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Pancreatic Neoplasms: HELP
Articles by Werner Hartwig
Based on 39 articles published since 2010
(Why 39 articles?)
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Between 2010 and 2020, W. Hartwig wrote the following 39 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
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 Editorial Prognosis of resected pancreatic cancer: is the refined resection margin status dispensable? 2012

Hartwig, Werner / Werner, Jens / Büchler, Markus W. · ·Langenbecks Arch Surg · Pubmed #22820875.

ABSTRACT: -- No abstract --

5 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.

6 Review Surgical resection strategies for locally advanced pancreatic cancer. 2015

Gluth, Alexander / Werner, Jens / Hartwig, Werner. ·Department of General, Visceral, Transplantation, Vascular, and Thoracic Surgery, LMU University Hospital, Marchioninistraße 15, 81377, Munich, Germany. · Department of General, Visceral, Transplantation, Vascular, and Thoracic Surgery, LMU University Hospital, Marchioninistraße 15, 81377, Munich, Germany. werner.hartwig@med.uni-muenchen.de. ·Langenbecks Arch Surg · Pubmed #26115737.

ABSTRACT: BACKGROUND: Despite all improvements in tumor diagnostics and treatment, pancreatic cancer is still the fourth leading cause of cancer-related death in the Western world. It is mostly diagnosed at a locally advanced or metastasized stage because of the lack of early symptoms. A radical margin-free surgical resection offers the only potential cure for locoregional disease. Over the last decades, several surgical strategies and techniques have evolved to optimize oncologic radical resections and thus to improve long-term outcome of patients. PURPOSE: The purpose of this review was to describe the various surgical strategies and techniques for locally advanced pancreatic cancer and to evaluate their influence on long-term outcome. CONCLUSIONS: Locally advanced pancreatic cancer should not generally be deemed unresectable. Various surgical techniques offer a good chance of margin-free tumor resection, even if surrounding organs or vessels are involved. Because of potentially higher peri- and postoperative morbidity rates, patients should be selected properly and are best treated in specialized high-volume centers.

7 Review [Cystic tumors of the pancreas: diagnosis and therapy]. 2015

D'Haese, Jan G / Hartwig, Werner / Angele, Martin / Werner, Jens. ·Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie am Klinikum, Universität München, Standort Großhadern Marchioninistr. 15, D-81377, München, Deutschland, Jens.Werner@med.uni-muenchen.de. ·MMW Fortschr Med · Pubmed #26015016.

ABSTRACT: -- No abstract --

8 Review Improvement of surgical results for pancreatic cancer. 2013

Hartwig, Werner / Werner, Jens / Jäger, Dirk / Debus, Jürgen / Büchler, Markus W. ·Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. · National Cancer Center, University of Heidelberg, Heidelberg, Germany. · Department of Radiation Oncology, University of Heidelberg, Heidelberg, Germany. · Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. Electronic address: markus.buechler@med.uni-heidelberg.de. ·Lancet Oncol · Pubmed #24079875.

ABSTRACT: Surgery is the only potential hope of cure for patients with pancreatic cancer. Advantageous tumour characteristics and complete tumour resection are the factors most relevant for a positive prognosis, so detection of premalignant or early invasive lesions, combined with safe and oncologically adequate surgery, is an important goal. The experience and volume of both the individual surgeon and hospital are of paramount importance to achieve low morbidity and adequate management of complications. Most pancreatic cancers are locally advanced or metastatic when diagnosed and need multimodal therapy. With increasing evidence on surgical and perioperative aspects of pancreatic cancer therapy, short-term and long-term outcomes of resectable and borderline resectable pancreatic cancer are improving.

9 Review Advanced-stage pancreatic cancer: therapy options. 2013

Werner, Jens / Combs, Stephanie E / Springfeld, Christoph / Hartwig, Werner / Hackert, Thilo / Büchler, Markus W. ·Department of General, Visceral, and Transplantation Surgery, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. ·Nat Rev Clin Oncol · Pubmed #23629472.

ABSTRACT: Pancreatic ductal adenocarcinoma is one of the most aggressive cancers, and surgical resection is a requirement for a potential cure. However, the majority of patients are diagnosed with advanced-stage disease, either metastatic (50%) or locally advanced cancer (30%). Although palliative chemotherapy is the standard of care for patients with metastatic disease, management of locally advanced adenocarcinoma is controversial. Several treatment options, including extended surgical resections, neoadjuvant therapy with subsequent resections, as well as palliative radiotherapy and/or chemotherapy, should be considered. However, there is little evidence available to support treatment options for locally advanced disease. As valid predictive biomarkers for stratification of therapy are not available today, future trials need to define the role of the different treatment options. This Review summarizes the current evidence and discusses available treatment options for both locally advanced and metastatic pancreatic adenocarcinoma.

10 Review Arterial resection during pancreatectomy for pancreatic cancer: a systematic review and meta-analysis. 2011

Mollberg, Nathan / Rahbari, Nuh N / Koch, Moritz / Hartwig, Werner / Hoeger, Yumiko / Büchler, Markus W / Weitz, Jürgen. ·Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Germany. ·Ann Surg · Pubmed #22064622.

