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Background: Postoperative pancreatic fistula (POPF) remains one of the most severe complications after pancreatic surgery. The methods for predicting pancreatic fistula are limited. We aimed to investigate the predictive value of body composition parameters measured by preoperative bioelectrical impedance analysis (BIA) on the development of POPF., Methods: A total of 168 consecutive patients undergoing pancreatic surgery from March 2022 to December 2022 at our institution were included in the study and randomly assigned at a 3:2 ratio to the training group and the validation group. All data, including previously reported risk factors for POPF and parameters measured by BIA, were collected. Risk factors were analyzed by univariable and multivariable logistic regression analysis. A prediction model was established to predict the development of POPF based on these parameters., Results: POPF occurred in 41 of 168 (24.4%) patients. In the training group of 101 enrolled patients, visceral fat area (VFA) (odds ratio [OR] = 1.077, P = 0.001) and fat mass index (FMI) (OR = 0.628, P = 0.027) were found to be independently associated with POPF according to multivariable analysis. A prediction model including VFA and FMI was established to predict the development of POPF with an area under the receiver operating characteristic curve (AUC) of 0.753. The efficacy of the prediction model was also confirmed in the internal validation group (AUC 0.785, 95% CI 0.659-0.911)., Conclusions: Preoperative assessment of body fat distribution by BIA can predict the risk of POPF after pancreatic surgery., (© 2024 The Author(s). Nutrition in Clinical Practice published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

Hazardous heavy metals and organic substances removal is of great significance for ensuring the safety of aquatic-ecosystem, yet the highly effective and selective extraction always remains challenging. To address this problem, magnetic hollow microcubes were fabricated through thermal carbonization of Fe 3 O 4 -COOH@ γ-CD-MOFs, and core-shell structured precursors were in-situ greenly constructed on a large scale via microwave-assisted self-assembly strategy. As noted, the development of secondary crystallization was utilized to achieve uniform dispersion of cores within MOFs frameworks and thus improved magnetic and adsorption ability of composites. Acquired magnetic Fe 3 O 4 @HC not only can harvest excellent extraction of heavy metals (Cd, Pb, and Cu of 129.87, 151.05, and 106.98 mg·g -1 ) but also exhibit highly selective adsorption ability for cationic organics (separation efficiency higher than 95.0 %). Impressively, Fe 3 O 4 @HC achieved outstanding adsorption (60-80 %) of Cd in realistic mussel cooking broth with no obvious loss in amino acid. Characterizations better offer mechanistic insight into the enhanced selectivity of positively charged pollutants can be attributed to synergistic effect of ions exchange and electrostatic interaction of abundant oxygen-containing functional groups. Our study provides a feasible route by rationally developing core-shell structured composites to promote the practical applications of sustainable water treatment and value-added utilization of processing by-products., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) involves a significant accumulation of cancer-associated fibroblasts (CAFs) as part of the host response to tumor cells. The origins and functions of transcriptionally diverse CAF populations in PDAC remain poorly understood. Tumor cell-intrinsic genetic mutations and epigenetic dysregulation may reshape the TME; however, their impacts on CAF heterogeneity remain elusive. SETD2, a histone H3K36 trimethyl-transferase, functions as a tumor suppressor. Through single-cell RNA sequencing, we identify a lipid-laden CAF subpopulation marked by ABCA8a in Setd2-deficient pancreatic tumors. Our findings reveal that tumor-intrinsic SETD2 loss unleashes BMP2 signaling via ectopic gain of H3K27Ac, leading to CAFs differentiation toward lipid-rich phenotype. Lipid-laden CAFs then enhance tumor progression by providing lipids for mitochondrial oxidative phosphorylation via ABCA8a transporter. Together, our study links CAF heterogeneity to epigenetic dysregulation in tumor cells, highlighting a previously unappreciated metabolic interaction between CAFs and pancreatic tumor cells., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The presence of pesticide residues in aquatic environments poses a significant threat to both aquatic ecosystems and human health. The presence of these residues can result in significant harm to aquatic ecosystems and can negatively impact the health of aquatic organisms. Consequently, this issue requires urgent attention and effective measures to mitigate its impact. However, developing sensitive and rapid detection methods remains a challenge. In this study, an all-in-one test strip, which integrated bioenzymes, nanoenzymes, and a chromogen, was developed in combination with an enzyme labeling instrument for a highly sensitive and convenient sensing of malathion residues. The oxidase activity of heme chloride (Hemin) in the strip can catalyze the oxidation of H 2 O 2 and 3,3',5,5'-tetramethylbenzidine (TMB) to produce a blue-colored oxide. Simultaneously, the alkaline phosphatase (ALP) present in the strip can break down l-ascorbic acid-2-phosphate to produce ascorbic acid (AA). This AA then acts to reduce the oxidized form of TMB, turning it into a colorless substance and leading to the disappearance of its fluorescent signal. In the presence of a pesticide, the activity of ALP is inhibited and formation of AA is blocked, thereby preventing the reduction of oxidized TMB and producing a colored signal. According to this principle, the integrated test strip detected the target pesticide with high performance as per the optical density value determined via an enzyme marker. The detection limit of the test strip was 0.209 ng/mL with good sensitivity. The method was used for detecting malathion in actual river water samples, and the recoveries were in the range of 93.53 %-96.87 %. The newly devised technique effectively identified malathion in samples of natural water. This research has introduced a novel approach for the precise and convenient surveillance of pesticide remnants. Additionally, these discoveries could inspire the advancement of proficient multi-enzyme detection systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: The surgical intervention approach to insulinomas in proximity to the main pancreatic duct remains controversial. Standard pancreatic resection is recommended by several guidelines; however, enucleation (EN) still attracts surgeons with less risk of late exocrine/endocrine insufficiency, despite a higher postoperative pancreatic fistula (POPF) rate. Recently, the efficacy and safety of preoperative pancreatic stent placement before the EN have been demonstrated. Thus, a multicentre open-label study is being conducted to evaluate the efficacy and safety of stent placement in improving the outcome of EN of insulinomas in proximity to the main pancreatic duct., Methods and Analysis: This is a prospective, randomised, open-label, superiority clinical trial conducted at multiple tertiary centres in China. The major eligibility criterion is the presence of insulinoma located in the head and neck of the pancreas in proximity (≤2 mm) to the main pancreatic duct. Blocked randomisation will be performed to allocate patients into the stent EN group and the direct EN group. Patients in the stent EN group will go through stent placement by the endoscopist within 24 hours before the EN surgery, whereas other patients will receive EN surgery directly. The primary outcome is the assessment of the superiority of stent placement in reducing POPF rate measured by the International Study Group of Pancreatic Surgery standard. Both interventions will be performed in an inpatient setting and regular follow-up will be performed. The primary outcome (POPF rate) will be tested for superiority with the Χ 2 test. The difference in secondary outcomes between the two groups will be analysed using appropriate tests., Ethics and Dissemination: The study has been approved by the Peking Union Medical College Hospital Institutional Review Board (K23C0195), Ruijin Hospital Ethics Committee (2023-314), Peking University First Hospital Ethics Committee (2024033-001), Institutional Review Board of Xuanwu Hospital of Capital Medical University (2023223-002), Ethics Committee of the First Affiliated Hospital of Xi'an Jiaotong University (XJTU1AF2023LSK-473), Institutional Review Board of Tongji Medical College Tongji Hospital (TJ-IRB202402059), Ethics Committee of Tongji Medical College Union Hospital (2023-0929) and Shanghai Cancer Center Institutional Review Board (2309282-16). The results of the study will be published in an international peer-reviewed journal., Trial Registration Number: NCT05523778., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess short-term and long-term outcomes following robotic enucleation (REn) of tumors in the proximal pancreas., Background: Despite the advantages of preserving function via pancreatic enucleation, controversies persist, since this can be associated with severe complications, such as clinically relevant postoperative pancreatic fistula, especially when performed near the main pancreatic duct. The safety and efficacy of REn in this context remain largely unknown., Methods: A retrospective analysis was performed of all patients who underwent REn for benign and low-grade malignant neoplasms in the pancreatic head and uncinate process between January 2005 and December 2021. Clinicopathologic, perioperative, and long-term outcomes were compared with a similar open enucleation (OEn) group., Results: Of 146 patients, 92 underwent REn with a zero conversion-to-open rate. REn was superior to OEn in terms of shorter operative time (90.0 minutes vs 120.0 minutes, P<0.001), decreased blood loss (20.0 mL vs 100.0 min, P=0.001), and lower clinically relevant postoperative pancreatic fistula rate (43.5% vs 61.1%, P=0.040). Bile leakage rate, major morbidity, 90-day mortality, and length of hospital stay were comparable between groups. No post-REn grade C POPF or grade IV/V complication was identified. Subgroup analyses for uncinate process tumors and proximity to the main pancreatic duct did not demonstrate inferior postoperative outcomes. In a median follow-up period of 50 months, REn outcomes were comparable to OEn regarding recurrence rate and pancreatic endocrine or exocrine function., Conclusions: REn for pancreatic head and uncinate process tumors improved clinically relevant outcomes without increased major complications compared to OEn, while demonstrating comparable long-term oncological and functional outcomes., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Although the molecular features of pancreatic ductal adenocarcinoma (PDAC) have been well described, the impact of detailed gene mutation subtypes on disease progression remained unclear. This study aimed to evaluate the impact of different TP53 mutation subtypes on clinical characteristics and outcomes of patients with PDAC., Methods: We included 639 patients treated with PDAC in Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine between Jan 2019 and Jun 2021. The genomic alterations of PDAC were analyzed, and the association of TP53 mutation subtypes and other core gene pathway alterations with patients' clinical characteristics were evaluated by Chi-squared test, Kaplan-Meier method and Cox regression model., Results: TP53 missense mutation was significantly associated with poor differentiation in KRAS mut PDAC (50.7% vs. 36.1%, P = 0.001). In small-sized (≤ 2 cm) KRAS mut tumors, significantly higher LNs involvement (54.8% vs. 23.5%, P = 0.010) and distal metastic rate (20.5% vs. 2.9%, P = 0.030) were observed in those with TP53 missense mutation instead of truncating mutation. Compared with TP53 truncating mutation, missense mutation was significantly associated with reduced DFS (6.6 [5.6-7.6] vs. 9.2 [5.2-13.3] months, HR 0.368 [0.200-0.677], P = 0.005) and OS (9.6 [8.0-11.1] vs. 18.3 [6.7-30.0] months, HR 0.457 [0.248-0.842], P = 0.012) in patients who failed to receive chemotherapy, while higher OS (24.2 [20.8-27.7] vs. 23.8 [19.0-28.5] months, HR 1.461 [1.005-2.124], P = 0.047) was observed in TP53 missense cases after chemotherapy., Conclusions: TP53 missense mutation was associated with poor tumor differentiation, and revealed gain-of-function properties in small-sized KRAS transformed PDAC. Nonetheless, it was not associated with insensitivity to chemotherapy, highlighting the neoadjuvant therapy before surgery as the potential optimized strategy for the treatment of a subset of patients., (© 2023. The Author(s).)

