Association between hypotension during pancreatectomy and development of postoperative diabetes.

CONTEXT: With advancements in long-term survival after pancreatectomy, post-pancreatectomy diabetes has become a concern, and the risk factors are not established yet. Pancreatic islets are susceptible to ischemic damage, though there is a lack of clinical evidence regarding glycemic deterioration. OBJECTIVE: To investigate association between hypotension during pancreatectomy and development of post-pancreatectomy diabetes. DESIGN: In this retrospective, longitudinal cohort study, we enrolled patients without diabetes who underwent distal pancreatectomy or pancreaticoduodenectomy between January 2005 and December 2018, from two referral hospitals in Korea. MAIN OUTCOME MEASURES: Intraoperative hypotension [IOH] was defined as a 20% or greater reduction in systolic blood-pressure. The primary and secondary outcomes were incident diabetes and postoperative Homeostatic Model Assessment [HOMA] indices. RESULTS: We enrolled 1,129 patients (average age, 59 years; 49% men; 35% distal pancreatectomy). IOH occurred in 83% (median duration, 25 minutes; interquartile range [IQR], 5-65). During a median follow-up of 3.9 years, diabetes developed in 284 patients (25%). The cumulative incidence of diabetes was proportional to increases in the duration and depth of IOH (P < 0.001). For the median duration in an IOH when compared to a reference time of 0 minute, the hazard ratio [HR] was 1.48 (95% CI, 1.14-1.92). The effect was pronounced with distal pancreatectomy compared to pancreaticoduodenectomy. Furthermore, the duration of IOH was inversely correlated with 1-year HOMA beta-cell function (P < 0.002), but not with HOMA insulin resistance. CONCLUSIONS: These results support the hypothesis that IOH during pancreatectomy may elevate risk of diabetes by inducing beta cell insufficiency.

CORRIGENDUM: Correction of the ethical statements. Training efficacy of robotic duct-to-mucosa pancreaticojejunostomy simulation using silicone models for surgical fellows.

[This corrects the article on p. 45 in vol. 106, PMID: 38205096.].

Systematic review on surveillance for non-resected branch-duct intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND: The management of branch-duct type intraductal papillary mucinous neoplasms (BD-IPMN) varies in existing guidelines. This study investigated the optimal surveillance protocol and safe discontinuation of surveillance considering natural history in non-resected IPMN, by systematically reviewing the published literature. METHODS: This review was guided by PRISMA. Research questions were framed in PICO format "CQ1-1: Is size criteria helpful to determine surveillance period? CQ1-2: How often should surveillance be carried out? CQ1-3: When should surveillance be discontinued? CQ1-4: Is nomogram predicting malignancy useful during surveillance?". PubMed was searched from January-April 2022. RESULTS: The search generated 2373 citations. After screening, 83 articles were included. Among them, 33 studies were identified for CQ1-1, 19 for CQ1-2, 26 for CQ1-3 and 12 for CQ1-4. Cysts <1.5 or 2 cm without worrisome features (WF) were described as more indolent, and most studies advised an initial period of surveillance. The median growth rate of cysts <2 cm ranged from 0.23 to 0.6 mm/year. Patients with cysts <2 cm showing no morphological changes and no WF after 5-years of surveillance have minimal malignancy risk of 0-2%. Two nomograms created with over 1000 patients had AUCs of around 0.8 and appear to be feasible in a real-world practice. CONCLUSIONS: For patients with suspected BD-IPMN <2 cm and no other WF, less frequent surveillance is recommended. Surveillance may be discontinued for cysts that remain stable during 5-year surveillance, with consideration of patient condition and life expectancy. With this updated surveillance strategy, patients with non-worrisome BD-IPMN should expect more streamlined management and decreased healthcare utilization.

Strengthening Multi-Factor Authentication Through Physically Unclonable Functions in PVDF-HFP-Phase-Dependent a-IGZO Thin-Film Transistors.

