Functional genomic analysis of the isolated potential probiotic Lactobacillus delbrueckii subsp. indicus TY-11 and its comparison with other Lactobacillus delbrueckii strains.

Probiotics refer to living microorganisms that exert a variety of beneficial effects on human health. On the contrary, they also can cause infection, produce toxins within the body, and transfer antibiotic-resistant genes to the other microorganisms in the digestive tract necessitating a comprehensive safety assessment. This study aimed to conduct functional genomic analysis and some relevant biochemical tests to uncover the probiotic potentials of Lactobacillus delbrueckii subsp. indicus TY-11 isolated from native yogurt in Bangladesh. We also performed transmission electron microscopic (TEM) analysis, comparative genomic study as well as phylogenetic tree construction with 332 core genes from 262 genomes. The strain TY-11 was identified as Lactobacillus delbrueckii subsp. indicus, whose genome (1,916,674 bp) contained 1911 CDS, and no gene was identified for either antibiotic resistance or toxic metabolites. It carried genes for the degradation of toxic metabolites, treatment of lactose intolerance, toll-like receptor 2-dependent innate immune response, heat and cold shock, bile salts tolerance, and acidic pH tolerance. Genes were annotated for inhibiting pathogenic bacteria by inhibitory substances [bacteriocin: Helveticin-J (331 bp) and Enterolysin-A (275 bp), hydrogen peroxide, and acid]; blockage of adhesion sites; and competition for nutrients. The genes involved in its metabolic pathway were detected as suitable for digesting indigestible nutrients in the human gut. The TY-11 genome possessed an additional 37 core genes of subspecies indicus which were deficient in the core genome of the most popular subsp. bulgaricus. During the phenotypic testing, the isolate TY-11 demonstrated high antagonistic activity (inhibition zone of 21.33 ± 1.53 mm) against Escherichia coli ATCC 8739 and was not sensitive to any of the 10 tested antibiotics. This study was the first study to explore the molecular insights into probiotic roles, including antimicrobial activities and antibiotic sensitivity, of a representative strain (TY-11) of Lactobacillus delbrueckii subsp. indicus. IMPORTANCE: This study aimed to conduct functional genomic analysis to uncover the probiotic potential of Lactobacillus delbrueckii subsp. indicus TY-11 isolated from native yogurt in Bangladesh. We also performed transmission electron microscopic (TEM) analysis, comparative genomic study as well as phylogenetic tree construction with 332 core genes from 262 genomes. In our current investigation, we revealed a number of common and unique excellences of the probiotic Lactobacillus delbrueckii subsp. indicus TY-11 that are likely to be important to illustrate its intestinal residence and probiotic roles. This is the first study to explore the molecular insights into intestinal residence and probiotic roles, including antimicrobial activities and antibiotic sensitivity, of a representative strain (TY-11) of Lactobacillus delbrueckii subsp. indicus.

Successful haploidentical hematopoietic stem cell transplantation for paroxysmal nocturnal hemoglobinuria with severe pancytopenia developed after long-term aplastic anemia treatment.

Haploidentical hematopoietic stem cell transplantation (HSCT) with posttransplant cyclophosphamide is an alternative treatment for aplastic anemia-paroxysmal nocturnal hemoglobinuria (PNH) syndrome with poor prognostic factors. Ravulizumab treatment for PNH before HSCT might have a beneficial effect.

Effects of transcutaneous auricular vagus nerve stimulation at left cymba concha on experimental pain as assessed with the nociceptive withdrawal reflex, and correlation with parasympathetic activity.

The aim of this study was to clarify the effects of transcutaneous auricular vagus nerve stimulation (taVNS) to the left cymba concha on the pain perception using nociceptive withdrawal reflex (NWR), which is known to be associated with chronic pain, and to investigate whether there is a relationship between taVNS-induced suppression of the NWR and parasympathetic activation. We applied either 3.0 mA, 100 Hz taVNS for 120 s on the left cymba concha (taVNS condition) or the left earlobe (Sham condition) for 20 healthy adults. NWR threshold was measured before (Baseline), immediately after (Post 0), 10 min (Post 10) and 30 min after (Post 30) stimulation. The NWR threshold was obtained from biceps femoris muscle by applying electrical stimulation to the sural nerve. During taVNS, electrocardiogram was recorded, and changes in autonomic nervous activity measured by heart rate variability (HRV) were analyzed. We found that the NWR thresholds at Post 10 and Post 30 increased compared with baseline in the taVNS group (10 min after: p = .008, 30 min after: p = .008). In addition, increased parasympathetic activity by taVNS correlated with a greater increase in NWR threshold at Post 10 and Post 30 (Post 10: p = .003; Post 30: p = .001). The present results of this single-blinded study demonstrate the pain-suppressing effect of taVNS on NWR threshold and suggest that the degree of parasympathetic activation during taVNS may predict the pain-suppressing effect of taVNS after its application.

