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Pancreatic Neoplasms: HELP
Articles by Jin He
Based on 77 articles published since 2010
(Why 77 articles?)
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Between 2010 and 2020, Jin He wrote the following 77 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Editorial Pancreaticoduodenectomy for pancreatic cancer: perspective from the United States. 2017

Ejaz, Aslam / He, Jin. ·Department of Surgery, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Department of Surgery, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. jhe11@jhmi.edu. ·Chin Clin Oncol · Pubmed #28249540.

ABSTRACT: -- No abstract --

2 Review Lessons learned from 29 lymphoepithelial cysts of the pancreas: institutional experience and review of the literature. 2018

Groot, Vincent P / Thakker, Sameer S / Gemenetzis, Georgios / Noë, Michaël / Javed, Ammar A / Burkhart, Richard A / Noveiry, Behnoud B / Cameron, John L / Weiss, Matthew J / VandenBussche, Christopher J / Fishman, Elliot K / Hruban, Ralph H / Wolfgang, Christopher L / Lennon, Anne Marie / He, Jin. ·Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Surgery, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht, The Netherlands. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Gastroenterology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Radiology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Gastroenterology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Radiology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: jhe11@jhmi.edu. ·HPB (Oxford) · Pubmed #29530477.

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

3 Review Pancreaticoduodenectomy with en bloc vein resection for locally advanced pancreatic cancer: a case series without venous reconstruction. 2018

Gage, Michele M / Reames, Bradley N / Ejaz, Aslam / Sham, Johnathan / Fishman, Elliot K / Weiss, Matthew J / Wolfgang, Christopher L / He, Jin. ·Department of Surgery,Johns Hopkins Hospital, Baltimore, MD, USA. · Department of Radiology, Johns Hopkins Hospital, Baltimore, MD, USA. · Department of Surgery,Johns Hopkins Hospital, Baltimore, MD, USA. jhe11@jhmi.edu. ·Chin Clin Oncol · Pubmed #29486566.

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

4 Review Geographical variation and trends in outcomes of laparoscopic spleen-preserving distal pancreatectomy with or without splenic vessel preservation: A meta-analysis. 2017

Yongfei, Hua / Javed, Ammar A / Burkhart, Richard / Peters, Niek A / Hasanain, Alina / Weiss, Matthew J / Wolfgang, Christopher L / He, Jin. ·Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA; Department of Surgery, Lihuili Eastern Hospital, Ningbo, China. · Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA. · Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA; University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. · Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA. Electronic address: jhe11@jhmi.edu. ·Int J Surg · Pubmed #28735894.

ABSTRACT: BACKGROUND: Distal pancreatectomy (DP) is performed to treat tumors of the pancreatic body and tail. Traditionally, splenectomy is performed with a DP, however, laparoscopic spleen-preserving DP (SPDP) using Warshaw's (splenic vessels ligation) or Kimura's (splenic vessels preservation) techniques have been reported. The clinical benefits of using either technique remain unclear. In this study, we conducted a meta-analysis to compare the clinical outcomes of patients undergoing Warshaw's and Kimura SPDP. This is the first study to evaluate the geographical variation in outcomes of Warshaw's and Kimura SPDP. METHODS: Databases of PubMed, Embase, and Cochrane library were used to identify studies reporting Warshaw's and Kimura SPDP. Clinical outcomes were compared. Pooled odds risk and weighted mean difference with 95% confidence interval were calculated using random effect models. RESULTS: Fourteen non-randomized controlled studies involving 945 patients met our selection criteria. 301 (31.9%) patients underwent Warshaw's SPDP; 644 (68.1%) underwent Kimura SPDP. Compared to Warshaw's SPDP, patients undergoing Kimura SPDP had a lower incidence of post-operative complications including spleen infarction (OR = 9.64, 95% CI = 5.79 to 16.05, P < 0.001) and gastric varices (OR = 11.88, 95% CI = 5.11 to 27.66, P < 0.001). The length of surgery was significantly shorter for Warshaw's SPDP (WMD = -18.12, 95%CI = -26.52 to -9.72, p < 0.001). Decreased blood loss was reported for patients undergoing Warshaw's SPDP (WMD = -59.72, 95%CI = -102.01 to -17.43, p = 0.006). There were no differences between the two groups' rates of conversion to an open procedure (P = 0.35), postoperative pancreatic fistula (P = 0.71), need for reoperation (P = 0.25), and length of hospital stay (P = 0.38). CONCLUSION: Both Warshaw's and Kimura are safe SPDP techniques. These data suggest Kimura SPDP is the preferred technique due to less risk of splenic infarct and gastric varices. Despite evidence of regional variation in volume performed (between Kimura and Warshaw's), there are no statistically significant differences in outcomes between these techniques.

5 Review Overcoming the resistance of pancreatic cancer to immune checkpoint inhibitors. 2017

Skelton, Richard A / Javed, Ammar / Zheng, Lei / He, Jin. ·The Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland. · Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland. ·J Surg Oncol · Pubmed #28628715.

ABSTRACT: Immunotherapy has become a new modality of cancer treatment, but has had a limited success in treating PDAC. A combination approach to immunotherapy, using both immune checkpoint inhibitors and immune activating agonists, is needed, as PDAC does not respond to single-agent checkpoint inhibitors. Studies have also supported using vaccine-based therapies to prime the tumor microenvironment of PDAC with effector T-cells. Other therapeutic strategies including epigenetic agents, stroma modulators, radiotherapy, and T-cell transfer therapies may also prime the tumor microenvironment to overcome resistance to immune checkpoint inhibitors.

6 Review Management of borderline and locally advanced pancreatic cancer: where do we stand? 2014

He, Jin / Page, Andrew J / Weiss, Matthew / Wolfgang, Christopher L / Herman, Joseph M / Pawlik, Timothy M. ·Jin He, Andrew J Page, Matthew Weiss, Christopher L Wolfgang, Timothy M Pawlik, Department of Surgery, Johns Hopkins Hospital, Baltimore, MD 21287, United States. ·World J Gastroenterol · Pubmed #24605025.

