|
1
|
Mauro A, Faverio C, Brizzi L, Mazza S, Scalvini D, Alfieri D, Cappellini A, Chicco F, Ciccioli C, Delogu C, Bardone M, Gallotti A, Pagani A, Torello Viera F, Anderloni A. Multidisciplinary Therapeutic Approaches to Pancreatic Cancer According to the Resectability Status. J Clin Med 2025; 14:1167. [PMID: 40004698 PMCID: PMC11856188 DOI: 10.3390/jcm14041167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 01/20/2025] [Accepted: 02/08/2025] [Indexed: 02/27/2025] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers, characterized by late diagnosis, rapid progression, and limited therapeutic options. Despite advancements, only 20% of patients are eligible for surgical resection at diagnosis, the sole curative treatment. Multidisciplinary evaluation is critical to optimize care, stratifying patients based on resectability into resectable, borderline resectable, locally advanced, and metastatic stages. Preoperative imaging, such as computed tomography (CT) and endoscopic ultrasound (EUS), remains central for staging, for vascular assessment, and tissue acquisition. Endoscopic and systemic approaches are pivotal for addressing complications like biliary obstruction and improving outcomes. Endoscopic retrograde cholangiopancreatography (ERCP) has been considered for years the gold standard for biliary drainage, although EUS-guided drainage is increasingly utilized due to its efficacy in both resectable and unresectable disease. Systemic therapies play a key role in neoadjuvant, adjuvant, and palliative settings, with ongoing trials exploring their impact on survival and resectability chance. This review highlights the evolving multidisciplinary approaches tailored to the disease stage, focusing on biliary drainage techniques, systemic therapies, and their integration into comprehensive care pathways for PDAC. The continuous refinement of these strategies offers incremental survival benefits and underscores the importance of personalized, multidisciplinary management.
Collapse
Affiliation(s)
- Aurelio Mauro
- Gastroenterology and Endoscopy Unit, IRCCS Foundation Policlinico San Matteo, 27100 Pavia, Italy
| | - Carlotta Faverio
- Medical Oncology Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Leonardo Brizzi
- Institute of Radiology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Stefano Mazza
- Gastroenterology and Endoscopy Unit, IRCCS Foundation Policlinico San Matteo, 27100 Pavia, Italy
| | - Davide Scalvini
- Gastroenterology and Endoscopy Unit, IRCCS Foundation Policlinico San Matteo, 27100 Pavia, Italy
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, 27100 Pavia, Italy
| | - Daniele Alfieri
- Gastroenterology and Endoscopy Unit, IRCCS Foundation Policlinico San Matteo, 27100 Pavia, Italy
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, 27100 Pavia, Italy
| | - Alessandro Cappellini
- Gastroenterology and Endoscopy Unit, IRCCS Foundation Policlinico San Matteo, 27100 Pavia, Italy
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, 27100 Pavia, Italy
| | - Fabio Chicco
- Gastroenterology & Digestive Endoscopy Unit, AO Lodi, 26900 Lodi, Italy
| | - Carlo Ciccioli
- Gastroenterology and Endoscopy Unit, IRCCS Foundation Policlinico San Matteo, 27100 Pavia, Italy
- Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, 90133 Palermo, Italy
| | - Claudia Delogu
- Gastroenterology and Endoscopy Unit, IRCCS Foundation Policlinico San Matteo, 27100 Pavia, Italy
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, 27100 Pavia, Italy
| | - Marco Bardone
- Gastroenterology and Endoscopy Unit, IRCCS Foundation Policlinico San Matteo, 27100 Pavia, Italy
| | - Anna Gallotti
- Institute of Radiology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Anna Pagani
- Medical Oncology Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Francesca Torello Viera
- Gastroenterology and Endoscopy Unit, IRCCS Foundation Policlinico San Matteo, 27100 Pavia, Italy
| | - Andrea Anderloni
- Gastroenterology and Endoscopy Unit, IRCCS Foundation Policlinico San Matteo, 27100 Pavia, Italy
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, 27100 Pavia, Italy
| |
Collapse
|
|
2
|
R S, J V, F P, DA B, A L, E G, A F, C T, L B, B E. 3D modeling to predict vascular involvement in resectable pancreatic adenocarcinoma. Heliyon 2025; 11:e41473. [PMID: 39850404 PMCID: PMC11754173 DOI: 10.1016/j.heliyon.2024.e41473] [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: 08/09/2024] [Revised: 11/27/2024] [Accepted: 12/23/2024] [Indexed: 01/25/2025] Open
Abstract
Background Current management of patients with borderline resectable pancreatic adenocarcinoma (BR-PDAC) depends on the degree of involvement of the major arterial and venous structures. The aim of this study was to evaluate 3D segmentation and printing to predict tumor size and vascular involvement of BR-PDAC to improve pre-operative planning of vascular resection and better select patients for neoadjuvant therapy. Methods We retrospectively evaluated 16 patients with BR-PDAC near vascular structures who underwent pancreatoduodenectomy (PD) with or without vascular resection between 2015 and 2021. The pre-operative computed tomography (CT) images were processed by segmentation with 3D reconstruction and printed as 3D models. Two radiologists specialized in pancreatic imaging and two pancreatic surgeons blindly and independently analyzed the pre-operative CT scans and 3D models using a defined checklist. Their evaluations were compared to the pre-operative 2D-CT reports utilized for patient management. A positive delta was defined by the 3D analysis resulting in greater accuracy in predicting vascular involvement as proven intraoperatively or histopathologically. Results Fourteen PD, one total pancreatectomy, and one exploratory laparotomy were performed. Ten patients had a positive delta concerning vascular involvement of the superior mesenteric or portal vein. Tumor extension was also more accurately evaluated by 3D modeling than by 2D-CT (p < 0.05). Conclusions Our pilot study demonstrates that 3D segmentation can provide additional information for choosing the best treatment strategy and surgical plain in patients with BR-PDAC. Especially for upcoming mini-invasive techniques like laparoscopic and robotic resections, better pre-operative planning is essential to allow safety and prevent vascular injury.
Collapse
Affiliation(s)
- Sguinzi R
- Department of General Surgery, Fribourg Cantonal Hospital, 1700, Fribourg, Switzerland
| | - Vidal J
- Department of Radiology, Fribourg Cantonal Hospital, 1700, Fribourg, Switzerland
| | - Poroes F
- Department of Radiology, Fribourg Cantonal Hospital, 1700, Fribourg, Switzerland
| | - Bartolucci DA
- Department of Radiology, Fribourg Cantonal Hospital, 1700, Fribourg, Switzerland
| | - Litchinko A
- Department of General Surgery, University Hospital of Geneva, 1205, Switzerland
| | - Gossin E
- University of Fribourg, Faculty of Science and Medicine - Section of Medicine, 1700, Fribourg, Switzerland
| | - Fingerhut A
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China
| | - Toso C
- Department of General Surgery, University Hospital of Geneva, 1205, Switzerland
| | - Buhler L
- Department of General Surgery, Fribourg Cantonal Hospital, 1700, Fribourg, Switzerland
| | - Egger B
- Department of General Surgery, Fribourg Cantonal Hospital, 1700, Fribourg, Switzerland
- University of Fribourg, Faculty of Science and Medicine - Section of Medicine, 1700, Fribourg, Switzerland
| |
Collapse
|
|
3
|
Corallo C, Al-Adhami AS, Jamieson N, Valle J, Radhakrishna G, Moir J, Albazaz R. An update on pancreatic cancer imaging, staging, and use of the PACT-UK radiology template pre- and post-neoadjuvant treatment. Br J Radiol 2025; 98:13-26. [PMID: 39460945 DOI: 10.1093/bjr/tqae217] [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: 12/12/2023] [Revised: 10/01/2024] [Accepted: 10/22/2024] [Indexed: 10/28/2024] Open
Abstract
Pancreatic ductal adenocarcinoma continues to have a poor prognosis, although recent advances in neoadjuvant treatments (NATs) have provided some hope. Imaging assessment of suspected tumours can be challenging and requires a specific approach, with pancreas protocol CT being the primary imaging modality for staging with other modalities used as problem-solving tools to facilitate appropriate management. Imaging assessment post NAT can be particularly difficult due to a current lack of robust radiological criteria to predict response and differentiate treatment induced fibrosis/inflammation from residual tumour. This review aims to provide an update of pancreatic ductal adenocarcinoma with particular focus on three points: tumour staging pre- and post-NAT including vascular assessment, structured reporting with introduction of the PAncreatic Cancer reporting Template-UK (PACT-UK) radiology template, and the potential future role of artificial intelligence in the diagnosis and staging of pancreatic cancer.
Collapse
Affiliation(s)
- Carmelo Corallo
- Department of Radiology, St James's University Hospital, Leeds LS9 7TF, United Kingdom
| | - Abdullah S Al-Adhami
- Department of Radiology, Glasgow Royal Infirmary, Glasgow G31 2ER, United Kingdom
| | - Nigel Jamieson
- HPB Unit, Glasgow Royal Infirmary, Glasgow G31 2ER, United Kingdom
| | - Juan Valle
- Division of Cancer Sciences, University of Manchester, Manchester M20 4GJ, United Kingdom
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4 BX, United Kingdom
| | | | - John Moir
- HPB Unit, Freeman Hospital, Newcastle Upon Tyne NE7 7DN, United Kingdom
| | - Raneem Albazaz
- Department of Radiology, St James's University Hospital, Leeds LS9 7TF, United Kingdom
- University of Leeds, Leeds LS2 9JT, United Kingdom
| |
Collapse
|
|
4
|
Rogers HK, Shah SL. Role of Endoscopic Ultrasound in Pancreatic Cancer Diagnosis and Management. Diagnostics (Basel) 2024; 14:1156. [PMID: 38893682 PMCID: PMC11171704 DOI: 10.3390/diagnostics14111156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 05/22/2024] [Accepted: 05/27/2024] [Indexed: 06/21/2024] Open
Abstract
The emergence of endoscopic ultrasound (EUS) has significantly impacted the diagnosis and management of pancreatic cancer and its associated sequelae. While the definitive role of EUS for pancreatic cancer remains incompletely characterized by currently available guidelines, EUS undoubtedly offers high diagnostic accuracy, the precise staging of pancreatic neoplasms, and the ability to perform therapeutic and palliative interventions. However, current challenges to EUS include limited specialized expertise and variability in operator proficiency. As the technology and techniques continue to evolve and become more refined, EUS is poised to play an increasingly integral role in shaping pancreatic cancer care.
