Curative Resection For Pancreatic Ductal Adenocarcinoma Research Articles

Survival Prediction after Curative Resection of Pancreatic Ductal Adenocarcinoma by Imaging-Based Intratumoral Necrosis.

We aimed to determine the histopathological characteristics and prognosis of curatively resected pancreatic ductal adenocarcinoma (PDAC) showing intratumoral necrosis on preoperative CT or MRI. This study consecutively included 102 patients who underwent upfront surgery with margin-negative resection from 2012 to 2020. All patients underwent both pancreatic CT and MRI within 1 month before surgery. Two radiologists independently assessed CT/MRI findings, including the presence of CT- and MRI-detected necrosis. Histopathological characteristics of PDACs according to CT or MRI detection of necrosis were evaluated. Disease-free survival (DFS) and overall survival (OS) were assessed by the Kaplan-Meier method and the Cox proportional hazards model. Among the 102 PDAC patients, 14 patients (13.7%) had CT-detected necrosis, and 16 patients (15.7%) had MRI-detected necrosis, of which 9 showed both CT- and MRI-detected necrosis. PDACs with CT- or MRI-detected necrosis demonstrated a significantly higher degree of histopathological necrosis than those without (p < 0.001). Multivariable analysis revealed that tumor size (hazard ratio [HR], 1.19; p = 0.040), tumor location (HR, 0.46; p = 0.009), and MRI-detected necrosis (HR, 2.64; p = 0.002) had independent associations with DFS. Only MRI-detected necrosis was significantly associated with OS (HR, 2.59; p = 0.004). Therefore, MRI-detected necrosis might be a potential imaging predictor of poor survival after curative resection of PDAC.

Postoperative hyperprogression disease of pancreatic ductal adenocarcinoma after curative resection: a retrospective cohort study

BackgroundPrognosis for patients recurred rapidly after resection of pancreatic ductal adenocarcinoma (PDAC) was extremely poor. We proposed the concept of postoperative hyper-progression disease (PO-HPD) to define recurrence within 2 months after surgery, explored the role of surgery for postoperative HPD patients and determined the predictive preoperative risk factors and genomic features of PO-HPD.Methods976 patients undergoing curative resection of PDAC were enrolled. Survival data of 1733 stage IV patients from the US Surveillance, Epidemiology and End Results database was also collected. Patients relapsed were grouped into 3 groups regarding of the recurrence time (within 2 months were PO-HPD, within 2 to 12 months were early recurrence (ER) and within > 12 months were late recurrence (LR)). Risk factors for PO-HPD were explored with logistic regression models. Genomic features of 113 patients were investigated using next-generation sequencing-based gene panel testing.Results718 of 976 cases relapsed, 101were PO-HPD, 418 were ER and 199 were LR. Total survival of PO-HPD was 12.5 months, shorter than that of ER (16.7 months) and LR (35.1 months), and verged on that of stage IV patients (10.6 months). Preoperative risk factors for PO-HPD included red blood cell count < 3.94*10^12/L, CA19–9 ≥ 288.6 U/mL, CA125 ≥ 22.3 U/mL and tumor size≥3.45 cm. Mutations of CEBPA, ATR and JAK1 were only identified in PO-HPD and they owned lower level of CN gain compared to others.ConclusionsPrognosis of PO-HPD was extremely poor and the role of surgery for PO-HPD should be prudently assessed.

Clinicopathological variables and risk factors for lung recurrence after resection of pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) has a high recurrence rate even after curative resection. Lung recurrence may have better outcomes than other recurrences. However, its detailed clinicopathological features are unclear. We investigated the clinicopathological features and risk factors for lung recurrence after pancreatectomy for PDAC. The study included 161 patients with potentially and borderline resectable PDAC who had undergone R0 or R1 pancreatectomy between January 2008 and December 2016. We retrospectively examined the prognosis and predictors for lung recurrence after curative resection. Seventeen patients (10.6%) had isolated lung recurrence. The median overall and recurrence-free survivals were 38.0 and 16.1 months, respectively. In multivariate analysis, para-aortic lymph node (PALN) metastasis (p=0.006) and female sex (p=0.027) were independent factors for lung recurrence. Lung recurrence had a better prognosis than other recurrences. PALN metastasis and female sex are independent risk factors for lung recurrence after curative resection for PDAC.