ABSTRACT: BACKGROUND: The majority of pancreatic cancers are diagnosed at an advanced stage. As surgical resection remains the only hope for cure, more aggressive surgical approaches have been advocated to increase resection rates. Institutions have begun to release data on their experience with pancreatectomy and simultaneous arterial resection (AR), which has traditionally been considered a general contraindication to resection. The aim of the present meta-analysis was to evaluate the perioperative and long-term outcomes of patients with AR during pancreatectomy for pancreatic cancer. METHODS: The Medline, Embase, and Cochrane Library and J-East databases were systematically searched to identify studies reporting outcome of patients who underwent pancreatectomy with AR for pancreatic cancer. Studies that reported perioperative and/or long-term results after pancreatectomy with AR were eligible for inclusion. Meta-analyses included comparative studies providing data on patients with and without AR and were performed using a random effects model. RESULTS: The literature search identified 26 studies including 366 and 2243 patients who underwent pancreatectomy with and without AR. All studies were retrospective cohort studies and the methodological quality was moderate to low. Meta-analyses revealed AR to be associated with a significantly increased risk for perioperative mortality [Odds ratio (OR) = 5.04; 95% confidence interval (CI), 2.69-9.45; P < 0.0001; I² = 24%], poor survival at 1 year (OR = 0.49; 95% CI, 0.31-0.78; P = 0.002; I² = 35%) and 3 years (OR = 0.39; 95% CI, 0.17-0.86; P = 0.02; I² = 49%) compared with patients without AR. The increased perioperative mortality (OR = 8.87; 95% CI, 3.40-23.13; P < 0.0001; I² = 5%) and lower survival rate at 1 year (OR = 0.50; 95% CI, 0.31-0.82; P = 0.006; I² = 40%) was confirmed in the comparison to patients undergoing venous resection. Despite substantial perioperative mortality, pancreatectomy with AR was associated with more favorable survival compared with patients who did not undergo resection for locally advanced disease. CONCLUSIONS: AR in patients undergoing pancreatectomy for pancreatic cancer is associated with a poor short and long-term outcome. Pancreatectomy with AR may, however, be justified in highly selected patients owing to the potential survival benefit compared with patients without resection. These patients should be treated within the bounds of clinical trials to assess outcomes after AR in the era of modern pancreatic surgery and multimodal therapy.

11 Clinical Trial Prognostic and predictive value of immunological parameters for chemoradioimmunotherapy in patients with pancreatic adenocarcinoma. 2015

Karakhanova, S / Ryschich, E / Mosl, B / Harig, S / Jäger, D / Schmidt, J / Hartwig, W / Werner, J / Bazhin, A V. ·Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany. · 1] Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany [2] National Centre for Tumor Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany. · National Centre for Tumor Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany. · 1] Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany [2] General and Visceral Surgery Center, 8002 Zurich, Switzerland. · Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, 81377 Munich, Germany. · 1] Department of General Surgery, University Hospital Heidelberg, 69120 Heidelberg, Germany [2] Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, 81377 Munich, Germany. ·Br J Cancer · Pubmed #25742476.

ABSTRACT: BACKGROUND: Chemoradioimmunotherapy of patients with pancreatic adenocarcinoma from the CapRI trial did not show any benefit of interferon-α in addition to a 5-fluorouracil (5FU)-based treatment. The aim of this study was to identify immunological parameters in patients from this trial to be used for predictive and/or prognostic purposes. METHODS: The following methods were used: tumour immunohistology, FACS analyses, cytokine measurement, as well as cytotoxicity and ELIspot. Immunological parameters were correlated with patients' survival using the Kaplan-Meier method. RESULTS: Irrespective of therapy type, high lymphocyte accumulation in tumours and frequencies of NK cells and effector (eff) CD8(+) T cells in peripheral blood of the patients were associated with patients' survival. Amount of CD3(+) and effector-memory CD8(+) blood lymphocytes, expression of CD152 and interleukin (IL)-2 serum level showed a predictive value for chemoradioimmunotherapy. Tumoural accumulation of CD3(+) and CD8(+) cells was predictive for outcome of chemotherapy alone. Besides, we identified the frequencies of CD3(+) lymphocytes, effCD8(+) T cells and NK cells in the peripheral blood of the patients, and IL-10 amount in serum, to be predictive values for 5FU-based chemotherapy. CONCLUSIONS: Immunological parameters, identified in this trial as possible markers, may be of interest in personalized medicine towards the improvement of the treatment and prognosis of pancreatic carcinoma patients.

12 Clinical Trial Clinical phase I/II trial to investigate neoadjuvant intensity-modulated short term radiation therapy (5 × 5 Gy) and intraoperative radiation therapy (15 Gy) in patients with primarily resectable pancreatic cancer - NEOPANC. 2012

Roeder, Falk / Timke, Carmen / Saleh-Ebrahimi, Ladan / Schneider, Lutz / Hackert, Thilo / Hartwig, Werner / Kopp-Schneider, Annette / Hensley, Frank W / Buechler, Markus W / Debus, Juergen / Huber, Peter E / Werner, Jens. ·Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. F.Roeder@dkfz.de. ·BMC Cancer · Pubmed #22443802.

