Sean Mulvihill - Academia.edu (original) (raw)

Papers by Sean Mulvihill

Research paper thumbnail of Early Detection of Sporadic Pancreatic Cancer

Research paper thumbnail of Causes of Death and Conditional Survival Estimates of Medium- and Long-term Survivors of Pancreatic Adenocarcinoma

JAMA Oncology, Aug 1, 2018

Research paper thumbnail of Disparities in utilization of treatment for clinical stage I-II pancreatic adenocarcinoma by area socioeconomic status and race/ethnicity

Research paper thumbnail of Serum IGFBP2 and MSLN as diagnostic and prognostic biomarkers for pancreatic cancer

Research paper thumbnail of Diminished Immune Surveillance during Histologic Progression of Intraductal Papillary Mucinous Neoplasms Offers a Therapeutic Opportunity for Cancer Interception

Clinical Cancer Research, Feb 23, 2022

Research paper thumbnail of Implications of inaccurate clinical nodal staging in pancreatic adenocarcinoma

Research paper thumbnail of Serum Osteopontin and Tissue Inhibitor of Metalloproteinase 1 as Diagnostic and Prognostic Biomarkers for Pancreatic Adenocarcinoma

Research paper thumbnail of Assessment of Serum Platelet Factor 4 as a Predictive Marker for VTE and as a Prognostic Biomarker in Pancreatic, Colorectal, Breast, and Lung Cancer

Journal of Surgical Research, Feb 1, 2012

Research paper thumbnail of County-level Variation in Use of Surgery and Cancer-specific Survival for Stage I-II Pancreatic Adenocarcinoma

Annals of Surgery, Apr 8, 2019

Research paper thumbnail of Abstract 3121: Characterization of immune profiling of pancreatic intraductal papillary mucinous neoplasm using multiplex immunofluorescence and image analysis approaches

Pancreatic intraductal papillary mucinous neoplasms (IPMN) are cystic mucin-secreting tumors that... more Pancreatic intraductal papillary mucinous neoplasms (IPMN) are cystic mucin-secreting tumors that arise within the pancreatic ductal system and are considered precursor lesions of pancreatic ductal adenocarcinoma. Profiling the immune infiltrate of IPMNs is essential to understand the immune mechanisms associated with the progression of IPMN. The aim of this study was to characterize the immune profiling of IPMN. We examined 31 formalin-fixed and paraffin-embedded tumor samples from surgically resected IPMN. The diagnostic slides were histologically reviewed by 2 expert pathologists in pancreas and classified as low-grade IPMN (low to intermediate grade dysplasia, N=11), high-grade IPMN (high grade dysplasia, N=18) and IPMN with invasive adenocarcinoma (N=2). Multiplex immunofluorescence (mIF) was used to characterize the immune profiling using two panels: Panel 1: PD-L1, PD1, CD3 (pan T cells), CD8 (T-cytotoxic), CD68 (macrophages), CK (AE1/AE3), DAPI. Panel 2: CD20 (B cells), CD45RO (T-memory), CD57 (NK), Granzyme B (NK and cytotoxic), FOXP3 (T reg), CK (AE1/AE3), DAPI. The slides were scanned using the Vectra multispectral microscope and analyzed by the InForm software (PerkinElmer). We quantified and co-localized immune phenotypes (epithelial cells PD-L1+; Total T-cell lymphocytes; T-cells antigen-experienced; Cytotoxic T-cells; Total macrophages; Macrophages PD-L1+; Total B-cell lymphocytes; Memory T cells; Granzyme B+ cells; Regulatory T cells; NK cells) in low grade dysplasia (LGD), high grade dysplasia (HGD), and invasive carcinoma areas in epithelial and stromal compartments. The Wilcoxon rank sum test or the Wilcoxon singed-rank test was used to test the equality of medians between two independent groups or paired samples, respectively. In all patients, HGD areas showed significantly higher density of macrophages (P= 0.041) and lower density of B-cell lymphocytes (P= 0.028) compared with LGD areas in the epithelial/stromal and epithelial compartments, respectively. Similar differences were observed when patients with high-grade IPMN (n=18) were analyzed for immune infiltrates in the HGD areas compared with LGD areas in the same tumor samples: HGD areas showed significantly higher density of macrophages (P= 0.035) and lower density of B-cell lymphocytes (P= 0.031). Patients with high-grade IPMN had significantly lower densities of B-cell lymphocytes (P= 0.011), T-cell lymphocytes (P= 0.034), and memory T-cells (P= 0.031) in the HGD areas when compared with LGD areas from patients with low-grade IPMN, in the epithelial compartment. No significant differences were found between LGD areas from patients who had high-grade IPMN and LGD areas from patients with low-grade IPMN. In conclusion, we characterized the immune landscape of IPMN and identified immune cell biomarkers associated with progression of IPMN. Citation Format: Luisa M. Solis, Naohiro Uraoka, Edwin Roger Parra, Yu Shen, Wei Wei, Mei Jiang, Barbara Mino, Kajsa Affolter, Courtney L. Scaife, Michele T. Yip-Schneider, C. Max Schmidt, Matthew Firpo, Sean Mulvihill, Eugene J. Koay,, Huamin Wang, Ignacio I. Wistuba, Anirban Maitra, Subrata Sen. Characterization of immune profiling of pancreatic intraductal papillary mucinous neoplasm using multiplex immunofluorescence and image analysis approaches [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3121.

