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Background We hypothesized that thermal damage accumulation during endoscopic submucosal dissection (ESD) causes the pathogenesis of post-ESD electrocoagulation syndrome (PECS). Aim To determine the association between Joule heat and the onset of PECS. Methods We performed a retrospective cohort study in patients who underwent colorectal ESD from May 2013 to March 2021 in Japan. We developed a novel device that measures swift coagulation time with a sensor adjacent to the electrosurgical coagulation unit foot switch, which enabled us to calculate total Joule heat. PECS was defined as localized abdominal pain (visual analogue scale ≥ 30 mm during hospitalization or increased by ≥ 20 mm from the baseline) and fever (temperature ≥ 37.5 degrees or white blood cell count ≥ 10000 µ/L). Patients exposed to more or less than the median Joule heat value were assigned to the high and low Joule heat groups, respectively. Statistical analyses included Mann-Whitney U and chi-square tests and logistic regression and receiver operating characteristic curve (ROC) analyses. Results We evaluated 151 patients. The PECS incidence was 10.6% (16/151 cases), and all patients were followed conservatively and discharged without severe complications. In multivariate analysis, high Joule heat was an independent PECS risk factor. The area under the ROC curve showing the correlation between PECS and total Joule heat was high [0.788 (95% confidence interval: 0.666-0.909)]. Conclusion Joule heat accumulation in the gastrointestinal wall is involved in the onset of PECS. ESD-related thermal damage to the peeled mucosal surface is probably a major component of the mechanism underlying PECS.

Objective Fibroblast growth factor receptor 2 (FGFR2) has been proposed as a novel druggable target in unresectable gastric cancer. FGFR2 alteration has been reported as associated with poor prognosis even in patients with gastric cancer who received systemic chemotherapy. This study aimed to evaluate the frequency of FGFR2 overexpression and gene amplification in clinical specimens from Japanese patients with recurrent or unresectable gastric cancer. Methods This observational study enrolled patients who were histologically or cytologically confirmed with unresectable HER2-negative or unknown gastric or gastroesophageal junctional adenocarcinoma treated with at least one previous chemotherapy. FGFR2 overexpression and gene amplification in the specimens were evaluated by immunohistochemical staining and fluorescence in situ hybridization methods, respectively. Results In a total of 173 eligible cases, FGFR2 immunohistochemistry score was evaluated as 0, 1, 2, 3 and 4 for 20, 80, 35, 28 and 10 cases, respectively. In 151 evaluable cases with FGFR2 immunohistochemistry scores of 1–4, FGFR2 copy number expressed as fluorescence in situ hybridization signals were detected as, A multicenter study evaluating the frequency of fibroblast growth factor receptor 2 overexpression and gene amplification in tumor specimen from Japanese patients with recurrent or unresectable gastric cancer.

AIM This study aimed to evaluate the real-world efficacy and safety of 12-week sofosbuvir/velpatasvir (SOF/VEL) treatment for patients with decompensated liver cirrhosis caused by hepatitis C virus (HCV) infection. METHODS A total 72 of patients with Child-Pugh (CP) class B or C were enrolled. We evaluated the sustained virologic response at 12 weeks after the end of treatment (SVR12), adverse events (AEs), and changes in the liver function. RESULTS All participants had genotype 1 or 2 HCV infection. At baseline, the numbers of patients with CP class B and C were 59 and 13, respectively. The overall SVR12 rate was 95.8% (69/72); 94.9% (56/59) in CP class B and 100% (13/13) in CP class C. The serum albumin level, prothrombin time and ascites were significantly improved (P

Recently, a clinical study using a Chronic Liver Disease Questionnaire (CLDQ) showed that ledipasvir/sofosbuvir (LDV/SOF)-treated patients' QOL was more favorable than that of IFN/ribavirin (RBV)-treated patients. However, no study has reported QOL assessment in clinical practice. In this study, we compared the QOL between patients treated with LDV/SOF and those treated with simeprevir (SMV)/peginterferon (Peg-IFN)/RBV to provide QOL information in clinical practice. The subjects were 169 patients with type I chronic hepatitis C or compensated cirrhosis C (Child-Pugh Grade A) who were treated with SMV/Peg-IFN/RBV or LDV/SOF in Hitachi General Hospital. The QOL was assessed ≥2 weeks after the start of administration using the Japanese version of the CLDQ (Kida et al., 2008 version). The total CLDQ score in the LDV/SOF group was significantly higher than in the SMV/Peg-IFN/RBV group (6.59 vs. 6.38, respectively, p=0.007). In particular, the scores for 4 domains (abdominal symptoms, systemic symptoms, activity, and emotional function) in the former were significantly higher than in the latter (p