Collapse
Affiliation(s)
- Hayley K. Rogers
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Shawn L. Shah
- Division of Digestive and Liver Diseases, Dallas VA Medical Center, VA North Texas Healthcare System, Dallas, TX 75216, USA
| |
Collapse
|
|
5
|
Han SY, Chon HK, Kim SH, Lee SH. Quality indicators of endoscopic ultrasound in the pancreatobiliary system: a brief review of current guidelines. Clin Endosc 2024; 57:158-163. [PMID: 37430396 PMCID: PMC10984746 DOI: 10.5946/ce.2023.064] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 03/26/2023] [Accepted: 03/31/2023] [Indexed: 07/12/2023] Open
Abstract
Since its development, the use of endoscopic ultrasonography (EUS) in the pancreas and the biliary tract has become increasingly important. The accuracy of EUS varies depending on the experience of the endoscopist. Hence, quality control measures using appropriate indicators are required to reduce these variations. American Society for Gastrointestinal Endoscopy and European Society of Gastrointestinal Endoscopy have announced the EUS quality indicators. Here, we reviewed the quality indicators of the EUS procedure in the current published guidelines.
Collapse
Affiliation(s)
- Sung Yong Han
- Division of Gastroenterology, Department of Internal Medicine and Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea
| | - Hyung Ku Chon
- Division of Biliopancreas, Department of Internal Medicine, Wonkwang University College of Medicine, Iksan, Korea
- Institute of Wonkwang Medical Science, Wonkwang University College of Medicine, Iksan, Korea
| | - Seong-Hun Kim
- Department of Internal Medicine, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea
| | - Sang Hyub Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - The Research Group for Endoscopic Ultrasound in Korean Society of Gastrointestinal Endoscopy
- Division of Gastroenterology, Department of Internal Medicine and Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea
- Division of Biliopancreas, Department of Internal Medicine, Wonkwang University College of Medicine, Iksan, Korea
- Institute of Wonkwang Medical Science, Wonkwang University College of Medicine, Iksan, Korea
- Department of Internal Medicine, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| |
Collapse
|
|
6
|
Otsuka Y, Kamata K. A review of contrast-enhanced harmonic endoscopic ultrasonography for pancreatic solid tumors. J Med Ultrason (2001) 2023:10.1007/s10396-023-01346-3. [PMID: 37584780 DOI: 10.1007/s10396-023-01346-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Accepted: 06/15/2023] [Indexed: 08/17/2023]
Abstract
Endoscopic ultrasonography (EUS) is superior to other imaging modalities in the detection of pancreatic masses, although differentiating the types of pancreatic masses detected on EUS remains challenging. However, the value of contrast-enhanced harmonic EUS (CH-EUS) using ultrasound contrast agents for this differentiation has been reported. CH-EUS plays a pivotal role in analysis of small lesions that can only be detected with EUS. Recently, CH-EUS was used for staging and/or determining the resectability of pancreatic cancer in several clinical trials. In addition, it is used to estimate the response of pancreatic cancer to chemotherapy and to determine the prognosis in cases of pancreatic cancer and pancreatic neuroendocrine neoplasms. It is also postulated that CH-EUS improves the diagnostic performance of endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) through complementary diagnoses using CH-EUS and EUS-FNAB, or CH-EUS-guided EUS-FNAB. Thus, CH-EUS has been employed for various qualitative diagnoses, including differentiation of pancreatic masses. Second-generation contrast agents such as Sonazoid are used clinically for ultrasound diagnostic imaging of liver and breast disease. The positioning of CH-EUS with Sonazoid as a test for the diagnosis of solid pancreatic tumors is an issue for further studies.
Collapse
Affiliation(s)
- Yasuo Otsuka
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, Japan
| | - Ken Kamata
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, Japan.
| |
Collapse
|
|
7
|
Zhao Y, Tang J, Jiang K, Liu SY, Aicher A, Heeschen C. Liquid biopsy in pancreatic cancer - Current perspective and future outlook. Biochim Biophys Acta Rev Cancer 2023; 1878:188868. [PMID: 36842769 DOI: 10.1016/j.bbcan.2023.188868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 01/14/2023] [Accepted: 01/16/2023] [Indexed: 02/27/2023]
Abstract
Pancreatic cancer is a lethal condition with a rising incidence and often presents at an advanced stage, contributing to abysmal five-year survival rates. Unspecific symptoms and the current lack of biomarkers and screening tools hamper early diagnosis. New technologies for liquid biopsies and their respective evaluation in pancreatic cancer patients have emerged over recent years. The term liquid biopsy summarizes the sampling and analysis of circulating tumor cells (CTCs), small extracellular vesicles (sEVs), and tumor DNA (ctDNA) from body fluids. The major advantages of liquid biopsies rely on their minimal invasiveness and repeatability, allowing serial sampling for dynamic insights to aid diagnosis, particularly early detection, risk stratification, and precision medicine in pancreatic cancer. However, liquid biopsies have not yet developed into a new pillar for clinicians' routine armamentarium. Here, we summarize recent findings on the use of liquid biopsy in pancreatic cancer patients. We discuss current challenges and future perspectives of this potentially powerful alternative to conventional tissue biopsies.
Collapse
Affiliation(s)
- Yaru Zhao
- Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiajia Tang
- Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ke Jiang
- Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shin-Yi Liu
- Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan; Research and Development Center for Immunology, China Medical University, Taichung, Taiwan
| | - Alexandra Aicher
- Precision Immunotherapy, Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
| | - Christopher Heeschen
- Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy.
| |
Collapse
|
|
8
|
Zhao B, Zhao B, Chen F. Diagnostic value of serum carbohydrate antigen 19-9 in pancreatic cancer: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2022; 34:891-904. [PMID: 35913776 DOI: 10.1097/meg.0000000000002415] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
Carbohydrate antigen 19-9 (CA19-9) is the most widely used serum biomarker for detecting pancreatic cancer (PC). Since early diagnosis is important for improving PC prognosis, a comprehensive understanding of the diagnostic performance of CA19-9 is critical. This study focused on comprehensive evaluation of the efficacy of CA19-9 in PC diagnosis. Literature research was based on the seven databases. Studies released from January 2002 to January 2022 focused on the efficacy of CA19-9 in the detection of PC were included. Summarized sensitivity, specificity, and sROC/accuracy of discrimination (AUC) were estimated. Potential publication bias was measured with Funnel plot and Egger's test. Meta-regression was performed to detect possible causes of heterogeneity. Subgroup analysis was used to assess the diagnostic efficacy of CA19-9 under different conditions. The study is registered on PROSPERO (CRD42021253861). Seventy-nine studies containing 20 991 participants who met the criteria were included. The pooled sensitivity, specificity, and AUC of CA19-9 in diagnose PC were 72% (95% CI, 71-73%), 86% (95% CI, 85-86%), and 0.8474 (95% CI, 0.8272-0.8676). Subgroup analysis suggested that the diagnostic efficiency of CA19-9 in studies with healthy controls was the highest, followed by intraductal papillary mucinous neoplasm, in pancreatitis and diabetes were consistent with the overall result. Our analysis showed that serum CA19-9 had high and stable diagnostic efficacy for PC (not affected by diabetes). Subgroup analysis showed that serum CA19-9 yielded highest effectiveness in the diagnosis of pancreatic precancerous lesions, which indicated an irreplaceable clinical value in the early detection and warning value for PC.
Collapse
Affiliation(s)
- Boqiang Zhao
- Xi'an Jiaotong University Health Science Center, Xi'an, China
- The First School of Clinical Medicine, Xi'an, China
| | - Boyue Zhao
- Xi'an Jiaotong University Health Science Center, Xi'an, China
- Department of Epidemiology and Biostatistics, School of Public Health, Xi'an, China
| | - Fangyao Chen
- Xi'an Jiaotong University Health Science Center, Xi'an, China
- Department of Epidemiology and Biostatistics, School of Public Health, Xi'an, China
| |
Collapse
|
|
9
|
Pande R, Chughtai S, Ahuja M, Brown R, Bartlett DC, Dasari BV, Marudanayagam R, Mirza D, Roberts K, Isaac J, Sutcliffe RP, Chatzizacharias NA. Para-aortic lymph node involvement should not be a contraindication to resection of pancreatic ductal adenocarcinoma. World J Gastrointest Surg 2022; 14:429-441. [PMID: 35734625 PMCID: PMC9160687 DOI: 10.4240/wjgs.v14.i5.429] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 03/19/2022] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Para-aortic lymph nodes (PALN) are found in the aortocaval groove and they are staged as metastatic disease if involved by pancreatic ductal adenocarcinoma (PDAC). The data in the literature is conflicting with some studies having associated PALN involvement with poor prognosis, while others not sharing the same results. PALN resection is not included in the standard lymphadenectomy during pancreatic resections as per the International Study Group for Pancreatic Surgery and there is no consensus on the management of these cases. AIM To investigate the prognostic significance of PALN metastases on the oncological outcomes after resection for PDAC. METHODS This is a retrospective cohort study of data retrieved from a prospectively maintained database on consecutive patients undergoing pancreatectomies for PDAC where PALN was sampled between 2011 and 2020. Statistical comparison of the data between PALN+ and PALN- subgroups, survival analysis with the Kaplan-Meier method and risk analysis with univariable and multivariable time to event Cox regression analysis were performed, specifically assessing oncological outcomes such as median overall survival (OS) and disease-free survival (DFS). RESULTS 81 cases had PALN sampling and 17 (21%) were positive. Pathological N stage was significantly different between PALN+ and PALN- patients (P = 0.005), while no difference was observed in any of the other characteristics. Preoperative imaging diagnosed PALN positivity in one case. OS and DFS were comparable between PALN+ and PALN- patients with lymph node positive disease (OS: 13.2 mo vs 18.8 mo, P = 0.161; DFS: 13 mo vs 16.4 mo, P = 0.179). No difference in OS or DFS was identified between PALN positive and negative patients when they received chemotherapy either in the neoadjuvant or in the adjuvant setting (OS: 23.4 mo vs 20.6 mo, P = 0.192; DFS: 23.9 mo vs 20.5 mo, P = 0.718). On the contrary, when patients did not receive chemotherapy, PALN disease had substantially shorter OS (5.5 mo vs 14.2 mo; P = 0.015) and DFS (4.4 mo vs 9.8 mo; P < 0.001). PALN involvement was not identified as an independent predictor for OS after multivariable analysis, while it was for DFS doubling the risk of recurrence. CONCLUSION PALN involvement does not affect OS when patients complete the indicated treatment pathway for PDAC, surgery and chemotherapy, and should not be considered as a contraindication to resection.
