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Zhu J, Xu T, Cao X, Pan D, Yao Z, Li Y, Wang H, Han Z. The impact of different dietary flavonoids on the risk of coronary heart disease in cancer patients and that on the prognosis of patients with cancer and coronary heart disease. Eur J Cancer Prev 2025; 34:214-220. [PMID: 39388175 PMCID: PMC11949199 DOI: 10.1097/cej.0000000000000928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 09/18/2024] [Indexed: 10/15/2024]
Abstract
The purpose of this study is to explore the risk of coronary heart disease (CHD) in cancer patients who consume different flavonoids, and the impact of flavonoids on the prognosis of cancer patients with CHD. We extracted dietary flavonoids data on 1454 patients diagnosed with cancer from the National Health and Nutrition Examination Survey and Food and Nutrient Database for Dietary Studies. Logistic regression analysis was used to explore the relationship between the intake of flavonoids and the risk of CHD. Cox proportional hazard model was used to explore the impact of flavonoids intake on prognosis in 148 patients with cancer and CHD. Malvidin intake increased the risk of CHD by 1% [odds ratio (OR) = 1.01, 95% confidence interval (CI): 1.00-1.02, P < 0.05] in cancer patients, while epicatechin and isorhamnetin reduced the risk of CHD by 3% (OR = 0.97, 95% CI: 0.94-1.00, P < 0.05) and 15% (OR = 0.85, 95% CI: 0.72-1.00, P < 0.05), respectively. Adjusted by age, sex, and race, malvidin intake increased the risk of CHD in cancer patients by 1% (OR = 1.01, 95% CI: 1.00-1.02, P < 0.05), isorhamnetin decreased the risk by 15% (OR = 0.85, 95% CI: 0.72-1.00, P < 0.05), and epicatechin showed no effect on the risk of CHD ( P > 0.05). No flavonoids had impact on the prognosis of patients with cancer and CHD ( P > 0.05). For patients with cancer, consuming malvidin increases the risk of CHD, while isorhamnetin reduces the risk. Consuming flavonoids has no impact on the prognosis of patients with cancer and CHD.
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Affiliation(s)
- Jingjing Zhu
- Department of Oncology, The Affiliated Hospital of Xuzhou Medical University
| | - Tao Xu
- Department of Cardiology, Xuzhou New Health Hospital, Xuzhou, Jiangsu, PR China
| | - Xu Cao
- Department of Oncology, The Affiliated Hospital of Xuzhou Medical University
| | - Di Pan
- Department of Oncology, The Affiliated Hospital of Xuzhou Medical University
| | - Zhiyuan Yao
- Department of Oncology, The Affiliated Hospital of Xuzhou Medical University
| | - Yuqi Li
- Department of Oncology, The Affiliated Hospital of Xuzhou Medical University
| | - Hongmei Wang
- Department of Oncology, The Affiliated Hospital of Xuzhou Medical University
| | - Zhengxiang Han
- Department of Oncology, The Affiliated Hospital of Xuzhou Medical University
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Chen W, Lin G, Li X, Feng Y, Mao W, Kong C, Hu Y, Gao Y, Yang W, Chen M, Yan Z, Xia S, Lu C, Xu M, Ji J. Dual-energy computed tomography for predicting histological grading and survival in patients with pancreatic ductal adenocarcinoma. Eur Radiol 2025; 35:2818-2832. [PMID: 39414655 DOI: 10.1007/s00330-024-11109-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 08/07/2024] [Accepted: 09/24/2024] [Indexed: 10/18/2024]
Abstract
OBJECTIVES We evaluated the value of dual-energy computed tomography (DECT) parameters derived from pancreatic ductal adenocarcinoma (PDAC) to discriminate between high- and low-grade tumors and predict overall survival (OS) in patients. METHODS Data were retrospectively collected from 169 consecutive patients with pathologically confirmed PDAC who underwent third-generation dual-source DECT enhanced dual-phase scanning before surgery between January 2017 and March 2023. Patients with prior treatments, other malignancies, small tumors, or poor-quality scans were excluded. Two radiologists evaluated three clinical and seven radiological features and measured sixteen DECT-derived parameters. Univariate and multivariate analyses were applied to select independent predictors. A prediction model and a corresponding nomogram were developed, and the area under the curve (AUC), calibration, and clinical applicability were assessed. The correlations between factors and OS were evaluated using Kaplan-Meier survival and Cox regression analyses. RESULTS One hundred sixty-nine patients were randomly divided into training (n = 118) and validation (n = 51) cohorts, among which 43 (36.4%) and 19 (37.3%) had high-grade PDAC confirmed by pathology, respectively. The vascular invasion, normalized iodine concentration in the venous phase, and effective atomic number in the venous phase were independent predictors for histological grading. A nomogram was constructed to predict the risk of high-grade tumors in PDAC, with AUCs of 0.887 and 0.844 in the training and validation cohorts, respectively. The nomogram exhibited good calibration and was more beneficial than a single parameter in both cohorts. Pathological- and nomoscore-predicted high-grade PDACs were associated with poor OS (all p < 0.05). CONCLUSIONS The nomogram, which combines DECT parameters and radiological features, can predict the histological grade and OS in patients with PDAC before surgery. KEY POINTS Question Preoperative determination of histological grade in PDAC is crucial for guiding treatment, yet current methods are invasive and limited. Findings A DECT-based nomogram combining vascular invasion, normalized iodine concentration, and effective atomic number accurately predicts histological grade and OS in PDAC patients. Clinical relevance The DECT-based nomogram is a reliable, non-invasive tool for predicting histological grade and OS in PDAC. It provides essential information to guide personalized treatment strategies, potentially improving patient management and outcomes.
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Affiliation(s)
- Weiyue Chen
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China
| | - Guihan Lin
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China
| | - Xia Li
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China
| | - Ye Feng
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China
| | - Weibo Mao
- Department of Pathology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
| | - Chunli Kong
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China
| | - Yumin Hu
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China
| | - Yang Gao
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China
| | - Weibin Yang
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China
| | - Minjiang Chen
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China
| | - Zhihan Yan
- Wenzhou Key Laboratory of Structural and Functional Imaging, Wenzhou, China
| | - Shuiwei Xia
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China
| | - Chenying Lu
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China
| | - Min Xu
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China
| | - Jiansong Ji
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China.
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China.
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Citterio D, Droz Dit Busset M, Sposito C, Mazzola M, Grandi S, Zironda A, Leoncini G, Simonotti N, Battiston C, Flores M, Ferrari G, Mazzaferro V. Prediction of early recurrence as a marker of surgical futility in pancreatic adenocarcinoma. Surg Oncol 2025; 59:102208. [PMID: 40086295 DOI: 10.1016/j.suronc.2025.102208] [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: 11/13/2024] [Revised: 02/06/2025] [Accepted: 03/04/2025] [Indexed: 03/16/2025]
Abstract
BACKGROUND Long-term survival after resection for pancreatic ductal adenocarcinoma (PDAC) is impaired by very high recurrence rates. When recurrence occurs within 6 months (early recurrence: ER) the benefit of surgery is equivalent to palliative chemotherapy in unresectable patients. Therefore, ER is a surrogate of surgical futility in PDAC. MATERIALS AND METHODS To investigate predictive factors of ER and its impact on survival, a training and a validation cohort of prospectively collected patients who underwent surgery for resectable or borderline-resectable PDAC were analyzed in two independent Pancreas Units during the same period. Logistic regression model on the training cohort identified independent predictors of ER, used to build a prognostic risk-score then tested on the validation cohort. RESULTS Out of 176 patients in the training cohort, 21.6 % experienced ER, with significant impact on survival (OS: 9.7 months vs. 32.7 months for ER vs. late/no recurrence, respectively). At multivariable analysis, three independent risk factors for ER were identified: Ca19.9 > 100 U/mL, G3 tumors and lack of adjuvant chemotherapy. Based on such features the derived ER-score stratified three prognostic classes at incremental risk of ER (12 %, 35 % and 53 %) with different OS (31.1, 19.7 and 9.3 months, respectively, p < 0.001). The ER predictive score was then tested on a validation cohort of 242 patients, 22.3 % of whom underwent ER. Despite significant differences in tumor-related features, the score was able to discriminate among the predicted ER-risk classes (15 %, 27 % and 53 %, respectively) and forecast significantly different OS (5.8, 19 and 31.1 months, p > 0.001). The discriminative capability of the score in the two cohorts was similar (training AUC = 0.72 vs. validation AUC = 0.68, p = 0.28). CONCLUSION An externally validated clinical score, able to identify three prognostic classes at incremental risk of developing ER after resection of PDAC is provided. In patients at high risk of ER, prediction of surgical futility may help in decision-making.
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Affiliation(s)
- Davide Citterio
- HPB Surgery, Liver Transplantation and Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Michele Droz Dit Busset
- HPB Surgery, Liver Transplantation and Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Carlo Sposito
- HPB Surgery, Liver Transplantation and Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Italy
| | - Michele Mazzola
- ASST Grande Ospedale Metropolitano Niguarda, Division of Minimally-invasive Surgical Oncology, Milan, Italy
| | - Samuele Grandi
- HPB Surgery, Liver Transplantation and Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Andrea Zironda
- ASST Grande Ospedale Metropolitano Niguarda, Division of Minimally-invasive Surgical Oncology, Milan, Italy
| | - Giuseppe Leoncini
- HPB Surgery, Liver Transplantation and Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Nicolò Simonotti
- HPB Surgery, Liver Transplantation and Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Carlo Battiston
- HPB Surgery, Liver Transplantation and Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Maria Flores
- HPB Surgery, Liver Transplantation and Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Giovanni Ferrari
- ASST Grande Ospedale Metropolitano Niguarda, Division of Minimally-invasive Surgical Oncology, Milan, Italy
| | - Vincenzo Mazzaferro
- HPB Surgery, Liver Transplantation and Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Italy.
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Gronkowska K, Robaszkiewicz A. Genetic dysregulation of EP300 in cancers in light of cancer epigenome control - targeting of p300-proficient and -deficient cancers. MOLECULAR THERAPY. ONCOLOGY 2024; 32:200871. [PMID: 39351073 PMCID: PMC11440307 DOI: 10.1016/j.omton.2024.200871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 10/04/2024]
Abstract
Some cancer types including bladder, cervical, and uterine cancers are characterized by frequent mutations in EP300 that encode histone acetyltransferase p300. This enzyme can act both as a tumor suppressor and oncogene. In this review, we describe the role of p300 in cancer initiation and progression regarding EP300 aberrations that have been identified in TGCA Pan-Cancer Atlas studies and we also discuss possible anticancer strategies that target EP300 mutated cancers. Copy number alterations, truncating mutations, and abnormal EP300 transcriptions that affect p300 abundance and activity are associated with several pathological features such as tumor grading, metastases, and patient survival. Elevated EP300 correlates with a higher mRNA level of other epigenetic factors and chromatin remodeling enzymes that co-operate with p300 in creating permissive conditions for malignant transformation, tumor growth and metastases. The status of EP300 expression can be considered as a prognostic marker for anticancer immunotherapy efficacy, as EP300 mutations are followed by an increased expression of PDL-1.HAT activators such as CTB or YF2 can be applied for p300-deficient patients, whereas the natural and synthetic inhibitors of p300 activity, as well as dual HAT/bromodomain inhibitors and the PROTAC degradation of p300, may serve as strategies in the fight against p300-fueled cancers.
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Affiliation(s)
- Karolina Gronkowska
- Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland
- Bio-Med-Chem Doctoral School of the University of Lodz and Lodz Institutes of the Polish Academy of Sciences, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland
| | - Agnieszka Robaszkiewicz
- Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland
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Arner EN, Alzhanova D, Westcott JM, Hinz S, Tiron CE, Blø M, Mai A, Virtakoivu R, Phinney N, Nord S, Aguilera KY, Rizvi A, Toombs JE, Reese TC, Fey V, Micklem D, Gausdal G, Ivaska J, Lorens JB, Brekken RA. AXL-TBK1 driven AKT3 activation promotes metastasis. Sci Signal 2024; 17:eado6057. [PMID: 39689180 DOI: 10.1126/scisignal.ado6057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 11/26/2024] [Indexed: 12/19/2024]
Abstract
The receptor tyrosine kinase AXL promotes tumor progression, metastasis, and therapy resistance through the induction of epithelial-mesenchymal transition (EMT). Here, we found that activation of AXL resulted in the phosphorylation of TANK-binding kinase 1 (TBK1) and the downstream activation of AKT3 and Snail, a transcription factor critical for EMT. Mechanistically, we showed that TBK1 directly bound to and phosphorylated AKT3 in a manner dependent on the multiprotein complex mTORC1. Upon activation, AKT3 interacted with and promoted the nuclear accumulation of Snail, which led to increased EMT as assessed by marker abundance. In human pancreatic ductal adenocarcinoma tissue, nuclear AKT3 colocalized with Snail and correlated with worse clinical outcomes. Primary mouse pancreatic cancer cells deficient in AKT3 showed reduced metastatic spread in vivo, suggesting selective AKT3 inhibition as a potential therapeutic avenue for targeting EMT in aggressive cancers.
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Affiliation(s)
- Emily N Arner
- Cancer Biology Graduate Program, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
- Department of Surgery and the Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Dina Alzhanova
- Department of Surgery and the Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Jill M Westcott
- Department of Surgery and the Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Stefan Hinz
- Department of Biomedicine and Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway
- BerGenBio ASA, Bergen, Norway
| | - Crina Elena Tiron
- Department of Biomedicine and Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway
- Regional Institute of Oncology, Iasi, Romania
| | | | | | - Reetta Virtakoivu
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland
- Department of Life Technologies, University of Turku, 20520 Turku, Finland
- InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland
| | - Natalie Phinney
- Cancer Biology Graduate Program, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
- Department of Surgery and the Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Silje Nord
- Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
| | | | - Ali Rizvi
- Department of Surgery and the Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Jason E Toombs
- Department of Surgery and the Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Tanner C Reese
- Cancer Biology Graduate Program, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - Vidal Fey
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland
- Department of Life Technologies, University of Turku, 20520 Turku, Finland
- InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland
| | | | | | - Johanna Ivaska
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland
- Department of Life Technologies, University of Turku, 20520 Turku, Finland
- InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland
| | - James B Lorens
- Department of Biomedicine and Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway
| | - Rolf A Brekken
- Cancer Biology Graduate Program, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
- Department of Surgery and the Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
- Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
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Seufferlein T, Mayerle J, Boeck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie Exokrines Pankreaskarzinom – Version 3.1. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1724-1785. [PMID: 39389105 DOI: 10.1055/a-2338-3716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
Affiliation(s)
| | | | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Gastroenterologie und Endokrinologie Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Medizinische Klinik und Poliklinik II Onkologie und Hämatologie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
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Seufferlein T, Mayerle J, Boeck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie Exokrines Pankreaskarzinom – Version 3.1. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:874-995. [PMID: 39389103 DOI: 10.1055/a-2338-3533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
Affiliation(s)
| | | | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Gastroenterologie und Endokrinologie Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Medizinische Klinik und Poliklinik II Onkologie und Hämatologie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
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Marino R, Ratti F, Casadei-Gardini A, Rimini M, Pedica F, Clocchiatti L, Aldrighetti L. The oncologic burden of residual disease in incidental gallbladder cancer: An elastic net regression model to profile high-risk features. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:108397. [PMID: 38815335 DOI: 10.1016/j.ejso.2024.108397] [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: 02/10/2024] [Revised: 05/04/2024] [Accepted: 05/07/2024] [Indexed: 06/01/2024]
Abstract
INTRODUCTION Incidental Gallbladder Cancer (IGBC) following cholecystectomy constitutes a significant portion of gallbladder cancer diagnoses. Re-exploration is advocated to optimize disease clearance and enhance survival rates. The consistent association of residual disease (RD) with inferior oncologic outcomes prompts a critical examination of re-resection's role as a modifying factor in the natural history of IGBC. METHODS All patients diagnosed with gallbladder cancer between 2012 and 2022 were included. An elastic net regularized regression model was employed to profile high-risk predictors of RD within the IGBC group. Survival outcomes were assessed based on resection margins and RD. RESULTS Among the 181 patients undergoing re-exploration for IGBC, 133 (73.5 %) harbored RD, while 48 (26.5 %) showed no evidence. The elastic net model, utilizing a selected λ = 0.029, identified six coefficients associated with the risk of RD: aspiration from cholecystectomy (0.141), hepatic tumor origin (1.852), time to re-exploration >8 weeks (1.879), positive margin status (2.575), higher T stage (1.473), and poorly differentiated tumors (2.241). Furthermore, the study revealed a median overall survival of 44 months (CI 38-60) for IGBC patients with no evidence of RD, compared to 31 months (23-42) for those with RD (p < 0.001). CONCLUSION Re-resection revealed a high incidence of RD (73.5 %), significantly correlating with poorer survival outcomes. The preoperative identification of high-risk features provides a reliable biological disease profile. This aids in strategic preselection of patients who may benefit from re-resection, underscoring the need to consolidate outcomes with tailored chemotherapy for those with unfavorable characteristics.
