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Background: Of the several methods used to prevent surgical site infection (SSI), diluted povidone-iodine (PI) lavage is used widely. However, the clinical utility of PI for preventing periprosthetic joint infection (PJI) remains controversial. The aim of this study was to perform a systematic review and meta-analysis of the utility of dilute PI lavage for preventing PJI in primary and revision surgery., Methods: This study was conducted in accordance with the PRISMA checklist for systematic reviews and meta-analyses. A comprehensive literature search of PubMed, CINAHL, ClinicalTrials.gov , and Cochrane Library databases was performed. The results are summarized qualitatively and as a meta-analysis of pooled odds ratios with 95% confidence intervals (95% CIs). Heterogeneity of treatment effects among studies was classified as low, moderate, or high, corresponding to I 2 values of < 25%, 25-50%, and > 50%. A random effects model was applied in cases of high heterogeneity; otherwise, the fixed effects model was applied. Subgroup analyses were conducted to identify potential sources of heterogeneity., Results: After the screening and eligibility assessment process, eight studies were finally extracted for analysis. Overall, the results showed that PI had no significant effect on PJI with ununified control group. However, subgroup analysis of studies with a saline control group revealed an odds ratio of 0.33 (95% CI, 0.16-0.71) for the PI group, suggesting a significant effect for preventing PJI., Conclusion: The systematic review and meta-analysis of the current literature demonstrates that diluted PI lavage is significantly better than saline solution lavage for preventing PJI., Level of Evidence: Level I, Systematic review and meta-analysis., (© 2021. The Author(s).)

Aims: Sarcopenia, one of the extracardiac factors for reduced functional capacity and poor outcome in heart failure (HF), may act differently between HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). We sought to investigate the impact of sarcopenia on mortality in HFpEF and HFrEF., Methods and Results: We performed a post hoc analysis of a multicentre prospective cohort study, including 942 consecutive older (age ≥65 years) hospitalized patients: 475 with HFpEF (ejection fraction ≥45%, age 81 ± 7 years, 48.8% men) and 467 with HFrEF (ejection fraction <45%, age 78 ± 8 years, 68.1% men). Sarcopenia was diagnosed according to the international criteria incorporating muscle strength (handgrip strength), physical performance (gait speed), and skeletal muscle mass (appendicular skeletal mass). The HFpEF group consisted of fewer patients with low appendicular skeletal muscle mass index measured using bioelectrical impedance analysis [<7.0 kg/m2 (men) and <5.7 (women); 22.1% vs. 31.0%, P = 0.003], and more patients with low handgrip strength [<26 kg (men) and <18 (women); 67.8% vs. 55.5%, P < 0.001], and slow gait speed [<0.8 m/s (both sexes); 54.5% vs. 41.1%, P < 0.001] than the HFrEF group, resulting in a similar sarcopenia prevalence in the two groups (18.1% vs. 21.6%, P = 0.191). Sarcopenia was an independent predictor of 1-year mortality in both HFpEF and HFrEF [hazard ratio (95% confidence interval) 2.42 (1.36-4.32), P = 0.003 in HFpEF and 2.02 (1.08-3.75), P = 0.027 in HFrEF; P for interaction = 0.666] after adjustment for other predictors., Conclusions: In older patients with HF, sarcopenia contributes to mortality similarly in HFpEF and HFrEF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

In 2009, the United States Institute of Medicine (IOM) reported the optimal gestational weight gain (GWG) during twin pregnancy based on the pre-pregnancy body mass index (BMI). However, there are ethnic variations in the relationship between GWG and pregnancy outcomes. We aimed to establish the criteria for optimal GWG during twin pregnancy in Japan. The study included cases of dichorionic diamniotic twin pregnancy registered in the Japan Society of Obstetrics and Gynecology Successive Pregnancy Birth Registry System between 2013 and 2017. We analyzed data for cases wherein both babies were appropriate for gestational age and delivered at term. Cases were classified into four groups based on the pre-pregnancy BMI: underweight (BMI <18.5 kg/m2), normal weight (18.5 kg/m2 ≤BMI< 25.0 kg/m2), overweight (25.0 kg/m2 ≤BMI< 30.0 kg/m2), and obese (BMI ≥30.0 kg/m2) and we calculated the 25th-75th percentile range for GWG for the cases. The 3,936 cases were included. The GWG ranges were 11.5-16.5 kg, 10.3-16.0 kg, 6.9-14.7 kg, and 2.2-11.7 kg in the underweight, normal weight, overweight, and obese groups, respectively. Thus, in the current study, the optimal GWG during twin pregnancy was lower than that specified by the IOM criteria. Factoring this in maternal management may improve the outcomes of twin pregnancies in Japan., Competing Interests: The authors have declared that no competing interests exist.

Background/aim: Oncotype DX recurrence score (RS) for breast cancer is a useful tool for determining chemotherapy indication but it is expensive and time-consuming. We determined whether four immuno-histochemical markers, namely human epidermal growth factor 2 (HER2), estrogen receptor (ER), progesterone receptor (PgR), and Ki-67, are predictive of an RS ≥26 in Japanese patients., Patients and Methods: The study included 95 Japanese patients evaluated for RS. A predictive model was created using logistic regression analysis., Results: The discriminant function was calculated as follows: p=1/{1+exp [-(4.611+1.2342×HER2-0.0813×ER- 0.0489 ×PgR+0.0857×Ki67)]}. Using a probability of 0.5 as the cutoff, the accuracy, sensitivity, specificity, positive predictive and negative predictive values were 90.5%, 72.2%, 94.8%, 76.4% and 93.5%, respectively., Conclusion: The model had a high negative predictive value in predicting RS ≥26 in Japanese patients, indicating that Oncotype DX testing may be omitted in patients with a negative result according to the predictive model., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Pirfenidone is an anti-fibrotic agent approved for idiopathic pulmonary fibrosis (IPF), and long-term treatment data and the effect of continuation after disease progression have been reported. The efficacy and safety of pirfenidone in fibrosing interstitial lung disease (ILD) patients without IPF have been recently reported in clinical trials; therefore, the benefits of long-term treatment are also expected. This study aims to analyze the long-term treatment data of pirfenidone and clarify the predictive factors for long-term use of pirfenidone in non-IPF patients., Methods: We retrospectively reviewed the records of consecutive fibrosing ILD patients who started using pirfenidone between 2008 and 2014., Results: Of the 266 fibrosing ILD patients, 167 patients had IPF, and 99 had non-IPF. Despite the non-significant differences in body size and pulmonary function between IPF and non-IPF patients, the non-IPF patients had better overall survival than the IPF patients (median 4.06 years vs. 2.09 years, p < 0.0001). In addition, the non-IPF patients had a significantly longer time to treatment discontinuation than the IPF patients (median 2.20 years vs. 1.20 years, p = 0.002). Multivariate logistic regression analysis for ≥2 years of use of pirfenidone showed that the percent predicted forced vital capacity (%FVC) and age were predictive factors common to both IPF and non-IPF patients., Conclusions: Our results indicate that non-IPF patients can continue using pirfenidone for longer durations than IPF patients. Initiation of pirfenidone for fibrosing ILD patients with higher %FVC and younger age would lead to long-term use of pirfenidone., Competing Interests: Conflict of interest T Katano, A Sekine, H Yamakawa, T Misumi, H Okabayashi, R Okuda, H Kitamura, S Komatsu, and E Hagiwara declare no potential conflicts of interest. S Ikeda, T Baba, and T Ogura received honoraria from Nippon Boehringer Ingelheim Co., Ltd, and T Ogura received honoraria from Shionogi Co. Ltd., (Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

SARS-CoV-2 whole-genome sequencing of samples from COVID-19 patients is useful for informing infection control. Datasets of these genomes assembled from multiple hospitals can give critical clues to regional or national trends in infection. Herein, we report a lineage summary based on data collected from hospitals located in the Tokyo metropolitan area. We performed SARS-CoV-2 whole-genome sequencing of specimens from 198 patients with COVID-19 at 13 collaborating hospitals located in the Kanto region. Phylogenetic analysis and fingerprinting of the nucleotide substitutions were performed to differentiate and classify the viral lineages. More than 90% of the identified strains belonged to Clade 20B, which has been prevalent in European countries since March 2020. Only two lineages (B.1.1.284 and B.1.1.214) were found to be predominant in Japan. However, one sample from a COVID-19 patient admitted to a hospital in the Kanto region in November 2020 belonged to the B.1.346 lineage of Clade 20C, which has been prevalent in the western United States since November 2020. The patient had no history of overseas travel or any known contact with anyone who had travelled abroad. Consequently, the Clade 20C strain belonging to the B.1.346 lineage appeared likely to have been imported from the western United States to Japan across the strict quarantine barrier. B.1.1.284 and B.1.1.214 lineages were found to be predominant in the Kanto region, but a single case of the B.1.346 lineage of clade 20C, probably imported from the western United States, was also identified. These results illustrate that a decentralized network of hospitals offers significant advantages as a highly responsive system for monitoring regional molecular epidemiologic trends.

