Background: Few studies have compared perioperative and oncological outcomes between minimally invasive pancreatoduodenectomy (MIPD) and open pancreatoduodenectomy (OPD) for pancreatic ductal adenocarcinoma (PDAC). Methods: A retrospective review of patients undergoing MIPD and OPD for PDAC from January 2011 to December 2017 was performed. Perioperative, oncological, and survival outcomes were analyzed before and after propensity score matching (PSM). Results: Data from 1048 patients were evaluated (76 MIPD, 972 OPD). After PSM, 73 patients undergoing MIPD were matched with 219 patients undergoing OPD. Operation times were longer for MIPD than OPD (392 vs. 327 min, p < 0.001). Postoperative hospital stays were shorter for MIPD patients than OPD patients (12.4 vs. 14.2 days, p = 0.040). The rate of overall complications and postoperative pancreatic fistula did not differ between the two groups. Adjuvant treatment rates were higher following MIPD (80.8% vs. 59.8%, p = 0.002). With the exception of perineural invasion, no differences were seen between the two groups in pathological outcomes. The median overall survival and disease-free survival rates did not differ between the groups. Conclusions: MIPD showed shorter postoperative hospital stays and comparable perioperative and oncological outcomes to OPD for selected PDAC patients. Future randomized studies will be required to validate these findings.
Although laparoscopic distal pancreatectomy (LDP) has become more popular, the postoperative complication rate remains high. We sought to identify the risk factors for post-LDP complications. We examined 1227 patients who underwent LDP between March 2005 and December 2015 at a single large-volume center. We used logistic regression for the analysis. The overall (13.2%) and major (3.3%) complication rates were determined. Postoperative pancreatic fistula was the most frequent complication, and 58 patients (4.7%) had clinically significant (grade B) pancreatic fistulas. No 90-day mortality was recorded. Long operative time (≥200 min), large estimated blood loss (≥320 mL), LDP performed by an inexperienced surgeon (<50 cases), and concomitant splenectomy were identified as risk factors for overall complications using a logistic regression model. For major complications, male sex (p = 0.020), long operative time (p = 0.005), and LDP performed by an inexperienced surgeon (p = 0.026) were significant predictive factors. Using logistic regression analysis, surgery-related factors, including long operative time and LDP performed by an inexperienced surgeon, were correlated with overall and major complications of LDP. As LDP is a technically challenging procedure, surgery-related variables emerged as the main risk factors for postoperative complications. Appropriate patient selection and sufficient surgeon experience may be essential to reduce the complications of LDP.
Several studies have compared laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD) in patients with periampullary carcinoma; however, only a few studies have made such a comparison on patients with ampulla of Vater cancer (AVC). We compared the perioperative and oncologic outcomes between LPD and OPD in patients with AVC using propensity-score-matched analysis. A total of 359 patients underwent PD due to AVC during the study period (76 LPD, 283 OPD). After propensity score matching, the LPD group showed significantly longer operation time than did the OPD group (400.2 vs. 344.6 min, p < 0.001). Nevertheless, the LPD group had fewer painkiller administrations (8.3 vs. 11.1, p < 0.049), fewer Grade II or more severe postoperative complications (15.9% vs. 34.8%, p = 0.012), and shorter postoperative hospital stays (13.7 vs. 17.3 days, p = 0.048), compared with the OPD group. There was no significant difference in recurrence-free outcomes and overall survival between the two groups (p = 0.754 and 0.768, respectively). Compared with OPD, LPD for AVC had comparative oncologic outcomes with less pain, less postoperative morbidity, and shorter hospital stays. LPD may serve as a promising alternative to OPD in patients with AVC.
In this study, we evaluated the prognostic value of inflammation-based prognostic scores in patients undergoing curative surgery for pancreatic ductal adenocarcinoma (PDAC). A retrospective analysis was conducted for 914 patients undergoing curative surgical resection for PDAC between January 2011 and April 2016. Inflammation-based scores of modified Glasgow Prognostic Score (mGPS), neutrophil-lymphocyte ratio, and platelet-lymphocyte ratio were assessed. mGPS was classified as high (1 or 2) or low (0). Median age was 63 (range, 33–88) years; 538 patients (58.9%) were male. A high mGPS was independently associated with poor overall survival (OS) and disease-free survival (DFS) (median OS: 25.4 months vs. 20.4 months, p = 0.001; median DFS: 11.6 months vs. 9.3 months, p = 0.002), poor OS in patients with TNM stage I PDAC (44 months vs. 24.8 months, p = 0.001), and poor OS and DFS in patients with tumors located at the pancreatic head or uncinate process (OS: 25.4 months vs. 20.4 months; p = 0.007, DFS: 11.4 months vs. 8.87 months; p = 0.005). Preoperative mGPS was a significant prognostic factor for PDAC after curative resection; thus, mGPS can be a useful prognostic predictive factor in patients with TNM stage I PDAC, especially for tumors located at the head and uncinate.
KRAS mutation is a major regulator in the tumor progression of pancreatic cancer. Here, we compared the frequency and mutation burden of KRAS mutation subtypes with paired tumor tissue and blood in patients and examined their clinical significance. DNA from tumor tissues and cell-free DNA (cfDNA) from preoperative blood were obtained from 70 patients with pancreatic cancer. Subtypes and mutation burdens of KRAS G12D and G12V mutations were evaluated using droplet digital PCR. Comparing the presence of mutations in tissue, accumulative and simultaneous mutations of G12D or G12V were identified of 67 (95.7%), and 48 patients (68.6%). Conversely, in blood, they were only identified in 18 (25.7%) and four (5.7%) patients; respectively. Next, comparing the mutation burden in tissue, the mutation burden varied from less than 0.1 to more than five, whereas that of cfDNA in blood was mostly between one and five, as cases with a mutation burden lower than 0.1 and higher than five were rare. Finally, the presence of the G12V mutation alone in cfDNA and the combination of the G12V mutation with elevated CA 19-9 levels were associated with poor recurrence-free survival. These fundamental data on the KRAS mutation subtypes and their clinical significance could support their potential as predictive markers for postoperative recurrence.
Retrospective studies on the association between metformin and clinical outcomes have mainly been performed on patients with non-resectable pancreatic ductal adenocarcinoma and may have been affected by time-related bias. To avoid this bias, recent studies have used time-varying analysis; however, they have only considered the start date of metformin use and not the stop date. We studied 283 patients with type 2 diabetes and pancreatic ductal adenocarcinoma following pancreaticoduodenectomy, and performed analysis using a Cox model with time-varying covariates, while considering both start and stop dates of metformin use. When start and stop dates were not considered, the metformin group showed significantly better survival. Compared with previous studies, adjusted analysis based on Cox models with time-varying covariates only considering the start date of postoperative metformin use showed no significant differences in survival. However, although adjusted analysis considering both start and stop dates showed no significant difference in recurrence-free survival, the overall survival was significantly better in the metformin group (Hazard ratio (HR), 0.747; 95% confidence interval (CI), 0.562–0.993; p = 0.045). Time-varying analysis incorporating both start and stop dates thus revealed that metformin use is associated with a higher overall survival following pancreaticoduodenectomy in patients with type 2 diabetes and pancreatic ductal adenocarcinoma.