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Abstract Aim To evaluate the feasibility and safety of total neoadjuvant therapy with long‐course chemoradiotherapy followed by consolidation chemotherapy in Japanese patients with locally advanced rectal cancer. Methods This prospective, multicenter, single‐arm, phase II trial was conducted at 10 centers. The eligibility criteria included age ≥20 y, locally advanced rectal cancer within 12 cm of the anal verge, and cT3‐4N0M or TanyN+M0 at diagnosis, enabling curative resection. The protocol treatment was capecitabine (1650 mg/m2/day)‐based long‐course chemoradiotherapy (50.4 Gy/28 fractions) and consolidation chemotherapy (CAPOX, four courses) followed by total mesorectal excision. Nonoperative management was allowed if a clinical complete response was achieved. The primary endpoint was the pathologic complete response rate. Results Among 28 enrolled patients (19 men, 9 women; median age, 69.5 [41–79] y), the long‐course chemoradiotherapy and consolidation chemotherapy completion rates were 100% and 96.4%, respectively. The clinical responses included clinical complete response, (35.7%, 10/28), near‐complete response (28.6%, 8/28), and incomplete response (32.1%, 9/28). Total mesorectal excision and nonoperative management were performed in 21 and six patients, respectively. The final analysis included 21 patients. Five patients (23.8% [90% confidence interval 11.8%–41.8%]) achieved pathologic complete response, while 10 of 28 patients (35.7%) achieved a pathological complete response or a sustained clinical complete response. No treatment‐related deaths occurred. Grade ≥3 adverse events included diarrhea (7.1%) and leukopenia (7.1%). Conclusion ENSEMBLE‐2 demonstrated comparable pathologic complete response rates and well‐tolerated safety of total neoadjuvant therapy with long‐course chemoradiotherapy followed by consolidation chemotherapy in Japanese patients with locally advanced rectal cancer.

Abstract Achalasia is a rare esophageal motility disorder characterized by nonrelaxation of the lower esophageal sphincter. Laparoscopic Heller myotomy (LHM) is the gold standard treatment for achalasia. Peroral endoscopic myotomy (POEM), a less invasive treatment, is performed extensively, and the selection of the intervention method remains debatable to date. In addition to the availability of extensive studies on short‐term outcomes, recent studies on the long‐term outcomes of LHM and POEM have shown similar clinical success after 5 y of follow‐up. However, gastroesophageal reflux disease (GERD) was more common in patients who had undergone POEM than in those who had undergone LHM. Moreover, existing studies have compared treatment outcomes in various disease states. Some studies have suggested that POEM is superior to LHM for patients with type III achalasia because POEM allows for a longer myotomy. Research on treatment for sigmoid types is currently in progress. However, the long‐term results comparing LHD and POEM are insufficient, and the best treatment remains controversial. Further research is needed, and treatment options should be discussed with patients and tailored to their individual needs and pathologies.

Abstract Background This study aimed to evaluate the efficacy of lateral lymph node dissection (LLND) for rectal cancer by comparing the local control in patients with and without pathological lateral lymph node metastasis (LLNM). Methods We included 189 patients with rectal cancer who underwent total mesorectal excision and LLND at 13 institutions between 2017 and 2019. Patients with and without pathological LLNM were defined as the pLLNM (+) and (−) groups, respectively. Propensity score‐matching helped to balance the basic characteristics of both groups. The incidences of local recurrence (LR) and lateral lymph node recurrence (LLNR) were compared between the groups. Results In the entire cohort, 39 of the 189 patients had pathological LLNM. The 3‐year LR and LLNR rates were 18.3% and 4.0% (p = 0.01) and 7.7% and 3.3% (p = 0.22) in the pLLNM (+) and (−) groups, respectively. After propensity score matching, the data from 62 patients were analyzed. No significant differences in LR or LLNR were observed between both groups. The 3‐year LR and LLNR rates were 16.4% and 9.8% (p = 0.46) and 9.7% and 9.8% (p = 0.99) in the pLLNM (+) and (−) groups, respectively. Conclusion LLND would lead to comparable local control in the pLLNM (+) and (−) groups if the clinicopathological characteristics except for LLNM are similar.

Background: Spatial and temporal heterogeneities of RAS and other molecular genes should be considered in the treatment of metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs); acquired RAS mutation is sometimes observed at disease progression of treatment with the anti-EGFR mAb. At the same time, discrepancy of RAS status from tissues and circulating tumor DNA (ctDNA) in the same patient is sometimes observed. Based on this, we commenced two observational studies to clarify these heterogeneities of RAS and BRAF in mCRC, using next generation sequencing from liquid biopsy. Methods/Design: RAS-trace study is an observational study to monitor ctDNA RAS/BRAF/PIK3CA status every 4-12 weeks using the Plasma-SeqSensei™ CRC RUO Kit (Sysmex Inostics GmbH) in mCRC with RAS/BRAF wild-type (wt) on tumor tissue. The primary endpoint was the time to the acquired RAS mutations. A total of 42 patients has been accrued. RAS-trace-2 study is also an observational study aimed at comparing the efficacy of the anti-EGFR mAb in ctDNA RAS/BRAF wt with ctDNA RAS or BRAF mutant mCRC patients, whose RAS/BRAF are wt in tumor tissue. The primary endpoint was progression-free survival in patients with ctDNA RAS/BRAF wt and RAS or BRAF mutant. A total of 240 patients will be accrued over 2 years. Discussion: These trials will help us understanding the clinical significance of spatial and temporal heterogeneities of RAS, BRAF and other genes, while optimizing the anti-EGFR mAb treatment strategies in mCRC.

Abstract Aim Obstructive colon cancer is locally advanced colon cancer with poor prognosis. However, the effect of neoadjuvant chemotherapy (NAC) on obstructive colon cancer remains unclear. Therefore, this study aimed to investigate the safety and efficacy of NAC in patients with obstructive colon cancer. Methods From January 2012 to December 2017, we collected patient data for clinical stage II/III obstructive colon cancer at seven Yokohama Clinical Oncology Group (YCOG) institutions. The long‐term outcomes of the NAC and non‐NAC groups were analyzed retrospectively after adjusting for patients' background characteristics using propensity score matching. Results Among the 202 eligible patients, propensity score matching extracted 51 patients each for the NAC and non‐NAC groups. After matching, the groups showed no marked differences in the background factors. All the patients in the NAC group underwent diverting stoma construction. Nineteen patients (37.3%) experienced grade 3–4 adverse events during NAC. The incidence of postoperative complications was similar between groups. The 5‐year progression‐free survival rates were 75.8% in the NAC group and 63.0% in the non‐NAC group (p = 0.22, log‐rank test). The 5‐year overall survival rates were 88.5% in the NAC group and 78.8% in the non‐NAC group (p = 0.09, log‐rank test). Conclusion Although NAC was feasible for obstructive colon cancer after diverting stoma construction, its effects on long‐term outcomes could not be proven.