Aims: We aimed to investigate changes of fecal short chain fatty acids (SCFAs) and their association with metabolic benefits after sleeve gastrectomy (SG). Specifically, whether pre-surgery SCFAs modify surgical therapeutic effects was determined., Methods: 62 participants with measurements of fecal SCFAs and metabolic indices before and 1, 3, 6 months after SG were included. Changes of fecal SCFAs and their association with post-surgery metabolic benefits were calculated. Then, participants were stratified by medians of pre-surgery fecal SCFAs and modification effects of pre-surgery fecal SCFAs on surgical therapeutic effects were investigated, through calculating interaction of group by surgery., Results: Fecal SCFAs were markedly changed by SG. Changes of propionate and acetate were positively correlated with serum triglycerides and total cholesterol, respectively. Notably, high pre-surgery fecal hexanoate group showed a better effect of SG treatment on lowering body weight (P=0.01), BMI (P=0.041) and serum triglycerides (P=0.031), and low pre-surgery fecal butyrate had a better effect of SG on lowering ALT (P=0.003) and AST (P=0.019)., Conclusion: Fecal SCFAs were changed and correlated with lipid profiles improvement after SG. Pre-surgery fecal hexanoate and butyrate were potential modifiers impacting metabolic benefits of SG., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shen, Chen, Wang, Sun, Lin, Ni, Chen, Zhang, Jin, Ying, Zou, Wang, Ye, Yuan, Yin, Cao, Zhang, Gu, Wang, Ning, Wang, Zhao, Hong and Liu.)

Background: Patients with resected pancreatic adenocarcinoma (PAAD) often experience short-term relapse and dismal survival, suggesting an urgent need to develop predictive and/or prognostic biomarkers for these populations. Given the potential associations of the human leukocyte antigen class I ( HLA -I) genotype with oncogenic mutational profile and immunotherapy efficacy, we aimed to assess whether differential HLA -I genotype could predict the postoperative outcomes in resected PAAD patients., Materials and Methods: HLA -I ( A , B , and C ) genotyping and somatic variants of 608 Chinese PAAD patients were determined by targeted next-generation sequencing of matched blood cells and tumor tissues. HLA - A / B alleles were classified with the available definition of 12 supertypes. The Kaplan-Meier curves of disease-free survival (DFS) and multivariable Cox proportional-hazards regression analyses were performed to determine the survival difference in 226 selected patients with radical resection. Early-stage (I-II) patients constituted the majority (82%, 185/226) and some stage I-II individuals with high-quality tumor samples were analyzed by RNA-sequencing to examine immunophenotypes., Results: Patients with HLA-A02 + B62 + B44 - had significantly shorter DFS (median, 239 vs. 410 days; hazard ratio=1.65, P =0.0189) than patients without this genotype. Notably, stage I-II patients carrying HLA-A02 + B62 + B44 - had sharply shorter DFS than those without HLA-A02 + B62 + B44 - (median, 237 vs. 427 days; hazard ratio=1.85, P =0.007). Multivariate analysis revealed that HLA-A02 + B62 + B44 - was associated with significantly inferior DFS ( P =0.014) in stage I-II patients but not in stage III patients. Mechanistically, HLA-A02 + B62 + B44 - patients were associated with a high rate of KRAS G12D and TP53 mutations, lower HLA-A expression, and less inflamed T-cell infiltration., Conclusion: The current results suggest that a specific combination of germline HLA-A02/B62/B44 supertype, HLA-A02 + B62 + B44 - , was a potential predictor for DFS in early-stage PAAD patients after surgery., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Alzheimer's disease (AD) is the most common neurodegenerative disease leading to dementia in the elderly. Ubiquitin proteasome system (UPS) is critical for protein homeostasis, while the functional decline of UPS with age contributes to the pathogenesis of AD. Ubiquitin-conjugating enzyme E2O (UBE2O), an E2-E3 hybrid enzyme, is a major component of UPS. However, its role in AD pathogenesis has not been fully defined., Objective: We aimed to identify the age-associated expression of UBE2O and its role AD pathogenesis., Methods: Western blot analysis were used to assess expression of UBE2O in organs/tissues and cell lines. Immunofluorescence staining was performed to examine the cellular distribution of UBE2O. Neuronal death was determined by the activity of lactate dehydrogenase., Results: UBE2O is highly expressed in the cortex and hippocampus. It is predominantly expressed in neurons but not in glial cells. The peak expression of UBE2O is at postnatal day 17 and 14 in the cortex and hippocampus, respectively. Moreover its expression is gradually reduced with age. Importantly, UBE2O is significantly reduced in both cortex and hippocampus of AD mice. Consistently, overexpression of amyloid-β protein precursor (AβPP) with a pathogenic mutation (AβPPswe) for AD reduces the expression of UBE2O and promotes neuronal death, while increased expression of UBE2O rescues AβPPswe-induced neuronal death., Conclusion: Our study indicates that age-associated reduction of UBE2O may facilitates neuronal death in AD, while increasing UBE2O expression or activity may be a potential approach for AD treatment by inhibiting neuronal death.

Background: The pre-adjuvant chemotherapy (PAC) status of postoperative pancreatic ductal adenocarcinoma (PDAC) patients has not been studied and elaborated well previously., Method: The association of PAC variables and prognoses was explored using a multivariable Cox model, restricted cubic spline analysis, and correlation analysis. The main outcomes were overall survival (OS) and progression-free survival (PFS). The secondary outcome was chemotherapy completeness (CHC)., Results: A total of 401 eligible patients were enrolled in sequential surgery and chemotherapy. The chemotherapy regimen, PAC fasting blood glucose (FBG), and elevated fasting blood glucose (eFBG) status were associated with CHC (regimen types: p = 0.005, continuous FBG: p = 0.014, eFBG status: p = 0.012). Early administration of adjuvant chemotherapy (<34 days) was a risk factor for the limited OS and PFS (OS: aHR: 1.61 [1.09-2.38], p = 0.016; PFS: aHR: 1.91 [1.29-2.82], p = 0.001). Patients with higher PAC body mass index (BMI), receiving Gemcap regimen, and with lower PAC tumor marker value were observed with better survival prognoses (PAC BMI: OS: 0.927 [0.875-0.983], p = 0.011; Gemcap: OS: 0.533 [0.312-0.913], p = 0.022; Gemcap: PFS: 0.560 [0.341-0.922], p = 0.023; PAC CA125: OS: 1.004 [1.002-1.006], p < 0.001; PAC CA125: PFS: 1.003 [1.000-1.005], p = 0.031; PAC CEA: OS: 1.050 [1.026-1.074], p < 0.001). The BMI decrease was mainly concentrated in the first 3 months of chemotherapy courses (first 3 months: p < 0.001; latter 3 months: p = 0.097). And CEA, compared to CA125 and CA199, was a better prognostic indicator (CEA: first 3 months: PFS p = 0.011, OS p < 0.001; latter 3 months: PFS p = 0.024, OS p = 0.041)., Conclusion: PDAC patients should be treated with adjuvant chemotherapy over 34 postoperative days. PAC sarcopenia was a risk factor for OS, but not PFS and limited CHC. Those with higher PAC FBG levels were more likely to finish chemotherapy. CEA, compared to CA125 and CA199, was a better prognostic indicator., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: We aimed to develop a nomogram to predict the survival and prognosis of adenosquamous carcinoma of the pancreas (ASCP)., Background: Adenosquamous carcinoma of the pancreas (ASCP) is a relatively rare histological subtype of pancreatic exocrine neoplasms. It was reported a worse survival in ASCP than in pancreatic adenocarcinoma (PDAC). Prediction of ASCP prognosis is of great importance., Methods: Histologically confirmed ASCP patients from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program database were finally enrolled and divided into development and internal validation cohorts. Moreover, a multi-center cohort of 70 patients from China was registered as the external validation. A nomogram was developed based on independent predictors of ASCP determined in multivariable analysis., Results: A total of 233 patients from SEER were finally included. Univariate and Multivariate analysis showed that tumor size, radiotherapy, chemotherapy, and lymph node ratio (LNR) were considered the independent prognostic indicators. We developed a nomogram according to these four parameters. The C index of the nomogram in the development cohort was 0.696. Through analysis of the area under the curve (AUC) of the different cohorts, we observed that the predictive efficacy of the nomogram for 1-, and 2-year overall survival (OS) were better than those of the American Joint Committee on Cancer (AJCC) TNM (8 th ) staging system both in the development and validation cohort. External validation confirmed that 1-year survival is 67.2% vs. 29.7%, similar to the internal cohort analysis., Conclusion: The nomogram showed good performance in predicting the survival of ASCP. It could help surgeons to make clinical decisions and develop further plans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ren, Ma, Jin, Ding, Jiang, Wu, Li, Yang, Han, Ma, Wu, Shi and Wang.)