Collapse
Affiliation(s)
- Rupaly Pande
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - Shafiq Chughtai
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - Manish Ahuja
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - Rachel Brown
- Department of Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - David C Bartlett
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - Bobby V Dasari
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - Ravi Marudanayagam
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - Darius Mirza
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - Keith Roberts
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - John Isaac
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - Robert P Sutcliffe
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - Nikolaos A Chatzizacharias
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| |
Collapse
|
|
10
|
Farr KP, Moses D, Haghighi KS, Phillips PA, Hillenbrand CM, Chua BH. Imaging Modalities for Early Detection of Pancreatic Cancer: Current State and Future Research Opportunities. Cancers (Basel) 2022; 14:cancers14102539. [PMID: 35626142 PMCID: PMC9139708 DOI: 10.3390/cancers14102539] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 05/18/2022] [Accepted: 05/19/2022] [Indexed: 02/06/2023] Open
Abstract
Simple Summary While survival rates for many cancers have improved dramatically over the last 20 years, patients with pancreatic cancer have persistently poor outcomes. The majority of patients with pancreatic cancer are not suitable for potentially curative surgery due to locally advanced or metastatic disease stage at diagnosis. Therefore, early detection would potentially improve survival of pancreatic cancer patients through earlier intervention. Here, we present clinical challenges in the early detection of pancreatic cancer, characterise high risk groups for pancreatic cancer and current screening programs in high-risk individuals. The aim of this scoping review is to investigate the role of both established and novel imaging modalities for early detection of pancreatic cancer. Furthermore, we investigate innovative imaging techniques for early detection of pancreatic cancer, but its widespread application requires further investigation and potentially a combination with other non-invasive biomarkers. Abstract Pancreatic cancer, one of the most lethal malignancies, is increasing in incidence. While survival rates for many cancers have improved dramatically over the last 20 years, people with pancreatic cancer have persistently poor outcomes. Potential cure for pancreatic cancer involves surgical resection and adjuvant therapy. However, approximately 85% of patients diagnosed with pancreatic cancer are not suitable for potentially curative therapy due to locally advanced or metastatic disease stage. Because of this stark survival contrast, any improvement in early detection would likely significantly improve survival of patients with pancreatic cancer through earlier intervention. This comprehensive scoping review describes the current evidence on groups at high risk for developing pancreatic cancer, including individuals with inherited predisposition, pancreatic cystic lesions, diabetes, and pancreatitis. We review the current roles of imaging modalities focusing on early detection of pancreatic cancer. Additionally, we propose the use of advanced imaging modalities to identify early, potentially curable pancreatic cancer in high-risk cohorts. We discuss innovative imaging techniques for early detection of pancreatic cancer, but its widespread application requires further investigation and potentially a combination with other non-invasive biomarkers.
Collapse
Affiliation(s)
- Katherina P. Farr
- School of Clinical Medicine, Faculty of Medicine & Health, UNSW, Sydney, NSW 2052, Australia; (K.S.H.); (B.H.C.)
- Correspondence:
| | - Daniel Moses
- Graduate School of Biomedical Engineering, UNSW, Sydney, NSW 2052, Australia;
| | - Koroush S. Haghighi
- School of Clinical Medicine, Faculty of Medicine & Health, UNSW, Sydney, NSW 2052, Australia; (K.S.H.); (B.H.C.)
- Department of General Surgery, Prince of Wales Hospital, Sydney, NSW 2052, Australia
| | - Phoebe A. Phillips
- Pancreatic Cancer Translational Research Group, School of Clinical Medicine, Lowy Cancer Research Centre, UNSW, Sydney, NSW 2052, Australia;
| | - Claudia M. Hillenbrand
- Research Imaging NSW, Division of Research & Enterprise, UNSW, Sydney, NSW 2052, Australia;
| | - Boon H. Chua
- School of Clinical Medicine, Faculty of Medicine & Health, UNSW, Sydney, NSW 2052, Australia; (K.S.H.); (B.H.C.)
- Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, Sydney, NSW 2052, Australia
| |
Collapse
|
|
11
|
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an intractable cancer and a leading cause of cancer deaths worldwide. Over 90% of patients die within 1 year of diagnosis. Deaths from PDAC are increasing and it remains a cancer of substantial unmet need. A number of factors contribute to its poor prognosis: namely, late presentation, early metastases and limited systemic therapy options because of chemoresistance. A variety of research approaches underway are aimed at improving patient survival. Here, we review high-risk groups and efforts for early detection. We examine recent developments in the understanding of complex molecular and metabolic alterations which accompany PDAC. We explore artificial intelligence and biological targets for therapy and examine the role of tumour stroma and the immune microenvironment. We also review recent developments with respect to the PDAC microbiome. It is hoped that current research efforts will translate into earlier diagnosis, improvements in treatment and better outcomes for patients.
Collapse
Affiliation(s)
- Martyn C Stott
- Department of Molecular & Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Sherrington Building, Liverpool, UK
| | - Lucy Oldfield
- Department of Molecular & Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Sherrington Building, Liverpool, UK
| | - Jessica Hale
- Department of Molecular & Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Sherrington Building, Liverpool, UK
| | - Eithne Costello
- Department of Molecular & Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Sherrington Building, Liverpool, UK
| | - Christopher M Halloran
- Department of Molecular & Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Sherrington Building, Liverpool, UK
| |
Collapse
|
|
12
|
Oppong KW, Nayar MK, Bekkali NLH, Maheshwari P, Haugk B, Darne A, Manas DM, French JJ, White S, Sen G, Pandanaboyana S, Charnley RM, Leeds JS. Impact of prior biliary stenting on diagnostic performance of endoscopic ultrasound for mesenteric vascular staging in patients with head of pancreas and periampullary malignancy. BMJ Open Gastroenterol 2022; 9:e000864. [PMID: 35301231 PMCID: PMC8932265 DOI: 10.1136/bmjgast-2021-000864] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Accepted: 02/13/2022] [Indexed: 12/02/2022] Open
Abstract
OBJECTIVE The diagnostic performance of endoscopic ultrasound (EUS) for stratification of head of pancreas and periampullary tumours into resectable, borderline resectable and locally advanced tumours is unclear as is the effect of endobiliary stents. The primary aim of the study was to assess the diagnostic performance of EUS for resectability according to stent status. DESIGN A retrospective study was performed. All patients presenting with a solid head of pancreas mass who underwent EUS and surgery with curative intent during an 8-year period were included. Factors with possible impact on diagnostic performance of EUS were analysed using logistic regression. RESULTS Ninety patients met inclusion criteria and formed the study group. A total of 49 (54%) patients had an indwelling biliary stent at the time of EUS, of which 36 were plastic and 13 were self-expanding metal stents (SEMS). Twenty patients underwent venous resection and reconstruction (VRR). Staging was successfully performed in 100% unstented cases, 97% plastic stent and 54% SEMS, p<0.0001. In successfully staged patients, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) for classification of resectability were 70%, 70%, 70%, 42% and 88%. For vascular involvement (VI), sensitivity, specificity, accuracy, PPV and NPV were 80%, 68%, 69%, 26% and 96%. Increasing tumour size OR 0.53 (95% CI, 0.30 to 0.95) was associated with a decrease in accuracy of VI classification. CONCLUSIONS EUS has modest diagnostic performance for stratification of staging. Staging was less likely to be completed when a SEMS was in situ. Staging EUS should ideally be performed before endoscopic retrograde cholangiopancreatography and biliary drainage.
Collapse
Affiliation(s)
- Kofi W Oppong
- HPB Unit, Freeman Hospital, Newcastle upon Tyne, UK
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Manu K Nayar
- HPB Unit, Freeman Hospital, Newcastle upon Tyne, UK
| | - Noor L H Bekkali
- Gastroenterology, Oxford University Hospitals NHS Foundation Trust, Oxford, Oxfordshire, UK
| | | | - Beate Haugk
- Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary, Newcastle upon Tyne, UK
| | - Antony Darne
- Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary, Newcastle upon Tyne, UK
| | - Derek M Manas
- HPB Unit, Freeman Hospital, Newcastle upon Tyne, UK
- Department of Surgery, Newcastle upon Tyne Hopsitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK
| | - Jeremy J French
- HPB Unit, Freeman Hospital, Newcastle upon Tyne, UK
- Department of Surgery, Newcastle upon Tyne Hopsitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK
| | - Steven White
- HPB Unit, Freeman Hospital, Newcastle upon Tyne, UK
- Department of Surgery, Newcastle upon Tyne Hopsitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK
| | - Gourab Sen
- HPB Unit, Freeman Hospital, Newcastle upon Tyne, UK
- Department of Surgery, Newcastle upon Tyne Hopsitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK
| | - Sanjay Pandanaboyana
- HPB Unit, Freeman Hospital, Newcastle upon Tyne, UK
- Department of Surgery, Newcastle upon Tyne Hopsitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK
- Population Health Sciences Institute, Newcastle University, Newcastele upon Tyne, UK
| | - Richard M Charnley
- HPB Unit, Freeman Hospital, Newcastle upon Tyne, UK
- Department of Surgery, Newcastle upon Tyne Hopsitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK
| | - John S Leeds
- HPB Unit, Freeman Hospital, Newcastle upon Tyne, UK
- Population Health Sciences Institute, Newcastle University, Newcastele upon Tyne, UK
| |
Collapse
|
|
13
|
Masuda H, Kotecha K, Maitra R, Gill AJ, Mittal A, Samra JS. Clinical suspicion of pancreatic cancer despite negative endoscopic ultrasound-guided fine-needle aspiration biopsy. ANZ J Surg 2021; 92:99-108. [PMID: 34636123 DOI: 10.1111/ans.17256] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Revised: 09/22/2021] [Accepted: 09/23/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND The early and accurate diagnosis of pancreatic ductal adenocarcinoma is vital for improving the efficacy of therapeutic interventions and to provide patients with the best chance of survival. While endoscopic ultrasound-fine needle aspiration (EUS-FNA) has been demonstrated to be a reliable and accurate diagnostic tool for solid pancreatic neoplasms, the ongoing management of patients with a high clinical suspicion for malignancy but with a negative EUS-FNA biopsy result can prove a challenge. METHODS We describe five patients from a single centre who presented for further work-up of a pancreatic mass and/or imaging features concerning for a periampullary malignancy. RESULTS All patients had at least one EUS-FNA biopsy performed which returned no malignant cells on cytology. Despite these negative cytology results, all patients underwent further invasive investigation through upfront resection (pancreaticoduodenectomy) or extra-pancreatic biopsy (laparoscopic biopsy of peritoneal nodule) due to worrisome features on imaging, biochemical factors and clinical presentation culminating in a high degree of suspicion for malignancy. The final tissue histopathological diagnosis in all patients was pancreatic ductal adenocarcinoma. CONCLUSION This case series highlights the important clinical findings, imaging and biochemical features which need to be considered in patients who have high suspicion for malignancy despite having a negative EUS-FNA cytology result. In these patients with a high index of suspicion, surgical intervention through an upfront resection or further invasive investigation should not be delayed.
