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The impacts of chemotherapy on patients with malignant gastrointestinal obstructions remain unclear, and multicenter evidence is lacking.To evaluate the effectiveness and safety of chemotherapy in patients with unresectable malignant gastrointestinal obstructions.We conducted a multicenter retrospective cohort study that compared the chemotherapy group who received any chemotherapeutics after interventions, including palliative surgery or self-expandable metal stent placement, for unresectable malignant gastrointestinal obstructionIn total, 470 patients in the chemotherapy group and 652 patients in the BSC group were analyzed. During the follow-up period of 54.1 mo, the median overall survival durations were 19.3 mo in the chemotherapy group and 5.4 mo in the BSC group (log-rank test,Chemotherapy after interventions for unresectable malignant gastrointestinal obstruction was associated with increased overall survival and patency duration.

Background: Oesophageal cancer comprises 2 different histological variants: oesophageal squamous-cell carcinoma (ESCC) and adenocarcinoma (EAC). While there are multiple therapeutic options for both types, patients with advanced or metastatic oesophageal cancer still suffer from poor prognosis. Aims: The study aimed to examine the association between the risk of oesophageal cancer and medications and to estimate the chemopreventive effects of commonly used drugs. Methods: A multicentre retrospective cohort study was conducted using data from 9 hospital databases of hospitalized patients between 2014 and 2019. The primary outcomes were ESCC and EAC. The association of oesophageal cancer with drug use and clinical factors was evaluated. Odds ratios (ORs) were adjusted for age, sex, Charlson comorbidity index scores, and smoking with/without gastro-oesophageal reflux disease. Results: The use of proton pump inhibitors (PPIs) (adjusted OR [aOR] 0.48, p < 0.0001), aspirin (aOR 0.32, p < 0.0001), cyclooxygenase-2 inhibitor (COX2I) (aOR 0.70, p = 0.0005), steroid (aOR 0.19, p < 0.0001), statin (aOR 0.43, p < 0.0001), and metformin (aOR 0.42, p < 0.0001) was associated with a lower risk of ESCC than that in non-use. The use of aspirin (aOR 0.33, p = 0.0006) and steroids (aOR 0.54, p = 0.022) was associated with a lower risk of EAC than that in non-use. Conclusion: COX2Is, statins, metformin, and PPIs could help in prevention of ESCC, and aspirin and steroids may be chemopreventive for both types of oesophageal cancer.

Purpose CT colonography enables three-dimensional measurement of colon length. However, previous studies using CT colonography have not examined the association with gender, age, physique, a history of laparotomy and bowel habits, all possible contributory factors to colon length. The aim of this study is to investigate factors associated with colon length. Materials and methods We conducted a post hoc analysis based on data obtained from a previous multi-center trial including 321 patients with positive fecal immunochemical tests who underwent CT colonography. Colon length was measured using a computer-generated center line and was divided at the iliac crest level into the distal and proximal colons. Bowel habits were classified into three groups: A—daily; B—once every 2 or 3 days; and C—less than once in 3 days. Statistical comparison was made using one-way ANOVA with Bonferroni’s correction. Results A total of 295 patients were analyzed. The entire colon length (cm, mean ± standard deviation) of individual patients was 150.3 ± 18.5 cm and ranged from 109.7 to 195.9 cm. The female colon was significantly longer than the male colon (154.3 ± 18.1 cm vs. 147.1 ± 18.3 cm; p = 0.022). Colon length showed trends associated with age (p = 0.18) and a history of laparotomy (p = 0.14). According to bowel habits, the entire colon measured 147.4 ± 17.9 in group A, 154.7 ± 18.5 in group B and 158.6 ± 18.3 in group C, and significant differences were observed for “A vs. C” (p = 0.002) and “A vs. B” (p = 0.014). In subgroup analysis by colon segment, the proximal colon trended similarly to the entire colon while there were no trends for the distal colon. Conclusions This study has clearly demonstrated that bowel habits and gender both correlate with the length of the entire colon measured by CT colonography, and in particular, the proximal colon. Secondary abstract Using CT colonography, we measured the colon length in 295 patients. The entire colon length was 150.3 ± 18.5 cm on average. Females and constipated (less frequent defecation) patients have a significantly longer colon, and in particular, the proximal colon. Colon length showed trends associated with age and a history of laparotomy.

The aim of this feasibility study was to evaluate the diagnostic accuracy of ultra-low-dose CT colonography using iterative reconstruction algorithms with reference to standard colonoscopy.Prior to this study, a phantom study was performed to investigate the optimal protocol for ultra-low-dose CT colonography. A total of 206 patients with average/high risk of colorectal cancer were recruited. After undergoing full bowel preparation, the patients were scanned in the prone and supine positions with the CT conditions set to 120 kV, standard deviation 45 to 50, and an adaptive iterative reconstruction algorithm applied. Two expert readers read the images independently. The main outcome measures were the per-patient and per-polyp accuracies for the detection of polyps ≥ 10 mm, with colonoscopy results as the reference standard.Two hundred patients (102 females, mean age 67.5 years) underwent both ultra-low-dose CT colonography and colonoscopy on the same day. The mean radiation exposure dose was 0.64 ± 0.34 mSv. On colonoscopy, 39 patients had 45 polyps ≥ 10 mm (non-polypoid morphology 7), including 4 cancers. Per-patient sensitivity, specificity, and accuracy of CT colonography for polyps ≥ 10 mm were 0.74, 0.96, and 0.92 for reader one, and 0.74, 0.99, and 0.94 for reader two, respectively. Per-polyp sensitivities for polyps ≥ 10 mm were 0.73 for reader one and 0.71 for reader two. On subgroup analysis by morphology, non-polypoid polyps ≥ 10 mm were not detected by both readers.Extreme ultra-low-dose CT colonography had an insufficient diagnostic performance for the detection of polyps ≥ 10 mm, because it was unable to detect non-polypoid polyps. This study showed that the problem with ultra-low-dose CT colonography was the lack of detectability of small-size polyps, especially non-polypoid polyps. To use ultra-low-dose CT colonography clinically, it is necessary to resolve the problems identified by this study.

