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Abstract Genomic alterations in tumors play a pivotal role in determining their clinical trajectory and responsiveness to treatment. Targeted panel sequencing (TPS) has served as a key clinical tool over the past decade, but advancements in sequencing costs and bioinformatics have now made whole-genome sequencing (WGS) a feasible single-assay approach for almost all cancer genomes in clinical settings. This paper reports on the findings of a prospective, single-center study exploring the real-world clinical utility of WGS (tumor and matched normal tissues) and has two primary objectives: (1) assessing actionability for therapeutic options and (2) providing clarity for clinical questions. Of the 120 patients with various solid cancers who were enrolled, 95 (79%) successfully received genomic reports within a median of 11 working days from sampling to reporting. Analysis of these 95 WGS reports revealed that 72% (68/95) yielded clinically relevant insights, with 69% (55/79) pertaining to therapeutic actionability and 81% (13/16) pertaining to clinical clarity. These benefits include the selection of informed therapeutics and/or active clinical trials based on the identification of driver mutations, tumor mutational burden (TMB) and mutational signatures, pathogenic germline variants that warrant genetic counseling, and information helpful for inferring cancer origin. Our findings highlight the potential of WGS as a comprehensive tool in precision oncology and suggests that it should be integrated into routine clinical practice to provide a complete image of the genomic landscape to enable tailored cancer management.

Background Infantile café au lait spot is a brown macule with various sizes (diameter: 0.5 cm–30 cm). Infantile giant café au lait spot (IGCALS) is a huge (diameter >20cm) irregular-shaped benign hyperpigmented skin disorder that arises in infants. There has been no clearly established laser treatment consensus for the treatment of IGCALS because infants are too fragile to receive laser treatment with long hours and broad areas along with the possibility of undesirable cosmetic results.Objectives This study investigated the safety and efficacy of Golden Parameter Therapy (GPT) using a high fluence 1064-nm Q-switched Nd:YAG laser (QSNL) for IGCALS treatment.Methods This study included 24 Korean patients with IGCALS. Twenty-one patients who were treated with a 1064-nm QSNL weekly for 30–50 treatment sessions with GPT. The parameters included a spot size of 7 mm, a fluence of 2.2 J/cm2 and a pulse rate of 10 Hz with one pass using a sliding-stacking technique over the IGCALS. In control group, three patients were treated with a 532-nm picosecond laser monthly for three treatment sessions with a spot size of 3 mm, a fluence of 1 J/cm2 and a pulse rate of 2 Hz.Results After the last treatment, 21 patients with IGCALS reached the complete removal of pigmented lesions, which can be considered optimal cosmetic results without any side effects such as purpura, crust, post-inflammatory hyperpigmentation, iatrogenic punctate leukoderma, and scarring. There are no recurrences in any patients after 6–21 months’ follow-up, but treatment failure occurred in three patients who were treated with 532 nm picosecond laser.Conclusions Convincingly, we argue that early intervention before 12 months of age with GPT using a high fluence 1064 nm QSNL is a safe, applicable and effective treatment for IGCALS, minimizing side effects without any recurrences.