Background: Sulforaphane (SFN), a phytochemical compound, which belongs to isothiocyanates family found in abundance in broccoli sprouts, potently induces a variety of antioxidant enzymes via nrf2-keap1 mediated pathway, thereby protects cells from injury induced by various kinds of oxidative stresses. We have previously shown that SFN protects gastric mucosa from oxidative injury induced by H. pylori infection. SFN also down-regulates histone deacetylase (HDAC) activity, thereby induces apoptosis and inhibits proliferation of tumor cells in variety of tissues. On the other hand, colon cancer has been increasing in Japan. Since numerous epidemiological studies have shown that colon cancer is inversely associated with intake of anti-oxidant vegetables, we examined if dietary SGS prevents colon tumorigenesis in mice, and in human subjects. Methods: 1. Effects of SFN on Colonic tumorigenesis in Mice Treated with Chemical Carcinogen: Effects of SFN on colonic tumorigenesis were examined in the ICR male mice, pretreated with a chemical carcinogen, azoxymethane (AOM) (15 mg/kg). The AOM-treated mice were fed for 8 weeks with or without sulforaphane glucosinolates (SGS: 2,200 ppm/kg/day), which is a precursor of SFN. Effects of SGS treatment on formation of the microscopic aberrant crypt foci (ACF), and the macroscopic tumors in colonic mucosa were evaluated. 2. Effects of SFN on formation of Colonic Aberrant Crypt Foci (ACF) in patients with colonic adenoma: Effects of intake of raw broccoli sprouts (BS), 50 g/day, which contains 220 mg SGS every other day, for 6 months on changes in the number of ACF in rectal mucosa was examined by colonoscopy in patients with colonic adenoma. 3. Effects of SFN on intestinal microbiota in human subjects: Effects of dietary intake of raw broccoli sprouts (BS), 20 g/day, which contains 88 mg SGS every other day, for 2 weeks on intestinal microbiota in healthy volunteers was assessed by measuring composition of stool bacteria, using T-RFLP method. In human studies, alfalfa sprouts, which contains no SFN was used as a placebo control. Results: 1. Daily administration of SGS suppressed formation of microscopic ACF and macroscopic colonic tumors in the AOM-pretreated mice in vivo. 2. Intake of BS for 6 months tended to decrease the number of colonic ACF in patients with colonic adenoma. 3. Intake of BS for 2 weeks increased percentages of Bifidobacterium and Clostridium XVIa, which has been shown to enhance protection of colonic mucosa by increasing butyrate production in colonic lumen. Conclusions: 1. SFN affords chemoprotection against colonic cancer, presumably by up-regulating nrf2-dependent antioxidant enzymes in normal colonic epithelial cells, and by inducing apoptosis of colonic tumor cells through inhibition of HDAC activity. The present study further suggests that changes in intestinal microbiota by SFN, may play a role in chemoprevention against colon cancer. Keywords: sulforaphane, colon cancer, chemoprevention, aberrant crypt foci, intestinal microbiota

BACKGROUND Sorafenib is an oral drug that prolongs overall survival (OS) in patients with hepatocellular carcinoma. Adverse events, including hand-foot skin reaction (HFSR), lead to permanent sorafenib discontinuation. AIM To clarify the association between interventions for adverse events and patient prognosis. METHODS We performed a retrospective, multicenter study of patients treated with sorafenib monotherapy between May 2009 and March 2018. We developed a mutual cooperation system that was initiated at the start of sorafenib treatment to effectively manage adverse events. The mutual cooperation system entailed patients receiving consultations during which pharmacists provided accurate information about sorafenib to alleviate the fear and anxiety related to adverse events. We stratified the patients into three groups: Group A, patients without HFSR but with pharmacist intervention; Group B, patients with HFSR and pharmacist interventions unreported to oncologists (nonmutual cooperation system); and Group C, patients with HFSR and pharmacist interventions known to oncologists (mutual cooperation system). OS and time to treatment failure (TTF) were evaluated using the Kaplan-Meier method. RESULTS We enrolled 134 patients (Group A, n = 41; Group B, n = 30; Group C, n = 63). The median OS was significantly different between Groups A and C (6.2 vs 13.9 mo, p < 0.01) but not between Groups A and B (6.2 vs 7.7 mo, P = 0.62). Group A vs Group C was an independent OS predictor (HR, 0.41; 95%CI: 0.25-0.66; P < 0.01). In Group B alone, TTF was significantly lower and the nonadherence rate was higher (P < 0.01). In addition, the Spearman’s rank correlation coefficients between OS and TTF in each group were 0.41 (Group A; P < 0.01), 0.13 (Group B; P = 0.51), and 0.58 (Group C; P < 0.01). There was a highly significant correlation between OS and TTF in Group C. However, there was no correlation between OS and TTF in Group B. CONCLUSION The mutual cooperation system increased treatment duration and improved prognosis in patients with HFSR. Future prospective studies (e.g., randomized controlled trials) and improved adherence could help prevent OS underestimation.

Risk factors for immune-related adverse events(irAEs)associated with immune checkpoint inhibitors(ICIs) remain to be obscure. Therefore, we evaluated the patient background and clinical findings to identify risk factors for the development of irAEs.The subjects consisted of 86 patients treated with ICIs between August 2018 and March 2020. They were classified into 2 groups who developed irAEs(irAE group)and did not develop irAEs(non-irAE group).The median age of the subjects was 70 years(39-84 years), and there were 65 males. The underlying disease was non-small cell lung cancer in 51 patients, gastric cancer in 14, renal cell cancer in 9, urothelial cancer in 11, and MSI-high small bowel cancer in 1. The irAE group, in whom treatment with ICIs was discontinued, included 16 patients(18.6%), and the non-irAE group included 70 patients(81.4%). The median number of treatment cycles was 8(1-91), and the median treatment period was 4 months(1-45 months). Evaluation in our hospital revealed no significant background factors, such as gender, age, or the treatment period, as risk factors for the development of eras. Lung disorders were frequently observed after the third-line treatment and in patients with non-small cell lung cancer.At present, the prediction of the development of irAEs is difficult. Careful follow-up observation and early irAEs management are important. In addition, further studies are necessary to identify risk factors for the development of irAEs.