For enhanced security in hardware-based security devices, it is essential to extract various independent characteristics from a single device to generate multiple keys based on specific values. Additionally, the secure destruction of authentication information is crucial for the integrity of the data. Doped amorphous indium gallium zinc oxide (a-IGZO) thin-film transistors (TFTs) using poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) induce a dipole doping effect through a phase-transition process, creating physically unclonable function (PUF) devices for secure user information protection. The PUF security key, generated at VGS = 20 V in a 20 × 10 grid, demonstrates uniformity of 42% and inter-Hamming distance (inter-HD) of 49.79% in the ß-phase of PVDF-HFP. However, in the γ-phase, the uniformity drops to 22.5%, and inter-HD decreases to 35.74%, indicating potential security key destruction during the phase transition. To enhance security, a multi-factor authentication (MFA) system is integrated, utilizing five security keys extracted from various TFT parameters. The security keys from turn-on voltage (VON), VGS = 20 V, VGS = 30 V, mobility, and threshold voltage (Vth) exhibit near-ideal uniformities and inter-HDs, with the highest values of 58% and 51.68%, respectively. The dual security system, combining phase transition and MFA, establishes a robust protection mechanism for privacy-sensitive user information.

Examining neoadjuvant treatment candidates in resectable pancreatic cancer based on tumor-vessel interactions and CA 19-9 levels: a retrospective cohort study.

INTRODUCTION: The applicability of neoadjuvant treatment (NAT) for resectable pancreatic ductal adenocarcinoma (PDAC) has arisen, however, high-level evidence is lacking. This study aimed to explore patient subgroups with high-risk resectable PDAC for selecting candidates who may benefit from NAT. METHODS: The 1132 patients with resectable or borderline resectable PDAC who underwent surgery between 2007 and 2021 were retrospectively reviewed. Patients with resectable PDAC without contact of major vessels (R-no contact) ( n =651), with contact of portal vein or superior mesenteric vein (PV/SMV) ≤180° (R-contact) ( n =306), and borderline resectable PDAC without arterial involvement (BR-V) ( n =175) were analyzed. RESULTS: The mean age was 64.3±9.8 years, and 647 patients (57.2%) were male. The median follow-up was 26 months in the entire cohort. Patients with resectable PDAC without vascular contact had the most improved overall survival (OS) (median; 31.5 months). OS did not significantly differ between NAT and upfront surgery in the entire resectable PDAC cohort. However, in R-contact group, NAT showed significantly improved OS compared to upfront surgery (33 vs. 23 months). Neoadjuvant FOLFIRINOX was showed a better OS than gemcitabine-based regimens in patients who underwent NAT (34 vs. 24 months). NAT was associated with a better survival in the patients with CA 19-9 level ≥150 U/ml, only when the tumor has PV/SMV contact in resectable disease (40 vs. 19 months, P =0.001). CONCLUSIONS: NAT can be considered as an effective treatment in patients with resectable PDAC, particularly when the tumor is in contact with PV/SMV and CA 19-9 ≥150 U/ml.

Clinical outcomes of minimally invasive (laparoscopic and robotic) versus open extended cholecystectomy: A multicenter propensity score matched study.

BACKGROUND: This multicenter study aimed to compare the clinical outcomes of minimally invasive extended cholecystectomy (MI-EC) versus open EC (O-EC) for patients with gallbladder cancer (GBC). METHODS: Patients who underwent EC (cholecystectomy, wedge resection of the liver bed, and regional lymphadenectomy) for GBC between 2010 and 2020 in three centers were included in the study. The clinicopathological data were compared after propensity score matching. Additional subgroup analysis on laparoscopic and robotic EC (L-EC and R-EC) was performed. RESULTS: A total of 377 patients were included: 308 for O-EC and 69 for MI-EC, respectively. The MI-EC group had a longer operative time (188.9 vs. 238.1 min, p < .001) and shorter hospital stay (9.0 vs. 7.2 days, p = .007), although no differences were found in operative blood loss, complication rate and survival outcome. In subgroup analysis, L-EC patients had a longer operative time (264.4 vs. 202.0 min, p = .001), compared to R-EC patients with comparable perioperative and survival outcomes. CONCLUSION: Although patients with MI-EC had a longer operation time and higher medical costs, the advantages were enhanced recovery with comparable short- and long-term outcomes. The operation time was less for R-EC patients than for L-EC patients, though the high cost still remains. The surgery type for EC can be selected according to the patient's condition, social status and surgeon's preference.

Optimal Surveillance Interval of Branch Duct Intraductal Papillary Mucinous Neoplasm of the Pancreas.