ABSTRACT: Many patients with pancreas cancer present with locally advanced pancreatic cancer (LAPC). The principle tools used for diagnosis and staging of LAPC include endoscopic ultrasound, axial imaging with computed tomography and magnetic resonance imaging, and diagnostic laparoscopy. The definition of resectability has historically been vague, as there is considerable debate and controversy as to the definition of LAPC. For the patient with LAPC, there is some level of involvement of the surrounding vascular structures, which include the superior mesenteric artery, celiac axis, hepatic artery, superior mesenteric vein, or portal vein. When feasible, most surgeons would recommend possible surgical resection for patients with borderline LAPC, with the goal of an R0 resection. For initially unresectable LAPC, neoadjuvant should be strongly considered. Specifically, these patients should be offered neoadjuvant therapy, and the tumor should be assessed for possible response and eventual resection. The efficacy of neoadjuvant therapy with this approach as a bridge to potential curative resection is broad, ranging from 3%-79%. The different modalities of neoadjuvant therapy include single or multi-agent chemotherapy combined with radiation, chemotherapy alone, and chemotherapy followed by chemotherapy with radiation. This review focuses on patients with LAPC and addresses recent advances and controversies in the field.

7 Clinical Trial Mutations in the pancreatic secretory enzymes 2018

Tamura, Koji / Yu, Jun / Hata, Tatsuo / Suenaga, Masaya / Shindo, Koji / Abe, Toshiya / MacGregor-Das, Anne / Borges, Michael / Wolfgang, Christopher L / Weiss, Matthew J / He, Jin / Canto, Marcia Irene / Petersen, Gloria M / Gallinger, Steven / Syngal, Sapna / Brand, Randall E / Rustgi, Anil / Olson, Sara H / Stoffel, Elena / Cote, Michele L / Zogopoulos, George / Potash, James B / Goes, Fernando S / McCombie, Richard W / Zandi, Peter P / Pirooznia, Mehdi / Kramer, Melissa / Parla, Jennifer / Eshleman, James R / Roberts, Nicholas J / Hruban, Ralph H / Klein, Alison Patricia / Goggins, Michael. ·Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Health Sciences Research, Mayo Clinic, Rochester, MN 55905. · Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5. · Population Sciences Division, Dana-Farber Cancer Institute, Boston, MA 02215. · Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213. · Division of Gastroenterology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104. · Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104. · Pancreatic Cancer Translational Center of Excellence, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104. · Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10017. · Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109. · Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201. · The Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada H3H 2R9. · The Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada H3A 1A3. · Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD 21287. · Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724. · InGenious Targeting Laboratory, Ronkonkoma, NY 11779. · Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; mgoggins@jhmi.edu. ·Proc Natl Acad Sci U S A · Pubmed #29669919.

ABSTRACT: To evaluate whether germline variants in genes encoding pancreatic secretory enzymes contribute to pancreatic cancer susceptibility, we sequenced the coding regions of

8 Article International validation and update of the Amsterdam model for prediction of survival after pancreatoduodenectomy for pancreatic cancer. 2020

van Roessel, Stijn / Strijker, Marin / Steyerberg, Ewout W / Groen, Jesse V / Mieog, J Sven / Groot, Vincent P / He, Jin / De Pastena, Matteo / Marchegiani, Giovanni / Bassi, Claudio / Suhool, Amal / Jang, Jin-Young / Busch, Olivier R / Halimi, Asif / Zarantonello, Laura / Groot Koerkamp, Bas / Samra, Jaswinder S / Mittal, Anubhav / Gill, Anthony J / Bolm, Louisa / van Eijck, Casper H / Abu Hilal, Mohammed / Del Chiaro, Marco / Keck, Tobias / Alseidi, Adnan / Wolfgang, Christopher L / Malleo, Giuseppe / Besselink, Marc G. ·Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands. · Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands. · Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Surgery, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. · Department of Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, UK. · Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. · Pancreatic Surgery Unit, Division of Surgery, Karolinska Institute at Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden. · Department of Surgery, Erasmus Medical Center, Erasmus University Rotterdam, Rotterdam, the Netherlands. · Department of Surgery, Royal North Shore Hospital, St Leonards, University of Sydney, Sydney, NSW, Australia. · Cancer Diagnosis and Pathology Group Kolling Institute of Medical Research and University of Sydney, Sydney, NSW, Australia. · Department of Surgery, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany. · Division of Surgical Oncology, Department of Surgery, University of Colorado at Denver-Anschutz Medical Campus, Aurora, CO, USA. · Section of Hepato-Pancreato-Biliary & Endocrine Surgery, Virginia Mason Medical Center, Seattle, WA, USA. · Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands. Electronic address: m.g.besselink@amsterdamumc.nl. ·Eur J Surg Oncol · Pubmed #31924432.

ABSTRACT: BACKGROUND: The objective of this study was to validate and update the Amsterdam prediction model including tumor grade, lymph node ratio, margin status and adjuvant therapy, for prediction of overall survival (OS) after pancreatoduodenectomy for pancreatic cancer. METHODS: We included consecutive patients who underwent pancreatoduodenectomy for pancreatic cancer between 2000 and 2017 at 11 tertiary centers in 8 countries (USA, UK, Germany, Italy, Sweden, the Netherlands, Korea, Australia). Model performance for prediction of OS was evaluated by calibration statistics and Uno's C-statistic for discrimination. Validation followed the TRIPOD statement. RESULTS: Overall, 3081 patients (53% male, median age 66 years) were included with a median OS of 24 months, of whom 38% had N2 disease and 77% received adjuvant chemotherapy. Predictions of 3-year OS were fairly similar to observed OS with a calibration slope of 0.72. Statistical updating of the model resulted in an increase of the C-statistic from 0.63 to 0.65 (95% CI 0.64-0.65), ranging from 0.62 to 0.67 across different countries. The area under the curve for the prediction of 3-year OS was 0.71 after updating. Median OS was 36, 25 and 15 months for the low, intermediate and high risk group, respectively (P < 0.001). CONCLUSIONS: This large international study validated and updated the Amsterdam model for survival prediction after pancreatoduodenectomy for pancreatic cancer. The model incorporates readily available variables with a fairly accurate model performance and robustness across different countries, while novel markers may be added in the future. The risk groups and web-based calculator www.pancreascalculator.com may facilitate use in daily practice and future trials.

9 Article Recurrent Rearrangements in PRKACA and PRKACB in Intraductal Oncocytic Papillary Neoplasms of the Pancreas and Bile Duct. 2020

Singhi, Aatur D / Wood, Laura D / Parks, Emma / Torbenson, Michael S / Felsenstein, Matthäus / Hruban, Ralph H / Nikiforova, Marina N / Wald, Abigail I / Kaya, Cihan / Nikiforov, Yuri E / Favazza, Laura / He, Jin / McGrath, Kevin / Fasanella, Kenneth E / Brand, Randall E / Lennon, Anne Marie / Furlan, Alessandro / Dasyam, Anil K / Zureikat, Amer H / Zeh, Herbert J / Lee, Kenneth / Bartlett, David L / Slivka, Adam. ·Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; Pittsburgh Liver Research Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Electronic address: singhiad@upmc.edu. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland. · Carnegie Mellon University, Pittsburgh, Pennsylvania. · Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, Rochester, Minnesota. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany. · Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. · Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. · Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. · Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. · Department of Surgery, University of Texas Southwestern, Dallas, Texas. ·Gastroenterology · Pubmed #31678302.