Recent studies have suggested that right- and left-sided colorectal cancers (CRCs) are molecularly distinct. In this study, we examined the association between the risk of right- and left-sided CRC and drug use to estimate their chemopreventive effects METHODS: This multicenter retrospective cohort study was conducted using the data of hospitalized patients between 2014 and 2019 from nine hospital databases. The primary outcomes were right- and left-sided CRC. We evaluated the association of CRCs with drug use and clinical factors. Odds ratios adjusted for age, sex, Charlson Comorbidity Index scores, and smoking status were calculated. We also compared the transcriptional profiling in precancerous lesions, including sessile serrated lesions (SSLs) RESULTS: A total of 307,938 patients, including 2745 with right-sided CRC and 4819 with left-sided CRC, were analyzed. The use of nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, cyclooxygenase-2 inhibitors, and steroids was associated with a lower risk of both right- and left-sided CRCs. In contrast, statins, other lipid-lowering agents, and metformin were associated with a lower risk of left-sided CRC. Transcriptomic analysis showed that SSL, which predominantly develops in the right colon, was associated with a lower expression of lipid metabolism-related genes.Targeting lipid metabolism may be useful for chemoprevention of left-sided CRCs, while development of right-sided CRCs may be independent of this pathway.

Simple Summary Helicobacter pylori is the most important cause of gastric cancer, and its eradication reduces the incidence of gastric cancer after endoscopic resection. However, incidence of metachronous gastric cancer is still high. More studies are needed to identify other chemopreventive drugs that may reduce the incidence of this disease. In this study, we focused on the alteration of the intragastric microbiome and examined the association between the use of antibiotics and probiotic drugs and risk of metachronous gastric cancer. Our findings suggest that the gut microbiome is associated with metachronous gastric cancer development. Abstract Metachronous gastric cancer often occurs after endoscopic resection. Appropriate management, including chemoprevention, is required after the procedure. This study was performed to evaluate the association between medication use and the incidence of metachronous gastric cancer after endoscopic resection. This multicenter retrospective cohort study was conducted with data from nine hospital databases on patients who underwent endoscopic resection for gastric cancer between 2014 and 2019. The primary outcome was the incidence of metachronous gastric cancer. We evaluated the associations of metachronous gastric cancer occurrence with medication use and clinical factors. Hazard ratios were adjusted by age and Charlson comorbidity index scores, with and without consideration of sex, smoking status, and receipt of Helicobacter pylori eradication therapy during the study period. During a mean follow-up period of 2.55 years, 10.39% (140/1347) of all patients developed metachronous gastric cancer. The use of antibiotics other than those used for H. pylori eradication was associated with a lower incidence of metachronous gastric cancer than was non-use (adjusted hazard ratio (aHR) 0.56, 95% confidence interval (CI) 0.38–0.85, p = 0.006). Probiotic drug use was also associated with a lower incidence of metachronous gastric cancer compared with non-use (aHR 0.29, 95% CI 0.091–0.91, p = 0.034). In conclusion, the use of antibiotics and probiotic drugs was associated with a decreased risk of metachronous gastric cancer. These findings suggest that the gut microbiome is associated with metachronous gastric cancer development.

Background and Aim Although gastric acid suppressants such as proton pump inhibitors (PPIs) and histamine‐2 receptor antagonists (H2RAs) are considered safe, the consequences of hypochlorhydria and hypergastrinemia caused by chronic use are unclear. This study aimed to investigate the association between the chronic use of gastric acid suppressants and high‐risk colorectal polyps, focusing on polyp size. Methods A population‐based, nested case–control study was conducted using data from the Japanese Diagnosis Procedure Combination database between 2014 and 2019. Cumulative PPI or H2RA use prior to polypectomy was evaluated during the study period. Endoscopic polypectomy was categorized as polypectomy 1 year prior to polypectomy. After adjusting for age, gender, and other confounders, a higher prevalence of high‐risk colorectal polyps was noted with PPI (OR: 2.67; 95% confidence interval: 2.37–3.01) and H2RA (OR: 1.86; 95% confidence interval: 1.52–2.26) use. Longer PPI or H2RA use was associated with increased risks of high‐risk colorectal polyps (P for trend, Chronic use of PPIs and H2RAs may be associated with high‐risk colorectal polyps. Requirements for long‐term gastric acid suppressant use should be reevaluated.