Collapse
Affiliation(s)
- Hiro Masuda
- Department of Upper Gastrointestinal Surgery, Royal North Shore Hospital, Sydney, New South Wales, Australia
| | - Krishna Kotecha
- Department of Upper Gastrointestinal Surgery, Royal North Shore Hospital, Sydney, New South Wales, Australia
| | - Rudra Maitra
- Department of Upper Gastrointestinal Surgery, Royal North Shore Hospital, Sydney, New South Wales, Australia
| | - Anthony J Gill
- Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia.,NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia.,Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia
| | - Anubhav Mittal
- Department of Upper Gastrointestinal Surgery, Royal North Shore Hospital, Sydney, New South Wales, Australia.,Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia.,School of Medicine, University of Notre Dame, Sydney, New South Wales, Australia
| | - Jaswinder S Samra
- Department of Upper Gastrointestinal Surgery, Royal North Shore Hospital, Sydney, New South Wales, Australia.,Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia
| |
Collapse
|
|
14
|
Gallo M, Adinolfi V, Morviducci L, Acquati S, Tuveri E, Ferrari P, Zatelli MC, Faggiano A, Argentiero A, Natalicchio A, D'Oronzo S, Danesi R, Gori S, Russo A, Montagnani M, Beretta GD, Di Bartolo P, Silvestris N, Giorgino F. Early prediction of pancreatic cancer from new-onset diabetes: an Associazione Italiana Oncologia Medica (AIOM)/Associazione Medici Diabetologi (AMD)/Società Italiana Endocrinologia (SIE)/Società Italiana Farmacologia (SIF) multidisciplinary consensus position paper. ESMO Open 2021; 6:100155. [PMID: 34020401 PMCID: PMC8144346 DOI: 10.1016/j.esmoop.2021.100155] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Accepted: 04/19/2021] [Indexed: 02/07/2023] Open
Abstract
Pancreatic cancer (PC) is a common cause of cancer-related death, due to difficulties in detecting early-stage disease, to its aggressive behaviour, and to poor response to systemic therapy. Therefore, developing strategies for early diagnosis of resectable PC is critical for improving survival. Diabetes mellitus is another major public health problem worldwide. Furthermore, diabetes can represent both a risk factor and a consequence of PC: nowadays, the relationship between these two diseases is considered a high priority for research. New-onset diabetes can be an early manifestation of PC, especially in a thin adult without a family history of diabetes. However, even if targeted screening for patients at higher risk of PC could be a promising approach, this is not recommended in asymptomatic adults with new-onset diabetes, due to the much higher incidence of hyperglycaemia than PC and to the lack of a safe and affordable PC screening test. Prompted by a well-established and productive multidisciplinary cooperation, the Italian Association of Medical Oncology (AIOM), the Italian Medical Diabetologists Association (AMD), the Italian Society of Endocrinology (SIE), and the Italian Society of Pharmacology (SIF) here review available evidence on the mechanisms linking diabetes and PC, addressing the feasibility of screening for early PC in patients with diabetes, and sharing a set of update statements with the aim of providing a state-of-the-art overview and a decision aid tool for daily clinical practice.
The incidence of PC is increasing and its prognosis is very poor; therefore, early detection is fundamental. New-onset diabetes may be an early manifestation of PC, often disappearing after its resection. Screening for PC is not currently recommended among people with new-onset diabetes, due to its high incidence. Thin subjects >50 years old at the time of diabetes onset, with sudden weight loss and severe hyperglycaemia are at higher risk. Currently some clinical models are promising for stratifying cancer risk in people with new-onset diabetes.
Collapse
Affiliation(s)
- M Gallo
- Endocrinology and Metabolic Diseases Unit of AO SS Antonio e Biagio e Cesare Arrigo of Alessandria, Alessandria, Italy.
| | - V Adinolfi
- Endocrinology and Diabetology Unit, ASL Verbano Cusio Ossola, Domodossola, Italy
| | - L Morviducci
- Diabetology and Nutrition Unit, Department of Medical Specialities, ASL Roma 1 - S. Spirito Hospital, Rome, Italy
| | - S Acquati
- Endocrinology Unit, Ospedale Pierantoni-Morgagni, Forlì, Italy
| | - E Tuveri
- Diabetology, Endocrinology and Metabolic Diseases Service, ATS Sardegna - ASSL Carbonia-Iglesias, Italy
| | - P Ferrari
- Palliative Care Unit, Istituti Clinici Scientifici Maugeri SPA SB, IRCCS, Pavia, Italy
| | - M C Zatelli
- Section of Endocrinology & Internal Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy
| | - A Faggiano
- Endocrinology Unit, Department of Clinical & Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - A Argentiero
- Medical Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy
| | - A Natalicchio
- Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy
| | - S D'Oronzo
- Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
| | - R Danesi
- Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - S Gori
- Oncologia Medica, IRCCS Ospedale Don Calabria-Sacro Cuore di Negrar, Verona, Italy
| | - A Russo
- Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy
| | - M Montagnani
- Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
| | - G D Beretta
- Medical Oncology Department, Humanitas Gavazzeni, Bergamo, Italy
| | - P Di Bartolo
- Ravenna Diabetes Center, Romagna Diabetes Managed Clinical Network - Romagna Local Health Authority, Ravenna, Italy
| | - N Silvestris
- Medical Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy; Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
| | - F Giorgino
- Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy
| |
Collapse
|
|
15
|
Non-coding RNA biomarkers in pancreatic ductal adenocarcinoma. Semin Cancer Biol 2020; 75:153-168. [PMID: 33049362 DOI: 10.1016/j.semcancer.2020.10.001] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 09/20/2020] [Accepted: 10/02/2020] [Indexed: 12/13/2022]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, which is usually diagnosed at an advanced stage. The late disease diagnosis, the limited availability of effective therapeutic interventions and lack of robust diagnostic biomarkers, are some of the primary reasons for the dismal 5-year survival rates (∼8%) in patients with PDAC. The pancreatic cancer develops through accumulation of a series of genomic and epigenomic alterations which lead to the transformation of normal pancreatic epithelium into an invasive carcinoma - a process that can take up to 15-20 years to develop, from the occurrence of first initiating mutational event. These facts highlight a unique window of opportunity for the earlier detection of PDAC, which could allow timely disease interception and improvement in the overall survival outcomes in patients suffering from this fatal malignancy. Non-coding RNAs (ncRNAs) have been recognized to play a central role in PDAC pathogenesis and are emerging as attractive candidates for biomarker development in various cancers, including PDAC. More specifically, the ncRNAs play a pivotal role in PDAC biology as they affect tumor growth, migration, and invasion by regulating cellular processes including cell cycle, apoptosis, and epithelial-mesenchymal transition. In this review, we focus on three types of well-established ncRNAs - microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) - and discuss their potential as diagnostic, prognostic and predictive biomarkers in PDAC.
Collapse
|
|
16
|
Loch FN, Asbach P, Haas M, Seeliger H, Beyer K, Schineis C, Degro CE, Margonis GA, Kreis ME, Kamphues C. Accuracy of various criteria for lymph node staging in ductal adenocarcinoma of the pancreatic head by computed tomography and magnetic resonance imaging. World J Surg Oncol 2020; 18:213. [PMID: 32811523 PMCID: PMC7436989 DOI: 10.1186/s12957-020-01951-3] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 07/07/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Lymph node staging of ductal adenocarcinoma of the pancreatic head (PDAC) by cross-sectional imaging is limited. The aim of this study was to determine the diagnostic accuracy of expanded criteria in nodal staging in PDAC patients. METHODS Sixty-six patients with histologically confirmed PDAC that underwent primary surgery were included in this retrospective IRB-approved study. Cross-sectional imaging studies (CT and/or MRI) were evaluated by a radiologist blinded to histopathology. Number and size of lymph nodes were measured (short-axis diameter) and characterized in terms of expanded morphological criteria of border contour (spiculated, lobulated, and indistinct) and texture (homogeneous or inhomogeneous). Sensitivities and specificities were calculated with histopathology as a reference standard. RESULTS Forty-eight of 66 patients (80%) had histologically confirmed lymph node metastases (pN+). Sensitivity, specificity, and Youden's Index for the criterion "size" were 44.2%, 82.4%, and 0.27; for "inhomogeneous signal intensity" 25.6%, 94.1%, and 0.20; and for "border contour" 62.7%, 52.9%, and 0.16, respectively. There was a significant association between the number of visible lymph nodes on preoperative CT and lymph node involvement (pN+, p = 0.031). CONCLUSION Lymph node staging in PDAC is mainly limited due to low sensitivity for detection of metastatic disease. Using expanded morphological criteria instead of size did not improve regional nodal staging due to sensitivity remaining low. Combining specific criteria yields improved sensitivity with specificity and PPV remaining high.