Correlation between pathology and quantitative ultrasonographic evaluation of pancreatic fat with ultrasonographic classification.

PURPOSE: No studies of the relationship between grayscale sonographic findings and pancreatic fat content have been reported to date. This study aimed to investigate the correlation between echogenicity and fat content of resected specimens using quantitative analysis. METHODS: Forty-two consecutive patients who underwent pancreatoduodenectomy or distal pancreatectomy for pancreatic tumors were enrolled in this study. Ultrasonographic images were compared with quantitative pathological analysis. Subjective evaluation of echogenicity was classified as hypoechoic, isoechoic, hyperechoic, and super hyperechoic. The total and intralobular fat areas were measured. RESULTS: The mean, median, modal, minimum, and maximum ultrasound gray values correlated with the proportion of total fat area (r = 0.349; 0.357, 0.486, 0.466, and 0.347; p = 0.024, 0.020, 0.014, 0.019, and 0.089, respectively), but did not correlate with the proportion of intralobular fat area. Subjective classification was correlated with median gray value (p < 0.001), intralobular fat area (p = 0.118), and total fat area (p = 0.011). Cases were classified as hypoechoic (n = 3), isoechoic (n = 7), hyperechoic (n = 30), and super hyperechoic (n = 2). The subjective classification was correlated with the median gray value (p < 0.001) and total fat area (p = 0.005), and not correlated with the intralobular fat area (p = 0.118). Hyperechoic or super hyperechoic pancreatic parenchyma contains over 19.7% fat. Computed tomography values correlated with the proportion of intralobular fat area (r = - 0.479, p = 0.004) and total fat area (r = - 0.541, p < 0.001). CONCLUSION: Echogenicity classified based on subjective evaluation and image analysis were correlated with the proportion of fat in the pancreas.

Skeletal muscle status and survival among patients with advanced biliary tract cancer.

BACKGROUND: Studies have demonstrated a prognostic role of sarcopenia (i.e., loss of skeletal muscle volume and functionality) in patients with various cancer types. In patients with biliary tract cancer, the quantity and quality of skeletal muscles and their serial changes have not been fully investigated in relation to survival outcomes. METHODS: We identified 386 patients with unresectable or recurrent biliary tract cancer and calculated skeletal muscle index (SMI) and skeletal muscle density (SMD) to estimate muscular quantity and quality, respectively, based on computed tomography images. Using the Cox regression model with adjustment for potential confounders, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS) according to skeletal muscle status and its serial change. RESULTS: Compared to patients without sarcopenia, patients with sarcopenia were associated with shorter PFS (multivariable HR, 1.60; 95% CI, 1.15-2.22; P = 0.005), but not with OS (P = 0.027) at the adjusted α level of 0.013. SMD at baseline was associated with OS (multivariable HR comparing the extreme quartiles, 1.52; 95% CI, 1.07-2.14; Ptrend = 0.012), but not with PFS (Ptrend = 0.13). A reduction in SMI rather than that in SMD was associated with OS. Progressive disease was a risk factor for reductions in SMI and SMD. CONCLUSIONS: Skeletal muscle quantity and quality and their serial changes were associated with survival outcomes in patients with advanced biliary tract cancer. Our data highlight the importance of designing nutritional and physical interventions for improvements in skeletal muscle status.

Involvement of GAT2/Slc6a13 in hypotaurine uptake at fetal-facing plasma membrane of syncytiotrophoblasts at mid-to-late gestation in rats and mice.

