Utility of a skin marker-less setup procedure using surface-guided imaging: a comparison with the traditional laser-based setup in extremity irradiation.

This study aimed to assess the feasibility of a skin marker-less patient setup using a surface-guided radiotherapy (SGRT) system for extremity radiotherapy. Twenty-five patients who underwent radiotherapy to the extremities were included in this retrospective study. The first group consisted of 10 patients and underwent a traditional setup procedure using skin marks and lasers. The second group comprised 15 patients and had a skin marker-less setup procedure that used an SGRT system only. To compare the two setup procedures for setup accuracy, the mean 3D vector shift magnitude was 0.9 mm for the traditional setup procedure and 0.5 mm for the skin marker-less setup procedure (p < 0.01). In addition, SGRT systems have been suggested to improve the accuracy and reproducibility of patient setups and consistently reduce interfractional setup errors. These results indicate that a skin marker-less patient setup procedure using an SGRT system is useful for extremity irradiation.

Proposal of an integrated staging system using albumin-bilirubin grade and serum alpha-fetoprotein values for predicting postoperative prognosis of recurrent hepatocellular carcinoma.

BACKGROUND: Because repeat hepatectomy for recurrent hepatocellular carcinoma is a potentially invasive procedure, it is necessary to identify patients who truly benefit from repeat hepatectomy. Albumin-bilirubin grading has been reported to predict survival in patients with hepatocellular carcinoma. However, as prognosis also depends on tumor factors, a staging system that adds tumor factors to albumin-bilirubin grading may lead to a more accurate prognostication in patients with recurrent hepatocellular carcinoma. METHODS: Albumin-bilirubin grading and serum alpha-fetoprotein levels were combined and the albumin-bilirubin-alpha-fetoprotein score was created ([albumin-bilirubin grading = 1; 1 point, 2 or 3; 2 points] + [alpha-fetoprotein<75 ng/mL, 0 points; ≥5, 1 point]). Patients were classified into three groups, and their characteristics and survival were evaluated. The predictive ability of the albumin-bilirubin-alpha-fetoprotein score was compared with that of the Cancer of the Liver Italian Program and the Japan Integrated Stage scores. RESULTS: Albumin-bilirubin-alpha-fetoprotein score significantly stratified postoperative survival (albumin-bilirubin-alpha-fetoprotein score = 1/2/3: 5-year recurrence-free survival [%]: 22.4/20.7/0.0, p < 0.001) and showed the highest predictive value for survival among the integrated systems (albumin-bilirubin-alpha-fetoprotein score/Japan Integrated Stage/Cancer of the Liver Italian Program: 0.785/0.708/0.750). CONCLUSIONS: Albumin-bilirubin-alpha-fetoprotein score is useful for predicting the survival of patients with recurrent hepatocellular carcinoma undergoing repeat hepatectomy.

Primary analysis of a prospective cohort study of Japanese patients with plasma cell neoplasms in the novel drug era (2016-2021).

The emergence of novel drugs has significantly improved outcomes of patients with plasma cell neoplasms (PCN). The Japanese Society of Hematology conducted a prospective observational study in newly diagnosed PCN patients between 2016 and 2021. The analysis focused on 1385 patients diagnosed with symptomatic PCN between 2016 and 2018. The primary endpoint was the 3-year overall survival (OS) rate among patients requiring treatment (n = 1284), which was 70.0% (95%CI 67.4-72.6%). Approximately 94% of these patients received novel drugs as frontline therapy. The 3-year OS rate was 90.3% (95%CI 86.6-93.1%) in the 25% of patients who received upfront autologous stem cell transplantation (ASCT), versus just 61.4% (95%CI 58.0-64.6%) in those who did not receive upfront ASCT. The only unfavorable prognostic factor that affected OS in ASCT recipients was an age of 65 or higher. For patients who did not receive ASCT, independent unfavorable prognostic factors included frontline treatment with conventional chemotherapies, international staging system score of 2/3, extramedullary tumors, and Freiberg comorbidity index of 2/3. This study unequivocally demonstrates that use of novel drugs improved OS in Japanese myeloma patients, and underscores the continued importance of upfront ASCT as the standard of care in the era of novel drugs.

