Search

Background Anastomotic disorder of the reconstructed gastric conduit is a life‐threating morbidity after thoracic esophagectomy. Although there are various reasons for anastomotic disorder, the present study focused on dislocation of the gastric conduit (DGC). Methods The study cohort comprised 149 patients who underwent transthoracic esophagectomy. The relationships between DGC and peri‐ and postoperative morbidities were analyzed retrospectively. Data were analyzed to determine whether body mass index (BMI) and extension of the gastric conduit were related to DGC. Uni‐ and multivariate Cox regression analyses were performed to identify the factors associated with anastomotic disorder. Results DGC was significantly related to anastomotic leakage (P, Anastomotic disorder is a life‐threating morbidity after esophagectomy. Anastomotic leakage, stricture, and mediastinal abscess/empyema are significantly related to dislocation of the gastric conduit.

Introduction: The COVID-19 outbreak abruptly restricted gastrointestinal (GI) endoscopy services during the first wave of the pandemic. We aimed to assess the impact of COVID-19 on the practice of GI endoscopy in Asian countries. Methods: This was an International Questionnaire-based Internet Survey conducted at multiple facilities by the International Gastrointestinal Consensus Symposium. A total of 166 respondents in Japan, China, Hong Kong, South Korea, Philippines, Thailand, Indonesia, and Singapore participated in this study. Results: The volume of endoscopic screening or follow-up endoscopies and therapeutic endoscopies were markedly reduced during the first wave of the pandemic, which was mainly attributed to the decreased number of outpatients, cancellations by patients, and adherence to the guidelines of academic societies. The most common indications for GI endoscopy during the first wave were GI bleeding, cholangitis or obstructive jaundice, and a highly suspicious case of neoplasia. The most common GI symptoms of COVID-19 patients during the infected period included diarrhea, nausea, and vomiting. The pandemic exacerbated some GI diseases, such as functional dyspepsia and irritable bowel syndrome. There were cases with delayed diagnosis of cancers due to postponed endoscopic procedures, and the prescription of proton pump inhibitors/potassium-competitive acid blockers, steroids, immunosuppressive agents, and biologics was delayed or canceled. The personal protective equipment used during endoscopic procedures for high-risk patients were disposable gloves, disposable gowns, N95 or equivalent masks, and face shields. However, the devices on the patient side during endoscopic procedures included modified surgical masks, mouthpieces with filters, and disposable vinyl boxes or aerosol boxes covering the head. Furthermore, the time for education, basic research, clinical research, and daily clinical practice decreased during the first wave. Conclusion: This study demonstrated that the COVID-19 pandemic profoundly affected the method of performing GI endoscopy and medical treatment for patients with GI diseases in Asian countries.

The clinical utility of plasma cell-free DNA in precision cancer medicine has not been established. A pilot study was conducted to investigate the clinical utility of comprehensive genomic profiling by liquid biopsy in a Japanese population. In this PROFILE study, 102 patients with advanced solid tumors who showed progression with standard systemic therapy underwent liquid biopsy between August 2017 and February 2020. Liquid biopsy was performed using Guardant360. Of the 102 patients, 56 were women, and the median age was 65 years. Regarding the types of cancer, 31 were hepatobiliary and pancreatic cancer, 17 were gastrointestinal cancer, and 13 were breast cancer. Frequently altered genes were TP53 (53.9%, 46/102), KRAS (25.5%, 26/102), PIK3CA (19.6%, 20/102), and EGFR (17.6%, 18/102). At least one genetic aberration was detected in 92 patients (90.2%). Actionable mutation was discovered in 88 patients (86.3%), and 67 patients (65.7%) were clinical trial candidates. Of the 102 patients, 22 (21.6%) were able to receive biomarker-matched therapy. Their best responses were as follows: 1 complete response, 3 partial responses, 7 stable diseases, and 11 progressive diseases. Additionally, the treated patients were divided on the basis of matching scores (≥ 50% vs. < 50%). The patients were divided into high and low groups. The high group had a higher disease control rate (DCR) of 75% compared with 20% in the low group (P = 0.010). The results indicate that liquid biopsy is useful for identifying actionable mutations associated with the clinical response of selected patients.

Hiroharu Kamioka,1 Yasunori Mori,2 Takahiko Horiuchi,3 Takahito Hayashi,4 Koichiro Ohmura,5 Satoru Yamaguchi,6 Mitsutoshi Kato7 1Faculty of Regional Environment Science, Tokyo University of Agriculture, Tokyo, Japan; 2Mie Prefecture Health and Environment Research Institute, Yokkaichi, Mie, Japan; 3Department of Internal Medicine, Kyushu University Beppu Hospital, Beppu, Oita, Japan; 4Department of Legal Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan; 5Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan; 6Department of Oriental Medicine, Saitama Medical University, Saitama, Japan; 7Kato Clinic of Internal Medicine, Tokyo, JapanCorrespondence: Hiroharu KamiokaFaculty of Regional Environment Science, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-Ku, Tokyo 156-8502, JapanTel/Fax +81 35477 2587Email h1kamiok@nodai.ac.jpPurpose: To clarify the relationship between daily hot water bathing (HWB) at home and glycemic control in middle-aged and elderly ambulatory patients with type 2 diabetes mellitus (T2DM).Methods: We defined hemoglobin A1c (HbA1c) as the main outcome. We set 7.0% based on the mean value of the dependent variable as the cut-off point for analysis. Frequency of HWB was an explanatory variable. A two-sample t-test was used to compare between groups with continuous variables. Multiple logistic regression analysis was performed for frequency, adjusted age, sex, BMI, T2DM duration (Model 1), and other confounding factors (Model 2). Odds ratio (OR) and 95% confidence interval (95% CI) were calculated.Results: Among 838 patients, there was a significant difference (p< 0.001) in age between males (n=528, 62.8± 8.7 years) and females (n=310, 65.0± 8.1 years). In Model 1, compared with participants who used HWB more than seven times a week, those with poorly controlled HbA1c were significantly associated with low frequency of HWB: four to six times a week (OR 1.32, 95% CI 0.87– 1.99) and less than three times a week (OR 1.43, 95% CI 0.98– 2.10); p-value for overall trend was 0.041. In Model 2, p-value for overall trend was 0.138.Conclusion: A higher frequency of HWB was moderately associated with a decreased risk of poor glycemic control in middle-aged and elderly ambulatory patients with T2DM.Keywords: hot water bathing, type 2 diabetes, hemoglobin A1c, middle-aged and elderly ambulatory patients

