Pancreatectomy For Pancreatic Ductal Adenocarcinoma Research Articles

Risk factors and oncological outcome of conversion in minimally invasive distal pancreatectomy for pancreatic ductal adenocarcinoma: a propensity score matched study

Background: Minimally invasive distal pancreatectomy (MIDP) for pancreatic ductal adenocarcinoma (PDAC) is associated with shorter hospital stay, less morbidity, decreased intra-operative blood loss and similar oncological outcomes. However, the high conversion rate to open (15–56%), remains worrisome. The risks factors and the impact of conversion on the oncological outcomes is yet to be determined. Methods: A post hoc analysis of the pan-European retrospective cohort including 1212 patients from 34 centres, undergoing MIDP and open distal pancreatectomy (ODP) for PDAC between January 1st 2007 and July 1st 2015. Potential risk factors for conversion were identified by multivariable logistic regression analysis. The reason for conversion was classified as non-urgent (i.e. extensive tumour involvement or adhesions) or urgent (i.e. bleeding or perforation). Patients after conversion were matched (ratio 1:2, match tolerance 0.001) via propensity scores to patients undergoing ODP. Results: Among 345 patients undergoing MIDP, there were 68 (20%) conversions, mostly because of a non-urgent reason (n = 40, 59%). The converted MIDP procedures had a longer operative time, more intra-operative blood loss, less R0 resections, longer hospital stay and a higher incidence of cancer recurrence. After matching (61 converted MIDP vs 122 ODP), no differences in R0 resection rate, recurrence and overall survival were seen. Urgent conversions were associated with, an increase in blood loss and morbidity without a difference in survival. 90-day mortality was comparable between all groups. While non-urgent conversions resulted in comparable blood loss and morbidity. Tumour proximity (<1 cm) to vascular structures other than splenic vessels on pre-operative imaging was found to be associated with an increased risk of conversion (OR 3.801, 95% CI 1.042–13.861), while increased BMI, tumour size and multivisceral involvement of tumour did not predict conversion. Conclusion: Patients undergoing MIDP for PDAC with tumour proximity to vascular structures on preoperative imaging have an increased risk of conversion. MIDP patients requiring a conversion for a non-urgent cause, have comparable surgical and oncological outcomes in comparison to oncological equivalent patients undergoing ODP.

The oncological safety in minimally invasive versus open distal pancreatectomy for pancreatic ductal adenocarcinoma: a systematic review and meta-analysis

The safety of minimally invasive distal pancreatectomy (MIDP) and open distal pancreatectomy (ODP) regarding oncological outcomes of pancreatic ductal adenocarcinoma (PDAC) remains inconclusive. Therefore, the aim of this study was to examine the oncological safety of MIDP and ODP for PDAC. Major databases including PubMed, Embase, Science Citation Index Expanded, and the Cochrane Library were searched for studies comparing outcomes in patients undergoing MIDP and ODP for PDAC from January 1994 to August 2018. In total, 11 retrospective comparative studies with 4829 patients (MIDP: 1076, ODP: 3753) were included. The primary outcome was long-term survival, including 3-year overall survival (OS) and 5-year OS. The 3-year OS (hazard ratio (HR): 1.03, 95% confidence interval (CI): 0.89, 1.21; P = 0.66) and 5-year OS (HR: 0.91, 95% CI: 0.65, 1.28; P = 0.59) showed no significant differences between the two groups. Furthermore, the positive surgical margin rate (weighted mean difference (WMD): 0.71, 95% CI: 0.56, 0.89, P = 0.003) was lower in the MIDP group. However, patients in the MIDP group had less intraoperative blood loss (WMD: −250.03, 95% CI: −359.68, −140.39; P < 0.00001), a shorter hospital stay (WMD: −2.76, 95% CI: −3.73, −1.78; P < 0.00001) and lower morbidity (OR: 0.57, 95% CI: 0.46, 0.71; P < 0.00001) and mortality (OR: 0.50, 95% CI: 0.31, 0.81, P = 0.005) than patients in the ODP group. The limited evidence suggested that MIDP might be safer with regard to oncological outcomes in PDAC patients. Therefore, future high-quality studies are needed to examine the oncological safety of MIDP.

