARL4C) is identified as a small GTP-binding protein, which is expressed by Wnt and EGF signaling and plays an important role in tubulogenesis of cultured cells and the ureters. ARL4C is little expressed in adult tissues, but it is highly expressed in lung cancer and colorectal cancer and shown to represent a molecular target for cancer therapy based on siRNA experiments. This study revealed that ARL4C is highly expressed in primary hepatocellular carcinoma (HCC) tumors and colorectal cancer liver metastases, and that ARL4C expression is associated with poor prognosis for these cancers. Chemically modified antisense oligonucleotides (ASO) against ARL4C effectively reduced ARL4C expression in both HCC and colorectal cancer cells and inhibited proliferation and migration of these cancer cells in vitro ARL4C ASOs decreased the PIK3CD mRNA levels and inhibited the activity of AKT in HCC cells, suggesting that the downstream signaling of ARL4C in HCC cells is different from that in lung and colon cancer cells. In addition, subcutaneous injection of ARL4C ASO was effective in reducing the growth of primary HCC and metastatic colorectal cancer in the liver of immunodeficient mice. ARL4C ASO accumulated in cancer cells more efficiently than the surrounding normal cells in the liver and decreased ARL4C expression in the tumor. These results suggest that ARL4C ASO represents a novel targeted nucleic acid medicine for the treatment of primary and metastatic liver cancers., (©2019 American Association for Cancer Research.)

Although the first-line treatment for hepatocellular carcinoma(HCC)is hepatectomy, extreme elderly(80 years or older) patients often tend to have a variety of underlying diseases and decreased cardiopulmonary function, which means that surgery involves a high risk. In this case, we examined the safety and efficacy of hepatectomy performed in an extreme elderly patient with HCC. Of the patients with HCC that underwent initial hepatectomy at Kobe University Hospital(n=348)between 2009 and 2015, 23 patients aged 80 years or older at the time of surgery(Group 1, n=23)and those younger than 80 years at the time(Group 2, n=325)were compared, based on parameters related to safety and prognosis. We did not identify differences between the 2 groups with respect to blood loss and operating time. Intraoperative blood transfusion was more common in Group 1. There was no significant difference between the 2 groups with respect to complications of Grade Ⅲ or higher. The median survival of Group 2 patients following hepatectomy(42 months)was better than that of Group 1 patients(34 months), but there was no significant difference between the 2 groups(p=0.429). Furthermore, when the same parameters were compared after adjusting for and matching propensity scores, there were no significant differences in complications, hospitalization periods, and prognosis between the 2 groups. Through proper assessment of oncologic factors and patient risk factors, hepatectomy can be performed safely and effectively even for extreme elderly patients with HCC. If there is no other disease regulating the prognosis, we can expect to achieve similar prognosis in non-extreme elderly patients. Hence, treatments should not be limited solely based on a patient being extremely elderly; rather, proactive treatments should be considered.

The patient was a 63-year-old man with hepatitis C. He discontinued combination therapy containing interferon and ribavirin because of the development of skin symptoms. A screening examination showed multiple early-stage hepatocellular carcinomas. He refused treatment and was followed up as an outpatient. During follow-up, his PIVKA-Ⅱ level remarkably elevated to 59,994mAU/mL. Computed tomography(CT)showed an enlarged tumor with portal invasion(vp2)in segment 8 and intrahepaticmetastasis. We performed right and partial hepatectomy. Three months later, CT showed multiple lung metastases. We initiated the daily administration of 800 mg of sorafenib. However, 6 months after hepatectomy, the lung metastases increased in size and number. We considered the therapeutic effect as progressive disease(PD)according to the RECIST criteria. We then initiated administering 120 mg of regorafenib daily as second-line therapy. In a course of the treatment containing sorafenib and regorafenib, the dose was reduced due to hand-foot skin reactions. 8.5 months after hepatectomy, the lung metastases significantly decreased in size. One year after hepatectomy, almost complete response(CR) was obtained, and no intrahepatic recurrence was found.

