96 results on '"Kelly J. Lafaro"'
Search Results
2. Multidisciplinary Care of Patients with Intrahepatic Cholangiocarcinoma: Updates in Management
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Kelly J. Lafaro, David Cosgrove, Jean-Francois H. Geschwind, Ihab Kamel, Joseph M. Herman, and Timothy M. Pawlik
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Cholangiocarcinoma is a highly fatal primary cancer of the bile ducts which arises from malignant transformation of bile duct epithelium. While being an uncommon malignancy with an annual incidence in the United States of 5000 new cases, the incidence has been increasing over the past 30 years and comprises 3% of all gastrointestinal cancers. Cholangiocarcinoma can be classified into intrahepatic (ICC) and extrahepatic (including hilar and distal bile duct) according to its anatomic location within the biliary tree with respect to the liver. This paper reviews the management of ICC, focusing on the epidemiology, risk factors, diagnosis, and surgical and nonsurgical management.
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- 2015
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3. Gd-EOB-DTPA-Enhanced MRI for Detection of Liver Metastases from Colorectal Cancer: A Surgeon’s Perspective!
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Kelly J. Lafaro, Panayota Roumanis, Aram N. Demirjian, Chandana Lall, and David K. Imagawa
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Colorectal cancer affects over one million people worldwide annually, with the liver being the most common site of metastatic spread. Adequate resection of hepatic metastases is the only chance for a cure in a subset of patients, and five-year survival increases to 35% with complete resection. Traditionally, computed tomographic imaging (CT) was utilized for staging and to evaluate metastases in the liver. Recently, the introduction of hepatobiliary contrast-enhanced magnetic resonance imaging (MRI) agents including gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Eovist in the United States, Primovist in Europe, or Gd-EOB-DTPA) has proved to be a sensitive method for detection of hepatic metastases. Accurate detection of liver metastases is critical for staging of colorectal cancer as well as preoperative planning.
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- 2013
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4. Cancer-cell-derived sialylated IgG as a novel biomarker for predicting poor pathological response to neoadjuvant therapy and prognosis in pancreatic cancer
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Ming Cui, Sami Shoucair, Quan Liao, Xiaoyan Qiu, Benedict Kinny-Köster, Joseph R. Habib, Elie M. Ghabi, Junke Wang, Eun Ji Shin, Sean X. Leng, Syed Z. Ali, Elizabeth D. Thompson, Jacquelyn W. Zimmerman, Christopher R. Shubert, Kelly J. Lafaro, Richard A. Burkhart, William R. Burns, Lei Zheng, Jin He, Yupei Zhao, Christopher L. Wolfgang, and Jun Yu
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Surgery ,General Medicine - Published
- 2023
5. Tailoring Adjuvant Chemotherapy to Biologic Response Following Neoadjuvant Chemotherapy Impacts Overall Survival in Pancreatic Cancer
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Elie M. Ghabi, Sami Shoucair, Ding Ding, Ammar A. Javed, Elizabeth D. Thompson, Lei Zheng, John L. Cameron, Christopher L. Wolfgang, Christopher R. Shubert, Kelly J. Lafaro, Richard A. Burkhart, William R. Burns, and Jin He
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Gastroenterology ,Surgery ,Article - Abstract
BACKGROUND: The role of postoperative chemotherapy in patients with resected pancreatic cancer who receive neoadjuvant treatment is unknown. Clinicians use changes in CA19-9 and histopathologic scores to assess treatment response. We sought to investigate if CA19-9 normalization in response to NAT can help guide the need for postoperative treatment. METHODS: Patients with elevated baseline CA19-9 (CA19-9 > 37U/mL) who received NAT followed by surgery between 2011 and 2019 were retrospectively reviewed. Treatment response was determined by CA19-9 normalization following NAT and histopathologic scoring. The role of postoperative chemotherapy was analyzed in light of CA19-9 normalization and histopathologic response. RESULTS: We identified and included 345 patients. Following NAT, CA19-9 normalization was observed in 125 patients (36.2%). CA19-9 normalization was associated with a favorable histopathologic response (41.6% vs 23.2%, p < 0.001) and a lower ypT (p < 0.001) and ypN stage (p = 0.003). Receipt of adjuvant chemotherapy was associated with improved overall survival in patients in whom CA19-9 did not normalize following NAT (26.8 vs 16.4 months, p = 0.008). In patients who received 5FU-based NAT and in whom CA19-9 did not normalize, receipt of 5FU-based adjuvant chemotherapy was associated with improved OS (p = 0.014). CONCLUSION: CA19-9 normalization in response to NAT was associated with favorable outcomes and can serve as a biomarker for treatment response. In patients where CA19-9 did not normalize, receipt of postoperative chemotherapy was associated with improved OS. These patients also benefited from additional 5FU-based postoperative chemotherapy following 5FU-based NAT.
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- 2022
6. A Delay in Adjuvant Therapy Is Associated With Worse Prognosis Only in Patients With Transitional Circulating Tumor Cells After Resection of Pancreatic Ductal Adenocarcinoma
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Ammar A, Javed, A, Floortje van Oosten, Joseph R, Habib, Alina, Hasanain, Benedict, Kinny-Köster, Georgios, Gemenetzis, Vincent, Groot, Ding, Ding, John L, Cameron, Kelly J, Lafaro, William R, Burns, Richard A, Burkhart, Jun, Yu, Jin, He, and Christopher L, Wolfgang
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Surgery - Abstract
The aim of the study was to assess the association of circulating tumor cells (CTCs) with survival as a biomarker in pancreatic ductal adenocarcinoma (PDAC) within the context of a delay in initiation of adjuvant therapy.Outcomes in patients with PDAC remain poor and are driven by aggressive systemic disease. While systemic therapies improve survival in resected patients, factors such as a delay in initiation of adjuvant therapy are associated with worse outcomes. CTCs have previously been shown to be predictive of survival.A retrospective study was performed on PDAC patients enrolled in the prospective CLUSTER trial (NCT02974764) on CTC-dynamics at the Johns Hopkins Hospital. CTCs were isolated based on size (ISET; Rarecells) and counted and characterized by subtype using immunofluorescence. The preoperative and postoperative blood samples were used to identify two CTC types: epithelial CTCs (eCTCs), expressing pan-cytokeratin, and transitional CTCs (trCTCs), expressing both pan-cytokeratin and vimentin. Patients who received adjuvant therapy were compared with those who did not. A delay in receipt of adjuvant therapy was defined as initiation of therapy ≥8 weeks after surgical resection. Clinicopathological features, CTCs characteristics, and outcomes were analyzed.Of 101 patients included in the study, 43 (42.5%) experienced a delay in initiation and 20 (19.8%) did not receive adjuvant therapy. On multivariable analysis, presence of transitional CTCs (trCTCs, P=0.002) and absence of adjuvant therapy (P=0.032) were associated with worse recurrence-free survival (RFS). Postoperative trCTC were associated with poorer RFS, both in patients with a delay in initiation (12.4 vs. 17.9 mo, P=0.004) or no administration of adjuvant chemotherapy (3.4 vs. NR, P=0.016). However, it was not associated with RFS in patients with timely initiation of adjuvant chemotherapy (P=0.293).Postoperative trCTCs positivity is associated with poorer RFS only in patients who either experience a delay in initiation or no receipt of adjuvant therapy. This study suggests that a delay in initiation of adjuvant therapy could potentially provide residual systemic disease (trCTCs) a window of opportunity to recover from the surgical insult. Future studies are required to validate these findings and explore the underlying mechanisms involved.
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- 2022
7. Association of Matrix Metalloproteinase 7 Expression With Pathologic Response After Neoadjuvant Treatment in Patients With Resected Pancreatic Ductal Adenocarcinoma
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Sami Shoucair, Jianan Chen, James R. Martinson, Joseph R. Habib, Benedict Kinny-Köster, Ning Pu, A. Floortje van Oosten, Ammar A. Javed, Eun Ji Shin, Syed Z. Ali, Kelly J. Lafaro, Christopher L. Wolfgang, Jin He, and Jun Yu
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Male ,Pancreatic Neoplasms ,Matrix Metalloproteinase 7 ,Humans ,Surgery ,Female ,Adenocarcinoma ,Neoadjuvant Therapy ,Carcinoma, Pancreatic Ductal ,Retrospective Studies ,Original Investigation - Abstract
IMPORTANCE: The use of neoadjuvant therapy (NAT) in resectable pancreatic ductal adenocarcinoma (PDAC) remains controversial. A favorable pathologic response (complete or marked tumor regression) to NAT is associated with better outcomes in patients with resected PDAC. The role of NAT for early systemic control compared with immediate surgical resection for PDAC is under investigation. In the era of precision medicine, biomarkers for patient selection and prediction of therapy response are crucial. OBJECTIVE: To evaluate the use of assessment for protein expression on fine-needle aspiration (FNA) biopsy specimens in predicting pathologic response to NAT in treatment-naive patients. DESIGN, SETTING, AND PARTICIPANTS: This was a single-institution prognostic study from a high-volume center for pancreatic cancer. All specimens were obtained between January 1, 2009, and December 31, 2018, with a median (SE) follow-up of 20.2 (1.4) months. Analysis of the data was performed from October 1, 2019, to April 30, 2021. Targeted RNA sequencing of frozen FNA biopsy specimens from a discovery cohort of 23 patients was performed to identify genes with aberrant expression that was associated with patients’ pathologic response to NAT. Immunohistochemical staining was performed on an additional 80 FNA biopsy specimens to assess expression of matrix metalloproteinase 7 (MMP-7) and its association with pathologic response. Receiver operating characteristic curves for prediction of favorable pathologic response were determined. RESULTS: In the discovery cohort (12 [52.1%] male; 3 [13.0%] Black and 20 [86.9%] White), RNA sequencing showed that lower MMP-7 expression was associated with favorable pathologic response (College of American Pathologists system scores of 0 [complete response] and 1 [marked response]). In the validation cohort (40 [50.0%] female; 9 [11.3%] Black and 71 [88.7%] White), patients with negative MMP-7 expression were significantly more likely to have a favorable pathologic response (odds ratio, 21.25; 95% CI, 6.19-72.95; P = .001). Receiver operating characteristic curves for prediction of favorable pathologic response from multivariable Cox proportional hazards regression modeling showed that MMP-7 expression increased the area under the curve from 0.726 to 0.906 (P
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- 2023
8. Postoperative Chemotherapy is Associated with Improved Survival in Patients with Node-Positive Pancreatic Ductal Adenocarcinoma After Neoadjuvant Therapy
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Gabriel D. Ivey, Sami Shoucair, Daniel J. Delitto, Joseph R. Habib, Benedict Kinny-Köster, Christopher R. Shubert, Kelly J. Lafaro, John L. Cameron, William R. Burns, Richard A. Burkhart, Elizabeth L. Thompson, Amol Narang, Lei Zheng, Christopher L. Wolfgang, and Jin He