Clinical and pathological factors associated with survival in patients with pancreatic cancer who receive adjuvant therapy after neoadjuvant therapy: A retrospective multi-institutional analysis.

BACKGROUND: Neoadjuvant therapy is being increasingly used for patients with pancreatic cancer. The role of adjuvant therapy in these patients is unclear. The purpose of this study was to identify clinical and pathologic characteristics that are associated with longer overall survival in patients with pancreatic cancer who receive adjuvant therapy after neoadjuvant therapy. METHODS: This study was conducted using multi-institutional data. All patients underwent surgery after at least 1 cycle of neoadjuvant therapy for pancreatic cancer. Patients who died within 3 months after surgery and were known to have distant metastasis or macroscopic residual disease were excluded. Mann-Whitney U test, χ2 analysis, Kaplan-Meier plot, and univariate and multivariate Cox regression analysis were performed as statistical analyses. RESULTS: In the present study, 529 patients with resected pancreatic cancer after neoadjuvant therapy were reviewed. For neoadjuvant therapy, 177 (33.5%) patients received neoadjuvant chemotherapy, and 352 (66.5%) patients received neoadjuvant chemoradiotherapy. The median duration of neoadjuvant therapy was 7.0 months (interquartile range, 5.0-8.7). Patients were followed for a median of 23.0 months after surgery. Adjuvant therapy was administered to 297 (56.1%) patients and was not associated with longer overall survival for the entire cohort (24 vs 22 months, P = .31). Interaction analysis showed that adjuvant therapy was associated with longer overall survival in patients who received less than 4 months neoadjuvant therapy (hazard ratio 0.40; 95% confidence interval 0.17-0.95; P = .03) or who had microscopic margin positive surgical resections (hazard ratio 0.56; 95% confidence interval 0.33-0.93; P = .03). CONCLUSION: In this retrospective study, there was a survival benefit associated with adjuvant therapy for patients who received less than 4 months of neoadjuvant therapy or had microscopic positive margins.

Machine Learning Based Prediction of Postoperative Pancreatic Fistula Following Pancreaticoduodenectomy.

OBJECTIVE: To develop a novel machine learning (ML) model to predict clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD). SUMMARY BACKGROUND DATA: Accurate prognostication of CR-POPF may allow for risk stratification and adaptive treatment strategies for potential PD candidates. However, antecedent models, such as the modified Fistula Risk Score (mFRS), are limited by poor discrimination and calibration. METHODS: All records entailing PD within the 2014-2018 ACS NSQIP were identified. Additionally, patients undergoing PD at our institution between 2013 and 2021 were queried from our local data repository. An eXtreme Gradient Boosting (XGBoost) model was developed to estimate the risk of CR-POPF using data from the ACS NSQIP and evaluated using institutional data. Model discrimination was estimated using the area under the receiver operating characteristic (AUROC) and precision recall curve (AUPRC). RESULTS: Overall, 12,281 and 445 patients undergoing PD were identified within the 2014-2018 ACS NSQIP and our institutional registry, respectively. Application of the XGBoost and mFRS scores to the internal validation dataset revealed that the former model had significantly greater AUROC (0.72 vs. 0.68, P<0.001) and AUPRC (0.22 vs. 0.18, P<0.001). Within the external validation dataset, the XGBoost model remained superior to the mFRS with an AUROC of 0.79 (95% CI 0.74-0.84) versus 0.75 (95% CI 0.70-0.80, P<0.001). In addition, AUPRC was higher for the XGBoost model, compared to the mFRS. CONCLUSIONS: Our novel ML model consistently outperformed the previously validated mFRS within internal and external validation cohorts, thereby demonstrating its generalizability and utility for enhancing prediction of CR-POPF.

The Impact of Pretransplant Use of Tyrosine Kinase Inhibitors on Allogeneic Stem Cell Transplantation in Patients with Chronic Myeloid Leukemia-A Single-institution Retrospective Study.