Abstract Aim We evaluated the safety of robotic surgery for right‐sided colon cancer in Japan. Methods This was a prospective, open‐label, single‐arm phase II trial conducted at two institutions. Patients ≥20 years old with stage I–III right‐sided colon cancer and scheduled for radical resection with ≥D2 lymph node dissection were eligible. The criterion for surgeons was experience performing robot‐assisted rectal resection in ≥40 cases. The primary endpoint was the postoperative complication rate ≤30 days after surgery. Results From August 2021 to February 2023, 42 patients were enrolled; three were excluded, with 39 analyzed as the full analysis set. The median age was 72 years, and the median body mass index was 23.2. The tumor was located in the cecum in 13 cases (33.3%), ascending colon in 20 cases (51.3%), and transverse colon in six cases (15.4%). Ileocolic resection was performed in 17 cases (43.5%) and right hemicolectomy in 22 cases (56.5%), both with D3 lymph node dissection. The median console time was 109 min, and the operative time was 170 min. The mean blood loss was 7.7 mL. Intracorporeal anastomosis was performed in 28 patients (71.8%). There were no conversions and no intraoperative adverse events. The median postoperative stay was 5 days. Postoperative complications occurred in four patients (10.2%; paralytic ileus [n = 3] and pneumonia [n = 1]). All postoperative complications were grade 1 or 2, with no mortalities noted. R0 resection was achieved in all patients. Conclusions This study demonstrated the safety and feasibility of robotic surgery for right‐sided colon cancer.

Objective:. To investigate the oncological outcomes after transanal total mesorectal excision (TaTME) for rectal cancer and risk factors for local recurrence (LR). Background:. A high LR rate with a multifocal pattern early after TaTME has been reported in Norway and the Netherlands, causing controversy over the oncological safety of this technique. Methods:. Twenty-six member institutions of the Japan Society of Laparoscopic Colorectal Surgery participated in this retrospective cohort study. A total of 706 patients with primary rectal cancer who underwent TaTME between January 2012 and December 2019 were included for analysis. The primary endpoint was the cumulative 3-year LR rate. Results:. A total of 253 patients had clinical stage III disease (35.8%) and 91 (12.9%) had stage IV. Intersphincteric resection was performed in 318 patients (45.0%) and abdominoperineal resection in 193 (27.3%). There was 1 urethral injury (0.1%). A positive resection margin (R1) was seen in 42 patients (5.9%). Median follow-up was 3.42 years, and the 2- and 3-year cumulative LR rates were 4.95% (95% confidence interval: 3.50–6.75) and 6.82% (95% confidence interval: 5.08–8.89), respectively. A multifocal pattern was observed in 14 (25%) of 56 patients with LR. Tumor height from the anal verge, pathological T4 disease, pathological stage III/IV, positive perineural invasion, and R1 resection were significant risk factors for LR in multivariable analysis. Conclusions:. In this selected cohort in which intersphincteric resection or abdominoperineal resection was performed in more than half of cases, oncological outcomes were acceptable during a median follow-up of more than 3 years.

This report describes the case of a 13-year-old boy with chronic insomnia and increased daytime sleepiness linked to excessive nocturnal media use. Implementing a restriction on digital device usage after 9 pm led to a significant improvement in the sleep duration with no adverse event. Throughout the 16-week treatment period, the total sleep time of the patient normalized, and the daytime sleepiness problem was resolved. This is an indication that the treatment was effective. This case emphasizes the potential of nighttime screentime restriction in treating pediatric chronic insomnia and highlights the importance of addressing screen time in sleep disorder management.

Abstract Aim To evaluate the feasibility and safety of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC) in Japan. Methods This prospective, multicenter, open‐label, single‐arm phase II trial was conducted at five institutions. The key eligibility criteria were age ≥ 20 years, LARC within 12 cm from the anal verge, and cT3‐4N0M0 or TanyN+M0 at the time of diagnosis that enabled curative resection. Preoperative short‐course radiation therapy (SCRT) 5 Gy × 5 days (total 25 Gy) + CAPOX (six courses) followed by total mesorectum excision (TME) was the treatment protocol. Non‐operative management (NOM) was allowed if clinical complete response (cCR) was obtained in the preoperative evaluation. The primary endpoint was the pathological complete response (pCR) rate. Results Thirty patients (male, n = 26; female, n = 4; median age, 62.5 [44–74] years; cT [T2, n = 1; T3, n = 25; T4, n = 4]; cN [N0, n = 13; N1, n = 13; N2, n = 4]) were enrolled. The final analysis included 30 patients in total. The completion rates were 100% for SCRT and 83% for CAPOX. TME and NOM were performed in 20 and seven patients, respectively. pCR was observed in six patients (30% [95% CI 14.0%–50.8%]). The primary endpoint was met. pCR+cCR was observed in 13 (43.3%) patients. There were no treatment‐related deaths. Grade ≥3 (CTCAE ver. 5.0) adverse events (≥20%), including diarrhea (23.3%) and neutropenia (23.3%). The median follow‐up period was 15.6 (10.5–22.8) months, with no recurrence or regrowth in NOM. Conclusions ENSEMBLE‐1 demonstrated satisfactory pCR and cCR, and well‐tolerated safety of TNT for patients with LARC in Japan.

Abstract Introduction Conventionally, the recommended duration of adjuvant chemotherapy of colon cancer had been 6 months. The IDEA Collaboration suggested that shortening capecitabin and oxaliplatin (CAPOX) adjuvant chemotherapy may be possible. S‐1 and oxaliplatin (SOX) treatment is standard treatment in metastatic colorectal cancer in Japan. The aim of this study was to optimize treatment dosage and duration of adjuvant SOX in stage III colon cancer. Methods This trial was as open‐label multi‐center randomized phase II study. Patients with stage III colon cancer were randomly assigned to 3 months or 6 months of adjuvant SOX treatment in different doses: 130 mg/m2 (3 months) or 100 mg/m2 (6 months) of oxaliplatin. The primary endpoint was 3‐year disease‐free survival (DFS) and the null hypothesis for the primary endpoint was that the 3‐year DFS was ≤72% in each arm and was tested with a one‐sided significance level of 10%. Results Eighty‐two patients were assigned to the 6 months arm and 81 to the 3 months arm. The 3‐year DFS was 75.0% (80% CI 67.95–80.72, p = 0.282) in the 6 months arm and 76.9% (80% CI 70.1–82.38, p = 0.171) in the 3 months arm. Treatment completion rate and relative dose intensity (RDI) were higher in 3 months than 6 months arm. The adverse events (AE) were similar in both arms. Conclusions The 3‐year DFS was not significantly superior to null hypothesis in both 3 months and 6 months arms for the stage III colon cancer. Primary endpoint was not achieved. The SOX regimen was not feasible in long‐term outcomes.

Introduction Pembrolizumab administration has become the standard of care for patients with urothelial carcinoma, though a variety of adverse events have been reported. Presented here is a rare case of pancreatitis that occurred as an immune‐related adverse event. Case presentation An 81‐year‐old man undergoing treatment with pembrolizumab for multiple lung metastases from renal pelvic cancer was presented with a fever and diagnosed with pancreatitis based on elevated pancreatic enzyme levels and imaging findings. There was no history of alcohol consumption or findings indicating gallstones, elevated liver enzymes, or abdominal complications. The patient was diagnosed with immune‐related adverse event pancreatitis and treated with Lactate Ringer's solution (3000 mL/day) and steroids, during which his condition improved. Conclusion Although pancreatitis is a rare complication, it should always be considered as a potential immune‐related adverse event in patients treated with an immune checkpoint inhibitor such as pembrolizumab.

