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Pancreatic Neoplasms: HELP
Articles by Keith D. Lillemoe
Based on 91 articles published since 2010
(Why 91 articles?)
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Between 2010 and 2020, K. Lillemoe wrote the following 91 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Guideline Definition of a standard lymphadenectomy in surgery for pancreatic ductal adenocarcinoma: a consensus statement by the International Study Group on Pancreatic Surgery (ISGPS). 2014

Tol, Johanna A M G / Gouma, Dirk J / Bassi, Claudio / Dervenis, Christos / Montorsi, Marco / Adham, Mustapha / Andrén-Sandberg, Ake / Asbun, Horacio J / Bockhorn, Maximilian / Büchler, Markus W / Conlon, Kevin C / Fernández-Cruz, Laureano / Fingerhut, Abe / Friess, Helmut / Hartwig, Werner / Izbicki, Jakob R / Lillemoe, Keith D / Milicevic, Miroslav N / Neoptolemos, John P / Shrikhande, Shailesh V / Vollmer, Charles M / Yeo, Charles J / Charnley, Richard M / Anonymous3060801. ·Department of Surgery, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. · Department of Surgery, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: D.J.Gouma@amc.nl. · Department of Surgery and Oncology, Pancreas Institute, University of Verona, Verona, Italy. · Department of First Surgery, Agia Olga Hospital, Athens, Greece. · Department of General Surgery, Instituto Clinico Humanitas IRCCS, University of Milan, Milan, Italy. · Department of HPB Surgery, Hopital Edouard Herriot, Lyon, France. · Department of Surgery, Karolinska Institutet at Karolinska University Hospital, Huddinge, Stockholm, Sweden. · Department of General Surgery, Mayo Clinic, Jacksonville, FL. · Department of General-, Visceral- and Thoracic-Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany. · Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. · Professorial Surgical Unit, University of Dublin, Trinity College, Dublin, Ireland. · Department of Surgery, Clinic Hospital of Barcelona, University of Barcelona, Barcelona, Spain. · First Department of Digestive Surgery, Hippokrateon Hospital, University of Athens, Athens, Greece; Section for Surgical Research, Department of Surgery, Medical University of Graz, Graz, Austria. · Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. · Department of Surgery, Massachusetts General Hospital and the Harvard Medical School, Boston, MA. · First Surgical Clinic, Clinical Center of Serbia, University of Belgrade, Belgrade, Serbia. · Department of Molecular and Clinical Cancer Medicine, Liverpool Cancer Research-UK Centre, University of Liverpool, Liverpool, UK. · Department of Gastrointestinal and HPB Surgical Oncology, Tata Memorial Hospital, Mumbai, India. · Department of Surgery, Penn Medicine, The University of Pennsylvania, Philadelphia, PA. · Department of Surgery, Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, PA. · Department of HPB & Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK. ·Surgery · Pubmed #25061003.

ABSTRACT: BACKGROUND: The lymph node (Ln) status of patients with resectable pancreatic ductal adenocarcinoma is an important predictor of survival. The survival benefit of extended lymphadenectomy during pancreatectomy is, however, disputed, and there is no true definition of the optimal extent of the lymphadenectomy. The aim of this study was to formulate a definition for standard lymphadenectomy during pancreatectomy. METHODS: During a consensus meeting of the International Study Group on Pancreatic Surgery, pancreatic surgeons formulated a consensus statement based on available literature and their experience. RESULTS: The nomenclature of the Japanese Pancreas Society was accepted by all participants. Extended lymphadenectomy during pancreatoduodenectomy with resection of Ln's along the left side of the superior mesenteric artery (SMA) and around the celiac trunk, splenic artery, or left gastric artery showed no survival benefit compared with a standard lymphadenectomy. No level I evidence was available on prognostic impact of positive para-aortic Ln's. Consensus was reached on selectively removing suspected Ln's outside the resection area for frozen section. No consensus was reached on continuing or terminating resection in cases where these nodes were positive. CONCLUSION: Extended lymphadenectomy cannot be recommended. Standard lymphadenectomy for pancreatoduodenectomy should strive to resect Ln stations no. 5, 6, 8a, 12b1, 12b2, 12c, 13a, 13b, 14a, 14b, 17a, and 17b. For cancers of the body and tail of the pancreas, removal of stations 10, 11, and 18 is standard. Furthermore, lymphadenectomy is important for adequate nodal staging. Both pancreatic resection in relatively fit patients or nonresectional palliative treatment were accepted as acceptable treatment in cases of positive Ln's outside the resection plane. This consensus statement could serve as a guide for surgeons and researchers in future directives and new clinical studies.

2 Guideline Extended pancreatectomy in pancreatic ductal adenocarcinoma: definition and consensus of the International Study Group for Pancreatic Surgery (ISGPS). 2014

Hartwig, Werner / Vollmer, Charles M / Fingerhut, Abe / Yeo, Charles J / Neoptolemos, John P / Adham, Mustapha / Andrén-Sandberg, Ake / Asbun, Horacio J / Bassi, Claudio / Bockhorn, Max / Charnley, Richard / Conlon, Kevin C / Dervenis, Christos / Fernandez-Cruz, Laureano / Friess, Helmut / Gouma, Dirk J / Imrie, Clem W / Lillemoe, Keith D / Milićević, Miroslav N / Montorsi, Marco / Shrikhande, Shailesh V / Vashist, Yogesh K / Izbicki, Jakob R / Büchler, Markus W / Anonymous1650795. ·Department of Surgery, Klinikum Großhadern, University of Munich, Munich, Germany. · Department of Gastrointestinal Surgery, Penn Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA. · Department of Digestive Surgery, Centre Hospitalier Intercommunal, Poissy, France. · Department of Surgery, Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, PA. · Department of Molecular and Clinical Cancer Medicine, Liverpool Cancer Research-UK Centre, University of Liverpool, Liverpool, UK. · Department of HPB Surgery, Hopital Edouard Herriot, Lyon, France. · Department of Surgery, Karolinska Institutet at Karolinska University Hospital, Huddinge, Stockholm, Sweden. · Department of General Surgery, Mayo Clinic, Jacksonville, FL. · Department of Surgery and Oncology, Pancreas Institute, University of Verona, Verona, Italy. · Department of General-, Visceral- and Thoracic-Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany. · Department of HPB & Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK. · Professorial Surgical Unit, University of Dublin, Trinity College, Dublin, Ireland. · Department of First Surgery, Agia Olga Hospital, Athens, Greece. · Department of Surgery, Clinic Hospital of Barcelona, University of Barcelona, Barcelona, Spain. · Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. · Department of Surgery, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. · Academic Unit of Surgery, University of Glasgow, Glasgow, UK. · Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA. · First Surgical Clinic, Clinical Center of Serbia, University of Belgrade, Belgrade, Serbia. · Department of General Surgery, Instituto Clinico Humanitas IRCCS, University of Milan, Milan, Italy. · Department of Gastrointestinal and HPB Surgical Oncology, Tata Memorial Hospital, Mumbai, India. · Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. Electronic address: markus.buechler@med.uni-heidelberg.de. ·Surgery · Pubmed #24856668.

ABSTRACT: BACKGROUND: Complete macroscopic tumor resection is one of the most relevant predictors of long-term survival in pancreatic ductal adenocarcinoma. Because locally advanced pancreatic tumors can involve adjacent organs, "extended" pancreatectomy that includes the resection of additional organs may be needed to achieve this goal. Our aim was to develop a common consistent terminology to be used in centers reporting results of pancreatic resections for cancer. METHODS: An international panel of pancreatic surgeons working in well-known, high-volume centers reviewed the literature on extended pancreatectomies and worked together to establish a consensus on the definition and the role of extended pancreatectomy in pancreatic cancer. RESULTS: Macroscopic (R1) and microscopic (R0) complete tumor resection can be achieved in patients with locally advanced disease by extended pancreatectomy. Operative time, blood loss, need for blood transfusions, duration of stay in the intensive care unit, and hospital morbidity, and possibly also perioperative mortality are increased with extended resections. Long-term survival is similar compared with standard resections but appears to be better compared with bypass surgery or nonsurgical palliative chemotherapy or chemoradiotherapy. It was not possible to identify any clear prognostic criteria based on the specific additional organ resected. CONCLUSION: Despite increased perioperative morbidity, extended pancreatectomy is warranted in locally advanced disease to achieve long-term survival in pancreatic ductal adenocarcinoma if macroscopic clearance can be achieved. Definitions of extended pancreatectomies for locally advanced disease (and not distant metastatic disease) are established that are crucial for comparison of results of future trials across different practices and countries, in particular for those using neoadjuvant therapy.