Background: Cachexia, characterized by loss of muscle with or without loss of fat mass, is a poor prognostic factor in patients with heart failure (HF). However, there is limited investigation on the prognostic impact of muscle and fat mass separately in HF. We hypothesized that muscle and fat mass have different effects on the prognosis of HF., Methods: This was an observational cohort study of 418 patients (59% were men) admitted with a diagnosis of HF (71 ± 13 years [mean ± standard deviation]), with left ventricular ejection fraction (LVEF) of 39 ± 16%, including 31.3%, 14.8%, and 53.8% of patients with preserved LVEF (LVEF ≥ 50%), mid-range LVEF (40-50%), and reduced (<40%) LVEF, respectively. Dual-energy X-ray absorptiometry was performed with the patients in the stable state after decongestion therapy., Results: The mean body mass index of patients was 22.1 ± 4.6 kg/m 2 , and the mean appendicular skeletal mass (ASM) index was 6.88 ± 1.23 kg/m 2 in men and 5.59 ± 0.92 in women; 54.1% of the patients showed reduced muscle mass defined by the international cut-off value (7.0 kg/m 2 for men and 5.4 for women). The mean fat mass was 20.4 ± 7.2% in men and 27.2 ± 8.6% in women. During a median follow-up of 37 months, 92 (22.0%) of 418 patients with HF died (1 and 3 year mortality: 8.4% and 17.3%, respectively). Lower values of both skeletal muscle and fat mass were independently associated with increased risk of mortality adjusted for age, sex, haemoglobin, New York Heart Association functional class, and height squared (hazard ratio with 95% confidence interval of 0.825 [0.747-0.908] per 1 kg increase of ASM, P < 0.001, and 0.954 [0.916-0.993] per 1 kg increase of fat mass, P = 0.018, respectively)., Conclusions: More than half of the patients with HF showed reduced muscle mass. Lower values of both muscle and fat mass were associated with higher mortality in HF., (© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Aim: This study aimed to clarify how the COVID-19 pandemic impacts psychological stress levels in postpartum women in Yokohama, Japan., Methods: We retrospectively compared the rates of positive screening tests for postpartum depression (Edinburgh Postnatal Depression Scale score of 9 or more or self-injury factors) and liaison/psychiatric intervention rates between pre-pandemic and pandemic groups of postpartum women who delivered a live birth at our tertiary perinatal center in Yokohama, Japan between January 2019 and May 2020. Those whose postpartum health screening was performed in 2019 (March-June 2019) were considered the pre-pandemic group, and those whose screening was performed between March and June 2020 were considered the pandemic group. Adjustments were made for maternal background, pregnancy, and delivery outcomes, including a history of psychiatric disorders, complications, preterm delivery, NICU admission, and maternal postpartum complications, and the data were analyzed using a logistic regression analysis., Results: Postpartum health screenings were performed on 339 women before the pandemic and 279 women during the pandemic. Positive screening rates for postpartum depression did not change before and during the pandemic (adjusted odds ratio 1.48, 95% confidence interval 0.885-2.46)., Conclusions: There was no apparent increase in maternal psychological stress due to the COVID-19 pandemic in Yokohama, Japan. Postpartum women responded differently in settings with varied levels of disease severity and social restrictions., (© 2021 Japan Society of Obstetrics and Gynecology.)

Background: Randomized controlled trials (RCTs) comparing intracorporeal anastomosis (IA) and extracorporeal anastomosis (EA) could not prove a significant reduction in postoperative stay and therefore did not provide sufficient evidence of IA. Recently, we reported a new intracorporeal anastomosis method and intracorporeal end-to-end anastomosis (IEEA). However, there have been no studies comparing intracorporeal side-to-side anastomosis (ISSA) to IEEA., Purpose: The main purpose of this study is to verify the superiority of IA over EA. The secondary purpose is to compare IEEA with ISSA., Methods: Patients scheduled to undergo laparoscopic colectomy for colon cancer are recruited to the CONNECT study (multicenter, single-blind, randomized controlled study), cases in which anastomosis by the double-stapling technique is planned will be excluded. The target sample size is set at 300 cases in total, which will be randomized into 3 groups (EA, IEEA, and ISSA) in a 2:1:1 ratio. The primary endpoint is the length of postoperative hospital stay in the IA and EA groups; the secondly endpoint is the anastomotic time in IEEA and ISSA groups. We will also evaluate SF-36 ver.2, EORTC QLQ-C30 ver.3, operator stress using SURG-TLX, and the long-term outcomes, such as 5-year disease-free survival and overall survival., Conclusions: This RCT will compare the postoperative length of stay between IA and EA in twice the number of cases of previous RCTs. Concurrently, although as a secondary purpose, this will be the first study to compare IEEA and ISSA., Trial Registration: This trial was registered with the UMIN Clinical Trials Registry in September 2020 as UMIN000041565.

Corticosteroids use in coronavirus disease 2019 (COVID-19) is controversial, especially in mild to severe patients who do not require invasive/noninvasive ventilation. Moreover, many factors remain unclear regarding the appropriate use of corticosteroids for COVID-19. In this context, this multicenter, retrospective, propensity score-matched study was launched to evaluate the efficacy of systemic corticosteroid administration for hospitalized patients with COVID-19 ranging in the degree of severity from mild to critically-ill disease. This multicenter, retrospective study enrolled consecutive hospitalized COVID-19 patients diagnosed January-April 2020 across 30 institutions in Japan. Clinical outcomes were compared for COVID-19 patients who received or did not receive corticosteroids, after adjusting for propensity scores. The primary endpoint was the odds ratio (OR) for improvement on a 7-point ordinal score on Day 15. Of 1092 COVID-19 patients analyzed, 118 patients were assigned to either the corticosteroid and non-corticosteroid group, after propensity score matching. At baseline, most patients did not require invasive/noninvasive ventilation (85.6% corticosteroid group vs. 89.8% non-corticosteroid group). The odds of improvement in a 7-point ordinal score on Day 15 was significantly lower for the corticosteroid versus non-corticosteroid group (OR, 0.611; 95% confidence interval [CI], 0.388-0.962; p = 0.034). The time to improvement in radiological findings was significantly shorter in the corticosteroid versus non-corticosteroid group (hazard ratio [HR], 1.758; 95% CI, 1.323-2.337; p < 0.001), regardless of baseline clinical status. The duration of invasive mechanical ventilation was shorter in corticosteroid versus non-corticosteroid group (HR, 1.466; 95% CI, 0.841-2.554; p = 0.177). Of the 106 patients who received methylprednisolone, the duration of invasive mechanical ventilation was significantly shorter in the pulse/semi-pulse versus standard dose group (HR, 2.831; 95% CI, 1.347-5.950; p = 0.006). In conclusion, corticosteroids for hospitalized patients with COVID-19 did not improve clinical status on Day 15, but reduced the time to improvement in radiological findings for all patients regardless of disease severity and also reduced the duration of invasive mechanical ventilation in patients who required intubation.Trial registration: This study was registered in the University hospital Medical Information Network Clinical Trials Registry on April 21, 2020 (ID: UMIN000040211).

Background: Rehabilitation is an effective procedure for promoting functional recovery after simultaneous bilateral total knee arthroplasty (TKA); however, it has been cited as a significant economic burden of medical care. We hypothesized that preoperative factors, including age, sex, body mass index, living alone, the knee society function score (KSS), the American society of anesthesiologists (ASA) class, hemoglobin (Hb), albumin level, mean range of motion, and the Kellgren-Lawrence grade, would predict prolonged rehabilitation utilization., Methods: In total, 191 patients undergoing simultaneous bilateral TKA in a single hospital were enrolled. The successful compliance group included patients who completed their rehabilitation program and could return to their residence within 3 weeks after surgery (n = 132), whereas the delayed group included the remaining patients (n = 59). Logistic regression analysis was performed using preoperative factors. A prediction scoring system was created using the regression coefficients from the logistic regression model., Results: Logistic regression analysis revealed that age (β = - 0.0870; P <  0.01) and Hb (β = 0.34; P <  0.05) were significantly associated with prolonged rehabilitation programs, whereas body mass index, living alone, KSS score, and ASA class were not significantly associated with successful completion of rehabilitation programs; however, these factors contributed to the prediction scoring formula, which was defined as follows: [Formula: see text] The C-statistic for the scoring system was 0.748 (95% confidence interval, 0.672-0.824). The positive and negative likelihood ratios were 2.228 (95% CI, 1.256-3.950) and 0.386 (95% CI, 0.263-0.566), respectively. These results showed an increase of 15-20% and a decrease of 20-25% in the risk of prolonged rehabilitation. The optimal cutoff point for balancing sensitivity and specificity was 3.5, with 66.6% sensitivity and 78.0% specificity., Conclusions: Older age and lower preoperative Hb were significantly associated with prolonged rehabilitation programs. We defined a new scoring formula using preoperative patient factors to predict prolonged rehabilitation utilization in patients undergoing simultaneous bilateral TKA.