Importance: Despite the increasing prevalence of intraductal papillary mucinous neoplasm (IPMN), data on the growth and malignant conversion rates based on long-term surveillance cohorts are limited. Many international guidelines recommend surveillance for benign lesions, but the optimal interval and duration are unclear. Objective: To determine the optimal surveillance protocol for IPMN and propose which patients may be exempted from surveillance. Design, Setting, and Participants: This large-scale, international cohort study examined data of 3825 patients with IPMN treated at 5 tertiary pancreatic centers. Included were patients with branch duct (BD) IPMN who underwent surveillance or surgery between January 1, 1988, and December 31, 2020. After a thorough review, 3656 patients were included in the analytic sample. Changes in cyst size, worrisome features or high-risk stigmata, and malignant conversion rates were assessed. Patients who underwent surveillance over 5 years were compared to suggest discontinuation of surveillance protocol. Clinical data collection began in January 1, 2021, and the mean (SD) follow-up duration was 84 (47.7) months. The data analysis was performed from May 2, 2022, through September 14, 2022. Exposure: The patients with BD-IPMN were followed up based on International Association of Pancreatology guidelines. Patients with suspicious malignant neoplasms during surveillance underwent surgical resection. Main Outcome and Measures: The main outcome of this study was the optimal follow-up interval and duration of BD-IPMN surveillance. The association among cyst size, growth rate, and progression was examined using descriptive statistics. Results: Of the 3656 patients with BD-IPMN in the analytic sample (1973 [54.0%] female; mean [SD] age, 63.7 [10.2] years), 172 (4.7%) were confirmed to have malignant lesions through surgery. Considering cyst growth, the time to develop worrisome features, and malignant conversion, a 1.5-, 1-, and 0.5-year surveillance interval could be optimal for cysts smaller than 20 mm, 20 to 30 mm, and 30 mm, respectively, after initial short-term (6-month) follow-up. Patients with cysts smaller than 20 mm, no worrisome features, and no growth during 5-year surveillance did not show malignant conversion after 5 years of follow-up and had time to progression of greater than 10 years. Conclusions: These findings suggest that BD-IPMN surveillance may depend on the size of the cyst and morphologic changes at the initial 6-month follow-up. For patients with small cysts (ie, <20 mm) with no morphologic changes during the initial 5-year surveillance period, surveillance may be discontinued for those unfit for surgery or who have a limited life expectancy of 10 years or less.

NPC1L1 rs217434 A > G as a Novel Single Nucleotide Polymorphism Related to Dyslipidemia in a Korean Population.

A relationship between cholesterol levels and Niemann-Pick C1-Like 1 (NPC1L1) polymorphisms in diverse populations was found in previous studies. However, relevant research on this association in the Korean population is relatively scarce. Therefore, the current study sought to examine the correlation between the NPC1L1 rs217434 A > G polymorphism and clinical as well as biochemical variables pertaining to dyslipidemia in the Korean population. This cross-sectional single-center study included 1404 Korean subjects aged 20-86 years, grouped based on dyslipidemia presence (normal and dyslipidemia) and genotype (AA or AG). After adjusting for sex and age, it was discovered that the dyslipidemia group's BMI, diastolic blood pressure, glucose-related indicators, lipid profile, high-sensitivity C-reactive protein (hs-CRP), and parameters of oxidative stress were considerably different from the normal group's values. When grouped according to genotype, individuals in the AG group exhibited greater total cholesterol, low-density lipoprotein cholesterol, hs-CRP, and 8-epi-prostaglandin F2α in comparison to those in the AA group. Moreover, individuals with dyslipidemia and the AG genotype exhibited unfavorable outcomes for lipid profiles, markers related to glucose and inflammation, and markers of oxidative stress. This study provided evidence for a relationship between the NPC1L1 rs217434 A > G genotype and dyslipidemia in the Korean population, which highlights the potential of the NPC1L1 rs217434 A > G genotype as an early predictor of dyslipidemia.

Training efficacy of robotic duct-to-mucosa pancreaticojejunostomy simulation using silicone models for surgical fellows.