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Affiliation(s)
- Rebecca Marino
- IRCCS San Raffaele Hospital, Hepatobiliary Surgery Division, 20132, Milan, Italy
| | - Francesca Ratti
- IRCCS San Raffaele Hospital, Hepatobiliary Surgery Division, 20132, Milan, Italy; University Vita-Salute San Raffaele, 20132, Milan, Italy.
| | | | - Margherita Rimini
- Department of Medical Oncology, IRCCS San Raffaele Hospital, 20132, Milan, Italy
| | - Federica Pedica
- Department of Experimental Oncology, Pathology Unit, San Raffaele Hospital, 20132, Milan, Italy
| | - Lucrezia Clocchiatti
- IRCCS San Raffaele Hospital, Hepatobiliary Surgery Division, 20132, Milan, Italy
| | - Luca Aldrighetti
- IRCCS San Raffaele Hospital, Hepatobiliary Surgery Division, 20132, Milan, Italy; University Vita-Salute San Raffaele, 20132, Milan, Italy
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Ross S, Sucandy I, Vasanthakumar P, Christodoulou M, Pattilachan T, Rosemurgy A. A comparative analysis of robotic versus open pancreaticoduodenectomy in octogenarians. J Robot Surg 2024; 18:183. [PMID: 38668931 DOI: 10.1007/s11701-024-01952-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 04/14/2024] [Indexed: 12/25/2024]
Abstract
Old age is a predictor of increased morbidity following pancreatic operations. This study was undertaken to compare the peri-operative variables between robotic and 'open' pancreaticoduodenectomy, in octogenarians (≥ 80 years of age). Since 2012, with IRB approval, we retrospectively followed 69 patients, who underwent robotic (n = 42) and 'open' (n = 27) pancreaticoduodenectomy. Statistical analysis was performed using chi-square test and Student's t test. Data are presented as median(mean ± SD), and significance accepted with 95% probability. Patients who underwent the robotic approach had a greater Charlson Comorbidity Index [6 (6 ± 1.6) vs 5 (5 ± 1.0), (p = 0.01)] and previous abdominal operations [n = 24 (57%) vs n = 9 (33%), (p = 0.04)]. The robotic approach led to longer operative time [426 (434 ± 95.8) vs 240 (254 ± 71.1) minutes, (p < 0.0001)], decreased blood loss [200 (291 ± 289.2) vs 426 (434 ± 95.8) mL (p = 0.008)], and decreased intraoperative blood transfusions (p < 0.05). Patients who underwent robotic pancreaticoduodenectomy had comparable and at times superior outcomes, consistent with the literature regarding robotic and 'open' pancreaticoduodenectomy. This study indicates that robotic pancreaticoduodenectomy continues to offer same benefits for patients of advanced age and demonstrates age should not be a preclusion to robotic operations.
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Affiliation(s)
- Sharona Ross
- Digestive Health Institute, AdventHealth, 3000 Medical Park Drive, Suite #500, Tampa, FL, 33613, USA.
| | - Iswanto Sucandy
- Digestive Health Institute, AdventHealth, 3000 Medical Park Drive, Suite #500, Tampa, FL, 33613, USA
| | | | - Maria Christodoulou
- Digestive Health Institute, AdventHealth, 3000 Medical Park Drive, Suite #500, Tampa, FL, 33613, USA
| | - Tara Pattilachan
- Digestive Health Institute, AdventHealth, 3000 Medical Park Drive, Suite #500, Tampa, FL, 33613, USA
| | - Alexander Rosemurgy
- Digestive Health Institute, AdventHealth, 3000 Medical Park Drive, Suite #500, Tampa, FL, 33613, USA
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10
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Wang L, Wang G, Wang P, Nie F. Pancreatic ductal adenocarcinoma: CEUS characteristics are correlated with pathological findings and help predict early recurrence after resection. JOURNAL OF CLINICAL ULTRASOUND : JCU 2024; 52:230-240. [PMID: 38018362 DOI: 10.1002/jcu.23622] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Revised: 11/16/2023] [Accepted: 11/17/2023] [Indexed: 11/30/2023]
Abstract
OBJECTIVES To identify characteristics of preoperative contrast-enhanced ultrasound (CEUS) that could predict early recurrence after curative resection of pancreatic ductal adenocarcinoma (PDAC). METHODS From January 2017 to September 2022, a total of 110 patients with PDAC (all confirmed by samples obtained via operation) who underwent CEUS within 1 month before surgery were enrolled. We proposed five CEUS enhancement patterns (Pattern I, homogeneous enhancement; Pattern II, heterogeneous enhancement without cystic components; pattern III, ring enhancement; Pattern IV, starry enhancement; Pattern V, heterogeneous enhancement with cystic components) of PDAC. Clinical-pathologic and CEUS characteristics for predicting early recurrence (recurrence within 1 year after curative resection) were analyzed. Important CEUS characteristics were compared with the pathological findings. RESULTS Tumor size and TNM stage were closely associated with early recurrence. Incomplete-enhancement and enhancement pattern III, IV and V at CEUS imaging were more prone to early recurrence. Incomplete-enhancement lesions had higher histological tumor grades, less frequent remaining acini, and more frequent necrosis within the tumor. PDACs with pattern I and II had lower histological tumor grades, and pattern III, IV and V had higher histological tumor grades. PDACs with pattern I, II and IV had less frequent intratumoral necrosis than PDACs with pattern III and V, and PDACs with pattern IV had lower MVD values. CONCLUSIONS PDACs with incomplete enhancement and enhancement pattern III, IV and V were more prone to early recurrence after attempted curative resection, and these important CEUS characteristics were closely related to the pathological findings of PDAC.
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Affiliation(s)
- Lan Wang
- Ultrasound Medical Center, Lanzhou University Second Hospital, Lanzhou, China
| | - Guojuan Wang
- Ultrasound Medical Center, Lanzhou University Second Hospital, Lanzhou, China
| | - Peihua Wang
- Ultrasound Medical Center, Lanzhou University Second Hospital, Lanzhou, China
| | - Fang Nie
- Ultrasound Medical Center, Lanzhou University Second Hospital, Lanzhou, China
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11
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Li D, Peng Q, Wang L, Cai W, Liang M, Liu S, Ma X, Zhao X. Preoperative prediction of disease-free survival in pancreatic ductal adenocarcinoma patients after R0 resection using contrast-enhanced CT and CA19-9. Eur Radiol 2024; 34:509-524. [PMID: 37507611 DOI: 10.1007/s00330-023-09980-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Revised: 05/18/2023] [Accepted: 05/28/2023] [Indexed: 07/30/2023]
Abstract
OBJECTIVES To investigate the efficiency of a combination of preoperative contrast-enhanced computed tomography (CECT) and carbohydrate antigen 19-9 (CA19-9) in predicting disease-free survival (DFS) after R0 resection of pancreatic ductal adenocarcinoma (PDAC). METHODS A total of 138 PDAC patients who underwent curative R0 resection were retrospectively enrolled and allocated chronologically to training (n = 91, January 2014-July 2019) and validation cohorts (n = 47, August 2019-December 2020). Using univariable and multivariable Cox regression analyses, we constructed a preoperative clinicoradiographic model based on the combination of CECT features and serum CA19-9 concentrations, and validated it in the validation cohort. The prognostic performance was evaluated and compared with that of postoperative clinicopathological and tumor-node-metastasis (TNM) models. Kaplan-Meier analysis was conducted to verify the preoperative prognostic stratification performance of the proposed model. RESULTS The preoperative clinicoradiographic model included five independent prognostic factors (tumor diameter on CECT > 4 cm, extrapancreatic organ infiltration, CECT-reported lymph node metastasis, peripheral enhancement, and preoperative CA19-9 levels > 180 U/mL). It better predicted DFS than did the postoperative clinicopathological (C-index, 0.802 vs. 0.787; p < 0.05) and TNM (C-index, 0.802 vs. 0.711; p < 0.001) models in the validation cohort. Low-risk patients had significantly better DFS than patients at the high-risk, defined by the model preoperatively (p < 0.001, training cohort; p < 0.01, validation cohort). CONCLUSIONS The clinicoradiographic model, integrating preoperative CECT features and serum CA19-9 levels, helped preoperatively predict postsurgical DFS for PDAC and could facilitate clinical decision-making. CLINICAL RELEVANCE STATEMENT We constructed a simple model integrating clinical and radiological features for the prediction of disease-free survival after curative R0 resection in patients with pancreatic ductal adenocarcinoma; this novel model may facilitate preoperative identification of patients at high risk of recurrence and metastasis that may benefit from neoadjuvant treatments. KEY POINTS • Existing clinicopathological predictors for prognosis in pancreatic ductal adenocarcinoma (PDAC) patients who underwent R0 resection can only be ascertained postoperatively and do not allow preoperative prediction. • We constructed a clinicoradiographic model, using preoperative contrast-enhanced computed tomography (CECT) features and preoperative carbohydrate antigen 19-9 (CA19-9) levels, and presented it as a nomogram. • The presented model can predict disease-free survival (DFS) in patients with PDAC better than can postoperative clinicopathological or tumor-node-metastasis (TNM) models.
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Affiliation(s)
- Dengfeng Li
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17, Panjiayuan Street South, Chaoyang District, Beijing, 100021, China
| | - Qing Peng
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Leyao Wang
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17, Panjiayuan Street South, Chaoyang District, Beijing, 100021, China
| | - Wei Cai
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17, Panjiayuan Street South, Chaoyang District, Beijing, 100021, China
| | - Meng Liang
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17, Panjiayuan Street South, Chaoyang District, Beijing, 100021, China
| | - Siyun Liu
- GE Healthcare (China), Beijing, 100176, China
| | - Xiaohong Ma
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17, Panjiayuan Street South, Chaoyang District, Beijing, 100021, China.
| | - Xinming Zhao
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17, Panjiayuan Street South, Chaoyang District, Beijing, 100021, China.
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12
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Zhu L, Shen S, Wang H, Zhang G, Yin X, Shi X, Gao S, Han J, Ren Y, Wang J, Jiang H, Guo S, Jin G. A neoadjuvant therapy compatible prognostic staging for resected pancreatic ductal adenocarcinoma. BMC Cancer 2023; 23:790. [PMID: 37612635 PMCID: PMC10463422 DOI: 10.1186/s12885-023-11181-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Accepted: 07/14/2023] [Indexed: 08/25/2023] Open
Abstract
OBJECTIVE To improve prediction, the AJCC staging system was revised to be consistent with upfront surgery (UFS) and neoadjuvant therapy (NAT) for PDAC. BACKGROUND The AJCC staging system was designed for patients who have had UFS for PDAC, and it has limited predictive power for patients receiving NAT. METHODS We examined 146 PDAC patients who had resection after NAT and 1771 who had UFS at Changhai Hospital between 2012 and 2021. The clinicopathological factors were identified using Cox proportional regression analysis, and the Neoadjuvant Therapy Compatible Prognostic (NATCP) staging was developed based on these variables. Validation was carried out in the prospective NAT cohort and the SEER database. The staging approach was compared to the AJCC staging system regarding predictive accuracy. RESULTS The NAT cohort's multivariate analysis showed that tumor differentiation and the number of positive lymph nodes independently predicted OS. The NATCP staging simplified the AJCC stages, added tumor differentiation, and restaged the disease based on the Kaplan-Meier curve survival differences. The median OS for NATCP stages IA, IB, II, and III was 31.7 months, 25.0 months, and 15.8 months in the NAT cohort and 30.1 months, 22.8 months, 18.3 months, and 14.1 months in the UFS cohort. Compared to the AJCC staging method, the NATCP staging system performed better and was verified in the validation cohort. CONCLUSIONS Regardless of the use of NAT, NATCP staging demonstrated greater predictive abilities than the existing AJCC staging approach for resected PDAC and may facilitate clinical decision-making based on accurate prediction of patients' OS.
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Affiliation(s)
- Lingyu Zhu
- Department of Pancreatic Hepatobiliary Surgery, Changhai Hospital, Naval Medical University, NO. 168 Changhai Road, Yangpu District, Shanghai, China
| | - Shuo Shen
- Department of Pancreatic Hepatobiliary Surgery, Changhai Hospital, Naval Medical University, NO. 168 Changhai Road, Yangpu District, Shanghai, China
| | - Huan Wang
- Department of Pancreatic Hepatobiliary Surgery, Changhai Hospital, Naval Medical University, NO. 168 Changhai Road, Yangpu District, Shanghai, China
| | - Guoxiao Zhang
- Department of Pancreatic Hepatobiliary Surgery, Changhai Hospital, Naval Medical University, NO. 168 Changhai Road, Yangpu District, Shanghai, China
| | - Xiaoyi Yin
- Department of Pancreatic Hepatobiliary Surgery, Changhai Hospital, Naval Medical University, NO. 168 Changhai Road, Yangpu District, Shanghai, China
| | - Xiaohan Shi
- Department of Pancreatic Hepatobiliary Surgery, Changhai Hospital, Naval Medical University, NO. 168 Changhai Road, Yangpu District, Shanghai, China
| | - Suizhi Gao
- Department of Pancreatic Hepatobiliary Surgery, Changhai Hospital, Naval Medical University, NO. 168 Changhai Road, Yangpu District, Shanghai, China
| | - Jiawei Han
- Department of Pancreatic Hepatobiliary Surgery, Changhai Hospital, Naval Medical University, NO. 168 Changhai Road, Yangpu District, Shanghai, China
| | - Yiwei Ren
- Department of Pancreatic Hepatobiliary Surgery, Changhai Hospital, Naval Medical University, NO. 168 Changhai Road, Yangpu District, Shanghai, China
| | - Jian Wang
- Department of Pancreatic Hepatobiliary Surgery, Changhai Hospital, Naval Medical University, NO. 168 Changhai Road, Yangpu District, Shanghai, China
| | - Hui Jiang
- Department of Pathology, Changhai Hospital, Naval Medical University, NO. 168 Changhai Road, Yangpu District, Shanghai, China.
| | - Shiwei Guo
- Department of Pancreatic Hepatobiliary Surgery, Changhai Hospital, Naval Medical University, NO. 168 Changhai Road, Yangpu District, Shanghai, China.
| | - Gang Jin
- Department of Pancreatic Hepatobiliary Surgery, Changhai Hospital, Naval Medical University, NO. 168 Changhai Road, Yangpu District, Shanghai, China.
