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Introduction: Indocyanine green fluorescence imaging (ICG-FI) reduces anastomotic leakage (AL) in rectal cancer surgery. However, no studies investigating risk factors for anastomotic leakage specific to the group using ICG-FI have ever previously been conducted. The purpose of this retrospective multicenter study was to ascertain the risk factors for AL in the group using ICG-FI. Methods: A total of 638 patients who underwent laparoscopic or robotic anterior resection for rectal cancer between April 2018 and March 2023 were included in this study. Patients were divided into two groups: the ICG-FI group (n= 269) and the non-ICG-FI group (n= 369) for comparative analysis. The effects of clinicopathological and treatment-related factors on AL in the ICG-FI group were evaluated using both univariate and multivariate analyses. Results: The incidence of AL in the ICG-FI group was 4.8%. Although there was no significant difference in the incidence of AL between the two groups, it was observed to be lower in the ICG-FI group. A multivariate analysis revealed a preoperative C-reactive protein-to-albumin ratio (CAR) ≥ 0.049 (odds ratio, 3.73; 95% confidence interval, 1.01–13.70; p= 0.048) as an independent risk factor for AL in the ICG-FI group. Conclusions: In this study, CAR was the only identified risk factor for AL in the ICG-FI group. It was suggested that CAR could be a criterion for early surgical intervention, prior to the escalation of risks, or for considering interventions such as diverting stoma creation.

Background and aims: Conversion to laparotomy is among the serious intraoperative complications and carries an increased risk of postoperative complications. In this cohort study, we investigated whether or not the Endoscopic Surgical Skill Qualification System (ESSQS) affects the conversion rate among patients undergoing laparoscopic surgery for rectal cancer. Methods: We performed a retrospective secondary analysis of data collected from patients undergoing laparoscopic surgery for cStage II and III rectal cancer from 2014 to 2016 across 56 institutions affiliated with the Japan Society of Laparoscopic Colorectal Surgery. Data from the original EnSSURE study were analyzed to investigate risk factors for conversion to laparotomy by performing univariate and multivariate analyses based on the reason for conversion. Results: Data were collected for 3,168 cases, including 65 (2.1%) involving conversion to laparotomy. Indicated conversion accounted for 27 cases (0.9%), while technical conversion accounted for 35 cases (1.1%). The multivariate analysis identified the following independent risk factors for indicated conversion to laparotomy: tumor diameter [mm] (odds ratio [OR] 1.01, 95% confidence interval [CI] 1.01–1.05, p = 0.0002), combined resection of adjacent organs [+/−] (OR 7.92, 95% CI 3.14–19.97, p < 0.0001), and surgical participation of an ESSQS-certified physician [−/+] (OR 4.46, 95% CI 2.01–9.90, p = 0.0002). The multivariate analysis identified the following risk factors for technical conversion to laparotomy: registered case number of institution (OR 0.99, 95% CI 0.99–1.00, p = 0.0029), institution type [non-university/university hospital] (OR 3.52, 95% CI 1.54–8.04, p = 0.0028), combined resection of adjacent organs [+/−] (OR 5.96, 95% CI 2.15–16.53, p = 0.0006), and surgical participation of an ESSQS-certified physician [−/+] (OR 6.26, 95% CI 3.01–13.05, p < 0.0001). Conclusions: Participation of ESSQS-certified physicians may reduce the risk of both indicated and technical conversion. Referral to specialized institutions, such as high-volume centers and university hospitals, especially for patients exhibiting relevant background risk factors, may reduce the risk of conversion to laparotomy and lead to better outcomes for patients. Trial Registration: This study was registered with the Japanese Clinical Trials Registry as UMIN000040645.

Certain genetic alterations and right-sided primary tumor location are associated with resistance to anti-epidermal growth factor (EGFR) treatment in metastatic colorectal cancer (mCRC). The phase 3 PARADIGM trial (n= 802) demonstrated longer overall survival with first-line anti-EGFR (panitumumab) versus antivascular endothelial growth factor (bevacizumab) plus modified FOLFOX6 in patients with RASwild-type mCRC with left-sided primary tumors. This prespecified exploratory biomarker analysis of PARADIGM (n= 733) evaluated the association between circulating tumor DNA (ctDNA) gene alterations and efficacy outcomes, focusing on a broad panel of gene alterations associated with resistance to EGFR inhibition, including KRAS, NRAS,PTENand extracellular domain EGFRmutations, HER2and METamplifications, and ALK, RETand NTRK1fusions. Overall survival was prolonged with panitumumab plus modified FOLFOX6 versus bevacizumab plus modified FOLFOX6 in patients with ctDNA that lacked gene alterations in the panel (that is, negative hyperselected; median in the overall population: 40.7 versus 34.4 months; hazard ratio, 0.76; 95% confidence interval, 0.62–0.92) but was similar or inferior with panitumumab in patients with ctDNA that contained any gene alteration in the panel (19.2 versus 22.2 months; hazard ratio, 1.13; 95% confidence interval, 0.83–1.53), regardless of tumor sidedness. Negative hyperselection using ctDNA may guide optimal treatment selection in patients with mCRC. ClinicalTrials.gov registrations: NCT02394834and NCT02394795.