ABSTRACT: BACKGROUND & AIMS: Intraductal oncocytic papillary neoplasms (IOPNs) of the pancreas and bile duct contain epithelial cells with numerous, large mitochondria and are cystic precursors to pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA), respectively. However, IOPNs do not have the genomic alterations found in other pancreatobiliary neoplasms. In fact, no recurrent genomic alterations have been described in IOPNs. PDACs without activating mutations in KRAS contain gene rearrangements, so we investigated whether IOPNs have recurrent fusions in genes. METHODS: We analyzed 20 resected pancreatic IOPNs and 3 resected biliary IOPNs using a broad RNA-based targeted sequencing panel to detect cancer-related fusion genes. Four invasive PDACs and 2 intrahepatic CCAs from the same patients as the IOPNs, were also available for analysis. Samples of pancreatic cyst fluid (n = 5, collected before surgery) and bile duct brushings (n = 2) were analyzed for translocations. For comparison, we analyzed pancreatobiliary lesions from 126 patients without IOPN (controls). RESULTS: All IOPNs evaluated were found to have recurring fusions of ATP1B1-PRKACB (n = 13), DNAJB1-PRKACA (n = 6), or ATP1B1-PRKACA (n = 4). These fusions also were found in corresponding invasive PDACs and intrahepatic CCAs, as well as in matched pancreatic cyst fluid and bile duct brushings. These gene rearrangements were absent from all 126 control pancreatobiliary lesions. CONCLUSIONS: We identified fusions in PRKACA and PRKACB genes in pancreatic and biliary IOPNs, as well as in PDACs and pancreatic cyst fluid and bile duct cells from the same patients. We did not identify these gene fusions in 126 control pancreatobiliary lesions. These fusions might be used to identify patients at risk for IOPNs and their associated invasive carcinomas.

10 Article Surgical Outcomes After Pancreatic Resection of Screening-Detected Lesions in Individuals at High Risk for Developing Pancreatic Cancer. 2020

Canto, Marcia Irene / Kerdsirichairat, Tossapol / Yeo, Charles J / Hruban, Ralph H / Shin, Eun Ji / Almario, Jose Alejandro / Blackford, Amanda / Ford, Madeline / Klein, Alison P / Javed, Ammar A / Lennon, Anne Marie / Zaheer, Atif / Kamel, Ihab R / Fishman, Elliot K / Burkhart, Richard / He, Jin / Makary, Martin / Weiss, Matthew J / Schulick, Richard D / Goggins, Michael G / Wolfgang, Christopher L. ·Division of Gastroenterology and Hepatology, Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Blalock 407, Baltimore, MD, 21287, USA. mcanto1@jhmi.edu. · Division of Gastroenterology and Hepatology, Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Blalock 407, Baltimore, MD, 21287, USA. · Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA. · Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA. · Department of Radiology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA. · Department of Surgery, University of Colorado School of Medicine, Denver, CO, USA. ·J Gastrointest Surg · Pubmed #31197699.

ABSTRACT: BACKGROUND: Screening high-risk individuals (HRI) can detect potentially curable pancreatic ductal adenocarcinoma (PDAC) and its precursors. We describe the outcomes of high-risk individuals (HRI) after pancreatic resection of screen-detected neoplasms. METHODS: Asymptomatic HRI enrolled in the prospective Cancer of the Pancreas Screening (CAPS) studies from 1998 to 2014 based on family history or germline mutations undergoing surveillance for at least 6 months were included. Pathologic diagnoses, hospital length of stay, incidence of diabetes mellitus, operative morbidity, need for repeat operation, and disease-specific mortality were determined. RESULTS: Among 354 HRI, 48 (13.6%) had 57 operations (distal pancreatectomy (31), Whipple (20), and total pancreatectomy (6)) for suspected pancreatic neoplasms presenting as a solid mass (22), cystic lesion(s) (25), or duct stricture (1). The median length of stay was 7 days (IQR 5-11). Nine of the 42 HRI underwent completion pancreatectomy for a new lesion after a median of 3.8 years (IQR 2.5-7.6). Postoperative complications developed in 17 HRI (35%); there were no perioperative deaths. New-onset diabetes mellitus after partial resection developed in 20% of HRI. Fourteen PDACs were diagnosed, 11 were screen-detected, 10 were resectable, and 9 had an R0 resection. Metachronous PDAC developed in remnant pancreata of 2 HRI. PDAC-related mortality was 4/10 (40%), with 90% 1-year survival and 60% 5-year survival, respectively. CONCLUSIONS: Screening HRI can detect PDAC with a high resectability rate. Surgical treatment is associated with a relatively short length of stay and low readmission rate, acceptable morbidity, zero 90-day mortality, and significant long-term survival. CLINICAL TRIAL REGISTRATION NUMBER: NCT2000089.

11 Article Surgical Resection of 78 Pancreatic Solid Pseudopapillary Tumors: a 30-Year Single Institutional Experience. 2020

Wright, Michael J / Javed, Ammar A / Saunders, Tyler / Zhu, Yayun / Burkhart, Richard A / Yu, Jun / He, Jin / Cameron, John L / Makary, Martin A / Wolfgang, Christopher L / Weiss, Matthew J. ·The John L. Cameron Division of Hepatobiliary and Pancreatic Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA. · The John L. Cameron Division of Hepatobiliary and Pancreatic Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA. mweiss5@jhmi.edu. · Pancreas Cancer Multidisciplinary Clinic, Liver Cancer Multidisciplinary Clinic, Surgical Oncology Fellowship, Miller Coulson Academy of Clinical Excellence, Johns Hopkins University, 600 N. Wolfe St. / Blalock 685, Baltimore, MD, 21287, USA. mweiss5@jhmi.edu. ·J Gastrointest Surg · Pubmed #31073801.

