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Abstract Background Portal hypertensive enteropathy (PHE) is a small-bowel lesion observed in patients with portal hypertension. The clinical significance of endoscopic findings in PHE remains unclear. We aimed to clarify the clinical significance and predictive factors of capsule endoscopic findings in patients with PHE based on long-term outcomes. Methods This retrospective study enrolled 55 patients with PHE (33 males and 22 females; median age, 64 years; range, 23–87) followed for > 3 years using capsule endoscopy (CE) between February 2009 and May 2023. We evaluated the clinical factors affecting PHE exacerbations and the effects of PHE exacerbations on gastrointestinal bleeding by comparing exacerbated and unchanged PHE groups. Results Overall, 3 (5%) patients showed improvement, 33 (60%) remained unchanged, and 19 (35%) showed exacerbation on follow-up CE. In the exacerbated group, the rates of worsened fibrosis-4 index, exacerbated esophageal varices, and exacerbated portal hypertensive gastropathy were significantly higher than those in the unchanged group (21%, 32%, and 42% vs. 3%, 6%, and 12%, respectively; P

Introduction: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is frequently associated with various gastrointestinal symptoms, including abdominal pain, vomiting, and diarrhea. Moreover, several cases of refractory diarrhea have been reported after COVID-19 recovery. Herein, we present a case of severe refractory diarrhea associated with COVID-19. Case Presentation: A 50-year-old man with no comorbidities was admitted to our hospital with SARS-CoV-2 pneumonia. His respiratory status deteriorated, and ventilatory management, including extracorporeal membrane oxygenation, was needed. The patient’s respiratory condition improved, resulting in a transfer to another hospital for rehabilitation. However, the patient developed diarrhea that worsened to 6,000–7,000 mL/day, and he was transferred to our hospital. We diagnosed the patient with enterocolitis caused by cytomegalovirus infection and treated him with ganciclovir on day 5 after transfer to our hospital. The diarrhea did not improve. We suspected enterocolitis associated with COVID-19 and administered a methylprednisolone pulse (intravenous injection, 1,000 mg/day for 3 days) on day 10 after transfer, resulting in a marked improvement in his symptoms. The prednisolone dose was tapered, and no recurrence of diarrhea was observed thereafter. Conclusion: The prevalence of COVID-19-associated enterocolitis is low, and the pathogenesis of the disease remains unclear. Prednisolone administration should be considered in cases of post-COVID-19 symptoms of severe diarrhea due to a possible abnormal immune response related to COVID-19.

BackgroundAdditional surgery with lymph node (LN) dissection is recommended for pT1 colorectal carcinoma (CRC) resected by endoscopy, based on pathological risk factors for LN metastasis (LNM), according to guidelines by the Japanese Society for Cancer of the Colon and Rectum (JSCCR), National Comprehensive Cancer Network (NCCN), and European Society for Medical Oncology (ESMO).MethodsWe retrospectively analyzed 560 consecutive patients with T1 CRC who underwent endoscopic resection alone (n=190) or initial or additional surgery with LN dissection (n=370) between 1992 and 2017 at Hiroshima University Hospital. Patients were classified into LNM low- and high-risk groups according to guidelines by the JSCCR, NCCN, and ESMO as follows. Patients without any specified pathological LNM risk factor were included in the LNM low-risk group, while the high-risk group comprised all other patients. We analyzed the LNM predictive ability of each guideline.ResultsThe LNM high-risk rate, sensitivity, specificity, positive and negative predictive values, accuracy of LNM risk, and AUC for LNM predictive ability were 82%, 100%, 19%, 9%, 100%, 26% and 0.596 in the JSCCR guidelines; 52%, 98%, 52%, 15%, 99%, 56%, and 0.749 in the NCCN; and 54%, 98%, 50%, 15%, 99%, 54%, and 0.743 in the ESMO, respectively.ConclusionsThe JSCCR guidelines could diagnose LNM in all cases but had the highest false-positive rate. It is important to reduce unnecessary additional surgeries for pT1 CRCs after ER.

Abstract Background The validity of endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) in older individuals with comorbidities remains unclear. Therefore, this study evaluated the safety and efficacy of ESD and additional treatment for ESCC in older adult patients. Methods The clinicopathological characteristics and clinical outcomes of 398 consecutive older adult patients (≥ 65 years) with 505 lesions who underwent ESD for ESCC at the Hiroshima University Hospital between September 2007 and December 2019 were retrospectively evaluated. Additionally, the prognoses of 381 patients who were followed up for > 3 years were assessed. Results The mean patient age and procedure time were 73.1 ± 5.8 years and 77.1 ± 43.5 min, respectively. The histological en bloc resection rate was 98% (496/505). Postoperative stenosis, perforation, pneumonia, and delayed bleeding were conservatively treated in 82 (16%), 19 (4%), 15 (3%), and 5 (1%) patients, respectively. The 5-year overall and disease-specific survival rates were 78.9% and 98.0%, respectively (mean follow-up time: 71.1 ± 37.3 months). Multivariate analysis showed that age and the American Society of Anesthesiologists classification of physical status class ≥III (hazard ratio: 1.27; 95% confidence interval: 1.01–1.59, p = 0.0392) were independently associated with overall survival. A significantly lower overall survival rate was observed in the high-risk follow-up group than in the low-risk follow-up and high-risk additional treatment groups (p

