Laparoscopic Pancreaticoduodenectomy Versus Conventional Open Approach for Patients With Pancreatic Duct Adenocarcinoma: An Up-to-Date Systematic Review and Meta-Analysis

BackgroundTo compare perioperative and oncological outcomes of pancreatic duct adenocarcinoma (PDAC) after laparoscopic versus open pancreaticoduodenectomy (LPD vs. OPD), we performed a meta-analysis of currently available propensity score matching studies and large-scale retrospective cohorts to compare the safety and overall effect of LPD to OPD for patients with PDAC.MethodsA meta-analysis was registered at PROSPERO and the registration number is CRD42021250395. PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched based on a defined search strategy to identify eligible studies before March 2021. Data on operative times, blood loss, 30-day mortality, reoperation, length of hospital stay (LOS), overall morbidity, Clavien–Dindo ≥3 complications, postoperative pancreatic fistula (POPF), blood transfusion, delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), and oncologic outcomes (R0 resection, lymph node dissection, overall survival, and long-term survival) were subjected to meta-analysis.ResultsOverall, we identified 10 retrospective studies enrolling a total of 11,535 patients (1,514 and 10,021 patients underwent LPD and OPD, respectively). The present meta-analysis showed that there were no significant differences in overall survival time, 1-year survival, 2-year survival, 30-day mortality, Clavien-Dindo ≥3 complications, POPF, DGE, PPH, and lymph node dissection between the LPD and OPD groups. Nevertheless, compared with the OPD group, LPD resulted in significantly higher rate of R0 resection (OR: 1.22; 95% CI 1.06–1.40; p = 0.005), longer operative time (WMD: 60.01 min; 95% CI 23.23–96.79; p = 0.001), lower Clavien–Dindo grade ≥III rate (p = 0.02), less blood loss (WMD: −96.49 ml; 95% CI −165.14 to −27.83; p = 0.006), lower overall morbidity rate (OR: 0.65; 95% CI 0.50 to 0.85; p = 0.002), shorter LOS (MD = −2.73; 95% CI −4.44 to −1.03; p = 0.002), higher 4-year survival time (p = 0.04), 5-year survival time (p = 0.001), and earlier time to starting adjuvant chemotherapy after surgery (OR: −10.86; 95% CI −19.42 to −2.30; p = 0.01).ConclusionsLPD is a safe and feasible alternative to OPD for patients with PDAC, and compared with OPD, LPD seemed to provide a similar OS.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails.

A personalized approach to pancreatic ductal adenocarcinoma and its application in surgical practice

Pancreatic duct adenocarcinoma is an aggressive tumor which constitutes the fourth leading cause of cancer-related mortality in the USA. Despite the fact that surgery is an integral part of treatment, 5-year survival rates remain unfavorable, partly because of the complex genetic background, delayed diagnosis and also the absence of effective therapeutic approaches. To optimize surgery’s results in recent years, the use of patients’ genetic profile has been implemented through classification into subtypes; subtypes based on mutations which could efficiently lead oncologists to the path of targeted novel neoadjuvant regimens. This approach aims to achieve the most effective selection of patients undergoing surgery, to increase the number of potentially resectable tumors and also control micro-metastases, aiming to extend overall survival.

An Organotypic Microcosm for the Pancreatic Tumor Microenvironment

Pancreatic duct adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related deaths in the next few years. Unfortunately, the development of novel therapies for PDAC has been challenged by a uniquely complex tumor microenvironment. The development of in vitro cancer organoids in recent years has demonstrated potential to increase therapies for patients with PDAC. Organoids have been established from PDAC murine and human tissues and they are representative of the primary tumor. Further, organoids have been shown beneficial in studies of molecular mechanisms and drug sensitivity testing. This review will cover the use of organoids to study PDAC development, invasiveness, and therapeutic resistance in the context of the tumor microenvironment, which is characterized by a dense desmoplastic reaction, hindered immune activity, and pro-tumor metabolic signaling. We describe investigations utilizing organoids to characterize the tumor microenvironment and also describe their limitations. Overall, organoids have great potential to serve as a versatile model of drug response and may be used to increase available therapies and improve survival for patients with PDAC.