Background
Data on long-term actual survival in patients with surgically resected pancreatic ductal adenocarcinoma (PDAC) are limited. The aim of this study was to evaluate the actual 5-year ...disease-specific survival (DSS) and post-recurrence survival (PRS) in patients who underwent pancreatectomy for PDAC.
Methods
Data from patients who underwent upfront surgical resection for PDAC between 2009 and 2014 were analyzed. Exclusion criteria included PDAC arising in the background of an intraductal papillary mucinous neoplasm and patients undergoing neoadjuvant therapy. All alive patients had a minimum follow-up of 60 months. Independent predictors of PRS, DSS, and survival > 5 years were searched.
Results
Of the 176 patients included in this study, 48 (27%) were alive at 5 years, but only 20 (11%) had no recurrence. Median PRS was 12 months. In the 154 patients after disease recurrence, independent predictors of shorter PRS were total pancreatectomy, G3 tumors, early recurrence (< 12 months from surgery), and no treatment at recurrence. Median DSS was 36 months. Independent predictors of DSS were CA19-9 at diagnosis > 200 U/mL, total pancreatectomy, N + status, G3 tumors and perineural invasion. Only the absence of perineural invasion was a favorable independent predictor of survival > 5 years.
Conclusion
More than one-quarter of patients who underwent upfront surgery for PDAC were alive after 5 years, although only 11% of the initial cohort were cancer-free. Long-term survival can also be achieved in tumors with more favorable biology in an upfront setting followed by adjuvant chemotherapy.
Background
The prognostic role of resection margins in pancreatic ductal adenocarcinoma (PDAC) is debated. This study aimed to investigate the impact that global and individual resection margin ...status after pancreatic head resection for PDAC has on disease-free survival (DFS) and disease-specific survival (DSS).
Methods
Surgical specimens of pancreaticoduodenectomy/total pancreatectomy performed for PDAC were examined with a standardized protocol. Surgical margin status (biliary, pancreatic neck, duodenal, anterior and posterior pancreatic, superior mesenteric vein groove and superior mesenteric artery margins) was classified as the presence of malignant cells (1) directly at the inked surface (
R
1 direct), (2) within less than 1 mm (
R
1 ≤ 1 mm), or (3) with a distance greater than 1 mm (
R
0). Patients with a positive neck margin at the final histology were excluded from the study.
Results
Of the 362 patients included in the study, 179 patients (49.4 %) had an
R
0 resection, 123 patients (34 %) had an
R
1 ≤ 1 mm resection, and 60 patients (16.6 %) had an
R
1 direct resection. The independent predictors of DFS were
R
1 direct resection (hazard ratio HR, 1.49),
R
1 ≤ 1 mm resection (HR, 1.38), involvement of one margin (HR, 1.36), and involvement of two margins or more (HR, 1.55). When surgical margins were analyzed separately, only
R
1 ≤ 1 mm superior mesenteric vein margin (HR, 1.58) and
R
1 direct posterior margin (HR, 1.69) were independently associated with DFS.
Conclusions
Positive
R
status is an independent predictor of DFS (
R
1 direct and
R
1 ≤ 1 mm definitions) and of DSS (
R
1 direct). The presence of multiple positive margins is a risk factor for cancer recurrence and poor survival. Different surgical margins could have different prognostic roles.
Background
Pancreatic ductal adenocarcinoma (PDAC) is currently the fourth leading cause of cancer-related death in the USA. A wealth of evidence has demonstrated the chemopreventive activity of ...aspirin, statins, and metformin against PDAC. The aim of this study is to investigate the effect of aspirin, statins, and metformin on disease-free survival (DFS) and disease-specific survival (DSS) in a large population of PDAC patients undergoing pancreatic resection.
Patients and Methods
All patients who underwent pancreatic resections between January 2015 and September 2018 were retrospectively reviewed. The potentially “chemopreventive agents” considered for the analysis were aspirin, statins, and metformin. Drug use was defined in case of regular assumption at least 6 months before diagnosis and regularly after surgery along the follow-up period.
Results
A total of 430 patients were enrolled in this study, with median DFS and DSS of 21 months (IQR 13–30) months and 34 (IQR 26–52) months, respectively. On multivariable analysis, use of aspirin was associated with better DFS (HR: 0.62;
p
= 0.038). Metformin was associated with better DFS, without reaching statistical significance (
p
= 0.083). Use of statins did not influence DFS in the studied population. Aspirin, metformin, and statins were not associated with better DSS on multivariable analysis. Factors influencing DSS were pT3/pT4, N1, N2, no adjuvant treatment, G3, and ASA score > 3.
