Safety and effectiveness of minimally invasive central pancreatectomy versus open central pancreatectomy: a systematic review and meta-analysis.

BACKGROUND: Central pancreatectomy is a surgical procedure for benign and low-grade malignant tumors which located in the neck and proximal body of the pancreas that facilitates the preservation of pancreatic endocrine and exocrine functions but has a high morbidity rate, especially postoperative pancreatic fistula (POPF). The aim of this systematic review and meta-analysis was to evaluate the safety and effectiveness between minimally invasive central pancreatectomy (MICP) and open central pancreatectomy (OCP) basing on perioperative outcomes. METHODS: An extensive literature search to compare MICP and OCP was conducted from October 2003 to October 2023 on PubMed, Medline, Embase, Web of Science, and the Cochrane Library. Fixed-effect models or random effects were selected based on heterogeneity, and pooled odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals (CIs) were calculated. RESULTS: A total of 10 studies with a total of 510 patients were included. There was no significant difference in POPF between MICP and OCP (OR = 0.95; 95% CI [0.64, 1.43]; P = 0.82), whereas intraoperative blood loss (MD = - 125.13; 95% CI [- 194.77, -55.49]; P < 0.001) and length of hospital stay (MD = - 2.86; 95% CI [- 5.00, - 0.72]; P = 0.009) were in favor of MICP compared to OCP, and there was a strong trend toward a lower intraoperative transfusion rate in MICP than in OCP (MD = 0.34; 95% CI [0.11, 1.00]; P = 0.05). There was no significant difference in other outcomes between the two groups. CONCLUSION: MICP was as safe and effective as OCP and had less intraoperative blood loss and a shorter length of hospital stay. However, further studies are needed to confirm the results.

Ballistic analysis of high-performance armor steel by numerical simulation.

In order to establish a connection between the ballistic performance and mechanical properties of armor steel, a ballistic simulation model was developed and subsequently validated for accuracy and reliability. The mechanical properties of the target plate were described using the Johnson-Cook constitutive relation. An analysis was conducted to investigate the impact of the J-C parameters of the target plate on its ballistic performance, revealing a strong linear relationship between them. Subsequently, a mathematical model represented as H = 14.82 - 0.0048A - 0.0023B + 5.95n - 81.3C was derived, and its accuracy was demonstrated to exceed 90%. This mathematical model can effectively predict the ballistic performance of the armor steel, even when its mechanical properties undergo variations during the production process. This prediction capability significantly contributes to reducing research costs and time.

A wafer scale thin film of ultra-small Sc2O3 nanocrystals on a 2D COF with high rigidity.

Scandium oxide (Sc2O3) has a wide range of applications in metallurgy, chemical industry, electronics and many other high-tech fields. However, most Sc2O3 materials exist in the powder or bulk form, while nanostructured Sc2O3 has rarely been reported as there is a lack of a common method to control its dimensionality, hindering the understanding of new properties and potential applications of nano-Sc2O3 materials. In this paper, we establish a procedure to synthesize a two-dimensional (2D) Sc2O3-covalent organic framework (COF) composite film where the crystal size of Sc2O3 domains is as small as ∼3 nm. The composite film is prepared by a Schiff base condensation reaction at the sharp n-pentane/water interface using a combination of surfactant-monolayer-assisted interfacial synthesis and laminar assembly polymerization methods. Then the conditions of nucleation and uniform film formation of the 2D Sc2O3/COF are explored further. Meanwhile, an atomic force microscopy indentation test shows that the material has a high Young's modulus of 89.1 ± 3.8 GPa, which is much higher than those of the majority of reported 2D polymer materials. We further extended this synthesis method to the preparation of Yb2O3 (ytterbium oxide) and/or Er2O3 (erbium oxide)-incorporated 2D COF composite films, verifying the universality of this strategy. This work provides an opportunity to vary the dimensionality of many kinds of metal oxides and explore the potential applications of low-dimensional Sc2O3 materials.