Abstract It is important to assess the prognosis and intervene before and after surgery in patients with hepatocellular carcinoma. This study aims to elucidate the association of outcomes and residual liver function after hepatectomy. A total of 176 patients who underwent the initial resection for hepatocellular carcinoma between January 2011 and March 2021 at Jichi Medical University were included. Hepatic clearance of the remnant liver was measured using 99mTc-galactosyl serum albumin scintigraphy. The log-rank test was used to analyze survival using the Kaplan–Meier method. Hazard ratios (HR) and 95% confidence intervals (CI) for overall survival were calculated using Cox’s proportional hazard model. In multivariate analysis, microvascular invasion, intraoperative blood loss, and hepatic clearance of the remnant liver were independently associated with overall survival. Hepatic clearance of the remnant liver was independently associated with recurrence free survival. This is the first report to show that lower residual liver function is associated with shorter survival in patients with hepatocellular carcinoma undergoing hepatectomy. Preoperative determination of remnant liver function may allow assessment of prognosis in patients planned to undergo resection of hepatocellular carcinoma. Preservation of liver functional reserve may be crucial for improved long-term outcomes after hepatectomy.

Abstract Aim To establish a new Japanese classification of synchronous peritoneal metastases from colorectal cancer. Methods This multi‐institutional, prospective, observational study enrolled patients who underwent surgery for colorectal cancer with synchronous peritoneal metastases. Overall survival rates were compared according to the various models using objective indicators. Each model was evaluated by Akaike's information criterion (AIC). The region of peritoneal metastases was evaluated by the peritoneal cancer index (PCI). Results Between October 2012 and December 2016, 150 patients were enrolled. The AIC of the present Japanese classification was 1020.7. P1 metastasis was defined as confined to two regions. The minimum AIC was obtained with the cutoff number of 10 or less for P2 metastasis and 11 or more for P3 metastasis. As for size, the best discrimination ability between P2 and P3 metastasis was obtained with a cutoff value of 3 cm. The AIC of the proposed classification was 1014.7. The classification was as follows: P0, no peritoneal metastases; P1, metastases localized to adjacent peritoneum (within two regions of PCI); P2, metastases to distant peritoneum, number ≤10 and size ≤3 cm; P3, metastases to distant peritoneum, number ≥11 or size >3 cm; P3a, metastases to distant peritoneum, number ≥11 and size ≤3 cm, or number ≤10 and size >3 cm; P3b, metastases to distant peritoneum, number ≥11 and size >3 cm. Conclusion This objective classification could improve the ability to discriminate prognosis in patients with synchronous peritoneal metastases from colorectal cancer.

Abstract Background Mechanically aligned total knee arthroplasty (MATKA) is a well-established procedure. Kinematically aligned TKA (KATKA) has been proposed to restore and preserve pre-arthritic knee anatomy. However, normal knee anatomy varies widely, and there have been concerns regarding restoring unusual anatomy. Accordingly, restricted KATKA (rKATKA) was introduced to reproduce constitutional knee anatomy within a safe range. This network meta-analysis (NMA) aimed to evaluate the clinical and radiological outcomes of the surgeries. Methods We performed a database search on August 20, 2022, which included randomized controlled trials (RCTs) comparing any two of the three surgical TKA techniques for knee osteoarthritis. We conducted a random-effects NMA within the frequentist framework and evaluated confidence in each outcome using the Confidence in Network Meta-Analysis tool. Results Ten RCTs with 1,008 knees and a median follow-up period of 1.5 years were included. The three methods might result in little to no difference in range of motion (ROM) between methods. In patient-reported outcome measures (PROMs), the KATKA might result in a slight improvement compared with the MATKA (standardized mean difference, 0.47; 95% confidence interval [CI], 0.16–0.78; very low confidence). There was little to no difference in revision risk between MATKA and KATKA. KATKA and rKATKA showed a slight valgus femoral component (mean difference [MD], -1.35; 95% CI, -1.95–[-0.75]; very low confidence; and MD, -1.72; 95% CI, -2.63–[-0.81]; very low confidence, respectively) and a slight varus tibial component (MD, 2.23; 95% CI, 1.22–3.24; very low confidence; and MD, 1.25; 95% CI, 0.01–2.49; very low confidence, respectively) compared with MATKA. Tibial component inclination and hip–knee–ankle angle might result in little to no difference between the three procedures. Conclusions KATKA and rKATKA showed similar ROM and PROMs and a slight variation in the coronal component alignment compared with MATKA. KATKA and rKATKA are acceptable methods in short- to mid-term follow-up periods. However, long-term clinical results in patients with severe varus deformity are still lacking. Surgeons should choose surgical procedures carefully. Further trials are warranted to evaluate the efficacy, safety, and subsequent revision risk.

Abstract Aim There have been no reports of searching for metastases to lymph nodes along the accessory middle colic artery (aMCA). The aim of this study was to investigate the metastasis rate of the aMCA for splenic flexural colon cancer. Methods Patients with histologically proven colon carcinoma located in the splenic flexure, clinically diagnosed as stage I‐III were eligible for this study. Patients were retrospectively and prospectively enrolled. The primary endpoint was frequency of lymph node metastasis to the aMCA (station 222‐acc and 223‐acc). The secondary endpoint was the frequency of lymph node metastasis to the middle colic artery (MCA) (station 222‐lt and 223) and left colic artery (LCA) (station 232 and 253). Results Between January 2013 and February 2021, a total of 153 consecutive patients were enrolled. The location of the tumor was 58% in the transverse colon and 42% in the descending colon. Lymph node metastases were observed in 49 cases (32%). The presence of aMCA rate was 41.8% (64 cases). The metastasis rates of stations 221, 222‐lt, and 223 were 20.0%, 1.6%, and 0%, and stations 231, 232, and 253 were 21.4%, 1.0%, and 0%, respectively. The metastasis rates of stations 222‐acc and 223‐acc were 6.3% (95% confidence interval: 1.7%‐15.2%) and 3.7% (95% confidence interval: 0.1%‐19%), respectively. Conclusions This study identified the distribution of lymph node metastases from splenic flexural colon cancer. If the aMCA is present, this vessel should be targeted for dissection, taking into account the frequency of lymph node metastasis.

Abstract Background Mixed lineage leukemia 1-rearranged (MLL1-r) acute leukemia patients respond poorly to currently available treatments and there is a need to develop more effective therapies directly disrupting the Menin‒MLL1 complex. Small-molecule–mediated inhibition of the protein‒protein interaction between Menin and MLL1 fusion proteins is a potential therapeutic strategy for patients with MLL1-r or mutated-nucleophosmin 1 (NPM1c) acute leukemia. In this study, we preclinically evaluated the new compound DS-1594a and its salts. Methods We evaluated the preclinical efficacy of DS-1594a as well as DS-1594a·HCl (the HCl salt of DS-1594a) and DS-1594a·succinate (the succinic acid salt of DS-1594a, DS-1594b) in vitro and in vivo using acute myeloid leukemia (AML)/acute lymphoblastic leukemia (ALL) models. Results Our results showed that MLL1-r or NPM1c human leukemic cell lines were selectively and highly sensitive to DS-1594a·HCl, with 50% growth inhibition values

Background: The prognostic importance of osteopenia in patients with intrahepatic cholangiocarcinoma (ICC) undergoing hepatectomy is unclear. The aim of this study was to evaluate the impact of osteopenia on survival in patients with ICC. Methods: A total of 71 patients who underwent hepatectomy at Jichi Medical University between July 2008 and June 2022 were included in this study. Non-contrast computed tomography scan images at the eleventh thoracic vertebra were used to assess bone mineral density. The cutoff value was calculated using a threshold value of 160 Hounsfield units. Overall survival curves were made using the Kaplan–Meier method and the log-rank test was used to evaluate survival. The hazard ratio (HR) and 95% confidence interval (CI) for overall survival were calculated using Cox’s proportional hazard model. Results: In multivariable analysis, osteopenia (HR 3.66, 95%CI 1.16–14.1, p = 0.0258) and the platelet–lymphocyte ratio (HR 6.26, 95%CI 2.27–15.9, p = 0.0008) were significant independent factors associated with overall survival. There were no significant independent prognostic factors for recurrence-free survival. Conclusions: Preoperative osteopenia is significantly associated with postoperative survival in patients with ICC undergoing hepatectomy.