Background: Progression of portal vein tumor thrombus directly affects the prognosis and treatment for patients with hepatocellular carcinoma; there are no data on the growth velocity of portal vein tumor thrombus. We analyzed the growth velocity of portal vein tumor thrombus and its risk factors to propose the best timing of surgical treatment for hepatocellular carcinoma with portal vein tumor thrombus., Methods: We retrospectively collected data on 57 hepatocellular carcinoma patients with portal vein tumor thrombus who underwent computed tomography twice preoperatively and hepatectomy between 2005 and 2015. To calculate the growth velocity of portal vein tumor thrombus, migration lengths of portal vein tumor thrombus were divided by the number of days. To identify risk factors for rapid growth of portal vein tumor thrombus, patients were classified according to the velocity: rapid (≥ 1.0 mm/day, n = 23) and slow (< 1.0 mm/day, n = 34)., Results: Median survival times of patients with portal vein tumor thrombus that invaded the ipsilateral second portal branch, ipsilateral first portal branch, and portal trunk were 42.9, 11.7, and 12.3 months, respectively. The average growth velocity of portal vein tumor thrombus was 0.9 ± 1.0 mm/day. Median estimated times required from ipsilateral second portal branch to ipsilateral first portal branch and ipsilateral first portal branch to portal trunk were 8.2 and 11.5 days, respectively. Liver fibrosis, alpha-fetoprotein, and extent of portal vein tumor thrombus were independent risk factors for rapid progression of portal vein tumor thrombus. Proteins induced by vitamin K absence or antagonist II, extent of portal vein tumor thrombus, and liver fibrosis, not rapid growth of portal vein tumor thrombus, were independent prognostic factors., Conclusion: An understanding of the rapid progression of portal vein tumor thrombus and its risk factors can be helpful in deciding an appropriate timing of surgical treatment for hepatocellular carcinoma with portal vein tumor thrombus., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Poor air quality is still a threat for human health in many parts of the world. In order to assess measures for emission reductions and improved air quality, three-dimensional atmospheric chemistry transport modeling systems are used in numerous research institutions and public authorities. These models need accurate emission data in appropriate spatial and temporal resolution as input. This paper reviews the most widely used emission inventories on global and regional scales and looks into the methods used to make the inventory data model ready. Shortcomings of using standard temporal profiles for each emission sector are discussed, and new methods to improve the spatiotemporal distribution of the emissions are presented. These methods are often neither top-down nor bottom-up approaches but can be seen as hybrid methods that use detailed information about the emission process to derive spatially varying temporal emission profiles. These profiles are subsequently used to distribute bulk emissions such as national totals on appropriate grids. The wide area of natural emissions is also summarized, and the calculation methods are described. Almost all types of natural emissions depend on meteorological information, which is why they are highly variable in time and space and frequently calculated within the chemistry transport models themselves. The paper closes with an outlook for new ways to improve model ready emission data, for example, by using external databases about road traffic flow or satellite data to determine actual land use or leaf area. In a world where emission patterns change rapidly, it seems appropriate to use new types of statistical and observational data to create detailed emission data sets and keep emission inventories up-to-date., Implications: Emission data are probably the most important input for chemistry transport model (CTM) systems. They need to be provided in high spatial and temporal resolution and on a grid that is in agreement with the CTM grid. Simple methods to distribute the emissions in time and space need to be replaced by sophisticated emission models in order to improve the CTM results. New methods, e.g., for ammonia emissions, provide grid cell-dependent temporal profiles. In the future, large data fields from traffic observations or satellite observations could be used for more detailed emission data.