TAS-102 improved the overall survival of metastatic colorectal cancer (CRC) patients with a median progression-free survival (PFS) in the RECOURSE trial. Subsequently, the combination of TAS-102 and bevacizumab was shown to extend the median PFS (C-TASK FORCE study). However, the study included patients who received second- and third-line treatment. Our study exclusively examined patients receiving this combination as a third-line treatment to investigate the clinical impact beyond cytotoxic doublets. This investigator-initiated, open-label, single-arm, multi-centered phase II study was conducted in Japan. Eligible CRC patients were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin in first- and second-line therapy. TAS-102 (35 mg/m2) was given orally twice daily on days 1–5 and 8–12 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion every 2 weeks. The primary endpoint was PFS and the secondary endpoints were time-to-treatment failure, response rate, overall survival (OS), and safety. Between June 2016 and August 2017, 32 patients were enrolled. All patients previously received bevacizumab. The median PFS was 4.5 months; the median overall survival was 9.3 months. Partial response was observed in two patients. The most common adverse events above grade 3 were neutropenia followed by thrombocytopenia. There were no non-hematological adverse events above grade 3 and no treatment-related deaths occurred. This study met its primary endpoint of PFS, which is comparable to the results of the C-TASK FORCE study. The TAS-102 and bevacizumab combination has the potential to be a therapeutic option for third-line treatment of metastatic CRC.

Objectives Previously, adjuvant chemotherapy using oxaliplatin was a standard treatment for patients with node-positive colorectal cancer (CRC) who underwent curative surgery. The factor predicting adverse events and therapeutic effect have not yet been established. Methods A retrospective cohort of 42 patients diagnosed with stage III CRC between April 2009 and March 2013 in our institution were included in this study. The indicators of host nutritional status were body weight (BW), body mass index (BMI), serum albumin, Onodera's prognostic nutritional index (OPNI), and Glasgow Prognostic Score (GPS). The indicators of host immunocompetence was total lymphocyte counts, total neutrophil counts, granulocytes/lymphocytes ratio (G/L ratio). Results The overall recurrence rate was 26.1%. Patients who had a recurrence were more likely to be older. The recurrence was not associated with type of regimen or adverse events. The cases with a few cumulative doses and relative dose intensity of oxaliplatin experienced significantly more recurrence. Nutritional status indicators, such as the serum albumin level, OPNI, and the modified Glasgow prognostic score (mGPS) were associated with the adjuvant chemotherapy outcome. Our study results indicated worse nutritional status induced worse disease-free survival (DFS) and more recurrence. Conclusion The host's nutritional status associated with outcomes in stage III CRC patients.

The recent increase in macrolide-resistant Mycoplasma pneumoniae (M. pneumoniae) in Asia has become a continuing problem. A point-of-care testing method that can quickly detect M. pneumoniae and macrolide-resistant mutations (MR mutations) is critical to proper antimicrobial use. Smart Gene TM (MIZUHO MEDY Co., Ltd. Tosu-City, Saga, Japan) is a compact and inexpensive fully automatic gene analyzer that combines amplification with polymerase chain reaction (PCR) and the quenching probe method to specify the gene and MR mutations simultaneously. We performed a clinical evaluation of this device and its reagents on pediatric patients with M. pneumoniae -suspected respiratory infections and evaluated the impact of the assay on antimicrobial selection. Using real-time PCR as a comparison control, the sensitivity of Smart Gene TM was 97.8% (44/45), its specificity was 93.3% (98/105) and its overall concordance rate was 94.7% (142/150). The overall concordance rate of Smart Gene TM diagnosis of MR mutations in comparison with sequence analysis was 100% (48/48). The ratio of MR mutations was significantly higher at high-level medical institutions than at a primary medical clinic (P = 0.023), and changes in antibiotic therapy to drugs other than macrolides was significantly more common in patients with MR mutations (P = 0.00024). Smart Gene TM demonstrated excellent utility in the diagnosis of M. pneumoniae and the selection of appropriate antimicrobials for MR mutations at primary medical institutions, which play a central role in community-acquired pneumonia care. The use of this device may reduce referrals to high-level medical institutions for respiratory infections, thereby reducing the medical and economic burden on patients.

Background/Aims: Functional gastrointestinal disorders (FGIDs) are diagnosed and classified using the latest Rome IV criteria, released in 2016. Epidemiology of FGID diagnosed by the Rome IV criteria and current clinical application of gastrointestinal motility testing in Asian countries are not well known. The aims of this survey are to elucidate the present situation of epidemiology and diagnostic tests of FGID in clinical practice in some East and Southeast Asian countries. Methods: The questionnaire focusing on current situation of FGID diagnosis and gastrointestinal motility testing was distributed to members of the International Gastroenterology Consensus Symposium study group and collected to be analyzed. Results: The prevalence rates of subtypes of both functional dyspepsia (FD) and irritable bowel syndrome (IBS) are relatively similar in all Asian countries. In these countries, most patients underwent both upper endoscopy and Helicobacter pylori test to diagnose FD. Colonoscopy was also frequently performed to diagnose IBS and chronic constipation. The frequency of gastrointestinal motility testing to examine gastric emptying and colonic transit time varied among Asian countries. Conclusions: This survey revealed epidemiology of FGIDs and current status of gastrointestinal motility testing in some East and Southeast Asian countries.