Background: Needlestick and sharps injuries (NSIs) are serious problems for dental health care workers (DHCWs) because they are at risk for occupational blood-borne infections. In this study, risk factors for NSIs in DHCWs at Tohoku University Hospital (TUH) in Japan over 19 years were analysed. Methods: NSI data of DHCWs at TUH from April 2002 to March 2020 were collected from the Exposure Prevention Information Network (EPINet) and statistically analysed. Results: A total of 195 NSIs occurred during the 19-year study period. Approximately 58.5% of NSIs occurred in DHCWs with less than 5 years of experience. Injection needles were the most frequent cause of NSIs (19.0%) followed by suture needles (13.3%) and ultrasonic scaler chips (12.8%). Needle injuries occurred mainly on the left hand, whereas ultrasonic scaler chip and bur injuries occurred on the right hand and other body parts whilst DHCWs were placing the instruments back on the dental unit hanging holder without removing the sharps. NSIs from other instruments primarily occurred on both hands and foot insteps during cleanup. No case of occupational blood-borne infection caused by NSIs was observed during the study period at TUH. Conclusions: NSIs occurred in DHCWs with less experience, and there were associations between the instruments, timing of use, and NSI site. EPINet was considered a valuable tool for monitoring NSIs in order to develop future strategies for minimising NSIs.

Background and Aims: Subclavian vein catheterisation (SVC) is more effective than internal jugular or femoral catheterisation and is linked to a lesser incidence of infection and patient discomfort. Whether the supraclavicular (SC) or infraclavicular (IC) approach is more effective for SVC is unclear in the previous systematic review. This updated review is designed to search the efficacy and safety of both approaches adopting the Grading of Recommendations Assessment, Development and Evaluation approach. Methods: In May 2022, we explored the databases of Embase, MEDLINE, CENTRAL, ClinicalTrials.gov and WHO-ICTRP for randomised controlled trials to compare the two approaches. Results: Seventeen trials (2482 cases) were included. In the primary outcomes, the SC approach likely reduces the failure proportion (relative risk [RR], 0.63; 95% confidence interval [CI], 0.47–0.86; I2 = 5%) and the incidence of malposition (RR, 0.23; 95% CI, 0.13–0.39; I2 = 0%) with moderate evidence and may slightly reduce the incidence of arterial puncture and pneumothorax (RR, 0.59; 95% CI, 0.29–1.22; I2 = 0%) with low evidence. In the secondary outcomes, the SC approach may decrease the access time and may increase the first-attempt success proportion. Conclusion: The SC approach for SVC should be selected after considering the clinician's expertise.

Abstract Soft gingiva is often compromised in gingival health; however, the underlying biological mechanisms remain unknown. Extracellular matrix (ECM) stiffness is involved in the progression of various fibroblast-related inflammatory disorders via cellular mechanotransduction. Gingival stiffness might regulate cellular mechanotransduction-mediated proinflammatory responses in gingival fibroblasts. This in vitro study aims to investigate the effects of substrate stiffness on proinflammatory responses in human gingival fibroblasts (hGFs). The hGFs isolated from two healthy donors cultured on type I collagen-coated polydimethylsiloxane substrates with different stiffnesses, representing soft (5 kPa) or hard (25 kPa) gingiva. Expression levels of proinflammatory mediators, prostaglandin E2 or interleukin-1β, in hGFs were significantly higher with the soft substrate than with the hard substrate, even without and with lipopolysaccharide (LPS) to induce inflammation. Expression levels of gingival ECM and collagen cross-linking agents in hGFs were downregulated more with the soft substrate than with the hard substrate through 14 days of culture. The soft substrate suppressed the expression of mechanotransduction-related transcriptional factors and activated the expression of inflammation-related factors, whereas the hard substrate demonstrated the opposite effects. Soft substrate induced proinflammatory responses and inhibition of ECM synthesis in hGFs by inactivating cellular mechanotransduction. This supports the importance of ECM stiffness in gingival health.

Background: Difficulties experienced by mothers in raising their children can be resolved using social networking services (SNSs). Being aware of issues associated with SNSs in such situations may be useful for supporting mothers. We herein review the issues associated with using SNSs to support mothers. Methods: This review was conducted using an electronic search engine to search for articles that described issues associated with using SNSs to support mothers, and which were published up to August 2022. Results: After screening, a total of 19 articles were included. We thematically categorized the contents into three major issues associated with using SNSs for support of mothers: (1) issues on the management side, (2) issues on the user side, and (3) social and environmental issues. The mainly discussed issues were the safety of using SNSs and/or securing and training human resources on the management side, busyness of mothers on the user side, as well as sociocultural and communication environment-related limitations as social and environmental issues. Conclusions: The issues we detected would aid in developing the use of SNSs as a tool to support mothers. Further research on these issues is needed.

Abstract Aim In Japan, we have not been able to validate the results of laparoscopic surgery for locally advanced rectal cancer using the universal index “circumferential resection margin (CRM).” Previously, we established a semi‐opened circular specimen processing method and validated its feasibility. In the PRODUCT trial, we aimed to assess CRM in patients with locally advanced rectal cancer who underwent laparoscopic rectal resection. Methods This was a multicenter, prospective, observational study. Eligible patients had histologically confirmed rectal adenocarcinoma located at or below 12 cm above the anal verge with clinical stage II or III and were scheduled for laparoscopic or robotic surgery. The primary endpoint was pathological CRM. CRM ≤1 mm was defined as positive. Results A total of 303 patients operated on between August 2018 and January 2020 were included in the primary analysis. The number of patients with clinical stage II and III was 139 and 164, respectively. Upfront surgery was performed for 213 patients and neoadjuvant therapy for 90 patients. The median CRM was 4.0 mm (IQR, 2.1‐8.0 mm), and CRM was positive in 26 cases (8.6%). Univariate and multivariate analyses demonstrated that a predicted CRM from the mesorectal fascia of ≤1 mm on MRI was the significant factor for positive CRM (P = .0012 and P = .0045, respectively). Conclusion This study showed the quality of laparoscopic rectal resection based on the CRM in Japan. Preoperative MRI is recommended for locally advanced rectal cancer to prevent CRM positivity.