The interim analysis of the CIRCULATE-Japan GALAXY observational study demonstrated the association of circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) detection with recurrence risk and benefit from adjuvant chemotherapy (ACT) in resectable colorectal cancer (CRC). This updated analysis with a 23-month median follow-up, including 2,240 patients with stage II–III colon cancer or stage IV CRC, reinforces the prognostic value of ctDNA positivity during the MRD window with significantly inferior disease-free survival (DFS; hazard ratio (HR): 11.99, P< 0.0001) and overall survival (OS; HR: 9.68, P< 0.0001). In patients who experienced recurrence, ctDNA positivity correlated with shorter OS (HR: 2.71, P< 0.0001). The significantly shorter DFS in MRD-positive patients was consistent across actionable biomarker subsets. Sustained ctDNA clearance in response to ACT was an indicator of favorable DFS and OS compared to transient clearance (24-month DFS: 89.0% versus 3.3%; 24-month OS: 100.0% versus 82.3%). True spontaneous clearance rate with no clinical recurrence was 1.9% (2/105). Overall, our findings provide evidence for the utility of ctDNA monitoring for post-resection recurrence and mortality risk stratification that could be used for guiding adjuvant therapy.

Background: OpClear® is a newly developed laparoscopic lens-cleaning device that can be attached to a laparoscope. The present study determined whether or not the use of a OpClear® reduces the multidimensional surgery-specific workload of the operator during laparoscopic colorectal surgery for colorectal cancer compared with the reference technique (warm saline) by a randomized controlled trial. Methods: Patients diagnosed with colorectal cancer and scheduled for laparoscopic colorectal surgery were randomly allocated to the warm saline arm or Opclear® arm. The primary endpoint was the multidimensional workload of the first operator (value of SURG-TLX). The secondary endpoints were the operative time and total number of lens washes outside the abdominal cavity. Results: Between March 2020 and January 2021, a total of 120 patients were enrolled in this study. A total of 4 patients were excluded from the full analysis set. A total of 116 patients (warm saline arm: 59 patients, Opclear® arm: 57 patients) were therefore analyzed. The baseline factors were well-balanced between the two arms. Regarding SURG-TLX, there was no significant difference in the overall workload between the two arms. Operators in the Opclear® arm required significantly less physical demand than in the warm saline arm (Opclear® arm: 6, warm saline arm: 7; p= 0.046). The operative time was similar between the two arms. The total number of lens washes outside the abdominal cavity in the Opclear® arm was significantly lower than that in the warm saline arm (Opclear® arm: 2, warm saline arm: 10; p&lt; 0.001). Conclusions: There was no significant difference in the overall workload, but the physical demand and total number of lens washes outside the abdominal cavity were significantly lower in the Opclear® arm than in the warm saline arm. The use of this device may thus help reduce operator stress in terms of physical demand.

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.

Histone acetylation is a post-translational modification of histones that is catalyzed by histone acetyltransferases (HATs) and plays an essential role in cellular processes. The HAT domain of EP300/CBP has recently emerged as a potential drug target for cancer therapy. Here, we describe the identification of the novel, highly potent, and selective EP300/CBP HAT inhibitor DS-9300. Our optimization efforts using a structure-based drug design approach based on the cocrystal structures of the EP300 HAT domain in complex with compounds 2and 3led to the identification of compounds possessing low-nanomolar EP300 HAT inhibitory potency and the ability to inhibit cellular acetylation of histone H3K27. Optimization of the pharmacokinetic properties in this series resulted in compounds with excellent oral systemic exposure, and once-daily oral administration of 16(DS-9300) demonstrated potent antitumor effects in a castrated VCaP xenograft mouse model without significant body weight loss.

Despite standard-of-care treatment, more than 30% of patients with resectable colorectal cancer (CRC) relapse. Circulating tumor DNA (ctDNA) analysis may enable postsurgical risk stratification and adjuvant chemotherapy (ACT) treatment decision-making. We report results from GALAXY, which is an observational arm of the ongoing CIRCULATE-Japan study (UMIN000039205) that analyzed presurgical and postsurgical ctDNA in patients with stage II–IV resectable CRC (n= 1,039). In this cohort, with a median follow-up of 16.74 months (range 0.49–24.83 months), postsurgical ctDNA positivity (at 4 weeks after surgery) was associated with higher recurrence risk (hazard ratio (HR) 10.0, P< 0.0001) and was the most significant prognostic factor associated with recurrence risk in patients with stage II or III CRC (HR 10.82, P< 0.001). Furthermore, postsurgical ctDNA positivity identified patients with stage II or III CRC who derived benefit from ACT (HR 6.59, P< 0.0001). The results of our study, a large and comprehensive prospective analysis of ctDNA in resectable CRC, support the use of ctDNA testing to identify patients who are at increased risk of recurrence and are likely to benefit from ACT.

We report the results of video observations of tiny (diameter less than 100 m) near-Earth objects (NEOs) with Tomo-e Gozen on the Kiso 105 cm Schmidt telescope. The rotational period of a tiny asteroid reflects its dynamical history and physical properties since smaller objects are sensitive to the Yarkovsky–O’Keefe–Radzievskii–Paddack (YORP) effect. We carried out video observations of 60 tiny NEOs at 2 fps from 2018 to 2021 and successfully derived the rotational periods and axial ratios of 32 NEOs including 13 fast rotators with rotational periods less than 60 s. The fastest rotator found during our survey is 2020 HS$_\mathsf {7}$with a rotational period of 2.99 s. We statistically confirmed that there is a certain number of tiny fast rotators in the NEO population, which have been missed with all previous surveys. We have discovered that the distribution of the tiny NEOs in a diameter and rotational period (D–P) diagram is truncated around a period of 10 s. The truncation with a flat-top shape is not explained well by either a realistic tensile strength of NEOs or the suppression of YORP by meteoroid impacts. We propose that the dependence of the tangential YORP effect on the rotational period potentially explains the observed pattern in the D–P diagram.