Background and Aim Proton pump inhibitors (PPIs) are a potential cause of gastric carcinogenesis after Helicobacter pylori eradication. Thus, appropriate management including chemoprevention is required. The aim of this study was to evaluate the association between nonsteroidal anti‐inflammatory drugs (NSAIDs) and the incidence of post‐eradication gastric cancer in PPI users. Methods A multicenter retrospective cohort study was conducted. Patients who used a PPI (≥30 days) after H. pylori eradication between 2014 and 2019 were analyzed in nine hospital databases. Gastric cancer incidence was a primary outcome, and their association with NSAIDs use and clinical factors was evaluated. Hazard ratios were adjusted by age, sex, smoking, and Charlson Comorbidity Index. Results During the mean follow‐up period of 2.38 years, 1.13% (31/2431) of all patients developed gastric cancer. The cumulative incidence of gastric cancer in PPI users was 0.25% at 1 year, 0.51% at 3 years, and 1.09% at 5 years in the NSAID users and 0.89% at 1 year, 2.32% at 3 years, and 3.61% at 5 years in nonusers. NSAIDs were associated with a lower gastric cancer risk (adjusted hazard ratio = 0.28, P = 0.005). No gastric cancer was observed in the cyclooxygenase‐2 inhibitor users (n = 256). NSAID use with high dose and long duration was significantly associated with a lower incidence of gastric cancer. Conclusion NSAIDs were associated with a 60% decrease in the gastric cancer incidence in H. pylori‐eradicated PPI users, with dose and duration response effects. NSAIDs may be effective for chemoprevention against PPI‐related gastric cancer., Nonsteroidal anti‐inflammatory drugs (NSAIDs) were associated with a 60% decrease in the gastric cancer incidence in Helicobacter pylori‐eradicated proton pump inhibitor (PPI) users, with dose and duration response effects. NSAIDs may be effective for chemoprevention against PPI‐related gastric cancer.

Takashi Kato,1 Koichi Nagata,2,3 Junta Yamamichi,4 Soichi Tanaka,5 Tetsuro Honda,6 Norihito Shimizu,7 Kenichi Utano,8 Michiaki Hirayama,9 Hiroshi Matsumoto,10 Shoichi Horita1 1Department of Internal Medicine, Hokkaido Gastroenterological Hospital, Sapporo, Japan; 2Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan; 3Cancer Screening Center, National Cancer Center Hospital, Tokyo, Japan; 4Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan; 5Department of Coloproctology, Matsuaikai Matsuda Hospital, Hamamatsu, Japan; 6Department of Gastroenterology, Nagasaki Harbor Medical Center, Nagasaki, Japan; 7Department of Radiology, Medical Corporation Matsuoka Clinic, Nara, Japan; 8Department of Coloproctology, Aizu Medical Center, Fukushima Medical University, Aizuwakamatsu, Fukushima, Japan; 9Department of Gastroenterology, Tonan Hospital, Sapporo, Japan; 10Department of Gastroenterology, Kawasaki Medical University School of Medicine, Kurashiki, JapanCorrespondence: Takashi KatoDepartment of Internal Medicine, Hokkaido Gastroenterological Hospital, Sapporo, Hokkaido 065-0041, JapanTel +8111-784-1811Fax +8111-784-1838Email tkskato45@gmail.comPurpose: Patients who test positive on the fecal immunochemical test (FIT) for colorectal cancer (CRC) are referred for colonoscopy for further diagnostic evaluation. Colonoscopy is not a perfect method and may be a challenge for some FIT-positive patients. Computed tomographic colonography (CTC) is an alternative method that is less invasive and allows examination of the whole colon. The study objective was to evaluate the preference of FIT-positive patients for either colonoscopy or CTC for CRC examination.Patients and Methods: Individuals older than 40 years with a positive FIT test at eight Japanese hospitals between December 2012 and July 2015 were invited to participate. Participants were given detailed information regarding colonoscopy and CTC before deciding on either examination. They completed questionnaires before the procedure regarding their preference and after the procedure regarding their experience.Results: The pre- and post-questionnaires of 846 and 834 participants, respectively, were analyzed. Participants preferred colonoscopy over CTC (colonoscopy, 72%; CTC, 28%). The possibility of obtaining biopsy samples and removing colorectal polyps during the procedure was the main reason for colonoscopy selection. Patients selected CTC to reduce discomfort but reported that CTC bowel preparation was more burdensome than colonoscopy bowel preparation. The overall experience of the examination did not differ between the groups.Conclusion: Colonoscopy is the standard examination for FIT-positive patients. However, when given a choice, almost one-third of participants chose CTC because they thought it would be a more “comfortable” examination. Clinicians should therefore be aware of patients’ potential preference for noninvasive colorectal examinations.Keywords: computed tomographic colonography, colonoscopy, patient preference, fecal immunochemical test

Background and Aims The effectiveness of vonoprazan relative to that of proton pump inhibitors (PPIs) after gastric endoscopic submucosal dissection (ESD) is unclear. Although previous studies used post-ESD ulcer healing as the outcome measure, post-ESD bleeding rate is the most objective and appropriate outcome measure because it has less ascertainment bias. We aimed to compare the post-ESD bleeding rates between vonoprazan and PPIs. Methods This nationwide population-based retrospective cohort study was conducted between 2014 and 2018 and involved 9 hospitals. After 2 days of intravenous PPI administration, either vonoprazan or PPI was administrated from postoperative day 2 to 30. Results Overall, data of 1715 patients (627 patient pairs) were analyzed through propensity score matching. The vonoprazan group had significantly lower post-ESD bleeding rates than the PPI group (overall, 11.9% vs 17.2%, P = .008; bleeding between days 2 and 30, 7.8% vs 11.8%, P = .015). The readmission rate because of post-ESD bleeding was lower in the vonoprazan group (2.4% vs 4.1%, P = .081). Blood transfusion (2.1% vs 3.0%, P = .15) and additional surgery because of delayed perforation (.5% vs 1.0%, P = .32) were not significantly different between the 2 groups. No deaths within 30 days occurred in both groups. On Cox regression analysis, vonoprazan use, lesion location (antrum), aspirin use, direct oral anticoagulant use, and Charlson Comorbidity Index (≥2) were associated with an increased risk of post-ESD bleeding within 30 days. Conclusions Vonoprazan has a lower post-ESD bleeding rate than PPIs. Further prospective studies are required to confirm these results.