Research paper thumbnail of Serum Platelet Factor 4 Is an Independent Predictor of Survival in Patients with Pancreatic Adenocarcinoma

Journal of Surgical Research, Feb 1, 2010

Research paper thumbnail of Accuracy of Diagnosing PDA, Neuroendocrine Tumors, and IPMN by EUS-FNA at a Single Institution

Journal of gastroenterology and hepatology research, 2015

Research paper thumbnail of Lymph Node Ratio in Pancreatic Adenocarcinoma After Preoperative Chemotherapy vs. Preoperative Chemoradiation and Its Utility in Decisions About Postoperative Chemotherapy

Journal of Gastrointestinal Surgery, Sep 5, 2018

Research paper thumbnail of Size and Importance of Socioeconomic Status-Based Disparities in Use of Surgery in Nonadvanced Stage Gastrointestinal Cancers

Annals of Surgical Oncology, Oct 11, 2019

Research paper thumbnail of Surgical overtreatment of pancreatic intraductal papillary mucinous neoplasms: Do the 2017 International Consensus Guidelines improve clinical decision making?

Research paper thumbnail of Biomarkers in pancreatic adenocarcinoma: current perspectives

OncoTargets and Therapy, Dec 1, 2016

Research paper thumbnail of Phenotype and Genotype of Pancreatic Cancer Cell Lines

Research paper thumbnail of Multianalyte Serum Biomarker Panel for Early Detection of Pancreatic Adenocarcinoma

JCO clinical cancer informatics, Mar 1, 2023

PURPOSE We determined whether a large, multianalyte panel of circulating biomarkers can improve d... more PURPOSE We determined whether a large, multianalyte panel of circulating biomarkers can improve detection of early-stage pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS We defined a biologically relevant subspace of blood analytes on the basis of previous identification in premalignant lesions or early-stage PDAC and evaluated each in pilot studies. The 31 analytes that met minimum diagnostic accuracy were measured in serum of 837 subjects (461 healthy, 194 benign pancreatic disease, and 182 early-stage PDAC). We used machine learning to develop classification algorithms using the relationship between subjects on the basis of their changes across the predictors. Model performance was subsequently evaluated in an independent validation data set from 186 additional subjects. RESULTS A classification model was trained on 669 subjects (358 healthy, 159 benign, and 152 early-stage PDAC). Model evaluation on a hold-out test set of 168 subjects (103 healthy, 35 benign, and 30 early-stage PDAC) yielded an area under the receiver operating characteristic curve (AUC) of 0.920 for classification of PDAC from non-PDAC (benign and healthy controls) and an AUC of 0.944 for PDAC versus healthy controls. The algorithm was then validated in 146 subsequent cases presenting with pancreatic disease (73 benign pancreatic disease and 73 early- and late-stage PDAC cases) and 40 healthy control subjects. The validation set yielded an AUC of 0.919 for classification of PDAC from non-PDAC and an AUC of 0.925 for PDAC versus healthy controls. CONCLUSION Individually weak serum biomarkers can be combined into a strong classification algorithm to develop a blood test to identify patients who may benefit from further testing.