Background: In 2010, the International Association of Diabetes and Pregnancy Study Group (IADPSG) proposed new criteria indicating that gestational diabetes mellitus (GDM) can be diagnosed if the fasting threshold of ≤92 mg/dL, 1-h threshold of ≤180 mg/dL, or 2-h threshold of ≤153 mg/dL are exceeded during the 75-g 2-h oral glucose tolerance test (OGTT) performed at 24-28 weeks of gestation. The World Health Organization (WHO) recommends using the proposed diagnostic threshold values of the IADPSG to diagnose GDM; however, it does not limit the timing of the 75-g OGTT. Since 2010 in Japan, GDM has been diagnosed using the same criteria as that proposed by the WHO. However, neither the JSOG nor the WHO has provided any evidence that it is appropriate to use a threshold beyond the range recommended by the IADPSG., Methods: This was a single-centre retrospective study based on the medical records and delivery registry database of our centre. We included women who underwent a 50-g glucose challenge test (GCT) with results < 140 mg/dL at 24-28 weeks of gestation and subsequently underwent a 75-g OGTT after 29 weeks of gestation with abnormal glucose tolerance suspected based on clinical findings. The reference values for the 75-g OGTT followed the IADPSG criteria. Subjects were classified into the normal glucose tolerance (NGT) group and the GDM group. The type of delivery and neonatal outcomes of the two groups were compared. A multivariable analysis was performed to match the backgrounds of both groups., Results: In total, the NGT and GDM group comprised 189 and 49 women, respectively. Emergency caesarean delivery rates were similar in the GDM and NGT groups (10.6 and 12.2%, respectively; adjusted odds ratio [OR], 1.25; 95% confidence interval [CI], 0.43-3.64; p = 0.74); however, the elective caesarean delivery rate was higher in the GDM group than in the NGT group (16.3 and 5.3%, respectively, adjusted OR, 3.60; 95% CI, 1.27-10.19; p = 0.01). No significant differences were observed in other maternal and neonatal outcomes between both groups., Conclusion: Although a diagnosis of GDM during the third trimester does not improve pregnancy outcomes, it increases the elective caesarean delivery rate.

Nivolumab is an increasingly used standard care treatment for heavily pretreated patients with advanced gastric cancer, with increasing clinical use in Japan. Data from retrospective studies on various tumors have shown the objective response rate to cytotoxic chemotherapy potentially improves after an exposure to immune checkpoint inhibitors. Based on these data, we conducted the multicenter observational REVIVE study to evaluate the efficacy and safety of cytotoxic chemotherapy in nivolumab-refractory or nivolumab-intolerant patients with advanced gastric cancer. Patients who are refractory or intolerant to nivolumab and scheduled to receive irinotecan monotherapy, oxaliplatin combination treatment or oral trifluridine/tipiracil hydrochloride therapy will be included. The primary end point is overall survival of nivolumab-pretreated patients with advanced gastric cancer after the cytotoxic chemotherapy. Clinical trial registration: UMIN000032182 (umin.ac.jp).

Background: Based on the results of the PACIFIC study, chemoradiotherapy followed by 1-year consolidation therapy with durvalumab was established as the standard of care for unresectable, locally advanced non-small-cell lung cancer (LA-NSCLC). However, some topics not foreseen in that design can be explored, including progression-free survival (PFS) and overall survival (OS) after the start of chemoradiotherapy, the proportion of patients who proceeded to consolidation therapy with durvalumab, and the optimal chemotherapeutic regimens. In Japan, the combination regimen of S-1 + cisplatin (SP), for which the results of multiple clinical studies have suggested a good balance of efficacy and tolerability, is frequently selected in clinical settings. However, the efficacy and safety of consolidation therapy with durvalumab following this SP regimen have not been evaluated. We therefore planned a multicenter, prospective, single-arm, phase II study., Methods: In treatment-naïve LA-NSCLC, two cycles of combination chemotherapy with S-1 (80-120 mg/body, Days 1-14) + cisplatin (60 mg/m 2 , Day 1) will be administered at an interval of 4 weeks, with concurrent thoracic radiotherapy (60 Gy). Responders will then receive durvalumab every 2 weeks for up to 1 year. The primary endpoint is 1-year PFS rate., Discussion: Compared with the conventional standard regimen in Japan, the SP regimen is expected to be associated with lower incidences of pneumonitis, esophagitis, and febrile neutropenia, which complicate the initiation of consolidation therapy with durvalumab, and have higher antitumor efficacy during chemoradiotherapy. Therefore, SP-based chemoradiotherapy is expected to be successfully followed by consolidation therapy with durvalumab in more patients, resulting in prolonged PFS and OS. Toxicity and efficacy results of the SP regimen in this study will also provide information important to the future establishment of the concurrent combination of chemoradiotherapy and durvalumab., Trial Registration: Japan Registry of Clinical Trials, jRCTs031190127, registered 1 November 2019, https://jrct.niph.go.jp/latest-detail/jRCTs031190127., Competing Interests: Conflict of interest statement: S.T. received research funding from AstraZeneca K.K. N.S. received personal fees as honoraria from Lily Japan, AstraZeneca K.K., MSD Oncology, Chugai Pharmaceutical, Taiho Pharmaceutical, Pfizer Japan Inc., Ono Pharmaceutical, Nippon Boehringer Ingelheim Co., Ltd., and Bristol-Myers Squibb Japan, and research funding from Nippon Boehringer Ingelheim Co., Ltd., (© The Author(s), 2021.)

Background: Ventral incisional hernia is a common problem after abdominal surgery. Most patients with these hernias present with greater omentum and gastrointestinal prolapse. However, hepatic herniation through a ventral incisional hernia is a rare phenomenon that has been seldom reported in the literature. We report the case of a ventral incisional hernia with hepatic herniation treated with laparoscopic repair., Case Presentation: A 68-year-old Japanese women with a history of myocardial resection for hypertrophic cardiomyopathy 1 year earlier was admitted to our hospital with symptoms of vomiting and epigastric pain. Physical examination showed a 4-cm epigastric mass. Abdominal computed tomography revealed left hepatic lobe herniation through the lower edge of a mid-sternal incision. We diagnosed the patient with a ventral incisional hernia with hepatic herniation. The patient underwent laparoscopic hernia repair. During an 18-month follow-up, no recurrence or symptoms have been observed., Conclusions: To the best of our knowledge, this is the first case report of laparoscopic repair of ventral incisional hernias with hepatic herniation. Laparoscopic repair was useful and suitable for this rare herniation due to its minimally invasive nature and ability to achieve sufficient visibility of the surgical field. Laparoscopic repair could be a potential treatment option for elective surgery for this disease, which is often treated conservatively.

Background: Converse Ω anastomosis is a recently developed technique of delta-shaped anastomosis for intracorporeal gastroduodenostomy to simplify the anastomotic procedures and reduce their potential risks. This study aimed to evaluate the safety and effectiveness of converse Ω anastomosis, comparing it with conventional extracorporeal Billroth-I anastomosis after laparoscopic distal gastrectomy (LDG) for gastric cancer., Patients and Methods: Among 169 gastric cancer patients who underwent LDG with Billroth-I anastomosis anastomosis between April 2013 and March 2018, we selected 100 patients by propensity score matching (50 in the converse Ω anastomosis group and 50 in the extracorporeal anastomosis group). Patients' characteristics, intraoperative outcomes, postoperative complications, and survival time were compared between the 2 groups., Results: Median anastomosis time was significantly longer in the converse Ω group than in the extracorporeal group (40.0 vs. 30.5 min, P=0.005). However, the total procedure time did not differ significantly between the groups. Intraoperative blood loss volume was significantly lower in the converse Ω group than in the extracorporeal anastomosis group (40 vs. 120 mL, P<0.001). There were no significant differences in the number of dissected lymph nodes, postoperative morbidity, mortality, or length of hospital stay. The postoperative body mass index and the prognostic nutritional index did not differ between the groups 1 year after surgery. There were no significant differences in overall survival and relapse-free survival between the 2 groups., Conclusions: Converse Ω anastomosis is feasible and safe. This novel technique can be adopted as a treatment option for reconstruction after LDG in patients with early-stage gastric cancer. Therefore, the risks and benefits of converse Ω anastomosis after LDG should be confirmed in larger cohorts., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Double common bile duct (DCBD) is an extremely rare congenital anomaly of the biliary system associated with serious complications. An association between DCBD and inadvertent bile duct injury during surgery has been reported. However, DCBD is difficult to diagnose preoperatively. We report a rare case of DCBD (type 3b), combined with cholelithiasis and cholecystitis, diagnosed preoperatively, and treated safely by laparoscopic cholecystectomy. A 79-year-old woman was admitted with a 1-week history of chest pain. Abdominal computed tomography revealed gallbladder distension with obvious wall thickening. Laparoscopic cholecystectomy was planned to determine the presence of stones in the common bile duct and an anomalous biliary tract. Magnetic resonance cholangiopancreatography (MRCP) was performed, and anomalous anatomy of the biliary tract was suspected. Drip infusion cholangiography with computed tomography (DIC-CT) showed type 3b DCBD. On hospital day 7, laparoscopic cholecystectomy was performed without accessory common bile duct resection. The postoperative course was uneventful, and the patient was discharged on postoperative day 5. To our knowledge, this is the first report of the successful diagnosis of DCBD using DIC-CT. MRCP and DIC-CT can be useful for the pre-operative diagnosis of DCBD to decrease the risk of bile duct injury during surgery.