We previously reported the first evidence of oncological benefits from a Japanese phase II trial of oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer (the FACOS study). We herein report the long-term survival and persistent oxaliplatin-related peripheral sensory neuropathy (PSN) for patients enrolled in this trial. Patients were scheduled to receive the mFOLFOX6 or CAPOX regimen in the adjuvant setting. The five-year overall survival (OS) rate and persistent PSN were evaluated. A total of 130 patients (mFOLFOX6, n = 73; CAPOX, n = 57) were eligible. The 5-year OS rate was 91.4%. No significant difference in the OS rate was observed between regimens (mFOLFOX6, 94.4%; CAPOX, 87.4%; P = 0.25). The incidence of PSN during adjuvant treatment was 55.4% in grade 1 (G1), 30.0% in G2, and 4.6% in G3. No patients showed G3 PSN at 12 months, but G1 or G2 residual PSN after 5 years was observed in 21.8% (G1, 20%; G2, 1.8%). Updated results from the FACOS study support the benefits of oxaliplatin-based adjuvant chemotherapy in terms of the long-term survival among Japanese patients with stage III colon cancer. However, long-term persistent PSN occurs in about 20% of survivors, counterbalancing the favorable OS.

Background Lymphatic malformation (LM) is a congenital disease caused by lymphatic vessel malformation. Although standard therapies for LMs are sclerotherapy and/or surgical excision, a new therapy using Japanese herbal medicine Eppikajutsuto (TJ-28) has been recently reported as clinically effective. We aimed to experimentally confirm the therapeutic effectiveness of TJ-28 for LMs. Methods LM lesions were generated in the mesentery and peritoneum of mice by intraperitoneal injection of Freund's incomplete adjuvant. Mice with LMs were treated by gavage or dietary administration of TJ-28 for 2 months. Formalin-fixed paraffin-embedded tissue sections of mesentery and peritoneum tissues were histologically and immunohistochemically examined by focusing on lymph nodes and perinodal lymph vessels. Results Multiple Freund's incomplete adjuvant-associated foreign-body granulomas were formed in the mesentery and peritoneum, resulting in congestion of lymph fluid and dilatation of lymph vessels. The numbers and sizes of lymph nodes were not significantly different between TJ-28-treated and control groups. However, the luminal areas of lymphatic vessels were reduced significantly in the TJ-28 treatment group by both gavage and dietary administrations. Conclusion TJ-28 conspicuously reduced congestion of lymph fluid. This is the first histopathological evaluation of LM model mice to study the effectiveness of oral TJ-28 treatment.

The infiltration of melted snow water and rainwater into snow can drastically change the form of snow layers. This process is an important factor affecting wet snow avalanches. Accordingly, numerous field surveys and cold room experiments have been conducted to investigate the distribution of water in snow. The common methods of water content measurement (calorimetric and dielectric methods) are implemented by disturbing snow samples to measure them. However, the resolutions obtained are of the order of several centimeters, which hinders the continuous measurement of the water content of a particular sample. Magnetic resonance imaging (MRI), which is typically used in the medical field, can be used to generate a high-resolution three-dimensional (3D) image of the water distribution in samples without destructing them. The luminance of images produced by MRI depends on the volumetric water content of the sample, with luminance increasing with volumetric liquid water content. Therefore, the volumetric liquid water content of the sample can be estimated from its luminance value. Considering this concept, we developed a method to measure the volumetric liquid water content of wet snow samples using MR images. To evaluate the developed method, we prepared several wet snow samples and measured their various volumetric liquid water contents using MRI (θMRI) and the calorimetric method (θcal). θMRI, and θcal showed good correlation when compared, with values in the range 0.02–0.46. Therefore, our system can accurately and non-destructively measure water content. The developed method using MRI can measure 3D volumetric liquid water contents with a high resolution (2 mm). Using the developed method, we investigated the hysteresis of the water retention curve of snow based on the measurements of a wetting process (boundary wetting curve) and a drying process (boundary drying curve) of the water retention curve for each sample. Our results indicate the existence of hysteresis in the snow water retention curves and the possibility of modeling it by adopting contexts of soil physics.

Background/Aims: To elucidate the current management of ulcerative colitis (UC)-associated cancer, a questionnaire-based survey was conducted to gather current opinions on colitis-associated cancer in different East Asian countries. Methods: The questionnaire, based on physicians, contains 9 questions focused on UC management and cancer surveillance. In addition, the questionnaire based on neoplastic cases, which contains 17 questions, was collected and analyzed. Results: With regard to the diagnosis of UC-associated cancer, most respondents started surveillance colonoscopy within 10 years from onset, favored targeted biopsies, and thought advanced imaging was useful. As for morphology, the frequency of elevated lesion and type 4 lesions was most common in early and advanced cancer, respectively. Peritoneal metastasis was frequently observed, and undifferentiated tumor was frequently developed. Laparoscopic surgery was widely used because it is less invasive. The prognostic outcome was poor, particularly in stage III and undifferentiated type. Conclusions: The current survey elucidated the current management in Asian countries and characteristics of colitis-associated cancer in these countries.