Research paper thumbnail of Data from Diminished Immune Surveillance during Histologic Progression of Intraductal Papillary Mucinous Neoplasms Offers a Therapeutic Opportunity for Cancer Interception

Research paper thumbnail of Supplementary Data from Diminished Immune Surveillance during Histologic Progression of Intraductal Papillary Mucinous Neoplasms Offers a Therapeutic Opportunity for Cancer Interception

Supplementary Data from Diminished Immune Surveillance during Histologic Progression of Intraduct... more Supplementary Data from Diminished Immune Surveillance during Histologic Progression of Intraductal Papillary Mucinous Neoplasms Offers a Therapeutic Opportunity for Cancer Interception

Research paper thumbnail of Early Detection of Sporadic Pancreatic Cancer

Research paper thumbnail of Causes of Death and Conditional Survival Estimates of Medium- and Long-term Survivors of Pancreatic Adenocarcinoma

JAMA Oncology, Aug 1, 2018

Research paper thumbnail of Disparities in utilization of treatment for clinical stage I-II pancreatic adenocarcinoma by area socioeconomic status and race/ethnicity

Research paper thumbnail of Serum IGFBP2 and MSLN as diagnostic and prognostic biomarkers for pancreatic cancer

Research paper thumbnail of Diminished Immune Surveillance during Histologic Progression of Intraductal Papillary Mucinous Neoplasms Offers a Therapeutic Opportunity for Cancer Interception

Clinical Cancer Research, Feb 23, 2022

Research paper thumbnail of Implications of inaccurate clinical nodal staging in pancreatic adenocarcinoma

Research paper thumbnail of Serum Osteopontin and Tissue Inhibitor of Metalloproteinase 1 as Diagnostic and Prognostic Biomarkers for Pancreatic Adenocarcinoma

Research paper thumbnail of Assessment of Serum Platelet Factor 4 as a Predictive Marker for VTE and as a Prognostic Biomarker in Pancreatic, Colorectal, Breast, and Lung Cancer

Journal of Surgical Research, Feb 1, 2012

Research paper thumbnail of County-level Variation in Use of Surgery and Cancer-specific Survival for Stage I-II Pancreatic Adenocarcinoma

Annals of Surgery, Apr 8, 2019

Research paper thumbnail of Abstract 3121: Characterization of immune profiling of pancreatic intraductal papillary mucinous neoplasm using multiplex immunofluorescence and image analysis approaches

Pancreatic intraductal papillary mucinous neoplasms (IPMN) are cystic mucin-secreting tumors that... more Pancreatic intraductal papillary mucinous neoplasms (IPMN) are cystic mucin-secreting tumors that arise within the pancreatic ductal system and are considered precursor lesions of pancreatic ductal adenocarcinoma. Profiling the immune infiltrate of IPMNs is essential to understand the immune mechanisms associated with the progression of IPMN. The aim of this study was to characterize the immune profiling of IPMN. We examined 31 formalin-fixed and paraffin-embedded tumor samples from surgically resected IPMN. The diagnostic slides were histologically reviewed by 2 expert pathologists in pancreas and classified as low-grade IPMN (low to intermediate grade dysplasia, N=11), high-grade IPMN (high grade dysplasia, N=18) and IPMN with invasive adenocarcinoma (N=2). Multiplex immunofluorescence (mIF) was used to characterize the immune profiling using two panels: Panel 1: PD-L1, PD1, CD3 (pan T cells), CD8 (T-cytotoxic), CD68 (macrophages), CK (AE1/AE3), DAPI. Panel 2: CD20 (B cells), CD45RO (T-memory), CD57 (NK), Granzyme B (NK and cytotoxic), FOXP3 (T reg), CK (AE1/AE3), DAPI. The slides were scanned using the Vectra multispectral microscope and analyzed by the InForm software (PerkinElmer). We quantified and co-localized immune phenotypes (epithelial cells PD-L1+; Total T-cell lymphocytes; T-cells antigen-experienced; Cytotoxic T-cells; Total macrophages; Macrophages PD-L1+; Total B-cell lymphocytes; Memory T cells; Granzyme B+ cells; Regulatory T cells; NK cells) in low grade dysplasia (LGD), high grade dysplasia (HGD), and invasive carcinoma areas in epithelial and stromal compartments. The Wilcoxon rank sum test or the Wilcoxon singed-rank test was used to test the equality of medians between two independent groups or paired samples, respectively. In all patients, HGD areas showed significantly higher density of macrophages (P= 0.041) and lower density of B-cell lymphocytes (P= 0.028) compared with LGD areas in the epithelial/stromal and epithelial compartments, respectively. Similar differences were observed when patients with high-grade IPMN (n=18) were analyzed for immune infiltrates in the HGD areas compared with LGD areas in the same tumor samples: HGD areas showed significantly higher density of macrophages (P= 0.035) and lower density of B-cell lymphocytes (P= 0.031). Patients with high-grade IPMN had significantly lower densities of B-cell lymphocytes (P= 0.011), T-cell lymphocytes (P= 0.034), and memory T-cells (P= 0.031) in the HGD areas when compared with LGD areas from patients with low-grade IPMN, in the epithelial compartment. No significant differences were found between LGD areas from patients who had high-grade IPMN and LGD areas from patients with low-grade IPMN. In conclusion, we characterized the immune landscape of IPMN and identified immune cell biomarkers associated with progression of IPMN. Citation Format: Luisa M. Solis, Naohiro Uraoka, Edwin Roger Parra, Yu Shen, Wei Wei, Mei Jiang, Barbara Mino, Kajsa Affolter, Courtney L. Scaife, Michele T. Yip-Schneider, C. Max Schmidt, Matthew Firpo, Sean Mulvihill, Eugene J. Koay,, Huamin Wang, Ignacio I. Wistuba, Anirban Maitra, Subrata Sen. Characterization of immune profiling of pancreatic intraductal papillary mucinous neoplasm using multiplex immunofluorescence and image analysis approaches [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3121.