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Surgery - Published
- 2022
9. Should non-invasive diffuse main-duct intraductal papillary mucinous neoplasms be treated with total pancreatectomy?
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William H. Burns, Kelly J. Lafaro, Jin He, Richard A. Burkhart, Matthew J. Weiss, John L. Cameron, Christopher L. Wolfgang, James F. Griffin, Joseph R. Habib, Ross M. Beckman, and Alex B. Blair
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medicine.medical_specialty ,endocrine system diseases ,Total pancreatectomy ,medicine.medical_treatment ,Pancreatic Intraductal Neoplasms ,Malignancy ,Main duct ,Article ,Pancreatectomy ,Humans ,Medicine ,Retrospective Studies ,Hepatology ,Intraductal papillary mucinous neoplasm ,business.industry ,Gastroenterology ,medicine.disease ,Pancreaticoduodenectomy ,Adenocarcinoma, Mucinous ,Pancreatic Neoplasms ,Partial Pancreatectomy ,medicine.anatomical_structure ,Dysplasia ,Radiology ,business ,Pancreas ,Carcinoma, Pancreatic Ductal ,Dilatation, Pathologic - Abstract
BACKGROUND: Main-duct (MD) intraductal papillary mucinous neoplasm (IPMN) is associated with malignancy risk. There is a lack of consensus on treatment (partial or total pancreatectomy) when the MD is diffusely involved. We sought to characterize the pancreatic remnant fate after partial pancreatectomy for non-invasive diffuse MD-IPMN. METHODS: Consecutive patients with partial pancreatectomy for non-invasive MD-IPMN from 2004 to 2016 were analyzed. Diffuse MD-IPMN was defined by preoperative imaging as dilation of the MD in the head of the pancreas more than 5mm and involving the whole gland. RESULTS: Of 127 patients with resected non-invasive MD-IPMN, 47 (37%) had diffuse MD involvement. Eleven of 47(23%) patients developed imaging evidence of progression or new cystic disease in the pancreatic remnant. Patients with diffuse MD-IPMN were older (73yrs vs 67yrs, p=0.009), more likely to receive a pancreaticoduodenectomy (96% vs 56%, p
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- 2022
10. Data from Precision Medicine in Pancreatic Cancer: Patient-Derived Organoid Pharmacotyping Is a Predictive Biomarker of Clinical Treatment Response
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Richard A. Burkhart, Elizabeth M. Jaffee, David T. Ting, Theodore S. Hong, Alec C. Kimmelman, David P. Ryan, James R. Eshlemann, David A. Tuveson, Lei Zheng, Ying S. Zou, Christopher L. Wolfgang, Jin He, Kelly J. Lafaro, William R. Burns, John L. Cameron, Christopher R. Shubert, Annamaria Szabolcs, Gabriel D. Ivey, Haley Zlomke, Reecha Suri, Jacquelyn W. Zimmerman, and Toni T. Seppälä
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Purpose:Patient-derived organoids (PDO) are a promising technology to support precision medicine initiatives for patients with pancreatic ductal adenocarcinoma (PDAC). PDOs may improve clinical next-generation sequencing (NGS) and enable rapid ex vivo chemotherapeutic screening (pharmacotyping).Experimental Design:PDOs were derived from tissues obtained during surgical resection and endoscopic biopsies and studied with NGS and pharmacotyping. PDO-specific pharmacotype is assessed prospectively as a predictive biomarker of clinical therapeutic response by leveraging data from a randomized controlled clinical trial.Results:Clinical sequencing pipelines often fail to detect PDAC-associated somatic mutations in surgical specimens that demonstrate a good pathologic response to previously administered chemotherapy. Sequencing the PDOs derived from these surgical specimens, after biomass expansion, improves the detection of somatic mutations and enables quantification of copy number variants. The detection of clinically relevant mutations and structural variants is improved following PDO biomass expansion. On clinical trial, PDOs were derived from biopsies of treatment-naïve patients prior to treatment with FOLFIRINOX (FFX). Ex vivo PDO pharmacotyping with FFX components predicted clinical therapeutic response in these patients with borderline resectable or locally advanced PDAC treated in a neoadjuvant or induction paradigm. PDO pharmacotypes suggesting sensitivity to FFX components were associated with longitudinal declines of tumor marker, carbohydrate-antigen 19–9 (CA-19–9), and favorable RECIST imaging response.Conclusions:PDOs established from tissues obtained from patients previously receiving cytotoxic chemotherapies can be accomplished in a clinically certified laboratory. Sequencing PDOs following biomass expansion improves clinical sequencing quality. High in vitro sensitivity to standard-of-care chemotherapeutics predicts good clinical response to systemic chemotherapy in PDAC.See related commentary by Zhang et al., p. 3176
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- 2023
11. Supplementary Figure from Precision Medicine in Pancreatic Cancer: Patient-Derived Organoid Pharmacotyping Is a Predictive Biomarker of Clinical Treatment Response
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Richard A. Burkhart, Elizabeth M. Jaffee, David T. Ting, Theodore S. Hong, Alec C. Kimmelman, David P. Ryan, James R. Eshlemann, David A. Tuveson, Lei Zheng, Ying S. Zou, Christopher L. Wolfgang, Jin He, Kelly J. Lafaro, William R. Burns, John L. Cameron, Christopher R. Shubert, Annamaria Szabolcs, Gabriel D. Ivey, Haley Zlomke, Reecha Suri, Jacquelyn W. Zimmerman, and Toni T. Seppälä
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Supplementary Figure from Precision Medicine in Pancreatic Cancer: Patient-Derived Organoid Pharmacotyping Is a Predictive Biomarker of Clinical Treatment Response
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- 2023
12. Supplementary Table from Precision Medicine in Pancreatic Cancer: Patient-Derived Organoid Pharmacotyping Is a Predictive Biomarker of Clinical Treatment Response
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Richard A. Burkhart, Elizabeth M. Jaffee, David T. Ting, Theodore S. Hong, Alec C. Kimmelman, David P. Ryan, James R. Eshlemann, David A. Tuveson, Lei Zheng, Ying S. Zou, Christopher L. Wolfgang, Jin He, Kelly J. Lafaro, William R. Burns, John L. Cameron, Christopher R. Shubert, Annamaria Szabolcs, Gabriel D. Ivey, Haley Zlomke, Reecha Suri, Jacquelyn W. Zimmerman, and Toni T. Seppälä
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Supplementary Table from Precision Medicine in Pancreatic Cancer: Patient-Derived Organoid Pharmacotyping Is a Predictive Biomarker of Clinical Treatment Response
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- 2023
13. Supplementary Data from Precision Medicine in Pancreatic Cancer: Patient-Derived Organoid Pharmacotyping Is a Predictive Biomarker of Clinical Treatment Response
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Richard A. Burkhart, Elizabeth M. Jaffee, David T. Ting, Theodore S. Hong, Alec C. Kimmelman, David P. Ryan, James R. Eshlemann, David A. Tuveson, Lei Zheng, Ying S. Zou, Christopher L. Wolfgang, Jin He, Kelly J. Lafaro, William R. Burns, John L. Cameron, Christopher R. Shubert, Annamaria Szabolcs, Gabriel D. Ivey, Haley Zlomke, Reecha Suri, Jacquelyn W. Zimmerman, and Toni T. Seppälä
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Supplementary Data from Precision Medicine in Pancreatic Cancer: Patient-Derived Organoid Pharmacotyping Is a Predictive Biomarker of Clinical Treatment Response
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- 2023
14. Supplemental figure legends from p120 Catenin Suppresses Basal Epithelial Cell Extrusion in Invasive Pancreatic Neoplasia
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Jennifer M. Bailey, Steven D. Leach, Christine A. Iacobuzio-Donahue, Mamoun Younes, Michael Goggins, Albert B. Reynolds, Anirban Maitra, Matthias Hebrok, Yanna Cao, Samuel G. Savidge, Nilotpal Roy, Hao Zhang, Kelly J. Lafaro, Ishrat Ahmed, Janivette Alsina, Kishore Polireddy, Yue J. Wang, and Audrey M. Hendley
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This document provides detailed captions for figures S1-S8.
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- 2023
15. Figures S1-S8 from p120 Catenin Suppresses Basal Epithelial Cell Extrusion in Invasive Pancreatic Neoplasia
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Jennifer M. Bailey, Steven D. Leach, Christine A. Iacobuzio-Donahue, Mamoun Younes, Michael Goggins, Albert B. Reynolds, Anirban Maitra, Matthias Hebrok, Yanna Cao, Samuel G. Savidge, Nilotpal Roy, Hao Zhang, Kelly J. Lafaro, Ishrat Ahmed, Janivette Alsina, Kishore Polireddy, Yue J. Wang, and Audrey M. Hendley
- Abstract
This file contains Figures S1-S8. Figure S1 shows examples of representative images used to score p120 catenin expression in human TMAs and pancreatic histology of mice with loss of p120 catenin. Figure S2 depicts recruitment of inflammation and a unique stromal composition in KCiMist1; p120f/wt and KCiMist1; p120f/f pancreata. Figure S3 shows that prominent basal epithelial cell extrusion in pancreata of KCiMist1; p120f/f mice is not associated with incomplete EMT. Figure S4 shows that pancreatic loss of p120 catenin in a mouse model of acute pancreatitis delays regeneration and results in significant recruitment of inflammation, observations which are mediated at least in part through activation of NF-kB. Figure S5 illustrates that a subset of epithelial cells extruding apically in KCiMist1; p120wt/wt, KCiMist1; p120f/wt, and KCiMist1; p120f/f pancreata express cleaved Caspase-3, while epithelial cells extruding basally do not express cleaved Caspase-3. Figure S6 depicts an analysis of chromosome content using Feulgen stain, which showed abnormal DNA content and aneuploidy in a subset of basally extruded epithelial cells in KCiMist1; p120f/f pancreata. Figure S7 shows mislocalized p120 catenin expression in greater than 95% isolated epithelial cells in human PDA. Figure S8 illustrates IPA results of microarray performed on GFP+ pancreatic cells of KCiMist1G; p120wt/wt and KCiMist1G; p120f/f mice as well as IHC of select targets identified from IPA results.
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- 2023
16. Supplemental table 1 from p120 Catenin Suppresses Basal Epithelial Cell Extrusion in Invasive Pancreatic Neoplasia
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Jennifer M. Bailey, Steven D. Leach, Christine A. Iacobuzio-Donahue, Mamoun Younes, Michael Goggins, Albert B. Reynolds, Anirban Maitra, Matthias Hebrok, Yanna Cao, Samuel G. Savidge, Nilotpal Roy, Hao Zhang, Kelly J. Lafaro, Ishrat Ahmed, Janivette Alsina, Kishore Polireddy, Yue J. Wang, and Audrey M. Hendley
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This table provides a description of antibodies used in this study.
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- 2023
17. Data from p120 Catenin Suppresses Basal Epithelial Cell Extrusion in Invasive Pancreatic Neoplasia
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Jennifer M. Bailey, Steven D. Leach, Christine A. Iacobuzio-Donahue, Mamoun Younes, Michael Goggins, Albert B. Reynolds, Anirban Maitra, Matthias Hebrok, Yanna Cao, Samuel G. Savidge, Nilotpal Roy, Hao Zhang, Kelly J. Lafaro, Ishrat Ahmed, Janivette Alsina, Kishore Polireddy, Yue J. Wang, and Audrey M. Hendley
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Aberrant regulation of cellular extrusion can promote invasion and metastasis. Here, we identify molecular requirements for early cellular invasion using a premalignant mouse model of pancreatic cancer with conditional knockout of p120 catenin (Ctnnd1). Mice with biallelic loss of p120 catenin progressively develop high-grade pancreatic intraepithelial neoplasia (PanIN) lesions and neoplasia accompanied by prominent acute and chronic inflammatory processes, which is mediated, in part, through NF-κB signaling. Loss of p120 catenin in the context of oncogenic Kras also promotes remarkable apical and basal epithelial cell extrusion. Abundant single epithelial cells exit PanIN epithelium basally, retain epithelial morphology, survive, and display features of malignancy. Similar extrusion defects are observed following p120 catenin knockdown in vitro, and these effects are completely abrogated by the activation of S1P/S1pr2 signaling. In the context of oncogenic Kras, p120 catenin loss significantly reduces expression of genes mediating S1P/S1pr2 signaling in vivo and in vitro, and this effect is mediated at least, in part, through activation of NF-κB. These results provide insight into mechanisms controlling early events in the metastatic process and suggest that p120 catenin and S1P/S1pr2 signaling enhance cancer progression by regulating epithelial cell invasion. Cancer Res; 76(11); 3351–63. ©2016 AACR.
