Recent Articles on Pancreatobiliary #Pathology – 2020-07-18

These are the recent articles on Pancreatobiliary Pathology:

To see all journal watch articles please visit: http://pbpath.org/journal-watch-upcoming-issue/

New Pancreas Articles


  • The role of genetic polymorphism within PD-L1 gene in cancer. Review

Experimental and molecular pathology 2020 Jul;():104494

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32679050

The maintenance of homeostasis of the immune system depends on the balance between excitatory and inhibitory signals. Programmed death ligand (PD-L1) is a molecule which downregulates the immune system targeting the programmed death receptor 1 (PD-1). Under physiological conditions, the receptor is constitutively expressed in lymphocytes. The PD-L1 / PD-1 pathway plays a key role in completing the immune response in the right way, preventing excessive stimulation of the cells of the immune system, protecting the organism against autoimmunity. Under pathological conditions PD-L1 expression may take place in tumor cells. Binding of PD-1 to its ligand on tumor cells suppresses T lymphocytes through a negative feedback. This mechanism allows abnormal cells to avoid destruction by the host immune system. The expression of PD-L1 in tumors has been described in many histological types of cancer: melanoma, lung cancer, breast and ovarian, pancreatic and esophagus adenocarcinoma, kidney tumors and bladder cancers as well as in hematopoietic malignancies. Many studies report a significant effect of PD-L1 polymorphisms on clinical parameters of patients. Studies of PD-L1 polymorphisms showed their influence on the stage of cancer, effectiveness of chemotherapy and prognosis after tumor resection. Further analysis of the polymorphisms may result in development of effective therapies that restore anti-tumor immunity. Inhibition of PD-L1 / PD-1 is one of the most promising immunotherapies for various types of cancer. This work was intended to present information about the impact of PD-L1 gene expression and polymorphisms on the clinical parameters of patients with cancer.

doi: https://doi.org/10.1016/j.yexmp.2020.104494



  • Non-inferiority comparative clinical trial between early oral REFEEDING and usual oral REFEEDING in predicted mild acute biliary pancreatitis

BMC gastroenterology 2020 Jul;20(1):228

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32677891

BACKGROUND: The aim of the study was to compare the onset of oral feeding in the first 24 h after hospital admission with usual oral refeeding and determine whether the timing of the onset of oral feeding influences the recurrence of pain or alters the blood levels of pancreatic enzymes in patients with predicted mild acute biliary pancreatitis.
METHODS: This non-inferiority randomized controlled trial was carried out between September 2018 and June 2019 after receiving authorization from the ethics committee for health research. Patients with a diagnosis of predicted mild acute biliary pancreatitis were divided into Group A (early oral refeeding, EOR) and Group B (usual oral refeeding, UOR). Outcome measures included pancreatic lipase levels, the systemic inflammatory response (concentrations of leukocytes), feasibility (evaluated by abdominal pain recurrence), the presence and recurrence of gastrointestinal symptoms and the length of hospital stay.
RESULTS: Two patients in the EOR group experienced pain relapse (3.2%), and four patients in the UOR group experienced pain relapse (6.77%) after oral refeeding (p = 0.379). The presence of nausea or vomiting after the onset of oral refeeding was not different between the two groups (p = 0.293). The onset of oral refeeding was approximately 48 h later in the UOR group. The length of hospital stay was 5 days in the EOR group and 8 days in the UOR group (p = 0.042), and this difference was also manifested in higher hospital costs in the UOR group (p = 0.0235).
CONCLUSION: Compared with usual oral refeeding, early oral refeeding is safe in predicted mild acute biliary pancreatitis patients, does not cause adverse gastrointestinal events, and reduces the length of hospital stay and costs.
TRIAL REGISTRATION: Early oral refeeding in mild acute pancreatitis (EORVsUOR). NCT04168801 , retrospectively registered (November 19, 2019).

doi: https://doi.org/10.1186/s12876-020-01363-3



  • Prognostic impact of CD73 expression and its relationship to PD-L1 in patients with radically treated pancreatic cancer

Virchows Archiv : an international journal of pathology 2020 Jul;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32676968