Objective: We aimed to develop new predictive models for excluding macrosomia using only maternal physical parameters, without sonographic examination. Methods: The present study retrospectively analyzed the medical records of pregnant women who delivered singleton infants at term at one obstetric hospital in an urban area in Japan from May 2005 to April 2017. We performed logistic regression analysis to predict macrosomia and created an integer risk scoring system based on the significant predictors. We also developed an alternative predictive regression model using machine learning with the random forest algorithm. Results: There were 203 cases of macrosomia among 15,263 eligible women. Although our scoring system had low specificity and positive predictive value, the negative predictive value for screening macrosomia was very high (0.996-1.000). The other model, using machine learning with the random forest algorithm to predict macrosomia, showed a negative predictive value of 0.99, which was similar to the results of our scoring system. Conclusions: Our integer scoring system is an easy and useful method for excluding macrosomia among pregnant women without sonographic examination.

Objective: Oral mucositis and diarrhea are adverse effects (AEs) of chemotherapy and chemoradiotherapy (CR/CRT) that commonly occur in patients of esophageal cancer (EC). We investigated whether Hangeshashinto (TJ-14)—a Japanese traditional medicine—could control oral mucositis, pain, incidence of esophagitis, and diarrhea in patients who underwent CT/CRT for EC. Methods: We enrolled 39 patients (36 men, 3 women) who underwent docetaxel- or cisplatin-based CT/CRT for EC between July 2012 and June 2014, of whom 19 used TJ-14 dissolved in water as an oral rinse 3 times a day over the first 2 courses of their treatment, and 20 (the control group) received no particular prophylaxis against mucositis. Their AEs, including mucositis, were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Results: Although incidences of oral mucositis, appetite loss, nausea, constipation, and vomiting did not significantly differ between the TJ-14 group and controls, diarrhea incidence was significantly lower in the TJ-14 group by the second treatment course (P = 0.0261 by per protocol set analyses). Conclusions: TJ-14 significantly decreases diarrhea caused by CT/CRT in patients treated for EC, although TJ-14 cannot prevent of causing oral mucositis.

18F‐Fluorodeoxyglucose positron emission tomography (FDG‐PET) is a useful imaging modality that reflects the tumor activity. However, FDG‐PET is mainly used for advanced cancer, not superficial cancer. In this study, we investigated the relationship between the superficial tumor depth of esophageal cancer and the FDG uptake to determine the indications for endoscopic resection (ER). From 2009 to 2017, 444 patients with esophageal cancer underwent esophagectomy or endoscopic submucosal dissection (ESD), and 195 patients were pathologically diagnosed with superficial cancer. Among them, 146 patients were examined by FDG‐PET before esophagectomy or ESD. In these 146 patients, the relationship between the pathological tumor depth and FDG uptake was analyzed. The mean maximum standardized uptake value in pT1a‐EP/LPM tumors was 1.362 ± 0.890, that in pT1a‐MM/pT1b‐SM1 tumors was 2.453 ± 1.872, and that in pT1b‐SM2/SM3 tumors was 4.265 ± 3.233 (P

Objective: This study aimed to investigate factors that predict bowel gangrene in sigmoid colon volvulus patients. Methods: Nine sigmoid colon volvulus cases were retrospectively analyzed for prediction of bowel necrosis. Laboratory parameters were extracted from medical records, and subsequently, a receiving operator curve for each parameter was drawn. Using these cut-off values, a comparison between the “with necrosis” and “without necrosis” groups was performed. Results: In the emergent cases, necrosis of the intestine was observed in 4 cases and not observed in 4 cases. The values of area under the curve were high in metabolic acidosis and white blood cell counts. For base excess, the cut off value was -2.4 mEq/L. A lower base excess is significantly associated with bowel gangrene (p = 0.029). For white blood cell count, the cut off value is 8400/mm3. A lower white blood cell counts is significantly associated with bowel gangrene (p = 0.029). Conclusions: In addition to physiological findings, blood gas analysis and white blood cell counts are useful to detect ischemia due to sigmoid volvulus.

The objective of this study was to analyze the short- and long-term treatment outcomes of patients with bowel perforation caused by obstructive colorectal cancer. From April 2003 to March 2013, 15 patients with bowel perforation caused by obstructive colorectal cancer underwent emergency surgery at our hospital. Clinical outcomes were retrospectively analyzed by age, sex, tumor location, tumor stage, preoperative APACHE II severity score, time to surgery from diagnosis, operative method, and postoperative complications. We studied short-term outcomes and long-term prognosis by overall survival. Ten men and 5 women, with a median age of 67.6 years, were enrolled in the study. The mortality rate was 20%, and the median APACHE II score was 15. The 11 patients who survived had significantly lower APACHE II scores than the 4 fatal cases (P = 0.02). Excluding the patient with stage IV cancer, the median overall survival was 18.9 months. Five patients (50%) had recurrence and distant metastasis. APACHE II score may be a useful predictive marker for short-term outcome and determining operative method in patients with bowel perforation caused by obstructive colorectal cancer. Perforation should be considered as a high-risk factor for cancer recurrence, most of which are peritoneal.

