Publications by authors named "Satoshi Matsumoto"

136 Publications

A PROXYL-Type Norbornene Polymer for High-Voltage Cathodes in Lithium Batteries.

Macromol Rapid Commun 2021 Aug 4:e2100374. Epub 2021 Aug 4.

Department of Applied Chemistry, Waseda University, Tokyo, 169-8555, Japan.

A newly designed radical polymer with a polynorbornene backbone and unsaturated derivative of tetramethylpyrrolidine 1-oxyl (PROXYL) as pendant groups displays reversible redox at 3.75 V (vs Li/Li ). The robust polymer design enables the high voltage while maintaining a promising cyclability (over 1000 cycles). The polymer is also beneficial as an additive to the regular lithium iron phosphate electrodes, where the quickly responding organic material facilitates the charging reactions catalytically.
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http://dx.doi.org/10.1002/marc.202100374DOI Listing
August 2021

Benchmarking surface tension measurement method using two oscillation modes in levitated liquid metals.

NPJ Microgravity 2021 Mar 9;7(1):10. Epub 2021 Mar 9.

University of Florida Department of Chemical Engineering, Gainesville, FL, USA.

The Faraday forcing method in levitated liquid droplets has recently been introduced as a method for measuring surface tension using resonance. By subjecting an electrostatically levitated liquid metal droplet to a continuous, oscillatory, electric field, at a frequency nearing that of the droplet's first principal mode of oscillation (known as mode 2), the method was previously shown to determine surface tension of materials that would be particularly difficult to process by other means, e.g., liquid metals and alloys. It also offers distinct advantages in future work involving high viscosity samples because of the continuous forcing approach. This work presents (1) a benchmarking experimental method to measure surface tension by excitation of the second principal mode of oscillation (known as mode 3) in a levitated liquid droplet and (2) a more rigorous quantification of droplet excitation using a projection method. Surface tension measurements compare favorably to literature values for Zirconium, Inconel 625, and Rhodium, using both modes 2 and 3. Thus, this new method serves as a credible, self-consistent benchmarking technique for the measurement of surface tension.
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http://dx.doi.org/10.1038/s41526-021-00137-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943785PMC
March 2021

Key bacterial taxa and metabolic pathways affecting gut short-chain fatty acid profiles in early life.

ISME J 2021 09 15;15(9):2574-2590. Epub 2021 Mar 15.

Yakult Central Institute, Kunitachi, Tokyo, Japan.

Infant gut microbiota development affects the host physiology throughout life, and short-chain fatty acids (SCFAs) are promising key metabolites mediating microbiota-host relationships. Here, we investigated dense longitudinally collected faecal samples from 12 subjects during the first 2 years (n = 1048) to identify early life gut SCFA patterns and their relationships with the microbiota. Our results revealed three distinct phases of progression in the SCFA profiles: early phase characterised by low acetate and high succinate, middle-phase characterised by high lactate and formate and late-phase characterised by high propionate and butyrate. Assessment of the SCFA-microbiota relationships revealed that faecal butyrate is associated with increased Clostridiales and breastfeeding cessation, and that diverse and personalised assemblage of Clostridiales species possessing the acetyl-CoA pathway play major roles in gut butyrate production. We also found an association between gut formate and some infant-type bifidobacterial species, and that human milk oligosaccharides (HMO)-derived fucose is the substrate for formate production during breastfeeding. We identified genes upregulated in fucose and fucosylated HMO utilisation in infant-type bifidobacteria. Notably, bifidobacteria showed interspecific and intraspecific variation in the gene repertoires, and cross-feeding of fucose contributed to gut formate production. This study provides an insight into early life SCFA-microbiota relationships, which is an important step for developing strategies for modulating lifelong health.
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http://dx.doi.org/10.1038/s41396-021-00937-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397723PMC
September 2021

Systemic Chemotherapy is a Promising Treatment Option for Patients with Colonic Stents: A Review.

J Anus Rectum Colon 2021 28;5(1):1-10. Epub 2021 Jan 28.

Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan.

Approximately 10% of patients with colorectal cancer (CRC) develop malignant large bowel obstruction (MLBO) at diagnosis. Furthermore, for 35% of patients with MLBO, curative primary tumor resection is unfeasible because of locally advanced disease and comorbidities. The practice of placing a self-expandable metallic stent (SEMS) has dramatically increased as an effective palliative treatment. Recent advances in systemic chemotherapy for metastatic CRC have significantly contributed to prolonging patients' prognosis and expanding the indications. However, the safety and efficacy of systemic chemotherapy in patients with SEMS have not been established. This review outlines the current status of this relatively new therapeutic strategy and future perspectives. Some reports on this topic have demonstrated that 1) systemic chemotherapy and the addition of molecular targeted agents contribute to prolonged survival in patients with SEMS; 2) delayed SEMS-related complications are a major concern, and this requires strict patient monitoring; however, primary tumor control by chemotherapy might result in decreased complications, especially regarding re-obstruction; and 3) using bevacizumab could be a risk factor for SEMS-related perforation, which may be lethal. Although this relatively new approach for unresectable stage IV obstructive CRC requires a well-planned clinical trial, this therapy could be promising for patients who are unideal candidates for emergency surgery and require immediate systemic chemotherapy.
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http://dx.doi.org/10.23922/jarc.2020-061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843144PMC
January 2021

TEMPO-Substituted Poly(ethylene sulfide) for Solid-State Electro-Chemical Charge Storage.