OBJECTIVE: We investigated factors associated with a reduction in the quality of life and their OR of patients with chronic hepatitis C who underwent ledipasvir/sofosbuvir therapy. METHODS: The subjects were 141 outpatients who had undergone ledipasvir/sofosbuvir therapy under a diagnosis of genotype I chronic hepatitis C or Child-Pugh A compensated cirrhosis at Hitachi General Hospital. The patient background before ledipasvir/sofosbuvir therapy, laboratory data and the Chronic Liver Disease Questionnaire scores during ledipasvir/sofosbuvir therapy were investigated. The Chronic Liver Disease Questionnaire consists of 29 questions, and the mean value is calculated as the overall score through a 7-step assessment by patients. Using two divisions: a Chronic Liver Disease Questionnaire score of

Objective. It is sometimes difficult to obtain complete/partial response of large hepatocellular carcinoma (HCC) nodules by trans-arterial chemoembolization/embolization (TACE/TAE). The aim is retrospective investigation of tumor response of large HCC nodules (>7 cm) treated by the new TACE technique, repeated alternate infusion of cisplatin solution, and sparse gelatin slurry under balloon occlusion (RAIB-TACE). Materials and Methods. A microballoon catheter was placed at a proximal portion of the hepatic artery (subsegmental to the lobar level hepatic artery), and alternate infusion of cisplatin solution and sparse gelatin slurry were repeated under balloon occlusion until stasis of gelatin slurry beyond the catheter was seen. RAIB-TACE of multiple proximal hepatic and extrahepatic collateral arteries were performed to treat hemi-lobe or more of the liver while avoiding infusion into gastric and cystic arteries for 19 large nodules (>7 cm) in 19 patients without portal venous invasion. All patients underwent dynamic CT/MRI 1–3 months after RAIB-TACE, and tumor response of each large nodule was evaluated based on modified RECIST criteria. Results. CR, PR, SD, and PD were achieved in 11, 8, 0, and 0 nodules, respectively. CR and PR were considered as success, and the ratio of success was 100%. Major complications were abscess formation in the necrotic nodule (n = 1) which was treated by drainage tube placement, and subsegmental level liver infarction (n = 1) which recovered uneventfully. Conclusion. New TACE technique, RAIB-TACE, was useful to achieve successful response of large HCC nodules.

Objective. It is difficult to control small hepatocellular carcinoma (HCC) nodules adjacent to the Glisson sheath (GS) by trans-arterial chemoembolization (TACE) probably due to multiple small tumor feeders directly branching from the trunk artery. The purpose of this study was to conduct a retrospective evaluation of a new TACE technique called the repeated alternate infusion of cisplatin solution and gelatin slurry distal to balloon occlusion (RAIB-TACE), for the treatment of small HCC nodules adjacent to GS. Materials and Methods. Small nodules less than 4 cm attached to proximal portion of the subsegmental to lobar level portal branch were retrospectively selected. Between January 2011 and April 2014, 29 nodules in 29 patients were treated by super-selective lipiodol TACE/balloon-occluded TACE (B-TACE) (Lip-TACE group). Since April 2014, treatment protocols for small nodules adjacent to GS were changed, and 14 nodules in 12 patients were treated by RAIB-TACE (RAIB-TACE group). In RAIB-TACE group, alternate infusion of cisplatin solution and sparse gelatin slurry (mixture of 80 mg of gelatin fragments and 20 mL of contrast medium) were repeated until arterial flow was ceased. In Lip-TACE group, lipiodol was used as drug carrier and dense gelatin slurry (mixture of 80 mg of gelatin fragments and 2 mL of contrast medium) as embolization material. Dynamic CT/MRI was obtained 1-3 months after TACE, and response of each nodule was evaluated basing on modified RECIST criteria. Results. In RAIB-TACE group, all 14 nodules (100%) were diagnosed as CR or PR. In Lip-TACE group, 18 of 29 (62.1%) were diagnosed as CR or PR. There was a statistically significant difference in objective response ratio between the groups (p=0.008, Fisher’s test). Biloma (n=1) and benign stricture of the right hepatic duct (n=1) were seen in RAIB-TACE group. The biloma shrunk without treatment and the patient had no symptom, but the patient with biliary stricture repeated cholangitis and was treated by administration of antibiotics. Conclusion. The study results show that RAIB-TACE is more effective than lipiodol TACE/B-TACE for small hepatocellular carcinoma adjacent to GS. We speculate that one of the reasons to explain why Lip-TACE is inferior to RAIB-TACE is that viscous lipiodol or dense gelatin slurry could not flow into small tumor feeders effectively.

To investigate the relationship between the onsets of multikinase inhibitor (MKI)-associated hand-foot skin reaction (HFSR) and prognosis under intervention by pharmacists after the introduction of sorafenib.We conducted a retrospective study involving 40 patients treated with sorafenib. Intervention by pharmacists began at the time of treatment introduction and continued until the appearance of symptomatic exacerbation or non-permissible adverse reactions. We examined the relationship between MKI-associated HFSR and overall survival (OS) after the initiation of treatment.The median OS was 10.9 mo in the MKI-associated HFSR group and 3.4 mo in the no HFSR group, showing a significant difference in multivariate analysis. A multivariate analysis of the time to treatment failure indicated that the intervention by pharmacists and MKI-associated HFSR were significant factors. The median cumulative dose and the mean medication possession ratio were significantly higher in the intervention group than in the non-intervention group. A borderline significant difference was observed in terms of OS in this group.Intervention by pharmacists increased drug adherence. Under increased adherence, MKI-associated HFSR was an advantageous surrogate marker. Intervention by healthcare providers needs to be performed for adequate sorafenib treatment.