Abstract Circulating tumor DNA (ctDNA), which circulates in the blood after being shed from cancer cells in the body, has recently gained attention as an excellent tumor marker. The purpose of this study was to evaluate whether ct human papillomavirus (HPV) 16 DNA (ctHPV16DNA) levels were associated with quantitative PET parameters in patients with HPV-positive head and neck (HN) squamous cell carcinoma (SCC). Fifty patients with oropharyngeal SCC (OPSCC) and 5 with SCC of unknown primary (SCCUP) before treatment were included. They all underwent blood sampling to test ctHPV16DNA levels and FDG PET-CT examinations. Quantitative PET parameters included SUVmax, metabolic tumor volume (MTV), MTV of whole-body lesions (wbMTV), and 56 texture features. ctHPV16DNA levels were compared to texture features of primary tumors in OPSCC patients (Group A) or the largest primary or metastatic lymph node lesions in OPSCC and SCCUP patients (Group B) and to other PET parameters. Spearman rank correlation test and multiple regression analysis were used to confirm the associations between ctHPV16DNA levels and PET parameters. ctHPV16DNA levels moderately correlated with wbMTV, but not with SUVmax or MTV in Groups A and B. ctHPV16DNA levels exhibited a weak negative correlation with low gray-level zone emphasis in Groups A and B. Multiple regression analysis revealed that wbMTV and high gray-level zone emphasis were the significant factors for ctHPV16DNA levels in Group B. These results were not observed in Group A. This study demonstrated that ctHPV16DNA levels correlated with the whole-body tumor burden and tumor heterogeneity visualized on FDG PET-CT in patients with HPV-positive HNSCC.

Abstract Background Methods to prevent esophageal stenosis (ES) after endoscopic submucosal dissection (ESD) for superficial esophageal squamous cell carcinoma (ESCC) have received increasing attention. Although steroid administration is a prophylactic treatment, the risk factors for ES during prophylactic steroid therapy remain unknown. Therefore, this study aimed to retrospectively evaluate the risk factors for refractory ES in patients administered prophylactic steroids after ESD for ESCC. Methods Among 795 patients with ESCC (854 lesions), 180 patients (211 lesions) administered local triamcinolone acetonide (TrA) and/or oral prednisolone were recruited for this study. We compared the total number of endoscopic balloon dilatation (EBD) procedures performed for post-ESD ES and clinical findings (tumor size, ESD history or chemoradiation therapy [CRT], entire circumferential resection, muscle layer damage, supplemental oral prednisolone administration, EBD with TrA injection, and additional CRT) between patients with refractory and non-refractory ES. EBD was continued until dysphagia resolved. We categorized cases requiring ≥ 8 EBD procedures as refractory postoperative stenosis and divided the lesions into two groups. Results Multivariate logistic regression analysis revealed that factors such as ESD history, CRT history, tumor size, and entire circumferential resection were independently associated with the development of refractory ES. The withdrawal rates of EBD at 3 years were 96.1% (52/53) and 58.5% (39/59) in the non-refractory and refractory groups, respectively. Conclusions Our data suggest that entire circumferential resection and CRT history are risk factors for refractory post-ESD ES in ESCC, even with prophylactic steroid administration.

Abstract Objectives Endoscopic submucosal dissection (ESD) for colorectal tumors with positive muscle‐retracting (MR) sign often results in incomplete resection or discontinuation owing to the difficulty of submucosal dissection. The present study aimed to evaluate the usefulness of endoscopic ultrasonography (EUS) in diagnosing the MR sign and performing ESD using the pocket‐creation method (PCM). Methods Thirty‐six cases of colorectal tumors with positive MR sign during ESD between January 2015 and December 2021 were retrospectively reviewed. Cases were divided into two groups: 1) the conventional method (CM) group, comprising 29 cases, and 2) the PCM group with seven cases, in which preoperative EUS and ESD using PCM were performed. Treatment outcomes were compared between the groups. The diagnostic yield of EUS for the MR sign was evaluated among large sessile tumors >20 mm in which preoperative EUS was performed. Results Histologic diagnosis was adenoma or Tis carcinoma in 12 cases (33%), T1 carcinoma in 18 cases (50%), T2 carcinoma in four cases (11%), and unevaluable in two cases (6%). The sensitivity and specificity of the EUS‐MR sign for large sessile tumors were 87.5% and 83.3%, respectively. ESD was achieved in all cases in the PCM group, although it was discontinued in eight cases (28%) in the CM group. There were significant differences between the PCM and CM groups in en bloc resection (100% vs. 48%, p = 0.013) and R0 resection rates (71% vs. 31%, p = 0.049). Conclusion The MR sign can be predicted by preoperative EUS, and ESD using PCM allows en bloc resection.