Background: Limited data are available regarding long-term oncological outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) who undergo robotic pancreatectomy (RP)., Method: All patients who underwent RP and open pancreatectomy (OP) for resectable PDAC between January 2011 and December 2019 were included. The RP group was matched 1:1 with OP group by propensity score matching (PSM). The oncological outcomes were collected and analyzed., Results: Overall, 1606 patients were included in this study. After PSM, a well-balanced cohort of 335 patients in each group was selected for further analysis. The RP group had shorter operative time (210 min vs. 240 min, P < 0.001), lower estimated blood loss (200 ml vs. 300 ml, P = 0.011), lower wound infection rates (4.5% vs. 10.1%, P = 0.005) and shorter length of postoperative hospital stay (15 days vs. 17 days, P = 0.001) compared to the OP group, with no significant differences in other perioperative outcomes. OS was comparable between the two groups (31 months vs. 28 months, P = 0.077); however, RFS was improved in the RP group (17 months vs. 14 months, P = 0.015). Subgroup analysis showed that patients who received adjuvant chemotherapy (AC) in the RP group had better RFS than the similar patient cohort in the OP group (17 months vs. 14 months, P = 0.024)., Conclusion: Robotic pancreatectomy is safe and oncologically effective for resectable PDAC. OS was comparable between RP and OP, and RFS was improved in the RP group, especially in patients who receive AC., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Venous resection and reconstruction (VR) is a feasible surgical technique to achieve optimal outcomes in selected patients with pancreatic ductal adenocarcinoma (PDAC) who undergo open pancreaticoduodenectomy (OPD). However, data regarding patient outcomes in patients who undergo VR in robotic-assisted pancreaticoduodenectomy (RPD) are scarce., Methods: All patients with a diagnosis of PDAC who underwent upfront open or robotic pancreatoduodenectomy with VR in a high-volume institution for pancreatic surgery between 2011 and 2019 were retrospectively reviewed. Perioperative and long-term outcomes were compared between the RPD and OPD cohorts., Results: A total of 84 patients were included in the final analysis, 14 patients underwent RPD with VR and 70 who had OPD with VR. Reconstructed venous patency, postoperative 30-day morbidity, and 90-day mortality were comparable; however, lymph node resection rates were lower in the RPC cohort (p = 0.029). No difference was identified in 3-year survival rates between the two groups (34.0% versus 25.7% respectively, p = 0.667)., Conclusion: RPD with VR is a feasible approach for patients with PDAC and venous invasion. Further studies are needed to assess long-term outcomes compared to the open approach., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Accurate diagnosis and grading are critical for pancreatic neuroendocrine neoplasm (pNEN) management. This study compares the diagnostic and grading value of 68 Ga-DOTATATE PET/MR and 18 F-FDG PET/MR for pNENs separately as well as in combination. A total of 36 patients with histologically confirmed pNENs, who underwent both 68 Ga-DOTATATE PET/MR and 18 F-FDG PET/MR within 2 weeks from 2020 to 2021, were retrospectively collected and analyzed. The maximum standardized uptake values of 68 Ga-DOTATATE (G-SUVmax) and 18 F-FDG (F-SUVmax) on PET and the minimum values of apparent diffusion coefficient (ADCmin) on MR were measured on the lesions with known histological grading (25 by surgery, 11 by biopsy). Receiver-operating characteristic analysis was applied to determine the cutoffs of these parameters or their combinations for differentiation between G1 and G2, as well as between low-grade and high-grade pNENs. The Spearman rank correlation coefficient was used to assess the correlation between the imaging parameters and the maximum tumor diameters. The detection rate of 68 Ga-DOTATATE PET imaging alone was 95%, 87.5%, and 37.5% for G1, G2, and G3, respectively. Adding 18 F-FDG PET or MR sequences of PET/MR increased the detection rate to 100% in all grades. Among the three parameters, G-SUVmax had the highest diagnostic rate in predicting tumor grade. It presented a sensitivity of 87.5% and a specificity of 80.0% with a cutoff value of 42.75 for differentiating G2 from G1 pNETs and a sensitivity and specificity of 100% and 71.4% with a cutoff value of 32.75 in predicting high-grade pNENs. The ratio of G-SUVmax to F-SUVmax (G-SUVmax/F-SUVmax) showed slight improvement in the diagnostic rate, while the product of G-SUVmax and ADCmin (G-SUVmax*ADCmin) did not improve the diagnostic rate. 68 Ga-DOTATATE PET/MR alone is sufficient for the diagnosis of pNENs and the prediction of various grades., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Zhao, Pan, Ju, Huang, Jiang, Jin and Zhang.)

Background: Pancreatoduodenectomy is a complex and challenging procedure that requires meticulous tissue dissection and proficient suturing skills. Minimally invasive surgery with the utilization of robotic platforms has demonstrated advantages in perioperative patient outcomes in retrospective studies. The development of robotic pancreatoduodenectomy (RPD) in specific has progressed significantly, since first reported in 2003, and high-volume centers in pancreatic surgery are reporting large patient series with improved pain management and reduced length of stay. However, prospective studies to assess objectively the feasibility and safety of RPD compared to open pancreatoduodenectomy (OPD) are currently lacking., Methods/design: The PORTAL trial is a multicenter randomized controlled, patient-blinded, parallel-group, phase III non-inferiority trial performed in seven high-volume centers for pancreatic and robotic surgery in China (> 20 RPD and > 100 OPD annually in each participating center). The trial is designed to enroll and randomly assign 244 patients with an indication for elective pancreatoduodenectomy for malignant periampullary and pancreatic lesions, as well as premalignant and symptomatic benign periampullary and pancreatic disease. The primary outcome is time to functional recovery postoperatively, measured in days. Secondary outcomes include postoperative morbidity and mortality, as well as perioperative costs. A sub-cohort of 128 patients with pancreatic adenocarcinoma (PDAC) will also be compared to assess the percentage of patients who undergo postoperative adjuvant chemotherapy within 8 weeks, in each arm. Secondary outcomes in this cohort will include patterns of disease recurrence, recurrence-free survival, and overall survival., Discussion: The PORTAL trial is designed to assess the feasibility and safety of RPD compared to OPD, in terms of functional recovery as described previously. Additionally, this trial will explore whether RPD allows increased access to postoperative adjuvant chemotherapy, in a sub-cohort of patients with PDAC., Trial Registration: ClinicalTrials.gov NCT04400357 . Registered on May 22, 2020., (© 2021. The Author(s).)

Background: Pancreatic adenocarcinoma (PAAD) is one of the most lethal carcinomas, and the current histopathological classifications are of limited use in clinical decision-making. There is an unmet need to identify new biomarkers for prognosis-informative molecular subtyping and ultimately for precision medicine., Methods: We profiled genomic alterations for 608 PAAD patients in a Chinese cohort, including somatic mutations, pathogenic germline variants and copy number variations (CNV). Using the CNV information, we performed unsupervised consensus clustering of these patients, differential CNV analysis and functional/pathway enrichment analysis. Cox regression was conducted for progression-free survival analysis, the elastic net algorithm used for prognostic model construction, and rank-based gene set enrichment analysis for exploring tumor microenvironments., Findings: Our data did not support prognostic value of point mutations in either highly mutated genes (such as KRAS, TP53, CDKN2A and SMAD4) or homologous recombination repair genes. Instead, associated with worse prognosis were amplified genes involved in DNA repair and receptor tyrosine kinase (RTK) related signalings. Motivated by this observation, we categorized patients into four molecular subtypes (namely repair-deficient, proliferation-active, repair-proficient and repair-enhanced) that differed in prognosis, and also constructed a prognostic model that can stratify patients with low or high risk of relapse. Finally, we analyzed publicly available datasets, not only reinforcing the prognostic value of our identified genes in DNA repair and RTK related signalings, but also identifying tumor microenvironment correlates with prognostic risks., Interpretation: Together with the evidence from genomic footprint analysis, we suggest that repair-deficient and proliferation-active subtypes are better suited for DNA damage therapies, while immunotherapy is highly recommended for repair-proficient and repair-enhanced subtypes. Our results represent a significant step in molecular subtyping, diagnosis and management for PAAD patients., Funding: This work was supported by the National Natural Science Foundation of China (grant numbers 81470894, 81502695, 81672325, 81871906, 82073326, 82103482 and 32170663), the Shanghai Sailing Program (grant number 20YF1426900), and the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning (awarded to H.F.)., Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: We aimed to describe our experience and the learning curve of 450 cases of robot-assisted pancreaticoduodenectomy (RPD) and optimize the surgical process so that our findings can be useful for surgeons starting to perform RPD., Summary Background Data: Robotic surgical systems were first introduced 20 years ago. Pancreaticoduodenectomy (PD) is a challenging surgery because of its technical difficulty. RPD may overcome some of these difficulties., Methods: The medical records of 450 patients who underwent RPD between May 2010 and December 2018 at the Shanghai Ruijin Hospital were retrospectively analyzed. Operative times and estimated blood loss (EBL) were analyzed and the learning curve was determined. A cumulative sum (CUSUM) analysis was used to identify the inflexion points. Other postoperative outcomes, postoperative complications, and long-term follow-up were also analyzed., Results: Operative time improved graduallyovertimefrom405.4 ± 112.9 minutes (case 1-50) to 273.6 ± 70 minutes (case 301-350) (P < 0.001). EBL improved from 410 ± 563.5 mL (case 1-50) to 149.0 ± 103.3 mL (case 351-400) (P< 0.001). According to the CUSUM curve, there were 3 phases in the RPD learning curve. The inflexion points were around cases 100 and 250. The incidence of pancreatic leak in the last 350 cases was significantly lower than that in the first 100 cases (30.0% vs 15.1%, P = 0.003)., Conclusions: RPD is safe and feasible for selected patients. Operative and oncologic outcomes were much improved after experience of 250 cases. Our optimization of the surgical process may have also contributed to this. Future prospective and randomized studies are needed to confirm our results., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Pancreatic cancer (PC) is one of the deadliest gastrointestinal cancers, accounting for the fourth highest number of cancer-related fatalities. Increasing data suggests that mesenchymal stem cells (MSCs) might influence the drug resistance of GC cells in the tumor microenvironment and play essential roles in drug resistance development. However, the precise underlying process remains a mystery. The purpose of this study was to look at the control of MSC-induced SNHG7 in pancreatic cancer. In vitro and in vivo sphere formation, colony formation, and flow cytometry investigations revealed the stemness and Folfirinox resistance in pancreatic cancer cells. To confirm the direct connections between SNHG7 and other related targets, RNA pulldown and immunoprecipitation tests were performed. MSC co-culture enhanced the stemness and Folfirinox resistance in pancreatic cancer cells according to the findings. MSC co-culture increased SNHG7 expression in pancreatic cancer cells, contributing to the stemness and Folfirinox resistance. We demonstrated that Notch1 interacted with SNHG7 and could reverse the facilitative effect of SNHG7 on the stemness and Folfirinox resistance in pancreatic cancer cells. Finally, our findings showed that MSCs increased SNHG7 expression in pancreatic cancer cells, promoting the stemness and Folfirinox resistance via the Notch1/Jagged1/Hes-1 signaling pathway. These findings could provide a novel approach and therapeutic target for pancreatic cancer patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cheng, Fan, Qin, Zhou, Yang, Ma, Shi and Jin.)