Abstract Why inflammation is common in ileal pouches with ulcerative colitis (UC) is unclear. We therefore clarified the morphological changes in pouches and afferent limbs (AL) of patients with UC and explored the relationship between these findings. We evaluated the morphological findings (histological and endoscopic inflammation as the Pouchitis Disease Activity Index [PDAI] histology subscore [hPDAI] and endoscopy subscore [ePDAI], inflammatory bowel disease [IBD]-specific findings using the IBD score [SIBD], colonic metaplasia using the colonic metaplasia score [CMS], and goblet cell [GC] ratio) in the pouch and AL of patients with UC. A total of 261 pouchoscopies were analyzed. The pouch body had a higher hPDAI (p

Epigenetic status–altering mutations in chromatin-modifying enzymes are a feature of human diseases, including many cancers. However, the functional outcomes and cellular dependencies arising from these mutations remain unresolved. In this study, we investigated cellular dependencies, or vulnerabilities, that arise when enhancer function is compromised by loss of the frequently mutated COMPASS family members MLL3 and MLL4. CRISPR dropout screens in MLL3/4-depleted mouse embryonic stem cells (mESCs) revealed synthetic lethality upon suppression of purine and pyrimidine nucleotide synthesis pathways. Consistently, we observed a shift in metabolic activity toward increased purine synthesis in MLL3/4-KO mESCs. These cells also exhibited enhanced sensitivity to the purine synthesis inhibitor lometrexol, which induced a unique gene expression signature. RNA-Seq identified the top MLL3/4 target genes coinciding with suppression of purine metabolism, and tandem mass tag proteomic profiling further confirmed upregulation of purine synthesis in MLL3/4-KO cells. Mechanistically, we demonstrated that compensation by MLL1/COMPASS was underlying these effects. Finally, we demonstrated that tumors with MLL3 and/or MLL4 mutations were highly sensitive to lometrexol in vitro and in vivo, both in culture and in animal models of cancer. Our results depicted a targetable metabolic dependency arising from epigenetic factor deficiency, providing molecular insight to inform therapy for cancers with epigenetic alterations secondary to MLL3/4 COMPASS dysfunction.

ABSTRACT Bacteriophages infecting Tetragenococcus halophilus, a halophilic lactic acid bacterium, have been a major industrial concern due to their detrimental effects on the quality of food products. Previously characterized tetragenococcal phages displayed narrow host ranges, but there is little information on these mechanisms. Here, we revealed the host’s determinant factors for phage susceptibility using two virulent phages, phiYA5_2 and phiYG2_4, that infect T. halophilus YA5 and YG2, respectively. Phage-resistant derivatives were obtained from these host strains, and mutations were found at the capsular polysaccharide (CPS) synthesis (cps) loci. Quantification analysis verified that capsular polysaccharide production by the cps derivatives from YG2 was impaired. Transmission electron microscopy observation confirmed the presence of filamentous structures outside the cell walls of YG2 and their absence in the cps derivatives of YG2. Phage adsorption assays revealed that phiYG2_4 adsorbed to YG2 but not its cps derivatives, which suggests that the capsular polysaccharide of YG2 is the specific receptor for phiYG2_4. Interestingly, phiYA5_2 adsorbed and infected cps derivatives of YG2, although neither adsorption to nor infection of the parental strain YG2 by phiYA5_2 was observed. The plaque-surrounding halos formed by phiYA5_2 implied the presence of the virion-associated depolymerase that degrades the capsular polysaccharide of YA5. These results indicated that the capsular polysaccharide is a physical barrier rather than a binding receptor for phiYA5_2 and that phiYA5_2 specifically overcomes the capsular polysaccharide of YA5. Thus, it is suggested that tetragenococcal phages utilize CPSs as binding receptors and/or degrade CPSs to approach host cells. IMPORTANCE T. halophilus is a halophilic lactic acid bacterium that contributes to the fermentation processes for various salted foods. Bacteriophage infections of T. halophilus have been a major industrial problem causing fermentation failures. Here, we identified the cps loci in T. halophilus as genetic determinants of phage susceptibility. The structural diversity of the capsular polysaccharide is responsible for the narrow host ranges of tetragenococcal phages. The information provided here could facilitate future studies on tetragenococcal phages and the development of efficient methods to prevent bacteriophage infections.

Increasing food loss and waste (FLW) is a global problem, and efforts are being made to use waste food as potential livestock feed material. The amount of self-supplied feed is lower in Japan than in other countries, and the government recommends FLW use for animal feed. Sake (Japanese rice wine) is a traditional alcoholic beverage. During the sake manufacturing process, large amounts of squeezed solids or “lees” (sake lees) are generated. Sake lees are nutritious and functional, but are prone to spoilage. In this study, we investigated whether sake lees should be mixed with animal feed immediately or after drying. To assess the usefulness of sake lees as a poultry feed ingredient and determine the effect of sake lees on intestinal immunity, we performed a feeding trial with three treatments: a raw sake lees (RSL) diet, dried sake lees (DSL) diet, and control diet. Three-week-old broilers were fed these diets (n＝8 per group) for two weeks. We then calculated feed efficiency and performed RT-qPCR to assess the effects of diet on intestinal immunity. The growth performance in the RSL diet group was equivalent to that in the control diet group. The DSL diet became difficult for broilers to eat, resulting in decreased growth performance. In the ileum of RSL-diet broilers, the mRNA expression levels of TGF-β1 and avian β-defensin (AvBD)12 were significantly increased compared to those of control diet broilers (p

Abstract Anal canal cancer (ACC) has been reported to be an uncommon cancer in Japan, as in the USA, Europe, and Australia. This retrospective multi‐institutional study was conducted to clarify the characteristics of ACC in Japan. First, the histological ACC type cases treated between 1991 and 2015 were collected. A detailed analysis of the characteristics of anal canal squamous cell carcinoma (SCC) cases was then conducted. The results of the histological types revealed that of the 1781 ACC cases, 435 cases (24.4%) including seven cases of adenosquamous cell carcinomas were SCC and 1260 cases (70.7%) were adenocarcinoma. However, the most common histological type reported in the USA, Europe, and Australia is SCC. Most ACC cases are adenocarcinomas and there is a low incidence of SCC in Japan which is different from the above‐mentioned countries. Moreover, we reclassified T4 into the following two groups based on tumor size: T4a (tumor diameter of 5 cm or less) and T4b (tumor diameter of more than 5 cm). The results of the TNM classification of SCC revealed that the hazard ratio (HR) to T1 of T2, T3, T4a, and T4b was 2.45, 2.28, 2.89, and 4.97, respectively. As T4b cases had a worse prognosis than T4a cases, we propose that T4 for anal canal SCC in Japan be subclassified into T4a and T4b.

Abstract Macrophage phagocytosis is an important research target to combat various inflammatory or autoimmune diseases; however, the phenomenon has never been controlled by artificial means. Titania nanospikes created by alkaline etching treatment can tune macrophage polarization toward a M1-like type and might regulate macrophage phagocytosis. This in vitro study aimed to determine whether the two-dimensional titania nanosurfaces created by alkaline etching treatment activated the macrophage phagocytosis by nanospike-mediated contact stimulation. On two-dimensional pure titanium sheets, alkaline etching treatments with different protocols created superhydrophilic nanosurfaces with hydroxyl function groups and moderate or dense nanospikes. Both types of titania nanosurfaces promoted the phagocytic activity of the mouse macrophage-like cell line, J774A.1, through upregulation of M1 polarization markers and phagocytosis-related receptors, such as toll-like receptors (TLR2 and 4). In contrast, the hydrophobic smooth or micro-roughened titanium surfaces did not activate macrophage phagocytosis or the expression of related receptors. These phenomena remained unchanged even under the antibody blockade of macrophage TLR2 but were either suppressed or augmented for each surface excited by ultraviolet irradiation. Titania nanospikes induced paxillin expression and provided physical stimuli to macrophages, the extent of which was positively correlated with TLR expression levels. Ligand stimulation with lipopolysaccharide did not upregulate macrophage TLR expression but further enhanced M1 marker expression by titania nanosurfaces. These results showed that the two-dimensional titania nanosurfaces activated macrophage phagocytosis by enhancing expression of phagocytosis-related receptors through nanospike-mediated contact stimulation, in assistance with physical surface properties, in a ligand-independent manner.

