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Teja M, Garrido MI, Ocanto A, Couñago F. Prognostic impact of inflammatory and nutritional biomarkers in pancreatic cancer. World J Clin Oncol 2025; 16:101191. [PMID: 39867733 PMCID: PMC11528899 DOI: 10.5306/wjco.v16.i1.101191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 09/28/2024] [Accepted: 10/10/2024] [Indexed: 10/30/2024] Open
Abstract
Pancreatic cancer is usually associated with a poor prognosis. Surgery is the main curative treatment but pancreatic operations are aggressive and new tools that help clinicians to predict surgical and prognostic outcomes are necessary. Lu et al recently published a retrospective, single centre cohort study evaluating the impact of seven nutritional and inflammatory markers in pancreatic cancer surgical patients: The albumin-to-globulin ratio, prognostic nutritional index (PNI), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), nutritional risk index, and the geriatric nutritional risk index. A significant correlation was found between the PNI, SII, NLR, and PLR and a hospital discharge of less than 15 days. In a univariable analysis, PNI, SII, NLR and PLR were significantly related to recurrence-free survival and, in a multivariable analysis PNI was associated with overall survival. Various meta-analyses corroborate the results in terms of prognosis but individual studies are discordant on their usefulness. Besides, the cut-off values for these markers vary significantly between studies and there are no clinical trials comparing them to identify the most relevant ones. These are limitations when implementing nutritional and inflammatory biomarkers into clinical practice and further studies are needed in order to answer these questions.
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Affiliation(s)
- Macarena Teja
- Department of Radiation Oncology, GenesisCare-San Francisco de Asís University Hospital, Madrid 28002, Spain
- Department of Radiation Oncology, GenesisCare-Vithas La Milagrosa University Hospital, Madrid 28010, Spain
| | - María I Garrido
- Department of Radiation Oncology, GenesisCare-San Francisco de Asís University Hospital, Madrid 28002, Spain
- Department of Radiation Oncology, GenesisCare-Vithas La Milagrosa University Hospital, Madrid 28010, Spain
| | - Abrahams Ocanto
- Department of Radiation Oncology, GenesisCare-San Francisco de Asís University Hospital, Madrid 28002, Spain
- Department of Radiation Oncology, GenesisCare-Vithas La Milagrosa University Hospital, Madrid 28010, Spain
| | - Felipe Couñago
- Department of Radiation Oncology, GenesisCare-San Francisco de Asís University Hospital, Madrid 28002, Spain
- Department of Radiation Oncology, GenesisCare-Vithas La Milagrosa University Hospital, Madrid 28010, Spain
- National Director, GenesisCare Spain, Madrid 28043, Spain
- Department of Medicine, School of Medicine, Health and Sport, European University of Madrid, Madrid 28670, Spain
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Matsumoto M, Shirai Y, Tsunematsu M, Okui N, Gocho T, Onda S, Furukawa K, Haruki K, Uwagawa T, Ikegami T. Changes in Skeletal Muscle Volume During Preoperative Chemotherapy Affect the Outcome of Pancreatic Cancer. Am Surg 2025; 91:115-125. [PMID: 39180397 DOI: 10.1177/00031348241278021] [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: 08/26/2024]
Abstract
BACKGROUND This study aimed to investigate the effects of changes in clinicopathological factors during preoperative chemotherapy for pancreatic cancer, including skeletal muscle volume, on recurrence and prognosis after pancreatectomy. METHODS Data from 41 patients who underwent resection for pancreatic cancer after preoperative chemotherapy from 2012 to 2021 were retrospectively reviewed. Skeletal muscle volume was substituted for the psoas muscle area (PMA) at the level of the third lumbar vertebra. We investigated the relationship of clinicopathological factors during preoperative chemotherapy with disease-free survival (DFS) and overall survival (OS). The association between clinicopathological factors and a decrease in PMA was investigated. RESULTS In the multivariate analyses for DFS and OS, the factors associated with recurrence were as follows: decrease in PMA (P = 0.003) and the absence of adjuvant therapy (P = 0.03), and the factors associated with poor prognosis were as follows: decrease in PMA (P = 0.04) and the absence of adjuvant therapy (P = 0.008), and the resectability of borderline resectable and unresectable-locally advanced tumors (P = 0.033). All patients with partial response according to the Response Evaluation Criteria in Solid Tumors (version 1.1) had no decrease in PMA (P = 0.01). The proportion of patients with Evans classification ≥ II was significantly higher in the group without a decrease in PMA (P = 0.02). The proportion of patients with an average relative dose intensity of adjuvant therapy ≥0.6 was significantly higher in the group without a decrease in PMA (P = 0.02). CONCLUSION Changes in preoperative skeletal muscle volume during preoperative chemotherapy for pancreatic cancer is a potential predictor of recurrence and prognosis after pancreatectomy.
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Affiliation(s)
- Michinori Matsumoto
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Japan
| | - Yoshihiro Shirai
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Japan
| | - Masashi Tsunematsu
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Japan
| | - Norimitsu Okui
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Japan
| | - Takeshi Gocho
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Japan
| | - Shinji Onda
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Japan
| | - Kenei Furukawa
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Japan
| | - Koichiro Haruki
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Japan
| | - Tadashi Uwagawa
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Japan
| | - Toru Ikegami
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Japan
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Matsumoto M, Uwagawa T, Shirai Y, Tsunematsu M, Furukawa K, Haruki K, Okui N, Okazaki K, Ishizaki S, Ikegami T. Impact of Preoperative Osteosarcopenia and Postoperative Administration of Pancrelipase on the Prognosis of Borderline Resectable and Unresectable Locally Advanced Pancreatic Cancer. Am Surg 2025; 91:65-75. [PMID: 39108198 DOI: 10.1177/00031348241272420] [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] [Indexed: 12/13/2024]
Abstract
BACKGROUND This study aimed to identify postoperative recurrence and prognostic factors, including osteosarcopenia for borderline resectable (BR) and unresectable locally advanced (UR-LA) pancreatic cancer and to examine the impact of postoperative pancreatic enzyme replacement therapy (PERT). METHODS We retrospectively examined 32 resected patients with BR and UR-LA pancreatic cancer. We investigated independent factors in the disease-free survival and overall survival. The relation of osteosarcopenia with the clinicopathological factors was investigated. Additionally, the association of the administration of a standard dose of pancrelipase, the amount of lipase required for patients with pancreatic exocrine insufficiency, for ≥6 months postoperatively with improvement of sarcopenia, osteopenia, and osteosarcopenia and completion rate of adjuvant chemotherapy was investigated. RESULTS Multivariate analyses identified osteosarcopenia (P = 0.049) and lymph node metastasis (P = 0.01) as independent recurrence predictors, and osteosarcopenia (P = 0.002), maximum tumor diameter ≥40 mm (P = 0.006), and no adjuvant therapy (P = 0.01) as independent prognostic predictors. In the osteosarcopenia group, serum CA19-9 levels were higher (P = 0.03). The administration of a standard dose of pancrelipase for ≥6 months postoperatively was none in the osteosarcopenia group (0% vs 42.9%, P = 0.01), while significantly improved postoperative sarcopenia (33% vs 0%, P = 0.004), increased number of cycles of adjuvant chemotherapy (n = 6 vs n = 3, P = 0.03), and the completion rate of adjuvant chemotherapy in excluding cases interrupted because of recurrence (86% vs 25%, P = 0.007). CONCLUSIONS Osteosarcopenia was an independent recurrent and prognostic factor in patients after pancreatectomy for locally advanced pancreatic cancer. Appropriate postoperative PERT may contribute to a better prognosis by improving sarcopenia and increasing the completion rate of adjuvant chemotherapy.
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Affiliation(s)
- Michinori Matsumoto
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Japan
| | - Tadashi Uwagawa
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Japan
| | - Yoshihiro Shirai
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Japan
| | - Masashi Tsunematsu
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Japan
| | - Kenei Furukawa
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Japan
| | - Koichiro Haruki
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Japan
| | - Norimitsu Okui
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Japan
| | - Kohei Okazaki
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Japan
| | - Shunta Ishizaki
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Japan
| | - Toru Ikegami
- Department of Surgery, The Jikei University School of Medicine, Minato-ku, Japan
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Zhang YY, Liu FH, Wang YL, Liu JX, Wu L, Qin Y, Zheng WR, Xing WY, Xu J, Chen X, Xu HL, Bao Q, Wang JY, Wang R, Chen XY, Wei YF, Zou BJ, Liu JC, Yin JL, Jia MQ, Gao S, Luan M, Wang HH, Gong TT, Wu QJ. Associations between peripheral whole blood cell counts derived indexes and cancer prognosis: An umbrella review of meta-analyses of cohort studies. Crit Rev Oncol Hematol 2024; 204:104525. [PMID: 39370059 DOI: 10.1016/j.critrevonc.2024.104525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 09/15/2024] [Accepted: 09/24/2024] [Indexed: 10/08/2024] Open
Abstract
Meta-analyses have reported conflicting data on the whole blood cell count (WBCC) derived indexes (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], and lymphocyte-to-monocyte ratio [LMR]) and cancer prognosis. However, the strength and quality of this evidence has not been quantified in aggregate. To grade the evidence from published meta-analyses of cohort studies that investigated the associations between NLR, PLR, and LMR and cancer prognosis. A total of 694 associations from 224 articles were included. And 219 (97.8%) articles rated as moderate-to-high quality according to AMSTAR. There were four associations supported by convincing evidence. Meanwhile, 165 and 164 associations were supported by highly suggestive and suggestive evidence, respectively. In this umbrella review, we summarized the existing evidence on the WBCC-derived indexes and cancer prognosis. Due to the direction of effect sizes is not completely consistent between studies, further research is needed to assess causality and provide firm evidence.
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Affiliation(s)
- Ying-Ying Zhang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Fang-Hua Liu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ya-Li Wang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Department of Information Center, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
| | - Jia-Xin Liu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Lang Wu
- Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, USA
| | - Ying Qin
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Wen-Rui Zheng
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Wei-Yi Xing
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Jin Xu
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xing Chen
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - He-Li Xu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Qi Bao
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Jia-Yi Wang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ran Wang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xi-Yang Chen
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yi-Fan Wei
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Bing-Jie Zou
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Jia-Cheng Liu
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Jia-Li Yin
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ming-Qian Jia
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China
| | - Song Gao
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Meng Luan
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
| | - Hui-Han Wang
- Department of Hematology, Shengjing Hospital of China Medical University, Shenyang, China.
| | - Ting-Ting Gong
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
| | - Qi-Jun Wu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China; Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; Key Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, China; Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China; NHC Key Laboratory of Advanced Reproductive Medicine and Fertility (China Medical University), National Health Commission, Shenyang, China.
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Varzaru B, Iacob RA, Bunduc S, Manea I, Sorop A, Spiridon A, Chelaru R, Croitoru A, Topala M, Becheanu G, Dumbrava M, Dima S, Popescu I, Gheorghe C. Prognostic Value of Circulating Cell-Free DNA Concentration and Neutrophil-to-Lymphocyte Ratio in Patients with Pancreatic Ductal Adenocarcinoma: A Prospective Cohort Study. Int J Mol Sci 2024; 25:2854. [PMID: 38474101 DOI: 10.3390/ijms25052854] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 02/25/2024] [Accepted: 02/26/2024] [Indexed: 03/14/2024] Open
Abstract
Circulating cell-free DNA (ccfDNA) quantity correlates with the clinical characteristics and prognosis of various cancer types. We investigated whether ccfDNA levels and the neutrophil-to-lymphocyte ratio (NLR) have prognostic value in patients with pancreatic ductal adenocarcinoma (PDAC). Peripheral blood was collected from 82 patients with PDAC prior to any diagnostic procedure or the administration of chemotherapy. Plasma DNA was isolated, and ccfDNA concentration and NLR were determined. We found that ccfDNA levels were correlated with age and tumor burden. Moreover, higher values of NLR (≥3.31) were linked with worse overall survival (OS) (4 vs. 10 months; log rank p = 0.011), and an elevated ccfDNA concentration (≥25.79 ng/mL) was strongly associated with shorter OS (4 vs. 8 months; log rank p = 0.009). According to the results of the multivariable Cox regression analysis, the baseline concentration of ccfDNA was an independent prognostic factor for OS (HR 0.45, 95% CI 0.21-0.97, p = 0.041). Furthermore, the combination of ccfDNA levels with NLR greatly enhanced the prognostic accuracy of PDAC patients. Our study demonstrates that ccfDNA concentration and NLR are independent predictors of survival in PDAC. Subsequent studies should validate this combination as a prognostic indicator in PDAC patients and assess its utility for guiding therapeutic decisions.