ABSTRACT: BACKGROUND: The current standard treatment, at least in Europe, for patients with primarily resectable tumors, consists of surgery followed by adjuvant chemotherapy. But even in this prognostic favourable group, long term survival is disappointing because of high local and distant failure rates. Postoperative chemoradiation has shown improved local control and overalls survival compared to surgery alone but the value of additional radiation has been questioned in case of adjuvant chemotherapy. However, there remains a strong rationale for the addition of radiation therapy considering the high rates of microscopically incomplete resections after surgery. As postoperative administration of radiation therapy has some general disadvantages, neoadjuvant and intraoperative approaches theoretically offer benefits in terms of dose escalation, reduction of toxicity and patients comfort especially if hypofractionated regimens with highly conformal techniques like intensity-modulated radiation therapy are considered. METHODS/DESIGN: The NEOPANC trial is a prospective, one armed, single center phase I/II study investigating a combination of neoadjuvant short course intensity-modulated radiation therapy (5 × 5 Gy) in combination with surgery and intraoperative radiation therapy (15 Gy), followed by adjuvant chemotherapy according to the german treatment guidelines, in patients with primarily resectable pancreatic cancer. The aim of accrual is 46 patients. DISCUSSION: The primary objectives of the NEOPANC trial are to evaluate the general feasibility of this approach and the local recurrence rate after one year. Secondary endpoints are progression-free survival, overall survival, acute and late toxicity, postoperative morbidity and mortality and quality of life. TRIAL REGISTRATION: NCT01372735.

13 Article Antimicrobial Peptide Human Neutrophil Peptide 1 as a Potential Link Between Chronic Inflammation and Ductal Adenocarcinoma of the Pancreas. 2018

Pausch, Thomas / Adolph, Sarah / Felix, Klaus / Bauer, Andrea S / Bergmann, Frank / Werner, Jens / Hartwig, Werner. · ·Pancreas · Pubmed #29683978.

ABSTRACT: OBJECTIVES: Defensins are antimicrobial peptides playing a role in innate immunity, in epithelial cell regeneration, and in carcinogenesis of inflammation-triggered malignancies. We analyzed this role in pancreatic ductal adenocarcinoma (PDAC) in the context of its association with chronic pancreatitis (CP). METHODS: Human tissue of healthy pancreas, CP, and PDAC was screened for defensins by immunohistochemistry. Defensin α 1 (human neutrophil peptide 1 [HNP-1]) expression was validated using mass spectrometry and microarray analysis. Human neutrophil peptide 1 expression and influences of proinflammatory cytokines (tumor necrosis factor α, interleukin 1β, and interferon γ) were studied in human pancreatic cancer cells (Colo 357, T3M4, PANC-1) and normal human pancreatic duct epithelial cells (HPDE). RESULTS: Accumulation of HNP-1 in malignant pancreatic ductal epithelia was seen. Spectrometry showed increased expression of HNP-1 in CP and even more in PDAC. At RNA level, no significant regulation was found. In cancer cells, HNP-1 expression was significantly higher than in HPDE. Proinflammatory cytokines significantly led to increased HNP-1 levels in culture supernatants and decreased levels in lysates of cancer cells. In HPDE cytokines significantly decreased HNP-1 levels. CONCLUSIONS: Inflammatory regulation of HNP-1 in PDAC tissue and cells indicates that HNP-1 may be a link between chronic inflammation and malignant transformation in the pancreas.

14 Article 3rd St. Gallen EORTC Gastrointestinal Cancer Conference: Consensus recommendations on controversial issues in the primary treatment of pancreatic cancer. 2017

Lutz, Manfred P / Zalcberg, John R / Ducreux, Michel / Aust, Daniela / Bruno, Marco J / Büchler, Markus W / Delpero, Jean-Robert / Gloor, Beat / Glynne-Jones, Rob / Hartwig, Werner / Huguet, Florence / Laurent-Puig, Pierre / Lordick, Florian / Maisonneuve, Patrick / Mayerle, Julia / Martignoni, Marc / Neoptolemos, John / Rhim, Andrew D / Schmied, Bruno M / Seufferlein, Thomas / Werner, Jens / van Laethem, Jean-Luc / Otto, Florian. ·CaritasKlinikum St. Theresia, Saarbrücken, Germany. Electronic address: m.lutz@caritasklinikum.de. · Department of Epidemiology and Preventive Medicine, School of Public Health, Monash University, The Alfred Centre, Melbourne, Australia. · Institut Gustave Roussy, Villejuif, France. · Department of Pathology, Universitätsklinikum Carl Gustav Carus, Dresden, Germany. · Department of Gastroenterology & Hepatology, Erasmus Medical Center, University Medical Center Rotterdam, The Netherlands. · Chirurgische Universitätsklinik, Heidelberg, Germany. · Department of Surgery, Institut Paoli Calmettes, Marseille, France. · Klinik für Viszerale und Transplantationschirurgie, Inselspital, Bern, Switzerland. · Department of Medical Oncology, Mount Vernon Cancer Centre, Northwood, UK. · Department of General, Visceral and Transplantation Surgery, Klinikum der Universität München, Munich, Germany. · Radiooncology Service, Hôpital Tenon (Hôpitaux Universitaires Est Parisien), Paris Cedex 20, France. · Université René Descartes, UFR Biomédicale des Saints-Pères, Paris, France. · University Cancer Center Leipzig (UCCL), University Medicine Leipzig, Germany. · Istituto Europeo di Oncologia, Divisione di Epidemiologia e Biostatistica, Milan, Italy. · Klinik und Poliklinik für Innere Medizin A, Universitätsmedizin, Greifswald, Germany; Medizinische Klinik und Poliklinik II, Klinikum der Universität München, Munich, Germany. · Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, TU München, Munich, Germany. · Department of Surgery, Liverpool University, Liverpool, UK. · University of Michigan, Ann Arbor, MI, USA. · Klinik für Chirurgie, Kantonsspital St. Gallen, St. Gallen, Switzerland. · Department of Internal Medicine I, Ulm University, Ulm, Germany. · Hopital Erasme, Anderlecht, Belgium. · Tumor- und Brustzentrum ZeTuP, St. Gallen, Switzerland. ·Eur J Cancer · Pubmed #28460245.