Background and study aims It remains unclear whether the experience of endoscopists affects clinical outcomes for acute lower gastrointestinal bleeding (ALGIB). We aimed to determine the feasibility and safety of colonoscopies performed by nonexperts using secondary data from a randomized controlled trial for ALGIB. Patients and methods We analyzed clinical outcomes in 159 patients with ALGIB who underwent colonoscopies performed by two groups of endoscopists: experts and nonexperts. We compared endoscopy outcomes, including identification of stigmata of recent hemorrhage (SRH), successful endoscopic treatment, adverse events (AEs), and clinical outcomes between the two groups, including 30-day rebleeding, transfusion, length of stay, thrombotic events, and 30-day mortality. Results Expert endoscopists alone performed colonoscopies in 96 patients, and nonexperts performed colonoscopies in 63 patients. The use of antiplatelets and warfarin was significantly higher in the expert group. The SRH identification rate (24.0 and 17.5 %), successful endoscopic treatment rate (95.0 and 100 %), rate of AEs during colonoscopy (0 and 0 %), transfusion rate (6.3 and 4.8 %), length of stay (8.0 and 6.4 days), rate of thrombotic events (0 and 1.8 %), and mortality (0 and 0 %) were not different between the expert and nonexpert groups. Rebleeding within 30 days occurred more often in the expert group than in the nonexpert group (14.3 vs. 5.4 % P = 0.0914). Conclusions The performance of colonoscopies for ALGIB by nonexperts did not result in worse clinical outcomes, suggesting that its use could be feasible for nonexperts for diagnosis and treatment of ALGIB.

Purpose To evaluate the diagnostic accuracy and patient acceptance of reduced-laxative computed tomographic (CT) colonography without computer-aided detection (CAD) for the detection of colorectal polypoid and non-polypoid neoplasms in a population with a positive recent fecal immunochemical test (FIT). Materials and Methods Institutional review board approval and written informed consent were obtained. This multicenter prospective trial enrolled patients who had positive FIT results. Reduced-laxative CT colonography and colonoscopy were performed on the same day. Patients received 380 mL polyethylene glycol solution, 20 mL iodinated oral contrast agent, and two doses of 20 mg mosapride the day before CT colonography. The main outcome measures were the accuracy of CT colonography for the detection of neoplasms 6 mm or larger in per-patient and per-lesion analyses and a survey of patient perceptions regarding the preparation and examination. The Clopper-Pearson method was used for assessing the 95% confidence intervals of per-patient and per-lesion accuracy. Survey scores were analyzed by using the Wilcoxon and χ2 tests. Results Three hundred four patients underwent both CT colonography and colonoscopy. Per-patient sensitivity, specificity, positive predictive value, and negative predictive value of CT colonography for detecting neoplasms 10 mm or larger were 0.91 (40 of 44), 0.99 (255 of 258), 0.93 (40 of 43), and 0.98 (255 of 259), respectively; these values for neoplasms 6 mm or larger were 0.90 (71 of 79), 0.93 (207 of 223), 0.82 (71 of 87), and 0.96 (207 of 215), respectively. Per-lesion sensitivities for detection of polypoid and non-polypoid neoplasms 10 mm or larger were 0.95 (40 of 42) and 0.67 (six of nine), respectively; those for neoplasms 6 mm or larger were 0.90 (104 of 115) and 0.38 (eight of 21), respectively (P < .05 for both). Patient acceptance of preparation and examination with CT colonography was significantly higher than that with colonoscopy, and 62% (176 of 282) of patients would choose CT colonography as the first examination if they have a positive FIT result in the future. Conclusion Reduced-laxative CT colonography without CAD is accurate in the detection of polypoid neoplasms 6 mm or larger but is less accurate in the detection of non-polypoid neoplasms. Reduced-laxative CT colonography has high patient acceptance and is an efficient triage examination for patients with a positive FIT. © RSNA, 2016 Online supplemental material is available for this article.

Aim It was examined whether the single embryo transfer policy makes the treatment period longer for couples to achieve their first live birth by assisted reproductive technology. Methods This study retrospectively analyzed women who started assisted reproductive technology at younger than 40 years of age in the authors’ organization. The treatment periods for couples to achieve the first live birth by assisted reproductive technology, between the women who started assisted reproductive technology from 2004 to 2009 (the double embryo transfer period group, n=250), in which the double embryo transfer was predominant, and the women who started assisted reproductive technology from 2010 to 2015 (the single embryo transfer period group, n=298), in which the single embryo transfer was predominant, were compared. Results The age at the start of assisted reproductive technology, pregnancy rate per embryo transfer, and rate of women who achieved a live birth by assisted reproductive technology per number of women who tried assisted reproductive technology were all significantly higher in the single embryo transfer period group. Among the women who achieved a live birth by assisted reproductive technology, the incidence of multiple births and severe ovarian hyperstimulation syndrome, the treatment period, and medical care costs needed to achieve the first live birth were all significantly lower in the single embryo transfer period group. Conclusion In the single embryo transfer period group, those women who were younger than 40 years of age achieved their first live birth by assisted reproductive technology more safely, quickly, and reasonably.