Laparoscopic distal pancreatectomy for pancreatic ductal adenocarcinoma: long-term oncologic outcomes following standard resection

Background: Oncologic outcomes of laparoscopic distal pancreatectomy remain unclear. This study aimed to examine the oncologic adequacy of standard laparoscopic distal pancreatectomy (SLDP) in patients with pancreatic ductal adenocarcinoma (PDAC). Methods: From January 2002 to March 2016, 207 patients underwent SLDP for PDAC at Oslo University Hospital - Rikshospitalet (Oslo, Norway) and Asan Medical Centre (Seoul, South Korea). After applying exclusion criteria, 186 patients were eligible for the analysis. Perioperative and oncologic variables were analyzed for association with recurrence and survival. Results: Median overall and recurrence-free survival (OS and RFS, respectively) were 32 and 16 months, while 5-year OS and RFS rates were 38.2% and 35.9%, respectively. Ninety-six (51.6%) patients developed recurrence - 56 (30.1%) extrapancreatic, 27 (14.5%) locoregional and 13 (7.0%) combined locoregional and extrapancreatic. Thirty-seven (19.9%) patients had early recurrence (within 6 months of surgery). In the multivariable analysis, tumor size > 3cm and no adjuvant chemotherapy were associated with early recurrence (p=0.017 and p=0.015, respectively). The Cox regression model showed that tumor size > 3cm and lymphovascular invasion resulted in decreased RFS and OS. Conclusion: SLDP is associated with satisfactory long-term oncologic outcomes in patients with PDAC. Tumor size > 3cm, no adjuvant chemotherapy and lymphovascular invasion are linked to poor prognosis.

SRPX2 and RAB31 are effective prognostic biomarkers in pancreatic cancer.

Introduction: SRPX2 and RAB31 play important roles in tumorigenesis and metastasis; however, their prognostic value in pancreatic cancer remains unclear. This study aimed to investigate the potential interactions and effects of SRPX2 and RAB31 on the diagnosis and prognosis of pancreatic cancer.Methods: The expression of SRPX2 and RAB31 in pancreatic tumor tissues and cells was evaluated through database mining of the Oncomine, Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, and validated the results through immunohistochemistry (IHC) and Western blot in our clinical database. Protein-protein interactions were explored by immunofluorescence and Co-immunoprecipitation (Co-IP). Two hundred tissue microarray specimens from patients (79 training and 121 validation), who underwent curative pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) were used. Additionally, the association between the SRPX2 and RAB31 and prognosis of PDAC patients after surgery was analyzed.Results: The expression of SRPX2 and RAB31 was highly increased in pancreatic cancer, and there was a significant positive correlation between these two proteins. Co-IP showed the direct interaction between SRPX2 and RAB31. Kaplan-Meier analysis showed that positive expression of SRPX2 and RAB31 was associated with reduced disease-free survival (DFS) and overall survival (OS) of PDAC patients in the training set and the validation sets. Furthermore, multivariate analysis indicated that the 8th edition TNM stage and combination of SRPX2 and RAB31 were independent prognostic factors that associated with OS and DFS in the training, and the validation sets, respectively.Conclusions: The combination of SRPX2 and RAB31 can be important markers for the prognosis of pancreatic cancer.

Reappraising the Concept of Conditional Survival After Pancreatectomy for Ductal Adenocarcinoma: A Bi-institutional Analysis.

To reappraise the concept of conditional survival (CS) following pancreatectomy for pancreatic ductal adenocarcinoma (PDAC), accounting for the patient's present disease status relative to recurrence. CS, defined as the probability of surviving an additional time frame based on accrued lifespan, offers dynamic survival projections as compared with baseline overall survival. Patients undergoing pancreatectomy for PDAC at 2 institutions from 2000 to 2013 were retrospectively analyzed. The 12-month CS was estimated separately for patients who were disease-free or with recurrence at the given time points. Next, the conditional probability of reaching 60-months of survival was examined in each conditioning set across strata of prognostic covariates, including American Joint Committee on Cancer stage, tumor grade, R-status, and adjuvant treatment. The study population consisted of 1005 patients. In disease-free patients, the 12-month CS increased as a function of time already survived, showing an opposite trend compared with overall survival. In patients who recurred, the 12-month CS was lower than the disease-free counterpart, especially within 24 months postoperatively. When stratifying by the levels of prognostic covariates, the 60-months CS estimates for disease-free patients tended to level off progressively, indicating that factors independently associated with survival at the time of pancreatectomy lost power over time. This concept did not apply to the conditioning set of patients with recurrence, where CS estimates across variables strata diverged with accrued lifespan. This paper provides new information on how prognosis following pancreatectomy for PDAC evolves over time, adjusting for the time the patient already survived, and for the patient's present disease status relative to recurrence.