ABSTRACT: The primary treatment of pancreatic cancer was the topic of the 3rd St. Gallen Conference 2016. A multidisciplinary panel reviewed the current evidence and discussed controversial issues in a moderated consensus session. Here we report on the key expert recommendations. It was generally accepted that radical surgical resection followed by adjuvant chemotherapy offers the only evidence-based treatment with a chance for cure. Initial staging should classify localised tumours as resectable or unresectable (i.e. locally advanced pancreatic cancer) although there remains a large grey-zone of potentially resectable disease between these two categories which has recently been named as borderline resectable, a concept which was generally accepted by the panel members. However, the definition of these borderline-resectable (BR) tumours varies between classifications due to their focus on either (i) technical hurdles (e.g. the feasibility of vascular resection) or (ii) oncological outcome (e.g. predicting the risk of a R1 resection and/or occult metastases). The resulting expert discussion focussed on imaging standards as well as the value of pretherapeutic laparoscopy. Indications for biliary drainage were seen especially before neoadjuvant therapy. Following standard resection, the panel unanimously voted for the use of adjuvant chemotherapy after R0 resection and considered it as a reasonable standard of care after R1 resection, even though the optimal pathologic evaluation and the definition of R0/R1 was the issue of an ongoing debate. The general concept of BR tumours was considered as a good basis to select patients for preoperative therapy, albeit its current impact on the therapeutic strategy was far less clear. Main focus of the conference was to discuss the limits of surgical resection and to identify ways to standardise procedures and to improve curative outcome, including adjuvant and perioperative treatment.

15 Article Outcomes after extended pancreatectomy in patients with borderline resectable and locally advanced pancreatic cancer. 2016

Hartwig, W / Gluth, A / Hinz, U / Koliogiannis, D / Strobel, O / Hackert, T / Werner, J / Büchler, M W. ·Departments of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. · Departments of General, Visceral and Transplantation Surgery, University of Munich, Munich, Germany. · Departments of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. markus.buechler@med.uni-heidelberg.de. ·Br J Surg · Pubmed #27686238.

ABSTRACT: BACKGROUND: In the recent International Study Group of Pancreatic Surgery (ISGPS) consensus on extended pancreatectomy, several issues on perioperative outcome and long-term survival remained unclear. Robust data on outcomes are sparse. The present study aimed to assess the outcome of extended pancreatectomy for borderline resectable and locally advanced pancreatic cancer. METHODS: A consecutive series of patients with primary pancreatic adenocarcinoma undergoing extended pancreatectomies, as defined by the new ISGPS consensus, were compared with patients who had a standard pancreatectomy. Univariable and multivariable analysis was performed to identify risk factors for perioperative mortality and characteristics associated with survival. Long-term outcome was assessed by means of Kaplan-Meier analysis. RESULTS: The 611 patients who had an extended pancreatectomy had significantly greater surgical morbidity than the 1217 patients who underwent a standard resection (42·7 versus 34·2 per cent respectively), and higher 30-day mortality (4·3 versus 1·8 per cent) and in-hospital mortality (7·5 versus 3·6 per cent) rates. Operating time of 300 min or more, extended total pancreatectomy, and ASA fitness grade of III or IV were associated with increased in-hospital mortality in multivariable analysis, whereas resections involving the colon, portal vein or arteries were not. Median survival and 5-year overall survival rate were reduced in patients having extended pancreatectomy compared with those undergoing a standard resection (16·1 versus 23·6 months, and 11·3 versus 20·6 per cent, respectively). Older age, G3/4 tumours, two or more positive lymph nodes, macroscopic positive resection margins, duration of surgery of 420 min or above, and blood loss of 1000 ml or more were independently associated with decreased overall survival. CONCLUSION: Extended resections are associated with increased perioperative morbidity and mortality, particularly when extended total pancreatectomy is performed. Favourable long-term outcome is achieved in some patients.

16 Article Acinar cell carcinoma of the pancreas: a rare disease with different diagnostic and therapeutic implications than ductal adenocarcinoma. 2016

Kruger, Stephan / Haas, Michael / Burger, Philipp Johannes / Ormanns, Steffen / Modest, Dominik Paul / Westphalen, Christoph Benedikt / Kleespies, Axel / Angele, Martin Kurt / Hartwig, Werner / Bruns, Christiane Josephine / Kirchner, Thomas / Werner, Jens / Heinemann, Volker / Boeck, Stefan. ·Department of Internal Medicine III, Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany. · Institute of Pathology, Ludwig-Maximilians-University of Munich, 81377, Munich, Germany. · Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, 81377, Munich, Germany. · Department of General, Visceral and Tumor Surgery, University of Cologne, 50937, Köln-Lindenthal, Germany. · Department of Internal Medicine III, Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany. stefan.boeck@med.uni-muenchen.de. ·J Cancer Res Clin Oncol · Pubmed #27629876.