3 Guideline Borderline resectable pancreatic cancer: a consensus statement by the International Study Group of Pancreatic Surgery (ISGPS). 2014

Bockhorn, Maximilian / Uzunoglu, Faik G / Adham, Mustapha / Imrie, Clem / Milicevic, Miroslav / Sandberg, Aken A / Asbun, Horacio J / Bassi, Claudio / Büchler, Markus / Charnley, Richard M / Conlon, Kevin / Cruz, Laureano Fernandez / Dervenis, Christos / Fingerhutt, Abe / Friess, Helmut / Gouma, Dirk J / Hartwig, Werner / Lillemoe, Keith D / Montorsi, Marco / Neoptolemos, John P / Shrikhande, Shailesh V / Takaori, Kyoichi / Traverso, William / Vashist, Yogesh K / Vollmer, Charles / Yeo, Charles J / Izbicki, Jakob R / Anonymous1640795. ·Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany. · Department of HPB Surgery, Hôpital Edouard Herriot, Lyon, France. · Academic Unit of Surgery, University of Glasgow, Glasgow, UK. · First Surgical Clinic, Clinical Center of Serbia, University of Belgrade, Belgrade, Serbia. · Department of Surgery, Karolinska Institutet at Karolinska University Hospital, Huddinge, Stockholm, Sweden. · Department of General Surgery, Mayo Clinic, Jacksonville, FL. · Department of Surgery and Oncology, Pancreas Institute, University of Verona, Verona, Italy. · Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. · Department of HPB & Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK. · Professorial Surgical Unit, University of Dublin, Trinity College, Dublin, Ireland. · Department of Surgery, Clinic Hospital of Barcelona, University of Barcelona, Barcelona, Spain. · First Department of Surgery, Agia Olga Hospital, Athens, Greece. · Department of Digestive Surgery, Centre Hospitalier Intercommunal, Poissy, France. · Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany. · Department of Surgery, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. · Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA. · Department of General Surgery, Instituto Clinico Humanitas IRCCS, University of Milan, Milan, Italy. · Department of Molecular and Clinical Cancer Medicine, Liverpool Cancer Research-UK Centre, University of Liverpool, Liverpool, UK. · Department of Gastrointestinal and HPB Surgical Oncology, Tata Memorial Centre, Mumbai, India. · Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. · St. Luke's Clinic - Center For Pancreatic and Liver Diseases, Boise, ID. · Department of Gastrointestinal Surgery, Penn Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA. · Department of Surgery, Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, PA. · Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany. Electronic address: izbicki@uke.de. ·Surgery · Pubmed #24856119.

ABSTRACT: BACKGROUND: This position statement was developed to expedite a consensus on definition and treatment for borderline resectable pancreatic ductal adenocarcinoma (BRPC) that would have worldwide acceptability. METHODS: An international panel of pancreatic surgeons from well-established, high-volume centers collaborated on a literature review and development of consensus on issues related to borderline resectable pancreatic cancer. RESULTS: The International Study Group of Pancreatic Surgery (ISGPS) supports the National Comprehensive Cancer Network criteria for the definition of BRPC. Current evidence supports operative exploration and resection in the case of involvement of the mesentericoportal venous axis; in addition, a new classification of extrahepatic mesentericoportal venous resections is proposed by the ISGPS. Suspicion of arterial involvement should lead to exploration to confirm the imaging-based findings. Formal arterial resections are not recommended; however, in exceptional circumstances, individual therapeutic approaches may be evaluated under experimental protocols. The ISGPS endorses the recommendations for specimen examination and the definition of an R1 resection (tumor within 1 mm from the margin) used by the British Royal College of Pathologists. Standard preoperative diagnostics for BRPC may include: (1) serum levels of CA19-9, because CA19-9 levels predict survival in large retrospective series; and also (2) the modified Glasgow Prognostic Score and the neutrophil/lymphocyte ratio because of the prognostic relevance of the systemic inflammatory response. Various regimens of neoadjuvant therapy are recommended only in the setting of prospective trials at high-volume centers. CONCLUSION: Current evidence justifies portomesenteric venous resection in patients with BRPC. Basic definitions were identified, that are currently lacking but that are needed to obtain further evidence and improvement for this important patient subgroup. A consensus for each topic is given.

4 Review Definition and classification of chyle leak after pancreatic operation: A consensus statement by the International Study Group on Pancreatic Surgery. 2017

Besselink, Marc G / van Rijssen, L Bengt / Bassi, Claudio / Dervenis, Christos / Montorsi, Marco / Adham, Mustapha / Asbun, Horacio J / Bockhorn, Maximillian / Strobel, Oliver / Büchler, Markus W / Busch, Olivier R / Charnley, Richard M / Conlon, Kevin C / Fernández-Cruz, Laureano / Fingerhut, Abe / Friess, Helmut / Izbicki, Jakob R / Lillemoe, Keith D / Neoptolemos, John P / Sarr, Michael G / Shrikhande, Shailesh V / Sitarz, Robert / Vollmer, Charles M / Yeo, Charles J / Hartwig, Werner / Wolfgang, Christopher L / Gouma, Dirk J / Anonymous1010883. ·Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: m.g.besselink@amc.nl. · Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · Department of Surgery and Oncology, Pancreas Institute, University of Verona, Verona, Italy. · Department of First Surgery, Agia Olga Hospital, Athens, Greece. · Department of Surgery, Humanitas Research Hospital and University, Milan, Italy. · Department of HPB Surgery, Hopital Edouard Herriot, HCL, UCBL1, Lyon, France. · Department of Surgery, Mayo Clinic, Jacksonville, FL. · Department of General-, Visceral-, and Thoracic-Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany. · Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. · Department of HPB & Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK. · Professorial Surgical Unit, University of Dublin, Trinity College, Dublin, Ireland. · Department of Surgery, Clinic Hospital of Barcelona, University of Barcelona, Barcelona, Spain. · First Department of Digestive Surgery, Hippokrateon Hospital, University of Athens, Athens, Greece; Section for Surgical Research, Department of Surgery, Medical University of Graz, Graz, Austria. · Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. · Department of Surgery, Massachusetts General Hospital and the Harvard Medical School, Boston, MA. · Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK. · Division of Subspecialty General Surgery, Mayo Clinic, Rochester, MN. · Department of GI and HPB Surgical Oncology, Tata Memorial Hospital, Mumbai, India. · Department of Surgical Oncology, Medical University in Lublin, Poland. · Department of Surgery, Penn Medicine, The University of Pennsylvania, Philadelphia, PA. · Department of Surgery, Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, PA. · Division of Pancreatic Surgery, Department of General, Visceral, and Transplantation Surgery, Ludwig Maximilians University, University of Munich, Germany. · Department of Surgery, Johns Hopkins Medicine, Baltimore, MD. ·Surgery · Pubmed #27692778.

ABSTRACT: BACKGROUND: Recent literature suggests that chyle leak may complicate up to 10% of pancreatic resections. Treatment depends on its severity, which may include chylous ascites. No international consensus definition or grading system of chyle leak currently is available. METHODS: The International Study Group on Pancreatic Surgery, an international panel of pancreatic surgeons working in well-known, high-volume centers, reviewed the literature and worked together to establish a consensus on the definition and classification of chyle leak after pancreatic operation. RESULTS: Chyle leak was defined as output of milky-colored fluid from a drain, drain site, or wound on or after postoperative day 3, with a triglyceride content ≥110 mg/dL (≥1.2 mmol/L). Three different grades of severity were defined according to the management needed: grade A, no specific intervention other than oral dietary restrictions; grade B, prolongation of hospital stay, nasoenteral nutrition with dietary restriction, total parenteral nutrition, octreotide, maintenance of surgical drains, or placement of new percutaneous drains; and grade C, need for other more invasive in-hospital treatment, intensive care unit admission, or mortality. CONCLUSION: This classification and grading system for chyle leak after pancreatic resection allows for comparison of outcomes between series. As with the other the International Study Group on Pancreatic Surgery consensus statements, this classification should facilitate communication and evaluation of different approaches to the prevention and treatment of this complication.