Macromol Rapid Commun 2021 Feb 18;42(4):e2000607. Epub 2021 Jan 18.

Department of Applied Chemistry, Waseda University, Tokyo, 169-8555, Japan.

A poly(ethylene sulfide) backbone is introduced as the main chain of a radical polymer. Anionic ring-opening polymerization of an episulfide monomer substituted with 2,2,6,6tetramethylpiperidin1oxyl (TEMPO), a robust nitroxide radical, yields the corresponding polythioether. Compared to the traditional poly(ethylene oxide) backbone, the new polymer shows a lower glass transition temperature (-10 °C), and about threefold higher solid-state ionic conductivity. The polythioether is also shown to improve the charge/discharge properties of a cathode in solid-state lithium-ion batteries.
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http://dx.doi.org/10.1002/marc.202000607DOI Listing
February 2021

Does the diameter of colonic stent influence the outcomes in bridge-to-surgery patients with malignant large bowel obstruction?

Surg Today 2021 Jun 28;51(6):986-993. Epub 2020 Nov 28.

Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.

Purpose: This study investigated the short- and long-term outcomes of 18- and 22-mm-diameter self-expandable metallic stent (SEMS) as a bridge to surgery (BTS) in patients with malignant large bowel obstruction (MLBO).

Methods: Sixty-nine pathological stage II and III colorectal cancer patients who underwent BTS were included in this multi-institutional retrospective study. Patients were divided into two groups regarding the diameter of SEMS: an 18-mm group (n = 30) and a 22-mm group (n = 39).

Results: There was no significant difference in the clinical success rate, but both of the two re-obstructions observed occurred in the 18-mm group. The 18-mm group showed a trend toward a higher incidence of overall postoperative complications (Clavien-Dindo grading ≥ II) than the 22-mm group (33.3% vs. 10.3%, P = 0.061). The 3-year disease-free and overall survival showed no significant differences between the 18- and 22-mm groups (78.2% vs. 68.8%, P = 0.753 and 92.8% vs. 82.1%, P = 0.471, respectively).

Conclusion: SEMS of 18 and 22 mm diameter confer statistically equivalent short- and long-term outcomes as a BTS.
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http://dx.doi.org/10.1007/s00595-020-02185-2DOI Listing
June 2021

Clinical Features and Pathogenic Mechanisms of Gastrointestinal Injury in COVID-19.

J Clin Med 2020 Nov 11;9(11). Epub 2020 Nov 11.

Yakult Central Institute for Microbiological Research, Kunitachi, Tokyo 186-0011, Japan.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the global coronavirus disease 2019 (COVID-19) outbreak. Along with the respiratory tract, the gastrointestinal (GI) tract is one of the main extra-pulmonary targets of SARS-CoV-2 with respect to symptom occurrence and is a potential route for virus transmission, most likely due to the presence of angiotensin-converting enzyme 2. Therefore, understanding the mechanisms of GI injury is crucial for a harmonized therapeutic strategy against COVID-19. This review summarizes the current evidence for the clinical features of and possible pathogenic mechanisms leading to GI injury in COVID-19.
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http://dx.doi.org/10.3390/jcm9113630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696882PMC
November 2020

[Pathological Complete Response in Multiple Advanced Rectal Cancers with Neoadjuvant CapeOX plus BV Therapy-A Case Report].

Gan To Kagaku Ryoho 2020 Sep;47(9):1383-1385

Dept. of Surgery, Kuriyama Central Hospital.

A 70-year-old male with defecation difficulties was referred to our hospital. A colonoscopy and computed tomography revealed multiple advanced rectal cancers in the rectosigmoid and lower rectum with swollen lymph nodes. After 6 courses of neoadjuvant capecitabine and oxaliplatin and bevacizumab without radiotherapy(CapeOX plus BV therapy), a colonoscopy revealed that the tumors had significantly reduced. A low anterior laparoscopic resection with diverting ileostomy was performed. Histopathological examination showed no residual tumor cells or lymph node metastasis. A final diagnosis of pathological complete response was made. The patient has currently survived 1-year disease-free. Neoadjuvant CapeOX plus BV therapy can be a promising therapeutic option for locally advanced rectal cancer.
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September 2020

Diffusion enhancement in a levitated droplet via oscillatory deformation.

Phys Rev E 2020 Sep;102(3-1):033109

Graduate School of System and Information Engineering, University of Tsukuba, Tsukuba, Ibaraki 305-8573, Japan.

Recent experimental results indicate that mixing is enhanced by a reciprocal flow induced inside a levitated droplet with an oscillatory deformation [T. Watanabe et al., Sci. Rep. 8, 10221 (2018)2045-232210.1038/s41598-018-28451-5]. Generally, reciprocal flow cannot convect the solutes in time average, and agitation cannot take place. In the present paper, we focus on the diffusion process coupled with the reciprocal flow. We theoretically derive that the diffusion process can be enhanced by the reciprocal flow, and the results are confirmed via numerical calculation of the over-damped Langevin equation with a reciprocal flow.
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http://dx.doi.org/10.1103/PhysRevE.102.033109DOI Listing
September 2020

Multiple Transporters and Glycoside Hydrolases Are Involved in Arabinoxylan-Derived Oligosaccharide Utilization in Bifidobacterium pseudocatenulatum.

Appl Environ Microbiol 2020 11 24;86(24). Epub 2020 Nov 24.