Introduction: The Asia-Pacific consensus on the management of gastroesophageal reflux disease (GERD) and the GERD treatment guidelines of 2015 drawn up by the Japanese Society of Gastroenterology were proposed, and GERD management in Asian regions was assumed to be performed based on these consensuses. In this environment, the current status of GERD management in clinical practice among Asian regions is less well-known. Objective: This questionnaire-based consensus survey was performed to clarify the current status of management of GERD in clinical practice in Asian regions. Methods: A questionnaire related to management of GERD was distributed to members of the International Gastroenterology Consensus Symposium Study Group. We analyzed the questionnaire responses and compared the results among groups. Results: The frequencies of erosive GERD (ERD), non-ERD, uninvestigated GERD, and Barrett’s esophagus varied significantly among Asian countries. The most important factor in diagnosing GERD was the presence of symptoms in all countries. A proton pump inhibitor was the most commonly prescribed drug to treat GERD in all countries. Endoscopic surveillance for GERD was performed regularly. Conclusion: This questionnaire survey revealed the current status of management of GERD in clinical practice in various Asian countries.

Background: This study aimed to examine the treatment outcomes of patients with brain metastases from esophageal cancer. Brain metastases from esophageal cancer are rare and have a poorer prognosis than brain metastases from lung and breast cancer. Methods: This study included patients who were diagnosed with and treated for esophageal cancer in our department and subsequently developed brain metastases between April 2010 and December 2014. We examined the differences in survival in patients based on receiving chemotherapy. Results: In total, 8 patients (7 men and 1 woman) with a mean age of 65 years (range 51–73) were included. Seven presented with neurologic symptoms. Two were diagnosed via computed tomography (CT), 5 via magnetic resonance imaging, and 1 via positron emission tomography/CT. They were treated using whole-brain irradiation or with a gamma knife. In 5 patients, chemotherapy was administered after treatment of the brain metastases. The mean survival from the start of treatment was 358 days (range 31–1196). Conclusion: The relatively successful local control of brain metastases in these patients indicates that long-term survival may be attainable via concomitant chemotherapy.

BACKGROUND/AIM Adequate mediastinal lymphadenectomy during thoracoscopic esophagectomy (TE) requires an extensive operating field. In order to rectify this problem, we developed slender tracheal forceps that can pass through a 12-mm trocar. PATIENTS AND METHODS TE in the prone position was performed in 58 patients with esophageal cancer using slender tracheal forceps. Perioperative and postoperative clinical data were compared against those of 61 patients who underwent transthoracic open esophagectomy (OE). RESULTS The mean duration of thoracic manipulation was significantly longer in the TE than OE group: 226.2 versus 171.3 minutes (p

Background/aim Esophageal squamous cell carcinoma (ESCC) is one of the most difficult malignancies to cure. C4d is a degradation product of the classical complement pathway and is suggested as an early diagnostic marker for other SCCs. The purpose of this study was to clarify the association of complement C4d with ESCC. Patients and methods Immunohistochemical staining for C4d was performed on surgical specimens obtained from 114 patients with ESCC. Results Positive C4d expression was observed in 70 (61.4%) cases and negative expression in 44 (38.6%) cases. There was a significant inverse correlation between C4d expression and depth of tumor invasion (p=0.0001), lymph node metastasis (p=0.011), lymphatic invasion (p=0.033), and TNM stage (p=0.0021). Kaplan-Meier analysis showed that negative C4d expression tended to lead to shorter overall survival (p=0.232). Conclusion C4d expression in ESCC might be useful in developing treatment strategies or suppression of ESCC.

Multigenic glutelins and monogenic globulin are major storage proteins accumulating in vacuole-derived protein body (PB-II) of rice (Oryza sativa L.) seeds. Because their interplay in PB-II formation was scarcely known, the effect of globulin-less mutation on glutelin accumulation was investigated. In globulin-less mutants, no phenotypic defect was found in seed and plant growth, while PB-II was deformed and apparent glutelin composition was changed, producing new glutelin α polypeptides X1–X5. 2D-PAGE of different combinations of globulin-less and glutelin subunit mutations suggested that the X1/X2, X3, and X4/X5 were derived from glutelin GluB1/GluB2/GluB4, GluA3, and GluA1/GluA2 subunits, respectively. Western blot with glutelin GluB4 subunit-specific and its variable region discriminable antibodies indicated at least in part the new spots X1/X2 are partially degraded products of GluB4 α polypeptides by the removal of 2–39 residues from C-terminus. Time course experiments with maturing seeds indicated the partial degradation of GluB4 occurred earlier (from 7 days after flowering) and higher than that of GluA1/GluA2. Considering the above results together with the fact that globulin accumulates at the periphery of PB-II and its absence produces deformed PB-II, globulin protects glutelins from proteinase digestion and thereby facilitates stable glutelin accumulation.

224 Background: The combination regimen of TAS-102 and bevacizumab as salvage-line therapy for metastatic colorectal cancer (mCRC) was established based on its high clinical effectiveness (C-TASK FORCE). Recently, our current phase II TAS-CC3 study demonstrated comparable median progression-free survival (PFS: 4.5m) and overall survival (OS: 9.2m) with exclusive inclusion of 3rd line therapy patients. However, practical predictors for its efficacy are lacking. This study evaluated inflammation-based scores as potential predictors for this combination therapy. Methods: This is a post hoc analysis of investigator-initiated, open-label, single-arm, multicentered phase II study (TAS-CC3) in Japan with 32 mCRC patients treated with the combination therapy. We investigated the predictive and prognostic values of pretreatment blood inflammation-based scores, including neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and lymphocyte-monocyte ratios (LMR), on disease-control (DC), PFS and OS. These were divided into two groups (high and low) using cut-off of each median values. This study was registered at the University Hospital Medical Information Network, as UMIN#000022438. Results: ROC curve analyses of 3 inflammation-based scores versus DC showed a best predictive performance in LMR, followed by NLR and PLR (AUC: 0.89, 0.85, and 0.68, respectively). The high LMR group had a significantly higher DC rate than the low group (87.5 vs. 43.8%, P= 0.023). Two patients showing partial responses were in the high group. The high LMR group showed significantly longer survivals compared with the low group (4.9 vs. 2.3m, respectively for median PFS, P= 0.014) (20.5 vs. 5.1m, respectively for median OS, P< 0.001). The values of LMR were significantly correlated with PFS and OS (r = 0.56: P< 0.001 and 0.62: P< 0.001, respectively). Conclusions: Pretreatment LMR is a valid predictive and prognostic biomarker for mCRC patients with TAS-102 and bevacizumab treatment and might be clinically useful for selecting patients of the responder. Clinical trial information: 000022438.