Research paper thumbnail of Serum Platelet Factor 4 Is an Independent Predictor of Survival in Patients with Pancreatic Adenocarcinoma

Journal of Surgical Research, Feb 1, 2010

Research paper thumbnail of Accuracy of Diagnosing PDA, Neuroendocrine Tumors, and IPMN by EUS-FNA at a Single Institution

Journal of gastroenterology and hepatology research, 2015

Research paper thumbnail of Lymph Node Ratio in Pancreatic Adenocarcinoma After Preoperative Chemotherapy vs. Preoperative Chemoradiation and Its Utility in Decisions About Postoperative Chemotherapy

Journal of Gastrointestinal Surgery, Sep 5, 2018

Research paper thumbnail of Size and Importance of Socioeconomic Status-Based Disparities in Use of Surgery in Nonadvanced Stage Gastrointestinal Cancers

Annals of Surgical Oncology, Oct 11, 2019

Research paper thumbnail of Surgical overtreatment of pancreatic intraductal papillary mucinous neoplasms: Do the 2017 International Consensus Guidelines improve clinical decision making?

Research paper thumbnail of Biomarkers in pancreatic adenocarcinoma: current perspectives

OncoTargets and Therapy, Dec 1, 2016

Research paper thumbnail of Phenotype and Genotype of Pancreatic Cancer Cell Lines

Research paper thumbnail of Multianalyte Serum Biomarker Panel for Early Detection of Pancreatic Adenocarcinoma

JCO clinical cancer informatics, Mar 1, 2023

PURPOSE We determined whether a large, multianalyte panel of circulating biomarkers can improve d... more PURPOSE We determined whether a large, multianalyte panel of circulating biomarkers can improve detection of early-stage pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS We defined a biologically relevant subspace of blood analytes on the basis of previous identification in premalignant lesions or early-stage PDAC and evaluated each in pilot studies. The 31 analytes that met minimum diagnostic accuracy were measured in serum of 837 subjects (461 healthy, 194 benign pancreatic disease, and 182 early-stage PDAC). We used machine learning to develop classification algorithms using the relationship between subjects on the basis of their changes across the predictors. Model performance was subsequently evaluated in an independent validation data set from 186 additional subjects. RESULTS A classification model was trained on 669 subjects (358 healthy, 159 benign, and 152 early-stage PDAC). Model evaluation on a hold-out test set of 168 subjects (103 healthy, 35 benign, and 30 early-stage PDAC) yielded an area under the receiver operating characteristic curve (AUC) of 0.920 for classification of PDAC from non-PDAC (benign and healthy controls) and an AUC of 0.944 for PDAC versus healthy controls. The algorithm was then validated in 146 subsequent cases presenting with pancreatic disease (73 benign pancreatic disease and 73 early- and late-stage PDAC cases) and 40 healthy control subjects. The validation set yielded an AUC of 0.919 for classification of PDAC from non-PDAC and an AUC of 0.925 for PDAC versus healthy controls. CONCLUSION Individually weak serum biomarkers can be combined into a strong classification algorithm to develop a blood test to identify patients who may benefit from further testing.

Research paper thumbnail of Data from Diminished Immune Surveillance during Histologic Progression of Intraductal Papillary Mucinous Neoplasms Offers a Therapeutic Opportunity for Cancer Interception

Research paper thumbnail of Supplementary Data from Diminished Immune Surveillance during Histologic Progression of Intraductal Papillary Mucinous Neoplasms Offers a Therapeutic Opportunity for Cancer Interception

Supplementary Data from Diminished Immune Surveillance during Histologic Progression of Intraduct... more Supplementary Data from Diminished Immune Surveillance during Histologic Progression of Intraductal Papillary Mucinous Neoplasms Offers a Therapeutic Opportunity for Cancer Interception