5 Review Intraductal Papillary Mucinous Neoplasm of the Pancreas: Current State of the Art and Ongoing Controversies. 2016

Fong, Zhi Ven / Ferrone, Cristina R / Lillemoe, Keith D / Fernández-Del Castillo, Carlos. ·Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA. ·Ann Surg · Pubmed #26727096.

ABSTRACT: With the widespread use and advances in radiographic imaging, Intraductal Papillary Mucinous Neoplasms (IPMNs) of the pancreas are identified with increasing frequency. Although many studies have addressed its biology and treatment, true understanding of its natural history continues to elude us. Its malignant potential places careproviders in a clinical dilemma of balancing the morbidity of pancreatectomy against the risk of malignant transformation while under continuous surveillance. Recently, there have been conflicting data published in the literature, generating more uncertainty in the field. In this article, we critically analyze the contrasting consensus guidelines from the International Association of Pancreatology and the American Gastroenterology Association, and address lingering questions and controversies. We also synthesize newly published data in the context of current standard of care, and provide a comprehensive review and recommendations for the clinical diagnosis, treatment, and follow-up strategy in the management of patients with Intraductal Papillary Mucinous Neoplasms.

6 Review Surgical management of pancreatic cancer--distal pancreatectomy. 2015

Parikh, Purvi Y / Lillemoe, Keith D. ·Department of Surgery, Stony Brook Medicine, Stony Brook, NY. · Harvard Medical School, Massachusetts General Hospital, Boston, MA. Electronic address: klillemoe@partners.org. ·Semin Oncol · Pubmed #25726056.

ABSTRACT: Distal pancreatectomy is the standard procedure for tumors located in the body and tail of the pancreas. In the last three decades, significant progress has been made with regard to technical aspects as well as perioperative care so that excellent mortality and morbidity rates can be achieved. Recently, there is growing evidence that distal pancreatectomy may be performed laparoscopically in selected patients, offering the advantages of minimally invasive surgery. Unfortunately, the oncologic outcomes for pancreatic adenocarcinoma remain poor, in part due to the late stage of presentation in most patients. We review the history of distal pancreatectomy, discuss current indications for performing this procedure, compare operative techniques in performing distal pancreatectomy, and review both the early complications seen in patients who have undergone a distal pancreatectomy and the long-term metabolic and oncologic outcomes of these patients.

7 Review Surgical palliation of pancreatic cancer. 2012

Conrad, Claudius / Lillemoe, Keith D. ·Harvard Medical School, Boston, MA, USA. ·Cancer J · Pubmed #23187845.

ABSTRACT: The surgical palliation of pancreatic cancer remains an important component of the treatment of this disease. The introduction of a new aggressive and effective chemotherapy regimen (FOLFIRINOX), interdisciplinary palliative care, and minimally invasive approaches for providing palliation are all factors that expand the role of the surgeon in the care of patients with unresectable disease. Currently, the role of the surgeon in the palliation of pancreatic cancer is (1) to identify patients with incurable disease (either preoperatively or intraoperatively), (2) to determine the optimal palliative technique to optimize results and preserve resources, and (3) to perform palliation of symptoms with low morbidity and mortality. The 3 most common symptoms of pancreatic cancer requiring surgical palliation are obstructive jaundice, gastric outlet obstruction, and tumor-associated pain. It is important that the surgeon recognizes the full range of surgical and nonoperative techniques available and contributes to the decision making as to the most appropriate method for each individual patient.

8 Review Pancreatic surgery for adenocarcinoma. 2012

Warshaw, Andrew L / Lillemoe, Keith D / Fernandez-del Castillo, Carlos. ·Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. awarshaw@partners.org ·Curr Opin Gastroenterol · Pubmed #22782020.

ABSTRACT: PURPOSE OF REVIEW: Pancreatic resection remains among the most formidable and complex of abdominal surgical operations. Nonetheless, recent observations have continued to provide incremental improvement in both our evidence for treatment regimens and the technology, resulting in better outcomes. RECENT FINDINGS: Neoadjuvant regimens appear to have promise, at least in local control and perhaps in long-term survival. More extensive operations focusing on perineural invasion along with minimally invasive laparoscopic and robotic techniques are attracting increasing attention. The effectiveness of major vascular resection remains controversial. Concentration of patients in centers of expertise has contributed to improved outcomes. SUMMARY: Improved management of pancreatic resections for cancer with more extensive and less-invasive surgical techniques has increased the number of patients who are candidates for effective surgical treatment.

9 Clinical Trial Total Neoadjuvant Therapy With FOLFIRINOX Followed by Individualized Chemoradiotherapy for Borderline Resectable Pancreatic Adenocarcinoma: A Phase 2 Clinical Trial. 2018

Murphy, Janet E / Wo, Jennifer Y / Ryan, David P / Jiang, Wenqing / Yeap, Beow Y / Drapek, Lorraine C / Blaszkowsky, Lawrence S / Kwak, Eunice L / Allen, Jill N / Clark, Jeffrey W / Faris, Jason E / Zhu, Andrew X / Goyal, Lipika / Lillemoe, Keith D / DeLaney, Thomas F / Fernández-Del Castillo, Carlos / Ferrone, Cristina R / Hong, Theodore S. ·Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston. · Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston. · Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston. ·JAMA Oncol · Pubmed #29800971.

ABSTRACT: Importance: Patients with borderline-resectable pancreatic ductal adenocarcinoma have historically poor outcomes with surgery followed by adjuvant chemotherapy. Evaluation of a total neoadjuvant approach with highly active therapy is warranted. Objective: To evaluate the margin-negative (R0) resection rate in borderline-resectable pancreatic ductal adenocarcinoma after neoadjuvant FOLFIRINOX (fluorouracil, irinotecan, and oxaliplatin) therapy and individualized chemoradiotherapy. Design, Setting, and Participants: A single-arm, phase 2 clinical trial was conducted at a large academic hospital with expertise in pancreatic surgery from August 3, 2012, through August 31, 2016, among 48 patients with newly diagnosed, previously untreated, localized pancreatic cancer determined to be borderline resectable by multidisciplinary review, who had Eastern Cooperative Oncology Group performance status 0 or 1 and adequate hematologic, renal, and hepatic function. Median follow-up for the analysis was 18.0 months among the 30 patients still alive at study completion. Interventions: Patients received FOLFIRINOX for 8 cycles. Upon restaging, patients with resolution of vascular involvement received short-course chemoradiotherapy (5 Gy × 5 with protons) with capecitabine. Patients with persistent vascular involvement received long-course chemoradiotherapy with fluorouracil or capecitabine. Main Outcomes and Measures: The primary outcome was R0 resection rate; secondary outcomes were median progression-free survival (PFS) and median overall survival (OS). Results: Of the 48 eligible patients, 27 were men and 21 were women, with a median age of 62 years (range, 46-74 years). Of the 43 patients who planned to receive 8 preoperative cycles of chemotherapy, 34 (79%) were able to complete all cycles. Twenty-seven patients (56%) had short-course chemoradiotherapy, while 17 patients (35%) had long-course chemoradiotherapy. R0 resection was achieved in 31 of the 48 eligible patients (65%; 95% CI, 49%-78%). Among the 32 patients who underwent resection, the R0 resection rate was 97% (n = 31). Median PFS among all eligible patients was 14.7 months (95% CI, 10.5 to not reached), with 2-year PFS of 43%; median OS was 37.7 months (95% CI, 19.4 to not reached), with 2-year OS of 56%. Among patients who underwent resection, median PFS was 48.6 months (95% CI, 14.4 to not reached) and median OS has not been reached, with a 2-year PFS of 55% and a 2-year OS of 72%. Conclusions and Relevance: Preoperative FOLFIRINOX followed by individualized chemoradiotherapy in borderline resectable pancreatic cancer results in high rates of R0 resection and prolonged median PFS and median OS, supporting ongoing phase 3 trials. Trial Registration: ClinicalTrials.gov Identifier: NCT01591733.