Collapse
Affiliation(s)
- Florian N Loch
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Surgery, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany.
| | - Patrick Asbach
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Radiology, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany
| | - Matthias Haas
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Radiology, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany
| | - Hendrik Seeliger
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Surgery, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany
| | - Katharina Beyer
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Surgery, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany
| | - Christian Schineis
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Surgery, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany
| | - Claudius E Degro
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Surgery, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany
| | - Georgios A Margonis
- The Johns Hopkins University School of Medicine, Department of Surgery, 600 N. Wolfe Street, Blalock 688, Baltimore, MD, 21287, USA
| | - Martin E Kreis
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Surgery, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany
| | - Carsten Kamphues
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Surgery, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany
| |
Collapse
|
|
17
|
Martin-Perez E, Domínguez-Muñoz JE, Botella-Romero F, Cerezo L, Matute Teresa F, Serrano T, Vera R. Multidisciplinary consensus statement on the clinical management of patients with pancreatic cancer. Clin Transl Oncol 2020; 22:1963-1975. [PMID: 32318964 PMCID: PMC7505812 DOI: 10.1007/s12094-020-02350-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 04/01/2020] [Indexed: 12/14/2022]
Abstract
Pancreatic cancer (PC) remains one of the most aggressive tumors with an increasing incidence rate and reduced survival. Although surgical resection is the only potentially curative treatment for PC, only 15–20% of patients are resectable at diagnosis. To select the most appropriate treatment and thus improve outcomes, the diagnostic and therapeutic strategy for each patient with PC should be discussed within a multidisciplinary expert team. Clinical decision-making should be evidence-based, considering the staging of the tumor, the performance status and preferences of the patient. The aim of this guideline is to provide practical and evidence-based recommendations for the management of PC.
Collapse
Affiliation(s)
- E Martin-Perez
- Department of Surgery, Hospital Universitario de La Princesa, Diego de Leon 62, 28006, Madrid, Spain.
| | - J E Domínguez-Muñoz
- Department of Gastroenterology and Hepatology, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
| | - F Botella-Romero
- Department of Endocrinology, Hospital General Universitario, Albacete, Spain
| | - L Cerezo
- Department of Radiation Oncology, Hospital Universitario de La Princesa, Madrid, Spain
| | - F Matute Teresa
- Department of Radiology, Hospital Clínico San Carlos, Madrid, Spain
| | - T Serrano
- Department of Pathology, Hospital Universitario de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.,Oncology Program, CIBEREHD National Biomedical Research Institute on Liver and Gastrointestinal Diseases, Instituto de Salud Carlos III, Madrid, Spain
| | - R Vera
- Department of Medical Oncology, Complejo Hospitalario de Navarra, Pamplona, Spain
| |
Collapse
|
|
18
|
Abstract
OBJECTIVES We aimed to determine the difference in endoscopic ultrasonography (EUS) images between portal vein (PV) and arterial invasion of pancreatic cancer and to develop criteria for arterial involvement. METHODS We reviewed EUS data of consecutive patients who underwent distal pancreatectomy from December 2010 to May 2017. We categorized the tumor-vessel relationship into 4 and 5 types, respectively, for the PV and arteries: (a) clear separation between tumor and vessel; (b) tumor border at vessel, echo-rich vessel wall uninterrupted; (c) echo-rich vessel wall interrupted; (d) vessel contour irregularity; and (e) arterial wall thickening or echogenic band surrounding the artery. We compared EUS outcomes with surgical and pathological results. RESULTS Overall, 56 patients underwent distal pancreatectomy, of whom 22 received en bloc celiac axis resection. The pathological invasion rates of PVs and arteries were 46.2% and 0% in (c), and 72.5% and 42.4% in (d) (P = 0.046, P = 0.016), respectively. The overall sensitivity and specificity were 92.1% and 83.2%, respectively, for diagnosing venous invasion and 70.0% and 84.4%, respectively, for arterial invasion. CONCLUSIONS Different EUS criteria may be necessary for diagnosing arterial and portal venous invasions. Criterion (d) might be appropriate for diagnosing arterial invasion.
Collapse
|
|
19
|
Yamada K, Kawashima H, Ohno E, Ishikawa T, Tanaka H, Nakamura M, Miyahara R, Ishigami M, Hirooka Y, Fujishiro M. Diagnosis of vascular invasion in pancreatic ductal adenocarcinoma using endoscopic ultrasound elastography. BMC Gastroenterol 2020; 20:81. [PMID: 32228472 PMCID: PMC7106834 DOI: 10.1186/s12876-020-01228-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Accepted: 03/19/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Vascular invasion is an important criterion for resectability and deciding the therapeutic strategy for pancreatic ductal adenocarcinoma (PDAC), but imaging diagnosis is currently difficult. Endoscopic ultrasound (EUS) elastography (EG) images have band-like artifacts on the border between tumor and vessel due to different movement if the tumor is not connected to the vessel, i.e., no invasion. Based on this phenomenon, we assessed the usefulness of EUS-EG in the diagnosis of vascular invasion in PDAC. METHODS The subjects were 44 out of 313 patients with PDAC who underwent EUS between January 2015 and November 2018, followed by surgery, no chemotherapy or radiotherapy, and pathological evaluation. Diagnostic accuracies of vascular invasion using dynamic computed tomography (CT), EUS B-mode and EUS-EG were compared with histopathological diagnosis. RESULTS In 44 subjects (48 sites) who underwent both dynamic CT and EUS-B mode, the sensitivity, specificity and accuracy were 0.733, 0.697 and 0.708 on dynamic CT (48 sites); 0.733, 0.606 and 0.646 in EUS B-mode (48 sites); and 0.917, 0.900 and 0.906 in EUS-EG (32 sites). In 27 subjects (29 sites) with a tumor contacting a vessel with no vascular obstruction or stenosis on dynamic CT, the sensitivity, specificity and accuracy were 0.556, 0.750 and 0.690 on dynamic CT; 0.667, 0.700 and 0.690 in EUS B-mode; and 0.889, 0.850 and 0.862 in EUS-EG. CONCLUSIONS These results suggest that EUS combined with EG improves diagnostic performance of vascular invasion in PDAC, especially in cases of which vascular invasion cannot be clearly assessed by dynamic CT.
Collapse
Affiliation(s)
- Kenta Yamada
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Hiroki Kawashima
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan.
| | - Eizaburo Ohno
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Takuya Ishikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Hiroyuki Tanaka
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Masanao Nakamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Ryoji Miyahara
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Yoshiki Hirooka
- Department of Liver, Biliary Tract and Pancreas Diseases, Fujita Health University, 1-98 kutsukake-cho dengakekakubo, Toyoake, 470-1192, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
| |
Collapse
|
|
20
|
Hwang YJ, Park SM, Ahn S, Lee JC, Park YS, Kim N. Accuracy of an administrative database for pancreatic cancer by international classification of disease 10 th codes: A retrospective large-cohort study. World J Gastroenterol 2019; 25:5619-5629. [PMID: 31602162 PMCID: PMC6785515 DOI: 10.3748/wjg.v25.i37.5619] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Revised: 09/03/2019] [Accepted: 09/11/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Korean National Health Insurance (NHI) claims database provides large-cohort. However, studies regarding accuracy of administrative database for pancreatic cancer (PC) have not been reported. We aimed to identify accuracy of NHI database regarding PC classified by international classification of disease (ICD)-10 codes. AIM To identify the accuracy and usefulness of administrative database in PC and the accurate ICD codes for PC with location. METHODS Study and control groups were collected from 2003 to 2016 at Seoul National University Bundang Hospital. Cases of PC were identified in NHI database by international classification of diseases, 10th revision edition (ICD-10 codes) supported with V codes. V code is issued by medical doctors for covering 95% of medical cost by Korean government. According to pathologic reports, definite or possible diagnoses were defined using medical records, images, and pathology. RESULTS A total of 1846 cases with PC and controls were collected. Among PC, only 410 (22.2%) cases were identified as specific cancer sites including head in 234 (12.7%) cases, tail in 104 (5.6%) cases and body in 72 (3.9%) cases. Among PC, 910 (49.3%) cases were diagnosed by definite criteria. Most of these were adenocarcinoma (98.0%). The rates of definite diagnosis of PC were highest in head (70.1%) followed by body (47.2%) and tail (43.3%). False-positive cases were pancreatic cystic neoplasm and metastasis to the pancreas. In terms of the overall diagnosis of PC, sensitivity, specificity, positive predictive value, and negative predictive value were 99.95%, 98.72%, 98.70%, and 99.95%, respectively. Diagnostic accuracy was similar both in terms of diagnostic criteria and tumor locations. CONCLUSION Korean NHI claims database collected according to ICD-10 code with V code for PC showed good accuracy.
Collapse
Affiliation(s)
- Young-Jae Hwang
- Departments of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam 13620, South Korea
| | - Seon Mee Park
- Department of Internal Medicine, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju 28644, South Korea
| | - Soomin Ahn
- Departments of Pathology, Seoul National University Bundang Hospital, Seoungnam 13620, South Korea
| | - Jong-Chan Lee
- Departments of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam 13620, South Korea
| | - Young Soo Park
- Departments of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam 13620, South Korea
| | - Nayoung Kim
- Departments of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam 13620, South Korea
- Department of Internal Medicine and Institute of Liver Research and Tumor Microenvironment Global Core Research Center, Seoul National University College of Medicine, Seoul 08826, South Korea
| |
Collapse
|
|
21
|
Fujii Y, Matsumoto K, Kato H, Saragai Y, Takada S, Mizukawa S, Muro S, Uchida D, Tomoda T, Horiguchi S, Tanaka N, Okada H. Diagnostic Ability of Convex-Arrayed Endoscopic Ultrasonography for Major Vascular Invasion in Pancreatic Cancer. Clin Endosc 2019; 52:479-485. [PMID: 31091868 PMCID: PMC6785423 DOI: 10.5946/ce.2018.163] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2018] [Accepted: 01/03/2019] [Indexed: 12/13/2022] Open
Abstract
Background/Aims This study aimed to examine the diagnostic ability of endoscopic ultrasonography (EUS) for major vascular invasion in pancreatic cancer and to evaluate the relationship between EUS findings and pathological distance.