Abstract Genome-wide screening is powerful method used to identify genes and pathways associated with a phenotype of interest. The simple eukaryote Dictyostelium discoideum has a unique life cycle and is often used as a crucial research model for a wide range of biological processes and rare metabolites. To address the inadequacies of conventional genetic screening approaches, we developed a highly efficient CRISPR/Cas9-based genome-wide screening system for Dictyostelium. A genome-wide library of 27,405 gRNAs and a kinase library of 4,582 gRNAs were compiled and mutant pools were generated. The resulting mutants were screened for defects in cell growth and more than 10 candidate genes were identified. Six of these were validated and five recreated mutants presented with growth abnormalities. Finally, the genes implicated in developmental defects were screened to identify the unknown genes associated with a phenotype of interest. These findings demonstrate the potential of the CRISPR/Cas9 system as an efficient genome-wide screening method.

Abstract Aim The aim of this study was to compare the outcomes of GM142, a newly developed gelatin film with a concave and convex structure to a commercially available conventional film, hyaluronate‐carboxymethylcellulose. Methods Patients with primary rectal cancer who were scheduled for diverting ileostomy during laparoscopic surgery were eligible for this study. Patients were randomized before surgery and an antiadhesion film was applied under the umbilical incision. The primary outcome was the incidence of adhesion under the midline incision confirmed by second‐look surgery for diverting ileostomy closure. The secondary outcomes were the adhesion severity score, the extent of adhesion score, the presence of intestinal obstruction, and the success of all patching. Results A total of 146 patients were enrolled. A total of 123 patients were included in the full analysis set. The primary outcome of “no adhesion” was observed in 66.1% in the GM142 group and 55.7% in the conventional film group. The noninferiority of GM142 to conventional film was confirmed (P = .0005). The secondary outcomes were similar between the groups. For the safety evaluation, there were no safety concerns regarding allergic reactions to gelatin or increased gelatin‐specific IgE antibody titers. Conclusions The noninferiority of GM142 to conventional film was shown. GM142 showed no major safety issues. The clinical safety profiles of GM142 suggested certain physiological benefits of the gelatin film as an adhesion barrier.

A 74-year-old man was diagnosed with bladder cancer and referred to our department. For definitive diagnosis, transurethral resection of the bladder tumor(TURBT) was performed. The pathological result showed plasmacytoid variant of urothelial carcinoma. Subsequently, robot-assisted radical cystectomy, lymph node dissection and ileal conduit was performed, but multiple bone metastases and periaortic lymph node metastases newly appeared 30 days later. Gemcitabine and cisplatin (GC) was started, and after 4 courses, the patient became Partial Response (PR), and was switched to Avelumab as maintenance therapy. After about 1 year of maintenance therapy, the patient is still in PR.

Abstract The effect of apical lymph node (APN) metastasis on the prognosis of colon cancer is unknown. The present study investigated the impact of APN metastasis on the prognosis of the patients with high-risk stage III colon cancer. This retrospective multi-institutional study included patients with pathological high-risk stage III colon cancer who underwent surgery between April 2009 and December 2014. Clinicopathological factors were examined by univariate and multivariate analyses to clarify independent risk factors for overall survival (OS) and relapse-free survival (RFS). A total of 185 patients were collected. The 5-year OS rates of patients with and without APN metastasis were 35.0% and 72.1%, respectively (p = 0.0014). The 5-year RFS rates of patients with and without APN metastasis was 16.2% and 57.2%, respectively (p = 0.0002). The rate of distant metastasis in patients with APN metastasis was significantly higher than that in patients without APN metastasis (68.8% vs. 36.7%, p = 0.012). The univariate analysis revealed that the differentiation, lymph node ratio, and APN metastasis were significantly associated with 5-year OS, and the preoperative CEA and CA19-9 levels and APN metastasis were significantly associated with 5-year RFS. The multivariate analysis showed that APN metastasis was an independent risk factor for 5-year OS and RFS. APN metastasis may be independently associated with the prognosis of patients with high-risk Stage III colon cancer.

Prescription doses of levodopa in patients with advanced Parkinson’s disease (PD) are generally lower in Japan than in the United States or Europe, although Japanese guidelines for the management of PD recommend increasing the dosage as the disease progresses. However, data regarding levodopa prescription practices in patients with advanced PD in the clinical setting are limited. This retrospective observational study analyzed patterns of drug use for patients with advanced PD in Japan using claims data from hospitalized patients in the Medical Data Vision Co. database. Eligible patients had at least two PD-associated claims in two different quarters between April 1, 2008, and November 30, 2018, and a 10-item activities of daily living score

Punch incision is an alternative to elliptical excision for treating epidermal inclusion cysts, but its efficacy has not been systematically reviewed. This study assessed the efficacy and safety of punch incision versus elliptical excision for epidermal inclusion cysts. Randomized controlled trials published through January 2021 that evaluated the performance of punch incision versus elliptical excision on epidermal inclusion cysts were identified through electronic databases and clinical registries. Version 2 of the Cochrane risk-of-bias tool for randomized trials tool was used. Review Manager software was used for the meta-analysis. Two trials (100 participants) were identified. The primary outcomes were recurrence rate (risk ratio, 2.40; 95% confidence interval [CI], 0.37–15.60 [favoring elliptical excision]), mean operative time (mean difference [MD], −5.28; 95% CI, −12.72 to 2.16 [favoring punch incision]), and mean postoperative wound length (MD, −11.67; 95% CI, −20.59 to −2.76 [favoring punch incision]). The evidence was low to moderate due to the small sample size and its considerable heterogeneity. The use of punch incision shortened the mean postoperative wound length and had comparable safety to that of elliptical excision.

Perivascular epithelioid cell tumor (PEComa) was introduced in the WHO classification of bone and soft tissue tumors in 2002, and Bladder PEComa is very rare. A 60-year-old man underwent TURBT after CT and cystoscopy revealed a 2.5 cm tumor with a concave center on the posterior wall of the bladder. Pathological examination revealed a perivascular epithelioid cell tumor, which was diagnosed as primary bladder PEComa after systemic examination. We report a case of partial bladder resection for bladder PEComa, a type of mesenchymal tumor that does not originate from the bladder mucosa.

The patient was referred to our department from neurosurgery for close examination of a renal mass that had been present in the lower pole of the kidney for approximately 2 year. Retrograde Pyelography and Ureteroscopy showed no obvious neoplastic lesion in the renal pelvis. Therefore, Percutaneous renal tumor biopsy was performed. The pathological result was Schwannoma. The patient was followed up for 1 year after the biopsy. No progression was observed for approximately 3 years after the renal mass was first discovered. Because renal schwannomas are extremely rare, we report this case with a literature review.

Objective:. This cohort study investigated short- and long-term postoperative outcomes of laparoscopic procedures for rectal cancer performed with versus without certified surgeons. Background:. In Japan, the Endoscopic Surgical Skill Qualification System (ESSQS) evaluates surgical skills deemed essential for laparoscopic surgery; however, it is unknown whether this certification contributes to procedural safety. Methods:. Outcomes of laparoscopic rectal resections for cStage II and III rectal cancer performed from 2014 to 2016 at 56 Japanese hospitals were retrospectively reviewed. The impact of having versus not having certified surgeons on postoperative complications and other short- and long-term outcomes were assessed. In cases with ESSQS-certified surgeons, surgeons attended surgery in the capacity of an operator, assistant, scope operator, or advisor. Results:. Overall, 3188 procedures were analyzed, with 2644 procedures performed with and 544 without ESSQS-certified surgeons. A multivariate logistic regression model showed that the adjusted odds ratio of postoperative complications after procedures performed with ESSQS-certified surgeons was 0.68 (95% confidence interval, 0.51–0.91; P = 0.009). The adjusted odds ratios for conversion and pathological R0 resection rates with ESSQS-certified surgeons were 0.20 (P < 0.001) and 2.10 (P = 0.04), respectively. Multiple linear regression analyses showed significantly shorter surgical duration and more harvested lymph nodes for operations performed with ESSQS-certified surgeons. Multivariate Cox regression showed that the adjusted hazard ratios for poor overall and recurrence-free survival after operations performed with ESSQS-certified surgeons were 0.88 (P = 0.35) and 1.04 (P = 0.71), respectively. Conclusions:. This study showed the superiority of the short-term postoperative results for laparoscopic rectal procedures performed with ESSQS-certified surgeons.