ABSTRACT: PURPOSE: Acinar cell carcinoma (ACC) of the pancreas is a very rare cancer, constituting 1 % of all malignant non-endocrine pancreatic tumors. Only very limited data exist to guide treatment in patients with advanced ACC. METHODS: Between 2000 and 2015, 15 patients with ACC were diagnosed and/or treated at our high-volume comprehensive cancer center. Medical records and correlating serum levels of the potential serum tumor markers CA 19-9, CEA and lipase were analyzed retrospectively. RESULTS: A substantial antitumor activity was observed for treatment regimens containing 5-FU and oxaliplatin with partial responses or prolonged disease stabilizations (>12 months) observed in 6 out of 7 patients (86 %). Activity was also observed for single-agent 5-FU and its oral prodrugs. Serum lipase levels were elevated in 7 of 12 patients with advanced disease (58 %), whereas CEA and CA 19-9 seemed to be of minor importance for ACC (elevated pre-treatment levels in 4/12 and 3/12 cases, respectively). In selected patients, repeated serum lipase measurements were available and accurately predicted response to chemotherapy and relapse after surgery. CONCLUSIONS: 5-FU- and oxaliplatin-containing regimens are active in advanced ACC. Lipase kinetics may be a useful novel tool to monitor the course of disease as well as treatment effects in ACC.

17 Article [Not Available]. 2016

D'Haese, Jan G / Hartwig, Werner / Werner, Jens. · ·Zentralbl Chir · Pubmed #27088269.

ABSTRACT: -- No abstract --

18 Article Isolated pulmonary metastases define a favorable subgroup in metastatic pancreatic cancer. 2016

Kruger, Stephan / Haas, Michael / Burger, Philipp Johannes / Ormanns, Steffen / Modest, Dominik Paul / Westphalen, Christoph Benedikt / Michl, Marlies / Kleespies, Axel / Angele, Martin Kurt / Hartwig, Werner / Bruns, Christiane Josephine / Niyazi, Maximilian / Roeder, Falk / Kirchner, Thomas / Werner, Jens / Heinemann, Volker / Boeck, Stefan. ·Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, D-81377 Munich, Germany. · Institute of Pathology, Ludwig-Maximilians-University of Munich, D-81377 Munich, Germany. · Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, D-81377 Munich, Germany. · Department of General, Abdominal and Vascular Surgery, Otto-von-Guericke-University, D-39120 Magdeburg, Germany. · Department of Radiation Oncology, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, D-81377 Munich, Germany. · Department of Radiation Oncology, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, D-81377 Munich, Germany; Department of Molecular Radiation Oncology, Deutsches Krebsforschungszentrum (DKFZ), D-69120 Heidelberg, Germany. · Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, D-81377 Munich, Germany. Electronic address: stefan.boeck@med.uni-muenchen.de. ·Pancreatology · Pubmed #27067420.

ABSTRACT: PURPOSE: Liver metastasis represents the first site of dissemination in >80% of metastatic pancreatic cancer (PC) patients. Pulmonary metastasis as first site of dissemination in PC is a rare event and might define a biologically distinct subgroup in metastatic PC. METHODS: Consecutive PC patients who were diagnosed or treated with isolated pulmonary metastases at our high-volume comprehensive cancer center were included in a prospectively maintained database between 2002 and 2015. Medical records and correlating computed tomography findings (CT) were retrospectively analyzed. RESULTS: A total of 40 PC patients with isolated pulmonary metastases were identified. Pulmonary metastases represented disease recurrence after initial resection of PC in 22 patients and disease progression of locally advanced pancreatic cancer in 5 patients. 14 out of 27 PC patients (56%) had received chemoradiotherapy for localized disease prior to pulmonary metastasis. Data on 1st-line treatment for pulmonary metastases was available for 38 patients: most patients (71%) received a gemcitabine-based chemotherapy regimen, 5 patients (13%) received best supportive care. After a median follow-up of 37.3 months, median survival after diagnosis of pulmonary metastasis was estimated with 25.5 months (95% CI 19.1-31.8); a significantly improved survival after diagnosis of pulmonary metastasis was observed for patients with less than 10 lung metastases (31.3 vs 18.7 months, p = 0.003) and for an unilateral localization of lung involvement (31.3 vs 21.8 months, p = 0.03). CONCLUSIONS: Our results suggest a favorable outcome of PC patients with isolated pulmonary metastases. Further research is warranted to elucidate the specific molecular characteristics of this rare subgroup.

19 Article Pancreaticoduodenectomy for adenocarcinoma of the pancreatic head is justified in elderly patients: A Retrospective Cohort Study. 2016

Renz, Bernhard W / Khalil, Philippe N / Mikhailov, Michael / Graf, Sandra / Schiergens, Tobias S / Niess, Hanno / Boeck, Stefan / Heinemann, Volker / Hartwig, Werner / Werner, Jens / Bruns, Christiane J / Kleespies, Axel. ·Department of General, Visceral, Transplantation, Vascular, and Thoracic Surgery, University of Munich, Campus Grosshadern, Munich, Germany; Pancreatic Cancer Center Munich, Comprehensive Cancer Center-LMU, University of Munich, Munich, Germany. · Department of General, Visceral, Transplantation, Vascular, and Thoracic Surgery, University of Munich, Campus Grosshadern, Munich, Germany. · Department of Haematology and Oncology, University of Munich, Campus Grosshadern, Germany; Pancreatic Cancer Center Munich, Comprehensive Cancer Center-LMU, University of Munich, Munich, Germany. · Department of General, Visceral, and Vascular Surgery, University of Magdeburg, Magdeburg, Germany. · Department of General, Visceral, Transplantation, Vascular, and Thoracic Surgery, University of Munich, Campus Grosshadern, Munich, Germany; Pancreatic Cancer Center Munich, Comprehensive Cancer Center-LMU, University of Munich, Munich, Germany. Electronic address: axel.kleespies@med.uni-muenchen.de. ·Int J Surg · Pubmed #26906329.