We investigated the impact of basal dietary sodium intake on the dapagliflozin-induced changes in albuminuria and blood pressure (BP) measured at home in patients with diabetic kidney disease (DKD).This was a secondary analysis of the Y-AIDA Study, in which DKD patients with estimated glomerular filtration rate (eGFR) ≥ 45 ml/min/1.73 m 2 and urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g creatinine were administered dapagliflozin for 24 weeks, and dapagliflozin significantly improved albuminuria levels and home BP profiles. The effects on UACR, home-measured BP, and eGFR were compared between high- and low-sodium intake groups (HS and LS groups), which were created using baseline urinary sodium-to-creatinine ratio of 84 participants with available basal sodium-to-creatinine ratios. At baseline, clinic-/home-measured BPs, UACR, and eGFR, were comparable in the two groups. After 24 weeks, the reductions from baseline in ln-UACR were comparable in the two groups. In contrast, the reductions in evening home systolic BP and eGFR from baseline were larger in HS than in LS (BP: - 13 ± 2.08 vs. - 6 ± 1.88, P = 0.020; eGFR: - 3.33 ± 1.32 vs. 0.37 ± 1.29, P = 0.049). The home BP-lowering effects of dapagliflozin are larger in HS than LS, concomitant with a larger reduction in eGFR, suggesting a dapagliflozin-induced improvement in glomerular relative hyperfiltration in HS.

Aims: To investigate whether the Institute of Medicine (IOM) guidelines for optimal gestational weight gain (GWG) in twin pregnancies are applicable to Japanese women., Methods: This was a retrospective study involving women who delivered full-term twins at our tertiary center diagnosed with a normal prepregnancy body mass index. The women were divided into two groups, according to the optimal GWG recommended by the IOM (16.8-24.5 kg): the adequate GWG (AGWG) group with GWG meeting the guidelines and the low GWG (LGWG) group with GWG below the guidelines. Next, the women were divided into two groups according to birthweight: a group with both twins born appropriate for gestational age (AGA group) and a group with one or both twins born small for gestational age (SGA group). Their GWG as well as their pregnancy outcomes were compared., Results: A total of 265 women were included. The AGWG group had a significantly higher proportion of hypertensive disorders of pregnancy than the LGWG group. There was no significant difference in the proportion of women with both twins born AGA or the rate of admission to the neonatal intensive care unit. Meanwhile, the median GWG in the AGA group was 13.6 kg, which was significantly higher than 12.0 kg in the SGA group. And even the median GWG in the AGA group was below the lower limit of the IOM guidelines., Conclusion: The optimal GWG for Japanese women with twin pregnancies may be below the IOM guidelines., (© 2020 Japan Society of Obstetrics and Gynecology.)

Cisplatin-based chemoradiotherapy is considered standard treatment for unresectable locally advanced non-small-cell lung cancer (LA-NSCLC). This study examined two regimens of chemotherapy in concurrent chemoradiation. Eligible patients with unresectable, radically irradible LA-NSCLC were randomized to either the SP (S-1 and cisplatin) or DP (docetaxel and cisplatin) arms with concurrent thoracic radiotherapy of 60 Gy, comprising 2 Gy per daily fraction. The primary endpoint was the overall survival (OS) rate at 2 years (the 2-year OS rate). From May 2011 to August 2014, 110 patients were enrolled. Of 106 eligible patients, the 2-year OS rates were 79% (95% CI: 66%-88%) and 69% (95% CI: 55%-80%) the SP and DP arms, respectively. The median progression-free survival was 11.6 months for the SP arm and 19.9 months for the DP arm, while the median survival time was 55.2 months for the SP arm and 50.8 months for the DP arm. Grade 3/4 leukopenia were more frequent in DP arm. The incidences of febrile neutropenia and pneumonitis tended to be higher in DP arm. There were no treatment-related deaths in either arm. The primary endpoint was met in both arms. The SP arm as a future reference regimen will be chosen due to fewer toxicities and better OS., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background/aim: Prophylactic splenectomy has shown no inferiority for tumors not invading the greater curvature side. Despite this, the clinical impact of prophylactic splenectomy for proximal advanced gastric cancer is not clear. This review aimed to clarify the impact of splenectomy for advanced gastric cancer in the upper third of the stomach., Materials and Methods: A systematic review and meta-analysis were conducted based on PubMed and EMBASE databases. The following search terms were used: "gastric cancer" OR "splenectomy" OR upper third of the stomach" OR preservation of the spleen., Results: Out of 765 articles, 18 studies (combined n=6,341) were included in the analysis. Four randomized controlled trials (RCT) and eight retrospective studies suggested the benefits of spleen-preserving gastrectomy. Six retrospective studies showed no significant benefit of spleen-preserving gastrectomy. Prophylactic splenectomy showed a close association with a higher incidence of postoperative morbidity (pancreatic fistula and anastomotic leakage) with no concomitant improvement in overall survival. Prophylactic splenectomy should not be routinely performed and RCTs are necessary to confirm the impact of splenectomy for cN(+) at the splenic hilum tumors and tumors invading the greater curvature., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Patient journeys for hypertensive individuals after detection at screening have not been well examined in a general population. Thus, we aimed to assess the medical treatment status and subsequent longitudinal changes in blood pressure in a middle-aged Japanese population., Methods: We conducted a cohort study using a nationwide Japanese health screening cohort, from April 2014 to March 2019. Among health screening participants aged 40-74 years who had not previously received treatment for hypertension, hypertensive patients were newly identified based on screening results, and their medical treatment status for hypertension during the year following their initial screening was assessed. The main outcomes were longitudinal changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) over 4 years after initial screening., Results: Of the 153,523 screening participants (mean age = 49.7 years), 16,720 (10.9%) and 4150 (2.7%) were newly detected as having hypertension, with baseline SBP of 140-159 mmHg (grade 1) and ≥ 160 mmHg (grade 2-3), respectively. Among them, 15.9% of the grade 1 hypertensive participants and 36.3% of the grade 2-3 hypertensive participants started receiving medical treatment during the year following initial screening. A linear generalised estimating equation with propensity score matching showed that receiving medical treatment was associated with 5.77 mmHg lower SBP (95% CI - 6.64 to - 4.90) and 3.82 mmHg lower DBP (95% CI - 4.47 to - 3.16) in the grade 1 hypertensive group, and 14.69 mmHg lower SBP (95% CI - 16.35 to - 13.04) and 8.42 mmHg lower DBP (95% CI - 9.49 to - 7.34) in the grade 2-3 hypertensive group., Conclusions: Health screenings detected hypertension in a substantial percentage of the middle-aged population in this study. However, detection was often followed by insufficient medical treatment and inappropriate blood pressure management. These findings indicate an inadequate link between health screenings and medical treatments in patients with hypertension.

Background/aim: This study aimed to evaluate the effect of intensity-modulated radiation therapy (IMRT) on the clinical outcomes of patients with lymph node (LN) oligo-recurrence and a controlled primary tumor., Patients and Methods: We retrospectively reviewed the medical records of 21 patients diagnosed with LN oligo-recurrence who received IMRT with curative intent. Patients with tumor of various primary sites and histopathological types were included in this study., Results: The 3-year overall survival (OS) and in-field progression-free survival (PFS) rates were 75% and 52%, respectively. Statistical analysis showed that lower dose to the gross tumor volume (GTV) and larger GTV were significantly associated with poorer OS; adenocarcinoma and lower dose to GTV were significantly associated with poorer in-field PFS. No patients experienced severe adverse events., Conclusion: IMRT may provide a safe and effective treatment for patients with LN oligo-recurrence. Tumor dose-escalation sparing normal tissue using IMRT technology may improve the OS and in-field PFS., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: The mutation rate of T790M might change the effective therapeutic sequence of EGFR tyrosine kinase inhibitors (TKIs). This simulation estimates the T790M positivity rate required for first-line first- or second-generation EGFR TKI to exceed overall progression-free survival (PFS) of first-line osimertinib., Methods: The PFS of each treatment with EGFR TKIs as first-line treatment, with osimertinib as second-line treatment among T790M-positive cases, and chemotherapy as second-line treatment among T790M-negative cases was set based on phase 3 trials. Overall PFS A of "upfront osimertinib" and overall PFS B of "first- or second-generation EGFR TKIs followed by osimertinib or chemotherapy" were simulated at different T790M mutation rates, to estimate the T790M mutation rate at which PFS B exceeds PFS A., Results: Upfront osimertinib: In the setting of PFS of 19 months with first-line osimertinib, the median overall PFS A was 24.8 months (95% confidence interval [CI]: 21.6-28.0 mo). Upfront first- or second-generation EGFR TKI: When the T790M positivity rate was set to 50% and the PFS of second-line osimertinib was 10 months, the total median PFS (PFS B) was 20.2 months (95% CI: 17.5-22.9 mo). Even at a T790M mutation rate of 100%, PFS B (24.7 mo; 95% CI: 21.9-27.9 mo) was shorter than PFS A., Conclusions: Even with a T790M mutation rate of 100%, upfront osimertinib treatment is associated with better median PFS than the upfront treatment with first- or second-generation EGFR TKIs. Consistent with the results of the FLAURA trial, with regard to EGFR TKI monotherapy in the first-line treatment, upfront osimertinib would contribute to good prognosis., (© 2020 The Authors.)