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- 2023
18. Incidence and Contemporary Management of Delayed Bleeding Following Pancreaticoduodenectomy
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Joseph R. Habib, Shanshan Gao, Ahn Joon Young, Elie Ghabi, Aslam Ejaz, William Burns, Richard Burkhart, Matthew Weiss, Christopher L. Wolfgang, John L. Cameron, Robert Liddell, Christos Georgiades, Kelvin Hong, Jin He, and Kelly J. Lafaro
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Hepatic Artery ,Incidence ,Humans ,Surgery ,Postoperative Hemorrhage ,Pancreaticoduodenectomy ,Retrospective Studies - Abstract
Delayed bleeding after pancreaticoduodenectomy (PD) is a life-threatening complication. However, the optimal management remains unclear. We summarize our experience of the management of delayed bleeding after PD and define the outcomes associated with different types of management.All patients who underwent a PD between January 1987 and June 2020 at Johns Hopkins University were retrospectively reviewed. Delayed bleeding was defined as bleeding on or after postoperative day 5 following PD. Incidence, outcomes, and trends were reported.Among the 6201 patients that underwent PD, delayed bleeding occurred in 130 (2.1%) at a median of 12 days (IQR: 9, 24) postoperation. The pattern of bleeding was classified as intraluminal (51.5%), extraluminal (40.8%), and mixed (7.7%). A clinically relevant postoperative pancreatic fistula and an intraabdominal abscess preceded the delayed bleeding in 43.1% and 31.5% of cases, respectively. Arterial pseudoaneurysm or bleeding from peripancreatic vessels was the most common reason (54.6%) with the gastroduodenal artery being the most common source (18.5%). Endoscopy, angiography, and reoperation were performed as a first-line approach in 35.4%, 52.3%, and 6.2% of patients, respectively. The overall mortality was 16.2% and decreased over the study period (p 0.01).Delayed bleeding following PD remains a life-threatening complication. The most common location of delayed bleeding is from the gastroduodenal artery. Angiography with embolization should be the initial approach for urgent bleeding with surgical re-exploration reserved for unstable patients or failed control of bleeding after interventional angiography or endoscopy.
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- 2022
19. Structured CT reporting of pancreatic ductal adenocarcinoma: impact on completeness of information and interdisciplinary communication for surgical planning
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Alina Hasanain, Jin He, Atif Zaheer, Rubab F. Malik, Amol Narang, Elliot K. Fishman, and Kelly J. Lafaro
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medicine.medical_specialty ,Pancreatic ductal adenocarcinoma ,Radiological and Ultrasound Technology ,business.industry ,Urology ,General surgery ,Gastroenterology ,Hepatology ,Surgical planning ,Likert scale ,Exact test ,Internal medicine ,Structured reporting ,medicine ,Main portal vein ,Radiology, Nuclear Medicine and imaging ,Interdisciplinary communication ,business - Abstract
With the rise in popularity of structured reports in radiology, we sought to evaluate whether free-text CT reports on pancreatic ductal adenocarcinoma (PDAC) staging at our institute met published guidelines and assess feedback of pancreatic surgeons comparing free-text and structured report styles with the same information content. We retrospectively evaluated 298 free-text preoperative CT reports from 2015 to 2017 for the inclusion of key tumor descriptors. Two surgeons independently evaluated 50 free-text reports followed by evaluation of the same reports in a structured format using a 7-question survey to assess the usefulness and ease of information extraction. Fisher’s exact test and Chi-square test for independence were utilized for categorical responses and an independent samples t test for comparing mean ratings of report quality as rated on a 5-point Likert scale. The most commonly included descriptors in free-text reports were tumor location (99%), liver lesions (97%), and suspicious lymph nodes (97%). The most commonly excluded descriptors were variant arterial anatomy and peritoneal/omental nodularity, which were present in only 23% and 42% of the reports, respectively. For vascular involvement, a mention of the presence or absence of perivascular disease with the main portal vein was most commonly included (87%). Both surgeons’ rating of overall report quality was significantly higher for structured reports (p
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- 2021
20. Comprehensive Analysis of Somatic Mutations in Driver Genes of Resected Pancreatic Ductal Adenocarcinoma Reveals KRAS G12D and Mutant TP53 Combination as an Independent Predictor of Clinical Outcome
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Ammar A. Javed, Christopher L. Wolfgang, Ning Pu, Sami Shoucair, Joseph R. Habib, A Floortje van Ooston, Kelly J. Lafaro, Jun Yu, Benedict Kinny-Köster, and Jin He
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Oncology ,medicine.medical_specialty ,Proportional hazards model ,business.industry ,Somatic cell ,Cancer ,medicine.disease_cause ,medicine.disease ,Surgical oncology ,CDKN2A ,Internal medicine ,Cohort ,medicine ,Surgery ,KRAS ,business ,Gene - Abstract
Background Prognosis in pancreatic ductal adenocarcinoma (PDAC) remains poor despite improved systemic therapies and surgical techniques. The identification of biomarkers to advance insight in tumor biology and achieve better individualized prognostication could help improve outcomes. Our aim was to elucidate the prognostic role of the four main driver mutations (KRAS, TP53, SMAD4, CDKN2A) and their combinations in resected PDAC. Patients and methods A retrospective analysis was conducted utilizing the cBioPortal database and National Cancer Institute's Cancer Genomic Atlas (TCGA) on patients in whom next-generation sequencing was performed on upfront resected PDAC from 2012 to 2020. Multivariable Cox regression was implemented to elucidate risk-adjusted predictors of overall (OS) and recurrence-free survival (RFS). Results were validated employing a Johns Hopkins Hospital (JHH) cohort.' Results In the discovery cohort (n = 587), increased number of mutated driver genes was associated with worse OS (p = 0.047). Specifically, patients with mutations in ≥ 2 driver genes had worse OS than ≤ 1 mutated gene (18.2 versus 32.3 months, p = 0.033). Co-occurrence of mutant (mt)KRAS p.G12D with mtTP53 (median OS, 25.9 months) conferred better prognosis than co-occurrence of other mtKRAS variants (p.G12V/R/other) with mtTP53 (median OS, 16.9 months, p = 0.038). The findings were validated using a JHH cohort. Multivariable risk-adjustment found co-occurrence of mtKRAS p.G12D with mtTP53 to be an independent predictor of beneficial OS and RFS [HR (95% CI): 0.18 (0.03-0.81) and 0.31 (0.11-0.89) respectively]. Conclusion In chemo-naive resected PDAC, combinations of mutations in the four driver genes are associated with prognosis. In patients with combined mtKRAS and mtTP53, KRAS p.G12D variant confers a better OS and RFS.
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- 2021
21. Study on augmented reality for robotic surgery bedside assistants
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Govinda Payyavula, Sherry M. Wren, Kirsten Tallmon, Yuman Fong, Simon P. DiMaio, Abigail Fong, Jonathan M. Sorger, Camille L. Stewart, and Kelly J. Lafaro
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business.industry ,Headset ,Health Informatics ,Video-Assisted Surgery ,Visualization ,Task (project management) ,Human–computer interaction ,Medicine ,Robot ,Surgery ,Robotic surgery ,Augmented reality ,business ,Surgical robot - Abstract
Robotic surgery bedside assistants play an important role in robotic procedures by performing intra-corporeal tasks while accommodating the physical presence of the robot. We hypothesized that an augmented reality headset enabling 3D intra-corporeal vision while facing the surgical field could decrease time and improve accuracy of robotic bedside tasks. Bedside assistants (one physician assistant, one medical student, three surgical trainees, and two attending surgeons) performed validated tasks within a mock abdominal cavity with a surgical robot docked. Tasks were performed with a bedside monitor providing 2D or 3D vision, or an optical see-through head-mounted augmented reality device with 2D or 3D vision. The effect of augmented reality device resolution on performance was also evaluated. For the simplest task of touching a straw, performance was generally high, regardless of mode of visualization. With more complex tasks, including stapling and pulling a ring along a path, 3D augmented reality decreased time and number of errors per task. 3D augmented reality allowed the physician assistant to perform at the level of an attending surgeon using 3D augmented reality (p = 0.08). All participants had improved times for the ring path task with better resolution (lower resolution 23 ± 11 s vs higher resolution 14 ± 4 s, p = 0.002). 3D augmented reality vision with high resolution decreased time and improved accuracy of more complex tasks, enabling a less experienced robotic surgical bedside assistant to function similar to attending surgeons. These data warrant further study with additional complex tasks and bedside assistants at various levels of training.
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- 2021
22. Characteristics and Outcomes of Percutaneous Biliary Interventions in the United States
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Clifford R. Weiss, Nima Hafezi-Nejad, Kelly J. Lafaro, Robert P. Liddell, Christopher R. Bailey, B. Holly, and Moustafa Abou Areda
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medicine.medical_specialty ,Percutaneous ,business.industry ,medicine.medical_treatment ,Psychological intervention ,Odds ratio ,Length of Stay ,Percutaneous transhepatic cholangiography ,medicine.disease ,Malignancy ,Comorbidity ,United States ,Hospitalization ,Sepsis ,Treatment Outcome ,Internal medicine ,Paralysis ,medicine ,Drainage ,Humans ,Radiology, Nuclear Medicine and imaging ,medicine.symptom ,business ,Retrospective Studies - Abstract
Objective To explore baseline characteristics, comorbidities, and clinical diagnoses in the prediction of outcomes for inpatient percutaneous biliary interventions in the United States. Methods Hospitalizations for percutaneous transhepatic cholangiography and percutaneous biliary drainage were studied using the National Inpatient Sample 2012 to 2015. Associations between baseline characteristics, comorbidities, clinical diagnoses, and outcomes were analyzed using multivariable regression modeling. Regional variations were studied in an exploratory analysis. Results Hospitalizations for percutaneous biliary interventions had average inpatient mortality of 3.8% ± 0.8% and length of stay of 7.6 ± 0.3 days. Hypertension was the most common comorbidity (50.5% ± 0.8%), and paralysis was associated with the highest inpatient mortality (19.1% ± 5.7%) and length of stay (11.4 ± 1.3 days). Compared with nonmalignant biliary-pancreatic disorders, sepsis was associated with the highest inpatient mortality (6.5% ± 1.1%; adjusted odds ratio [aOR]: 5.2 [3.9-7.0]) and length of stay (9.0 ± 3.0 days; aOR: 2.2 [1.9-2.5]), followed by underlying malignancy (mortality of 5.5% ± 0.6%; aOR: 2.3 [1.7-3.0]; length of stay of 8.3 ± 0.2 days; aOR: 1.6 [1.4-1.8]). The observed associations were independent of baseline characteristics and comorbidities. With regard to regional variations, the Middle Atlantic states had the lengthiest hospital stays (38.8% ± 2.0% >8 days) and the East South Central states had the highest inpatient mortality (6.6% ± 1.6%) while having the highest frequency of malignancy (37.9% ± 3.7%) and the lowest frequency of postoperative cases (15.2% ± 2.4%). Conclusion In addition to baseline characteristics and comorbidities, sepsis and malignancy were determinants of higher mortality and increased length of stay in hospitalizations for percutaneous biliary interventions. We observed significant regional variations in clinical diagnoses and outcomes across the United States.