ABSTRACT: BACKGROUND: The increasing elderly population is an inevitable trend worldwide in developed countries. Therefore, we aimed to assess the experience of a tertiary pancreatic center with a very homogenous population comprising only patients diagnosed with PDAC of the pancreatic head in patients older than 75 years of age compared to their younger counterparts regarding the benefit in life expectancy and tumor biological aggressiveness. METHODS: 300 patients underwent partial pancreaticoduodenectomy (PD) or pylorus preserving pancreaticoduodenectomy (PPPD) for PDAC of the pancreatic head between 2002 and 2012 and were evaluated with regard to their co-morbidities, clinicopathological and perioperative variables, postoperative morbidity, mortality and long term survival. Therefore, two groups according to the age at the procedure (A: <75 years, n = 241, B: ≥75 years, n = 59) were designed. RESULTS: There were no differences between groups with regard to gender, performed procedure (PPPD or PD), operation time, blood loss, tumor invasiveness and grade of tumor differentiation, R-status, lymph node ratio, 30-day mortality, length of stay and adjuvant chemotherapy. Extended resections including total pancreatectomy were slightly more often performed in younger patients (p = 0.071) and trended toward a higher rate of surgical complications in patients <75 years of age (p = 0.183). A higher rate of preoperative co-morbidities in elderly patients (group B), was associated with more postoperative non-surgical complications (p = 0.002) in this group of patients. However, the median overall survival (19.2 vs. 18.4 months) did not differ significantly between groups. CONCLUSIONS: Major pancreatic surgery for ductal adenocarcinoma of the pancreatic head is justified in elderly patients. With careful patients' selection and prudent perioperative management, elderly patients will have a similar long term outcome despite the higher rate of postoperative morbidity based on non-surgical complications.

20 Article Total pancreatectomy for primary pancreatic neoplasms: renaissance of an unpopular operation. 2015

Hartwig, Werner / Gluth, Alexander / Hinz, Ulf / Bergmann, Frank / Spronk, Pauline E R / Hackert, Thilo / Werner, Jens / Büchler, Markus W. ·*Department of General, Visceral, and Transplantation Surgery; †Division of Biostatistics; and ‡Institute of Pathology, University of Heidelberg, Heidelberg, Germany. ·Ann Surg · Pubmed #24979606.

ABSTRACT: OBJECTIVE: To assess the long-term survival and quality of life in total pancreatectomies and to identify risk factors for perioperative morbidity and mortality. BACKGROUND: Total pancreatectomy may be required in locally advanced or centrally located pancreatic neoplasms to achieve complete tumor clearance, but available data on short- and long-term results are limited. METHODS: A total of 434 consecutive total pancreatectomies for primary pancreatic or periampullary tumors were performed between October 2001 and September 2012 at the authors' institution and were prospectively documented and analyzed. Long-term outcome was assessed using Kaplan-Meier and quality of life analysis (EORTC-QLQ-C30 and PAN26). Uni- and multivariate analysis was performed to identify perioperative risk factors and predictors for long-term survival. RESULTS: Extended total pancreatectomies were performed in 54% of cases, with arterial and portal vein resections in 15% and 32%, respectively. Overall 30-day and in-hospital mortality rates were 3.7% and 7.8%, respectively. High blood loss, long operative time, and arterial resections were independently associated with increased perioperative mortality (P ≤ 0.018). In malignant disease, median and 5-year survival were good for standard total pancreatectomies (28.6 months and 24.3%, respectively) and were significantly impaired after vascular resections (P < 0.001). Poor tumor grading, high American Joint Commission on Cancer tumor stage, age more than 70 years, and an R1 resection were independent prognostic parameters. Long-term global quality of life was comparable with a matched healthy control group. CONCLUSIONS: Standard total pancreatectomy, if needed, is associated with good long-term outcome in pancreatic cancer. Marked surgical morbidity and impaired survival associated with vascular resections reflect the invasiveness of extended total pancreatectomies and the underlying advanced malignant disease.

21 Article Acinar cell carcinomas of the pancreas: a molecular analysis in a series of 57 cases. 2014

Bergmann, Frank / Aulmann, Sebastian / Sipos, Bence / Kloor, Matthias / von Heydebreck, Anja / Schweipert, Johannes / Harjung, Andreas / Mayer, Philipp / Hartwig, Werner / Moldenhauer, Gerhard / Capper, David / Dyckhoff, Gerhard / Freier, Kolja / Herpel, Esther / Schleider, Anja / Schirmacher, Peter / Mechtersheimer, Gunhild / Klöppel, Günter / Bläker, Hendrik. ·Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 224, D-69120, Heidelberg, Germany, frank.bergmann@med.uni-heidelberg.de. ·Virchows Arch · Pubmed #25298229.