Impact of the controlling nutritional status (CONUT) score on the prognosis after curative resection of pancreatic adenocarcinoma

Introduction: The controlling nutritional status (CONUT) score has been established as a useful tool to evaluate immune-nutritional status. This study aimed to retrospectively investigate the impact of the CONUT score on short- and long-term outcomes in patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma (PDAC). Methods: Between April 2002 and April 2016, 344 consecutive patients who underwent curative resection of PDAC without neoadjuvant therapy were analysed. After the best predictive value of the CONUT score for survival was explored, predictors of overall survival (OS) were identified using Kaplan-Meier analyses, the log-rank test and Cox multivariable analysis. Correlations between the CONUT score and postoperative complications were analysed using the Mann-Whitney U test and Spearman`s rank correlation. Results: The median survival times of patients with high and low CONUT scores were 18.0 and 26.8 months, respectively. The high CONUT score group showed significantly lower OS than that of the low CONUT score group in the univariate analysis (P = 0.002). In contrast, no significant difference in recurrence-free survival was found (P = 0.43). The multivariate analysis demonstrated that a high CONUT score was an independent prognostic risk factor for OS (hazard ratio: 1.64, P = 0.003). The CONUT score showed no association with postoperative pancreatic fistula, the Clavien-Dindo grade or the postoperative hospital stay. Conclusion: The CONUT score, which is a measure of immune-nutritional status, was an independent prognostic risk factor for OS in patients with PDAC after pancreatectomy and was not associated with RFS or postoperative complications.

Predictors for survival in patients undergoing distal pancreatectomy for pancreatic ductal adenocarcinoma (DIPLOMA): a Pan-European Cohort

Predictors for survival in patients undergoing distal pancreatectomy for pancreatic ductal adenocarcinoma (DIPLOMA): a Pan-European Cohort

MRI of pancreatic ductal adenocarcinoma: texture analysis of T2-weighted images for predicting long-term outcome.

To assess the association between T2-weighted imaging (T2WI) texture-analysis parameters and the pathological aggressiveness or long-term outcomes in pancreatic ductal adenocarcinoma (PDAC) patients. A total of 66 patients (mean age 65.3 ± 9.0years) who underwent preoperative MRI followed by pancreatectomy for PDAC between 2013 and 2015 were included in this study. A radiologist performed a texture analysis twice on one axial image using commercial software. Differences in the tex parameters, according to pathological factors, were analyzed using a Student's t test or an ANOVA with Tukey's test. Univariate and multivariate Cox proportional hazards regression analyses were used to evaluate the association between tex parameters and recurrence-free survival (RFS) or overall survival (OS). The mean follow-up time was 18.5months, and there were 58 recurrences and 39 deaths. The mean of the positive pixel (MPP)-related factors was significantly lower in poorly differentiated tumors than in well-differentiated tumors as well as in cases with perineural invasion. The univariate Cox proportional hazards analysis showed a significant association between the tex parameters and RFS or OS. However, only tumor size was statistically significant after the multivariate analysis. Only tumor size and entropy with medium texture were significantly associated with OS after the multivariate analysis. Tumor size was a significant predictive factor for RFS and OS in PDAC patients. Although entropy with medium texture analysis was significantly associated with OS, there were also limitations in the texture analysis; thus, further study is necessary.

Implications of the Pattern of Disease Recurrence on Survival Following Pancreatectomy for Pancreatic Ductal Adenocarcinoma.