10 Clinical Trial Circulating tumor cells found in patients with localized and advanced pancreatic cancer. 2015

Kulemann, Birte / Pitman, Martha B / Liss, Andrew S / Valsangkar, Nakul / Fernández-Del Castillo, Carlos / Lillemoe, Keith D / Hoeppner, Jens / Mino-Kenudson, Mari / Warshaw, Andrew L / Thayer, Sarah P. ·From the *Department of Surgery and †Andrew L. Warshaw Institute for Pancreatic Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA; ‡Department of Surgery, University Hospital Freiburg, Freiburg, Germany; §Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; and ║Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE. ·Pancreas · Pubmed #25822154.

ABSTRACT: OBJECTIVES: Isolation of circulating tumor cells (CTCs) holds the promise of diagnosing and molecular profiling cancers from a blood sample. Here, we test a simple new low-cost filtration device for CTC isolation in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Peripheral blood samples drawn from healthy donors and PDAC patients were filtered using ScreenCell devices, designed to capture CTCs for cytologic and molecular analysis. Giemsa-stained specimens were evaluated by a pancreatic cytopathologist blinded to the histological diagnosis. Circulating tumor cell DNA was subjected to KRAS mutational analysis. RESULTS: Spiking experiments demonstrated a CTC capture efficiency as low as 2 cells/mL of blood. Circulating tumor cells were identified by either malignant cytology or presence of KRAS mutation in 73% of 11 patients (P = 0.001). Circulating tumor cells were identified in 3 of 4 patients with early (≤American Joint Committee on Cancer stage IIB) and in 5 of 7 patients with advanced (≥ American Joint Committee on Cancer stage III) PDAC. No CTCs were detected in blood from 9 health donors. CONCLUSIONS: Circulating tumor cells can be found in most patients with PDAC of any stage, whether localized, locally advanced, or metastatic. The ability to capture, cytologically identify, and genetically analyze CTCs suggests a possible tool for the diagnosis and characterization of genetic alterations of PDAC.

11 Clinical Trial Phase I study of neoadjuvant accelerated short course radiation therapy with photons and capecitabine for resectable pancreatic cancer. 2014

Wo, Jennifer Y / Mamon, Harvey J / Ferrone, Cristina R / Ryan, David P / Blaszkowsky, Lawrence S / Kwak, Eunice L / Tseng, Yolanda D / Napolitano, Brian N / Ancukiewicz, Marek / Swanson, Richard S / Lillemoe, Keith D / Fernandez-del Castillo, Carlos / Hong, Theodore S. ·Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, United States. Electronic address: jwo@partners.org. · Department of Radiation Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, United States. · Department of General Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, United States. · Department of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, United States. · Harvard Radiation Oncology Program, Boston, United States. · Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, United States. · Department of General Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, United States. ·Radiother Oncol · Pubmed #24231241.

ABSTRACT: PURPOSE: In this phase I study, we sought to determine the feasibility and tolerability of neoadjuvant short course radiotherapy (SC-CRT) delivered with photon RT with concurrent capecitabine for resectable pancreatic adenocarcinoma. MATERIALS AND METHODS: Ten patients with localized, resectable pancreatic adenocarcinoma were enrolled from December 2009 to August 2011. In dose level I, patients received 3 Gy × 10. In dose level 2, patients received 5 Gy × 5 (every other day). In dose level 3, patients received 5 Gy × 5 (consecutive days). Capecitabine was given during weeks 1 and 2. Surgery was performed 1-3 weeks after completion of chemotherapy. RESULTS: With an intended accrual of 12 patients, the study was closed early due to unexpected intraoperative complications. Compared to the companion phase I proton study, patients treated with photons had increased intraoperative RT fibrosis reported by surgeons (27% vs. 63%). Among those undergoing a Whipple resection, increased RT fibrosis translated to an increased mean OR time of 69 min. Dosimetric comparison revealed significantly increased low dose exposure to organs at risk for patients treated with photon RT. CONCLUSIONS: This phase I experience evaluating the tolerability of neoadjuvant SC-CRT with photon RT closed early due to unexpected intraoperative complications.

12 Clinical Trial A lethally irradiated allogeneic granulocyte-macrophage colony stimulating factor-secreting tumor vaccine for pancreatic adenocarcinoma. A Phase II trial of safety, efficacy, and immune activation. 2011

Lutz, Eric / Yeo, Charles J / Lillemoe, Keith D / Biedrzycki, Barbara / Kobrin, Barry / Herman, Joseph / Sugar, Elizabeth / Piantadosi, Steven / Cameron, John L / Solt, Sara / Onners, Beth / Tartakovsky, Irena / Choi, Miri / Sharma, Rajni / Illei, Peter B / Hruban, Ralph H / Abrams, Ross A / Le, Dung / Jaffee, Elizabeth / Laheru, Dan. ·Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. ·Ann Surg · Pubmed #21217520.

ABSTRACT: PURPOSE: Surgical resection provides the only possibility of cure for pancreas cancer. A standard adjuvant approach has not been established. We tested the safety and efficacy of a granulocyte-macrophage colony-stimulating factor (GM-CSF)-based immunotherapy administered in patients with resected pancreatic adenocarcinoma. PATIENTS AND METHODS: A single institution phase II study of 60 patients with resected pancreatic adenocarcinoma was performed. Each immunotherapy treatment consisted of a total of 5 × 108 GM-CSF-secreting cells distributed equally among 3 lymph node regions. The first immunotherapy treatment was administered 8 to 10 weeks after surgical resection. Subsequently, patients received 5-FU based chemoradiation. Patients who remained disease-free after completion of chemoradiotherapy received treatments 2 to 4, each 1 month apart. A fifth and final booster was administered 6 months after the fourth immunotherapy. The primary endpoint was disease free survival and secondary endpoints were overall survival and toxicity, and the induction of mesothelin specific T cell responses. RESULTS: The median disease-free survival is 17.3 months (95% CI, 14.6-22.8) with median survival of 24.8 months (95% CI, 21.2-31.6). The administration of immunotherapy was well tolerated. In addition, the post-immunotherapy induction of mesothelin-specific CD8+ T cells in HLA-A1+ and HLA-A2+patients correlates with disease-free survival. CONCLUSIONS: An immunotherapy approach integrated with chemoradiation is safe and demonstrates an overall survival that compares favorably with published data for resected pancreas cancer. These data suggest additional boost immunotherapies given at regular intervals beyond 1 year postsurgery should be tested in future studies, and provide the rationale for conducting a multicenter phase II study.

13 Article Diabetes mellitus is associated with unfavorable pathologic features, increased postoperative mortality, and worse long-term survival in resected pancreatic cancer. 2020

Hank, Thomas / Sandini, Marta / Qadan, Motaz / Weniger, Maximilian / Ciprani, Debora / Li, Annie / Ferrone, Cristina R / Warshaw, Andrew L / Lillemoe, Keith D / Fernández-Del Castillo, Carlos. ·Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. · Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: CFernandez@mgh.harvard.edu. ·Pancreatology · Pubmed #31706821.

ABSTRACT: BACKGROUND: The risk of pancreatic ductal adenocarcinoma (PDAC) is increased in patients with diabetes mellitus (DM), particularly in those with new-onset DM. However, the impact of DM on outcomes following pancreatic surgery is not fully understood. We sought to explore the effects of DM on post-resection outcomes in patients undergoing either upfront resection or following neoadjuvant treatment (NAT). METHODS: Resections for PDAC between 2007 and 2016 were identified from a prospectively-maintained database. Data on demographics, pathology, and perioperative outcomes were compared between patients with or without DM. Survival analysis was performed using Kaplan-Meier curves and adjusted for confounders by a Cox-proportional hazards model. RESULTS: 662 patients were identified, of whom 277 (41.8%) had DM. Diabetics were more likely to be male, had higher BMI, and higher ASA-scores. At pathology, DM was associated with larger tumors (30 vs. 26 mm; p = 0.041), higher rates of lymph-node involvement (69% vs. 59%; p = 0.031) and perineural invasion (88% vs. 82%; p = 0.026). Despite having similar rates of complications, diabetics experienced higher 30-day mortality (3.2% vs. 0.8%; p = 0.019). Median overall survival was worse in diabetic patients (18 vs. 34 months; p < 0.001); this effect was more pronounced in patients with NAT (18 vs. 54 months; p < 0.001). At multivariate analysis, DM was confirmed as an independent predictor of post-resection survival. CONCLUSION: DM is a common comorbidity in PDAC and is associated with unfavorable pathology, as well as worse postoperative and oncologic outcomes. The blunted effect on survival is more pronounced in patients who undergo resection following NAT.