OBJECTIVE--Chronic hypoxia has been recognized as a key regulator in renal tubulointerstitial fibrosis, as seen in diabetic nephropathy, which is associated with the activation of hypoxiainducible factor (HIF)-1α. We assess here the effects of the biguanide, metformin, on the expression of HIF-1α in diabetic nephropathy using renal proximal tubular cells and type 2 diabetic rats. RESEARCH DESIGN AND METHODS--We explored the effects of metformin on the expression of HIF-1α using human renal proximal tubular epithelial cells (HRPTECs). Male Zucker diabetic fatty (ZDF; Gmi-fa/fa) rats were treated from 9 to 39 weeks with metformin (250 mg x [kg.sup.-1] x [day.sup.-1]) or insulin. RESULTS--Metformin inhibited hypoxia-induced HIF-1α accumulation and the expression of HIF-1-targeted genes in HRPTECs. Although metformin activated the downstream pathways of AMP-activated protein kinase (AMPK), neither the AMPK activator, AICAR, nor the mTOR inhibitor, rapamycin, suppressed hypoxia-induced HIF-1α expression. In addition, knockdown of AMPK-α did not abolish the inhibitory effects of metformin on HIF-1α expression. The proteasome inhibitor, MG-132, completely eradicated the suppression of hypoxia-induced HIF-1α accumulation by metformin. The inhibitors of mitochondrial respiration similarly suppressed hypoxia-induced HIF-1α expression. Metformin significantly decreased ATP production and oxygen consumption rates, which subsequently led to increased cellular oxygen tension. Finally, metformin, but not insulin, attenuated tubular HIF-1α expression and pimonidazole staining and ameliorated tubular injury in ZDF rats. CONCLUSIONS--Our data suggest that hypoxia-induced HIF1-α accumulation in diabetic nephropathy could be suppressed by the antidiabetes drug, metformin, through the repression of oxygen consumption. Diabetes 60:981-992, 2011, Diabetic nephropathy now is a leading cause of end-stage renal failure and therefore constitutes a major component of progressive kidney disease. Chronic hypoxia and tubulointerstitial fibrosis presently are considered to [...]

We propose an interface for easily accessing a variety of content using the metaphor of reading poetry. The interface is designed to search content by turning the pages of a book-like device. Using the device, the user can easily access desired content without pressing buttons many times, using complex graphical user interfaces, or using a scroll bar to scroll excessively. The prototype we developed can control TV, radio, and media files stored in an HDD and browse the Internet. The interface can be applied as a controller for products such as PCs, TVs, and mobile devices (1). Index Terms--User interface, interaction style, content browsing, tangible interface.

We propose two TV interfaces for freely accessing a rich variety of content stored on a large-capacity HDD by continuous multi-channel recording. The first is designed to handle multi-stream data received by multiple TV tuners and to simultaneously search multiple TV channels. The second is designed to handle specific time ranges and to search for scenes within those ranges. These interfaces can be incorporated into commercial products such as PCs, TVs, and HDD recorders (1). Index Terms--multiple TV tuners, large-capacity HDD, continuous-recording, contents browsing interfaces.

Background: Attachment of leukemic cells to vascular endothelial cells induces the vascular endothelial cells to release endothelial cell-derived interleukin 8 (endothelial IL-8), which then induces leukemic cells to undergo apoptosis. NB4, a human promyelocytic leukemic cell line that expresses high levels of cell-surface CD13/aminopeptidase N, does not undergo endothelial IL-8-induced apoptosis. Consequently, we investigated the relationship between cell-surface aminopeptidase activity and endothelial IL-8 induction of apoptosis in various leukemic cell lines. Methods: CD13/aminopeptidase N activity and IL-8-induced apoptosis were examined in leukemic cell lines. Endothelial IL-8-induced apoptosis was examined further in NB4 cells, K562 cells (human chronic myelogenous leukemic cells expressing low levels of CD13/aminopeptidase N), CD13/aminopeptidase N-transfected K562 (K562/CD13) cells that overexpress aminopeptidase, and mock-transfected K562 cells (vector only). These cells were also cocultured with a vascular endothelial cell layer to investigate the association between aminopeptidase activity and apoptosis in this system. All statistical tests were two-sided. Results: Endothelial IL-8 induced apoptosis in K562 cells but not in K562/CD13 cells. A combination of an aminopeptidase inhibitor (such as bestatin) and endothelial IL-8 induced apoptosis in NB4 cells and K562/CD13 cells (2.88-fold difference [95% confidence interval {CI} = 1.82-fold to 3.94-fold], P = .004 for bestatin-treated NB4 cells and 4.31-fold difference [95% CI = 3.52-fold to 5.10-fold], P