Yakult Central Institute, Tokyo, Japan

Arabinoxylan hydrolysates (AXH) are the hydrolyzed products of the major components of the dietary fiber arabinoxylan. AXH include diverse oligosaccharides varying in xylose polymerization and side residue modifications with arabinose at the O-2 and/or O-3 position of the xylose unit. Previous studies have reported that AXH exhibit prebiotic properties on gut bifidobacteria; moreover, several adult-associated bifidobacterial species (e.g., and subsp. ) are known to utilize AXH. In this study, we tried to elucidate the molecular mechanisms of AXH utilization by , which is a common bifidobacterial species found in adult feces. We performed transcriptomic analysis of YIT 4072, which identified three upregulated gene clusters during AXH utilization. The gene clusters encoded three sets of ATP-binding cassette (ABC) transporters and five enzymes belonging to glycoside hydrolase family 43 (GH43). By characterizing the recombinant proteins, we found that three solute-binding proteins of ABC transporters showed either broad or narrow specificity, two arabinofuranosidases hydrolyzed either single- or double-decorated arabinoxylooligosaccharides, and three xylosidases exhibited functionally identical activity. These data collectively suggest that the transporters and glycoside hydrolases, encoded in the three gene clusters, work together to utilize AXH of different sizes and with different side residue modifications. Thus, our study sheds light on the overall picture of how these proteins collaborate for the utilization of AXH in and may explain the predominance of this symbiont species in the adult human gut. Bifidobacteria commonly reside in the human intestine and possess abundant genes involved in carbohydrate utilization. Arabinoxylan hydrolysates (AXH) are hydrolyzed products of arabinoxylan, one of the most abundant dietary fibers, and they include xylooligosaccharides and those decorated with arabinofuranosyl residues. The molecular mechanism by which , a common bifidobacterial species found in adult feces, utilizes structurally and compositionally variable AXH has yet to be extensively investigated. In this study, we identified three gene clusters (encoding five GH43 enzymes and three solute-binding proteins of ABC transporters) that were upregulated in YIT 4072 during AXH utilization. By investigating their substrate specificities, we revealed how these proteins are involved in the uptake and degradation of AXH. These molecular insights may provide a better understanding of how resident bifidobacteria colonize the colon.
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http://dx.doi.org/10.1128/AEM.01782-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688211PMC
November 2020

Evaluation of the safety and efficacy of suction-tip forceps, a new tool for laparoscopic surgery, for gastric cancer.

Asian J Endosc Surg 2021 Apr 10;14(2):232-240. Epub 2020 Sep 10.

Department of Digestive Surgery, Nippon Medical School, Tokyo, Japan.

Introduction: Laparoscopic surgery is a minimally invasive surgery; however, obstacles to its functional optimization remain. Surgical ports can accommodate only one instrument at a time so complex exchange manipulations are necessary during surgery which increases operation times and patient risk. We developed a new laparoscopic instrument that functions as both forceps and a suction tube, which renders intraoperative tool exchange unnecessary. This pilot study was undertaken to evaluate the safety and efficacy of this novel dual-function device in laparoscopic surgery for gastric cancer.

Methods: This single-center pilot study assessed patient safety during and after laparoscopic distal gastrectomy for gastric cancer with the suction-forceps using intraoperative video and clinical follow-up, respectively. To evaluate instrument efficacy, we measured the time interval between the start of any bleeding and the start of aspiration ("suction access time") and compared this time with that of a conventional surgical setup.

Results: In total 15 patients participated, with all procedures being successful. No excess tissue damage occurred during surgery. Suction access time was significantly shorter in cases of bleeding when the suction-tip forceps were used for aspiration (2.01 seconds) compared to an ordinary suction tube (12.5 seconds; P < .01).

Conclusion: These findings suggest that our new suction-tip forceps are a useful, safe, and efficacious operative tool. This surgical innovation may considerably simplify gastric laparoscopic surgery. This pilot study was registered with Japan Clinical Trial Registration on 22 June 2017 (registration number: UMIN000027879).
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http://dx.doi.org/10.1111/ases.12858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048834PMC
April 2021

Prognostic Role of the Platelet-to-Lymphocyte Ratio for Patients With Metastatic Colorectal Cancer Treated With Aflibercept.

In Vivo 2020 Sep-Oct;34(5):2667-2673

Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan.

Background/aim: The efficacy of aflibercept plus 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) therapy has been demonstrated in patients with metastatic colorectal cancer (mCRC) in global and Japanese clinical trials. However, a practical biomarker to predict its efficacy is lacking.

Patients And Methods: This was a single-institution retrospective study of 21 patients with mCRC consecutively treated with aflibercept plus FOLFIRI from March 2018 to July 2019. We investigated the association and predictive value of pretreatment blood inflammation and immune-based scores, including the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio, using their median values as cut-offs, in regard to disease control (DC), progression-free (PFS), and overall (OS) survival.

Results: The number of patients in each treatment line of aflibercept was as follows: Second, 14 (66.7%); third, four (19.0%); fourth, two (9.5%); eighth, one (4.8%). The median number of aflibercept treatment courses was seven (range=2-17). The median follow-up time was 391 days. In univariate analysis, patients with DC had a significantly lower PLR than those without DC. Only the PLR was significantly negatively associated with PFS, but not with OS. Multivariate analysis showed a significantly poor prognostic impact of a high PLR on PFS (hazard ratio=10.28; p=0.003).

Conclusion: A low pretreatment PLR might be a predictor of aflibercept efficacy in patients with mCRC and may be clinically useful for selecting patient responders.
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http://dx.doi.org/10.21873/invivo.12086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652534PMC
June 2021

Impacts of Habitual Diets Intake on Gut Microbial Counts in Healthy Japanese Adults.