Objective Chronic myeloid leukemia (CML) is a malignant hematological disorder, and allogeneic stem cell transplantation (allo-SCT) was its only curative treatment until the introduction of tyrosine kinase inhibitors (TKIs). Allo-SCT is still considered for CML patients who are resistant to TKIs and in an advanced phase. Currently, second- and third-generation (2/3 G) TKIs are typically incorporated into the first-line treatment of CML. However, the impact of 2/3 G TKIs on subsequent allo-SCT remains unclear. We therefore evaluated the effect of 2/3 G TKIs on allo-SCT. Methods We retrospectively evaluated the effect of pretransplant therapy with TKIs on the outcome of allo-SCT for CML using clinical data at our institution. Patients or Materials Thirty-two CML patients who received their first allo-SCT procedure at our institute from 2001 to 2020 were included. We divided the patients into three subgroups based on TKI treatment before allo-SCT. Patients receiving no TKIs, only imatinib (IM), and 2/3 G TKIs were classified into the Non-TKI, IM, and 2/3 G TKI groups, respectively. Results In a univariate analysis, the pretransplant use of 2/3 G TKIs was significantly associated with a higher 5-year overall survival (91.7%) and relapse-free survival (75.0%) than the use of IM (37.5% and 12.5%) in patients presenting with or progressing to the advanced phase. In addition, pretransplant use of 2/3 G TKIs did not increase the incidence of graft-versus-host disease (GVHD). Conclusions We demonstrated that the pretransplant use of 2/3 G TKIs was safe and improved the outcome of CML patients who presented with or progressed to the advanced phase without increasing the frequency of GVHD.

Extracellular vesicle­mediated RNA editing may underlie the heterogeneity and spread of hepatocellular carcinoma in human tissue and in vitro.

Extracellular vesicles (EVs) produced by various cells, including tumor cells, carry biomolecules to neighboring cells. In hepatocellular carcinoma (HCC), adenosine to inosine RNA editing of antizyme inhibitor 1 (AZIN1), specifically regulated by adenosine deaminase acting on RNA­1 (ADAR1), promotes carcinogenesis. The present study examined if EVs and ADAR1 in the EVs released from HCC cells are transferred to neighboring cells in co­culture systems and reporter assay. Distribution of the ADAR1 expression in human tissues were examined by immunohistochemistry. EVs released from HCC cells containing ADAR1 were delivered to neighboring HCC cells and non­cancerous hepatocytes. The increased ADAR1 protein levels resulted in serine to glycine substitution at residue 367 of AZIN1, which augmented transformation potential and increased aggressive behavior of cancer cells. In clinically resected samples, ADAR1 distribution was highly heterogeneous within the tumor specimen and denser in non­cancerous tissue surrounding the HCC tissue. These observations suggested that ADAR1 protein may be delivered from HCC cells to neighboring cells via EVs and that EV­mediated RNA editing may serve a pivotal role in determining HCC heterogeneity and spread.

Micro-hepatocellular carcinoma with bile duct tumor thrombus mimicking intrahepatic intraductal papillary neoplasm of the bile duct: a case report.

BACKGROUND: Microhepatocellular carcinoma with a gross bile duct tumor thrombus is extremely rare, making the correct preoperative diagnosis difficult. CASE PRESENTATION: A 78-year-old man was referred to our department for close examination of a liver tumor that was incidentally detected using ultrasonography. Blood tests revealed normal levels of tumor markers. Abdominal ultrasonography showed a 2-cm-sized hyperechoic mass with indistinct borders and hypoechoic margins at the origin of the right hepatic duct. Dynamic computed tomography showed a tumor with arterial phase predominance, a heterogeneous contrast effect, and prolonged enhancement. Cystic structures were observed in the tumors. In addition, localized dilatation of the caudate lobe bile duct was observed near the tumor. Cholangiography showed that the common bile duct, right and left hepatic ducts, and secondary branches did not have dilatation or stenosis. Biopsies of the bile duct revealed no malignancy. Under suspicion of intrahepatic intraductal papillary neoplasm of the bile duct, right hemi-hepatectomy was performed. The extrahepatic bile duct was preserved, because no tumor was found at the margin of the right hepatic duct during intraoperative frozen diagnosis. Macroscopically, the lesion was an 18 × 15 mm tumor occupying a dilated intrahepatic bile duct near the right hepatic duct, with a soft, fine papillary tumor. Based on morphology and immunostaining, tumor matched with moderately differentiated hepatocellular carcinoma. In addition, a 2 mm-sized hepatocellular carcinoma was observed in the liver parenchyma near the bile duct, where the tumor was located. CONCLUSIONS: Based on these findings, the patient was diagnosed with small hepatocellular carcinoma with a gross bile duct tumor thrombus. The cystic part seen on the preoperative images was considered as a gap between the bile duct and the tumor thrombus. The patient recovered well with no signs of recurrence 20 months after surgery.