Preoperative risk factors and cumulative incidence of temporary ileostomy non-closure after sphincter-preserving surgery for rectal cancer: a meta-analysis.

BACKGROUND: Temporary ileostomy (TI) has proven effective in reducing the severity of anastomotic leakage after rectal cancer surgery; however, some ileostomies fail to reverse over time, leading to conversion into a permanent stoma (PS). In this study, we aimed to investigate the preoperative risk factors and cumulative incidence of TI non-closure after sphincter-preserving surgery for rectal cancer. MATERIALS AND METHODS: We conducted a meta-analysis after searching the Embase, Web of Science, PubMed, and MEDLINE databases from their inception until November 2023. We collected all published studies on the risk factors related to TI non-closure after sphincter-preserving surgery for rectal cancer. RESULTS: A total of 1610 studies were retrieved, and 13 studies were included for meta-analysis, comprising 3026 patients. The results of the meta-analysis showed that the identified risk factors included older age (p = 0.03), especially > 65 years of age (p = 0.03), male sex (p = 0.009), American Society of Anesthesiologists score ≥ 3 (p = 0.004), comorbidity (p = 0.001), and distant metastasis (p < 0.001). Body mass index, preoperative hemoglobin, preoperative albumin, preoperative carcinoma embryonic antigen, tumor location, neoadjuvant chemoradiotherapy, smoking, history of abdominal surgery, and open surgery did not significantly change the risk of TI non-closure. CONCLUSION: We identified five preoperative risk factors for TI non-closure after sphincter-preserving surgery for rectal cancer. This information enables surgeons to identify high-risk groups before surgery, inform patients about the possibility of PS in advance, and consider performing protective colostomy or Hartmann surgery.

Clinical Outcomes of Ileostomy Closure during versus after Adjuvant Chemotherapy in Patients with Rectal Cancer.

Background: Protective ileostomy can effectively prevent severe anastomotic leakage after rectal cancer surgery; however, the optimal timing for ileostomy closure during adjuvant chemotherapy remains unclear. This study aimed to explore the safety and long-term outcomes of early ileostomy closure during adjuvant chemotherapy. Method: Patients who underwent laparoscopic rectal cancer surgery combined with protective ileostomy and adjuvant chemotherapy between April 2017 and April 2021 were retrospectively evaluated. Patients were divided into an early closure group during chemotherapy (group A) and a late closure group after chemotherapy (group B). Results: A total of 215 patients were included in this study, with 115 in group A and 100 in group B. There were no significant differences in demographic and clinical characteristics between the two groups. In group A, durations of stoma status (p < 0.001) and low anterior resection syndrome (LARS) (p < 0.001) were shorter, and rectal stenosis (p=0.036) and stoma-related complications (p=0.007), especially stoma stenosis (p=0.041), were less common. However, compliance with chemotherapy was worse (p=0.009). There were no significant differences in operative time, postoperative hospital stay, postoperative complications, incidence and severity of LARS, disease-free survival, or overall survival between groups. Conclusion: Early ileostomy closure can effectively reduce the duration of stoma status, duration of LARS, rectal stenosis, and stoma-related complications while not affecting surgical complications and oncological outcomes. Ileostomy closure should not be delayed because of adjuvant chemotherapy. However, follow-up should be strengthened to increase compliance and integrity with chemotherapy.

Effectiveness and safety of self-pulling and latter transection reconstruction in totally laparoscopic right hemicolectomy.