Background: Metabolic syndrome (MetS) is highly related to the excessive accumulation of visceral adipose tissue (VAT). Quantitative measurements of VAT are commonly applied in clinical practice for measurement of metabolic risks; however, it remains largely unknown whether the texture of VAT can evaluate visceral adiposity, stratify MetS and predict surgery-induced weight loss effects., Methods: 675 Chinese adult volunteers and 63 obese patients (with bariatric surgery) were enrolled. Texture features were extracted from VATs of the computed tomography (CT) scans and machine learning was applied to identify significant imaging biomarkers associated with metabolic-related traits., Findings: Combined with sex, ten VAT texture features achieved areas under the curve (AUCs) of 0.872, 0.888, 0.961, and 0.947 for predicting the prevalence of insulin resistance, MetS, central obesity, and visceral obesity, respectively. A novel imaging biomarker, RunEntropy, was identified to be significantly associated with major metabolic outcomes and a 3.5-year follow-up in 338 volunteers demonstrated its long-term effectiveness. More importantly, the preoperative imaging biomarkers yielded high AUCs and accuracies for estimation of surgery responses, including the percentage of excess weight loss (%EWL) (0.867 and 74.6%), postoperative BMI group (0.930 and 76.1%), postoperative insulin resistance (0.947 and 88.9%), and excess visceral fat loss (the proportion of visceral fat reduced over 50%; 0.928 and 84.1%)., Interpretation: This study shows that the texture features of VAT have significant clinical implications in evaluating metabolic disorders and predicting surgery-induced weight loss effects., Funding: The complete list of funders can be found in the Acknowledgement section., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Robotic-assisted minimally invasive surgery is associated with worse oncologic outcomes for some but not other types of cancers. We conducted a propensity score-matched analysis to compare oncologic outcomes of robotic-assisted laparoscopic (RPD) vs. open pancreatoduodenectomy (OPD) for pancreatic ductal adenocarcinoma (PDAC)., Methods: Treatment-naïve PDAC patients undergoing either RPD or OPD at our hospital between January 2013 and December 2017 were included. Propensity score matching was conducted at a ratio of 1:2. The primary outcome was disease-free survival (DFS) and overall survival (OS)., Results: A total of 672 cases were identified. The propensity score-matched cohort included 105 patients receiving RPD and 210 patients receiving OPD. The 2 groups did not differ in the number of retrieved lymph nodes [11 (7-16) vs. 11 (6-17), P = 0.622] and R0 resection rate (88.6% vs. 89.0%, P = 0.899). There was no statistically significant difference in median DFS (14 [95% CI 11-22] vs. 12 [95% CI 10-14] months (HR 0.94; 95% CI 0.87-1.50; log-rank P = 0.345) and median OS (27 [95% CI 22-35] vs. 20 [95% CI 18-24] months (HR 0.77; 95% CI 0.57-1.04; log-rank P = 0.087) between the two groups. Multivariate COX analysis showed that RPD was not an independent predictor of DFS (HR 0.90; 95% CI 0.68-1.19, P = 0.456) or OS (HR 0.77; 95% CI 0.57-1.05, P = 0.094)., Conclusion: Comparable DFS and OS were observed between patients receiving RPD and OPD. This preliminary finding requires further confirmation with prospective randomized controlled trials.

Objective: To compare the short-term and long-term outcomes between robot-assisted middle pancreatectomy (RMP) and robot-assisted distal pancreatectomy (RDP)., Methods: From August 2010 to May 2018, more than 800 patients were diagnosed with benign or low-grade malignant pancreatic tumours. According to the inclusion criteria, a total of 164 patients were included in our study. Among them 123 patients received RMP and 41 patients received RDP with spleen-preserving. These patients were divided into two groups, and propensity score matching (PSM) was used to minimize bias. Short-term and long-term outcomes were recorded and analysed., Results: After 1:1 matching, 38 cases of RMP and RDP were recorded and the baseline data was balanced. In the RMP group, 14 patients (36.8%) were female. In the RDP group, 13 patients (34.2%) were female. RDP had advantages in short-term outcomes including overall morbidity (28.9% vs. 60.5%, p = 0.011), Severe morbidity (0 vs. 10.5%, p = 0.017), clinical-relevant postoperative pancreatic fistula (CR-POPF) rate (10.5% vs. 36.8%, p = 0.007) and postoperative length of hospital stay (16.5 ± 8.6 days vs. 23.6 ± 12.9 days, p = 0.006). The operative time was similar; however, there were less estimated blood loss (EBL) in RMP group (31.3 ± 33.0 ml vs. 62.3 ± 38.2 ml, p<0.001). Patients in these two groups had a similar result in preservation of the pancreatic function. There was no statistic difference in incidence rate of exocrine and endocrine insufficiency between two groups (2.6% vs. 7.9%, p = 0.608; 5.3% vs. 10.5%, p = 0.671)., Conclusion: For benign or low-grade malignant tumours located at the neck of the pancreas, RMP and RDP could both be considered. The morbidity especially CR-POPF rate after RDP would be lower, but RMP would be more helpful in reducing EBL. RMP should be chosen with caution as it did not show a huge advantage in preserving normal pancreatic function. Further prospective randomised studies should be designed to compare these two types of surgery., (© 2020 John Wiley & Sons Ltd.)

Background: This study aimed to compare the short-term outcomes of open and robotic-assisted distal pancreatectomy (ODP and RDP) for benign and low-grade malignant tumors., Methods: The patients who underwent RDP and ODP for benign or low-grade malignant pancreatic tumors at our center were included. After PSM at a 1:1 ratio, the perioperative variations in the two cohorts were compared., Results: After 1:1 PSM, 219 cases of RDP and ODP were recorded. The RDP cohort showed advantages in the operative duration [120 (90-150) min vs 175 (130-210) min, P < 0.001], estimated blood loss [50 (30-175) ml vs 200 (100-300) ml, P < 0.001], spleen preservation rate (63.5% vs 26.5%, P < 0.001), infection rate (4.6% vs 12.3%, P = 0.006), and gastrointestinal function recovery [3 (2-4) vs. 3 (3-5), P = 0.019]. There were no significant differences in postoperative pancreatic fistula, postoperative hemorrhage, and delayed gastric emptying. Multivariate analysis showed that RDP (HR 0.24; 95% CI 0.16-0.36, P < 0.001), age (HR 1.02; 95% CI 1.00-1.03, P = 0.033), tumor size (HR 1.28; 95% CI 1.17-1.40, P < 0.001), pathological inflammatory neoplasm type (HR 5.12; 95% CI 2.22-11.81, P < 0.001), and estimated blood loss (HR 1.003; 95% CI 1.001-1.004, P < 0.001) were independent predictors of spleen preservation; RDP (HR 0.27; 95% CI 0.17-0.43, P < 0.001), age (HR 1.02; 95% CI 1.00-1.03, P = 0.022), elevated CA 19-9 level (HR 2.55; 95% CI 1.02-6.39, P = 0.046), tumor size (HR 1.44; 95% CI 1.29-1.61, P < 0.001), pathological inflammatory neoplasm type (HR 4.48; 95% CI 1.69-11.85, P = 0.003), and estimated blood loss (HR 1.003; 95% CI 1.001-1.004, P < 0.001) were independent predictors of spleen preservation with the Kimura technique., Conclusion: RDP has advantages in the operative time, blood loss, spleen preservation, infection rate, and gastrointestinal function recovery over ODP in treating benign and low-grade malignant pancreatic tumors. The robotic-assisted approach was an independent predictor of spleen preservation and use of the Kimura technique.