N2 Lymph Node Metastasis Is a Useful Predictor of Recurrence in Patients With Stage III Rectal Cancer Undergoing Adjuvant Chemotherapy Using Tegafur-uracil/leucovorin.

BACKGROUND/AIM: Fluoropyrimidine therapy or oxaliplatin combination therapy is recommended for patients with stage III colorectal cancer as adjuvant chemotherapy (AC). However, the criterion for selecting these regimens is still unclear in patients with stage III rectal cancer (RC). In order to select an appropriate regimen of AC for such patients, it is needed to identify characteristics associated with tumor recurrence. PATIENTS AND METHODS: The records of 45 patients with stage III RC undergoing AC using tegafur-uracil/leucovorin (UFT/LV) were retrospectively reviewed. The cut-off value of characteristics was determined using a receiver operating characteristic curve for recurrence. Univariate analyses using Cox-Hazard model for predicting recurrence were performed with clinical characteristics. Survival analysis was performed using Kaplan-Meier method and log-rank test. RESULTS: Thirty patients (66.7%) completed AC using UFT/LV. Fifteen patients (33.3%) did not complete AC because of adverse events, tumor recurrence and others. Sixteen patients (35.6%) had recurrence. Univariate analyses revealed that lymph node metastasis (N2/N1) (p=0.002) was associated with tumor recurrence. Survival analysis showed that lymph node metastasis (N2/N1) could stratify recurrence-free survival (p<0.001). CONCLUSION: N2 lymph node metastasis can predict tumor recurrence in patients with stage III RC undergoing AC using UFT/LV.

Thioredoxin-2 Regulates SqrR-Mediated Polysulfide-Responsive Transcription via Reduction of a Polysulfide Link in SqrR.

Polysulfide plays an essential role in controlling various physiological activities in almost all organisms. We recently investigated the impact of polysulfide metabolic enzymes on the temporal dynamics of cellular polysulfide speciation and transcriptional regulation by the polysulfide-responsive transcription factor SqrR in Rhodobacter capsulatus. However, how the polysulfidation of thiol groups in SqrR is reduced remains unclear. In the present study, we examined the reduction of polysulfidated thiol residues by the thioredoxin system. TrxC interacted with SqrR in vitro and reduced the polysulfide crosslink between two cysteine residues in SqrR. Furthermore, we found that exogenous sulfide-induced SqrR de-repression during longer culture times is maintained upon disruption of the trxC gene. These results establish a novel signaling pathway in SqrR-mediated polysulfide-induced transcription, by which thioredoxin-2 restores SqrR to a transcriptionally repressed state via the reduction of polysulfidated thiol residues.

Polysulfide metabolizing enzymes influence SqrR-mediated sulfide-induced transcription by impacting intracellular polysulfide dynamics.