A 72-year-old man underwent endoscopic submucosal dissection for early gastric cancer at antrum in July 2015. The histopathological examination revealed an adenocarcinoma invading the deep submucosal layer(SM2)with lymphatic invasion, consistent with the diagnosis of non-curative resection. Additional surgery was recommended, and he underwent laparoscopic distal gastrectomy in August 2015. The histopathological examination of resected specimen revealed there were no lymph node metastases, and postoperative diagnosis was Stage I A. However, 8 months after the surgery, abdominal enhanced computed tomography(CT)revealed an enlargement of para-aortic lymph node. Positron emission tomography-CT showed high accumulation at the enlarged lymph node. A para-aortic lymph node metastasis was suspected, and laparoscopic lymph node dissection was performed in July 2016. The histopathological examination revealed lymph node metastasis of gastric cancer. He was given systematic chemotherapy using S-1 plus cisplatin after the surgery, and has been followed-up without recurrences for 21 months after the first operation. Although recurrence of the para-aortic lymph nodes was assumed as part of a systemic metastasis, some population certainly benefit from multidisciplinary treatment including surgical approach.

A 63-year-old woman had recurrences of metastatic rectal cancer in the lung, peritoneum, and ovary. Regorafenib was administered at 160mg/day as third-line chemotherapy. The patient developed Grade(Gr)3 hand-foot syndrome(HFS) and Gr 2 rash, but the abdominal distension and pain were relieved by the 1st course. Analgesics could be reduced and regorafenib was administrated at reduced dosage. The patient received keishi-bukuryo-gan(EK-25)and sai-rei-tou(TJ-114) for HFS. At the beginning of therapy, ovarian metastases were not reduced and showed poor contrast enhancement on CT. Serum levels of lactate dehydrogenase(LDH)and tumor markers were increased. During the 4th course of therapy, ovarian metastases tended to shrink and serum levels of LDH and tumor markers were decreased. Ovarian metastases showed a partial response(PR)after the 6th course. Lung metastases showed a progressive disease during the 2nd course, but a PR after the 3rd course, and were not apparent after the 6th course. Reduction of metastases was maintained at 16 months after the start of therapy, and HFS was assessed at Gr 2 or lower. Physical, laboratory, and imaging findings should be carefully evaluated prior to long-term administration of regorafenib.

A 38-year-old man underwent right hepatectomy for a huge hepatocellular carcinoma(HCC)in the right hepatic lobe. Four months later, recurrent and metastatic disease were observed in the remnant liver and right lung, respectively. We performed a hepatectomy for the recurrent lesion because transcatheter arterial chemoembolization (TACE) was not effective. After surgery, we initiated sorafenib treatment for the lung metastases. One year later, the lung metastases worsened and metastases were observed in the mediastinal lymph nodes, and both metastatic lesions were resected. Seven months later, para-aortic lymph nodal metastasis was observed and dissected. Three months later, metastasis to the supraclavicular lymph node was observed. We performed particle radiation therapy and a complete response was achieved. One year later, metastases in both lungs were observed and resected. Despite continued sorafenib administration throughout the clinical course, a metastasis to the left adrenal gland was observed. This lesion was extirpated because no other recurrent lesions were detected. At 4 years and 6 months after the first operation, no other recurrences have occurred. Currently, sorafenib is the initial drug of choice for HCC with extrahepatic metastases. It is possible to improve the prognosis of patients with HCC and extrahepatic metastases by applying surgical treatment during the course of sorafenib administration.

Single epithelial-derived tumor cells have been shown to induce apical and basolateral (AB) polarity by expression of polarization-related proteins. However, physiological cues and molecular mechanisms for AB polarization of single normal epithelial cells are unclear. When intestinal epithelial cells 6 (IEC6 cells) were seeded on basement membrane proteins (Matrigel), single cells formed an F-actin cap on the upper cell surface, where apical markers accumulated, and a basolateral marker was localized to the rest of the cell surface region, in a Wnt5a signaling-dependent manner. However, these phenotypes were not induced by type I collagen. Rac1 activity in the noncap region was higher than that in the cap region, whereas Rho activity increased toward the cap region. Wnt5a signaling activated and inhibited Rac1 and RhoA, respectively, independently through Tiam1 and p190RhoGAP-A, which formed a tertiary complex with Dishevelled. Furthermore, Wnt5a signaling through Rac1 and RhoA was required for cystogenesis of IEC6 cells. These results suggest that Wnt5a promotes the AB polarization of IEC6 cells through regulation of Rac and Rho activities in a manner dependent on adhesion to specific extracellular matrix proteins.