INTRODUCTION: Hypotaurine, a precursor to taurine, is known for its antioxidant properties and is prominently present in fetal plasma and the placenta. Our previous research revealed that ezrin-knockout mice experience fetal growth retardation, coinciding with reduced hypotaurine levels in fetal plasma. This study aims to elucidate the expression and role of hypotaurine transporters within the placenta. METHODS: We employed quantitative RT-PCR to measure mRNA expression of GAT transporter family members in the placenta during mid-to-late gestation. LC/MS/MS was used to analyze the distribution of hypotaurine in different placental subregions. Immunohistochemistry was utilized to examine the localization of GAT2 in mice. Placental hypotaurine uptake from fetal circulation was studied via umbilical perfusion in rats. RESULTS: Among hypotaurine transporters, GAT2 exhibited increased mRNA and protein expression in murine placenta during mid-to-late gestation. Notably, GAT2/Slc6a13 mRNA and hypotaurine were most concentrated in the labyrinth of murine placenta. In contrast, enzymes responsible for hypotaurine synthesis, such as cysteine dioxygenase, cysteine sulfinic acid decarboxylase, and 2-aminoethanethiol dioxygenase, showed minimal expression in the labyrinth. These findings suggest that GAT2 is a key determinant of hypotaurine levels in the placental labyrinth. Immunohistochemical examination unveiled that GAT2 was predominantly localized on the fetal-facing plasma membrane within syncytiotrophoblasts, which co-localized with ezrin. In rat umbilical perfusion experiments, the GAT2/3 and TauT inhibitor, SNAP-5114, significantly reduced hypotaurine extraction from fetal circulation to the placenta. DISCUSSION: The results suggest that GAT2 plays a pivotal role in the concentrative uptake of hypotaurine from fetal plasma within syncytiotrophoblasts of the placenta.

A comparison of diagnostic utility of new endoscopic scraper combined cell block method and conventional brush catheter for biliary tract cancer.

Background/Aims: The sensitivities of endoscopic trans-papillary pathologic diagnosis of biliary tract cancer (BTC) are unsatisfactory. Recently, the diagnostic utility of the endoscopic scraper device, Trefle for biliary stricture has been reported. The Trefle can be guided to the target biliary stricture over the guidewire and is as easy to use as the conventional brush catheter (CBC). This study evaluated the efficacy and safety of Trefle-assisted tissue acquisition combined cell block method and CBC cytology for biliary strictures due to BTCs. Methods: We retrospectively reviewed consecutive patients with biliary strictures in whom CBC cytology or Trefle-assisted tissue acquisition under endoscopic retrograde cholangiopancreatography was performed for suspected BTCs from January 2015 to June 2022 at our institution. Results: 173 patients (CBC group; n = 55, Trefle group; n = 118) were enrolled in this study. The sensitivity, specificity, and accuracy of CBC cytology for BTC were 68.3%/100%/76.4%. On the other hand, the sensitivity, specificity, and accuracy of Trefle-assisted tissue acquisition for BTC were 93.7%/95.7%/94.1%, showing superior sensitivity (p < 0.001) and accuracy (p = 0.002) compared to that of CBC. Conclusions: Compared to CBC cytology, Trefle-assisted tissue acquisition has superior diagnostic performance while maintaining procedural simplicity and is considered useful for diagnosing malignant biliary stricture.

Retrospective comparative study of new slim-delivery and conventional large-cell stents for stent-in-stent methods for hilar malignant biliary obstruction.

OBJECTIVES: Endoscopic management of unresectable hilar malignant biliary obstruction (HMBO) is technically challenging, and effectiveness of stent-in-stent using large-cell, metal stents was reported. A new, large-cell stent with a 6F tapered delivery system was recently developed. The aim of this study was to compare clinical outcomes of slim-delivery and conventional large-cell stents. METHODS: This was a multicenter retrospective comparative study of stent-in-stent methods using slim-delivery stents (Niti-S Large Cell SR Slim Delivery [LC slim-delivery]) and conventional stents (Niti-S large-cell D-type; LCD) for unresectable HMBO. RESULTS: Eighty-three patients with HMBO were included; 31 LC slim-delivery and 52 LCD. Overall technical and clinical success rates were 100% and 90% in LC slim-delivery group and 98% and 88% in LCD group. Use of the LC slim-delivery was associated with shorter stent placement time in the multiple regression analysis, with a stent placement time of 18 and 23 min in LC slim-delivery and LCD groups, respectively. The early adverse event (AE) rate of LC slim-delivery was 10%, with no cholangitis or cholecystitis as compared to 23% in the LCD group. Recurrent biliary obstruction (RBO) rates and time to RBO were comparable between the two groups: 35% and 44%, and 8.5 and 8.0 months in LC slim-delivery and LCD groups, respectively. The major cause of RBO was tumor ingrowth (82%) in the LC slim-delivery group and sludge (43%) and ingrowth (48%) in LCD group. CONCLUSION: Stent-in-stent methods using LC slim-delivery shortened stent placement time with low early AE rates and comparable time to RBO in patients with HMBO.

