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1
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Qin D, Xi P, Huang K, Jiang L, Yao Z, Wei R, Li S. Nomogram for predicting post-progression-free survival in patients with recurrent pancreatic ductal adenocarcinoma after radical surgery: a retrospective analysis. Front Med (Lausanne) 2024; 11:1486750. [PMID: 39712186 PMCID: PMC11659012 DOI: 10.3389/fmed.2024.1486750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 11/20/2024] [Indexed: 12/24/2024] Open
Abstract
BACKGROUND Radical resection is the only curative method for patients with pancreatic adenocarcinoma (PDAC). However, nearly 85% of PDAC patients suffer from local or distant recurrence within 5 years after curative resection. The progression of recurrent lesions accelerates the mortality rate in PDAC patients. However, the influence of clinicopathological factors on post-progression-free survival (PPFS), defined as the period from tumor recurrence to the timing of the progression of recurrent lesions, has rarely been discussed. The present study aimed to explore the independent prognostic factors for PPFS and construct a nomogram for PPFS prediction. MATERIALS AND METHODS The 200 recurrent PDAC patients were divided into training and validation groups by leave-one-out cross-validation. The patients' clinicopathological characteristics were compared through a chi-square test. Meanwhile, these factors were enrolled in the univariate and multivariate COX regression to find the independent prognostic factors of PPFS. Moreover, the Kaplan-Meier survival analysis based on the independent prognostic factors was performed. Finally, we constructed a nomogram model for PPFS prediction, followed by an effectiveness examination. RESULTS PDAC patients who received multi-agent chemotherapy after surgery showed a longer PPFS than the single-agent chemotherapy group. PDAC patients who received multi-agent chemotherapy after recurrence showed a similar PPFS compared to the single-agent chemotherapy group. Local recurrence with distant metastases, early recurrence, lympho-vascular invasion, higher T stage, and higher N stage predicted shorter PPFS in recurrent PDAC patients. Finally, a nomogram to indicate the progression of recurrent lesions was constructed. CONCLUSION Multi-agent chemotherapy is recommended for PDAC patients after surgery. Meanwhile, single-agent chemotherapy also deserves consideration after tumor recurrence. Moreover, the nomogram could be used in PPFS prediction.
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Affiliation(s)
| | | | | | | | | | - Ran Wei
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Shengping Li
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
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Loch FN, Kamphues C, Rieger F, Beyer K, Rayya W, Schineis C, Klauschen F, Horst D, Schallenberg S, Dragomir MP. Stepwise Analysis of Resection Margin Impact on Survival and Distant Metastasis in Pancreatic Head Ductal Adenocarcinoma. Int J Surg Pathol 2024; 32:1429-1440. [PMID: 38303519 PMCID: PMC11528963 DOI: 10.1177/10668969241229342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 12/28/2023] [Accepted: 01/09/2024] [Indexed: 02/03/2024]
Abstract
The prognostic role of tumor cells in pancreatic ductal adenocarcinoma (PDAC) of the pancreatic head with direct microscopic infiltration (DMI) or in close proximity (≤1 mm) to the resection margin (RM) remains unclear. This single-center, retrospective study included specimens from 75 patients who underwent oncological resection of pancreatic head PDAC between February 2013 and July 2020. Two pathologists independently re-measured the distance between tumors and the multiple RMs. The impact of RM involvement for DMI, tumor cells within ≤1 mm, in general, and for individual RMs on overall survival (OS) and development of distant pulmonary (PM) and hepatic (HM) metastasis was analyzed. DMI of RMs was significantly associated with a shorter OS (median 5 vs 19 months, P = .02). The presence of tumor cells within ≤1 mm of RMs yielded a negative impact on OS with a trend toward significance (median 9 vs 21 months, P = .09). DMI and tumor cells within ≤1 mm of the pancreatic transection margin (PRM), individually, had a significant negative impact on OS (median 4 vs 19 months and 6 vs 19 months, P < .05), but not for any other individual RM. RM involvement of ≤1 mm of only the vascular circumferential resection margin (VCRM) resulted in a shorter time to HM development (P = 0.05). DMI of the posterior circumferential resection margin (PCRM) and VCRM, individually, showed shorter time to PM (P < .05). Potential clinical considerations include extended intraoperative evaluation of the PRM (1 mm) and intensified preoperative prediction of R1 resection as a basis for neoadjuvant therapy.
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Affiliation(s)
- Florian N. Loch
- Department of Surgery, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | | | - Freschta Rieger
- Department of Surgery, Park-Klinik Weißensee, Berlin, Germany
| | - Katharina Beyer
- Department of Surgery, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Wael Rayya
- Department of Surgery, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Christian Schineis
- Department of Surgery, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Frederick Klauschen
- Institute of Pathology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
- BIFOLD - The Berlin Institute for the Foundations of Learning and Data, Berlin, Germany
- Institute of Pathology, Ludwig-Maximilians-University Munich, München, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - David Horst
- Institute of Pathology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Simon Schallenberg
- Institute of Pathology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Mihnea P. Dragomir
- Institute of Pathology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
- Berlin Institute of Health at Charité, Berlin, Germany
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Huynh AS, Cohen AS, Doligalski M, Casagni TJ, Moberg VE, Huang X, Morse J, Abrahams D, Lloyd MC, Centeno BA, Baldwin MK, McLaughlin ML, Vagner J, Morse DL. Intraoperative Guidance of Pancreatic Cancer Resection Using a Toll-like Receptor 2-Targeted Fluorescence Molecular Imaging Agent. CANCER RESEARCH COMMUNICATIONS 2024; 4:2877-2887. [PMID: 39320054 PMCID: PMC11536076 DOI: 10.1158/2767-9764.crc-24-0244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Revised: 07/01/2024] [Accepted: 09/23/2024] [Indexed: 09/26/2024]
Abstract
To increase the achievement of negative R0 surgical margins and increase the low survival rates of pancreatic cancer, improvements in assessing tumor margins during surgical resections are needed. This can be accomplished by using pancreatic cancer-targeted fluorescence molecular imaging agents to intraoperatively detect tumor margins in real time. Because Toll-like receptor 2 (TLR2) is broadly expressed among many cancer types including pancreatic adenocarcinomas, a high-affinity TLR2-targeted fluorescence molecular imaging agent (TLR2L-800) was developed. We investigate the potential for increased survival by employing real-time intraoperative tumor detection in a preclinical orthotopic human pancreatic xenograft tumor model using TLR2L-800. Three cohorts of nude mice bearing orthotopic human pancreatic xenograft tumors were intravenously injected with TLR2L-800. At 24 hours postinjection, one cohort underwent in vivo fluorescence-guided surgical removal of tumors using a real-time fluorescence imaging platform, a second cohort underwent visible light surgery (VLS), and a third cohort did not undergo surgery. A fourth, nontumor-bearing cohort was administered TLR2L-800 with no surgery. At 41 days postsurgery, the survival rates were 53% for the fluorescence-guided surgery (FGS) group and 0% for both the VLS and the tumor-bearing no-surgery group. The overall 200-day survival rate of 35% for the FGS group was significant compared with 0% for the VLS group (P value = 0.0018). This study demonstrates the potential of increasing disease-free survival for patients with pancreatic cancer by increasing the attainment of R0 margins using a novel tumor-targeted lipopeptide ligand-based fluorescence molecular imaging agent, TLR2L-800, during real-time FGS. SIGNIFICANCE Human TLR2 is broadly expressed among pancreatic adenocarcinomas, and the highly specific TLR2L-800 fluorescence molecular imaging agent has potential for use in fluorescence-guided surgery to increase R0 margins and improve patient survival.
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Affiliation(s)
- Amanda S. Huynh
- Department of Metabolism and Physiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida
| | - Allison S. Cohen
- Department of Metabolism and Physiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida
| | - Michael Doligalski
- Department of Metabolism and Physiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida
| | - Todd J. Casagni
- Department of Comparative Medicine, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida
| | - Valerie E. Moberg
- Department of Metabolism and Physiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida
| | - Xuan Huang
- Department of Metabolism and Physiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida
| | - Jennifer Morse
- Department of Comparative Medicine, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida
| | - Dominique Abrahams
- Department of Metabolism and Physiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida
| | - Mark C. Lloyd
- Analytic Microscopy Core, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida
| | - Barbara A. Centeno
- Department of Anatomic Pathology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida
| | - Margaret K. Baldwin
- Department of Comparative Medicine, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida
| | - Mark L. McLaughlin
- Department of Pharmaceutical Sciences, West Virginia University, Morgantown, West Virginia
| | - Josef Vagner
- BIO5 Institute, University of Arizona, Tucson, Arizona
| | - David L. Morse
- Department of Metabolism and Physiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida
- Small Animal Imaging Laboratory, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida
- Department of Oncologic Sciences, University of South Florida, Tampa, Florida
- Department of Physics, University of South Florida, Tampa, Florida
- Department of Medical Engineering, University of South Florida, Tampa, Florida
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Schuhbaur J, Surovtsova I, Seufferlein T, Kokh D, Szotyori-Artz G, Winzler C, Schütz J, Uhl W, Tannapfel A, Morakis P. Prognostic value of the CRM-status in pancreatic ductal adenocarcinoma - data from a regional cancer registry. BMC Cancer 2024; 24:1280. [PMID: 39407151 PMCID: PMC11481764 DOI: 10.1186/s12885-024-12995-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 09/25/2024] [Indexed: 10/19/2024] Open
Abstract
BACKGROUND Ductal pancreatic adenocarcinoma (PDAC) still has a dismal prognosis even when deemed resectable. A cancer free resection margin (R0) is associated with a more favourable prognosis than the presence of tumour cells at resection margin (R1). However, the precise definition of the R0 status is still a matter of debate in PDAC. For a more accurate determination of R0 in PDAC the concept of circumferential resection margins (CRM) has been established and has been incorporated into the German national S3 guideline on exocrine pancreatic cancer. However, an international standardized nomenclature of CRM is still missing, and the clinical value of the CRM concept is not yet fully established. Here we evaluate whether the CRM status as defined in the national German S3 guideline corresponds with overall and progression free survival in PDAC using data from the regional cancer registry of the State of Baden Württemberg in Germany. METHODS Data from the cancer registry of the State of Baden-Württemberg, Germany, were used to assess the relationship between CRM-status and progression free survival (PFS) as well as 3-year overall survival (OS) using documented patients diagnosed with resectable ductal adenocarcinoma of the pancreas between 2015 and 2020. Patients were residents of the State of Baden-Württemberg and underwent surgery for PDAC. The R-status was assessed according to the national German S3 guideline with R0 wide/CRM- when CRM is > 1 mm from the tumour, R0 narrow/CRM + when CRM is ≤ 1 mm from the tumour and R1 when tumour cells are found at the resection margin. RESULTS In total we identified 1098 cases surgically treated for pancreatic cancer and fulfilling the inclusion criteria. 340 patients had an R0 wide/CRM- resection, 410 patients an R0 narrow/CRM + resection, and 348 patients an R1 resection. The R0 wide/CRM- status was associated with a significantly increased median OS rate compared to the other two groups (51,5%, 37,4% and 26,7% for R0 wide/CRM-, R0 narrow/CRM + and R1, respectively). mPFS was also longer in the R0 wide/CRM- group. These findings were robust with regards to grading and tumour location. CONCLUSIONS CRM is prognostic for patients with resectable PDAC making the pathological assessment of the R-status according to the CRM concept worthwhile.
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Affiliation(s)
- Jasmin Schuhbaur
- Klinik für Innere Medizin I, Universitätsklinikum Ulm, Albert-Einstein-Allee 23, D-89081, Ulm, Germany
| | - Irina Surovtsova
- Klinische Landesregisterstelle Baden-Württemberg GmbH, Krebsregister Baden-Württemberg, Stuttgart, Germany
| | - Thomas Seufferlein
- Klinik für Innere Medizin I, Universitätsklinikum Ulm, Albert-Einstein-Allee 23, D-89081, Ulm, Germany.
| | - Daria Kokh
- Klinische Landesregisterstelle Baden-Württemberg GmbH, Krebsregister Baden-Württemberg, Stuttgart, Germany
| | - Gertrud Szotyori-Artz
- Geschäftsstelle Qualitätskonferenzen bei der Klinischen Landesregisterstelle Baden-Württemberg GmbH, Krebsregister Baden-Württemberg, Stuttgart, Germany
| | - Claudia Winzler
- Geschäftsstelle Qualitätskonferenzen bei der Klinischen Landesregisterstelle Baden-Württemberg GmbH, Krebsregister Baden-Württemberg, Stuttgart, Germany
| | - Juliane Schütz
- Klinik für Innere Medizin I, Universitätsklinikum Ulm, Albert-Einstein-Allee 23, D-89081, Ulm, Germany
| | - Waldemar Uhl
- Klinik für Allgemein- und Viszeralchirurgie, Ruhr Universität Bochum, Standort St. Josef Hospital, Gudrunstraße 56, 44791, Bochum, Germany
| | - Andrea Tannapfel
- Institut für Pathologie der Ruhr-Universität Bochum am Berufsgenossenschaftlichen Universitätsklinikum, Bergmannsheil Bürkle-de-la-Camp-Platz 1, D-44789, Bochum, Germany
| | - Philipp Morakis
- Geschäftsstelle Qualitätskonferenzen bei der Klinischen Landesregisterstelle Baden-Württemberg GmbH, Krebsregister Baden-Württemberg, Stuttgart, Germany
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5
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Seufferlein T, Mayerle J, Boeck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie Exokrines Pankreaskarzinom – Version 3.1. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1724-1785. [PMID: 39389105 DOI: 10.1055/a-2338-3716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
Affiliation(s)
| | | | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Gastroenterologie und Endokrinologie Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Medizinische Klinik und Poliklinik II Onkologie und Hämatologie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
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6
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Seufferlein T, Mayerle J, Boeck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie Exokrines Pankreaskarzinom – Version 3.1. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:e874-e995. [PMID: 39389103 DOI: 10.1055/a-2338-3533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
Affiliation(s)
| | | | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Gastroenterologie und Endokrinologie Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Medizinische Klinik und Poliklinik II Onkologie und Hämatologie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
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7
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Elshami M, Wu VS, Stitzel HJ, Hue JJ, Loftus AW, Kyasaram RK, Shanahan J, Ammori JB, Hardacre JM, Ocuin LM. To Revise or Not Revise? Isolated Margin Positivity in Localized Pancreatic Ductal Adenocarcinoma. Ann Surg Oncol 2024; 31:6170-6179. [PMID: 38896228 PMCID: PMC11300499 DOI: 10.1245/s10434-024-15616-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Accepted: 05/26/2024] [Indexed: 06/21/2024]
Abstract
BACKGROUND The study determined the proportion of patients with pancreatic adenocarcinoma (PDAC) who had margin-positive disease and no other adverse pathologic findings (APF) using institutional and administrative datasets. METHODS Patients with clinical stage I or II PDAC in the National Cancer Database (NCDB 2010-2020) and those who underwent pancreatectomy at the authors' institution (2010-2021) were identified. Isolated margin positivity (IMP) was defined as a positive surgical margin with no APF (negative nodes, no lymphovascular/perineural invasion). RESULTS The study included 225 patients from the authors' institution and 23,598 patients from the NCDB. The margin-positive rates were 21.8% and 20.3%, and the IMP rates were 0.4% and 0.5%, respectively. In the institutional cohort, 68.4% of the patients had recurrence, and most of the patients (65.6%) had distant recurrences. The median recurrence-free survival (RFS) was 63.3 months for no APF, not reached for IMP, 14.8 months for negative margins & 1 APF, 20.3 months for positive margins & 2 APFs, and 12.9 months with all APF positive. The patients in the NCDB with IMP had a lower median OS than the patients with no APF (20.5 vs 390 months), but a higher median OS than those with margin positivity plus 1 APF (20.5 vs 18.0 months) or all those with APF positivity (20.5 vs 15.4 months). Based on institutional rates of IMP, any margin positivity, neck margin positivity (NMP), and no APF, the fraction of patients who might benefit from neck margin revision was 1 in 100,000, and those likely to benefit from any margin revision was 1 in 18,500. In the NCDB, those estimated to derive potential benefit from margin revision was 1 in 25,000. CONCLUSIONS Isolated margin positivity in resected PDAC is rare, and most patients experience distant recurrence. Revision of IMP appears unlikely to confer benefit to most patients.