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Affiliation(s)
- Bianca Varzaru
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Razvan Andrei Iacob
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, 022238 Bucharest, Romania
| | - Stefania Bunduc
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, 022238 Bucharest, Romania
| | - Ioana Manea
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Andrei Sorop
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Andreea Spiridon
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Raluca Chelaru
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Adina Croitoru
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, 022238 Bucharest, Romania
| | - Mihaela Topala
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Gabriel Becheanu
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, 022238 Bucharest, Romania
| | - Mona Dumbrava
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, 022238 Bucharest, Romania
| | - Simona Dima
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, 022238 Bucharest, Romania
| | - Irinel Popescu
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, 022238 Bucharest, Romania
| | - Cristian Gheorghe
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, 022238 Bucharest, Romania
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Rompen IF, Habib JR, Wolfgang CL, Javed AA. Anatomical and Biological Considerations to Determine Resectability in Pancreatic Cancer. Cancers (Basel) 2024; 16:489. [PMID: 38339242 PMCID: PMC10854859 DOI: 10.3390/cancers16030489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 01/11/2024] [Accepted: 01/19/2024] [Indexed: 02/12/2024] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains associated with poor outcomes with a 5-year survival of 12% across all stages of the disease. These poor outcomes are driven by a delay in diagnosis and an early propensity for systemic dissemination of the disease. Recently, aggressive surgical approaches involving complex vascular resections and reconstructions have become more common, thus allowing more locally advanced tumors to be resected. Unfortunately, however, even after the completion of surgery and systemic therapy, approximately 40% of patients experience early recurrence of disease. To determine resectability, many institutions utilize anatomical staging systems based on the presence and extent of vascular involvement of major abdominal vessels around the pancreas. However, these classification systems are based on anatomical considerations only and do not factor in the burden of systemic disease. By integrating the biological criteria, we possibly could avoid futile resections often associated with significant morbidity. Especially patients with anatomically resectable disease who have a heavy burden of radiologically undetected systemic disease most likely do not derive a survival benefit from resection. On the contrary, we could offer complex resections to those who have locally advanced or oligometastatic disease but have favorable systemic biology and are most likely to benefit from resection. This review summarizes the current literature on defining anatomical and biological resectability in patients with pancreatic cancer.
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Affiliation(s)
- Ingmar F. Rompen
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY 10016, USA
- Department of General, Visceral, and Transplantation Surgery, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Joseph R. Habib
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY 10016, USA
| | - Christopher L. Wolfgang
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY 10016, USA
| | - Ammar A. Javed
- Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY 10016, USA
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Wang H, Xie D, Wang S, Wu L, Chu Y, Yang P, He W, Wang J. The value of preoperative neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and red blood cell distribution width in predicting positive surgical margin after laparoscopic radical prostatectomy. Cancer Rep (Hoboken) 2024; 7:e1977. [PMID: 38258491 PMCID: PMC10849998 DOI: 10.1002/cnr2.1977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 12/07/2023] [Accepted: 12/28/2023] [Indexed: 01/24/2024] Open
Abstract
BACKGROUND Prostate cancer (PCa) is one of the most common malignant tumors in men, and laparoscopic radical prostatectomy (LRP) is commonly used to treat localized and advanced PCa. Positive surgical margin (PSM) is one of the most frequent problems faced by surgeons. AIMS This study aimed to explore the value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and red blood cell distribution width (RDW) in predicting PSM after LRP. METHODS AND RESULTS Three hundred and twenty patients with PCa were admitted and underwent LRP in Beijing Chaoyang Hospital from January 2017 to June 2023. Patients were randomly divided into a training set (225 cases) and a validation set (95 cases) in a 7:3 ratio. NLR, PLR, and RDW were significantly higher in the PSM group than in the negative surgical margins (NSM) group. In addition, the NLR, PLR, and RDW values correlated with clinical T stage, Gleason score, and seminal vesicle invasion in the PSM group. In training set, ROC curve analysis revealed that the optimal cutoff values of NLR, PLR, and RDW for predicting postoperative PSM in PCa were 2.31, 115.40, and 12.85%, respectively. Multivariate Logistic regression analysis showed NLR and RDW were the clinical independent predictors. The area under the curve (AUC, 0.770, 95% CI 0.709-0.831) for postoperative PSM was the highest when a combination of the three parameters was used, with sensitivity and specificity of 62.5% and 85.2%, respectively. In validation set, the AUC values for NLR, PLR, RDW and the three markers combined were 0.708, 0.675, 0.723, and 0.780, respectively. Correlation analysis showed that in the PSM group, NLR was positively correlated with PLR and RDW, and PLR was positively correlated with RDW. By contrast, in the NSM group, a positive association was only found between NLR and PLR. CONCLUSIONS Higher preoperative NLR, PLR, and RDW values were associated with postoperative PSM. Additionally, the three markers combined may be useful to predict PSM.
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Affiliation(s)
- Hao Wang
- Department of UrologyBeijing Chaoyang Hospital, Capital Medical UniversityBeijingChina
| | - Dawei Xie
- Department of UrologyBeijing Chaoyang Hospital, Capital Medical UniversityBeijingChina
| | - Siqi Wang
- Department of UrologyBeijing Chaoyang Hospital, Capital Medical UniversityBeijingChina
| | - Liyang Wu
- Department of UrologyBeijing Chaoyang Hospital, Capital Medical UniversityBeijingChina
| | - Yifan Chu
- Department of UrologyCapital Medical University Daxing Teaching HospitalBeijingChina
| | - Pushen Yang
- Department of UrologyBeijing Chaoyang Hospital, Capital Medical UniversityBeijingChina
| | - Weifeng He
- Department of UrologyBeijing Chaoyang Hospital, Capital Medical UniversityBeijingChina
| | - Jianwen Wang
- Department of UrologyBeijing Chaoyang Hospital, Capital Medical UniversityBeijingChina
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Varzaru B, Iacob RA, Croitoru AE, Iacob SM, Radu CE, Dumitrescu SM, Gheorghe C. Real-Life Results of Palliative Chemotherapy in Metastatic Pancreatic Ductal Adenocarcinoma. Cancers (Basel) 2023; 15:3500. [PMID: 37444612 DOI: 10.3390/cancers15133500] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 07/02/2023] [Accepted: 07/03/2023] [Indexed: 07/15/2023] Open
Abstract
PURPOSE To assess the efficacy of FOLFIRINOX(FFX), gemcitabine-based regimens (GB), and gemcitabine monotherapy (Gem) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). METHODS This is a retrospective study that included 83 patients with mPDAC treated with first-line chemotherapy (L1) with either FFX, GB or Gem between 2015 and 2017. Progression-free survival (PFS) for L1 and second-line chemotherapy (L2) (PFS-L1 and PFS-L2) and overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS Median PFS-L1 for FFX, GB and Gem groups was 9 months (95% (Confidence Interval) CI 2.76-15.24), 5 months (95%CI 3.44-6.56), and 5 months (95%CI 3.76-6.24), respectively (p = 0.04). OS was 14 months (95%CI 11.16-16.85), 12 months (95%CI: 9.44-11.56), and 7 months (95%CI: 5.7-8.3) for patients treated with FFX, GB, and Gem, respectively (p = 0.0001). ECOG-PS (0/1) (Hazard Ratio (HR) 6.74, p = 0.002), age > 70 years (HR 0.25, p = 0.04), body tumors (HR 2.8, p = 0.048), CA19-9 > 39 U/mL (HR 0.26, p = 0.02), and neutrophil-to-lymphocyte ratio (NLR) > 4.15 (HR 6.76, p = 0.001) were independent prognostic factors for PFS-L1. Male gender (HR 3.02, p = 0.026), ECOG-PS (0/1) (HR 4.21, p = 0.003), L1 with FFX (HR 0.255, p = 0.007), and NLR > 4.15 (HR 2.65, p = 0.04) were independent prognostic factors of OS. PFS-L2 (HR 6.91, p = 0.013) and OS-L2 (HR 6.95, p = 0.037) were significantly higher in patients first treated with FFX. CONCLUSIONS The OS of patients who receive FFX or GB is comparable. The best PFS-L1 belongs to the FFX group. Male gender, ECOG-PS 0/1, the FFX regimen, and NLR > 4.15 were independent predictors of OS. PFS-L2 and OS-L2 were favorably impacted by L1 with FFX.
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Affiliation(s)
- Bianca Varzaru
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Gastroenterology Department, Sanador Clinical Hospital, 010991 Bucharest, Romania
| | - Razvan A Iacob
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, 022238 Bucharest, Romania
| | - Adina E Croitoru
- Oncology Department, Fundeni Clinical Institute, 022238 Bucharest, Romania
- Faculty of Medicine, Titu Maiorescu University, 040441 Bucharest, Romania
| | - Speranta M Iacob
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, 022238 Bucharest, Romania
| | | | | | - Cristian Gheorghe
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, 022238 Bucharest, Romania
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9
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Russell TB, Labib PLZ, Aroori S. Five-year follow-up after pancreatoduodenectomy performed for malignancy: A single-centre study. Ann Hepatobiliary Pancreat Surg 2023; 27:76-86. [PMID: 36168824 PMCID: PMC9947371 DOI: 10.14701/ahbps.22-039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 07/13/2022] [Accepted: 07/21/2022] [Indexed: 11/17/2022] Open
Abstract
Backgrounds/Aims The aim of this study was to describe short- and long-term outcomes of patients who underwent pancreatoduodenectomy (PD) at a typical United Kingdom hepatopancreatobiliary unit. Methods A retrospective analysis of all PD patients with histologically-confirmed pancreatic ductal adenocarcinoma (PDAC), ampullary adenocarcinoma (AA), or distal cholangiocarcinoma (CC) from September 1st, 2006 to May 31st, 2015 was carried out. The following information was obtained: demographics, comorbidities, preoperative investigations, neoadjuvant treatment, operative details, postoperative management, complications, adjuvant treatment, five-year recurrence, and five-year survival. Effects of selected preoperative variables on short- and long-term outcomes were investigated. Results Of 271 included patients, 57.9% had PDAC, 25.8% had AA, and 16.2% had CC. In total, 67.9% experienced morbidity and 17.3% developed a Clavien-Dindo grade ≥ III complication. The 90-day mortality was 3.3%. Clinically-relevant postoperative pancreatic fistula, bile leak, gastrojejunal leak, postpancreatectomy haemorrhage and delayed gastric emptying affected 8.1%, 4.1%, 0.0%, 9.2%, and 19.9% of patients, respectively. American Society of Anesthesiologists grade III-VI correlated with overall morbidity (p = 0.002) and major morbidity (p = 0.009), but not 90-day mortality or five-year survival. The same pattern was observed in patients with a preoperative serum bilirubin > 29 μmol/L and/or a neutrophil/lymphocyte ratio > 3.1. Five-year cancer recurrence and five-year survival were 68.3% and 22.5%, respectively. PDAC patients had higher five-year recurrence but lower five-year survival rates (both p = 0.001). Conclusions In our series, the majority of patients experienced a complication. However, few patients experienced major morbidity. Surgical risk factors did not affect five-year survival.
