VFR travel generated by international students: The case of Japanese students in Australia

The visiting friends and relatives (VFR) market is one of the largest and most rapidly growing global tourism markets. Although much research has been carried out on this market since the early 1990s, these studies have largely been in the Western context, with Asian VFR travellers receiving little attention. To extend our understanding of the international VFR market, this study focused on Japanese international students studying in Australia. Through a series of in-depth interviews with 26 students, their roles and experiences as VFR hosts and the behaviours of the VFR travellers who visited them were explored. The results show that the majority of the students not only played important roles in motivating their friends and relatives to visit their study destinations but also recognised these roles. A number of unique behaviours on the part of Japanese VFR travellers, such as accommodation use and information searches, were also observed. The study\u27s findings extend our understanding of the VFR market. The study suggests that international students are important resources for tourism practitioners because they can trigger international visits by friends and relatives

無症候性腎機能障害が膵頭十二指腸切除術後臨床経過に及ぼす影響

BACKGROUND: Although recent large-scale clinical studies have shown that preoperative renal insufficiency is associated with increased risk of postoperative complications after pancreatoduodenectomy (PD), it is unknown whether asymptomatic renal dysfunction has an impact on postoperative course after PD. METHODS: Two hundred and fifty-four patients who underwent PD between 2007 and 2013 were enrolled. Renal function was evaluated by the preoperative estimated glomerular filtration rate (eGFR). Patients were divided into two groups according to the cutoff value of 55 of eGFR. RESULTS: Thirty-five patients were classified as the low eGFR group, while 219 were classified as the normal group. There were differences between groups in age, comorbidity and pancreatic texture. The incidence of overall postoperative complication, grade B/C pancreatic fistula and severe complication in the low eGFR group was significantly higher than that in the normal group. Multivariate analysis identified low eGFR as an independent risk factor for severe postoperative complications and grade B/C pancreatic fistula after PD. However, there were no differences in mortality and survival between the low and normal eGFR groups. CONCLUSIONS: We have demonstrated for the first time that preoperative asymptomatic renal dysfunction may be a significant risk factor for severe morbidity and clinically relevant pancreatic fistula after PD.博士（医学）・乙第1394号・平成29年3月15日© 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.This is the peer reviewed version of the following article: http://dx.doi.org/10.1002/jhbp.286, which has been published in final form at http://dx.doi.org/10.1002/jhbp.286. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving

ヒト膵癌におけるNectin-4発現の腫瘍増殖、血管新生に対する効果と臨床的意義

BACKGROUND: Nectin-4 belongs to the nectin family that has diverse physiological and pathological functions in humans. Recent studies have also suggested some roles for Nectin-4 in several human cancers. However, the precise roles and clinical relevance of Nectin-4 in tumors are largely unknown. METHODS: Nectin-4 expression was investigated in 123 patients with pancreatic cancer by immunohistochemistry. Furthermore, we investigated the association of Nectin-4 in pancreatic cancer with tumor proliferation, angiogenesis and immunity by using immunohistochemistry and siRNA interference method. RESULTS: Patients with high Nectin-4 expression had poorer postoperative prognosis than those with low expression. Importantly, multivariate analysis indicated that Nectin-4 expression had a significant independent prognostic value in pancreatic cancer (HR = 1.721, 1.085-2.730; P = 0.021). Tumor Nectin-4 expression was significantly correlated with Ki67 expression. In addition, siRNA-mediated gene silencing of Nectin-4 significantly inhibited the cell proliferation in human pancreatic cancer cells, Capan-2 and BxPC-3. Furthermore, Nectin-4 expression was also positively correlated with VEGF expression and intratumoral microvessel density. However, there were no significant correlations of tumor Nectin-4 expression with tumor-infiltrating T cells. CONCLUSION: Nectin-4 is a significant prognostic predictor, and may play a critical role in pancreatic cancer. Nectin-4 may be novel therapeutic target for pancreatic cancer.博士（医学）・乙第1400号・平成29年6月28日Copyright © Nishiwada et al.; licensee BioMed Central. 2015 : This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