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Affiliation(s)
- Mohamedraed Elshami
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Victoria S Wu
- Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Henry J Stitzel
- Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Jonathan J Hue
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Alexander W Loftus
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Ravi K Kyasaram
- Department of Cancer Informatics, University Hospitals Cleveland Medical Center/Seidman Cancer Center, Cleveland, OH, USA
| | - John Shanahan
- Department of Cancer Informatics, University Hospitals Cleveland Medical Center/Seidman Cancer Center, Cleveland, OH, USA
| | - John B Ammori
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Jeffrey M Hardacre
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Lee M Ocuin
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
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Usui M, Uchida K, Hayasaki A, Kishiwada M, Mizuno S, Watanabe M. Prognostic impact of the distance from the anterior surface to tumor cells in pancreatoduodenectomy with neoadjuvant chemoradiotherapy for pancreatic ductal adenocarcinoma. PLoS One 2024; 19:e0307876. [PMID: 39058712 PMCID: PMC11280245 DOI: 10.1371/journal.pone.0307876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Accepted: 07/13/2024] [Indexed: 07/28/2024] Open
Abstract
PURPOSE Several reports have shown the importance of margins in pancreatoduodenectomy (PD) specimens; however, whether anterior surfaces are included as margins varies among reports. In this study, we aimed to examine the impact of the anterior surface on disease-free survival (DFS) and overall survival (OS). METHOD In total, 98 patients who underwent PD after chemoradiotherapy for pancreatic ductal adenocarcinoma at Mie University Hospital between January 1, 2012, and December 31, 2019, were included. We investigated the prognostic impact of the distance from the anterior surface to tumor cells on DFS and OS using a log-rank test. Multivariate analysis was performed using Cox proportional hazards analysis. RESULTS A significant difference in DFS and OS was observed up to a distance of 5 mm from the anterior surface of tumor cells. The multivariate analysis revealed that the distance from the anterior surface to tumor cells (≤5 mm) was an independent poor prognostic factor for DFS and OS. CONCLUSION In patients with PD treated with neoadjuvant therapy, the distance from the anterior surface to tumor cells is an important assessment and should be included in the pathology report.
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Affiliation(s)
- Miki Usui
- Department of Oncologic Pathology, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Katsunori Uchida
- Department of Oncologic Pathology, Mie University Graduate School of Medicine, Tsu, Mie, Japan
- Department of Pathology, Kansai Medical University, Hirakata, Osaka, Japan
| | - Aoi Hayasaki
- Department of Hepato-Biliary-Pancreatic and Transplant Surgery, Mie University School of Medicine, Tsu, Mie, Japan
| | - Masashi Kishiwada
- Department of Hepato-Biliary-Pancreatic and Transplant Surgery, Mie University School of Medicine, Tsu, Mie, Japan
| | - Shugo Mizuno
- Department of Hepato-Biliary-Pancreatic and Transplant Surgery, Mie University School of Medicine, Tsu, Mie, Japan
| | - Masatoshi Watanabe
- Department of Oncologic Pathology, Mie University Graduate School of Medicine, Tsu, Mie, Japan
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9
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Quero G, De Sio D, Fiorillo C, Lucinato C, Panza E, Biffoni B, Langellotti L, Laterza V, Scaglione G, Taglioni F, Massimiani G, Menghi R, Rosa F, Mezza T, Alfieri S, Tondolo V. Resection Margin Status and Long-Term Outcomes after Pancreaticoduodenectomy for Ductal Adenocarcinoma: A Tertiary Referral Center Analysis. Cancers (Basel) 2024; 16:2347. [PMID: 39001409 PMCID: PMC11240367 DOI: 10.3390/cancers16132347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 06/14/2024] [Accepted: 06/24/2024] [Indexed: 07/16/2024] Open
Abstract
The influencing role of resection margin (R) status on long-term outcomes, namely overall (OS) and disease-free survival (DFS), after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) is not still clear. The aim of this study is to evaluate the prognostic impact of R status after PD and to define tumor characteristics associated with a positive resection margin (R1). All PDs for PDAC performed between 2012 and 2023 were retrospectively enrolled. The effect of R status, patient clinico-demographic features, and tumor features on OS and DFS were assessed. One-hundred and sixty-seven patients who underwent PD for PDAC were included in the study. R0 was achieved in 105 cases (62.8%), while R1 was evidenced in 62 patients (37.1%). R1 was associated with a decreased OS (23 (13-38) months) as compared to R0 (36 (21-53) months) (p = 0.003). Similarly, DFS was shorter in R1 patients (10 (6-25) months) as compared to the R0 cohort (18 (9-70) months) (p = 0.004), with a consequent higher recurrence rate in cases of R1 (74.2% vs. 64.8% in the R0 group; p = 0.04). In the multivariate analysis, R1 and positive lymph nodes (N+) were the only independent influencing factors for OS (OR: 1.6; 95% CI: 1-2.5; p = 0.03 and OR: 1.7; 95% CI: 1-2.8; p = 0.04) and DFS (OR: 1.5; 95% CI: 1-2.1; p = 0.04 and OR: 1.8; 95% CI: 1.1-2.7; p = 0.009). Among 111 patients with N+ disease, R1 was associated with a significantly decreased DFS (10 (8-11) months) as compared to R0N+ patients (16 (11-21) months) (p = 0.05). In conclusion, the achievement of a negative resection margin is associated with survival benefits, particularly in cases of N1 disease. In addition, R0 was recognized as an independent prognostic feature for both OS and DFS. This further outlines the relevant role of radical surgery on long-term outcomes.
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Affiliation(s)
- Giuseppe Quero
- Pancreatic Surgery Unit, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, Italy; (G.Q.); (C.F.); (C.L.); (E.P.); (B.B.); (L.L.); (V.L.); (F.T.); (G.M.); (R.M.); (F.R.); (S.A.)
- Gemelli Pancreatic Center, CRMPG (Advanced Pancreatic Research Center), Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, Italy;
- Dipartimento di Scienze Mediche e Chirurgiche, Università Cattolica del Sacro Cuore di Roma, 00168 Rome, Italy;
| | - Davide De Sio
- Pancreatic Surgery Unit, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, Italy; (G.Q.); (C.F.); (C.L.); (E.P.); (B.B.); (L.L.); (V.L.); (F.T.); (G.M.); (R.M.); (F.R.); (S.A.)
| | - Claudio Fiorillo
- Pancreatic Surgery Unit, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, Italy; (G.Q.); (C.F.); (C.L.); (E.P.); (B.B.); (L.L.); (V.L.); (F.T.); (G.M.); (R.M.); (F.R.); (S.A.)
| | - Chiara Lucinato
- Pancreatic Surgery Unit, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, Italy; (G.Q.); (C.F.); (C.L.); (E.P.); (B.B.); (L.L.); (V.L.); (F.T.); (G.M.); (R.M.); (F.R.); (S.A.)
| | - Edoardo Panza
- Pancreatic Surgery Unit, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, Italy; (G.Q.); (C.F.); (C.L.); (E.P.); (B.B.); (L.L.); (V.L.); (F.T.); (G.M.); (R.M.); (F.R.); (S.A.)
| | - Beatrice Biffoni
- Pancreatic Surgery Unit, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, Italy; (G.Q.); (C.F.); (C.L.); (E.P.); (B.B.); (L.L.); (V.L.); (F.T.); (G.M.); (R.M.); (F.R.); (S.A.)
| | - Lodovica Langellotti
- Pancreatic Surgery Unit, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, Italy; (G.Q.); (C.F.); (C.L.); (E.P.); (B.B.); (L.L.); (V.L.); (F.T.); (G.M.); (R.M.); (F.R.); (S.A.)
| | - Vito Laterza
- Pancreatic Surgery Unit, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, Italy; (G.Q.); (C.F.); (C.L.); (E.P.); (B.B.); (L.L.); (V.L.); (F.T.); (G.M.); (R.M.); (F.R.); (S.A.)
| | - Giulia Scaglione
- Unità Operativa Complessa Anatomia Patologica Generale, Dipartimento di Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, Italy;
| | - Flavia Taglioni
- Pancreatic Surgery Unit, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, Italy; (G.Q.); (C.F.); (C.L.); (E.P.); (B.B.); (L.L.); (V.L.); (F.T.); (G.M.); (R.M.); (F.R.); (S.A.)
| | - Giuseppe Massimiani
- Pancreatic Surgery Unit, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, Italy; (G.Q.); (C.F.); (C.L.); (E.P.); (B.B.); (L.L.); (V.L.); (F.T.); (G.M.); (R.M.); (F.R.); (S.A.)
| | - Roberta Menghi
- Pancreatic Surgery Unit, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, Italy; (G.Q.); (C.F.); (C.L.); (E.P.); (B.B.); (L.L.); (V.L.); (F.T.); (G.M.); (R.M.); (F.R.); (S.A.)
| | - Fausto Rosa
- Pancreatic Surgery Unit, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, Italy; (G.Q.); (C.F.); (C.L.); (E.P.); (B.B.); (L.L.); (V.L.); (F.T.); (G.M.); (R.M.); (F.R.); (S.A.)
- Dipartimento di Scienze Mediche e Chirurgiche, Università Cattolica del Sacro Cuore di Roma, 00168 Rome, Italy;
| | - Teresa Mezza
- Gemelli Pancreatic Center, CRMPG (Advanced Pancreatic Research Center), Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, Italy;
- Dipartimento di Scienze Mediche e Chirurgiche, Università Cattolica del Sacro Cuore di Roma, 00168 Rome, Italy;
| | - Sergio Alfieri
- Pancreatic Surgery Unit, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, Italy; (G.Q.); (C.F.); (C.L.); (E.P.); (B.B.); (L.L.); (V.L.); (F.T.); (G.M.); (R.M.); (F.R.); (S.A.)
- Gemelli Pancreatic Center, CRMPG (Advanced Pancreatic Research Center), Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, Italy;
- Dipartimento di Scienze Mediche e Chirurgiche, Università Cattolica del Sacro Cuore di Roma, 00168 Rome, Italy;
| | - Vincenzo Tondolo
- Dipartimento di Scienze Mediche e Chirurgiche, Università Cattolica del Sacro Cuore di Roma, 00168 Rome, Italy;
- General Surgery Unit, Fatebenefratelli Isola Tiberina—Gemelli Isola, 00186 Rome, Italy
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10
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López JC, Ielpo B, Iglesias M, Pinilla FB, Sánchez-Velázquez P. The impact of vascular margin invasion on local recurrence after pancreatoduodenectomy in pancreatic adenocarcinoma. Langenbecks Arch Surg 2024; 409:122. [PMID: 38607450 PMCID: PMC11009726 DOI: 10.1007/s00423-024-03301-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Accepted: 03/26/2024] [Indexed: 04/13/2024]
Abstract
PURPOSE Pancreatic ductal adenocarcinoma (PADC) still has nowadays a very impaired long-term survival. Most studies are focused on overall survival; however, local recurrence occurs about up to 50% of cases and seems to be highly related with margin resection status. We aim to analyze the impact of vascular resection margins on local recurrence (LR) and to assess its impact on overall and disease-free survival. METHODS Eighty out of 191 patients who underwent pancreatoduodenectomy in a university hospital between 2006 and 2021 with PDAC diagnosis were analyzed and vascular margin status specifically addressed. Univariate and multivariate were performed. Time to LR was compared by using the Kaplan-Meier method and prognostic factors assessed using Cox regression hazards model. RESULTS LR appeared in 10 (50%) of the overall R1 resections in the venous margin and 9 (60%) in the arterial one. Time to LR was significantly shorter when any margin was overall affected (23.2 vs 44.7 months, p = 0.01) and specifically in the arterial margin involvement (13.7 vs 32.1 months, p = 0.009). Overall R1 resections (HR 2.61, p = 0.013) and a positive arterial margin (HR 2.84, p = 0.012) were associated with local recurrence on univariate analysis, whereas arterial positive margin remained significant on multivariate analysis (HR 2.70, p = 0.031). CONCLUSIONS Arterial margin invasion is correlated in our cohort with local recurrence. Given the limited ability to modify this margin intraoperatively, preoperative therapies should be considered to improve local margin clearance.
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Affiliation(s)
| | - Benedetto Ielpo
- Department of Surgery, Division of Hepato-Biliary and Pancreatic Surgery, University Hospital del Mar-IMIM (Hospital del Mar Medical Research Institute), Universitat Pompeu Fabra, 08003, Barcelona, Spain
| | - Mar Iglesias
- Pompeu-Fabra University, Barcelona, Spain
- Department of Surgery, Division of Hepato-Biliary and Pancreatic Surgery, University Hospital del Mar-IMIM (Hospital del Mar Medical Research Institute), Universitat Pompeu Fabra, 08003, Barcelona, Spain
- Department of Pathology, University Hospital del Mar-IMIM (Hospital del Mar Medical Research Institute), Universitat Pompeu-Fabra, Barcelona, Spain
| | - Fernando Burdío Pinilla
- Department of Surgery, Division of Hepato-Biliary and Pancreatic Surgery, University Hospital del Mar-IMIM (Hospital del Mar Medical Research Institute), Universitat Pompeu Fabra, 08003, Barcelona, Spain
| | - Patricia Sánchez-Velázquez
- Department of Surgery, Division of Hepato-Biliary and Pancreatic Surgery, University Hospital del Mar-IMIM (Hospital del Mar Medical Research Institute), Universitat Pompeu Fabra, 08003, Barcelona, Spain.
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11
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Jeune F, Collard M, Augustin J, Guedj N, Marchese U, Rouquette A, Cunha AS, Sebagh M, Pessaux P, Avérous G, Wagner M, Bachet JB, Vaillant JC, Sauvanet A, Gaujoux S. Splenic vein tumor thrombosis is a major prognostic factor in distal pancreatic adenocarcinoma. Surgery 2024; 175:1111-1119. [PMID: 38071135 DOI: 10.1016/j.surg.2023.10.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 09/11/2023] [Accepted: 10/25/2023] [Indexed: 03/17/2024]
Abstract
BACKGROUND The prognostic value of splenic vessel involvement in distal pancreatic adenocarcinoma remains controversial. The aim of the study was to assess its prognostic relevance in a large multicenter cohort. METHODS Patients who underwent pancreatosplenectomy for distal pancreatic adenocarcinoma were identified from 5 pancreatic surgical centers. A pathology review of the surgical specimens was performed to assess splenic vessel involvement, defined as invasion of the vessel's adventitia or deeper, and confirm the presence of splenic vein tumor thrombosis. Prognostic factors associated with overall and relapse-free survival were evaluated. RESULTS 149 patients underwent upfront surgery. Splenic vascular involvement was observed in 69 of them (46.3%). A parietal infiltration of the splenic artery or splenic vein was observed in 26 (17.5%) and 49 patients (32.8%), respectively. A pathologic tumor thrombosis of the splenic vein was identified in 22 patients (14.8%) and associated with larger tumors (>20 mm) (P = .023), more perineural (P = .017), and lymphovascular (P = .002) invasion, and more positive lymph node (P = .001). After a median follow-up of 50.8 months (95% confidence interval: 44.3-57.3), the cumulative 5-year overall and relapse-free survival were 46.2% and 33%, respectively. In multivariate analysis, in addition to lymph node metastasis (hazard ratio = 1.8; 95% confidence interval [1.1-3.1]; P = .023) and perineural invasion (hazard ratio = 3.5; 95% confidence interval [1.3-9.7]; P = .016), presence of splenic vein tumor thrombosis was the only splenic vascular involvement that affected independently the overall survival (HR = 2.3; 95% confidence interval [ 1.3-4.3]; P = .006). CONCLUSION In resectable distal pancreatic adenocarcinoma, a pathologic tumor thrombosis of the splenic vein is an independent prognostic factor of overall survival. To define the perioperative oncological strategy, a preoperative evaluation of splenic vessel involvement and thrombosis is needed.
