Search

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Pharmaceutical and personal care products (PPCPs), including antibiotics, azole anti-fungals, non-steroid anti-inflammatory drugs, lipid regulators, parabens, antiseptics, and bisphenol A, were investigated in groundwater and reservoirs in the vicinity of two municipal landfills in the metropolis of Guangzhou, South China. Dehydroerythromycin, sulfamethoxazole, fluconazole, salicylic acid, methylparaben, triclosan, and bisphenol A were the mostly frequently detected PPCPs in the groundwater at low ng L − 1 levels. In the reservoirs, the PPCPs were widely detected at higher frequencies and concentrations, especially sulfamethoxazole, propiconazole, and ibuprofen, with maximal concentrations above 1 μg L − 1 . The PPCPs in the groundwater did not show significant seasonal differences or spatial trends. However, in the reservoirs, higher PPCP concentrations were observed in spring than in other seasons. The anti-bacterials in the groundwater posed medium risks to algae. In the reservoirs, the sulfonamides and macrolides posed low to high risks, while ibuprofen, salicylic acid, and clofibric acid presented low to medium risks to aquatic organisms. Overall, the results showed that the PPCP contaminants and subsequent ecological risks in the groundwater and surface water in the vicinity of the landfills may be of serious concern. More research is needed to better correlate the landfill leachates and PPCP contamination in the nearby aquatic environments. [ABSTRACT FROM AUTHOR]

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.)

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).)

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.)