Abstract Background Tumor cells of diffuse-type gastric cancer (DGC) are discohesive and infiltrate into the stroma as single cells or small subgroups, so the stroma significantly impacts DGC progression. Cancer-associated fibroblasts (CAFs) are major components of the tumor stroma. Here, we identified CAF-specific secreted molecules and investigated the mechanism underlying CAF-induced DGC progression. Methods We conducted transcriptome analysis for paired normal fibroblast (NF)-CAF isolated from DGC patient tissues and proteomics for conditioned media (CM) of fibroblasts. The effects of fibroblasts on cancer cells were examined by transwell migration and soft agar assays, western blotting, and in vivo. We confirmed the effect of blocking tubulointerstitial nephritis antigen-like 1 (TINAGL1) in CAFs using siRNA or shRNA. We evaluated the expression of TINAGL1 protein in frozen tissues of DGC and paired normal stomach and mRNA in formalin-fixed, paraffin-embedded (FFPE) tissue using RNA in-situ hybridization (RNA-ISH). Results CAFs more highly expressed TINAGL1 than NFs. The co-culture of CAFs increased migration and tumorigenesis of DGC. Moreover, CAFs enhanced the phosphorylation of focal adhesion kinase (FAK) and mesenchymal marker expression in DGC cells. In an animal study, DGC tumors co-injected with CAFs showed aggressive phenotypes, including lymph node metastasis. However, increased phosphorylation of FAK and migration were reduced by blocking TINAGL1 in CAFs. In the tissues of DGC patients, TINAGL1 was higher in cancer than paired normal tissues and detected with collagen type I alpha 1 chain (COL1A1) in the same spot. Furthermore, high TINAGL1 expression was significantly correlated with poor prognosis in several public databases and our patient cohort diagnosed with DGC. Conclusions These results indicate that TINAGL1 secreted by CAFs induces phosphorylation of FAK in DGC cells and promotes tumor progression. Thus, targeting TINAGL1 in CAFs can be a novel therapeutic strategy for DGC.

Abstract Background Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment (TME) that play an important role in cancer progression. Although the mechanism by which CAFs promote tumorigenesis has been well investigated, the underlying mechanism of CAFs activation by neighboring cancer cells remains elusive. In this study, we aim to investigate the signaling pathways involved in CAFs activation by gastric cancer cells (GC) and to provide insights into the therapeutic targeting of CAFs for overcoming GC. Methods Alteration of receptor tyrosine kinase (RTK) activity in CAFs was analyzed using phospho-RTK array. The expression of CAFs effector genes was determined by RT-qPCR or ELISA. The migration and invasion of GC cells co-cultured with CAFs were examined by transwell migration/invasion assay. Results We found that conditioned media (CM) from GC cells could activate multiple receptor tyrosine kinase signaling pathways, including ERK, AKT, and STAT3. Phospho-RTK array analysis showed that CM from GC cells activated PDGFR tyrosine phosphorylation, but only AKT activation was PDGFR-dependent. Furthermore, we found that connective tissue growth factor (CTGF), a member of the CCN family, was the most pronouncedly induced CAFs effector gene by GC cells. Knockdown of CTGF impaired the ability of CAFs to promote GC cell migration and invasion. Although the PDGFR-AKT pathway was pronouncedly activated in CAFs stimulated by GC cells, its pharmacological inhibition affected neither CTGF induction nor CAFs-induced GC cell migration. Unexpectedly, the knockdown of SRC and SRC-family kinase inhibitors, dasatinib and saracatinib, significantly impaired CTGF induction in activated CAFs and the migration of GC cells co-cultured with CAFs. SRC inhibitors restored the reduced expression of epithelial markers, E-cadherin and Zonula Occludens-1 (ZO-1), in GC cells co-cultured with CAFs, as well as CAFs-induced aggregate formation in a 3D tumor spheroid model. Conclusions This study provides a characterization of the signaling pathways and effector genes involved in CAFs activation, and strategies that could effectively inhibit it in the context of GC. Video Abstract

Abstract Splenic hilar (no.10) lymph node dissection during total gastrectomy is no longer recommended for advanced proximal gastric cancer. However, the treatment efficacy of no.10 lymph node dissection in Borrmann type 4 tumors remains unclear. We enrolled 539 patients who underwent total gastrectomy for Borrmann type 4 tumors between 2006 and 2016 in four major institutions in Korea. We compared the long-term survival of the no.10 lymph node dissection (n = 309) and no-dissection groups (n = 230) using the propensity score (inverse probability of treatment weighting). The treatment effects of no.10 lymph node dissection were estimated in the weighted sample using the Cox proportional hazards regression model with a robust sandwich-type variance estimator. After inverse probability of treatment weighting, there were 540.4 patients in the no.10 lymph node dissection group and 532.7 in the no-dissection group. The two groups showed well-balanced baseline characteristics, including tumor node metastasis stage. The 5-year survival rates in the no.10 lymph node dissection and no-dissection groups were 45.7% and 38.6%, respectively (log-rank p = 0.036, hazard ratio 0.786, 95% confidence interval 0.630–0.982). Multivariate analysis revealed that no.10 lymph node dissection was an independent favorable prognostic factor (adjusted hazard ratio 0.747, 95% confidence interval 0.593–0.940) after adjusting for other prognostic factors. Sensitivity analyses in other inverse probability of treatment weighting models and the propensity score matching model showed similar results. Patients undergoing no.10 lymph node dissection showed improved survival compared to those without. No.10 lymph node dissection is recommended during total gastrectomy for patients with Borrmann type 4 gastric cancer.

