organotypic-slice-cultures-as-preclinical-models-tumor

Organotypic Slice Cultures as Preclinical Models of Tumor Microenvironment in Primary Pancreatic Cancer and Metastasis

Realistic preclinical models of primary pancreatic cancer and metastasis are urgently needed to test the therapy response ex vivo and facilitate ...

University Medical Center Schleswig-Holstein

Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of death from cancer. Its 5-year survival rate is less than 5%. This poor prognosis is mostly due to the cancer's early invasion and metastasis formation, leading to an initial diagnosis at an advanced incurable stage in the majority of patients. The only potentially curative treatment is radical surgical resection. The effect of current chemotherapeutics or radiotherapy is limited. Novel therapeutic strategies are therefore much needed. One of the hallmarks of PDAC is its abundant desmoplastic (stromal) reaction. The Hedgehog (Hh) signaling pathway is critical for embryologic development of the pancreas. Aberrant Hh signaling promotes pancreatic carcinogenesis, the maintenance of the tumor microenvironment and stromal growth. The canonical Hh-pathway in the tumor stroma has been targeted widely but has not yet lead to hopeful clinical results. Targeting both the tumor and its surrounding stroma through Hh pathway inhibition by also targeting non-canonical pathways as apparent in the tumor cell may therefore be a novel treatment strategy for PDAC. 

Regulation mechanisms of the hedgehog pathway in pancreatic cancer: a review.

 Borderline resectability in pancreatic cancer (PDAC) is currently debated.  Patients undergoing pancreatic resections for PDAC were identified from a prospectively maintained database. As new borderline criteria, the presence of any superior mesenterico-portal vein alteration (SMPV) and perivascular stranding of the superior mesenteric artery (SMA) was evaluated in preoperative imaging. The accuracy of established radiological borderline criteria as compared to the new borderline criteria in predicting R status (sensitivity/negative predictive value) and overall survival was assessed. (3)  118 patients undergoing pancreatic resections for PDAC from 2013 to 2018 were identified. Forty-three (36.4%) had radiological perivascular SMA stranding and 55 (46.6%) had SMPV alterations. Interrater reliability was 90% for SMA stranding and 87% for SMPV alterations. The new borderline definition including SMPV alterations and perivascular SMA stranding was the best predictor of conventional R status ( = 0.040, sensitivity 53%, negative predictive value 81%) and Leeds/Wittekind circumferential margin status ( = 0.050, sensitivity 73%, negative predictive value 79%) as compared to established borderline resectability definition criteria. Perivascular SMA stranding qualified as an independent negative prognostic parameter (HR 3.066, 95% CI 1.078-5.716,  = 0.036). : The radiological evaluation of any SMPV alteration and perivascular SMA stranding predicts R status and overall survival in PDAC patients, and may serve to identify potential candidates for neoadjuvant therapy.

Systematic Analysis of Accuracy in Predicting Complete Oncological Resection in Pancreatic Cancer Patients-Proposal of a New Simplified Borderline Resectability Definition.

In view of the limited capacities in intensive care units and the increasing economic burden, identification of risk factors could allow better and more efficient planning. Therefore, the aim of this study was to assess independent risk factors for the duration of intensive care unit stay after pancreatoduodenectomy (PD).

Risk Stratification for the Intensive Care Unit Following Pancreaticoduodenectomy.

The postoperative quality of life (QoL) after pancreatic surgery is frequently impaired. The aim of this study was to evaluate the QoL after pancreatic surgery and its influencing risk factors. Furthermore, an age-adjusted comparison with the normal population of Germany was performed.

Article	Year
Regulation mechanisms of the hedgehog pathway in pancreatic cancer: a review. JOP : Journal of the pancreas\| PubMed ID: 25640779	2015
Systematic Analysis of Accuracy in Predicting Complete Oncological Resection in Pancreatic Cancer Patients-Proposal of a New Simplified Borderline Resectability Definition. Cancers\| PubMed ID: 32260453	2020
Risk Stratification for the Intensive Care Unit Following Pancreaticoduodenectomy. Zentralblatt fur Chirurgie\| PubMed ID: 33045755	2020
Evaluation of Postoperative Quality of Life After Pancreatic Surgery and Determination of Influencing Risk Factors. Pancreas\| PubMed ID: 33835967	2021

Steffen Deichmann

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