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13
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Zhang G, Bao C, Liu Y, Wang Z, Du L, Zhang Y, Wang F, Xu B, Zhou SK, Liu R. 18F-FDG-PET/CT-based deep learning model for fully automated prediction of pathological grading for pancreatic ductal adenocarcinoma before surgery. EJNMMI Res 2023; 13:49. [PMID: 37231321 DOI: 10.1186/s13550-023-00985-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 04/17/2023] [Indexed: 05/27/2023] Open
Abstract
BACKGROUND The determination of pathological grading has a guiding significance for the treatment of pancreatic ductal adenocarcinoma (PDAC) patients. However, there is a lack of an accurate and safe method to obtain pathological grading before surgery. The aim of this study is to develop a deep learning (DL) model based on 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) for a fully automatic prediction of preoperative pathological grading of pancreatic cancer. METHODS A total of 370 PDAC patients from January 2016 to September 2021 were collected retrospectively. All patients underwent 18F-FDG-PET/CT examination before surgery and obtained pathological results after surgery. A DL model for pancreatic cancer lesion segmentation was first developed using 100 of these cases and applied to the remaining cases to obtain lesion regions. After that, all patients were divided into training set, validation set, and test set according to the ratio of 5:1:1. A predictive model of pancreatic cancer pathological grade was developed using the features computed from the lesion regions obtained by the lesion segmentation model and key clinical characteristics of the patients. Finally, the stability of the model was verified by sevenfold cross-validation. RESULTS The Dice score of the developed PET/CT-based tumor segmentation model for PDAC was 0.89. The area under curve (AUC) of the PET/CT-based DL model developed on the basis of the segmentation model was 0.74, with an accuracy, sensitivity, and specificity of 0.72, 0.73, and 0.72, respectively. After integrating key clinical data, the AUC of the model improved to 0.77, with its accuracy, sensitivity, and specificity boosted to 0.75, 0.77, and 0.73, respectively. CONCLUSION To the best of our knowledge, this is the first deep learning model to end-to-end predict the pathological grading of PDAC in a fully automatic manner, which is expected to improve clinical decision-making.
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Affiliation(s)
- Gong Zhang
- Medical School of Chinese PLA, Beijing, China
- Faculty of Hepato-Biliary-Pancreatic Surgery, The First Medical Center of Chinese People's Liberation Army (PLA) General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Chengkai Bao
- School of Biomedical Engineering, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
- Suzhou Institute for Advanced Research, University of Science and Technology of China, Suzhou, Jiangsu, China
| | - Yanzhe Liu
- Faculty of Hepato-Biliary-Pancreatic Surgery, The First Medical Center of Chinese People's Liberation Army (PLA) General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Zizheng Wang
- Senior Department of Hepatology, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Lei Du
- Department of Nuclear Medicine, The First Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Yue Zhang
- School of Biomedical Engineering, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
- Suzhou Institute for Advanced Research, University of Science and Technology of China, Suzhou, Jiangsu, China
| | - Fei Wang
- Faculty of Hepato-Biliary-Pancreatic Surgery, The First Medical Center of Chinese People's Liberation Army (PLA) General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Baixuan Xu
- Department of Nuclear Medicine, The First Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.
| | - S Kevin Zhou
- School of Biomedical Engineering, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
- Suzhou Institute for Advanced Research, University of Science and Technology of China, Suzhou, Jiangsu, China.
| | - Rong Liu
- Faculty of Hepato-Biliary-Pancreatic Surgery, The First Medical Center of Chinese People's Liberation Army (PLA) General Hospital, 28 Fuxing Road, Beijing, 100853, China.
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14
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Eddfair MM, Abdulrahman O, Alqawi O, Assidi M, Buhmeida A, Elturki A, Jebriel A, Elfagieh M, Ermiah E. Correlations of demographical and clinicopathological features with patient outcome of pancreatic ductal adenocarcinoma: A retrospective study (2010-2018) from a Libyan Cohort. J Cancer Res Ther 2023; 19:745-752. [PMID: 37470604 DOI: 10.4103/jcrt.jcrt_1778_21] [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] [Indexed: 11/04/2022]
Abstract
Objective The aim of the study was to study the correlations of demographical and clinicopathological variables of patients with pancreatic ductal adenocarcinoma (PDAC) and evaluate the association of these variables with patients' survival outcomes. Patients and Methods A retrospective analysis of 123 patients with PDAC were diagnosed and treated at the National Cancer Institute, Misurata, Libya during the 2010-2108 period. Data for demographics, clinicopathological, biological variables, risk factors, presentation, treatment, and survival-related data were collected from the patients' medical records. Results The mean age of patient was 61.2 years (range: 19-90 years) and most of patients (80.5%) were aged >50 years. For gender distribution, PDAC was more frequent in males (59.3%). Abdominal pain was the most frequent presenting symptom (84.6%) and 78% (96 patients) among them had head tumors. Most patients (80.5%) presented with unresectable tumor at diagnosis. Disease-free survival was better in patients with early stage (P < 0.0001), low-grade tumor (P = 0.001), resectable tumor (P < 0.0001), and with carcinoembryonic antigen levels <5 ng/ml (P = 0.004). Multivariate Cox's regression analysis showed that tumor stage is an independent poor survival factor (P = 0.002). Age at diagnosis, gender, family history, and position of tumor did not show any significant associations with patient outcome. Conclusion Libyan patients with PDAC had different demographics, clinicopathological, and biological variables. Typically, they presented with unresectable tumor, advanced stages, and had very short survival times. These results urge us to conduct in-depth biomolecular research studies to identify effective early diagnostics and therapeutics biomarkers in order to fight this disease before it escalates.
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Affiliation(s)
| | - Othman Abdulrahman
- Department of Medical Oncology, National Cancer Institute, Misurata, Libya
| | - Omar Alqawi
- Biotechnology Research Centre, National Cancer Institute-Misurata, Misurata 218-51, Libya
| | - Mourad Assidi
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University; Medical Laboratory Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Abdelbaset Buhmeida
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University; Medical Laboratory Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Abdulfattah Elturki
- Department of Medical Oncology and Haematology, National Cancer Institute, Misurata, Libya
| | - Abdalla Jebriel
- Department of Medical Oncology, National Cancer Institute, Misurata, Libya
| | - Mohamed Elfagieh
- Department of Surgery, National Cancer Institute, Misurata, Libya
| | - Eramah Ermiah
- Medical Research Unit, National Cancer Institute, Misurata, Libya
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15
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Xu Q, Wang W, Hu H, Ji S. Screening of potential pain genes in pancreatic ductal adenocarcinoma (PDAC) based on bioinformatics methods. J Gastrointest Oncol 2023; 14:420-428. [PMID: 36915423 PMCID: PMC10007930 DOI: 10.21037/jgo-23-94] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 02/16/2023] [Indexed: 03/03/2023] Open
Abstract
Background We aimed to identify cancer pain genes in pancreatic ductal adenocarcinoma (PDAC) using bioinformatic tools to provide evidence for pain treatment in PDAC patients. Methods The GSE50570 data were obtained from the high-throughput Gene Expression Omnibus (GEO) database and subsequently analyzed. A volcano map, principal component analysis (PCA) map, box plot, and heat map were drawn, and a Venn diagram was constructed by comparison with human secreted histone genes. The differentially expressed secreted histone genes in PDAC were obtained. Then, Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed, followed by protein-protein interaction (PPI) network analysis and key genetic screening. Results In comparison to normal samples, the expression of 81 secreted protein-related genes was downregulated, and the expression of 12 secreted protein-related genes was upregulated in PDAC. According to the GO and KEGG enrichment analysis results, these differentially expressed genes are mainly involved in the PI3K-Akt signaling pathway, protein digestion and absorption, extracellular matrix (ECM) receptor interaction, AGE-RAGE (advanced glycation endproducts-the Receptor of Advanced Glycation Endproducts) signaling pathway, relaxin signaling pathway, interleukin-17 (IL-17) signaling pathway, and transforming growth factor-β (TGF-β) signaling pathway, affecting the different manifestations of PDAC cancer pain. We used Cytoscape software to construct a protein interaction network of common differentially expressed genes and obtained three clusters with high scores. Our literature review found that several genes, including PTGS2, VCAN, and CCL2, were directly related to cancer pain occurrence. Conclusions By data mining the PDAC tumor expression, dozens of differentially expressed genes were identified in this study, several of which have been associated with the frequency and severity of cancer pain. This study provides an important foundation for the pain treatment of PDAC tumor patients.
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Affiliation(s)
- Qian Xu
- Department of Anesthesiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Wei Wang
- Department of Anesthesiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Hongyu Hu
- Department of Anesthesiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Shujuan Ji
- Department of Anesthesiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
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Zaborienė I, Strakšytė V, Ignatavičius P, Barauskas G, Dambrauskienė R, Žvinienė K. Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Measuring Perfusion in Pancreatic Ductal Adenocarcinoma and Different Tumor Grade: A Preliminary Single Center Study. Diagnostics (Basel) 2023; 13:521. [PMID: 36766626 PMCID: PMC9914475 DOI: 10.3390/diagnostics13030521] [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: 12/07/2022] [Revised: 01/18/2023] [Accepted: 01/24/2023] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Dynamic contrast-enhanced magnetic resonance imaging is a noninvasive imaging modality that can supply information regarding the tumor anatomy and physiology. The aim of the study was to analyze DCE-MRI perfusion parameters in normal pancreatic parenchymal tissue and PDAC and to evaluate the efficacy of this diagnostic modality in determining the tumor grade. METHODS A single-center retrospective study was performed. A total of 28 patients with histologically proven PDAC underwent DCE-MRI; the control group enrolled 14 patients with normal pancreatic parenchymal tissue; the radiological findings were compared with histopathological data. The study patients were further grouped according to the differentiation grade (G value): well- and moderately differentiated and poorly differentiated PDAC. RESULTS The median values of Ktrans, kep and iAUC were calculated lower in PDAC compared with the normal pancreatic parenchymal tissue (p < 0.05). The mean value of Ve was higher in PDAC, compared with the normal pancreatic tissue (p < 0.05). Ktrans, kep and iAUC were lower in poorly differentiated PDAC, whereas Ve showed no differences between groups. CONCLUSIONS Ve and iAUC DCE-MRI perfusion parameters are important as independent diagnostic criteria predicting the probability of PDAC; the Ktrans and iAUC DCE-MRI perfusion parameters may serve as effective independent prognosticators preoperatively identifying poorly differentiated PDAC.
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Affiliation(s)
- Inga Zaborienė
- Department of Radiology, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania
| | - Vestina Strakšytė
- Department of Radiology, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania
| | - Povilas Ignatavičius
- Department of Surgery, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania
| | - Giedrius Barauskas
- Department of Surgery, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania
| | - Rūta Dambrauskienė
- Department of Oncology and Hematology, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania
| | - Kristina Žvinienė
- Department of Radiology, Lithuanian University of Health Sciences, LT-50161 Kaunas, Lithuania
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Mohamad Sehmi MN, Ahmad Fauzi MF, Wan Ahmad WSHM, Wan Ling Chan E. Pancreatic cancer grading in pathological images using deep learning convolutional neural networks. F1000Res 2022; 10:1057. [PMID: 37767358 PMCID: PMC10521057 DOI: 10.12688/f1000research.73161.2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/08/2022] [Indexed: 09/29/2023] Open
Abstract
Background: Pancreatic cancer is one of the deadliest forms of cancer. The cancer grades define how aggressively the cancer will spread and give indication for doctors to make proper prognosis and treatment. The current method of pancreatic cancer grading, by means of manual examination of the cancerous tissue following a biopsy, is time consuming and often results in misdiagnosis and thus incorrect treatment. This paper presents an automated grading system for pancreatic cancer from pathology images developed by comparing deep learning models on two different pathological stains. Methods: A transfer-learning technique was adopted by testing the method on 14 different ImageNet pre-trained models. The models were fine-tuned to be trained with our dataset. Results: From the experiment, DenseNet models appeared to be the best at classifying the validation set with up to 95.61% accuracy in grading pancreatic cancer despite the small sample set. Conclusions: To the best of our knowledge, this is the first work in grading pancreatic cancer based on pathology images. Previous works have either focused only on detection (benign or malignant), or on radiology images (computerized tomography [CT], magnetic resonance imaging [MRI] etc.). The proposed system can be very useful to pathologists in facilitating an automated or semi-automated cancer grading system, which can address the problems found in manual grading.
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Seufferlein T, Mayerle J, Böck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie zum exokrinen Pankreaskarzinom – Langversion 2.0 – Dezember 2021 – AWMF-Registernummer: 032/010OL. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e812-e909. [PMID: 36368658 DOI: 10.1055/a-1856-7346] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Affiliation(s)
| | | | - Stefan Böck
- Medizinische Klinik und Poliklinik III, Universitätsklinikum München, Germany
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Universitätsklinikum, Heidelberg, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Universitätsklinikum Hamburg-Eppendorf Medizinische Klinik und Poliklinik II Onkologie Hämatologie, Hamburg, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
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19
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Liao H, Li Y, Yang Y, Liu H, Zhang J, Liang H, Yan G, Liu Y. Comparison of Multiple Radiomics Models for Identifying Histological Grade of Pancreatic Ductal Adenocarcinoma Preoperatively Based on Multiphasic Contrast-Enhanced Computed Tomography: A Two-Center Study in Southwest China. Diagnostics (Basel) 2022; 12:diagnostics12081915. [PMID: 36010267 PMCID: PMC9406915 DOI: 10.3390/diagnostics12081915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 08/06/2022] [Accepted: 08/06/2022] [Indexed: 11/16/2022] Open
Abstract
Background: We designed and validated the value of multiple radiomics models for diagnosing histological grade of pancreatic ductal adenocarcinoma (PDAC), holding a promise of assisting in precision medicine and providing clinical therapeutic strategies. Methods: 198 PDAC patients receiving surgical resection and pathological confirmation were enrolled and classified as 117 low-grade PDAC and 81 high-grade PDAC group. An external validation group was used to assess models’ performance. Available radiomics features were selected using GBDT algorithm on the basis of the arterial and venous phases, respectively. Five different machine learning models were built including k-nearest neighbour, logistic regression, naive bayes model, support vector machine, and random forest using ten times tenfold cross-validation. Multivariable logistic regression analysis was applied to establish clinical model and combined model. The models’ performance was assessed according to its predictive performance, calibration curves, and decision curves. A nomogram was established for visualization. Survival analysis was conducted for stratifying the overall survival prior to treatment. Results: In the training group, the RF model demonstrated the optimal predictive ability and robustness with an AUC of 0.943; the SVM model achieved the secondary performance, followed by Bayes model. In the external validation group, these three models (Bayes, RF, SVM) also achieved the top three predictive ability. A clinical model was built by selected clinical features with an AUC of 0.728, and combined model was established by an RF model and a clinical model with an AUC of 0.961. The log-rank test revealed that the low-grade group survived longer than the high-grade group. Conclusions: The multiphasic CECT radiomics models offered an accurate and noninvasive perspective to differentiate histological grade in PDAC and advantages of machine learning models including RF, SVM and Bayes were more remarkable.
