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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. [ABSTRACT FROM AUTHOR]

Abstract: The peptide segment of prostatic acid phosphatase (PAP248–286) 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 PAP248–286 through an in silico study. Three derivatives of suramin, NF110, NF279, and NF340, are selected. All of these sulfonated molecules bind to PAP248–286 and alter the conformation of the peptide, even though they have various structures, sizes, and configurations. The compounds bind with PAP248–286 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 PAP248–286 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 PAP248–286, blocking interactions between the peptides. Therefore, these compounds are important in inhibiting the aggregation of PAP248–286. Herein, we provide useful information to develop new efficient microbicides to antagonize seminal amyloid fibrils and to block HIV transmission. [ABSTRACT FROM AUTHOR]

RuO2–Au compositenanoparticles (RuO2–Au CNPs) are synthesized viaa simple calcination of RuNPsand AuNPs encapsulated within extra-large mesocages of mesoporoussilica (EP-FDU-12). Both the Ru/Au ratio (0.02:0.2) and the nanostructureof the mesoporous supports are critical for its successful formation.Surface-enhanced Raman scattering (SERS) effects are observed forRuO2composite because of the interaction between RuO2and Au of the RuO2–Au CNPs. The nanocontactmodifies the electronic and chemical properties of Au and RuO2, respectively, which in turn benefits their catalytic performancewith enhanced activities and reduced coking-deposition content ingas-phase cyclohexanol-selective oxidation. [ABSTRACT FROM AUTHOR]

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.)

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: 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.)

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.)

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: 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.

Traditional post-surgical chemotherapy for pancreatic cancer is notorious for its devastating side effects due to the high dosage required. On the other hand, legitimate concerns have been raised about nanoparticle-mediated drug delivery because of its potential cytotoxicity. Therefore, we explored the local delivery of a reduced dosage of FOLFIRINOX, a four-drug regimen comprising oxaliplatin, leucovorin, irinotecan, and fluorouracil, for pancreatic cancer using a biocompatible drug-eluting scaffold as a novel chemotherapy strategy after palliative surgery. In vitro assays showed that FOLFIRINOX in the scaffold caused massive apoptosis and thereby a decrease in the viability of pancreatic cancer cells, confirming the chemotherapeutic capability of the drug-eluting scaffold. In vivo studies in an orthotopic murine xenograft model demonstrated that the FOLFIRINOX in the scaffold had antitumorigenic and antimetastatic effects comparable with those achieved by intraperitoneal injection, despite the dose released by the scaffold being roughly two thirds lower. A mechanistic study attributed our results to the excellent ability of the FOLFIRINOX in the scaffold to destroy the CD133(+)CXCR4(+) cell population responsible for pancreatic tumorigenesis and metastasis. This clinically oriented study gives rise to a promising alternative strategy for postsurgical management of pancreatic cancer, featuring a local chemotherapeutic effect with considerable attenuation of side effects.