Susanna W.L. de Geus

Selecting Tumor-Specific Molecular Targets in Pancreatic Adenocarcinoma: Paving the Way for Image-Guided Pancreatic Surgery

PurposeThe purpose of this study was to identify suitable molecular targets for tumor-specific imaging of pancreatic adenocarcinoma.ProceduresThe expression of eight potential imaging targets was assessed by the target selection criteria (TASC)—score and immunohistochemical analysis in normal pancreatic tissue (n = 9), pancreatic (n = 137), and periampullary (n = 28) adenocarcinoma.ResultsIntegrin αvβ6, carcinoembryonic antigen (CEA), epithelial growth factor receptor (EGFR), and urokinase plasminogen activator receptor (uPAR) showed a significantly higher (all p < 0.001) expression in pancreatic adenocarcinoma compared to normal pancreatic tissue and were confirmed by the TASC score as promising imaging targets. Furthermore, these biomarkers were expressed in respectively 88 %, 71 %, 69 %, and 67 % of the pancreatic adenocarcinoma patients.ConclusionsThe results of this study show that integrin αvβ6, CEA, EGFR, and uPAR are suitable targets for tumor-specific imaging of pancreatic adenocarcinoma.

Selecting Targets for Tumor Imaging: An Overview of Cancer-Associated Membrane Proteins:

Tumor targeting is a booming business: The global therapeutic monoclonal antibody market accounted for more than

Surgical management of chronic pancreatitis: current utilization in the United States

78 billion in 2012 and is expanding exponentially. Tumors can be targeted with an extensive arsenal of monoclonal antibodies, ligand proteins, peptides, RNAs, and small molecules. In addition to therapeutic targeting, some of these compounds can also be applied for tumor visualization before or during surgery, after conjugation with radionuclides and/or near-infrared fluorescent dyes. The majority of these tumor-targeting compounds are directed against cell membrane-bound proteins. Various categories of targetable membrane-bound proteins, such as anchoring proteins, receptors, enzymes, and transporter proteins, exist. The functions and biological characteristics of these proteins determine their location and distribution on the cell membrane, making them more, or less, accessible, and therefore, it is important to understand these features. In this review, we evaluate the characteristics of cancer-associated membrane proteins and discuss their overall usability for cancer targeting, especially focusing on imaging applications.

Neoadjuvant therapy versus upfront surgery for resected pancreatic adenocarcinoma: A nationwide propensity score matched analysis

BACKGROUND Surgical intervention is uncommon in chronic pancreatitis. Literature largely describes single institution or international experiences. This study describes US-based chronic pancreatitis surgical management. METHODS Retrospective analysis of chronic pancreatitis patients in the Healthcare Cost and Utilization Project Florida State Inpatient Database 2007-2011. Patients with malignancy or congenital abnormalities were excluded. Univariate analysis using the chi-square test. The number of readmissions, inpatient length of stay and cost using Wilcoxons signed-rank test. Multivariate analysis of surgery by logistic regression. RESULTS Twenty-one thousand four hundred and forty-five patients with chronic pancreatitis. 10.8% (2 307) underwent surgery including 1652 cholecystectomies, 564 drainage procedures and 498 pancreatectomies. Procedures decreased from 12.1% to 8.3% over time (P < 0.001), but intervention within 3 months increased (7.2% to 8.4%; P = 0.017). 15.3% (3 278) had pancreatic cysts/pseudocysts and 43.4% (9 312) had diabetes. The median numbers of admissions were 2 [interquartile range (IQR) 1,5] and 3 (IQR 2,7) among non-surgical and surgical patients, respectively (P < 0.001). Predictors of surgery were fewer co-morbidities, private insurance, and either diabetes mellitus or pancreatic cyst/pseudocyst. CONCLUSION Chronic pancreatitis leads to numerous inpatient readmissions, but surgical intervention only occurs in a minority of cases. Complicated patients are more likely to undergo surgery. The complexities of chronic pancreatitis management warrant early multidisciplinary evaluation and ongoing consideration of surgical and non-surgical options.

Stereotactic body radiotherapy for unresected pancreatic cancer: A nationwide review

Background. Neoadjuvant therapy is an emerging paradigm in pancreatic cancer care; however, its role for resectable disease remains controversial in the absence of conclusive randomized controlled trials. The purpose of the present study is to assess the impact of neoadjuvant therapy on survival in resected pancreatic cancer patients by clinical stage. Methods. A retrospective cohort study using the National Cancer Data Base from 2004 to 2012 including nonmetastatic pancreatic adenocarcinoma patients who underwent pancreatectomy and initiated chemotherapy. Propensity score matching within each stage was used to account for potential selection bias between patients undergoing neoadjuvant therapy and upfront surgery. Overall survival was compared by the Kaplan‐Meier method. Results. In the study, 1,541 and 7,159 patients received neoadjuvant therapy followed by surgery and upfront surgery succeeded by adjuvant therapy, respectively. In clinical stage III pancreatic cancer (n = 486), neoadjuvant therapy was associated with significant survival benefit after matching (median survival 22.9 vs 17.3 months; log‐rank P < .0001) compared with conventional upfront surgery followed by adjuvant therapy; however, no survival difference was found between the 2 treatment sequences in patients with clinical stage I (n = 3,149; median survival, 26.2 vs 25.7 months; P = .4418) and II (n = 5,065; median survival, 23.5 vs 23.0 months; P = .7751) disease after matching. Conclusion. The survival impact of neoadjuvant therapy is stage‐dependent. Neoadjuvant therapy does not disadvantage survival compared with conventional upfront surgery followed by adjuvant therapy in any stage, and is associated with a significant survival advantage in stage III pancreatic cancer.