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Affiliation(s)
- Hongfan Liao
- College of Medical Informatics of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China
| | - Yongmei Li
- Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Yaying Yang
- Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, China
| | - Huan Liu
- GE Healthcare, Shanghai 201203, China
| | - Jiao Zhang
- Department of Radiology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China
| | - Hongwei Liang
- Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Gaowu Yan
- Department of Radiology, Suining Central Hospital, Suining 429000, China
| | - Yanbing Liu
- College of Medical Informatics of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China
- Correspondence:
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20
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Seufferlein T, Mayerle J, Böck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie zum exokrinen Pankreaskarzinom – Kurzversion 2.0 – Dezember 2021, AWMF-Registernummer: 032/010OL. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:991-1037. [PMID: 35671996 DOI: 10.1055/a-1771-6811] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Affiliation(s)
| | | | - Stefan Böck
- Medizinische Klinik und Poliklinik III, Universitätsklinikum München, Germany
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Universitätsklinikum, Heidelberg, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Universitätsklinikum Hamburg-Eppendorf Medizinische Klinik und Poliklinik II Onkologie Hämatologie, Hamburg, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
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21
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Philipson E, Engström C, Naredi P, Bourghardt Fagman J. High expression of p62/SQSTM1 predicts shorter survival for patients with pancreatic cancer. BMC Cancer 2022; 22:347. [PMID: 35354432 PMCID: PMC8969328 DOI: 10.1186/s12885-022-09468-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 03/28/2022] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Accumulation of the signal adaptor protein p62 has been demonstrated in many forms of cancer, including pancreatic ductal adenocarcinoma (PDAC). Although data from experimental studies suggest that p62 accumulation accelerates the development of PDAC, the association between p62 protein expression and survival in PDAC patients is unclear. METHODS Thirty-three tumor specimens from PDAC patients treated by primary surgery were obtained. Immunohistochemical expression of p62, microtubule-associated protein 1A/1B-light chain 3 (LC3), and nuclear factor-erythroid factor 2-related factor 2 (NRF2) in tumor tissue was examined for associations with clinicopathological characteristics and disease-specific survival (DSS). RESULTS There was no association between p62 expression and any of the clinicopathological variables. However, high p62 protein expression in tumor cells was significantly associated with shorter DSS (7 months vs. 29 months, p = 0.017). The hazard ratio for death in patients with high p62 protein expression in tumor cells was 2.88 (95% confidence interval: 1.17-7.11, p = 0.022). In multivariable analysis, high p62 expression was an independent prognostic factor for shorter DSS (p = 0.020) when follow up time was more than 5 years. LC3 and NRF2 staining was not associated with survival or other clinicopathological parameters. CONCLUSION Our results show that high p62 protein expression in tumor cells is associated with shorter survival following pancreatic tumor resection. This association supports a role for p62 as a prognostic marker in patients with PDAC treated by primary surgery.
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Affiliation(s)
- Eva Philipson
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Department of Surgery, Sahlgrenska University Hospital, Sahlgrenska, Vita Stråket 12, paviljong plan 2, SE-413 45, Gothenburg, Sweden
| | - Cecilia Engström
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Department of Surgery, Sahlgrenska University Hospital, Sahlgrenska, Vita Stråket 12, paviljong plan 2, SE-413 45, Gothenburg, Sweden
| | - Peter Naredi
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Department of Surgery, Sahlgrenska University Hospital, Sahlgrenska, Vita Stråket 12, paviljong plan 2, SE-413 45, Gothenburg, Sweden
| | - Johan Bourghardt Fagman
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. .,Department of Surgery, Sahlgrenska University Hospital, Sahlgrenska, Vita Stråket 12, paviljong plan 2, SE-413 45, Gothenburg, Sweden.
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22
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Sánchez-Ramírez D, Medrano-Guzmán R, Candanedo-González F, De Anda-González J, García-Rios LE, Pérez-Koldenkova V, Gutiérrez-de la Barrera M, Rodríguez-Enríquez S, Velasco-Velázquez M, Pacheco-Velázquez SC, Piña-Sánchez P, Mayani H, Gómez-Delgado A, Monroy-García A, Martínez-Lara AK, Montesinos JJ. High expression of both desmoplastic stroma and epithelial to mesenchymal transition markers associate with shorter survival in pancreatic ductal adenocarcinoma. Eur J Histochem 2022; 66:3360. [PMID: 35174683 PMCID: PMC8883614 DOI: 10.4081/ejh.2022.3360] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 02/09/2022] [Indexed: 12/24/2022] Open
Abstract
Desmoplastic stroma (DS) and the epithelial-to-mesenchymal transition (EMT) play a key role in pancreatic ductal adenocarcinoma (PDAC) progression. To date, however, the combined expression of DS and EMT markers, and their association with variations in survival within each clinical stage and degree of tumor differentiation is unknown. The purpose of this study was to investigate the association between expression of DS and EMT markers and survival variability in patients diagnosed with PDAC. We examined the expression levels of DS markers alpha smooth muscle actin (α-SMA), fibronectin, and vimentin, and the EMT markers epithelial cell adhesion molecule (EPCAM), pan-cytokeratin, and vimentin, by immunohistochemistry using a tissue microarray of a retrospective cohort of 25 patients with PDAC. The results were examined for association with survival by clinical stage and by degree of tumor differentiation. High DS markers expression -α-SMA, fibronectin, and vimentin- was associated with decreased survival at intermediate and advanced clinical stages (p=0.006-0.03), as well as with both poorly and moderately differentiated tumor grades (p=0.01-0.02). Interestingly, the same pattern was observed for EMT markers, i.e., EPCAM, pan-cytokeratin, and vimentin (p=0.00008-0.03). High expression of DS and EMT markers within each clinical stage and degree of tumor differentiation was associated with lower PDAC survival. Evaluation of these markers may have a prognostic impact on survival time variation in patients with PDAC.
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Affiliation(s)
- Damián Sánchez-Ramírez
- Mesenchymal Stem Cells Laboratory, Oncology Research Unit, Oncology Hospital, National Medical Center, IMSS, Mexico City.
| | - Rafael Medrano-Guzmán
- Department of Sarcomas, Oncology Hospital, High Specialty Medical Unit (UMAE), National Medical Center, IMSS, Mexico City.
| | - Fernando Candanedo-González
- Department of Pathology, Oncology Hospital, High Specialty Medical Unit (UMAE), National Medical Center, IMSS, Mexico City.
| | - Jazmín De Anda-González
- Department of Pathology, Oncology Hospital, High Specialty Medical Unit (UMAE), National Medical Center, IMSS, Mexico City.
| | - Luis Enrique García-Rios
- Department of Sarcomas, Oncology Hospital, High Specialty Medical Unit (UMAE), National Medical Center, IMSS, Mexico City.
| | - Vadim Pérez-Koldenkova
- National Laboratory of Advanced Microscopy-IMSS, National Medical Center, Siglo XXI IMSS, Mexico City.
| | | | | | - Marco Velasco-Velázquez
- Department of Pharmacology and Peripheral Research Unit in Translational Biomedicine (CMN 20 de noviembre, ISSSTE), School of Medicine, UNAM, Mexico City.
| | | | - Patricia Piña-Sánchez
- Molecular Oncology Laboratory, Oncology Research Unit, Oncology Hospital, National Medical Center, IMSS, Mexico City.
| | - Héctor Mayani
- Hematopoietic Stem Cells Laboratory, Oncology Research Unit, Oncology Hospital, National Medical Center, IMSS, Mexico City.
| | - Alejandro Gómez-Delgado
- Infectious and Parasitic Diseases, Medical Research Unit, Pediatric Hospital, National Medical Center, IMSS, Mexico City.
| | - Alberto Monroy-García
- Immunology and Cancer Laboratory, Oncology Research Unit, Oncology Hospital, National Medical Center (IMSS), Mexico City.
| | - Ana Karen Martínez-Lara
- Mesenchymal Stem Cells Laboratory, Oncology Research Unit, Oncology Hospital, National Medical Center, IMSS, Mexico City.
| | - Juan José Montesinos
- Mesenchymal Stem Cells Laboratory, Oncology Research Unit, Oncology Hospital, National Medical Center, IMSS, Mexico City.
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23
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Hong S, Song KB, Hwang DW, Lee JH, Lee W, Jun E, Kwon J, Park Y, Park SY, Kim N, Shin D, Kim H, Sung M, Ryu Y, Kim SC. Preoperative serum carbohydrate antigen 19-9 levels predict early recurrence after the resection of early-stage pancreatic ductal adenocarcinoma. World J Gastrointest Surg 2021; 13:1423-1435. [PMID: 34950431 PMCID: PMC8649558 DOI: 10.4240/wjgs.v13.i11.1423] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 05/31/2021] [Accepted: 08/23/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is a serious disease with a poor prognosis. Only a minority of patients undergo surgery due to the advanced stage of the disease, and patients with early-stage disease, who are expected to have a better prognosis, often experience recurrence. Thus, it is important to identify the risk factors for early recurrence and to develop an adequate treatment plan. AIM To evaluate the predictive factors associated with the early recurrence of early-stage PDAC. METHODS This study enrolled 407 patients with stage I PDAC undergoing upfront surgical resection between January 2000 and April 2016. Early recurrence was defined as a diagnosis of recurrence within 6 mo of surgery. The optimal cutoff values were determined by receiver operating characteristic (ROC) analyses. Univariate and multivariate analyses were performed to identify the risk factors for early recurrence. RESULTS Of the 407 patients, 98 patients (24.1%) experienced early disease recurrence: 26 (26.5%) local and 72 (73.5%) distant sites. In total, 253 (62.2%) patients received adjuvant chemotherapy. On ROC curve analysis, the optimal cutoff values for early recurrence were 70 U/mL and 2.85 cm for carbohydrate antigen 19-9 (CA 19-9) levels and tumor size, respectively. Of the 181 patients with CA 19-9 level > 70 U/mL, 59 (32.6%) had early recurrence, compared to 39 (17.4%) of 226 patients with CA 19-9 level ≤ 70 U/mL (P < 0.001). Multivariate analysis revealed that CA 19-9 level > 70 U/mL (P = 0.006), tumor size > 2.85 cm (P = 0.004), poor differentiation (P = 0.008), and non-adjuvant chemotherapy (P = 0.025) were significant risk factors for early recurrence in early-stage PDAC. CONCLUSION Elevated CA 19-9 level (cutoff value > 70 U/mL) can be a reliable predictive factor for early recurrence in early-stage PDAC. As adjuvant chemotherapy can prevent early recurrence, it should be recommended for patients susceptible to early recurrence.
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Affiliation(s)
- Sarang Hong
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul 05505, South Korea
| | - Ki Byung Song
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul 05505, South Korea
| | - Dae Wook Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul 05505, South Korea
| | - Jae Hoon Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul 05505, South Korea
| | - Woohyung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul 05505, South Korea
| | - Eunsung Jun
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul 05505, South Korea
| | - Jaewoo Kwon
- Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, South Korea
| | - Yejong Park
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul 05505, South Korea
| | - Seo Young Park
- Department of Statistics and Data Science, Korea National Open University, Seoul 03087, South Korea
| | - Naru Kim
- Department of Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, Gyeonggido 11765, South Korea
| | - Dakyum Shin
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul 05505, South Korea
| | - Hyeyeon Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul 05505, South Korea
| | - Minkyu Sung
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul 05505, South Korea
| | - Yunbeom Ryu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul 05505, South Korea
| | - Song Cheol Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, Seoul 05505, South Korea
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24
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Park JM, Mau CZ, Chen YC, Su YH, Chen HA, Huang SY, Chang JS, Chiu CF. A case-control study in Taiwanese cohort and meta-analysis of serum ferritin in pancreatic cancer. Sci Rep 2021; 11:21242. [PMID: 34711879 PMCID: PMC8553768 DOI: 10.1038/s41598-021-00650-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 10/06/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer is one of the most lethal diseases which lack an early diagnostic marker. We investigated whether serum ferritin (SF) reflects risk for pancreatic cancer and potential genes that may contribute ferritin and pancreatic cancer risks. We performed a meta-analysis of relevant studies on SF and pancreatic cancer risk by searching articles in PUBMED and EMBASE published up to 1 March 2020. We also collected serum samples from Taipei Medical University Joint Biobank and compared SF levels in 34 healthy controls and 34 pancreatic cancer patients. An Oncomine database was applied as a platform to explore a series of genes that exhibited strong associations between ferritin and pancreatic cancer. Herein, we show that high levels of SF can indicate risk of pancreatic cancer, suggesting SF as the new tumor marker that may be used to help pancreatic cancer diagnosis. We also found that expressions of iron homeostasis genes (MYC, FXN) and ferroptosis genes (ALOX15, CBS, FDFT1, LPCAT3, RPL8, TP53, TTC35) are significantly altered with pancreatic tumor grades, which may contribute to differential expression of ferritin related to pancreatic cancer prognosis.
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Affiliation(s)
- Ji Min Park
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, 11031, Taiwan.,Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei, 11031, Taiwan.,TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, 11031, Taiwan
| | - Chen-Zou Mau
- Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei, 11031, Taiwan
| | - Yang-Ching Chen
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, 11031, Taiwan.,Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei, 11031, Taiwan
| | - Yen-Hao Su
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, 11301, Taiwan.,Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, Taiwan.,Department of General Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11301, Taiwan.,TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, 11031, Taiwan
| | - Hsin-An Chen
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, 11301, Taiwan.,Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, Taiwan.,Department of General Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11301, Taiwan.,TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, 11031, Taiwan
| | - Shih-Yi Huang
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, 11031, Taiwan.,Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei, 11031, Taiwan.,Nutrition Research Center, Taipei Medical University Hospital, Taipei, 11031, Taiwan
| | - Jung-Su Chang
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, 11031, Taiwan. .,Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei, 11031, Taiwan. .,Nutrition Research Center, Taipei Medical University Hospital, Taipei, 11031, Taiwan.
| | - Ching-Feng Chiu
- Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei, 11031, Taiwan. .,Nutrition Research Center, Taipei Medical University Hospital, Taipei, 11031, Taiwan. .,TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, 11031, Taiwan.
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25
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Mohamad Sehmi MN, Ahmad Fauzi MF, Wan Ahmad WSHM, Wan Ling Chan E. Pancreatic cancer grading in pathological images using deep learning convolutional neural networks. F1000Res 2021. [DOI: 10.12688/f1000research.73161.1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Background: Pancreatic cancer is one of the deadliest forms of cancer. The cancer grades define how aggressively the cancer will spread and give indication for doctors to make proper prognosis and treatment. The current method of pancreatic cancer grading, by means of manual examination of the cancerous tissue following a biopsy, is time consuming and often results in misdiagnosis and thus incorrect treatment. This paper presents an automated grading system for pancreatic cancer from pathology images developed by comparing deep learning models on two different pathological stains. Methods: A transfer-learning technique was adopted by testing the method on 14 different ImageNet pre-trained models. The models were fine-tuned to be trained with our dataset. Results: From the experiment, DenseNet models appeared to be the best at classifying the validation set with up to 95.61% accuracy in grading pancreatic cancer despite the small sample set. Conclusions: To the best of our knowledge, this is the first work in grading pancreatic cancer based on pathology images. Previous works have either focused only on detection (benign or malignant), or on radiology images (computerized tomography [CT], magnetic resonance imaging [MRI] etc.). The proposed system can be very useful to pathologists in facilitating an automated or semi-automated cancer grading system, which can address the problems found in manual grading.