ABSTRACT: BACKGROUND: Solid pseudopapillary tumors (SPTs) are rare, benign tumors of the pancreas that present as heterogeneous masses. We sought to evaluate the short- and long-term outcomes of surgical resected SPTs. Patients managed via initial surveillance were compared to those who underwent upfront resection. METHODS: A prospectively maintained institutional database was used to identify patients who underwent surgical resection for a SPT between 1988 and 2018. Data on clinicopathological features and outcomes were collected and analyzed. RESULTS: Seventy-eight patients underwent surgical resection for SPT during the study period. The mean age was 34.0 ± 14.6 years and a majority were female (N = 67, 85.9%) and white (N = 46, 58.9%). Thirty patients (37.9%) were diagnosed incidentally. Imaging-based presumed diagnosis was SPT in 49 patients (62.8%). A majority were located in the body or tail of the pancreas (N = 47, 60.3%), and 48 patients (61.5%) underwent a distal pancreatectomy. The median tumor size was 4.0 cm (IQR, 3.0-6.0), nodal disease was present in three patients (3.9%), and R0 resection was performed in all patients. No difference was observed in clinicopathological features and outcomes between patients who were initially managed via surveillance and those who underwent upfront resection. None of the patients under surveillance had nodal disease or metastasis at the time of resection; however, one of them developed recurrence of disease 95.1 months after resection. At a median follow-up of 36.1 months (IQR, 8.1-62.1), 77 (%) patients were alive and one patient (1.3%) had a recurrence of disease at 95.1 months after resection and subsequently died due to disease. CONCLUSIONS: SPTs are rare pancreatic tumors that are diagnosed most frequently in young females. While a majority are benign and have an indolent course, malignant behavior has been observed. Surgical resection can result in exceptional outcomes.

12 Article Pancreatic Nerve Sheath Tumors: a Single Institutional Series and Systematic Review of the Literature. 2020

Javed, Ammar A / Wright, Michael J / Hasanain, Alina / Chang, Kevin / Burkhart, Richard A / Hruban, Ralph H / Thompson, Elizabeth / Fishman, Elliot K / Cameron, John L / He, Jin / Wolfgang, Christopher L / Weiss, Matthew J. ·Departments of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA. · Departments of Pathology, Johns Hopkins Hospital, Baltimore, MD, USA. · Departments of Radiology, Johns Hopkins Hospital, Baltimore, MD, USA. · Departments of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA. mweiss5@jhmi.edu. · , Baltimore, USA. mweiss5@jhmi.edu. ·J Gastrointest Surg · Pubmed #30941687.

ABSTRACT: INTRODUCTION: Improvement in imaging has resulted in frequent diagnosis of benign and premalignant pancreatic tumors. Pancreatic nerve sheath (PNS) tumors are one of the rarest pancreatic tumors. Literature on PNS is limited and their biology is poorly understood. Here, we report the largest series of PNS tumors to date and review the literature to evaluate the current data available on PNS tumors. METHODS: An institutional database was used to identify patients who underwent resection for PNS tumors. Clinicopathological characteristics and outcomes of these patients were reported. Furthermore, a review of literature was performed. RESULTS: From January 1994 through December 2016, seven patients underwent resection for PNS tumors. The median age was 57.7 years (IQR, 44.9-61.9) and the sex was approximately equally distributed (male = 4; 57.1%). Three (42.9%) patients were diagnosed incidentally and six (85.7%) were misdiagnosed as having other pancreatic tumors. The median tumor size was 2.1 (IQR 1.8-3.0) cm and six (85.7%) had no nodal disease. At a median follow-up of 15.5 (IQR 13.7-49.3) months, six patients were alive without evidence of disease and one patient was lost to follow-up. The literature review identified 49 studies reporting 54 patients with PNS tumors. Forty-six were misdiagnosed as having other pancreatic tumors. The median tumor size was 3.6 (range 1-20) cm, nodal disease was present in six patients (22.2%), and no patient had distant metastatic disease. At the time of last follow-up, all patients were free of disease. CONCLUSION: This is the largest single institution series on PNS tumors reported to date. These tumors are rare and are often misdiagnosed, given their radiological characteristics. PNS tumors have a benign course of disease and surgical resection results in favorable long-term outcomes.

13 Article Genetic Analysis of Small Well-differentiated Pancreatic Neuroendocrine Tumors Identifies Subgroups With Differing Risks of Liver Metastases. 2020

Pea, Antonio / Yu, Jun / Marchionni, Luigi / Noe, Michael / Luchini, Claudio / Pulvirenti, Alessandra / de Wilde, Roeland F / Brosens, Lodewijk A / Rezaee, Neda / Javed, Ammar / Chianchiano, Peter / Gobbo, Stefano / Regi, Paolo / Salvia, Roberto / Bassi, Claudio / He, Jin / Weiss, Matthew J / Cameron, John L / Offerhaus, G Johan A / Hruban, Ralph H / Lawlor, Rita T / Scarpa, Aldo / Heaphy, Christopher M / Wood, Laura D / Wolfgang, Christopher L. ·Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD. · Department of Surgery, The Pancreas Institute, Verona, Italy. · Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD. · Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy. · Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands. · Department of Pathology, Pederzoli Hospital, Peschiera, Italy. · Department of Surgery, Pederzoli Hospital, Peschiera, Italy. · ARC-Net Applied Research on Cancer Center, University and Hospital Trust of Verona, Verona, Italy. ·Ann Surg · Pubmed #30339629.

ABSTRACT: OBJECTIVE: The aim of this study was to investigate the key molecular alterations in small primary pancreatic neuroendocrine tumors (PanNETs) associated with the development of liver metastases. BACKGROUND: Well-differentiated PanNETs with small size are typically indolent; however, a limited subset metastasize to the liver. METHODS: A total of 87 small primary PanNETs (<3 cm), including 32 metastatic cases and 55 nonmetastatic cases after a 5-year follow-up, were immunolabeled for DAXX/ATRX and analyzed for alternative lengthening of telomeres (ALT) by Fluorescence In Situ Hybridization. A subset of these cases, 24 that metastasized and 24 that did not metastasize, were assessed by targeted next-generation sequencing and whole-genome copy number variation. RESULTS: In the entire cohort, high Ki-67 (OR 1.369; 95% CI 1.121-1.673; P = 0.002), N-stage (OR 4.568; 95% CI 1.458-14.312; P = 0.009), and ALT-positivity (OR 3.486; 95% CI 1.093-11.115; P = 0.035) were independently associated with liver metastases. In the subset assessed by next-generation sequencing and copy number variation analysis, 3 molecular subtypes with differing risks of liver metastases were identified. Group 1 (n = 15; 73% metastasized) was characterized by recurrent chromosomal gains, CN-LOH, DAXX mutations, and ALT-positivity. Group 2 (n = 19; 42% metastasized, including 5 G1 tumors) was characterized by limited copy number alterations and mutations. Group 3 (n = 14; 35% metastasized) were defined by chromosome 11 loss. CONCLUSIONS: We identified genomic patterns of small PanNETs associated with a different risk for liver metastases. Molecular alterations, such as DAXX mutations, chromosomal gains, and ALT, are associated with an increased risk of metastasis in small PanNETs. Therefore, targeted sequencing and/or ALT analysis may help in the clinical decisions for these small PanNETs.

