scholarly journals Recurrence Patterns for Pancreatic Ductal Adenocarcinoma after Upfront Resection Versus Resection Following Neoadjuvant Therapy: A Comprehensive Meta-Analysis

2020 ◽  
Vol 9 (7) ◽  
pp. 2132
Author(s):  
Bathiya Ratnayake ◽  
Alina Y. Savastyuk ◽  
Manu Nayar ◽  
Colin H. Wilson ◽  
John A. Windsor ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Neoadjuvant Therapy ◽  
Recurrence Rate ◽  
Locoregional Recurrence ◽  
Ductal Adenocarcinoma ◽  
Resectable Pancreatic Cancer ◽  
Recurrence Rates ◽  
Recurrence Patterns ◽  
Patterns Of Recurrence

Background: Neoadjuvant therapy (NAT) represents a paradigm shift in the management of patients with pancreatic ductal adenocarcinoma (PDAC) with perceived benefits including a higher R0 rate. However, it is unclear whether NAT affects the sites and patterns of recurrence after surgery. This review seeks to compare sites and patterns of recurrence after resection between patients undergoing upfront surgery (US) or after NAT. Methods: The EMBASE, SCOPUS, PubMed, and Cochrane library databases were systematically searched to identify eligible studies that compare recurrence patterns between patients who had NAT (followed by resection) with those that had US. The primary outcome included site-specific recurrence. Results: 26 articles were identified including 4986 patients who underwent resection. Borderline resectable pancreatic cancer (BRPC, 47% 1074/2264) was the most common, followed by resectable pancreatic cancer (RPC 42%, 949/2264). The weighted overall recurrence rates were lower among the NAT group, 63.4% vs. 74% (US) (OR 0.67 (CI 0.52–0.87), p = 0.006). The overall weighted locoregional recurrence rate was lower amongst patients who received NAT when compared to US (12% vs. 27% OR 0.39 (CI 0.22–0.70), p = 0.004). In BRPC, locoregional recurrence rates improved with NAT (NAT 25.8% US 37.7% OR 0.62 (CI 0.44–0.87), p = 0.007). NAT was associated with a lower weighted liver recurrence rate (NAT 19.4% US 30.1% OR 0.55 (CI 0.34–0.89), p = 0.023). Lung and peritoneal recurrence rates did not differ between NAT and US cohorts (p = 0.705 and p = 0.549 respectively). NAT was associated with a significantly longer weighted mean time to first recurrence 18.8 months compared to US (15.7 months) (OR 0.18 (CI 0.05–0.32), p = 0.015). Conclusion: NAT was associated with lower overall recurrence rate and improved locoregional disease control particularly for those with BRPC. Although the burden of liver metastases was less, there was no overall effect upon distant metastatic disease.

scholarly journals Analysis of the Curative Effect of Neoadjuvant Therapy on Pancreatic Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Liqiong Yang ◽  
Yun Bai ◽  
Qing Li ◽  
Jie Chen ◽  
Fangfang Liu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Neoadjuvant Therapy ◽  
Adverse Reactions ◽  
Neoadjuvant Chemoradiotherapy ◽  
Primary Treatment ◽  
R0 Resection ◽  
Resectable Pancreatic Cancer ◽  
Recurrence Rates ◽  
Borderline Resectable

The prevalence of pancreatic cancer is sharply increasing recently, which significantly increases the economic burden of the population. At present, the primary treatment of resectable pancreatic cancer is surgical resection, followed by chemotherapy with or without radiation. However, the recurrence rates remain high even after R0 resection. This treatment strategy does not distinguish undetected metastatic disease, and it is prone to postoperative complications. Neoadjuvant therapies, including neoadjuvant chemotherapy and radiotherapy, is being increasingly utilized in borderline resectable as well as resectable pancreatic cancer. This review summarized and discussed clinical trials of neoadjuvant therapy for pancreatic cancer, comparing resection rates, outcome measures, and adverse reactions between neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy.

scholarly journals Neoadjuvant Treatment for Borderline Resectable Pancreatic Ductal Adenocarcinoma

2018 ◽  
Vol 36 (6) ◽  
pp. 455-461 ◽  
Author(s):  
Benedikt Kaufmann ◽  
Daniel Hartmann ◽  
Jan G. D’Haese ◽  
Pavel Stupakov ◽  
Dejan Radenkovic ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Neoadjuvant Therapy ◽  
Neoadjuvant Treatment ◽  
Ductal Adenocarcinoma ◽  
Preoperative Treatment ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Treatment Regimens ◽  
Dismal Prognosis ◽  
First Choice