Background & Aims We performed a large, multicenter, randomized controlled trial to determine the efficacy and safety of early colonoscopy on outcomes of patients with acute lower gastrointestinal bleeding (ALGIB). Methods We performed an open-label study at 15 hospitals in Japan of 170 patients with ALGIB randomly assigned (1:1) to groups that underwent early colonoscopy (within 24 hours of initial visit to the hospital) or elective colonoscopy (24–96 hours after hospital admission). The primary outcome was identification of stigmata of recent hemorrhage (SRH). Secondary outcomes were rebleeding within 30 days, endoscopic treatment success, need for transfusion, length of stay, thrombotic events within 30 days, death within 30 days, and adverse events. Results SRH were identified in 17 of 79 patients (21.5%) in the early colonoscopy group vs 17 of 80 patients (21.3%) in the elective colonoscopy group (difference, 0.3; 95% confidence interval, –12.5 to 13.0; P = .967). Rebleeding within 30 days of hospital admission occurred in 15.3% of patients in the early colonoscopy group and 6.7% of patients in the elective colonoscopy group (difference, 8.6; 95% confidence interval, –1.4 to 18.7); there were no significant differences between groups in successful endoscopic treatment rate, transfusion rate, length of stay, thrombotic events, or death within 30 days. The adverse event of hemorrhagic shock occurred during bowel preparation in no patient in the early group vs 2 patients (2.5%) in the elective colonoscopy group. Conclusions In a randomized controlled study, we found that colonoscopy within 24 hours after hospital admission did not increase SRH or reduce rebleeding compared with colonoscopy at 24–96 hours in patients with ALGIB. ClinicalTrials.gov, Numbers: UMIN000021129 and NCT03098173

Background and Aims: Progesterone production of human cultured luteinizing granulosa cells was reported to be modified by extracellular matrix, suggesting that extracellular matrix regulates luteinization of granulosa cells after ovulation. In the present study, the relationship among laminin, fibronectin, progesterone and estradiol in follicular fluid along with oocyte quality was analyzed to estimate the physiological role of extracellular matrix in follicular luteinization and oocyte quality during ovulation.

Aims: It is well documented that maternal morbidity and neonatal morbidity and mortality increase alike in high‐order multiple (HOM) births. There have, however, been few reports concerning the costs of maternal and neonatal medical care associated with HOM births. This is the first such report on the situation in Japan.

Background The clinical benefit of early colonoscopy within 24 h of arrival in patients with severe acute lower gastrointestinal bleeding (ALGIB) remains controversial. This trial will compare early colonoscopy (performed within 24 h) versus elective colonoscopy (performed between 24 and 96 h) to examine the identification rate of stigmata of recent hemorrhage (SRH) in ALGIB patients. We hypothesize that, compared with elective colonoscopy, early colonoscopy increases the identification of SRH and subsequently improves clinical outcomes. Methods This trial is an investigator-initiated, multicenter, randomized, open-label, parallel-group trial examining the superiority of early colonoscopy over elective colonoscopy (standard therapy) in ALGIB patients. The primary outcome measure is the identification of SRH. Secondary outcomes include 30-day rebleeding, success of endoscopic treatment, need for additional endoscopic examination, need for interventional radiology, need for surgery, need for transfusion during hospitalization, length of stay, 30-day thrombotic events, 30-day mortality, preparation-related adverse events, and colonoscopy-related adverse events. The sample size will enable detection of a 9% SRH rate in elective colonoscopy patients and a SRH rate of ≥ 26% in early colonoscopy patients with a risk of type I error of 5% and a power of 80%. Discussion This trial will provide high-quality data on the benefits and risks of early colonoscopy in ALGIB patients. Trial registration UMIN-CTR Identifier, UMIN000021129. Registered on 21 February 2016; ClinicalTrials.gov Identifier, NCT03098173. Registered on 24 March 2017. Electronic supplementary material The online version of this article (10.1186/s13063-018-2558-y) contains supplementary material, which is available to authorized users.

It is well documented that maternal morbidity and neonatal morbidity and mortality increase alike in high-order multiple (HOM) births. There have, however, been few reports concerning the costs of maternal and neonatal medical care associated with HOM births. This is the first such report on the situation in Japan. All triplet and quadruplet pregnancies managed at this institution from before 16 weeks’ gestation, and delivered at no earlier than 22 weeks’ gestation, between 1997 and 2002 were included. Prophylactic cervical ligature, hospitalization to prevent premature labor from 23 weeks’ gestation until delivery, and delivery by cesarean section, were all routine for HOM pregnancies. All women with singleton and twin pregnancies, who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) and also delivered their babies at no earlier than 22 weeks’ gestation at this institution, between 1997 and 2002, were also examined as controls. Prophylactic cervical ligature, preventive hospitalization, and cesarean section were not routine in the control group. The average gestational ages at delivery in singleton (n = 58), twin (n = 21), triplet (n = 14) and quadruplet (n = 1) pregnancies, were 39.4, 35.6, 31.9 and 25.1 weeks, respectively (P < 0.001 by Anova). Birthweights were 2886 ±425 g, 2117 ± 623 g, 1430 ± 373 g, and 633 ± 77 g (mean ± SD), respectively (P < 0.001). The average inpatient medical care cost for mother and child(ren), from maternal admissions after 12 weeks’ gestation to the discharge of all family members from hospital, was ¥703 279 yen (∼US$5861), ¥4 903 270 (∼US$40 861), ¥11 810 327 (∼US$98 419), and ¥44 961 000 (∼US$374 675), respectively (P< 0.001). The present study outlined the high costs of medical care for HOM pregnancies. Not only from a medical viewpoint, but also from the viewpoint of medical costs, it is important to avoid HOM pregnancies as a result of infertility treatment.