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Affiliation(s)
- Florence Jeune
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.
| | - Maxime Collard
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, APHP, Beaujon Hospital, University of Paris-Cité, Clichy, France
| | - Jérémy Augustin
- Department of Pathology, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
| | - Nathalie Guedj
- Department of Pathology, AP-HP, Beaujon Hospital, Clichy, France
| | - Ugo Marchese
- Department of Digestive and Endocrine Surgery, AP-HP, Cochin Hospital, Paris, France
| | | | - Antonio Sa Cunha
- Department of Hepato-Biliary-Pancreatic Surgery, Liver Center Transplant, Paul Brousse Hospital, Paris-Saclay University, Villejuif, France
| | - Mylène Sebagh
- Department of Pathology, Paul Brousse Hospital, Paris-Saclay University, Villejuif, France
| | - Patrick Pessaux
- Department of Viscerale and Digestive surgery, Nouvel Hopital Civil, University of Strasbourg, Strasbourg, France
| | - Gerlinde Avérous
- Department of Pathology, Hôpitaux Universitaires de Strasbourg, University of Strasbourg, Strasbourg, France
| | - Mathilde Wagner
- Department of Radiology, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
| | - Jean-Baptiste Bachet
- Department of Hepatogastroenterology and Digestive Oncology, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
| | - Jean-Christophe Vaillant
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
| | - Alain Sauvanet
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, APHP, Beaujon Hospital, University of Paris-Cité, Clichy, France
| | - Sébastien Gaujoux
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France; Department of Digestive and Endocrine Surgery, AP-HP, Cochin Hospital, Paris, France
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12
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Aaquist T, Fristrup CW, Hasselby JP, Hamilton-Dutoit S, Eld M, Pfeiffer P, Mortensen MB, Detlefsen S. Prognostic value of margin clearance in total and distal pancreatectomy specimens with pancreatic ductal adenocarcinoma in a Danish population-based nationwide study. Pathol Res Pract 2024; 254:155077. [PMID: 38277754 DOI: 10.1016/j.prp.2023.155077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Revised: 12/27/2023] [Accepted: 12/30/2023] [Indexed: 01/28/2024]
Abstract
BACKGROUND The prognostic role of resection margin status following total (TP) and distal (DP) pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) is insufficiently evaluated. In Denmark, pancreatic surgery, including the postoperative pathological examination of the resection specimens, is confined to four centres, all reporting to the Danish Pancreatic Cancer Database (DPCD). In this Danish population-based nationwide study on TP and DP for PDAC from 2015-2019, based on data from DPCD, we evaluated whether there is a prognostically relevant minimum margin clearance definition and whether certain margins hold independent prognostic information. METHODS Clinical and pathological data were retrieved from DPCD and supplemented by review of pathology reports and re-microscopy, if needed. One of the study pathologists performed all re-microscopy. The prognostic significance of margin status was evaluated by dichotomisation of the TP cohort (n = 101) and the DP cohort (n = 90) into involved and uninvolved groups, using different clearance definitions (0.5 - ≥3.0 mm). RESULTS Following TP, direct involvement of the superior mesenteric artery (SMA) margin had independent prognostic value. When using a clearance definition of ≥ 0.5 or ≥ 1.5 mm for SMA, median survival for R0 versus R1 was 19 (95% CI 14-26) versus 10 (95% CI 5-20) months (p = 0.010), and 21 (95% CI 15-30) versus 10 (95% CI 8-19) months (p = 0.011), respectively. Overall margin status was not of significant prognostic importance following neither DP nor TP. CONCLUSION In this Danish population-based nationwide study, SMA margin involvement was a significant isolated prognostic factor following TP, whereas combined assessment of all circumferential margins did not hold statistically significant prognostic information. Following DP, resection margin status did not affect survival.
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Affiliation(s)
- Trine Aaquist
- Department of Pathology, Odense University Hospital, Odense, Denmark; Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Odense Patient data Exploratory Network-OPEN, Odense University Hospital, Odense, Denmark
| | - Claus W Fristrup
- Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Odense Patient data Exploratory Network-OPEN, Odense University Hospital, Odense, Denmark; Department of Surgery, Odense University Hospital, Odense, Denmark
| | - Jane P Hasselby
- Department of Pathology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
| | | | - Mikkel Eld
- Department of Pathology, Aalborg University Hospital, Aalborg, Denmark
| | - Per Pfeiffer
- Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Oncology, Odense University Hospital, Odense, Denmark
| | - Michael B Mortensen
- Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Surgery, Odense University Hospital, Odense, Denmark
| | - Sönke Detlefsen
- Department of Pathology, Odense University Hospital, Odense, Denmark; Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Odense Patient data Exploratory Network-OPEN, Odense University Hospital, Odense, Denmark.
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13
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Leonhardt CS, Pils D, Qadan M, Jomrich G, Assawasirisin C, Klaiber U, Sahora K, Warshaw AL, Ferrone CR, Schindl M, Lillemoe KD, Strobel O, Fernández-del Castillo C, Hank T. The Revised R Status is an Independent Predictor of Postresection Survival in Pancreatic Cancer After Neoadjuvant Treatment. Ann Surg 2024; 279:314-322. [PMID: 37042245 PMCID: PMC10782940 DOI: 10.1097/sla.0000000000005874] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/13/2023]
Abstract
OBJECTIVE To investigate the oncological outcomes of patients with pancreatic ductal adenocarcinoma (PDAC) who had an R 0 or R 1 resection based on the revised R status (1 mm) after neoadjuvant therapy (NAT). BACKGROUND The revised R status is an independent prognostic factor in upfront-resected PDAC; however, the significance of 1 mm margin clearance after NAT remains controversial. METHODS Patients undergoing pancreatectomy after NAT for PDAC were identified from 2 prospectively maintained databases. Clinicopathological and survival data were analyzed. The primary outcomes were overall survival (OS), recurrence-free survival (RFS), and pattern of recurrence in association with R 0 >1 mm and R 1 ≤1 mm resections. RESULTS Three hundred fifty-seven patients with PDAC were included after NAT and subsequent pancreatic resection. Two hundred eight patients (58.3%) received FOLFIRINOX, 41 patients (11.5%) received gemcitabine-based regimens, and 299 individuals (83.8%) received additional radiotherapy. R 0 resections were achieved in 272 patients (76.2%) and 85 patients (23.8%) had R 1 resections. Median OS after R 0 was 41.0 months, compared with 20.6 months after R 1 resection ( P = 0.002), and even longer after additional adjuvant chemotherapy ( R 0 44.8 vs R1 20.1 months; P = 0.0032). Median RFS in the R 0 subgroup was 17.5 months versus 9.4 months in the R 1 subgroup ( P < 0.0001). R status was confirmed as an independent predictor for OS ( R 1 hazard ratio: 1.56, 95% CI: 1.07-2.26) and RFS ( R 1 hazard ratio: 1.52; 95% CI: 1.14-2.0). In addition, R 1 resections were significantly associated with local but not distant recurrence ( P < 0.0005). CONCLUSIONS The revised R status is an independent predictor of postresection survival and local recurrence in PDAC after NAT. Achieving R 0 resection with a margin of at least 1 mm should be a primary goal in the surgical treatment of PDAC after NAT.
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Affiliation(s)
- Carl-Stephan Leonhardt
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Dietmar Pils
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Motaz Qadan
- Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA
| | - Gerd Jomrich
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Charnwit Assawasirisin
- Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA
| | - Ulla Klaiber
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Klaus Sahora
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Andrew L. Warshaw
- Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA
| | - Cristina R. Ferrone
- Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA
| | - Martin Schindl
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Keith D. Lillemoe
- Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA
| | - Oliver Strobel
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | | | - Thomas Hank
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria
- Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA
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14
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Aaquist T, Fristrup CW, Hasselby JP, Hamilton-Dutoit S, Eld M, Pfeiffer P, Mortensen MB, Detlefsen S. Prognostic importance of margin clearance in ampullary adenocarcinoma following pancreaticoduodenectomy in a Danish population-based nationwide study. HPB (Oxford) 2024; 26:241-250. [PMID: 37996299 DOI: 10.1016/j.hpb.2023.10.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Revised: 04/01/2023] [Accepted: 10/07/2023] [Indexed: 11/25/2023]
Abstract
BACKGROUND In this Danish nationwide population-based study, we evaluated the prognostically relevant minimum tumour-free margin width following pancreaticoduodenectomy (PD) for ampullary adenocarcinoma (AAC) and evaluated whether certain margins hold independent prognostic information. METHODS We included 128 patients who underwent PD for AAC from 2015 to 2019. Clinical and pathological data including well-known prognostic factors were retrieved from the Danish Pancreatic Cancer Database. Missing data were obtained by review of pathology reports and re-microscopy of resection specimens. All PD specimens were examined using a standardised pathological protocol including multicolour inking, axial slicing and exact reporting of margin widths. The cohort was dichotomised into involved and uninvolved groups, using different margin clearance definitions (0.5-≥3.0 mm). RESULTS Following PD for AAC, margin clearance of ≥1 mm was independently associated with improved chance of survival compared with <1 mm (HR: 0.30, 95 % CI: 0.14-0.64 (p = 0.002)). Posterior and anterior margin widths were narrower compared with superior mesenteric artery and vein margins. Posterior margin and anterior surface had isolated prognostic significance in multivariable analysis. CONCLUSION Following PD for AAC, margin clearance of at least 1 mm is independently associated with improved survival. Our data further indicate that anterior surface and posterior margin hold particular prognostic value.
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Affiliation(s)
- Trine Aaquist
- Department of Pathology, Odense University Hospital, Odense, Denmark; Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Odense Patient Data Exploratory Network-OPEN, Odense University Hospital, Odense, Denmark
| | - Claus W Fristrup
- Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Odense Patient Data Exploratory Network-OPEN, Odense University Hospital, Odense, Denmark; Department of Surgery, Odense University Hospital, Odense, Denmark
| | - Jane P Hasselby
- Department of Pathology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
| | | | - Mikkel Eld
- Department of Pathology, Aalborg University Hospital, Aalborg, Denmark
| | - Per Pfeiffer
- Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Oncology, Odense University Hospital, Odense, Denmark
| | - Michael B Mortensen
- Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Surgery, Odense University Hospital, Odense, Denmark
| | - Sönke Detlefsen
- Department of Pathology, Odense University Hospital, Odense, Denmark; Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Odense Patient Data Exploratory Network-OPEN, Odense University Hospital, Odense, Denmark.
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15
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Leonhardt CS, Hank T, Pils D, Gustorff C, Sahora K, Schindl M, Verbeke CS, Strobel O, Klaiber U. Prognostic impact of resection margin status on survival after neoadjuvant treatment for pancreatic cancer: systematic review and meta-analysis. Int J Surg 2024; 110:453-463. [PMID: 38315795 PMCID: PMC10793837 DOI: 10.1097/js9.0000000000000792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 09/10/2023] [Indexed: 02/07/2024]
Abstract
BACKGROUND A greater than 1 mm tumour-free resection margin (R0 >1 mm) is a prognostic factor in upfront-resected pancreatic ductal adenocarcinoma. After neoadjuvant treatment (NAT); however, the prognostic impact of resection margin (R) status remains controversial. METHODS Randomised and non-randomised studies assessing the association of R status and survival in resected pancreatic ductal adenocarcinoma after NAT were sought by systematic searches of MEDLINE, Web of Science and CENTRAL. Hazard ratios (HR) and their corresponding 95% CI were collected to generate log HR using the inverse-variance method. Random-effects meta-analyses were performed and the results presented as weighted HR. Sensitivity and meta-regression analyses were conducted to account for different surgical procedures and varying length of follow-up, respectively. RESULTS Twenty-two studies with a total of 4929 patients were included. Based on univariable data, R0 greater than 1 mm was significantly associated with prolonged overall survival (OS) (HR 1.76, 95% CI 1.57-1.97; P<0.00001) and disease-free survival (DFS) (HR 1.66, 95% CI 1.39-1.97; P<0.00001). Using adjusted data, R0 greater than 1 mm was significantly associated with prolonged OS (HR 1.65, 95% CI 1.39-1.97; P<0.00001) and DFS (HR 1.76, 95% CI 1.30-2.39; P=0.0003). Results for R1 direct were comparable in the entire cohort; however, no prognostic impact was detected in sensitivity analysis including only partial pancreatoduodenectomies. CONCLUSION After NAT, a tumour-free margin greater than 1 mm is independently associated with improved OS as well as DFS in patients undergoing surgical resection for pancreatic cancer.
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Affiliation(s)
- Carl-Stephan Leonhardt
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Thomas Hank
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Dietmar Pils
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Charlotte Gustorff
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Klaus Sahora
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Martin Schindl
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Caroline S. Verbeke
- Department of Pathology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Oliver Strobel
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Ulla Klaiber
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
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16
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Pedrazzoli S. Currently Debated Topics on Surgical Treatment of Pancreatic Ductal Adenocarcinoma: A Narrative Review on Surgical Treatment of Borderline Resectable, Locally Advanced, and Synchronous or Metachronous Oligometastatic Tumor. J Clin Med 2023; 12:6461. [PMID: 37892599 PMCID: PMC10607532 DOI: 10.3390/jcm12206461] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 09/29/2023] [Accepted: 10/04/2023] [Indexed: 10/29/2023] Open
Abstract
BACKGROUND Previously considered inoperable patients (borderline resectable, locally advanced, synchronous oligometastatic or metachronous pancreatic adenocarcinoma (PDAC)) are starting to become resectable thanks to advances in chemo/radiotherapy and the reduction in operative mortality. METHODS This narrative review presents a chosen literature selection, giving a picture of the current state of treatment of these patients. RESULTS Neoadjuvant therapy (NAT) is generally recognized as the treatment of choice before surgery. However, despite the increased efficacy, the best pathological response is still limited to 10.9-27.9% of patients. There are still limited data on the selection of possible NAT responders and how to diagnose non-responders early. Multidetector computed tomography has high sensitivity and low specificity in evaluating resectability after NAT, limiting the resection rate of resectable patients. Ca 19-9 and Positron emission tomography are giving promising results. The prediction of early recurrence after a radical resection of synchronous or metachronous metastatic PDAC, thus identifying patients with poor prognosis and saving them from a resection of little benefit, is still ongoing, although some promising data are available. CONCLUSION In conclusion, high-level evidence demonstrating the benefit of the surgical treatment of such patients is still lacking and should not be performed outside of high-volume centers with interdisciplinary teams of surgeons and oncologists.
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Barberio M, Pizzicannella M, Barbieri V, Benedicenti S, Mita MT, Rubichi F, Altamura A, Giaracuni G, Crafa F, Milizia A, Viola MG. Inframesocolic main pancreatic vessels-first approach for minimally invasive radical antegrade modular pancreaticosplenectomy (RAMPS): technical description and first experience. Updates Surg 2023; 75:1729-1734. [PMID: 37466897 DOI: 10.1007/s13304-023-01594-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Accepted: 07/12/2023] [Indexed: 07/20/2023]
Abstract
Radical modular antegrade pancreaticosplenectomy (RAMPS) improves posterior tumor-free margins during resections of pancreatic neoplasia involving the body or tail. However, minimally invasive RAMPS is technically challenging and has been reported seldom. We present for the first time a minimally invasive RAMPS technique with an innovative approach providing early dissection and control of the main peripancreatic vessels from an inframesocolic embryonal window, suitable for laparoscopy and robotics. Minimally invasive RAMPS with inframesocolic main pancreatic vessels-first approach was performed at the Tricase Hospital (Italy) from May 2017 to April 2022 in 11 consecutive patients with neoplastic lesions of the pancreas (8 laparoscopic RAMPS and 3 robotic RAMPS). Among the laparoscopic cases, 1 included a portal vein tangential resection and 1 a celiac artery resection (modified Appleby procedure). There were no conversions, no Clavien-Dindo complications > 2, all resections' margins were tumor free, and no 90-day mortality.
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Affiliation(s)
- Manuel Barberio
- Department of Surgery, Ospedale Card. G. Panico, Via Pio X 4, 73039, Tricase, Italy.
- Department of Research, Institute Against Digestive Cancer (IRCAD), 1, Place de l'Hôpital, 67091, Strasbourg, France.
| | - Margherita Pizzicannella
- Department of Surgery, Ospedale Card. G. Panico, Via Pio X 4, 73039, Tricase, Italy
- IHU Institute of Image-Guided Surgery, Strasbourg, France
| | - Vittoria Barbieri
- Department of Surgery, Ospedale Card. G. Panico, Via Pio X 4, 73039, Tricase, Italy
| | - Sara Benedicenti
- Department of Surgery, Ospedale Card. G. Panico, Via Pio X 4, 73039, Tricase, Italy
| | - Maria Teresa Mita
- Department of Surgery, Ospedale Card. G. Panico, Via Pio X 4, 73039, Tricase, Italy
| | - Francesco Rubichi
- Department of Surgery, Ospedale Card. G. Panico, Via Pio X 4, 73039, Tricase, Italy
| | - Amedeo Altamura
- Department of Surgery, Ospedale Card. G. Panico, Via Pio X 4, 73039, Tricase, Italy
| | - Gloria Giaracuni
- Department of Surgery, Ospedale Card. G. Panico, Via Pio X 4, 73039, Tricase, Italy
| | - Francesco Crafa
- Department of Surgery, Ospedale San G. Moscati, Avellino, Italy
| | - Antonio Milizia
- Department of Surgery, Ospedale Card. G. Panico, Via Pio X 4, 73039, Tricase, Italy
- Department of Surgery, Ospedale Universitario, Verona, Italy
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18
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Qin D, Wei R, Huang K, Wang R, Ding H, Yao Z, Xi P, Li S. Prognostic effect of CD73 in pancreatic ductal adenocarcinoma for disease-free survival after radical surgery. J Cancer Res Clin Oncol 2023; 149:7805-7817. [PMID: 37032378 DOI: 10.1007/s00432-023-04703-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 03/17/2023] [Indexed: 04/11/2023]
Abstract
PURPOSE Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a high potency of metastasis or recurrence after radical resection. Effective predictors for metastasis and recurrence postoperatively were dominant for the development of systemic adjuvant treatment regimens. The ATP hydrolase correlated gene CD73 was described as a promoter in tumor growth and immune escape of PDAC. However, there lacked research focused on the role of CD73 in PDAC metastasis. This study aimed to investigate the expression of CD73 in PDAC patients with different outcomes as well as the prognostic effect of CD73 for disease-free survival (DFS). METHODS The expression level of CD73 in cancerous samples from 301 PDAC patients was evaluated by immunohistochemistry (IHC) and translated into a histochemistry score (H-score) by the HALO analysis system. Then, the CD73 H-score was involved in multivariate Cox regression along with other clinicopathological characteristics to find independent prognostic factors for DFS. Finally, a nomogram was constructed based on those independent prognostic factors for DFS prediction. RESULTS Higher CD73 expression was found in PDAC patients with tumor metastasis postoperatively. Meanwhile, higher CD73 expressions were also investigated in PDAC patients diagnosed with advanced N stage and T stage. Furthermore, CD73 H-score along with tumor margin status, CA19-9, 8th N stage, and adjuvant chemotherapy was indicated as independent prognostic factors for DFS in PDAC patients. The nomogram based on these factors predicted DFS in a good manner. CONCLUSION CD73 was associated with PDAC metastasis and served as an effective prognostic factor for DFS in PDAC patients after radical surgery.