Background: We reported favorable short-term results of laparoscopic surgery in a randomized study comparing open and laparoscopic surgery for elderly patients with colorectal cancer (CRC). The purpose of this study is to clarify the long-term outcomes of the laparoscopic surgery for elderly patients with CRC. Methods: The inclusion criteria were ≥ 75 years, adenocarcinoma, ≤ T4a, M0 and elective surgery. The patients were randomly allocated to open or laparoscopic surgery according to the tumor location. The survival rates, recurrence and reasons for death were compared. Result: One hundred patients (right colon 43, left colon 28, rectum 29) were included in each group. Eight patients who underwent open surgery and 2 patients who underwent laparoscopic surgery were excluded from the analysis because of metastatic diseases and other malignancies found during the operations. One hundred ninety patients (98 open, 98 laparoscopic) were analyzed. There was no difference in the backgrounds excluding more patients with vascular invasion in the laparoscopic rectal cancer. There were no differences in the 5-year overall survival rate (open vs. laparoscopic; 78.9% vs. 82.1%, p= 0.638), 5-year disease-free survival rate (70.5% vs. 62.8%, p= 0.276), 5-year recurrence-free survival rate (76.1% vs. 72.1%, p= 0.419), or 5-year cancer-specific survival rate (86.1% vs. 80.5%, p= 0.208). No differences in survival were detected in the analyses of stage and tumor location. There was no significant difference in the overall recurrence rate or recurrence site. However, distant lymph node metastases and local recurrences were more common after laparoscopic surgery than after open surgery. There was no difference in the cause of death. More than half of the patients died from other diseases in both groups (57.9% vs. 52.6%, p= 0.765). Conclusion: Laparoscopic surgery showed similar long-term results compared to open surgery in elderly patients with CRC. Laparoscopic surgery is an effective surgical procedure for elderly patients with CRC. Graphic Abstract:

Background: There are few reports on large-scale trials for the long-term outcomes regarding laparoscopic lateral lymph node dissection (LLND). We evaluated the short- and long-term outcomes of laparoscopic versus open LLND for locally advanced middle/lower rectal cancer using a propensity score-matched analysis. Methods: From January 2005 to December 2016, consecutive clinical stage II to III middle/lower rectal cancer patients who underwent total mesorectal excision (TME) plus LLND were retrospectively collected at three institutions. Laparoscopic LLND was compared with open LLND for the surgical and oncological outcomes, including the long-term survival, using a propensity score-matched analysis. Results: A total of 325 patients were collected. There were 142 patients who underwent open TME plus LLND (open group) and 183 patients who underwent laparoscopic TME plus LLND (laparoscopic group). A total of 93 patients each were matched to each group. Compared to the open group, the laparoscopic group had a significantly longer operative time (327 vs. 377 min; p= 0.002) but significantly less blood loss (540 vs. 50 ml; p&lt; 0.001), fewer Clavian-Dindo grade ≥ 2 postoperative complications (49.5% vs. 34.4%; p= 0.037) and shorter postoperative hospital stay (18 vs. 14 days; p= 0.008). Furthermore, the rate of urinary retention was significantly lower in the laparoscopic group than in the open group (16.1% vs. 6.5%; p= 0.037). The estimated 3-year overall survival, relapse-free survival, and cumulative incidence of local recurrence were 91.4%, 73.1%, and 3.4% in the open group and 90.3%, 74.2%, and 4.3% in the laparoscopic group (p= 0.879, 0.893, 0.999), respectively. Conclusions: This study showed that laparoscopic LLND had advantages over an open approach, such as less blood loss, fewer postoperative complications, and a shorter postoperative hospital stay, and the oncologic outcomes were similar to the open approach. Laparoscopic LLND could be a viable standard approach to LLND for advanced middle/lower rectal cancer surgery.

Background: Incisional hernia (IH) is a common complication after colorectal surgery. However, the risk factors for incisional hernia after laparoscopic colorectal surgery (LCRS) have not been fully elucidated. This retrospective study analyzed the incidence rate of IH and evaluated the risk factors for IH after LCRS. Methods: This was a retrospective multi-institution study of 423 colorectal cancer patients conducted between September 2012 and December 2014 in Yokohama Clinical Oncology Group. The diagnosis of IH was based on computed tomography and physical examination findings. The patient-, tumor-, and surgery-related variables were examined by univariate and multivariate analyses. Results: A total of 423 patients were analyzed. The median follow-up period was 48.4 months. IH was observed in 36 patients (8.5%). The 1-year incidence of IH was 5.2%, and the 4-year incidence was 8.5%. A multivariate analysis showed that preoperative umbilical hernia (odds ratio [OR] 5.71; 95% confidence interval [CI] 2.02–16.10; p= 0.001) and a visceral fat area (VFA) ≥ 100 cm2(OR 2.74; 95% CI 1.08–6.96; p= 0.035) were independent risk factors of IH after LCRS. Conclusions: The risk factors of IH after LCRS were preoperative umbilical hernia and VFA ≥ 100 cm2. In the case with an umbilical hernia or VFA ≥ 100 performing LCRS, it should likely NOT have a peri-umbilical extraction site and should be considered for an alternate site like a low transverse or Pfannenstiel incision.