Abstract Various prospective surgical trials have been conducted on treating patients with gastric cancer. In clinical practice, patients and surgeons may hesitate to participate in prospective surgical trials due to trial-related complications. In this study, we evaluated the effects of participation in prospective surgical trials on surgical outcomes after radical gastrectomy for gastric cancer. This study included 1689 patients who underwent curative gastrectomy for gastric cancer between 2016 and 2020. The propensity score weighting (PSW) method was used to adjust for differences in baseline clinicopathological characteristics between patients who participated and those who did not participate in prospective surgical clinical trials. Perioperative outcomes and overall survival were compared between groups. Of the 1689 patients, 309 (18.3%) participated in surgical clinical trials (SCT group). Before PSW, the SCT group had a similar operation time, intraoperative blood loss, complications, major complications, and hospital stay as the non-SCT group but had superior overall survival. After PSW, overall survival and perioperative outcomes were not significantly different between the groups. The present study suggests that participation in prospective surgical trials was not associated with surgical outcomes. Patients and surgeons may participate in prospective surgical trials without fearing adverse effects on surgical outcomes.

Abstract Background Personalized survival prediction is important in gastric cancer patients after gastrectomy based on large datasets with many variables including time‐varying factors in nutrition and body morphometry. One year after gastrectomy might be the optimal timing to predict long‐term survival because most patients experience significant nutritional change, muscle loss, and postoperative changes in the first year after gastrectomy. We aimed to develop a personalized prognostic artificial intelligence (AI) model to predict 5 year survival at 1 year after gastrectomy. Methods From a prospectively built gastric surgery registry from a tertiary hospital, 4025 gastric cancer patients (mean age 56.1 ± 10.9, 36.2% females) treated gastrectomy and survived more than a year were selected. Eighty‐nine variables including clinical and derived time‐varying variables were used as input variables. We proposed a multi‐tree extreme gradient boosting (XGBoost) algorithm, an ensemble AI algorithm based on 100 datasets derived from repeated five‐fold cross‐validation. Internal validation was performed in split datasets (n = 1121) by comparing our proposed model and six other AI algorithms. External validation was performed in 590 patients from other hospitals (mean age 55.9 ± 11.2, 37.3% females). We performed a sensitivity analysis to analyse the effect of the nutritional and fat/muscle indices using a leave‐one‐out method. Results In the internal validation, our proposed model showed AUROC of 0.8237, which outperformed the other AI algorithms (0.7988–0.8165), 80.00% sensitivity, 72.34% specificity, and 76.17% balanced accuracy. In the external validation, our model showed AUROC of 0.8903, 86.96% sensitivity, 74.60% specificity, and 80.78% balanced accuracy. Sensitivity analysis demonstrated that the nutritional and fat/muscle indices influenced the balanced accuracy by 0.31% and 6.29% in the internal and external validation set, respectively. Our developed AI model was published on a website for personalized survival prediction. Conclusions Our proposed AI model provides substantially good performance in predicting 5 year survival at 1 year after gastric cancer surgery. The nutritional and fat/muscle indices contributed to increase the prediction performance of our AI model.