A 50s man receiving dialysis for chronic kidney disease due to IgA nephropathy underwent laparoscopic reversal via Hartmann 's procedure for rectal cancer and multiple liver metastases, followed by chemotherapy for the liver metastases. Following a single course of mFOLFOX therapy, bevacizumab was administered for 8 courses, resulting in tumor shrinkage and a decrease in tumor marker levels. The initial doses were 60mg/m2 oxaliplatin and 280(bolus injection)and 1,680mg/m2 (continuous infusion)of 5-FU. Subsequently, these doses were adjusted to be administered every 3 weeks. No serious adverse events other than neutropenia(Grade3 ), anorexia(Grade1 ), and hiccups(Grade1)were noted.

"Immunosuppression and hepatitis B measures and guidelines for chemotherapy" were announced in 2009. However, a fulminant case that appeared when the guidelines were not observed was reported, and de novo hepatitis prevention is an urgent problem. The rate of compliance with these guidelines as of January 2014 was 20.4%, but this rose to 34.3%after the alert indication for de novo hepatitis prevention was set on an electronic chart system from June 2014. The rate of compliance increased to 63.9% at a hospital where de novo hepatitis alerts were put on clinical cards in April 2015, but it gradually decreased thereafter. HBV-DNA measurement was 100% in compliance with the guidelines from August 2016 when HB antigen, HB antibody, and anti-hepatitis B core antigen measurements were all performed in March 2016 because the pharmacists practiced physician order support duties at that time. This helped to reduce the burden on physicians, and the physician order support duties by the pharmacist were educational. Thus, de novo hepatitis prevention may contribute to safe cancer chemotherapy.

The present study sought to establish a standard third-line eradication regimen for Helicobacter pylori in Japan.Subjects were 204 patients with H. pylori infection in whom the standard Japanese first- and second-line eradication therapies had proven unsuccessful. Patients were randomly assigned to one of the following third-line eradication therapy groups: (1) LA group: lansoprazole (LPZ) 30 mg 4 times a day (qid) + amoxicillin (AMPC) 500 mg qid for two weeks; (2) LAL group: LPZ 30 mg twice a day (bid) + AMPC 750 mg bid + levofloxacin (LVFX) 300 mg bid for one week; (3) LAS group: LPZ 30 mg bid + AMPC 750 mg bid + sitafloxacin (STFX) 100 mg bid for one week. Patients for whom these therapies failed underwent a crossover fourth-line eradication regimen. Drug sensitivity was also tested for AMPC, clarithromycin (CAM), MNZ, LVFX, and STFX.Drug resistance rates prior to third-line eradication therapy were 86.4 % for CAM, 71.3 % for MNZ, 57.0 % for LVFX, 8.2 % for AMPC, and 7.7 % for STFX. Intention-to-treat analysis of third-line eradication therapy eradication rates showed a significantly higher rate in the LAS group (70.0 %) compared with the LA group (54.3 %; p0.05) and the LAL group (43.1 %; p0.001). The significantly lower rate in the LAL group than the LAS group was caused by bacterial resistance to LVFX.The findings suggest that triple therapy with PPI, AMPC, and STFX for one week would be an effective standard third-line eradication regimen for H. pylori in Japan.

Background There are differences in the histological diagnostic criteria for early stage gastrointestinal carcinoma between Western and Japanese pathologists. Western histological criteria of carcinoma are “presence of stromal invasion of neoplastic cells”, while Japanese criteria are “the degree of cytological and structural abnormality of neoplastic cells, regardless of stromal invasion”. The aim of the present study is to clarify and review the present status of the Western and Japanese histological criteria of early stage esophageal squamous cell carcinoma (SCC) and also to clarify their significance and accuracy. Methods Twenty-nine Polish, German, and Japanese pathologists participated in this study. A total of 18 histological slides of biopsy, endoscopic submucosal dissection (ESD), and surgical resection of esophageal squamous lesions were diagnosed using a virtual slide system. Results Most of noninvasive (intraepithelial) carcinomas diagnosed by Japanese pathologists were diagnosed as high- or low-grade dysplasia (intraepithelial neoplasia) or reactive atypia by the majority of Polish and German pathologists. Diagnoses of not only high-grade dysplasia but also low-grade dysplasia or reactive lesion by Western criteria were given for many biopsy specimens of cases in which the corresponding ESD or surgical specimens showed definite stromal invasion. Conclusion There still exist differences in the histological diagnostic criteria for early stage esophageal carcinoma between Western and Japanese pathologists. The Japanese diagnostic criteria could improve agreement of diagnoses between biopsy and resected specimens of esophageal SCC. Moreover, diagnostic approaches using Western criteria may cause delay in the early diagnosis and treatment of esophageal SCC.