Obesity is an important risk factor for metabolic syndrome and obstructive sleep apnea (OSA). Bariatric surgery has been shown to effectively reduce weight and obesity-related comorbidities. However, the prevalence and severity of OSA in obese patients with different baseline metabolic states and the improvements of OSA after bariatric surgery remain unknown. The main aims of this study were to ascertain the prevalence of OSA in young Chinese obese patients with different metabolic states and to evaluate their respective OSA remission after laparoscopic sleeve gastrectomy. We first performed a cross-sectional study involving 123 metabolically healthy obese patients and 200 metabolically unhealthy obese patients (who had the same age and BMI ranges) to estimate the prevalence of OSA at baseline. Then we performed a retrospective study, which was registered at ClinicalTrials.gov (ref. NCT02653430) of 67 patients who underwent laparoscopic sleeve gastrectomy to evaluate the remission of OSA. Metabolically healthy and unhealthy obese patients had similar apnea-hypopnea index levels (16.6 ± 22.0 vs. 16.7 ± 18.7 events/h, P = 0.512) and prevalence of OSA (66.7% vs. 69.0%, P = 0.662). Male sex, age, waist circumference and lower liver-to-spleen ratio were independent risk factors for OSA. After laparoscopic sleeve gastrectomy, no difference was found in the decrease in body mass index (BMI) change (10.8 ± 4.8 vs. 10.8 ± 3.0 kg/m 2 , P = 0.996) or the decrease in the apnea-hypopnea index (18.9 ± 24.6 vs. 17.0 ± 24.0 events/h, P = 0.800). The remission of moderate-to-severe OSA was observed in the MHO (36.3%; 54.5-18.2%, P = 0.125) and MUO (32.2%; 66.1-33.9%, P = 0.001) patients. These results suggest that, in patients with obesity, metabolic syndrome does not add extra risk for the prevalence or severity of OSA. Both metabolically healthy and unhealthy obese patients could benefit equally from laparoscopic sleeve gastrectomy in terms of weight loss and obstructive sleep apnea remission., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Chen, Ye, Jin, Sun, Zhang, Zhao, Zhang, Wang, Gu and Hong.)

Objectives: There are few reports about the survival rate of patients with pancreatic adenosquamous cancer (PASC). This study evaluated and analyzed prognostic factors of patients with resectable pancreatic adenosquamous cancer (rPASC), which might fulfill the blank in the research of PASC., Methods: In this study, we identified and analyzed 55 patients who were diagnosed with rPASC from January 2013 to May 2019 at the Pancreatic Disease Center of the Shanghai Ruijin Hospital affiliated with Shanghai Jiaotong University School of Medicine. Age, sex, BMI, tumor position, and other important demographic data were collected and analyzed. The follow-up was updated by December 31th, 2019 with a median follow-up of nine months., Results: Among the 55 patients, 23 (41.8%) patients were female, and the mean age was 62.0 ± 10.3 years. The median overall survival (OS) time was 10 ± 2.1 months, and the median disease-free survival (DFS) time was 4 ± 0.9 months. The 1-year, 3-year, and 5-year survival rates were 40.9, 17.5, and 11.6%, respectively. The multivariate analysis showed that normal serum level of Ca199 (HR = 0.464, 95% CI = 0.222-0.970, P = 0.041) and Ca125 (HR = 0.441, 95% CI = 0.233-0.835, P = 0.012) were independent favorable prognostic factors., Conclusion: Patients with rPASC had poor survival. The 5-year survival rate was only 11.6%. Normal serum levels of Ca199 and Ca125 were independent favorable prognostic factors that predicted prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shi, Wang, Wu, Xie, Jin, Peng, Deng, Chen and Shen.)

Background: Total pancreatectomy (TP) is a complex surgical procedure with significant postoperative morbidity. Despite the narrowed range of indications for TP, the introduction of neoadjuvant chemotherapy and the increasing complexity of surgical resections performed in high-volume centers has increased the number of annually performed TPs, especially regarding malignant disease. The introduction of robotic-assisted pancreatic surgery has provided a novel and minimally invasive approach for TP, yet the feasibility of this technique is still unknown. This study assessed the safety and efficacy of robotic-assisted total pancreatectomy (RTP) compared to conventional open total pancreatectomy (OTP)., Methods: All patients who underwent TP between March 2015 and July 2019 in a high-volume institution for pancreatic surgery were included in this retrospective study. Clinical data and perioperative outcomes were derived from the prospectively maintained institutional database. A 1:1 propensity score matching (PSM) method was utilized to compare the RTP and OTP cohorts to minimize bias., Results: A standardized surgical protocol was utilized for RTP following a learning curve of RPD and RDP. The median operative time for patients who underwent RTP was significantly decreased compared to those who underwent OTP [300 (IQR, 250-360) vs. 360 min (IQR, 300-525), P=0.031]. Additionally, en bloc resection and spleen-preserving rates were also higher in the RTP cohort. Major 30-day morbidity (Clavien-Dindo > IIIa) and 90-day mortality were similar between the two cohorts. After a median follow-up time of 15 (IQR, 8-24) months, both the RTP and OTP cohorts had a comparable quality of life regarding exocrine and endocrine insufficiency., Conclusions: RTP appears to be safe and feasible when utilized in high-volume centers for the indicated management of benign and highly selected malignant pancreatic disease. However, further prospective randomized studies are needed to assess the feasibility of this approach., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/hbsn.2020.03.19). The authors have no conflicts of interest to declare., (2020 Hepatobiliary Surgery and Nutrition. All rights reserved.)

Objective: Pancreatic neuroendocrine tumors (pNETs) causing ectopic adrenal corticotropic hormone (ACTH) syndrome (EAS) are rare and aggressive with little known information. We aimed to elucidate the clinical features and molecular mechanisms of pNETs with EAS by methylation analysis., Methods: Seven patients with ectopic ACTH-secreting pNETs who were diagnosed at Shanghai Clinical Endocrine and Metabolic Diseases Center and Pancreatic Disease Center in Ruijin Hospital between 2001 and 2019 were enrolled. Twenty patients with ectopic ACTH-secreting thymic neuroendocrine tumors (TNETs) and 7 with nonfunctional pNETs (nf-pNETs) were also enrolled as controls. We collected clinical data and measured POMC promoter CpG methylation., Results: All 7 patients had elevated ACTH and urinary free cortisol (UFC) levels with positive ACTH staining in the pancreas and were diagnosed with ectopic ACTH-secreting pNET. Of the 7 patients, 6 underwent surgery and 1 underwent transarterial embolization (TAE). Two patients were free of disease after surgery; 2 died within 90 days after surgery; and 3 had metastases and died within 1 year. Compared with ACTH-secreting TNETs, ACTH-secreting pNETs had similar clinical and biochemical features but a significantly poorer prognosis. POMC promoter CpG methylation was significantly lower in ACTH-secreting pNETs than in nf-pNETs and normal pancreas., Conclusions: ACTH-secreting pNETs are aggressive and fatal. Surgery is definitively curative for patients with resectable primary tumors without metastasis. Pro-opiomelanocortin (POMC) promoter hypomethylation caused pNETs to produce ACTH. This study further supplements the genetic features of ACTH-secreting NETs., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Our study examined the association between molecular features and clinical results of pancreatic ductal adenocarcinoma (PDAC) patients, aiming to explore the genomic determinants of the recurrence and prognosis of PDAC after surgical removal., Methods: This retrospective study analyzed 181 PDAC patients who received pancreatectomy and adjuvant chemotherapy, with 67 patients in the training set. An internal validation set of 48 patients and an external validation set of 66 patients were used to validate the result. Comprehensive genomic profiling was performed on formalin-fixed paraffin-embedded (FFPE) tumor specimens to determine genomic features using the designed cancer-related gene panel based on next-generation sequencing (NGS)., Results: Significant differences were identified between the late recurrence (LR) group and early recurrence (ER) group in tumor copy number instability (CNI) levels. Next, the utility of low CNI (the middle and lowest tertile) with regard to predicting LR was confirmed in the training, internal, and external validation sets. Further univariate and multivariate analyses revealed that CNI was an independent predictive and prognostic biomarker, and had higher predictive accuracy for LR than CA19-9 level, pathological stage, tumor size, and age. In addition, CNI combined with lymph node (LN) metastasis status could provide a more accurate model for predicting LR of PDAC., Conclusion: We discovered and validated the association between CNI and clinical outcome in 181 patients with resectable PDAC, demonstrating the utility of lower tumor CNI levels as biomarkers of postoperative LR and favorable prognosis. Moreover, the combination of CNI and LN metastasis status elevated the predictive accuracy and illuminated strategies for patient stratification., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: Middle pancreatectomy (MP) is safe and feasible in patients with benign or low-grade malignant tumors located at the neck or proximal body of the pancreas. As a tissue-sparing operation, MP can preserve normal pancreatic function and reduce the risk of postoperative endocrine and exocrine insufficiency. However, the morbidity, especially the postoperative pancreatic fistula (POPF) rate, remains high. A robot-assisted surgical system may provide patients with less trauma; however, there are few reports on robot-assisted middle pancreatectomy (RMP). We describe the experience of RMP at our center to illustrate the learning curve (LC)., Methods: From August 2010 to July 2017, 100 patients underwent RMP in the Pancreatic Disease Center of Shanghai Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine. Patient characteristics, operative outcomes, and oncological outcomes were collected and analyzed. The CUSUM curve was analyzed according to operative time and estimated blood loss (EBL) and was used to describe the LC and identify the flexion points., Results: Among the 100 patients who underwent RMP in our hospital, the mean age was 47.5 ± 14.2 years, and 69 patients were female. From the CUSUM curve, we found two flexion points: cases 12 and 44. After 44 cases, the rate of improvement was much faster. We separated the patients into two groups based on the LC (cases 1-44 and cases 45-100). There were significant improvements in operative time (173.1 ± 44.7 min vs. 137.3 ± 30.1 min, p < 0.001) and EBL (103.4 ± 90.0 ml vs. 69.3 ± 53.9 ml, p = 0.021). The overall POPF rate was 32% (32/100), while the incidence rate of biochemical leakage was 14% (14/100). However, there was no significant difference in the risk of POPF or other complications between the two groups. The postoperative length of stay (LOS) was also not different. The 90-day mortality rate was 1%. From our long-term follow-up, pancreatic function was preserved in most patients, with only three cases of endocrine insufficiency and two cases of exocrine insufficiency., Conclusion: RMP was helpful and a good choice for the selected patients. PF was the main complication and has not been improved until now. There were two flexion points in the LC at cases 12 and 44. More cases are needed to gain more experience. A larger sample size and prospective studies are needed to verify the advantage of RMP.