Sulfide plays essential roles in controlling various physiological activities in almost all organisms. Although recent evidence has demonstrated that sulfide is endogenously generated and metabolized into polysulfides inside the cells, the relationship between polysulfide metabolism and polysulfide-sensing mechanisms is not well understood. To better define this interplay between polysulfide metabolism and sensing in cells, we investigated the role of polysulfide-metabolizing enzymes such as sulfide:quinone oxidoreductase (SQR) on the temporal dynamics of cellular polysulfide speciation and on the transcriptional regulation by the persulfide-responsive transcription factor SqrR in Rhodobacter capsulatus. We show that disruption of the sqr gene resulted in the loss of SqrR repression by exogenous sulfide at longer culture times, which impacts the speciation of intracellular polysulfides of Δsqr vs. wild-type strains. Both the attenuated response of SqrR and the change in polysulfide dynamics of the Δsqr strain is fully reversed by the addition to cells of cystine-derived polysulfides, but not by glutathione disulfide (GSSG)-derived polysulfides. Furthermore, cysteine persulfide (CysSSH) yields a higher rate of oxidation of SqrR relative to glutathione persulfide (GSSH), which leads to DNA dissociation in vitro. The oxidation of SqrR was confirmed by a mass spectrometry-based kinetic profiling strategy that showed distinct polysulfide-crosslinked products obtained with CysSSH vs. GSSH. Taken together, these results establish a novel association between the metabolism of polysulfides and the mechanisms for polysulfide sensing inside the cells.

Acute limb ischemia due to severe heparin-included thrombocytopenia with thrombosis during puerperium.

We present the case of a 39-year-old pregnant woman who had intrauterine fetal death and imminent uterine rupture and underwent cesarean section. She also underwent catheter embolization for hemorrhagic shock due to bleeding from the uterine artery, and heparin-containing saline was used. On day 7 of hospitalization, she felt severe pain in her right lower leg, and computed tomography (CT) revealed focal nonocclusive thrombus formations in the right common and external iliac artery. After intravenous heparin administration, she suddenly developed dyspnea, her blood pressure dropped, and her platelet count decreased. We diagnosed her with heparin-induced thrombocytopenia (HIT). Although we discontinued heparin and switched to argatroban, CT after 5 days revealed subtotal occlusion of the right iliac artery by a massive thrombus. We performed surgical thrombectomy using a Fogarty catheter, but blood flow was not restored. Therefore, we administered urokinase continuously with catheter-directed thrombolysis (CDT). The thrombus in the iliac artery gradually cleared and was successfully eliminated. However, the patient developed gangrene in her right lower leg, and we decided to perform an above-knee amputation of the right leg. She was discharged with a prosthetic leg and prescribed 15 mg of rivaroxaban per day. Learning objective: HIT is a known serious side effect of heparin administration, and it can sometimes be fatal. HIT treatment using aggressive thrombectomy procedures may be ineffective since such procedures may accelerate thrombus formation when the coagulation cascade is highly activated. In this case, CDT may have to be considered as the first-line treatment before Fogarty thrombectomy when argatroban therapy fails.

Total Steroid Intake is Associated With Hospital Mortality in Patients With Pan-Peritonitis due to Colorectal Perforation.

BACKGROUND: Patients with pan-peritonitis (PP) due to colorectal perforation have high mortality rate because colorectal perforation causes septic shock. The association between total steroid intake (TSI) and hospital mortality of such patients is not clear. METHODS: One hundred forty-two patients who underwent surgery for PP due to colorectal perforation were reviewed. Patients were divided into two groups by 8000 mg of TSI. The cut-off value of TSI was determined using a receiver operating characteristic curve for hospital mortality. RESULTS: The cut-off value of TSI for hospital mortality was 8000 mg. Patients with TSI>8000 mg had high rate of hemodialysis, hospital mortality, and elevated neutrophil ratio (>95%) compared with those with TSI≤8000 mg. Multivariate analyses revealed that TSI (>8000/≤8000, mg) (OR, 9.669; 95% CI, 1.011-92.49; P = .049) was significantly associated with hospital mortality as well as bleeding volume (>1000/≤1000, mL) (OR, 26.08; 95% CI, 3.566-190.4; P = .001), lymphocyte ratio (≤4/>4, %) (OR, 7.988; 95% CI, 1.498-42.58; P = .015) and C-reactive protein (≤7.5/>7.5, mg/dL) (OR, 41.66; 95% CI, 4.784-33.33; P = .001). DISCUSSION: There was a significant association between TSI and hospital mortality in patients with PP due to colorectal perforation as well as intraoperative bleeding and systemic inflammatory markers.