Background and Aims Progesterone production of human cultured luteinizing granulosa cells was reported to be modified by extracellular matrix, suggesting that extracellular matrix regulates luteinization of granulosa cells after ovulation. In the present study, the relationship among laminin, fibronectin, progesterone and estradiol in follicular fluid along with oocyte quality was analyzed to estimate the physiological role of extracellular matrix in follicular luteinization and oocyte quality during ovulation.

Purpose To evaluate the pregnancy rate (PR) of unstimulated intrauterine insemination (IUI). Methods This was a retrospective study in a private fertility clinic. Between 2004 and 2013, a total of 4,045 women underwent 17,830 cycles of unstimulated IUI. The etiologies of subfertility in the couples were unexplained (51 %), male factor (36 %), coital problems (9.5 %), and cervical factor (3.5 %). Results The PRs/cycle, between the 1st and 9th trials, in women 42 years of age were 8.2, 7.3, 5.5, 3.6, and 0.9 %, respectively. In 10,076 cycles in which the male partner had a total motile sperm count ≥5 million, the PRs in the respective age groups were 9.9, 8.6, 6.1, 4.8, and 1.2 %. The largest‐sized reported PRs for clomiphene citrate (CC)/IUI in the respective age groups were 11.5, 9.2, 7.3 4.3, and 1.0 % (4,199 cycles in total, Dovey et al., FertilSteril, 2008;90:2281–2286). There were no significant differences in PRs between unstimulated IUI and CC/IUI. Conclusion PR for unstimulated IUI was similar to the reported PR for CC/IUI. Although this was a retrospective study without a control group, to reduce multiple pregnancy rate, we believe that unstimulated IUI is a reasonable treatment.

Mannitol lysine crystal violet brilliant green agar (MLCB) is widely used in Japan for Salmonella isolation because the medium has been commercially available. Colonies of Salmonella on MLCB appear colorless with black centers due to H2S gas production; however, most Citrobacter freundii also produce H2S gas. In order to distinguish H2S-positive Salmonella from C. freundii we have improved MLCB. To MLCB was added 1% lactose (L-MLCB). The relation for pH and black center colony formation was examined. The pH of MLCB and L-MLCB inoculated with Salmonella species was slightly acid after 7 h, but the pH of L-MLCB inoculated with C. freundii did not become acid for 24 h. The colony of C. freundii did not have a black center because the production of acid from lactose lowers the pH below 10 where it is needed for H2S to react with iron to produce black pigments. Of 99 Salmonella strains including 13 serotypes tested, all strains had the same colony morphologies on MLCB and L-MLCB. When MLCB and L-MLCB were evaluated with 36 C. freundii strains isolated from foods, only colonies on MLCB had black centers. We conclude that L-MLCB is useful for detection of nonlactose-fermenting, H2S-positive Salmonella in food samples.

We previously reported that human ovarian cells express integrin β1 families. The physiological role(s) of integrins was investigated using in vitro human granulosa cell culture and in vivo mouse ovulation model. In human luteinizing granulosa cell culture obtained from the patients undergoing in vitro fertilization treatment, laminin, which is a ligand for integrin α6β1, suppressed the production of progesterone by granulosa cells. On the other hand, the anti-α6 monoclonal antibody (mAb) GoH3, which partially inhibits the interaction between integrin α6β1 and laminin, enhanced production of progesterone by 2-fold of the control under the culture with laminin, indicating that integrin α6β1 regulates the luteinization of human granulosa cell during the periovulatory phase. In an immature superovulated 13-day-old ICR (CD-1) mice model, intraperitoneal administration of GoH3 induced successful ovulation, whereas no ovulation was observed in the GoH3-nontreated groups, showing that integrin α6β1 is related to gonadotropin-induced follicular growth. These findings suggest that the interaction between integrin α6β1 and laminin plays an important role in the corpus luteum formation and follicular growth.