Wnts activate at least two signaling pathways, the β-catenin-dependent and -independent pathways. Although the β-catenin-dependent pathway is known to contribute to G1-S transition, involvement of the β-catenin-independent pathway in cell cycle regulation remains unclear. Here, we show that Wnt5a signaling, which activates the β-catenin-independent pathway, is required for cytokinesis. Dishevelled 2 (Dvl2), a mediator of Wnt signaling pathways, was localized to the midbody during cytokinesis. Beside the localization of Dvl2, Fz2, a Wnt receptor, was detected in the midbody with the endosomal sorting complex required for transport III (ESCRT-III) subunit, CHMP4B. Depletion of Wnt5a, its receptors, and Dvl increased multinucleation. The phenotype observed in Wnt5a-depleted cells was rescued by the addition of purified Wnt5a but not Wnt3a, which is a ligand for the β-catenin-dependent pathway. Moreover, depletion of Wnt5a signaling caused loss of stabilized microtubules and mislocalization of CHMP4B at the midbody, which affected abscission. Inhibition of the stabilization of microtubules at the midbody led to the mislocalization of CHMP4B, while depletion of CHMP4B did not affect the stabilization of microtubules, suggesting that the correct localization of CHMP4B depends on microtubules. Fz2 was localized to the midbody in a Rab11-dependent manner, probably along stabilized microtubules. Fz2 formed a complex with CHMP4B upon Wnt5a stimulation and was required for proper localization of CHMP4B at the midbody, while CHMP4B was not necessary for the localization of Fz2. These results suggest that Wnt5a signaling positions ESCRT-III in the midbody properly for abscission by stabilizing midbody microtubules.

We report a case of multiple advanced hepatocellular carcinomas (HCC) with bilobar distribution treated by combination therapy of hepatectomy and particle therapy (carbon ion therapy). A 73-year-old man who had been pointed out hepatic tumors on abdominal CT was referred to our hospital in February 2010. Advanced HCCs; 8 cm Vp3 and 6 cm in the left lobe, 4 cm in the posterior segment, and 1 .5 cm in the S8 area, were detected by abdominal dynamic CT and EOB-MRI etc. Curative resection was not applied due to insufficiency of liver function and unfavorable anatomical tumor locations. Accordingly we have developed a novel combination therapy of hepatectomy and particle therapy. First we performed left lobectomy in March 2010, followed by administration of particle therapy to the posterior segment for local control in May. Then, transcatheter arterial chemoembolization was administered 4 times for residual tumors. The patient survives for 15 months after the initial therapy with good local control.

In December 2008, a 43-year-old male who had been pointed out a nodular shadow in the right upper field on a chest radiography was admitted to hospital. A 35 mm mass infiltrating to superior vena cava in the right upper lobe of the lung, and 32 mm mass in the liver at S7 were detected by CT. Pathological diagnosis of the liver tumor was adenocarcinoma. Under the diagnosis of lung carcinoma and liver metastasis, systemic chemotherapy was started from January 2009. Radiofrequency ablation (RFA) therapy was added for liver S7 mass in February, and radiation therapy was performed for lung mass in December. The lung lesion has markedly reduced, but the liver lesion recurred in October 2009, which continued to grow up to 80 mm until August 2010. He presented to our hospital with the diagnosis of liver metastasis of controlled primary lung cancer. In October, we performed right hepatectomy with diaphragma and right lung resection. The pathological diagnosis was intrahepatic cholangiocarcinoma. Multiple recurrences in remnant liver, lung and peritoneal metastasis were detected in January 2011. For intrahepatic cholangiocarcinoma, hepatectomy is the only established treatment, and RFA treatment remains controversial. Clinical diagnosis of multiple cancers should be decided with caution.