When the medical fee system was revised in 2012, the category of perioperative oral management was newly organized. However, the calculation of additional fees for such management required referral from medical to dental departments. In addition, requests for such management were limited, possibly owing to an increased burden on doctors engaged in outpatient services. This study examined the usefulness of an approach to promote patients' use of dental services by increasing their awareness of the importance of oral management. In this approach, pharmacists explained doctors' instructions to patients at a chemotherapy center within the study facility. Explanations were provided to 114 patients, 75 (65.8%) of whom subsequently used dental services in the facility. For patients using dental services, oral care was performed most frequently (40; 53.3%), followed by invasive procedures (23; 30.7%). Furthermore, the facility's ethics committee approved a survey to measure the satisfaction of patients undergoing chemotherapy at the center. Of the 110 patients invited to participate in the survey, 77(70.0%) did not respond. Researchers concluded the low response rate was associated with patients' belief that dental services were intended primarily for treating oral cavities and their lack of awareness of the importance of preventive dental care. However, in 2014, the number of calculations of additional fees for perioperative oral management markedly increased each month after the above-mentioned approach, from 62 (January) to 162 (December). Both the hospital-to family and family-to-hospital dentist referral rates significantly increased, from 11.2% and 10.7%, respectively (June 2013), to 21.0% and 41.9%, respectively(June 2014). Future evaluations of the outcomes of perioperative oral management and promoting cooperation between medical and dental communities may be necessary.

Background/Aim Ecabet sodium has an anti-H. pylori effect. We assessed the efficacy of ecabet sodium in the rescue therapy for the eradication of H. pylori. Methods A total of 74 patients with failed eradication of H. pylori after triple therapy with lansoprazole 30 mg bid, amoxicillin 750 mg bid and clarithromycin 200 mg bid were enrolled. They were randomly assigned to the three treatment groups as follows: LAC, lansoprazole 30 mg + amoxicillin 750 mg + clarithromycin 200 mg bid for 1 week; LAC2E, lansoprazole 30 mg bid + amoxicillin 750 mg bid + clarithromycin 200 mg bid + ecabet sodium 2 g bid for 1 week; and LA2E, lansoprazole 30 mg bid + amoxicillin 750 mg bid + ecabet sodium 2 g bid for 2 weeks. Eradication of H. pylori was assessed by the 13C-urea breath test after treatment. Results Eradication rates in intention-to-treat and per-protocol analyses were 20.0% (95% CI: 6.8-40.7) and 20.0% (6.8-40.7) with LAC, respectively, and 16.0% (4.5-36.1) and 17.4% (5.0-38.8) with LAC2E. In contrast, respective rates with LA2E were 75% (53.3-90.2) and 85.7% (63.7-97.0), which were significantly higher than those with LAC (p

In May 2014, tablets containing both trifluridine and tipiracil hydrochloride (Lonsurf® tablets) were launched in Japan ahead of other countries, for the treatment of advanced/relapsed unresectable colorectal cancer. The benefits of these tablets in terms of a new therapeutic option have been demonstrated. However, the manufacturer has requested healthcare professionals to help develop safety measures for the appropriate and safe use of the tablets. In this study, we evaluated the efficacy and safety of the tablets in 16 patients who received the tablets at our hospital. Among the 4 evaluable patients, none achieved a complete or partial response. One patient (25.0%) had stable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines outlined in the General Rules of the Study of Colorectal Cancer (The 8th Edition). Lonsurf® is considered to be a third-line (or later) treatment. Among the 16 cases studied, Lonsurf® was used as a third-, fourth-, and fifth-line treatment in 9, 6, and 1 cases, respectively. Therefore, Grade 3 or worse toxicities were a potential concern. Despite a high incidence of Grade 3 or worse neutropenia (7 of the 16 patients [43.8%]), none of the patients were hospitalized due to neutropenia or other treatment-related adverse events. Pharmacists have made 126 proposals to physicians regarding the use of Lonsurf®, 121 (96.0%) of which have been adopted. All of the adverse reactions experienced by our patients were resolved after supportive therapy.

Aim Selective balloon-occluded transarterial chemoembolization (B-TACE) enables strong TACE; infusion of more volume of lipiodol emulsion and forceful injection of embolization materials. The aim of this study is to analyze the efficacy of B-TACE for patients with one or two hepatocellular carcinoma (HCC) nodules compared with conventional super-selective TACE using a microcatheter (C-TACE). Methods We retrospectively selected patients without previous history of TACE, with one or two HCC nodules, with performance status 0/1, and with liver function of Child–Pugh score A/B. Between 2008 and 2010, a 3-Fr microballoon catheter was used for targeted TACE (B-TACE group). Between 2005 and 2008, a 2-Fr microcatheter was used (C-TACE group). Control rates of primary nodule, overall survival rates and tumor-free rates in the liver were calculated for each group using the Kaplan–Meier method. Univariate analysis was performed to compare between the groups using the log–rank test. Multivariate analysis was performed for analysis of prognostic factors using Cox’s proportional hazard model. The factors were B-TACE versus C-TACE, Child–Pugh score A versus B, single nodule versus double, large nodule versus small , elder versus not, and prior radiofrequency ablation treatment versus not. Results Control rates of the primary nodule were improved by B-TACE. B-TACE was an independent factor to improve both control rates of the primary nodule and overall survival rates. Child–Pugh score A was an independent factor to increase overall survival rates. There was no statistically significant difference in overall survival or tumor-free survival rates between the groups. Conclusion B-TACE was an independent factor to improve overall survival rates on multivariate analysis, but there was no significant difference in overall survival rates between B-TACE and C-TACE groups on univariate analysis.