Nutrients 2020 Aug 12;12(8). Epub 2020 Aug 12.

Yakult Central Institute, 5-11 Izumi, Kunitachi-shi, Tokyo 186-8650, Japan.

Although diet is an important factor influencing gut microbiota, there are very few studies regarding that relationship in Japanese people. Here, we analyzed the relationship between habitual dietary intake surveyed by food frequency questionnaire and the quantitative features of gut bacteria by quantitative PCR and next generation sequencer in 354 healthy Japanese adults. The α-diversity of gut microbiota was positively correlated with the intake of mushrooms and beans and negatively correlated with the intake of grains. The β-diversity was significantly associated with the intake of fruits, mushrooms, seaweeds, seafoods, and alcoholic beverages. Multiple linear regression analysis of the relationship between food groups associated with the diversity of gut microbiota and the number of gut bacteria at the genus level found 24 significant associations, including a positive association between alcoholic beverages and the number of . These results support that habitual dietary intake influenced the diversity of gut microbiota and was strongly associated with the number of specific gut bacteria. These results will help us to understand the complex relationship between habitual diet and gut microbiota of the Japanese.
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http://dx.doi.org/10.3390/nu12082414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468936PMC
August 2020

Effects of Sphingolipid Fractions from Golden Oyster Mushroom (Pleurotus citrinopileatus) on Apoptosis Induced by Inflammatory Stress in an Intestinal Tract in vitro Model.

J Oleo Sci 2020 Sep 13;69(9):1087-1093. Epub 2020 Aug 13.

Department of Life and Food Science, Obihiro University of Agriculture and Veterinary Medicine.

Previously, we reported that the polar lipid fraction from the golden oyster mushroom, Pleurotus citrinopileatus, suppresses colon injuries which result from apoptosis induced by inflammatory stresses in vivo and in vitro (Yamashita et al., J. Oleo Sci., 69, 751-757 (2020)). Here, we investigated the use of lipid classes in mushroom polar lipid fraction in alleviating colon injury using differentiated Caco-2 cells as an intestinal tract model. The mushroom polar lipid fraction was separated into four fractions using silica thin layer chromatography. Each mushroom polar lipid fraction suppressed lipopolysaccharide (LPS)-induced decreases in the viability of intestinal cells, and the effects of sphingolipid fractions were significantly stronger than those of fraction that did not contain sphingolipids. Addition of sphingolipid fractions suppressed the expression of apoptosis-related proteins (e.g., death receptors and caspases) in the LPS-treated cells. Mushroom polar lipids, especially sphingolipids suppress intestinal apoptosis induced by inflammatory stress, and highly polar sphingolipids may exert stronger suppressive effects.
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http://dx.doi.org/10.5650/jos.ess20105DOI Listing
September 2020

Polar Lipid Fraction from Golden Oyster Mushrooms (Pleurotus citrinopileatus) Suppresses Colon Injuries from Inflammatory Stresses in vivo and in vitro.

J Oleo Sci 2020 ;69(7):751-757

Department of Life and Food Science, Obihiro University of Agriculture and Veterinary Medicine.

The rising incidence of inflammatory bowel disease (IBD) in East Asian countries has necessitated the implementation of preventive methods in the form of dietary supplementation and changes in dietary habits. We have previously reported that dietary golden oyster mushroom (Pleurotus citrinopileatus) ethanol extract (GOMEE) suppresses intestinal inflammation in mouse models of IBD induced by dextran sulfate sodium salt (DSS). Here, we investigated the components of GOMEE that exert suppressive effects on colon inflammation in vivo and in vitro. The total lipid fraction was extracted from GOMEE, and the polar and neutral lipid fractions were subsequently separated via solvent fractionation. Mice were assigned to dietary groups-control, 1% total lipid, 1% polar lipid, or 1% neutral lipid diet-and fed the respective diets for one week; mice were administered 1.5% DSS in drinking water ad libitum for 20 days. Dietary supplementation with the total or polar lipid fraction alleviated DSS-induced chorionic crypt injury as determined by morphological observation, while dietary supplementation with the neutral lipid fraction did not produce such effects. In the in vitro study, using differentiated Caco-2 cells as the colon model, treatment with the total or polar lipid fraction suppressed cell decrease by lipopolysaccharide (LPS)-induced apoptosis whereas treatment with the neutral lipid fraction did not. Moreover, accumulation of glucosylceramide (GlcCer), a fungal sphingolipid, was observed in the intestinal cells after treatment with polar lipid fraction. These results suggest that the active components of GOMEE that suppress colon inflammation are polar lipids, especially GlcCer. The structure of mushroom GlcCer differs from that of the plant counterpart and is therefore expected to exert different food functions.
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http://dx.doi.org/10.5650/jos.ess20050DOI Listing
November 2020

Oral Administration of the Food-Derived Hydrophilic Antioxidant Ergothioneine Enhances Object Recognition Memory in Mice.

Curr Mol Pharmacol 2021 ;14(2):220-233

Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-1192, Japan.

Background: The enhancement of learning and memory through food-derived ingredients is of great interest to healthy individuals as well as those with diseases. Ergothioneine (ERGO) is a hydrophilic antioxidant highly contained in edible golden oyster mushrooms (Pleurotus cornucopiae var. citrinopileatus), and systemically absorbed by its specific transporter, carnitine/organic cation transporter OCTN1/SLC22A4.