A Comparative Study of Survivor Outcomes between Preoperative Evaluation Using CT Alone and Combined CT and MRI in Patients with Pancreatic Ductal Adenocarcinoma.

PurposeTo compare the recurrence pattern, disease-free survival (DFS), and overall survival (OS) after curative surgery for pancreatic ductal adenocarcinoma (PDAC) in patients who underwent preoperative evaluation with CT alone or in combination with MRI, and to compare the prognosis according to the first recurrence site.Materials and MethodsWe retrospectively evaluated 152 patients who underwent R0 resection of PDAC. Preoperative CT or combined CT and MRI were performed for 103 and 49 patients, respectively. Two radiologists recorded the location and date of the first recurrence in consensus. The recurrence pattern, DFS, and OS were compared between the two groups. OS was analyzed according to the first recurrence site.ResultsIn both groups, liver metastasis was the most common recurrence pattern. DFS (p = 0.247) or OS (p = 0.067) showed no significant difference between the two groups. OS according to the first recurrence site was the lowest for liver metastasis, followed by locoregional recurrence (p < 0.001).ConclusionThere were no significant differences in the recurrence pattern, DFS, or OS between patients evaluated with preoperative CT alone or with CT and MRI after curative resection of PDAC. Liver metastasis was the most common tumor recurrence pattern with the lowest OS.

Early versus delayed initiation of adjuvant treatment for pancreatic cancer.

BackgroundPancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor showing a tendency for early recurrence, even after curative resection. Although adjuvant treatment improves survival, it is unclear whether early adjuvant treatment initiation yields better outcomes in patients with PDAC.MethodsWe retrospectively enrolled 113 patients who underwent chemotherapy or chemoradiotherapy after curative resection of PDAC: Fifty-six and 57 patients were in the early and delayed groups, respectively based on the median time of treatment initiation (35 days [range, 20–83 days]).ResultsPatient baseline characteristics were comparable in both groups, except for grade III or IV postoperative complications (5.4% in the early group vs. 22.8% in the delayed group). With a median 20.3-month follow-up, the overall survival (OS) and disease-free survival (DFS) times were 29.5 and 14.7 months, respectively. The early group had significantly prolonged OS (39.1 vs. 21.1 months, p = 0.018) and DFS (18.8 vs. 10.0 months, p = 0.034), compared to the delayed group. Among 71 patients who completed planned adjuvant treatment, patients in the early group tended to have longer, though not statistically significant, OS and DFS times than those in the delayed group. In 67 patients without postoperative complications, patients in the early group had longer OS (42.8 vs. 20.5 months, p = 0.002) and DFS (19.6 vs. 9.1 months, p = 0.005) than those in the delayed group. By multivariate analysis, incompletion of treatment (hazard ratio [HR]: 4.039, 95% confidence interval [CI]: 2.334–6.992), delayed treatment initiation (HR: 1.822, 95% CI: 1.081–3.070), and positive angiolymphatic invasion (HR: 2.116, 95% CI: 1.160–3.862) were significantly associated with shorter OS.ConclusionsAdjuvant treatment should be delivered earlier and completed for better outcomes in resected PDAC patients, especially without postoperative complications.

Factors influencing receipt of adjuvant chemotherapy after surgery for pancreatic cancer: a two-center retrospective cohort study

Objective: The addition of adjuvant chemotherapy after surgical resection has improved survival rates for patients with pancreatic ductal adenocarcinoma (PDAC). However, outside clinical trials, many operated patients still do not receive adjuvant chemotherapy due to clinical and tumor-related factors. The aim of this study was to investigate factors that may influence the receipt of adjuvant chemotherapy and the effect on long-term survival.Materials and methods: Patients undergoing macroscopically curative resection for PDAC at the University Hospitals in Lund and Linköping, Sweden, between 1 January 2007 and 31 December 2015, were retrospectively reviewed. Clinical and pathological data were compared between adjuvant and non-adjuvant chemotherapy groups and factors affecting chemotherapy receipt were analyzed by multiple logistic regression. Multivariable Cox regression analysis was performed to select predictive variables for survival.Results: A total of 233 patients were analyzed. Adjuvant chemotherapy was administered to 167 patients (71.7%). The likelihood of receiving adjuvant chemotherapy decreased with age, OR 0.91, 95% CI 0.86–0.95, p < .001. Moreover, patients with severe postoperative complications (Clavien–Dindo grade ≥ III) were less likely to receive adjuvant chemotherapy, OR 0.31, 95% CI 0.14–0.71, p = .005. The presence of lymph node metastases on histopathological reporting was associated with increased likelihood of initiating adjuvant chemotherapy, OR 2.19, 95% CI 1.09–4.40, p = .028. Adjuvant chemotherapy was an independent factor for prolonged survival on multivariable Cox regression analysis, HR 0.45 (95% CI 0.31–0.65), p < .001.Conclusions: Age, postoperative complications and the presence of lymph node metastases affect the likelihood of receiving adjuvant chemotherapy after PDAC surgery.

