Prognostic impacts of participation in prospective surgical clinical trials on surgical outcomes in gastric cancer patients.

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.

Deep learning using computed tomography to identify high-risk patients for acute small bowel obstruction: development and validation of a prediction model : a retrospective cohort study.

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.

Characterization of Clofazimine as a Potential Substrate of Drug Transporter.

In this study, we explored clofazimine (CFZ) as a potential substrate of uptake and efflux transporters that might be involved in CFZ disposition, using transporter gene overexpressing cell lines in vitro. The intracellular concentrations of CFZ were significantly increased in the presence of selective inhibitors of P-gp and BCRP, which include verapamil, cyclosporine-A, PSC-833, quinidine, Ko143, and daunorubicin. In a bidirectional transport assay using transwell cultures of cell lines overexpressing P-gp and BCRP, the mean efflux ratios of CFZ were found to be 4.17 ± 0.63 and 3.37 ± 1.2, respectively. The Km and maximum rate of uptake (Vmax) were estimated to be 223.3 ± 14.73 µM and 548.8 ± 87.15 pmol/min/mg protein for P-gp and 381.9 ± 25.07 µM and 5.8 ± 1.22 pmol/min/mg protein for BCRP, respectively. Among the uptake transporters screened, the CFZ uptake rate was increased 1.93 and 3.09-fold in HEK293 cell lines overexpressing OAT1 and OAT3, respectively, compared to the control cell lines, but no significant uptake was observed in cell lines overexpressing OCT1, OCT2, OATP1B1, OATP1B3, OATP2B1, or NTCP. Both OAT1- and OAT3-mediated uptake was inhibited by the selective inhibitors diclofenac, probenecid, and butanesulfonic acid. The Km and Vmax values of CFZ were estimated to be 0.63 ± 0.15 µM and 8.23 ± 1.03 pmol/min/mg protein, respectively, for OAT1 and 0.47 ± 0.1 µM and 17.81 ± 2.19 pmol/min/mg protein, respectively, for OAT3. These findings suggest that CFZ is a novel substrate of BCRP, OAT1, and OAT3 and a known substrate of P-gp in vitro.

Prevention of Gallstones After Bariatric Surgery using Ursodeoxycholic Acid: A Narrative Review of Literatures.

Obesity by itself is a factor in the development of gallstone disease, and periods of weight loss after bariatric surgery further increase the risk of gallstone formation. In patients with obesity, hypersecretion of cholesterol may increase the risk of gallstone formation, which is approximately five-fold higher than that in the general population. The incidence of gallstone formation after bariatric surgery is 10-38% and often associated with a proportional increase in the risk of developing biliary complications. Routine postoperative administration of ursodeoxycholic acid (UDCA) is recommended to prevent gallstone formation. Several randomized trials have indicated that UDCA can effectively prevent gallstones and reduce the risk of cholecystectomy after bariatric procedures. The effective daily dose of UDCA in each study ranged from 500 to 1,200 mg, and it may be considered at least during the period of rapid weight loss (first 3-6 months postoperatively) to decrease the incidence of symptomatic gallstones.

Prediction of Survival Outcomes Based on Preoperative Clinical Parameters in Gastric Cancer.

BACKGROUND: Few current preoperative risk assessment tools provide essential, optimized treatment for gastric cancer. The purpose of this study was to develop and validate a nomogram that uses preoperative data to predict survival and risk assessments. METHODS: A survival prediction model was constructed using data from a developmental cohort of 1251 patients with stage I to III gastric cancer who underwent curative resection between January 2005 and December 2008 at Ajou University Hospital, Korea. The model was internally validated for discrimination and calibrated using bootstrap resampling. To externally validate the model, data from a validation cohort of 2012 patients with stage I to III gastric cancer who underwent surgery at multiple centers in Korea between January 2001 and June 2006 were analyzed. Analyses included the model's discrimination index (C-index), calibration plots, and decision curve that predict overall survival. RESULTS: Eight independent predictors, including age, sex, clinical tumor size, macroscopic features, body mass index, histology, clinical stages, and tumor location, were considered for developing the nomogram. The discrimination index was 0.816 (adjusted C-index) in the developmental cohort and 0.781 (adjusted C-index) in the external validation cohort. Additionally, in both the developmental and validation datasets, age and tumor size were significantly correlated with each other and were independent indicators for survival (P < 0.05). CONCLUSIONS: We developed a new nomogram by using the most common and significant preoperative parameters that can help to identify high-risk patients before treatment and help clinicians to make appropriate decisions for patients with stage I to III gastric cancer.