Objectives: This phase I/II study assessed the efficacy and safety of combination therapy with carboplatin (CBDCA) and nab-paclitaxel (nab-PTX) in advanced elderly patients (aged ≥75 years) with advanced squamous cell lung cancer (SqCLC)., Materials and Methods: In this phase I study, the doses of carboplatin at an area under the curve (AUC) of 5 or 6 mg/mL/min on day 1 (levels 1 and 2, respectively) were administered along with weekly nab-PTX (100 mg/m 2 ) on days 1, 8, and 15 every 4 weeks for up to 6 cycles using a modified 3 + 3 design. The primary endpoint for the phase II study was the 6-month progression-free survival (6 m PFS) rate., Results: A total of 46 patients were enrolled in this study. Ten patients were enrolled in the phase I part. At dose level 1, 2/7 patients showed dose-limiting toxicities (DLTs) of grade 3 diarrhea and febrile neutropenia; at dose level 2, 1/3 patient exhibited grade 3 anorexia as a DLT. The recommended dose was determined to be level 2. Efficacy was then evaluated in 39 patients enrolled in a phase II study. The median number of cycles was 4 (range, 1-6), and the median follow-up time was 17.5 months (range, 5.6-28.9 months). The 6 m PFS rate was 59.4% (90% confidence interval [CI], 44.8%-71.4%), and the primary endpoint was met. The median overall survival time was 23.5 months (95% CI, 11.6-35.4), and the median PFS was 6.8 months (95% CI, 5.4-9.1). The response rate was 54%, and the disease control rate was 92%. Sixteen patients (41%) received immune checkpoint inhibitors post-study. Common grade 3 or 4 toxicities were neutropenia (61.5%), anemia (46.2%), thrombocytopenia (17.9%), and febrile neutropenia (15.4%)., Conclusion: Combination chemotherapy consisting of CBDCA with weekly nab-PTX had a promising efficacy and acceptable toxicities in elderly patients (aged ≥75 years) with advanced SqCLC., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Lynch syndrome (LS), which is known as a hereditary cancer syndrome, is distinguished by microsatellite instability, represented by the altered number of repetitive sequences in the coding and/or non-coding region. Immunohistochemical staining (IHC) of DNA mismatch repair (MMR) proteins (e.g., MLH1, MSH2, MSH6, and PMS2) has been recognized as an useful technique for screening of LS. Previous study has shown that the assessment of IHC, however, requires specific caution due to variable staining patterns even without germline mutations in MMR genes., Case Presentation: A 48-year-old man, who had been treated for anaplastic astrocytoma, was referred to our department for the precise examination of progressing anemia. Whole-body examination revealed two advanced carcinomas in descending colon and stomach. A hypo-vascular mass lesion was detected in liver as well. Pathological diagnosis (on surgical specimens) was poorly differentiated adenocarcinoma in descending colon, moderately differentiated tubular adenocarcinoma in stomach, and liver metastasis, which is possibly from colon. It was suspected that this case would be Turcot's syndrome-type-1 due to its specific family history having two cases of colon cancer within the second relatives. Pathogenic frameshift mutations in codon 618 of MLH1 gene was identified. Immunohistochemical analyses (IHC) demonstrated complete loss of MLH1 immuno-expression as well as of PMS2 except for those in brain tumor. Although frameshift mutation was not found in MSH6 gene, histological expression of MSH6 was patchy in primary colon carcinoma and was completely lost in the metastatic site in liver. MSH6 expression in gastric carcinoma, a coincidental cancer in this case, was intact. An abnormal (C)8 region was identified by the cloned PCR of colon and liver tumors but not from gastric cancer. Frameshift mutation in a (C)8 tract in exon 5 of the MSH6 gene was also detected in liver metastasis., Conclusion: This case supports a plausible mechanism, proposed by a previous literature, for the reduced expression of MSH6 in a somatic mutation manner, which might preferentially happen in colon cancer rather than in stomach carcinoma in MLH1/PMS2-deficient type of Turcot's syndrome type 1.

Aim: Although rectal neuroendocrine tumors (NETs) are considered to be rare low-grade malignancies when lymph node metastasis (LNM) is present, their degree of malignancy is comparable to that of colorectal cancer (CRC). However, it remains unclear as to which patients require radical lymph node dissection. The aim of this study was to elucidate the risk factors for LNM and develop a risk-scoring system for LNM to help determine appropriate therapeutic approaches., Methods: In this study, we examined 103 patients with rectal NETs who underwent local resection (n = 55) or radical resection with LN dissection (n = 48). We evaluated each pathological feature, including the depth of submucosal invasion (SM depth) and tumor budding grade., Results: According to our univariate analyses and previous reports, the significant five risk factors for LNM were weighted with point values: 2 points for tumor size ≥ 15 mm and muscularis invasion, and 1 point each for SM depth ≥ 2000 µm, positive lymphovascular invasion, budding grade 3, and vertical margin. The area under the receiver operating curve for the scoring system was 0.899 (95% CI: 0.843-0.955). When a score of 2 was used as the cut-off value, the sensitivity and specificity for the prediction of LNM were 100% and 72.1%, respectively., Conclusions: The risk-scoring system for LNM of rectal NETs showed high diagnostic performance. Using this risk-scoring system, it is possible to predict the risk of LNM and thereby potentially avoid unnecessary surgery. Further prospective external validation studies should be performed. The study was registered in the Japanese Clinical Trials Registry as UMIN000036658., Competing Interests: Conflict of Interest: The authors declare no conflicts of interest in association with the present study., (© 2020 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

Background: Interstitial pneumonia (IP) is one of the most common and poor prognostic comorbidities in patients with small cell lung cancer (SCLC). The pharmacotherapy for SCLC occasionally induces fatal acute exacerbation of comorbid IP, especially in patients with idiopathic pulmonary fibrosis (IPF). Safe and effective pharmacotherapy is of greater importance in patients with SCLC and IPF, because SCLC presents a poor prognosis without systemic treatment. Nintedanib is expected to restrain acute exacerbation and present angiogenesis-inhibiting effects., Methods: The TORG1835/NEXT-SHIP study is the world's first multi-center, single-arm, phase II trial for unresectable limited or extensive disease SCLC with IPF. The patients receive carboplatin (area under the curve 5, day 1), etoposide (<75 years old: 100 mg/m 2 ; ⩾75 years old: 80 mg/m 2 ; days 1-3), and nintedanib (150 mg twice a day) every 3 weeks for four cycles. After completion or discontinuation of carboplatin plus etoposide, the patients continue nintedanib until the discontinuation criteria are met. The primary endpoint is the incidence of acute exacerbation of IPF at 28 days after last administration of cytotoxic anti-cancer agents. We set an expected value of 5% and a threshold value of 20%. Taking statistical points (a/b errors: 0.05/0.75) and ineligible patients into account, the sample size was set at 33. The key secondary endpoints are time to first acute exacerbation of IPF, overall response rate, progression-free survival, overall survival, and toxicities., Discussion: Because there is no clinical trial for unresectable SCLC with IPF, our study would provide a major impact on clinical practice., Trial Registration: Japan Registry of Clinical Trials, jRCTs031190119, registered date: October 18, 2019 - Retrospectively registered, https://jrct.niph.go.jp/en-latest-detail/jRCTs031190119., Competing Interests: Conflict of interest: SI received honoraria from Boehringer Ingelheim. TO received honoraria and research funding from Boehringer Ingelheim. TK received honoraria from Boehringer Ingelheim, Takeda Pharmaceutical, Pfizer, and Bristol-Myers Squibb; and research funding from Pfizer and Bristol-Myers Squibb. HK received honoraria from Boehringer Ingelheim and Bristol-Myers Squibb; and research funding from Boehringer Ingelheim. TI received honoraria from Boehringer Ingelheim. TY received honoraria from Boehringer Ingelheim, Takeda Pharmaceutical, and Pfizer; and research funding from Boehringer Ingelheim and Takeda Pharmaceutical. HO received research funding from Bristol-Myers Squibb and Takeda Pharmaceutical. TM declared no potential conflicts of interest with any companies or organizations whose products or services might be discussed in this article., (© The Author(s), 2020.)