14 Article Disparities in the Use of Chemotherapy in Patients with Resected Pancreatic Ductal Adenocarcinoma. 2019

Wright, Michael J / Overton, Heidi N / Teinor, Jonathan A / Ding, Ding / Burkhart, Richard A / Cameron, John L / He, Jin / Wolfgang, Christopher L / Weiss, Matthew J / Javed, Ammar A. ·The John L. Cameron Division of Hepatobiliary and Pancreatic Surgery, The Johns Hopkins Hospital, 600 N. Wolfe St. / Blalock 1222A, Baltimore, MD, 2I287, USA. · The John L. Cameron Division of Hepatobiliary and Pancreatic Surgery, The Johns Hopkins Hospital, 600 N. Wolfe St. / Blalock 1222A, Baltimore, MD, 2I287, USA. ajaved1@jhmi.edu. ·J Gastrointest Surg · Pubmed #31270718.

ABSTRACT: BACKGROUND: Introduction of effective systemic therapies for pancreatic ductal adenocarcinoma (PDAC) has demonstrated survival benefit. However, chemotherapy remains underutilized in these patients. We sought to investigate the implications of disparities on the trends in utilization of chemotherapy. METHODS: A retrospective study using the Surveillance, Epidemiology, and End Results (SEER) database identified patients who underwent surgical resection for PDAC from 1998 to 2014. Clinicopathologic, demographic, racial, and geographical factors were analyzed to assess associations with receipt of chemotherapy and disease-specific survival. RESULTS: A total of 15,585 patients were included in the study. A majority (N = 9953, 63.9%) received chemotherapy. Factors associated with poorer odds of receiving chemotherapy included older age (p < 0.001), African-American race (p = 0.003), and living in the Southwest region of the USA (p < 0.001). Married patients were at higher odds of receiving chemotherapy (all p < 0.001). Receipt of chemotherapy was independently associated with improved disease-specific survival (p < 0.001). CONCLUSIONS: Receipt of chemotherapy results in an improved survival in patients with resected PDAC. Demographic, racial, and geographic factors influence the rate of receipt of chemotherapy. Despite prior reports, these trends have not changed over the recent decades.

15 Article Intraductal Papillary Mucinous Neoplasms Arise From Multiple Independent Clones, Each With Distinct Mutations. 2019

Fischer, Catherine G / Beleva Guthrie, Violeta / Braxton, Alicia M / Zheng, Lily / Wang, Pei / Song, Qianqian / Griffin, James F / Chianchiano, Peter E / Hosoda, Waki / Niknafs, Noushin / Springer, Simeon / Dal Molin, Marco / Masica, David / Scharpf, Robert B / Thompson, Elizabeth D / He, Jin / Wolfgang, Christopher L / Hruban, Ralph H / Roberts, Nicholas J / Lennon, Anne Marie / Jiao, Yuchen / Karchin, Rachel / Wood, Laura D. ·Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Institute for Computational Medicine, Johns Hopkins University, Baltimore, Maryland; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland. · McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. · State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. · Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Medicine, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Institute for Computational Medicine, Johns Hopkins University, Baltimore, Maryland; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: karchin@jhu.edu. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: ldwood@jhmi.edu. ·Gastroenterology · Pubmed #31175866.

ABSTRACT: BACKGROUND & AIMS: Intraductal papillary mucinous neoplasms (IPMNs) are lesions that can progress to invasive pancreatic cancer and constitute an important system for studies of pancreatic tumorigenesis. We performed comprehensive genomic analyses of entire IPMNs to determine the diversity of somatic mutations in genes that promote tumorigenesis. METHODS: We microdissected neoplastic tissues from 6-24 regions each of 20 resected IPMNs, resulting in 227 neoplastic samples that were analyzed by capture-based targeted sequencing. Somatic mutations in genes associated with pancreatic tumorigenesis were assessed across entire IPMN lesions, and the resulting data were supported by evolutionary modeling, whole-exome sequencing, and in situ detection of mutations. RESULTS: We found a high prevalence of heterogeneity among mutations in IPMNs. Heterogeneity in mutations in KRAS and GNAS was significantly more prevalent in IPMNs with low-grade dysplasia than in IPMNs with high-grade dysplasia (P < .02). Whole-exome sequencing confirmed that IPMNs contained multiple independent clones, each with distinct mutations, as originally indicated by targeted sequencing and evolutionary modeling. We also found evidence for convergent evolution of mutations in RNF43 and TP53, which are acquired during later stages of tumorigenesis. CONCLUSIONS: In an analysis of the heterogeneity of mutations throughout IPMNs, we found that early-stage IPMNs contain multiple independent clones, each with distinct mutations, indicating their polyclonal origin. These findings challenge the model in which pancreatic neoplasms arise from a single clone. Increasing our understanding of the mechanisms of IPMN polyclonality could lead to strategies to identify patients at increased risk for pancreatic cancer.

16 Article Defining and Predicting Early Recurrence in 957 Patients With Resected Pancreatic Ductal Adenocarcinoma. 2019

Groot, Vincent P / Gemenetzis, Georgios / Blair, Alex B / Rivero-Soto, Roberto J / Yu, Jun / Javed, Ammar A / Burkhart, Richard A / Rinkes, Inne H M Borel / Molenaar, I Quintus / Cameron, John L / Weiss, Matthew J / Wolfgang, Christopher L / He, Jin. ·Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Surgery, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht, The Netherlands. ·Ann Surg · Pubmed #31082915.

ABSTRACT: OBJECTIVES: To establish an evidence-based cut-off to differentiate between early and late recurrence and to compare clinicopathologic risk factors between the two groups. SUMMARY BACKGROUND DATA: A clear definition of "early recurrence" after pancreatic ductal adenocarcinoma resection is currently lacking. METHODS: Patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma between 2000 and 2013 were included. Exclusion criteria were neoadjuvant therapy and incomplete follow-up. A minimum P-value approach was used to evaluate the optimal cut-off value of recurrence-free survival to divide the patients into early and late recurrence cohorts based on subsequent prognosis. Potential risk factors for early recurrence were assessed with logistic regression models. RESULTS: Of 957 included patients, 204 (21.3%) were recurrence-free at last follow-up. The optimal length of recurrence-free survival to distinguish between early (n = 388, 51.5%) and late recurrence (n = 365, 48.5%) was 12 months (P < 0.001). Patients with early recurrence had 1-, and 2-year post-recurrence survival rates of 20 and 6% compared with 45 and 22% for the late recurrence group (both P < 0.001). Preoperative risk factors for early recurrence included a Charlson age-comorbidity index ≥4 (OR 1.65), tumor size > 3.0 cm on computed tomography (OR 1.53) and CA 19-9 > 210 U/mL (OR 2.30). Postoperative risk factors consisted of poor tumor differentiation grade (OR 1.66), microscopic lymphovascular invasion (OR 1.70), a lymph node ratio > 0.2 (OR 2.49), and CA 19-9 > 37 U/mL (OR 3.38). Adjuvant chemotherapy (OR 0.28) and chemoradiotherapy (OR 0.29) were associated with a reduced likelihood of early recurrence. CONCLUSION: A recurrence-free interval of 12 months is the optimal threshold for differentiating between early and late recurrence, based on subsequent prognosis.