After radical resection of pancreatic ductal adenocarcinoma (PDAC), approximately 80% of patients will develop disease recurrence. It remains unclear to what extent the location of recurrence carries prognostic significance. Additionally, stratifying the pattern of recurrence may lead to a deeper understanding of the heterogeneous biological behavior of PDAC. The aim of this study was to characterize the relationship of recurrence patterns with survival in patients with resected PDAC. This single-center cohort study included patients undergoing pancreatectomy at the Johns Hopkins Hospital between 2000 and 2013. Exclusion criteria were neoadjuvant therapy and incomplete follow-up. Sites of first recurrence were stratified into five groups and survival outcomes were estimated using Kaplan-Meier curves. The association of specific recurrence locations with overall survival (OS) was analyzed using Cox proportional-hazards models with and without landmark analysis. Accurate follow-up data were available for 877 patients, 662 (75.5%) of whom had documented recurrence at last follow-up. Patients with multiple-site (n = 227, 4.7months) or liver-only recurrence (n = 166, 7.2months) had significantly worse median survival after recurrence when compared with lung- (n = 93) or local-only (n = 158) recurrence (15.4 and 9.7months, respectively). On multivariable analysis, the unique recurrence patterns had variable predictive values for OS. Landmark analyses, with landmarks set at 12, 18, and 24months, confirmed these findings. This study demonstrates that specific patterns of PDAC recurrence result in different survival outcomes. Furthermore, distinct first recurrence locations have unique independent predictive values for OS, which could help with prognostic stratification and decisions regarding treatment after the diagnosis of recurrence.

Su1351 - Long-Term Outcomes after Pancreatectomy for Pancreatic Ductal Adenocarcinoma in Elderly Patients: Special Reference to Postoperative Adjuvant Chemotherapy

Su1351 - Long-Term Outcomes after Pancreatectomy for Pancreatic Ductal Adenocarcinoma in Elderly Patients: Special Reference to Postoperative Adjuvant Chemotherapy

Patterns, Timing, and Predictors of Recurrence Following Pancreatectomy for Pancreatic Ductal Adenocarcinoma.

To describe accurately the pattern, timing, and predictors of disease recurrence after a potentially curative resection for pancreatic ductal adenocarcinoma (PDAC). After surgery for PDAC, most patients will develop disease recurrence. Understanding the patterns and timing of disease failure can help guide improvements in therapy. Patients who underwent pancreatectomy for PDAC at the Johns Hopkins Hospital between 2000 and 2010 were included. Exclusion criteria were incomplete follow-up records, follow-up <24 months, and neoadjuvant therapy. The first recurrence site was recorded and recurrence-free survival (RFS) was estimated using Kaplan-Meier curves. Predictive factors for specific recurrence patterns were assessed by univariate and multivariate analyses using Cox-proportional hazard regression models. From the identified cohort of 1103 patients, 692 patients had comprehensive and detailed follow-up data available. At a median follow-up of 25.3 months, 531 (76.7%) of the 692 had recurred after a median RFS of 11.7 months. Most patients recurred at isolated distant sites (n = 307, 57.8%), while isolated local recurrence was seen in 126 patients (23.7%). Liver-only recurrence (n = 134, 25.2%) tended to occur early (median 6.9 mo), while lung-only recurrence (n = 78, 14.7%) occurred later (median 18.6 mo). A positive lymph node ratio >0.2 was a strong predictor for all distant disease recurrence. Patients receiving adjuvant chemotherapy or chemoradiotherapy had fewer recurrences and a longer RFS of 18.0 and 17.2 months, respectively. Specific recurrence locations have different predictive factors and possess distinct RFS curves, supporting the hypothesis that unique biological differences exist among tumors leading to distinct patterns of recurrence.

AB097. P071. Implications of the pattern of disease recurrence on survival following pancreatectomy for pancreatic ductal adenocarcinoma

AB097. P071. Implications of the pattern of disease recurrence on survival following pancreatectomy for pancreatic ductal adenocarcinoma

Defining and Predicting Early Recurrence in 957 Patients With Resected Pancreatic Ductal Adenocarcinoma.