Importance: Robot-assisted pancreaticoduodenectomy (RPD) has been reported to be safe and feasible. As a new technique, RPD has a learning curve similar to that of other types of minimally invasive pancreatic surgery such as laparoscopic pancreaticoduodenectomy. To our knowledge, no reports exist on the outcomes of open pancreaticoduodenectomy (OPD) and RPD after the learning curve., Objective: To analyze and evaluate the actual advantages of RPD., Design, Setting, and Participants: Between May 2010 and December 2018, 450 patients underwent RPD in the Shanghai Ruijin Hospital affiliated with Shanghai Jiaotong University in Shanghai, China, a high-volume pancreatic disease center. According to our previous study, an important flexion point in the learning curve is 250 cases. Data on the last 200 RPD cases were collected from January 2017 to December 2018. During that period, 634 patients underwent OPD. These patients were divided into 2 groups, and propensity score matching was used to minimize bias. The demographic data and operative outcomes were collected and analyzed. Analysis began May 2019., Exposures: Robot-assisted pancreaticoduodenectomy and OPD., Main Outcomes and Measures: The short-term operative outcomes of RPD and OPD., Results: After 1:1 matching, 187 cases of RPD and OPD were recorded. In the RPD group, 78 patients (41.7%) were women, and the mean (SD) age was 60.9 (11.4) years. In the OPD group, 80 patients (42.8%) were women, and the mean (SD) age was 60.1 (10.8) years. Robot-assisted pancreaticoduodenectomy had advantages in operative time (mean [SD], 279.7 [76.3] minutes vs 298.2 [78.3] minutes; P = .02), estimated blood loss (mean [SD], 297.3 [246.8] mL vs 415.2 [497.9] mL; P = .002), and postoperative length of hospital stay (mean [SD], 22.4 [16.7] days vs 26.1 [16.3] days; P = .03). However, there was no significant difference in the R0 resection rate and incidence rate of postoperative complications, such as postoperative pancreatic fistula, bile leak, and delayed gastric emptying. The incidence rates of postoperative bleeding and reoperation in the RPD group were similar to those in the OPD group, with no statistically significant difference., Conclusions and Relevance: After passing the learning curve, RPD had advantages in operative time and blood loss compared with OPD. There were no differences in postoperative complications such as postoperative pancreatic fistula, bile leak, and delayed gastric emptying. However, patients recovered more quickly after RPD than after OPD. A prospective randomized clinical trial is needed in the future to verify these results.

Background: The significance of surgical resection in the treatment of metastatic pancreatic ductal adenocarcinoma (PDAC) is currently unclear. This study aimed to summarize and clarify the experience of surgical treatment of M1 PDAC in our center and evaluate whether it may offer benefits to some metastatic PDAC patients., Methods: We analyzed the data of the patients with M1 PDAC who underwent synchronous tumor resection between 2003 and 2014 at Ruijin Hospital. Simultaneously, clinical data for M1 PDAC patients who underwent palliative bypass or exploratory laparotomy only was also collected during the same period as control. Every patient was followed up at least 3 years after hospitalization. The follow-up endpoint was December 31, 2017., Results: A total of 36 patients underwent synchronous tumor resection; of them, 7 received postoperative adjuvant chemotherapy. Their 1-, 2-, and 3-year survival rates were 27.3%, 21.2%, and 7.1%, respectively, and the overall survival was 7.9 months. The overall survival of the palliative bypass and exploratory laparotomy groups was only 4 and 3.7 months, respectively (P<0.05)., Conclusions: It is unclear whether synchronous tumor resection can benefit M1 PDAC patients due to tumor heterogeneity and differences in tumor burden. However, our current experience indicated that synchronous tumor resection can be safely performed and might be appropriate for some highly selected patients due to the relatively longer survival time. Combined (neo)adjuvant chemotherapy would further prolong overall survival in these patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jgo.2020.03.02). The authors have no conflicts of interest to declare., (2020 Journal of Gastrointestinal Oncology. All rights reserved.)

BACKGROUND Pancreatic cancer is a highly malignant tumor characterized by poor prognosis. TNM stage cannot always provide accurate prediction of prognosis, which is vital for individualized treatment. Therefore, a novel way to identify patients with poor prognosis after radical surgery is urgently needed. MATERIAL AND METHODS The nomogram was established based on a discovery cohort that included 554 patients with PDAC who had received radical surgery from 2012 to 2016. The clinicopathological data were collected. Poor prognosis was evaluated using 25 features, in which appropriate features for a prediction model were identified. A prediction model incorporating the selected features was established. The discriminative capacity was assessed by C-index, calibration by calibration plot, and clinical usefulness by decision curve. The bootstrapping approach was used to perform internal validation. RESULTS Characteristics included in the nomogram were coronary artery disease and stroke history, elevated CA125, AJCC stage >II, R0 resection, operating time >6 h, poor differentiation, nerve invasion, length of stay >30 days, and postoperative complications. A C-index of 0.713 indicated good discrimination of the prediction model, and the calibration curve showed acceptable calibration. Survival analysis showed that this model had better discriminative capacity than the AJCC staging system and could distinguish relatively good prognosis from poor prognosis in patients at stage II (especially IIa) and IV. CONCLUSIONS Our study presents a valid and practical model to predict prognosis of pancreatic cancer patients, which contributes to individualized therapy by assisting surgeons to predict poor prognosis in patients who received radical surgery.

Background: The aim of this study was to determine the feasibility, safety, and rate of postoperative complications after robot-assisted middle pancreatectomy compared with open middle pancreatectomy., Methods: This retrospective study was conducted in Shanghai Ruijin Hospital, China, involving 170 patients who underwent robot-assisted middle pancreatectomy or open middle pancreatectomy from December 2010 to December 2017. Patients were in 1 of 2 groups: robot-assisted middle pancreatectomy (n = 110) and open middle pancreatectomy (n = 60)., Results: Among the 110 patients who underwent robot-assisted middle pancreatectomy, age, operation time, blood loss, and tumor size were 47 ± 14 y, 162 ± 63 min, 88 ± 93 mL, and 2.4±1.3 cm (mean ± standard deviation), respectively. Among the 60 patients who underwent open middle pancreatectomy, age, operation time, blood loss, and tumor size were 53 ± 14 y, 208 ± 52 min, 195 ± 165 mL, and 2.5 ± 1.4 cm (mean ± standard deviation), respectively. Mean operation time and blood loss were less in the robot-assisted middle pancreatectomy group (P < .001 each). Overall morbidity rate in the robot-assisted middle pancreatectomy group was 51.8% and 40% in open middle pancreatectomy group (P = .140). Clinically relevant postoperative pancreatic fistulas developed in 38 (34.5%) patients in the robot-assisted middle pancreatectomy group and 13 (22%) in the open middle pancreatectomy group (P = .105). A total of 10 patients in the robot-assisted middle pancreatectomy group and 3 patients in the open middle pancreatectomy group required a reoperation or angiographic embolization because of postoperative bleeding. The mean hospital stay was similar in the 2 groups (25 ± 13 d versus and 24 ± 18 d). There was 1 postoperative death in each group because of postoperative bleeding and a pulmonary embolus, respectively. The tumors in this study included 65 serous cystic neoplasms, 6 mucinous cystic neoplasms, 35 intraductal papillary mucinous neoplasms, 29 pancreatic neuroendocrine tumors, 31 solid pseudopapillary tumors, 1 paraganglioma, and 3 pancreatic cysts., Conclusion: Middle pancreatectomy is a safe and effective robotic operative procedure, and when possible, robot-assisted middle pancratectomy might be the preferred method, because it was associated with decreased operative time and decreased blood loss. The lesser operation time might be attributed to different reconstruction methods that were chosen in the open and robotic approach. Pancreatic fistula remains the major complication., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Pancreatic surgeries are one of the most complex surgical procedures in general surgery that require highly experienced surgical technics and intensive postoperative care. Meanwhile the application of enhanced recovery after surgery (ERAS) program in pancreatic surgery is limited. The aim of this study was to attempt a new ERAS pathway specifically for patients after distal pancreatectomy (DP)., Methods: Between May 2016 and November 2016, 29 patients undergoing DP in Shanghai Ruijin Hospital pancreatic disease center received the ERAS pathway. Meanwhile 19 patients were implemented traditional care. Complications, readmissions, mortality, length of stay (LOS) and drainage-tube-off day were compared and evaluated in the two groups., Results: Median length of stay was significantly reduced (18.37±2.55 days in ERAS group; 27.42±7.60 days in the control group) and drainage-tube-off days (5.89±2.41 versus 26.68±7.35 days). And no patient discharged with a drainage tube in ERAS group compared while 7 patients (36.8%) discharged with drainage tube in the conventional group. Postoperative pancreatic fistula (POPF) rate was decreased in ERAS group but not significantly. Readmission rates, as well as mortality, did not change over time. 9 patients were found postoperative abdominal fluid collections in ERAS group, and only 2 patients were confirmed real pancreatic fistula., Conclusions: Implementing the new ERAS program for DP may contribute to a decrease of LOS and drainage-tube-off days with a promising outcome. Therefore, an ERAS pathway specifically for DP should be established., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr.2019.10.26). The authors have no conflicts of interest to declare., (2019 Translational Cancer Research. All rights reserved.)

Metastasis is a key component of cancer progression and is strongly associated with poor prognosis. Perineural invasion is thought to be related to pain, tumor recurrence, and other conditions. However, the exact molecular mechanism is unclear. This study was conducted to identify the key components and signaling pathways involved in the perineural invasion of pancreatic cancer and alterations in the phenotype after the interaction between the dorsal root ganglion (DRG) and pancreatic cancer cells. The results indicated that the p38 mitogen-activated protein kinase signaling pathway was activated after coculture of the DRG and pancreatic cancer cells and lead to the promotion of cell growth and chemoresistance., (© 2019 Wiley Periodicals, Inc.)