化学療法を施行した膵癌患者に対する喫煙の影響

OBJECTIVE: Smoking may affect pharmacokinetics of chemotherapeutic agents and hemodynamics of the smokers, thereby influencing adverse events and efficacy of chemotherapy in patients with pancreatic cancer (PC). The aim of this study was to clarify how smoking totally affected patients with PC receiving current chemotherapy. METHODS: We evaluated the impact of smoking status on the performance of chemotherapy and survival in 262 patients with PC including 158 resectable and 104 unresectable PC. RESULTS: There were more male and younger patients in current smokers than in nonsmokers. In unresectable PC, current smokers had more metastatic tumors than locally advanced tumors compared with nonsmokers. In current smokers receiving chemotherapy, the baseline white blood cell count, neutrophil count, and hemoglobin concentration were significantly higher in current smokers than in nonsmokers. Furthermore, grades 3 to 4 neutropenia was observed more often in nonsmokers than smokers. On the other hand, the performance and efficacy of the planned adjuvant chemotherapy were similar between smokers and nonsmokers. More importantly, there was no significant difference in overall prognosis between smokers and nonsmokers receiving chemotherapy. CONCLUSIONS: Smoking status has no significant impact on the efficacy of current chemotherapy for both resectable and unresectable PC.博士（医学）・乙第1393号・平成29年3月15日Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.This is a non-final version of an article published in final form in "http://dx.doi.org/10.1097/MPA.0000000000000395

Aberrant High Expression of B Lymphocyte Chemokine (Blc/Cxcl13) by C11b+Cd11c+ Dendritic Cells in Murine Lupus and Preferential Chemotaxis of B1 Cells towards Blc

We observed here that the expression of B lymphocyte chemokine (BLC/CXCL13) was markedly enhanced in the thymus and kidney in aged (NZB × NZW)F1 (BWF1) mice developing lupus nephritis, but not in similarly aged NZB and NZW mice. BLC-positive cells were present in the cellular infiltrates in the target organs with a reticular pattern of staining. CD11b+CD11c+ dendritic cells were increased in the thymus and spleen in aged BWF1 mice and identified as the major cell source for BLC. CD4+ T cells as well as B cells were dramatically increased in the thymus in aged BWF1 mice, whereas no increase was observed in aged NZB and NZW mice. B1/B2 ratio in the thymus was significantly higher than those in the spleen and peripheral blood in aged BWF1 mice. Interestingly, BLC showed preferential chemotactic activity for B1 cells derived from several mouse strains, including nonautoimmune mice. Cell surface CXCR5 expression on B1 cells was significantly higher than that on B2 cells. Thus, aberrant high expression of BLC by myeloid dendritic cells in the target organs in aged BWF1 mice may play a pivotal role in breaking immune tolerance in the thymus and in recruiting autoantibody-producing B cells in the development of murine lupus

80歳以上の高齢者膵癌に対する膵切除の意義

Background: There is increasing need to evaluate the surgical indication of pancreatic cancer in very elderly patients. However, the available clinical data are limited, and the optimal treatment is still controversial. The aim of this study was to evaluate the benefit of pancreatic resection in pancreatic cancer patients over the age of 80. Methods: Between 2005 and 2012, 26 octogenarian patients who received pancreatic resection and 20 who received chemotherapy for pancreatic cancer were retrospectively reviewed. Clinicopathological factors, chemotherapy administration status, and survival were compared. Univariate and multivariate analysis of prognostic factors for survival was performed. Results: Postoperative major complication rate was 8%, with no mortality. The one-year survival rate and median survival time of the surgery and chemotherapy groups were 50% and 45%, and 12.4 months and 11.7 months, respectively (P = 0.263). Of the 26 resected cases, 6 completed the planned adjuvant chemotherapy treatment course. The median survival time of those 6 completed cases was significantly longer than that of the 20 not completed cases (23.4 versus 10.0 months, P = 0.034). Furthermore, a multivariate analysis of the 26 resected cases showed that distant metastasis (HR 3.206, 95%CI 1.005-10.22, P = 0.049) and completion of the planned adjuvant therapy (HR 4.078, 95%CI 1.162-14.30, P = 0.028) were independent prognostic factors of surgical resection. Conclusions: Surgical resection was safe, but not superior to chemotherapy for pancreatic cancer in octogenarians. In the very elderly, only selected patients may benefit from pancreatic resection.博士（医学）・乙第1513号・令和3年12月21日Copyright © 2015 IAP and EPC. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved

Pathophysiological analysis of detrusor overactivity following partial bladder outlet obstruction