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26
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Ng KYY, Chow EWX, Jiang B, Lim C, Goh BKP, Lee SY, Teo JY, Tan DMY, Cheow PC, Ooi LLPJ, Chow PKH, Lee JJX, Kam JH, Koh YX, Jeyaraj PR, Tan EK, Choo SP, Chan CY, Chung AYF, Tai D. Resected pancreatic adenocarcinoma: An Asian institution's experience. Cancer Rep (Hoboken) 2021; 4:e1393. [PMID: 33939335 PMCID: PMC8551988 DOI: 10.1002/cnr2.1393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 03/08/2021] [Accepted: 03/25/2021] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Pancreatic adenocarcinoma (PDAC) is highly lethal. Surgery offers the only chance of cure, but 5-year overall survival (OS) after surgical resection and adjuvant therapy remains dismal. Adjuvant trials were mostly conducted in the West enrolling fit patients. Applicability to a general population, especially Asia has not been described adequately. AIM We aimed to evaluate the clinical outcomes, prognostic factors of survival, pattern, and timing of recurrence after curative resection in an Asian institution. METHODS AND RESULTS The clinicopathologic and survival outcomes of 165 PDAC patients who underwent curative resection between 1998 and 2013 were reviewed retrospectively. Median age at surgery was 62.0 years. 55.2% were male, and 73.3% had tumors involving the head of pancreas. The median OS of the entire cohort was 19.7 months. Median OS of patients who received adjuvant chemotherapy was 23.8 months. Negative predictors of survival include lymph node ratio (LNR) of >0.3 (HR = 3.36, P = .001), tumor site involving the body or tail of pancreas (HR = 1.59, P = .046), presence of perineural invasion (PNI) (HR = 2.36, P = .018) and poorly differentiated/undifferentiated tumor grade (HR = 1.86, P = .058). The median time to recurrence was 8.87 months, with 66.1% and 81.2% of patients developing recurrence at 12 months and 24 months respectively. The most common site of recurrence was the liver. CONCLUSION The survival of Asian patients with resected PDAC who received adjuvant chemotherapy is comparable to reported randomized trials. Clinical characteristics seem similar to Western patients. Hence, geographical locations may not be a necessary stratification factor in RCTs. Conversely, lymph node ratio and status of PNI ought to be incorporated.
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Affiliation(s)
- Kennedy Yao Yi Ng
- Division of Medical OncologyNational Cancer Centre SingaporeSingapore
| | | | - Bochao Jiang
- Division of Medical OncologyNational Cancer Centre SingaporeSingapore
| | - Cindy Lim
- Division of Clinical Trials and Epidemiological SciencesNational Cancer Centre SingaporeSingapore
| | - Brian Kim Poh Goh
- Department of Hepatopancreatobiliary and Transplantation SurgerySingapore General HospitalSingapore
- Division of Surgical OncologyNational Cancer Centre SingaporeSingapore
- Duke‐NUS Graduate Medical SchoolSingapore
| | - Ser Yee Lee
- Surgical Associates, National Cancer Centre SingaporeSingapore
| | - Jin Yao Teo
- Department of Hepatopancreatobiliary and Transplantation SurgerySingapore General HospitalSingapore
- Duke‐NUS Graduate Medical SchoolSingapore
| | - Damien Meng Yew Tan
- Duke‐NUS Graduate Medical SchoolSingapore
- Department of Gastroenterology and HepatologySingapore General HospitalSingapore
| | - Peng Chung Cheow
- Department of Hepatopancreatobiliary and Transplantation SurgerySingapore General HospitalSingapore
- Division of Surgical OncologyNational Cancer Centre SingaporeSingapore
- Duke‐NUS Graduate Medical SchoolSingapore
| | - London Lucien Peng Jin Ooi
- Department of Hepatopancreatobiliary and Transplantation SurgerySingapore General HospitalSingapore
- Division of Surgical OncologyNational Cancer Centre SingaporeSingapore
- Duke‐NUS Graduate Medical SchoolSingapore
| | - Pierce Kah Hoe Chow
- Department of Hepatopancreatobiliary and Transplantation SurgerySingapore General HospitalSingapore
- Division of Surgical OncologyNational Cancer Centre SingaporeSingapore
- Duke‐NUS Graduate Medical SchoolSingapore
| | | | - Juinn Huar Kam
- Department of Hepatopancreatobiliary and Transplantation SurgerySingapore General HospitalSingapore
| | - Ye Xin Koh
- Department of Hepatopancreatobiliary and Transplantation SurgerySingapore General HospitalSingapore
| | - Prema Raj Jeyaraj
- Department of Hepatopancreatobiliary and Transplantation SurgerySingapore General HospitalSingapore
| | - Ek Khoon Tan
- Department of Hepatopancreatobiliary and Transplantation SurgerySingapore General HospitalSingapore
| | - Su Pin Choo
- Division of Medical OncologyNational Cancer Centre SingaporeSingapore
- Curie Oncology, Graduate Medical SchoolSingapore General HospitalSingapore
| | - Chung Yip Chan
- Department of Hepatopancreatobiliary and Transplantation SurgerySingapore General HospitalSingapore
- Duke‐NUS Graduate Medical SchoolSingapore
| | - Alexander Yaw Fui Chung
- Department of Hepatopancreatobiliary and Transplantation SurgerySingapore General HospitalSingapore
- Division of Surgical OncologyNational Cancer Centre SingaporeSingapore
- Duke‐NUS Graduate Medical SchoolSingapore
| | - David Tai
- Division of Medical OncologyNational Cancer Centre SingaporeSingapore
- Duke‐NUS Graduate Medical SchoolSingapore
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Verbeke C, Webster F, Brosens L, Campbell F, Del Chiaro M, Esposito I, Feakins RM, Fukushima N, Gill AJ, Kakar S, Kench JG, Krasinskas AM, van Laethem JL, Schaeffer DF, Washington K. Dataset for the reporting of carcinoma of the exocrine pancreas: recommendations from the International Collaboration on Cancer Reporting (ICCR). Histopathology 2021; 79:902-912. [PMID: 34379823 DOI: 10.1111/his.14540] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 08/04/2021] [Accepted: 08/08/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND AND OBJECTIVES Current guidelines for the pathology reporting on pancreatic cancer differ in certain aspects, resulting in divergent reporting practice and a lack of comparability of data. Here we report on a new international dataset for the pathology reporting of resection specimens with cancer of the exocrine pancreas (ductal adenocarcinoma and acinar cell carcinoma). The dataset was produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter-)national pathology and cancer organisations. METHODS AND RESULTS According to the ICCR's rigorous process for dataset development, an international expert panel consisting of pancreatic pathologists, a pancreatic surgeon and an oncologist produced a set of core and non-core data items based on a critical review and discussion of current evidence. Commentary was provided for each data item to explain the rationale for selecting it as a core or non-core element, its clinical relevance, and to highlight potential areas of disagreement or lack of evidence, in which case a consensus position was formulated. Following international public consultation, the document was finalised and ratified, and the dataset, which includes a synoptic reporting guide, was published on the ICCR website. CONCLUSIONS This first international dataset for cancer of the exocrine pancreas is intended to promote high quality, standardised pathology reporting. Its widespread adoption will improve consistency of reporting, facilitate multidisciplinary communication and enhance comparability of data, all of which will help to improve the management of pancreatic cancer patients.
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Affiliation(s)
- Caroline Verbeke
- Department of Pathology, University of Oslo, Oslo University Hospital, Oslo, Norway
| | - Fleur Webster
- International Collaboration on Cancer Reporting, Sydney, Australia
| | - Lodewijk Brosens
- Department of Pathology, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands and Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Fiona Campbell
- Department of Pathology, Royal Liverpool University Hospital, Liverpool, United Kingdom
| | - Marco Del Chiaro
- Department of Surgery, University of Colorado Denver - Anschutz Medical Campus, Aurora, 80045, Colorado, United States
| | - Irene Esposito
- Institute of Pathology, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Roger M Feakins
- Department of Histopathology, Royal Free Hospital, London, United Kingdom
| | | | - Anthony J Gill
- Sydney Medical School, The University of Sydney, Sydney, Australia.,Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, St Leonards, Australia.,NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, Australia
| | - Sanjay Kakar
- Department of Pathology, University of California, M590 San Francisco, United States
| | - James G Kench
- Sydney Medical School, The University of Sydney, Sydney, Australia.,Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, New South Wales Health Pathology, Camperdown, Australia
| | - Alyssa M Krasinskas
- Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, United States
| | - Jean-Luc van Laethem
- Department of Gastroenterology and Medical Oncology, Hôpital Erasme and Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
| | - David F Schaeffer
- Division of Anatomic Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada.,Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Kay Washington
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Centre, Nashville, Tennessee, United States
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König AK, Gros H, Hinz U, Hank T, Kaiser J, Hackert T, Bergmann F, Büchler MW, Strobel O. Refined prognostic staging for resected pancreatic cancer by modified stage grouping and addition of tumour grade. Eur J Surg Oncol 2021; 48:113-120. [PMID: 34344573 DOI: 10.1016/j.ejso.2021.07.020] [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: 02/28/2021] [Revised: 06/26/2021] [Accepted: 07/21/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND With changes in T and N categories the 8th edition of the AJCC/UICC TNM staging system for pancreatic cancer resulted in improved prognostic staging, but inconsistencies were observed with specific stage groups. Tumour grading remains disregarded in prognostic staging. We aimed to validate the current staging system and to investigate the possibility of further optimization by integration of grading. METHODS 1946 patients undergoing upfront surgical resection for pancreatic adenocarcinoma from 10/2001 to 12/2015 were identified from a prospective institutional database. Survival analyses based on the 8th UICC TNM edition were performed and rare TNM subgroups were reallocated based on survival. The impact of tumour grade on stage-specific survival was assessed and a TNMG staging system was developed. RESULTS The 8th UICC staging system accurately stratified prognosis except for comparable survival in stages IB (pT2N0M0) and IIA (pT3N0M0). Regrouping of pT3N0M0 and pT1N1M0 to IB and of pT1N2M0 to II resulted in a modified staging system with higher consistency. High tumour grade (G3&G4 vs G1&G2) was associated with a significantly shorter survival in all new stage groups except for stage IV modified UICC. A TNMG-based prognostic stage grouping in which high tumour grade results in grouping with tumours of the next higher pTNM-stage resulted in improvement of prognostication in non-metastatic pancreatic cancer. CONCLUSIONS The 8th edition of the UICC TNM staging system leaves room for improvement. A TNMG staging system with adjustments in group-allocation of specific rarely occurring pTNM subgroups and integration of tumour grade results in improved prognostic stratification.
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Affiliation(s)
- Anna-Katharina König
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Hélène Gros
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Ulf Hinz
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Thomas Hank
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Jörg Kaiser
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Frank Bergmann
- Department of Pathology, University Hospital Heidelberg, Germany
| | - Markus W Büchler
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Oliver Strobel
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany.
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29
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Wu C, Hou SZ, Wu Z, Huang X, Wang Z, Tian B. Prognostic Nomogram for patients undergoing radical Pancreaticoduodenectomy for adenocarcinoma of the pancreatic head. BMC Cancer 2021; 21:624. [PMID: 34044806 PMCID: PMC8161963 DOI: 10.1186/s12885-021-08295-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 05/05/2021] [Indexed: 02/08/2023] Open
Abstract
Background Radical pancreaticoduodenectomy is the most common treatment strategy for patients diagnosed with adenocarcinoma of the pancreatic head. Few studies have reported the clinical characteristics and treatment efficacies of patients undergoing radical pancreaticoduodenectomy for adenocarcinoma of the pancreatic head. Methods A total of 177 pancreatic head cancer patients who underwent radical pancreaticoduodenectomy and were pathologically confirmed as having pancreatic ductal adenocarcinoma were screened in the West China Hospital of Sichuan University. The multivariate analysis results were implemented to construct a nomogram. The concordance index (c-index), the area under the curve (AUC) and calibration were utilized to evaluate the predictive performance of the nomogram. Results The prognostic nutritional index (PNI), the lymph node ratio (LNR) and the American Joint Committee on Cancer (AJCC) staging served as independent prognostic factors and were used to construct the nomogram. The c-indexes of the nomogram were 0.799 (confidence interval (CI), 0.741–0.858) and 0.732 (0.657–0.807) in the primary set and validation set, respectively. The AUCs of the nomogram at 1 and 3 years were 0.832 and 0.783, which were superior to the AJCC staging values of 0.759 and 0.705, respectively. Conclusions The nomogram may be used to predict the prognosis of radical resection for adenocarcinoma of the pancreatic head. These findings may represent an effective model for the developing an optimal therapeutic schedule for malnourished patients who need early effective nutritional intervention and may promote the treatment efficacy of resectable adenocarcinoma of the pancreatic head. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-08295-5.
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Affiliation(s)
- Chao Wu
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan Province, China
| | - Sheng Zhong Hou
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan Province, China
| | - Zuowei Wu
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan Province, China
| | - Xing Huang
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan Province, China
| | - Zihe Wang
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan Province, China
| | - Bole Tian
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan Province, China.
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30
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Shantarevich MY, Karmazanovsky GG, Egorkina AB, Kurochkina AI, Kriger AG, Kalinin DV, Stashkiv VI. [Computed tomography in determining the differentiation of ductal adenocarcinoma of pancreatic head]. Khirurgiia (Mosk) 2021:11-19. [PMID: 33710821 DOI: 10.17116/hirurgia202103111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
OBJECTIVE To evaluate the features of «hypervascular rim», tumor dimensions and density as prognostic factors of differentiation of pancreatic head adenocarcinoma. MATERIAL AND METHODS Pancreatoduodenectomy was performed in 311 patients with pancreatic head adenocarcinoma for the period 2013-2019. A retrospective study included 81 patients who met the following criteria: available data of morphological and immunohistological examination indicating tumor grade from Grade 1 to Grade 3, as well as available preoperative CT images in four phases (native, arterial, portal and delayed). Tumor dimensions, density of the pancreas, adenocarcinoma and abdominal aorta by the phases of contrast enhancement were analyzed in all patients. Moreover, we estimated coefficient of relative enhancement change. Perifocal hypervascular enhancement was assessed in arterial and portal phases. Contrast-enhanced MRI was performed in 15 out of 81 patients. MR images were analyzed regarding a hypervascular rim, and the last one was compared with CT images. RESULTS There was no significant difference in density values between different tumor grades. Coefficient of relative enhancement change >1 was observed in 63.64% of highly-differentiated tumors. REC ≤1 was found in 85.11% of tumors grade 2 and 82.6% of tumors grade 3 (p=0.005). According to Chi-square test, there was a correlation between tumor differentiation and hypervascular rim (p=0.03). Moderate and low differentiation was observed in 96.42% of tumors with perifocal enhancement. Hypervascular rim was absent in 81.82% of tumors grade 1. Adenocarcinoma grade 2 was found in 85.71% of cases with unclear perifocal enhancement. CONCLUSION Preoperative contrast-enhanced CT is valuable to assume the tumor grade in patients with pancreatic head adenocarcinoma due to assessment of hypervascular rim and REC.