After fosaprepitant (FOS)was added to the National Health Insurance drug reimbursement price list, we switched the route of administration of antiemetics from oral to intravenous in chemotherapy regimens for colon cancer to improve patient medication adherence. However, because the number of patients reporting application-site disorders after administration of FOS increased, we monitored the incidence of these disorders in patients with colon cancer to identify ways to avoid them. In our prospective study, patients receiving conventional FOS dosing regimens (control group)were compared with those receiving diluted FOS solutions (study group). There were no significant differences between the two groups with respect to the incidence of application-site disorders, and contrary to expectations, the incidence was higher in the study group than in the control group. On the basis of the principle of non-maleficence and the availability of alternative therapies using oral aprepitant (APR), we terminated this study early and adopted the basic strategy that all patients with application-site disorders, except for those with central venous access devices, should be treated with oral APR after confirming their preferences.

Summary Aim This large-scale study was designed to investigate the incidence of gastric cancer after Helicobacter pylori (H. pylori) eradication in Japan. Methods This study was a retrospective multicentre study performed at 23 centres in Japan. Patients in whom H. pylori had been successfully eradicated and those in whom the infection persisted were entered into the study if they had undergone an upper endoscopic examination at least once a year for five consecutive years. The incidence rates of gastric cancer during follow-up were compared between those whose infections had been successfully eradicated and those with persistent H. pylori infection. Results Three-thousand twenty-one patients were enrolled. The median follow-up was 7.7 years for the infected group and 5.9 years for the eradicated group. Gastric cancer developed in 23 (1%) of those in whom H. pylori was successfully eradicated compared with 44 (4%) of those with persistent H. pylori infection (OR = 0.36; 95% CI = 0.22–0.62). Conclusion This large-scale retrospective clinical study in Japan, which has a high mortality rate for gastric cancer, indicates that H. pylori eradication may prevent the development of gastric cancer.

Background and study aims: The optimal method of perioperative management of antiplatelet agents during endoscopic procedures that carry a high risk of bleeding is still controversial. The aim of this study was to evaluate the safety of continuing aspirin treatment during these procedures in an Asian population. Patients and methods: A multicenter, prospective, observational cohort study was conducted at six high volume endoscopy centers in Japan. The study included patients at high risk of thromboembolism who were regularly taking antiplatelet agents (e. g. thienopyridine derivatives and aspirin). Enrolled patients continued their aspirin therapy, and underwent endoscopic procedures that had a high risk of bleeding for treatment of lesions in the upper and lower gastrointestinal tracts. The primary end point was the rate of major bleeding complications after endoscopic procedures. Results: The study was terminated in accordance with predetermined safety criteria because 7 of 28 consecutive patients experienced major bleeding complications (25.0 %; 95 % confidence interval 10.7 % – 44.9 %). All major bleeding complications occurred following endoscopic submucosal dissection (ESD; 6 stomach, 1 colon). Univariate analysis showed that postoperative administration of thienopyridine derivatives was the only significant factor associated with postoperative bleeding (P = 0.01). Subanalysis of gastric ESD (23 lesions in 19 patients) confirmed that the administration of thienopyridine derivatives (P = 0.01) and that of multiple agents (P = 0.02) were the significant factors. All bleeding complications (postoperative day 11.2 ± 3.5) occurred after resuming thienopyridine derivative therapy postoperatively (postoperative day 2.3 ± 2.4). Conclusion: In Asian patients taking thienopyridine derivatives with aspirin, cautious postoperative care is necessary for those undergoing endoscopic procedures that are associated with a high risk of bleeding, especially gastric ESD. Continuation of aspirin alone during these endoscopic procedures may be acceptable. Study registration: UMIN000009176.

稀な肝原発の血管原性悪性腫瘍の2例を経験した. 症例1は, 46歳男性, 健診の超音波検査によって発見された. 腹部CTおよびMRI検査にて10×9cm大の肝腫瘍が認められ, 血管腫として経過観察された. 4カ月後に下腿浮腫と, 超音波検査上肝腫瘍の増大が認められ入院した. 肝動脈塞栓術, 化学療法を施行したが, 入院第57病日に死亡した. 死後の肝生検にて血管肉腫と診断された. 症例2は, 82歳女性, 多発性脳梗塞によるParkinson症候群にて通院中に体重減少あり, 腹部超音波およびCT検査を施行, 多発性肝腫瘍と脾腫瘍が認められた. 他臓器に悪性腫瘍を示唆する所見なく, 肝原発の悪性腫瘍と考えられた. 肝生検施行したが, 診断に至らず, 肝腫瘍発見2カ月後に死亡した. 剖検の結果, 脾転移をともなう肝類上皮性血管内皮腫を診断された. 当疾患は, 我々が検索し得た範囲で本邦で53例が報告されており, この中では最高齢発症であった.

Balloon-occluded retrograde transvenous obliteration (BRTO) is an established therapy for gastric varices, but it has been used less frequently for mesenteric varices. This report describes the successful management of mesenteric varices with BRTO performed via an abdominal wall collateral vein detected on contrast medium-enhanced computed tomography.