Immune suppressing molecule CD73 is overexpressed in various cancers and associated with poor survival. Little is so far known about the predictive value of CD73 in pancreatic ductal adenocarcinoma (PDAC). The purpose of this study was to investigate the prognostic significance of CD73 in PDAC. The study material consisted of 110 radically treated patients for PDAC. Tissue microarray blocks were constructed and stained immunohistochemically using CD73 antibody. Staining intensity and numbers of stained tumour cells, inflammatory cells, stroma, and blood vessels were assessed. High-level CD73 expression in tumour cells was positively associated with PD-L1 expression, perineural invasion, and histopathological grade. CD73 positivity in tumour-infiltrating lymphocytes was significantly associated with lymph node metastasis. Lymphocytic CD73 positivity was also associated with staining positivity in both stroma and vascular structures. In addition, CD73 positivity in vascular structures and stroma were associated with each other. There were no significant associations between CD73 positive tumour cells and CD73 positivity in any other cell types. PD-L1 expression was associated with CD73 staining positivity in stroma (p = 0.007) and also with histopathological grade (p = 0.033) and T class (p = 0.016) of the primary tumour. CD73 positivity in tumour cells was significantly associated with poor disease-specific (p = 0.021) and overall survival (p = 0.016). In multivariate analysis, CD73 positivity in tumour cells was an independent negative prognostic factor together with histopathological grade, TNM stage, and low immune cell score. In conclusion, high CD73 expression in tumour cells is associated with poor survival in PDAC independently of the number of tumour-infiltrating lymphocytes or TNM stage.

doi: https://doi.org/10.1007/s00428-020-02888-4



  • Evidencing a pancreatic ductal adenocarcinoma subpopulation sensitive to the proteasome inhibitor Carfilzomib

Clinical cancer research : an official journal of the American Association for Cancer Research 2020 Jul;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32669378

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer. Multiple chemotherapeutic drugs have been tested to improve patient prognosis; however, the clinical efficacy of these treatments is low. One of the most controversial family of drugs are the proteasome inhibitors, which have displayed promising effects in pre-clinical studies, but low clinical performance. Here we unravel a specific transcriptomic signature that discriminates a subgroup of patients sensitive to the proteasome inhibitor Carfilzomib.
EXPERIMENTAL DESIGN: First, we identified a subpopulation of PDAC derived primary cells cultures (PDPCC) sensitive to the proteasome inhibitor Carfilzomib. Then, we selected a transcriptomic signature that predicts Carfilzomib chemosensitivity using independent component analysis on the transcriptome of PDPCC. Finally, we validated the signature in an independent cohort of PDAC biopsy derived pancreatic organoids.
RESULTS: Sensitive phenotype was characterized by a high expression of genes related with a cornified/squamous pathways and a down regulation of epithelial-mesenchymal transition genes. Interestingly, Carfilzomib sensitive transcriptomic profile did not show any association with the proteasome activity but strongly correlates with ATF4 and CHOP expression which are key markers of the unfolded protein response and critical to trigger the cell death program. Concordantly, sensitive phenotype showed a high level of the novo RNA and protein synthesis compared to the resistant one and, most important, cell death induced by Carfilzomib is dependent of the translational activity.
CONCLUSION: We demonstrate the existence of a Carfilzomib sensitive PDAC subgroup with a specific transcriptomic phenotype that could explain the biological reason for this responsiveness.

doi: https://doi.org/10.1158/1078-0432.CCR-20-1232



  • A Phase I/II Study of Veliparib (ABT-888) in combination with 5-Fluorouracil and Oxaliplatin in Patients with Metastatic Pancreatic Cancer

Clinical cancer research : an official journal of the American Association for Cancer Research 2020 Jul;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32669374

Background Up to 17% of pancreatic cancer (PDAC) patients harbor pathogenic (germline or somatic) mutations in a homologous recombination, DNA damage response and repair (HR-DDR) gene, such as BRCA1/2, or PALB2. Platinum-based chemotherapy, or treatment with PARP inhibitors are of particular benefit in these patients. However, there may be even greater benefit when platinums and PARP inhibitors are combined. Patients and Methods We performed a single-arm, open-label, phase I/II study of the PARP inhibitor, veliparib, with 5-fluorouracil (no 5FU bolus) and oxaliplatin (FOLFOX) for patients with metastatic PDAC. Thirty-one patients were enrolled in a Phase I dose escalation of veliparib (40mg to 250mg BID, days 1-7 of each 14 day cycle), to identify the recommended phase II dose (RP2D) of veliparib for the combination. Another 33 patients were enrolled in two parallel Phase II trials to assess the objective response rate (ORR) in untreated or in previously treated patients. If available, germline or somatic testing was collected to identify pathogenic HR-DDR mutations. Results The combination of veliparib and FOLFOX was tolerable at a RP2D of veliparib of 200mg BID. The primary endpoint for both Phase II cohorts was met, and the ORR overall was 26%. There was greater activity in platinum-naïve patients, and those who harbored a pathogenic HR-DDR mutation. Specifically, the ORR of HR-DDR mutated, platinum-naive patients was 57%. Conclusions The combination of veliparib and FOLFOX was safe for patients with metastatic PDAC and showed promising activity particularly in patients with platinum-naive disease that harbors a pathogenic HR-DDR mutation.

doi: https://doi.org/10.1158/1078-0432.CCR-20-1301


New GallBladder Articles

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New BileDuct Articles

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New Ampulla Articles

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