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Affiliation(s)
- Thomas Brendon Russell
- Department of HPB Surgery, University Hospitals Plymouth NHS Trust, Plymouth, United Kingdom
| | | | - Somaiah Aroori
- Department of HPB Surgery, University Hospitals Plymouth NHS Trust, Plymouth, United Kingdom,Corresponding author: Somaiah Aroori, MD, FRCS Department of HPB Surgery, University Hospitals Plymouth NHS Trust, Derriford Road, Plymouth PL6 8DH, United Kingdom Tel: +44-7837388342, E-mail: ORCID: https://orcid.org/0000-0002-5613-6463
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10
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Paiella S, Azzolina D, Trestini I, Malleo G, Nappo G, Ricci C, Ingaldi C, Vacca PG, De Pastena M, Secchettin E, Zamboni G, Maggino L, Corciulo MA, Sandini M, Cereda M, Capretti G, Casadei R, Bassi C, Mansueto G, Gregori D, Milella M, Zerbi A, Gianotti L, Salvia R. Body composition parameters, immunonutritional indexes, and surgical outcome of pancreatic cancer patients resected after neoadjuvant therapy: A retrospective, multicenter analysis. Front Nutr 2023; 10:1065294. [PMID: 36860690 PMCID: PMC9968808 DOI: 10.3389/fnut.2023.1065294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Accepted: 01/23/2023] [Indexed: 02/17/2023] Open
Abstract
Background and aims Body composition parameters and immunonutritional indexes provide useful information on the nutritional and inflammatory status of patients. We sought to investigate whether they predict the postoperative outcome in patients with pancreatic cancer (PC) who received neoadjuvant therapy (NAT) and then pancreaticoduodenectomy. Methods Data from locally advanced PC patients who underwent NAT followed by pancreaticoduodenectomy between January 2012 and December 2019 in four high-volume institutions were collected retrospectively. Only patients with two available CT scans (before and after NAT) and immunonutritional indexes (before surgery) available were included. Body composition was assessed and immunonutritional indexes collected were: VAT, SAT, SMI, SMA, PLR, NLR, LMR, and PNI. The postoperative outcomes evaluated were overall morbidity (any complication occurring), major complications (Clavien-Dindo ≥ 3), and length of stay. Results One hundred twenty-one patients met the inclusion criteria and constituted the study population. The median age at the diagnosis was 64 years (IQR16), and the median BMI was 24 kg/m2 (IQR 4.1). The median time between the two CT-scan examined was 188 days (IQR 48). Skeletal muscle index (SMI) decreased after NAT, with a median delta of -7.8 cm2/m2 (p < 0.05). Major complications occurred more frequently in patients with a lower pre-NAT SMI (p = 0.035) and in those who gained in subcutaneous adipose tissue (SAT) compartment during NAT (p = 0.043). Patients with a gain in SMI experienced fewer major postoperative complications (p = 0.002). The presence of Low muscle mass after NAT was associated with a longer hospital stay [Beta 5.1, 95%CI (1.5, 8.7), p = 0.006]. An increase in SMI from 35 to 40 cm2/m2 was a protective factor with respect to overall postoperative complications [OR 0.43, 95% (CI 0.21, 0.86), p < 0.001]. None of the immunonutritional indexes investigated predicted the postoperative outcome. Conclusion Body composition changes during NAT are associated with surgical outcome in PC patients who receive pancreaticoduodenectomy after NAT. An increase in SMI during NAT should be favored to ameliorate the postoperative outcome. Immunonutritional indexes did not show to be capable of predicting the surgical outcome.
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Affiliation(s)
- Salvatore Paiella
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, Verona, Italy,*Correspondence: Salvatore Paiella ✉
| | - Danila Azzolina
- Department of Environmental and Preventive Science, University of Ferrara, Ferrara, Italy
| | - Ilaria Trestini
- Dietetics Services, Hospital Medical Direction, University Hospital Trust of Verona, Verona, Italy
| | - Giuseppe Malleo
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Gennaro Nappo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy,IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Claudio Ricci
- Pancreatic Surgery Unit, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, University of Bologna, Bologna, Italy,Department of Internal Medicine and Surgery (DIMEC), S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Carlo Ingaldi
- Pancreatic Surgery Unit, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, University of Bologna, Bologna, Italy,Department of Internal Medicine and Surgery (DIMEC), S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Pier Giuseppe Vacca
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Matteo De Pastena
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Erica Secchettin
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Giulia Zamboni
- Radiology Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Laura Maggino
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Maria Assunta Corciulo
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, Padua, Italy
| | - Marta Sandini
- General Surgery Unit, University of Siena, Siena, Italy
| | - Marco Cereda
- School of Medicine and Surgery, University of Milano-Bicocca and HPB Unit, San Gerardo Hospital Monza, Monza, Italy
| | - Giovanni Capretti
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy,IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Riccardo Casadei
- Pancreatic Surgery Unit, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, University of Bologna, Bologna, Italy,Department of Internal Medicine and Surgery (DIMEC), S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Claudio Bassi
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, Verona, Italy
| | | | - Dario Gregori
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, Padua, Italy
| | - Michele Milella
- Section of Oncology, Department of Medicine, University of Verona Hospital Trust, Verona, Italy
| | - Alessandro Zerbi
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy,IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Luca Gianotti
- School of Medicine and Surgery, University of Milano-Bicocca and HPB Unit, San Gerardo Hospital Monza, Monza, Italy
| | - Roberto Salvia
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, Verona, Italy,Roberto Salvia ✉
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11
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Wang Y, Wang Q, Yang TW, Yin JM, Wei F, Liu H, Yang PX, Li J, Liu N, Zhu Y, Chen D. Analysis of Immune and Inflammatory Microenvironment Characteristics of Noncancer End-Stage Liver Disease. J Interferon Cytokine Res 2023; 43:86-97. [PMID: 36749162 DOI: 10.1089/jir.2022.0172] [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: 02/08/2023] Open
Abstract
Chronic liver injury eventually progresses to cirrhosis and end-stage liver disease (ESLD), which are the leading causes of death in patients with liver disease worldwide. ESLD has a variety of etiologies and a complex pathogenesis. This study analyzed the characteristics of ESLD by studying the immune microenvironment and inflammatory microenvironment of ESLD caused by 4 noncancer diseases, including HBV-ALF, ALF, AILD, and AH. We collected transcriptome data from noncancer ESLD patients, collected liver tissue samples and blood samples from ESLD liver transplant patients, and analyzed the immune and inflammatory microenvironments in the liver and blood. The results showed that with the exception of HBV-induced ESLD, there were no significant differences in immune microenvironment scores among patients with ESLD caused by other noncancer diseases. Moreover, there were no significant differences in the inflammatory microenvironment in the liver and blood of patients with ESLD caused by the 4 noncancer diseases. Furthermore, we found that the cytokine, IL-15, could predict the prognosis of ESLD patients.
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Affiliation(s)
- Yang Wang
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing, China
| | - Qi Wang
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing, China.,Beijing DiTan Hospital, Capital Medical University, Beijing, China.,Organ Transplant Center, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Tong Wang Yang
- Hunan Key Laboratory of Research and Development of Novel Pharmaceutical Preparations, Academician Workstation, Changsha Medical University, Changsha, China.,Organ Transplant Center, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Ji Ming Yin
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing, China
| | - Feili Wei
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing, China
| | - Huan Liu
- Organ Transplant Center, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Peng Xiang Yang
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing, China
| | - Jiaxi Li
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing, China
| | - Ning Liu
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing, China
| | - Yunxia Zhu
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing, China
| | - Dexi Chen
- Beijing Institute of Hepatology, Beijing You An Hospital, Capital Medical University, Beijing, China
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12
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KARAYİĞİT A, ÖZDEMİR DB, DİZEN H, ÜNAL B. Factors independently associated with prognosis in patients operated for pancreatic cancer: Assessing the role of various parameters including red cell distribution width, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio. JOURNAL OF HEALTH SCIENCES AND MEDICINE 2022. [DOI: 10.32322/jhsm.1137856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Objective: We aimed to assess whether, among other parameters, preoperative red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) values were associated with prognosis in patients operated for pancreatic cancer (PC).
Material and Method: This retrospective cohort was conducted from February 1, 2016 to February 1, 2021 at the general surgery department of a university hospital in Turkey. A total of 75 patients histologically diagnosed with PC who had undergone surgery were included in the study.
Results: The PLR values of patients with poorly differentiated and undifferentiated tumors were found to be higher than those with moderately and highly differentiated tumors. Also, there was a significant relationship between PLR values and the length of hospital stay. PLR values increased as the length of hospital stay increased. There was a statistically significant positive correlation between CA 19-9 levels and NLR and PLR. High total bilirubin level was related with increased risk of death, while adjuvant chemotherapy recipients had 4.049-fold lower risk of death than those without adjuvant chemotherapy.
Conclusion: Our results indicate that preoperative NLR, PLR and RDW cannot be used as prognostic indicators of mortality in patients with operated PC, but high PLR appears to be associated with lower level of tumor differentiation and prolonged hospital stay. We also found that high total bilirubin was a poor prognostic factor, while adjuvant chemotherapy was a good prognostic factor. Further multicenter, prospective studies with larger sample sizes will help to verify these results.
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Affiliation(s)
- Ahmet KARAYİĞİT
- ADANA ŞEHİR EĞİTİM VE ARAŞTIRMA HASTANESİ, CERRAHİ ONKOLOJİ KLİNİĞİ
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13
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Gupta V, Chaudhari V, Shrikhande SV, Bhandare MS. Does Preoperative Serum Neutrophil to Lymphocyte Ratio (NLR), Platelet to Lymphocyte Ratio (PLR), and Lymphocyte to Monocyte Ratio (LMR) Predict Prognosis Following Radical Surgery for Pancreatic Adenocarcinomas? Results of a Retrospective Study. J Gastrointest Cancer 2022; 53:641-648. [PMID: 34406625 DOI: 10.1007/s12029-021-00683-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/30/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND Pretherapy serum neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) have been shown to predict prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). However, the published literature is conflicting; hence, we aimed to evaluate their role in predicting survival outcomes in operated patients of PDAC. METHODS A retrospective analysis was performed in all operated cases of PDAC who underwent curative resection between 2011 and 2018. The pretherapy NLR, PLR, and LMR were calculated and analyzed with respect to pathological and survival outcomes RESULTS: One hundred thirty-four operated patients were included. The median overall survival for NLR of less than 2, 2.7, and 5 was 30.8, 27.2, and 27.5 months and for NLR of more than 2, 2.7, and 5 was 22.9, 21.6, and 21.5 months, respectively, and was statistically insignificant (p-value-0.32, 0.91, 0.34, respectively). Similarly, the PLR was not significant for a cutoff of 150 (p-value-0.27), and LMR was not significant for a cutoff of 2.8 (p-value-0.13) and 4.8 (p-value-0.11). On univariate analysis age, CA 19-9 levels, perineural invasion, margin positivity, lymph node positivity, and TNM stage were found to have a significant correlation with overall survival. However, on multivariate analysis, only TNM stage was found to be significant. CONCLUSION The NLR, PLR, and LMR do not correlate with overall survival in operated patients with PDAC in this study. A combination of inflammatory markers or their dynamic testing might probably achieve prognostic significance.
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Affiliation(s)
- Vikas Gupta
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, Maharashtra, India
| | - Vikram Chaudhari
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, Maharashtra, India
| | - Shailesh V Shrikhande
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, Maharashtra, India
| | - Manish S Bhandare
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400012, Maharashtra, India.
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14
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Fukushima G, Abe K, Kitago M, Iwasaki E, Hirata A, Takemura R, Ishii R, Yagi H, Abe Y, Hasegawa Y, Fukuhara S, Hori S, Tanaka M, Nakano Y, Yokose T, Shimane G, Kitagawa Y. Association Between Clinical Backgrounds and Malignant Progression of Suspected Intraductal Papillary Mucinous Neoplasm. Pancreas 2022; 51:617-623. [PMID: 36099509 DOI: 10.1097/mpa.0000000000002064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Some intraductal papillary mucinous neoplasms (IPMNs) have malignant potential and can become pancreatic cancer. The mechanism behind the malignant progression of IPMN remains unknown. We aimed to identify the risk factors and interactions between backgrounds for IPMN. METHODS We retrospectively enrolled 980 patients of pancreatic cancer or suspected IPMN (sIPMN) who underwent endoscopic ultrasound or retrograde cholangiopancreatography. We classified them into pancreatic cancer, high-risk sIPMN, and low-risk sIPMN, and investigated the risk factors for high-risk sIPMN. RESULTS Smoking habits (odds ratio [OR], 3.74; 95% confidence interval [CI], 2.04-6.85; P < 0.001), serum carbohydrate antigen 19-9 ≥37 U/mL (OR, 6.30; 95% CI, 2.88-13.80; P < 0.001), and family history of cancers (OR, 2.38; 95% CI, 1.30-4.37; P = 0.005) were independent risk factors for high-risk suspected IPMN. Odds ratios of diabetes and neutrophil-to-lymphocyte ratio of 2.45 or greater were significantly higher in patients with a family history of cancer than those without a family history of cancer (OR, 3.28; 95% CI, 0.52-20.80 vs 1.85; 95% CI, 0.78-4.41; OR, 2.44; 95% CI, 0.81-7.34 vs 1.24; 95% CI, 0.67-2.30, respectively). CONCLUSIONS Understanding the interactions between background factors can effectively prevent IPMNs' malignant transformation.