17 Article Negative Pressure Wound Therapy for Surgical-site Infections: A Randomized Trial. 2019

Javed, Ammar A / Teinor, Jonathan / Wright, Michael / Ding, Ding / Burkhart, Richard A / Hundt, John / Cameron, John L / Makary, Martin A / He, Jin / Eckhauser, Frederic E / Wolfgang, Christopher L / Weiss, Matthew J. ·The John L. Cameron Division of Hepatobiliary and Pancreatic Surgery, The Johns Hopkins Hospital, Baltimore, MD. · Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD. ·Ann Surg · Pubmed #31082899.

ABSTRACT: OBJECTIVE: This study seeks to evaluate the efficacy of negative pressure wound therapy for surgical-site infection (SSI) after open pancreaticoduodenectomy. BACKGROUND: Despite improvement in infection control, SSIs remain a common cause of morbidity after abdominal surgery. SSI has been associated with an increased risk of reoperation, prolonged hospitalization, readmission, and higher costs. Recent retrospective studies have suggested that the use of negative pressure wound therapy can potentially prevent this complication. METHODS: We conducted a single-center randomized, controlled trial evaluating surgical incision closure during pancreaticoduodenectomy using negative pressure wound therapy in patients at high risk for SSI. We randomly assigned patients to receive negative pressure wound therapy or a standard wound closure. The primary end point of the study was the occurrence of a postoperative SSI. We evaluated the economic impact of the intervention. RESULTS: From January 2017 through February 2018, we randomized 123 patients at the time of closure of the surgical incision. SSI occurred in 9.7% (6/62) of patients in the negative pressure wound therapy group and in 31.1% (19/61) of patients in the standard closure group (relative risk = 0.31; 95% confidence interval, 0.13-0.73; P = 0.003). This corresponded to a relative risk reduction of 68.8%. SSIs were found to independently increase the cost of hospitalization by 23.8%. CONCLUSIONS: The use of negative pressure wound therapy resulted in a significantly lower risk of SSIs. Incorporating this intervention in surgical practice can help reduce a complication that significantly increases patient harm and healthcare costs.

18 Article Understanding genetic features of pancreatic neoplasm. 2019

He, Jin / Zhang, Zhi-Gang / Yu, Xianjun. ·Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. jhe11@jhmi.edu. · State Key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute Shanghai Jiao Tong University, Shanghai 200127, China. zzhang@shsci.org. · Department of Pancreatic & Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Shanghai Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China. yuxianjun@fudanpci.org. ·Chin Clin Oncol · Pubmed #31070036.

ABSTRACT: -- No abstract --

19 Article Recurrence after neoadjuvant therapy and resection of borderline resectable and locally advanced pancreatic cancer. 2019

Groot, Vincent P / Blair, Alex B / Gemenetzis, Georgios / Ding, Ding / Burkhart, Richard A / Yu, Jun / Borel Rinkes, Inne H M / Molenaar, I Quintus / Cameron, John L / Weiss, Matthew J / Wolfgang, Christopher L / He, Jin. ·Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Surgery, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht, the Netherlands. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Surgery, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht, the Netherlands. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: jhe11@jhmi.edu. ·Eur J Surg Oncol · Pubmed #31023560.

ABSTRACT: INTRODUCTION: The incidence, timing, and implications of recurrence in patients who underwent neoadjuvant treatment and surgical resection of borderline resectable (BRPC) or locally advanced (LAPC) pancreatic cancer are not well established. MATERIALS AND METHODS: Patients with BRPC/LAPC who underwent post-neoadjuvant resection between 2007 and 2015 were included. Associations between clinicopathologic characteristics and specific recurrence locations, recurrence-free survival (RFS), and overall survival from resection (OS) were assessed using Cox regression analyses. RESULTS: For 231 included patients, median survival from diagnosis and resection were 28.0 and 19.8 months, respectively. After a median RFS of 7.9 months, 189 (81.8%) patients had recurred. Multiple-site (n = 87, 46.0%) and liver-only recurrence (n = 28, 14.8%) generally occurred earlier and resulted in significantly worse OS when compared to local-only (n = 52, 27.5%) or lung-only recurrence (n = 18, 9.5%). Microscopic perineural invasion, yN1-yN2 status and elevated pre-surgery CA 19-9 >100 U/mL were associated with both local-only and multiple-site/liver-only recurrence. R1-margin was associated with local-only recurrence (HR 2.03). yN1-yN2 status and microscopic perineural invasion were independent predictors for both poor RFS and OS, while yT3-yT4 tumor stage (HR 1.39) and poor tumor differentiation (HR 1.60) were only predictive of poor OS. Adjuvant therapy was independently associated with both prolonged RFS (HR 0.73; median 7.0 vs. 10.9 months) and OS (HR 0.69; median 15.4 vs. 22.7 months). CONCLUSION: Despite neoadjuvant therapy leading to resection and relatively favorable pathologic tumor characteristics in BRPC/LAPC patients, more than 80% of patients experienced disease recurrence, 72.5% of which occurred at distant sites.

20 Article Promoter methylation of ADAMTS1 and BNC1 as potential biomarkers for early detection of pancreatic cancer in blood. 2019

Eissa, Maryam A L / Lerner, Lane / Abdelfatah, Eihab / Shankar, Nakul / Canner, Joseph K / Hasan, Nesrin M / Yaghoobi, Vesal / Huang, Barry / Kerner, Zachary / Takaesu, Felipe / Wolfgang, Christopher / Kwak, Ruby / Ruiz, Michael / Tam, Matthew / Pisanic, Thomas R / Iacobuzio-Donahue, Christine A / Hruban, Ralph H / He, Jin / Wang, Tza-Huei / Wood, Laura D / Sharma, Anup / Ahuja, Nita. ·Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Surgery, Yale-New Haven Health, Yale University, School of Medicine, P.O. Box 208062, New Haven, CT, 06520-8062, USA. · Johns Hopkins Institute for NanoBioTechnology, The Johns Hopkins University, Baltimore, MD, USA. · Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA. · Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · The Sol Goldman Pancreatic Cancer Research Center, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, MD, USA. · Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. nita.ahuja@yale.edu. · Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. nita.ahuja@yale.edu. · The Sol Goldman Pancreatic Cancer Research Center, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, MD, USA. nita.ahuja@yale.edu. · Department of Surgery, Yale-New Haven Health, Yale University, School of Medicine, P.O. Box 208062, New Haven, CT, 06520-8062, USA. nita.ahuja@yale.edu. ·Clin Epigenetics · Pubmed #30953539.