The vertical allocation of emissions has a major impact on results of Chemistry Transport Models. However, in Europe it is still common to use fixed vertical profiles based on rough estimates to determine the emission height of point sources. This publication introduces a set of new vertical profiles for the use in chemistry transport modeling that were created from hourly gridded emissions calculated by the SMOKE for Europe emission model. SMOKE uses plume rise calculations to determine effective emission heights. Out of more than 40,000 different vertical emission profiles 73 have been chosen by means of hierarchical cluster analysis. These profiles show large differences to those currently used in many emission models. Emissions from combustion processes are released in much lower altitudes while those from production processes are allocated to higher altitudes. The profiles have a high temporal and spatial variability which is not represented by currently used profiles., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

This case is a 69-year-old woman. We diagnosed gastric cancer and cholecystolithiasis by close inspection of abdominal pain. Because preoperative diagnosis was T2N0M0, Stage I B, we performed an operation. Many lesser tubercles were shown, and were diagnosed as peritoneal metastases pathologically. The tumor in corpus ventriculi infiltrated out of gastric serosa. We judged that curative resection was impossible and finished the operation after giving an intra-abdominal dosage of cisplatin(CDDP)at 85mg. After operation, 3 courses of performed S-1/CDDP combination chemotherapy were performed. Because we observed contraction of the main lesion and could not point out the peritoneal metastases and ascitis, we performed a second look operation. All the nodules found with peritoneal and rectouterine excavation had disappeared and we performed distal gastrectomy. The postoperative diagnosis was pT2(MP), pN0CY0, Stage I B, Cur A, therapy grade 1a. Chemotherapy does succeed, and this is a valuable case in which a radical operation could be performed.

From research on PM(2.5) and PM(10) in 2007/2008 in the Netherlands, it was concluded that the coarse fraction (PM(2.5-10)) attributed 60% and 50% respectively, to the urban-regional and street-urban increments of PM(10). Contrary to Scandinavian and Mediterranean countries which exhibit significant seasonal variation in the coarse fraction of particulate matter (PM), in the Netherlands the coarse fraction in PM at a street location is rather constant during the year. Non-exhaust emissions by road traffic are identified as the main source for coarse PM in urban areas. Non-exhaust emissions mainly originate from re-suspension of accumulated deposited PM and road wear related particles, while primary tire and brake wear hardly contribute to the mass of non-exhaust emissions. However, tire and brake wear can clearly be identified in the total mass through the presence of the heavy metals: zinc, a tracer for tire wear and copper, a tracer for brake wear. The efficiency of road sweeping and washing to reduce non-exhaust emissions in a street-canyon in Amsterdam was investigated. The increments of the coarse fraction at a kerbside location and a housing façade location versus the urban background were measured at days with and without sweeping and washing. It was concluded that this measure did not significantly reduce non-exhaust emissions., (Copyright 2010 Elsevier B.V. All rights reserved.)

A 52-year-old man underwent distal gastrectomy for gastric cancer in July 2000. In July 2005, abdominal CT and barium study of the colon revealed peritoneal recurrence, and chemotherapy of S-1 was started. Within 2 courses, the serum CEA level increased, so combination chemotherapy of S-1 and cisplatin (CDDP) was begun. After 7 courses, the regimen was switched to S-1+paclitaxel (PTX). However, the patient developed digital numbness within 8 courses and single-agent chemotherapy with S-1 was restarted. In July 2007, he developed abdominal distension, and abdominal CT showed a large amount of ascites. S-1+CDDP was administered again, however, and we had to change the regimen within 3 courses due to fatigue and appetite loss. S-1 was restarted, but soon severe fatigue and appetite loss restricted the use of chemotherapeutic agents, and he died in December. This patient had been alive for 2 years and 5 months since peritoneal recurrence was diagnosed. We concluded that S-1-based sequential chemotherapy was effective for recurrent gastric cancer.