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Affiliation(s)
- Dailei Qin
- State Key Laboratory of Oncology in South China, Department of Hepatobiliary and Pancreatic Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Ran Wei
- State Key Laboratory of Oncology in South China, Department of Hepatobiliary and Pancreatic Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Kewei Huang
- State Key Laboratory of Oncology in South China, Department of Clinical Laboratory, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Ruiqi Wang
- State Key Laboratory of Oncology in South China, Department of Hepatobiliary and Pancreatic Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Honglu Ding
- State Key Laboratory of Oncology in South China, Department of Hepatobiliary and Pancreatic Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Zehui Yao
- State Key Laboratory of Oncology in South China, Department of Hepatobiliary and Pancreatic Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Pu Xi
- State Key Laboratory of Oncology in South China, Department of Hepatobiliary and Pancreatic Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China
| | - Shengping Li
- State Key Laboratory of Oncology in South China, Department of Hepatobiliary and Pancreatic Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
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Aaquist T, Fristrup CW, Hasselby JP, Hamilton-Dutoit S, Eld M, Pfeiffer P, Mortensen MB, Detlefsen S. Prognostic significance of margin clearance in pancreaticoduodenectomy specimens with pancreatic ductal adenocarcinoma in a Danish population-based nationwide study. HPB (Oxford) 2023; 25:826-835. [PMID: 37173163 DOI: 10.1016/j.hpb.2023.03.016] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 03/22/2023] [Accepted: 03/23/2023] [Indexed: 05/15/2023]
Abstract
BACKGROUND In this nationwide population-based cohort study, we investigated the overall minimum margin width that is independently associated with improved survival following pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) and evaluated whether certain margins or surfaces hold independent prognostic significance. METHODS Data from 367 patients who underwent PD for PDAC in the period 2015-2019 were retrieved from the Danish Pancreatic Cancer Database. Missing data were obtained by review of pathology reports and re-microscopy of resection specimens. Surgical specimens were evaluated using a standardised pathological protocol involving multicolour inking, axial slicing and exact reporting of circumferential margin clearances in 0.5 mm increments. RESULTS When categorised according to margin widths of <0.5, <1.0, <1.5, <2.0, <2.5 and <3.0 mm, R1 resections were detected in 34%, 57%, 75%, 78%, 86% and 87% of cases, respectively. In multivariable analyses, an overall margin clearance of ≥1.5 mm was associated with improved survival compared with a clearance of <1.5 mm (HR 0.70 95% CI 0.51-0.97 (p = 0.031)). When evaluating the margins separately, no margin had independent prognostic significance. CONCLUSION Margin clearance of at least 1.5 mm was independently associated with improved survival following PD for PDAC.
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Affiliation(s)
- Trine Aaquist
- Department of Pathology, Odense University Hospital, Odense, Denmark; Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Odense Patient Data Exploratory Network - OPEN, Odense University Hospital, Odense, Denmark
| | - Claus W Fristrup
- Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Odense Patient Data Exploratory Network - OPEN, Odense University Hospital, Odense, Denmark; Department of Surgery, Odense University Hospital, Odense, Denmark
| | - Jane P Hasselby
- Department of Pathology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
| | | | - Mikkel Eld
- Department of Pathology, Aalborg University Hospital, Aalborg, Denmark
| | - Per Pfeiffer
- Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Oncology, Odense University Hospital, Odense, Denmark
| | - Michael B Mortensen
- Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Surgery, Odense University Hospital, Odense, Denmark
| | - Sönke Detlefsen
- Department of Pathology, Odense University Hospital, Odense, Denmark; Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Odense Patient Data Exploratory Network - OPEN, Odense University Hospital, Odense, Denmark.
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20
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Lee KF, Lok HT, Fung AKY, Kung JWC, Lo EYJ, Chong CCN, Wong J, Ng KKC, Lai PBS. The Impact of Involved Resection Margin on Recurrence and Survival After Pancreaticoduodenectomy for Periampullary Carcinoma, with Emphasis on Pancreatic Head Carcinoma. World J Surg 2023; 47:717-728. [PMID: 36335279 DOI: 10.1007/s00268-022-06816-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/15/2022] [Indexed: 11/08/2022]
Abstract
BACKGROUND The supposed adverse effect of involved resection margin during pancreaticoduodenectomy (PD) for periampullary carcinoma or pancreatic head carcinoma (CaP) on long-term oncological outcomes is still inconclusive. METHODS This is a retrospective study on periampullary carcinoma undergoing PD. Patients with R0 (margin clear) resection were compared to patients with R1 (microscopically directly involved margin) resection. Patients with gross involved margin (R2 resection) were excluded. Long-term oncological outcomes measured included incidence and site of recurrent disease, overall survival (OS) and disease-free survival (DFS). A subgroup analysis was made on patients with CaP. RESULTS Between January 2003 and December 2019, 203 PD were identified for present study. The incidence of R1 resection was common (12% in periampullary carcinoma and 20% in CaP). In periampullary carcinoma, R1 resection had greater proportion of CaP, lesser proportion of carcinoma of ampulla (CaA), more perineural invasion, more lymph node (LN) metastasis. R1 group had a shorter OS and DFS, but no difference in the incidence and site of recurrent disease. In the subgroup of CaP (91 patients), R1 group did not differ from R0 group except for more LN metastasis. There was no difference in incidence and site of recurrent disease, OS and DFS. On multivariable analysis, R1 resection was not an independent factor for OS and DFS for periampullary carcinoma or for CaP only. CONCLUSION Involved resection margin was not uncommon. It was not associated with higher incidence of recurrent disease including local recurrence, and was not an independent prognosticator for OS and DFS.
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Affiliation(s)
- Kit-Fai Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, 30-32, Ngan Shing Street, Shatin, N.T, Hong Kong SAR, China.
| | - Hon-Ting Lok
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, 30-32, Ngan Shing Street, Shatin, N.T, Hong Kong SAR, China
| | - Andrew K Y Fung
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, 30-32, Ngan Shing Street, Shatin, N.T, Hong Kong SAR, China
| | - Janet W C Kung
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, 30-32, Ngan Shing Street, Shatin, N.T, Hong Kong SAR, China
| | - Eugene Y J Lo
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, 30-32, Ngan Shing Street, Shatin, N.T, Hong Kong SAR, China
| | - Charing C N Chong
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, 30-32, Ngan Shing Street, Shatin, N.T, Hong Kong SAR, China
| | - John Wong
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, 30-32, Ngan Shing Street, Shatin, N.T, Hong Kong SAR, China
| | - Kelvin K C Ng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, 30-32, Ngan Shing Street, Shatin, N.T, Hong Kong SAR, China
| | - Paul B S Lai
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, 30-32, Ngan Shing Street, Shatin, N.T, Hong Kong SAR, China
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21
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Obonyo D, Uslar VN, Münding J, Weyhe D, Tannapfel A. The impact of resection margin distance on survival and recurrence in pancreatic ductal adenocarcinoma in a retrospective cohort analysis. PLoS One 2023; 18:e0281921. [PMID: 36800357 PMCID: PMC9937496 DOI: 10.1371/journal.pone.0281921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 02/04/2023] [Indexed: 02/18/2023] Open
Abstract
BACKGROUND The prognostic effect of resection margin status following pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) remains controversial, even with the implementation of standardized pathological assessment. We therefore investigated the impact of resection margin (RM) status and RM distance in curative resected PDAC on overall survival (OS), disease-free survival (DFS) and recurrence. METHOD 108 patients were retrieved from a prospectively maintained database of a certified pancreatic cancer center. Distribution and relationships between circumferential resection margin (CRM) involvement (CRM≤1mm; CRM>1mm; CRM≥2mm) and their prognostic impact on OS and DFS were assessed using Kaplan-Meier statistics and the Log-Rank test. Multivariate logistic regression was used explain the development of a recurrence 12 months after surgery. RESULTS 63 out of 108 patients had medial RM and 32 posterior RM involvement. There was no significant difference in OS and DFS between CRM≤1mm and CRM>1mm resections. Clearance at the medial margin of ≥2mm had an impact on OS and DFS, (RM≥2mm vs. RM<2mm: median OS 29.8 vs 16.8 months, median DFS 19.6 vs. 10.3 months). Multivariate analysis demonstrated that age, medial RM ≥2mm, lymph node status and chemotherapy were prognostic factors for OS and DFS. Posterior RM had no influence on OS or DFS. CONCLUSION Not all RM seem to have the same impact on OS and DFS, and a clearance of 1mm for definition of a negative RM (i.e. CRM>1mm) seems not sufficient. Future studies should include more patients to stratify for potential confounders we could not account for. TRIAL REGISTRATION This study was registered with the German Clinical Trials Registry (reference number DRKS0017425).
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Affiliation(s)
- Dennis Obonyo
- University Hospital for Visceral Surgery, Carl von Ossietzky University Oldenburg, Oldenburg, Germany
| | - Verena Nicole Uslar
- University Hospital for Visceral Surgery, Carl von Ossietzky University Oldenburg, Oldenburg, Germany
- * E-mail:
| | - Johanna Münding
- Institute for Pathology, Ruhr University Bochum, Bochum, Germany
| | - Dirk Weyhe
- University Hospital for Visceral Surgery, Carl von Ossietzky University Oldenburg, Oldenburg, Germany
| | - Andrea Tannapfel
- Institute for Pathology, Ruhr University Bochum, Bochum, Germany
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22
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The Timing of Surgery Following Stereotactic Body Radiation Therapy Impacts Local Control for Borderline Resectable or Locally Advanced Pancreatic Cancer. Cancers (Basel) 2023; 15:cancers15041252. [PMID: 36831594 PMCID: PMC9954439 DOI: 10.3390/cancers15041252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 02/14/2023] [Accepted: 02/14/2023] [Indexed: 02/18/2023] Open
Abstract
We aimed to evaluate the impact of time from stereotactic body radiation therapy (SBRT) to surgery on treatment outcomes and post-operative complications in patients with borderline resectable or locally advanced pancreatic cancer (BRPC/LAPC). We conducted a single-institutional retrospective analysis of patients with BRPC/LAPC treated from 2016 to 2021 with neoadjuvant chemotherapy followed by SBRT and surgical resection. Covariates were stratified by time from SBRT to surgery. A Cox regression model was used to identify variables associated with survival outcomes. In 171 patients with BRPC/LAPC, the median time from SBRT to surgery was 6.4 (range: 2.7-25.3) weeks. Hence, patients were stratified by the timing of surgery: ≥6 and <6 weeks after SBRT. In univariable Cox regression, surgery ≥6 weeks was associated with improved local control (LC, HR 0.55, 95% CI 0.30-0.98; p = 0.042), pathologic node positivity, elevated baseline CA19-9, and inferior LC if of the male sex. In multivariable analysis, surgery ≥6 weeks (p = 0.013; HR 0.46, 95%CI 0.25-0.85), node positivity (p = 0.019; HR 2.09, 95% CI 1.13-3.88), and baseline elevated CA19-9 (p = 0.002; HR 2.73, 95% CI 1.44-5.18) remained independently associated with LC. Clavien-Dindo Grade ≥3B complications occurred in 4/63 (6.3%) vs. 5/99 (5.5%) patients undergoing surgery <6 weeks and ≥6 weeks after SBRT (p = 0.7). In summary, the timing of surgery ≥6 weeks after SBRT was associated with improved local control and low post-operative complication rates, irrespective of the surgical timing. Further investigation of the influence of surgical timing following radiotherapy is warranted.
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23
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Dreyer SB, Rae S, Bisset K, Upstill-Goddard R, Gemenetzis G, Johns AL, Dickson EJ, Mittal A, Gill AJ, Duthie F, Pea A, Lawlor RT, Scarpa A, Salvia R, Pulvirenti A, Zerbi A, Marchesi F, McKay CJ, Biankin AV, Samra JS, Chang DK, Jamieson NB. The Impact of Molecular Subtyping on Pathological Staging of Pancreatic Cancer. Ann Surg 2023; 277:e396-e405. [PMID: 36745763 PMCID: PMC9831035 DOI: 10.1097/sla.0000000000005050] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND The long-term outcomes following surgical resection for pancreatic ductal adenocarcinoma (PDAC) remains poor, with only 20% of patients surviving 5 years after pancreatectomy. Patient selection for surgery remains suboptimal largely due to the absence of consideration of aggressive tumor biology. OBJECTIVE The aim of this study was to evaluate traditional staging criteria for PDAC in the setting of molecular subtypes. METHODS Clinicopathological data were obtained for 5 independent cohorts of consecutive unselected patients, totaling n = 1298, including n = 442 that underwent molecular subtyping. The main outcome measure was disease-specific survival following surgical resection for PDAC stratified according to the American Joint Commission for Cancer (TNM) staging criteria, margin status, and molecular subtype. RESULTS TNM staging criteria and margin status confers prognostic value only in tumors with classical pancreatic subtype. Patients with tumors that are of squamous subtype, have a poor outcome irrespective of favorable traditional pathological staging [hazard ratio (HR) 1.54, 95% confidence interval (CI) 1.04-2.28, P = 0.032]. Margin status has no impact on survival in the squamous subtype (16.0 vs 12.1 months, P = 0.374). There were no differences in molecular subtype or gene expression of tumors with positive resection margin status. CONCLUSIONS Aggressive tumor biology as measured by molecular subtype predicts poor outcome following pancreatectomy for PDAC and should be utilized to inform patient selection for surgery.
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Affiliation(s)
- Stephan B Dreyer
- Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, Scotland, United Kingdom
- West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom
| | - Sarah Rae
- Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, Scotland, United Kingdom
| | - Kirsty Bisset
- West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom
| | - Rosie Upstill-Goddard
- Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, Scotland, United Kingdom
| | - Georgios Gemenetzis
- West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom
| | - Amber L Johns
- The Kinghorn Cancer Centre, 370 Victoria Street, Darlinghurst and Garvan Institute of Medical Research, Sydney, NSW, Australia
| | - Euan J Dickson
- West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom
| | - Anubhav Mittal
- Department of Surgery, Royal North Shore Hospital, St Leonards, Sydney, NSW, Australia
- University of Sydney, Sydney, NSW, Australia
| | - Anthony J Gill
- The Kinghorn Cancer Centre, 370 Victoria Street, Darlinghurst and Garvan Institute of Medical Research, Sydney, NSW, Australia
- Cancer Diagnosis and Pathology Group Kolling Institute of Medical Research and Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, NSW, Australia
- Northern Clinical School, Faculty of Medicine, University of Sydney, Sydney, Australia
| | - Fraser Duthie
- Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
| | - Antonio Pea
- Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, Scotland, United Kingdom
- General and Pancreatic Surgery Department, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Rita T Lawlor
- ARC-Net Research Center, University and Hospital Trust of Verona, Verona, Italy
| | - Aldo Scarpa
- ARC-Net Research Center, University and Hospital Trust of Verona, Verona, Italy
- Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Verona, Italy; Pancreatic Surgery Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Roberto Salvia
- General and Pancreatic Surgery Department, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | | | - Alessandro Zerbi
- University of Sydney, Sydney, NSW, Australia
- Department of Biomedical Sciences, Humanitas University, Pieve Emanule, Milan, Italy
| | - Federica Marchesi
- Department of Immunology, IRCCS Humanitas Research Hospital, Rozzano, Italy; and
- Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
| | - Colin J McKay
- Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, Scotland, United Kingdom
- West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom
| | - Andrew V Biankin
- Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, Scotland, United Kingdom
- West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom
| | - Jaswinder S Samra
- Department of Surgery, Royal North Shore Hospital, St Leonards, Sydney, NSW, Australia
| | - David K Chang
- Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, Scotland, United Kingdom
- West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom
| | - Nigel B Jamieson
- Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, Scotland, United Kingdom
- West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom
- Department of Surgery, Royal North Shore Hospital, St Leonards, Sydney, NSW, Australia
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Yamazaki H, Sugino K, Katoh R, Masudo K, Matsuzu K, Kitagawa W, Nagahama M, Rino Y, Ito K. Impact of Local Control on Clinical Course in Stage IVC Anaplastic Thyroid Carcinoma. World J Surg 2022; 46:3034-3042. [PMID: 36127501 DOI: 10.1007/s00268-022-06739-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/03/2022] [Indexed: 01/14/2023]
Abstract
BACKGROUND The present study investigated the association between local resection and cause of death in anaplastic thyroid carcinoma (ATC) patients with stage IVC disease. METHODS A total of 54 ATC patients with stage IVC disease were included in the study. Information including patient characteristics, laboratory data including complete blood count, treatment, and death were collected for analysis. RESULTS The median overall survival (OS) for patients with or without resection was 8.4 [95% confidence interval (CI) 5.9-14.4)] and 4.2 (95% CI 2.5-6.2) months, respectively (p < 0.001). No patients survived without resection at 1 year. Univariate analysis revealed that resection (p < 0.001) and radiotherapy (p = 0.018) were significantly associated with OS. Multivariate analysis revealed that resection (hazard ratio 0.257; 95% CI 0.115-0.575; p < 0.001) was the only independent prognostic factor of OS. In ATC patients with known resection status, the median OS for the patients with a resection status of R0/1 (n = 28) and R2 (n = 7) were 13.0 (95% CI 7.5-18.7) and 1.7 (95% CI 0.1-6.2) months, respectively (p < 0.001). The most common specific cause of death was respiratory insufficiency (35%), followed by airway obstruction (25%) and cerebral cardiovascular-related death (5%). The frequency of airway obstruction was significantly lower in patients with resection (p = 0.018). CONCLUSIONS Resection probably impacts on clinical course in ATC patients despite the presence of distant metastasis. However, R2 resection is likely to be harmful and surgeons should carefully consider the resectability of thyroid tumors.
