Recent Articles on Pancreatobiliary #Pathology – 2020-07-30

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


  • Systematic Review and Metaanalysis of Lymph Node Metastases of Resected Pancreatic Neuroendocrine Tumors

Annals of surgical oncology 2020 Jul;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32720049

BACKGROUND: The optimal surgical strategy for pancreatic neuroendocrine tumors (PNETs) is unknown. However, current guidelines recommend a watch-and-wait strategy for small nonfunctional PNETs (NF-PNETs). The aim of this study is to investigate the risk stratification and prognostic significance of lymph node metastasis (LNM) of PNETs to guide decision-making for lymphadenectomy.
PATIENTS AND METHODS: The MEDLINE and Web of Science databases were systematically searched for studies reporting either risk factors of LNM in resected PNETs or survival of patients with LNM. The weighted average incidence of LNM was calculated according to tumor characteristics. Random-effects metaanalyses were performed, and pooled hazard ratios (HR) and their 95% confidence intervals (CI) were calculated to determine the impact of LNM on overall survival (OS). In subgroup analyses, NF-PNETs were assessed.
RESULTS: From a total of 5883 articles, 98 retrospective studies with 13,374 patients undergoing resection for PNET were included. In all PNETs, the weighted median rates of LNM were 11.5% for small (≤ 2 cm) PNETs and 15.8% for G1 PNETs. In NF-PNETs, the rates were 11.2% for small PNETs and 10.3% for G1 PNETs. LNM of all PNETs (HR 3.87, 95% CI 3.00-4.99, P < 0.001) and NF-PNETs (HR 4.98, 95% CI 2.81-8.83, P < 0.001) was associated with worse OS.
CONCLUSIONS: LNM is potentially prevalent even in small and well-differentiated PNETs and is associated with worse prognosis. A watch-and-wait strategy for small NF-PNETs should be reappraised, and oncologic resection with lymphadenectomy can be considered. Prospective and controlled studies are needed in the future.

doi: https://doi.org/10.1245/s10434-020-08850-7



  • Low dose Hsp90 inhibitor selectively radiosensitizes HNSCC and Pancreatic xenografts

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

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32718999

PURPOSE: Treatment approaches using Hsp90 inhibitors at their maximum tolerated doses have not produced selective tumor toxicity. Inhibition of Hsp90 activity causes degradation of client proteins including those involved in recognizing and repairing DNA lesions. We hypothesized that if DNA repair proteins were degraded by concentrations of an Hsp90 inhibitor below those required to cause non-specific cytotoxicity, significant tumor-selective radiosensitization might be achieved.
EXPERIMENTAL DESIGN: Tandem Mass Tagged (TMT)-mass spectrometry (MS) was performed to determine the effect of a sub-cytotoxic concentration of the Hsp90 inhibitor, AT13387 (Onalespib) on global protein abundance. The effect of AT13387 on in vitro radio-sensitization was assessed using a clonogenic assay. Pharmacokinetic (PK) profiling was performed in mice bearing xenografts. Finally, the effect of low-dose AT13387 on the radiosensitization of three tumor models was assessed.
RESULTS: A sub-cytotoxic concentration of AT13387 reduced levels of DNA repair proteins, without affecting the majority of Hsp90 clients. The PK study using one-third of the maximum tolerated dose (MTD) showed 40-fold higher levels of AT13387 in tumors compared to plasma. This low dose enhanced Hsp70 expression in peripheral blood mononuclear cells (PBMC), which is a biomarker of Hsp90 inhibition. Low dose monotherapy was ineffective but, when combined with radiotherapy (RT), produced significant tumor growth inhibition.
CONCLUSIONS: The current study shows that a significant therapeutic ratio can be achieved by a low dose of Hsp90 inhibitor in combination with radiotherapy. Hsp90 inhibition, even at a low dose, can be monitored by measuring Hsp70 expression in PBMC in human studies.

doi: https://doi.org/10.1158/1078-0432.CCR-19-3102


New GallBladder Articles


  • Early pathogenesis of cystic fibrosis gallbladder disease in a porcine model

Laboratory investigation; a journal of technical methods and pathology 2020 Jul;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32719544

Hepatobiliary disease causes significant morbidity in people with cystic fibrosis (CF), yet this problem remains understudied. We previously found that newborn CF pigs have microgallbladders with significant luminal obstruction in the absence of infection and consistent inflammation. In this study, we sought to better understand the early pathogenesis of CF pig gallbladder disease. We hypothesized that loss of CFTR would impair gallbladder epithelium anion/liquid secretion and increase mucin production. CFTR was expressed apically in non-CF pig gallbladder epithelium but was absent in CF. CF pig gallbladders lacked cAMP-stimulated anion transport. Using a novel gallbladder epithelial organoid model, we found that Cl- or HCO3- was sufficient for non-CF organoid swelling. This response was absent for non-CF organoids in Cl-/HCO3–free conditions and in CF. Single-cell RNA-sequencing revealed a single epithelial cell type in non-CF gallbladders that coexpressed CFTR, MUC5AC, and MUC5B. Despite CF gallbladders having increased luminal MUC5AC and MUC5B accumulation, there was no significant difference in the epithelial expression of gel-forming mucins between non-CF and CF pig gallbladders. In conclusion, these data suggest that loss of CFTR-mediated anion transport and fluid secretion contribute to microgallbladder development and luminal mucus accumulation in CF.

doi: https://doi.org/10.1038/s41374-020-0474-8


New BileDuct Articles

Today there is no new Bile Duct Article.

New Ampulla Articles

Today there is no new Ampulla Article.

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