Background: Laparoscopic right hemicolectomy is a standard treatment modality for right colon cancer. However, performing intracorporeal anastomosis (IA) for totally laparoscopic right hemicolectomy (TLRH) remains a challenge for some surgeons. To simplify IA in TLRH we used self-pulling and latter transection (SPLT) reconstruction in TLRH, and compared this procedure with overlap IA and laparoscopy-assisted right hemicolectomy (LARH) in order to evaluate its safety and effectiveness. Methods: Patients with right colon cancer who underwent SPLT-TLRH, TLRH with overlap IA or LARH between July 2019 and June 2023 were evaluated retrospectively. Basic information, oncological features, perioperative outcomes, and postoperative complications were compared between groups. Results: In total, 188 patients with right colon cancer that underwent SPLT-TLRH (n = 60), TLRH(n=21) or LARH (n = 107) were included in the study. No patient required conversion to open surgery. The operation time in SPLT-TLRH group was significantly shorter than that in TLRH group (P<0.05). Compared with LARH group, SPLT-TLRH group had significantly longer distal margins, shorter skin incisions (P < 0.001), time to first flatus, time to first defecation, and postoperative hospital stays (P<0.05). Conclusion: We introduced SPLT to TLRH. The SPLT-TLRH group demonstrated better short-term outcomes. Therefore, we believe that SPLT reconstruction is effective and safe in TLRH for right colon cancer, and can simplify reconstruction.

Insight into the intrinsic activity of various transition metal sulfides for efficient hydrogen evolution reaction.

The electrocatalytic hydrogen evolution reaction (HER) is an efficient approach to convert sustainable energy sources into clean energy carriers, H2. Although various transition metal sulfides (TMSs) have been reported as promising alternatives to precious metal-based catalysts, the top catalyst among TMSs remains unclear as there is a dearth of high-quality studies that provide a 'fair' comparison of the performance of these TMSs synthesized and tested under the same conditions. In this work, layered transition metal sulfides (MS2: MoS2, WS2, VS2) and non-layered transition metal sulfides (MxSy: FeS2, CoSx, NiS) were obtained by a straightforward hydrothermal method, and thus a comprehensive platform was established for the comparison of the intrinsic activity of these materials in the HER. Experimental results demonstrate that layered MS2 exhibits better performance than non-layered MxSy in acidic electrolytes, while CoSx and NiS can catalyze hydrogen evolution more effectively under alkaline conditions due to structural reconfiguration. MoS2 shows the best HER performance in both acidic and alkaline electrolytes, particularly in 1 M KOH solution. This work provides guidance for the optimal design of transition metal electrocatalysts, and structural engineering strategies can be used to further enhance their catalytic activity.

Pedicled ligament flaps during pancreatoduodenectomy are associated with reduced hemorrhage from hepatic artery and gastroduodenal artery stump during pancreatoduodenectomy: a systematic review, meta-analysis and trial sequential analysis.

BACKGROUND: The aim of this study was to investigate whether pedicled ligament flaps (PLF) covering around the hepatic and gastroduodenal artery stump can provide better clinical outcomes in pancreatoduodenectomy (PD). METHODS: We conducted a comprehensive search of databases (inception to January 2023) to identify studies comparing PD with or without PLF covering the skeletonized arteries. The perioperative and postoperative outcomes were compared. Pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated using fixed-effects models. RESULTS: Ten studies were included in the qualitative synthesis. Six studies with 3538 patients met the inclusion criteria for the meta-analysis. Patients in the PLF group had a significantly lower rate of PPH from the hepatic artery or gastroduodenal artery stump (H/G PPH) (OR: 0.41; 95 % CI, 0.22-0.75; P < 0.01) and overall PPH (OR: 0.65; 95 % CI, 0.46-0.93; P = 0.02). There were no significant differences between the two groups in terms of morbidity, grade B/C postoperative pancreatic fistula (B/C POPF), delayed gastric emptying (DGE), reoperation, or mortality. CONCLUSION: Prophylactic pedicled ligament flaps covering around the skeletonized arteries significantly reduced overall PPH and H/G PPH, and it seemed to have no obvious influence on other complications.

Rapid, in situ synthesis of ultra-small silicon particles for boosted lithium storage capability through ultrafast Joule heating.