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- 2021
23. Precision medicine in pancreatic cancer: Patient derived organoid pharmacotyping is a predictive biomarker of clinical treatment response
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Toni T. Seppälä, Jacquelyn W. Zimmerman, Reecha Suri, Haley Zlomke, Gabriel D. Ivey, Annamaria Szabolcs, Christopher R. Shubert, John L. Cameron, William R. Burns, Kelly J. Lafaro, Jin He, Christopher L. Wolfgang, Ying S. Zou, Lei Zheng, David A. Tuveson, James R. Eshlemann, David P. Ryan, Alec C. Kimmelman, Theodore S. Hong, David T. Ting, Elizabeth M. Jaffee, Richard A. Burkhart, ATG - Applied Tumor Genomics, and HUS Abdominal Center
- Subjects
Cancer Research ,3122 Cancers ,THERAPY ,Article ,Organoids ,Pancreatic Neoplasms ,Oncology ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers, Tumor ,SURVIVAL ,Humans ,Precision Medicine ,Biomarkers ,Carcinoma, Pancreatic Ductal - Abstract
Purpose: Patient-derived organoids (PDO) are a promising technology to support precision medicine initiatives for patients with pancreatic ductal adenocarcinoma (PDAC). PDOs may improve clinical next-generation sequencing (NGS) and enable rapid ex vivo chemotherapeutic screening (pharmacotyping). Experimental Design: PDOs were derived from tissues obtained during surgical resection and endoscopic biopsies and studied with NGS and pharmacotyping. PDO-specific pharmacotype is assessed prospectively as a predictive biomarker of clinical therapeutic response by leveraging data from a randomized controlled clinical trial. Results: Clinical sequencing pipelines often fail to detect PDAC-associated somatic mutations in surgical specimens that demonstrate a good pathologic response to previously administered chemotherapy. Sequencing the PDOs derived from these surgical specimens, after biomass expansion, improves the detection of somatic mutations and enables quantification of copy number variants. The detection of clinically relevant mutations and structural variants is improved following PDO biomass expansion. On clinical trial, PDOs were derived from biopsies of treatment-naïve patients prior to treatment with FOLFIRINOX (FFX). Ex vivo PDO pharmacotyping with FFX components predicted clinical therapeutic response in these patients with borderline resectable or locally advanced PDAC treated in a neoadjuvant or induction paradigm. PDO pharmacotypes suggesting sensitivity to FFX components were associated with longitudinal declines of tumor marker, carbohydrate-antigen 19–9 (CA-19–9), and favorable RECIST imaging response. Conclusions: PDOs established from tissues obtained from patients previously receiving cytotoxic chemotherapies can be accomplished in a clinically certified laboratory. Sequencing PDOs following biomass expansion improves clinical sequencing quality. High in vitro sensitivity to standard-of-care chemotherapeutics predicts good clinical response to systemic chemotherapy in PDAC. See related commentary by Zhang et al., p. 3176
- Published
- 2022
24. Technical progress in robotic pancreatoduodenectomy: TRIANGLE and periadventitial dissection for retropancreatic nerve plexus resection
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Joseph R. Habib, Thilo Hackert, Ammar A. Javed, Elliot K. Fishman, Jin He, Christopher L. Wolfgang, Benedict Kinny-Köster, Sami Shoucair, Kelly J. Lafaro, and A. Floortje van Oosten
- Subjects
medicine.medical_specialty ,Common hepatic artery ,business.industry ,Nerve plexus ,Vascular surgery ,Dissection ,medicine.anatomical_structure ,Cardiothoracic surgery ,medicine.artery ,medicine ,Surgery ,Robotic surgery ,Radiology ,Superior mesenteric artery ,Superior mesenteric vein ,business - Abstract
The resection of retropancreatic nerve plexuses for pancreatic head cancer became standard of care during open pancreatoduodenectomy to minimize local recurrences. Since more surgical centers are progressing on the learning curve, robotically-assisted pancreatoduodenectomy is now increasingly performed with decreasing anatomic exclusion criteria. To achieve comparable and favorable oncologic outcomes, advanced surgical techniques should be transferred and implemented when performing robotic resections. The nomenclature and anatomic principles of retropancreatic nerve plexuses and three different levels of dissections are utilized based on established definitions. The en bloc dissection in the “TRIANGLE” area (triangular-shaped retropancreatic space enclosed by the common hepatic artery, superior mesenteric artery, and superior mesenteric vein/portal vein) and the periadventitial dissection of arteries for non-tunica media-invading tumors were executed robotically. Both can be utilized to achieve a radical dorsal and medial margin. Video recordings are provided to illustrate varying TRIANGLE dissections. To accomplish oncologic non-inferiority, established principles from open pancreatic resections can be incorporated precisely and safely, overcoming the lack of haptic feedback while exploiting the technological advantages of the robotically-assisted platform.
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- 2021
25. Ovarian Metastasis from Pancreatic Ductal Adenocarcinoma
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Jun Yu, Joseph R. Habib, Elliot K. Fishman, Elizabeth D. Thompson, Sami Shoucair, Ammar A. Javed, William R. Burns, Shamsher Pasha, Subhan Khan, Jin He, Kelly J. Lafaro, Benedict Kinny-Köster, Brigitte M. Ronnett, Richard A. Burkhart, Ralph H. Hruban, and Christopher L. Wolfgang
- Subjects
Oncology ,medicine.medical_specialty ,endocrine system diseases ,business.industry ,medicine.medical_treatment ,Retrospective cohort study ,Vascular surgery ,medicine.disease ,Cardiac surgery ,Ovarian disease ,Cardiothoracic surgery ,Internal medicine ,Pancreatectomy ,medicine ,Carcinoma ,Surgery ,business ,Abdominal surgery - Abstract
Pancreatic ductal adenocarcinoma (PDAC) has a high propensity for systemic dissemination. Ovarian metastases are rare and poorly described. We identified PDAC cases with ovarian metastasis from a prospectively maintained registry. We reported on the association between outcomes and clinicopathologic factors. Recurrence-free (RFS) and overall survival (OS) were calculated using Kaplan–Meier analysis. Twelve patients with PDAC and synchronous or metachronous ovarian metastases were identified. Nine patients (75%) underwent pancreatectomy for localized PDAC and developed metachronous ovarian recurrence. The median OS for all patients was 25.4 (IQR:15.4–82.9) months. For the nine patients with metachronous ovarian metastasis, the median RFS and OS were 14.2 (IQR:7.2–58.3) and 44.6 (IQR:18.6–82.9) months, respectively. Nodal disease, poor grade, vascular invasion in the pancreatic primary, and bilateral ovarian disease tended to confer worse outcomes. Patients with resected PDAC and ovarian recurrence tend to have a comparable disease course to more common patterns of recurrence. Primaries with nodal disease, poorer grade, vascular invasion, and bilateral ovarian disease were indicative of more aggressive disease biology. The ideal management remains largely unknown, and future collaborative efforts should optimize therapeutic strategies.
- Published
- 2021
26. Periadventitial dissection of the superior mesenteric artery for locally advanced pancreatic cancer: Surgical planning with the 'halo sign' and 'string sign'
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Richard A. Burkhart, Jin He, Christopher L. Wolfgang, Elliot K. Fishman, Kelly J. Lafaro, John L. Cameron, Joseph R. Habib, Benedict Kinny-Köster, Ammar A. Javed, William R. Burns, Floortje van Oosten, and Elizabeth D. Thompson
- Subjects
medicine.medical_specialty ,business.industry ,Dissection (medical) ,medicine.disease ,SMA ,Surgical planning ,medicine.anatomical_structure ,medicine.artery ,Pancreatic cancer ,medicine ,Surgery ,Superior mesenteric artery ,Radiology ,medicine.symptom ,Stage (cooking) ,business ,Halo sign ,Artery - Abstract
Most patients diagnosed with pancreatic cancer are classified as nonoperative candidates based on the contemporary guidelines of resectability. The advent of more potent control of systemic disease using neoadjuvant chemotherapy has enabled more aggressive operative interventions. In our multidisciplinary practice, patients with Stage III, locally advanced pancreatic cancer and superior mesenteric artery (SMA) encasement are now carefully triaged with high quality, preoperative imaging to determine if they can be considered candidates for operative resection with periadventitial dissection of the SMA. Patients displaying a "halo sign," where the encased SMA remains fully patent and free from arterial invasion, are now candidates for SMA periadventitial dissection. This procedure involves the surgical stripping of the infiltrated neurolymphatic tissue off the SMA leaving behind a bare "skeletonized artery." Alternatively, the "string sign" involving the SMA confers a more likely case of arterial invasion, where a complete oncologic resection cannot be achieved successfully. This method of patient selection in case of SMA involvement abandons the traditional metrics of circumferential degrees of the arterial encasement to guide surgical decisions. Our institutional approach has allowed us to meaningfully expand our operative methods of resection with the potential for improved longitudinal outcomes to pancreatic cancer patients who were deprived historically from the more effective and possibly curative treatment.
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- 2021
27. Impact of Margin Status on Survival in Patients with Pancreatic Ductal Adenocarcinoma Receiving Neoadjuvant Chemotherapy
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Christopher L. Wolfgang, Michael J. Wright, Daniel Delitto, William R. Burns, Richard A. Burkhart, John L. Cameron, Ding Ding, Ryan K. Schmocker, Kelly J. Lafaro, and Jin He
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Male ,medicine.medical_specialty ,Surgical margin ,FOLFIRINOX ,medicine.medical_treatment ,Leucovorin ,030230 surgery ,Irinotecan ,Gastroenterology ,Disease-Free Survival ,Pancreaticoduodenectomy ,03 medical and health sciences ,0302 clinical medicine ,Interquartile range ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Adjuvant therapy ,Humans ,Prospective Studies ,Pancreas ,Aged ,Neoplasm Staging ,Retrospective Studies ,business.industry ,Hazard ratio ,Margins of Excision ,Middle Aged ,Neoadjuvant Therapy ,Oxaliplatin ,Pancreatic Neoplasms ,Radiation therapy ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Pancreatectomy ,Female ,Surgery ,CA19-9 ,Fluorouracil ,Neoplasm Recurrence, Local ,business ,Carcinoma, Pancreatic Ductal ,Follow-Up Studies - Abstract
Background Historically, a positive margin after pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) was associated with decreased survival. In an era when neoadjuvant chemotherapy (NAC) is being used frequently, the prognostic significance of margin status is unclear. Study Design Patients with localized PDAC who received NAC and underwent pancreatectomy from 2011 to 2018 were identified from a single-institution database. Patients with fewer than 2 months of NAC, R2 resection, or fewer than 90 days of follow-up were excluded. A positive margin included tumors within 1 mm of the surgical margin. Results Four hundred and sixty-eight patients met inclusion criteria. Median age was 65 years and 53% were female. Preoperative clinical staging demonstrated that most had locally advanced (n = 222 [47%]) or borderline resectable (n = 172 [37%]) disease. Median follow-up was 18.5 months (interquartile range 10.6 to 30.0 months). Median duration of NAC was 119 days (interquartile range 87 to 168 days). FOLFIRINOX was first-line therapy for 67%, and 73% received neoadjuvant radiotherapy. Most underwent pancreaticoduodenectomy (69%). Forty percent were node-positive and 80% had an R0 resection. Fifty-six percent received at least 1 cycle of adjuvant therapy. Median overall survival and recurrence-free survival were 22.0 months (95% CI, 19.4 to 25.1 months) and 11.0 months (95% CI, 10.0 to 12.1 months). On multivariate analysis, margin status was not a significant predictor of overall survival or recurrence-free survival. Factors associated with overall survival included clinical stage, duration of NAC, nodal status, histopathologic treatment response score, and receipt of adjuvant chemotherapy. Conclusions Microscopic margin positivity is not associated with recurrence and survival in localized PDAC patients resected after treatment with NAC. Aggressive surgical extirpation in high-volume centers should be considered in selected patients after extensive NAC.