One of the main reasons for the dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) is its late diagnosis. At the time of presentation, only approximately 15–20% of all patients with PDAC are considered resectable and around 30% are considered borderline resectable. A surgical approach, which is the only curative option, is limited in borderline resectable patients by local involvement of surrounding structures. In borderline resectable pancreatic cancer (BRPC), neoadjuvant treatment regimens have been introduced with the rationale to downstage and downsize the tumor in order to enable resection and eliminate ­microscopic distant metastases. However, there are no official guidelines for the preoperative treatment of BRPC. In the majority of cases, patients are administered ­Gemcitabine-based or FOLFIRINOX-based chemotherapy regimens with or without radiation. Radiologic restaging after neoadjuvant therapy has to be judged with caution when it comes to predict tumor response and resectability, since inflammation induced by neoadjuvant therapy may mimic solid tumor. Patients who do not show any disease progression during neoadjuvant therapy should be offered surgical exploration, since a high percentage is likely to undergo resection with negative margins (R0) and, thus, achieve improved overall survival although imaging judged it unlikely. Despite the promising new approaches of neoadjuvant treatment regimens during the last 2 decades, surgery remains the first choice if the tumor appears to be primary resectable at the time of diagnosis. At present, there are no international guidelines regarding the preoperative treatment of BRPC. Therefore, in order to standardize and adjust neoadjuvant treatment in the future, new guidelines have to be determined on the basis of upcoming prospective randomized studies.

scholarly journals Meta-analysis of the impact of neoadjuvant therapy on patterns of recurrence in pancreatic ductal adenocarcinoma

BJS Open ◽  
2018 ◽  
Vol 2 (2) ◽  
pp. 52-61 ◽  
Author(s):  
S. Schorn ◽  
I. E. Demir ◽  
N. Samm ◽  
F. Scheufele ◽  
L. Calavrezos ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Neoadjuvant Therapy ◽  
Meta Analysis ◽  
Ductal Adenocarcinoma ◽  
The Impact ◽  
Patterns Of Recurrence

scholarly journals A Proteomic Study on the Personalized Protein Corona of Liposomes. Relevance for Early Diagnosis of Pancreatic DUCTAL Adenocarcinoma and Biomarker Detection

2021 ◽  
Vol 2 (2) ◽  
pp. 82-93
Author(s):  
Luca Digiacomo ◽  
Francesca Giulimondi ◽  
Daniela Pozzi ◽  
Alessandro Coppola ◽  
Vincenzo La Vaccara ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Diagnosis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Protein Corona ◽  
Detection Sensitivity ◽  
Ductal Adenocarcinoma ◽  
Protein Biomarkers ◽  
Ca 19.9 ◽  
Proteomic Study

Due to late diagnosis, high incidence of metastasis, and poor survival rate, pancreatic cancer is one of the most leading cause of cancer-related death. Although manifold recent efforts have been done to achieve an early diagnosis of pancreatic cancer, CA-19.9 is currently the unique biomarker that is adopted for the detection, despite its limits in terms of sensitivity and specificity. To identify potential protein biomarkers for pancreatic ductal adenocarcinoma (PDAC), we used three model liposomes as nanoplatforms that accumulate proteins from human plasma and studied the composition of this biomolecular layer, which is known as protein corona. Indeed, plasma proteins adsorb on nanoparticle surface according to their abundance and affinity to the employed nanomaterial, thus even small differences between healthy and PDAC protein expression levels can be, in principle, detected. By mass spectrometry experiments, we quantified such differences and identified possible biomarkers for PDAC. Some of them are already known to exhibit different expressions in PDAC proteomes, whereas the role of other relevant proteins is still not clear. Therefore, we predict that the employment of nanomaterials and their protein corona may represent a useful tool to amplify the detection sensitivity of cancer biomarkers, which may be used for the early diagnosis of PDAC, with clinical implication for the subsequent therapy in the context of personalized medicine.

scholarly journals The role of FDG PET/CT or PET/MRI in assessing response to neoadjuvant therapy for patients with borderline or resectable pancreatic cancer: a systematic literature review

2021 ◽  
Author(s):  
Laura Evangelista ◽  
Pietro Zucchetta ◽  
Lucia Moletta ◽  
Simone Serafini ◽  
Gianluca Cassarino ◽  
...  
Keyword(s):  
Neoadjuvant Therapy ◽  
Fdg Pet ◽  
Standardized Uptake Value ◽  
Response To Therapy ◽  
Ductal Adenocarcinoma ◽  
Resectable Pancreatic Cancer ◽  
Number Of Patients ◽  
Pet Ct ◽  
Fdg Pet Ct