Methods In total, 57 consecutive patients who underwent EUS for pancreatic cancer before surgery were retrospectively reviewed. EUS image findings were divided into four types according to the relationship between the tumor and major vessel (types 1 and 2: invasion, types 3 and 4: non-invasion). We also compared the EUS findings and pathologically measured distances between the tumors and evaluated vessels.
Results The sensitivity, specificity, and accuracy of EUS diagnosis for vascular invasion were 89%, 92%, and 91%, respectively, in the veins and 83%, 94%, and 93%, respectively, in the arteries. The pathologically evaluated distances of cases with type 2 EUS findings were significantly shorter than those of cases with type 3 EUS findings in both the major veins (median [interquartile range], 96 [0–742] µm vs. 2,833 [1,076–5,694] µm, p=0.012) and arteries (623 [0–854] µm vs. 3,097 [1,396–6,000] µm, p=0.0061). All cases with a distance of ≥1,000 µm between the tumors and main vessels were correctly diagnosed.
Conclusions Tumors at a distance ≥1,000 µm from the main vessels were correctly diagnosed by EUS.
Collapse
Affiliation(s)
- Yuki Fujii
- Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Kazuyuki Matsumoto
- Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Hironari Kato
- Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Yosuke Saragai
- Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Saimon Takada
- Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Sho Mizukawa
- Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Shinichiro Muro
- Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Daisuke Uchida
- Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Takeshi Tomoda
- Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Shigeru Horiguchi
- Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Noriyuki Tanaka
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Science, Okayama, Japan
| |
Collapse
|
|
22
|
Singhi AD, Koay EJ, Chari ST, Maitra A. Early Detection of Pancreatic Cancer: Opportunities and Challenges. Gastroenterology 2019; 156:2024-2040. [PMID: 30721664 PMCID: PMC6486851 DOI: 10.1053/j.gastro.2019.01.259] [Citation(s) in RCA: 468] [Impact Index Per Article: 78.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Revised: 01/08/2019] [Accepted: 01/15/2019] [Indexed: 12/17/2022]
Abstract
Most patients with pancreatic ductal adenocarcinoma (PDAC) present with symptomatic, surgically unresectable disease. Although the goal of early detection of PDAC is laudable and likely to result in significant improvement in overall survival, the relatively low prevalence of PDAC renders general population screening infeasible. The challenges of early detection include identification of at-risk individuals in the general population who would benefit from longitudinal surveillance programs and appropriate biomarker and imaging-based modalities used for PDAC surveillance in such cohorts. In recent years, various subgroups at higher-than-average risk for PDAC have been identified, including those with familial risk due to germline mutations, a history of pancreatitis, patients with mucinous pancreatic cysts, and elderly patients with new-onset diabetes. The last 2 categories are discussed at length in terms of the opportunities and challenges they present for PDAC early detection. We also discuss current and emerging imaging modalities that are critical to identifying early, potentially curable PDAC in high-risk cohorts on surveillance.
Collapse
Affiliation(s)
- Aatur D Singhi
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Eugene J Koay
- Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas; Sheikh Ahmed Center for Pancreatic Cancer Research, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Suresh T Chari
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
| | - Anirban Maitra
- Sheikh Ahmed Center for Pancreatic Cancer Research, University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas
| |
Collapse
|
|
23
|
Zhang L, Sanagapalli S, Stoita A. Challenges in diagnosis of pancreatic cancer. World J Gastroenterol 2018; 24:2047-2060. [PMID: 29785074 PMCID: PMC5960811 DOI: 10.3748/wjg.v24.i19.2047] [Citation(s) in RCA: 347] [Impact Index Per Article: 49.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 04/28/2018] [Accepted: 05/11/2018] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer is a growing source of cancer related death, yet has poor survival rates which have not improved in the last few decades. Its high mortality rate is attributed to pancreatic cancer biology, difficulty in early diagnosis and the lack of standardised international guidelines in assessing suspicious pancreatic masses. This review aims to provide an update in the current state of play in pancreatic cancer diagnosis and to evaluate the benefits and limitations of available diagnostic technology. The main modalities discussed are imaging with computed tomography, magnetic resonance imaging, endoscopic ultrasound and positron emission tomography and tissue acquisition with fine needle aspiration. We also review the improvements in the techniques used for tissue acquisition and the opportunity for personalised cancer medicine. Screening of high risk individuals, promising biomarkers and common mimickers of pancreatic cancer are also explored, as well as suggestions for future research directions to allow for earlier detection of pancreatic cancer. Timely and accurate diagnosis of pancreatic cancer can lead to improvements in the current poor outcome of this disease.
Collapse
Affiliation(s)
- Lulu Zhang
- Department of Gastroenterology, St. Vincent’s Hospital Sydney, Darlinghurst 2010, NSW, Australia
| | - Santosh Sanagapalli
- Department of Gastroenterology, St. Vincent’s Hospital Sydney, Darlinghurst 2010, NSW, Australia
| | - Alina Stoita
- Department of Gastroenterology, St. Vincent’s Hospital Sydney, Darlinghurst 2010, NSW, Australia
| |
Collapse
|
|
24
|
Kang MJ, Jang JY, Kwon W, Kim SW. Clinical significance of defining borderline resectable pancreatic cancer. Pancreatology 2018; 18:139-145. [PMID: 29274720 DOI: 10.1016/j.pan.2017.12.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Revised: 11/21/2017] [Accepted: 12/06/2017] [Indexed: 12/11/2022]
Abstract
Since the introduction of the concept of borderline resectable pancreatic cancer (BRPC), various definitions of this disease entity have been suggested. However, there are several obstacles in defining this disease category. The current diagnostic criteria of BRPC mainly focuses on its expanded 'technical resectability'; however, they are difficult to interpret because of their ambiguity using potential subjective or arbitrary terminology, In addition, limitations in current imaging technology and a lack of evidence in radiological-pathological-clinical correlation make it difficult to refine the criteria. On the other hand, neoadjuvant treatment is usually applied to increase the R0 resection rate of BRPC focusing on the 'oncological curability'. However, evidence is needed concerning the effect of neoadjuvant treatment by quality-controlled prospective randomized clinical trials based on a standardized radiologic and pathologic reporting system. In conclusion, there are two aspects in the current concept of BRPC, which are technical resectability and oncological curability. Although the recent evolution of surgical techniques is expanding the scope of technical resectability, it should not be overlooked that the disease entity must be defined based on the evidence of oncological curability.
Collapse
Affiliation(s)
- Mee Joo Kang
- Korea International Cooperation Agency, Republic of Korea
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sun-Whe Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
| |
Collapse
|
|
25
|
Ghaneh P, Hanson R, Titman A, Lancaster G, Plumpton C, Lloyd-Williams H, Yeo ST, Edwards RT, Johnson C, Abu Hilal M, Higginson AP, Armstrong T, Smith A, Scarsbrook A, McKay C, Carter R, Sutcliffe RP, Bramhall S, Kocher HM, Cunningham D, Pereira SP, Davidson B, Chang D, Khan S, Zealley I, Sarker D, Al Sarireh B, Charnley R, Lobo D, Nicolson M, Halloran C, Raraty M, Sutton R, Vinjamuri S, Evans J, Campbell F, Deeks J, Sanghera B, Wong WL, Neoptolemos JP. PET-PANC: multicentre prospective diagnostic accuracy and health economic analysis study of the impact of combined modality 18fluorine-2-fluoro-2-deoxy-d-glucose positron emission tomography with computed tomography scanning in the diagnosis and management of pancreatic cancer. Health Technol Assess 2018; 22:1-114. [PMID: 29402376 PMCID: PMC5817411 DOI: 10.3310/hta22070] [Citation(s) in RCA: 66] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Pancreatic cancer diagnosis and staging can be difficult in 10-20% of patients. Positron emission tomography (PET)/computed tomography (CT) adds precise anatomical localisation to functional data. The use of PET/CT may add further value to the diagnosis and staging of pancreatic cancer. OBJECTIVE To determine the incremental diagnostic accuracy and impact of PET/CT in addition to standard diagnostic work-up in patients with suspected pancreatic cancer. DESIGN A multicentre prospective diagnostic accuracy and clinical value study of PET/CT in suspected pancreatic malignancy. PARTICIPANTS Patients with suspected pancreatic malignancy. INTERVENTIONS All patients to undergo PET/CT following standard diagnostic work-up. MAIN OUTCOME MEASURES The primary outcome was the incremental diagnostic value of PET/CT in addition to standard diagnostic work-up with multidetector computed tomography (MDCT). Secondary outcomes were (1) changes in patients' diagnosis, staging and management as a result of PET/CT; (2) changes in the costs and effectiveness of patient management as a result of PET/CT; (3) the incremental diagnostic value of PET/CT in chronic pancreatitis; (4) the identification of groups of patients who would benefit most from PET/CT; and (5) the incremental diagnostic value of PET/CT in other pancreatic tumours. RESULTS Between 2011 and 2013, 589 patients with suspected pancreatic cancer underwent MDCT and PET/CT, with 550 patients having complete data and in-range PET/CT. Sensitivity and specificity for the diagnosis of pancreatic cancer were 88.5% and 70.6%, respectively, for MDCT and 92.7% and 75.8%, respectively, for PET/CT. The maximum standardised uptake value (SUVmax.) for a pancreatic cancer diagnosis was 7.5. PET/CT demonstrated a significant improvement in relative sensitivity (p = 0.01) and specificity (p = 0.023) compared with MDCT. Incremental likelihood ratios demonstrated that PET/CT significantly improved diagnostic accuracy in all scenarios (p < 0.0002). PET/CT correctly changed the staging of pancreatic cancer in 56 patients (p = 0.001). PET/CT influenced management in 250 (45%) patients. PET/CT stopped resection in 58 (20%) patients who were due to have surgery. The benefit of PET/CT was limited in patients with chronic pancreatitis or other pancreatic tumours. PET/CT was associated with a gain in quality-adjusted life-years of 0.0157 (95% confidence interval -0.0101 to 0.0430). In the base-case model PET/CT was seen to dominate MDCT alone and is thus highly likely to be cost-effective for the UK NHS. PET/CT was seen to be most cost-effective for the subgroup of patients with suspected pancreatic cancer who were thought to be resectable. CONCLUSION PET/CT provided a significant incremental diagnostic benefit in the diagnosis of pancreatic cancer and significantly influenced the staging and management of patients. PET/CT had limited utility in chronic pancreatitis and other pancreatic tumours. PET/CT is likely to be cost-effective at current reimbursement rates for PET/CT to the UK NHS. This was not a randomised controlled trial and therefore we do not have any information from patients who would have undergone MDCT only for comparison. In addition, there were issues in estimating costs for PET/CT. Future work should evaluate the role of PET/CT in intraductal papillary mucinous neoplasm and prognosis and response to therapy in patients with pancreatic cancer. STUDY REGISTRATION Current Controlled Trials ISRCTN73852054 and UKCRN 8166. FUNDING The National Institute for Health Research Health Technology Assessment programme.