To establish an evidence-based cut-off to differentiate between early and late recurrence and to compare clinicopathologic risk factors between the two groups. A clear definition of "early recurrence" after pancreatic ductal adenocarcinoma resection is currently lacking. Patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma between 2000 and 2013 were included. Exclusion criteria were neoadjuvant therapy and incomplete follow-up. A minimum P-value approach was used to evaluate the optimal cut-off value of recurrence-free survival to divide the patients into early and late recurrence cohorts based on subsequent prognosis. Potential risk factors for early recurrence were assessed with logistic regression models. Of 957 included patients, 204 (21.3%) were recurrence-free at last follow-up. The optimal length of recurrence-free survival to distinguish between early (n = 388, 51.5%) and late recurrence (n = 365, 48.5%) was 12 months (P < 0.001). Patients with early recurrence had 1-, and 2-year post-recurrence survival rates of 20 and 6% compared with 45 and 22% for the late recurrence group (both P < 0.001). Preoperative risk factors for early recurrence included a Charlson age-comorbidity index ≥4 (OR 1.65), tumor size > 3.0 cm on computed tomography (OR 1.53) and CA 19-9 > 210 U/mL (OR 2.30). Postoperative risk factors consisted of poor tumor differentiation grade (OR 1.66), microscopic lymphovascular invasion (OR 1.70), a lymph node ratio > 0.2 (OR 2.49), and CA 19-9 > 37 U/mL (OR 3.38). Adjuvant chemotherapy (OR 0.28) and chemoradiotherapy (OR 0.29) were associated with a reduced likelihood of early recurrence. A recurrence-free interval of 12 months is the optimal threshold for differentiating between early and late recurrence, based on subsequent prognosis.

Differences in the pattern and timing of recurrence in patients after upfront or post-neoadjuvant pancreatectomy for pancreatic ductal adenocarcinoma

Differences in the pattern and timing of recurrence in patients after upfront or post-neoadjuvant pancreatectomy for pancreatic ductal adenocarcinoma

Long-Term Outcomes After Pancreatectomy for Pancreatic Ductal Adenocarcinoma in Elderly Patients: Special Reference to Postoperative Adjuvant Chemotherapy.

The benefit of pancreatectomy for elderly patients with pancreatic ductal adenocarcinoma (PDAC) remains controversial. Moreover, adjuvant chemotherapy (AC) for elderly patients has not been fully evaluated. We investigated the long-term outcomes after pancreatectomy for PDAC in elderly patients with special reference to AC. The medical records of 123 patients who underwent pancreatectomy for PDAC from 2007 to 2016 were retrospectively reviewed. The patients were divided into two groups: young (<75years) and elderly patients (≥75years). The study population comprised 91 young and 32 elderly patients. The postoperative clinical courses were not different between the two groups. AC was more frequently administered to young (85%) than elderly patients (66%; P=0.04). The weekly dose of tegafur/gimeracil/oteracil potassium (S1) for AC was significantly lower in elderly (median 423mg/m2) than young patients (median 491mg/m2; P=0.02). The prevalence of adverse events and the completion rate of AC were not significantly different between the two groups. There were no significant differences in recurrence-free survival (P=0.73) or overall survival (P=0.68) between the two groups in univariate analysis. Receipt of AC was not a significant independent factor for survival, and completion of planned AC was a significant independent factor for recurrence-free survival and overall survival in multivariate analysis. The benefit of pancreatectomy for PDAC was the same between young and elderly patients. Completion of planned AC was important, and lowered-dose AC using S1 for elderly patients might be safe and therapeutically useful.

Laparoscopic distal pancreatectomy for pancreatic ductal adenocarcinoma: Long-term oncologic outcomes after standard resection