The purpose of this study was to clarify the relationship of daily hot water bathing at home (DHW) and hot water spa bathing (HSPA) with the number of underlying diseases in middle-aged and elderly ambulatory patients. We defined the number of underlying diseases as the main outcome and dependent (criterion) variable. The frequency and time of DHW and the frequency of HSPA were set as explanatory variables. Multiple logistic regression analysis was performed for each frequency and time, adjusted age and sex. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated. Among the 1261 patients who participated, there was no significant difference in age between males (n = 508, 72.8 ± 6.8 years) and females (n = 753, 73.5 ± 6.9 years). There was also no significant age difference between males (number of diseases: 2.7 ± 2.0 pts.) and females (number of diseases: 2.7 ± 2.1 pts.) in the occurrence of underlying diseases. Frequency and time of DHW were not associated with the occurrence of underlying diseases. However, compared with participants who utilized hot water spa at least once a week, the occurrence of underlying diseases was significantly associated with bathing frequency: one to three times per month (OR 2.72, 95% CI 1.63–4.52); twice or five times a year (OR 1.92, 95% CI 1.25–2.94). In conclusion, lower frequency of HSPA was significantly associated with increased risk of the occurrence of underlying diseases in middle-aged and elderly ambulatory patients. However, the relationship between proactive use of hot water spa and patients’ mental and physical support should be clarified by well-designed cohort studies. The present study was registered as UMIN000033018 by the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) in Japan (refer: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000037643 ).

Waardenburg syndrome (WS) has the characteristic clinical features caused by the embryologic abnormality of neural crest cells. WS patients sometimes suffer from functional intestinal obstruction. When it is Hirschsprung disease (HD), the WS is diagnosed as type 4 WS. We report a case of WS which did not have myenteric ganglion cells in the sigmoid colon and rectum. Whether to diagnosis this case as type 1 or 4 WS is controversial. Moreover, this is the third report which has peristalsis failure caused by abnormal myenteric plexus. In all three cases, the eosinophils had aggregated in the myenteric layer of the transition zone. During embryonic life, enteric ganglion cells migrate to the myenteric layer from the proximal to the distal side sequentially and, subsequently, to the submucosal layer through the circular muscle. Therefore, we hypothesize that myenteric ganglion cells that had already migrated were eliminated by an eosinophil-mediated mechanism in these three cases. We believe this report may be helpful to elucidate the pathogenesis of some types of HD.

Chromated copper arsenate (CCA) is used as a wood preservative worldwide. Exposure to it may adversely affect human health. Some events have increased human exposure to CCA, including the Great East Japan Earthquake, which generated a large amount of lumber debris from CCA-treated woods. We elucidated the toxicity due to daily exposure to CCA over a 4-week period at doses of 0, 8, 40, and 80 mg/kg/day in Wistar Hannover rats. Chromium (Cr) and arsenic (As), but not copper, were detected in the plasma samples of rats treated with various doses of CCA. Males and females showed sedation, and males had poor body weight gain. The clinical pathologies observed in both sexes included hypochromic and microcytic anemia, hepatic and renal dysfunction, and changes in lipid and glucose levels. Histopathologically, males and females showed forestomach hyperkeratosis, mucosal epithelial hyperplasia in the small intestine, rectal goblet cell hypertrophy, and lipofuscin deposition in the proximal renal tubule. Females showed diffuse hepatocellular hypertrophy with increased 8-hydroxydeoxyguanosine levels. These results indicated that oral administration of CCA mainly affected hematopoietic, gastrointestinal, hepatic, and renal systems owing to the toxic effects of As and/or Cr. Major toxic effects were observed in both sexes receiving 40 and 80 mg/kg/day.

Background/Aims: Because salvage surgery after definitive chemoradiotherapy for esophageal cancer is associated with high postoperative mortality and morbidity, minimally invasive methods are desirable. We analyzed the validity of minimally invasive salvage operations (MISO). Methods: Twenty-five patients underwent salvage operation between 2010 and 2016 in our institution, 10 having undergone right transthoracic salvage esophagectomy (TTSE group), 6 transhiatal salvage esophagectomy (THSE), 6 salvage lymphadenectomy (SLA), and 3 salvage endoscopic submucosal dissection (SESD). Patients who had undergone THSE, SLA, or SESD were categorized as the MISO group. Short- and long-term outcomes were assessed. Results: The mean duration of surgery was significantly shorter in the SLA groups than in the TTSE group (p = 0.0248). Blood loss was significantly less in the SLA than the TTSE group (p = 0.0340). Intensive care unit stay was shorter in the THSE than the TTSE group (p = 0.0412). There was no significant difference in postoperative mortality between the MISO and THSE groups. Postoperative hospital stay was significantly shorter in the SLA than the TTSE group (p = 0.0061). Patients’ survivals did not differ significantly between the MISO and TTSE groups (p = 0.752). Multivariate analysis revealed that residual disease (R0; HR 4.872, 95% CI 1.387–17.110, p = 0.013) was the only independent factor influencing overall survival. Conclusion: MISO is preferable because short-term outcomes are better and long-term outcomes do not differ from those of TTSE.