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Affiliation(s)
| | | | | | | | - Aya Hirata
- Preventive Medicine and Public Health, Keio University School of Medicine
| | - Ryo Takemura
- Clinical and Translational Research Center, Keio University Hospital, Tokyo, Japan
| | - Ryota Ishii
- Clinical and Translational Research Center, Keio University Hospital, Tokyo, Japan
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15
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Toyoda J, Sahara K, Maithel SK, Abbott DE, Poultsides GA, Wolfgang C, Fields RC, He J, Scoggins C, Idrees K, Shen P, Endo I, Pawlik TM. Prognostic Utility of Systemic Immune-Inflammation Index After Resection of Extrahepatic Cholangiocarcinoma: Results from the U.S. Extrahepatic Biliary Malignancy Consortium. Ann Surg Oncol 2022; 29:7605-7614. [PMID: 35768667 DOI: 10.1245/s10434-022-12058-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 06/05/2022] [Indexed: 12/18/2022]
Abstract
BACKGROUND We sought to define the association of the systemic immune inflammation index (SII) with prognosis and adjuvant therapy benefit among patients undergoing resection of extrahepatic cholangiocarcinoma (eCCA). METHODS The impact of SII on overall (OS) and recurrence-free survival (RFS) following resection of eCCA was assessed and compared with other inflammatory markers and traditional prognostic factors. Propensity score matching (PSM) was used to determine the impact of adjuvant therapy (AT) on OS and RFS relative to low versus high SII. RESULTS Patients with high versus low SII had worse 5-year OS (15.9% vs. 27.9%) and RFS (12.4% vs. 20.9%) (both p < 0.01). On multivariate analysis, high SII remained associated with worse OS (HR = 1.50, 95% CI 1.20-1.87) and RFS (HR = 1.46, 95% CI 1.18-1.81). Patients with T1/2 disease and a high-SII had worse 5-year OS versus individuals with T3/4 disease and low-SII (5-year OS: T1/2 & low-SII 35.6%, T1/2 & high-SII 16.4%, T3/4 & low-SII 22.1%, T3/4 & high-SII 15.6%, p < 0.01). Similarly, 5-year OS was comparable among individuals with N0 and high-SII versus N1 and low-SII (5-year OS: N0 & high-SII 23.2%, N1 and low-SII 19.8%, p = 0.95). On PSM, AT improved OS and RFS among patients with high SII (5-year OS: 22.5% vs. 12.3%, p < 0.01, 5-year RFS: 19.0% vs. 12.5%; p = 0.01) but not individuals with low SII (5-year OS: 22.9% vs. 26.9%; p = 0.98, 5-year RFS: 18.5% vs. 19.9%; p = 0.94). CONCLUSIONS SII was independently associated with postoperative OS and RFS following curative-intent resection of eCCA. High SII up-staged patients relative T- and N-categories and identified patients with high SII as the most likely to benefit from AT.
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Affiliation(s)
- Junya Toyoda
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Kota Sahara
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan.,Department of Surgery, The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Daniel E Abbott
- Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA
| | - George A Poultsides
- Department of Surgery, Stanford University Medical Center, Stanford, CA, USA
| | | | - Ryan C Fields
- Department of Surgery, Washington University School of Medicine, St Louis, MO, USA
| | - Jin He
- Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Charles Scoggins
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, KY, USA
| | - Kamran Idrees
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Perry Shen
- Department of Surgery, Wake Forest University, Winston-Salem, NC, USA
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH, USA.
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16
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Rich NE, Parvathaneni A, Sen A, Odewole M, Arroyo A, Mufti AR, Kerr TA, Grant L, Tujios SR, Mayo MJ, Lee WM, Yang JD, Yokoo T, Gopal P, Hoshida Y, Zhu H, Yopp AC, Marrero JA, Singal AG. High Neutrophil-Lymphocyte Ratio and Delta Neutrophil-Lymphocyte Ratio Are Associated with Increased Mortality in Patients with Hepatocellular Cancer. Dig Dis Sci 2022; 67:2666-2676. [PMID: 33939138 DOI: 10.1007/s10620-021-07001-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 04/14/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND The neutrophil-lymphocyte ratio (NLR) has been proposed as a prognostic biomarker for cirrhosis and non-liver malignancies. We aimed to evaluate the prognostic value of NLR in a diverse cohort of patients with hepatocellular carcinoma (HCC). METHODS We performed a retrospective study of patients diagnosed with HCC between 2008 and 2017 at two large US health systems. We used Cox proportional hazard and multivariable ordinal logistic regression models to identify factors associated with overall survival and response to first HCC treatment, respectively. Primary variables of interest were baseline NLR and delta NLR, defined as the difference between pre- and post-treatment NLR. RESULTS Among 1019 HCC patients, baseline NLR was < 5 in 815 (80.0%) and ≥ 5 in 204 (20.0%). Patients with NLR ≥ 5 had a higher proportion of infiltrative tumors (36.2% vs 22.3%), macrovascular invasion (39.6% vs 25.5%), metastatic disease (20.6% vs 11.4%), and AFP > 200 ng/mL (45.6% vs 33.8%). Baseline NLR ≥ 5 was independently associated with higher mortality (median survival 4.3 vs 15.1 months; adjusted HR 1.70, 95%CI 1.41-2.06), with differences in survival consistent across BCLC stages. After adjusting for baseline covariates including NLR, delta NLR > 0.26 was also independently associated with increased mortality (HR 1.42, 95%CI 1.14-1.78). In a secondary analysis, high NLR was associated with lower odds of response to HCC treatment (20.2% vs 31.6%; adjusted OR 0.55, 95%CI 0.32-0.95). CONCLUSIONS In a large Western cohort of patients with HCC, high baseline NLR and delta NLR were independent predictors of mortality. IMPACT NLR is an inexpensive test that may be a useful component of future HCC prognostic models.
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Affiliation(s)
- Nicole E Rich
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA.
| | - Aarthi Parvathaneni
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA
| | - Ahana Sen
- Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX, USA
| | - Mobolaji Odewole
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA
| | - Ana Arroyo
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA
| | - Arjmand R Mufti
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA
| | - Thomas A Kerr
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA
| | - Lafaine Grant
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA
| | - Shannan R Tujios
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA
| | - Marlyn J Mayo
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA
| | - William M Lee
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA
| | - Ju Dong Yang
- Division of Digestive and Liver Diseases, Comprehensive Transplant Center and Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Takeshi Yokoo
- Department of Radiology, UT Southwestern Medical Center, Dallas, TX, USA
| | - Purva Gopal
- Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA
| | - Yujin Hoshida
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA
| | - Hao Zhu
- Children's Research Institute, UT Southwestern Medical Center, Dallas, TX, USA
| | - Adam C Yopp
- Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA
| | - Jorge A Marrero
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA
| | - Amit G Singal
- Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, 5959 Harry Hines Blvd, POB 1, Suite 420, Dallas, TX, 75390-8887, USA
- Department of Population and Data Sciences, UT Southwestern Medical Center, Dallas, TX, USA
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Schlanger D, Popa C, Pașca S, Seicean A, Al Hajjar N. The role of systemic immuno-inflammatory factors in resectable pancreatic adenocarcinoma: a cohort retrospective study. World J Surg Oncol 2022; 20:144. [PMID: 35513845 PMCID: PMC9074307 DOI: 10.1186/s12957-022-02606-1] [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: 01/22/2022] [Accepted: 04/14/2022] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Pancreatic cancer is an aggressive malignancy, surgery being the only potentially curative treatment. The systemic inflammatory response is an important factor in the development of cancer. There is still controversy regarding its role in pancreatic cancer. METHODS Our study is a retrospective observational cohort study. We included patients diagnosed with pancreatic ductal adenocarcinoma (PDAC), who underwent surgical resection in our hospital, between January 2012 and December 2019. We gathered information from preoperative and postoperative blood tests. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), prognostic nutritional index (PNI) and systemic immune-inflammation index (SII) were determined. RESULTS We included 312 patients. All the immune-inflammatory scores assessed significantly changed after the surgery. The impact on overall survival of these markers showed that only some of the postoperative scores predicted survival: high PLR had a negative prognostic impact, while high lymphocyte and PNI values had a positive effect on overall survival. DISCUSSION The circulating immune cells and their values integrated in the assessed prognostic scores suffer statistically significant changes after curative pancreatic surgery. Only the postoperative values of lymphocyte count, PLR, and PNI seem to influence the overall survival in PDAC. TRIAL REGISTRATION ClinicalTrials.gov-identifier NCT05025371 .
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Affiliation(s)
- D. Schlanger
- “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania. Street Emil Isac no. 13, 400023 Cluj-Napoca, Romania
- Surgery Department, Regional Institute of Gastroenterology and Hepatology “Prof. Dr. O. Fodor”, Cluj-Napoca, Romania. Street Croitorilor no. 19-21, 400162 Cluj-Napoca, Romania
| | - C. Popa
- “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania. Street Emil Isac no. 13, 400023 Cluj-Napoca, Romania
- Surgery Department, Regional Institute of Gastroenterology and Hepatology “Prof. Dr. O. Fodor”, Cluj-Napoca, Romania. Street Croitorilor no. 19-21, 400162 Cluj-Napoca, Romania
| | - S. Pașca
- Department of Haematology, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania. Street Emil Isac no. 13, 400012 Cluj-Napoca, Romania
| | - A. Seicean
- “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania. Street Emil Isac no. 13, 400023 Cluj-Napoca, Romania
- Gastroenterology Department, Regional Institute of Gastroenterology and Hepatology “Prof. Dr. O. Fodor”, Cluj-Napoca, Romania. Street Croitorilor no 19-21, 400162 Cluj-Napoca, Romania
| | - N. Al Hajjar
- “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania. Street Emil Isac no. 13, 400023 Cluj-Napoca, Romania
- Surgery Department, Regional Institute of Gastroenterology and Hepatology “Prof. Dr. O. Fodor”, Cluj-Napoca, Romania. Street Croitorilor no. 19-21, 400162 Cluj-Napoca, Romania
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18
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Hung YH, Chen LT, Hung WC. The Trinity: Interplay among Cancer Cells, Fibroblasts, and Immune Cells in Pancreatic Cancer and Implication of CD8 + T Cell-Orientated Therapy. Biomedicines 2022; 10:biomedicines10040926. [PMID: 35453676 PMCID: PMC9026398 DOI: 10.3390/biomedicines10040926] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Revised: 04/15/2022] [Accepted: 04/17/2022] [Indexed: 02/01/2023] Open
Abstract
The microenvironment in tumors is complicated and is constituted by different cell types and stromal proteins. Among the cell types, the abundance of cancer cells, fibroblasts, and immune cells is high and these cells work as the “Trinity” in promoting tumorigenesis. Although unidirectional or bidirectional crosstalk between two independent cell types has been well characterized, the multi-directional interplays between cancer cells, fibroblasts, and immune cells in vitro and in vivo are still unclear. We summarize recent studies in addressing the interaction of the “Trinity” members in the tumor microenvironment and propose a functional network for how these members communicate with each other. In addition, we discuss the underlying mechanisms mediating the interplay. Moreover, correlations of the alterations in the distribution and functionality of cancer cells, fibroblasts, and immune cells under different circumstances are reviewed. Finally, we point out the future application of CD8+ T cell-oriented therapy in the treatment of pancreatic cancer.
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Affiliation(s)
- Yu-Hsuan Hung
- National Institute of Cancer Research, National Health Research Institutes, Tainan 704, Taiwan;
| | - Li-Tzong Chen
- National Institute of Cancer Research, National Health Research Institutes, Tainan 704, Taiwan;
- Division of Hematology & Oncology, Department of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 804, Taiwan
- Center for Cancer Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
- Correspondence: (L.-T.C.); (W.-C.H.)
| | - Wen-Chun Hung
- National Institute of Cancer Research, National Health Research Institutes, Tainan 704, Taiwan;
- Correspondence: (L.-T.C.); (W.-C.H.)