Successful Steroid Treatment of Pembrolizumab-induced Agranulocytosis That Developed after Splenectomy in a Patient with Non-small-cell Lung Cancer.

Neutropenia, a rare immune-related adverse event, affects patients receiving treatment with immune checkpoint inhibitors (ICIs). We herein report a case of pembrolizumab-induced agranulocytosis. An 83-year-old man was diagnosed with advanced-stage lung carcinoma concomitant with splenomegaly complicated by hypersplenism, causing pancytopenia. To avoid the risk of bone marrow suppression due to cytotoxic chemotherapy, pembrolizumab monotherapy was chosen. However, the patient developed agranulocytosis despite the resolution of pancytopenia through splenectomy performed after the fourth pembrolizumab cycle. Neutrophil counts improved after steroid treatment but not after granulocyte colony-stimulating factor treatment. This case demonstrated that neutropenia can sometimes develop abruptly after several ICI therapy cycles.

The Sulfide-Responsive SqrR/BigR Homologous Regulator YgaV of Escherichia coli Controls Expression of Anaerobic Respiratory Genes and Antibiotic Tolerance.

Compositions and activities of bacterial flora in the gastrointestinal tract significantly influence the metabolism, health, and disease of host humans and animals. These enteric bacteria can switch between aerobic and anaerobic growth if oxygen tension becomes limited. Interestingly, the switching mechanism is important for preventing reactive oxygen species (ROS) production and antibiotic tolerance. Studies have also shown that intracellular and extracellular sulfide molecules are involved in this switching control, although the mechanism is not fully clarified. Here, we found that YgaV, a sulfide-responsive transcription factor SqrR/BigR homolog, responded to sulfide compounds in vivo and in vitro to control anaerobic respiratory gene expression. YgaV also responded to H2O2 scavenging in the enteric bacterium Escherichia coli. Although the wild-type (WT) showed increased antibiotic tolerance under H2S-atmospheric conditions, the ygaV mutant did not show such a phenotype. Additionally, antibiotic sensitivity was higher in the mutant than in the WT of both types in the presence and absence of exogenous H2S. These results, therefore, indicated that YgaV-dependent transcriptional regulation was responsible for maintaining redox homeostasis, ROS scavenging, and antibiotic tolerance.

Local transplantation of syngeneic adipose stromal vascular fraction ameliorates damaged anal sphincter function in a rat model of vaginal distension.

BACKGROUND: The adipose stromal vascular fraction contains abundant mesenchymal stem cells and is utilized for cell therapy of male stress urinary incontinence. The purpose of this paper was to explore the effect of local transplantation of the stromal vascular fraction on improvement of damaged anal sphincter function. METHODS: A rat model of vaginal distension was used as a model of damaged anal sphincter function. The adipose stromal vascular fraction was separated from the inguinal fat of syngeneic green fluorescent protein transgenic rats and delivered into the internal anal sphincter of vaginal distension rats. The maximum resting pressure was evaluated during insertion and withdrawal of the catheter at 4 or 10 days after vaginal distension treatment to estimate anal sphincter function. Green fluorescent protein-transfected human-adipose-derived mesenchymal stem cells were transplanted into the internal anal sphincter of nude rats. Hematoxylin-eosin and Masson trichrome staining were performed to evaluate tissue damage and collagen synthesis. Transplanted cells were identified using a green fluorescent protein antibody and a human-specific antibody. Activation of the transplanted human-ADSC was evaluated by quantitative RT-PCR RESULTS: The mean maximum resting pressure (during catheter withdrawal) of vaginal distension rats was significantly lower than that of control rats, and stromal vascular fraction injection normalized it 4 days after treatment (control: 5.66 ± 0.98, vaginal distension: 4.04 ± 1.28, vaginal distension + stromal vascular fraction: 5.92 ± 1.28 [mmHg, control versus vaginal distension: P = .039; vaginal distension versus vaginal distension + stromal vascular fraction: P = .007]). Histological examination showed that vaginal distension disrupted the internal anal sphincter, and the transplanted syngeneic stromal vascular fraction survived for 10 days. Transplanted xenogeneic human-adipose-derived mesenchymal stem cells survived in the internal anal sphincter of nude rats for 4 and 10 days. Genes related to extracellular remodeling were up-regulated in the transplanted human-adipose-derived mesenchymal stem cells CONCLUSION: Syngeneic and heterotopic transplanted adipose-derived mesenchymal stem cells engrafted in the internal anal sphincter and ameliorated damaged anal sphincter function in a rat model of vaginal distension.