Large-scale use of leaded gasoline was an important source of the neurotoxin lead in the European environment. After a sequence of regulations on the allowed gasoline lead content and, eventually, a ban on the use of lead additives in gasoline, road transport was no longer considered a source of atmospheric lead. Currently a discrepancy exists between measured atmospheric lead concentrations and model-predicted concentrations, suggesting that lead emissions to the atmosphere may be underestimated. Recently it was suggested that lead emission from unleaded gasoline combustion is still an important source and may (partly) fill the gap between modelled and observed atmospheric lead concentrations. In this paper we assess the plausibility of the latter suggestion by following various emission estimation methodologies. The uncertainty of lead emissions from road transport is further reduced by chemical analysis of fuel samples. The result of our assessment is that lead from road transport fuel combustion is not the missing lead source needed to fill the gap between modelled and observed lead concentrations. Road transport is still a source of lead through brake wear and a small contribution from exhaust emissions but this contributes no more than 5-8% of the EU25 total emission.

A 50-year-old man undergoing operations for sigmoid colon cancer, small intestine invasion, and liver metastasis was given adjuvant chemotherapy postoperatively. During the course, lung, brain and bone metastasis were found, FOLFIRI therapy was started. Fifth FOLFIRI therapy was performed, but on the night of the next day, he was transported on an emergency basis to our hospital because of a coma. Laboratory examination revealed hyperammonemia, so aminoleban was started for its treatment. After 3 days in the hospital, consciousness and serum ammonia were improved. Cases of hyperammonemia caused by 5-FU have been reported in the literature, and this case was diagnosed with the same. Hyperammonemia should be taken into account as a differential diagnosis in the disturbance of consciousness in chemotherapy.

Microbial production in anoxic wetland rice soils is a major source of atmospheric CH4 the most important non-CO2 greenhouse gas. Much higher CH4 emissions from well managed irrigated rice fields in the wet than in the dry season could not be explained by seasonal differences in temperature. We hypothesized that high CH4 emissions in the wet season are caused by low grain to biomass ratios. In a screenhouse experiment, removing spikelets to reduce the plants' capacity to store photosynthetically fixed C in grains increased CH4 emissions, presumably via extra C inputs to the soil. Unfavorable conditions for spikelet formation in the wet season may similarly explain high methane emissions. The observed relationship between reduced grain filling and CH4 emission provides opportunities to mitigate CH4 emissions by optimizing rice productivity.

Ultrastructural alterations of rat ventral prostate were studied following the administration of peplomycin sulfate (NK631) to evaluate the efficacy of this drug to the human prostatic carcinoma. The rats as experimental animals were divided into 3 groups: control, castrated and NK631 administration ones with 5 mg per kg per day. Rat body weight and ventral prostatic weight were measured at 4, 7 and 14 days after the treatment. Simultaneously prostatic tissue samples were obtained for electron microscopic study. The ventral prostatic weight and body weight ratio (VBW) was utilized in respect to the prostatic weight to compared the experimental groups with control ones. The VBW was significantly decreased at 14 days after castration. NK631 administration showed only minor decrease at 14 days duration. However, statistics for control and NK631 were different. Ultrastructurally, normal rat ventral prostate demonstrated to contain abundant rough endoplasmic reticulum and well developed GOLGI apparatus and round nucleus. After castration, ventral prostatic cells lost their normal cytoplasmic configuration with the atrophy of rough endoplasmic reticulum and GOLGI apparatus, while secondary lysosomes were occasionally found in the cytoplasm. During the course of NK631 administration, the changes were detected in the cytoplasm with marked vacuolization and degeneration of rough endoplasmic reticulum as well as disappearances of cytoplasmic matrix. Nucleus was also affected with the marked indentation of nuclear membrane and disappearance of nucleoplasm. From the present preliminary investigation, NK631 could induce the cytostatic changes to rat ventral prostate. Therefore, NK631 would be suggested to contribute to the treatment of prostatic carcinoma. It is hoped that as more experimental studies are processed, a deeper understanding of the effect of NK631 would be clarified.