Background: Approximately 10% of patients with non-small cell lung cancer (NSCLC) are complicated with comorbid interstitial pneumonia (IP) with a poor prognosis. The pharmacotherapy for advanced lung cancer occasionally induces fatal acute exacerbation of pre-existing IP. Due to the lack of prospective studies, there is an urgent need to establish a safe and effective pharmacotherapy, especially for second-line or later settings. Atezolizumab, an anti-programmed cell death-ligand 1 antibody, is thought to be the safest candidate for second-line therapy among various immune checkpoint inhibitors. Moreover, compared with patients without IP, the patients with comorbid IP may have higher tumor mutation burden (TMB) or microsatellite instability (MSI), which are partly associated with a more favorable response to immune checkpoint inhibitors., Methods: The Thoracic Oncology Research Group 1936/AMBITIOUS study is an ongoing, multicenter, single-arm, phase II trial to assess the safety and efficacy of atezolizumab for pretreated advanced/recurrent patients with NSCLC complicated with idiopathic, chronic fibrotic IP with a forced vital capacity of >70%. The patients will receive atezolizumab (1200 mg, day 1) every 3 weeks until the discontinuation criteria are met. The primary end point of this study is the 1-year survival rate, and a sample size of 38 patients is set. As a translational research, we will perform the analysis of TMB, somatic mutations, and MSI for nucleic acids extracted from archival tumor samples., Discussion: Since there is no standard second-line or later therapy of advanced NSCLC with IP, the results of this study are expected to have a major impact on clinical practice., Trial Registration: Japan Registry of Clinical Trials, jRCTs031190084, registered 26 August 2019 - retrospectively registered, https://jrct.niph.go.jp/en-latest-detail/jRCTs031190084., Competing Interests: Conflict of interest statement: S Ikeda, T Kato, H Kenmotsu, S Iwasawa, and T Yamanaka received honoraria from Chugai Pharmaceutical. T Kato, H Kenmotsu, S Iwasawa, T Yamanaka, and H Okamoto received research funding from Chugai Pharmaceutical. T Ogura, T Iwasawa, R Kasajima, Y Miyagi, and T Misumi declare no potential conflicts of interest with any companies or organizations whose products or services might be discussed in this article., (© The Author(s), 2020.)

Background/objectives: Severe acute pancreatitis (SAP) has a high mortality rate despite ongoing attempts to improve prognosis through a various therapeutic modalities. This study aimed to delineate etiology-based routes that may guide clinical decisions for the treatment of SAP., Methods: Using data from a recent retrospective multicenter study in Japan, we analyzed the association between clinical outcomes, mainly in-hospital mortality and pancreatic infection, and various etiologies while considering confounding factors. We performed additional multivariate analyses and built decision tree models., Results: The 1097 participating patients were classified into the following groups by etiology: alcohol (n = 436, 39.7%); cholelithiasis (n = 230, 21.0%); idiopathic (n = 227, 20.7%); and others (n = 204, 18.6%). Mortality at hospital discharge was 8.4%, 12.2%, 16.7%, and 16.2% in the alcohol, cholelithiasis, idiopathic, and others groups, respectively. According to multivariable analysis, early enteral nutrition (EN) was significantly associated with reduced in-hospital mortality only in the cholelithiasis group. However, there was a consistent association between age and the need for mechanical ventilation and increased mortality, regardless of etiology. Our decision tree models presented different contributing factors depending on the etiology and patient background. Interaction analysis showed that EN and the use of prophylactic antibiotics may influence these results differently according to etiology., Conclusions: No study has yet used comprehensive models to investigate etiology-related prognostic factors for SAP; our results can, therefore, be used as a reference for improving clinical decisions., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

We aimed to investigate the optimal range of gestational weight gain (GWG) for Japanese underweight (body mass index <18.5 kg/m 2 ) women using the Japanese Birth Registry System. The study subjects included underweight women who were divided into groups according to the GWG recommendations of the Ministry of Health, Labour and Welfare (MHLW) (9-12 kg): <9.0 kg, group A; 9-12 kg, group B; and >12 kg, group C. The subjects were then classified according to the recommendations of the Institute of Medicine (IOM) (12.7-18.1 kg): <12.7 kg, group D; 12.7-18.1 kg, group E; and >18.1 kg, group F. In total, 148,135 cases were analysed. The frequencies of small for gestational age, preterm delivery, and caesarean delivery were as follows: 19.3%, 22.7%, and 28.5% for group A; 11.7%, 8.7%, and 22.8% for group B; 8.0%, 4.9%, and 21.5% for group C; 15.0%, 14.7%, and 25.2% for group D; 8.0%, 5.3%, and 21.5% for group E; and 7.0%, 5.5%, and 25.0% for group F, respectively. These results indicated that groups C and E had the best outcomes. Therefore, the IOM guidelines seem more appropriate than the MHLW guidelines. Therefore, the MHLW recommended GWG guidelines require revision.

A 76-year-old man was diagnosed with type 1 early gastric cancer. Attempted ESD on the lesion resulted in perforation, and distal gastrectomy with D1+dissection was performed. After 1 year and 6 months, a mass measuring 2.4 cm appeared in the abdominal wall. Cytological examination revealed adenocarcinoma, and the patient was diagnosed with abdominal wall metastasis of gastric cancer. There were no evidences of recurrence in the other organs, and extraction was performed. After 6 months, 1 year, and 2 years, the same metastases were found in the abdominal wall, and repeated extractions were performed. All 4 masses had resulted from the metastasis of gastric cancer, but the patient has been alive without recurrence for 1 year and 6 months after the surgery.

Background: A retrospective study was performed to evaluate the predictive factors for performing curative-intent surgery and prognostic factors for long-term survival of patients undergoing surgery for stage IV gastric cancer., Patients and Methods: Between 2001 and 2017, 271 patients with stage IV gastric cancer with distant metastasis who underwent systemic chemotherapy were enrolled. Logistic regression analysis was performed to evaluate predictive factors for curative-intent surgery. Cox proportional hazards regression model was applied for patients who were subsequently treated with curative-intent surgery to identify prognostic factors for long-term survival., Results: Curative-intent surgery was performed in 48 patients (17.7%). Median survival time was significantly longer in the surgery group than in the nonsurgery group (53 vs. 11 months, p < 0.0001). R0 resection was performed in 35 patients (72.9%). The three-year overall survival (OS) rates of the R0, R1, and R2 surgery groups were 75.4%, 33.3%, and 25.0%, respectively (p = 0.0002). Logistic regression analysis revealed that lymphogenous distant metastasis alone (odds ratio = 3.276, p = 0.004), positive lavage cytology alone (6.394, 0.014), doublet or triplet chemotherapy (4.064, 0.034), and high Glasgow prognostic score (0.276, 0.001) were independent predictive factors for performing curative-intent surgery. Among patients undergoing surgery, the Cox proportional hazards regression model for OS showed that R0 surgery was an independent prognostic factor for favorable OS (hazard ratio 0.188, p = 0.022)., Conclusions: Patients with lymphogenous distant metastasis alone, P0CY1 alone, good immunonutritional status, and doublet/triplet chemotherapy are candidates for performing effective curative-intent surgery. R0 surgery is crucial for improving long-term survival after surgery.