Objectives: The present study aimed to identify patients with locally advanced rectal cancer in whom preoperative radiotherapy (RT) can be omitted. Methods: This study was a retrospective multi-institutional study for patients with pathological stage II and III rectal cancer who underwent surgery without preoperative therapy between January 2008 and December 2012. Clinicopathological factors were examined by univariate and multivariate analyses to clarify independent risk factors of local recurrence (LR). Results: The 5-year cumulative local recurrence rate (LRR) of 815 patients was 11.2%. Independent predictive factors of LR were determined by a multivariate analysis to be a tumor location of

Here, we report our experience with a 5-mm trocar site hernia (TSH) near a stoma. This is the first report describing the relationship between TSH and extraperitoneal colostomy. A 72-year-old man underwent laparoscopic abdominoperineal resection with extraperitoneal sigmoid colostomy and partial hepatectomy for rectal cancer accompanied by synchronous liver metastasis (pT3N1aM1a Stage IVA Union for International Cancer Control [UICC] 8th edition). The surgical procedures were completely performed without morbidity. After 1 year, he presented to our hospital with sudden nausea. Computed tomography (CT) revealed small bowel obstruction due to a 5-mm TSH, 1 cm from the stoma. The patient underwent laparoscopic hernia repair. The incidence of a 5-mm TSH is low. However, an abdominal wall vulnerability caused by the extensive exfoliation of the retroperitoneum due to the construction of the colostomy was observed, and the extraperitoneal colostomy influenced the onset of the 5-mm TSH. When the port and hernia sites are located in close proximity to each other, even a 5-mm trocar site may increase the incidence of TSH.

Abstract Aim Stage II‐IV colorectal cancers are subdivided according to TNM categories. However, stage I cases are a single category, despite the inclusion of both T1 and T2 cases, which may have different outcomes. The aim of this study was to evaluate the usefulness of subdividing stage I colorectal cancers by T category. Methods From 1984 to 2015, 844 patients with stage I colorectal cancer (T1: 446, T2: 398) underwent colorectal resection with lymph node dissection at three hospitals. The long‐term survival and recurrence rates were compared between T1 and T2. A Cox regression analysis was used to evaluate the risk factors associated with cancer recurrence. Results A comparison of the T1 and T2 groups revealed significant differences in 5‐year overall (95.9% vs 91.4%, P = .008), recurrence‐free (94.8% vs 87.1%, P = .0007), and cancer‐specific survival (97.6% vs 93.6%, P = .004), and in the overall (2.5% vs 6.8%, P = .003), local (0.2% vs 1.5%, P = .04), and lymph node recurrence rates (0.2% vs 1.5%, P = .04). All local and lymph node recurrences were associated with lower rectal cancer, and this difference was significant. The Cox multivariate analysis identified male sex (P = .01, hazard ratio: 4.00, 95% confidence interval: 1.38‐11.55), T2 (P = .02, hazard ratio: 2.98, 95% confidence interval: 1.17‐7.60), and venous invasion (P = .03, hazard ratio: 2.38, 95% confidence interval: 1.12‐5.10) as risk factors for recurrence. Conclusions The subdivision of stage I colorectal cancer according to T category clearly reflected the long‐term outcomes.

Introduction Helicobacter pylori (H. pylori) is a bacterium that causes chronic gastroduodenal infection and affects various systemic diseases. An increase in the blood level of C-reactive protein (CRP; a systemic inflammatory marker), at a low-grade chronic inflammation level, is observed in cases of infection. However, the effect of H. pylori eradication on CRP remains undetermined. Therefore, we aimed to see the circulating CRP levels in eradicated patients through a meta-analysis. Material and methods The PubMed database was searched from its inception to June 2020. Studies that described the CRP levels following H. pylori eradication were collected. A random-effects meta-analysis was then performed using an inverse variance with standardized mean difference. Results A total of 10 eligible studies (642 subjects in total) were available. The median age in the studies was 49.9 years old. The CRP level was 6.0 (median) mg/L before H. pylori eradication and 5.8 (median) mg/L after eradication. From the results of overall meta-analysis, there was found to be a significant reduction in the CRP levels with H. pylori eradication (standardized mean difference: -0.64; 95% confidence interval: -1.02 to -0.27). The result was not similarly confirmed in a subanalysis of the available randomized controlled trials. Conclusions Weak evidence exists in terms of the effects of H. pylori eradication on the reduced CRP levels. Further research is called for.

A micro-physiological system is generally fabricated using soft materials, such as polydimethylsiloxane silicone (PDMS), and seeks an inflammatory osteolysis model for osteoimmunological research as one of the development needs. Microenvironmental stiffness regulates various cellular functions via mechanotransduction. Controlling culture substrate stiffness may help spatially coordinate the supply of osteoclastogenesis-inducing factors from immortalized cell lines, such as mouse fibrosarcoma L929 cells, within the system. Herein, we aimed to determine the effects of substrate stiffness on the osteoclastogenesis-inducing potential of L929 cells via cellular mechanotransduction. L929 cells showed increased expression of osteoclastogenesis-inducing factors when cultured on type I collagen-coated PDMS substrates with soft stiffness, approximating that of soft tissue sarcomas, regardless of the addition of lipopolysaccharide to augment proinflammatory reactions. Supernatants of L929 cells cultured on soft PDMS substrates promoted osteoclast differentiation of the mouse osteoclast precursor RAW 264.7 by stimulating the expression of osteoclastogenesis-related gene markers and tartrate-resistant acid phosphatase activity. The soft PDMS substrate inhibited the nuclear translocation of YES-associated proteins in L929 cells without reducing cell attachment. However, the hard PDMS substrate hardly affected the cellular response of the L929 cells. Our results showed that PDMS substrate stiffness tuned the osteoclastogenesis-inducing potential of L929 cells via cellular mechanotransduction.

Background: Previous Japanese studies have led to the erroneous conclusion of antioxidant capacity (AOC) intakes of the overall Japanese diet due to limitations in the number and types of food measured, especially in rice and seafood intake. The aims of the study were to construct an AOC database of foods representative of the typical Japanese diet and to clarify the high contributors to AOC intake from the overall diet of the Japanese population. Methods: Commonly consumed foods were estimated using 3-day dietary records (DRs) over the four seasons among 55 men and 58 women in Japan. To generate an AOC database suitable for the typical Japanese diet, hydrophilic (H-)/lipophilic (L-) oxygen radical absorbance capacity (ORAC) values of foods in each food group were measured via validated methods using the food intake rankings. Subsequently, we estimated the AOC intake and the AOC characteristics of a typical Japanese diet. Results: Of 989 food items consumed by the participants, 189 food items were measured, which covered 78.8% of the total food intake. The most commonly consumed types of antioxidant-containing food were tea, soybean products, coffee, and rice according to H-ORAC, and soybean products, fish and shellfish, vegetables, and algae according to L-ORAC. Conclusions: The characteristics of high AOC intake in rice and seafood more appropriately reflected the Japanese-style diet. Further studies are expected to clarify the association between food-derived AOC and its role in preventing or ameliorating lifestyle-related diseases.