We previously raised a murine monoclonal antibody (mAb), OG-1, against human granulosa cells (GC) and reported that human GC express the OG-1 antigen with the highest immunoreactivity during the periovulatory phase. Later, we showed that the OG-1 antigen is identical to human integrin alpha 6, and that human GC express integrin alpha 6 beta 1, but not alpha 6 beta 4. In the present study, we examined the expression of laminin (LN), the ligand for integrin alpha 6 beta 1. Flow cytometry showed that LN was bound to the cell surface of some GC obtained from preovulatory follicles of patients undergoing in vitro fertilization. Immunohistochemistry showed that LN was detected between luteinizing GC in the early corpora lutea. To examine the effect of LN on steroidogenesis by human luteinizing GC, GC obtained from patients undergoing in vitro fertilization were cultured on mouse LN-coated or noncoated plastic dishes in medium containing 5% FCS for 24 h. In the absence or presence in hCG (1 IU/mL), GC cultured on LN-coated dishes produced 0.70- and 0.67-fold less progesterone than those on noncoated dishes, respectively (P < 0.05). We examined the effect of the interaction of integrin alpha 6 beta 1 and LN on steroidogenesis by human luteinizing GC. We cultured GC with 5 micrograms/mL of the anti-alpha 6 mAb GoH3, which inhibits the interaction between human integrin alpha 6 beta 1 and mouse LN, or with a control rat mAb (TER199) on mouse LN-coated dishes in serum-free medium for 24 h. In the absence or presence of hCG (1 IU/mL), GC cultured with GoH3 produced 1.97- and 1.94-fold more progesterone than the control cells (P < 0.01 and P < 0.05, respectively). In contrast, when GC were cultured on dishes coated with type IV collagen, progesterone production was not enhanced by GoH3. Furthermore, the anti-alpha 6 mAb OG-1, which does not inhibit the interaction between integrin alpha 6 beta 1 and LN, had no effect on the progesterone production by GC cultured on LN. These results indicate that LN suppresses the luteinization of human luteinizing GC via integrin alpha 6 beta 1 and that integrin alpha 6 beta 1 regulates the luteinization of human GC during the periovulatory phase.

To identify differentiation antigens of granulosa cells, we have raised two monoclonal antibodies against porcine granulosa cells (POG-2 antibody) and human granulosa cells (OG-1 antibody). Analysis of N-terminal amino acid sequences of purified OG-1 and POG-2 antigens revealed that they were identical to human integrin alpha 6 and its porcine homolog, respectively. An immunohistochemical study showed that integrin alpha 6 was highly expressed on granulosa cells in preovulatory follicles in the human ovary, whereas it was highly expressed on granulosa cells in small follicles in the porcine ovary. As a common characteristic of integrin alpha 6 expression in both ovaries, granulosa cells located in inner layers, which are not in contact with the basal lamina, expressed integrin alpha 6 on the cell surface. This expression profile suggests that the interaction between integrin and extracellular matrices occurs in the granulosa cells located in inner layers. This cell surface interaction is reported to modulate soluble signals to the cells. Since the expression of integrin alpha 6 on inner-layer granulosa cells is related to stages of differentiation, this interaction may be involved in folliculogenesis.

Endoscopic submucosal dissection (ESD) has emerged as a novel technique for achieving en bloc resection for superficial neoplasms limited to the mucosa. ESD was originally developed in Japan as a method of endoscopic resection of superficial gastric cancers. In our hospital, ESD has been used concurrently in other parts of the gastrointestinal tract, including the esophagus and colorectum from the beginning of its development. However, ESD in the duodenum is considered more challenging than other parts. From August 2005 to March 2008, a total of 15 superficial duodenal neoplastic lesions in 14 patients were treated with endoscopic resection. Of these, nine underwent ESD. We report our experience with duodenal ESD with a combination of ST hood and hook knife.

Testicular sperm can be obtained from patients with non-obstructive azoospermia. However, there is not enough evidence concerning whether fresh or frozen-thawed sperm is better for successful pregnancy. We retrospectively compared initial treatment results of intracytoplasmic sperm injection using fresh and frozen-thawed testicular sperm in our institution. From August 1997 to May 2006, a total of 27 cases including 18 cases using fresh sperm (269 oocytes) and 9 cases using frozen sperm (97 oocytes) were evaluated. In the fresh and frozen sperm groups 33.4 and 32.9%, respectively, developed good quality embryo. There was no significant difference between the two groups in successful pregnancy and birth rates.

We designed a rapid, quantitative turbidimetric immunoassay for serum antistreptolysin-O (ASO), based on the immunoprecipitating velocity with purified streptolysin-O (SLO), which can be measured turbidimetrically at 340 nm. The assay system involves polyoxyethylene mono-p-nonylphenyl ether to accelerate and enhance the immunoprecipitation reaction. No antibody excess phenomenon is observed, up to 1,700 U/ml. Grossly icteric sera can be assayed. Patient sera gave acceptable results. Free cholesterol offers no interference. The standard curve is linear for values up to 800 U/ml. Results measured by the proposed method and those by the conventional microtitration method correlated well. Analytical recovery averaged 90.1% (80.3%-102.5%). Within-run and day-to-day CVs ranged from 2.1% to 3.5% and from 2.5% to 6.9%, respectively. Working SLO is stable for at least 15 days at 4 degrees C. The proposed method has proven to be superior to other available methods for measuring serum ASO.

Cervicoisthmic pregnancy has a high risk of abortion or preterm delivery, and only 11 cases of live birth have been reported since 1980. In addition, almost all cases require blood transfusion and hysterectomy because of profuse bleeding after delivery of the placenta. A 39-year-old nulliparous woman who became pregnant after a fourth intracytoplasmic sperm injection was diagnosed with cervicoisthmic pregnancy on ultrasonography at 6 weeks' gestation. A healthy neonate was delivered by cesarean section at 32 weeks, but hysterectomy and blood transfusion were required. Perinatal management is discussed.