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19
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Yoon SJ, Kim H, Lee O, Jung JH, Lim CS, Shin YC, Kwon W, Jang JY, Shin SH, Heo JS, Han IW. Development and external validation of a nomogram with inflammatory markers for predicting invasiveness of intraductal papillary mucinous neoplasm of pancreas. Medicine (Baltimore) 2022; 101:e29036. [PMID: 35356913 PMCID: PMC10684245 DOI: 10.1097/md.0000000000029036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 02/19/2022] [Indexed: 11/26/2022] Open
Abstract
ABSTRACT Recent studies have reported that inflammatory markers, such as neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and advanced lung cancer inflammation index, are associated with invasiveness of intraductal papillary mucinous neoplasm (IPMN). This study aimed to develop and validate a new nomogram that includes inflammatory markers for predicting the invasiveness of IPMN.The data of 365 patients who underwent surgical resection for IPMN at 4 centers between 1995 and 2016 were retrospectively reviewed to develop a new nomogram. For external validation, a separate patient cohort was used. The predictive ability of the nomogram was evaluated using the area under the receiver operating characteristic curve.The new nomogram was developed using the following variables which were identified as risk factors for invasive IPMN: body mass index, preoperative serum bilirubin level, carbohydrate antigen 19-9, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, advanced lung cancer inflammation index, main duct type, presence of solid portion, and tumor size. After external validation, the area under the curve value was 0.649 (95% CI: 0.578-0.720, P < .001).To the best of our knowledge, this study is the first to predict and externally validate the invasiveness in IPMN using inflammatory markers. Further research is necessary to improve predictability of the model for selecting patients for surgical resection.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - In Woong Han
- Correspondence: In Woong Han, Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School ofMedicine, 81, Irwon-ro, Gangnam-gu, Seoul 06351, South Korea (e-mail: ).
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20
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Li Q, Feng Z, Miao R, Liu X, Liu C, Liu Z. Prognosis and survival analysis of patients with pancreatic cancer: retrospective experience of a single institution. World J Surg Oncol 2022; 20:11. [PMID: 34996486 PMCID: PMC8742338 DOI: 10.1186/s12957-021-02478-x] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Accepted: 12/07/2021] [Indexed: 12/15/2022] Open
Abstract
Background The overall survival of patients with pancreatic cancer is extremely low. Despite multiple large-scale studies, identification of predictors of patient survival remains challenging. This study aimed to investigate the prognostic factors for pancreatic cancer. Methods The clinical data of 625 patients with pancreatic cancer treated at Shengjing Hospital of China Medical University from January 2013 to December 2017 were collected. Results Of 625 patients, 569 were followed from 1 to 75 months. The median overall survival was 9.3 months. The overall 1-, 3-, and 5-year survival rates were 37.8%, 15.1%, and 10.5%, respectively. Cox proportional hazards model indicated that baseline carbohydrate antigen 199 level, neutrophil-lymphocyte ratio, operative procedure, lymph node metastasis, number of distant organ metastasis, and postoperative adjuvant chemotherapy were independent prognostic factors of patients with pancreatic cancer. Baseline carbohydrate antigen 199 level, degree of weight loss, operative procedure, lymph node metastasis, number of distant organ metastasis, and postoperative adjuvant chemotherapy were independent prognostic factors of pancreatic head cancer subgroup. Baseline carbohydrate antigen 199 level, carcinoembryonic antigen level, total bilirubin level, neutrophil-lymphocyte ratio, peripancreatic invasion, number of distant organ metastasis, and postoperative adjuvant chemotherapy were independent prognostic factors of the pancreatic body/tail cancer subgroup. Conclusions Higher carbohydrate antigen 199 levels, neutrophil-lymphocyte ratio, lymph node metastasis and distant organ metastasis predict a poor prognosis in patients with pancreatic cancer. Early detection, early radical surgery and adjuvant chemotherapy are needed to improve prognosis for this deadly disease.
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Affiliation(s)
- Qi Li
- Department of General Surgery, Shengjing Hospital of China Medical University, 110004, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning Province, China
| | - Zijian Feng
- Department of General Surgery, Shengjing Hospital of China Medical University, 110004, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning Province, China
| | - Ruyi Miao
- Department of General Surgery, Shengjing Hospital of China Medical University, 110004, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning Province, China
| | - Xun Liu
- Department of General Surgery, Shengjing Hospital of China Medical University, 110004, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning Province, China
| | - Chenxi Liu
- Department of General Surgery, Shengjing Hospital of China Medical University, 110004, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning Province, China
| | - Zhen Liu
- Department of General Surgery, Shengjing Hospital of China Medical University, 110004, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning Province, China.
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21
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Topkan E, Selek U, Haksoyler V, Kucuk A, Durankus NK, Sezen D, Bolukbasi Y, Pehlivan B. Postchemoradiotherapy Neutrophil-to-Lymphocyte Ratio Predicts Distant Metastasis and Survival Results in Locally Advanced Pancreatic Cancers. Int J Clin Pract 2022; 2022:7473649. [PMID: 35685603 PMCID: PMC9159257 DOI: 10.1155/2022/7473649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 11/15/2021] [Accepted: 11/24/2021] [Indexed: 11/17/2022] Open
Abstract
MATERIALS AND METHODS Our retrospective research included a sum of 126 LAPAC patients who received CCRT. The NLR was calculated for each patient based on the complete blood count test results obtained on the last day of the CCRT. The availability of optimal cutoff(s) that might dichotomize the whole cohort into two groups with significantly different clinical outcomes was searched using receiver operating characteristic (ROC) curve analysis. Primary and secondary endpoints were the potential association between the post-CCRT NLR measures and distant metastasis-free survival (DMFS) and overall survival (OS) outcomes. RESULTS The median follow-up duration was 14.7 months (range: 2.4-94.5). The median and 3-year OS and DMFS rates for the whole group were 15.3 months (95% confidence interval: 12.4-18.2) and 14.5%, and 8.7 months (95% CI: 6.7-10.7) and 6.3% separately. The ROC curve analysis findings separated the patients into two groups on a rounded NLR cutoff of 3.1 (area under the curve (AUC): 75.4%; sensitivity: 74.2%; specificity: 73.9%) for OS and DMFS: NLR <3.1 (N = 62) and NLR ≥3.1 (N = 64), respectively. Comparisons between the NLR groups displayed that the median OS (11.4 vs. 21.4 months; P < 0.001) and DMFS (6.0 vs. 16.0 months; P < 0.001) lengths were significantly shorter in the NLR ≥3.1 group than its NLR <3.1 counterparts, as well as the 3-year actuarial DM rate (79.7% vs. 50.0%; P=0.003). The N1-2 nodal stage, CA 19-9>90 U/mL, and NLR >3.1 were found to be independent predictors of poor prognosis in the multivariate analysis. CONCLUSION The present study found that the posttreatment NLR ≥3.1 was independently linked with a higher risk of DM and subsequent degraded survival outcomes in unresectable LAPAC patients managed with exclusive CCRT.
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Affiliation(s)
- Erkan Topkan
- Department of Radiation Oncology, Baskent University Medical Faculty, Adana, Turkey
| | - Ugur Selek
- Department of Radiation Oncology, Koc University Schoolof Medicine, Istanbul, Turkey
- The University of Texas MD Anderson Cancer Center, Division of Radiation Oncology, Houston, TX 77030, USA
| | | | - Ahmet Kucuk
- Clinic of Radiation Oncology, Mersin Education and Research Hospital, Mersin, Turkey
| | | | - Duygu Sezen
- Department of Radiation Oncology, Koc University Schoolof Medicine, Istanbul, Turkey
| | - Yasemin Bolukbasi
- Department of Radiation Oncology, Koc University Schoolof Medicine, Istanbul, Turkey
- The University of Texas MD Anderson Cancer Center, Division of Radiation Oncology, Houston, TX 77030, USA
| | - Berrin Pehlivan
- Department of Radiation Oncology, Bahcesehir University, Istanbul, Turkey
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22
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Kim H, Jung W, Chan Shin Y, Han IW, Byun Y, Lee HW, Heo JS, Choi DW, Lim CS. The diagnostic and prognostic values of inflammatory markers in intraductal papillary mucinous neoplasm. HPB (Oxford) 2021; 23:1623-1628. [PMID: 34001453 DOI: 10.1016/j.hpb.2021.04.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Revised: 12/07/2020] [Accepted: 04/06/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Intraductal papillary mucinous neoplasm (IPMN) is an broad-spectrum disease from benign to malignant. Inflammatory markers are known as prognostic predictors in various diseases. The purpose of this study was to determine the predictive value of inflammatory markers for prognosis in IPMN. METHODS From April 1995 to December 2016, patients who underwent pancreatectomy with pathologically confirmed IPMN at four tertiary centers were enrolled. Patients with a history of pancreatitis or cholangitis, and other malignancies were excluded. Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and advanced lung cancer inflammation index (ALI) were calculated. RESULTS Of all, ninety-eight patients (26.8%) were diagnosed as invasive IPMN. The NLR and PLR were significantly elevated in invasive IPMN than in non-invasive disease (2.0 vs 1.8, p = 0.004; 117.1 vs 107.4, p = 0.009, respectively). ALI was significantly higher in non-invasive IPMN than in invasive disease (58.1 vs 45.9, p < 0.001). In multivariate analysis, only NLR showed significant association among the inflammatory markers studied (p = 0.044). In invasive IPMN, the five-year recurrence-free survival rate for NLR less than 3.5 was superior to the rest (59.1 vs 42.2, p = 0.023). CONCLUSION NLR may help to rightly select IPMN patients who will require surgery and may serve as a useful prognostic factor.
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Affiliation(s)
- Hongbeom Kim
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Surgery, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Republic of Korea
| | - Woohyun Jung
- Department of Surgery, Ajou University Hospital, Ajou University College of Medicine, Suwon, Republic of Korea
| | - Yong Chan Shin
- Department of Surgery, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Republic of Korea
| | - In W Han
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul, Republic of Korea
| | - Yoonhyeong Byun
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Hae W Lee
- Department of Surgery, Boramae Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jin S Heo
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul, Republic of Korea
| | - Dong W Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul, Republic of Korea
| | - Chang-Sup Lim
- Department of Surgery, Boramae Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
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23
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van der Sijde F, Mustafa DAM, Vietsch EE, Katsikis PD, van Eijck CHJ. Circulating Immunological Biomarkers: Prognosis of Pancreatic Cancer Patients Reflected by the Immune System. Pancreas 2021; 50:933-941. [PMID: 34643608 DOI: 10.1097/mpa.0000000000001862] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
ABSTRACT To date, little advances have been made toward new and more effective therapies for pancreatic ductal adenocarcinoma (PDAC). Discovery of prognostic and predictive biomarkers is needed to stratify patients for available treatments and to elucidate how new therapies could be developed. Recent studies have made clear that the immune system is not only affected in the microenvironment of the primary tumor and it is also systemically disrupted in PDAC patients. Under normal circumstances, the immune system is in perfect balance with both proinflammatory and anti-inflammatory components present. In this review, we focus on circulating immunological characteristics including immune cells and their subtypes, cytokines, and immune checkpoints in the peripheral blood not only to understand the poor prognosis of PDAC patients but also to find new leads for new innovative therapies.
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Affiliation(s)
| | | | | | - Peter D Katsikis
- Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
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24
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Vasconcelos de Matos L, Coelho A, Cunha R, Fernandes L, Fontes E Sousa M, Neves MT, Cardoso D, Malheiro M, Graça J, Santos Silva E, Plácido A, Martins A. Association of Weight Change, Inflammation Markers and Disease Staging with Survival of Patients Undergoing Chemotherapy for Pancreatic Adenocarcinoma. Nutr Cancer 2021; 74:546-554. [PMID: 33749421 DOI: 10.1080/01635581.2021.1903049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
INTRODUCTION Cancer-associated-cachexia represents a systemic syndrome of unintended weight-loss (WL) and systemic inflammation, affecting >80% patients with pancreatic adenocarcinoma (PA). We aimed to evaluate the association of weight change (WC) with survival of patients treated with chemotherapy (ChT) for PA and the influence of disease staging. We also studied the prognostic and predictive value of inflammation-based scores. METHODS Observational, retrospective cohort study. Individuals were divided into two cohorts, according to WC (WL ≥5% vs. non-WL <5%) after ChT. Main endpoints were weight change and survival time. Statistical analysis was performed using Stata software. RESULTS Sixty-five patients were included (median age 69; 48% female), 60% with advanced disease. At 3 months after ChT start, 54% experienced WL. Advanced disease independently predicted WL (OR 2.10; 95% CI, 1.11-19.6; p = 0.041). With median follow-up of 14.8 mo, median survival time of patients with WL was 18.5 mo, vs. 33.2 vs. for non-WL (HR 2.28; 95% CI, 1.15-4.52; p = 0.019). In patients with early-stage disease, WL was associated with decreased survival time (21.9 vs. 67.6 mo; HR 23.68; 95% CI 2.39-234.75; p = 0.007), while the association of WL on survival time in advanced disease was not significant (HR 0.74; 95% CI, 0.34-1.60; p = 0.449). The multivariate survival model showed that WL (HR 1.11, 95% CI 1.03-1.20, p = 0.005) and cachexia (HR 3.76, 95% CI 1.07-13-18), p = 0.041) were associated with survival time, as well as location in body or tail (HR 3.05; 95% CI, 1.75-5.31; p < 0.001) and high Neutrophil-to-lymphocyte ratio (NLR) at 3 months (HR 6.20; 95% CI, 2.59-14.87; p < 0.001). CONCLUSION WL was an independent prognostic factor for survival. Particularly in early stage disease, interventions targeting this modifiable factor may translate into better outcomes for PA patients. NLR may be a surrogate marker of systemic inflammatory status in this setting.