Abstract Aim The present study aimed to examine the effect of continuing antiplatelet therapy in the perioperative period for patients undergoing laparoscopic resection for colorectal cancer who had received preoperative antiplatelet therapy. Methods This retrospective, multicenter, observational study included patients who underwent laparoscopic surgery for colorectal cancer between January 2011 and May 2020. The study population was limited to patients who used antiplatelet therapy preoperatively. Results A total of 214 colorectal cancer patients who received antiplatelet therapy preoperatively were included in the present study. Eighty‐nine patients underwent surgery under the continuation of antiplatelet therapy, and 125 patients underwent surgery under the discontinuation of antiplatelet therapy before surgery. There were no significant differences between the two groups with regard to intraoperative blood loss (P = .889), intraoperative blood transfusion (P = 1.000), and conversion to laparotomy (P = 1.000). There were no significant differences between the two groups in the incidence of postoperative hemorrhagic complications (Clavien‐Dindo Grade ≥II, P = .453; Grade ≥III, P = .572) or three‐point major adverse cardiovascular events (P = .268). However, there were two cases of postoperative non‐fatal stroke in the discontinued antiplatelet therapy group. Conclusions The present study revealed that there were no significant differences in the surgical outcomes and postoperative complications between colorectal cancer patients who underwent laparoscopic resection with the continuation of antiplatelet therapy in the perioperative period and those in whom antiplatelet therapy was discontinued during the perioperative period. From the viewpoint of cardiovascular and cerebrovascular risk, it may be better for patients undergoing laparoscopic surgery for colorectal cancer to continue antiplatelet therapy. This study was registered with the Japanese Clinical Trials Registry as UMIN000038707 (http://www.umin.ac.jp/ctr/index.htm).

ABSTRACT Tetragenococcus halophilus, a halophilic lactic acid bacterium, is used in the fermentation process of soy sauce manufacturing. For many years, bacteriophage infections of T. halophilus have been a major industrial problem that causes fermentation failure. However, studies focusing on the mechanisms of tetragenococcal host-phage interactions are not sufficient. In this study, we generated two phage-insensitive derivatives from the parental strain T. halophilus WJ7, which is susceptible to the virulent phage phiWJ7. Whole-genome sequencing of the derivatives revealed that insertion sequences were transposed into a gene encoding poly(ribitol phosphate) polymerase (TarL) in both derivatives. TarL is responsible for the biosynthesis of ribitol-containing wall teichoic acid, and WJ7 was confirmed to contain ribitol in extracted wall teichoic acid, but the derivative was not. Cell walls of WJ7 irreversibly adsorbed phiWJ7, but those of the phage-insensitive derivatives did not. Additionally, 25 phiWJ7-insensitive derivatives were obtained, and they showed mutations not only in tarL but also in tarI and tarJ, which are responsible for the synthesis of CDP-ribitol. These results indicate that phiWJ7 targets the ribitol-containing wall teichoic acid of host cells as a binding receptor. IMPORTANCE Information about the mechanisms of host-phage interactions is required for the development of efficient strategies against bacteriophage infections. Here, we identified the ribitol-containing wall teichoic acid as a host receptor indispensable for bacteriophage infection. The complete genome sequence of tetragenococcal phage phiWJ7 belonging to the family Rountreeviridae is also provided here. This study could become the foundation for a better understanding of host-phage interactions of tetragenococci.

Abstract Aim The present study clarified the effect on the health‐related quality of life and patient satisfaction of single‐incision laparoscopic colectomy compared with multiport laparoscopic colectomy for colorectal cancer. Methods We conducted a multicenter, randomized, control trial comparing single‐incision and multiport laparoscopic colectomy for colon cancer. We performed a pre‐planned secondary analysis of health‐related quality of life and patient satisfaction data of 200 patients. Health‐related quality of life was evaluated using the Japanese 36‐item Short Form Health Survey (SF‐36) version 2.0 before surgery and at 1 month after surgery. Patient satisfaction was compared using seven questionnaires at 1 month after surgery. Results One hundred patients were assigned to each group. After excluding 18 patients (9.0%) who did not complete the SF‐36, 182 patients (91.0%) were included in the analysis (92 cases of single‐incision laparoscopic colectomy and 90 cases of multiport laparoscopic colectomy). The SF‐36 scores at 1 month after surgery were not significantly different between the two arms. The role physical, bodily pain, vitality and physical component summary were significantly lower at 1 month after surgery than before in both groups. However, the role emotional was significantly lower after surgery than before only in the single‐incision laparoscopic colectomy group. In terms of patient satisfaction at 1 month after surgery, there were no significant differences in any of the seven items on the questionnaire. Conclusions Single‐incision laparoscopic colectomy was similar to multiport laparoscopic colectomy in terms of health‐related quality of life and patient satisfaction. However, single‐incision laparoscopic colectomy may be inferior than multiport laparoscopic colectomy in terms of the role emotional.

Abstract We report a case of an encapsulated fat necrosis without significant medical history. To differentiate from liposarcoma, it should be recognized that a half of abdominal encapsulated fat necrosis cases have a history of inflammation and surgery.

Abstract Aim Although rectal neuroendocrine tumors (NETs) are considered to be rare low‐grade malignancies when lymph node metastasis (LNM) is present, their degree of malignancy is comparable to that of colorectal cancer (CRC). However, it remains unclear as to which patients require radical lymph node dissection. The aim of this study was to elucidate the risk factors for LNM and develop a risk‐scoring system for LNM to help determine appropriate therapeutic approaches. Methods In this study, we examined 103 patients with rectal NETs who underwent local resection (n = 55) or radical resection with LN dissection (n = 48). We evaluated each pathological feature, including the depth of submucosal invasion (SM depth) and tumor budding grade. Results According to our univariate analyses and previous reports, the significant five risk factors for LNM were weighted with point values: 2 points for tumor size ≥ 15 mm and muscularis invasion, and 1 point each for SM depth ≥ 2000 µm, positive lymphovascular invasion, budding grade 3, and vertical margin. The area under the receiver operating curve for the scoring system was 0.899 (95% CI: 0.843‐0.955). When a score of 2 was used as the cut‐off value, the sensitivity and specificity for the prediction of LNM were 100% and 72.1%, respectively. Conclusions The risk‐scoring system for LNM of rectal NETs showed high diagnostic performance. Using this risk‐scoring system, it is possible to predict the risk of LNM and thereby potentially avoid unnecessary surgery. Further prospective external validation studies should be performed. The study was registered in the Japanese Clinical Trials Registry as UMIN000036658.

3,6-diphenyltetrazine (DPT) is an electron-deficient π-conjugated molecule with a perfectly planar structure and high crystallinity. In this study, discharge-charge tests of crystalline DPT as a cathode material for sodium ion batteries were conducted. DPT showed an initial reversible capacity of 102 mAh/g (theoretical capacity 114 mAh/g), corresponding to one electron reaction. The plateau of the discharge-charge profiles was observed at 1.9–2.1 V vs. Na/Na+. According to the ex-situ XRD, FT-IR, and XPS measurements to investigate the discharge-charge mechanism, the redox center was identified as the conjugated tetrazine ring. DPT was in a crystalline form in both the charged and discharged state and indicated the potential as a reversible Na ion host.