Abstract Deep neuromuscular block (NMB) has been increasingly utilized, but its role in reducing intraoperative opioid requirement has yet to be investigated. Surgical pleth index (SPI) quantifies nociception. We investigated the effects of deep NMB on SPI-guided remifentanil administration in laparoscopic herniorrhaphy. Total 128 patients undergoing laparoscopic inguinal herniorrhaphy were randomly allocated to two groups of NMB: deep (n = 64) and moderate (n = 64). The remifentanil dose was assessed during intubation, from skin incision until CO2 insertion, and pneumoperitoneum. Mean infusion rate of remifentanil during pneumoperitoneum was higher in moderate NMB group than in deep NMB group (0.103 [0.075–0.143] µg/kg/min vs. 0.073 [0.056–0.097] µg/kg/min, p

Abstract Textbook outcome is a composite quality measurement of short-term outcomes for evaluating complex surgical procedures. We compared textbook outcome and survival of robotic total gastrectomy (RTG) with those of laparoscopic total gastrectomy (LTG). We retrospectively reviewed 395 patients (RTG, n = 74; LTG, n = 321) who underwent curative total gastrectomy for gastric cancer via minimally invasive approaches from 2009 to 2018. We performed propensity score matched analysis to adjust for potential selection bias. Textbook outcome included a negative resection margin, no intraoperative complication, retrieved lymph nodes > 15, no severe complication, no reintervention, no unplanned intensive care unit admission, hospitalization ≤ 21 days, no readmission after discharge, and no postoperative mortality. Survival outcomes included 3-year overall and relapse-free survival rates. After matching, 74 patients in each group were selected. Textbook outcome was similar in the RTG and LTG groups (70.3% and 75.7%, respectively), although RTG required a longer operative time. The quality metric least often achieved was the presence of severe complications in both groups (77.0% in both groups). There were no differences in the 3-year overall survival rate (98.6% and 89.7%, respectively; log-rank P = 0.144) and relapse-free survival rate between the RTG and LTG groups (97.3% and 87.0%, respectively; log-rank P = 0.167). Textbook outcome and survival outcome of RTG were similar to those of LTG for gastric cancer.

PurposeThe discrepancy between preoperative and final pathological staging has been a long-standing challenge for the application of clinical trials or appropriate treatment options. This study aimed to demonstrate the accuracy of preoperative staging of locally advanced gastric cancer using data from a large-scale randomized clinical trial.Materials and methodsOf the 1050 patients enrolled in the clinical trial, 26 were excluded due to withdrawal of consent (n = 20) or non-surgery (n = 6). The clinical and pathological staging was compared. Risk factor analysis for underestimation was performed using univariate and multivariate analyses.ResultsRegarding T staging by computed tomography, accuracy rates were 74.48, 61.62, 58.56, and 85.16% for T1, T2, T3 and T4a, respectively. Multivariate analysis for underestimation of T staging revealed that younger age, ulcerative gross type, circular location, larger tumor size, and undifferentiated histology were independent risk factors. Regarding nodal status estimation, 54.9% of patients with clinical N0 disease were pathologic N0, and 36.4% of patients were revealed to have pathologic N0 among clinical node-positive patients. The percentage of metastasis involvement at the D1, D1+, and D2 lymph node stations significantly increased with the advanced clinical N stage. Among all patients, 29 (2.8%), including 26 with peritoneal seeding, exhibited distant metastases.ConclusionsEstimating the exact pathologic staging remains challenging. A thorough evaluation is mandatory before treatment selection or trial enrollment. Moreover, we need to set a sufficient case number when we design the clinical trial considering the stage migration.