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Affiliation(s)
- Haruhiko Yamazaki
- Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, 4-57 Urafunecho, Minamiku, Yokohama City, Kanagawa, 232-0024, Japan. .,Department of Surgery, Ito Hospital, 4-3-6, Jingumae, Shibuya-ku, Tokyo, 150-8308, Japan.
| | - Kiminori Sugino
- Department of Surgery, Ito Hospital, 4-3-6, Jingumae, Shibuya-ku, Tokyo, 150-8308, Japan
| | - Ryohei Katoh
- Department of Pathology, Ito Hospital, 4-3-6, Jingumae, Shibuya-ku, Tokyo, 150-8308, Japan
| | - Katsuhiko Masudo
- Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, 4-57 Urafunecho, Minamiku, Yokohama City, Kanagawa, 232-0024, Japan
| | - Kenichi Matsuzu
- Department of Surgery, Ito Hospital, 4-3-6, Jingumae, Shibuya-ku, Tokyo, 150-8308, Japan
| | - Wataru Kitagawa
- Department of Surgery, Ito Hospital, 4-3-6, Jingumae, Shibuya-ku, Tokyo, 150-8308, Japan
| | - Mitsuji Nagahama
- Department of Surgery, Ito Hospital, 4-3-6, Jingumae, Shibuya-ku, Tokyo, 150-8308, Japan
| | - Yasushi Rino
- Department of Surgery, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama City, Kanagawa, 236-0004, Japan
| | - Koichi Ito
- Department of Surgery, Ito Hospital, 4-3-6, Jingumae, Shibuya-ku, Tokyo, 150-8308, Japan
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Seufferlein T, Mayerle J, Böck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie zum exokrinen Pankreaskarzinom – Langversion 2.0 – Dezember 2021 – AWMF-Registernummer: 032/010OL. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e812-e909. [PMID: 36368658 DOI: 10.1055/a-1856-7346] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Affiliation(s)
| | | | - Stefan Böck
- Medizinische Klinik und Poliklinik III, Universitätsklinikum München, Germany
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Universitätsklinikum, Heidelberg, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Universitätsklinikum Hamburg-Eppendorf Medizinische Klinik und Poliklinik II Onkologie Hämatologie, Hamburg, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
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26
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Fossaert V, Mimmo A, Rhaiem R, Rached LJ, Brasseur M, Brugel M, Pegoraro F, Sanchez S, Bouché O, Kianmanesh R, Piardi T. Neoadjuvant chemotherapy for borderline resectable and upfront resectable pancreatic cancer increasing overall survival and disease-free survival? Front Oncol 2022; 12:980659. [PMID: 36387257 PMCID: PMC9640996 DOI: 10.3389/fonc.2022.980659] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 09/06/2022] [Indexed: 08/29/2023] Open
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic neoplasm. Surgery is the factual curative option, but most patients present with advanced disease. In order to increase resectability, results of neoadjuvant chemotherapy (NAC) on metastatic disease were extrapolated to the neoadjuvant setting by many centers. The aim of our study was to retrospectively evaluate the outcome of patients who underwent upfront surgery (US)-PDAC and borderline (BR)-PDAC, and those resected after NAC to determine prognostic factors that might affect the outcome in these resected patients. METHODS One hundred fifty-one patients between January 2012 and March 2021 in our department were reviewed. Epidemiological characteristics and pre-operative induction treatment were assessed. Pathological reports were analyzed to evaluate the quality of oncological resection (R0/R1). Post-operative mortality and morbidity and survival data were reviewed. RESULTS One hundred thirteen patients were addressed for US, and 38 were considered BR and referred for surgery after induction chemotherapy. The pancreatic resection R0 was 71.5% and R1 28.5%. pT3 rate was significantly higher in the US than BR (58,4% vs 34,2%, p= 0.005). The mean OS and DFS rates were 29.4 months 15.9 months respectively. There was no difference between OS and DFS of US vs BR patients. N0 patients had significantly longer OS and DFS (p=<0.001). R0 patients had significantly longer OS (p=0.03) and longer DFS (P=0.08). In the multivariate analysis, the presence of postoperative pancreatic fistula, R1 resection, N+ and not access to adjuvant chemotherapy were bad prognostic factors of OS. CONCLUSIONS Our study suggests the benefits of NAC for BR patients in downstaging tumors and rendering them amenable to resection, with same oncological result compared to US.
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Affiliation(s)
- Violette Fossaert
- Department of Oncological Digestive Surgery, Hepatobiliary and Pancreatic Surgery Unit, University Reims Champagne-Ardenne, Reims, France
| | - Antonio Mimmo
- Department of Oncological Digestive Surgery, Hepatobiliary and Pancreatic Surgery Unit, University Reims Champagne-Ardenne, Reims, France
| | - Rami Rhaiem
- Department of Oncological Digestive Surgery, Hepatobiliary and Pancreatic Surgery Unit, University Reims Champagne-Ardenne, Reims, France
| | - Linda J. Rached
- Department of Oncological Digestive Surgery, Hepatobiliary and Pancreatic Surgery Unit, University Reims Champagne-Ardenne, Reims, France
| | - Mathilde Brasseur
- Department of Digestive Medical Oncology, University Reims Champagne-Ardenne, Reims, France
| | - Mathias Brugel
- Department of Digestive Medical Oncology, University Reims Champagne-Ardenne, Reims, France
| | - Francesca Pegoraro
- Department of Oncological Digestive Surgery, Hepatobiliary and Pancreatic Surgery Unit, University Reims Champagne-Ardenne, Reims, France
- Division of Hepato-Bilio-Pancreatic, Minimally Invasive, Robotic Surgery and Kidney Transplantation, Department of Clinical Medicine and Surgery, Federico II University Hospital, Naples, Italy
| | - Stephane Sanchez
- Pôle Territorial Santé Publique et Performance des Hôpitaux Champagne Sud, University Reims Champagne-Ardenne, Troyes, France
| | - Olivier Bouché
- Department of Digestive Medical Oncology, University Reims Champagne-Ardenne, Reims, France
| | - Reza Kianmanesh
- Department of Oncological Digestive Surgery, Hepatobiliary and Pancreatic Surgery Unit, University Reims Champagne-Ardenne, Reims, France
| | - Tullio Piardi
- Department of Oncological Digestive Surgery, Hepatobiliary and Pancreatic Surgery Unit, University Reims Champagne-Ardenne, Reims, France
- Department of Surgery, Hepato-Bilio-Pancreatic and Metabolic Unit, University Reims Champagne-Ardenne, Troyes, France
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27
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Holm MB, Verbeke CS. Prognostic Impact of Resection Margin Status on Distal Pancreatectomy for Ductal Adenocarcinoma. Curr Oncol 2022; 29:6551-6563. [PMID: 36135084 PMCID: PMC9498008 DOI: 10.3390/curroncol29090515] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 09/08/2022] [Accepted: 09/12/2022] [Indexed: 11/16/2022] Open
Abstract
Pancreatic cancer is associated with a poor prognosis. While surgical resection is the only treatment option with curative intent, most patients die of locoregional and/or distant recurrence. The prognostic impact of the resection margin status has received much attention. However, the evidence is almost exclusively related to pancreatoduodenectomies, while corresponding data for distal pancreatectomy specimens are limited. The key data, such as the rate of microscopic margin involvement (“R1”), the site of margin involvement, and the impact of R1 on patient outcome, are divergent between studies and do not currently allow any general conclusions. The main reasons for the variability in the published data are the small size of the study cohorts and their heterogeneity, as well as the marked divergence in pathology examination practices. The latter is a consequence of the lack of concrete guidance, both for grossing and microscopic examination. The increasing administration of neoadjuvant chemo(radio)therapy introduces a further factor of uncertainty as the conventional definition of a tumour-free margin (“R0”) based on 1 mm clearance is inadequate for these specimens. This review discusses the published data regarding the prognostic impact of margin status in distal pancreatectomy specimens along with the challenges and uncertainties that are related to the assessment of the margins.
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Affiliation(s)
- Maia Blomhoff Holm
- Department of Pathology, Faculty of Medicine, University of Oslo, 0372 Oslo, Norway
- Department of Pathology, Oslo University Hospital, 0424 Oslo, Norway
| | - Caroline Sophie Verbeke
- Department of Pathology, Faculty of Medicine, University of Oslo, 0372 Oslo, Norway
- Department of Pathology, Oslo University Hospital, 0424 Oslo, Norway
- Correspondence: ; Tel.: +47-405-578-36
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28
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Seufferlein T, Mayerle J, Böck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie zum exokrinen Pankreaskarzinom – Kurzversion 2.0 – Dezember 2021, AWMF-Registernummer: 032/010OL. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:991-1037. [PMID: 35671996 DOI: 10.1055/a-1771-6811] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Affiliation(s)
| | | | - Stefan Böck
- Medizinische Klinik und Poliklinik III, Universitätsklinikum München, Germany
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Universitätsklinikum, Heidelberg, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Universitätsklinikum Hamburg-Eppendorf Medizinische Klinik und Poliklinik II Onkologie Hämatologie, Hamburg, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
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29
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Brunner M, Krautz C, Weber GF, Grützmann R. [Better Therapy for Pancreatic Cancer through More Radical Surgery?]. Zentralbl Chir 2022; 147:173-187. [PMID: 35378558 DOI: 10.1055/a-1766-7643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Despite advances in the treatment of pancreatic cancer, the survival of affected patients remains limited. A more radical surgical therapy could help to improve the prognosis, in particular by reducing the local recurrence rate, which is around 45% in patients with resected pancreatic cancer. In addition, patients with oligometastatic pancreatic cancer could also benefit from a more radical indication for surgery.Based on an analysis of the literature, important principles of pancreatic cancer surgery were examined.Even if even more radical surgical approaches such as an "extended" lymphadenectomy or a standard complete pancreatectomy do not bring any survival advantage, complete resection of the tumour (R0), a thorough locoregional lymphadenectomy and an adequate radical dissection in the area of the peripancreatic vessels including periarterial nerve plexuses should be the standard of pancreatic carcinoma resections. Whenever necessary to achieve an R0 resection, resections of the pancreas have to be extended, as well as additional venous vascular resections and multivisceral resections had to be performed. Simultaneous arterial vascular resections as part of pancreatic resections as well as surgical resections in oligometastatic patients should, however, be reserved for selected patients. These aspects of the surgical technique in pancreatic carcinoma mentioned above must not be neglected from the point of view of an "existing limited prognosis". On the contrary, they form the absolutely necessary basis in order to achieve good survival results in combination with system therapy. However, it may always be necessary to adapt these standards according to the age, comorbidities and wishes of the patient.
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Affiliation(s)
- Maximilian Brunner
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - Christian Krautz
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - Georg F Weber
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - Robert Grützmann
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Erlangen, Erlangen, Deutschland
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30
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Leonhardt CS, Niesen W, Kalkum E, Klotz R, Hank T, Büchler MW, Strobel O, Probst P. Prognostic relevance of the revised R status definition in pancreatic cancer: meta-analysis. BJS Open 2022; 6:zrac010. [PMID: 35301513 PMCID: PMC8931487 DOI: 10.1093/bjsopen/zrac010] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 12/15/2021] [Accepted: 01/17/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND The prognostic impact of margin status is reported with conflicting results after pancreatic cancer resection. While some studies validated an uninvolved resection margin (R0) 1 mm or more of tumour clearance, others have failed to show benefit. This systematic review and meta-analysis aimed to investigate the effects of margin definitions on median overall survival (OS). METHODS MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for studies reporting associations between resection margins and OS between 2010 and 2021. Data regarding margin status (R0 circumferential resection margin (CRM) negative (CRM-), R0 CRM positive (CRM+), R0 direct, and R1 and OS were extracted. Hazard ratios (HRs) were pooled with a random-effects model. The risk of bias was evaluated with the Quality in Prognosis Studies (QUIPS) tool. RESULTS The full texts of 774 studies were screened. In total, 21 studies compromising 6056 patients were included in the final synthesis. In total, 188 (24 per cent) studies were excluded due to missing margin definitions. The R0 (CRM+) rate was 50 per cent (95 per cent confidence interval (c.i.) 0.40 to 0.61) and the R0 (CRM-) rate was 38 per cent (95 per cent c.i. 0.29 to 0.47). R0 (CRM-) resection was independently associated with improved OS compared to combined R1 and R0 (CRM+; HR 1.36, 95 per cent c.i. 1.23 to 1.56). CONCLUSION The revised R status was confirmed as an independent prognosticator compared to combined R0 (CRM+) and R1. The limited number of studies, non-standardized pathology protocols, and the varying number of margins assessed hamper comparability.
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Affiliation(s)
- Carl Stephan Leonhardt
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Willem Niesen
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Eva Kalkum
- Study Center of the German Society of Surgery, University of Heidelberg, Heidelberg, Germany
| | - Rosa Klotz
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Study Center of the German Society of Surgery, University of Heidelberg, Heidelberg, Germany
| | - Thomas Hank
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Markus Wolfgang Büchler
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Oliver Strobel
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Pascal Probst
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Study Center of the German Society of Surgery, University of Heidelberg, Heidelberg, Germany
- Department of Surgery, Cantonal Hospital Thurgau, Frauenfeld, Switzerland
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31
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Mangieri CW, Valenzuela CD, Erali RA, Shen P, Howerton R, Clark CJ. Prognostic Effect of Aberrant Right Hepatic Artery with Pancreaticoduodenectomy: Focus on Hepatic Recurrence. Ann Surg Oncol 2022; 29:3219-3228. [DOI: 10.1245/s10434-022-11341-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 12/31/2021] [Indexed: 11/18/2022]
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32
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Sahakyan MA, Verbeke CS, Tholfsen T, Ignjatovic D, Kleive D, Buanes T, Lassen K, Røsok BI, Labori KJ, Edwin B. Prognostic Impact of Resection Margin Status in Distal Pancreatectomy for Ductal Adenocarcinoma. Ann Surg Oncol 2022; 29:366-375. [PMID: 34296358 PMCID: PMC8677636 DOI: 10.1245/s10434-021-10464-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Accepted: 06/29/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND Resection margin status is considered one of the few surgeon-controlled parameters affecting prognosis in pancreatic ductal adenocarcinoma (PDAC). While studies mostly focus on resection margins in pancreatoduodenectomy, little is known about their role in distal pancreatectomy (DP). This study aimed to investigate resection margins in DP for PDAC. METHODS Patients who underwent DP for PDAC between October 2004 and February 2020 were included (n = 124). Resection margins and associated parameters were studied in two consecutive time periods during which different pathology examination protocols were used: non-standardized (period 1: 2004-2014) and standardized (period 2: 2015-2020). Microscopic margin involvement (R1) was defined as ≤1 mm clearance. RESULTS Laparoscopic and open resections were performed in 117 (94.4%) and 7 (5.6%) patients, respectively. The R1 rate for the entire cohort was 73.4%, increasing from 60.4% in period 1 to 83.1% in period 2 (p = 0.005). A significantly higher R1 rate was observed for the posterior margin (35.8 vs. 70.4%, p < 0.001) and anterior pancreatic surface (based on a 0 mm clearance; 18.9 vs. 35.4%, p = 0.045). Pathology examination period, poorly differentiated PDAC, and vascular invasion were associated with R1 in the multivariable model. Extended DP, positive anterior pancreatic surface, lymph node ratio, perineural invasion, and adjuvant chemotherapy, but not R1, were significant prognostic factors for overall survival in the entire cohort. CONCLUSIONS Pathology examination is a key determinant of resection margin status following DP for PDAC. A high R1 rate is to be expected when pathology examination is meticulous and standardized. Involvement of the anterior pancreatic surface affects prognosis.