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Affiliation(s)
- Leonor Vasconcelos de Matos
- Department of Medical Oncology Hospital São Francisco Xavier, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal
| | - Andreia Coelho
- Department of Medical Oncology Hospital São Francisco Xavier, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal
| | - Renato Cunha
- Medical Oncology Department, Hospital do Espírito Santo, Évora, Portugal
| | - Leonor Fernandes
- Department of Medical Oncology Hospital São Francisco Xavier, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal
| | | | - Maria Teresa Neves
- Department of Medical Oncology Hospital São Francisco Xavier, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal
| | - Débora Cardoso
- Department of Medical Oncology Hospital São Francisco Xavier, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal
| | - Mariana Malheiro
- Department of Medical Oncology Hospital São Francisco Xavier, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal.,Medical Oncology Department, Hospital CUF Tejo, Lisboa, Portugal
| | - Joana Graça
- Department of Medical Oncology Hospital São Francisco Xavier, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal
| | - Eugénia Santos Silva
- Dietetic and Nutrition Department, Instituto Português de Oncologia de Lisboa, Portugal
| | - Ana Plácido
- Department of Medical Oncology Hospital São Francisco Xavier, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal
| | - Ana Martins
- Department of Medical Oncology Hospital São Francisco Xavier, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal
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Shang J, Han X, Zha H, Tao H, Li X, Yuan F, Chen G, Wang L, Ma J, Hu Y. Systemic Immune-Inflammation Index and Changes of Neutrophil-Lymphocyte Ratio as Prognostic Biomarkers for Patients With Pancreatic Cancer Treated With Immune Checkpoint Blockade. Front Oncol 2021; 11:585271. [PMID: 33718140 PMCID: PMC7943876 DOI: 10.3389/fonc.2021.585271] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 01/07/2021] [Indexed: 12/26/2022] Open
Abstract
The efficacy of current treatment regimens for pancreatic cancer (PC) remains unsatisfactory. In recent years, immune checkpoint blockade (ICB) therapy has shown promising anti-tumor outcomes in many malignancies, including PC. Inexpensive and readily available biomarkers which predict therapeutic responses and prognosis are in critical need. Systemic immune-inflammation index (SII) and neutrophil-lymphocyte ratio (NLR) are emerging predictors for prognosis of various tumors. We aim to investigate the prognostic significance of baseline SII, NLR, and their changes in PC patients treated with ICB. Our retrospective analysis included PC patients treated with ICB therapy in the Chinese PLA General Hospital. All demographic, biological, and clinical data were extracted from medical records. Relative changes of SII after two doses of ICB were defined as ΔSII% and calculated as (SIIafter 2 doses-SIIbaseline)/SIIbaseline, and so was the case for ΔNLR%. Overall survival (OS) and progression-free survival (PFS) were compared using Kaplan-Meier curves. The prognostic significance of baseline SII, NLR, and their changes was assessed in univariate and multivariate analyses using the Cox proportional hazard regression model. In total, 122 patients with PC treated with ICB were included in the present analysis. Elevated baseline SII (HR=3.28; 95% CI:1.98–5.27; P=0.03) and ΔNLR% (HR=2.21; 95% CI:1.03–4.74; P=0.04) were significantly correlated with an increased risk of death. For PC patients receiving ICB combined with chemotherapies or radiotherapies as the first-line treatment, increased baseline SII was a negative predictor for both OS (HR=8.06; 95% CI:1.71–37.86; P=0.01) and PFS (HR=2.84; 95%CI:1.37–10.38; P=0.04). Our study reveals the prognostic value of baseline SII and NLR changes in PC patients receiving ICB therapy. The clinical utility of these prognostic biomarkers needs to be further studied in prospective studies.
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Affiliation(s)
- Jin Shang
- Department of Oncology, Chinese People's Liberation Army General Hospital, People's Liberation Army School of Medicine, Beijing, China.,Department of Health Service, Guard Bureau of the Joint Staff Department, Central Military Commission of People's Liberation Army, Beijing, China
| | - Xiao Han
- Department of Oncology, Chinese People's Liberation Army General Hospital, People's Liberation Army School of Medicine, Beijing, China
| | - Haoran Zha
- Department of Oncology, People's Liberation Army Rocket Force Characteristic Medical Center, Beijing, China
| | - Haitao Tao
- Department of Oncology, Chinese People's Liberation Army General Hospital, People's Liberation Army School of Medicine, Beijing, China
| | - Xiaoyan Li
- Department of Oncology, Chinese People's Liberation Army General Hospital, People's Liberation Army School of Medicine, Beijing, China
| | - Fang Yuan
- Department of Oncology, Chinese People's Liberation Army General Hospital, People's Liberation Army School of Medicine, Beijing, China
| | - Guangying Chen
- Department of Oncology, Chinese People's Liberation Army General Hospital, People's Liberation Army School of Medicine, Beijing, China
| | - Lijie Wang
- Department of Oncology, Chinese People's Liberation Army General Hospital, People's Liberation Army School of Medicine, Beijing, China
| | - Junxun Ma
- Department of Oncology, Chinese People's Liberation Army General Hospital, People's Liberation Army School of Medicine, Beijing, China
| | - Yi Hu
- Department of Oncology, Chinese People's Liberation Army General Hospital, People's Liberation Army School of Medicine, Beijing, China
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Yamakoshi Y, Tanaka H, Sakimura C, Mori T, Deguchi S, Yoshii M, Tamura T, Toyokawa T, Lee S, Muguruma K, Hirakawa K, Ohira M. Association between the preoperative neutrophil-to-lymphocyte ratio and tertiary lymphoid structures surrounding tumor in gastric cancer. Mol Clin Oncol 2021; 14:76. [PMID: 33680464 PMCID: PMC7922788 DOI: 10.3892/mco.2021.2238] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 02/12/2021] [Indexed: 11/24/2022] Open
Abstract
The neutrophil-to-lymphocyte ratio (NLR) has been reported to be associated with a poor prognosis in various types of cancer. We previously reported that an antitumor immune response was induced by tertiary lymphoid structures (TLSs) surrounding tumor, and increased TLS was an independent prognostic factor in patients with gastric cancer. The present study examined the stratification based on the correlation between the preoperative NLR and TLS density in gastric cancer. A total of 199 patients who underwent surgery for stage Ib-IV gastric cancer were included in the study. Receiver operating characteristic curve analysis was used to determine the appropriate cut-off values of the preoperative NLR and the TLS density. The prognostic factors were evaluated in a multivariate analysis. The median NLR was 2.18 (mean ± SD, 2.7±2.04). A total of 91 patients with an NLR ≥2.33 was classified into the high NLR group. The overall survival was significantly improved in patients with a low NLR than in those with a high NLR. Additionally, the low NLR group tended to have a high TLS density. The multivariate analysis indicated that the preoperative NLR and TLS density were independent risk factors. When the patients were classified into the high and low NLR and TLS groups and the survival rates were compared, the prognosis was significantly improved in the low NLR and high TLS group than in the other groups. The preoperative NLR may be associated with the presence of TLSs surrounding the tumor, and the combination of NLR and TLS may be useful for the stratification of patient prognosis. The present results suggested that the NLR and TLS density may be surrogate markers for immunotherapy against gastric cancer.
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Affiliation(s)
- Yoshihito Yamakoshi
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Hiroaki Tanaka
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Chie Sakimura
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Takuya Mori
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Sota Deguchi
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Mami Yoshii
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Tatsuro Tamura
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Takahiro Toyokawa
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Shigeru Lee
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Kazuya Muguruma
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Kosei Hirakawa
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Masaichi Ohira
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
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Systemic Immune-Inflammation Index Is a Prognostic Predictor in Patients with Intrahepatic Cholangiocarcinoma Undergoing Liver Transplantation. Mediators Inflamm 2021; 2021:6656996. [PMID: 33628115 PMCID: PMC7899762 DOI: 10.1155/2021/6656996] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 02/03/2021] [Accepted: 02/05/2021] [Indexed: 02/07/2023] Open
Abstract
Background It was reported that systemic immune inflammation index (SII) was related to poor prognosis in a variety of cancers. We aimed to investigate the ability of the prognostic predictors of SII in patients with intrahepatic cholangiocarcinoma (iCCA) undergoing liver transplantation (LT). Methods The 28 iCCA patients who underwent LT at our hospital between 2013 and 2018 were reviewed. Kaplan–Meier survival curves and Cox regression analyses were used to evaluate the prognostic significance of SII. Patients were divided into the high and low SII groups according to the cut-off value. Results The 1-, 3-, and 5-year OS rates were significantly lower in the high SII group (85.7%, 28.6%, and 21.4%, respectively) than in the low SII group (92.9%, 71.4%, and 57.2%, respectively; P = 0.009). The 1-, 3-, and 5-year RFS rates were, respectively, 57.1%, 32.7%, and 21.8% in the high SII group and 85.7%, 61.1%, and 61.1% in the low SII group (P = 0.021). SII ≥ 447.48 × 109/L (HR 0.273, 95% CI 0.082–0.908; P = 0.034) was an independent prognostic factor for OS. Conclusions Our results showed that SII can be used to predict the survival of patients with iCCA who undergo LT.
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Xu D, Zhang K, Li M, Neoptolemos JP, Wu J, Gao W, Wu P, Cai B, Yin J, Shi G, Lu Z, Jiang K, Miao Y. Prognostic Nomogram for Resected Pancreatic Adenocarcinoma: A TRIPOD-Compliant Retrospective Long-Term Survival Analysis. World J Surg 2020; 44:1260-1269. [PMID: 31900571 DOI: 10.1007/s00268-019-05325-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Prognostic prediction had been widely used in various cancer entities, from early screening to end-stage patient caring. Currently, there is hardly any well-validated nomogram which exists for long-term survival prediction in pancreatic adenocarcinoma (PC) patients in a post-surgery setting. Our objectives are to identify possible prognostic factors in PC patients following radical resection and to develop a prognostic nomogram based on independent survival predictors. METHODS From 2009 to 2014, a total of 432 PC patients who underwent curative intended surgeries with complete follow-up data were included in this current retrospective long-term survival analysis. Clinicopathological data were extracted from medical records, and all missing values (percentage 0.9-8.3%) were imputed five times with the "PMM" method. Cox proportional hazards models were utilized. A nomogram was formulated based on results from the multivariate regression model so as to predict OS at 1-, 2- and 3-year as well as median OS. Validations, including discrimination and calibration, were carried out with 1000 bootstrap resamples. External validation was conducted in order to verify the accuracy of our nomogram at 1 and 2 years by utilizing the clinicopathological data of 122 PC patients who underwent curative intended surgeries in 2015 in our centre. RESULTS Age, abdominal pain, back pain, tumour location, preoperative neutrophil-lymphocyte ratio, preoperative CA19-9, tumour differentiation, microscopic nerve invasion, microscopic vascular invasion, T stage, lymph node ratio, M stage and adjuvant chemotherapy were all assembled into nomogram. The concordance index (C-index) of internal and external validation was 0.702 and 0.688, respectively. The C-index of the TNM staging system was 0.572 (P < 0.001 vs. nomogram). CONCLUSION Our prognostic nomogram based on clinicopathological parameters shows good performance in long-term survival prediction in PC patients following radical surgery and could play a role in further clinical utilization.