The impact of resection margin status on pancreatic cancer-associated survival: A meta-analysis

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is characterized by low rates of resectability and high rates of local recurrence or distal metastases after curative resection due to early spread of tumor cells around peripancreatic nerves and vessels. Studies that analyzed the impact of margin/resection (R0/R1) status on overall survival reported on conflicting results, largely due to geographic differences in the definition margin status. Therefore, the present study dissected the impact of resection status on the survival of PDAC patients after curative resection included in studies from different continents. Method: Pubmed, Medline and Embase were screened for the terms “pancreatic ductal adenocarcinoma”, “pancreatic cancer”, “resection status”, “R0“, “R1”, and survival”. All articles meeting the predefined criteria were critically analyzed on relevance and the meta-analysis was performed by pooling only those studies that reported univariate and/or multivariate hazard ratios/HR. Results: After elimination of studies that lacked PDAC-specific survival rates, a total of 86 studies that analyzed the correlation between R0/R1 status and PDAC-associated survival were included in the meta-analysis. The pooled HR analysis showed a marked impact of resection status on PDAC-specific survival (HR: 1.49; CI 1.43–1.54; p < 0.00001). In a subset analysis of studies (n = 40) that primarily investigated prognostic factors in clinical cohorts, R1 was again associated with a worse overall survival than R0 status (HR: 1.46; CI 1.40–1.52; p < 0.00001). Conclusions: Despite intercontinental discrepancies in the definition of the circumferential resection margins, microscopically clear tumor margins are associated with a favorable overall survival after curative resection for PDAC.

Adjunctive role of preoperative liver magnetic resonance imaging added to computed tomography among resected pancreatic cancer patients.

207 Background: Multi-detector computed tomography using pancreatic protocol (pCT) has been a preferred diagnostic imaging modality before resection of the pancreatic ductal adenocarcinoma (PDAC), because an adjunctive role of liver magnetic resonance imaging (MRI) is still unclear. The current study evaluated whether liver MRI added to pCT can help to select proper surgical candidates, and reduce the risk of early recurrence, eventually result in longer survival in resected PDAC patients. Methods: Among 197 PDAC patients who underwent curative-intended surgery, 167 patients who achieved complete resection with no grossly visible tumor were enrolled retrospectively. All patients had no metastatic lesions on pCT and/or MRI, preoperatively. Among them, 102 patients underwent pCT alone (CT group), and 65 patients liver MRI as well as pCT (MRI group). Results: By adding the liver MRI, hepatic metastases were newly discovered in 3 of 58 patients (5.2%) with no hepatic lesions on pCT and in 17 of 53 patients (32.1%) with indeterminate hepatic lesions on pCT. Among 167 patients who achieved R0/R1 resection, the median overall and disease-free survival were 20.1 vs 29.3 months and 8.5 vs 10.0 months in the CT and the MRI group, respectively (p = 0.011 and = 0.012), during median follow-up of 16.4 months. 80 (78.4%) patients in the CT group and 39 (60.0%) in the MRI group experienced recurrence during follow-up. Cumulative initial hepatic recurrence rate was higher in the CT group than in the MRI group (43.7% vs 18.5% at 1yr and 57.4% vs 26.9% at 2yr, p &lt; 0.001), although the other sites recurrence did not differ in both groups. Conclusions: Liver MRI added to pCT has an incremental value in detecting PDAC hepatic metastases. Furthermore, because PDAC patients who underwent resection after liver MRI as well as pCT expect lower rate of hepatic recurrence and better survival than pCT alone, therefore, liver MRI added to pCT is needed to patients who planned curative resection of PDAC.