Prognostic value of hypocholesterolemia in patients with gastric cancer.

BACKGROUND: According to previous studies, low serum total cholesterol (TC) is associated with higher cancer incidence and mortality. However, the prognostic implications of preoperative TC in patients with gastric cancer (GC) remain to be determined. METHODS: A total of 1251 patients with GC, who underwent radical gastrectomy between 2005 and 2008, were recruited. Propensity score weighting (PSW) based on a generalized boosted method (GBM) was used to control for selection bias. RESULTS: After balancing the preoperative and operative covariates, low TC was associated with high incidence of complications (severe complication rate: 15.2% (Low TC) vs. 4.7% (Normal TC) vs 5.5% (High TC); p = 0.004). In multivariable analysis, lowering TC was associated with poor OS and RFS in weighted population. [OS: hazard ratio (HR) = 0.92; 95% CI = 0.867-0.980; P = 0.009 and RFS: HR = 0.93; 95% CI = 0.873-0.988; P = 0.02]. CONCLUSIONS: Preoperative TC is a useful predictor of postoperative survival and postoperative complications in patients with stage I-III GC and may help to identify high-risk patients for rational therapy, including nutritional support, and timely follow-up.

Long-term Comparison of Robotic and Laparoscopic Gastrectomy for Gastric Cancer: A Propensity Score-weighted Analysis of 2084 Consecutive Patients.

OBJECTIVE: To compare long-term outcomes between robotic and LG approaches using propensity score weighting based on a generalized boosted method to control for selection bias. SUMMARY OF BACKGROUND DATA: Minimally invasive surgical approaches for GC are increasing, yet limited evidence exists for long-term outcomes of robotic gastrectomy (RG). METHODS: Patients (n = 2084) with GC stages I-III who underwent LG or RG between 2009 and 2017 were analyzed. Generalized boosted method was used to estimate a propensity score derived from all available preoperative characteristics. Long-term outcomes were compared using the adjusted Kaplan-Meier method and the weighted Cox proportional hazards regression model. RESULTS: After propensity score weighting, the population was balanced. Patients who underwent RG showed reduced blood loss (16 mL less, P = 0.025), sufficient lymph node harvest from the initial period, and no changes in surgical outcomes over time. With 52-month median follow-up, no difference was noted in 5-year overall survival in unweighted [91.5% in LG vs 94% in RG; hazard ratio (HR), 0.71; 95% confidence interval (CI), 0.46-1.1; P = 0.126] and weighted populations (94.2% in LG vs 93.2% in RG; HR, 0.88; 95% CI, 0.52-1.48; P = 0.636). There were no differences in 5-year recurrence-free survival (RFS), with unweighted 5-year RFS of 95.4% for LG and 95.2% for RG (HR, 0.95; 95% CI, 0.55-1.64; P = 0.845) and weighted 5-year RFS of 96.3% for LG and 95.3% for RG (HR, 1.24; 95% CI, 0.66-2.33; P = 0.498). CONCLUSIONS: After balancing covariates, RG demonstrated reliable surgical outcomes from the beginning. Long-term survival after RG and LG for GC was similar.

The Learning Curve of Linear-Shaped Gastroduodenostomy Associated with Totally Laparoscopic Distal Gastrectomy.

BACKGROUND: Linear-shaped gastroduodenostomy (LSGD) is a new method of intracorporeal reconstruction that is simpler to perform and associated with a lower rate of bile reflux than delta-shaped anastomosis. Here, we analyzed the learning curve of LSGD in totally laparoscopic distal gastrectomy. METHODS: The cumulative sum method was used to retrospectively analyze consecutive gastric cancer patients undergoing intracorporeal gastroduodenostomy after distal gastrectomy between January 2009 and May 2016. The duration of surgery, postoperative complications, hospital stay, and endoscopic findings in the postoperative period and the first, third, and fifth year were evaluated according to the two phases of the learning curve (learning period versus mastery period). RESULTS: Data from 222 patients were included in the analysis. The LSGD learning period was 29 cases. The surgical time in mastery period was significantly shorter than the learning period (124.9 ± 34.5 versus 168.2 ± 42.0 min, p < 0.001). The incidence of minor complications was significantly reduced after the learning period (p = 0.041), although there was no statistically significant difference in the rate of major complications. The long-term endoscopic findings showed that the presence of residual food decreased over the time (p = 0.022). CONCLUSIONS: LSGD can be mastered easily after a reasonable number of cases and was associated with safe and satisfactory short- and long-term outcomes before and after learning curve.