Purpose: In the era of minimally invasive surgery (MIS), robotic pancreatoduodenectomy (PD) is actively performed, and clinical fellows need to thoroughly prepare for MIS-PD during the training process. Although pancreaticojejunostomy (PJ) is a difficult anastomosis that requires repeated practice, there are obstacles preventing its practice that concerns patient safety and limited time in the actual operating room. This study evaluated the efficacy of simulation-based training of robotic duct-to-mucosa PJ using pancreatic and intestinal silicone models using a scoring system. Methods: Three pancreatobiliary clinical fellows who had never performed a real robotic PJ participated in this study. Each trainee, who was well acquainted with master's video created by a senor surgeon, performed the robotic PJ procedures 9 times, and 3 independent pancreatobiliary surgeons assessed the videos and analyzed the scores using a blind method. Results: The mean robotic PJ times for the 3 trainees were 42.8 and 29.1 minutes for the first and 9th videos, respectively. The mean score was 13.8 (range, 6-17) for the first video and 17.7 (range, 15-19) for the 9th video. When comparing earlier and later attempts, the PJ time decreased significantly (2,201.67 seconds vs. 2,045.50 seconds, P = 0.007), whereas test scores increased significantly (total score 14.22 vs. 16.89, P = 0.011). Conclusion: This robotic education system will help pancreatobiliary trainees overcome the learning curves efficiently and quickly without raising ethical concerns associated with animal models or direct practice with human subjects. This will be of practical assistance to trainees preparing for MIS-PD.

Glucolipotoxicity Suppressed Autophagy and Insulin Contents in Human Islets, and Attenuation of PERK Activity Enhanced Them in an ATG7-Dependent Manner.

BACKGRUOUND: Administration of pancreatic endoplasmic reticulum kinase inhibitor (PERKi) improved insulin secretion and hyperglycemia in obese diabetic mice. In this study, autophagic balance was studied whether to mediate it. METHODS: Human islets were isolated from living patients without diabetes. PERKi GSK2606414 effects were evaluated in the islets under glucolipotoxicity by palmitate. Islet insulin contents and secretion were measured. Autophagic flux was assessed by microtubule associated protein 1 light chain 3 (LC3) conversion, a red fluorescent protein (RFP)-green fluorescent protein (GFP)- LC3 tandem assay, and P62 levels. For mechanical analyses, autophagy was suppressed using 3-methyladenine in mouse islets. Small interfering RNA for an autophagy-related gene autophagy related 7 (Atg7) was transfected to interfere autophagy. RESULTS: PERKi administration to mice decreased diabetes-induced P62 levels in the islets. Glucolipotoxicity significantly increased PERK phosphorylation by 70% and decreased insulin contents by 50% in human islets, and addition of PERKi (40 to 80 nM) recovered both. PERKi also enhanced glucose-stimulated insulin secretion (6-fold). PERKi up-regulated LC3 conversion suppressed by glucolipotoxicity, and down-regulated P62 contents without changes in P62 transcription, indicating enhanced autophagic flux. Increased autophagosome-lysosome fusion by PERKi was visualized in mouse islets, where PERKi enhanced ATG7 bound to LC3. Suppression of Atg7 eliminated PERKi-induced insulin contents and secretion. CONCLUSION: This study provided functional changes of human islets with regard to autophagy under glucolipotoxicity, and suggested modulation of autophagy as an anti-diabetic mechanism of PERKi.

In Neoadjuvant FOLFIRINOX Chemotherapy for Pancreatic Ductal Adenocarcinoma, Which Response is the More Reliable Indicator for Prognosis, Radiologic or Biochemical?