Objective: This study aims to examine the possible enhancement of object recognition memory by oral administration of ERGO in normal mice.

Methods: Novel object recognition test, spatial recognition test, LC-MS/MS, Golgi staining, neuronal culture, western blotting, immunocytochemistry, and quantitative RT-PCR were utilized.

Result: After oral administration of ERGO (at a dose of 1-50 mg/kg) three times per week for two weeks in ICR mice, the novel object recognition test revealed a longer exploration time for the novel object than for the familiar object. After oral administration of ERGO, the spatial recognition test also revealed a longer exploration time for the spatially moved object than the unmoved one in mice fed ERGO-free diet. The discrimination index was significantly higher in the ERGO-treated group than the control in both behavioral tests. ERGO administration led to an increase in its concentration in the plasma and hippocampus. The systemic concentration reached was relevant to those found in humans after oral ERGO administration. Golgi staining revealed that ERGO administration increased the number of matured spines in the hippocampus. Exposure of cultured hippocampal neurons to ERGO elevated the expression of the synapse formation marker, synapsin I. This elevation of synapsin I was inhibited by the tropomyosin receptor kinase inhibitor, K252a. Treatment with ERGO also increased the expression of neurotrophin-3 and -5, and phosphorylated mammalian target of rapamycin in hippocampal neurons.

Conclusion: Oral intake of ERGO may enhance object recognition memory at its plasma concentration achievable in humans, and this enhancement effect could occur, at least in part, through the promotion of neuronal maturation in the hippocampus.
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http://dx.doi.org/10.2174/1874467213666200212102710DOI Listing
January 2021

Postoperative non-steroidal anti-inflammatory drugs and anastomotic leakage after gastrointestinal anastomoses: Systematic review and meta-analysis.

Ann Gastroenterol Surg 2020 Jan 2;4(1):64-75. Epub 2019 Dec 2.

Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery Nippon Medical School Tokyo Japan.

Aim: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to control postoperative pain; however, their postoperative use has been associated with anastomotic leakage after gastrointestinal surgery. This systematic review and meta-analysis aimed to determine the correlation between the use of NSAIDs and anastomotic leakage.

Methods: We conducted a comprehensive electronic literature search up to August 2018 to identify studies comparing anastomotic leakage in patients with and without postoperative NSAID use following gastrointestinal surgery. We then carried out a meta-analysis using random-effects models to calculate odds ratios (OR) with 95% confidence intervals (CI).

Results: Twenty-four studies were included in this meta-analysis, including a total of 31 877 patients. Meta-analysis showed a significant association between NSAID use and anastomotic leakage (OR 1.73; 95% CI = 1.31-2.29,  < .0001). Subgroup analyses showed that non-selective NSAIDs, but not selective cyclooxygenase-2 inhibitors, were significantly associated with anastomotic leakage. However there was no significant subgroup difference between selective and non-selective NSAIDs.

Conclusion: Results of this meta-analysis indicate that postoperative NSAID use is associated with anastomotic leakage following gastrointestinal surgeries. Caution is warranted when using NSAIDs for postoperative analgesic control in patients with gastrointestinal anastomoses.
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http://dx.doi.org/10.1002/ags3.12300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992684PMC
January 2020

Metabolic endotoxemia promotes neuroinflammation after focal cerebral ischemia.

J Cereb Blood Flow Metab 2020 12 7;40(12):2505-2520. Epub 2020 Jan 7.

Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.

Lipopolysaccharide (LPS) is a major component of the outer membrane of Gram-negative bacteria and a potent inflammatory stimulus for the innate immune response via toll-like receptor (TLR) 4 activation. Type 2 diabetes is associated with changes in gut microbiota and impaired intestinal barrier functions, leading to translocation of microbiota-derived LPS into the circulatory system, a condition referred to as metabolic endotoxemia. We investigated the effects of metabolic endotoxemia after experimental stroke with transient middle cerebral artery occlusion (MCAO) in a murine model of type 2 diabetes () and phenotypically normal littermates (). Compared to mice, mice exhibited an altered gut microbial composition, increased intestinal permeability, and higher plasma LPS levels. In addition, mice presented increased infarct volumes and higher expression levels of LPS, TLR4, and inflammatory cytokines in the ischemic brain, as well as more severe neurological impairments and reduced survival rates after MCAO. Oral administration of a non-absorbable antibiotic modulated the gut microbiota and improved metabolic endotoxemia and stroke outcomes in mice; these effects were associated with reduction of LPS levels and neuroinflammation in the ischemic brain. These data suggest that targeting metabolic endotoxemia may be a novel potential therapeutic strategy to improve stroke outcomes.
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http://dx.doi.org/10.1177/0271678X19899577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820690PMC
December 2020

Preoperative lymphocyte-to-monocyte ratio predicts postoperative infectious complications after laparoscopic colorectal cancer surgery.

Int J Clin Oncol 2020 Apr 28;25(4):633-640. Epub 2019 Nov 28.

Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.

Background And Aim: Postoperative infectious complications (POI), which can increase length of hospital stay, medical cost, and worsen overall survival, are a concern in minimally invasive colorectal cancer (CRC) surgeries. Recent reports showed that relatively new inflammation-based score, lymphocyte-to-monocyte ratio (LMR) is an independent predictor of long-term outcomes after CRC surgeries. In this study, LMR was evaluated as a predictor of short-term postoperative outcomes.