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Affiliation(s)
- Dong Xu
- Pancreas Center and Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Kai Zhang
- Pancreas Center and Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Mingna Li
- Pathology Department, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - J P Neoptolemos
- Pancreas Center and Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.,Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Junli Wu
- Pancreas Center and Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Wentao Gao
- Pancreas Center and Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Pengfei Wu
- Pancreas Center and Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Baobao Cai
- Pancreas Center and Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Jie Yin
- Pancreas Center and Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Guodong Shi
- Pancreas Center and Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Zipeng Lu
- Pancreas Center and Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
| | - Kuirong Jiang
- Pancreas Center and Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
| | - Yi Miao
- Pancreas Center and Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
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Turpin A, el Amrani M, Bachet JB, Pietrasz D, Schwarz L, Hammel P. Adjuvant Pancreatic Cancer Management: Towards New Perspectives in 2021. Cancers (Basel) 2020; 12:E3866. [PMID: 33371464 PMCID: PMC7767489 DOI: 10.3390/cancers12123866] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Revised: 12/18/2020] [Accepted: 12/19/2020] [Indexed: 02/06/2023] Open
Abstract
Adjuvant chemotherapy is currently used in all patients with resected pancreatic cancer who are able to begin treatment within 3 months after surgery. Since the recent publication of the PRODIGE 24 trial results, modified FOLFIRINOX has become the standard-of-care in the non-Asian population with localized pancreatic adenocarcinoma following surgery. Nevertheless, there is still a risk of toxicity, and feasibility may be limited in heavily pre-treated patients. In more frail patients, gemcitabine-based chemotherapy remains a suitable option, for example gemcitabine or 5FU in monotherapy. In Asia, although S1-based chemotherapy is the standard of care it is not readily available outside Asia and data are lacking in non-Asiatic patients. In patients in whom resection is not initially possible, intensified schemes such as FOLFIRINOX or gemcitabine-nabpaclitaxel have been confirmed as options to enhance the response rate and resectability, promoting research in adjuvant therapy. In particular, should oncologists prescribe adjuvant treatment after a long sequence of chemotherapy +/- chemoradiotherapy and surgery? Should oncologists consider the response rate, the R0 resection rate alone, or the initial chemotherapy regimen? And finally, should they take into consideration the duration of the entire sequence, or the presence of limited toxicities of induction treatment? The aim of this review is to summarize adjuvant management of resected pancreatic cancer and to raise current and future concerns, especially the need for biomarkers and the best holistic care for patients.
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Affiliation(s)
- Anthony Turpin
- UMR9020-UMR-S 1277 Canther-Cancer Heterogeneity, Plasticity and Resistance to Therapies, University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, F-59000 Lille, France;
- Medical Oncology Department, CHU Lille, University of Lille, F-59000 Lille, France
| | - Mehdi el Amrani
- Department of Digestive Surgery and Transplantation, Lille University Hospital, F-59000 Lille, France;
| | - Jean-Baptiste Bachet
- Department of Hepatogastroenterology and GI Oncology, La Pitié-Salpêtrière Hospital, INSERM UMRS 1138, Université de Paris, F-75013 Paris, France;
| | - Daniel Pietrasz
- Department of Digestive, Oncological, and Transplant Surgery, Paul Brousse Hospital, Paris-Saclay University, F-94800 Villejuif, France;
| | - Lilian Schwarz
- Department of Digestive Surgery, Rouen University Hospital and Université de Rouen Normandie, F-76100 Rouen, France;
| | - Pascal Hammel
- Service d’Oncologie Digestive et Médicale, Hôpital Paul Brousse (AP-HP), 12 Avenue Paul Vaillant Couturier, F-94800 Villejuif, France
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Cupp MA, Cariolou M, Tzoulaki I, Aune D, Evangelou E, Berlanga-Taylor AJ. Neutrophil to lymphocyte ratio and cancer prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies. BMC Med 2020; 18:360. [PMID: 33213430 PMCID: PMC7678319 DOI: 10.1186/s12916-020-01817-1] [Citation(s) in RCA: 330] [Impact Index Per Article: 66.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 10/15/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Although neutrophils have been linked to the progression of cancer, uncertainty exists around their association with cancer outcomes, depending on the site, outcome and treatments considered. We aimed to evaluate the strength and validity of evidence on the association between either the neutrophil to lymphocyte ratio (NLR) or tumour-associated neutrophils (TAN) and cancer prognosis. METHODS We searched MEDLINE, Embase and Cochrane Database of Systematic Reviews from inception to 29 May 2020 for systematic reviews and meta-analyses of observational studies on neutrophil counts (here NLR or TAN) and specific cancer outcomes related to disease progression or survival. The available evidence was graded as strong, highly suggestive, suggestive, weak or uncertain through the application of pre-set GRADE criteria. RESULTS A total of 204 meta-analyses from 86 studies investigating the association between either NLR or TAN and cancer outcomes met the criteria for inclusion. All but one meta-analyses found a hazard ratio (HR) which increased risk (HR > 1). We did not find sufficient meta-analyses to evaluate TAN and cancer outcomes (N = 9). When assessed for magnitude of effect, significance and bias related to heterogeneity and small study effects, 18 (9%) associations between NLR and outcomes in composite cancer endpoints (combined analysis), cancers treated with immunotherapy and some site specific cancers (urinary, nasopharyngeal, gastric, breast, endometrial, soft tissue sarcoma and hepatocellular cancers) were supported by strong evidence. CONCLUSION In total, 60 (29%) meta-analyses presented strong or highly suggestive evidence. Although the NLR and TAN hold clinical promise in their association with poor cancer prognosis, further research is required to provide robust evidence, assess causality and test clinical utility. TRIAL REGISTRATION PROSPERO CRD42017069131 .
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Affiliation(s)
- Meghan A Cupp
- Department of Epidemiology & Biostatistics, MRC Centre for Environment and Health, School of Public Health, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London, W21PG, UK
| | - Margarita Cariolou
- Department of Epidemiology & Biostatistics, MRC Centre for Environment and Health, School of Public Health, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London, W21PG, UK
| | - Ioanna Tzoulaki
- Department of Epidemiology & Biostatistics, MRC Centre for Environment and Health, School of Public Health, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London, W21PG, UK
- Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece
| | - Dagfinn Aune
- Department of Epidemiology & Biostatistics, MRC Centre for Environment and Health, School of Public Health, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London, W21PG, UK
- Department of Nutrition, Bjørknes University College, Oslo, Norway
- Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway
| | - Evangelos Evangelou
- Department of Epidemiology & Biostatistics, MRC Centre for Environment and Health, School of Public Health, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London, W21PG, UK
- Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece
| | - Antonio J Berlanga-Taylor
- Department of Epidemiology & Biostatistics, MRC Centre for Environment and Health, School of Public Health, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London, W21PG, UK.
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Neutrophil to lymphocyte ratio predicts prognosis in unresectable pancreatic cancer. Sci Rep 2020; 10:18758. [PMID: 33127996 PMCID: PMC7599218 DOI: 10.1038/s41598-020-75745-8] [Citation(s) in RCA: 64] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Accepted: 10/16/2020] [Indexed: 01/04/2023] Open
Abstract
Inflammation-based prognostic indicators have been developed to predict the prognosis in patients with pancreatic cancer. However, prognostic indices have not been established in patients with unresectable pancreatic cancer, including those without indication for chemotherapy at diagnosis. This study aimed to identify the predictors in all patients with unresectable pancreatic cancer. We retrospectively analyzed data of 119 patients with unresectable pancreatic cancer from June 2006 to September 2018. The following laboratory parameters were evaluated: the Glasgow Prognostic Score (GPS), modified GPS, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein albumin (CRP/Alb) ratio, and prognostic nutritional index (PNI). We performed time-dependent receiver operating characteristic analysis, overall survival (OS) analysis, and univariate and multivariate analyses to determine the prognostic factors in patients with unresectable pancreatic cancer. The cut-off value for NLR was determined to be 3.74. The 6-month OS rates in low and high NLR groups were 75.5% and 18.8% (P < 0.001). In the univariate analysis, advanced age (P = 0.003), metastatic pancreatic cancer (P = 0.037), no treatment (P < 0.001), worse Eastern Cooperative Oncology Group Performance Status (ECOG-PS) (P < 0.001), high GPS (P < 0.001), high modified GPS (P < 0.001), high NLR (P < 0.001), high PLR (P = 0.002), high CRP/Alb ratio (P < 0.001), and low PNI (P < 0.001) were identified as the prognostic factors. The multivariate analysis revealed that metastatic pancreatic cancer (P = 0.046), no treatment (P < 0.001), worse ECOG-PS (P = 0.002), and high NLR (P < 0.001) were independently associated with OS. We revealed that the high NLR could be an independent indicator of poor prognosis in patients with unresectable pancreatic cancer.
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Factors predicting survival in patients with locally advanced pancreatic cancer undergoing pancreatectomy with arterial resection. Updates Surg 2020; 73:233-249. [PMID: 32978753 PMCID: PMC7889566 DOI: 10.1007/s13304-020-00883-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 09/03/2020] [Indexed: 02/07/2023]
Abstract
Pancreatectomy with arterial resection is a treatment option in selected patients with locally advanced pancreatic cancer. This study aimed to identify factors predicting cancer-specific survival in this patient population. A single-Institution prospective database was used. Pre-operative prognostic factors were identified and used to develop a prognostic score. Matching with pathologic parameters was used for internal validation. In a patient population with a median Ca 19.9 level of 19.8 U/mL(IQR: 7.1–77), cancer-specific survival was predicted by: metabolic deterioration of diabetes (OR = 0.22, p = 0.0012), platelet count (OR = 1.00; p = 0.0013), serum level of Ca 15.3 (OR = 1.01, p = 0.0018) and Ca 125 (OR = 1.02, p = 0.00000137), neutrophils-to-lymphocytes ratio (OR = 1.16; p = 0.00015), lymphocytes-to-monocytes ratio (OR = 0.88; p = 0.00233), platelets-to-lymphocytes ratio (OR = 0.99; p = 0.00118), and FOLFIRINOX neoadjuvant chemotherapy (OR = 0.57; p = 0.00144). A prognostic score was developed and three risk groups were identified. Harrell’s C-Index was 0.74. Median cancer-specific survival was 16.0 months (IQR: 12.3–28.2) for the high-risk group, 24.7 months (IQR: 17.6–33.4) for the intermediate-risk group, and 39.0 months (IQR: 22.7–NA) for the low-risk group (p = 0.0003). Matching the three risk groups against pathology parameters, N2 rate was 61.9, 42.1, and 23.8% (p = 0.04), median value of lymph-node ratio was 0.07 (IQR: 0.05–0.14), 0.04 (IQR:0.02–0.07), and 0.03 (IQR: 0.01–0.04) (p = 0.008), and mean value of logarithm odds of positive nodes was − 1.07 ± 0.5, − 1.3 ± 0.4, and − 1.4 ± 0.4 (p = 0.03), in the high-risk, intermediate-risk, and low-risk groups, respectively. An online calculator is available at www.survivalcalculator-lapdac-arterialresection.org. The prognostic factors identified in this study predict cancer-specific survival in patients with locally advanced pancreatic cancer and low Ca 19.9 levels undergoing pancreatectomy with arterial resection.
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Pointer DT, Roife D, Powers BD, Murimwa G, Elessawy S, Thompson ZJ, Schell MJ, Hodul PJ, Pimiento JM, Fleming JB, Malafa MP. Neutrophil to lymphocyte ratio, not platelet to lymphocyte or lymphocyte to monocyte ratio, is predictive of patient survival after resection of early-stage pancreatic ductal adenocarcinoma. BMC Cancer 2020; 20:750. [PMID: 32782024 PMCID: PMC7422564 DOI: 10.1186/s12885-020-07182-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 07/14/2020] [Indexed: 12/11/2022] Open
Abstract
Background NLR, PLR, and LMR have been associated with pancreatic ductal adenocarcinoma (PDAC) survival. Prognostic value and optimal cutpoints were evaluated to identify underlying significance in surgical PDAC patients. Methods NLR, PLR, and LMR preoperative values were available for 277 PDAC patients who underwent resection between 2007 and 2015. OS, RFS, and survival probability estimates were calculated by univariate, multivariable, and Kaplan-Meier analyses. Continuous and dichotomized ratio analysis determined best-fit cutpoints and assessed ratio components to determine primary drivers. Results Elevated NLR and PLR and decreased LMR represented 14%, 50%, and 50% of the cohort, respectively. OS (P = .002) and RFS (P = .003) were significantly decreased in resected PDAC patients with NLR ≥5 compared to those with NLR < 5. Optimal prognostic OS and RFS cutpoints for NLR, PLR, and LMR were 4.8, 192.6, and 1.7, respectively. Lymphocytes alone were the primary prognostic driver of NLR, demonstrating identical survival to NLR. Conclusions NLR is a significant predictor of OS and RFS, with lymphocytes alone as its primary driver; we identified optimal cutpoints that may direct future investigation of their prognostic value. This study contributes to the growing evidence of immune system influence on outcomes in early-stage pancreatic cancer.