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- 2021
28. Defining a minimum number of examined lymph nodes improves the prognostic value of lymphadenectomy in pancreas ductal adenocarcinoma
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Ralph H. Hruban, Zhiyao Chen, William R. Burns, Ding Ding, Elizabeth D. Thompson, Shanshan Gao, Kelly J. Lafaro, Michael Beckman, John L. Cameron, Lingdi Yin, Haijie Hu, Jin He, Richard A. Burkhart, Michele M. Gage, Jun Yu, Yayun Zhu, Ross Beckman, Ning Pu, Michael J. Wright, and Christopher L. Wolfgang
- Subjects
Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,030230 surgery ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Stage (cooking) ,Pancreas ,Lymph node ,Neoplasm Staging ,Hepatology ,business.industry ,Gastroenterology ,Cancer ,Prognosis ,medicine.disease ,Pancreatic Neoplasms ,Survival Rate ,Binomial distribution ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Pancreatectomy ,Lymph Node Excision ,Lymphadenectomy ,Lymph Nodes ,Lymph ,business ,Carcinoma, Pancreatic Ductal - Abstract
Background Lymph node (LN) metastasis is associated with decreased survival following resection for pancreatic ductal adenocarcinoma (PDAC). In N0 disease, increasing total evaluated LN (ELN) correlates with improved outcomes suggesting patients may be understaged when LNs are undersampled. We aim to assess the optimal number of examined lymph nodes (ELN) following pancreatectomy. Methods Data from 1837 patients undergoing surgery were prospectively collected. The binomial probability law was utilized to analyze the minimum number of examined LNs (minELN) and accurately characterize each histopathologic stage. LN ratio (LNR) was compared to American Joint Committee on Cancer (AJCC) guidelines. Results As ELN total increased, the likelihood of finding node positive disease increased. An evaluation based upon the binomial probability law suggested an optimal minELN of 12 for accurate AJCC N staging. As the number of ELNs increased, the discriminatory capacity of alternative strategies to characterize LN disease exceeded that offered by AJCC N stage. Conclusion This is the first study dedicated to optimizing histopathologic staging in PDAC using models of minELN informed by the binomial probability law. This study highlights two separate cutoffs for ELNs depending upon prognostic goal and validates that 12 LNs are adequate to determine AJCC N stage for the majority of patients.
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- 2021
29. Minimal main pancreatic duct dilatation in small branch duct intraductal papillary mucinous neoplasms associated with high-grade dysplasia or invasive carcinoma
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Joseph R. Habib, Richard A. Burkhart, Lindsey Manos, Matthew J. Weiss, Ross Beckman, Atif Zaheer, Neda Rezaee, William R. Burns, Alex B. Blair, Ralph H. Hruban, Christopher L. Wolfgang, John L. Cameron, Neda Amini, Kelly J. Lafaro, Jin He, Anne Marie Lennon, and Elliot K. Fishman
- Subjects
medicine.medical_specialty ,Disease ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Aged ,Retrospective Studies ,Pancreatic duct ,Invasive carcinoma ,Hepatology ,business.industry ,Pancreatic Ducts ,Small branch ,Jaundice ,medicine.disease ,Adenocarcinoma, Mucinous ,Dilatation ,Pancreatic Neoplasms ,medicine.anatomical_structure ,Dysplasia ,030220 oncology & carcinogenesis ,Pancreatitis ,030211 gastroenterology & hepatology ,medicine.symptom ,business ,Duct (anatomy) ,Carcinoma, Pancreatic Ductal - Abstract
The aim of this study was to determine the incidence of high-grade dysplasia (HGD) or invasive carcinoma in patients with small branch duct intraductal papillary mucinous neoplasms (BD-IPMNs).923 patients who underwent surgical resection for an IPMN were identified. Sendai-negative patients were identified as those without history of pancreatitis or jaundice, main pancreatic duct size (MPD)5 mm, cyst size3 cm, no mural nodules, negative cyst fluid cytology for adenocarcinoma, or serum carbohydrate antigen 19-9 (CA 19-9)37 U/L.BD-IPMN was identified in 388 (46.4%) patients and 89 (22.9%) were categorized as Sendai-negative. Overall, 68 (17.5%) of BD-IPMN had HGD and 62 (16.0%) had an associated invasive-carcinoma. Among the 89 Sendai-negative patients, 12 (13.5%) had IPMNs with HGD and only one patient (1.1%) had invasive-carcinoma. Of note, older age (OR 1.13, 95% CI 1.03-1.23; P = 0.008) and minimal dilation of MPD (OR 11.3, 95% CI 2.40-53.65; P = 0.002) were associated with high-risk disease in Sendai-negative patients after multivariable risk adjustment.The risk of harboring a high-risk disease remains low in small BD-IPMNs. However, Sendai-negative patients who are older than 65 years old and those with minimal dilation of MPD (3-5 mm) are at greater risk of high-risk lesions and should be given consideration to be included as a "worrisome feature" in a future guidelines update.
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- 2021
30. Invasive and Noninvasive Progression After Resection of Noninvasive Intraductal Papillary Mucinous Neoplasms
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Elliot K. Fishman, Jin He, Joseph R. Habib, Matthew J. Weiss, Jun Yu, Atif Zaheer, Lindsey Manos, William R. Burns, Kelly J. Lafaro, Benedict Kinny-Köster, Richard A. Burkhart, Neda Rezaee, Alex B. Blair, Ralph H. Hruban, Neda Amini, John L. Cameron, and Christopher L. Wolfgang
- Subjects
medicine.medical_specialty ,Pancreatic Intraductal Neoplasms ,Disease ,Lesion ,03 medical and health sciences ,Pancreatectomy ,0302 clinical medicine ,medicine ,Humans ,Cumulative incidence ,Risk factor ,Retrospective Studies ,Pancreatic duct ,business.industry ,Cancer ,medicine.disease ,Adenocarcinoma, Mucinous ,Pancreatic Neoplasms ,medicine.anatomical_structure ,Dysplasia ,030220 oncology & carcinogenesis ,Cohort ,030211 gastroenterology & hepatology ,Surgery ,Radiology ,medicine.symptom ,business ,Carcinoma, Pancreatic Ductal - Abstract
OBJECTIVE To define frequencies, pattern of progression (invasive versus non-invasive), and risk factors of progression of resected non-invasive IPMNs BACKGROUND:: There is a risk of progression in the remnant pancreas after resection of intraductal papillary mucinous neoplasms (IPMNs). METHODS 449 consecutive patients with resected IPMNs from 1995-2018 were included to the study. Patients with invasive carcinoma or with follow-up < 6 months were excluded. Non-invasive progression was defined as a new IPMN, increased main pancreatic duct (MPD) size, and increased size of an existing lesion (5 mm compared to preoperative imaging). Invasive progression was defined as development of invasive cancer in the remnant pancreas or metastatic disease. RESULTS With a median follow-up of 48.9 months, progression was identified in 124 patients (27.6%); 108(24.1%) with non-invasive and 16(3.6%) with invasive progression. Median progression follow-up was longer for invasive progression (85.4 vs. 55.9 months; P = 0.001). Five- and 10-year estimates for a cumulative incidence of invasive progression were 6.4% and 12.9% versus 26.9% and 41.5% for non-invasive progression. After risk-adjustment, multifocality (HR 4.53, 95%CI 1.34-15.26; P = 0.02) and high-grade dysplasia (HGD) in the original resection (HR 3.60, 95%CI 1.13-11.48; P = 0.03) were associated with invasive progression. CONCLUSIONS Progression to invasive carcinoma can occur years after the surgical resection of a non-invasive IPMN. HGD in the original resection is a risk factor for invasive progression but some cases of low-grade dysplasia also progressed to cancer. Patients with high-risk features such as HGD and multifocal cysts should be considered for more intensive surveillance and represent an important cohort for future trials such as anti-inflammatory or prophylactic immunotherapy.
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- 2020
31. Duodenal, ampullary, and pancreatic neuroendocrine tumors: Oncologic outcomes are driven by tumor biology and tissue of origin
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Kelly J. Lafaro, Ryan K. Schmocker, Jin He, Richard A. Burkhart, Ammar A. Javed, William R. Burns, John L. Cameron, Christopher L. Wolfgang, Michael J. Wright, and Ding Ding
- Subjects
Adult ,Male ,Ampulla of Vater ,medicine.medical_specialty ,Common Bile Duct Neoplasms ,Context (language use) ,Neuroendocrine tumors ,Gastroenterology ,Pancreaticoduodenectomy ,03 medical and health sciences ,0302 clinical medicine ,Duodenal Neoplasms ,Interquartile range ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Ampulla ,Aged ,Neoplasm Staging ,AJCC staging system ,Cancer staging ,Aged, 80 and over ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Tumor Burden ,Pancreatic Neoplasms ,Survival Rate ,Neuroendocrine Tumors ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Duodenum ,Female ,030211 gastroenterology & hepatology ,Surgery ,Neoplasm Recurrence, Local ,Pancreas ,business ,Follow-Up Studies - Abstract
Background Periampullary neuroendocrine tumors (NETs) arise from the duodenum, ampulla, and periampullary pancreas. Duodenal and ampullary NETs are rare and may have distinct biologic behavior from pancreatic NETs (P-NETs). We examined the outcomes of these entities. Methods An institutional database was queried for patients undergoing resection for pancreatic head, duodenal, or ampullary NETs from 2000 to 2018. Patients with MEN1 syndrome or follow up less than 12 months were excluded. Results Three hundred and ten patients were identified. Tumor locations were ampulla (n = 15), duodenum (n = 35) and pancreas (n = 260). Median follow-up and recurrence-free survival (RFS) were 60.9 (interquartile range [IQR]: 34.8-99.3) and 171.7 (IQR: 84.0-NR) months. Clinicopathologic data and survival outcomes were similar for duodenal and ampullary NETs (RFS: p = .347 and overall survival [OS]: p = .246) and were combined into an intestinal subtype (IS) group. There were no differences in OS or RFS when comparing IS-NET and P-NET. On multivariate analysis, tissue of origin was not associated with risk of recurrence. The current American Joint Committee on Cancer staging guidelines, which account for origin tissue, were predictive of outcomes for all subtypes. Conclusion Tissue of origin does not appear to impact long-term outcomes when comparing IS-NETs and P-NETs. The AJCC staging system offers good discriminatory capacity in the context of the tissue type.