Patients And Methods: This was a single-institutional retrospective study of 211 consecutive patients who had undergone laparoscopic CRC surgery with primary tumor resection from January 2014 to August 2015 at Nippon Medical School Chiba Hokusoh Hospital. The patients were divided into two groups (no POI; n = 176 and POI; n = 35). The associations between inflammation-based scores, namely neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and LMR, and the occurrence of POI were investigated. Receiving operator characteristic curve analysis was used to determine the cutoff point of preoperative LMR.

Results: Low LMR (cut-off 3.46), long operative time, and smoking were found to be independent predictors of POI in a multivariate analysis (LMR: Odds ratio 5.61, 95% confidence interval 1.98-15.9, P = 0.001). Patients with low LMR also appeared to have more advanced and aggressive tumours.

Conclusion: This is the first study to report that the lower LMR is a predictive factor of POI after laparoscopic CRC surgery, and it may provide additional information for treatment decisions to prevent POI.
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http://dx.doi.org/10.1007/s10147-019-01583-yDOI Listing
April 2020

Facile Synthesis of Poly(Glycidyl Ether)s with Ionic Pendant Groups by Thiol-Ene Reactions.

Macromol Rapid Commun 2020 Jan 21;41(1):e1900399. Epub 2019 Oct 21.

Department of Applied Chemistry, Waseda University, Tokyo, 169-8555, Japan.

Poly(glycidyl ether)s having trifluoromethanesulfonylimide or imidazolium pendant groups are synthesized by thiol-ene reactions. The precise synthesis of a precursor polymer, poly(allyl glycidyl ether), and the following click reactions enable the facile preparation of the polyelectrolytes with the controlled length of main and side chains. The low glass transition temperature (<<0 °C) of the polyethers is beneficial to provide a conductivity as high as 10 S cm at room temperature, without compositing any additives. The synthetic approach has advantages of clearly comparing the structural effects of the introduced functional groups and facilely preparing the comprehensive types of polymers.
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http://dx.doi.org/10.1002/marc.201900399DOI Listing
January 2020

[Long-Term Complete Response in an Unresectable Advanced Gastric Cancer Patient Treated with Low-Dose S-1].

Gan To Kagaku Ryoho 2019 Oct;46(10):1573-1575

Dept. of Surgery, Nippon Medical School Chiba Hokusoh Hospital.

After undergoing an upper gastrointestinal endoscopy, a 74-year-old woman with anemia was diagnosed with advanced lower gastric cancer. We performed laparotomy and identified the tumor as unresectable because of the direct invasion to the pancreas. S-1 was administered at 60mg/day for 2 weeks followed by 1-week discontinuation. After 6 weeks, we changed the schedule to the same dosage of S-1 for 1 week followed by 2-week discontinuation. CT and endoscopic findings showed complete response after 64weeks of S-1 administration. Since then, S-1 has been maintained at 60mg/day intermittently for 14 days in 7 weeks accordingto the patient's condition. The patient is currently doingwell with a complete response for more than 5 years.
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October 2019

Clinical factors associated with bacterial translocation in Japanese patients with type 2 diabetes: A retrospective study.

PLoS One 2019 19;14(9):e0222598. Epub 2019 Sep 19.

Department of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan.

Objective: To explore clinical factors associated with bacterial translocation in Japanese patients with type 2 diabetes mellitus (T2DM).

Methods: The data of 118 patients with T2DM were obtained from two previous clinical studies, and were retrospectively analyzed regarding the clinical parameters associated with bacterial translocation defined as detection of bacteremia and levels of plasma lipopolysaccharide binding protein (LBP), the latter of which is thought to reflect inflammation caused by endotoxemia.

Results: LBP level was not significantly different between patients with and without bacteremia. No clinical factors were significantly correlated with the detection of bacteremia. On the other hand, plasma LBP level was significantly correlated with HbA1c (r = 0.312), fasting blood glucose (r = 0.279), fasting C-peptide (r = 0.265), body mass index (r = 0.371), high-density lipoprotein cholesterol (r = -0.241), and inflammatory markers (high-sensitivity C-reactive protein, r = 0.543; and interleukin-6, r = 0.456). Multiple regression analysis identified body mass index, HbA1c, high-sensitivity C-reactive protein, and interleukin-6 as independent determinants of plasma LBP level.

Conclusion: The plasma LBP level was similar in patients with and without bacteremia. While both bacteremia and LBP are theoretically associated with bacterial translocation, the detection of bacteremia was not associated with LBP level in T2DM.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222598PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752875PMC
March 2020

Pretreatment Neutrophil-to-Lymphocyte Ratio Predicts Survival After TAS-102 Treatment of Patients With Metastatic Colorectal Cancer.

Anticancer Res 2019 Aug;39(8):4343-4350

Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan.

Background/aim: TAS-102 is recommended as salvage-line therapy for metastatic colorectal cancer (mCRC), but practical predictors for its efficacy are lacking.

Patients And Methods: In a single-institutional retrospective study of 33 patients treated with TAS-102, we investigated the predictive value of the pretreatment neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and lymphocyte-monocyte (LMR) ratios for progression-free (PFS) and overall (OS) survival. Predictive ability using cut-offs of the median value (3.14) and 5 for NLR were compared.

Results: In univariate analysis, Eastern Cooperative Oncology Group performance score, NLR, and PLR were negatively significantly associated with PFS and OS. The number of treatment lines was negatively associated with PFS. The NLR cut-off of 5 was superior to the median value. Multivariate analyses showed a significant prognostic impact for NLR at cut-off 5 (hazard ratio(HR)=6.26, p=0.02 for PFS; HR=6.97, p=0.07 for OS).