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Affiliation(s)
- M Yu Shantarevich
- Vishnevsky National Medical Research Center of Surgery, Moscow, Russia
| | - G G Karmazanovsky
- Vishnevsky National Medical Research Center of Surgery, Moscow, Russia.,Pirogov Russian National Research Medical University, Moscow, Russia
| | - A B Egorkina
- Vishnevsky National Medical Research Center of Surgery, Moscow, Russia
| | - A I Kurochkina
- Federal Research Institute for Health Organization and Informatics, Moscow, Russia
| | - A G Kriger
- Vishnevsky National Medical Research Center of Surgery, Moscow, Russia
| | - D V Kalinin
- Vishnevsky National Medical Research Center of Surgery, Moscow, Russia
| | - V I Stashkiv
- Vishnevsky National Medical Research Center of Surgery, Moscow, Russia
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31
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Ferdoushi A, Griffin N, Marsland M, Xu X, Faulkner S, Gao F, Liu H, King SJ, Denham JW, van Helden DF, Jobling P, Jiang CC, Hondermarck H. Tumor innervation and clinical outcome in pancreatic cancer. Sci Rep 2021; 11:7390. [PMID: 33795769 PMCID: PMC8017010 DOI: 10.1038/s41598-021-86831-w] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Accepted: 03/09/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer is a highly aggressive malignancy characterized by poor survival, recurrence after surgery and resistance to therapy. Nerves infiltrate the microenvironment of pancreatic cancers and contribute to tumor progression, however the clinicopathological significance of tumor innervation is unclear. In this study, the presence of nerves and their cross-sectional size were quantified by immunohistochemistry for the neuronal markers S-100, PGP9.5 and GAP-43 in a series of 99 pancreatic cancer cases versus 71 normal adjacent pancreatic tissues. A trend was observed between the presence of nerves in the tumor microenvironment of pancreatic cancer and worse overall patient survival (HR = 1.8, 95% CI 0.77-4.28, p = 0.08). The size of nerves, as measured by cross-sectional area, were significantly higher in pancreatic cancer than in the normal adjacent tissue (p = 0.002) and larger nerves were directly associated with worse patient survival (HR = 0.41, 95% CI 0.19-0.87, p = 0.04). In conclusion, this study suggests that the presence and size of nerves within the pancreatic cancer microenvironment are associated with tumor aggressiveness.
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Affiliation(s)
- Aysha Ferdoushi
- School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, 2308, Australia
- Hunter Medical Research Institute, University of Newcastle, New Lambton, NSW, 2305, Australia
- Department of Biotechnology and Genetic Engineering, Mawlana Bhashani Science and Technology University, Tangail, 1902, Bangladesh
| | - Nathan Griffin
- School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, 2308, Australia
- Hunter Medical Research Institute, University of Newcastle, New Lambton, NSW, 2305, Australia
| | - Mark Marsland
- School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, 2308, Australia
- Hunter Medical Research Institute, University of Newcastle, New Lambton, NSW, 2305, Australia
| | - Xiaoyue Xu
- School of Population Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, 2052, Australia
| | - Sam Faulkner
- School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, 2308, Australia
- Hunter Medical Research Institute, University of Newcastle, New Lambton, NSW, 2305, Australia
| | - Fangfang Gao
- School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, 2308, Australia
- Hunter Medical Research Institute, University of Newcastle, New Lambton, NSW, 2305, Australia
| | - Hui Liu
- Department of Biochemistry and Molecular Biology, School of Laboratory Medicine, Bengbu Medical College, Bengbu, 233030, People's Republic of China
| | - Simon J King
- Hunter Medical Research Institute, University of Newcastle, New Lambton, NSW, 2305, Australia
| | - James W Denham
- Hunter Medical Research Institute, University of Newcastle, New Lambton, NSW, 2305, Australia
- School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, 2308, Australia
| | - Dirk F van Helden
- School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, 2308, Australia
- Hunter Medical Research Institute, University of Newcastle, New Lambton, NSW, 2305, Australia
| | - Phillip Jobling
- School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, 2308, Australia
- Hunter Medical Research Institute, University of Newcastle, New Lambton, NSW, 2305, Australia
| | - Chen Chen Jiang
- Hunter Medical Research Institute, University of Newcastle, New Lambton, NSW, 2305, Australia
- School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, 2308, Australia
| | - Hubert Hondermarck
- School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, 2308, Australia.
- Hunter Medical Research Institute, University of Newcastle, New Lambton, NSW, 2305, Australia.
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Badovinac D, Goričar K, Zavrtanik H, Petrič M, Lavrin T, Mavec N, Dolžan V, Tomažič A, Lenassi M. Plasma Extracellular Vesicle Characteristics Correlate with Tumor Differentiation and Predict Overall Survival in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Surgery with Curative Intent. J Pers Med 2021; 11:77. [PMID: 33525618 PMCID: PMC7910876 DOI: 10.3390/jpm11020077] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 01/15/2021] [Accepted: 01/26/2021] [Indexed: 12/11/2022] Open
Abstract
Better preoperative characterization of patients with pancreatic ductal adenocarcinoma (PDAC) would aid in treatment optimization. Extracellular vesicles (EV) are promising, largely unexplored biomarkers in PDAC. This study aimed to evaluate if plasma EV characteristics are associated with PDAC clinical characteristics and overall survival (OS). The prospective cohort included 34 PDAC patients undergoing surgery with curative intent. Patient data and plasma samples were collected preoperatively, intraoperatively and one month postoperatively. Small plasma EV (sEV) concentration and size were determined by nanoparticle-tracking analysis. A Mann-Whitney test, Spearman's rho and Cox regression were used in statistical analysis. Preoperatively, patients with poorly differentiated tumors had significantly larger plasma sEVs when compared to patients with well/moderately differentiated tumors (mean diameter 176.9 vs. 149.2 nm, p = 0.021), the sEV size even enabling discrimination of the two groups (AUC = 0.742, 95% CI = 0.560-0.923). Plasma sEV characteristics were also a predictor of OS in multivariable analysis. Patients with a more than 33.8% increase in sEV concentration after one month had 7.2 months shorter median OS (p = 0.002), while patients with a more than 28.0% decrease in sEV size had 9.2 months shorter median OS (p = 0.045). Plasma sEV concentration and size correlate with tumor differentiation and may predict OS in PDAC patients. In the future, plasma sEV characteristics could contribute to improved patient stratification for optimized treatment.
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Affiliation(s)
- David Badovinac
- Department of Abdominal Surgery, University Medical Centre Ljubljana, Zaloška 7, 1000 Ljubljana, Slovenia; (D.B.); (H.Z.); (M.P.)
| | - Katja Goričar
- Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia; (K.G.); (T.L.); (N.M.); (V.D.)
| | - Hana Zavrtanik
- Department of Abdominal Surgery, University Medical Centre Ljubljana, Zaloška 7, 1000 Ljubljana, Slovenia; (D.B.); (H.Z.); (M.P.)
| | - Miha Petrič
- Department of Abdominal Surgery, University Medical Centre Ljubljana, Zaloška 7, 1000 Ljubljana, Slovenia; (D.B.); (H.Z.); (M.P.)
| | - Teja Lavrin
- Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia; (K.G.); (T.L.); (N.M.); (V.D.)
| | - Nina Mavec
- Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia; (K.G.); (T.L.); (N.M.); (V.D.)
| | - Vita Dolžan
- Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia; (K.G.); (T.L.); (N.M.); (V.D.)
| | - Aleš Tomažič
- Department of Abdominal Surgery, University Medical Centre Ljubljana, Zaloška 7, 1000 Ljubljana, Slovenia; (D.B.); (H.Z.); (M.P.)
- Department of Surgery, Faculty of Medicine, University of Ljubljana, Zaloška 7, 1000 Ljubljana, Slovenia
| | - Metka Lenassi
- Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia; (K.G.); (T.L.); (N.M.); (V.D.)
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Wang J, Lyu SC, Zhou L, Wang H, Pan F, Jiang T, Lang R, He Q. Prognostic analysis of pancreatic carcinoma with portal system invasion following curative resection. Gland Surg 2021; 10:35-49. [PMID: 33633960 PMCID: PMC7882355 DOI: 10.21037/gs-20-495] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 09/18/2020] [Indexed: 01/08/2023]
Abstract
BACKGROUND To analyze the related factors affecting the prognosis of pancreatic carcinoma with portal system invasion. METHODS We retrospectively analyzed the clinical data of 118 patients with portal venous system invasion in Beijing Chaoyang Hospital between January 2011 and December 2018. Only patients with borderline resectable pancreatic cancer were included in this study. Borderline pancreatic cancer was defined according to NCCN (The National Comprehensive Cancer Network) guidelines. All patients underwent surgical treatment combined with vascular resection and reconstruction. The prognosis was evaluated according to the follow-up results, and the related risk factors for prognosis were analyzed. The survival curve was drawn by Kaplan-Meier method, and the survival rate was compared by log-rank test. Multivariate Cox regression was used to analyze the prognostic factors. RESULTS In our research, all of 126 patients were successfully completed the operations. Complications occurred in 29.7% of patients and perioperative death in 4.0%. A total of 118 patients were followed up and the followed-up rate was 97.5% (118/121). The overall 1-year, 2-year and 3-year survival rates were 49.2%, 27.1% and 19.8%, And the median survival time was 20 months. Multivariate analysis showed that preoperative CA19-9 (RR 1.449, 95% CI: 1.053-1.994), N status (RR 2.533, 95% CI: 1.337-4.798), degree of tumor differentiation (RR 1.592, 95% CI: 1.064-2.381) and venous invasion depth (RR 2.03, 95% CI: 1.504-2.758) were independent risk factors for the prognosis. CONCLUSIONS The long-term prognosis of pancreatic carcinoma patients with portal system invasion is poor. The venous invasion depth is an independent risk factor for the prognosis of pancreatic carcinoma with portal system invasion, the deeper of venous invasion, the worse the prognosis, and poorly differentiated tumors have the worst prognosis. Other independent risk factors included N status and the preoperative CA19-9. Those may help with patients' selection for different treatment protocols.
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Affiliation(s)
- Jing Wang
- Department of Hepatobiliary and Pancreatic Splenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Shao-Cheng Lyu
- Department of Hepatobiliary and Pancreatic Splenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Lin Zhou
- Department of Hepatobiliary and Pancreatic Splenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Han Wang
- Department of Hepatobiliary and Pancreatic Splenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Fei Pan
- Department of Hepatobiliary and Pancreatic Splenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Tao Jiang
- Department of Hepatobiliary and Pancreatic Splenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Ren Lang
- Department of Hepatobiliary and Pancreatic Splenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Qiang He
- Department of Hepatobiliary and Pancreatic Splenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
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34
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Duorui N, Shi B, Zhang T, Chen C, Fang C, Yue Z, Wu P, Wu Z, Huang X, Li M. The contemporary trend in worsening prognosis of pancreatic acinar cell carcinoma: A population-based study. PLoS One 2020; 15:e0243164. [PMID: 33332471 PMCID: PMC7746196 DOI: 10.1371/journal.pone.0243164] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Accepted: 11/14/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Primary acinar cell carcinoma (ACC) is a rare exocrine tumor of the pancreas with unclear clinical characteristics. Our goal was to determine the incidence and update the clinical characteristics and outcomes of ACC. METHODS Through the Surveillance, Epidemiology, and End Results (SEER) database, we identified 252 patients with the latest diagnosis of ACC (2004-2016). The age-adjusted incidence (AAI) was calculated using the SEER*Stat Software version 8.3.6. The Kaplan-Meier method was used to draw survival curves and differences among them were compared by the log-rank test. Cox proportional hazards models were used to evaluate factors that had independent predictive effects on the overall survival. RESULTS The AAI of pancreatic ACC was on the rise with the mean age at diagnosis of 63.79±14.79 years. Most patients (15.9%) had poorer differentiated tumors. The patients presented with distant stage were 54.4% compared with 53.1% between 1988 and 2003. The 1-, 2-, and 5-years survival rates for pancreatic ACC patients were 53.5%, 34.6%,17.5%, respectively (compared with 78.5%, 67.0%, and 42.8%, between 1988 and 2003). The multivariate COX analysis showed that the patient's age, surgery, chemotherapy, and summary stage, but not marital status were independent prognosis factors for ACC. CONCLUSIONS Pancreatic ACC is a highly malignant tumor with an increasing incidence in recent years. The rate of distant metastasis is increasing and the survival rate is worse than in the past, suggesting that it may require more aggressive treatment and follow-up. Surgery, radiotherapy, and chemotherapy are all effective treatments, but prospective studies are still needed to verify them.
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Affiliation(s)
- Nie Duorui
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Bin Shi
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Tao Zhang
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Chuyao Chen
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Chongkai Fang
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Zhijun Yue
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Peng Wu
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Zhiming Wu
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Xuewu Huang
- Cancer center, Guangzhou University of Traditional Chinese Medicine First Affiliated Hospital, Guangzhou, Guangdong, China
| | - Meng Li
- Department of Oncology, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
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35
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Equipping the American Joint Committee on Cancer Staging for Resectable Pancreatic Ductal Adenocarcinoma with Tumor Grade: A Novel Staging System. JOURNAL OF ONCOLOGY 2020; 2020:9093729. [PMID: 33014058 PMCID: PMC7525311 DOI: 10.1155/2020/9093729] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/15/2020] [Revised: 08/29/2020] [Accepted: 09/05/2020] [Indexed: 12/13/2022]
Abstract
Background The 8th American Joint Committee on Cancer (AJCC) staging system for pancreatic ductal adenocarcinoma (PDAC) outperforms its previous version in reproducibility but not in survival discrimination. Tumor grade, an indicator of the aggressive biology of PDAC, has been suggested as a reliable prognostic factor. This study aimed to construct a novel staging system with greater prognostication for resectable PDAC by incorporating tumor grade into the 8th AJCC system. Methods A total of 9966 patients with resectable PDAC from the Surveillance Epidemiology and End Results (SEER) database were randomly separated into training and interval validation sets. Another 324 patients from our center were included as an external validation set. We proposed a novel staging system by sorting the substages yielded by a combination of T, N, and tumor grade based on their overall survival (OS) and grouping them into several stages. Prognostic homogeneity and discrimination were determined using the likelihood ratio χ 2 and the linear trend χ 2 test, respectively. Prognostic accuracies were evaluated by the area under the receiver operating characteristics curve (AUC). Results Using the 8th AJCC system, the prognosis of patients within the same stage was quite heterogeneous among different substages. The multivariate Cox model identified the tumor grade (hazard ratio 1.333, 95% confidence interval 1.250-1.423, p < 0.001) was an independent prognostic factor of the OS. In the training set, the AUC, homogeneity, and discriminatory ability were superior for the novel staging system than for the 8th AJCC system (0.642 vs. 0.615, 403.4 vs. 248.6, and 335.1 vs. 218.0, respectively). Similar results were observed in the internal and external validation sets. Conclusions The novel staging system incorporating tumor grade into the 8th AJCC system was associated with better prognostic accuracy, homogeneity, and discriminatory ability among resectable PDAC patients. Moreover, the novel staging system also allowed possibly adjuvant chemotherapy decisions.