A 45-year-old Japanese woman underwent a laparoscopy-assisted vaginal hysterectomy. Insertion of a trocar injured the left common iliac artery and vein, which were repaired within 2.5 hours. Postoperatively the patient presented an acute compartment syndrome of the left leg. Fasciotomy and rehabilitation rescued her from functional disturbances.

A novel synthetic peptide immunogen targeting the human immunodeficiency virus type-1 (HIV-1) coreceptor CXCR4 was evaluated for its capacity to induce CXCR4-specific antibodies with anti-HIV-1 activity in BALB/c mice and cynomolgus monkeys. A cyclic closed-chain dodecapeptide mimicking the conformation-specific domain of CXCR4 (cDDX4) was prepared in which Gly-Asp, as the dipeptide forming a spacer arm, links the amino and carboxyl termini of the decapeptidyl linear chain (linear DDX4, Asn176 to Ile185) derived from the undecapeptidyl arch (UPA; Asn176 to Cys186) of extracellular loop 2 (ECL-2) in CXCR4. Immunization of BALB/c mice with cDDX4 conjugated with a multiple-antigen peptide (cDDX4-MAP) induced conformational epitope-specific antibodies, and monoclonal antibody IA2-F9 reacted with cDDX4, but not with linear DDX4, as determined by real-time biomolecular interaction analysis using surface plasmon resonance. The antibody also reacted with cells expressing CXCR4 but not with cells expressing the other HIV coreceptor, CCR5. Furthermore, the antibody inhibited the replication of HIV-1 X4 virus (using CXCR4), as shown by an infection assay using both MAGIC-5 cells and MT4 cells, but not that of HIV-1 R5 virus (using CCR5). The antibody weakly interfered with chemotaxis induced by stromal cell-derived factor-1 alpha in THP-1 cells or moderately inhibited the chemotaxis of Molt4#8 cells under the same conditions. In addition, immunization of cynomolgus monkeys also induced cDDX4-specific antibodies with anti-HIV activity. Taken together, these results indicate that cDDX4 conjugated with a multi-antigen peptide induces the conformational epitope-specific antibodies to the undecapeptidyl arch of CXCR4 may be a novel candidate immunogen for preventing disease progression in HIV-1-infected individuals.

Testicular sperm extraction (TESE) was performed on patients with non-obstructive azoospermia using the conventional or microdissection technique. First, conventional TESE was attempted on all patients. If the sperm was retrieved successfully, the TESE procedure was terminated. Microdissection TESE was indicated only for patients for whom the conventional sperm retrieval was unsuccessful. Sperm was successfully retrieved with conventional TESE from four (24%) of 17 patients with non-obstructive azoospermia. The remaining 13 patients underwent microdissection TESE and sperm was successfully retrieved from four of them. Application of the microdissection technique resulted in an improvement in sperm retrieval rates from 24% with conventional TESE to 48% when combined with the microdissection technique. None of the patients showed any acute or chronic complications after TESE. Intracytoplasmic sperm injection (ICSI) was performed on five of the eight patients with successful sperm retrieval and the partner of four of these patients became pregnant and progressed to delivery. These results indicate the usefulness of microdissection for improving the sperm retrieval rate in men with non-obstructive azoospermia.

Previously, it has been shown that integrin alpha6beta1 expressed on human granulosa cells regulates luteinization in co-operation with its ligand, laminin. In this study, integrin alpha2 was immunohistochemically demonstrated to be expressed on granulosa and large luteal cells. It was also detected on luteinizing theca interna cells after ovulation. Immunoreactive collagen type IV, which is one of the ligands for integrin alpha2beta1, was detected around granulosa cells in the pre-ovulatory follicles and its expression was rapidly increased during ovulation. By flow cytometry, collagen type IV was detected on the cell surface of luteinizing granulosa cells isolated from pre-ovulatory follicles, confirming the physiological interaction between granulosa cells and collagen type IV. Collagen type IV in follicular fluid was positively related with progesterone concentration. In 4-day cultures of granulosa cells, collagen type IV in the media was significantly increased by human chorionic gonadotrophin (HCG). The progesterone production was significantly attenuated when granulosa cells were cultured on collagen type IV-coated dishes, suggesting that collagen type IV suppresses granulosa cell luteinization. These findings show that collagen type IV, a ligand for integrin alpha2beta1, is rapidly produced around luteinizing granulosa cells during ovulation, probably under the control of luteinizing hormone (LH) and suggest that collagen type IV is a new parameter and/or regulator of granulosa cell luteinization in the periovulatory phases.

We previously reported that the intraperitoneal and intrabursal administration of bestatin, an aminopeptidase inhibitor, enhanced follicular growth and ovulation in immature mice. In this study, we examined the effect of bestatin on follicular growth and ovulation under the conditions in which the ovarian response to gonadotropins was suppressed. Immature female mice were exposed to 72-h continuous lighting (on days 20-22 of life), or to 24-h starvation (on day 20). On days 20-22, bestatin (4 mg/ml, 100 microl) or PBS (100 microl) was administered ip. 4 times and pregnant mare serum gonadotropin (PMSG, 5 IU) and hCG (5 IU) were given on days 21 and 23, respectively. The numbers of ovulated oocytes per mice were significantly attenuated by both stresses. Bestatin significantly enhanced the numbers of ovulated oocytes under both lighting (49.5+/-7.0 vs. 28.0+/-5.5) and starvation (28.6+/-2.6 vs. 20.2+/-2.0) stresses (with vs. without bestatin, P