14 Article Cross Validation of the Monoclonal Antibody Das-1 in Identification of High-Risk Mucinous Pancreatic Cystic Lesions. 2019

Das, Koushik K / Geng, Xin / Brown, Jeffrey W / Morales-Oyarvide, Vicente / Huynh, Tiffany / Pergolini, Ilaria / Pitman, Martha B / Ferrone, Cristina / Al Efishat, Mohammad / Haviland, Dana / Thompson, Elizabeth / Wolfgang, Christopher / Lennon, Anne Marie / Allen, Peter / Lillemoe, Keith D / Fields, Ryan C / Hawkins, William G / Liu, Jingxia / Castillo, Carlos Fernandez-Del / Das, Kiron M / Mino-Kenudson, Mari. ·Division of Gastroenterology, Washington University, St Louis, Missouri. Electronic address: k.das@wustl.edu. · Division of Gastroenterology, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey. · Division of Gastroenterology, Washington University, St Louis, Missouri. · Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts. · Deparment of Pathology, Massachusetts General Hospital, Boston, Massachusetts. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland. · Department of Surgery Johns Hopkins School of Medicine, Baltimore, Maryland. · Division of Gastroenterology, Johns Hopkins School of Medicine, Baltimore, Maryland. · Department of Surgery, Washington University, St Louis, Missouri. · Deparment of Pathology, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: mminokenudson@partners.org. ·Gastroenterology · Pubmed #31175863.

ABSTRACT: BACKGROUND & AIMS: Although pancreatic cystic lesions (PCLs) are frequently and incidentally detected, it is a challenge to determine their risk of malignancy. In immunohistochemical and enzyme-linked immunosorbent assay (ELISA) analyses of tissue and cyst fluid from pancreatic intraductal papillary mucinous neoplasms, the monoclonal antibody Das-1 identifies those at risk for malignancy with high levels of specificity and sensitivity. We aimed to validate the ability of Das-1 to identify high-risk PCLs in comparison to clinical guidelines and clinical features, using samples from a multicenter cohort. METHODS: We obtained cyst fluid samples of 169 PCLs (90 intraductal papillary mucinous neoplasms, 43 mucinous cystic neoplasms, and 36 non-mucinous cysts) from patients undergoing surgery at 4 tertiary referral centers (January 2010 through June 2017). Histology findings from surgical samples, analyzed independently and centrally re-reviewed in a blinded manner, were used as the reference standard. High-risk PCLs were those with invasive carcinomas, high-grade dysplasia, or intestinal-type intraductal papillary mucinous neoplasms with intermediate-grade dysplasia. An ELISA with Das-1 was performed in parallel using banked cyst fluid samples. We evaluated the biomarker's performance, generated area under the curve values, and conducted multivariate logistic regression using clinical and pathology features. RESULTS: The ELISA for Das-1 identified high-risk PCLs with 88% sensitivity, 99% specificity, and 95% accuracy, at a cutoff optical density value of 0.104. In 10-fold cross-validation analysis with 100 replications, Das-1 identified high-risk PCLs with 88% sensitivity and 98% specificity. The Sendai, Fukuoka, and American Gastroenterological Association guideline criteria identified high-risk PCLs with 46%, 52%, and 74% accuracy (P for comparison to Das-1 ELISA <.001). When we controlled for Das-1 in multivariate regression, main pancreatic duct dilation >5 mm (odds ratio, 14.98; 95% confidence interval, 2.63-108; P < .0012), main pancreatic duct dilation ≥1 cm (odds ratio, 47.9; 95% confidence interval, 6.39-490; P < .0001), and jaundice (odds ratio, 6.16; 95% confidence interval, 1.08-36.7; P = .0397) were significantly associated with high-risk PCLs. CONCLUSIONS: We validated the ability of an ELISA with the monoclonal antibody Das-1 to detect PCLs at risk for malignancy with high levels of sensitivity and specificity. This biomarker might be used in conjunction with clinical guidelines to identify patients at risk for malignancy.

15 Article Major Complications Independently Increase Long-Term Mortality After Pancreatoduodenectomy for Cancer. 2019

Sandini, M / Ruscic, K J / Ferrone, C R / Qadan, M / Eikermann, M / Warshaw, A L / Lillemoe, K D / Castillo, Carlos Fernández-Del. ·Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 15 Parkman ST, Boston, MA, 02114-02115, USA. · Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. · Department of Surgery, Massachusetts General Hospital, Harvard Medical School, 15 Parkman ST, Boston, MA, 02114-02115, USA. cfernandez@mgh.harvard.edu. ·J Gastrointest Surg · Pubmed #30225794.

ABSTRACT: BACKGROUND: Postoperative major morbidity has been associated with worse survival gastrointestinal tumors. This association remains controversial in pancreatic cancer (PC). We analyzed whether major complications after surgical resection affect long-term survival. METHODS: Records of all PC patients resected from 2007 to 2015 were reviewed. Major morbidity was defined as any grade-3 or higher 30-day complications, per the Clavien-Dindo Classification. Patients who died within 90 days after surgery were excluded from survival analysis. RESULTS: Of 616 patients, 81.7% underwent pancreatoduodenectomy (PD) and 18.3% distal pancreatectomy (DP). Major complications occurred in 19.1% after PD and 15.9% after DP. In patients who survived > 90 days, the likelihood of receiving adjuvant treatment was 43.9% if major complications had occurred, vs. 68.5% if not (p < 0.001), and those who received it started the treatment median 10 days later compared with uncomplicated patients (median 60 days (50-72) vs. 50 days (41-61), p = 0.001). By univariate analysis, in addition to the conventional pathology-related prognostic determinants and the receipt of adjuvant treatment, major complications worsened long-term survival after PD (median OS 26 months vs. 15, p = 0.008). A difference was also seen after DP, but it did not reach statistical significance, likely related to the small sample size (median OS 33 months vs. 18, p = 0.189). At multivariate analysis for PD, major postoperative complications remained independently associated with worse survival [HR 1.37, 95%CI (1.01-1.86)]. CONCLUSIONS: Major surgical complications after pancreaticoduodenectomy are associated with worse long-term survival in pancreatic cancer. This effect is independent of the receipt of adjuvant treatment.

16 Article Predictors of Resectability and Survival in Patients With Borderline and Locally Advanced Pancreatic Cancer who Underwent Neoadjuvant Treatment With FOLFIRINOX. 2019

Michelakos, Theodoros / Pergolini, Ilaria / Castillo, Carlos Fernández-Del / Honselmann, Kim C / Cai, Lei / Deshpande, Vikram / Wo, Jennifer Y / Ryan, David P / Allen, Jill N / Blaszkowsky, Lawrence S / Clark, Jeffrey W / Murphy, Janet E / Nipp, Ryan D / Parikh, Aparna / Qadan, Motaz / Warshaw, Andrew L / Hong, Theodore S / Lillemoe, Keith D / Ferrone, Cristina R. ·Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA. · Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA. · Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA. · Department of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA. ·Ann Surg · Pubmed #29227344.