High-capacity anodes, especially silicon, suffer from huge volume fluctuations and electrode material pulverization during lithiation/delithiation. An accessible solution to this issue is to construct nano-silicon anodes with optimized particle size and a conductive matrix. In this work, we introduce a novel strategy for the in situ, rapid synthesis of ultra-small silicon nanoparticles uniformly embedded within carbonized nanosheets (us-Si/C) through swift high-temperature thermal radiative heating of sizable silicon nanoparticles (SiNPs). The us-Si/C anode shows ample capability to accommodate volume fluctuations during the lithiation/delithiation processes. The as-prepared anode exhibits a specific capacity of 920 mA h g-1 after 1000 cycles at a current density of 2 A g-1, indicating the advantages of the well-tailored structure. Additionally, the us-Si/C electrode can maintain an areal capacity of approximately 1.55 mA h cm-2 after 200 cycles at a high loading of 3.66 mg cm-2. Moreover, it presents practical applicability when assembled into LFP (lithium iron phosphate)//us-Si/C full cells. This preparation method presents great promise for achieving roll-to-roll manufacturing for practical applications due to its simplicity and efficiency.

Risk factors for anastomotic stenosis after radical resection of rectal cancer: A systematic review and meta-analysis.

Radical resection of rectal cancer is a safe and effective treatment, but there remain several complications related to anastomosis. We aimed to assess the risk factors and incidence of rectal anastomotic stenosis (AS) after rectal cancer resection. We conducted a systematic review and meta-analysis after searching PubMed, Embase, Web of Science, and Medline databases from inception until May 2023. Data are reported as the combined odds ratio (OR) for categorical variables and the weighted mean difference (WMD) for continuous variables. Six hundred and fifty-nine studies were retrieved, nine (3031 patients) of which were included in the meta-analysis. Young age (WMD = -3.09, P = 0.0002), male sex (OR = 1.53, P = 0.0002), smoking (OR = 1.54, P = 0.009), radiotherapy (OR = 2.34, P = 0.0002), protective stoma (OR = 2.88, P = 0.007), intersphincteric resection surgery (OR = 6.28, P = 0.05), anastomotic fistula (OR = 3.72, P = 0.003), and anastomotic distance (WMD = -3.11, P = 0.0006) were identified as factors that increased the risk of AS, while staple (OR = 0.39, P < 0.001) was a protective factor. The incidence of AS after rectal cancer resection was approximately 17% (95% CI: 13%-21%). We identified eight risk factors and one protective factor associated with AS after rectal cancer resection. These factors may be combined in future studies to develop a more comprehensive and accurate prediction model related to AS after rectal cancer resection.

Demonstration of an 800G CDM-SDM coherent PON utilizing weakly coupled multicore fibers with CDM tributary manipulation.

In this Letter, we present an experimental demonstration of downstream signaling in a 16 × 50 Gbit/s coherent passive optical network (CPON) using the code and space division multiplexing (CDM-SDM) approach. We realize optical SDM through the utilization of a 4-core weakly coupled multicore fiber (WC-MCF), enhancing the total available optical launch power at the optical line terminal (OLT). This enhancement significantly improves the power budget for CPONs that connect with a large number of optical network units (ONUs). At the second stage of the CPON, four CDM-assigned ONUs are connected to individual cores of the WC-MCF, thereby supporting the connectivity of up to 16 ONUs. Through experiments, we have noted substantial disparities in the downstream signaling performance among individual CDM-assigned ONUs, particularly as the capacity is increased to 800 Gbit/s. To address this issue, we have employed an innovative approach by leveraging space-time coding techniques to manipulate the CDM tributaries, to achieve a balanced reception performance for all ONUs within the CPON. We believe that the proposed CDM-SDM CPON scheme, complemented by the advanced DSP flow chart, holds significant promise for future PON systems characterized by substantial capacity and extensive connectivity.

Reinforced stapling does not reduce postoperative pancreatic fistula in distal pancreatectomy: a systematic review and meta-analysis.