BACKGROUND: In this era of increasing neoadjuvant chemotherapy, methods for evaluating responses to neoadjuvant chemotherapy are still diverse among institutions. Additionally, the efficacy of adjuvant chemotherapy for patients undergoing neoadjuvant chemotherapy remains unclear. Therefore, this retrospective study was performed to evaluate the effectiveness of methods for assessing response to neoadjuvant chemotherapy and the need for adjuvant chemotherapy in treating patients with non-metastatic pancreatic ductal adenocarcinoma. METHODS: The study identified 150 patients who underwent neoadjuvant FOLFIRINOX chemotherapy followed by curative-intent pancreatectomy. The patients were stratified by biochemical response based on the normalization of carbohydrate antigen 19-9 and by radiologic response based on size change at imaging. RESULTS: The patients were classified into the following three groups based on their response to neoadjuvant chemotherapy and prognosis: biochemical responders (BR+), radiology-only responders (BR-/RR+), and non-responders (BR-/RR-). The 3-year overall survival rate was higher for BR+ (71.0%) than for BR-/RR+ (53.6%) or BR-/RR- (33.1%) (P < 0.001). Response to neoadjuvant chemotherapy also was identified as a significant risk factor for recurrence in a comparison between BR-/RR+ and BR+ (hazard ratio [HR], 2.15; 95% confidence interval [CI] 1.19-3.88; P = 0.011) and BR-/RR- (HR, 3.82; 95% CI 2.41-6.08; P < 0.001). Additionally, regardless of the response to neoadjuvant chemotherapy, patients who completed adjuvant chemotherapy had a significantly higher 3-year overall survival rate than those who did not. CONCLUSIONS: This response evaluation criterion for neoadjuvant chemotherapy is feasible and can significantly predict prognosis. Additionally, completion of adjuvant chemotherapy could be helpful to patients who undergo neoadjuvant chemotherapy regardless of their response to neoadjuvant chemotherapy.

Efficacy of local treatment for isolated liver metastasis after pancreatectomy in pancreatic ductal adenocarcinoma: A propensity score-matched analysis.

BACKGROUND: Although attempts of local treatment for isolated liver recurrence in patients with pancreatic ductal adenocarcinoma (PDAC) have increased, the efficacy remains unclear. Therefore, we aimed to evaluate the effect of local treatment for recurrent liver lesions after pancreatectomy on the survival of patients with PDAC. METHODS: Patients who were diagnosed with isolated liver recurrence after pancreatectomy at a high-volume center were included. We classified these patients based on the treatment options after recurrence and performed propensity score matching to minimize confounding. RESULTS: Median with interquartile range survival after recurrence was significantly longer for patients who underwent local treatment for recurrent liver lesions plus chemotherapy (22.0 [17.0-29.0] months) than those treated with chemotherapy alone (13.0 [7.0-21.0] months, p = .027). In multivariate analysis, not only local treatment for recurrent liver lesions plus chemotherapy (hazard ratio [95% confidence interval], 0.55 [0.32-0.94]; p = .030) but also indicators for systemically controlled tumor such as late recurrence (0.57 [0.35-0.92]; p = .021), chemotherapy for ≥6 months (0.25 [0.15-0.42]; p < .001), and disease control by chemotherapy (0.36 [0.22-0.60]; p < .001) were identified as favorable prognostic factors. CONCLUSIONS: PDAC patients with stable recurrent liver lesions should be considered a candidate for local treatment.

Inadequacy of the eighth edition of the American Joint Committee on Cancer pancreatic cancer staging system for invasive carcinoma associated with premalignant lesions in the pancreas: an analysis using the National Cancer Database.

BACKGROUND: Invasive carcinomas arising from premalignant lesions are currently staged by the same criteria as conventional pancreatic ductal adenocarcinoma. METHODS: Clinicopathologic information and survival data were extracted through a thorough search of histology codes from National Cancer Database (2006-2016). A total of 723 patients with invasive intraductal papillary mucinous neoplasm and mucinous cystic neoplasm were analyzed. RESULTS: The median age was 67 years, and 351 patients (48.5%) were male. There were 212 (29.3%), 232 (32.1%), 272 (37.6%), and 7 (1.0%) patients with T1, T2, T3, and T4 classification. Extrapancreatic extension (EPE) was present in 284 (39.3%). Age (HR = 1.504, 95% CI 1.196-1.891), R1 or R2 resection (HR = 1.585, 95% CI 1.175-2.140), and EPE (HR = 1.598, 95% CI 1.209-2.113) were independent prognostic factors for overall survival. Size criteria did not significantly affect survival. The median survival was 115.9 months for patients without EPE, compared to 34.2 months for those with EPE. EPE discriminated survival better than tumor size. DISCUSSION: The T classification of the eighth edition AJCC staging system is not adequate for invasive carcinomas associated with premalignant lesions of the pancreas. They merit a separate, dedicated staging system that uses appropriate prognostic factors.

Metabolic changes preceding bladder cancer occurrence among Korean men: a nested case-control study from the KCPS-II cohort.