Abstract Colorectal adenomas with squamoid morules are rare; however, colorectal adenocarcinomas are even rarer. Herein, we present a case of colorectal adenocarcinoma with squamoid morules arising from the transverse colon. A 60‐year‐old Japanese man underwent a colonoscopy, and a Type 0‐Is polyp was detected in the transverse colon. The endoscopic findings suggested a high possibility of carcinoma invasion into the deep submucosa. However, endoscopic mucosal resection was performed due to the patient's preference. Histopathologically, the tumor cells mostly formed atypical glandular structures corresponding to adenocarcinomas. Solid nests were observed in parts of the tumor, composed of round, small to short spindles. Immunohistochemically, p63 was positive in some areas, CK20 was negative, and the Ki‐67 positive cell rate was almost zero, suggesting a squamoid morule. Based on the above findings, colorectal adenocarcinoma with a squamoid morule was diagnosed; only the fifth case was reported worldwide. Squamoid morules should be carefully differentiated from squamous components of adenosquamous carcinomas.

Abstract Objectives Complete en‐bloc resection of pedunculated colorectal carcinoma is necessary for a proper pathological diagnosis. However, due to poor visibility, large pedunculated colorectal carcinomas are difficult to snare and resect en‐bloc using endoscopic resection or polypectomy. Additionally, the bleeding risk of large pedunculated colorectal carcinomas is relatively high. We aimed to assess the feasibility and safety of endoscopic submucosal dissection for large pedunculated colorectal carcinomas. Methods We conducted a retrospective multicenter cohort study to assess 36 consecutive patients with 36 large pedunculated colorectal carcinomas who underwent endoscopic submucosal dissection and evaluated the outcomes of endoscopic submucosal dissection. Furthermore, patients were divided into two groups according to the procedure time, and the factors related to the procedure time were assessed. Results The mean tumor size was 34.1 ± 9.9 mm. The en‐bloc, complete en‐bloc, and curative resection rates were 97% (35/36), 97% (35/36), and 81% (29/36), respectively. The rate of severe bleeding during the procedure was 11% (4/36); however, it could be controlled endoscopically in all patients. The rate of intraoperative perforation and delayed bleeding was 0% (0/36). Delayed perforations occurred in one patient that required surgery. A long procedure time was correlated with the location of the flexure and poor endoscope operability. No recurrence was observed in any patient. None of the patients died of colorectal carcinoma. Conclusions Our results showed the feasibility and safety of endoscopic submucosal dissection for large pedunculated colorectal carcinomas.

Abstract Objectives Underwater endoscopic mucosal resection (UEMR) is a simpler procedure for superficial non‐ampullary duodenal epithelial tumors (SNADET) than conventional endoscopic mucosal resection (cEMR). This study aimed to evaluate whether cEMR can be substituted by UEMR for SNADET in terms of effectiveness, safety, and learning curve. Methods A total of 157 consecutive patients with 203 SNADETs ≤20 mm in diameter, including 107 lesions resected by cEMR and 96 lesions resected by UEMR, between January 2019 and May 2023, were retrospectively recruited. The treatment outcomes were compared between the cEMR and UEMR groups. The risk factors for incomplete resection by UEMR were analyzed using univariate and multivariate analyses. Lesions in the UEMR group were divided chronologically into five periods; thereafter, the en bloc resection rate and procedure time were compared. Results No significant differences existed between the cEMR and UEMR groups in the mean procedure time (3.9 min vs. 3.6 min, p = 0.1380) or en bloc resection rate (91% vs. 94%, p = 0.4138). No perforation was observed in either group. Tumor size was an independent risk factor for incomplete resection using UEMR (p

Abstract Background and Aim The purpose of this study was to analyze factors associated with the overall survival (OS) of atezolizumab/bevacizumab combination therapy for advanced hepatocellular carcinoma (aHCC). We also assessed the OS of patients with ineffective therapy and those who discontinued treatment owing to adverse events (AEs). Methods This retrospective multicenter study involved 139 patients with aHCC who received atezolizumab/bevacizumab combination therapy between November 2020 and September 2022. Results The median duration of treatment was 136.5 days, and the median observation period was 316 days. The overall response rate was 40%, and the disease control rate was 78% according to mRECIST criteria. Grade ≥2 AEs occurred in 63 patients (43%) and led to treatment discontinuation in 16 patients. Multivariate analysis revealed that treatment response and occurrence of grade ≥2 AEs after therapy, as well as low level of albumin‐bilirubin (ALBI) grade and low level of des‐gamma carboxy prothrombin (DCP) before therapy, were extracted as factors that contributed to OS. Log‐rank tests with the Kaplan–Meier method showed significant differences in OS among these factors. The OS of patients who discontinued owing to AEs was significantly shorter than that of other patients. Conclusion Not only factors before therapy but also treatment response and the appearance of AEs are involved in OS for atezolizumab/bevacizumab combination therapy. Although the development of AEs also contributed to OS, appropriate management of AEs is important to avoid discontinuing treatment with this combination.