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Malleo G, Maggino L, Nobile S, Casciani F, Cacciatori N, Paiella S, Luchini C, Rusev B, Capelli P, Marchegiani G, Bassi C, Salvia R. Reappraisal of nodal staging and study of lymph node station involvement in distal pancreatectomy for body-tail pancreatic ductal adenocarcinoma. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2020; 46:1734-1741. [PMID: 32327367 DOI: 10.1016/j.ejso.2020.04.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 04/03/2020] [Accepted: 04/08/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND The pattern of nodal spread in body-tail pancreatic ductal adenocarcinoma (PDAC) has been poorly investigated. This study analyzed the characteristics of lymph node (LN) involvement and the prognostic role of nodal metastases stratified by LN stations. METHODS All upfront distal pancreatectomies (DPs) for PDAC (2000-2017) with complete information on station 8,10,11, and 18 were included. Clinico-pathological correlates and survival were investigated using uni- and multivariable analyses. RESULTS Among 100 included patients, 28 were N0, 42 N1 and 30 N2. The median number of examined LN was 32 (IQR 26-44). Tumor size at preoperative imaging increased across N-classes. Preoperative size >27.5 mm was associated with N2 status. The frequency of nodal metastases at stations 8, 9, 10, 11, and 18 was 12.0%, 10.9%, 3.0%, 71.0%, and 19%, respectively. The pattern of LN spread was independent from primary tumor location (with tail tumors metastasizing to station 8/9 and body tumors to station 10), while it was highly associated with N-class. At multivariable analysis, tumor grading, adjuvant treatment, station 9 and 10 metastases were independent prognostic factors in node-positive patients. CONCLUSIONS In patients undergoing upfront DP for PDAC preoperative tumor size is associated with the degree of nodal spread. While station 11 was the most frequently involved, only station-9 and 10 metastases were independent prognostic factors. The site of nodal metastases was somewhat unpredictable based on tumor location. This data has potential implications for allocating patients to neoadjuvant treatment and supports the performance of routine splenectomy during DP for PDAC.
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Affiliation(s)
- Giuseppe Malleo
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy.
| | - Laura Maggino
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Sara Nobile
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Fabio Casciani
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Nicolò Cacciatori
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Salvatore Paiella
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Claudio Luchini
- Department of Pathology and Diagnostics, University of Verona Hospital Trust, Verona, Italy
| | - Borislav Rusev
- ARC-Net Research Center, University of Verona, Verona, Italy
| | - Paola Capelli
- Department of Pathology and Diagnostics, University of Verona Hospital Trust, Verona, Italy
| | - Giovanni Marchegiani
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Claudio Bassi
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
| | - Roberto Salvia
- Unit of General and Pancreatic Surgery, Department of Surgery and Oncology, University of Verona Hospital Trust, Verona, Italy
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Ren H, Wu CR, Aimaiti S, Wang CF. Development and validation of a novel nomogram for predicting the prognosis of patients with resected pancreatic adenocarcinoma. Oncol Lett 2020; 19:4093-4105. [PMID: 32382348 PMCID: PMC7202273 DOI: 10.3892/ol.2020.11495] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Accepted: 03/06/2020] [Indexed: 12/15/2022] Open
Abstract
The survival prediction for patients with resected pancreatic adenocarcinoma by using the Tumor-Node-Metastasis (TNM) staging system remains limited. A nomogram is a efficient tool that can be used to predict the outcome of patients with various types of malignancy. The present study aimed to develop and validate a nomogram for patients with resected pancreatic adenocarcinoma. A total of 368 patients (258 in the training set and 110 in the validation set) who underwent pancreatic adenocarcinoma resection at the China National Cancer Center between January 2008 and October 2018 were included in the present study. The nomogram was established according to the results from Cox multivariate analysis, which was validated by discrimination and calibration. The area under the receiver operating characteristic curve (AUC) was determined to assess the accuracy of survival predictions. The results from multivariate analysis in the training set demonstrated that blood transfusion, T-stage, N-stage, tumor grade, capsule invasion, carbohydrate antigen 199, neutrophil percentage and adjuvant therapy were independent prognostic factors for overall survival (OS; all P<0.05). Subsequently, a nomogram predicting the 1-year, 3-year and 5-year OS rates, with favorable calibration, was established based on the independent prognostic factors. The concordance indices of the nomogram were higher compared with the TNM staging system in both training and validation sets. Furthermore, a clear risk stratification system based on the nomogram was used to classify patients into the three following groups: Low-risk group (≤168), moderate-risk group (168–255) and high-risk group (>255). The risk stratification system demonstrated an improved ability in predicting the 1-year, 3-year and 5-year OS rates compared with the TNM system (AUC, 0.758, 0.709 and 0.672 vs. AUC, 0.614, 0.604 and 0.568; all P<0.05). The present study developed and validated a nomogram for patients with resected pancreatic adenocarcinoma by including additional independent prognostic factors, including tumor marker, immune index, surgical information, pathological data and adjuvant therapy. Taken together, the results from the present study indicated an improved performance of the nomogram in predicting the prognosis of patients with resected pancreatic adenocarcinoma compared with the TNM staging system.
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Affiliation(s)
- Hu Ren
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Chao-Rui Wu
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Saderbieke Aimaiti
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Cheng-Feng Wang
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
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Wang H, Liu J, Xia G, Lei S, Huang X, Huang X. Survival of pancreatic cancer patients is negatively correlated with age at diagnosis: a population-based retrospective study. Sci Rep 2020; 10:7048. [PMID: 32341400 PMCID: PMC7184604 DOI: 10.1038/s41598-020-64068-3] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Accepted: 03/18/2020] [Indexed: 12/18/2022] Open
Abstract
In this population-based retrospective study, we aimed to investigate the association between age at diagnosis and prognosis of pancreatic cancer (PC) patients using data from the National Cancer Institute's Surveillance, Epidemiology, and the End Results database. Different factors for stratification, like race, sex, year of diagnosis, pathological grade, American Joint Committee on Cancer stage, historic stage, and tumour location, were included to compare the survival rates of patients of different age groups, and the five-year survival rate was calculated. Multivariate analysis using Cox regression was performed to control for confounder bias, and the hazard ratio was calculated. In total, 126,066 patients were enrolled in this study. The five-year PC-specific survival of patients aged 20-40 years was almost three times that of patients aged >40 years. Stratified by race, sex, year of diagnosis, pathological grade, clinical stage, and tumour location, a descending trend of survival was observed with an increase in age. On multivariate analysis, the mortality risk of PC patients aged 40-80 years was twice that of patients aged <40 years; however, patients aged >80 years had a mortality risk three times that of patients aged <40 years. The survival rate of PC patients has improved in the last few decades. Age at diagnosis is a significant and negative prognostic factor for PC, and patients diagnosed at a relatively earlier stage had the best survival.
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Affiliation(s)
- Hongcheng Wang
- Department of General Surgery, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Jiazhe Liu
- Department of Hepatobiliary and Pancreatic Surgery, Minhang Branch, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Guanggai Xia
- Department of General Surgery, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Shizhou Lei
- Department of General Surgery, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Xiuyan Huang
- Department of General Surgery, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
| | - Xinyu Huang
- Department of General Surgery, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
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Chang N, Cui L, Luo Y, Chang Z, Yu B, Liu Z. Development and multicenter validation of a CT-based radiomics signature for discriminating histological grades of pancreatic ductal adenocarcinoma. Quant Imaging Med Surg 2020; 10:692-702. [PMID: 32269929 DOI: 10.21037/qims.2020.02.21] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Background The histological grade of pancreatic cancer is an important independent predictor of outcome. However, we lack a method for safely and accurately obtaining the pathological grade before surgery. Radiomics has been used to discriminate between histological grades in tumors. We aimed to develop and validate a radiomics signature for the preoperative prediction of histological grades of pancreatic ductal adenocarcinoma (PDAC) that was based on contrast-enhanced computed tomography (CE-CT). Methods This study comprised 301 patients with pathologically confirmed PDAC who were randomly divided into a training (n=151) and test group (n=150). Radiomics features were selected by a support vector machine (SVM) model, and a radiomics signature was generated by the least absolute shrinkage and selection operator (LASSO) model. An additional 100 patients from 2 other medical centers were used for external validation. Receiver operating characteristic (ROC) curve analysis was used to assess the model and to identify the optimal cutoff value. Results The radiomics signatures between high-grade and low-grade PDACs in the training and test groups were significantly different (P<0.05). The areas under the curve (AUCs) of the training and test datasets were 0.961 and 0.910, respectively. The optimal cutoff value of the radiomics score was 0.426. In the external validation dataset, the difference between the radiomics signatures of high-grade versus low-grade PDACs was also significant (P<0.05). The radiomics signature for the external validation data had an AUC of 0.770. Conclusions The CE-CT-based radiomics signature showed moderate predictive accuracy for differentiating low-grade from high-grade PDAC and should become a new noninvasive method for the preoperative prediction of histological grades of PDAC.
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Affiliation(s)
- Na Chang
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Lingling Cui
- Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang 110001, China
| | - Yahong Luo
- Department of Radiology, Liaoning Cancer Institute and Hospital, Shenyang 110000, China
| | - Zhihui Chang
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Bing Yu
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Zhaoyu Liu
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, China
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Zhai S, Huo Z, Ying X, Jin J, Wang Y, Lu X, Deng X. A Nomogram for Individual Prediction of Poor Prognosis After Radical Surgery in Patients with Primary Pancreatic Duct Adenocarcinoma. Med Sci Monit 2020; 26:e918882. [PMID: 32088726 PMCID: PMC7051101 DOI: 10.12659/msm.918882] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Background Pancreatic cancer is a highly malignant tumor characterized by poor prognosis. TNM stage cannot always provide accurate prediction of prognosis, which is vital for individualized treatment. Therefore, a novel way to identify patients with poor prognosis after radical surgery is urgently needed. Material/Methods The nomogram was established based on a discovery cohort that included 554 patients with PDAC who had received radical surgery from 2012 to 2016. The clinicopathological data were collected. Poor prognosis was evaluated using 25 features, in which appropriate features for a prediction model were identified. A prediction model incorporating the selected features was established. The discriminative capacity was assessed by C-index, calibration by calibration plot, and clinical usefulness by decision curve. The bootstrapping approach was used to perform internal validation. Results Characteristics included in the nomogram were coronary artery disease and stroke history, elevated CA125, AJCC stage >II, R0 resection, operating time >6 h, poor differentiation, nerve invasion, length of stay >30 days, and postoperative complications. A C-index of 0.713 indicated good discrimination of the prediction model, and the calibration curve showed acceptable calibration. Survival analysis showed that this model had better discriminative capacity than the AJCC staging system and could distinguish relatively good prognosis from poor prognosis in patients at stage II (especially IIa) and IV. Conclusions Our study presents a valid and practical model to predict prognosis of pancreatic cancer patients, which contributes to individualized therapy by assisting surgeons to predict poor prognosis in patients who received radical surgery.
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Affiliation(s)
- Shuyu Zhai
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (mainland)
| | - Zhen Huo
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (mainland)
| | - Xiayang Ying
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (mainland)
| | - Jiabin Jin
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (mainland)
| | - Yue Wang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (mainland)
| | - Xiongxiong Lu
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (mainland)
| | - Xiaxing Deng
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (mainland)
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The Systemic-immune-inflammation Index Independently Predicts Survival and Recurrence in Resectable Pancreatic Cancer and its Prognostic Value Depends on Bilirubin Levels: A Retrospective Multicenter Cohort Study. Ann Surg 2020; 270:139-146. [PMID: 29334554 DOI: 10.1097/sla.0000000000002660] [Citation(s) in RCA: 195] [Impact Index Per Article: 39.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Our aim was to determine the prognostic significance of the systemic-immune-inflammation index (SIII) in patients with resectable pancreatic cancer, using cancer-specific survival as the primary outcome. BACKGROUND Pancreatic cancer is associated with a dysfunctional immune system and poor prognosis. We examined the prognostic significance of the SIII in patients with resectable pancreatic ductal adenocarcinoma (PDAC) and the effects of bilirubin on this index. METHODS We retrospectively assessed all pancreatic resections performed between 2004 and 2015 at 4 tertiary referral centers to identify pathologically confirmed PDAC patients. Baseline clinicopathologic characteristics, preoperative laboratory values such as absolute neutrophil, lymphocyte, and platelet counts, C-reactive protein, albumin, bilirubin, and CA19-9 levels, and also follow-up information, were collected. The associations of the calculated inflammatory indices with outcome were both internally and externally validated. RESULTS In all, 590 patients with resectable PDAC were included. The discovery and validation cohort included 170 and 420 patients, respectively. SIII >900 [hazard ratio (HR) 2.32, 95% confidence interval (CI) 1.55-3.48], lymph node ratio (HR 3.75, 95% CI 2.08-6.76), and CA19.9 >200 kU/L (HR 1.62, 95% CI 1.07-2.46) were identified as independent predictors of cancer-specific survival. Separate model analysis confirmed that preoperative SIII contributed significantly to prognostication. However, SIII appeared to lose its prognostic significance in patients with bilirubin levels above 200 μmol/L. CONCLUSIONS SIII is an independent predictor of cancer-specific survival and recurrence in patients with resectable PDAC. SIII may lose its prognostic significance in patients with high bilirubin levels. Properly designed prospective studies are needed to further confirm this hypothesis.
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Comparison of Tumor Regression Grading of Residual Pancreatic Ductal Adenocarcinoma Following Neoadjuvant Chemotherapy Without Radiation: Would Fewer Tier-Stratification Be Favorable Toward Standardization? Am J Surg Pathol 2020; 43:334-340. [PMID: 30211728 DOI: 10.1097/pas.0000000000001152] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
To assess whether the College of American Pathologists (CAP) and the Evans grading systems for neoadjuvant chemotherapy without radiation-treated pancreatectomy specimens are prognostic, and if a 3-tier stratification scheme preserves data granularity. Conducted retrospective review of 32 patients with ordinary pancreatic ductal adenocarcinoma treated with neoadjuvant therapy without radiation followed by surgical resection. Final pathologic tumor category (AJCC eighth edition) was 46.9% ypT1, 34.4% ypT2, and 18.7% ypT3. Median follow-up time was 29.8 months, median disease-free survival (DFS) was 19.6 months, and median overall survival (OS) was 34.2 months. CAP score 1, 2, 3 were present in 5 (15.6%), 18 (56.3%), and 9 (28.1%) patients, respectively. Evans grade III, IIb, IIa, and I were present in 10 (31.2%), 8 (25.0%), 7 (21.9%), and 7 (21.9%) patients, respectively. OS (CAP: P=0.005; Evans: P=0.001) and DFS (CAP: P=0.003; Evans: P=0.04) were statistically significant for both CAP and Evans. Stratified CAP scores 1 and 2 versus CAP score 3 was statistically significant for both OS (P=0.002) and DFS (P=0.002). Stratified Evans grades I, IIa, and IIb versus Evans grade III was statistically significant for both OS (P=0.04) and DFS (P=0.02). CAP, Evans, and 3-tier stratification are prognostic of OS and DFS.