Feasibility of Linear-Shaped Gastroduodenostomy during the Performance of Totally Robotic Distal Gastrectomy.

PURPOSE: Although linear-shaped gastroduodenostomy (LSGD) was reported to be a feasible and reliable method of Billroth I anastomosis in patients undergoing totally laparoscopic distal gastrectomy (TLDG), the feasibility of LSGD for patients undergoing totally robotic distal gastrectomy (TRDG) has not been determined. This study compared the feasibility of LSGD in patients undergoing TRDG and TLDG. MATERIALS AND METHODS ALL C: onsecutive patients who underwent LSGD after distal gastrectomy for gastric cancer between January 2009 and December 2017 were analyzed retrospectively. Propensity score matching (PSM) analysis was performed to reduce the selection bias between TRDG and TLDG. Short-term outcomes, functional outcomes, learning curve, and risk factors for postoperative complications were analyzed. RESULTS: This analysis included 414 patients, of whom 275 underwent laparoscopy and 139 underwent robotic surgery. PSM analysis showed that operation time was significantly longer (163.5 vs. 132.1 minutes, P<0.001) and postoperative hospital stay significantly shorter (6.2 vs. 7.5 days, P<0.003) in patients who underwent TRDG than in patients who underwent TLDG. Operation time was the independent risk factor for LSGD after intracorporeal gastroduodenostomy. Cumulative sum analysis showed no definitive turning point in the TRDG learning curve. Long-term endoscopic findings revealed similar results in the two groups, but bile reflux at 5 years showed significantly better improvement in the TLDG group than in the TRDG group (P=0.016). CONCLUSIONS: LSGD is feasible in TRDG, with short-term and long-term outcomes comparable to that in TLDG. LSGD may be a good option for intracorporeal Billroth I anastomosis in patients undergoing TRDG.

Real-time Vessel Navigation Using Indocyanine Green Fluorescence during Robotic or Laparoscopic Gastrectomy for Gastric Cancer.

PURPOSE: Identification of the infrapyloric artery (IPA) type is a key component of pylorus-preserving gastrectomy. As the indocyanine green (ICG) fluorescence technique is known to help visualize blood vessels and flow during reconstruction, we speculated that this emerging technique would be helpful in identifying the IPA type. MATERIALS AND METHODS: From August 2015 to February 2016, 20 patients who underwent robotic or laparoscopic gastrectomy were prospectively enrolled. After intravenous injection of approximately 3 mL of ICG (2.5 mg/mL), a near-infrared fluorescence apparatus was applied. The identified shape of the IPA was confirmed by examining the actual anatomy following infrapyloric dissection. RESULTS: The mean interval time between ICG injection and visualization of the artery was 22.2 seconds (range, 14-30 seconds), and the mean duration of the arterial phase was 16.1 seconds (range, 9-30 seconds). The overall positive predictive value (PPV) of ICG fluorescence in identifying the IPA type was 80% (16/20). The IPA type was incorrectly predicted in four patients, all of whom were obese with a body mass index (BMI) of more than 25 kg/m2. CONCLUSIONS: Our preliminary results indicate that intraoperative vascular imaging using the ICG fluorescence technique may be helpful for robotic or laparoscopic pylorus-preserving gastrectomy.

Billroth II with Braun Enteroenterostomy Is a Good Alternative Reconstruction to Roux-en-Y Gastrojejunostomy in Laparoscopic Distal Gastrectomy.

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.

Modified overlap method using knotless barbed sutures (MOBS) for intracorporeal esophagojejunostomy after totally laparoscopic gastrectomy.