Conclusions
The results suggest that chronic use of aspirin is associated with increased DFS but not with better DSS after surgical resection in patients with PDAC.
Current treatment of potentially resectable pancreatic ductal adenocarcinoma (PDAC) includes pancreatic resection followed by adjuvant therapy. Aim of this study is to identify factors that are ...related with overall and early recurrence after pancreatectomy for PDAC.
Retrospective analysis of patients with histologically confirmed PDAC who underwent pancreatectomy between September 2009 and December 2014. Early relapse was defined as recurrence within 12 months after surgery. Univariate/multivariate analysis was performed to identify prognostic factors for recurrence.
261 patients were included (54% males, mean age 67 years). Neoadjuvant and adjuvant treatments were performed in 55 (21%) and 243 (93%) patients. Overall morbidity was 56% with a rate of grade 3–4 Clavien–Dindo complications of 25%. Median disease-free survival was 18 months. Multivariate analysis identified nodal metastases (OR: 3.6) and perineural invasion (OR: 2.14) as independent predictors of disease recurrence in the entire cohort. 76 patients (29%) had an early recurrence. Poorly differentiated tumors (OR: 3.019) and grade 3–4 Clavien–Dindo complications (OR: 3.05) were independent risk factors for early recurrence.
Although overall recurrence is associated with tumor-related factors, severe postoperative complications represent an independent predictor of early recurrence. Patients at increased risk of severe postoperative complications may benefit from neoadjuvant therapy.
The choice of the most appropriate suture threads for pancreatic anastomoses may play an important role in reducing the incidence of post-operative pancreatic fistula (POPF). The literature on this ...topic is still not conclusive. The aim of this study was to analyze the mechanical characteristics of suture materials to find the best suture threads for pancreatic anastomoses. A single-axial electromagnetic actuation machine was used to obtain the stress-deformation relationship curves and to measure both the ultimate tensile strength (UTS) and the Young's modulus at the 0-3% deformation range (E
) of four different suture materials (Poliglecaprone 25, Polydioxanone, Polyglactin 910, and Polypropylene) at baseline and after incubation in saline solution, bile, and pancreatic juice for 1, 3, and 7 days. Polydioxanone and Polypropylene showed stable values of UTS and E
in all conditions. Polyglactin 910 presented significant UTS and E
variations between different time intervals in all types of liquids analyzed. Poliglecaprone 25 lost half of its strength in all biological liquids analyzed but maintained low E
values, which could reduce the risk of lacerations of soft tissues. These results suggest that Polydioxanone and Poliglecaprone 25 could be the best suture materials to use for pancreatic anastomoses. In vivo experiments will be organized to obtain further confirmations of this in vitro evidence.
We systematically evaluate the current evidence regarding Ki-67 as a prognostic factor in pancreatic neuroendocrine neoplasms to evaluate the differences of this marker in primary tumors and in ...distant metastases as well as the values of Ki-67 obtained by fine needle aspiration and by histology.
The literature search was carried out using the MEDLINE/PubMed database, and only papers published in the last 10 years were selected.
The pancreatic tissue suitable for Ki-67 evaluation was obtained from surgical specimens in the majority of the studies. There was a concordance of 83% between preoperative and postoperative Ki-67 evaluation. Pooling the data of the studies which compared the Ki-67 values obtained in both cytological and surgical specimens, we found that they were not related. The assessment of Ki-67 was manual in the majority of the papers considered for this review. In order to eliminate manual counting, several imaging methods have been developed but none of them are routinely used at present. Twenty-two studies also explored the role of Ki-67 utilized as a prognostic marker for pancreatic neuroendocrine neoplasms and the majority of them showed that Ki-67 is a good prognostic marker of disease progression. Three studies explored the Ki-67 value in metastatic sites and one study demonstrated that, in metachronous and synchronous liver metastases, there was no significant variation in the index of proliferation.
Ki-67 is a reliable prognostic marker for pancreatic neuroendocrine neoplasms.