BACKGROUND: Bladder cancer (BLCA) research in Koreans is still lacking, especially in focusing on the prediction of BLCA. The current study aimed to discover metabolic signatures related to BLCA onset and confirm its potential as a biomarker. METHODS: We designed two nested case-control studies using Korean Cancer Prevention Study (KCPS)-II. Only males aged 35-69 were randomly selected and divided into two sets by recruitment organizations [set 1, BLCA (n = 35) vs. control (n = 35); set 2, BLCA (n = 31) vs. control (n = 31)]. Baseline serum samples were analyzed by non-targeted metabolomics profiling, and OPLS-DA and network analysis were performed. Calculated genetic risk score (GRS) for BLCA from all KCPS participants was utilized for interpreting metabolomics data. RESULTS: Critical metabolic signatures shown in the BLCA group were dysregulation of lysine metabolism and tryptophan-indole metabolism. Furthermore, the prediction model consisting of metabolites (lysine, tryptophan, indole, indoleacrylic acid, and indoleacetaldehyde) reflecting these metabolic signatures showed mighty BLCA predictive power (AUC: 0.959 [0.929-0.989]). The results of metabolic differences between GRS-high and GRS-low groups in BLCA indicated that the pathogenesis of BLCA is associated with a genetic predisposition. Besides, the predictive ability for BLCA on the model using GRS and five significant metabolites was powerful (AUC: 0.990 [0.980-1.000]). CONCLUSION: Metabolic signatures shown in the present research may be closely associated with BLCA pathogenesis. Metabolites involved in these could be predictive biomarkers for BLCA. It could be utilized for early diagnosis, prognostic diagnosis, and therapeutic targets for BLCA.

Non-invasive biomarkers for early diagnosis of pancreatic cancer risk: metabolite genomewide association study based on the KCPS-II cohort.

BACKGROUND: Pancreatic cancer is a lethal disease with a high mortality rate. The difficulty of early diagnosis is one of its primary causes. Therefore, we aimed to discover non-invasive biomarkers that facilitate the early diagnosis of pancreatic cancer risk. METHODS: The study subjects were randomly selected from the Korean Cancer Prevention Study-II and matched by age, sex, and blood collection point [pancreatic cancer incidence (n = 128) vs. control (n = 256)]. The baseline serum samples were analyzed by non-targeted metabolomics, and XGBoost was used to select significant metabolites related to pancreatic cancer incidence. Genomewide association study for the selected metabolites discovered valuable single nucleotide polymorphisms (SNPs). Moderation and mediation analysis were conducted to explore the variables related to pancreatic cancer risk. RESULTS: Eleven discriminant metabolites were selected by applying a cut-off of 4.0 in XGBoost. Five SNP presented significance in metabolite-GWAS (p ≤ 5 × 10-6) and logistic regression analysis. Among them, the pair metabolite of rs2370981, rs55870181, and rs72805402 displayed a different network pattern with clinical/biochemical indicators on comparison with allelic carrier and non-carrier. In addition, we demonstrated the indirect effect of rs59519100 on pancreatic cancer risk mediated by γ-glutamyl tyrosine, which affects the smoking status. The predictive ability for pancreatic cancer on the model using five SNPs and four pair metabolites with the conventional risk factors was the highest (AUC: 0.738 [0.661-0.815]). CONCLUSIONS: Signatures involving metabolites and SNPs discovered in the present research may be closely associated with the pathogenesis of pancreatic cancer and for use as predictive biomarkers allowing early pancreatic cancer diagnosis and therapy.

Association of Bypass Surgery and Mortality in Moyamoya Disease.