ABSTRACT: BACKGROUND: Despite improvements in cancer management, most pancreatic cancers are still diagnosed at an advanced stage. We have recently identified promoter DNA methylation of the genes ADAMTS1 and BNC1 as potential blood biomarkers of pancreas cancer. In this study, we validate this biomarker panel in peripheral cell-free tumor DNA of patients with pancreatic cancer. RESULTS: Sensitivity and specificity for each gene are as follows: ADAMTS1 87.2% and 95.8% (AUC = 0.91; 95% CI 0.71-0.86) and BNC1 64.1% and 93.7% (AUC = 0.79; 95% CI 0.63-0.78). When using methylation of either gene as a combination panel, sensitivity increases to 97.3% and specificity to 91.6% (AUC = 0.95; 95% CI 0.77-0.90). Adding pre-operative CA 19-9 values to the combined two-gene methylation panel did not improve sensitivity. Methylation of ADAMTS1 was found to be positive in 87.5% (7/8) of stage I, 77.8% (7/9) of stage IIA, and 90% (18/20) of stage IIB disease. Similarly, BNC1 was positive in 62.5% (5/8) of stage I patients, 55.6% (5/9) of stage IIA, and 65% (13/20) of patients with stage IIB disease. The two-gene panel (ADAMTS1 and/or BNC1) was positive in 100% (8/8) of stage I, 88.9% (8/9) of stage IIA, and 100% (20/20) of stage IIB disease. The sensitivity and specificity of the two-gene panel for localized pancreatic cancer (stages I and II), where the cancer is eligible for surgical resection with curative potential, was 94.8% and 91.6% respectively. Additionally, the two-gene panel exhibited an AUC of 0.95 (95% CI 0.90-0.98) compared to 57.1% for CA 19-9 alone. CONCLUSION: The methylation status of ADAMTS1 and BNC1 in cfDNA shows promise for detecting pancreatic cancer during the early stages when curative resection of the tumor is still possible. This minimally invasive blood-based biomarker panel could be used as a promising tool for diagnosis and screening in a select subset of high-risk populations.

21 Article Isolated pulmonary recurrence after resection of pancreatic cancer: the effect of patient factors and treatment modalities on survival. 2019

Groot, Vincent P / Blair, Alex B / Gemenetzis, Georgios / Ding, Ding / Burkhart, Richard A / van Oosten, A Floortje / Molenaar, I Quintus / Cameron, John L / Weiss, Matthew J / Yang, Stephen C / Wolfgang, Christopher L / He, Jin. ·Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Surgery, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht, the Netherlands. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Surgery, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht, the Netherlands. · Department of Thoracic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: jhe11@jhmi.edu. ·HPB (Oxford) · Pubmed #30777697.

ABSTRACT: BACKGROUND: The literature suggests favorable survival for patients with isolated pulmonary recurrence after resection of pancreatic ductal adenocarcinoma (PDAC) as compared to other recurrence patterns. Within this cohort, it remains unclear what factors are associated with improved survival. METHODS: Patients who developed pulmonary recurrence after pancreatectomy were selected from a prospective database. Predictors for post-recurrence survival (PRS) were analyzed using a multivariable Cox regression model. RESULTS: Ninety-six patients were included. Median recurrence-free survival (RFS), PRS and overall survival (OS) were 16.3, 18.8 and 39.6 months, respectively. Further systemic treatment and/or metastasectomy (n = 64, 67%) was associated with significantly improved PRS and OS when compared to best supportive care (n = 35, 22%) (26.3 vs. 5.3 and 48.1 vs. 18.4, respectively; both P < 0.001). Patients who were able to undergo metastasectomy (n = 19) achieved a PRS and OS of 35.0 and 68.9 months, respectively. More than 5 pulmonary lesions, symptoms and CA 19-9 ≥100 U/mL at time of recurrence were predictive of decreased PRS. A recurrence-free interval of >16 months and treatment for recurrence were independently associated with improved PRS. CONCLUSIONS: Isolated pulmonary recurrence occurs in 13% of patients with recurrent PDAC and is associated with a median OS of 40 months. Aggressive treatment in highly selected patients was correlated with improved survival.

22 Article Prevalence of Germline Mutations Associated With Cancer Risk in Patients With Intraductal Papillary Mucinous Neoplasms. 2019

Skaro, Michael / Nanda, Neha / Gauthier, Christian / Felsenstein, Matthäus / Jiang, Zhengdong / Qiu, Miaozhen / Shindo, Koji / Yu, Jun / Hutchings, Danielle / Javed, Ammar A / Beckman, Ross / He, Jin / Wolfgang, Christopher L / Thompson, Elizabeth / Hruban, Ralph H / Klein, Alison P / Goggins, Michael / Wood, Laura D / Roberts, Nicholas J. ·Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medical Oncology, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. · The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. · Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: nrobert8@jhmi.edu. ·Gastroenterology · Pubmed #30716324.

ABSTRACT: BACKGROUND & AIMS: Many patients with pancreatic adenocarcinoma carry germline mutations associated with increased risk of cancer. It is not clear whether patients with intraductal papillary mucinous neoplasms (IPMNs), which are precursors to some pancreatic cancers, also carry these mutations. We assessed the prevalence of germline mutations associated with cancer risk in patients with histologically confirmed IPMN. METHODS: We obtained nontumor tissue samples from 315 patients with surgically resected IPMNs from 1997 through 2017, and we sequenced 94 genes with variants associated with cancer risk. Mutations associated with increased risk of cancer were identified and compared with individuals from the Exome Aggregation Consortium. RESULTS: We identified 23 patients with a germline mutation associated with cancer risk (7.3%; 95% confidence interval, 4.9-10.8). Nine patients had a germline mutation associated with pancreatic cancer susceptibility (2.9%; 95% confidence interval, 1.4-5.4). More patients with IPMNs carried germline mutations in ATM (P < .0001), PTCH1 (P < .0001), and SUFU (P < .0001) compared with controls. Patients with IPMNs and germline mutations associated with pancreatic cancer were more like to have concurrent invasive pancreatic carcinoma compared with patients with IPMNs without these mutations (P < .0320). CONCLUSIONS: In sequence analyses of 315 patients with surgically resected IPMNs, we found that almost 3% to carry mutations associated with pancreatic cancer risk. More patients with IPMNs and germline mutations associated with pancreatic cancer had concurrent invasive pancreatic carcinoma compared with patients with IPMNs without these mutations. Genetic analysis of patients with IPMNs might identify those at greatest risk for cancer.