Abstract Background Although the tumor stroma in solid tumors like gastric cancer (GC) plays a crucial role in chemo-resistance, specific targets to inhibit the interaction between the stromal and cancer cells have not yet been utilized in clinical practice. The present study aims to determine whether cancer-associated fibroblasts (CAFs), a major component of the tumor stroma, confer chemotherapeutic resistance to GC cells, and to discover potential targets to improve chemo-response in GC. Methods To identify CAF-specific proteins and signal transduction pathways affecting chemo-resistance in GC cells, secretome and transcriptome analyses were performed. We evaluated the inhibiting effect of CAF-specific protein in in vivo and in vitro models and investigated the expression of CAF-specific protein in human GC tissues. Results Secretome and transcriptome data revealed that interleukin-6 (IL-6) is a CAF-specific secretory protein that protects GC cells via paracrine signaling. Furthermore, CAF-induced activation of the Janus kinase 1-signal transducer and activator of transcription 3 signal transduction pathway confers chemo-resistance in GC cells. CAF-mediated inhibition of chemotherapy-induced apoptosis was abrogated by the anti-IL-6 receptor monoclonal antibody tocilizumab in various experimental models. Clinical data revealed that IL-6 was prominently expressed in the stromal portion of GC tissues, and IL-6 upregulation in GC tissues was correlated with poor responsiveness to chemotherapy. Conclusions Our data provide plausible evidence for crosstalk between GC cells and CAFs, wherein IL-6 is a key contributor to chemoresistance. These findings suggest the potential therapeutic application of IL-6 inhibitors to enhance the responsiveness to chemotherapy in GC.

The objective of this study is to develop a mortality prediction model for patients undergoing gastric cancer surgery based on body morphometry, nutritional, and surgical information. Using a prospectively built gastric surgery registry from the Asan Medical Center (AMC), 621 gastric cancer patients, who were treated with surgery with no recurrence of cancer, were selected for the development of the prediction model. Input features (i.e., body morphometry, nutritional, surgical, and clinicopathologic information) were selected in the collected data based on the XGBoost analysis results and experts’ opinions. A convolutional neural network (CNN) framework was developed to predict the mortality of patients undergoing gastric cancer surgery. Internal validation was performed in split datasets of the AMC, whereas external validation was performed in patients in the Ajou University Hospital. Fifteen features were selected for the prediction of survival probability based on the XGBoost analysis results and experts’ suggestions. Accuracy, F1 score, and area under the curve of our CNN model were 0.900, 0.909, and 0.900 in the internal validation set and 0.879, 0.882, and 0.881 in the external validation set, respectively. Our developed CNN model was published on a website where anyone could predict mortality using individual patients’ data. Our CNN model provides substantially good performance in predicting mortality in patients undergoing surgery for gastric cancer, mainly based on body morphometry, nutritional, and surgical information. Using the web application, clinicians and gastric cancer patients will be able to efficiently manage mortality risk factors.

Diffuse Gastric Cancer (DGC) is increasingly being considered separate to intestinal type gastric cancer; several fusions events have been reported as drivers of the disease but few of those have been subsequently validated. Here the authors perform RNA-seq on early-onset DGC patients who had not been treated with chemotherapy or radiation and identify a previously unknown fusion.

Background. We investigated the results of quality control study prior to phase III trial of sentinel lymph node navigation surgery (SNNS). Methods. Data were reviewed from 108 patients enrolled in the feasibility study of laparoscopic sentinel basin dissection (SBD) in gastric cancer. Seven steps contain tracer injection at submucosa (step 1) and at four sites (step 2) by intraoperative esophagogastroduodenoscopy (EGD), leakage of tracer (step 3), injection within 3 minutes (step 4), identification of at least one sentinel basin (SB) (step 5), evaluation of sentinel basin nodes (SBNs) by frozen biopsy (step 6), and identification of at least five SBNs at back table and frozen sections (step 7). Results. Failure in step 7 (n=23) was the most common followed by step 3 (n=15) and step 6 (n=13). We did not find any differences of clinicopathological factors between success and failure group in steps 1~6. In step 7, body mass index (BMI) was only the significant factor. The success rate was 97.1% in patients with BMI