Purpose: This study aimed to determine the outcome of pancreatic metastatic renal cell carcinoma (PmRCC) after treatment and share the relevent results., Methods: In total, 13 patients with PmRCC were diagnosed and treated in our institution from December 2013 to October 2017. We retrospectively reviewed the records and analyzed the patient demographics, perioperative outcomes, and overall survival. Simultaneously, our experience including treatment and misdiagnosis was shared., Results: The median time between nephrectomy and reoperation for pancreatic recurrence was 11 years (range 1-20 years). Four patients had multiple tumors and nine patients had solitary tumor. Five patients accepted distal pancreatectomy, and five patients underwent pancreaticoduodenectomy. One patient underwent total pancreatectomy, one patient underwent duodenum-preserving pancreatic head resection plus distal pancreatectomy, and one patient underwent exploratory laparotomy and gastrointestinal bypass due to widespread metastasis with clear obstructive symptoms. The misdiagnosis rate of preoperative diagnosis at our center was 69.2% (9/13). The median follow-up duration was 26 months (range 7-53 months, until June 2018). By the end of follow-up, 12 patients were alive and one patient died of gastrointestinal bleeding within 1 month after surgery., Conclusions: PmRCCs are uncommon, but pancreatic metastasectomy has a relatively good prognosis and may, therefore, be a good therapeutic choice for patients with PmRCCs. Because PmRCC occurs long after the primary tumor resection, long-term follow-up is necessary. Besides, detailed medical history and specific manifestation in imaging features could contribute to avoiding misdiagnosis.

The peptide segment of prostatic acid phosphatase (PAP 248-286 ) aggregates to form SEVI (semen-derived enhancer of virus infection) amyloid fibrils. These are characteristic seminal amyloids that have the ability to promote the effect of HIV infection. In this paper, we explore the binding of sulfonated compounds with PAP 248-286 through an in silico study. Three derivatives of suramin, NF110, NF279, and NF340, are selected. All of these sulfonated molecules bind to PAP 248-286 and alter the conformation of the peptide, even though they have various structures, sizes, and configurations. The compounds bind with PAP 248-286 through multiple interactions, such as hydrogen-bonding interactions, hydrophobic interactions, π-π stacking interactions, and electrostatic interactions. However, NF110, which has an X-shaped configuration, has the highest binding affinity of the three derivatives investigated. We also perform surface plasmon resonance and a Congo red assay to validate the results. The interactions between PAP 248-286 and the sulfonated compounds are proposed to depend on the orientations of the sulfonate groups and the specific configurations of the compounds instead of the number of sulfonate groups. NF110 molecules occupy the exposed binding sites of PAP 248-286 , blocking interactions between the peptides. Therefore, these compounds are important in inhibiting the aggregation of PAP 248-286 . Herein, we provide useful information to develop new efficient microbicides to antagonize seminal amyloid fibrils and to block HIV transmission.

BACKGROUND Robotic assisted pancreaticoduodenectomy (RPD) is reported to be safe and feasible. Internal hernia (IH) after RPD is a serious but rarely reported complication. MATERIAL AND METHODS We retrospectively reviewed data of 231 patients who underwent RPD from October 2010 to December 2016. The incidence, symptoms, time of presentation, and outcome were investigated. RESULTS Five patients (2.6%) were diagnosed with IH. Significant correlation (P<0.001) between IH and transverse mesocolon defect was confirmed. In patients without defect closure, the incidence of IH was 62.5%, while patients who received defect closure experienced no IH. The median time between initial surgery and occurrence of IH was 76 days. The main symptoms were abdominal pain, nausea, and vomiting. All patients received abdominal computed tomography (CT) and were suspected to have IH according to imaging and symptoms. All patients underwent reoperation (2 laparoscopic and 3 open surgery). The median length of hospital stay was 13 days. No patient experienced a relapse after treatment. CONCLUSIONS Abdominal pain, nausea, and vomiting were common symptoms in our study patients who underwent RPD. IH should be suspected if there is a positive finding on CT. Timely reoperation is necaAbdominal pain, nausea, and vomiting were common symptoms in our study patients who underwent RPD. IH should be suspected if there is a positive finding on CT. Timely reoperation is necessary because IH may cause intestinal ischemia. Meticulous closure of the mesenteric defect is vital to avoid IH.essary because IH may cause intestinal ischemia. Meticulous closure of the mesenteric defect is vital to avoid IH.

Background: IRX3 was recently reported as the effector of the FTO variants. We aimed to test IRX3's roles in the browning program and to evaluate the association between the genetic variants in IRX3 and human obesity., Methods: IRX3 expression was examined in beige adipocytes in human and mouse models, and further validated in induced beige adipocytes. The browning capacity of primary preadipocytes was assessed with IRX3 knockdown. Luciferase reporter analysis and ChIP assay were applied to investigate IRX3's effects on UCP1 transcriptional activity. Moreover, genetic analysis of IRX3 was performed in 861 young obese subjects and 916 controls., Results: IRX3 expression was induced in the browning process and was positively correlated with the browning markers. IRX3 knockdown remarkably inhibited UCP1 expression in induced mouse and human beige adipocytes, and also repressed the uncoupled oxygen consumption rate. Further, IRX3 directly bound to UCP1 promoter and increased its transcriptional activity. Moreover, 17 rare heterozygous missense/frameshift IRX3 variants were identified, with a significant enrichment in obese subjects (P=0.038, OR=2.27; 95% CI, 1.02-5.05)., Conclusions: IRX3 deficiency repressed the browning program of white adipocytes partially by regulating UCP1 transcriptional activity. Rare variants of IRX3 were associated with human obesity., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

CCL17 is well known for its ability to engage CCR4 + CD8 + T cells, which have been shown to play a critical role in preventing tumorigenesis. In this study, we attempted to inhibit in vivo pancreatic tumorigenesis by engaging murine CCR4 + CD8 + T cells through a drug-eluting scaffold with a payload of CCL17. The drug-eluting scaffold was fabricated by electrospinning polyglyconate and porcine gelatin. The electrospun scaffold featured randomly distributed non-woven fibers with diameters ranging from 1μm to 4μm. The in vitro study confirmed that scaffolding materials were non-cytotoxic to pancreatic cancer cells. The in vivo study showed an increased presence of murine CCR4 + CD8 + T cells into the tumor mass treated with drug-eluting scaffold compared to those with non-eluting scaffold or the control groups. The weights of tumor masses were 132.04mg±12.25mg in the control group, 158.12mg±18.98mg in the NES group and 96.22mg±14.56mg in the DES group, respectively. The volumes of tumor masses were 1035.21mm 3 ±128.97mm 3 in the control group, 978.56mm 3 ±110.19mm 3 in the NES group and 634.35mm 3 ±87.12mm 3 in the DES group, respectively. Further study showed that the increased presence of CCR4 + CD8 + T cells also inhibited the hepatic metastasis of pancreatic cancer cells. Our study shed a new light on the post-operative treatment of pancreatic cancer to prevent the recurrence., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Emerging evidence has linked the gut microbiome to human obesity. We performed a metagenome-wide association study and serum metabolomics profiling in a cohort of lean and obese, young, Chinese individuals. We identified obesity-associated gut microbial species linked to changes in circulating metabolites. The abundance of Bacteroides thetaiotaomicron, a glutamate-fermenting commensal, was markedly decreased in obese individuals and was inversely correlated with serum glutamate concentration. Consistently, gavage with B. thetaiotaomicron reduced plasma glutamate concentration and alleviated diet-induced body-weight gain and adiposity in mice. Furthermore, weight-loss intervention by bariatric surgery partially reversed obesity-associated microbial and metabolic alterations in obese individuals, including the decreased abundance of B. thetaiotaomicron and the elevated serum glutamate concentration. Our findings identify previously unknown links between intestinal microbiota alterations, circulating amino acids and obesity, suggesting that it may be possible to intervene in obesity by targeting the gut microbiota.

Bioaccumulation and trophic transfer in ecosystems is an important criterion for assessing environmental risks of contaminants. This study investigated bioaccumulation and biomagnification of 13 organic ultraviolet absorbents (UVAs) in marine wildlife organisms in the Pearl River Estuary, South China Sea. The UVAs could accumulate in the organisms with biota - sediment accumulation factors (BSAF) of 0.003-2.152. UV531 was the most abundant and showed the highest tendency to accumulate in the organisms with a median BSAF of 1.105. The UVAs demonstrated species - and compound-specific accumulation in the marine organism. Fishes showed significantly higher capability than the cephalopods and crustaceans in accumulation of the UVAs. Habitat did not demonstrate obvious impact on accumulation of the UVA. On the other hand, benzophenone-3, UV328, and UV234 showed significantly higher concentration in the detritus feeding fishes than carnivorous and planktivorous fishes, suggesting governing effect of dietary habits of the organisms on bioaccumulation of these UVAs. Direct uptake from growth media was a significant exposure pathway of the organisms to the UVAs. The estimated trophic magnification factors and biomagnification factors revealed that UV329, UV531, and octocrylene could potentially biomagnify in the marine food web., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The most effective and radical treatment for pancreatic neuroendocrine tumors (PNETs) is surgical resection. Minimally invasive surgery has been increasingly used in pancreatectomy. Initial results in robotic distal pancreatectomy (RDP) have been encouraging. Nonetheless, data comparing outcomes of RDP with those of laparoscopic distal pancreatectomy (LDP) in treating PNETs are rare. The aim of this study was to compare the safety and efficacy of RDP and LDP for PNETs., Methods: From September 2010 to January 2017, operative parameters and perioperative outcomes in an initial experience with 43 consecutive patients undergoing RDP were collected and compared with those in 31 patients undergoing LDP., Results: Patients undergoing RDP and LDP demonstrated equivalent age, sex, ASA score, tumor location and tumor size. Operating time, length of resected pancreas, postoperative length of hospital stay and rates of conversion to open, pancreatic fistula, transfusion and reoperation were not statistically different. Patients in the RDP group were associated with significantly higher overall (79.1 vs. 48.4 %, P = 0.006) and Kimura spleen preservation rates (72.1 vs. 16.1%, P < 0.001) and had reduced risk of excessive blood loss (50 vs. 200mL, P < 0.001). Oncological outcomes in this series were superior for the RDP group with more lymph node harvest for G2 and G3 PNETs (3.5 vs. 2, P = 0.034)., Conclusions: Both RDP and LDP are efficacious and safe methods in treating PNETs located in the body or tail of pancreas. Robotic approach offers advantages with less intraoperative blood loss, higher spleen preservation rate and more lymph node harvest. It may be sensible to choose RDP for patients who fit indications for scheduled spleen preservation.