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- 2020
32. An Aggressive Approach to Locally Confined Pancreatic Cancer: Defining Surgical and Oncologic Outcomes Unique to Pancreatectomy with Celiac Axis Resection (DP-CAR)
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Ding Ding, Kelly J. Lafaro, Matthew J. Weiss, Christopher L. Wolfgang, Ammar A. Javed, William R. Burns, Michael J. Wright, Michael J Beckman, John L. Cameron, Jin He, Richard A. Burkhart, and Ryan K. Schmocker
- Subjects
medicine.medical_specialty ,Chyle ,business.industry ,medicine.medical_treatment ,Induction chemotherapy ,030230 surgery ,medicine.disease ,Pancreaticoduodenectomy ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,Surgical oncology ,Median follow-up ,030220 oncology & carcinogenesis ,Concomitant ,Pancreatic cancer ,Pancreatectomy ,medicine ,business - Abstract
Modern chemotherapeutics have led to improved systemic disease control for patients with locally advanced pancreatic cancer (LAPC). Surgical strategies such as distal pancreatectomy with celiac axis resection (DP-CAR) are increasingly entertained. Herein we review procedure-specific outcomes and assess biologic rationale for DP-CAR. A prospectively maintained single-institution database of all pancreatectomies was queried for patients undergoing DP-CAR. We excluded all patients for whom complete data were not available and those who were not treated with contemporary multi-agent therapy. Data were supplemented with dedicated chart review and outreach for long-term oncologic outcomes. Fifty-four patients underwent DP-CAR between 2008 and 2018. The median age was 62.7 years. Ninety-eight percent received induction chemotherapy. Arterial reconstruction was performed in 17% and concomitant visceral resection in 30%. The R0 resection rate was 87%. Postoperative complications were common (43%) with chyle leak being the most frequent (17%). Length of stay was 8 days, readmission occurred in one-third, and 90-day mortality was 2%. Disease recurrence occurred in 74% during a median follow up of 17.4 months. Median recurrence-free (RFS) and overall survival (OS) were 9 and 25 months, respectively. Following modern induction paradigms, DP-CAR can be performed with low mortality, manageable morbidity, and excellent rates of margin-negative resection in high-volume settings. The profile of complications of DP-CAR is distinct from pancreaticoduodenectomy and simple distal pancreatectomy. OS and RFS are similar to those undergoing resection of borderline resectable and resectable disease. Improved systemic disease control will likely lead to increasing utilization of aggressive surgical approaches to LAPC.
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- 2020
33. Prognostic impact of tumor location in resected gallbladder cancer: A national cohort analysis
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Yuman Fong, Susanne G. Warner, Andrew M. Blakely, Gagandeep Singh, Kelly J. Lafaro, Mustafa Raoof, Laleh G. Melstrom, and Byrne Lee
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Male ,medicine.medical_specialty ,Multivariate analysis ,Gastroenterology ,Article ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Cholecystectomy ,Gallbladder cancer ,Tumor location ,Stage (cooking) ,Aged ,Neoplasm Staging ,Retrospective Studies ,Cancer staging ,Aged, 80 and over ,Proportional hazards model ,business.industry ,Cancer ,General Medicine ,Middle Aged ,medicine.disease ,Primary tumor ,Survival Rate ,Oncology ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Female ,Gallbladder Neoplasms ,030211 gastroenterology & hepatology ,Surgery ,business ,Carcinoma in Situ ,Follow-Up Studies - Abstract
BACKGROUND AND OBJECTIVES: Tumor location (peritoneal vs hepatic) has been incorporated in the 8th edition of the American Joint Committee on Cancer Staging system for gallbladder cancer. However, larger studies are needed to confirm the prognostic impact of tumor location. METHODS: Patients with pathologically-confirmed gallbladder cancer with information on primary tumor location were included from the National Cancer Database (2009–2012). We compared patients with hepatic-side tumors to those on the peritoneal side. Survival data were plotted using the Kaplan-Meier method. Prognostic factors were modeled with a multivariate Cox Proportional Hazards Model. Primary outcome was overall survival (OS). RESULTS: A total of 1251 patients were included. In comparison to patients with peritoneal-sided tumors, patients with hepatic-sided tumors were more likely to: be of higher pT stage (pT3: 49% vs 24%; P < .001); node positive (31% vs 24%; P = .016); undergo liver resection (53% vs 25%; P < .001); or have positive margins (29% vs 16%; P < .001). However, on multivariate analysis, there was no difference in OS between the groups (HR, 0.97; 95% CI, 0.79–1.18; P = .753). Liver resection was associated with improved survival regardless of tumor location in pT2 tumors (peritoneal: HR, 0.57; P = .034; hepatic: HR, 0.67; P < .001). CONCLUSIONS: This study failed to demonstrate the independent prognostic value of primary tumor location in patients with gallbladder cancer.
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- 2020
34. The impact of financial toxicity in gastrointestinal cancer patients
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Laleh G. Melstrom, Kelly J. Lafaro, Matthew Loscalzo, Karen Clark, Susanne G. Warner, Arthur X. Li, and Christopher J. LaRocca
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Male ,Biopsychosocial model ,Psychological intervention ,030230 surgery ,Logistic regression ,03 medical and health sciences ,0302 clinical medicine ,Surveys and Questionnaires ,Humans ,Medicine ,Gastrointestinal cancer ,Poverty ,Aged ,Gastrointestinal Neoplasms ,Finance ,business.industry ,Cancer ,Odds ratio ,Middle Aged ,medicine.disease ,Confidence interval ,Distress ,030220 oncology & carcinogenesis ,Income ,Female ,Surgery ,business ,Stress, Psychological - Abstract
Biopsychosocial distress screening is a critical component of comprehensive cancer care. Financial issues are a common source of distress in this patient population. This study uses a biopsychosocial distress screening tool to determine the factors associated with financial toxicity and the impact of these stressors on gastrointestinal cancer patients.A 48-question, proprietary distress screening tool was administered to patients with gastrointestinal malignancies from 2009 to 2015. This validated, electronically-administered tool is given to all new patients. Responses were recorded on a 5-point Likert scale from 1 (not a problem) to 5 (very severe problem), with responses rated at ≥3 indicative of distress. Univariate and multivariate logistic regressions were used to analyze the data.Most of the 1,027 patients had colorectal (50%) or hepatobiliary (31%) malignancies. Additionally, 34% of all patients expressed a high level of financial toxicity. Age greater than 65 (odds ratio: 0.63, 95% confidence interval: 0.47-0.86, P.01), college education (odds ratio: 0.53, 95% confidence interval: 0.38-0.73, P.0001), being partnered (odds ratio: 0.61, 95% confidence interval: 0.44-0.84, P.01), and annual income greater than $40,000 (odds ratio: 0.27, 95% confidence interval: 0.19-0.38, P.0001) were all protective against financial toxicity on univariate analysis. Also, heavy tobacco use was associated significantly with increased distress on univariate analysis (odds ratio: 2.79, 95% confidence interval: 1.38-5.78, P.01). With the exception of partnered status (odds ratio: 1.18, 95% confidence interval: 0.76-1.85, P = .46), all these variables retained their significant association with financial toxicity in the multivariate model.Financial toxicity impacts a large number of cancer patients. Further study of at-risk populations may identify patients who would benefit from pre-emptive education and counseling interventions as part of their routine cancer care.
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- 2020
35. Surgeon and patient perceptions of cure in advanced gastrointestinal malignancies: Are we on the same page?
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Susanne G. Warner, Jenny Rodriguez, Laleh G. Melstrom, Arthur X. Li, Matthew Loscalzo, F. Lennie Wong, Kelly J. Lafaro, and Karen Clark
- Subjects
medicine.medical_specialty ,Concordance ,Decision Making ,Malignancy ,03 medical and health sciences ,0302 clinical medicine ,Pain control ,Surveys and Questionnaires ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Digestive System Surgical Procedures ,Gastrointestinal Neoplasms ,Surgeons ,Physician-Patient Relations ,business.industry ,Communication ,General surgery ,Cancer ,General Medicine ,Prognosis ,medicine.disease ,Patient perceptions ,Oncology ,030220 oncology & carcinogenesis ,Candidacy ,Life expectancy ,Feasibility Studies ,Perception ,030211 gastroenterology & hepatology ,Surgery ,business - Abstract
BACKGROUND AND OBJECTIVES Effective communication is essential to complex shared decision making and is associated with improved recovery and pain control. However, patients and surgeons often have disparate expectations of treatment efficacy and perceptions of cure for advanced malignancies. This study measures correlation of patient and surgeon expectations with perceptions of cure. METHODS Our prospective study surveying surgeon-patient dyads before and after surgical consultation was performed for advanced abdominal malignancy between July and November 2017 at a single NCI designated cancer center using electronic questionnaires. RESULTS Patients and surgeons' own opinions regarding surgical candidacy (Q1), chance at cure (Q2), and life expectancy (Q3) did not measurably change from pre- to postvisit survey as evidenced by unchanged response concordance (patients Q1 P = .82; Q2 P = .81; and Q3 P = .53; surgeon responses Q1: P = .17; Q2: P = .32; and Q3: P = .50). Patient and surgeon perception of likelihood of cure and of estimated life expectancy remained discordant in pre- and postvisit surveys (Q2: P = .006 and Q3: P = .03). CONCLUSIONS These data highlight the stark differences between patient and surgeon perceptions of cure and prognosis of gastrointestinal cancers. These results prove that a larger scale study using this electronic questionnaire is feasible and important to better understand these differences and enhance shared decision making.
- Published
- 2020
36. The Association of Tumor Laterality and Survival After Cytoreduction for Colorectal Carcinomatosis
- Author
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Oliver S. Eng, Philip H.G. Ituarte, Andrew M. Blakely, Kelly J. Lafaro, Byrne Lee, Marwan Fakih, and Mustafa Raoof
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Colon ,Colorectal cancer ,California ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Humans ,Medicine ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Proportional hazards model ,Carcinoma ,Cytoreduction Surgical Procedures ,Middle Aged ,medicine.disease ,Primary tumor ,Cancer registry ,Chemotherapy, Cancer, Regional Perfusion ,030220 oncology & carcinogenesis ,Laterality ,Cohort ,Female ,030211 gastroenterology & hepatology ,Surgery ,Treatment factors ,Colorectal Neoplasms ,business ,Cytoreductive surgery - Abstract
Primary tumor location has emerged as an important surrogate for tumor biology in metastatic colorectal cancer treated with systemic chemotherapy. It is unclear if primary tumor location is associated with survival after cytoreductive surgery (CRS) with or without heated intraperitoneal chemotherapy (HIPEC) for colorectal carcinomatosis.Study of a contemporary cohort merged data from the California Cancer Registry, 2004-2012, and the Office of Statewide Health Planning and Development inpatient database. For patients undergoing CRS/HIPEC, clinicopathologic variables, treatment characteristics, and survival were compared by right versus left colon primary site. Survival was analyzed by Cox proportional hazards.Of 272 patients identified, 128 (47.1%) had right-sided tumors. Left- and right-sided cohorts had similar patient, tumor, and treatment factors. Patients with left-sided primary tumors had significantly prolonged overall survival (mean 34 versus 15.5 mo, P = 0.0010). Factors independently associated with decreased overall survival included age80 (HR 7.0, P 0.0001), advanced T4 stage (HR 3.6, P = 0.0031), and positive lymph nodes (HR 2.2, P = 0.0004). Metachronous peritoneal involvement (HR 0.38, P 0.0001) and left-sided primary tumors (HR 0.72, P = 0.041) were independently associated with improved overall survival.This study identifies location of primary tumor as an important determinant of long-term survival after CRS/HIPEC. Patients with left-sided tumors have a more favorable prognosis.