Mesopancreatic Stromal Clearance Defines Curative Resection of Pancreatic Head Cancer and Can Be Predicted Preoperatively by Radiologic Parameters: A Retrospective Study.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a strong fibrotic stromal reaction and diffuse growth pattern. Peritumoral fibrosis is often evident during surgery but only distinguishable from tumor by microscopic examination. The aim of this study was to investigate the role of clearance of fibrotic stromal reaction at the mesopancreatic resection margin as a criterion for radical resection and preoperative assessment of resectability.Mesopancreatic stromal clearance status (S-status) was defined as the presence or absence (S+/S0) of fibrotic stromal reaction at the mesopancreatic resection margin. Detailed retrospective clinicopathologic re-evaluation of margin status and preoperative cross-sectional imaging was performed in a cohort of 91 patients operated for pancreatic head PDAC from 2001 to 2011.Conventional margin positive resection (R+, tumor cells directly at the margin) was found in 36%. However, S-status further divided the margin negative (R0) group into patients with median survival of 14 months versus 31 months (S+ versus S0, P = 0.005). Overall rate of S+ was 53%. S-status and lymph node ratio constituted the only independent predictors of survival. Stranding of the superior mesenteric artery fat sheath was the only independent radiologic predictor of S+ resection, and achieved a 71% correct prediction of S-status.Mesopancreatic stromal clearance is a major determinant of curative resection in PDAC, and preoperative prediction by cross-sectional imaging is possible, setting the basis for a new definition of borderline resectability.

Tu1904 Prognostic Impact of Pancreatic Intraepithelial Neoplasia-III Accompanying Chronic Pancreatitis in Patients Who Underwent R0 Resection for Pancreatic Adenocarcinoma

Background: The clinical significance of pancreatic intraepithelial neoplasia (PanIN)-III, known as carcinoma in situ of pancreatic ductal adenocarcinoma (PDAC), remains unclear yet. Recent research showed inflammation enhanced early cellular invasion of PanIN-III by facilitating epithelial to mesenchymal transition (EMT), even before frank malignancy in experimental model. Therefore we decided to investigate whether PanIN-III accompanying chronic pancreatitis (CP) might have an important prognostic impact in patient who underwent curative resection for PDAC. Methods: Medical records of 125 PDAC patients with R0 resection were reviewed. Presence and grade of PanIN and CP in resected specimen were determined based on College of American Pathologists protocol. Overall survival (OS) and disease free survival (DFS) were analyzed according to PanIN-III and CP. Results: CP was observed in 27.2% (34/125) of resected specimen and PanIN-III in 25.6% (32/125). In the group with CP, PanIN-III was associated with poor prognosis in univariate analysis (4.3 months vs. 15.5 months, P=0.021 for DFS and 16.3 months vs. 30.9 months, P=0.004 for OS), whereas PanIN-III was not a prognostic factor in the group without CP. When we divided into two groups [PanIN-III accompanying CP (n=12) vs. the others (n=113)], it showed that median DFS and OS were significantly shorter in PanIN-III and CP group than those of the others (4.3 months and 16.3 months vs. 11.3 months and 21.3 months, p= 0.034 and p=0.019, respectively). In multivariate analysis, PanIN-III accompanying CP remained a statistically significant poor prognostic factor (HR: 2.97; 95% CI: 1.36 to 6.30; P=0.006 for DFS, HR: 2.31; 95% CI: 1.13 to 4.73; P=0.022 for OS using Cox proportional hazard ratio). Conclusions: PanIN-III accompanying CP might influence on poor long-term outcomes in patients who underwent R0 resection for PDAC. Therefore, it would support that chronic inflammation could enhance the dissemination of carcinoma in situ.

Tu1905 Exploring the Relevance and Effect Size of Factors Associated With the Outcome of Pancreatic Cancer Screening in High-Risk Individuals