Postoperative pancreatic fistula (POPF) is a severe complication after distal pancreatectomy (DP); however, it is unclear how to effectively reduce the incidence. The purpose of this meta-analysis is to determine whether reinforced stapling reduces POPF after DP. From February 2007 to April 2023, a comprehensive search of electronic data and references was conducted in PubMed/Medline, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews. In this study, the perioperative outcomes were evaluated for the reinforced stapler (RS) group and the standard stapler (SS) group in DP using Review Manager Software. Using fixed- or random-effects models, pooled odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated. In total, three randomized clinical trials (RCTs) with 425 patients and five observational clinical studies (OCS) with 318 patients were included. In pooled meta-analyses from RCTs, there was no difference between the two groups in the incidence of POPF (OR = 0.79; 95% CI [0.47,1.35]; P = 0.39), intraoperative blood loss (MD = 10.66; 95% CI [- 28.83,50.16]; P = 0.6), operative time (MD = 9.88; 95% CI [- 8.92,28.67]; P = 0.3), major morbidity (OR = 1.12; 95% CI [0.67,1.90]; P = 0.66), reoperation (OR = 0.97; 95% CI [0.41,2.32]; P = 0.95), readmission (OR = 0.99; 95% CI [0.57,1.72]; P = 0.97) or hospital stay (MD = - 0.95; 95% CI [- 5.22,3.31]; P = 0.66). However, the results of POPF and readmission were favorable for RS in the OCS group.

Preparation of heterojunction C3N4/WO3 photocatalyst for degradation of microplastics in water.

In this study, a WO3/g-C3N4 composite photocatalyst was synthesized via a hydrothermal method and characterized for its potential application in photocatalytic H2 generation from PET degradation. XRD analysis revealed that the hexagonal WO3 crystal structure was achieved after 10 h of hydrothermal time, with particles of suitable size for uniform loading on the g-C3N4 surface. SEM images showed the successful loading of WO3 nanorods onto the g-C3N4 surface, significantly increasing the specific surface area. FTIR and UV-vis diffuse reflectance spectroscopy confirmed the formation of a Z-type heterojunction between WO3 and g-C3N4. Photoluminescence measurements indicated a reduced rate of electron-hole pair recombination in the composite. The 30% WO3/g-C3N4 composite demonstrated a high H2 evolution rate of 14.21 mM and excellent stability in PET solution under visible light irradiation. 1H NMR and EPR spectroscopy analyses revealed the degradation of PET into small molecular compounds and the generation of active radicals, including ·O2-, during the reaction. Overall, the WO3/g-C3N4 composite exhibited promising potential for photocatalytic H2 production and PET degradation.

An Orthotopic Resection Surgical Technique Using an Inferior Infracolic Approach for Laparoscopic Pancreaticoduodenectomy.

The no-touch isolation technique has been widely used in cancer surgery as a strategy to prevent cancer cells from spreading; however, it is difficult to apply in laparoscopic pancreaticoduodenectomy (LPD). Here, we describe an orthotopic resection surgical technique that applies a no-touch principle for LPD and can help with the in situ resection of tumors. In implementing this surgical strategy, Kocher's maneuver was not performed first. Instead, after the exploration of the abdominal cavity, the distal stomach and the pancreatic neck were transected. Then, the dissection of the uncinate process of the pancreas, the duodenum, and the superior mesenteric vein and artery is carried out via an inferior infracolic approach. Finally, the pancreatic head and duodenum were removed in situ. Among the 41 patients who underwent this technique, two (4.9%) required conversion to open surgery due to uncontrolled bleeding. The average operative time was 335 min (248-1055 min). The mean estimated blood loss was 300 mL (50-1250 mL). Two patients (4.9%) underwent combined PV resection and reconstruction; six patients (14.6%) required a blood transfusion; two patients (4.9%) suffered from postoperative bleeding; two patients (4.9%) suffered from Grade B pancreatic fistulas; one patient (2.4%) suffered from bile leakage; and three patients (7.3%) suffered from abdominal fluid collection. No patients died during the perioperative period. Therefore, orthotopic LPD using an inferior infracolic approach is safe and feasible for patients with malignant pancreatic head and periampullary tumors. However, further investigations are required to elucidate its oncological benefits.

A Medical Assistive Robot for Telehealth Care During the COVID-19 Pandemic: Development and Usability Study in an Isolation Ward.