Background/aim: To evaluate whether factors related to the clinical staging of lymph node (LN) metastasis diagnosed by 18 F-fluorodeoxyglucose positron-emission tomography/computed tomography (PET/CT) correspond to poor survival in esophageal squamous cell cancer (ESCC) patients treated with concurrent chemoradiotherapy (CCRT)., Patients and Methods: A total of 69 patients with curative intent and no prior treatment for ESCC or simultaneous treatment for synchronous cancers were investigated. A maximum standardized uptake value (SUVmax) on the highest image pixel in the LN ≥2.5 was considered positive. Location of the involved LN and its impact on survival were analyzed., Results: In the univariate analysis of location, metastasis of the abdominal site, regional abdominal LN, and left gastric LN station negatively affected overall survival (OS) and disease-free survival (DFS). Other adverse clinical factors influencing OS included T4, clinical stage IVA and body mass index <21.2. In terms of DFS, a further unfavorable factor was primary tumor SUVmax ≥10.4. Abdominal site LN metastasis affected both OS and DFS in multivariate analysis., Conclusion: LN metastasis diagnosed by PET/CT in abdominal sites was an independent predictor affecting both OS and DFS in ESCC patients who underwent curative CCRT., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The Y-AIDA study was designed to investigate the renal- and home blood pressure (BP)-modulating effects of add-on dapagliflozin treatment in Japanese individuals with type 2 diabetes mellitus (T2DM) and albuminuria., Methods: We conducted a prospective, multicenter, single-arm study. Eighty-six patients with T2DM, HbA1c 7.0-10.0%, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m 2 , and urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g creatinine (gCr) were enrolled, and 85 of these patients were administered add-on dapagliflozin for 24 weeks. The primary and key secondary endpoints were change from baseline in the natural logarithm of UACR over 24 weeks and change in home BP profile at week 24., Results: Baseline median UACR was 181.5 mg/gCr (interquartile range 47.85, 638.0). Baseline morning, evening, and nocturnal home systolic/diastolic BP was 137.6/82.7 mmHg, 136.1/79.3 mmHg, and 125.4/74.1 mmHg, respectively. After 24 weeks, the logarithm of UACR decreased by 0.37 ± 0.73 (P < 0.001). In addition, changes in morning, evening, and nocturnal home BP from baseline were as follows: morning systolic/diastolic BP - 8.32 ± 11.42/- 4.18 ± 5.91 mmHg (both P < 0.001), evening systolic/diastolic BP - 9.57 ± 12.08/- 4.48 ± 6.45 mmHg (both P < 0.001), and nocturnal systolic/diastolic BP - 2.38 ± 7.82/- 1.17 ± 5.39 mmHg (P = 0.0079 for systolic BP, P = 0.0415 for diastolic BP). Furthermore, the reduction in UACR after 24 weeks significantly correlated with an improvement in home BP profile, but not with changes in other variables, including office BP. Multivariate linear regression analysis also revealed that the change in morning home systolic BP was a significant contributor to the change in log-UACR., Conclusions: In Japanese patients with T2DM and diabetic nephropathy, dapagliflozin significantly improved albuminuria levels and the home BP profile. Improved morning home systolic BP was associated with albuminuria reduction. Trial registration The study is registered at the UMIN Clinical Trials Registry (UMIN000018930; http://www.umin.ac.jp/ctr/index-j.htm ). The study was conducted from July 1, 2015 to August 1, 2018.

Hepatic pseudolymphoma is a very rare benign reactive lymphoid hyperplasia associated with autoimmunity and chronic inflammatory liver diseases such as primary biliary cirrhosis and may mimic hepatocellular carcinoma. This diagnosis should be suspected in female with a suspicious single tumor. Close monitoring is needed in view of its premalignant nature., Competing Interests: None declared., (© 2019 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Background/aims: Strategies for an effective intervention after chronic kidney disease (CKD) screening have not been well examined. We describe the rationale and design of a protocol of a pragmatic randomized controlled trial (RCT) to test the effect of a behavioral intervention using the nudge approach in behavioral economics on CKD patients' visiting behaviors to physicians and change in their kidney function after CKD screening., Methods: The RCT will include CKD patients (N = 4500) detected at screening (estimated glomerular filtration rate [eGFR] <60 mL/min/1.74 m 2 or urine protein ≥1+), aged 40-63 years. The two intervention groups will receive a "usual letter" and "nudge-based letter," while the control group will only receive a conventional follow-up. Our primary outcome is proportion of patients' visiting physicians for 6 months after the intervention; the secondary outcome is change in the eGFR at 2 years after the intervention., Results: We developed an efficient intervention program after CKD screening and designed the pragmatic RCT to assess its effectiveness in the real world. Our trial is unique in that it investigates the effect of the nudge approach in behavioral economics. By the end of 2018, we have enrolled 1,692 participants, and randomized 677 participants into the usual letter group, 677 participants into the nudge-based letter group, and 338 participants into the control group. We have confirmed that health checkup data could identify a large number of eligible participants., Conclusion: The trial's results will contribute to filling in the gap between screening and subsequent medical interventions for preventing CKD progression.

Introduction: This study evaluated efficacy and safety/tolerability of roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, in Japanese anemic non-dialysis-dependent chronic kidney disease (NDD-CKD) patients., Methods: In this phase 2, double-blind, 24-week study, NDD-CKD patients were randomized to oral placebo or roxadustat (50, 70, or 100 mg) three times weekly (TIW) for 6 weeks followed by dose adjustments to maintain hemoglobin (Hb) at 10-12 g/dL for 18 weeks; patients meeting pre-defined criteria were re-randomized to TIW or once-weekly dosing. The primary end point was rate of rise of Hb (g/dL/week) during the first 6 weeks; secondary end points included response rate (Hb ≥ 10.0 g/dL and increase in Hb from baseline ≥ 1 g/dL) and mean Hb and change from baseline in Hb at weeks 18-24. The main safety outcomes were vital signs, laboratory test results, electrocardiograms, and frequency of treatment-emergent adverse events., Results: Of 107 patients randomized, 83 completed the study. The mean (SD) rate of rise of Hb during the first 6 weeks was - 0.052 (0.142) for placebo and + 0.200 (0.160), + 0.453 (0.256), and + 0.570 (0.240) for roxadustat 50-, 70-, and 100-mg TIW groups, respectively (p < 0.001). Response rate was 14.8% for placebo and 81.5%, 100%, and 100% for roxadustat TIW groups (p < 0.001). Change in Hb from baseline at weeks 18-24 was - 0.17 (0.61) for placebo and + 1.10 (0.71), + 1.33 (0.82), and + 1.55 (0.88) g/dL for roxadustat TIW groups (p < 0.001). No deaths or major adverse cardiac events occurred with roxadustat., Conclusion: Roxadustat was well tolerated and effective in correcting Hb levels within 6 weeks in Japanese anemic NDD-CKD patients., Trial Registration: ClinicalTrials.gov: NCT01964196. Registered 15 October 2013 (retrospectively registered)., Funding: Astellas Pharma Inc.

We encountered 2 cases of colorectal liver metastasis with biliarydilatation mimicking cholangiocarcinoma. Case 1: A 70- year-old male patient, who was diagnosed with colorectal cancer and underwent transverse colectomy3 years prior, was preoperativelydiagnosed with cholangiocarcinoma with biliarydilatation of the medial and lateral segments. He underwent left hemi-hepatectomy. The pathological diagnosis was colorectal liver metastasis with intra-biliarytumor thrombosis. Case 2: A 67-year-old male patient was diagnosed with descending colon cancer and cholangiocarcinoma with biliarydilatation of the medial segment. He underwent left hemi-colectomyand left hemi-hepatectomy. The pathological diagnosis was descending colon cancer and colorectal liver metastasis with biliaryinfiltration. The immunopathological findings showed double positivityfor CK20 and CDX2 antibodies and negativityfor CK7 antibodyin these cancer lesions.

Introduction: The frequency of small bowel bleeding is relatively low and the process for the diagnosis and treaVtment remains difficult. Here, we report a case of massive small bowel bleeding due to arteriovenous malformation (AVM), treated by a combination of double-balloon endoscopy and laparoscopic resection., Presentation of Case: A 59-year-old man was admitted to our hospital due to a hemorrhagic stool. The patient presented transient hemorrhagic shock and contrast-enhanced CT revealed a hyper-vascularized tumor in the small bowel. India ink tattooing for the responsible lesion with double-balloon endoscopy was performed. The tattooed lesion was easily confirmed during the subsequent laparoscopic observation and segmental resection was done. Pathological examination showed arteriovenous malformation of the small bowel., Discussion: Prior to laparoscopic resection, the localization of the responsible area might be a significant consideration when the lesion is invisible. Endoscopic marking with DBE enables intraluminal detection and laparoscopic observation from the serosal side., Conclusion: Preoperative marking with the use of double-balloon endoscopy followed by laparoscopic resection might be an optimal option for the treatment of massive small intestinal bleeding., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The aim of this study was to predict increased alcohol and tobacco use in Fukushima nuclear power plant (NPP) workers 3 years after a nuclear disaster., Methods: Surveys were conducted in two postdisaster waves (Wave 1: 2 to 3 months; Wave 2: 32 months). Adjusted risk ratio (aRR) was computed to assess the covariates of increased alcohol and tobacco use in Wave 2., Results: Increased alcohol use was associated with age of 29 years or less [aRR (95% confidence interval (95% CI): 1.26 (1.01 to 1.57)], major property loss [1.25 (95% CI 1.02 to 1.55)], and high posttraumatic stress responses (PTSRs) [1.34 (95% CI 1.08 to 1.67)] in Wave 1. Increased tobacco use was associated with age of 29 years or less [1.46 (95% CI 1.12 to 1.90)] and high PTSR [1.62 (95% CI 1.25 to 2.10)] in Wave 1 (P < 0.05)., Conclusion: The workers' increased alcohol and tobacco use were predicted by major property loss (alcohol), age of 29 years or less, and high PTSR (alcohol/tobacco) in Wave 1.

