Faculty Bibliography

BACKGROUND:The impact of neoadjuvant stereotactic body radiation therapy on postoperative complications for patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma remains unclear. Limited studies have compared neoadjuvant stereotactic body radiation therapy versus conventional chemoradiation therapy. A retrospective study was performed to determine if perioperative complications were different among patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma receiving neoadjuvant stereotactic body radiation therapy or chemoradiation therapy. METHODS:Patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma who underwent neoadjuvant chemotherapy with stereotactic body radiation therapy or chemoradiation therapy followed by pancreatectomy at the Johns Hopkins Hospital between 2008 and 2015 were included. Predictive factors for severe complications (Clavien grade ≥ III) were assessed by univariate and multivariate analyses. RESULTS:A total of 168 patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma underwent neoadjuvant chemotherapy and RT followed by pancreatectomy. Sixty-one (36%) patients underwent stereotactic body radiation therapy and 107 (64%) patients received chemoradiation therapy. Compared with the chemoradiation therapy cohort, the neoadjuvant stereotactic body radiation therapy cohort was more likely to have locally advanced pancreatic ductal adenocarcinoma (62% vs 43% P = .017) and require a vascular resection (54% vs 37%, P = .027). Multiagent chemotherapy was used more commonly in the stereotactic body radiation therapy cohort (97% vs 75%, P < .001). Postoperative complications (Clavien grade ≥ III 23% vs 28%, P = .471) were similar between stereotactic body radiation therapy and chemoradiation therapy cohort. No significant difference in postoperative bleeding or infection was noted in either group. CONCLUSION:Compared with chemoradiation therapy, neoadjuvant stereotactic body radiation therapy appears to offer equivalent rates of perioperative complications in patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma despite a greater percentage of locally advanced disease and more complex operative treatment.

OBJECTIVE:The aim of this study was to identify the optimal fistula mitigation strategy following pancreaticoduodenectomy. BACKGROUND:The utility of technical strategies to prevent clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreatoduodenectomy (PD) may vary by the circumstances of the anastomosis. The Fistula Risk Score (FRS) identifies a distinct high-risk cohort (FRS 7 to 10) that demonstrates substantially worse clinical outcomes. The value of various fistula mitigation strategies in these particular high-stakes cases has not been previously explored. METHODS:This multinational study included 5323 PDs performed by 62 surgeons at 17 institutions. Mitigation strategies, including both technique related (ie, pancreatogastrostomy reconstruction; dunking; tissue patches) and the use of adjuvant strategies (ie, intraperitoneal drains; anastomotic stents; prophylactic octreotide; tissue sealants), were evaluated using multivariable regression analysis and propensity score matching. RESULTS:A total of 522 (9.8%) PDs met high-risk FRS criteria, with an observed CR-POPF rate of 29.1%. Pancreatogastrostomy, prophylactic octreotide, and omission of externalized stents were each associated with an increased rate of CR-POPF (all P < 0.001). In a multivariable model accounting for patient, surgeon, and institutional characteristics, the use of external stents [odds ratio (OR) 0.45, 95% confidence interval (95% CI) 0.25-0.81] and the omission of prophylactic octreotide (OR 0.49, 95% CI 0.30-0.78) were independently associated with decreased CR-POPF occurrence. In the propensity score matched cohort, an "optimal" mitigation strategy (ie, externalized stent and no prophylactic octreotide) was associated with a reduced rate of CR-POPF (13.2% vs 33.5%, P < 0.001). CONCLUSIONS:The scenarios identified by the high-risk FRS zone represent challenging anastomoses associated with markedly elevated rates of fistula. Externalized stents and omission of prophylactic octreotide, in the setting of intraperitoneal drainage and pancreaticojejunostomy reconstruction, provides optimal outcomes.