Background Patients with moyamoya disease (MMD) have a high risk of stroke or death. We investigated whether extracranial to intracranial bypass surgery can reduce mortality by preventing strokes in patients with MMD. Methods and Results This nationwide retrospective cohort study encompassed patients with MMD registered under the Rare Intractable Diseases program via the Relieved Co-Payment Policy between 2006 and 2019, using the Korean National Health Insurance Service database. Following a 4-year washout period, landmark analyses were employed to assess mortality and stroke occurrence between the bypass surgery group and the nonsurgical control group at specific time points postindex date (1 month and 3, 6, 12, and 36 months). The study included 18 480 patients with MMD (mean age, 40.7 years; male to female ratio, 1:1.86) with a median follow-up of 5.6 years (interquartile range, 2.5-9.3; mean, 6.1 years [SD, 4.0 years]). During 111 775 person-years of follow-up, 265 patients in the bypass surgery group and 1144 patients in the nonsurgical control group died (incidence mortality rate of 618.1 events versus 1660.3 events, respectively, per 105 person-years). The overall adjusted hazard ratio (HR) revealed significantly lower all-cause mortality in the bypass surgery group from the 36-month landmark time point, for any stroke mortality from 3- and 6-month landmark time points, and for hemorrhagic stroke mortality from the 6-month landmark time point. Furthermore, the overall adjusted HRs for hemorrhagic stroke occurrence were beneficially maintained from all 5 landmark time points in the bypass surgery group. Conclusions Bypass surgery in patients with MMD was associated with a lower risk of all-cause and hemorrhagic stroke mortality and hemorrhagic stroke occurrence compared with nonsurgical control.

Reconsidering the absence of extrapancreatic extension in T staging for pancreatic adenocarcinoma in the AJCC (8th ed) Staging Manual using the National Cancer Database.

PURPOSE: Although the concept of extrapancreatic extension (EPEx) was removed in the eighth edition of the American Joint Committee on Cancer pancreatic cancer staging system, several studies have supported the prognostic significance of EPEx. This study aimed to investigate the significance of EPEx in pancreatic ductal adenocarcinoma (PDAC) using the National Cancer Database (NCDB). METHODS: Data of patients who underwent resection for PDAC between 2006 and 2016 were extracted and analyzed from the NCDB. Cases arising from premalignant lesions, those with metastases, and those treated with neoadjuvant therapy were excluded. RESULTS: Among 37,634 patients, the median overall survival was 23 months and the 5-year survival rate was 22.7%. The EPEx prevalence was the lowest for T1 stage (63.2%) and increased with each T-stage (T2:83.4%, T3:85.8%). The overall survival was better in EPEx-negative patients than in EPEx-positive patients (median 33.7 vs. 21.5 months; p<0.001). When the T-stages were stratified by EPEx, EPEx-positive patients showed worse survival in all T-stages than EPEx-negative patients. Survival was comparable between T1 EPEx-positive and T2 or T3 EPEx-negative patients (p=0.088 and p=0.178, respectively). Furthermore, T2 and T3 EPEx-negative patients had similar survival to each other (p=0.877), and distinctly superior survival compared to T2 and T3 EPEx-positive patients (p<0.001). CONCLUSIONS: EPEx was an important prognostic factor in the overall cohort and in differentiating between T stages. This study strongly suggests that staging systems should reinstate EPEx and apply it to all T-stages, especially in T1, where EPEx was absent in 36% of patients.

Self-Assembled Monolayer Doping for MoTe2 Field-Effect Transistors: Overcoming PN Doping Challenges in Transition Metal Dichalcogenides.

Transition metal dichalcogenides (TMDs) have gained significant attention as next-generation semiconductor materials that could potentially overcome the integration limits of silicon-based electronic devices. However, a challenge in utilizing TMDs as semiconductors is the lack of an established PN doping method to effectively control their electrical properties, unlike those of silicon-based semiconductors. Conventional PN doping methods, such as ion implantation, can induce lattice damage in TMDs. Thus, chemical doping methods that can control the Schottky barrier while minimizing lattice damage are desirable. Here, we focus on the molybdenum ditelluride (2H-MoTe2), which has a hexagonal phase and exhibits ambipolar field-effect transistor (FET) properties due to its direct band gap of 1.1 eV, enabling concurrent transport of electrons and holes. We demonstrate the fabrication of p- or n-type unipolar FETs in ambipolar MoTe2 FETs using self-assembled monolayers (SAMs) as chemical dopants. Specifically, we employ 1H,1H,2H,2H perfluorooctyltriethoxysilane and (3-aminopropyl)triethoxysilane as SAMs for chemical doping. The selective SAMs effectively increase the hole and electron charge transport capabilities in MoTe2 FETs by 18.4- and 4.6-fold, respectively, due to the dipole effect of the SAMs. Furthermore, the Raman shift of MoTe2 by SAM coating confirms the successful p- and n-type doping. Finally, we demonstrate the fabrication of complementary inverters using SAMs-doped MoTe2 FETs, which exhibit clear full-swing capability compared to undoped complementary inverters.