Collapse
Affiliation(s)
- Paula Ghaneh
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
| | - Robert Hanson
- Liverpool Cancer Research UK Cancer Trials Unit, University of Liverpool, Liverpool, UK
| | - Andrew Titman
- Department of Mathematics and Statistics, Lancaster University, Lancaster, UK
| | - Gill Lancaster
- Department of Mathematics and Statistics, Lancaster University, Lancaster, UK
| | - Catrin Plumpton
- Centre for Health Economics and Medicines Evaluation, Bangor University, Bangor, UK
| | - Huw Lloyd-Williams
- Centre for Health Economics and Medicines Evaluation, Bangor University, Bangor, UK
| | - Seow Tien Yeo
- Centre for Health Economics and Medicines Evaluation, Bangor University, Bangor, UK
| | | | - Colin Johnson
- Faculty of Medicine, University of Southampton, Southampton, UK
| | - Mohammed Abu Hilal
- Department of Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | | | - Tom Armstrong
- Department of Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Andrew Smith
- Department of Gastrointestinal Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Andrew Scarsbrook
- Department of Radiology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Colin McKay
- Department of Surgery, Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde, Glasgow, UK
| | - Ross Carter
- Department of Surgery, Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde, Glasgow, UK
| | - Robert P Sutcliffe
- Department of Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Simon Bramhall
- Department of General Surgery, Wye Valley NHS Trust, Hereford, UK
| | - Hemant M Kocher
- Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, London, UK
| | - David Cunningham
- Gastrointestinal and Lymphoma Unit, Royal Marsden NHS Foundation Trust, London, UK
| | - Stephen P Pereira
- Institute for Liver and Digestive Health, University College London Hospitals NHS Foundation Trust, London, UK
| | - Brian Davidson
- Department of Surgery, Royal Free London NHS Foundation Trust, London, UK
| | - David Chang
- Department of Surgery, Royal Blackburn Hospital, East Lancashire Hospitals NHS Trust, Blackburn, UK
| | - Saboor Khan
- Department of Surgery, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
| | - Ian Zealley
- Department of Surgery, Ninewells Hospital and Medical School, NHS Tayside, Dundee, UK
| | - Debashis Sarker
- Department of Oncology, King's College Hospital NHS Foundation Trust, London, UK
| | - Bilal Al Sarireh
- Department of Surgery, Morriston Hospital, Abertawe Bro Morgannwg University Health Board, Swansea, UK
| | - Richard Charnley
- Department of Surgery, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Dileep Lobo
- Faculty of Medicine and Life Sciences, University of Nottingham, Nottingham, UK
| | - Marianne Nicolson
- Department of Oncology, Aberdeen Royal Infirmary, NHS Grampian, Aberdeen, UK
| | - Christopher Halloran
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
| | - Michael Raraty
- Department of Surgery, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
| | - Robert Sutton
- Department of Surgery, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
| | - Sobhan Vinjamuri
- Department of Nuclear Medicine, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
| | - Jonathan Evans
- Department of Radiology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
| | - Fiona Campbell
- Department of Pathology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
| | - Jon Deeks
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Bal Sanghera
- Paul Strickland Scanner Centre, Mount Vernon Hospital, Middlesex, UK
| | - Wai-Lup Wong
- Paul Strickland Scanner Centre, Mount Vernon Hospital, Middlesex, UK
| | - John P Neoptolemos
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
| |
Collapse
|
|
26
|
Crippa S, Cirocchi R, Maisonneuve P, Partelli S, Pergolini I, Tamburrino D, Aleotti F, Reni M, Falconi M. Systematic review and meta-analysis of prognostic role of splenic vessels infiltration in resectable pancreatic cancer. Eur J Surg Oncol 2017; 44:24-30. [PMID: 29183639 DOI: 10.1016/j.ejso.2017.10.217] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2017] [Revised: 10/02/2017] [Accepted: 10/23/2017] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Identification of factors associated with dismal survival after surgery in resectable pancreatic ductal adenocarcinoma is important to select patients for neoadjuvant treatment. The present meta-analysis aimed to compare the results of distal pancreatectomy for resectable adenocarcinoma of the pancreatic body-tail with and without splenic vessels infiltration. METHODS A systematic search was performed of PubMed, Embase and the Cochrane Library in accordance with PRISMA guidelines. The inclusion criteria were studies including patients who underwent distal pancreatectomy for pancreatic cancer with or without splenic vessels infiltration. 5-year overall survival (OS) was the primary outcomes. Meta-analysis was carried out applying time-to-event method. RESULTS Six articles with 423 patients were analysed. Patients with pathological splenic artery invasion had a worse survival compared with those without infiltration (Hazard ratio 1.76, 95% CI 1.36-2.28; P < 0.0001). A similar results was found when considering pathological splenic vessels infiltration, showing that survival was significantly poorer when splenic vein infiltration was present (Hazard ratio 1.51, 95% CI 1.19-1.93; P = 0.0009). CONCLUSIONS This meta-analysis showed worse survival for patients with splenic vessels infiltration undergoing distal pancreatectomy for pancreatic cancer. Splenic vessels infiltration represents the stigmata of a more aggressive disease, although resectable.
Collapse
Affiliation(s)
- Stefano Crippa
- Division of Pancreatic Surgery, Vita e Salute University, San Raffaele Scientific Institute, Milan, Italy; Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy
| | - Roberto Cirocchi
- Department of General and Oncologic Surgery, University of Perugia, St. Maria Hospital, Terni, Italy
| | - Patrick Maisonneuve
- Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy
| | - Stefano Partelli
- Division of Pancreatic Surgery, Vita e Salute University, San Raffaele Scientific Institute, Milan, Italy; Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy
| | - Ilaria Pergolini
- Department of Surgery, Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy
| | - Domenico Tamburrino
- Division of Pancreatic Surgery, Vita e Salute University, San Raffaele Scientific Institute, Milan, Italy; Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy
| | - Francesca Aleotti
- Division of Pancreatic Surgery, Vita e Salute University, San Raffaele Scientific Institute, Milan, Italy; Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy
| | - Michele Reni
- Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy; Department of Oncology, San Raffaele Scientific Institute, Milan, Italy
| | - Massimo Falconi
- Division of Pancreatic Surgery, Vita e Salute University, San Raffaele Scientific Institute, Milan, Italy; Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy.
| |
Collapse
|
|
27
|
Hempel S, Plodeck V, Mierke F, Distler M, Aust DE, Saeger HD, Weitz J, Welsch T. Para-aortic lymph node metastases in pancreatic cancer should not be considered a watershed for curative resection. Sci Rep 2017; 7:7688. [PMID: 28794500 PMCID: PMC5550512 DOI: 10.1038/s41598-017-08165-w] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Accepted: 07/07/2017] [Indexed: 12/12/2022] Open
Abstract
No international consensus regarding the resection of the para-aortic lymph node (PALN) station Ln16b1 during pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) has been reached. The present retrospectively investigated 264 patients with PDAC who underwent curative pancreatoduodenectomy or total pancreatectomy between 2005–2015. In 95 cases, the PALN were separately labelled and histopathologically analysed. Metastatic PALN (PALN+) were found in 14.7% (14/95). PALN+ stage was associated with increased regional lymph node metastasis. The median overall survival (OS) of patients with metastatic PALN and with non-metastatic PALN (PALN−) was 14.1 and 20.2 months, respectively. Five of the PALN+ patients (36%) survived >19 months. The OS of PALN+ and those staged pN1 PALN− was not significantly different (P = 0.743). Patients who underwent surgical exploration or palliative surgery (n = 194) had a lower median survival of 8.8 (95% confidence interval: 7.3–10.1) months. PALN status could not be reliably predicted by preoperative computed tomography. We concluded that the survival data of PALN+ cases is comparable with advanced pN+ stages; one-third of the patients may expect longer survival after radical resection. Therefore, routine refusal of curative resection in the case of PALN metastasis is not indicated.
Collapse
Affiliation(s)
- Sebastian Hempel
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
| | - Verena Plodeck
- Department of Diagnostic and Interventional Radiology, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
| | - Franz Mierke
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
| | - Marius Distler
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
| | - Daniela E Aust
- Institute for Pathology, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
| | - Hans-Detlev Saeger
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
| | - Jürgen Weitz
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
| | - Thilo Welsch
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany.
| |
Collapse
|
|
28
|
Kyrochristos ID, Glantzounis GK, Ziogas DE, Gizas I, Schizas D, Lykoudis EG, Felekouras E, Machairas A, Katsios C, Liakakos T, Cho WC, Roukos DH. From Clinical Standards to Translating Next-Generation Sequencing Research into Patient Care Improvement for Hepatobiliary and Pancreatic Cancers. Int J Mol Sci 2017; 18:E180. [PMID: 28106782 PMCID: PMC5297812 DOI: 10.3390/ijms18010180] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2016] [Revised: 12/19/2016] [Accepted: 12/27/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatobiliary and pancreatic (HBP) cancers are associated with high cancer-related death rates. Surgery aiming for complete tumor resection (R0) remains the cornerstone of the treatment for HBP cancers. The current progress in the adjuvant treatment is quite slow, with gemcitabine chemotherapy available only for pancreatic ductal adenocarcinoma (PDA). In the advanced and metastatic setting, only two targeted drugs have been approved by the Food & Drug Administration (FDA), which are sorafenib for hepatocellular carcinoma and erlotinib for PDA. It is a pity that multiple Phase III randomized control trials testing the efficacy of targeted agents have negative results. Failure in the development of effective drugs probably reflects the poor understanding of genome-wide alterations and molecular mechanisms orchestrating therapeutic resistance and recurrence. In the post-ENCODE (Encyclopedia of DNA Elements) era, cancer is referred to as a highly heterogeneous and systemic disease of the genome. The unprecedented potential of next-generation sequencing (NGS) technologies to accurately identify genetic and genomic variations has attracted major research and clinical interest. The applications of NGS include targeted NGS with potential clinical implications, while whole-exome and whole-genome sequencing focus on the discovery of both novel cancer driver genes and therapeutic targets. These advances dictate new designs for clinical trials to validate biomarkers and drugs. This review discusses the findings of available NGS studies on HBP cancers and the limitations of genome sequencing analysis to translate genome-based biomarkers and drugs into patient care in the clinic.