Chemotherapy-induced nausea and vomiting(CINV)is the most unpleasant side effect for patients receiving cancer chemotherapy. Moderately emetic anticancer drugs show a wide range of emetic frequencies, and the use or nonuse of antiemetics is optionally described without specifics. In the present study, we clarified the state of CINV presentation caused by moderately emetic anticancer drugs using the MASCC Antiemesis Tool, a nausea-and-vomiting evaluation tool developed by the Multinational Association of Supportive Care in Cancer(MASCC)for patients with colorectal cancer. Of the 32 subjects, 5 (15.6%)had vomiting and 22(68.8%)experienced nausea. The timing of their occurrence and their nausea scores were accurately and easily clarified. This study's findings suggested that the current regimens need to be reviewed, particularly because all patients exhibited late nausea; therefore, we modified our antiemetic regimens through the Cancer Chemotherapy Regimen Review Board of this hospital. After the modification was introduced, significant improvement was seen in the control of both acute and late nausea/vomiting.

In the author's hospital, pharmacists' outpatient clinics were initiated in April 2010, and the department of breast surgery there has provided guidance on oral anti-cancer medication, but with difficulty in adopting proposals for supportive therapy made after the doctor's consultation on the same day. Under such circumstances, this study examined methods for conducting interviews with patients before the doctor's consultation in cases where oral molecular-targeted drugs are necessary.To promote next-generation skill-mix team medicine in order to improve the continuity of treatment and optimize therapeutic effects.Patients being treated with oral molecular-targeted drugs in Hitachi General Hospital were studied.Outcomes were assessed through medication-monitoring reports, while conducting a questionnaire regarding duties of pharmacists coordinating molecular-targeted drugs.Within the study period, 245/259(94. 6%)of proposals for prescriptions were adopted in 95 patients, among which 212/245(86. 5%) proposed supportive therapy. Improvement in conditions was observed in all patients treated with supportive therapy. The mean duration of sorafenib administration among 19 patients before and after the pharmacist's intervention was 66±20. 3 and 102±30. 8 days, respectively. The main reason for the need of pharmacists coordinating molecular-targeted drugs was: security among all patients; "support for adverse event management"among all doctors; and "proposals for prescription" among all nurses.The mean duration of sorafenib administration prolonged by the pharmacist's intervention and consequent reduction in side effects may have directly improved the continuity of treatment. Furthermore, when reflecting on each prescription, the pharmacist's expertise may have facilitated pharmacological intervention. In the future, it may also be necessary to promote pharmacist-led consultations supporting patients' informed choice of drugs.

We set out to see if nutritional assessment(management)using MUST could be useful for patients undergoing outpatient chemotherapy.The study sample consisted of 197 patients undergoing outpatient chemotherapy between June 2010 and November 2010. The results of MUST, serum albumin levels, and nutritional intervention were investigated.High- and medium-risk patients requiring nutritional therapy was comprised of 17/78 breast cancer(21. 8%), 16/63 hematologic malignancy(25. 4%), and 26/56 colonic cancer(46. 4%)patients.Moreover, the serum albumin level in high- and medium-risk patients was likely to decrease compared to low-risk patients, suggesting the usefulness of MUST.It is important to assess nutritional status focusedon simplicity, objectivity, andspeedin outpatient chemotherapy. Assessment of patients' nutritional status and cancer treatment compliance are expected to be improved using MUST.

Objective A multicentre cohort follow-up study of a large number of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma was conducted to elucidate the long-term outcome of the disease after Helicobacter pylori eradication. Methods 420 patients with gastric low-grade MALT lymphoma who had undergone successful H pylori eradication and been followed up for at least 3 years were registered from 21 participating institutes. Responders to treatment were defined as patients whose post-treatment biopsies showed complete histological response (ChR) or probable minimal residual disease (pMRD). Treatment failure was defined as the status of progressive disease or lymphoma relapse after ChR/pMRD. Results 323 patients (77%) responded to H pylori eradication. A logistic regression analysis showed that absence of H pylori , submucosal invasion determined by endoscopic ultrasonography and t(11;18)/ API2-MALT1 were independent predictors of resistance to H pylori eradication. During the follow-up periods ranging from 3.0 to 14.6 years (mean 6.5 years, median 6.04 years), the disease relapsed in 10 of 323 responders (3.1%) while progressive disease was found in 27 of 97 non-responders (27%). Thus, 37 of 420 patients (8.8%) were regarded as treatment failures. Of these 37 patients, transformation into diffuse large B cell lymphoma occurred in nine patients. Among the non-responders and relapsed patients, 17 patients were subjected to a ‘watch and wait’ strategy while 90 patients underwent second-line treatments including radiotherapy (n=49), chemotherapy (n=26), surgical resection (n=6), chemoradiotherapy (n=5), antibiotic treatment (n=2), rituximab monotherapy (n=1) or endoscopic resection (n=1). Probabilities of freedom from treatment failure, overall survival and event-free survival after 10 years were 90%, 95% and 86%, respectively. Cox multivariate analysis revealed endoscopic non-superficial type to be an independent prognostic factor for adverse freedom from treatment failure, overall survival and event-free survival. Conclusions The excellent long-term outcome of gastric MALT lymphoma after H pylori eradication was confirmed by this large-scale follow-up study.