Background. Although Billroth II (BII) reconstruction is simpler and faster than Billroth I or Roux-en-Y (RY) reconstruction in patients undergoing totally laparoscopic distal gastrectomy (TLDG), BII reconstruction is associated with several complications, including more severe bile reflux. BII Braun anastomosis may be a better alternative to RY reconstruction. Methods. This retrospective study included 56 consecutive patients who underwent TLDG for gastric cancer, followed by BII Braun or RY reconstruction, between January 2013 and December 2015. Surgical outcomes, including length of operation, quantity of blood lost, and postoperative complications, were compared in the two groups. Results. Clinicopathological characteristics did not differ between the BII Braun and RY groups. Mean length of operation was significantly longer in the RY than the BII Braun group (157.3 min versus 134.6 min, p < 0.010), but length of hospital stay, blood loss, and complication rate did not differ between the two groups. Ileus occurred in three patients (10.0%) in the RY group. Endoscopic findings 6 months after surgery showed bile reflux in seven (28%) patients in the BII Braun group and five (17.2%) in the RY group (p = 0.343), but no significant differences in rate of gastric residue or degree of gastritis in the remnant stomach in the two groups. Conclusions. B-II Braun anastomosis is a good alternative to RY reconstruction, reducing length of operation and ileus after TLDG.

It has been well established that the long-term prognosis of intrahepatic duct stones (IHDS) is complicated by the late development of biliary cirrhosis with associated intrahepatic cholangiocarcinoma (IHCC). Despite recent improvements in imaging studies, accurate preoperative diagnosis of IHCC is difficult. Therefore, we attempted to elucidate the clinical features of patients with IHDS with IHCC. Methods: We reviewed 80 patients with IHDS and divided them into two groups. The DS group included 72 patients who had only IHDS. The second group was defined as the CC group and included eight patients who had IHDS and IHCC. For diagnosis of IHDS and confirmation of coexisting IHCC, patients underwent various radiological evaluations and additional laboratory tests, such as serum carbohydrate antigen 19-9 (CA 19-9). Results: There was no significant difference in the symptoms and stone characteristics between the two groups. For the CC group, liver resection was performed in four patients. Three patients underwent curative resection, but only one of these patients was alive at 36 months without recurrence. Conclusion: IHCC with IHDS was difficult to diagnose in the early phase. Therefore, while performing diagnostic studies and surgery for IHDS, one should always consider the possibility of coexisting cholangiocarcinoma.

The levels of organic acids representing metabolic pathway end products are important indicators of physiological status, and may be associated with metabolic changes in cancer. The aim of this study is to investigate the levels of organic acids in cancerous and normal tissues from gastric cancer patients and to confirm the role of metabolic alterations in gastric carcinogenesis. Organic acids in normal and cancerous tissues from forty-five patients with gastric adenocarcinoma were investigated by gas chromatography-mass spectrometry in selected ion monitoring mode as methoxime/tert-butyldimethylsilyl derivatives. We analysed the significant differences in the levels of organic acids in normal and cancer tissues and investigated the correlation of these levels in cancer tissues with clinicopathological features. The levels of Krebs cycle components, including α-ketoglutaric acid, succinic acid, fumaric acid, malic acid and oxaloacetic acid, were significantly increased in cancer tissues compared to normal tissues. In addition, the levels of glycolytic products, including pyruvic acid and lactic acid, as well as the levels of ketone bodies, including 3-hydroxybutyric acid, were also significantly increased in cancer tissues compared to normal tissues. The levels of ketone bodies in cancer tissues with differentiated histology and in intestinal-type cancer tissues were significantly increased. The organic acid profiling analysis described here may be a generally useful clinical tool for understanding the complexity of metabolic events in gastric adenocarcinoma, and organic acids may have potential as metabolic markers for the future discovery of diagnostic and therapeutic modalities.