23 Article Determining the optimal number of examined lymph nodes for accurate staging of pancreatic cancer: An analysis using the nodal staging score model. 2019

Hua, Jie / Zhang, Bo / Xu, Jin / Liu, Jiang / Ni, Quanxing / He, Jin / Zheng, Lei / Yu, Xianjun / Shi, Si. ·Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China; Shanghai Pancreatic Cancer Institute, Shanghai, China. · Department of Surgery, The Pancreatic Cancer Precision Medicine Center of Excellence Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Surgery, The Pancreatic Cancer Precision Medicine Center of Excellence Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, The Pancreatic Cancer Precision Medicine Center of Excellence Program, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China; Shanghai Pancreatic Cancer Institute, Shanghai, China. Electronic address: yuxianjun88@hotmail.com. · Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China; Shanghai Pancreatic Cancer Institute, Shanghai, China. Electronic address: shisi@fudanpci.org. ·Eur J Surg Oncol · Pubmed #30685327.

ABSTRACT: INTRODUCTION: The aim of this study was to determine the optimal number of examined lymph nodes (ELNs) for accurate staging of pancreatic cancer using the nodal staging score model. MATERIALS AND METHODS: Clinicopathological data for patients with resected pancreatic cancer were collected from SEER database (development cohort [DC]) and Fudan University Shanghai Cancer Center database (validation cohort [VC]). Multivariable models were constructed to assess how the number of ELNs was associated with stage migration and overall survival (OS). Using the β-binomial distribution, we developed a nodal staging score model from the DC and tested it with the VC. RESULTS: Both cohorts exhibited significant proportional increases from node-negative to node-positive disease (DC: odds ratio [OR], 1.047; P < 0.001; VC: OR, 1.035; P < 0.001) and improved OS (DC: hazard ratio [HR], 0.982; P < 0.001; VC: HR, 0.979; P < 0.001) as ELNs increased. Nodal staging scores escalated separately as ELNs increased for different tumor (T) stages, with plateaus at 16, 21, and 23 LNs (cut-offs) for T1, T2, and T3 tumors, respectively. Multivariable analysis indicated that examining more LNs than the corresponding cut-off value was a significant survival predictor (DC: HR, 0.813; P < 0.001; VC: HR, 0.696; P = 0.028). CONCLUSION: The optimal number of ELNs for adequate staging of pancreatic cancer was related to T stage. We recommend examining at least 16, 21, and 23 LNs for T1, T2, and T3 tumors, respectively, as a nodal staging quality measure for both surgery and pathological analysis.

24 Article Pancreatic cancer arising in the remnant pancreas is not always a relapse of the preceding primary. 2019

Luchini, Claudio / Pea, Antonio / Yu, Jun / He, Jin / Salvia, Roberto / Riva, Giulio / Weiss, Matthew J / Bassi, Claudio / Cameron, John L / Hruban, Ralph H / Goggins, Michael / Wolfgang, Christopher L / Scarpa, Aldo / Wood, Laura D / Lawlor, Rita T. ·Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Surgery, University and Hospital Trust of Verona, Verona, Italy. · Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Oncology, Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Medicine, Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. cwolfga2@jhmi.edu. · Department of Oncology, Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. cwolfga2@jhmi.edu. · Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy. aldo.scarpa@univr.it. · ARC-Net Research Center, University of Verona, Verona, Italy. aldo.scarpa@univr.it. · ARC-Net Research Center, University of Verona, Verona, Italy. ·Mod Pathol · Pubmed #30467323.

ABSTRACT: This study aimed to understand the biology of pancreatic ductal adenocarcinoma that arises in the remnant pancreas after surgical resection of a primary pancreatic ductal adenocarcinoma, using integrated histological and molecular analysis. Patients who underwent a completion pancreatectomy for local recurrence following resection of a primary pancreatic ductal adenocarcinoma were studied with histological analysis and next-generation sequencing of the primary and the recurrent cancer. Of six patients that met the inclusion criteria, three cases were classified as "true" recurrences, i.e., the primary and the cancer in the remnant pancreas shared both morphological features and molecular alterations. Two cases were identified as having independent cancers that exhibited different histological and molecular profiles. In the remaining case, the relationship could not be determined. Pancreatic ductal adenocarcinoma that arises in the remnant pancreas can be either a second primary or a "true" relapse of the preceding primary. The differentiation of second primaries from local recurrences may have important implications for patient management.

25 Article Single-cell sequencing defines genetic heterogeneity in pancreatic cancer precursor lesions. 2019

Kuboki, Yuko / Fischer, Catherine G / Beleva Guthrie, Violeta / Huang, Wenjie / Yu, Jun / Chianchiano, Peter / Hosoda, Waki / Zhang, Hao / Zheng, Lily / Shao, Xiaoshan / Thompson, Elizabeth D / Waters, Kevin / Poling, Justin / He, Jin / Weiss, Matthew J / Wolfgang, Christopher L / Goggins, Michael G / Hruban, Ralph H / Roberts, Nicholas J / Karchin, Rachel / Wood, Laura D. ·Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD, USA. · Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA. · Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA. · McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. ·J Pathol · Pubmed #30430578.

ABSTRACT: Intraductal papillary mucinous neoplasms (IPMNs) are precursors to pancreatic cancer; however, little is known about genetic heterogeneity in these lesions. The objective of this study was to characterize genetic heterogeneity in IPMNs at the single-cell level. We isolated single cells from fresh tissue from ten IPMNs, followed by whole genome amplification and targeted next-generation sequencing of pancreatic driver genes. We then determined single-cell genotypes using a novel multi-sample mutation calling algorithm. Our analyses revealed that different mutations in the same driver gene frequently occur in the same IPMN. Two IPMNs had multiple mutations in the initiating driver gene KRAS that occurred in unique tumor clones, suggesting the possibility of polyclonal origin or an unidentified initiating event preceding this critical mutation. Multiple mutations in later-occurring driver genes were also common and were frequently localized to unique tumor clones, raising the possibility of convergent evolution of these genetic events in pancreatic tumorigenesis. Single-cell sequencing of IPMNs demonstrated genetic heterogeneity with respect to early and late occurring driver gene mutations, suggesting a more complex pattern of tumor evolution than previously appreciated in these lesions. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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