Confined-microtubule assembly shapes three-dimensional cell wall structures in xylem vessels.

Properly patterned deposition of cell wall polymers is prerequisite for the morphogenesis of plant cells. A cortical microtubule array guides the two-dimensional pattern of cell wall deposition. Yet, the mechanism underlying the three-dimensional patterning of cell wall deposition is poorly understood. In metaxylem vessels, cell wall arches are formed over numerous pit membranes, forming highly organized three-dimensional cell wall structures. Here, we show that the microtubule-associated proteins, MAP70-5 and MAP70-1, regulate arch development. The map70-1 map70-5 plants formed oblique arches in an abnormal orientation in pits. Microtubules fit the aperture of developing arches in wild-type cells, whereas microtubules in map70-1 map70-5 cells extended over the boundaries of pit arches. MAP70 caused the bending and bundling of microtubules. These results suggest that MAP70 confines microtubules within the pit apertures by altering the physical properties of microtubules, thereby directing the growth of pit arches in the proper orientation. This study provides clues to understanding how plants develop three-dimensional structure of cell walls.

High proton conductivity within the 'Norby gap' by stabilizing a perovskite with disordered intrinsic oxygen vacancies.

Proton conductors are attractive materials with a wide range of potential applications such as proton-conducting fuel cells (PCFCs). The conventional strategy to enhance the proton conductivity is acceptor doping into oxides without oxygen vacancies. However, the acceptor doping results in proton trapping near dopants, leading to the high apparent activation energy and low proton conductivity at intermediate and low temperatures. The hypothetical cubic perovskite BaScO2.5 may have intrinsic oxygen vacancies without the acceptor doping. Herein, we report that the cubic perovskite-type BaSc0.8Mo0.2O2.8 stabilized by Mo donor-doing into BaScO2.5 exhibits high proton conductivity within the 'Norby gap' (e.g., 0.01 S cm-1 at 320 °C) and high chemical stability under oxidizing, reducing and CO2 atmospheres. The high proton conductivity of BaSc0.8Mo0.2O2.8 at intermediate and low temperatures is attributable to high proton concentration, high proton mobility due to reduced proton trapping, and three-dimensional proton diffusion in the cubic perovskite stabilized by the Mo-doping into BaScO2.5. The donor doping into the perovskite with disordered intrinsic oxygen vacancies would be a viable strategy towards high proton conductivity at intermediate and low temperatures.

Development and external validation of a nomogram for prediction of post-endoscopic retrograde cholangiopancreatography pancreatitis.

BACKGROUND AND AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is widely performed for management of pancreatobiliary diseases; however, post-ERCP pancreatitis (PEP) remains as an unsolved problem. Although various risk factors for PEP have been reported, the prediction of PEP remains controversial. This study aimed to develop a predictive model for PEP. METHODS: Consecutive patients undergoing ERCP for biliary indications at two centers were retrospectively studied. Using data from a training cohort, we utilized a multivariable model to select five variables to construct a nomogram. The predictive model was internally and externally validated. Based on the nomogram, the patients were categorized into low-, moderate-, and high-risk groups. RESULTS: Using the data of 2224 patients in the training cohort, five variables were selected to generate a nomogram: 1) sex, 2) indication for ERCP, 3) difficult cannulation, 4) guidewire insertion into the pancreatic duct, and 5) endoscopic sphincterotomy or sphincteroplasty. The most significant risk factor was endoscopic papillary balloon dilation such as endoscopic sphincterotomy or sphincteroplasty. The bias-corrected concordance index was 0.72 in the training cohort and 0.72 in the validation cohort. Calibration curves for both cohorts demonstrated good agreement between the predicted and observed frequencies of the actual outcome. In the validation cohort, PEP developed in 5.0% and 14% of patients in the moderate- and high-risk groups, respectively. CONCLUSIONS: We successfully developed a good predictive model for PEP. The prevention of PEP in high risk patients should be investigated further.

The Usefulness of the Alpha-Retroflex Position in Biliary Cannulation on Single-Balloon Enteroscopy-Assisted Endoscopic Retrograde Cholangiopancreatography in Patients with Roux-en-Y Gastrectomy: A Retrospective Study.