ABSTRACT: OBJECTIVE: The aim of this study was to determine (1) whether preoperative factors can predict resectability of borderline resectable (BR) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant FOLFIRINOX, (2) which patients might benefit from adjuvant therapy, and (3) survival differences between resected BR/LA patients who received neoadjuvant FOLFIRINOX and upfront resected patients. BACKGROUND: Patients with BR/LA PDAC are often treated with FOLFIRINOX to obtain a margin-negative resection, yet selection of patients for resection remains challenging. METHODS: Clinicopathologic data of PDAC patients surgically explored between 04/2011-11/2016 in a single institution were retrospectively collected. RESULTS: Following neoadjuvant FOLFIRINOX, 141 patients were surgically explored (BR: 49%, LA: 51%) and 110 (78%) were resected. Resected patients had lower preoperative CA 19-9 levels (21 vs 40 U/mL, P = 0.03) and smaller tumors on preoperative computed tomography (CT) scan (2.3 vs 3.0 cm, P = 0.03), but no predictors of resectability were identified. Median overall survival (OS) was 34.2 months from diagnosis for all FOLFIRINOX patients and 37.7 months for resected patients. Among resected patients, preoperative CA 19-9 >100 U/mL and >8 months between diagnosis and surgery predicted a shorter postoperative disease-free survival (DFS); Charlson comorbidity index >1, preoperative CA 19-9 >100 U/mL and tumor size (>3.0 cm on CT or >2.5 cm on pathology) predicted decreased OS. DFS and OS were significantly better for BR/LA PDAC patients treated with neoadjuvant FOLFIRINOX compared with upfront resected patients (DFS: 29.1 vs 13.7, P < 0.001; OS: 37.7 vs 25.1 months from diagnosis, P = 0.01). CONCLUSION: BR/LA PDAC patients with no progression on neoadjuvant FOLFIRINOX should be offered surgical exploration. Except size, traditional pathological parameters fail to predict survival among resected FOLFIRINOX patients. Resected FOLFIRINOX patients have survival that appears to be superior than that of resectable patients who go directly to surgery.

17 Article Intraoperative Dexamethasone Decreases Infectious Complications After Pancreaticoduodenectomy and is Associated with Long-Term Survival in Pancreatic Cancer. 2018

Sandini, Marta / Ruscic, Katarina J / Ferrone, Cristina R / Warshaw, Andrew L / Qadan, Motaz / Eikermann, Matthias / Lillemoe, Keith D / Fernández-Del Castillo, Carlos. ·Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA. · Department of Anesthesia, Critical Care, and Pain Medicine, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA. · Department of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA. CFERNANDEZ@mgh.harvard.edu. ·Ann Surg Oncol · Pubmed #30298316.

ABSTRACT: BACKGROUND: Dexamethasone is administered intraoperatively to prevent anesthesia-related nausea and vomiting and to reduce postoperative opioid administration. However, the adverse effects of corticosteroids on anastomotic healing and wound infection as well as oncologic outcomes remain unclear. We analyzed the effect of intraoperative dexamethasone administration on surgical outcomes after pancreaticoduodenectomy and on long-term survival in pancreatic cancer patients. METHODS: A total of 679 pancreaticoduodenectomies from a prospectively maintained database were analyzed. Surgical outcomes were compared between patients who received intraoperative dexamethasone and those who did not. Kaplan-Meier curves and Cox-regression survival analysis were performed in patients with pancreatic cancer. A propensity analysis was done to reduce the inherent bias of retrospective design. RESULTS: Patients who received dexamethasone (117, 17.2%) were younger and more likely to be female than those who did not (p = 0.001). Overall and 30-day major morbidity were similar among all resected patients, although there were fewer infectious complications in the dexamethasone group (18.8% vs. 28.5%, p = 0.032). In pancreatic cancer patients, dexamethasone was associated with significantly improved median overall survival (46 vs. 22 months, p = 0.017). This effect occurred independently of stage, pathologic characteristics, or adjuvant therapy, with adjusted hazard ratios, derived from pre-propensity and post-propensity analysis, of 0.67 (0.47-0.97) and 0.57 (0.37-0.87), respectively. CONCLUSIONS: A single intraoperative dose of dexamethasone did not increase morbidity after pancreaticoduodenectomy and, in fact, was associated with a decrease in infectious complications. The treatment was independently associated with improved overall survival in patients with pancreatic adenocarcinoma, an effect that cannot be explained and needs further validation in a prospective setting.

18 Article Are Staging Computed Tomography (CT) Scans of the Chest Necessary in Pancreatic Adenocarcinoma? 2018

Mehtsun, Winta T / Chipidza, Fallon E / Fernández-Del Castillo, Carlos / Hemingway, Katherine / Fong, Zhi Ven / Chang, David C / Pandharipande, Pari / Clark, Jeffrey W / Allen, Jill / Hong, Theodore S / Wo, Jennifer Y / Warshaw, Andrew L / Lillemoe, Keith D / Ferrone, Cristina R. ·Department of Surgery, Massachusetts General Hospital, Boston, MA, USA. · Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA. · Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA. · Department of Radiology, Massachusetts General Hospital, Boston, MA, USA. · Department of Medical Oncology, Massachusetts General Hospital, Boston, MA, USA. · Department of Surgery, Massachusetts General Hospital, Boston, MA, USA. cferrone@partners.org. ·Ann Surg Oncol · Pubmed #30276641.

ABSTRACT: BACKGROUND: There is no consensus on the use of chest imaging in pancreatic ductal adenocarcinoma (PDAC) patients. Among PDAC patients, we examined the use of chest computed tomography (CT) over time and determined whether the use of chest CT led to a survival difference or change in management via identification of indeterminate lung nodules (ILNs). METHODS: Retrospective clinical data was collected for patients diagnosed with PDAC from 1998 to 2014. We examined the proportion of patients undergoing staging chest CT scan and those who had ILN, defined as ≥ 1 well-defined, noncalcified lung nodule(s) ≤ 1 cm in diameter. We determined time to overall survival (OS) using multivariate Cox regression. We also assessed changes in management of PDAC patients who later developed lung metastasis only. RESULTS: Of the 2710 patients diagnosed with PDAC, 632 (23%) had greater than one chest CT. Of those patients, 451 (71%) patients had ILNs, whereas 181 (29%) had no ILNs. There was no difference in median overall survival in patients without ILNs (16.4 [13.6, 19.0] months) versus those with ILN (14.8 [13.6, 15.8] months, P = 0.18). Examining patients who developed isolated lung metastases (3.3%), we found that staging chest CTs did not lead to changes in management of the primary abdominal tumor. CONCLUSIONS: Survival did not differ for PDAC patients with ILNs identified on staging chest CTs compared with those without ILNs. Furthermore, ILN identification did not lead to changes in management of the primary abdominal tumor, questioning the utility of staging chest CTs for PDAC patients.

19 Article Association Between Changes in Body Composition and Neoadjuvant Treatment for Pancreatic Cancer. 2018

Sandini, Marta / Patino, Manuel / Ferrone, Cristina R / Alvarez-Pérez, Carlos A / Honselmann, Kim C / Paiella, Salvatore / Catania, Matteo / Riva, Luca / Tedesco, Giorgia / Casolino, Raffaella / Auriemma, Alessandra / Salandini, Maria C / Carrara, Giulia / Cristel, Giulia / Damascelli, Anna / Ippolito, Davide / D'Onofrio, Mirko / Lillemoe, Keith D / Bassi, Claudio / Braga, Marco / Gianotti, Luca / Sahani, Dushyant / Fernández-Del Castillo, Carlos. ·Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. · Department of Surgery, School of Medicine and Surgery, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy. · Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. · Department of Surgery, The Pancreas Institute, Policlinico GB Rossi, University of Verona Hospital Trust, Verona, Italy. · Department of Radiology, The Pancreas Institute, Policlinico GB Rossi, University of Verona Hospital Trust, Verona, Italy. · Department of Radiology, School of Medicine and Surgery, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy. · Department of Oncology, The Pancreas Institute, Policlinico GB Rossi, University of Verona Hospital Trust, Verona, Italy. · Department of Surgery, Vita-Salute San Raffaele University, Milan, Italy. · Department of Radiology, Vita-Salute San Raffaele University, Milan, Italy. ·JAMA Surg · Pubmed #29801062.

