Elevated protein lactylation promotes immunosuppressive microenvironment and therapeutic resistance in pancreatic ductal adenocarcinoma.

Metabolic reprogramming shapes tumor microenvironment (TME) and may lead to immunotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Elucidating the impact of pancreatic cancer cell metabolism in the TME is essential to therapeutic interventions. "Immune cold" PDAC is characterized by elevated lactate levels resulting from tumor cell metabolism, abundance of pro-tumor macrophages, and reduced cytotoxic T cell in the TME.

Risk Factors, Manifestations, and Implications of Chyle Leak -Following Pancreatic Surgery: The Volume May Outweigh the Milky Appearance of the Drainage in a Chyle Leak.

Objective: To identify the risk factors, manifestations, and clinical implications of chyle leak (CL) after pancreatic surgery, and to reappraise the International Study Group for Pancreatic Surgery (ISGPS) definition and classification of CL.

Summary Background Data: The risk factors, clinical scenarios, and management of CL after pancreatic surgery remain controversial.

Methods: Data from patients who underwent pancreatic surgery between January 2019 and July 2023 were retrieved from an institutional database.

The role of adjuvant transcatheter arterial chemoembolization following repeated curative resection/ablation for hepatocellular carcinoma with early recurrence: a propensity score matching analysis.

Background: The role of adjuvant transcatheter arterial chemoembolization (TACE) following repeated resection/ablation for recurrent hepatocellular carcinoma (HCC) remains uncertain. The aim of this study was to assess the effectiveness of adjuvant TACE following repeated resection or ablation in patients with early recurrent HCC.

Methods: Information for patients who underwent repeated surgery or radiofrequency ablation (RFA) for early recurrent HCCs (< 2 years) at our institution from January 2017 to December 2020 were collected.

Targeting cancer-associated fibroblast autophagy renders pancreatic cancer eradicable with immunochemotherapy by inhibiting adaptive immune resistance.

Accumulating evidence suggests that cancer-associated fibroblast (CAF) macroautophagy/autophagy is crucial in tumor development and may be a therapeutic target for pancreatic ductal adenocarcinoma (PDAC). However, the role of CAF autophagy during immune surveillance and cancer immunotherapy is unclear. The present study revealed that the inhibition of CAF autophagy suppresses tumor development in immune-deficient xenografts.

Targeting leucine-rich repeat serine/threonine-protein kinase 2 sensitizes pancreatic ductal adenocarcinoma to anti-PD-L1 immunotherapy.

Pancreatic ductal adenocarcinoma (PDAC) is not sensitive to immune checkpoint blockade therapy, and negative feedback of tumor immune evasion might be partly responsible. We isolated CD8+ T cells and cultured them in vitro. Proteomics analysis was performed to compare changes in Panc02 cell lines cultured with conditioned medium, and leucine-rich repeat kinase 2 (LRRK2) was identified as a differential gene.

Targeting ubiquitin-specific protease 8 sensitizes anti-programmed death-ligand 1 immunotherapy of pancreatic cancer.

Programmed death-1 (PD-1) and its ligand programmed death-ligand 1 (PD-L1) help tumor cells evade immune surveillance, and are regarded as important targets of anti-tumor immunotherapy. Post-translational modification of PD-L1 has potential value in immunosuppression. Here, we identified that ubiquitin-specific protease 8 (USP8) deubiquitinates PD-L1.

Adjuvant therapy with gemcitabine and stereotactic body radiation therapy versus gemcitabine alone for resected stage II pancreatic cancer: a prospective, randomized, open-label, single center trial.

Background: The role of adjuvant radiation in pancreatic adenocarcinoma (PDAC) remains unclear. We aimed to investigate the efficacy of gemcitabine combined with stereotactic body radiation therapy (SBRT) as adjuvant therapy for resected stage II PDAC.

Methods: In this single-center randomized controlled trial, patients with stage II PDAC that underwent margin-negative resection were randomly assigned to gemcitabine-alone adjuvant chemotherapy or adjuvant SBRT followed by gemcitabine chemotherapy.

RCAN1-mediated calcineurin inhibition as a target for cancer therapy.

Cancer is the leading cause of mortality worldwide. Regulator of calcineurin 1 (RCAN1), as a patent endogenous inhibitor of calcineurin, plays crucial roles in the pathogenesis of cancers. Except for hypopharyngeal and laryngopharynx cancer, high expression of RCAN1 inhibits tumor progression.

Combination cancer immunotherapy targeting TNFR2 and PD-1/PD-L1 signaling reduces immunosuppressive effects in the microenvironment of pancreatic tumors.

Backgrounds: In advanced pancreatic ductal adenocarcinoma (PDAC), immune therapy, including immune checkpoint inhibitors, has limited efficacy, encouraging the study of combination therapy.