Abstract Background Esophageal squamous cell carcinoma (ESCC) is sometimes detected in non‐drinker and non‐smoker females who are considered to have very low risk of ESCC development in daily practice. This study examined the clinicopathological and genomic characteristics of ESCCs in females with no history of drinking and smoking. Methods The sample comprised 118 ESCC lesions occurring in 95 female patients who underwent endoscopic submucosal dissection at our department between January 2008 and December 2019. The patients were categorized into two groups: 51 lesions in 49 patients with no history of drinking and smoking (nondrinker/nonsmoker [NDNS] group) and 69 lesions in 45 patients with a history of drinking or smoking (drinker/smoker [DS] group). We analyzed the differences in clinicopathological and cancerous genomic characteristics between the groups. Significant genomic alterations were validated using immunohistochemistry. Results Multiple logistic regression revealed that older age, fewer multiple Lugol‐voiding lesions (LVLs), and reflux esophagitis (RE) were independently associated with the occurrence of ESCCs in the NDNS group. ESCC lesions in the NDNS group were predominantly located in the mid‐thoracic esophagus, posterior wall side, with 0‐IIa, the aspect ratio of the lesion >2 (vertical/horizontal), and endoscopic keratinization. Genetic analysis showed that CDKN2A driver alterations were significantly more frequent and KMT2D alterations were significantly less frequent in the NDNS group than in the DS group. KMT2D alterations were strongly correlated with immunostaining. Conclusion Older nondrinker, nonsmoker females with RE and fewer multiple LVLs may develop longitudinal 0‐IIa ESCC with keratinization of the posterior wall of the mid‐thoracic esophagus. ESCCs in nondrinker, nonsmoker females had fewer KMT2D alterations and more CDKN2A alterations, which may be a biomarker for treatment.

Abstract Digital phenotyping, particularly the use of plant 3D models, is a promising method for high‐throughput plant evaluation. Although many recent studies on the topic have been published, further research is needed to apply it to breeding research and other related fields. In this study, using a 3D model phenotyping system we developed, we reconstructed and analyzed 20 accessions of zoysiagrass (Zoysia spp.), including three species and their hybrid, over a period of 1 year. Artificial neural network with three hidden layers was able to effectively remove nonplant parts while retaining plant parts that were incorrectly removed using the cropping method, offering a robust and flexible approach for post‐processing of 3D models. The system also demonstrated its ability to accurately evaluate a range of traits, including height, area, and color using red green blue (RGB)‐based vegetation indices. The results showed a high correlation between the estimated volume obtained from voxel 3D model and dry weight, enabling its use as a non‐destructive method for measuring plant volume. In addition, we found that the green red normalized difference index from RGB‐based indices was similar to the commonly used normalized difference vegetation index in controlled illumination conditions. These results demonstrate the potential for three‐dimensional model phenotyping to facilitate plant breeding, particularly in the field of turfgrass and feed crops.

Abstract A highly sensitive and highly multiplexed quantification technique for nucleic acids is necessary to predict and evaluate cancer treatment by liquid biopsy. Digital PCR (dPCR) is a highly sensitive quantification technique, but conventional dPCR discriminates multiple targets by the color of the fluorescent dye of the probe, which limits multiplexing beyond the number of colors of fluorescent dyes. We previously developed a highly multiplexed dPCR technique combined with melting curve analysis. Herein, we improved the detection efficiency and accuracy of multiplexed dPCR with melting curve analysis to detect KRAS mutations in circulating tumor DNA (ctDNA) prepared from clinical samples. The mutation detection efficiency was increased from 25.9% of the input DNA to 45.2% by shortening the amplicon size. The limit of detection of mutation was improved from 0.41 to 0.06% by changing the mutation type determination algorithm for G12A, resulting in a limit of detection of less than 0.2% for all the target mutations. Then, ctDNA in plasma from pancreatic cancer patients was measured and genotyped. The measured mutation frequencies correlated well with those measured by conventional dPCR, which can measure only the total frequency of KRAS mutants. KRAS mutations were detected in 82.3% of patients with liver or lung metastasis, which was consistent with other reports. Accordingly, this study demonstrated the clinical utility of multiplex dPCR with melting curve analysis to detect and genotype ctDNA from plasma with sufficient sensitivity.

Abstract Background and Aim Molecular‐targeted therapies such as sorafenib and lenvatinib have long been used as first‐line treatment for advanced hepatocellular carcinoma (aHCC). However, adverse events or limited therapeutic effects may necessitate the change to another therapeutic option, known as post‐progression therapy. To investigate the significance of post‐progression therapy, we analyzed the outcomes of aHCC patients following first‐line molecular‐targeted therapy in a real‐world study. Methods This retrospective, multicenter study involved patients with aHCC who received sorafenib or lenvatinib as first‐line therapy between January 2011 and September 2021. Results In total, 513 patients were analyzed: 309 treated with sorafenib and 204 with lenvatinib. The overall response and disease control rates were 15 and 50%, respectively, in the sorafenib group and 30 and 75%, respectively, in the lenvatinib group (P