Surgical resection is the only curative option in patients with pancreatic ductal adenocarcinoma. Little is known about the oncologic outcomes of laparoscopic distal pancreatectomy. This bi-institutional study aimed to examine the long-term oncologic results of standard laparoscopic distal pancreatectomy in a large cohort of patients with pancreatic ductal adenocarcinoma. From January 2002 to March 2016, 207 patients underwent standard laparoscopic distal pancreatectomy for pancreatic ductal adenocarcinoma at Oslo University Hospital-Rikshospitalet (Oslo, Norway) and Asan Medical Centre (Seoul, Republic of Korea). After the exclusion criteria were applied (distant metastases at operation, conversion to an open operation, loss to follow-up), 186 patients were eligible for the analysis. Perioperative and oncologic variables were analyzed for association with recurrence and survival. Median overall and recurrence-free survivals were 32 and 16months, while 5-year overall and recurrence-free survival rates were estimated to be 38.2% and 35.9%, respectively. Ninety-six (52%) patients developed recurrence: 56 (30%) extrapancreatic, 27 (15%) locoregional, and 13 (7%) combined locoregional and extrapancreatic. Thirty-seven (19.9%) patients had early recurrence (within 6months of operation). In the multivariable analysis, tumor size >3cm and no adjuvant chemotherapy were associated with early recurrence (P=.017 and P=.015, respectively). The Cox regression model showed that tumor size >3cm and lymphovascular invasion were independent predictors of decreased recurrence-free and overall survival. Standard laparoscopic distal pancreatectomy is associated with satisfactory long-term oncologic outcomes in patients with pancreatic ductal adenocarcinoma. Several risk factors, such as tumor size >3cm, no adjuvant chemotherapy, and lymphovascular invasion, are linked to poor prognosis after standard laparoscopic distal pancreatectomy.

Tu1389 - Prognostic Impact of Additional Pancreatic Resection for Cancer Positive Cut Margins During Distal Pancreatectomy for Pancreatic Ductal Adenocarcinoma

Tu1389 - Prognostic Impact of Additional Pancreatic Resection for Cancer Positive Cut Margins During Distal Pancreatectomy for Pancreatic Ductal Adenocarcinoma

Adjuvant therapy (AT) following resection of pancreatic ductal adenocarcinoma (PDAC): Are patients from rural, remote areas disadvantaged?

373 Background: AT with chemotherapy (CT) + radiation (RT) has been shown to improve PDAC survival over surgery alone. Although race and socioeconomic status can affect outcomes in PDAC, the impact of rural or remote residence on the delivery and effect of AT has not been studied. Methods: Patients undergoing pancreatectomy for PDAC were identified from the National Cancer Data Base between 2006 and 2013. Individuals were classified as living in a metro area, urban/rural adjacent to metro area (URA), and urban/rural remote area (URR). Patients with less than 6 months follow-up were excluded. Logistic regression was performed to assess residence as a predictor of receiving AT. Overall survival (OS) as a function of inhabitance was estimated by the method of Kaplan and Meier and prognostic factors were identified by Cox regression. Results: A total of 32,521 individuals underwent pancreatectomy for PDAC. The majority of AT was delivered in academic research facilities in 56% of patients while only 29% of patients received both CT and RT. Univariate analysis demonstrated individuals in URR were less likely to receive CT (55% vs 58%, p &lt; 0.01) but not RT (30% vs 31%, p &lt; 0.261) and had a longer interval to AT (82 vs 75 days, p &lt; 0.009) than those in metro areas. However on multivariate analysis URR inhabitance was no longer predictive of any form of AT (OR = 0.892, 95% CI: 0.792-1.006, p = 0.062). Hispanic ethnicity, Medicaid insurance, uninsured status, and lower education were all predictive of decreased likelihood of receiving AT. Median OS was inferior for URR dwellers with pathologic T2 and T3 tumors compared to those in metro areas (19.8 vs. 24.4 months, p = 0.044 and 17.5 vs. 19.4 months, p &lt; 0.001). Cox regression revealed URR location remained independently associated with poorer OS (HR 1.076, 95% CI: 1.008-1.149, p &lt; 0.029). Conclusions: While living in a URR does not lead to reduced access to AT, it is associated with a worse OS in resected PDAC. This may be due to inadequate AT or other socioeconomic factors present in URR patients. Attention must be focused on improving oncologic care for groups susceptible to treatment disparities.

Development of metachronous or recurrent lesion in the remnant pancreas after partial pancreatectomy for pancreatic ductal adenocarcinoma

Development of metachronous or recurrent lesion in the remnant pancreas after partial pancreatectomy for pancreatic ductal adenocarcinoma

Number of harvested lymph nodes and stage migration effect in distal pancreatectomy for pancreatic ductal adenocarcinoma

Number of harvested lymph nodes and stage migration effect in distal pancreatectomy for pancreatic ductal adenocarcinoma