Purpose: The usability of a new surgical navigation system that provides patient-specific vascular information for robotic gastrectomy in gastric cancer remains unexplored for laparoscopic gastrectomy owing to differences in surgical environments. This study aimed to evaluate the applicability and safety of this navigation system in laparoscopic gastrectomy and to compare the post-operative outcomes between procedures with and without its use. Materials and Methods: Between June 2022 and July 2023, 38 patients across 2 institutions underwent laparoscopic gastrectomy using a navigation system (navigation group). The technical feasibility, safety, and accuracy of detecting variations in vascular anatomy were measured. The perioperative outcomes were compared with 114 patients who underwent laparoscopic gastrectomy without a navigation system (non-navigation group) using 1:3 propensity score matching during the same study period. Results: In all patients in the navigation group, no adverse events associated with the navigation system occurred during surgery in any patient in the navigation group. No accidental vessel injuries necessitate auxiliary procedures. All vessels encountered during the gastrectomy were successfully reconstructed and visualized. Patient demographics and operative data were comparable between the 2 groups. The navigation group exhibited a significantly lower overall complication rate (10.5%) than the non-navigation group (26.3%, P=0.043). Notably, pancreas-related complications were absent in the navigation group but occurred in eight cases in the non-navigation group (7.0%, P=0.093), although the difference was not statistically significant. Conclusions: The patient-specific surgical navigation system demonstrated clinical feasibility and safety for laparoscopic gastrectomy for gastric cancer, potentially reducing complication rates compared with laparoscopic gastrectomy without its use. [ABSTRACT FROM AUTHOR]

Backgrounds: Strong evidence is lacking as no confirmatory randomized controlled trials (RCTs) have compared the efficacy of totally laparoscopic distal gastrectomy (TLDG) with laparoscopy-assisted distal gastrectomy (LADG). The authors performed an RCT to confirm if TLDG is different from LADG. Methods: The KLASS-07 trial is a multi-centre, open-label, parallel-group, phase III, RCT of 442 patients with clinical stage I gastric cancer. Patients were enroled from 21 cancer care centres in South Korea between January 2018 and September 2020 and randomized to undergo TLDG or LADG using blocked randomization with a 1:1 allocation ratio, stratified by the participating investigators. Patients were treated through R0 resections by TLDG or LADG as the full analysis set of the KLASS-07 trial. The primary endpoint was morbidity within postoperative day 30, and the secondary endpoint was quality of life (QoL) for 1 year. This trial is registered at ClinicalTrials.gov (NCT 03393182). Results: Four hundred forty-two patients were randomized (222 to TLDG, 220 to LADG), and 422 patients were included in the pure analysis (213 and 209, respectively). The overall complication rate did not differ between the two groups (TLDG vs. LADG: 12.2% vs. 17.2%). However, TLDG provided less postoperative ileus and pulmonary complications than LADG (0.9% vs. 5.7%, P=0.006; and 0.5% vs. 4.3%, P=0.035, respectively). The QoL was better after TLDG than after LADG regarding emotional functioning at 6 months, pain at 3 months, anxiety at 3 and 6 months, and body image at 3 and 6 months (all P<0.05). However, these QoL differences were resolved at 1 year. Conclusions: The KLASS-07 trial confirmed that TLDG is not different from LADG in terms of postoperative complications but has the advantages to reduce ileus and pulmonary complications. TLDG can be a good option to offer better QoL in terms of pain, body image, emotion, and anxiety at 3-6 months. [ABSTRACT FROM AUTHOR]

Abstract Background The necessity to develop high lipid-producing microalgae is emphasized for the commercialization of microalgal biomass, which is environmentally friendly and sustainable. Nannochloropsis are one of the best industrial microalgae and have been widely studied for their lipids, including high-value polyunsaturated fatty acids (PUFAs). Many reports on the genetic and biological engineering of Nannochloropsis to improve their growth and lipid contents have been published. Results We performed insertional mutagenesis in Nannochloropsis salina, and screened mutants with high lipid contents using fluorescence-activated cell sorting (FACS). We isolated a mutant, Mut68, which showed improved growth and a concomitant increase in lipid contents. Mut68 exhibited 53% faster growth rate and 34% higher fatty acid methyl ester (FAME) contents after incubation for 8 days, resulting in a 75% increase in FAME productivity compared to that in the wild type (WT). By sequencing the whole genome, we identified the disrupted gene in Mut68 that encoded trehalose-6-phosphate (T6P) synthase (TPS). TPS is composed of two domains: TPS domain and T6P phosphatase (TPP) domain, which catalyze the initial formation of T6P and dephosphorylation to trehalose, respectively. Mut68 was disrupted at the TPP domain in the C-terminal half, which was confirmed by metabolic analyses revealing a great reduction in the trehalose content in Mut68. Consistent with the unaffected N-terminal TPS domain, Mut68 showed moderate increase in T6P that is known for regulation of sugar metabolism, growth, and lipid biosynthesis. Interestingly, the metabolic analyses also revealed a significant increase in stress-related amino acids, including proline and glutamine, which may further contribute to the Mut68 phenotypes. Conclusion We have successfully isolated an insertional mutant showing improved growth and lipid production. Moreover, we identified the disrupted gene encoding TPS. Consistent with the disrupted TPP domain, metabolic analyses revealed a moderate increase in T6P and greatly reduced trehalose. Herein, we provide an excellent proof of concept that the selection of insertional mutations via FACS can be employed for the isolation of mutants with improved growth and lipid production. In addition, trehalose and genes encoding TPS will provide novel targets for chemical and genetic engineering, in other microalgae and organisms as well as Nannochloropsis.