Background and study aims Prevention of bleeding and perforation during gastric endoscopic submucosal dissection (ESD) is important. Scissor-type knives can accurately grasp and incise the targeted tissue using electrosurgical currents, thereby eliminating unexpected incisions. The SB Knife GX, a scissor-type knife specialized for gastric ESD, was released in June 2016 in Japan. The aim of the present study was to evaluate the efficacy and safety of gastric ESD using the SB Knife GX. Patients and methods A total of 716 patients who underwent gastric ESD at Hiroshima University Hospital between July 2016 and December 2020 were retrospectively reviewed. From these, 671 patients underwent ESD using the IT Knife 2 (IT-2 group), while 45 underwent ESD using an SB Knife GX (SB-GX group). After propensity score matching, the procedure time, specimen size, en bloc and complete resection rates, and intraoperative bleeding, delayed bleeding, and perforation rates were evaluated. Results No significant differences were observed in mean procedure time (SB-GX group: 115 ± 165 min; IT-2 group: 95 ± 61 min; P = 0.82) and en bloc and complete resection rates between the two groups. Intraoperative bleeding rates were significantly lower in the SB-GX group than in the IT-2 group (18 % vs. 40 %; P = 0.01), and there were no differences in delayed bleeding (4 % vs. 4 %) or perforation (0 % vs. 4 %) between the two groups. Conclusions The SB Knife GX was proven to be useful for control of intraoperative bleeding during gastric ESD, although the procedure time tended to be longer.

Objectives: The aim of this study was to determine whether age correlates with amplitude and latency, when full-field electroretinography (ERG) is performed using skin electrodes. The ability of pulse reference power line noise reduction (PURE) to dampen the noise associated with the use of skin electrodes, was also investigated. Methods: ERG was performed on 77 eyes in 77 healthy subjects (mean age: 55.6±19.0 years; age range: 9 to 86 years). Subjects with –5D or higher myopia, Emery-Little grade III or higher cataracts, retinal disease, uveitis, glaucoma, ≤5 mm mydriasis, or a history of intraocular surgery other than cataract surgery, were excluded. The active, reference, and ground electrodes were placed on the lower eyelid, outer canthus, and earlobe, respectively. Responses were averaged 10 times for dark-adapted (DA) ERGs, and 32 to 64 times for light-adapted (LA) ERGs. Noise was removed using the PURE method. Results: The DA ERGs without PURE were so noisy that the amplitude or latency could not be determined, whereas those with PURE were comparatively quieter. ERG with PURE demonstrated a significant negative correlation between age and amplitude and a significant positive correlation between age and latency. Conclusions: We could record the measurable ERG waveforms with skin electrodes by using the PURE method, especially in fewer averaged conditions. It is suggested that skin electrode with PURE is suitable to examine the pathological ERGs, and other types of electrodes. It is recommended that the aging effect should be taken into consideration when pathological ERGs are evaluated.

Abstract Background In Japan, endoscopic submucosal dissection (ESD) is standardized for large colorectal tumors. However, its validity in the elderly population is unclear. We aimed to evaluate the safety and efficacy of ESD for colorectal tumors in elderly patients aged over 80 years. Methods ESD was performed on 178 tumors in 165 consecutive patients aged over 80 years between December 2008 and December 2018. We retrospectively evaluated the clinicopathological characteristics and clinical outcomes of ESD. We also assessed the prognosis of 160 patients followed up for more than 12 months. Results The mean patient age was 83.7 ± 3.1 years. The number of patients with comorbidities was 100 (62.5%). Among all patients, 106 (64.2%) were categorized as class 1 or 2 according to the American Society of Anesthesiologists classification of physical status (ASA-PS), and 59 (35.8%) were classified as class 3. The mean procedure time was 97.7 ± 79.3 min. The rate of histological en bloc resection was 93.8% (167/178). Delayed bleeding in 11 cases (6.2%) and perforation in 7 cases (3.9%) were treated conservatively. The 5-year survival rate was 89.9%. No deaths from primary disease (mean follow-up time: 35.3 ± 27.5 months) were observed. Overall survival rates were significantly lower in the non-curative resection group that did not undergo additional surgery than in the curative resection group (P = 0.0152) and non-curative group that underwent additional surgery (P = 0.0259). Overall survival rates were higher for ASA-PS class 1 or 2 patients than class 3 patients (P = 0.0105). Metachronous tumors (> 5 mm) developed in 9.4% of patients. Conclusions ESD for colorectal tumors in patients aged over 80 years is safe. Colorectal cancer-associated deaths were prevented although comorbidities pose a high risk of poor prognosis.