BACKGROUND: The COVID-19 pandemic is affecting the mental and emotional well-being of patients, family members, and health care workers. Patients in the isolation ward may have psychological problems due to long-term hospitalization, the development of the epidemic, and the inability to see their families. A medical assistive robot (MAR), acting as an intermediary of communication, can be deployed to address these mental pressures. OBJECTIVE: CareDo, a MAR with telepresence and teleoperation functions, was developed in this work for remote health care. The aim of this study was to investigate its practical performance in the isolation ward during the pandemic. METHODS: Two systems were integrated into the CareDo robot. For the telepresence system, a web real-time communications solution is used for the multiuser chat system and a convolutional neural network is used for expression recognition. For the teleoperation system, an incremental motion mapping method is used for operating the robot remotely. A clinical trial of this system was conducted at First Affiliated Hospital, Zhejiang University. RESULTS: During the clinical trials, tasks such as video chatting, emotion detection, and medical supplies delivery were performed via the CareDo robot. Seven voice commands were set for performing system wakeup, video chatting, and system exiting. Durations from 1 to 3 seconds of common commands were set to improve voice command detection. The facial expression was recorded 152 times for a patient in 1 day for the psychological intervention. The recognition accuracy reached 95% and 92.8% for happy and neutral expressions, respectively. CONCLUSIONS: Patients and health care workers can use this MAR in the isolation ward for telehealth care during the COVID-19 pandemic. This can be a useful approach to break the chains of virus transmission and can also be an effective way to conduct remote psychological intervention.

Mitochondria-Targeting and Multiresponsive Nanoplatform Based on AIEgens for Synergistic Chemo-Photodynamic Therapy and Enhanced Immunotherapy.

Although photodynamic therapy (PDT) has become an attractive strategy for cancer treatment, its clinical application still suffers from some limitations, including insufficient delivery of photosensitizers, hypoxic tumor environment, and the development of PDT resistance. To address these limitations, a new class of mitochondria-targeting and fluorinated polymer with aggregation-induced emission characteristics was fabricated to sensitize PDT and co-deliver chemotherapeutic drugs. The amphiphilic fluoropolymer was able to efficiently carry oxygen and SN-38 (the active metabolite of irinotecan) and self-assemble into multifunctional micellar nanoparticles (SN-38-TTCF@O2 NPs). Upon internalization into tumor cells, these NPs could successfully escape lysosomes, selectively target mitochondria, efficiently produce reactive oxygen species (ROS) under light irradiation, and release drugs in response to ROS. In the HCT116 tumor xenograft model, they preferentially accumulated in tumor tissue and significantly alleviated tumor hypoxia, resulting in synergistic chemo-PDT efficacy without distinct toxicity. Furthermore, the nanoscale chemo-PDT induced immunogenic cell death, promoted the recruitment and activation of cytotoxic T lymphocytes, and ultimately augmented the anti-tumor efficacy of anti-PD-1 antibody in the murine CT26 tumor model. These results may provide novel insights into the development of efficient chemo-PDT nanomedicine to improve the outcome of immunotherapy.

Laparoscopic versus open central pancreatectomy: a propensity score-matched analysis in a single centre.