Collapse
Affiliation(s)
- Ioannis D Kyrochristos
- Centre for Biosystems and Genome Network Medicine, Ioannina University, 45110 Ioannina, Greece.
- Department of Surgery, Ioannina University Hospital, 45110 Ioannina, Greece.
| | | | - Demosthenes E Ziogas
- Centre for Biosystems and Genome Network Medicine, Ioannina University, 45110 Ioannina, Greece.
- Department of Surgery, 'G. Hatzikosta' General Hospital, 45001 Ioannina, Greece.
| | | | - Dimitrios Schizas
- 1st Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece.
| | - Efstathios G Lykoudis
- Department of Plastic Surgery, Ioannina University School of Medicine, 45110 Ioannina, Greece.
| | - Evangelos Felekouras
- 1st Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece.
| | - Anastasios Machairas
- Third Department of Surgery, Attikon General Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece.
| | - Christos Katsios
- Department of Surgery, Ioannina University Hospital, 45110 Ioannina, Greece.
| | - Theodoros Liakakos
- 1st Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece.
| | - William C Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong, China.
| | - Dimitrios H Roukos
- Centre for Biosystems and Genome Network Medicine, Ioannina University, 45110 Ioannina, Greece.
- Department of Surgery, Ioannina University Hospital, 45110 Ioannina, Greece.
- Biomedical Research Foundation of the Academy of Athens (BRFAA), 11527 Athens, Greece.
| |
Collapse
|
|
29
|
Bell R, Ao BT, Ironside N, Bartlett A, Windsor JA, Pandanaboyana S. Meta-analysis and cost effective analysis of portal-superior mesenteric vein resection during pancreatoduodenectomy: Impact on margin status and survival. Surg Oncol 2017; 26:53-62. [PMID: 28317585 DOI: 10.1016/j.suronc.2016.12.007] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2016] [Revised: 11/21/2016] [Accepted: 12/29/2016] [Indexed: 12/25/2022]
Abstract
INTRODUCTION The benefit of portal-superior mesenteric vein resection (PSMVR) with pancreatoduodenectomy (PD) remains controversial. This study assesses the impact of PSMVR on resection margin status and survival. METHOD An electronic search was performed to identify relevant articles. Pooled odds ratios were calculated for outcomes using the fixed or random-effects models for meta-analysis. A decision analytical model was developed for estimating cost effectiveness. RESULTS Sixteen studies with 4145 patients who underwent pancreatoduodenectomy were included: 1207 patients had PSMVR and 2938 patients had no PSMVR. The R1 resection rate and post-operative mortality was significantly higher in PSMVR group (OR1.59[1.35, 1.86] p=<0.0001, and OR1.72 [1.02,2.92] p = 0.04 respectively). The overall survival at 5-years was worse in the PSMVR group (HR0.20 [0.07,0.55] P = 0.020). Tumour size (p = 0.030) and perineural invasion (P = 0.009) were higher in the PSMVR group. Not performing PSMVR yielded cost savings of $1617 per additional month alive without reduction in overall outcome. CONCLUSION On the basis of retrospective data this study shows that PD with PSMVR is associated with a higher R1 rate, lower 5-year survival and is not cost-effective. It appears that PD with PSMVR can only be justified if R0 resection can be achieved. The continuing challenge is accurate selection of these patients.
Collapse
Affiliation(s)
- Richard Bell
- Department of HPB and Transplant Surgery, St James Hospital, Leeds, UK
| | - Braden Te Ao
- Department of Biostatistics and Epidemiology, Auckland University of Technology, Auckland, New Zealand
| | - Natasha Ironside
- HPB/Upper GI Unit, Department of Hepatobiliary and Pancreatic Surgery, Auckland City Hospital, New Zealand
| | - Adam Bartlett
- HPB/Upper GI Unit, Department of Hepatobiliary and Pancreatic Surgery, Auckland City Hospital, New Zealand; Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - John A Windsor
- HPB/Upper GI Unit, Department of Hepatobiliary and Pancreatic Surgery, Auckland City Hospital, New Zealand; Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Sanjay Pandanaboyana
- HPB/Upper GI Unit, Department of Hepatobiliary and Pancreatic Surgery, Auckland City Hospital, New Zealand; Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
| |
Collapse
|
|
30
|
Iordache S, Albulescu DM, Săftoiu A. The borderline resectable/locally advanced pancreatic ductal adenocarcinoma: EUS oriented. Endosc Ultrasound 2017; 6:S83-S86. [PMID: 29387698 PMCID: PMC5774081 DOI: 10.4103/eus.eus_68_17] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Affiliation(s)
- Sevastiţa Iordache
- Department of Gastroenterology, Research Center in Gastroenterology and Hepatology, University of Medicine and Pharmacy Craiova, Craiova, Romania
| | - Dana-Maria Albulescu
- Department of Imaging, Research Center in Gastroenterology and Hepatology, University of Medicine and Pharmacy Craiova, Craiova, Romania
| | - Adrian Săftoiu
- Department of Gastroenterology, Research Center in Gastroenterology and Hepatology, University of Medicine and Pharmacy Craiova, Craiova, Romania
| |
Collapse
|
|
31
|
Barreto SG, Windsor JA. Justifying vein resection with pancreatoduodenectomy. Lancet Oncol 2016; 17:e118-e124. [PMID: 26972858 DOI: 10.1016/s1470-2045(15)00463-5] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Revised: 10/21/2015] [Accepted: 10/27/2015] [Indexed: 12/13/2022]
|
|
32
|
Gonçalves B, Soares JB, Bastos P. Endoscopic Ultrasound in the Diagnosis and Staging of Pancreatic Cancer. GE-PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2015; 22:161-171. [PMID: 28868399 PMCID: PMC5580187 DOI: 10.1016/j.jpge.2015.04.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Accepted: 04/23/2015] [Indexed: 02/08/2023]
Abstract
Pancreatic cancer is one of the digestive cancers with the poorest prognosis, so an early and correct diagnosis is of utmost importance. With the development of new therapeutic options an accurate staging is essential. Endoscopic ultrasonography (EUS) has a major role in all stages of the management of these patients. EUS has a high accuracy in the diagnosis of pancreatic adenocarcinoma and the possibility to perform fine-needle aspiration/biopsy (FNA/FNB) increases the diagnostic yield of EUS. There is still no consensus on the several technical aspects of FNA, namely on the rapid on-site evaluation (ROSE), the diameter and type of needle, the number of passes and the use of stylet and suction. Contrast-enhanced EUS (CE-EUS) and EUS elastography (EUS-E) have been used in recent years as an adjunct to EUS-FNA. Given the higher sensitivity of these techniques a negative cytology by EUS-FNA should not exclude malignancy when CE-EUS and/or EUS-E are suggestive of pancreatic neoplasia. EUS remains one of the main methods in the staging of pancreatic adenocarcinoma, namely to further evaluate patients with non-metastatic disease that appears resectable on initial imaging. EUS is crucial for an accurate preoperative evaluation of pancreatic cancer which is essential to choose the correct management strategy. The possibility to obtain samples from suspicious lesions or lymph nodes, by means of EUS-guided fine-needle aspiration as well as the use of contrast-enhanced and elastography, makes EUS an ideal modality for the diagnosis and staging of pancreatic cancer.
Collapse
Affiliation(s)
- Bruno Gonçalves
- Gastroenterology Department, Hospital de Braga, Braga, Portugal
| | | | - Pedro Bastos
- Gastroenterology Department, Hospital de Braga, Braga, Portugal
| |
Collapse
|
|
33
|
Pedrazzoli S. Extent of lymphadenectomy to associate with pancreaticoduodenectomy in patients with pancreatic head cancer for better tumor staging. Cancer Treat Rev 2015; 41:577-87. [PMID: 26045226 DOI: 10.1016/j.ctrv.2015.04.013] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Revised: 04/28/2015] [Accepted: 04/29/2015] [Indexed: 01/14/2023]
Abstract
OBJECTIVES To define the extent of lymphadenectomy to associate with surgery for pancreatic head cancer. BACKGROUND Pancreaticoduodenectomy with extended lymphadenectomy fails to prolong patient survival. METHODS Prospective randomized and nonrandomized controlled trials (RCTs and NRCTs), meta-analyses, retrospective reviews, consensus conferences and pre- and intraoperative diagnoses of lymph node (LN) metastases were retrieved. Standard and extended lymphadenectomies were reviewed, including their effects on postoperative complications, mortality rate and long-term survival. The minimum total number of LN examined (TNLE) for adequate tumor staging, and the incidence of metastasis to each LN station were also considered. A pros and cons analysis was performed on the removal of each LN station. RESULTS Eleven retrospective studies (2514 patients), five prospective NRCTs (545 patients), and five prospective RCTs (586 patients) described different lymphadenectomies, which obtained similar long-term results. Five meta-analyses showed they did not influence long-term survival. However, N status is an important component of tumor staging. The recommended minimum TNLE is 15. The percent incidence of metastasis to each LN station was calculated considering at least 385 and up to 3725 patients. Preoperative imaging and intraoperative exploration frequently fail to identify metastatic nodes. A pros and cons analysis suggests that lymph node status is better established removing the following LN stations: 6, 8a-p, 12a-b-c, 13a-b, 14a-b-c-d, 16b1, 17a-b. Metastasis to 16b1 LNs significantly worsens prognosis. Their removal and frozen section examination, before proceeding with resection, may contraindicate resection. CONCLUSION A standard lymphadenectomy demands an adequate TNLE and removal of the LN stations metastasizing more frequently, without increasing the surgical risk.
Collapse
|