The past, present, and future status of multimodality treatment for resectable/borderline resectable pancreatic ductal adenocarcinoma

Background Many patients with borderline resectable/locally advanced pancreatic ductal adenocarcinoma (borderline resectable [BR]/locally advanced [LA] pancreatic ductal adenocarcinoma [PDAC]) undergoing resection will have positive resection margins (R1), which is associated with poor prognosis. It might be useful to preoperatively predict the margin (R) status. Methods Data from patients with BR/LA PDAC who underwent a pancreatectomy between 2008 and 2018 at Brigham and Women’s Hospital were retrospectively reviewed. Logistic regression analysis was used to evaluate the association between R status and relevant preoperative factors. Significant predictors of R1 resection on univariate analysis ( P < .1) were entered into a stepwise selection using the Akaike information criterion to define the final model. Results A total of 142 patients with BR/LA PDAC were included in the analysis, 60(42.3%) had R1 resections. In stepwise selection, the following factors were identified as positive predictors of an R1 resection: evidence of lymphadenopathy at diagnosis (OR = 2.06, 95% CI: 0.99-4.36, P = .056), the need for pancreaticoduodenectomy (OR = 3.81, 96% CI: 1.15-15.70, P = .040), extent of portal vein/superior mesenteric vein involvement at restaging (<180°, OR = 3.57, 95% CI: 1.00-17.00, P = .069, ≥180°, OR = 7,32, 95% CI: 1.75-39.87, P = .010), stable CA 19-9 serum levels (less than 50% decrease from diagnosis to restaging, OR = 2.27, 95% CI: 0.84-6.36 P = .107), and no preoperative FOLFIRINOX (OR = 2.17, 95% CI: 0.86-5.64, P = .103). The prognostic nomogram based on this model yielded a probability of achieving an R1 resection ranging from <5% (0 factors) to >70% (all 5 factors). Conclusions Relevant preoperative clinicopathological characteristics accurately predict positive resection margins in patients with BR/LA PDAC before resection. With further development, this model might be used to preoperatively guide surgical decision-making in patients with BR/LA PDAC.

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Pancreatic Ductal Adenocarcinoma: Preclinical in vitro and ex vivo Models

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.741162 ◽

2021 ◽

Vol 9 ◽

Author(s):

Beate Gündel ◽

Xinyuan Liu ◽

Matthias Löhr ◽

Rainer Heuchel

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Ex Vivo ◽

Treatment Options ◽

3D Cell Culture ◽

Therapy Resistance ◽

Ductal Adenocarcinoma ◽

The Past ◽

Slow Progress

Pancreatic ductal adenocarcinoma (PDAC) is one of the most overlooked cancers despite its dismal median survival time of 6 months. The biggest challenges in improving patient survival are late diagnosis due to lack of diagnostic markers, and limited treatment options due to almost complete therapy resistance. The past decades of research identified the dense stroma and the complex interplay/crosstalk between the cancer- and the different stromal cells as the main culprits for the slow progress in improving patient outcome. For better ex vivo simulation of this complex tumor microenvironment the models used in PDAC research likewise need to become more diverse. Depending on the focus of the investigation, several in vitro and in vivo models for PDAC have been established in the past years. Particularly, 3D cell culture such as spheroids and organoids have become more frequently used. This review aims to examine current PDAC in vitro models, their inherent limitations, and their successful implementations in research.

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Comment on “Perineural Invasion In Pancreatic Ductal Adenocarcinoma—What Can We Learn From The Past?’’

Annals of Surgery Open ◽

10.1097/as9.0000000000000062 ◽

2021 ◽

Vol 2 (2) ◽

pp. e062

Author(s):

Xiaofei Shen

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Perineural Invasion ◽

Ductal Adenocarcinoma ◽

The Past

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Pancreatic Ductal Adenocarcinoma (PDAC) Organoids: The Shining Light at the End of the Tunnel for Drug Response Prediction and Personalized Medicine

Cancers ◽

10.3390/cancers12102750 ◽

2020 ◽

Vol 12 (10) ◽

pp. 2750

Author(s):

Pierre-Olivier Frappart ◽

Thomas G. Hofmann

Keyword(s):

Personalized Medicine ◽

Pancreatic Ductal Adenocarcinoma ◽

Drug Response ◽

Treatment Options ◽

Response Prediction ◽

Ductal Adenocarcinoma ◽

Chemotherapy Treatment ◽

The Past ◽

Therapeutic Tools ◽

And Personalized Medicine

Pancreatic ductal adenocarcinoma (PDAC) represents 90% of pancreatic malignancies. In contrast to many other tumor entities, the prognosis of PDAC has not significantly improved during the past thirty years. Patients are often diagnosed too late, leading to an overall five-year survival rate below 10%. More dramatically, PDAC cases are on the rise and it is expected to become the second leading cause of death by cancer in western countries by 2030. Currently, the use of gemcitabine/nab-paclitaxel or FOLFIRINOX remains the standard chemotherapy treatment but still with limited efficiency. There is an urgent need for the development of early diagnostic and therapeutic tools. To this point, in the past 5 years, organoid technology has emerged as a revolution in the field of PDAC personalized medicine. Here, we are reviewing and discussing the current technical and scientific knowledge on PDAC organoids, their future perspectives, and how they can represent a game change in the fight against PDAC by improving both diagnosis and treatment options.

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