Background: The clinical significance of pancreatic intraepithelial neoplasia (PanIN)-III, known as carcinoma in situ of pancreatic ductal adenocarcinoma (PDAC), remains unclear yet. Recent research showed inflammation enhanced early cellular invasion of PanIN-III by facilitating epithelial to mesenchymal transition (EMT), even before frank malignancy in experimental model. Therefore we decided to investigate whether PanIN-III accompanying chronic pancreatitis (CP) might have an important prognostic impact in patient who underwent curative resection for PDAC. Methods: Medical records of 125 PDAC patients with R0 resection were reviewed. Presence and grade of PanIN and CP in resected specimen were determined based on College of American Pathologists protocol. Overall survival (OS) and disease free survival (DFS) were analyzed according to PanIN-III and CP. Results: CP was observed in 27.2% (34/125) of resected specimen and PanIN-III in 25.6% (32/125). In the group with CP, PanIN-III was associated with poor prognosis in univariate analysis (4.3 months vs. 15.5 months, P=0.021 for DFS and 16.3 months vs. 30.9 months, P=0.004 for OS), whereas PanIN-III was not a prognostic factor in the group without CP. When we divided into two groups [PanIN-III accompanying CP (n=12) vs. the others (n=113)], it showed that median DFS and OS were significantly shorter in PanIN-III and CP group than those of the others (4.3 months and 16.3 months vs. 11.3 months and 21.3 months, p= 0.034 and p=0.019, respectively). In multivariate analysis, PanIN-III accompanying CP remained a statistically significant poor prognostic factor (HR: 2.97; 95% CI: 1.36 to 6.30; P=0.006 for DFS, HR: 2.31; 95% CI: 1.13 to 4.73; P=0.022 for OS using Cox proportional hazard ratio). Conclusions: PanIN-III accompanying CP might influence on poor long-term outcomes in patients who underwent R0 resection for PDAC. Therefore, it would support that chronic inflammation could enhance the dissemination of carcinoma in situ.

Tu1906 Outcomes of Unilateral vs Bilateral Drainage in Cholangiocarcinoma-Report From a Cancer Speciality Insititute(CSI)

Background: The clinical significance of pancreatic intraepithelial neoplasia (PanIN)-III, known as carcinoma in situ of pancreatic ductal adenocarcinoma (PDAC), remains unclear yet. Recent research showed inflammation enhanced early cellular invasion of PanIN-III by facilitating epithelial to mesenchymal transition (EMT), even before frank malignancy in experimental model. Therefore we decided to investigate whether PanIN-III accompanying chronic pancreatitis (CP) might have an important prognostic impact in patient who underwent curative resection for PDAC. Methods: Medical records of 125 PDAC patients with R0 resection were reviewed. Presence and grade of PanIN and CP in resected specimen were determined based on College of American Pathologists protocol. Overall survival (OS) and disease free survival (DFS) were analyzed according to PanIN-III and CP. Results: CP was observed in 27.2% (34/125) of resected specimen and PanIN-III in 25.6% (32/125). In the group with CP, PanIN-III was associated with poor prognosis in univariate analysis (4.3 months vs. 15.5 months, P=0.021 for DFS and 16.3 months vs. 30.9 months, P=0.004 for OS), whereas PanIN-III was not a prognostic factor in the group without CP. When we divided into two groups [PanIN-III accompanying CP (n=12) vs. the others (n=113)], it showed that median DFS and OS were significantly shorter in PanIN-III and CP group than those of the others (4.3 months and 16.3 months vs. 11.3 months and 21.3 months, p= 0.034 and p=0.019, respectively). In multivariate analysis, PanIN-III accompanying CP remained a statistically significant poor prognostic factor (HR: 2.97; 95% CI: 1.36 to 6.30; P=0.006 for DFS, HR: 2.31; 95% CI: 1.13 to 4.73; P=0.022 for OS using Cox proportional hazard ratio). Conclusions: PanIN-III accompanying CP might influence on poor long-term outcomes in patients who underwent R0 resection for PDAC. Therefore, it would support that chronic inflammation could enhance the dissemination of carcinoma in situ.

Prognostic impact of pancreatic intraepithelial neoplasia (PanIN)-III accompanying chronic pancreatitis in patients who underwent R0 resection for pancreatic adenocarcinoma.