AbstractThe aim of the present systematic review is to examine the role of fluorodeoxyglucose (FDG) positron emission tomography (PET) associated with computed tomography (CT) or magnetic resonance imaging (MRI) in assessing response to preoperative chemotherapy or chemoradiotherapy (CRT) for patients with borderline and resectable pancreatic ductal adenocarcinoma (PDAC). Three researchers ran a database query in PubMed, Web of Science and EMBASE. The total number of patients considered was 488. The most often used parameters of response to therapy were the reductions in the maximum standardized uptake value (SUVmax) or the peak standardized uptake lean mass (SULpeak). Patients whose SUVs were higher at the baseline (before CRT) were associated with a better response to therapy and a better overall survival. SUVs remaining high after neoadjuvant therapy correlated with a poor prognosis. Available data indicate that FDG PET/CT or PET/MRI can be useful for predicting and assessing response to CRT in patients with resectable or borderline PDAC.

scholarly journals Roles of autophagy and metabolism in pancreatic cancer cell adaptation to environmental challenges

2017 ◽  
Vol 313 (5) ◽  
pp. G524-G536 ◽  
Author(s):  
Sandrina Maertin ◽  
Jason M. Elperin ◽  
Ethan Lotshaw ◽  
Matthias Sendler ◽  
Steven D. Speakman ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Oxidative Phosphorylation ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Environmental Stresses ◽  
Ductal Adenocarcinoma ◽  
Cell Adaptation ◽  
Autophagy Inhibition ◽  
Dependent Mechanism

Pancreatic ductal adenocarcinoma (PDAC) displays extensive and poorly vascularized desmoplastic stromal reaction, and therefore, pancreatic cancer (PaCa) cells are confronted with nutrient deprivation and hypoxia. Here, we investigate the roles of autophagy and metabolism in PaCa cell adaptation to environmental stresses, amino acid (AA) depletion, and hypoxia. It is known that in healthy cells, basal autophagy is at a low level, but it is greatly activated by environmental stresses. By contrast, we find that in PaCa cells, basal autophagic activity is relatively high, but AA depletion and hypoxia activate autophagy only weakly or not at all, due to their failure to inhibit mechanistic target of rapamycin. Basal, but not stress-induced, autophagy is necessary for PaCa cell proliferation, and AA supply is even more critical to maintain PaCa cell growth. To gain insight into the underlying mechanisms, we analyzed the effects of autophagy inhibition and AA depletion on PaCa cell metabolism. PaCa cells display mixed oxidative/glycolytic metabolism, with oxidative phosphorylation (OXPHOS) predominant. Both autophagy inhibition and AA depletion dramatically decreased OXPHOS; furthermore, pharmacologic inhibitors of OXPHOS suppressed PaCa cell proliferation. The data indicate that the maintenance of OXPHOS is a key mechanism through which autophagy and AA supply support PaCa cell growth. We find that the expression of oncogenic activation mutation in GTPase Kras markedly promotes basal autophagy and stimulates OXPHOS through an autophagy-dependent mechanism. The results suggest that approaches aimed to suppress OXPHOS, particularly through limiting AA supply, could be beneficial in treating PDAC. NEW & NOTEWORTHY Cancer cells in the highly desmoplastic pancreatic ductal adenocarcinoma confront nutrient [i.e., amino acids (AA)] deprivation and hypoxia, but how pancreatic cancer (PaCa) cells adapt to these conditions is poorly understood. This study provides evidence that the maintenance of mitochondrial function, in particular, oxidative phosphorylation (OXPHOS), is a key mechanism that supports PaCa cell growth, both in normal conditions and under the environmental stresses. OXPHOS in PaCa cells critically depends on autophagy and AA supply. Furthermore, the oncogenic activation mutation in GTPase Kras upregulates OXPHOS through an autophagy-dependent mechanism.

Patterns of recurrence after curative resection of pancreatic ductal adenocarcinoma

2009 ◽  
Vol 35 (6) ◽  
pp. 600-604 ◽  
Author(s):  
A. Van den broeck ◽  
G. Sergeant ◽  
N. Ectors ◽  
W. Van Steenbergen ◽  
R. Aerts ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Curative Resection ◽  
Ductal Adenocarcinoma ◽  
Patterns Of Recurrence

41 Cathepsin D Expression in Pancreatic Ductal Adenocarcinoma (PDAC) Cells Increases Proliferation and Reduces Survival of Pancreatic Cancer Patients

2015 ◽  
Vol 148 (4) ◽  
pp. S-13
Author(s):  
Ujjwal M. Mahajan ◽  
Enno Langhoff ◽  
Eithne Costello ◽  
William Greenhalf ◽  
Christopher Halloran ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Patients ◽  
Cathepsin D ◽  
Ductal Adenocarcinoma
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