BACKGROUND:The outcomes of sporadic pancreatic ductal adenocarcinoma (PDAC) patients with germline mutations of BRCA1/BRCA2 remains unclear. The prognostic significance of BRCA1/BRCA2 mutations on survival is not well established. STUDY DESIGN:We performed targeted next-generation sequencing (NGS) to identify BRCA1/BRCA2 germline mutations in resected sporadic PDAC cases from 2000 to 2015. Germline BRCA mutation carriers were matched by age and tumor location to those with BRCA1/BRCA2 wild-type genes from our institutional database. Demographics, clinicopathologic features, overall survival (OS), and disease-free survival (DFS) were abstracted from medical records and compared between the 2 cohorts. RESULTS:Twenty-two patients with sporadic cancer and BRCA1 (n = 4) or BRCA2 (n = 18) germline mutations and 105 wild-type patients were identified for this case-control study. The BRCA1/BRCA2 mutations were associated with inferior median OS (20.2 vs 27.8 months, p = 0.034) and DFS (8.4 vs 16.7 months, p < 0.001) when compared with the matched wild-type controls. On multivariable analyses, a BRCA1/BRCA2 mutation (hazard ratio [HR] 2.10, p < 0.001), positive margin status (HR 1.72, p = 0.021), and lack of adjuvant therapy (HR 2.38, p < 0.001), were all independently associated with worse survival. Within the BRCA1/BRCA2 mutated group, having had platinum-based adjuvant chemotherapy (n = 10) was associated with better survival than alternative chemotherapy (n = 8) or no adjuvant therapy (n = 4) (31.0 vs 17.8 vs 9.3 months, respectively, p < 0.001). CONCLUSIONS:Carriers of BRCA1/BRCA2 mutation with sporadic PDAC had a worse survival after pancreatectomy than their BRCA wild-type counterparts. However, platinum-based chemotherapy regimens were associated with markedly improved survival in patients with BRCA1/BRCA2 mutations, with survival differences no longer appreciated with wild-type patients.

INTRODUCTION:, Inc., Seattle, WA) and second, the ISET system (Rarecells Diagnostics, France), a CTC detection method based on cell size-exclusion. METHODS:system), and pancytokeratin, vimentin (Vim) and CD45 (ISET system). RESULTS:system was moderately correlated with the PanCK+/Vim- CTCs, and strongly correlated with the PanCK+/Vim+ CTCs (r = 0.700, P = 0.004 and r = 0.810, P < 0.001, respectively). CONCLUSION:Our results highlight significant disparities in the enumeration and phenotype of CTCs detected by both techniques. Although the median amount of CTCs/7.5 mL differed significantly, total CTC counts of both methods were strongly correlated. For future studies, a more uniform approach to the isolation and definition of CTCs based on immunofluorescent stains is needed to provide reproducible results that can be correlated with clinical outcomes.

Earlier detection is key to reducing cancer deaths. Here, we describe a blood test that can detect eight common cancer types through assessment of the levels of circulating proteins and mutations in cell-free DNA. We applied this test, called CancerSEEK, to 1005 patients with nonmetastatic, clinically detected cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast. CancerSEEK tests were positive in a median of 70% of the eight cancer types. The sensitivities ranged from 69 to 98% for the detection of five cancer types (ovary, liver, stomach, pancreas, and esophagus) for which there are no screening tests available for average-risk individuals. The specificity of CancerSEEK was greater than 99%: only 7 of 812 healthy controls scored positive. In addition, CancerSEEK localized the cancer to a small number of anatomic sites in a median of 83% of the patients.