Introduction: Infections caused by multidrug-resistant bacteria (MDR) occur more frequently after pancreaticoduodenectomy (PD) compared to other abdominal surgeries, and infective complications ...represent a major determinant of postoperative morbidity following PD. Preoperative biliary stent (PBS) placement often leads to biliary contamination, which plays a significant role in postoperative infections. The aim of this study is to evaluate the impact of MDR contamination on short-term postoperative outcomes in patients undergoing PD and to evaluate the relationship between MDR bacteria, PBS, and bile contamination. Methods: This is a retrospective study based on a prospectively maintained database including 825 consecutive patients who underwent pancreaticoduodenectomies (PDs). All procedures were performed by experienced pancreatic surgeons at a high-volume center and the patients were managed according to the same perioperative enhanced recovery protocol. Results: MDR bacteria were present in 17.5% of bile cultures, exclusively within the stented group. At the multivariate analysis, the development of major postoperative complications (MPC) was correlated with the presence of MDR bacteria in the bile (OR 1.66, 95% CI: 1.1–2.52; p = 0.02). MDR bacteria were detected early in the surgical drainage in 144 out of 825 patients (12.1%), with 72.2% having a previous biliary stent placement and 27.8% without stents (p < 0.001). Moreover, the development of an MPC was associated with the presence of MDR bacteria in the drainage (OR = 1.81, 95% CI: 1.21–2.73, p = 0.0042). Conclusions: We demonstrated that MDR contamination worsens the short-term outcomes of patients undergoing PDs. Specifically, when MDR bacteria are present in both the bile and drainage, there is a statistically significant increase in the incidence of major postoperative complications (MPC). Our data suggest that the majority of MDR surgical site infections stem from biliary contamination resulting from the placement of a preoperative biliary stent (PBS).
Survival after surgery for pancreatic ductal adenocarcinoma (PDAC) remains poor, due to early recurrence (ER) of the disease. A global definition of ER is lacking and different cut-off values (6, 8, ...and 12 months) have been adopted. The aims of this study were to define the optimal cut-off for the definition of ER and predictive factors for ER.
Recurrence was recorded for all consecutive patients undergoing upfront surgery for PDAC at our institute between 2010 and 2017. Receiver operating characteristic (ROC) curves were utilized, to estimate the optimal cut-off for the definition of ER as a predictive factor for poor post-progression survival (PPS). To identify predictive factors of ER, univariable and multivariable logistic regression models were used.
Three hundred and fifty one cases were retrospectively evaluated. The recurrence rate was 76.9%. ER rates were 29.0%, 37.6%, and 47.6%, when adopting 6, 8, and 12 months as cut-offs, respectively. A significant difference in median PPS was only shown between ER and late recurrence using 12 months as cut-off (
= 0.005). In the multivariate analysis, a pre-operative value of CA 19-9 > 70.5 UI/L (OR 3.10 (1.41-6.81);
= 0.005) and the omission of adjuvant treatment (OR 0.18 (0.08-0.41);
< 0.001) were significant predictive factors of ER.
A twelve-months cut-off should be adopted for the definition of ER. Almost 50% of upfront-resected patients presented ER, and it significantly affected the prognosis. A high preoperative value of CA 19-9 and the omission of adjuvant treatment were the only predictive factors for ER.
Previous studies show encouraging oncologic outcomes for neoadjuvant chemotherapy (NACT) in the setting of pancreatic ductal adenocarcinoma (PDAC). However, recent literature reported an increased ...clinical burden in patients undergoing pancreaticoduodenectomy (PD) following NACT. Therefore, the aim of our study was to assess the impact of NACT on postoperative outcomes and recovery after PD.
A retrospective propensity score-matched study was performed including all patients who underwent PD for PDAC in a single center between 2015 and 2018. Patients treated with NACT for resectable, borderline resectable or locally advanced PDAC were matched based on nearest neighbor propensity scores in a 1:1 ratio to patients who underwent upfront resection. Propensity scores were calculated using 7 perioperative variables, including gender, age, BMI, ASA score, Charlson-Deyo comorbidity score, fistula risk score (FRS), vascular resection. Primary outcome was the number and severity of complications at 90-days after surgery measured by the comprehensive complication index (CCI). Data are reported as median (IQR) or number of patients (%).
Of 283 resected patients, 95 (34%) were treated with NACT. Before matching, NACT patients were younger, had less comorbidities (Charlson-Deyo score 0 vs. 1,
= 0.04), similar FRS 2 (0-3) for both groups, and more vascular resections performed
= 28 (30%) vs.
= 26 (14%),
< 0.01. After propensity-score matching, preoperative and intraoperative characteristics were comparable. Postoperatively, CCI was similar between groups 8.7 (0-29.6) for both groups,
= 0.59. NACT patients had a non-statistically significant increase in superficial incisional surgical site infections
= 12 (13%) vs. 6 (6%),
= 0.14, while no difference was found for overall infectious complications and organ-space SSI. The occurrence of clinically-relevant pancreatic fistula was similar between groups 10 (11%) vs. 13 (14%),
= 0.51. No difference was found between groups for length of hospital stay 8 (7-15) vs. 8 (7-14) days,
= 0.62, and functional recovery outcomes.
After propensity score adjustment for perioperative risk factors, NACT did not worsen postoperative outcomes and functional recovery following PD for PDAC compared to upfront resection.
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