246 Background: The clinical significance of pancreatic intraepithelial neoplasia (PanIN)-III, known as carcinoma in situ of pancreatic ductal adenocarcinoma (PDAC), remains unclear yet. Recent research showed inflammation enhanced early cellular invasion of PanIN-III by facilitating epithelial to mesenchymal transition (EMT), even before frank malignancy in experimental model. Therefore we decided to investigate whether PanIN-III accompanying chronic pancreatitis (CP) might have an important prognostic impact in patient who underwent curative resection for PDAC. Methods: Medical records of 199 PDAC patients with R0 resection were reviewed. Presence and grade of PanIN and CP in resected specimen were determined based on College of American Pathologists protocol. Overall survival (OS) and disease free survival (DFS) were analyzed according to PanIN-III and CP. Results: CP was observed in 19.6% (39/199) of resected specimen and PanIN-III in 21.1% (42/199). In the group with CP, PanIN-III was associated with poor prognosis in univariate analysis (16.6 months vs. 32.0 months, P=0.001 for OS and 7.5 months vs. 15.1 months, p=0.012 for DFS), whereas PanIN-III was not a prognostic factor in the group without CP. When we divided into two groups [PanIN-III accompanying CP (n=12) vs. the others (n=187)], it showed that median DFS and OS were significantly shorter in PanIN-III and CP group than those of the others (7.5 months and 16.6 months vs. 12.4 months and 26.0 months, p=0.017 and p=0.003, respectively). In multivariate analysis, PanIN-III accompanying CP remained a statistically significant poor prognostic factor (HR: 2.06; 95% CI: 1.008 to 4.221; p=0.048 for OS, HR: 2.6; 95% CI: 1.267 to 5.462; P=0.009 for DFS using Cox proportional hazard ratio). Conclusions: PanIN-III accompanying CP might influence on poor long-term outcomes in patients who underwent R0 resection for PDAC. Therefore, it would support that chronic inflammation could enhance the dissemination of carcinoma in situ.

Impact of Preoperative Diabetes on Long-Term Survival After Curative Resection of Pancreatic Adenocarcinoma: A Systematic Review and Meta-Analysis

Diabetes mellitus (DM) is coupled to the risk and symptomatic onset of pancreatic ductal adenocarcinoma (PDAC). The important question whether DM influences the prognosis of resected PDAC has not been systematically evaluated in the literature. We therefore performed a systematic review and meta-analysis evaluating the impact of preoperative DM on survival after curative surgery. The databases Medline, Embase, Web of Science, and the Cochrane Library were searched for studies reporting on the impact of preoperative DM on survival after PDAC resection. Hazard ratios and 95 % confidence intervals (CI) were extracted. The meta-analysis was calculated using the random-effects model. The data search identified 4,365 abstracts that were screened for relevant articles. Ten retrospective studies with a cumulative sample size of 4,471 patients were included in the qualitative review. The mean prevalence of preoperative DM was 26.7 % (1,067 patients), and all types of pancreatic resections were considered. The meta-analysis included 8 studies and demonstrated that preoperative DM is associated with a worse overall survival after curative resection of PDAC (hazard ratio 1.32, 95 % CI 1.46-1.60, P = 0.004). Only 2 studies reported separate data for new-onset and long-standing DM. To our knowledge, this is the first meta-analysis evaluating long-term survival after PDAC resection in normoglycemic and diabetic patients, demonstrating a significantly worse outcome in the latter group. The mechanism behind this observation and the question whether different antidiabetic medications or early control of DM can improve survival in PDAC should be evaluated in further studies.

Investigating the prognostic value of venous and arterial invasion in pancreatic ductal adenocarcinoma with elastica van gieson staining

Background: Microvascular invasion in pancreatic ductal adenocarcinoma (PDAC) is known to be a poor prognostic indicator and risk of metastasis. Recent studies have highlighted the discrepancy in reporting vascular invasion and the need of improved techniques. Aims: To determine whether the standard detection rate of vascular invasion by means of haematoxylin and eosin (H&E) staining in PDAC can be enhanced by the use of elastica van Gieson (EVG), allowing the detection of vascular invasion to be performed more easily and be more comprehensive. To assess prognostic implications of enhanced vascular invasion detection on prediction of cancer-specific survival in PDAC. Methods: Retrospective analysis of 42 patients with PDAC who had undergone a pancreatico-duodenectomy with curative intent between 2001 – 2008 was performed. Serial sections were stained with H&E and EVG respectively. The incidence of venous and arterial invasion was recorded and compared between the two stains. Results: Venous invasion was identified in 24 patients (57%) with H&E compared to 37 patients (88%) with EVG. Arterial invasion was identified in 7 patients (17%) with H&E compared to 29 patients (69%) with EVG. Conclusions: The use of EVG in PDAC resulted in a significantly higher rate of venous and arterial invasion to be identified. The presence of arterial invasion resulted in a significantly improved prediction of overall survival when compared to routine H&E assessment. The study provides good evidence that EVG staining should be tested prospectively by incorporation into the pathological assessment of venous and arterial invasion in patients undergoing potentially curative resection of PDAC. Take-home message: The use of an elastica van Gieson stain in pancreatic ductal adenocarinoma resulted in a significantly higher rate of venous and arterial invasion to be identified compared to routine H&E staining. The presence of arterial invasion using the elastica stain resulted in a significantly improved prediction of cancer-specific survival when compared to routine H&E staining. Abstract previously presented? yes (West of Scotland Surgical Association) Any disclosures? no ()