ABSTRACT: Pancreatic acinar cell carcinomas (PACs) are rare but are distinct aggressive neoplasms that phenotypically differ from pancreatic ductal adenocarcinomas (PDACs) and pancreatic neuroendocrine neoplasms (PNENs). Despite recent work on the genetic changes of PACs, their molecular pathogenesis is still poorly understood. In this study, we focus on a comparative genomic hybridization analysis. Based on frequent chromosomal imbalances, the involvement of DCC and c-MYC in the pathogenesis of PACs is further investigated. Moreover, we examine markers harboring potential therapeutic relevance (K-RAS, BRAF, EGFR, MGMT, HSP90, L1CAM, Her2). PACs revealed a microsatellite stable, chromosomal unstable genotype, defined by recurrent chromosomal losses of 1p, 3p, 4q, 5q, 6q, 8p, 9p, 11q, 13q, 16q, and 18, as well as gains of 1q, 7, 8q, 12, 17q, and 20q. Subsets of PAC displayed reduction/loss of DCC (79 %) and c-MYC-amplification (17 %). Significant EGFR expression occurred in 42 %, HSP90 expression in 98 %, L1CAM expression in 72 %, and loss of MGMT in 26 %. Two cases carried a K-RAS mutation. Mutations of EGFR or BRAF were not detected. All cases were Her2/neu-negative. PACs display characteristic chromosomal imbalances which are distinctly different from those in pancreatic ductal adenocarcinomas and pancreatic neuroendocrine neoplasms. Our findings suggest that DCC and c-MYC alterations may play an important role in the pathogenesis of PACs. Furthermore, EGFR, MGMT, HSP90, and L1CAM may be useful as therapeutic markers and predictors of response to therapy in a subset of PACs.

22 Article When to perform a pancreatoduodenectomy in the absence of positive histology? A consensus statement by the International Study Group of Pancreatic Surgery. 2014

Asbun, Horacio J / Conlon, Kevin / Fernandez-Cruz, Laureano / Friess, Helmut / Shrikhande, Shailesh V / Adham, Mustapha / Bassi, Claudio / Bockhorn, Maximilian / Büchler, Markus / Charnley, Richard M / Dervenis, Christos / Fingerhutt, Abe / Gouma, Dirk J / Hartwig, Werner / Imrie, Clem / Izbicki, Jakob R / Lillemoe, Keith D / Milicevic, Miroslav / Montorsi, Marco / Neoptolemos, John P / Sandberg, Aken A / Sarr, Michael / Vollmer, Charles / Yeo, Charles J / Traverso, L William / Anonymous710789. ·Department of General Surgery, Mayo Clinic, Jacksonville, FL. Electronic address: Asbun.Horacio@mayo.edu. · Professorial Surgical Unit, University of Dublin, Trinity College, Dublin, Ireland. · 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 Surgical Oncology, Tata Memorial Centre, Mumbai, India. · Department of HPB Surgery, Hopital Edouard Herriot, Lyon, France. · 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 General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. · Department of HPB & Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK. · Department of First Surgery, Agia Olga Hospital, Athens, Greece. · Department of Digestive Surgery, Centre Hospitalier Intercommunal, Poissy, France. · Department of Surgery, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. · Acacdemic Unit of Surgery, Univesity 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 Molecular and Clinical Cancer Medicine, Liverpool Cancer Research-UK Centre, University of Liverpool, Liverpool, UK. · Department of Surgery, Karolinska Institutet at Karolinska University Hospital, Huddinge, Stockholm, Sweden. · Department of Gastroenterologic and General Surgery, Mayo Clinic, Rochester, MN. · 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. · St. Luke's Clinic - Center For Pancreatic and Liver Diseases, Boise, ID. ·Surgery · Pubmed #24661765.

ABSTRACT: BACKGROUND: Pancreatoduodenectomy (PD) provides the best chance for cure in the treatment of patients with localized pancreatic head cancer. In patients with a suspected, clinically resectable pancreatic head malignancy, the need for histologic confirmation before proceeding with PD has not historically been required, but remains controversial. METHODS: An international panel of pancreatic surgeons working in well-known, high-volume centers reviewed the literature and worked together to establish a consensus on when to perform a PD in the absence of positive histology. RESULTS: The incidence of benign disease after PD for a presumed malignancy is 5-13%. Diagnosis by endoscopic cholangiopancreatography brushings and percutaneous fine-needle aspiration are highly specific, but poorly sensitive. Aspiration biopsy guided by endoscopic ultrasonography (EUS) has greater sensitivity, but it is highly operator dependent and increases expense. The incidence of autoimmune pancreatitis (AIP) in the benign resected specimens is 30-43%. EUS-guided Trucut biopsy, serum levels of immunoglobulin G4, and HISORt (Histology, Imaging, Serology, Other organ involvement, and Response to therapy) are used for diagnosis. If AIP is suspected but not confirmed, the response to a short course of steroids is helpful for diagnosis. CONCLUSION: In the presence of a solid mass suspicious for malignancy, consensus was reached that biopsy proof is not required before proceeding with resection. Confirmation of malignancy, however, is mandatory for patients with borderline resectable disease to be treated with neoadjuvant therapy before exploration for resection. When a diagnosis of AIP is highly suspected, a biopsy is recommended, and a short course of steroid treatment should be considered if the biopsy does not reveal features suspicious for malignancy.

23 Article Pylorus resection or pylorus preservation in partial pancreatico-duodenectomy (PROPP study): study protocol for a randomized controlled trial. 2013

Hackert, Thilo / Bruckner, Thomas / Dörr-Harim, Colette / Diener, Markus K / Knebel, Phillip / Hartwig, Werner / Strobel, Oliver / Fritz, Stefan / Schneider, Lutz / Werner, Jens / Büchler, Markus W. ·Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, Heidelberg, 69120, Germany. Thilo_Hackert@med.uni-heidelberg.de ·Trials · Pubmed #23410208.