Although there are guidelines for the management of antithrombotic agents during the periendoscopic period, gaps between various guidelines create a confusing situation in daily clinical practice. The purpose of this study was to examine the current management of antithrombotic agents during the periendoscopic period in Japan.This is a prospective cohort study in 12 high-volume endoscopy centers in Japan. A total of 970 outpatients receiving antithrombotic agents underwent endoscopies (705 esophagogastroduodenoscopies and 265 colonoscopies) with or without invasive procedures. Main outcome measures are adverse events in these patients.Need for cessation of antithrombotics before endoscopy was mostly determined by non-gastroenterologists (51%) who are unfamiliar with the Japan Gastroenterological Endoscopy Society (JGES) guideline, although cessation periods after endoscopy for most patients were determined by endoscopists (78%). Consequently, most patients underwent endoscopy without cessation (25%) or after a cessation period of 6-7 days (33%), indicating low permeation of the JGES guideline in Japan. Among 970 patients, two patients experienced major complications that may be related to thromboembolic events or gastrointestinal bleeding (95% confidence interval [CI]: 0-0.7%). One of these patients died due to sudden onset ventricular tachycardia. Invasive procedures, including 40 biopsies and two mucosal resections, were performed in 42 patients without cessation of antithrombotics, and no patients experienced major complications (95% CI: 0-8.4%).This study revealed a conflicting clinical environment due to absence of a unified guideline in Japan. Further accumulation of data is mandatory to establish a unified guideline based upon solid evidence.

Background and Aims: Although there are guidelines for the management of antithrombotic agents during the periendoscopic period, gaps between various guidelines create a confusing situation in daily clinical practice. The purpose of this study was to examine the current management of antithrombotic agents during the periendoscopic period in Japan. Methods: This is a prospective cohort study in 12 high-volume endoscopy centers in Japan. A total of 970 outpatients receiving antithrombotic agents underwent endoscopies (705 esophagogastroduodenoscopies and 265 colonoscopies) with or without invasive procedures. Main outcome measures are adverse events in these patients. Results: Need for cessation of antithrombotics before endoscopy was mostly determined by non-gastroenterologists (51%) who are unfamiliar with the Japan Gastroenterological Endoscopy Society (JGES) guideline, although cessation periods after endoscopy for most patients were determined by endoscopists (78%). Consequently, most patients underwent endoscopy without cessation (25%) or after a cessation period of 6–7 days (33%), indicating low permeation of the JGES guideline in Japan. Among 970 patients, two patients experienced major complications that may be related to thromboembolic events or gastrointestinal bleeding (95% confidence interval [CI]: 0–0.7%). One of these patients died due to sudden onset ventricular tachycardia. Invasive procedures, including 40 biopsies and two mucosal resections, were performed in 42 patients without cessation of antithrombotics, and no patients experienced major complications (95% CI: 0–8.4%). Conclusions: This study revealed a conflicting clinical environment due to absence of a unified guideline in Japan. Further accumulation of data is mandatory to establish a unified guideline based upon solid evidence.

We report herein the case of a 42-year-old man in whom dyspnea on exertion was found to be caused by isolated tricuspid stenosis. Two-dimensional echocardiogram showed thickening of the tricuspid valve with a markedly enlarged right atrium. A color-flow Doppler examination-revealed severe tricuspid stenosis without regurgitation and a Doppler-derived tricuspid diastolic pressure gradient of 23 mmHg. At the time of surgery, the patient was noted to have a stenotic tricuspid valve with thickened leaflets, fused commissures, and almost normal chorda tendineae. The valve leaflets were teased apart to the scattered specimen, and tricuspid valve replacement was successfully performed. Microscopic examination of the specimen demonstrated infective endocarditis. Isolated acquired tricuspid stenosis is extremely rare and, to our knowledge, this is the first case of infective endocarditis being involved as the primary cause.

Isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) is a potentially fatal condition that is difficult to diagnose. The authors diagnosed IAD in a patient who presented with recurrent oesophageal ulceration resulting in oesophageal stenosis. The recurrent oesophageal ulcers were due to frequent nausea and vomiting that were the presenting digestive symptoms of adrenal insufficiency. Severe hypoglycaemia during this patient9s course suggested the diagnosis of adrenal insufficiency. This case is educational because digestive symptoms are the most common symptoms in patients with adrenal insufficiency, but the diagnosis of adrenal insufficiency in such patients is not easy.

A 58-year-old man was admitted to our hospital because of hematemesis. Laboratory tests indicated microcytic hypochromic anemia and iron overload. We performed urgent endoscopic examination, and diagnosed bleeding from esophagogastric varices. Abdominal CT showed liver cirrhosis and marked splenomegaly, but no evidence of gastrorenal shunt. The varices were treated by Hassab's operation and splenectomy. Pathologic examination revealed hepatocytes in the cirrhotic nodules filled with iron pigment. The cause of the liver cirrhosis was considered to be due to iron overload resulting from thalassemia. We diagnosed the cause of the microcytic anemia as thalassemia by gene analysis, which revealed heterozygosity of a deletion (deltabeta thalassemia Jpn-type II) and one point mutation (-31A--G).

脾膿瘍を合併した活動期大動脈弁感染性心内膜炎の1例を報告した. 症例は25歳, 男性. 抜歯後の発熱を主訴に来院. 血液培養で Streptococcus viridans を検出, 心臓超音波検査で大動脈弁に1cm大の疣贅と大動脈弁閉鎖不全を認めた. 多剤抗生剤治療にもかかわらず発熱は続いた. 左上腹部痛が出現したため腹部造影CTを行ったところ広範囲の脾梗塞像を認めた. 心不全が急激に悪化したため, 感染性心内膜炎の活動期に大動脈弁置換術と脾臓摘出術を同時に行った. 大動脈弁は2尖弁であった. 脾臓は菌塊による広範囲の塞栓, 膿瘍の所見であった. 術後経過は順調で現在2年が経過したが感染の再燃はない.