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Mukherjee L, Bui HD, Keikhosravi A, Loeffler A, Eliceiri KW. Super-resolution recurrent convolutional neural networks for learning with multi-resolution whole slide images. JOURNAL OF BIOMEDICAL OPTICS 2019; 24:1-15. [PMID: 31837128 PMCID: PMC6910074 DOI: 10.1117/1.jbo.24.12.126003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Accepted: 11/20/2019] [Indexed: 06/10/2023]
Abstract
We study a problem scenario of super-resolution (SR) algorithms in the context of whole slide imaging (WSI), a popular imaging modality in digital pathology. Instead of just one pair of high- and low-resolution images, which is typically the setup in which SR algorithms are designed, we are given multiple intermediate resolutions of the same image as well. The question remains how to best utilize such data to make the transformation learning problem inherent to SR more tractable and address the unique challenges that arises in this biomedical application. We propose a recurrent convolutional neural network model, to generate SR images from such multi-resolution WSI datasets. Specifically, we show that having such intermediate resolutions is highly effective in making the learning problem easily trainable and address large resolution difference in the low and high-resolution images common in WSI, even without the availability of a large size training data. Experimental results show state-of-the-art performance on three WSI histopathology cancer datasets, across a number of metrics.
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Affiliation(s)
- Lopamudra Mukherjee
- University of Wisconsin–Whitewater, Department of Computer Science, Whitewater, Wisconsin, United States
| | - Huu Dat Bui
- University of Wisconsin–Whitewater, Department of Computer Science, Whitewater, Wisconsin, United States
| | - Adib Keikhosravi
- University of Wisconsin–Madison, Department of Biomedical Engineering, Madison, Wisconsin, United States
| | - Agnes Loeffler
- MetroHealth Medical Center, Department of Pathology, Cleveland, Ohio, United States
| | - Kevin W. Eliceiri
- University of Wisconsin–Madison, Department of Biomedical Engineering, Madison, Wisconsin, United States
- Morgridge Institute for Research, Madison, Wisconsin, United States
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Kuraishi Y, Uehara T, Kobayashi Y, Nakajima T, Watanabe T, Shimizu A, Ota H, Tanaka E. Correlation of clinicopathological features and leucine-rich repeat-containing G-protein-coupled receptor 5 expression in pancreatic ductal adenocarcinoma. Pathol Res Pract 2019; 215:152623. [PMID: 31543221 DOI: 10.1016/j.prp.2019.152623] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2019] [Revised: 08/25/2019] [Accepted: 09/05/2019] [Indexed: 12/13/2022]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer. Previous studies have established leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) as a cancer stem cell marker in gastrointestinal cancers. However, few reports have examined LGR5 in PDAC. Here we examined LGR5 expression and its clinicopathological significance in PDAC. We evaluated LGR5 expression in 78 PDAC patients who underwent surgical resection in our institution using RNAscope, a newly described RNA in situ hybridization technique. All 78 PDAC cases expressed LGR5 in cancer tissues, and LGR5 expression was prominent in the gland-forming part. LGR5 expression was significantly higher in patients with low histological grade (G1-G2) (p < 0.001) and early clinical stage (p = 0.004). Univariate analysis showed that low LGR5 expression (p = 0.034) was significantly associated with worse overall survival. However, LGR5 expression did not remain a predictor of prognosis in multivariate analysis (p = 0.639). All PDAC cases showed LGR5 expression to varying degrees, indicating LGR5 might be a cancer stem cell marker of PDAC, as in gastrointestinal cancer. Reduced LGR5 expression in tumor cells was associated with worse prognosis in PDAC. Further studies are required to elucidate the relationship between tumor progression and LGR5 expression in PDAC.
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Affiliation(s)
- Yasuhiro Kuraishi
- Department of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Takeshi Uehara
- Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
| | - Yukihiro Kobayashi
- Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan
| | - Tomoyuki Nakajima
- Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan
| | - Takayuki Watanabe
- Department of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Akira Shimizu
- Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Hiroyoshi Ota
- Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan; Department of Biomedical Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan
| | - Eiji Tanaka
- Department of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan
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Abstract
The aim of this study was to evaluate outcomes of patients with resectable pancreatic adenocarcinoma (PDAC) who underwent neoadjuvant chemotherapy. The MEDLINE and PubMed databases were searched to identify relevant original articles investigating neoadjuvant therapy in resectable PDAC. Qualitative analyses were performed to investigate patient selection, disease stage, impact on perioperative outcomes, and cost-effectiveness. Forty-three studies met inclusion criteria for this review. Neoadjuvant chemotherapy for upfront resectable PDAC is cost-effective, safe, may result in lower stage disease and has potential survival advantages. With proper patient selection, neoadjuvant chemotherapy is an appropriate approach for upfront resectable PDAC. Nevertheless, the risk for disease progression and losing a curative surgical window highlights the need for appropriate patient identification, further discovery of superior biomarkers or molecular profiles representative of positive treatment response, and additional prospective comparative study.
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Larson BK, Guan M, Placencio V, Tuli R, Hendifar AE. Stromal hyaluronan accumulation is associated with low tumor grade and nodal metastases in pancreatic ductal adenocarcinoma. Hum Pathol 2019; 90:37-44. [PMID: 31121193 DOI: 10.1016/j.humpath.2019.05.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Revised: 05/08/2019] [Accepted: 05/08/2019] [Indexed: 12/18/2022]
Abstract
Pancreatic ductal adenocarcinoma is an aggressive malignancy characterized by abundant desmoplastic stroma. Hyaluronan is a prominent stromal component of pancreatic ductal adenocarcinoma and is associated with unique clinical-pathological profiles in other tumor types. The current study aimed to delineate clinical and pathological features associated with hyaluronan accumulation in pancreatic ductal adenocarcinoma using a novel hyaluronan-binding assay currently being used in a clinical trial targeting hyaluronan. Sixty-four formalin-fixed, paraffin-embedded samples of pancreatic ductal adenocarcinomas from 49 patients treated at a single tertiary care hospital were stained. Fifty-two percent of tumors had high levels of hyaluronan. High levels were associated with low tumor grade and lymph node metastases, novel associations not previously seen in pancreatic ductal adenocarcinoma. This study has elucidated a novel clinical-pathological profile in pancreatic ductal adenocarcinomas using a new assay, suggesting hyaluronan may act as a biomarker for a subset of pancreatic tumors that could be targeted by hyaluronan-degrading agents.
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Affiliation(s)
- Brent K Larson
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048
| | - Michelle Guan
- Division of Hematology and Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048
| | - Veronica Placencio
- Division of Hematology and Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048
| | - Richard Tuli
- Department of Radiation Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048
| | - Andrew E Hendifar
- Division of Hematology and Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048.
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47
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Lu J, Zhou L, Yang G, Liang ZY, Zhou WX, You L, Yuan D, Li BQ, Guo JC, Zhao YP. Clinicopathological and prognostic significance of MKK4 and MKK7 in resectable pancreatic ductal adenocarcinoma. Hum Pathol 2019; 86:143-154. [DOI: 10.1016/j.humpath.2018.11.026] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Revised: 11/19/2018] [Accepted: 11/30/2018] [Indexed: 01/14/2023]
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Ma SJ, Hermann GM, Prezzano KM, Serra LM, Iovoli AJ, Singh AK. Adjuvant chemotherapy followed by concurrent chemoradiation is associated with improved survival for resected stage I-II pancreatic cancer. Cancer Med 2019; 8:939-952. [PMID: 30652417 PMCID: PMC6434497 DOI: 10.1002/cam4.1967] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Revised: 12/12/2018] [Accepted: 12/18/2018] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND This National Cancer Database (NCDB) analysis evaluates the clinical outcomes of postoperative chemotherapy followed by concurrent chemoradiation (C + CRT) compared to concurrent chemoradiation (CRT) alone or adjuvant chemotherapy alone (C) for resected pancreatic cancer. METHODS The NCDB was queried for primary stage I-II, cT1-3N0-1M0, resected pancreatic adenocarcinoma treated with adjuvant C, CRT, or C + CRT (2004-2015). Patients treated with C + CRT were compared with those treated with C (cohort C) and CRT (cohort CRT). Baseline patient, tumor, and treatment characteristics were examined. Kaplan-Meier analysis, multivariable Cox proportional hazards method, forest plot, and propensity score matching were used. RESULTS Among 5667 patients, median follow-up was 34.7, 45.2, and 39.7 months for the C, CRT, and C + CRT cohorts, respectively. By multivariable analysis for all patients, C and CRT had worse OS compared to C + CRT. Treatment interactions were seen among pathologically node-positive disease. C + CRT was favored in 1-3 and 4+ positive lymph node diseases when compared to C or CRT alone, but none of the treatment options were significantly favored in node negative disease. Using propensity score matching, 2152 patients for cohort C and 1774 patients for cohort CRT were matched. C + CRT remained significant for improved OS for both cohort C (median OS 23.3 vs 20.0 months) and cohort CRT (median OS 23.4 vs 20.8 months). CONCLUSION This NCDB study using propensity score matched analysis suggests an OS benefit for C + CRT compared to C or CRT alone following surgical resection of pancreatic cancer, particularly for patients with pathologically positive lymph nodes.
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Affiliation(s)
- Sung Jun Ma
- Department of Radiation MedicineRoswell Park Comprehensive Cancer CenterBuffaloNew York
| | - Gregory M. Hermann
- Department of Radiation MedicineRoswell Park Comprehensive Cancer CenterBuffaloNew York
| | - Kavitha M. Prezzano
- Department of Radiation MedicineRoswell Park Comprehensive Cancer CenterBuffaloNew York
| | - Lucas M. Serra
- Jacobs School of Medicine and Biomedical SciencesUniversity at Buffalo, The State University of New YorkBuffaloNew York
| | - Austin J. Iovoli
- Jacobs School of Medicine and Biomedical SciencesUniversity at Buffalo, The State University of New YorkBuffaloNew York
| | - Anurag K. Singh
- Department of Radiation MedicineRoswell Park Comprehensive Cancer CenterBuffaloNew York
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Lee JH, Woo SM, Hong EK, Park SJ, Han SS, Kim TH, Lee JH, Lee WJ. Cytopathological results of initial endoscopic ultrasound-guided fine needle aspiration for primary mass and prognosis in pancreatic cancer patients. Cytopathology 2018; 30:173-178. [PMID: 30570774 DOI: 10.1111/cyt.12675] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Revised: 11/20/2018] [Accepted: 12/02/2018] [Indexed: 01/24/2023]
Abstract
OBJECTIVES Clinical outcomes remain unclear in patients suspected of having pancreatic cancer with indeterminate endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) results. This work aimed to investigate the prognosis of pancreatic cancer patients with indeterminate findings at initial EUS-FNA. METHODS Findings in all patients who underwent EUS-FNA for suspected pancreatic cancer between 2008 and 2015 at the National Cancer Center, Korea, were retrospectively reviewed. A final diagnosis of pancreatic ductal adenocarcinoma was based on pathology reports. RESULTS Of the 144 patients evaluated, 113 (78%) were diagnosed as being positive/suspicious for malignancy on cytological evaluation and 31 (22%) as having atypia/negative/non-diagnostic findings at initial EUS-FNA but subsequently diagnosed with pancreatic ductal adenocarcinoma. Tumour size, clinical stage and treatment modalities did not differ significantly between these two groups. Median overall survival was significantly shorter in patients diagnosed (11.3 ± 0.74 months; 95% confidence interval [CI], 9.4-12.8 months) than non-diagnosed (16.9 ± 2.34 months; 95% CI, 12.0-17.4 months) on initial EUS-FNA (P = .024). Multivariate Cox regression analysis showed that a non-diagnosis on initial EUS-FNA was independently associated with better overall survival (hazard ratio, 0.58; 95% CI, 0.38-0.88; P = .011). CONCLUSIONS Non-diagnostic results on initial EUS-FNA of a primary mass may be associated with better prognosis in patients with pancreatic cancer.
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Affiliation(s)
- Jung Hwan Lee
- Center for Liver Cancer, National Cancer Center, Goyang-si, Gyeonggi-do, Korea
| | - Sang Myung Woo
- Center for Liver Cancer, National Cancer Center, Goyang-si, Gyeonggi-do, Korea
| | - Eun Kyung Hong
- Center for Liver Cancer, National Cancer Center, Goyang-si, Gyeonggi-do, Korea
| | - Sang-Jae Park
- Center for Liver Cancer, National Cancer Center, Goyang-si, Gyeonggi-do, Korea
| | - Sung-Sik Han
- Center for Liver Cancer, National Cancer Center, Goyang-si, Gyeonggi-do, Korea
| | - Tae Hyun Kim
- Center for Liver Cancer, National Cancer Center, Goyang-si, Gyeonggi-do, Korea
| | - Ju Hee Lee
- Center for Liver Cancer, National Cancer Center, Goyang-si, Gyeonggi-do, Korea
| | - Woo Jin Lee
- Center for Liver Cancer, National Cancer Center, Goyang-si, Gyeonggi-do, Korea
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50
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Muralidhar V, Nipp RD, Mamon HJ, Punglia RS, Hong TS, Ferrone C, Fernandez-Del Castillo C, Parikh A, Nguyen PL, Wo JY. Association Between Very Small Tumor Size and Decreased Overall Survival in Node-Positive Pancreatic Cancer. Ann Surg Oncol 2018; 25:4027-4034. [PMID: 30298331 DOI: 10.1245/s10434-018-6832-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND In pancreatic adenocarcinoma (PDAC), increasing tumor size usually correlates with a worse prognosis. However, patients with a very small primary tumor who experience lymph node involvement may have a different disease biology. This study sought to determine the interaction between tumor size and lymph node involvement in terms of overall survival (OS). METHODS The study identified 17,073 patients with a diagnosis of M0 resected PDAC between 1983 and 2013 using the Surveillance, Epidemiology, and End Results database. The patients were stratified by lymph node involvement (N0 vs N+) and T stage (T1a-T1b vs T1c vs T2 vs T3 vs T4). The Kaplan-Meier method was used to estimate OS, and Cox regression analysis was used to compare survival between subgroups after adjustment for patient-specific factors. RESULTS Lymph node involvement and T stage significantly interacted (p < 0.001). Among the patients with node-negative disease, 5-year OS decreased monotonically with increasing T stage (59.1%, 30.6%, 22.9%, 16.6%, and 8.0%, respectively; p < 0.001). In contrast, among the patients with node-positive disease, those with T1a-T1b tumors (< 10 mm) had worse 5-year OS than those with T1c tumors (7.4% vs 17.6%; adjusted hazard ratio, 0.70; 95% confidence interval, 0.50-0.97; p = 0.034) and similar survival compared with those who had T2, T3, or T4 tumors (9.7%, 8.2%, and 4.8%, respectively; p > 0.2 in all cases). CONCLUSIONS Among patients with lymph node-positive PDAC, very small primary tumors are associated with decreased OS. This finding raises the possibility that small tumors capable of lymph node metastasis might represent more biologically aggressive cancers.
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Affiliation(s)
| | - Ryan D Nipp
- Department of Medical Oncology, Massachusetts General Hospital, Boston, MA, USA
| | - Harvey J Mamon
- Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA, USA
| | - Rinaa S Punglia
- Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA, USA
| | - Theodore S Hong
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA
| | - Cristina Ferrone
- Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
| | | | - Aparna Parikh
- Department of Medical Oncology, Massachusetts General Hospital, Boston, MA, USA
| | - Paul L Nguyen
- Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA, USA
| | - Jennifer Y Wo
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA.
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