ABSTRACT: Importance: Sarcopenia and sarcopenic obesity have been associated with poor outcomes in unresectable pancreatic cancer (PC). Neoadjuvant treatment (NT) is used increasingly to improve resectability; however, its effects on fat and muscle body composition have not been characterized. Objectives: To evaluate whether NT affects muscle mass and adipose tissue in patients with borderline resectable PC (BRPC) and locally advanced PC (LAPC) and determine whether there were potential differences between patients who ultimately underwent resection and those who did not. Design, Setting, and Participants: In this retrospective cohort study conducted at 4 academic medical centers, 193 patients with BRPC and LAPC undergoing surgical exploration after NT who had available computed tomographic scans (both at diagnosis and preoperatively) and confirmed pancreatic ductal adenocarcinoma were evaluated. The study was conducted from January 2013 to December 2015. Data analysis was performed from September 2016 to May 2017. Measurement of body compartments was evaluated with volume assessment software before and after NT. A radiologist blinded to the patient outcome assessed the areas of skeletal muscle, total adipose tissue, and visceral adipose tissue through a standardized protocol. Exposures: Receipt of NT. Main Outcomes and Measures: Achievement of pancreatic resection at surgical exploration after the receipt of NT. Results: Of the 193 patients with complete radiologic imaging available after NT, 96 (49.7%) were women; mean (SD) age at diagnosis was 64 (11) years. Most patients received combined therapy with fluorouracil, irinotecan, oxaliplatin, leucovorin, and folic acid (124 [64.2%]) and 86 (44.6%) received chemoradiotherapy as well. The median interval between pre-NT and post-NT imaging was 6 months (interquartile range [IQR], 4-7 months). All body compartments significantly changed. The adipose compound decreased (median total adipose tissue area from 284.0 cm2; IQR, 171.0-414.0 to 250.0 cm2; IQR, 139.0-363.0; P < .001; median visceral adipose tissue area from 115.2 cm2; IQR, 59.9-191.0 to 97.7 cm2; IQR, 48.0-149.0 cm2; P < .001), whereas the lean mass slightly improved (median skeletal muscle from 122.1 cm2; IQR, 99.3-142.0 to 123 cm2; IQR 104.8-152.5 cm2; P = .001). Surgical resection was achievable in 136 (70.5%) patients. Patients who underwent resection had experienced a 5.9% skeletal muscle area increase during NT treatment, whereas those who did not undergo resection had a 1.7% decrease (P < .001). Conclusions and Relevance: Patients with PC experience a significant loss of adipose tissue during neoadjuvant chemotherapy, but no muscle wasting. An increase in muscle tissue during NT is associated with resectability.

20 Article Staging Laparoscopy Not Only Saves Patients an Incision, But May Also Help Them Live Longer. 2018

Sell, Naomi M / Fong, Zhi Ven / Del Castillo, Carlos Fernandez / Qadan, Motaz / Warshaw, Andrew L / Chang, David / Lillemoe, Keith D / Ferrone, Cristina R. ·Department of Surgery, Massachusetts General Hospital, Boston, MA, USA. · Department of Surgery, Massachusetts General Hospital, Boston, MA, USA. cferrone@mgh.harvard.edu. ·Ann Surg Oncol · Pubmed #29388123.

ABSTRACT: BACKGROUND: Approximately 20-40% of patients with "resectable" pancreatic adenocarcinoma (PDAC) by imaging criteria have metastatic disease on exploration. Our aim was to assess the potential impact of staging laparoscopy versus upfront laparotomy in "resectable" patients found to have metastatic PDAC. METHODS: Clinicopathologic data was retrospectively collected for all patients with PDAC undergoing an operation with curative intent between 2001-2015 at a single institution. RESULTS: Of the 1001 patients undergoing surgical evaluation, 151 had unsuspected metastatic PDAC. Staging laparoscopy was performed in 59% (89/151) of patients, while 41% (62/151) underwent an exploratory laparotomy with or without prophylactic bypass. There were no differences in patient demographics and preoperative CA 19-9 levels between the staging laparoscopy and exploratory laparotomy groups. However, staging laparoscopy was more often performed for pancreatic body/tail lesions (85% vs 60% for pancreatic head lesions, p < 0.001). Patients who only underwent laparoscopy started palliative chemotherapy more quickly (17.9 days vs 39.9 days in the laparotomy group, p < 0.001). There was no difference in the 30 day or lifetime incidence of postoperative cholangitis, gastric outlet obstruction, or biliary stent placement between groups. The median overall survival for the staging laparoscopy group (11.4 months) was significantly longer than the laparotomy group (8.3 months, p < 0.001). In a cox regression analysis adjusting for clinicopathologic variables, staging laparoscopy was associated with significantly improved overall survival when compared to the laparotomy group (HR 0.53, 95% C.I. 0.34-0.82, p = 0.005). CONCLUSION: For patients diagnosed with metastatic PDAC at the time of surgical exploration, staging laparoscopy was associated with a shorter time to chemotherapy and improved overall survival when compared to those explored without laparoscopy.

21 Article Intraductal Papillary Mucinous Neoplasm of the Pancreas in Young Patients: Tumor Biology, Clinical Features, and Survival Outcomes. 2018

Morales-Oyarvide, Vicente / Mino-Kenudson, Mari / Ferrone, Cristina R / Warshaw, Andrew L / Lillemoe, Keith D / Sahani, Dushyant V / Pergolini, Ilaria / Attiyeh, Marc A / Al Efishat, Mohammad / Rezaee, Neda / Hruban, Ralph H / He, Jin / Weiss, Matthew J / Allen, Peter J / Wolfgang, Christopher L / Fernández-Del Castillo, Carlos. ·Department of Surgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Wang Ambulatory Care Center 460, Boston, MA, 02114, USA. · Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. · Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Surgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Wang Ambulatory Care Center 460, Boston, MA, 02114, USA. cfernandez@partners.org. ·J Gastrointest Surg · Pubmed #29047068.

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

22 Article Multi-institutional Validation Study of Pancreatic Cyst Fluid Protein Analysis for Prediction of High-risk Intraductal Papillary Mucinous Neoplasms of the Pancreas. 2018

Al Efishat, Mohammad A / Attiyeh, Marc A / Eaton, Anne A / Gönen, Mithat / Prosser, Denise / Lokshin, Anna E / Castillo, Carlos Fernández-Del / Lillemoe, Keith D / Ferrone, Cristina R / Pergolini, Ilaria / Mino-Kenudson, Mari / Rezaee, Neda / Dal Molin, Marco / Weiss, Matthew J / Cameron, John L / Hruban, Ralph H / D'Angelica, Michael I / Kingham, T Peter / DeMatteo, Ronald P / Jarnagin, William R / Wolfgang, Christopher L / Allen, Peter J. ·Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY. · Department of Pathology, University of Pittsburgh Cancer Institute, Pittsburgh, PA. · Department of Surgery, Massachusetts General Hospital, Boston, MA. · Department of Pathology, Massachusetts General Hospital, Boston, MA. · Department of Surgery, Johns Hopkins Hospital, Baltimore, MD. · Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD. ·Ann Surg · Pubmed #28700444.

ABSTRACT: OBJECTIVE: Preliminary work by our group suggested that proteins within the pancreatic cyst fluid (CF) may discriminate degree of IPMN dysplasia. We sought to externally validate these markers and determine whether their inclusion in a preoperative clinical nomogram could increase diagnostic accuracy. SUMMARY BACKGROUND DATA: IPMN is the most common radiographically identifiable precursor to pancreatic cancer; however, the timing and frequency of its malignant progression are unknown, and there are currently no reliable preoperative tests that can determine the grade of dysplasia in IPMN. METHODS: Clinical and radiographic data, as well as CF samples, were obtained from 149 patients who underwent resection for IPMN at 1 of 3 institutions. High-risk disease was defined as the presence of high-grade dysplasia or invasive carcinoma. Multianalyte bead array analysis (Luminex) of CF was performed for 4 protein markers that were previously associated with high-risk disease. Logistic regression models were fit on training data, with and without adjustment for a previously developed clinical nomogram and validated with an external testing set. The models incorporating clinical risk score were presented graphically as nomograms. RESULTS: Within the group of 149 resected patients, 89 (60%) had low-risk disease, and 60 (40%) had high-risk disease. All 4 CF markers (MMP9, CA72-4, sFASL, and IL-4) were overexpressed in patients with high-risk IPMN (P < 0.05). Two predictive models based on preselected combinations of CF markers had concordance indices of 0.76 (Model-1) and 0.80 (Model-2). Integration of each CF marker model into a previously described clinical nomogram leads to increased discrimination compared with either the CF models or nomogram alone (c-indices of 0.84 and 0.83, respectively). CONCLUSIONS: This multi-institutional study validated 2 CF protein marker models for preoperative identification of high-risk IPMN. When combined with a clinical nomogram, the ability to predict high-grade dysplasia was even stronger.