Laparoscopic surgery reduced frequency of postoperative small bowel obstruction, and hospital stay compared with open surgery in a cohort of patients with colorectal cancer: a propensity score matching analysis.

BACKGROUND: Laparoscopic surgery (LS) is reported to reduce postoperative complications and hospital stay compared with open surgery (OP). Because patient selection may have been biased in previous studies, propensity score matching (PSM) analysis was used in this study to test the benefits of LS compared with OP. METHODS: A total of 759 patients with stage I-III colorectal cancer undergoing curative surgery were retrospectively reviewed. To minimize confounding bias between LS and OP groups, a 1:1 PSM analysis was performed based on adjuvant chemotherapy, age, albumin, body mass index, American Society of Anesthesiologists physical status depth of tumor, gender, lymph node dissection, maximum tumor size, obstructive tumor, previous abdominal surgery, pathological stage, tumor differentiation, and tumor location. Statistical analyses including chi-square test, Mann-Whitney U test, univariate analyses and Kaplan-Meier method and log-rank test were performed using the data after PSM to investigate the benefits of LS compared with OP. RESULTS: After PSM analysis, 460 patients remained in the study. The LS group had lower intraoperative blood loss (34 ± 70 vs 237 ± 391, mL; P < 0.001), lower frequency of postoperative small bowel obstruction (SBO) (17/213 vs 30/230; P = 0.045), lower rate of nasogastric tube insertion (7/223 vs 17/213; P = 0.036), and shorter postoperative hospital stay (13 ± 10 vs 25 ± 47, day; P < 0.001) than the OP group. Univariate analyses showed that LS significantly reduced the risk of postoperative SBO (odds ratio [OR] 0.532; 95% confidence interval [CI] 0.285-0.995; P = 0.048) and nasogastric tube insertion (OR 0.393; 95% CI 0.160-0.967; P = 0.042) compared with OP. There were no significant differences in OS and RFS between the groups. CONCLUSIONS: LS reduced intraoperative blood loss, frequency of postoperative SBO, rate of nasogastric tube insertion, and postoperative hospital stay compared with OP.

Persulfide-Responsive Transcription Factor SqrR Regulates Gene Transfer and Biofilm Formation via the Metabolic Modulation of Cyclic di-GMP in Rhodobacter capsulatus.

Bacterial phage-like particles (gene transfer agents-GTAs) are widely employed as a crucial genetic vector in horizontal gene transfer. GTA-mediated gene transfer is induced in response to various stresses; however, regulatory mechanisms are poorly understood. We found that the persulfide-responsive transcription factor SqrR may repress the expression of several GTA-related genes in the photosynthetic bacterium Rhodobacter capsulatus. Here, we show that the sqrR deletion mutant (ΔsqrR) produces higher amounts of intra- and extracellular GTA and gene transfer activity than the wild type (WT). The transcript levels of GTA-related genes are also increased in ΔsqrR. In spite of the presumption that GTA-related genes are regulated in response to sulfide by SqrR, treatment with sulfide did not alter the transcript levels of these genes in the WT strain. Surprisingly, hydrogen peroxide increased the transcript levels of GTA-related genes in the WT, and this alteration was abolished in the ΔsqrR strain. Moreover, the absence of SqrR changed the intracellular cyclic dimeric GMP (c-di-GMP) levels, and the amount of c-di-GMP was correlated with GTA activity and biofilm formation. These results suggest that SqrR is related to the repression of GTA production and the activation of biofilm formation via control of the intracellular c-di-GMP levels.