Methods: Tumor necrosis factor receptor 2 (TNFR2) was analyzed via immunohistochemistry, immunofluorescence, western blotting, and ELISAs. The in vitro mechanism that TNFR2 regulates programmed cell death 1 ligand 1 (PD-L1) was investigated using immunofluorescence, immunohistochemistry, flow cytometry, western blotting, and chromatin immunoprecipitation (ChIP).

NEK2 inhibition triggers anti-pancreatic cancer immunity by targeting PD-L1.

Despite the substantial impact of post-translational modifications on programmed cell death 1 ligand 1 (PD-L1), its importance in therapeutic resistance in pancreatic cancer remains poorly defined. Here, we demonstrate that never in mitosis gene A-related kinase 2 (NEK2) phosphorylates PD-L1 to maintain its stability, causing PD-L1-targeted pancreatic cancer immunotherapy to have poor efficacy. We identify NEK2 as a prognostic factor in immunologically "hot" pancreatic cancer, involved in the onset and development of pancreatic tumors in an immune-dependent manner.

Non-cytomembrane PD-L1: An atypical target for cancer.

Programmed death ligand 1 (PD-L1) has conventionally been considered as a type I transmembrane protein that can interact with its receptor, programmed cell death 1 (PD-1), thus inducing T cell deactivation and immune escape. However, targeting the PD-1/PD-L1 axis has achieved adequate clinical responses in very few specific malignancies. Recent studies have explored the extracellularly and subcellularly located PD-L1, namely, nuclear PD-L1 (nPD-L1), cytoplasmic PD-L1 (cPD-L1), soluble PD-L1 (sPD-L1), and extracellular vesicle PD-L1 (EV PD-L1), which might shed light on the resistance to anti-PD1/PDL1 therapy.

Regulator of calcineurin 1 gene isoform 4 in pancreatic ductal adenocarcinoma regulates the progression of tumor cells.

Therapeutic strategies to treat pancreatic ductal adenocarcinoma (PDAC) remain unsatisfying and limited. Therefore, it is imperative to fully determine the mechanisms underlying PDAC progression. In the present study, we report a novel role of regulator of calcineurin 1, isoform 4 (RCAN1.

Endogenous Interleukin 18 Suppresses Liver Regeneration After Hepatectomy in Mice.

The comprehensive role of interleukin (IL) 18 during liver regeneration is barely studied. Our aim is to evaluate the role of IL18 in liver regeneration after partial hepatectomy (PH) in mice. The expression profile of IL18 in the liver and the gut after 70% PH was measured.

Development of a Novel Multiparametric MRI Radiomic Nomogram for Preoperative Evaluation of Early Recurrence in Resectable Pancreatic Cancer.

Background: In pancreatic cancer, methods to predict early recurrence (ER) and identify patients at increased risk of relapse are urgently required.

Purpose: To develop a radiomic nomogram based on MR radiomics to stratify patients preoperatively and potentially improve clinical practice.

Study Type: Retrospective.

External validation of alternative fistula risk score (a-FRS) for predicting pancreatic fistula after pancreatoduodenectomy.

Background: The utility of the proposed alternative fistula risk score (a-FRS) for predicting risk of clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD) has not been validated widely.

Methods: This retrospective analysis included data of patients undergoing open and laparoscopic PD during March 2012-May 2018 in our institution. The predictive abilities of a-FRS and original-FRS were compared.

Surgical management and outcome of grade-C pancreatic fistulas after pancreaticoduodenectomy: A retrospective multicenter cohort study.

Background: Management strategies for grade-C postoperative pancreatic fistula (POPF) following pancreaticoduodenectomy (PD) vary. The aim of this study was to evaluate surgical indications, approaches, and outcomes of grade-C POPF following PD.

Materials And Methods: The clinical data of grade-C POPF patients from 9 high-volume institutions between January 1, 2012 and December 31, 2016 were retrospectively reviewed.

Pyogenic Liver Abscess After Pancreaticoduodenectomy: A Single-Center Experience.

Background: Pancreaticoduodenectomy (PD) is a complex procedure with a morbidity rate of 40%-50%. We evaluated the incidence, associated factors, etiologic characteristics, and outcome of pyogenic liver abscess (PLA), a rare infectious complication of PD.

Methods: We retrospectively assessed the data of patients who underwent PD (n = 326) between January 2012 and February 2017 at a single institution.

Pancreas-preserving management of grade-C pancreatic fistula and a novel bridging technique for repeat pancreaticojejunostomy: An observational study.

Purpose: Optimal surgical strategy for grade-C postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) is not justified. External wirsungostomy is feasible. However, the subsequent repeat pancreaticojejunostomy (PJ) is challenging.