We had experience with a case of mesenchymal hamartoma of the chest wall (MHCW) with fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT). We reported the first case of asymptomatic MHCW in a child with preoperative PET/CT. Mesenchymal hamartoma of the chest wall is a rare benign tumor that usually presents as a visible chest wall mass or respiratory problems secondary to compression of the lung in early infancy. It is often reported that malignant transformation is extraordinarily rare. Positron emission tomography/CT is useful for diagnosis of malignancy. There is no report of MHCW in a child with preoperative PET/CT before. We examined an asymptomatic 1-year-old girl with an incidental finding on a chest x-ray. Scans of CT and PET/CT were performed before surgical resection. After surgery, the resected tumor was examined histologically. Chest x-ray and CT scan of the chest confirmed a 25- × 20-mm round shaped intrapleural mass containing calcification and destructing the rib, arising from the third rib. Scan of PET/CT demonstrated the mass with light FDG accumulation. Histologically, the mass was homogenous, with thick funicular of hyaline cartilage interdigitating with scattered fiber. There were no malignant cells. No malignant MHCW was demonstrated in the mass, with light FDG accumulation by PET/CT. PET/CT might be a useful tool to distinguish malignant MHCW in children.

BACKGROUND/AIM The purpose of this study was to identify adverse prognostic factors for patients with advanced esophageal cancer undergoing chemotherapy with docetaxel, cisplatin and 5-fluorouracil (DCF). PATIENTS AND METHODS The study cohort comprised of 45 patients with advanced esophageal cancer who underwent induction DCF therapy followed by esophagectomy or chemoradiotherapy. Treatment outcomes and factors affecting early recurrence and death were analyzed. RESULTS Overall 3-year survival was 61.4%, and 3-year disease-free survival was 44.7%. Clinically evident lymph node metastasis and clinical stage were associated with recurrence within 1 year and death within 2 years. Low maximum standardized uptake value (SUVmax) after induction DCF therapy and small decreases in SUVmax from pre- to post-DCF therapy were also predictors of recurrence and poor prognosis. CONCLUSION Induction DCF therapy may be ineffective for advanced-stage esophageal cancer and clinical lymph node metastasis (≥N2, ≥stage IIIB). Moreover, small decreases in SUVmax DCF therapy are associated with early disease relapse and death.

Billroth-I (BI) is a simple, physiological method of reconstruction following distal gastrectomy. In actuality, postoperative QOL is by no means favorable due to the high incidence of post-gastrectomy syndrome. The aim of this study is to assess the safety and efficacy of boomerang-shaped jejunal interposition (BJI) after distal gastrectomy. Sixty-six patients with early gastric cancer underwent the BI procedure (n = 33) or BJI (n = 33) after distal gastrectomy, following which they were compared for 5 years. Tumor characteristics, operative details, postoperative complications and complaints, number of meals, and body weight were analyzed. Patients were followed up by endoscopy every 12 months. There were no significant differences in the incidence of postoperative complications. The incidence of heartburn (30 vs. 0 %, P = 0.0009) and oral bitterness (33 vs. 6 %, P = 0.0112) were significantly lower in the BJI cases. Endoscopic findings revealed significantly lower incidences of reflux esophagitis (24 vs. 0 %, P = 0.0051) and remnant gastritis (70 vs. 3 %, P

Gastrectomy with D2 lymphadenectomy plus postoperative chemotherapy is the standard treatment for resectable locally advanced gastric cancer in Japan. However, the prognosis of patients with serosa-positive tumors remains unsatisfactory because of peritoneal recurrence. This study aimed to investigate the validity of neoadjuvant therapy with docetaxel, cisplatin, and S-1 (DCS) in patients with locally advanced gastric cancer. Thirty patients with locally advanced gastric cancer underwent neoadjuvant DCS therapy at Dokkyo Medical University Hospital between June 2013 and October 2015. Gastrectomy and D2 lymphadenectomy were performed after two cycles of preoperative DCS therapy. The clinical responses of the primary gastric tumors based on endoscopic findings were partial response in 17 patients (57%) and stable disease in 13 patients (43%). Analysis of pathological response in the primary gastric lesions showed grade 1a in five patients (17%), grade 1b in nine patients (30%), grade 2 in 11 patients (37%), and grade 3 in five patients (17%). Twenty-four patients (80%) remained alive after a median follow-up period of 31 months. The 2- and 3-year overall survival rates in all patients were 89 and 70%, respectively. The 2-year overall survival rate in pathological responders (grade 1b-3) was 96%, compared with 50% in pathological non-responders (grade 1a) (P = 0.00187). Pathological responders had a significantly higher survival rate than non-responders. These results indicate that neoadjuvant DCS therapy may improve the prognosis in patients with serosa-positive locally advanced gastric cancer.

The gastric ulcer drug teprenone has central nervous system effects, specifically reducing depression-like behavior in mice., Heat shock proteins (HSPs) are stress-induced chaperones that are involved in neurological disease. Although increasingly implicated in behavioral disorders, the mechanisms of HSP action, and the relevant functional pathways, are still unclear. We examined whether oral administration of geranylgeranylacetone (GGA), a known HSP inducer, produced an antidepressant effect in a social defeat stress model of depression in mice. We also investigated the possible molecular mechanisms involved, particularly focusing on hippocampal neurogenesis and neurotrophic factor expression. In stressed mice, hippocampal HSP105 expression decreased. However, administration of GGA increased HSP105 expression and improved depression-like behavior, induced hippocampal cell proliferation, and elevated brain-derived neurotrophic factor (BDNF) levels in mouse hippocampus. Co-treatment with GGA and the BDNF receptor inhibitor K252a suppressed the antidepressant effects of GGA. HSP105 knockdown decreased BDNF mRNA levels in HT22 hippocampal cell lines and hippocampal tissue and inhibited the GGA-mediated antidepressant effect. These observations suggest that GGA administration is a therapeutic candidate for depressive diseases by increasing hippocampal BDNF levels via HSP105 expression.