Introduction: Balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP) is a useful therapeutic procedure that provides promising results in patients with surgically altered anatomy. However, biliary cannulation in BE-ERCP remains challenging. Therefore, in patients with Roux-en-Y gastrectomy, this study aimed to evaluate a BE-ERCP cannulation strategy that includes the newly developed alpha-retroflex scope position. Methods: This was a retrospective review of 52 patients with Roux-en-Y gastrectomy who underwent BE-ERCP at two centers between April 2017 and December 2022. In these patients, three types of scope position had been used for biliary cannulation: straight (S-position), J-retroflex (J-position), and alpha-retroflex (A-position). First, the S-position was used for biliary cannulation. Then, if biliary cannulation was difficult with this position, the J-position was used, followed by the A-position, if necessary. Results: The biliary cannulation success rate was 96.6% (50/52). The S-, J-, and A-positions achieved successful biliary cannulation in 24 (48%), 14 (28%), and 12 patients (24%), respectively. No adverse events, including post-ERCP pancreatitis and perforation, occurred. Conclusion: This was the first study of a cannulation strategy that included the A-position in addition to the S- and J-positions. The study showed that the A-position is feasible and safe in BE-ERCP in patients with Roux-en-Y gastrectomy.

Gemcitabine plus nab-paclitaxel for pancreatic cancer and interstitial lung disease: A nationwide longitudinal study.

Interstitial lung disease (ILD) is an adverse event associated with gemcitabine administration. Gemcitabine plus nab-paclitaxel, which is now a first-line chemotherapy regimen for pancreatic cancer (PC), may increase the risk of ILD; however, large-scale clinical data on this are limited. Thus, this study aimed to elucidate the incidence and risk factors of ILD in patients with PC receiving gemcitabine plus nab-paclitaxel. Through the Diagnosis Procedure Combination database, a Japanese nationwide inpatient database with outpatient data, we identified consecutive patients with PC who received gemcitabine-based chemotherapy between July 2010 and March 2019 at 205 hospitals. Competing-risk analysis was used to examine the cumulative incidence and risk factors of ILD. Among the 6163 patients who received gemcitabine plus nab-paclitaxel, we documented 168 patients (2.7%) who developed ILD with cumulative incidence rates (95% confidence intervals [CIs]) of 2.0% (1.6%-2.4%), 2.7% (2.2%-3.1%), and 3.1% (2.6%-3.6%) at 3, 6, and 12 months, respectively. Compared with patients with PC who received gemcitabine monotherapy, those who received gemcitabine plus nab-paclitaxel had an adjusted subdistribution hazard ratio (SHR) for ILD of 1.93 (95% CI: 1.51-2.47). Older age was associated with a high risk of ILD in patients receiving gemcitabine plus nab-paclitaxel (adjusted SHR comparing ≥75 to ≤74 years, 1.61; 95% CI: 1.16-2.24). In conclusion, this study demonstrated the clinical course of gemcitabine plus nab-paclitaxel-associated ILD in patients with PC. When gemcitabine plus nab-paclitaxel is administered to elderly patients with PC, symptoms associated with ILD must be monitored.

Diagnostic utility of quantitative analysis of microRNA in bile samples obtained during endoscopic retrograde cholangiopancreatography for malignant biliary strictures.

BACKGROUND: The sensitivity of bile cytology for malignant biliary strictures is not adequate. To overcome this limitation, we evaluated whether quantitative analysis of microRNAs (miRNAs) in bile can provide a precise diagnosis of malignant biliary strictures due to pancreatic cancer (PC) and biliary tract cancer (BTC). METHODS: This was a retrospective evaluation of miRNA levels in stored bile samples of patients with PC, BTC or benign biliary stricture obtained during biliary drainage from April 2019 to December 2021 at our institution. A total of 113 patients (PC; n = 40, BTC; n = 38, control; n = 35) were enrolled. The miRNA candidates to be quantified were determined with microarray analysis from each 3 patients with PC, BTC and controls. RESULTS: Using microarray analysis, we confirmed four significantly up-regulated miRNAs (miR-1275, miR-6891-5p, miR-7107-5p, miR-3197) in patients with PC and BTC compared to control patients. Quantitative PCR was then performed in 113 bile samples for these miRNAs. miR-1275 was significantly upregulated in PC (p = 0.003) and BTC (p = 0.049) compared to controls, miR-6891-5p was significantly upregulated in PC compared to controls (p = 0.025). In particular, a combination of bile cytology and miR-1275 in bile showed a sensitivity of 77.5% (95% CI, 70.7-77.5%), specificity of 100% (95% CI, 92.2-100%) and an area under the curve (AUC) of 0.93, and provided a significantly greater additional diagnostic effect than bile cytology alone (p = 0.014). CONCLUSIONS: This study suggest that bile miRNAs could be potential biomarkers for pancreato-biliary diseases, particularly miR-1275 and miR-6891-5p may be helpful in the diagnosis of PC and BTC.