　Introduction: Detrusor overactivity (DO) following partial bladder outlet obstruction (PBOO) is a common urological condition in humans, with 50-70% patients with PBOO complicated with DO. The pathological mechanisms of DO following PBOO are largely unknown, but inflammatory changes may play a key role. We hypothesized that inflammation is important in the earlier pathophysiological phase before overproduction of oxidative stress in DO following PBOO. Therefore, we investigated the relationships among bladder function, ischemia, oxidative stress and inflammation in DO following PBOO in PBOO model mice.　Materials and Methods: C57BL/6J male mice aged 10 to 15 weeks were used in the study. PBOO model mice were created surgically by ligation of the proximal urethra with 5-0 nylon suture under inhalation anesthesia. Sham-operated mice were used as controls. Pathophysiological changes in the bladder at 1, 3 and 5 weeks after creation of the PBOO model mice were compared with those in sham-operated mice using functional, histological, biochemical and immunohistochemical analyses.　Results: Functional analysis using a pressure flow study showed increased maximum detrusor pressure at 1 week and DO from 3 to 5 weeks after creation of the PBOO model. Histological analysis using hematoxylin-eosin and Masson-Trichrome staining showed greater invasion of inflammatory cells and fibrosis in PBOO model mice compared with sham-operated mice at 3 and 5 weeks. Inflammatory cells were mainly present in interstitial tissue, and fibrosis gradually infiltrated from interstitial tissue to the muscular layer. Ischemia analysis showed significantlyincreased HIF-1α in PBOO model mice at all time points. Oxidative stress analysis indicated significantly increased levels of ROS from 1 week and 8-OHdG from 3weeks in PBOO model mice. An inflammation-related proteome assay showed high levels of colony stimulating factor (CSF) family proteins at 1 week and IL-2, IL-3, IL-17A, IL-23, MMP-3, MMP-9 and periostin from 3 to 5 weeks in PBOO model mice.　Conclusions: Oxidative stress and inflammatory changes showed contemporaneous increase in pathophysiology of detrusor overactivity following partial bladder outlet obstruction. Especially, CSF family and ROS changes are showed in the early stage, and might be a predict marker in the pathophysiology of DO following PBOO at the early stage

Pathological analysis of spermatic dysfunction following testicular ischemia-reperfusion injury\n

　Introduction & Objectives: Torsion, which may result in testicular ischemia, requires emergency surgery to restore testicular blood flow. However, the risk of spermatic dysfunction remains even if surgery is performed. The pathology of spermatic dysfunction in testicular ischemia-reperfusion injury (TIRI) remains unclear. A previous study showed the relevance of inflammation and oxidative stress in the other organs of ischemia-reperfusion injury. We hypothesized that inflammation and oxidative stress play key roles in causing spermatic dysfunction following TIRI. We investigated the pathophysiology of spermatic dysfunction in TIRI focusing on inflammatory changes using TIRI model mice.　Materials and Methods: The study used C57BL/6J male mice aged 10 to 15 weeks. To create TIRI model mice, the unilateral (left side) testicular vessels were clamped using Dieffenbach clamps (Bulldog clamps) for 1 hour and de-clamped. The bilateral testes were removed at 0 (ischemic state), 1, 3, and 5 weeks after creating the TIRI model mice. Spermatic changes following TIRI were investigated by analyzing the histology of the testes and semen and assessing levels of inflammation and oxidative stress. Semen was collected from the bilateral cauda epididymites and investigated using the sperm motility analysis system (SMAS).　Results: Histological analysis after hematoxylin-eosin staining showed tissue thickening in interstitial tissues at week 1 and 3 on the left (affected) testis, and week 1, 3 and 5 on the right (unaffected) testis. The infiltration of lymphocytes-predominant inflammatory cells were observed at week 1 and week 3 on the left (affected) testis. The destruction of ductal structures and giant cells were observed at weeks 3 and 5 on the left (affected) testis and week 5 on the right (unaffected) testis. SMAS showed significantly decreased spermatic concentration and motility in both testes of TIRI model mice compared with those of sham-operated mice at weeks 1, 3 and 5. Inflammation analysis using an inflammation-related proteome assay showed significantly increased levels of cytokines (IL-2, IL-3, IL-17A, and IL-23) and chemokines (CCL2, CCL5, CXCL1, and CX3CL1) at weeks 1, 3, and 5 in both testes of TIRI model mice. For the assessment of oxidative stress, enzyme-linked immuno-sorbent assay (ELISA) for 8-hydroxy-2’-deoxyguanosine (8-OHdG) was performed, which showed that levels of 8-OHdG were significantly increased in the left (affected) testis of TIRI model mice compared with that of sham-operated mice at all observation periods. Meanwhile, ELISA showed that levels of 8-OHdG in the right (unaffected) testis were significantly increased in TIRI model mice at weeks 3 and 5 compared with that of sham-operated mice.　Conclusions: Spermatic dysfunction following TIRI is induced by inflammation and oxidative stress. Inflammation and oxidative stress may be novel regulatory factors to prevent spermatic dysfunction following TIRI