Background and Aims: The Baveno VI criteria enable non-invasive screening for esophageal varices. However, these criteria were established based on studies examining a large proportion of patients with viral hepatitis and relatively few patients with non-alcoholic fatty liver disease (NAFLD). Furthermore, because vibration-controlled transient elastography (VCTE) has a high incidence of measurement error, improved criteria are needed. We aimed to develop criteria based on magnetic resonance elastography (MRE) even among patients with NAFLD., Methods: We performed a cross-sectional analysis of patients who had undergone MRE and/or VCTE as well as an esophagogastroduodenoscopy. The patients were classified as having either a low risk or a high risk of varices. The optimal cut-offs for ruling out esophageal varices were calculated for the MRE and VCTE liver stiffness measurement (LSM), the platelet count in an estimation cohort, and the cut-offs were then evaluated using validation cohorts composed of patients who had undergone only MRE or VCTE., Results: The study included 627 patients (39% with NAFLD). The optimal cut-off values for the MRE-LSM and the platelet count were 4.2 kPa and 18.0 × 10 4 /μL, respectively. An MRE-LSM of 4.2 kPa plus a platelet count of 18.0 × 10 4 /μL had a negative predictive value of 1.00 for both low-risk plus high-risk varices as well as for high-risk varices in a validation cohort, enabling the presence of varices to be ruled out., Conclusions: Magnetic resonance elastography might enable a safer avoidance of screening endoscopy, with a smaller measurement error, among patient populations with a high prevalence of NAFLD., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

A 71-year-old man was diagnosed as having Type 2 gastric cancer(tub2, HER2-negative). Abdominal computed tomography( CT)revealed bulky metastatic lymph nodes around the stomach and para-aorta(No. 16a2, b1). Our clinical diagnosis was cT4a(SE)N+M1(PAN), cStage Ⅳb, and SOX therapy was immediately administered. After 3 courses of chemotherapy, the treatment effect was PR, and after 6 courses, the patient was diagnosed with ycT2(MP)N0M0, ycStageⅠB. No Grade 2 or higher adverse events were observed during chemotherapy. At this stage, we determined that radical resection was feasible; thus, distal gastrectomy and D3 dissection(para-aortic lymph node dissection)were performed. No cancer cells were found in the primary lesion on histopathology. The histological response of the primary lesion was Grade 3, and the lymph node was Grade 2b. On follow-up observation, the patient is alive without tumor recurrence at 1 year postoperatively.

Although many anticancer agents for gastric cancer have been developed, the prognosis for many patients remains poor. Recently, costimulatory immune molecules that reactivate antitumor immune responses by utilizing the host immune system have attracted attention as new therapeutic strategies. CD137 is a costimulatory molecule that reportedly potentiates the antitumor activity of tumor-targeting monoclonal antibodies (mAbs) by enhancing antibody-dependent cellular cytotoxicity. However, it remains unclear whether CD137 stimulates tumor-regulatory activity in gastric cancer. In this study, we investigated the antitumor effects of CD137 stimulation on gastric cancer cells administered tumor-targeting mAbs. Our results showed that human natural killer (NK) cells were activated by expressing CD137 after encountering trastuzumab-coated gastric cancer cells, and that stimulation of activated NK cells in the presence of trastuzumab and recombinant human CD137 ligand (rhCD137L) enhanced cytotoxicity and release of cytokines (IFN-γ, TNF, granzyme A, or granzyme B) as compared with activated NK cells with trastuzumab alone (p < 0.05). By combination treatment with rhCD137L, similar effects were obtained regarding cancer cell cytotoxicity in the presence of cetuximab (p < 0.01). Moreover, we revealed that CD137 expression was dependent upon the affinity between the Fc portion of the antibodies and FcγRIIIa of NK cells based on results indicating that human IgG1 and IgG3 subclasses enhanced CD137 expression (p < 0.001). These results confirmed that FcγRIIIA polymorphisms (158 V/V) enhanced CD137 expression to a greater degree than 158 F polymorphisms (p = 0.014). Our results suggested that CD137 stimulation could promote the effects of tumor-targeting mAbs in gastric cancer, and that further investigation of antibody binding affinity and in vivo activities might improve therapeutic strategies related to the treatment of gastric cancer patients., Competing Interests: The authors have declared that no competing interests exist.

Aim: To evaluate whether patients with T1 esophageal squamous cell carcinoma receiving definitive radiotherapy can be managed without concurrent chemotherapy, and the role of 18 F-fluorodeoxyglucose positron-emission tomography with computed tomography (FDG-PET/CT) in demonstrating local control (LC)., Patients and Methods: Twenty-four out of 37 patients with newly-diagnosed T1 EC treated with definitive radiotherapy between July 2009 and July 2016 were retrospectively analyzed. FDG-PET/CT was performed before treatment. Eleven patients were assigned to a concurrent chemoradiotherapy (CRT) group. Thirteen were placed in a no-CRT group. The two groups were compared and univariate analysis of clinical factors influencing the prognosis in each group was conducted., Results: Mean radiotherapy doses were 59.2 Gy in the no-CRT group and 55.5 Gy in the CRT group (p=0.025). Overall survival, disease-free survival, and LC rates at 2 years were lower in the no-CRT group compared to the CRT group. Disease-free survival and LC rates at 2 years were significantly lower in the patients with FDG-avid primary tumor in the no-CRT group (p=0.002 and p=0.002, respectively). All patients with FDG-avid primary tumors in the no-CRT group developed local recurrence., Conclusion: It is important to note that all patients with FDG-avid primary tumor in the no-CRT group developed local recurrence. This would suggest that concurrent chemotherapy is an integral part of disease management in patients with T1 esophageal squamous cell carcinoma., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Inferior vena cava (IVC) aneurysms are extremely rare. Patients can be asymptomatic, have thrombosis, rupture, or pulmonary embolism. Thrombosis of the IVC aneurysm may mimic a retroperitoneal tumor. Surgical treatment of abdominal venous aneurysms with thrombosis is warranted and is necessary for the management of intraoperative bleeding and thrombosis.

Longitudinal binary data are commonly encountered in clinical trials. Multiple imputation is an approach for getting a valid estimation of treatment effects under an assumption of missing at random mechanism. Although there are a variety of multiple imputation methods for the longitudinal binary data, a limited number of researches have reported on relative performances of the methods. Moreover, when focusing on the treatment effect throughout a period that has often been used in clinical evaluations of specific disease areas, no definite investigations comparing the methods have been available. We conducted an extensive simulation study to examine comparative performances of six multiple imputation methods available in the SAS MI procedure for longitudinal binary data, where two endpoints of responder rates at a specified time point and throughout a period were assessed. The simulation study suggested that results from naive approaches of a single imputation with non-responders and a complete case analysis could be very sensitive against missing data. The multiple imputation methods using a monotone method and a full conditional specification with a logistic regression imputation model were recommended for obtaining unbiased and robust estimations of the treatment effect. The methods were illustrated with data from a mental health research.

We report a case of pneumonectomy followed by radical pancreatectomy after oral administration of TS-1 for pancreatic cancer with complications ofa lung tumor. The patient was a 66-year-old woman. A pancreatic tail tumor and 2 lung nodules were detected on CT scans, and were diagnosed as pancreatic cancer and metastatic lung cancer. During a total of1 1 courses ofTS -1 therapy, the pancreatic tumor tended to contract, but both pulmonary nodules remained unchanged. Due to differences in treatment effect, double cancers of the lung and pancreas were suspected, rather than metastatic lung cancers. We performed a VATS partial resection of the left lower lobe for diagnostic therapy. The pathological diagnosis revealed an inflammatory myofibroblastic tumor and a primary lung cancer. We diagnosed that a radical pancreatectomy was possible and performed distal pancreatectomy. Pathological diagnosis confirmed an invasive pancreatic ductal carcinoma. Oral administration ofTS -1 was performed as adjuvant chemotherapy after surgery. Liver metastasis was observed 10 months after pancreatectomy, and GEM therapy was initiated. Peritoneal dissemination was observed at 2 years following pancreatectomy, and the patient died at 2 years and 9 months. TS-1 therapy for synchronous lung tumors and pancreatic cancer with careful observation allowed for a definitive radical resection. This method was an effective treatment for lung nodules with pancreatic cancer.

A 66-year-old man was diagnosed with unresectable distal gastric cancer due to a locally advanced tumor and peritoneal dissemination. After gastrojejunostomy, he underwent S-1 plus cisplatin combination chemotherapy. After 2 courses of chemotherapy, weekly paclitaxel(PTX)was administered as second-line chemotherapy owing to tumor growth(PD). Although 4 courses of chemotherapy had been administered, he developed carcinomatous peritonitis and was hospitalized urgently. Despite diuretic therapy and drainage, the malignant ascites was not adequately controlled. However, he started ramucirumab (RAM)plus PTX chemotherapy as third-line therapy and ascites subsequently reduced, he regained oral intake and was discharged from hospital.