Background: The short-term results of single-incision laparoscopic colectomy (SILC) showed the safety, feasibility, and effectiveness when performed by skilled laparoscopic surgeons. However, the long-term complications, such as SILC-associated incisional hernia, have not been evaluated. The aim of this study was to determine the incidence of incisional hernia after SILC compared with multi-port laparoscopic colectomy (MPC) for colon cancer. Methods: From March 2012, to March 2015, a total of 200 patients were enrolled in this study. The patients were randomized to the MPC arm and SILC arm. A total of 200 patients (MPC arm; 100 patients, SILC arm; 100 patients) were therefore analyzed. In all cases the specimen was extracted through the umbilical port, which was extended according to the size of the specimen. A diagnosis of incisional hernia was made either based on a physical examination or computed tomography. Results: The baseline factors were well balanced between the arms. The median follow-up period was 42.4 (range 9.4–70.0) months. Twenty-one patients were diagnosed with incisional hernia, giving an incidence rate of 12.1% in the MPC arm and 9.0% in the SILC arm at 36 months (P= 0.451). In the multivariate analysis, the body mass index (≥ 25 kg/m2) (hazard ratio [HR] 3.03; 95% confidence interval [CI] 1.03–8.92; P= 0.044), umbilical incision (≥ 5.0 cm) (HR 3.22; 95% CI 1.16–8.93; P= 0.025), and history of umbilical hernia (HR 3.16; 95% CI 1.02–9.77; P= 0.045) were shown to be correlated with incisional hernia. Conclusions: We found no significant difference in the incidence of incisional hernia after SILC arm versus MPC arm with a long-term follow-up. However, this result may be biased because all specimens were harvested through the umbilical port.

Glioma-associated oncogene homolog 3 (GLI3), whose main function is to inhibit GLI1, has been associated with neuronal differentiation in medulloblastoma. However, it is not clear what molecular subtype(s) show increased GLI3 expression. GLI3 levels were assessed by immunohistochemistry in 2 independent cohorts, including a total of 88 cases, and found to be high in both WNT- and SHH-activated medulloblastoma. Analysis of bulk mRNA expression data and single cell RNA sequencing studies confirmed that GLI1and GLI3are highly expressed in SHH-activated medulloblastoma, whereas GLI3but not GLI1is highly expressed in WNT-activated medulloblastoma. Immunohistochemical analysis has shown that GLI3 is expressed inside the neuronal differentiated nodules of SHH-activated medulloblastoma, whereas GLI1/2 are expressed in desmoplastic areas. In contrast, GLI3 is diffusely expressed in WNT-activated medulloblastoma, whereas GLI1 is suppressed. Our data suggest that GLI3 may be a master regulator of neuronal differentiation and morphology in these subgroups.

Background: Fluorescence imaging by means of Indocyanine green (ICG) has been applied to intraoperatively determine the perfusion of the anastomosis. The purpose of this Individual Participant Database meta-analysis was to assess the effectiveness in decreasing the incidence of anastomotic leak (AL) after rectal cancer surgery. Methods: We searched PubMed, Embase, Cochrane Library and ClinicalTrial.gov, EU Clinical Trials and ISRCTN registries on September 1st, 2019. We considered eligible those studies comparing the assessment of anastomotic perfusion during rectal cancer surgery by intraoperative use of ICG fluorescence compared with standard practice. We defined as primary outcome the incidence of AL at 30 days after surgery. The studies were assessed for quality by means of the ROBINS-I and the Cochrane risk tools. We calculated odds ratios (ORs) using the Individual patient data analysis, restricted to rectal lesions, according to original treatment allocation. Results: The review of the literature and international registries produced 15 published studies and 5 ongoing trials, for 9 of which the authors accepted to share individual participant data. 314 patients from two randomized trials, 452 from three prospective series and 564 from 4 non-randomized studies were included. Fluorescence imaging significantly reduced the incidence of AL (OR 0.341; 95% CI 0.220–0.530; p&lt; 0.001), independent of age, gender, BMI, tumour and anastomotic distance from the anal verge and neoadjuvant therapy. Also, overall morbidity and reintervention rate were positively influenced by the use of ICG. Conclusions: The incidence of AL may be reduced when ICG fluorescence imaging is used to assess the perfusion of a colorectal anastomosis. Limitations relate to the consistent number of non-randomized studies included and their heterogeneity in defining and assessing AL. Ongoing large randomized studies will help to determine the exact role of routine ICG fluorescence imaging may decrease the incidence of AL in surgery for rectal cancer.

ABSTRACTThe lactic acid bacterium Tetragenococcus halophilus, which is used as a starter to brew soy sauce, comprises both cluster-forming strains and dispersed strains. The cluster-forming strains are industrially useful for obtaining clear soy sauce, because the cell clusters are trapped by filter cloth when the soy sauce mash is pressed. However, the molecular mechanism underlying cell cluster formation is unknown. Whole genome sequence analysis and subsequent target sequence analysis revealed that the cluster-forming strains commonly have functional defects in N-acetylglucosaminidase CseA, a peptidoglycan hydrolase. CseA is a multimodular protein that harbors a GH73 domain and six peptidoglycan-binding LysM domains. Recombinant CseA hydrolyzed peptidoglycan and promoted cell separation. Functional analysis of truncated CseA derivatives revealed that the LysM domains play an important role in efficient peptidoglycan degradation and cell separation. Taken together, the results of this study identify CseA as a factor that greatly affects the cluster formation in T. halophilus.