PURPOSE: Laparoscopic central pancreatectomy (LCP) has been implemented in pancreatic surgery; however, open surgery is still the predominant approach for central pancreatectomy (CP). Our objective was to compare LCP with open CP (OCP). METHODS: Data were collected from patients with tumours located in the pancreatic neck and proximal body who underwent CP in the Department of Pancreatic Surgery West China Hospital from January 1, 2010, to June 30, 2019. A comparison between the LCP and OCP groups was performed. RESULTS: Fifteen patients underwent CP via the laparoscopic approach, and 96 patients underwent CP via the open approach. Using 1:2 propensity score matching (PSM), 12 patients in the LCP group were matched to 21 in the OCP group. Regarding safety, postoperative pancreatic fistula (POPF) was not significantly different between the two groups (13.3% vs. 12.5%, P = 1.000), even with PSM (16.7% vs. 14.3%, P = 1.000). However, regarding effectiveness, the operative time in the OCP group was significantly shorter than that in the LCP group before (307.0 ± 92.3 ml vs. 220.6 ± 63.6 ml, P < 0.000) and after (300.3 ± 90.2 ml vs. 212.7 ± 44.4 ml, P = 0.002) PSM. Regarding length of stay (LOS), there was no difference between the two groups before (13.1 ± 13.7 days vs. 12.7 ± 10.1 days, P = 0.376) and after PSM (14.4 ± 15.1 days vs. 14.5 ± 16.2 days, P = 0.985). The length of the resected pancreas was shorter in the OCP group than in the LCP group before PSM (50.0 ± 13.2 mm vs. 41.1 ± 11.1 mm, P = 0.043). However, there was no difference between the two groups after PSM (47.9 ± 12.5 mm vs. 37.9 ± 10.4 mm, P = 0.084). Moreover, the other variables showed no difference between the two groups before and after PSM. CONCLUSION: LCP can demonstrate similar safety and effectiveness to OCP, even in the early stages of the learning curve.

A Phase I Study of Gemcitabine/Nab-Paclitaxel/S-1 Chemotherapy in Patients With Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Systemic chemotherapy is the primary treatment in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). More effective treatment options are highly awaited. The aim of this study was to evaluate the toxicity and feasibility of gemcitabine/nab-paclitaxel/S-1 (GAS) chemotherapy on a 21-day cycle in patients with locally advanced or metastatic PDAC, determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of S-1 in this regimen, and explore preliminary efficacy. METHODS: Eligible patients with locally advanced or metastatic PDAC received GAS chemotherapy on a 21-day cycle. Fixed-dose nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) were given intravenously on days 1 and 8. Different doses of S-1 were given orally twice daily from day 1 to day 14 in a 3+3 dose escalation design. According to patients` body surface area, the dose-escalation design was as follows: patients with a body surface area of 1.25-1.5 m2 received S-1 40 mg/day initially and the dose was increased to 60 mg or 80 mg. Patients with a body surface area of more than 1.5 m2 received S-1 60 mg/day initially and the dose was increased to 80 mg or 100 mg. The primary endpoints were to evaluate the toxicity and determine the DLT and MTD of S-1. The secondary endpoint was to evaluate efficacy, including best objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). adverse events (AEs) were evaluated according to the NCI-CTCAE 5.0. Tumor response was assessed using the RECIST 1.1. RESULTS: A total of 21 eligible patients were included. Due to the infrequence of patients with a body surface area of 1.25-1.5 m2, only 2 patients were included in cohort of S-1 40 mg. The dose-escalation for patients in this group failed to be enrolled completely. For patients with a body surface area of more than 1.5 m2, 3 DLTs in 7 patients were detected at cohort of S-1 100 mg (grade 3 thrombocytopenia with hemorrhage, grade 3 rash, and grade 3 mucositis/stomatitis). S-1 80 mg/day (body surface area: >1.5 m2) was considered to be the MTD in GAS chemotherapy on a 21-day cycle. No grade 4 AEs or treatment-related deaths were observed. The most commonly occurring hematologic AE of any grade was anemia (38.1%). The most frequent nonhematologic AEs of any grade were peripheral neuropathy (38.1%), dyspepsia (23.8%), constipation (23.8%), and alopecia (23.8%). Response assessment showed that the best ORR was 36.8% (7 of 19 patients) and the DCR was 94.7% (18 of 19 patients). The median PFS was 5.3 (95% CI, 4.6 to 6.0) months and the median OS was 10.3 (95% CI, 8.1 to 12.5) months. CONCLUSION: GAS chemotherapy (21-day cycle) with nab-paclitaxel 125 mg/m2, gemcitabine 1000 mg/m2, and S-1 80 mg/day (body surface area: >1.5 m2) was found to have acceptable toxicity and significant clinical control in patients with locally advanced or metastatic PDAC. We conclude that further trials with this combination are warranted. (Trial Identifier: ChiCTR1900027833 [chictr.org]).