Oncologic safety of robotic extended cholecystectomy for gallbladder cancer.

BACKGROUND: Although laparoscopic cholecystectomy is applicable for the treatment of early gallbladder cancer (GBC), minimally invasive surgery is not widely used for advanced GBC. This is because advanced GBCs necessitate complicated surgical techniques, including lymph node dissection and liver resection. Robotic extended cholecystectomy (REC) is thought to overcome the limitations of laparoscopic surgery, but oncological safety studies are lacking. Therefore, in this study, we aimed to evaluate the oncologic outcomes of REC compared with those of open extended cholecystectomy (OEC). METHODS: A total of 125 patients, who underwent extended cholecystectomy for GBC with tentative T2 or higher stage between 2018 and 2021, were included and stratified by surgical methods. To minimize the confounding factors, 1:1 propensity-score matching was performed between the patients who underwent REC and those who underwent OEC. RESULTS: Regarding short-term outcomes, the REC group showed significantly lower estimated blood loss (382.7 vs. 717.2 mL, P = 0.020) and shorter hospital stay (6.9 vs. 8.5 days, P = 0.042) than the OEC group. In addition, the REC group had significantly lower subjective pain scores than the OEC group from the day of surgery through the 5th postoperative day (P = 0.006). Regarding long-term outcomes, there were no significant differences in the 3-year [5-year] overall survival (OS) and disease-free survival (DFS) rates between the REC group [OS, 92.3% (92.3%); DFS, 84.6% (72.5%)] and the OEC group [OS, 96.8% (96.8%); DFS, 78.2% (78.2%)] (P = 0.807 for OS and 0.991 for DFS). CONCLUSIONS: In this study, REC showed superior short-term outcomes to OEC and no difference in long-term survival outcomes. Additionally, REC was superior to OEC in terms of postoperative pain. Therefore, REC may be a feasible option with early recovery compared with OEC for patients with advanced GBC.

The Possible Effect of Dietary Fiber Intake on the Metabolic Patterns of Dyslipidemia Subjects: Cross-Sectional Research Using Nontargeted Metabolomics.

BACKGROUND: Dyslipidemia is important because of its association with various metabolic complications. Numerous studies have sought to obtain scientific evidence for managing dyslipidemia patients. OBJECTIVES: This study aims to identify differences in the nutritional traits of dyslipidemia subjects based on metabolite patterns. METHODS: Dyslipidemia (n = 73) and control (n = 80) subjects were included. Dyslipidemia was defined as triglycerides ≥200 mg/dL, total cholesterol ≥240 mg/dL, low density lipoprotein cholesterol ≥160 mg/dL, high-density lipoprotein cholesterol <40 mg/dL (men) or 50 mg/dL (women), or lipid-lowering medicine use. Nontargeted metabolomics based on ultra-high performance liquid chromatography-mass spectrometry identified plasma metabolites, and K-means clustering was used to reconstitute groups based on the similarity of metabolomic patterns across all subjects. Then, with eXtreme Gradient Boosting, metabolites significantly contributing to the new grouping were selected. Statistical analysis was conducted to analyze traits demonstrating appreciable differences between the groups. RESULTS: Dyslipidemia subjects were divided into 2 groups based on whether they were (n = 24) or were not (n = 56) in a similar metabolic state as the controls by K-means clustering. The considerable contribution of 4 metabolites (3-hydroxybutyrylcarnitine, 2-octenal, 1,3,5-heptatriene, and 5ß-cholanic acid) to this new subset of dyslipidemia was confirmed by eXtreme Gradient Boosting. Furthermore, fiber intake was significantly higher in dyslipidemia subjects whose metabolic state was similar to that of the control than in the dissimilar group (P = 0.002). Moreover, significant correlations were observed between the 4 metabolites and fiber intake. Regression analysis determined that the ideal cutoff for fiber intake was 17.28 g/d. CONCLUSIONS: Dyslipidemia patients who consume 17.28 g/d or more of dietary fiber may maintain similar metabolic patterns to healthy individuals, with substantial effects on the changes in the concentrations of 4 metabolites. Our findings could be applied to developing dietary guidelines for dyslipidemia patients.