Conclusion: The pretreatment NLR is a prognostic biomarker for patients with mCRC who receive TAS-102 treatment.
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http://dx.doi.org/10.21873/anticanres.13602DOI Listing
August 2019

Blood Galectin-3 Levels Predict Postoperative Complications after Colorectal Cancer Surgery.

J Nippon Med Sch 2019 ;86(3):142-148

Department of Surgery, Nippon Medical School.

Background: Recent studies suggested that galectin-3 may act as a pro-inflammatory damage-associated molecular pattern. The aim of this study is to investigate the association between blood galectin-3 and postoperative complications (POC) after colorectal cancer (CRC) surgery.

Methods: Blood samples were taken from 35 patients with CRC before surgery, immediately after surgery, and on postoperative days (POD) 1, 3, 5, and 7. Blood galectin-3 and interleukin-6 levels were measured by commercially available ELISA. Patients were divided into those with (POC group) and without POC (no-POC group).

Results: Significantly higher galectin-3 levels were observed pre- and postoperatively in the POC group (n=10) compared with those of the no-POC group (n=25). Galectin-3 levels on POD1 showed the best predictive potential for POC (cut-off: 3.18 pg/mL, area under the curve: 0.868).

Conclusions: These results indicate that increased perioperative blood galectin-3 levels may be associated with POC after CRC surgery.
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http://dx.doi.org/10.1272/jnms.JNMS.2019_86-302DOI Listing
December 2019

Short-term outcomes of a self-expandable metallic stent as a bridge to surgery vs. a transanal decompression tube for malignant large-bowel obstruction: a meta-analysis.

Surg Today 2019 Sep 23;49(9):728-737. Epub 2019 Feb 23.

Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo, Tokyo, 113-8603, Japan.

Purpose: Preoperative intestinal decompression, using either a self-expandable metallic stent (SEMS) as a bridge to surgery (BTS) or a transanal decompression tube (TDT), provides an alternative to emergency surgery for malignant large-bowel obstruction (MLBO). We conducted this meta-analysis to compare the short-term outcomes of SEMS placement as a BTS vs. TDT placement for MLBO.

Methods: We conducted a comprehensive electronic search of literature published up to March, 2018, to identify studies comparing the short-term outcomes of BTS vs. TDT. Decompression device-related and surgery-related variables were evaluated and a meta-analysis was performed using random-effects models to calculate odd ratios with 95% confidence intervals.

Results: We analyzed 14 nonrandomized studies with a collective total of 581 patients: 307 (52.8%) who underwent SEMS placement as a BTS and 274 (47.2%) who underwent TDT placement. The meta-analyses showed that the BTS strategy conferred significantly better technical and clinical success, helped to maintain quality of life by allowing free food intake and temporal discharge, promoted laparoscopic one-stage surgery without stoma creation, and had equivalent morbidity and mortality to TDT placement.

Conclusions: Although the long-term outcomes are as yet undetermined, the BTS strategy using SEMS placement could be a new standard of care for preoperative decompression to manage MLBO.
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http://dx.doi.org/10.1007/s00595-019-01784-yDOI Listing
September 2019

Liquid Biopsy for the Management of Patients with Colorectal Cancer.

Digestion 2019 14;99(1):39-45. Epub 2018 Dec 14.

Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan.

Background: Liquid biopsy is a collective term that refers to the analysis of tumor-derived biomarkers isolated from biological fluids of cancer patients. Recently, many authors reported the usefulness of liquid biopsy for the management of malignancy. Summary and Key Messages: The peripheral blood of cancer patients is a pool of cells and/or cell products derived from the primary or metastatic tumor, including circulating tumor cells (CTCs), circulating free (cf) DNA or RNA, and exosomes containing proteins, nucleic acids, and lipids. CTCs are tumor cells that can be isolated from peripheral blood. Free circulating DNA with a tumor-specific mutation is called circulating tumor DNA (ctDNA). Some patients who undergo curative surgery experience recurrent disease, which can be due to the presence of minimal residual disease (MRD). Thus, MRD indicates a high risk of relapse. Detection of ctDNA or CTC after surgery is a direct proof of MRD. Molecular volume (e.g., the number of CTCs and level of ctDNA) might reflect tumor burden, thus high molecular volume may indicate poor prognosis. The most notable application of liquid biopsy in cancer is to understand spatial and temporal heterogeneities. Heterogeneity is one of the causes of refractoriness and hampers prediction of chemotherapeutic effect. Emerging mutations that are not present in primary tumors but are found in their metastases can be detected in ctDNA. Some colorectal cancer patients with wild-type RAS do not respond to epidermal growth factor receptor blockade. In a subset of these patients, RAS mutation is detected in ctDNA, indicating heterogeneity.
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http://dx.doi.org/10.1159/000494411DOI Listing
April 2019

[Physicians' Directions about Artificial Hydration and Nutrition at End-of-Life].

Gan To Kagaku Ryoho 2018 Nov;45(11):1631-1635

Dept. of Palliative Care, Nippon Medical School Chiba Hokusoh Hospital.

Purpose: To conduct a questionnaire survey to elicit physicians' directions about artificialhydration and nutrition at end-oflife.

Methods: A questionnaire was sent to 2,773 randomly selected Japanese physicians who were registrants of Rakuten Research Inc.(Tokyo, Japan). Of the respondents, 500 returned the questionnaire, and their reposes were analyzed. The Fisher's exact test was used to compare the respective responses.