PURPOSE:To explore seromarker levels for associations with outcomes in locally advanced pancreatic cancer (LAPC) patients who received chemotherapy and stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS:Serum from LAPC patients in 2 prospective trials of hypofractionated SBRT (5-6.6 Gy × 5) was collected before SBRT. Proximity ligation assay quantified the expression levels of 36 pancreatic cancer-specific candidate seromarkers: Axl, BMP2, CA 125, CA 19-9, CEA, CXCL-1/6/9/10, EGFR, Gas6, Her2, IGF-2, IGFBP-2/3/7, IL-6/6Ra/7/8/12, mesothelin, MMP-1/2/3/7, osteopontin, PDGFRa, PDK1, PF4, RegIV, SPARC, TGF-β, VEGF-A/D, and YKL40. Seromarker values were log transformed owing to log-normal distribution of the values, and Cox regression analysis was performed to assess for any association with overall survival. The Benjamini-Hochberg method was used to control for a false discovery rate (FDR) of only 10%. RESULTS:Sixty-four patients with LAPC were included. No clinical factors (including surgical resection, receipt of pre-SBRT chemotherapy, receipt of post-SBRT chemotherapy, performance status, and age) or potential biomarkers in the panel were associated with improved survival in this cohort after application of the FDR correction. Potential prognostic factors for improved survival for future investigation included surgical resection (P=.007, adjusted P=.153) and the serum expression of IL-8 (P=.006, adjusted P=.153), CA 19-9 (P=.031, adjusted P=.377), and MMP-1 (P=.036, adjusted P=.377). CONCLUSIONS:These data explore the expression of a panel of proteins in pre-SBRT serum of LAPC patients in the context of a conservative FDR correction. None of the clinical factors or expression levels of the serum proteins were found to be associated with survival; however, IL-8, CA 19-9, and MMP-1 were highlighted as possible candidates warranting inclusion in future seromarker studies in the ongoing efforts to identify tools for risk stratification and treatment allocation in LAPC.

: The pancreatic surgery program at Johns Hopkins is recognized as being among the top programs in the field. It is part of the newly formed John L. Cameron Division of HPB surgery. This division of surgery is a highly productive group of academic surgeons in terms of clinical volume, research endeavors, and education. The division functions as part of a large multidisciplinary group at Johns Hopkins. The program has an interesting history and can trace its roots back to the actions of a single individual-John L. Cameron. The John L. Cameron Division of HPB surgery and the Johns Hopkins Pancreas Disease program would not exist without him. It is the program that Dr Cameron built.

Resection with clean margin (R0 resection) is associated with better survival in patients with pancreatic cancer. Over the last decade, advancements in preoperative chemotherapy and radiation therapy in pancreatic cancer have led to expansion of indications for surgical resection. Current guidelines define pancreatic cancer with unreconstructable vascular involvement as locally advanced, or surgically unresectable. We present our experience in managing patients with locally advanced pancreatic cancer with a very unique series of patients who achieved R0 resection despite "unresectable" vascular involvement. Additionally, we review current guidelines, the ability to predict venous resection by imaging, outcomes after venous resection and reconstruction, published patency rates of venous reconstructions, and potential future implications of this novel technique.

AIM/OBJECTIVE:The aim of this paper is to describe the characteristics of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas in young patients. METHODS:We evaluated 1693 patients from the Pancreatic Surgery Consortium who underwent resection for IPMN and classified them as younger or older than 50 years of age at the time of surgery. We assessed the relationship of age with clinical, radiological, pathological, and prognostic features. RESULTS:We identified 90 (5%) young patients. Age was not associated with differences in main pancreatic duct size (P = 0.323), presence of solid components (P = 0.805), or cyst size (P = 0.135). IPMNs from young patients were less likely to be of gastric type (37 vs. 57%, P = 0.005), and more likely to be of oncocytic (15 vs. 4%, P = 0.003) and intestinal types (44 vs. 26%, P = 0.004). Invasive carcinomas arising from IPMN were less common in young patients (17 vs. 27%, P = 0.044), and when present they were commonly of colloid type (47 vs. 31% in older patients, P = 0.261) and had better overall survival than older patients (5-year, 71 vs. 37%, log-rank P = 0.031). CONCLUSION/CONCLUSIONS:Resection for IPMN is infrequent in young patients, but when they are resected, IPMNs from young patients demonstrate different epithelial subtypes from those in older patients and more favorable prognosis.