The development of BCR-ABL1 tyrosine kinase inhibitors (TKIs) markedly improved the prognosis of patients with chronic myeloid leukemia (CML). Approximately 50% of patients who achieve deep molecular response (DMR) remain in treatment-free remission (TFR) even after discontinuation of TKIs. Although TKIs may achieve clinical “cure” after TKI treatment for specific periods, there are no reliable biomarkers for predicting the response to TKIs and the probability of TFR in CML. An increase in natural killer (NK) cells in the peripheral blood of TKI-treated CML patients is correlated with better outcomes, suggesting that TKIs induce antitumor NK cell immunity against CML cells. Killer immunoglobulin-like receptors (KIRs) are highly polymorphic NK cell receptors that play important roles in the regulation of immune responses. The identification of allelic polymorphisms of KIRs by next-generation sequencing uncovered novel aspects of KIRs. Here we summarize the current knowledge of the genetic and immunological aspects of KIRs and discuss the association between allelic polymorphisms of KIRs and TKI-treated CML.

Abstract Background An educational and training program is required for generalization of Japan NBI Expert Team (JNET) classification. However, there is no detailed report on the learning curve of the diagnostic accuracy of endoscopists using JNET classification. We examined the effect of an educational lecture on beginners and less experienced endoscopists for improving their diagnostic accuracy of colorectal lesions by JNET classification. Methods Seven beginners with no endoscopy experience (NEE group), 7 less experienced endoscopists (LEE group), and 3 highly experienced endoscopists (HEE group) performed diagnosis using JNET classification for randomized NBI images of colorectal lesions from 180 cases (Type 1: 22 cases, Type 2A: 105 cases, Type 2B: 33 cases, and Type 3: 20 cases). Next, the NEE and LEE groups received a lecture on JNET classification, and all 3 groups repeated the diagnostic process. We compared the correct diagnosis rate and interobserver agreement before and after the lecture comprehensively and for each JNET type. Results In the HEE group, the correct diagnosis rate was more than 90% with good interobserver agreements (kappa value: 0.78–0.85). In the NEE and LEE groups, the correct diagnosis rate (NEE: 60.2 → 68.0%, P

Two veterinary personnel in Japan were infected with severe fever with thrombocytopenia syndrome virus (SFTSV) while handling a sick cat. Whole-genome sequences of SFTSV isolated from the personnel and the cat were 100% identical. These results identified a nosocomial outbreak of SFTSV infection in an animal hospital without a tick as a vector.

Abstract Objectives There are some endoscopic resection (ER) methods for neuroendocrine tumors (NETs), however, which method is most useful remains unclear. This study aimed to compare the outcomes of different ER techniques, such as conventional endoscopic mucosal resection (cEMR), endoscopic submucosal dissection (ESD), and endoscopic submucosal resection with a ligation device (ESMR‐L) for rectal NETs. Methods We retrospectively analyzed 96 consecutive patients with 102 rectal NETs of less than 10 mm in diameter who underwent ER between January 2001 and December 2019 at Hiroshima University Hospital. We compared the clinical outcomes of each ER method (cEMR 60 lesions, ESD 21 lesions, and ESMR‐L 21 lesions), divided according to the treatment periods, and evaluated the risk factors for vertical margin (VM) positivity in relation to clinicopathological and endoscopic characteristics. Results As for the mean procedure time, ESD took significantly longer to perform than the other methods. The histological complete resection rate was 80% (48/60) for cEMR, 85.7% (18/21) for ESD, and 100% (21/21) for ESMR‐L, and the VM positive rate was 20% (12/60) for cEMR, 14.3% (3/21) for ESD, and 0% (0/21) for ESMR‐L, with no significant difference. However, the tumor‐front‐to‐VM distance was significantly longer in the ESMR‐L group than in the cEMR and ESD groups. cEMR and ESD were both significant risk factors for VM positivity. No perforation or local recurrence was observed in all methods. Conclusions ESMR‐L is the most useful ER method for small rectal NETs.

Abstract Objectives A single‐balloon overtube (SBO) can improve poor scope operability during colonic endoscopic submucosal dissection (ESD). We aimed to evaluate the clinical usefulness of SBO for ESD in the proximal colon and the predictive factors for cases in which SBO is useful. Methods A total of 88 tumors located in the proximal colon resected by balloon‐assisted ESD (BA‐ESD) using SBO and 461 tumors resected by conventional ESD (C‐ESD) between June 2015 and November 2020 were considered. Seventy‐eight tumors each in the BA‐ESD and C‐ESD groups were matched by propensity score matching. ESD outcomes were compared between the groups, and a decision tree analysis was performed to explore the predictive factors for cases in which SBO is useful. Results There were no significant differences between the groups in the major outcomes such as en bloc resection rate (95% vs. 99%, p = 0.17), R0 resection rate (92% vs. 96%, p = 0.30), mean dissection speed (16 mm2/min vs. 16 mm2/min, p = 0.53), and intraoperative perforation rate (5% vs. 6%, p = 0.73). Even when considering cases with poor preoperative scope operability, there were no significant differences between the groups. Comparison of tumors ≥40 mm in diameter between the groups confirmed that the intraoperative perforation rate was significantly lower in the BA‐ESD group than in the C‐ESD group (0% vs. 24%, p = 0.0188). Conclusion SBO is useful for ESD of tumors ≥40 mm in diameter in the proximal colon to prevent intraoperative perforation, which usually has a long procedure time.