The effects of transcranial electrical stimulation of the left dorsolateral prefrontal cortex on tactile spatial discrimination performance.

The dorsolateral prefrontal cortex (DLPFC) plays a key role in tactile perceptual discrimination performance. Both transcranial random noise stimulation (tRNS) and anodal transcranial pulsed current stimulation (tPCS) have been shown to modulate neural activity in cortical regions. In this study, we aimed to determine whether tRNS and anodal tPCS over the left DLPFC would improve tactile perceptual discrimination performance of the right index finger in healthy neurological individuals. Subjects underwent a grating orientation task before, immediately after, and 30 min after applying tRNS in Experiment 1 or anodal tPCS in Experiment 2. tRNS application on the left DLPFC tended to enhance tactile perceptual discrimination performance. In contrast, the application of anodal tPCS over the left DLPFC did not affect tactile perceptual discrimination performance. These findings indicate that transcranial electrical stimulation to the left DLPFC may improve tactile perceptual discrimination performance, with effects that depend on stimulus modality.

Beta resting-state functional connectivity predicts tactile spatial acuity.

Tactile perception is a complex phenomenon that is processed by multiple cortical regions via the primary somatosensory cortex (S1). Although somatosensory gating in the S1 using paired-pulse stimulation can predict tactile performance, the functional relevance of cortico-cortical connections to tactile perception remains unclear. We investigated the mechanisms by which corticocortical and local networks predict tactile spatial acuity in 42 adults using magnetoencephalography (MEG). Resting-state MEG was recorded with the eyes open, whereas evoked responses were assessed using single- and paired-pulse electrical stimulation. Source data were used to estimate the S1-seed resting-state functional connectivity (rs-FC) in the whole brain and the evoked response in the S1. Two-point discrimination threshold was assessed using a custom-made device. The beta rs-FC revealed a negative correlation between the discrimination threshold and S1-superior parietal lobule, S1-inferior parietal lobule, and S1-superior temporal gyrus connection (all P < 0.049); strong connectivity was associated with better performance. Somatosensory gating of N20m was also negatively correlated with the discrimination threshold (P = 0.015), with weak gating associated with better performance. This is the first study to demonstrate that specific beta corticocortical networks functionally support tactile spatial acuity as well as the local inhibitory network.

Early skeletal muscle mass decline is a prognostic factor in patients receiving gemcitabine plus nab-paclitaxel for unresectable pancreatic cancer: a retrospective observational study.

PURPOSE: Patients with pancreatic cancer often have cancer cachexia at diagnosis. Recent studies suggested that loss of skeletal muscle mass was related to cancer cachexia, which hindered continuance of chemotherapy and could be one of prognostic factors in pancreatic cancer, however the association remains unclear in patients receiving gemcitabine and nab-paclitaxel (GnP). METHODS: We retrospectively studied 138 patients with unresectable pancreatic cancer receiving first-line GnP at the University of Tokyo from January 2015 to September 2020. We calculated body composition in CT images before chemotherapy and at initial evaluation, and evaluated the association of both body composition before chemotherapy and its changes at initial evaluation. RESULTS: Compared by skeletal muscle mass index (SMI) change rate between pre-chemotherapy and initial evaluation, there were statistically significantly differences in the median OS: 16.3 months (95%CI 12.3-22.7) and 10.3 months (95%CI 8.3-18.1) between SMI change rate ≥ -3.5% and < -3.5% groups (P = 0.01). By multivariate analysis for OS, CA19-9 (HR 3.34, 95%CI 2.00-5.57, P < 0.01), PLR (HR 1.68, 95%CI 1.01-2.78, P = 0.04), mGPS (HR 2.32, 95%CI 1.47-3.65, P < 0.01) and relative dose intensity (HR 2.21, 95%CI 1.42-3.46, P < 0.01) were significantly poor prognostic factors. SMI change rate (HR 1.47, 95%CI 0.95-2.28, P = 0.08) showed a trend to poor prognosis. Sarcopenia before chemotherapy was not significantly associated with PFS or OS. CONCLUSION: Early skeletal muscle mass decline was associated with poor OS. Further investigation is warranted whether the maintenance of skeletal muscle mass by nutritional support would improve prognosis.