ABSTRACTSome wild Zygosaccharomyces rouxiiimpair the quality of soy sauce through the generation of unpleasant odors induced by the formation of flor. Flor formation in Z. rouxiidepends on the expression of the FLO11Dgene, which is a homolog of the FLO11gene that encodes a cell surface protein in Saccharomyces cerevisiae. FLO11expression in S. cerevisiaeis regulated by multiple pathways. To investigate the regulation of FLO11Dexpression in Z. rouxii, we created 13 gene knockout mutants (STE12, TEC1, HOG1, MSS11, FLO8, MSN1, MSN2/4, SKO1, TUP1, CYC8, YAK1, MIG1, and SFL1) related to those pathways and examined whether these mutants form flor. Unexpectedly, SFL1knockout mutant could only form a very weak flor due to decreased FLO11Dexpression, suggesting that SFL1acts as a potential activator of flor formation through FLO11Dexpression. This result is in contrast to S. cerevisiae SFL1, which acts as a repressor of FLO11expression.

Alkali metal carboxylates, which are readily available and widely used as food additives, were found to promote the ring-opening polymerization (ROP) of trimethylene carbonate (TMC) to produce poly(trimethylene carbonate) (PTMC). The sodium acetate-catalyzed ROP of TMC proceeded in the presence of an alcohol initiator under solvent-free conditions, even at very low catalyst loadings of 0.01–0.0001 mol%. This ROP system enabled the synthesis of PTMCs with predicted molecular weights ranging from 2400 to 11 700 g mol−1and narrow dispersities (~1.23).

Background: Recent studies have shown the potential benefit of indocyanine green fluorescence imaging (ICG-FI) in lowering the anastomotic leakage (AL) rates by changing the surgical plan. The aim of this study was to evaluate the effect of ICG-FI on the AL rates in laparoscopic low anterior resection (LAR) for rectal cancer. Methods: From September 2014 to December 2017, data from patients who underwent laparoscopic LAR for rectal cancer were collected and analyzed. The primary endpoint was the AL rate within 30 days after surgery. The incidence of AL in patients who underwent ICG (ICG-FI group) was compared with that in patients who did not undergo ICG (non-ICG-FI group) using propensity score matching. Results: Data from 550 patients were collected from 3 institutions. A total of 211 patients were matched in both groups by the propensity score. ICG-FI shifted the point of the proximal colon transection line toward the oral side in 12 patients (5.7%). The AL rates of Clavien–Dindo (CD) grade ≥ II and ≥ III were 10.4% (22/211) and 9.5% (20/211) in the non-ICG-FI group and 4.7% (10/211) and 2.8% (6/211) in the ICG-FI group, respectively. ICG-FI significantly reduced the AL rate of CD grade ≥ II and ≥ III (odds ratio (OR) 0.427; 95% confidence interval (CI) 0.197–0.926; p= 0.042 and OR 0.280; CI 0.110–0.711; p= 0.007, respectively). The rate of reoperation was significantly lower (OR 0.192; CI 0.042–0.889; p= 0.036) and the postoperative hospital stay significantly shorter (mean difference 2.62 days; CI 0.96–4.28; p= 0.002) in the ICG-FI group than in the non-ICG-FI group. Conclusions: ICG-FI was associated with significantly lower odds of AL in laparoscopic LAR for rectal cancer. Clinical trial: The study was registered with the Japanese Clinical Trials Registry as UMIN000032654.

In rectal anterior resection, a clear consensus regarding the optimal level of inferior mesenteric artery (IMA) ligation does not exist because of a lack of randomized trials. We conducted a randomized trial to determine if the IMA should be tied at the origin (high tie, HT) or distal to the left colic artery (low tie, LT) (HTLT study). This study is a subanalysis of HTLT study for laparoscopic surgery. All candidates were randomly divided into the HT or LT groups. The lymph node dissection around the origin of the IMA was performed in the LT group. The stratified factor was the approach (open or laparoscopy). Evaluation parameters were operative factors, short-term and long-term results. In the present study, laparoscopic surgeries were examined as subgroup analysis. From June 2006 to September 2012, 331 patients were registered. Two hundred and fifteen patients (107 for HT: 108 for LT) underwent laparoscopic surgeries. There was no difference between the groups in background. The incidence of anastomotic leakage (HT: LT %) showed no significant differences for grade 2 or higher (11.2:9.3), and grade 3 or higher (2.8:4.6). There were no differences in operative time (200:205 min), blood loss (15:15 ml), number of dissected lymph nodes (22:20), and postoperative hospital stay (10:10 days). The incidence of bowel obstruction in HT was significant (3.7 vs. 0%, p= 0.043). There were no significant differences in overall survival (5-year: 91.3 vs. 90.2%, p= 0.850) and disease-free survival (5-year: 83.2 vs. 78.0%, p= 0.525). There were no differences in the first recurrent site and death reason between both groups. The risk factors for leakage were being male and an anastomotic level in a multivariate analysis by logistic regression. The IMA ligation level was unrelated to anastomotic leakage. No significant difference was detected in long-term results between HT and LT.

Injury of the internal carotid artery (ICA) in the cavernous portion is one of the most critical complications of transsphenoidal surgery (TSS), especially in cases of coexistence with a pituitary adenoma (PA) and ICA aneurysm.