Retrospective Study of the Correlation Between Pathological Tumor Size and Survival After Curative Resection of T3 Pancreatic Adenocarcinoma: Proposal for Reclassification of the Tumor Extending Beyond the Pancreas Based on Tumor Size

BackgroundEven though most patients who undergo resection of pancreatic adenocarcinoma have T3 disease with extra-pancreatic tumor extension, T3 disease is not currently classified by tumor size. The aim of this study was to modify the current TNM classification of pancreatic adenocarcinoma to reflect the influence of tumor size.MethodsA total of 847 consecutive pancreatectomy patients were recruited from multiple centers. Optimum tumor size cutoff values were calculated by receiver operating characteristics analysis for tumors limited to the pancreas (T1/2) and for T3 tumors. In our modified TNM classification, stage II was divided into stages IIA (T3aN0M0), IIB (T3bN0M0), and IIC (T1-3bN1M0) using tumor size cutoff values. The usefulness of the new classification was compared with that of the current classification using Akaike’s information criterion (AIC).ResultsThe optimum tumor size cutoff value distinguishing T1 and T2 was 2 cm, while T3 was divided into T3a and T3b at a tumor size of 3 cm. The median survival time of the stages IIA, IIB, and IIC were 44.7, 27.6, and 20.3 months, respectively. There were significant differences of survival between stages IIA and IIB (P = 0.02) and between stages IIB and IIC (P = 0.03). The new classification showed better performance compared with the current classification based on the AIC value.ConclusionsThis proposed new TNM classification reflects the influence of tumor size in patients with extra-pancreatic tumor extension (T3 disease), and the classification is useful for predicting mortality

Preventive effect of indoleamine 2,3-dioxygenase 1 inhibition on lipopolysaccharide-induced prostatitis

　Introduction and Objectives: Bacterial infections are the main cause of acute prostatitis and are treated with appropriate antimicrobial therapy. However, approximately 5% of patients continue to have inflammatory symptoms even after receiving antibacterial therapy, leading to refractory conditions. Bacterial prostatitis requires additional therapy, focusing on inflammatory changes. Indoleamine 2,3-dioxygenase 1 (IDO1) catalysis is the first rate-limiting step of tryptophan metabolism. IDO1 is expressed in the prostate and plays a key role in the immune response. As the first step in investigating the relationship between acute prostatitis and IDO1, we investigated the preventive effect of IDO1 inhibition on lipopolysaccharide (LPS)- induced prostatitis using IDO knockout (Ido1 −/−) mice in this study.　Materials and Methods: The study used Ido1 −/− and wild-type (Ido1 +/+) C57BL/6J malemice aged 10–15 weeks. LPS Escherichia coli O26 (100μg/PBS, 100μL) was administered transurethrally into the lower urinary tract to create a mouse model of LPS-induced prostatitis. The prostates were removed 1, 3, 5, and 7 days after creating the model mice. Histological, immunohistochemical, and biochemical analyses were used to compare the preventive effect in Ido1 −/− mice compared with that in Ido1+/+ mice.　Results: HE staining showed suppression of ductal destruction following infiltration of inflammatory cells in Ido1 −/− mice compared with Ido1 +/+ mice. The enzyme-linked immunosorbent assay (ELISA) method was used for kynurenine pathway analysis, which showed significantly maintained tryptophan levels and decreased L-kynurenine levels in Ido1 −/− mice compared to Ido1 +/+ mice. The IDO1 assay in Ido1 +/+ mice showed significantly increased levels during all observation periods after creating the model compared with that under normal conditions. Immunofluorescent staining using five types of cytokines and chemokines (IL-2, IL-4, IL-17, CCL2, and CCL3) related to the pathophysiology of acute prostatitis showed decreased expression of these cytokines and chemokines in Ido1 -/- mice compared with Ido1 +/+ mice. Inflammation-related proteome assays showed decreased levels of IL-1β, IL-4, IL-5, IL-6, IL-17, CCL2, CCL3, CXCL1, CXCL11, and tissue inhibitor of matrix metalloproteinases (TIMP)-1 in Ido1 −/− mice compared with Ido1 −/− mice during all observation periods after model creation.　Conclusions: IDO1 is involved in LPS-induced prostatitis through cytokines and chemokines. IDO1 inhibition contributes to the prevention of LPS-induced prostatitis. IDO1 inhibition has the potential to serve as an additional therapy for acute prostatitis