A variety of personal care products have been classified as emerging contaminants (ECs). Occurrence, fate, spatial and vertical profiles of 13 ultraviolet absorbents, triclocarban (TCC) and its dechlorinated products, triclosan (TCS), 2-phenylphenol and parabens were investigated in riverine and estuarine sediment of the Pearl River catchment, China. Bisphenol A (BPA), a widely applied plasticizer, was also investigated. The ECs were widely present in the bed sediment. TCC was the most abundant with a maximum concentration of 332ngg -1 dry weight. The other prominent ECs included BPA, TCS, octocrylene, and benzotriazole UV stabilizers UV326 and UV328. Treated wastewater effluent was the major source of the ECs in the riverine sediment. TCC, BPA, TCS, methyparaben, UV531, UV326, and UV328 were also detected throughout the estuarine sediment cores, indicating their persistence in the sediment. Temporal trends of the ECs in the sediment cores reflected a combined effect of industrial development, population growth, human life quality improvement, and waste treatment capacity in the Pearl River Delta over the last decades. TCC dechlorination products were frequently detected in the bed sediment with higher levels near treated effluent outlets but only occasionally observed in the sediment cores, suggesting insignificant in-situ TCC dechlorination in the sediment., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: As a tissue-sparing procedure, pancreatic enucleation has become an alternative for benign or borderline pancreatic tumours; it has been proved to be safe and feasible. To date, a large sample size of robotic pancreatic enucleation has not been reported. This study aimed to discuss the clinical evaluation and postoperative complications after robotic pancreatic enucleation and compare it with open surgery., Methods: Patients who underwent robotic or open pancreatic enucleation during December 2010-December 2014 at Shanghai Ruijin Hospital, affiliated with the Shanghai Jiaotong University School of Medicine in China, were included. Clinical data were collected and analysed., Results: Patients were divided into an open group and a robotic group: 26 patients underwent robotic pancreatic enucleation, of whom 13 patients were female. The mean age was 51.7 years, the operation time was 125.7 ± 58.8 min, blood loss was 49.4 ± 33.4 ml and mean tumour size was 18.8 ± 7.9 mm; 17 patients underwent open pancreatic enucleation, of whom 11 were female. The mean age was 54.6 ± 17.2 min, blood loss was 198.5 ± 70.7 ml and mean tumour size was 3.5 ± 1.9 cm. Pathology included insulinomas, intrapancreatic mucinous neoplasmas (IPMNs), pancreatic neuro-endocrine tumours (PNETs), solid pseudopapillary tumours (SPTs) and serous cystadenomas (SCAs). Robotic pancreatic enucleations were associated with less trauma, shorter operation time, less blood loss and faster wound recovery compared with open pancreatic enucleation. Pancreatic fistulas (PFs) were the main complication that occurred in the robotic group; infection also occurred in the open group. All patients recovered after effective drainage and the use of somatostatin. The mean follow-up time was 25 months. No recurrence was discovered, and one patient in the open group suffered endocrine insufficiency., Conclusion: Robotic pancreatic enucleation is a safe and effective surgical procedure for pancreatic benign and borderline tumours. It produces less trauma than open pancreatic enucleation and might extend the indications for enucleation. The PF rate after surgery is still high and a long-term follow-up needs to be performed. Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)

Metabolite identification is crucial for revealing metabolic pathways and comprehensive potential toxicities of polycyclic aromatic hydrocarbons (PAHs) in human body. In this work, a quasi-targeted analysis strategy was proposed for metabolite identification of monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) in human urine using liquid chromatography triple quadruple mass spectrometry (LC-QqQ-MS/MS) combined with liquid chromatography high resolution mass spectrometry (LC-HRMS). Potential metabolites of OH-PAHs were preliminarily screened out by LC-QqQ-MS/MS in association with filtering in a self-constructed information list of possible metabolites, followed by further identification and confirmation with LC-HRMS. The developed method can provide more reliable and systematic results compared with traditional untargeted analysis using LC-HRMS. In addition, data processing for LC-HRMS analysis were greatly simplified. This quasi-targeted analysis method was successfully applied to identifying phase I and phase II metabolites of OH-PAHs in human urine. Five metabolites of hydroxynaphthalene, seven of hydroxyfluorene, four of hydroxyphenanthrene, and three of hydroxypyrene were tentatively identified. Metabolic pathways of PAHs in human body were putatively revealed based on the identified metabolites. The experimental results will be valuable for investigating the metabolic processes of PAHs in human body, and the quasi-targeted analysis strategy can be expanded to the metabolite identification and profiling of other compounds in vivo., (Copyright © 2016 Elsevier B.V. All rights reserved.)

BACKGROUND Postoperative pancreatic fistulas (POPFs) due to anastomotic leaks are always closely related to significant morbidity and mortality following pancreaticoduodenectomy (PD). A series of modified anastomotic methods have been proposed. The object of our study was to provide a novel anastomotic method for operations involving the Child technique, termed the "whole-layer tightly appressed anastomosis technique". MATERIAL AND METHODS An improved pancreatic whole-layer suture technique was used when we performed the duct-to-mucosa pancreaticojejunostomies; this method ensured the tight joining of the pancreatic stump and jejunum and decreased the pinholes in the pancreatic stump. This new method was used in 41 patients, and was compared with the traditional duct-to-mucosa anastomosis technique that was used in 50 patients as controls. RESULTS The POPF rate was much lower in the new method group than in the control group (6, 14.63% and 20, 40.00%, respectively, P=0.010). There were 5 grade A POPF patients and 1 grade B POPF patient in the study group. In the control group there were 12 grade A POPFs patients, 7 grade B POPFs patients, and 1 grade C POPF patient. The study group exhibited a lower morbidity rate (7, 17.07% vs. 16, 32.00%, P=0.022) and a reduced hospital stay (17.16 d vs. 22.92 d, P=0.001). CONCLUSIONS The whole-layer tightly appressed anastomosis technique presented in our study is a safer anastomotic method than the traditional duct-to-mucosa pancreaticojejunostomy technique. This new technique effectively reduced the incidence of POPF after PD and decreased the postoperative morbidity.

Background: To explore the effectiveness, safety, and efficacy of the robot-assisted surgery in the radical resection of pancreatic ductal adenocarcinoma (PDAC)., Methods: The clinical data of 72 patients with PDAC who underwent radical resection using the da Vinci Surgical System from April 2010 to December 2014 were retrospectively analyzed., Results: Among these 72 patients, three were converted to conventional laparotomy due to the vascular invasion or due to the difficulties in tissue isolation from the surrounding organs. Among 39 patients who underwent the pancreatoduodenectomy, the average operative time was 395.3±118.8 min, and the mean intra-operative blood loss was 447.3±269.9 mL. Among 31 patients who underwent the distal pancreatectomy (DP), the average operative time was 185.5±74.1 min, and the mean intra-operative blood loss was 267.1±305.3 mL. In two patients who received the middle pancreatectomy (MP), the average operative time was 225 min and mean intra-operative blood loss was 100 mL. Among all the 72 patients, an average of 4.2±2.6 lymph nodes were dissected, with an average hospital stay of 22.6±10.7 days. Complications were observed in 18 patients, which included pancreatic fistula (n=11), bile leak (n=5), anastomotic bleeding (n=2), pancreatic fistula complicated with portal vein thrombosis (n=1), and anastomotic bleeding complicated with acute renal failure (n=1). Except that one patient died due to post-operative bleeding and acute renal failure, all the other patients were cured after conservative treatment. These 72 patients were followed for 1-45 (15.6±5.8) months, during which 10 patients died. Eleven patients suffered from recurrence or metastasis, among which 6 had local recurrence, 4 had liver metastasis, and 1 had ascites accompnaied with incision site tumor metastasis., Conclusions: Radical resection of PDAC by robotic surgical system is safe and feasible. It has less surgical trauma and enables faster post-operative recovery, and therefore can achieve the lymph node dissection scope and tumor resection margin required by the standards of radical resection for pancreatic cancer. Nevertheless, its long-term efficacy requires further validation.

Rationale: Ultra-high-performance liquid chromatography coupled with electrospray ionization mass spectrometry (UPLC/ESI-MS) has been frequently used for chemical analysis. A redox reaction in the ESI source has been observed during the ionization process. However, it is still unclear whether this redox reaction can take place on UPLC columns., Methods: In this study, the oxidation reactions potentially occurring on UPLC columns were investigated using polyphenols including baicalin, baicalein, propyl gallate (PG), quercetin-3-rhamnoside (QR), rutin, naringin and 2,3,5,4'-tetrahydroxystilbene-2-Ο-β-D-glucoside (THS-G) as model compounds. The on-column oxidation reaction was ascertained by post-column infusion of antioxidants such as ammonium sulfide ((NH4)2S). The oxidized products were reduced to their parent forms in the ESI source. This on-column oxidation reaction was further confirmed by means of post-column infusion of baicalin solution., Results: On-column oxidation reactions were observed and confirmed for baicalin, baicalein, PG, rutin, and QR. The exact reaction site was located at the outlet frits of the UPLC columns. (NH4)2S was proved to be the most suitable reducing agent among the tested antioxidants for eliminating negative effects caused by on-column oxidation reaction. It was subsequently proposed to be an efficient additive to suppress oxidation reactions in the ESI source., Conclusions: Oxidation reactions can take place at the outlet frits of UPLC columns. Ascertaining on-column oxidation reactions and consequently eliminating relevant negative effects are of great interest for determination of oxidation-sensitive compounds such as polyphenols., (Copyright © 2015 John Wiley & Sons, Ltd.)