BACKGROUND: Compared to end-to-side anastomosis with a circular stapler, the overlap method is favored for intracorporeal esophagojejunostomy because it facilitates handling of the stapler, even in narrow spaces, and wider anastomosis. However, it associates with technical difficulties during anastomosis, including difficult traction on the esophageal stump that necessitates stay sutures. Here, we introduce a new modified overlap method that employs knotless barbed sutures (MOBS) and report the outcomes of our case series. METHOD: All consecutive patients who underwent intracorporeal esophagojejunostomy in 2015-2016 were included. All patients underwent surgery as follows: After esophageal transection with a linear stapler, two V-loc 90 sutures (Covidien, Mansfield, MA, USA) were sutured in the center of the stapled line. The opening was made between the two threads, and the intraluminal space was identified. The jejunum was ascended toward the esophageal stump by inserting a 45-mm-long linear staple. The anastomosis was made at the space between the right and left crura. After firing the linear stapler, the entry hole was closed bidirectionally using the pre-sutured threads. RESULTS: Forty patients underwent MOBS (27 by laparoscopy; 13 by robot). Mean total operative and MOBS procedural times were 180.6 and 22.4 min, respectively. Mean hospital stay was 6.9 days. Two patients had major complications (5.0 %). There were no anastomosis-related complications. Laparoscopy and robot subgroups did not differ in mean MOBS procedural times (22.2 vs. 22.7 min, p = 0.787). CONCLUSION: MOBS is a safe and feasible method that is a good option for intracorporeal esophagojejunostomy after laparoscopic gastrectomy.

Can Robotic Gastrectomy Surpass Laparoscopic Gastrectomy by Acquiring Long-Term Experience? A Propensity Score Analysis of a 7-Year Experience at a Single Institution.

PURPOSE: It is hypothesized that robotic gastrectomy may surpass laparoscopic gastrectomy after the operators acquire long-term experience and skills in the manipulation of robotic arms. This study aimed to evaluate the long-term learning curve of robotic distal gastrectomy (RDG) for gastric cancer compared with laparoscopic distal gastrectomy (LDG). MATERIALS AND METHODS: From October 2008 to December 2015, patients who underwent LDG (n=809) were matched to patients who underwent RDG (n=232) at a 1:1 ratio, by using a propensity score matching method after stratification for the operative year. The surgical outcomes, such as trends of operative time, blood loss, and complication rate, were compared between the two groups. RESULTS: The RDG group showed a longer operative time (171.3 minutes vs. 147.6 minutes, P<0.001) but less estimated blood loss (77.6 ml vs. 116.6 ml, P<0.001). The complication rate and postoperative recovery did not differ between the two groups. The RDG group showed a longer operative time and similar estimated blood loss compared with the LDG group after 5 years of experience (operative time: 159.2 minutes vs. 136.0 minutes in 2015, P=0.003; estimated blood loss: 72.9 ml vs. 78.1 ml in 2015, P=0.793). CONCLUSIONS: In terms of short-term surgical outcomes, RDG may not surpass LDG after a long-term experience with the technique.

Is There any Role of Visceral Fat Area for Predicting Difficulty of Laparoscopic Gastrectomy for Gastric Cancer?

PURPOSE: Obesity is associated with morbidity following gastric cancer surgery, but whether obesity influences morbidity after laparoscopic gastrectomy (LG) remains controversial. The present study evaluated whether body mass index (BMI) and visceral fat area (VFA) predict postoperative complications. MATERIALS AND METHODS: A total of 217 consecutive patients who had undergone LG for gastric cancer between May 2003 and December 2005 were included in the present study. We divided the patients into two groups ('before learning curve' and 'after learning curve') based on the learning curve effect of the surgeon. Each of these groups was sub-classified according to BMI (<25 kg/m(2) and ≥25 kg/m(2)) and VFA (<100 cm(2) and ≥100 cm(2)). Surgical outcomes, including operative time, quantity of blood loss, and postoperative complications, were compared between BMI and VFA subgroups. RESULTS: The mean operative time, length of hospital stay, and complication rate were significantly higher in the before learning curve group than in the after learning curve group. In the subgroup analysis, complication rate and length of hospital stay did not differ according to BMI or VFA; however, for the before learning curve group, mean operative time and blood loss were significantly higher in the high VFA subgroup than in the low VFA subgroup (P=0.047 and P=0.028, respectively). CONCLUSIONS: VFA may be a better predictive marker than BMI for selecting candidates for LG, which may help to get a better surgical outcome for inexperienced surgeons.