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Affiliation(s)
- Mushegh A Sahakyan
- The Intervention Centre, Rikshospitalet, Oslo University Hospital, Oslo, Norway.
- Division of Emergencies and Critical Care, Department of Research and Development, Oslo University Hospital, Oslo, Norway.
- Department of Surgery N1, Yerevan State Medical University, Yerevan, Armenia.
| | - Caroline S Verbeke
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Pathology, Rikshospitalet, Oslo University Hospital, Oslo, Norway
| | - Tore Tholfsen
- Department of Hepato-Pancreato-Biliary Surgery, Rikshospitalet, Oslo University Hospital, Oslo, Norway
| | - Dejan Ignjatovic
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Digestive Surgery, Akershus University Hospital, Lørenskog, Norway
| | - Dyre Kleive
- Department of Hepato-Pancreato-Biliary Surgery, Rikshospitalet, Oslo University Hospital, Oslo, Norway
| | - Trond Buanes
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Kristoffer Lassen
- Department of Hepato-Pancreato-Biliary Surgery, Rikshospitalet, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway
| | - Bård I Røsok
- Department of Hepato-Pancreato-Biliary Surgery, Rikshospitalet, Oslo University Hospital, Oslo, Norway
| | - Knut Jørgen Labori
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Hepato-Pancreato-Biliary Surgery, Rikshospitalet, Oslo University Hospital, Oslo, Norway
| | - Bjørn Edwin
- The Intervention Centre, Rikshospitalet, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Hepato-Pancreato-Biliary Surgery, Rikshospitalet, Oslo University Hospital, Oslo, Norway
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33
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Sohn HJ, Kim H, Kim SJ, Lee KB, Han Y, Lee JM, Kang JS, Kwon W, Chie EK, Kim H, Jang JY. Oncologic outcomes according to the location and status of resection margin in pancreas head cancer: role of radiation therapy in R1 resection. Ann Surg Treat Res 2022; 102:10-19. [PMID: 35071115 PMCID: PMC8753382 DOI: 10.4174/astr.2022.102.1.10] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 11/13/2021] [Accepted: 12/03/2021] [Indexed: 11/30/2022] Open
Abstract
Purpose The clinical significance of margin status in pancreatic head cancer is still controversial due to the nonstandardized definition of R status and pathologic reporting. This study aims to evaluate the impact of the margin status including location and the role of radiation therapy in pancreatic head cancer. Methods A total of 314 patients who underwent curative-intent surgery for pancreatic head cancer between 2010 and 2017 were analyzed. Demographics, survival, and local recurrences were compared according to 2 definitions: 0-mm R1 as direct involvement and 1-mm R1 as close resection margin less than 1 mm. The specific margins were divided into 4 groups according to the location around the pancreas: pancreas transection, anterior surface, posterior surface, and vessel (superior mesenteric artery/superior mesenteric vein) margin. Results The 0-mm R1-rate was 15.6%, and increased to 36.3% in 1-mm R1. The median overall survival rate of 0-mm R0 vs. R1 was 26 months vs. 16 months (P = 0.052) and that of 1-mm R0 vs. R1 was 27 months vs. 18 months, respectively (P = 0.016). In individual margins, posterior, anterior surface, and pancreas transection margin involvement were associated with poor outcome, and the 1 mm posterior surface involvement was an independent risk factor for disease-free survival (hazard ratio, 1.63). Adjuvant radiation therapy had oncologic benefits, especially in R1 patients (P = 0.011) compared to R0 patients (P = 0.088). Conclusion Margin status, especially 1-mm R1 status is an important predictive factor, and involved posterior surface has a clinical impact. Patients with positive margins should be considered adjuvant radiation therapy.
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Affiliation(s)
- Hee Ju Sohn
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hongbeom Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Sun Joo Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung Bun Lee
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
| | - Youngmin Han
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jung Min Lee
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Seung Kang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Eui Kyu Chie
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea
| | - Haeryoung Kim
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Comparative Recurrence Analysis of Pancreatic Adenocarcinoma after Resection. JOURNAL OF ONCOLOGY 2021; 2021:3809095. [PMID: 34721578 PMCID: PMC8553472 DOI: 10.1155/2021/3809095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 09/26/2021] [Accepted: 10/11/2021] [Indexed: 11/18/2022]
Abstract
Purpose The relation between tumor sites of pancreatic ductal adenocarcinoma (PDAC) and recurrence was not fully investigated before. We aimed to describe the differences of recurrent patterns in PDAC of head and body/tail after curative surgery. Methods The recurrent patterns of PDAC were compared and the associations with clinical characteristics were analyzed in these patients. Prognostic factors of overall survival (OS) and progression-free survival (PFS) were analyzed and validated. Predictive systems were constructed and measured by the area under the AUC curve and concordance index (C-index). Results A total of 302 PDAC patients were included in this study, including 247 patients with PDAC of head and another 55 patients with PDAC of body/tail. Patients who developed tumor recurrence within 24 months after resection had significantly shorter OS in both groups. Liver metastasis occupied most of the tumor progressions and diminished while local recurrence increased gradually over time. The variation trends were similar for patients in both groups while these changes were more pronounced for patients in the head group. Local recurrence and liver-only metastasis seemed to indicate a better OS. Furthermore, predictive systems for OS and PFS prediction based on independent risk factors were established and showed significant higher values of AUC and C-indexes compared with the TNM stage system. Conclusions Different characteristics of progressions for PDAC of head and body/tail suggested biological heterogeneity. The exploration of these variations helps to provide personalized management of recurrence in PDAC.
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Soer EC, Verbeke CS. Pathology reporting of margin status in locally advanced pancreatic cancer: challenges and uncertainties. J Gastrointest Oncol 2021; 12:2512-2520. [PMID: 34790412 PMCID: PMC8576237 DOI: 10.21037/jgo-20-391] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 12/04/2020] [Indexed: 12/24/2022] Open
Abstract
Chemo(radio)therapy is becoming the new standard for patients with locally advanced pancreatic cancer. In case of tumor regression on imaging, surgical resection can be undertaken, albeit often with the need for extended procedures. Reevaluation of the current routine pathology procedures is required to establish the appropriate histopathological approach of the resulting specimens. This review focusses on margin status, which is universally considered a core data item of the pathology report, of relevance to both the management of the individual patient and the evaluation of the result of surgery in this particular patient group. As explained in this review, due to the cytoreductive effect of neoadjuvant therapy, the conventional definition of a tumor-free margin ("R0") based on 1 mm clearance is not adequate. Furthermore, the complexity of many of the specimens following extended or multivisceral en bloc surgical resection make margin assessment challenging. These large specimens require extensive sampling, which is not always easily implemented in daily practice. At present, there is marked divergence in pathology practice, and consequently, neither the true R0-rate nor the exact prognostic effect of the margin status have been definitively established for resected locally advanced pancreatic cancer. A concerted effort towards uniform and optimal margin assessment is unfortunately still lacking.
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Affiliation(s)
- Eline C. Soer
- Department of Pathology, Amsterdam Medical Center, Amsterdam, The Netherlands
| | - Caroline S. Verbeke
- Department of Pathology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Pathology, Oslo University Hospital, Oslo, Norway
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Dhall D, Shi J, Allende DS, Jang KT, Basturk O, Adsay NV, Kim GE. Towards a More Standardized Approach to Pathologic Reporting of Pancreatoduodenectomy Specimens for Pancreatic Ductal Adenocarcinoma: Cross-continental and Cross-specialty Survey From the Pancreatobiliary Pathology Society Grossing Working Group. Am J Surg Pathol 2021; 45:1364-1373. [PMID: 33899790 PMCID: PMC8446290 DOI: 10.1097/pas.0000000000001723] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
In recent literature and international meetings held, it has become clear that there are significant differences regarding the definition of what constitutes as margins and how best to document the pathologic findings in pancreatic ductal adenocarcinoma. To capture the current practice, Pancreatobiliary Pathology Society (PBPS) Grossing Working Group conducted an international multispecialty survey encompassing 25 statements, regarding pathologic examination and reporting of pancreatic ductal adenocarcinoma, particularly in pancreatoduodenectomy specimens. The survey results highlighted several discordances; however, consensus/high concordance was reached for the following: (1) the pancreatic neck margin should be entirely submitted en face, and if tumor on the slide, then it is considered equivalent to R1; (2) uncinate margin should be submitted entirely and perpendicularly sectioned, and tumor distance from the uncinate margin should be reported; (3) all other surfaces (including vascular groove, posterior surface, and anterior surface) should be examined and documented; (4) carcinoma involving separately submitted celiac axis specimen should be staged as pT4. Although no consensus was achieved regarding what constitutes R1 versus R0, most participants agreed that ink on tumor or at and within 1 mm to the tumor is equivalent to R1 only in areas designated as a margin, not surface. In conclusion, this survey raises the awareness of the discordances and serves as a starting point towards further standardization of the pancreatoduodenectomy grossing and reporting protocols.
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Affiliation(s)
- Deepti Dhall
- Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL, USA
| | - Jiaqi Shi
- Department of Pathology, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA
| | - Daniela S Allende
- Department of Pathology, Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Kee-Taek Jang
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Olca Basturk
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Nazmi Volkan Adsay
- Department of Pathology, Koç University and American Hospital, Istanbul, Turkey
| | - Grace E. Kim
- Department of Pathology, University of California San Francisco, San Francisco, CA
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Ng KYY, Chow EWX, Jiang B, Lim C, Goh BKP, Lee SY, Teo JY, Tan DMY, Cheow PC, Ooi LLPJ, Chow PKH, Lee JJX, Kam JH, Koh YX, Jeyaraj PR, Tan EK, Choo SP, Chan CY, Chung AYF, Tai D. Resected pancreatic adenocarcinoma: An Asian institution's experience. Cancer Rep (Hoboken) 2021; 4:e1393. [PMID: 33939335 PMCID: PMC8551988 DOI: 10.1002/cnr2.1393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 03/08/2021] [Accepted: 03/25/2021] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Pancreatic adenocarcinoma (PDAC) is highly lethal. Surgery offers the only chance of cure, but 5-year overall survival (OS) after surgical resection and adjuvant therapy remains dismal. Adjuvant trials were mostly conducted in the West enrolling fit patients. Applicability to a general population, especially Asia has not been described adequately. AIM We aimed to evaluate the clinical outcomes, prognostic factors of survival, pattern, and timing of recurrence after curative resection in an Asian institution. METHODS AND RESULTS The clinicopathologic and survival outcomes of 165 PDAC patients who underwent curative resection between 1998 and 2013 were reviewed retrospectively. Median age at surgery was 62.0 years. 55.2% were male, and 73.3% had tumors involving the head of pancreas. The median OS of the entire cohort was 19.7 months. Median OS of patients who received adjuvant chemotherapy was 23.8 months. Negative predictors of survival include lymph node ratio (LNR) of >0.3 (HR = 3.36, P = .001), tumor site involving the body or tail of pancreas (HR = 1.59, P = .046), presence of perineural invasion (PNI) (HR = 2.36, P = .018) and poorly differentiated/undifferentiated tumor grade (HR = 1.86, P = .058). The median time to recurrence was 8.87 months, with 66.1% and 81.2% of patients developing recurrence at 12 months and 24 months respectively. The most common site of recurrence was the liver. CONCLUSION The survival of Asian patients with resected PDAC who received adjuvant chemotherapy is comparable to reported randomized trials. Clinical characteristics seem similar to Western patients. Hence, geographical locations may not be a necessary stratification factor in RCTs. Conversely, lymph node ratio and status of PNI ought to be incorporated.
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Affiliation(s)
- Kennedy Yao Yi Ng
- Division of Medical OncologyNational Cancer Centre SingaporeSingapore
| | | | - Bochao Jiang
- Division of Medical OncologyNational Cancer Centre SingaporeSingapore
| | - Cindy Lim
- Division of Clinical Trials and Epidemiological SciencesNational Cancer Centre SingaporeSingapore
| | - Brian Kim Poh Goh
- Department of Hepatopancreatobiliary and Transplantation SurgerySingapore General HospitalSingapore
- Division of Surgical OncologyNational Cancer Centre SingaporeSingapore
- Duke‐NUS Graduate Medical SchoolSingapore
| | - Ser Yee Lee
- Surgical Associates, National Cancer Centre SingaporeSingapore
| | - Jin Yao Teo
- Department of Hepatopancreatobiliary and Transplantation SurgerySingapore General HospitalSingapore
- Duke‐NUS Graduate Medical SchoolSingapore
| | - Damien Meng Yew Tan
- Duke‐NUS Graduate Medical SchoolSingapore
- Department of Gastroenterology and HepatologySingapore General HospitalSingapore
| | - Peng Chung Cheow
- Department of Hepatopancreatobiliary and Transplantation SurgerySingapore General HospitalSingapore
- Division of Surgical OncologyNational Cancer Centre SingaporeSingapore
- Duke‐NUS Graduate Medical SchoolSingapore
| | - London Lucien Peng Jin Ooi
- Department of Hepatopancreatobiliary and Transplantation SurgerySingapore General HospitalSingapore
- Division of Surgical OncologyNational Cancer Centre SingaporeSingapore
- Duke‐NUS Graduate Medical SchoolSingapore
| | - Pierce Kah Hoe Chow
- Department of Hepatopancreatobiliary and Transplantation SurgerySingapore General HospitalSingapore
- Division of Surgical OncologyNational Cancer Centre SingaporeSingapore
- Duke‐NUS Graduate Medical SchoolSingapore
| | | | - Juinn Huar Kam
- Department of Hepatopancreatobiliary and Transplantation SurgerySingapore General HospitalSingapore
| | - Ye Xin Koh
- Department of Hepatopancreatobiliary and Transplantation SurgerySingapore General HospitalSingapore
| | - Prema Raj Jeyaraj
- Department of Hepatopancreatobiliary and Transplantation SurgerySingapore General HospitalSingapore
| | - Ek Khoon Tan
- Department of Hepatopancreatobiliary and Transplantation SurgerySingapore General HospitalSingapore
| | - Su Pin Choo
- Division of Medical OncologyNational Cancer Centre SingaporeSingapore
- Curie Oncology, Graduate Medical SchoolSingapore General HospitalSingapore
| | - Chung Yip Chan
- Department of Hepatopancreatobiliary and Transplantation SurgerySingapore General HospitalSingapore
- Duke‐NUS Graduate Medical SchoolSingapore
| | - Alexander Yaw Fui Chung
- Department of Hepatopancreatobiliary and Transplantation SurgerySingapore General HospitalSingapore
- Division of Surgical OncologyNational Cancer Centre SingaporeSingapore
- Duke‐NUS Graduate Medical SchoolSingapore
| | - David Tai
- Division of Medical OncologyNational Cancer Centre SingaporeSingapore
- Duke‐NUS Graduate Medical SchoolSingapore
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Tonini V, Zanni M. Pancreatic cancer in 2021: What you need to know to win. World J Gastroenterol 2021; 27:5851-5889. [PMID: 34629806 PMCID: PMC8475010 DOI: 10.3748/wjg.v27.i35.5851] [Citation(s) in RCA: 79] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 07/14/2021] [Accepted: 08/23/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer is one of the solid tumors with the worst prognosis. Five-year survival rate is less than 10%. Surgical resection is the only potentially curative treatment, but the tumor is often diagnosed at an advanced stage of the disease and surgery could be performed in a very limited number of patients. Moreover, surgery is still associated with high post-operative morbidity, while other therapies still offer very disappointing results. This article reviews every aspect of pancreatic cancer, focusing on the elements that can improve prognosis. It was written with the aim of describing everything you need to know in 2021 in order to face this difficult challenge.