- Published
- 2020
37. Robotic pancreaticoduodenectomy for pancreatic cancer: a narrative review
- Author
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Kimberly E. Kopecky, Kelly J. Lafaro, and Jin He
- Subjects
Radiology, Nuclear Medicine and imaging ,Surgery - Published
- 2023
38. Technical progress in robotic pancreatoduodenectomy: TRIANGLE and periadventitial dissection for retropancreatic nerve plexus resection
- Author
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Benedict, Kinny-Köster, Joseph R, Habib, Ammar A, Javed, Sami, Shoucair, A Floortje, van Oosten, Elliot K, Fishman, Kelly J, Lafaro, Christopher L, Wolfgang, Thilo, Hackert, and Jin, He
- Subjects
Pancreatic Neoplasms ,Pancreatectomy ,Robotic Surgical Procedures ,Dissection ,Humans ,Pancreaticoduodenectomy - Abstract
The resection of retropancreatic nerve plexuses for pancreatic head cancer became standard of care during open pancreatoduodenectomy to minimize local recurrences. Since more surgical centers are progressing on the learning curve, robotically-assisted pancreatoduodenectomy is now increasingly performed with decreasing anatomic exclusion criteria. To achieve comparable and favorable oncologic outcomes, advanced surgical techniques should be transferred and implemented when performing robotic resections.The nomenclature and anatomic principles of retropancreatic nerve plexuses and three different levels of dissections are utilized based on established definitions.The en bloc dissection in the "TRIANGLE" area (triangular-shaped retropancreatic space enclosed by the common hepatic artery, superior mesenteric artery, and superior mesenteric vein/portal vein) and the periadventitial dissection of arteries for non-tunica media-invading tumors were executed robotically. Both can be utilized to achieve a radical dorsal and medial margin. Video recordings are provided to illustrate varying TRIANGLE dissections.To accomplish oncologic non-inferiority, established principles from open pancreatic resections can be incorporated precisely and safely, overcoming the lack of haptic feedback while exploiting the technological advantages of the robotically-assisted platform.
- Published
- 2021
39. Comprehensive Analysis of Somatic Mutations in Driver Genes of Resected Pancreatic Ductal Adenocarcinoma Reveals KRAS G12D and Mutant TP53 Combination as an Independent Predictor of Clinical Outcome
- Author
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Sami, Shoucair, Joseph R, Habib, Ning, Pu, Benedict, Kinny-Köster, A Floortje, van Ooston, Ammar A, Javed, Kelly J, Lafaro, Jin, He, Christopher L, Wolfgang, and Jun, Yu
- Subjects
Pancreatic Neoplasms ,Proto-Oncogene Proteins p21(ras) ,Mutation ,Biomarkers, Tumor ,Humans ,Tumor Suppressor Protein p53 ,Prognosis ,Carcinoma, Pancreatic Ductal ,Retrospective Studies - Abstract
Prognosis in pancreatic ductal adenocarcinoma (PDAC) remains poor despite improved systemic therapies and surgical techniques. The identification of biomarkers to advance insight in tumor biology and achieve better individualized prognostication could help improve outcomes. Our aim was to elucidate the prognostic role of the four main driver mutations (KRAS, TP53, SMAD4, CDKN2A) and their combinations in resected PDAC.A retrospective analysis was conducted utilizing the cBioPortal database and National Cancer Institute's Cancer Genomic Atlas (TCGA) on patients in whom next-generation sequencing was performed on upfront resected PDAC from 2012 to 2020. Multivariable Cox regression was implemented to elucidate risk-adjusted predictors of overall (OS) and recurrence-free survival (RFS). Results were validated employing a Johns Hopkins Hospital (JHH) cohort.'In the discovery cohort (n = 587), increased number of mutated driver genes was associated with worse OS (p = 0.047). Specifically, patients with mutations in ≥ 2 driver genes had worse OS than ≤ 1 mutated gene (18.2 versus 32.3 months, p = 0.033). Co-occurrence of mutant (mt)KRAS p.G12D with mtTP53 (median OS, 25.9 months) conferred better prognosis than co-occurrence of other mtKRAS variants (p.G12V/R/other) with mtTP53 (median OS, 16.9 months, p = 0.038). The findings were validated using a JHH cohort. Multivariable risk-adjustment found co-occurrence of mtKRAS p.G12D with mtTP53 to be an independent predictor of beneficial OS and RFS [HR (95% CI): 0.18 (0.03-0.81) and 0.31 (0.11-0.89) respectively].In chemo-naïve resected PDAC, combinations of mutations in the four driver genes are associated with prognosis. In patients with combined mtKRAS and mtTP53, KRAS p.G12D variant confers a better OS and RFS.
- Published
- 2021
40. ASO Visual Abstract: Comprehensive Analysis of Somatic Mutations in Driver Genes of Resected Pancreatic Ductal Adenocarcinoma Shows KRAS G12D and Mutant TP53 Combination as an Independent Predictor of Clinical Outcome
- Author
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Sami Shoucair, Joseph R. Habib, Ning Pu, Benedict Kinny-Köster, A. Floortje van Ooston, Ammar A. Javed, Kelly J. Lafaro, Jin He, Christopher L. Wolfgang, and Jun Yu
- Subjects
Oncology ,Surgery - Published
- 2022
41. Lymphovascular Invasion Predicts Lymph Node Involvement in Small Pancreatic Neuroendocrine Tumors
- Author
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Jonathan Kessler, Philip H.G. Ituarte, Kelly J. Lafaro, Andrew M. Blakely, Daneng Li, Sue Chang, Gagandeep Singh, and Byrne Lee
- Subjects
Adult ,Male ,Subset Analysis ,medicine.medical_specialty ,Adolescent ,Databases, Factual ,Lymphovascular invasion ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,030209 endocrinology & metabolism ,Neuroendocrine tumors ,Gastroenterology ,030218 nuclear medicine & medical imaging ,Young Adult ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Endocrinology ,Internal medicine ,Pancreatic cancer ,medicine ,Humans ,Neoplasm Invasiveness ,Stage (cooking) ,Lymph node ,Aged ,Endocrine and Autonomic Systems ,business.industry ,Cancer ,Middle Aged ,medicine.disease ,Pancreatic Neoplasms ,Neuroendocrine Tumors ,medicine.anatomical_structure ,Lymphatic Metastasis ,Female ,Lymphadenectomy ,business - Abstract
Introduction: Pancreatic neuroendocrine tumors (p-NETS) are increasing in incidence, and prognostic factors continue to evolve. The benefit of lymphadenectomy for p-NETS ≤2 cm remains unclear. We sought to determine the significance of lymphovascular invasion (LVI) for small p-NETS. Methods: The National Cancer Database was queried for patients with p-NETS ≤2 cm and with ≥1 evaluated lymph node (LN), years 2004–2015. Demographic, clinical, and treatment characteristics were analyzed. Multivariate logistic regression was performed to identify predictors of LN positivity. Results: Among 2,499 patients identified, tumor location was delineated as the head (26%), body (18%), tail (38%), or unspecified (18%); 74% were well-differentiated versus 10% moderate, 2% poor, and 14% unknown. LVI occurred in 11%. A median of 9 LNs were evaluated; overall positivity was 18%. Mean survival was significantly longer in node-negative patients (115 vs. 95 months, log-rank p < 0.0001). LVI was the strongest predictor of node involvement (OR 10.4, p < 0.0001) when controlling for tumor size, grade, and location. Subset analysis of patients with known LVI status, grade, location, and mitoses found that LVI was more likely in the setting of moderate-to-high tumor grade, 1–2 cm size, pancreatic head location, and high mitotic rate. Among patients with ≥2 of these 4 factors, 25% were node-positive. Conclusions: Presence of LVI was the strongest predictor of node positivity. LVI on endoscopic biopsy should prompt resection and regional LN dissection to fully stage patients with small p-NETS. Patients with other high-risk factors should also be considered for resection and regional lymphadenectomy.
- Published
- 2019
42. Primary Tumor Sidedness is Predictive of Survival in Colon Cancer Patients Treated with Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy: A US HIPEC Collaborative Study
- Author
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Vikrom K. Dhar, Jordan M. Cloyd, Jonathan B. Greer, Callisia N. Clarke, Byrne Lee, Mohammad Y. Zaidi, Laura A. Lambert, Daniel E. Abbott, Maria C. Russell, Sameer H. Patel, Nadege Fackche, Courtney Pokrzywa, Kelly J. Lafaro, Andrew M. Lowy, Ahmed Ahmed, Harveshp Mogal, Ryan J. Hendrix, Jennifer L. Leiting, Travis E. Grotz, Sean P. Dineen, Jeffrey J. Sussman, Sophie Dessureault, Kaitlyn J. Kelly, Jula Veerapong, Nikhil V. Kotha, Joel M. Baumgartner, Andrew J. Lee, and Keith Fournier
- Subjects
Adult ,Male ,medicine.medical_specialty ,Colorectal cancer ,Gastroenterology ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Surgical oncology ,Internal medicine ,medicine ,Humans ,Survival rate ,Peritoneal Neoplasms ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Hazard ratio ,Retrospective cohort study ,Cytoreduction Surgical Procedures ,Hyperthermia, Induced ,Middle Aged ,Prognosis ,medicine.disease ,Combined Modality Therapy ,Primary tumor ,Survival Rate ,Oncology ,Chemotherapy, Cancer, Regional Perfusion ,030220 oncology & carcinogenesis ,Colonic Neoplasms ,Peritoneal Cancer Index ,Female ,030211 gastroenterology & hepatology ,Surgery ,Hyperthermic intraperitoneal chemotherapy ,business ,Follow-Up Studies - Abstract
The clinical relevance of primary tumor sidedness is not fully understood in colon cancer patients with peritoneal metastasis treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). This was a retrospective cohort study of a multi-institutional database of patients with peritoneal surface malignancy at 12 participating high-volume academic centers from the US HIPEC Collaborative. Overall, 336 patients with colon primary tumors who underwent curative-intent CRS with or without HIPEC were identified; 179 (53.3%) patients had right-sided primary tumors and 157 (46.7%) had left-sided primary tumors. Patients with right-sided tumors were more likely to be older, male, have higher Peritoneal Cancer Index (PCI), and have a perforated primary tumor, but were less likely to have extraperitoneal disease. Patients with complete cytoreduction (CC-0/1) had a median disease-free survival (DFS) of 11.5 months (95% confidence interval [CI] 7.6–15.3) versus 13.1 months (95% CI 9.5–16.8) [p = 0.158] and median overall survival (OS) of 30 months (95% CI 23.5–36.6) versus 45.4 months (95% CI 35.9–54.8) [p = 0.028] for right- and left-sided tumors; respectively. Multivariate analysis revealed that right-sided primary tumor was an independent predictor of worse DFS (hazard ratio [HR] 1.75, 95% CI 1.19–2.56; p =0.004) and OS (HR 1.72, 95% CI 1.09–2.73; p = 0.020). Right-sided primary tumor was an independent predictor of worse DFS and OS. Relevant clinicopathologic criteria, such as tumor sidedness and PCI, should be considered in patient selection for CRS with or without HIPEC, and guide stratification for clinical trials.