Glucuronidation of fimasartan, a new angiotensin receptor antagonist, is mainly mediated by UGT1A3.

1. Fimasartan is an angiotensin receptor II antagonist used to treat patients with hypertension. This drug is mainly excreted into bile as either the parent compound or a glucuronide conjugate. In this study, we examined the glucuronidation of fimasartan and characterized the UDP-glucuronosyltransferases (UGTs) responsible for the glucuronidation. 2. Only one type of fimasartan glucuronide was observed after incubation with pooled human liver microsomes (HLMs) and was identified as an N2-glucuronide based on comparison with an authentic standard. 3. Among the 12 UGT isoforms tested, UGT1A1, UGT1A3 and UGT2B7 showed catalytic activity toward fimasartan glucuronidation. The intrinsic clearance (CLint) of UGT1A3 was 68.5- and 21.4-fold higher than that of UGT1A1 and UGT2B7, respectively, and the estimated relative contribution of UGT1A3 in human liver was 94.1%. Both chemical inhibition and correlation studies demonstrated that fimasartan glucuronidation activity in HLMs was significantly related with UGT1A3 activity. Fimasartan glucuronide was identified as a substrate for P-glycoprotein (Pgp) and breast cancer response protein (BCRP). 4. These findings collectively indicate that UGT1A3 is the major UGT isoform responsible for the glucuronidation of fimasartan, and this glucuronide is excreted from hepatocytes via MDR1 and BCRP.

Structure-oriented versus process-oriented approach to enhance efficiency for emergency room operations: what lessons can we learn?

The efficiency and quality of a healthcare system can be defined as interactions among the system structure, processes, and outcome. This article examines the effect of structural adjustment (change in floor plan or layout) and process improvement (critical pathway implementation) on performance of emergency room (ER) operations for acute cerebral infarction patients. Two large teaching hospitals participated in this study: Korea University (KU) Guro Hospital and KU Anam Hospital. The administration of Guro adopted a structure-oriented approach in improving its ER operations while the administration of Anam employed a process-oriented approach, facilitating critical pathways and protocols. To calibrate improvements, the data for time interval, length of stay, and hospital charges were collected, before and after the planned changes were implemented at each hospital. In particular, time interval is the most essential measure for handling acute stroke patients because patients' survival and recovery are affected by the promptness of diagnosis and treatment. Statistical analyses indicated that both redesign of layout at Guro and implementation of critical pathways at Anam had a positive influence on most of the performance measures. However, reduction in time interval was not consistent at Guro, demonstrating delays in processing time for a few processes. The adoption of critical pathways at Anam appeared more effective in reducing time intervals than the structural rearrangement at Guro, mainly as a result of the extensive employee training required for a critical pathway implementation. Thus, hospital managers should combine structure-oriented and process-oriented strategies to maximize effectiveness of improvement efforts.

Different transport activity of human triallelic MDR1 893Ala/Ser/Thr variant and its association with herb extracts.

Individual pharmacokinetic differences for herb-drug interaction have been associated with genetic variations of the multidrug resistance (MDR) gene. A high level expression of MDR protein increases cellular efflux and might decrease drug sensitivity. This study investigated the drug efflux activity difference of human MDR1 triallelic variant 2677G/T/A (rs2032582), as a nonsynonymous 893Ala/Ser/Thr, using Xenopus laevis oocytes and MDR1 overexpressing LLC-PK1 cells. Two MDR1 variants (2667T/893Ser and 2667A/893Thr) were generated using human MDR1 cDNA (2677G/893Ala). No significant difference in the expression of MDR1 893Ala/Ser/Thr was found in X. laevis oocytes. However, the MDR1 2667A/893Thr variant interestingly showed a significant decrease of efflux activity for both digoxin and daunorubicin compared with those of 893Ala and 893Ser variants. In further investigation assessing the inhibitory effects of three herbal extracts on MDR1, 893Ala and 893Ser showed significant decreases of efflux activities in treatments with P. cocos (p = 0.005 for 893Ser) and D. dasycarpus (p = 0.0009 for 893Ala; p = 0.002 for 893Ser) in X. laevis oocytes. The results in this study suggest that herbal medicines could interact with other drugs and change the therapeutic effects depending on the genetic polymorphisms of individuals.