Regional variation in the treatment of pancreatic adenocarcinoma: Decreasing disparities with multimodality therapy

The role of conventional radiotherapy in the management of pancreatic cancer has yet to be elucidated. Over the past decade, stereotactic body radiotherapy (SBRT) has emerged as a novel therapeutic option in pancreatic cancer care. This study evaluated the survival impact of SBRT on patients with unresected pancreatic cancer.

Evolution and impact of lymph node dissection during pancreaticoduodenectomy for pancreatic cancer

Background. Survival in pancreatic cancer remains poor with curative potential dependent on operative resection. We reviewed national adherence to practice guidelines to evaluate regional variation in the treatment and survival of patients with pancreatic cancer. Methods. Retrospective cohort review of adults with pancreatic adenocarcinoma using the National Cancer Data Base from 2006 to 2013. Overall survival was compared by the Kaplan‐Meier method and Cox proportional hazards models. Sequential multivariate logistic regression models were generated for odds of: a) diagnosis in stage I/II, b) resection, and c) receipt of multimodality therapy, defined as operative resection plus chemotherapy with or without radiation. Five geographic regions of the United States were used for analyses. Results. A total of 115,952 patients were identified. At least 22% of patients in all stages received no treatment, with only 38.4% and 32.3% of stage I and II patients receiving multimodality therapy. On unadjusted analysis, the Northeast had the greatest survival for all stages of disease, most pronounced for stage I where patients lived 2 to 3 more months (log‐rank P < .0001). While adjusted odds of early diagnosis and resection were comparable or greater across regions relative to the Northeast, patients who underwent resection in the Northeast were significantly more likely to receive multimodality therapy. Multivariate Cox modeling for patients receiving multimodality therapy accounted for differences in 3 of 4 remaining regions. Conclusion. Regional variations exist in pancreatic cancer treatment and survival. While providing multimodality cancer‐directed therapy can help mitigate these differences, survival with pancreatic cancer needs to be interpreted in the context of overall health, underlying risk factors, and life expectancy.

Unique predictors and economic burden of superficial and deep/organ space surgical site infections following pancreatectomy

Background. Insufficient examination of lymph nodes after pancreaticoduodenectomy can lead some pancreatic cancer patients with N1 disease to be misclassified as N0. We examined trends in lymph node dissection throughout time and investigated how these changes affect lymph node status and its prognostic value. Methods. The National Cancer Data Base was queried for patients with nonmetastatic pancreatic adenocarcinoma (2004–2013) who underwent classic pancreaticoduodenectomy with antrectomy. Logistic regression was performed for odds of node positivity. Kaplan‐Meier curves and Cox proportional hazards models were used to assess the impact of lymph node status on overall survival for patients diagnosed during 2‐year intervals from 2004–2012. Results. Median number of examined lymph nodes was 10 (interquartile range 6–15) in 2004 vs 17 (interquartile range 12–24) in 2013. Number of lymph nodes examined was a significant predictor of N1 disease (P < .0001), with a plateau at 30 nodes. N1 disease increased from 64.4% to 68.0% (P < .0001). Survival for both N1 and N0 subgroups improved. In successive multivariate models, N0 versus N1 status was consistently protective for overall survival (P < .0001), but there was no change in the magnitude of its hazard ratio over time (overall hazard ratio 0.691; 95% confidence interval 0.660–0.723). Conclusion. Contemporary patients have an adequate number of nodes examined during standard pancreaticoduodenectomy. This, along with rising rates of N1 cancer detection and improved survival for both node‐positive and node‐negative patients, suggest more accurate classification of lymph node status. However, no increased benefit is achieved beyond 30 nodes. Overall, lymph node status remains a strong prognosticator for overall survival.

Prognostic Impact of Urokinase Plasminogen Activator Receptor Expression in Pancreatic Cancer: Malignant Versus Stromal Cells

BACKGROUND Surgical site infections (SSIs) are common following pancreatectomy and associated with significant morbidity and economic burden. We sought to identify distinct predictors for superficial versus deep/organ space SSIs and their effects on surgical outcomes. METHODS ACS-NSQIP targeted pancreatectomy 2014 and 2015 databases were queried. Univariate and multivariate models were developed for both types of SSI, length of stay (LOS), and readmission. Costs were estimated based on Centers for Medicare & Medicaid Services (CMS) recommendations. RESULTS Of 8093 patients, there were 422 (5.2%) superficial and 1005 (12.4%) deep/organ space SSIs. On multivariate analyses, preoperative biliary stenting was predictive only for superficial SSI (OR: 2.21), while BMI of 25-29.9 (OR: 1.25) and BMI ≥30 kg/m2 (OR: 1.53), pancreatic duct size <3 mm (OR: 1.30), and intermediate (OR: 1.67) versus hard gland texture were predictors of deep/organ-space SSI. Superficial and deep/organ space SSIs were independent predictors of prolonged LOS (OR: 1.74 vs 1.80) and readmission (OR: 2.59 vs 6.57). Additional readmission costs per patient secondary to superficial SSI and deep/organ space SSI were

Massachusetts Healthcare Reform and Trends in Emergent Colon Resection.

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