ABSTRACT: BACKGROUND: Partial pancreatico-duodenectomy (PD) is the standard treatment for tumors of the pancreatic head. Today, preservation of the pylorus has been widely accepted as the surgical standard in this procedure. A common postoperative complication is the occurrence of delayed gastric emptying (DGE), which causes impairment of oral intake andpatients' quality of life, prolongation of hospital stay and delay of further treatment (for example adjuvant chemotherapy). In a small number of two retrospective and one randomized studies, a modification by resection of the pylorus with preservation of the stomach has shown to reduce DGE incidence. The aim of the present study is to investigate the effect of pylorus resection on postoperative DGE in PD. METHODS/DESIGN: Patients undergoing elective PD for any indication equal or older than 18 years and who have given informed consent will be included. Patients will be randomized to either PD with pylorus preservation or PD with pylorus resection and complete stomach preservation. Sample size (n = 89 patients per group) is calculated on an assumed difference in DGE incidence of 20%. Primary study endpoint is DGE within 30 days; secondary endpoints are operation time, blood loss, morbidity, mortality, hospital stay and quality of life (QoL). DISCUSSION: DGE is a relevant clinical problem following PD with a great impact on patients' recovery, length of hospital stay, QoL and consecutive adjuvant therapies. As there is no causal therapy, prevention of DGE is essential to improve outcome. The technical modification of pylorus resection may offer a simple and effective method for this purpose. The present study is designed to increase the existing body of evidence and potentially change the future standard surgical procedure of PD. TRIAL REGISTRATION: German Clinical Trials Register DRKS00004191.

24 Article CA19-9 in potentially resectable pancreatic cancer: perspective to adjust surgical and perioperative therapy. 2013

Hartwig, Werner / Strobel, Oliver / Hinz, Ulf / Fritz, Stefan / Hackert, Thilo / Roth, Constanze / Büchler, Markus W / Werner, Jens. ·Department of General Surgery, University of Heidelberg, Heidelberg, Germany. ·Ann Surg Oncol · Pubmed #23247983.

ABSTRACT: PURPOSE: In pancreatic cancer, genetic markers to aid clinical decision making are still lacking. The present study was designed to determine the prognostic role of perioperative serum tumor marker carbohydrate antigen 19-9 (CA19-9) in pancreatic adenocarcinoma, with a focus on implications for pre- and postoperative therapeutic consequences. METHODS: Of a total of 1,626 consecutive patients who underwent surgery for primary pancreatic adenocarcinoma, data from 1,543 patients with preoperative serum levels of CA19-9 were evaluated for tumor stage, resectability, and prognosis. Preoperative to postoperative CA19-9 changes were analyzed for long-term survival. A control cohort of 706 patients with chronic pancreatitis was used to assess the predictability of malignancy by CA19-9 and the effects of hyperbilirubinemia on CA19-9 levels. RESULTS: The more that preoperative CA19-9 increased, the lower were tumor resectability and survival rates. Resectability and 5-year survival varied from 80 to 38 % and from 27 to 0 % for CA19-9 <37 versus ≥4,000 U/ml, respectively. The R0 resection rate was as low as 15 % in all patients with CA19-9 levels ≥1,000 U/ml. CA19-9 increased with the stage of the disease and was highest in AJCC stage IV. Patients with an early postoperative CA19-9 increase had a dismal prognosis. Hyperbilirubinemia did not markedly affect CA19-9 levels (correlation coefficient ≤0.135). CONCLUSIONS: In patients with pancreatic adenocarcinoma, CA19-9 predicts resectability, stage of disease, as well as survival. Highly elevated preoperative or increasing postoperative CA19-9 levels are associated with low resectability and poor survival rates, and demand the adjustment of surgical and perioperative therapy.

25 Article Re-resection for isolated local recurrence of pancreatic cancer is feasible, safe, and associated with encouraging survival. 2013

Strobel, Oliver / Hartwig, Werner / Hackert, Thilo / Hinz, Ulf / Berens, Viktoria / Grenacher, Lars / Bergmann, Frank / Debus, Jürgen / Jäger, Dirk / Büchler, Markus / Werner, Jens. ·Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany. ·Ann Surg Oncol · Pubmed #23233235.

ABSTRACT: BACKGROUND: Local recurrence of pancreatic cancer occurs in 80% of patients within 2 years after potentially curative resections. Around 30% of patients have isolated local recurrence (ILR) without evidence of metastases. In spite of localized disease these patients usually only receive palliative chemotherapy and have a short survival. PURPOSE: To evaluate the outcome of surgery as part of a multimodal treatment for ILR of pancreatic cancer. METHODS: All consecutive operations performed for suspected ILR in our institution between October 2001 and October 2009 were identified from a prospective database. Perioperative outcome, survival, and prognostic parameters were assessed. RESULTS: Of 97 patients with histologically proven recurrence, 57 (59%) had ILR. In 40 (41%) patients surgical exploration revealed metastases distant to the local recurrence. Resection was performed in 41 (72%) patients with ILR, while 16 (28%) ILR were locally unresectable. Morbidity and mortality were 25 and 1.8% after resections and 10 and 0% after explorations, respectively. Median postoperative survival was 16.4 months in ILR versus 9.4 months in metastatic disease (p < 0.0001). In ILR median survival was significantly longer after resection (26.0 months) compared with exploration without resection (10.8 months, p = 0.0104). R0 resection was achieved in 18 patients and resulted in 30.5 months median survival. Presence of metastases, incomplete resection, and high preoperative CA 19-9 serum values were associated with lesser survival. CONCLUSIONS: Resection for isolated local recurrence of pancreatic cancer is feasible, safe, and associated with favorable survival outcome. This concept warrants further evaluation in other institutions and in randomized controlled trials.

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