High Expression of Delta-Like Ligand 4 Predicts Poor Prognosis After Curative Resection for Pancreatic Cancer

Delta-like ligand 4 (DLL4)-Notch signaling plays a key role in tumor angiogenesis, but its prognostic value in patients with pancreatic ductal adenocarcinoma (PDAC) remains unclear. Our aim was to determine whether high DLL4 expression is correlated with poor prognosis after curative resection for PDAC. Surgical specimens obtained from 89 patients with PDAC were immunohistochemically assessed for DLL4 and vascular endothelial growth factor receptor 2 (VEGFR-2) expression. Prognostic significance of DLL4 expression was evaluated by Kaplan-Meier method and Cox regression. The correlations of DLL4 expression with VEGFR-2 expression, tumor stage, and lymph node metastasis were examined by chi-square test and multivariate logistic regression. There were 38 (42.7%) and 51 patients who showed high and low DLL4 expression, respectively. Survival curves showed that patients with low DLL4 expression had a significantly better survival than those with high DLL4 expression (P < .001). Multivariate survival analysis demonstrated that high DLL4 expression was independently associated with both reduced overall survival (hazard ratio [HR] 2.24; 95% confidence interval [95% CI] 1.14-4.38) and reduced progression-free survival (HR 2.37; 95% CI 1.22-4.60). Multivariate logistic regression analyses showed that high DLL4 expression was independently associated with both advanced tumor stage (odds ratio [OR] 6.84; 95% CI 2.42-9.36) and lymph node metastasis (OR 3.27; 95% CI 1.04-10.34). We also found a positive correlation between DLL4 and VEGFR-2 expression (P < .001). High DLL4 expression is significantly associated with poor prognosis for surgically resected PDAC, advanced tumor stage, and lymph node metastasis. Application of adjuvant therapy targeting DLL4-Notch signaling may improve prognosis.

Patterns of recurrence after curative resection of pancreatic ductal adenocarcinoma

Aims Despite curative surgery for pancreatic ductal adenocarcinoma (PDAC), most patients develop cancer recurrence and die from metastatic disease. Understanding of the patterns of failure after surgery can lead to new insights for novel therapeutic modalities. The aim of the present study is to describe the patterns of recurrence after curative resection of PDAC. Methods A retrospective analysis was performed of 145 consecutive resections for PDAC between 1998 and 2005 (M/F 75/70; median (range) age 67 years (32–85 y)). The location of the first and consecutive recurrences, and the time interval to cancer recurrence after surgical resection was studied. The magnitude of tumour-free margin was less than a millimetre in 48 patients, whereas a positive surgical margin was observed in 27 patients. The median duration of follow-up was 18.5 (range 0.3–116.8) months. Results Cancer recurrence was observed in 110 patients. The first location of recurrence was locoregional in 19, extra-pancreatic in 66, and combined locoregional and extra-pancreatic in 25 patients. Extra-pancreatic recurrence developed in the liver in 57, peritoneal in 35, pulmonary in 15, and retroperitoneal in 5 patients. The median (95% CI) overall (OS) and disease-free (DFS) survival was 18.7 (15.7–23.5) and 9.8 (7.5–12.4) months, respectively. The type of cancer recurrence did not significantly influence OS, while the resection margin status had a prognostic effect. Conclusion The vast majority of patients who undergo potentially curative surgery for PDAC develop cancer recurrence located in the abdominal cavity. Surgical resection margins with tumour involvement and tumour-free margins of less then 1 mm are negative prognostic factors. Further research on better local surgical control, peri-operative locoregional treatment, and more effective adjuvant systemic therapy is necessary to improve long-term survival of patients with curable PDAC.