23 Article Tolerability and Long-term Outcomes of Dose-Painted Neoadjuvant Chemoradiation to Regions of Vessel Involvement in Borderline or Locally Advanced Pancreatic Cancer. 2018

Wo, Jennifer Y / Niemierko, Andrzej / Ryan, David P / Blaszkowsky, Lawrence S / Clark, Jeffrey W / Kwak, Eunice L / Lillemoe, Keith D / Drapek, Lorraine N / Zhu, Andrew X / Allen, Jill N / Faris, Jason E / Murphy, Janet E / Nipp, Ryan / Fernandez-Del Castillo, Carlos / Ferrone, Cristina R / Hong, Theodore S. ·Departments of Radiation Oncology. · Medical Oncology. · General Surgery, Massachusetts General Hospital, Boston, MA. ·Am J Clin Oncol · Pubmed #28134673.

ABSTRACT: PURPOSE: We reviewed our experience involving patients with borderline resectable or locally advanced pancreatic cancer, treated with the dose-painted (DP) boost technique to regions of vessel involvement which preclude upfront surgical resection. We evaluated patient outcomes with respect to tolerability and treatment outcomes. MATERIALS AND METHODS: We retrospectively reviewed 99 patients with borderline resectable (n=25) or locally advanced pancreatic cancer (n=74) treated with DP-neoadjuvant chemoradiation from 2010 to 2015. Tumor and regional lymph nodes were prescribed 50.4 Gy and the region around the involved blood vessel was boosted to 58.8 Gy in 28 fractions. The primary outcome was acute toxicity and late duodenal toxicity. Secondary outcomes included conversion to surgical resectability, local failure, disease-free survival, and overall survival (OS). Cox proportional hazards models were performed to evaluate for predictors of survival. RESULTS: All but 1 patient completed chemoradiation. The rates of grade 2+ and 3+ nausea were 40% and 12%, respectively. With regards to late toxicity, 5 patients developed potential RT-related grade 3+ duodenal complications including duodenal ulceration/bleeding (n=3) and duodenal stricture (n=2). With a median follow-up of 15 months, the median OS was 18.1 months. Among 99 patients in our study, 37 patients underwent surgical resection. For patients who underwent surgical resection (n=37), the median OS was 30.9 months. On multivariate analysis, only normalization of CA 19-9 post-RT was associated with improved OS. CONCLUSIONS: We found that DP-neoadjuvant chemoradiation to regions of vessel involvement is both feasible and well tolerated. In addition, we demonstrated that over one third of patients with initially deemed unresectable disease were able to undergo surgical resection after receiving neoadjuvant therapy including DP-chemoradiation.

24 Article Development and Validation of a Multi-institutional Preoperative Nomogram for Predicting Grade of Dysplasia in Intraductal Papillary Mucinous Neoplasms (IPMNs) of the Pancreas: A Report from The Pancreatic Surgery Consortium. 2018

Attiyeh, Marc A / Fernández-Del Castillo, Carlos / Al Efishat, Mohammad / Eaton, Anne A / Gönen, Mithat / Batts, Ruqayyah / Pergolini, Ilaria / Rezaee, Neda / Lillemoe, Keith D / Ferrone, Cristina R / Mino-Kenudson, Mari / Weiss, Matthew J / Cameron, John L / Hruban, Ralph H / D'Angelica, Michael I / DeMatteo, Ronald P / Kingham, T Peter / Jarnagin, William R / Wolfgang, Christopher L / Allen, Peter J. ·Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY. · Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD. · Department of Pathology, Massachusetts General Hospital, Boston, MA. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD. ·Ann Surg · Pubmed #28079542.

ABSTRACT: OBJECTIVE: Previous nomogram models for patients undergoing resection of intraductal papillary mucinous neoplasms (IPMNs) have been relatively small single-institutional series. Our objective was to improve upon these studies by developing and independently validating a new model using a large multiinstitutional dataset. SUMMARY BACKGROUND DATA: IPMNs represent the most common radiographically identifiable precursor lesions of pancreatic cancer. They are a heterogenous group of neoplasms in which more accurate markers of high-grade dysplasia or early invasive carcinoma could help avoid unnecessary surgery in 1 case and support potentially curative intervention (resection) in another. METHODS: Prospectively maintained databases from 3 institutions were queried for patients who had undergone resection of IPMNs between 2005 and 2015. Patients were separated into main duct [main and mixed-type (MD)] and branch duct (BD) types based on preoperative imaging. Logistic regression modeling was used on a training subset to develop 2 independent nomograms (MD and BD) to predict low-risk (low- or intermediate-grade dysplasia) or high-risk (high-grade dysplasia or invasive carcinoma) disease. Model performance was then evaluated using an independent validation set. RESULTS: We identified 1028 patients who underwent resection for IPMNs [MD: n = 454 (44%), BD: n = 574 (56%)] during the 10-year study period. High-risk disease was present in 487 patients (47%). Patients with high-risk disease comprised 71% and 29% of MD and BD groups, respectively (P <0.0001). MD and BD nomograms were developed on the training set [70% of total (n = 720); MD: n = 318, BD: n = 402] and validated on the test set [30% (n = 308); MD: n = 136, BD: n = 172]. The presence of jaundice was almost exclusively associated with high-risk disease (57 of 58 patients, 98%). Cyst size >3.0 cm, solid component/mural nodule, pain symptoms, and weight loss were significantly associated with high-risk disease. C-indices were 0.82 and 0.81 on training and independent validation sets, respectively; Brier scores were 0.173 and 0.175, respectively. CONCLUSIONS: For patients with suspected IPMNs, we present an independently validated model for the prediction of high-risk disease.

25 Article Intraoperative Radiotherapy in the Era of Intensive Neoadjuvant Chemotherapy and Chemoradiotherapy for Pancreatic Adenocarcinoma. 2018

Keane, Florence K / Wo, Jennifer Y / Ferrone, Cristina R / Clark, Jeffrey W / Blaszkowsky, Lawrence S / Allen, Jill N / Kwak, Eunice L / Ryan, David P / Lillemoe, Keith D / Fernandez-Del Castillo, Carlos / Hong, Theodore S. ·Harvard Radiation Oncology Program, Harvard Medical School. · Departments of Radiation Oncology. · Surgery. · Medicine, Division of Medical Oncology, Massachusetts General Hospital, Boston, MA. ·Am J Clin Oncol · Pubmed #27740973.

ABSTRACT: OBJECTIVES: Improved outcomes with FOLFIRINOX or gemcitabine with nab-paclitaxel in the treatment of metastatic pancreatic adenocarcinoma (PDAC) have prompted incorporation of these regimens into neoadjuvant treatment of locally advanced unresectable PDAC. Whereas some patients remain unresectable on surgical exploration, others are able to undergo resection after intensive neoadjuvant treatment. We evaluated outcomes and toxicity associated with use of intensive neoadjuvant treatment followed by intraoperative radiotherapy (IORT) in combination with resection or exploratory laparotomy. METHODS: We retrospectively analyzed patients with locally advanced unresectable or borderline-resectable PDAC who received intensive neoadjuvant treatment with induction chemotherapy and chemoradiotherapy followed by exploratory laparotomy in an IORT-equipped operating suite between 2010 and 2015. Surgical outcomes and overall survival (OS) were compared. RESULTS: Of 68 patients, 41 (60.3%) underwent resection, 18 (26.5%) had unresectable disease, and 9 (13.2%) had distant metastases. Of 41 resectable patients, 22 received IORT for close/positive resection margins on intraoperative frozen section. There was no significant difference in operative times or morbidity with addition of IORT to resection. Median OS was 26.6 months for all patients who underwent resection, 35.1 months for patients who underwent resection and IORT, and 24.5 months for patients who underwent resection alone (P=NS). Of 18 patients with unresectable disease, all but 1 received IORT, with median OS of 24.8 months. IORT was associated with increased hospital stay (4 vs. 3.5 d), but no significant difference in operative times or morbidity. CONCLUSIONS: IORT in addition to intensive neoadjuvant chemotherapy and chemoradiotherapy was not associated with increased toxicity when used with resection or exploratory laparotomy, and was associated with encouraging survival rates in patients with close/positive margins and patients with unresectable disease.

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