The significance of antibody-identified epitopes stimulating humoral alloimmunity is not well understood in the identification of non-permissive human leukocyte antigen (HLA) mismatching patterns in hematopoietic stem cell transplantation (HSCT). This was a retrospective study in a cohort of 9,991 patients who underwent their first HSCT for hematologic malignancies from unrelated bone marrow donors in the Transplant Registry Unified Management Program (TRUMP). HLA eplet mismatches (EMM) were quantified using HLAMatchmaker (HLAMM). The median age of patients was 48 years (range, 16 to 77). The number of EMM in recipient-donor pairs in our study population ranged from 0 to 37 in HLA class I (median, 0) and 0 to 60 in HLA class II (median, 1). In addition to the known high-risk mismatch patterns in the Japanese cohort, HLA-C EMM in the GVH direction was associated with a significantly higher risk for grade III-IV aGVHD, leading to a higher risk of non-relapse mortality and lower overall survival (compared with HLA-C matched patients, HR 1.67, 95% CI 1.44–1.95; HR 1.39, 95% CI 1.25–1.54; HR 1.20, 95% CI 1.10–1.30, respectively). HLAMM-based epitope matching might be useful for identifying patients who are at high risk for serious complications after HSCT from HLA mismatched unrelated donors.

Local adaptation contributes to plant colonization across extreme environmental gradients. Here, the authors reconstruct the colonization history of Lotus japonicus in Japan and identify extreme genetic signatures of local adaptation to a cold climate using genome resequencing and common garden experiments.

Background Verrucous carcinoma (VC) is a rare variant of squamous cell carcinoma. Although VC is considered radioresistant, concrete evidence for this is absent. Methods We obtained data on VC treated with surgery or radiation from the Surveillance, Epidemiology, and End Results database. Treatment selection bias was reduced by propensity score matching. Overall survival (OS) and disease-specific survival (DSS) rates were estimated using the Kaplan-Meier method. Hazard ratios (HRs) were estimated using Cox proportional hazards models. Results Five-year OS rates in the radiation and surgery groups were 72.7% and 72.0%, respectively (P = 0.111); five-year DSS rates in the same were 86.7% and 88.4%, respectively (P = 0.234). HRs of radiation compared with surgery were 1.68 (95% confidence interval (CI), 0.96–2.95) for OS and 1.95 (95% CI, 0.69–5.53) for DSS. Conclusions Similar prognoses were observed in patients with VC treated with radiation and surgery. VC can be treated using radiation.

Animals display characteristic behavioural patterns when performing a task, such as the spiraling of a soaring bird or the surge-and-cast of a male moth searching for a female. Identifying such recurring sequences occurring rarely in noisy behavioural data is key to understanding the behavioural response to a distributed stimulus in unrestrained animals. Existing models seek to describe the dynamics of behaviour or segment individual locomotor episodes rather than to identify the rare and transient sequences of locomotor episodes that make up the behavioural response. To fill this gap, we develop a lexical, hierarchical model of behaviour. We designed an unsupervised algorithm called "BASS" to efficiently identify and segment recurring behavioural action sequences transiently occurring in long behavioural recordings. When applied to navigating larval zebrafish, BASS extracts a dictionary of remarkably long, non-Markovian sequences consisting of repeats and mixtures of slow forward and turn bouts. Applied to a novel chemotaxis assay, BASS uncovers chemotactic strategies deployed by zebrafish to avoid aversive cues consisting of sequences of fast large-angle turns and burst swims. In a simulated dataset of soaring gliders climbing thermals, BASS finds the spiraling patterns characteristic of soaring behaviour. In both cases, BASS succeeds in identifying rare action sequences in the behaviour deployed by freely moving animals. BASS can be easily incorporated into the pipelines of existing behavioural analyses across diverse species, and even more broadly used as a generic algorithm for pattern recognition in low-dimensional sequential data.

Despite the growing constellation of genetic loci linked to common traits, these loci have yet to account for most heritable variation, and most act through poorly understood mechanisms. Recent machine learning (ML) systems have used hierarchical biological knowledge to associate genetic mutations with phenotypic outcomes, yielding substantial predictive power and mechanistic insight. Here, we use an ontology-guided ML system to map single nucleotide variants (SNVs) focusing on 6 classic phenotypic traits in natural yeast populations. The 29 identified loci are largely novel and account for ~17% of the phenotypic variance, versus

Background. IVIG is occasionally used for preventing and treating severe infections of patients who are to undergo transplantation. Administration of IVIG, which includes high-titer antibodies (Abs) against HLA class I and II, might have a substantial influence on the HLA Ab test results of these patients. However, this issue has remained unreported. Methods. Anti-HLA Ab titers were determined in 4 types of IVIG preparations, fresh frozen plasma, and the sera of 11 patients with hematological diseases before and after IVIG administration. Results. Although anti-HLA Abs were not detected in any of the fresh frozen plasma products, various anti-HLA class I and II Abs were detected in all 4 IVIG preparations. Six out of 11 patients who had received IVIG showed a low titer of anti-HLA class II Abs, which were not detected before IVIG administration. Conversely, no anti-HLA class I Abs were detected in any of the 11 patients. Furthermore, all 4 (100%) patients who were positive for anti-HLA class II Abs initially and were assessable became negative for anti-HLA Abs after the discontinuation of IVIG treatment (median, d 79; range, d 22–192). Conclusions. IVIG preparations consist of high-titer anti-HLA class I and II Abs, but the latter can be transiently detected in the sera of patients who had received IVIG. When these patients are screened for the presence of donor-specific Abs, some may be incorrectly deemed positive for HLA class II Abs. Thus, caution is necessary when only donor-specific Abs specific to class II HLAs are detected in patients.