Laparoscopic surgery has been widely accepted for the treatment of colorectal cancer; however, long-term outcomes in elderly patients remain controversial. The midterm results of a randomized trial comparing open surgery with laparoscopic surgery in elderly patients with colorectal cancer are presented. This was a randomized trial comparing open surgery with laparoscopic surgery in elderly patients with colorectal cancer. The primary outcome was complication rate, and secondary outcomes included 3-year recurrence-free survival and overall survival. A total of 200 patients were randomly assigned to open surgery or laparoscopic surgery between 2008 and 2012. The main study objective was to compare the midterm outcomes of open surgery with those of laparoscopic surgery in elderly patients with colorectal cancer. This trial is registered with Clinical Trials.gov (NCT01862562). There were no differences between the laparoscopic surgery group and open surgery group in the 3-year overall survival rate (91.5% for laparoscopic surgery vs. 90.6% for open surgery, p= 0.638) or the 3-year recurrence-free survival rate (84.8% for laparoscopic surgery vs. 88.2% for open surgery, p= 0.324). The local recurrence rate was significantly higher in the laparoscopic surgery group than in the open surgery group in rectal cancer (13.8% for laparoscopic surgery vs. 0% for open surgery, p= 0.038). In subgroup analysis according to tumor location, there were no significant differences in the 3-year overall survival rate or 3-year recurrence-free survival rate between the two treatment groups. The midterm outcomes of laparoscopic surgery are similar to those of open surgery in elderly patients with colorectal cancer.

Transient receptor potential vanilloid 1 (TRPV1) was identified as a receptor of capsaicin, which is a pungent ingredient in hot red peppers. Due to its relevance for nociception, a physiological and pharmacological study of TRPV1 has also been developed. Therefore, it is important to enrich scientific knowledge regarding the TRPV1 activating or inhibiting compounds. In this study, we fractionated soy sauce based on the human TRPV1 (hTRPV1) activity using column chromatography and purified 5-(9H-pyrido[3,4-b]indol-1-yl)-2-furanmethanol (perlolyrine) as an hTRPV1-activating compound. Additionally, perlolyrine activates the human transient receptor potential ankyrin 1 (hTRPA1). The EC50of hTRPV1 and hTRPA1 were 2.87 and 1.67 μmol L−1, respectively. HPLC quantification of soy sauces showed that they contain 2.22–12.13 μmol L−1of perlolyrine. The sensory evaluation revealed that perlolyrine has taste modification effect. The results of this study, for the first time, suggest that perlolyrine induces the activation of hTRPV1 and hTRPA1.

There are no standardised criteria for the ‘regional’ pericolic node in colon cancer, which represents a major cause of the international uncertainty regarding the optimal bowel resection margin. This study aimed to determine ‘regional’ pericolic nodes based on prospective lymph node (LN) mapping.

Supplemental Digital Content is available in the text.

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 <60 upon hospital discharge (as a proxy for advanced PD). The primary endpoint was the prescribed dosage of levodopa at the index hospitalization. Dosages of other PD drugs (medications with an on-label indication for PD) and non-PD drugs were also assessed. Overall, 4029 patients met the inclusion criteria (mean age, 76.9 years; 83.3% aged ≥70 years). At the index date, 74.0% were receiving levodopa. Patients received a median of one PD drug in addition to levodopa, and 27.4% and 20.2% received one or two concomitant PD drugs, respectively. Patients received a median of two non-PD drugs. The median levodopa dosage and total levodopa equivalent dosage (LED) at the index hospitalization were 418.2 and 634.8 mg/day (adjusted for body weight, 9.0 and 13.7 mg/kg/day), respectively. The median levodopa and total LED dosage in each 6-month increment during the 5 years before and after the index date ranged between 263.9 and 330.2 mg/day (5.0 and 6.5 mg/kg/day) and 402.0 and 504.9 mg/day (8.3 and 10.1 mg/kg/day), respectively. This study suggests that many Japanese patients with advanced PD could receive more intensive treatment with higher doses of levodopa.

Supplemental Digital Content is available in the text.

We have developed a next-generation temporary fixing agent for electronic materials. This fixing agent allows for film peel-off via immersion in hot water while retaining strong adhesiveness, which can resist various forms of processing. Although thermoplastic adhesives (known as waxes) have been previously used as temporary fixing agents, problems related to their safety and workability were observed because they melt at high temperatures during the adhesion process. In addition, environmental issues were encountered due to the use of organic solvents in the cleaning process that was performed after peel-off. Conversely, our temporary fixing agent is expected to compensate for such limitations because it possesses advantageous characteristics, such as curing capabilities over short durations at room temperature using redox polymerization or photopolymerization, peel-off via immersion in hot water, and a film-type peel-off. Such fixing agents are becoming the de facto standard for use in the processing of capacitive touch sensors in glass covers, for example, in smartphones and tablet PCs.

A lipophilic oxygen radical absorbance capacity (L-ORAC) assay is an evaluation of the antioxidant capacity of solutions of lipophilic compounds. The concentrations of fluorescein k]radical generator k]and Trolox standard solutions were optimized to improve the precision of the assay. An interlaboratory study using two antioxidant solutions and three food extracts as test samples conducted in accordance with harmonized protocol demonstrated satisfactory L-ORAC measurements; the intermediate precision relative standard deviations (RSRDint) ranged from 7.0 to 16.7% k]the reproducibility relative standard deviations (RSDR) ranged from 14.8 to 19.4% k]and the HorRat values ranged from 1.35 to 1.78.