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Affiliation(s)
- Valeria Tonini
- Department of Medical Sciences and Surgery, University of Bologna- Emergency Surgery Unit, IRCCS Sant’Orsola Hospital, Bologna 40121, Italy
| | - Manuel Zanni
- University of Bologna, Emergency Surgery Unit, IRCCS Sant'Orsola Hospital, Bologna 40121, Italy
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Tomasello G, Ghidini M, Ghidini A, Trevisan F, Celotti A, Russo A, Gambini D, Indini A, Rijavec E, Bareggi C, Galassi B, Petrelli F. Total neoadjuvant therapy for initially inoperable pancreatic cancer: A systematic review of phase 2-3 studies. Radiother Oncol 2021; 164:13-19. [PMID: 34509562 DOI: 10.1016/j.radonc.2021.09.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Revised: 08/31/2021] [Accepted: 09/01/2021] [Indexed: 12/21/2022]
Abstract
INTRODUCTION Patients with initially inoperable non-metastatic pancreatic cancer (PC) have a poor prognosis, often similar to those with metastatic disease. Neoadjuvant chemotherapy (CT) plus concomitant or sequential radiotherapy (RT) may cause tumor shrinkage and allow for radical surgery. We pooled data of studies in which patients with locally advanced (unresectable) or borderline resectable PC were treated with a course of induction (or consolidation) CT followed or preceded by neoadjuvant CTRT regimen. MATERIALS AND METHODS We searched articles, including phase 2 or 3 studies, published in English from 2010 up to December 2020 in PubMed, SCOPUS, the Cochrane Library, and EMBASE. The primary outcomes were the pooled radical and R0 resection rates, median PFS and OS of included patients (those included in the intent to treat analysis). RESULTS A total of 28 studies were finally considered eligible for inclusion in quantitative analysis for a total of 2446 patients with locally advanced/borderline resectable PC. Overall the pooled rate of resection was 29.7% (95%CI 26.7-32.8%). In patients who completed the CT + CTRT program, the overall resection rate was 31.8% (95% 28.4-35.4%). After exclusion of studies that included resectable PCs, the overall resection rate was 19.9% (95%CI 17.3-22.7%). In studies were all patients had unresectable PC (n = 20 studies), the resection rate was 12.1% (95%CI 10-14.5%). In two studies that enrolled all borderline resectable PCs the resection rate was 59.2% (95%CI 48.9-68.8%). The pooled R0 resection rate was 68.7% (95%CI 64.7-72.3%). The median pooled OS was 15.7 months (95%CI 14-17.2 months) and the median pooled PFS was 10.7 (95%CI 9.3-12.1 months). CONCLUSIONS Surgery is a treatment option in about one third of patients with initially inoperable PC, following total neoadjuvant therapy. In unresectable cases the resection rate was 12%. Median OS and PFS rates were comparable with historical data of advanced PCs. Optimal integration and sequence of chemo- and radiotherapy in unresectable PC must still be defined.
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Affiliation(s)
- Gianluca Tomasello
- Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
| | - Michele Ghidini
- Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Antonio Ghidini
- Medical Oncology Unit, Casa di Cura Igea, Milan, Italy; GISCAD (Gruppo Italiano Studio Carcinomi Apparato Digerente)
| | | | - Andrea Celotti
- General Surgery 2, ASST Bergamo Ovest, Ospedale di Treviglio, Italy
| | - Alessandro Russo
- General Surgery 2, ASST Bergamo Ovest, Ospedale di Treviglio, Italy
| | - Donatella Gambini
- Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Alice Indini
- Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Erika Rijavec
- Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Claudia Bareggi
- Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Barbara Galassi
- Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Fausto Petrelli
- Oncology Unit, ASST Bergamo Ovest, Ospedale di Treviglio, Italy; GISCAD (Gruppo Italiano Studio Carcinomi Apparato Digerente)
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Silke J, O’Reilly LA. NF-κB and Pancreatic Cancer; Chapter and Verse. Cancers (Basel) 2021; 13:4510. [PMID: 34572737 PMCID: PMC8469693 DOI: 10.3390/cancers13184510] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 08/29/2021] [Accepted: 08/30/2021] [Indexed: 02/07/2023] Open
Abstract
Pancreatic Ductal Adenocarcinoma (PDAC) is one of the world's most lethal cancers. An increase in occurrence, coupled with, presently limited treatment options, necessitates the pursuit of new therapeutic approaches. Many human cancers, including PDAC are initiated by unresolved inflammation. The transcription factor NF-κB coordinates many signals that drive cellular activation and proliferation during immunity but also those involved in inflammation and autophagy which may instigate tumorigenesis. It is not surprising therefore, that activation of canonical and non-canonical NF-κB pathways is increasingly recognized as an important driver of pancreatic injury, progression to tumorigenesis and drug resistance. Paradoxically, NF-κB dysregulation has also been shown to inhibit pancreatic inflammation and pancreatic cancer, depending on the context. A pro-oncogenic or pro-suppressive role for individual components of the NF-κB pathway appears to be cell type, microenvironment and even stage dependent. This review provides an outline of NF-κB signaling, focusing on the role of the various NF-κB family members in the evolving inflammatory PDAC microenvironment. Finally, we discuss pharmacological control of NF-κB to curb inflammation, focussing on novel anti-cancer agents which reinstate the process of cancer cell death, the Smac mimetics and their pre-clinical and early clinical trials.
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Affiliation(s)
- John Silke
- Inflammation Division, Walter and Eliza Hall Institute of Medical Research (WEHI), Parkville, VIC 3052, Australia;
- Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia
| | - Lorraine Ann O’Reilly
- Inflammation Division, Walter and Eliza Hall Institute of Medical Research (WEHI), Parkville, VIC 3052, Australia;
- Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia
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Verbeke C, Webster F, Brosens L, Campbell F, Del Chiaro M, Esposito I, Feakins RM, Fukushima N, Gill AJ, Kakar S, Kench JG, Krasinskas AM, van Laethem JL, Schaeffer DF, Washington K. Dataset for the reporting of carcinoma of the exocrine pancreas: recommendations from the International Collaboration on Cancer Reporting (ICCR). Histopathology 2021; 79:902-912. [PMID: 34379823 DOI: 10.1111/his.14540] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 08/04/2021] [Accepted: 08/08/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND AND OBJECTIVES Current guidelines for the pathology reporting on pancreatic cancer differ in certain aspects, resulting in divergent reporting practice and a lack of comparability of data. Here we report on a new international dataset for the pathology reporting of resection specimens with cancer of the exocrine pancreas (ductal adenocarcinoma and acinar cell carcinoma). The dataset was produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter-)national pathology and cancer organisations. METHODS AND RESULTS According to the ICCR's rigorous process for dataset development, an international expert panel consisting of pancreatic pathologists, a pancreatic surgeon and an oncologist produced a set of core and non-core data items based on a critical review and discussion of current evidence. Commentary was provided for each data item to explain the rationale for selecting it as a core or non-core element, its clinical relevance, and to highlight potential areas of disagreement or lack of evidence, in which case a consensus position was formulated. Following international public consultation, the document was finalised and ratified, and the dataset, which includes a synoptic reporting guide, was published on the ICCR website. CONCLUSIONS This first international dataset for cancer of the exocrine pancreas is intended to promote high quality, standardised pathology reporting. Its widespread adoption will improve consistency of reporting, facilitate multidisciplinary communication and enhance comparability of data, all of which will help to improve the management of pancreatic cancer patients.
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Affiliation(s)
- Caroline Verbeke
- Department of Pathology, University of Oslo, Oslo University Hospital, Oslo, Norway
| | - Fleur Webster
- International Collaboration on Cancer Reporting, Sydney, Australia
| | - Lodewijk Brosens
- Department of Pathology, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands and Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Fiona Campbell
- Department of Pathology, Royal Liverpool University Hospital, Liverpool, United Kingdom
| | - Marco Del Chiaro
- Department of Surgery, University of Colorado Denver - Anschutz Medical Campus, Aurora, 80045, Colorado, United States
| | - Irene Esposito
- Institute of Pathology, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Roger M Feakins
- Department of Histopathology, Royal Free Hospital, London, United Kingdom
| | | | - Anthony J Gill
- Sydney Medical School, The University of Sydney, Sydney, Australia.,Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, St Leonards, Australia.,NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, Australia
| | - Sanjay Kakar
- Department of Pathology, University of California, M590 San Francisco, United States
| | - James G Kench
- Sydney Medical School, The University of Sydney, Sydney, Australia.,Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, New South Wales Health Pathology, Camperdown, Australia
| | - Alyssa M Krasinskas
- Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, United States
| | - Jean-Luc van Laethem
- Department of Gastroenterology and Medical Oncology, Hôpital Erasme and Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
| | - David F Schaeffer
- Division of Anatomic Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada.,Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Kay Washington
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Centre, Nashville, Tennessee, United States
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Garnier J, Ewald J, Poizat F, Traversari E, Marchese U, Palen A, Delpero JR, Turrini O. Prospective Evaluation of Resection Margins Using Standardized Specimen Protocol Analysis among Patients with Distal Cholangiocarcinoma and Pancreatic Ductal Adenocarcinoma. J Clin Med 2021; 10:jcm10153247. [PMID: 34362031 PMCID: PMC8348230 DOI: 10.3390/jcm10153247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Revised: 07/09/2021] [Accepted: 07/21/2021] [Indexed: 11/16/2022] Open
Abstract
PURPOSE Using a standardized specimen protocol analysis, this study aimed to evaluate the resection margin status of patients who underwent resection for either distal cholangiocarcinoma (DC) or pancreatic ductal adenocarcinoma (PDAC). This allowed a precise millimetric analysis of each inked margin. METHODS From 2010 to 2018, 355 consecutively inked specimens from patients with PDAC (n = 288) or DC (n = 67) were prospectively assessed. We assessed relationships between the tumor and the following margins: transection of the pancreatic neck, bile duct, posterior surface, margin toward superior mesenteric artery, and the surface of superior mesenteric vein/portal vein groove. Resection margins were evaluated using a predefined cut-off value of 1 mm; however, clearances of 0 and 1.5 mm were also evaluated. RESULTS Patients with DC were mostly men (64% vs. 49%, p = 0.028), of older age (68 yo vs. 65, p = 0.033), required biliary stenting more frequently (93% vs. 77%, p < 0.01), and received less neoadjuvant treatment (p < 0.001) than patients with PDAC. The venous resection rate was higher among patients with PDAC (p = 0.028). Postoperative and 90-day mortality rates were comparable. Patients with PDAC had greater tumor size (28.6 vs. 24 mm, p = 0.01) than those with DC. The R1 resection rate was comparable between the two groups, regardless of the clearance margin. Among the three types of resection margins, a venous groove was the most frequent in both entities. In multivariate analysis, the R1 resection margin did not influence patient survival in either PDAC or DC. CONCLUSION Our standardized specimen protocol analysis showed that the R1 resection rate was comparable in PDAC and DC.
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Affiliation(s)
- Jonathan Garnier
- Department of Surgical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.E.); (E.T.); (U.M.); (A.P.)
- Correspondence:
| | - Jacques Ewald
- Department of Surgical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.E.); (E.T.); (U.M.); (A.P.)
| | - Flora Poizat
- Department of Pathology, Institut Paoli-Calmettes, 13009 Marseille, France;
| | - Eddy Traversari
- Department of Surgical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.E.); (E.T.); (U.M.); (A.P.)
| | - Ugo Marchese
- Department of Surgical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.E.); (E.T.); (U.M.); (A.P.)
| | - Anais Palen
- Department of Surgical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France; (J.E.); (E.T.); (U.M.); (A.P.)
| | - Jean Robert Delpero
- Department of Surgical Oncology, Institut Paoli-Calmettes, CRCM, Aix-Marseille University, 13009 Marseille, France; (J.R.D.); (O.T.)
| | - Olivier Turrini
- Department of Surgical Oncology, Institut Paoli-Calmettes, CRCM, Aix-Marseille University, 13009 Marseille, France; (J.R.D.); (O.T.)
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Murphy KJ, Chambers CR, Herrmann D, Timpson P, Pereira BA. Dynamic Stromal Alterations Influence Tumor-Stroma Crosstalk to Promote Pancreatic Cancer and Treatment Resistance. Cancers (Basel) 2021; 13:3481. [PMID: 34298706 PMCID: PMC8305001 DOI: 10.3390/cancers13143481] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 07/03/2021] [Accepted: 07/07/2021] [Indexed: 12/18/2022] Open
Abstract
Many cancer studies now recognize that disease initiation, progression, and response to treatment are strongly influenced by the microenvironmental niche. Widespread desmoplasia, or fibrosis, is fundamental to pancreatic cancer development, growth, metastasis, and treatment resistance. This fibrotic landscape is largely regulated by cancer-associated fibroblasts (CAFs), which deposit and remodel extracellular matrix (ECM) in the tumor microenvironment (TME). This review will explore the prognostic and functional value of the stromal compartment in predicting outcomes and clinical prognosis in pancreatic ductal adenocarcinoma (PDAC). We will also discuss the major dynamic stromal alterations that occur in the pancreatic TME during tumor development and progression, and how the stromal ECM can influence cancer cell phenotype, metabolism, and immune response from a biochemical and biomechanical viewpoint. Lastly, we will provide an outlook on the latest clinical advances in the field of anti-fibrotic co-targeting in combination with chemotherapy or immunotherapy in PDAC, providing insight into the current challenges in treating this highly aggressive, fibrotic malignancy.
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Affiliation(s)
- Kendelle J. Murphy
- The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; (K.J.M.); (C.R.C.); (D.H.)
- St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
| | - Cecilia R. Chambers
- The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; (K.J.M.); (C.R.C.); (D.H.)
- St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
| | - David Herrmann
- The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; (K.J.M.); (C.R.C.); (D.H.)
- St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
| | - Paul Timpson
- The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; (K.J.M.); (C.R.C.); (D.H.)
- St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
| | - Brooke A. Pereira
- The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; (K.J.M.); (C.R.C.); (D.H.)
- St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
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44
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Zeeshan MS, Ramzan Z. Current controversies and advances in the management of pancreatic adenocarcinoma. World J Gastrointest Oncol 2021; 13:472-494. [PMID: 34163568 PMCID: PMC8204360 DOI: 10.4251/wjgo.v13.i6.472] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Revised: 03/22/2021] [Accepted: 05/25/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic adenocarcinoma is a lethal disease with a mortality rate that has not significantly improved over decades. This is likely due to several challenges unique to pancreatic cancer. Most patients with pancreatic cancer are diagnosed at a late stage of disease due to the lack of specific symptoms prompting an early investigation. A small subset of patients who are diagnosed at an early stage have a better chance at survival with curative surgical resection, but most patients still succumb to the disease in a few years. The dismal overall prognosis is due to suspected micro-metastasis at an early stage. Due to this reason, there is a recent interest in treating all patients with pancreatic cancers with systemic therapy upfront (including the ones that are surgically resectable). This approach is still not the standard of care due to the lack of robust prospective data available. Recent advancements in treatment regimens of chemotherapy, radiation and immunotherapy have improved the overall short-term survival but the long-term survival still remains poor. Novel approaches in diagnosis and treatment have shown promise in clinical studies but long-term clinical data is lacking. The following manuscript presents an overview of the epidemiology, diagnosis, staging, recent advances, novel approaches and controversies in the management of pancreatic adenocarcinoma.
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Affiliation(s)
- Muhammad Shehroz Zeeshan
- Gastrointestinal Section, Department of Medicine, Texas Health Harris Methodist Hospital, Fort Worth, TX 76104, United States
| | - Zeeshan Ramzan
- Gastrointestinal Section, Department of Medicine, Texas Health Harris Methodist Hospital, Fort Worth, TX 76104, United States
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45
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Datta J, Willobee BA, Ryon EL, Shah MM, Drebin JA, Kooby DA, Merchant NB. Contemporary Reappraisal of Intraoperative Neck Margin Assessment During Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma: A Review. JAMA Surg 2021; 156:489-495. [PMID: 33533898 DOI: 10.1001/jamasurg.2020.5676] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Importance Although margin-negative (R0) resection is the gold standard for surgical management of localized pancreatic ductal adenocarcinoma (PDAC), the question of how to manage the patient with a microscopically positive intraoperative neck margin (IONM) during pancreaticoduodenectomy remains controversial. Observations In the absence of randomized clinical trials, we critically evaluated high-quality retrospective studies examining the oncologic utility of re-resecting positive IONMs during pancreaticoduodenectomy for PDAC (2000-2019). Several studies have concluded that additional pancreatic resection to achieve an R0 margin in IONM-positive cases does not influence survival. The largest is a multi-institutional study of 1399 patients undergoing pancreaticoduodenectomy, which demonstrated that in comparison with patients undergoing R0 resection (n = 1196; median survival, 21 months), those with either final R1 resections (n = 131) or undergoing margin conversion from IONM-positive to R0 resection on permanent section (n = 72) demonstrated similar median survival times (13.7 and 11.9 months, respectively). Conversely, recent reports suggest that the conversion of IONM to R0 resection with additional resection or even total pancreatectomy may be associated with improved survival. The discordance between these conflicting studies could be explained in part by the influence of biologic and physiologic selection on the association of IONM re-resection and survival. Since most studies did not include patients receiving modern combination chemotherapy regimens, the intersection between margin status, tumor biology, and chemoresponsiveness remains unclear. Furthermore, there are no dedicated data to guide surgical management in IONM-positive pancreaticoduodenectomy for patients receiving neoadjuvant chemotherapy. Conclusions and Relevance Although data regarding the oncologic utility of additional resection to achieve a tumor-free margin following initial IONM positivity during pancreaticoduodenectomy for PDAC are conflicting, they suggest that IONM positivity may be a surrogate for biologic aggressiveness that is unlikely to be mitigated by the extent of surgical resection. The complex relationship between margin status and chemoresponsiveness warrants exploration in studies including patients receiving increasingly effective neoadjuvant chemotherapy.