Results: Of the 500 physicians, 22.4%(112)chose to discontinue artificialhydration and nutrition for those who are at terminalstage and could no longer communicate. On the other hand, 20.8%(104/500)of the physicians chose to continue artificialhydration and nutrition for those who were confined to bed and had the tendency to self-remove drip infusion or other tubes. Significantly more physicians who were working in hospitals than in private clinics chose to continue artificial hydration and nutrition(27% vs 3%; p<0.00001).

Conclusion: Our findings revealed that 20.8% of physicians did not know about the latest evidence of end-of-life care to uphold patient dignity until the end-of-life. As our results might be different from the practice in other facilities located abroad, we must adopt prudent guidelines for palliative and end-of-life care and enlighten physicians and medical students regarding the current guidelines.
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November 2018

Colonic stent-induced mechanical compression may suppress cancer cell proliferation in malignant large bowel obstruction.

Surg Endosc 2019 04 31;33(4):1290-1297. Epub 2018 Aug 31.

Department of Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.

Background: The short-term safety and efficacy of insertion of a self-expandable metallic colonic stent (SEMS) followed by elective surgery, "bridge to surgery (BTS)", for malignant large bowel obstruction (MLBO) have been well described; however, the influence on long-term oncological outcomes is unclear. The aim of this study was to evaluate changes in oncological characteristics in colorectal cancer (CRC) tissues after SEMS insertion, focusing on growth factors, cell cycle and apoptosis.

Methods: From January 2013 to September 2014, a total of 25 patients with MLBO who underwent BTS at our single institution were retrospectively included. Paired CRC tissue samples before (endoscopic biopsy) and after SEMS insertion (surgically resected) were collected from each patient. EGFR, VEGF, Ki-67, p27 and TUNEL expression were determined by immunohistochemistry.

Results: No clinical or subclinical perforations evaluated by mechanical ulceration pathologically were observed. Epithelial exfoliation, tumour necrosis, infiltration of inflammatory cells and fibrosis were observed in SEMS-inserted surgically-resected specimens. Overall, 84% (21/25) and 60% (15/25) of patients exhibited no change or a decrease in staining category, respectively, for EGFR and VEGF expression after SEMS insertion. A significant decrease in Ki-67 expression was observed in surgically-resected specimens compared with endoscopic biopsy specimens (P < 0.01). The upstream cell cycle inhibitor, p27, was significantly increased after SEMS insertion (P = 0.049).

Conclusions: Although the long-term safety of BTS should be determined in a future clinical trial, mechanical compression by SEMS may suppress cancer cell proliferation and this result could provide some insights into the issue.
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http://dx.doi.org/10.1007/s00464-018-6411-xDOI Listing
April 2019

Placement of a self-expandable metallic stent as a bridge to surgery for large bowel obstruction induced by effective neoadjuvant therapy: report of three cases.

Surg Case Rep 2018 Aug 23;4(1):100. Epub 2018 Aug 23.

Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo, Tokyo, 113-8603, Japan.

Background: Self-expandable metallic stent placement is a widely performed palliative procedure or bridge to surgery for obstructive colorectal cancer. However, the feasibility of this procedure for large bowel obstruction induced by effective neoadjuvant therapy is unclear.

Case Presentation: We herein report three such cases involving a 61-year-old man who underwent neoadjuvant chemoradiotherapy for lower rectal cancer, a 56-year-old woman who underwent neoadjuvant chemotherapy for lower rectal cancer, and a 63-year-old woman who underwent neoadjuvant chemotherapy for lower rectal cancer. All were emergently hospitalized with large bowel obstruction that developed while undergoing neoadjuvant therapy. Colonoscopy revealed smooth strictures caused by effective neoadjuvant therapy. Self-expandable metallic stents were placed across the obstruction as a bridge to surgery, and laparoscopic low anterior resection was uneventfully performed in all patients.

Conclusions: We successfully treated three patients with large bowel obstruction induced by a good response to neoadjuvant therapy using self-expandable metallic stents as a bridge to surgery. Further studies with larger sample sizes are warranted to assess the feasibility of this strategy.
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http://dx.doi.org/10.1186/s40792-018-0509-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6107482PMC
August 2018

Single-port laparoscopic-assisted resection for a large abdominal cystic lymphangioma: a case report.

Surg Case Rep 2018 Aug 13;4(1):92. Epub 2018 Aug 13.

Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan.

Background: We report the case of a young woman with a large abdominal cystic lymphangioma that was successfully resected using single-port laparoscopic-assisted cystectomy. This avoided the need for a large surgical incision, as would result during conventional laparotomy.

Case Presentation: A 17-year-old young woman was admitted to our hospital complaining of abdominal pain that had persisted for 3 days. Computed tomography revealed a 10 × 10 × 10-cm low-density area in the mid-abdomen, and magnetic resonance imaging showed a large abdominal cystic lesion. A mesenteric cyst was suspected, and single-port laparoscopic-assisted resection was performed. The cyst fluid was aspirated using a tissue adhesive, a suction tube with negative pressure, and a 16-gage over-the-needle catheter and syringe. The tumor size was reduced without any spillage of cyst fluid into the abdominal cavity. Then, the shrunken cystic tumor was successfully removed via the small wound and resected outside the abdomen. Pathological findings revealed an abdominal cystic lymphangioma derived from the greater omentum.

Conclusions: Our procedure was easy to perform and required no special materials. Therefore, it could be applied to various cases, such as for abdominal cystic diseases.
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http://dx.doi.org/10.1186/s40792-018-0501-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089858PMC
August 2018
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