Georgios Gemenetzis

IPMNs with co-occurring invasive cancers: neighbours but not always relatives

Objective Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions that can give rise to invasive pancreatic carcinoma. Although approximately 8% of patients with resected pancreatic ductal adenocarcinoma have a co-occurring IPMN, the precise genetic relationship between these two lesions has not been systematically investigated. Design We analysed all available patients with co-occurring IPMN and invasive intrapancreatic carcinoma over a 10-year period at a single institution. For each patient, we separately isolated DNA from the carcinoma, adjacent IPMN and distant IPMN and performed targeted next generation sequencing of a panel of pancreatic cancer driver genes. We then used the identified mutations to infer the relatedness of the IPMN and co-occurring invasive carcinoma in each patient. Results We analysed co-occurring IPMN and invasive carcinoma from 61 patients with IPMN/ductal adenocarcinoma as well as 13 patients with IPMN/colloid carcinoma and 7 patients with IPMN/carcinoma of the ampullary region. Of the patients with co-occurring IPMN and ductal adenocarcinoma, 51% were likely related. Surprisingly, 18% of co-occurring IPMN and ductal adenocarcinomas were likely independent, suggesting that the carcinoma arose from an independent precursor. By contrast, all colloid carcinomas were likely related to their associated IPMNs. In addition, these analyses showed striking genetic heterogeneity in IPMNs, even with respect to well-characterised driver genes. Conclusion This study demonstrates a higher prevalence of likely independent co-occurring IPMN and ductal adenocarcinoma than previously appreciated. These findings have important implications for molecular risk stratification of patients with IPMN.

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

BackgroundAfter 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.ObjectiveThe aim of this study was to characterize the relationship of recurrence patterns with survival in patients with resected PDAC.MethodsThis 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.ResultsAccurate follow-up data were available for 877 patients, 662 (75.5%) of whom had documented recurrence at last follow-up. Patients with multiple-site (nu2009=u2009227, 4.7xa0months) or liver-only recurrence (nu2009=u2009166, 7.2xa0months) had significantly worse median survival after recurrence when compared with lung- (nu2009=u200993) or local-only (nu2009=u2009158) recurrence (15.4 and 9.7xa0months, respectively). On multivariable analysis, the unique recurrence patterns had variable predictive values for OS. Landmark analyses, with landmarks set at 12, 18, and 24xa0months, confirmed these findings.ConclusionsThis 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.

Analogous detection of circulating tumor cells using the AccuCyte®-CyteFinder® system and ISET system in patients with locally advanced and metastatic prostate cancer

Circulating tumor cells (CTCs) can provide important information on patients prognosis and treatment efficacy. Currently, a plethora of methods is available for the detection of these rare cells. We compared the outcomes of two of those methods to enumerate and characterize CTCs in patients with locally advanced and metastatic prostate cancer (PCa). First, the selection‐free AccuCyte® − CyteFinder® system (RareCyte®, Inc., Seattle, WA) and second, the ISET system (Rarecells Diagnostics, France), a CTC detection method based on cell size‐exclusion.

Lessons learned from 29 lymphoepithelial cysts of the pancreas: institutional experience and review of the literature

BACKGROUNDnLymphoepithelial cysts (LECs) are rare pancreatic cystic lesions. Since LECs are benign, preoperative diagnosis is important to differentiate from a cystic neoplasm and avoid unnecessary surgery. The aim of this study was to identify clinical, radiographic and cytopathologic features associated with LECs.nnnMETHODSnA retrospective review was performed of patients diagnosed with LEC between 1995 and 2017 at our hospital. Clinicopathologic and radiographic imaging features were documented.nnnRESULTSnOf 29 patients with pancreatic LEC, 22 underwent surgical resection. The majority were male (n = 24) with a median age of 55 years (range, 21-74). During the evaluation, all patients underwent a CT, with endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) biopsy (n = 22) and/or MRI/MRCP (n = 11) performed in a smaller number of patients. A combination of exophytic tumor growth on imaging and the presence of specific cytomorphologic features on the EUS-FNA cytology biopsy led to the correct diagnosis of LEC and prevention of unnecessary surgery in 7 patients.nnnDISCUSSIONnDifferentiating LECs from premalignant pancreatic cystic neoplasms remains difficult. Findings of an exophytic growth pattern of the lesion on abdominal imaging and the presence of specific cytomorphologic features in the EUS-FNA biopsy could help clinicians diagnose LEC preoperatively.

AB015. S015. Circulating tumor cells dynamics in pancreatic adenocarcinoma correlate with disease status: data from a prospective trial

Background: Previous retrospective studies demonstrated that circulating tumor cells (CTCs) subtypes in patients with pancreatic ductal adenocarcinoma (PDAC) correlate with disease-specific survival. Herein, we report results of a prospective observational trial on CTC dynamics to assess their clinical significance. Methods: The CLUSTER trial is a prospective longitudinal study on PDAC CTC dynamics (NCT02974764). Multiple peripheral blood samples are collected from 160 consecutively enrolled patients with PDAC diagnosis. CTCs are enriched using an isolation-by-size assay, and their phenotype is characterized by immunofluorescence. Results: Two major CTC subtypes are identified in all patients: epithelial CTCs (eCTCs) and mesenchymal CTCs (mCTCs). Patients who previously received neoadjuvant chemotherapy have significantly lower total CTCs (tCTCs) and mCTCs, compared to untreated patients eligible for upfront resection (P<0.001). In multivariable logistic regression analysis, preoperative numbers of tCTCs and mCTCs are the only predictors of early recurrence and disease-associated mortality, within 12 months from surgery (P=0.03). Surgical resection of the primary tumor results in significant reduction in CTC burden across all cell subtypes (P<0.001). Longitudinal monitoring of CTCs postoperatively shows an increase in CTC numbers within a median time of 2 months, prior to radiological evidence of disease recurrence. Conclusions: We report novel findings regarding CTCs from a large prospective trial in patients undergoing PDAC resection. CTC dynamics reflect response to treatment and progression of disease, providing important information on clinical outcomes, not available by current tumor markers and imaging.

Long-Term Outcomes of 98 Surgically Resected Metastatic Tumors in the Pancreas

PurposeThe goal of this study was to assess the outcomes and characteristics of patients who underwent pancreatectomy for metastatic disease to the pancreas.MethodsPatients who underwent surgical resection of metastatic disease to the pancreas from 1988 to 2016 were identified using a prospectively maintained database. Data on clinicopathological features and outcomes of these patients were analyzed. Cox proportional hazard models were employed to identify patient-specific risk factors that influence survival.ResultsNinety-seven patients underwent 98 pancreatic metastasectomies from July 1988 through March 2016 for metastatic disease from 13 different primary cancers. Pancreaticoduodenectomy, distal pancreatectomy, and total pancreatectomy were performed in 49 (50xa0%), 37 (38xa0%), and 12 (12xa0%) patients, respectively. Postoperative complications occurred in 55 (56xa0%) patients, while 3 (3xa0%) perioperative deaths occurred. Median follow-up was 2.0xa0years, with a median survival of 3.2xa0years. Multivariate analysis revealed that older patients [hazard ratio (HR) 1.04/year; pxa0=xa00.006], non-renal cell carcinomas (HR 5.07; pxa0<xa00.001), vascular invasion (HR 3.53; pxa0<xa00.001), and positive resection margins (HR 2.62; pxa0=xa00.008) were independently associated with an increased risk of mortality.ConclusionsPancreatic metastasectomy is safe and feasible in well-selected patients and is associated with acceptable long-term survival.