- Published
- 2019
43. The Paradoxical Web of Pancreatic Cancer Tumor Microenvironment
- Author
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Kelly J. Lafaro and Laleh G. Melstrom
- Subjects
0301 basic medicine ,Stromal cell ,endocrine system diseases ,medicine.disease_cause ,Article ,Pathology and Forensic Medicine ,Extracellular matrix ,03 medical and health sciences ,Drug Delivery Systems ,0302 clinical medicine ,Stroma ,Pancreatic cancer ,Tumor Microenvironment ,Humans ,Medicine ,Tumor microenvironment ,business.industry ,medicine.disease ,digestive system diseases ,Desmoplasia ,Pancreatic Neoplasms ,030104 developmental biology ,Drug Resistance, Neoplasm ,Tumor progression ,030220 oncology & carcinogenesis ,Disease Progression ,Cancer research ,medicine.symptom ,business ,Carcinogenesis ,Carcinoma, Pancreatic Ductal - Abstract
Pancreatic ductal adenocarcinoma (PDAC) is increasing in incidence and is projected to become the second leading cause of cancer death in the United States. Despite significant advances in understanding the disease, there has been minimal increase in PDAC patient survival. PDAC tumors are unique in the fact that there is significant desmoplasia. This generates a large stromal compartment composed of immune cells, inflammatory cells, growth factors, extracellular matrix, and fibroblasts, comprising the tumor microenvironment (TME), which may represent anywhere from 15% to 85% of the tumor. It has become evident that the TME, including both the stroma and extracellular component, plays an important role in tumor progression and chemoresistance of PDAC. This review will discuss the multiple components of the TME, their specific impact on tumorigenesis, and the multiple therapeutic targets.
- Published
- 2019
44. Mo1675: MANAGEMENT OF PERIPANCREATIC PERIPHERAL NERVE SHEATH (PPNS) TUMORS
- Author
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Feras Shamoun, Elie Ghabi, Elizabeth Thompson, Richard Burkhart, Christopher L. Wolfgang, John Cameron, Kelly J. Lafaro, William R. Burns, and Jin He
- Subjects
Hepatology ,Gastroenterology - Published
- 2022
45. 427: TAILORING ADJUVANT CHEMOTHERAPY TO BIOLOGIC RESPONSES FOLLOWING NEOADJUVANT CHEMOTHERAPY IMPACTS OVERALL SURVIVAL IN PANCREATIC CANCER
- Author
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Elie Ghabi, Sami Shoucair, Ammar A. Javed, Ding Ding, Elizabeth Thompson, Lei Zheng, John Cameron, Christopher L. Wolfgang, Christopher Shubert, Kelly J. Lafaro, Richard Burkhart, William R. Burns, and Jin He
- Subjects
Hepatology ,Gastroenterology - Published
- 2022
46. Surgical Decision Making in Pancreatic Ductal Adenocarcinoma: Modeling Prognosis Following Pancreatectomy in the Era of Induction and Neoadjuvant Chemotherapy
- Author
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Patrick Bou-Samra, Jin He, Benedict Kinny-Köster, Richard A. Burkhart, Christopher L. Wolfgang, John L. Cameron, Jun Yu, Ranim Alsaad, Kelly J. Lafaro, Elisabetta Sereni, Ding Ding, Joseph R. Habib, Ammar A. Javed, and William R. Burns
- Subjects
Oncology ,Chemotherapy ,medicine.medical_specialty ,business.industry ,Concordance ,medicine.medical_treatment ,Induction chemotherapy ,Perioperative ,Disease ,Internal medicine ,Pancreatectomy ,Cohort ,Medicine ,Surgery ,business ,Survival analysis - Abstract
Objective To develop a predictive model of oncologic outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) undergoing resection after neoadjuvant or induction chemotherapy use. Background Early recurrence following surgical resection for PDAC is common. The use of neoadjuvant chemotherapy prior to resection may increase the likelihood of long-term systemic disease control. Accurately characterizing an individual's likely oncologic outcome in the perioperative setting remains challenging. Methods Data from patients with PDAC who received chemotherapy prior to pancreatectomy at a single high-volume institution between 2007-2018 were captured in a prospectively collected database. Core clinicopathologic data were reviewed for accuracy and survival data were abstracted from the electronic medical record and national databases. Cox-proportional regressions were used to model outcomes and develop an interactive prognostic tool for clinical decision-making. Results A total of 581 patients were included with a median OS and RFS of 29.5 (26.5-32.5) and 16.6 (15.8-17.5) months, respectively. Multivariable analysis demonstrates OS and RFS were associated with type of chemotherapeutic used and the number of chemotherapy cycles received preoperatively. Additional factors contributing to survival models included: tumor grade, histopathologic response to therapy, nodal status, and administration of adjuvant chemotherapy. The models were validated using an iterative bootstrap method and with randomized cohort splitting. The models were well calibrated with concordance indices of 0.68 and 0.65 for the final OS and RFS models, respectively. Conclusion We developed an intuitive and dynamic decision-making tool that can be useful in estimating OS, RFS and location-specific disease recurrence rates. This prognostic tool may add value to patient care in discussing the benefits associated with surgical resection for PDAC.
- Published
- 2021
47. Anatomic Criteria Determine Resectability in Locally Advanced Pancreatic Cancer
- Author
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Richard A. Burkhart, Lei Zheng, Daniel A. Laheru, Christopher L. Wolfgang, Matthew J. Weiss, Alex B. Blair, Minako Nagai, Kelly J. Lafaro, Jin He, Georgios Gemenetzis, Joseph M. Herman, Ding Ding, Elliot K. Fishman, Ralph H. Hruban, Amol Narang, Vincent P. Groot, Ammar A. Javed, William R. Burns, and John L. Cameron
- Subjects
Chemotherapy ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Anatomical structures ,Interdisciplinary Studies ,urologic and male genital diseases ,Resection ,Locally advanced pancreatic cancer ,Radiation therapy ,Pancreatic Neoplasms ,Oncology ,Surgical oncology ,Induction therapy ,medicine ,Humans ,Surgery ,In patient ,Radiology ,Prospective Studies ,business - Abstract
The introduction of multi-agent chemotherapy and radiation therapy has facilitated potential resection with curative intent in selected locally advanced pancreatic cancer (LAPC) patients with excellent outcomes. Nevertheless, there remains a remarkable lack of consensus on the management of LAPC. We sought to describe the outcomes of patients with LAPC and objectively define the multidisciplinary selection process for operative exploration based on anatomical factors. Consecutive patients with LAPC were evaluated for pancreatic surgery in the multidisciplinary clinic of a high-volume institution, between 2013 and 2018. Prospective stratification (LAPC-1, LAPC-2, and LAPC-3), based on the involvement of regional anatomical structures, was performed at the time of presentation prior to the initiation of treatment. Resection rates and patient outcomes were evaluated and correlated with the initial anatomic stratification system. Overall, 415 patients with LAPC were included in the study, of whom 84 (20%) were successfully resected, with a median overall survival of 35.3 months. The likelihood of operative exploration was associated with the pretreatment anatomic LAPC score, with a resection rate of 49% in patients classified as LAPC-1, 32% in LAPC-2, and 11% in LAPC-3 (p
- Published
- 2021
48. ASO Visual Abstract: Anatomic Criteria Determine Resectability in Locally Advanced Pancreatic Cancer
- Author
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Amol Narang, John L. Cameron, Minako Nagai, Lei Zheng, Ammar A. Javed, Ding Ding, William R. Burns, Kelly J. Lafaro, Joseph M. Herman, Christopher L. Wolfgang, Alex B. Blair, Ralph H. Hruban, Vincent P. Groot, Jin He, Richard A. Burkhart, Georgios Gemenetzis, Elliot K. Fishman, Daniel A. Laheru, and Matthew J. Weiss
- Subjects
medicine.medical_specialty ,Oncology ,Surgical oncology ,business.industry ,medicine ,MEDLINE ,Surgery ,Radiology ,business ,Locally advanced pancreatic cancer - Published
- 2021
49. Academic Productivity in Hepatopancreatobiliary Surgeons: Identifying Benchmarks Associated With Rank in North America
- Author
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Christopher J. LaRocca, Laleh G. Melstrom, Yuman Fong, Kelly J. Lafaro, Amit S. Khithani, Susanne G. Warner, and Paul Wong
- Subjects
Adult ,Male ,Canada ,Faculty, Medical ,media_common.quotation_subject ,Efficiency ,03 medical and health sciences ,0302 clinical medicine ,Promotion (rank) ,Research Support as Topic ,Hepatopancreaticobiliary surgery ,Medicine ,Humans ,Fellowships and Scholarships ,Productivity ,media_common ,Publishing ,Surgeons ,Medical education ,business.industry ,Rank (computer programming) ,Gastroenterology ,General Medicine ,Middle Aged ,Achievement ,United States ,Benchmarking ,National Institutes of Health (U.S.) ,030220 oncology & carcinogenesis ,Female ,business ,030217 neurology & neurosurgery - Abstract
Background Academic achievement is an integral part of the promotion process; however, there are no standardized metrics for faculty or leadership to reference in assessing this potential for promotion. The aim of this study was to identify metrics that correlate with academic rank in hepatopancreaticobiliary (HPB) surgeons. Materials and Methods Faculty was identified from 17 fellowship council accredited HPB surgery fellowships in the United States and Canada. The number of publications, citations, h-index values, and National Institutes of Health (NIH) funding for each faculty member was captured. Results Of 111 surgeons identified, there were 31 (27%) assistant, 39 (35%) associate, and 41 (36%) full professors. On univariate analysis, years in practice, h-index, and a history of NIH funding were significantly associated with a surgeon’s academic rank ( P < .05). Years in practice and h-index remained significant on multivariate analysis ( P < .001). Discussion Academic productivity metrics including h-index and NIH funding are associated with promotion to the next academic rank.
- Published
- 2020
50. Robotic assistance for quick and accurate image-guided needle placement
- Author
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Camille L. Stewart, Yuman Fong, Kelly J. Lafaro, Joseph D. Femino, Abigail Fong, Brooke Crawford, and Christopher J. LaRocca
- Subjects
medicine.medical_specialty ,Percutaneous ,Computed tomography ,Article ,03 medical and health sciences ,0302 clinical medicine ,Robotic Surgical Procedures ,Surgical technology ,medicine ,Humans ,Medical physics ,medicine.diagnostic_test ,business.industry ,Phantoms, Imaging ,Ct guidance ,Robotics ,Surgery ,Radiation exposure ,Needles ,030220 oncology & carcinogenesis ,Needle placement ,030211 gastroenterology & hepatology ,Artificial intelligence ,business ,Tomography, X-Ray Computed ,Robotic arm - Abstract
Computed tomography (CT) image-guided procedures including biopsy, drug delivery, and ablation are gaining increasing application in medicine. Robotic technology holds the promise for allowing surgeons, and other proceduralists, access to such CT guided procedures by potentially shortening training, improving accuracy, decreasing needle passes, and reducing radiation exposure. We evaluated surgeon learning and proficiency for image-guided needle placement with an FDA-cleared robotic arm. Five out of six surgeons had no prior CT guided procedural experience, while one had prior experience with freehand CT guided needle placement. All surgeons underwent a 60-minute training with the MAXIO robot (Perfint Healthcare, Redmond, WA). The robot was used to place needles into three different pre-specified targets on a spine model. Performance time, procedural errors, and needle placement accuracy were recorded. All participants successfully placed needles into the targets using the robotic arm. The average time for needle placement was 3:44 ± 1:43 minutes. Time for needle placement decreased with subsequent attempts, with average third placement taking 2:29 ± 1:51 minutes less than the first attempt. The average vector distance from the target was 2.3 ± 1.2 mm. One error resulted in the need for reimaging by CT scan. No errant needle placement occurred. Surgeons (attending fellows and residents) without previous experience and minimal training could successfully place percutaneous needles under CT guidance quickly, accurately, and reproducibly using a robotic arm. This suggests that robotic technology may be used to facilitate surgeon adoption of CT image-guided needle-based procedures in the future.
- Published
- 2020
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