Objectives: Surveillance colonoscopy after endoscopic resection (ER) for adenomatous polyps reduces the incidence and mortality of colorectal cancer (CRC). However, its significance in the elderly population is uncertain. The study aimed to determine whether surveillance colonoscopy should be discontinued in the elderly population. Methods: We enrolled 105 patients who underwent baseline colonoscopy between January 2004 and December 2009 and were subsequently followed-up over 5 years in our institution. All had diminutive colorectal polyps and were aged

Plant hormones have been identified to be versatile signaling molecules essential for plant growth, development, and stress response. Their content levels vary depending on the species, and they also change in response to any external stimuli. Thus, simultaneous quantification of multiple plant hormones is required to understand plant physiology. Sensitive and quantitative analysis using liquid chromatography-linked mass spectrometry (LC-MS/MS) has been used in detecting plant hormones; however, quantification without stable isotopes is yet to be established. In this study, we quantified seven representative plant hormones of Lotus japonicus, which is a model legume for standard addition method. Accurate masses for monoisotopic ions of seven phytohormones were determined for high-resolution mass spectrometry (HR-MS). Selected ion monitoring (SIM) mode based on accurate masses was used in detecting phytohormones in the roots, stems, and leaves. Evaluation of matrix effects showed ion suppression ranging from 10.2% to 87.3%. Both stable isotope dilution and standard addition methods were able to detect plant hormones in the roots, stems, and leaves, with no significant differences in using both approaches and thus a standard addition method can be used to quantify phytohormones in L. japonicus. The method will be effective, especially when stable isotopes are not available to correct for matrix effects.

The Japan Gastroenterological Endoscopy Society (JGES) guidelines recommend continued warfarin treatment during gastroenterological endoscopic procedures with a high risk of bleeding as an alternative to heparin replacement in patients on warfarin therapy. However, there is insufficient evidence to support the use of warfarin in colorectal endoscopic resection (ER). The present study is aimed at verifying the risk of bleeding after ER for colorectal neoplasia (CRN) in patients with continued warfarin use. This was a single-center retrospective cohort study using clinical records. We assessed 126 consecutive patients with 159 CRNs who underwent ER (endoscopic mucosal resection, 146 cases; endoscopic submucosal dissection, 13 cases) at Hiroshima University Hospital between January 2014 and December 2019. Patients were divided into two groups: the heparin replacement group (79 patients with 79 CRNs) and the continued warfarin group (47 patients with 80 CRNs). One-to-one propensity score matching was performed to compare the bleeding rate after ER between the groups. The rate of bleeding after ER was significantly higher in the heparin replacement group than in the continued warfarin group for both before (10.1% vs. 1.3%, respectively; P=0.0178) and after (11.9% vs. 0%, respectively; P=0.0211) propensity score matching. None of the patients experienced thromboembolic events during the perioperative period. The risk of bleeding after colorectal ER was significantly lower in patients with continued warfarin use than in those with heparin replacement. Our data supports the recommendations of the latest JGES guidelines for patients receiving warfarin therapy.

With the increasing use of capsule endoscopy (CE), screening tests for the small bowel can be performed with minimal invasiveness. However, occasionally, the entire small bowel cannot be observed because of decreased peristalsis of the stomach. For such cases, we perform delivery of CE by an endoscope. We retrospectively examined the usefulness of the endoscopic delivery method using a retrieval net for patients with CE stagnation in the stomach. From 2,270 patients who underwent small-bowel CE at Hiroshima University Hospital from January 2013 to January 2020, 29 consecutive patients (1.3% of the total number) in whom the small bowel could not be observed due to CE stagnation in the stomach at the time of the initial CE underwent the endoscopic delivery method using a retrieval net for secondary small-bowel CE. This study included 16 male (55%) and 13 female (45%) patients with a mean age of 69.2±13.2 years. 11 patients (38%) had a history of gastrointestinal surgical resection. The entire small bowel could be observed in 19 patients (66%), and CE reached the terminal ileum in the remaining patients. A history of gastrointestinal surgical resection was significantly more frequent in the group where the entire small bowel could not be observed. The rate of small-bowel lesion detection was 55% (16/29). There were no adverse events associated with our endoscopic delivery method. Thus, the endoscopic delivery method using a retrieval net for patients with initial CE stagnation in the stomach may be safe and useful for the detection of small-bowel lesions.