Although surgeons have tried to reduce the number of ports in order to achieve better cosmesis and less postoperative pain, it may lead to increased risk for complications. Herein, we introduce a technique, “laparoscopic bowel-lifting (LBL) technique,” which helps to reduce ports without additional trocars.

In surgical treatment of elderly patients, securing the safety of surgery and radical cure must be balanced. Our purpose was to verify the safety and validity of laparoscopic surgery for the treatment of colorectal cancer in elderly patients. Patients with cTis–T4a colorectal cancer who were 75 years or older were randomized to receive open or laparoscopic surgery. Exclusion criteria were patients who had a bulky tumor, rectal cancer that required pelvic side wall lymphadenectomy, and history of colon resection. Patients were divided according to tumor location (right colon, left colon, and rectum). The short-term outcomes were compared between the two groups. One hundred patients (right 43, left 28, and rectum 29) were registered in each group from August 2008 to August 2012. There were no differences in patient characteristics between the two groups. Three patients were converted from laparoscopic to open, because of bleeding, excision of peritoneum metastasis, and patient’s desire, respectively. In the short-term results (open:laparoscopic), there were significant differences in the rates of complications (36:23 %) and ileus (12:4 %), amount of blood loss (157:63 mL), and duration of surgery (150:172 min). There were no significant differences in the pathological margins, and the number of dissected lymph nodes. In the subgroup analysis according to the tumor location, there were significant differences in the rate of complications (39.4:22.5 %), amount of blood loss (135:42 mL), duration of surgery (139:160 min), and length of postoperative stay (13.0:10.0 days) in the colon cancer. There were no significant differences in short-term results in the rectal cancer. Laparoscopic surgery in elderly colorectal cancer patients did not result in a difference in radical cure compared with open surgery, and the short-term results except the duration of surgery were excellent. It is an effective procedure for elderly patients with colorectal cancer, especially colon cancer.

► We investigated the effects of different LET radiation in A. oryzae. ► Both γ-rays and ion beams induced base substitutions, frameshifts, deletions. ► Both γ-rays and ion beams induced genome-wide large-scale mutations in A. oryzae. ► Some differences in the types and frequencies of mutations were found. ► Our results provide new basic insights into the mutation breeding of A. oryzae.

Official Methods of Analysis of AOAC International (OMA) 2006.07 was originally designed for quantifying flavonol aglycones in ginkgo dietary supplements. To determine whether the method is applicable to the quantification of flavonol aglycones in lyophilized onion samples, single- and multi-laboratory validation studies were performed. Triplicated measurements on 3 different days revealed that the mean quercetin content was 3.48 g/kg dry weight, and the relative repeatability standard deviation (RSDr) and the relative intermediate standard deviation (RSDint) were 0.8 and 1.8%, respectively. The recovery of quercetin-3-O-glucoside spiked at 3 different amounts (1.56, 3.12, and 6.24 g/kg dry weight of onion) ranged from 98.42 to 100.31%, and the RSDrand RSDintranged from 2.2 to 5.9%, and from 3.4 to 5.2%, respectively. A multi-laboratory validation study showed that the mean quercetin contents were 2.80 and 6.61 g/kg dry weight, and that satisfactory inter-laboratory precision (RSDrand RSDRranged from 0.41 to 0.92%, and from 6.73 to 7.62%, respectively); all HorRat values were less than 2. These results indicate that OMA 2006.07 is applicable to the determination of the quercetin content of lyophilized onion samples.

Abstract: Background: Single-incision laparoscopic surgery (SILS) has been used for colorectal cancer as a minimally invasive procedure. However, there are still difficulties concerning effective triangulation and countertraction. The study’s purpose was to clarify the usefulness of the colon-lifting technique (CLT) in SILS for colorectal cancer. Methods: SILS was performed for cancer (cT2N0 or less) of the right-sided colon (near the ileocecum), sigmoid, or rectosigmoid. The SILS™ Port was used for transumbilical access. A suture string was inserted through the abdominal wall and passed through the mesocolon. The colon was retracted anteriorly and fixed to the abdominal wall. The main mesenteric vessels were placed under tension. Lymph node dissection was performed by medial approach. Short-term surgical outcomes and access port costs were compared between SILS (using CLT) and the standard multiport technique (MPT). The two groups were case-matched by propensity scoring. Analyzed variables included preoperative Dukes stage and tumor location. Results: From June 2009 to April 2011, 27 patients underwent SILS, and from April 2005 to April 2011, 85 patients underwent MPT. Propensity scoring generated 23 matched patients per group for SILS versus MPT comparisons. There were no significant differences in operating time, blood loss, early complications, postoperative analgesic frequency, or length of hospital stay. One MPT patient was converted to open surgery (4.5%); no SILS patients were converted. There were no significant differences in the length of distal cut margin and the number of harvested lymph nodes, except incision length (SILS vs. MPT: 33 vs. 55 mm, P < 0.001). Significant differences favored SILS in access instrument cost (SILS vs. MPT: 62,761 vs. 77,130 Japanese yen, P < 0.001). Conclusions: SILS performed using CLT was safe and effective in providing radical treatment of cT2N0 cancer in the right-sided colon, sigmoid, or rectosigmoid. SILS was advantageous with respect to cosmesis and lower cost of access instruments.