Backgrounds: This study aimed to compare the incidence of bile reflux, quality of life (QoL), and nutritional status among Billroth II (BII), Billroth II with Braun anastomosis (BII-B), and Roux-en-Y (RY) reconstruction after laparoscopic distal gastrectomy (LDG). Materials and Methods: We reviewed the prospective data of 397 patients from a multicentre database who underwent LDG for gastric cancer between 2018 and 2020 at 20 tertiary teaching hospitals in Korea. Postoperative endoscopic findings, QoL surveys using the European Organization for Research and Treatment of Cancer questionnaire (C30 and STO22), and nutritional and surgical outcomes were compared among groups. Results: In endoscopic findings, bile reflux was the lowest in the RY group (n=67), followed by the BII-B (n=183) and BII groups (n =147) at 1 year (3.0 vs. 67.8 vs. 84.4%, all P<0.05). The anti-reflux capability of BII-B was statistically better than that of BII, but not as perfect as that of RY. From the perspective of QoL, BII-B was not inferior to RY, but better than BII reconstruction in causing fewer STO22 reflux symptoms at 6 and 12 months. However, only RY caused fewer C30 nausea symptoms than BII at 6 and 12 months, but not BII-B. Nutritional status and morbidities were similar among the three groups, and the operative time did not differ between the BII-B and RY groups. Conclusions: BII-B cannot substitute for RY in preventing bile reflux, shortening the operative time, or reducingmorbidities. Regarding short-term QoL, BII-B was sufficient to reduce STO22 reflux symptoms but failed to reduce C30 nausea symptoms postoperatively. [ABSTRACT FROM AUTHOR]

Objective: To build a novel classifier using an optimized 3D-convolutional neural network for predicting high-grade small bowel obstruction (HGSBO). Summary background data: Acute SBO is one of the most common acute abdominal diseases requiring urgent surgery. While artificial intelligence and abdominal computed tomography (CT) have been used to determine surgical treatment, differentiating normal cases, HGSBO requiring emergency surgery, and low-grade SBO (LGSBO) or paralytic ileus is difficult. Methods: A deep learning classifier was used to predict high-risk acute SBO patients using CT images at a tertiary hospital. Images from three groups of subjects (normal, nonsurgical, and surgical) were extracted; the dataset used in the study included 578 cases from 250 normal subjects, with 209 HGSBO and 119 LGSBO patients; over 38 000 CT images were used. Data were analyzed from 1 June 2022 to 5 February 2023. The classification performance was assessed based on accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve. Results: After fivefold cross-validation, the WideResNet classifier using dual-branch architecture with depth retention pooling achieved an accuracy of 72.6%, an area under receiver operating characteristic of 0.90, a sensitivity of 72.6%, a specificity of 86.3%, a positive predictive value of 74.1%, and a negative predictive value of 86.6% on all the test sets. Conclusions: These results show the satisfactory performance of the deep learning classifier in predicting HGSBO compared to the previous machine learning model. The novel 3D classifier with dual-branch architecture and depth retention pooling based on artificial intelligence algorithms could be a reliable screening and decision-support tool for high-risk patients with SBO. [ABSTRACT FROM AUTHOR]