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Affiliation(s)
- Jashodeep Datta
- Division of Surgical Oncology, Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida.,Sylvester Comprehensive Cancer Center, Miami, Florida
| | - Brent A Willobee
- Division of Surgical Oncology, Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida
| | - Emily L Ryon
- Division of Surgical Oncology, Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida
| | - Mihir M Shah
- Winship Cancer Institute, Department of Surgery, Emory University School of Medicine, Atlanta, Georgia
| | - Jeffrey A Drebin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - David A Kooby
- Winship Cancer Institute, Department of Surgery, Emory University School of Medicine, Atlanta, Georgia
| | - Nipun B Merchant
- Division of Surgical Oncology, Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida.,Sylvester Comprehensive Cancer Center, Miami, Florida
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46
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Nappo G, Borzomati D, Zerbi A, Spaggiari P, Boggi U, Campani D, Mrowiec S, Liszka Ł, Coppola A, Amato M, Petitti T, Vistoli F, Montorsi M, Perrone G, Coppola R, Caputo D. The Role of Pathological Method and Clearance Definition for the Evaluation of Margin Status after Pancreatoduodenectomy for Periampullary Cancer. Results of a Multicenter Prospective Randomized Trial. Cancers (Basel) 2021; 13:2097. [PMID: 33926138 PMCID: PMC8123600 DOI: 10.3390/cancers13092097] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 04/21/2021] [Accepted: 04/22/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND There is extreme heterogeneity in the available literature on the determination of R1 resection rate after pancreatoduodenectomy (PD); consequently, its prognostic role is still debated. The aims of this multicenter randomized study were to evaluate the effect of sampling and clearance definition in determining R1 rate after PD for periampullary cancer and to assess the prognostic role of R1 resection. METHODS PD specimens were randomized to Leeds Pathology Protocol (LEEPP) (group A) or the conventional method adopted before the study (group B). R1 rate was determined by adopting 0- and 1-mm clearance; the association between R1, local recurrence (LR) and overall survival (OS) was also evaluated. RESULTS One-hundred-sixty-eight PD specimens were included. With 0 mm clearance, R1 rate was 26.2% and 20.2% for groups A and B, respectively; with 1 mm, R1 rate was 60.7% and 57.1%, respectively (p > 0.05). Only in group A was R1 found to be a significant prognostic factor: at 0 mm, median OS was 36 and 20 months for R0 and R1, respectively, while at 1 mm, median OS was not reached and 30 months. At multivariate analysis, R1 resection was found to be a significant prognostic factor independent of clearance definition only in the case of the adoption of LEEPP. CONCLUSIONS The 1 mm clearance is the most effective factor in determining the R1 rate after PD. However, the pathological method is crucial to accurately evaluate its prognostic role: only R1 resections obtained with the adoption of LEEPP seem to significantly affect prognosis.
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Affiliation(s)
- Gennaro Nappo
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center—IRCCS, Via Manzoni 56, 20089 Rozzano, Italy; (G.N.); (A.Z.)
| | - Domenico Borzomati
- Department of Surgery, Università Campus Bio-Medico di Roma, 00128 Rome, Italy; (D.B.); (R.C.); (D.C.)
| | - Alessandro Zerbi
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center—IRCCS, Via Manzoni 56, 20089 Rozzano, Italy; (G.N.); (A.Z.)
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Milan, Italy;
| | - Paola Spaggiari
- Pathology Unit, Humanitas Clinical and Research Center—IRCCS, Via Manzoni 56, 20089 Rozzano, Italy; (P.S.); (U.B.); (F.V.)
| | - Ugo Boggi
- Pathology Unit, Humanitas Clinical and Research Center—IRCCS, Via Manzoni 56, 20089 Rozzano, Italy; (P.S.); (U.B.); (F.V.)
- Division of General and Transplant Surgery, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, 56126 Pisa, Italy
| | - Daniela Campani
- Pathology Unit, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, 56126 Pisa, Italy;
| | - Sławomir Mrowiec
- Department of Gastrointestinal Surgery, Medical University of Silesia, 40-055 Katowice, Poland;
| | - Łukasz Liszka
- Department of Pathomorphology and Molecular Diagnostics, Medical University of Silesia, 40-055 Katowice, Poland;
| | - Alessandro Coppola
- Department of Surgery, Università Campus Bio-Medico di Roma, 00128 Rome, Italy; (D.B.); (R.C.); (D.C.)
| | - Michela Amato
- Pathology Unit, Campus Bio-Medico University of Rome, 00128 Rome, Italy; (M.A.); (G.P.)
| | - Tommasangelo Petitti
- Department of Public Health, Hygiene and Statistics, Campus Bio-Medico University of Rome, 00128 Rome, Italy;
| | - Fabio Vistoli
- Pathology Unit, Humanitas Clinical and Research Center—IRCCS, Via Manzoni 56, 20089 Rozzano, Italy; (P.S.); (U.B.); (F.V.)
- Division of General and Transplant Surgery, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, 56126 Pisa, Italy
| | - Marco Montorsi
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Milan, Italy;
- Department of Surgery, Humanitas Clinical and Research Center—IRCCS, Via Manzoni 56, 20089 Rozzano, Italy
| | - Giuseppe Perrone
- Pathology Unit, Campus Bio-Medico University of Rome, 00128 Rome, Italy; (M.A.); (G.P.)
| | - Roberto Coppola
- Department of Surgery, Università Campus Bio-Medico di Roma, 00128 Rome, Italy; (D.B.); (R.C.); (D.C.)
| | - Damiano Caputo
- Department of Surgery, Università Campus Bio-Medico di Roma, 00128 Rome, Italy; (D.B.); (R.C.); (D.C.)
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47
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Rift CV, Lund EL, Scheie D, Hansen CP, Hasselby JP. Histopathological evaluation of resected intraductal papillary mucinous neoplasms reveals distinct patterns of invasion in associated carcinomas. Hum Pathol 2021; 113:47-58. [PMID: 33915115 DOI: 10.1016/j.humpath.2021.04.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 04/18/2021] [Accepted: 04/19/2021] [Indexed: 10/21/2022]
Abstract
Invasive intraductal papillary mucinous neoplasms (inv-IPMNs) have a better prognosis than regular pancreatic ductal adenocarcinoma (PDAC), but no association with status of surgical margins and microscopic infiltration patterns has previously been described. The aim of this study is to review patterns of invasion and the predictive value of clinical guidelines in terms of rates of resection of high-grade dysplasia (HGD) and cancer among intraductal papillary mucinous neoplasms (IPMNs). Consecutively, resected IPMNs between 2011 and 2017 were analyzed. Data were obtained from a prospectively maintained database. A total of 132 patients were identified. Out of these, 38 patients with inv-IPMNs, initially identified as solid lesions suspicious of cancer, were compared with a control group of 101 patients with ordinary PDAC. Lower rates of vascular invasion, perineural invasion, lymph node metastasis, advanced T stage, and R1 status were characteristic of the inv-IPMNs in addition to better overall survival (OS) for a low tumor stage. Furthermore, as novel findings, the PDACs presented with resection margin involvement of 3 or more positive margins (31.3% vs. 9.5%, p = 0.044), associated with poor OS. Of the patients presenting as pT3, the inv-IPMN less often invaded more than one extrapancreatic anatomical structure (40.1% vs. 63.9%, p = 0.03). Regarding the predictive value of clinical guidelines, the frequency of resected HGD in IPMNs with high-risk stigmata (n = 54) and IPMNs with worrisome features was 30.7%, and the frequency of invasive carcinoma was 5.7%. In conclusion, we report a low resection rate of high-risk IPMNs and present novel findings describing inv-IPMNs as a less infiltrative phenotype compared with regular PDAC.
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Affiliation(s)
- Charlotte Vestrup Rift
- Department of Pathology, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
| | - Eva Løbner Lund
- Department of Pathology, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
| | - David Scheie
- Department of Pathology, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
| | - Carsten Palnæs Hansen
- Department of Surgery, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, DK 2100 Copenhagen, Denmark
| | - Jane Preuss Hasselby
- Department of Pathology, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
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48
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Rittmann MC, Hussung S, Braun LM, Klar RFU, Biesel EA, Fichtner-Feigl S, Fritsch R, Wittel UA, Ruess DA. Plasma biomarkers for prediction of early tumor recurrence after resection of pancreatic ductal adenocarcinoma. Sci Rep 2021; 11:7499. [PMID: 33820913 PMCID: PMC8021576 DOI: 10.1038/s41598-021-86779-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 03/19/2021] [Indexed: 01/01/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a disease with a very unfavorable prognosis. Surgical resection represents the only potentially curative treatment option, but recurrence after complete resection is almost certain. In an exploratory attempt we here aimed at identifying preoperative plasma protein biomarkers with the potential to predict early recurrence after resection of PDAC. Peripheral blood samples from 14 PDAC patients divided into three groups according to their time to tumor recurrence after curatively intended resection (early: < 6 months, medium: 6–12 months, late: > 12 months) underwent targeted proteome analysis. Proteins most strongly discriminating early and late recurrence were then examined in a number of established PDAC cell lines and their culture supernatants. Finally, PDAC organoid lines from primary tumors of patients with early and late recurrence were analyzed for confirmation and validation of results. In total, 23 proteins showed differential abundance in perioperative plasma from PDAC patients with early recurrence when compared to patients with late recurrence. Following confirmation of expression on a transcriptional and translational level in PDAC cell lines we further focused on three upregulated (MAEA, NT5E, AZU1) and two downregulated proteins (ATP6AP2, MICA). Increased expression of NT5E was confirmed in a subset of PDAC organoid cultures from tumors with early recurrence. MICA expression was heterogeneous and ATP6AP2 levels were very similar in both organoids from early and late recurrent tumors. Most strikingly, we observed high MAEA expression in all tested PDAC (n = 7) compared to a non-cancer ductal organoid line. MAEA also demonstrated potential to discriminate early recurrence from late recurrence PDAC organoids. Our study suggests that identification of plasma protein biomarkers released by tumor cells may be feasible and of value to predict the clinical course of patients. Prediction of recurrence dynamics would help to stratify up-front resectable PDAC patients for neoadjuvant chemotherapy approaches in an individualized fashion. Here, MAEA and NT5E were the most promising candidates for further evaluation.
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Affiliation(s)
- Marie-Claire Rittmann
- Department of General and Visceral Surgery, Medical Center and Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany
| | - Saskia Hussung
- Department of Medicine I, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany.,Department of Medical Oncology and Hematology, Zurich University Hospital, Zurich, Switzerland
| | - Lukas M Braun
- Department of General and Visceral Surgery, Medical Center and Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany.,Department of Medicine I, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Rhena F U Klar
- Department of Medicine I, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Esther A Biesel
- Department of General and Visceral Surgery, Medical Center and Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany
| | - Stefan Fichtner-Feigl
- Department of General and Visceral Surgery, Medical Center and Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany
| | - Ralph Fritsch
- Department of Medicine I, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany.,Department of Medical Oncology and Hematology, Zurich University Hospital, Zurich, Switzerland
| | - Uwe A Wittel
- Department of General and Visceral Surgery, Medical Center and Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany.
| | - Dietrich A Ruess
- Department of General and Visceral Surgery, Medical Center and Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany
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49
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A Critical Assessment of Postneoadjuvant Therapy Pancreatic Cancer Regression Grading Schemes With a Proposal for a Novel Approach. Am J Surg Pathol 2021; 45:394-404. [PMID: 33074853 DOI: 10.1097/pas.0000000000001601] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Currently, there is no consensus on the optimal tumor response score (TRS) system to assess regression in pancreatic cancers resected after neoadjuvant therapy. We developed a novel TRS (Royal North Shore [RNS] system) based on estimating the percentage of tumor bed occupied by viable cancer and categorized into 3 tiers: grade 1 (≤10%), grade 2 (11% to 75%), and grade 3 (>75%). We assessed 147 resected carcinomas with this and other TRS systems (College of American Pathologists [CAP], MD Anderson Cancer Center [MDACC], and Evans). The 3-tiered RNS system predicted median survival after surgery for grades 1, 2, and 3 of 54, 23, and 9 months, respectively (P<0.05). The CAP, MDACC, and Evans systems also predicted survival (P<0.05) but less consistently. The median survival for MDACC and CAP grade 0 (complete regression) was less than MDACC grade 1 and CAP grades 1 and 2. There was no difference in survival between CAP grades 2 and 3 (P=0.960), Evans grades 1 and 2a (P=0.395), and Evans grades 2a and 2b (P=0.587). Interobserver concordance was weak for CAP (κ=0.431), moderate for MDACC (κ=0.691), minimal for Evans (κ=0.307), and moderate to strong for RNS (κ=0.632 to 0.84). Of age, sex, size, stage, grade, perineural and vascular invasion, extrapancreatic extension, margin status, and RNS score, only RNS score, vascular invasion, and extrapancreatic extension predicted survival in univariate analysis. Only extrapancreatic extension (P=0.034) and RNS score (P<0.0001) remained significant in multivariate analysis. We conclude that the RNS system is a reproducible and powerful predictor of survival after resection for pancreatic cancers treated with neoadjuvant therapy and should be investigated in larger cohorts.
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50
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Weyhe D, Obonyo D, Uslar VN, Stricker I, Tannapfel A. Predictive factors for long-term survival after surgery for pancreatic ductal adenocarcinoma: Making a case for standardized reporting of the resection margin using certified cancer center data. PLoS One 2021; 16:e0248633. [PMID: 33735191 PMCID: PMC7971889 DOI: 10.1371/journal.pone.0248633] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 03/02/2021] [Indexed: 12/15/2022] Open
Abstract
Factors for overall survival after pancreatic ductal adenocarcinoma (PDAC) seem to be nodal status, chemotherapy administration, UICC staging, and resection margin. However, there is no consensus on the definition for tumor free resection margin. Therefore, univariate OS as well as multivariate long-term survival using cancer center data was analyzed with regards to two different resection margin definitions. Ninety-five patients met inclusion criteria (pancreatic head PDAC, R0/R1, no 30 days mortality). OS was analyzed in univariate analysis with respect to R-status, CRM (circumferential resection margin; positive: ≤1mm; negative: >1mm), nodal status, and chemotherapy administration. Long-term survival >36 months was modelled using multivariate logistic regression instead of Cox regression because the distribution function of the dependent data violated the requirements for the application of this test. Significant differences in OS were found regarding the R status (Median OS and 95%CI for R0: 29.8 months, 22.3–37.4; R1: 15.9 months, 9.2–22.7; p = 0.005), nodal status (pN0 = 34.7, 10.4–59.0; pN1 = 17.1, 11.5–22.8; p = 0.003), and chemotherapy (with CTx: 26.7, 20.4–33.0; without CTx: 9.7, 5.2–14.1; p < .001). OS according to CRM status differed on a clinically relevant level by about 12 months (CRM positive: 17.2 months, 11.5–23.0; CRM negative: 29.8 months, 18.6–41.1; p = 0.126). A multivariate model containing chemotherapy, nodal status, and CRM explained long-term survival (p = 0.008; correct prediction >70%). Chemotherapy, nodal status and resection margin according to UICC R status are univariate factors for OS after PDAC. In contrast, long-term survival seems to depend on wider resection margins than those used in UICC R classification. Therefore, standardized histopathological reporting (including resection margin size) should be agreed upon.
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Affiliation(s)
- Dirk Weyhe
- University Hospital for Visceral Surgery, Pius-Hospital, Carl von Ossietzky University Oldenburg, Oldenburg, Germany
| | - Dennis Obonyo
- University Hospital for Visceral Surgery, Pius-Hospital, Carl von Ossietzky University Oldenburg, Oldenburg, Germany
| | - Verena Nicole Uslar
- University Hospital for Visceral Surgery, Pius-Hospital, Carl von Ossietzky University Oldenburg, Oldenburg, Germany
- * E-mail:
| | - Ingo Stricker
- Institute for Pathology, Ruhr University Bochum, Bochum, Germany
| | - Andrea Tannapfel
- Institute for Pathology, Ruhr University Bochum, Bochum, Germany
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