Although salvage esophagectomies are widely performed, reports on salvage lymphadenectomy (SL) are few. We review our SL cases to clarify the indications. Fifty-five patients with esophageal cancer underwent chemoradiotherapy or radiotherapy, including 3 patients with single lymph node (LN) recurrences and one with allochronic double cervical node recurrence. Our department removed 5 recurrent LNs from these 4 patients. In Case 1, right supraclavicular LN was judged to be metastatic and R0 resection was carried out; he is alive without recurrence. In Case 2, we found, allochronically, metastases in his left cervical paraesophageal LN and left supraclavicular LN; residual tumors were R1 in both lesions. He is alive despite esophageal recurrence. In Case 3, a lymphadenectomy was performed on his thoracic para-aortic LN; however, tumor was removed incompletely, and he died 4 months after SL from disease progression. In Case 4, a subcarinal LN was thought to be metastatic, and was removed but no malignant tissues detected. He died 17 months after SL from pneumonia. Our experiences suggest that some patients survive relatively long with SL. Moreover, molecular examination of resected lesions could guide subsequent therapies. SL might be more widely used for these patients if not otherwise contraindicated.

The purpose of this study was to evaluate the presence of extracapsular invasion (ECI) in positive sentinel lymph nodes (SLNs) as a predictor of disease recurrence in breast cancer. SLN biopsy was performed on 318 breasts of 316 breast cancer patients, of which 50 (15.7%) had positive SLNs. Six (12.0%) of these 50 cases had disease recurrence. The clinicopathologic features of these cases were reviewed. The ECI at SLNs was not significantly associated with disease recurrence. The recurrence-free interval by Kaplan-Meier curves did not differ significantly among patients with and without ECI at SLNs. On the other hand, metastasis at non-SLNs was observed in 12 cases (24.0%) among the 50 cases with positive SLNs, and in the non-SLN metastasis group there were 7 patients with ECI at non-SLNs. Three of 7 cases with ECI at non-SLNs had disease recurrence and none of those 5 without ECI at non-SLNs had disease recurrence. Our current study suggests that the presence of ECI at metastatic SLNs is not associated with recurrent disease in breast cancer. Our results also imply that patients with ECI at positive non-SLNs have a high risk of disease recurrence.

The optimal timing of early oral intake after surgery has not been fully established. The objective of this study was to compare early oral intake at postoperative day 1 after resection of colorectal cancer with that of day 2 to identify the optimal timing for resumption of oral intake in such patients. Consecutive patients with colorectal cancer who underwent elective colorectal resection were separated into two groups. Sixty-two patients began a liquid diet on the first postoperative day (POD1 group) and 58 patients began on POD2 (POD2 group) and advanced to a regular diet within the next 24 hours as tolerated. As for gastrointestinal recovery, the first passage of flatus was experienced, on average, on postoperative day 3.1 ± 1.0 in the POD2 group and on day 2.3 ± 0.7 in the POD1 group. The first defecation was also significantly earlier in patients in the POD1 group than those in the POD2 group (POD 3.2 ± 1.2 versus 4.2 ± 1.4, respectively). No statistical difference was found between the two groups in terms of postoperative complications. Our results suggest that very early feeding on POD1 after colorectal resection is safe and feasible and that induced a quicker recovery of postoperative gastrointestinal movement in patients.

614 Background: TAS-102 improved overall survival of metastatic colorectal cancer (mCRC) patients with median progression free survival (PFS) of 2.0 months (RECOURSE trial). Subsequently, the combination of TAS-102 and bevacizumab has been shown to extend median PFS with 3.7 months (C-TASK FORCE). However, this study included patients with 2nd line and 3rd line chemotherapy. Our study was planned exclusively for patients receiving this combination as a 3rd line chemotherapy to investigate clinical impact of this combination beyond cytotoxic doublet. Methods: This phase II study was conducted in investigator-initiated, open-label, single-arm, multicentered manner in Japan. Eligible patients were 20-80 years old, and had to have an ECOG performance status of 0 or 1; had confirmed unresectable mCRC with histologically diagnosed adenocarcinoma; were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin in the 1st and the 2nd line chemotherapy. TAS-102 (35 mg/ m²) was given orally twice daily on days 1–5 and 8–12 in a 4-weeks cycle, and bevacizumab (5 mg/ kg) was administered by intravenous infusion for 30 minutes in every 2 weeks. The primary endpoint was progression free survival (PFS), and the secondary endpoints were time to treatment failure (TTF), response rate (RR), overall survival (OS), and safety. Results: Between June 2016 and August 2017, 32 pts were enrolled. The median PFS was 4.5 months, and the median OS was 9.3 months. Partial response was observed in 2 patients. The most common adverse events above grade 3 were neutropenia (15 patients) followed by thrombocytopenia (4 patients). Treatment-related serious adverse events were reported in 1 patient. There were no non-hematologic adverse events above grade 3. No treatment-related deaths occurred. Conclusions: This is the first study which involves the combination TAS-102 and bevacizumab as the 3rd line chemotherapy in the setting beyond cytotoxic doublet for the patients with mCRC. This study met its primary endpoint PFS, which is comparable to the results of C-TASK FORCE study. This combination has a potential to be one of therapeutic options of the 3rd line chemotherapy for mCRC. Clinical trial information: 000022438.