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Affiliation(s)
- David T Pointer
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr, Tampa, FL, 33612, USA
| | - David Roife
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr, Tampa, FL, 33612, USA
| | - Benjamin D Powers
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr, Tampa, FL, 33612, USA
| | - Gilbert Murimwa
- Department of Surgery, University of Texas Southwestern, Dallas, TX, USA
| | - Sameh Elessawy
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr, Tampa, FL, 33612, USA
| | - Zachary J Thompson
- Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Michael J Schell
- Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Pamela J Hodul
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr, Tampa, FL, 33612, USA
| | - Jose M Pimiento
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr, Tampa, FL, 33612, USA
| | - Jason B Fleming
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr, Tampa, FL, 33612, USA
| | - Mokenge P Malafa
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr, Tampa, FL, 33612, USA.
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Ren A, Li Z, Zhang X, Deng R, Ma Y. Inflammation-Based Prognostic Scores in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma After Liver Transplantation. J Hepatocell Carcinoma 2020; 7:101-106. [PMID: 32766175 PMCID: PMC7368363 DOI: 10.2147/jhc.s259992] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Accepted: 06/21/2020] [Indexed: 12/14/2022] Open
Abstract
Background Inflammation-based prognostic scores including systemic immune-inflammation index (SII), platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) have prognostic value in various cancers. We investigated the prognostic value of SII, PLR and NLR in patients who underwent liver transplantation (LT) for HBV-related hepatocellular carcinoma (HCC). Methods We retrospectively analyzed the records of 189 patients who underwent LT for HBV-related HCC. The receiver operating characteristic (ROC) curve was used to determine the optimal SII, PLR and NLR cut-off value. Overall survival (OS) and recurrence-free survival (RFS) following LT were calculated. The Kaplan–Meier method and the Cox proportional hazards model were used to evaluate the prognostic value of SII, PLR and NLR. Results The 1-, 3-, and 5-year OS rates were significantly lower in the high SII group (74.1%, 34.2%, and 32.3%, respectively) than in the low SII group (78.5%, 66.9%, and 59.9%, respectively; p = 0.000). The 1-, 3-, and 5-year RFS rates were, respectively, 75.9%, 59.7%, and 49.4% in the high SII group and 93.3%, 80.2%, and 73.7% in the low SII group (p = 0.000). Finally, OS curves were plotted by the Kaplan–Meier method and compared using the Log rank test. High PLR and NLR scores were also associated with poor OS (p = 0.000 and p = 0.003) and poor RFS (p = 0.000 and p = 0.000). The multivariate analysis demonstrated that AFP ≥400 ng/mL, high MELD score, largest tumor size ≥5cm, SII ≥449.61, NLR ≥5.29, and PLR ≥98.52 were independent prognostic factors for OS. Conclusion High SII, PLR and NLR are significantly poor prognostic factors for overall survival and recurrence-free survival in patients with HBV-related hepatocellular carcinoma after liver transplantation.
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Affiliation(s)
- Ao Ren
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Zhongqiu Li
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Xuzhi Zhang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Ronghai Deng
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Yi Ma
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China
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Systemic but not MDSC-specific IRF4 deficiency promotes an immunosuppressed tumor microenvironment in a murine pancreatic cancer model. Cancer Immunol Immunother 2020; 69:2101-2112. [PMID: 32448983 PMCID: PMC7511276 DOI: 10.1007/s00262-020-02605-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Accepted: 05/12/2020] [Indexed: 02/06/2023]
Abstract
Pancreatic ductal adenocarcinoma is characterized by a strong immunosuppressive network with a dense infiltration of myeloid cells including myeloid-derived suppressor cells (MDSC). Two distinct populations of MDSC have been defined: polymorphonuclear MDSC (PMN-MDSC) and monocytic MDSC (M-MDSC). Several factors influence the development and function of MDSC including the transcription factor interferon regulatory factor 4 (IRF4). Here, we show that IRF4 deficiency accelerates tumor growth and reduces survival, accompanied with a dense tumor infiltration with PMN-MDSC and reduced numbers of CD8+ T cells. As IRF4 has been described to modulate myeloid cell development and function, particularly of PMN-MDSC, we analyzed its role using MDSC-specific IRF4 knockout mice with the Ly6G or LysM knock-in allele expressing Cre recombinase and Irf4flox. In GM-CSF-driven bone marrow cultures, IRF4 deficiency increased the frequency of MDSC-like cells with a strong T cell suppressive capacity. Myeloid (LysM)-specific depletion of IRF4 led to increased tumor weight and a moderate splenic M-MDSC expansion in tumor-bearing mice. PMN cell (Ly6G)-specific depletion of IRF4, however, did not influence tumor progression or MDSC accumulation in vivo in accordance with our finding that IRF4 is not expressed in PMN-MDSC. This study demonstrates a critical role of IRF4 in the generation of an immunosuppressive tumor microenvironment in pancreatic cancer, which is independent of IRF4 expression in PMN-MDSC.
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Guo SW, Shen J, Gao JH, Shi XH, Gao SZ, Wang H, Li B, Yuan WL, Lin L, Jin G. A preoperative risk model for early recurrence after radical resection may facilitate initial treatment decisions concerning the use of neoadjuvant therapy for patients with pancreatic ductal adenocarcinoma. Surgery 2020; 168:1003-1014. [PMID: 32321665 DOI: 10.1016/j.surg.2020.02.013] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Revised: 01/05/2020] [Accepted: 02/07/2020] [Indexed: 12/31/2022]
Abstract
BACKGROUND Neoadjuvant chemotherapy may benefit patients with pancreatic ductal adenocarcinoma with resectable and borderline disease. Inappropriate use of neoadjuvant therapy, however, may lead to the loss of therapeutic opportunities. Until an effective prediction model of individual drug sensitivity is established, no accurate model exists to help surgeons decide on the appropriate use of neoadjuvant chemotherapy. We hypothesized that early recurrence in patients undergoing upfront, early resection may be an indication for neoadjuvant chemotherapy. Therefore, we aimed to use preoperative clinical parameters to establish a model of early recurrence to select patients at high risk for neoadjuvant chemotherapy. METHODS Patients who underwent resection for pancreatic ductal adenocarcinoma between January 2014 and November 2017 were analyzed retrospectively. After the minimum P-value approach, the patients were divided into three groups: early recurrence, middle recurrence, and late/non-recurrence. Preoperative clinicopathologic factors that could predict early recurrence were included in a Cox proportional hazards regression model for univariate and multivariate analyses. The factors related to early recurrence were included to establish nomogram and decision tree models, which were then validated in 68 patients. RESULTS We found that 235 (72.5%) of 324 patients had recurrence with a median recurrence-free survival of 210 days. The early recurrence, middle recurrence, and late/non-recurrence groups differed in preoperative carbohydrate antigen 19-9 and carcinoembryonic antigen levels, "resectability" on cross-sectional imaging, resection requiring a vascular resection, T stage, tumor size, and adjuvant chemotherapy. The best cutoff value of early recurrence was the first 162 days postoperatively. Univariate and multivariate analyses showed that selected preoperative chief complaints, lymph node enlargement and resectability on cross-sectional imaging, preoperative carbohydrate antigen 19-9 levels >210 kU/L, and a neutrophil/lymphocyte ratio >4.2 were independent predictors for early recurrence. CONCLUSION We have successfully built a prediction model of early recurrence of patients with pancreatic ductal adenocarcinoma with the optimal cutoff early-recurrence value of 162 days. Our nomogram and decision tree models may be used to select those at high risk for early recurrence to guide preoperative decision-making concerning the use of neoadjuvant therapy in those patients who have "resectable" disease and not only the more classic criteria of borderline resectability.
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Affiliation(s)
- Shi-Wei Guo
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Navy Military Medical University (Second Military Medical University), 200433 Shanghai, China
| | - Jing Shen
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Navy Military Medical University (Second Military Medical University), 200433 Shanghai, China; Department of General Surgery, No.971 Hospital of Navy, 266071, Qingdao, Shandong, China
| | - Jun-Hui Gao
- Shanghai Biotecan Pharmaceuticals Co., Ltd., Zhangjiang Center for Translational Medicine, 201204 Shanghai, China
| | - Xiao-Han Shi
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Navy Military Medical University (Second Military Medical University), 200433 Shanghai, China
| | - Sui-Zhi Gao
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Navy Military Medical University (Second Military Medical University), 200433 Shanghai, China
| | - Huan Wang
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Navy Military Medical University (Second Military Medical University), 200433 Shanghai, China
| | - Bo Li
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Navy Military Medical University (Second Military Medical University), 200433 Shanghai, China
| | - Wei-Lan Yuan
- Shanghai Biotecan Pharmaceuticals Co., Ltd., Zhangjiang Center for Translational Medicine, 201204 Shanghai, China
| | - Ling Lin
- Shanghai Biotecan Pharmaceuticals Co., Ltd., Zhangjiang Center for Translational Medicine, 201204 Shanghai, China
| | - Gang Jin
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Navy Military Medical University (Second Military Medical University), 200433 Shanghai, China.
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Systemic Immune-Inflammation Index (SII) Predicts Poor Survival in Pancreatic Cancer Patients Undergoing Resection. J Gastrointest Surg 2020; 24:610-618. [PMID: 30923999 PMCID: PMC7064450 DOI: 10.1007/s11605-019-04187-z] [Citation(s) in RCA: 97] [Impact Index Per Article: 19.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Accepted: 02/26/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND The systemic immune-inflammation index based on peripheral neutrophil, lymphocyte, and platelet counts has shown a prognostic impact in several malignancies. The aim of this study was to determine the prognostic role of systemic immune-inflammation index in patients with pancreatic ductal adenocarcinoma undergoing resection. METHODS Consecutive patients who underwent surgical resection at the department of surgery at the Medical University of Vienna between 1995 and 2014 were included into this study. The systemic immune-inflammation index was calculated by the formula platelet*neutrophil/lymphocyte. Optimal cutoffs were determined using Youden's index. Uni- and multivariate analyses were calculated by the Cox proportional hazard regression model for overall survival. RESULTS Three hundred twenty-one patients were included in this study. Clinical data was achieved from a prospective patient database. In univariate survival analysis, elevated systemic immune-inflammation index was found to be significantly associated with shortened patients' overall survival (p = 0.007). In multivariate survival analysis, systemic immune-inflammation index remained an independent prognostic factor for overall survival (p = 0.004). No statistical significance could be found for platelet to lymphocyte ratio and neutrophil to lymphocyte ratio in multivariate analysis. Furthermore, area under the curve analysis showed a higher prognostic significance for systemic immune-inflammation index, compared to platelet to lymphocyte ratio and neutrophil to lymphocyte ratio. CONCLUSION A high systemic immune-inflammation index is an independent, preoperative available prognostic factor in patients with resectable pancreatic ductal adenocarcinoma and is superior to platelet to lymphocyte ratio and neutrophil to lymphocyte ratio for predicting overall survival in pancreatic ductal adenocarcinoma patients.
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Kawada T. Neutrophil-to-lymphocyte ratio as an indicator of prognosis in patients with pancreatic cancer. HPB (Oxford) 2019; 21:1791. [PMID: 31320242 DOI: 10.1016/j.hpb.2019.06.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Accepted: 06/25/2019] [Indexed: 12/12/2022]
Affiliation(s)
- Tomoyuki Kawada
- Department of Hygiene and Public Health, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo 113-8602, Japan.
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Unveiling the mechanisms of immune evasion in pancreatic cancer: may it be a systemic inflammation responsible for dismal survival? Clin Transl Oncol 2019; 22:81-90. [DOI: 10.1007/s12094-019-02113-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Accepted: 04/09/2019] [Indexed: 02/07/2023]
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Prognostic factors for disease-free survival in patients with pancreatic ductal adenocarcinoma after surgery: a single center experience. JOURNAL OF PANCREATOLOGY 2019. [DOI: 10.1097/jp9.0000000000000011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
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Severe Neutropenia is Associated with Better Clinical Outcomes in Patients with Advanced Pancreatic Cancer Who Receive Modified FOLFIRINOX Therapy. Cancers (Basel) 2018; 10:cancers10110454. [PMID: 30453583 PMCID: PMC6265962 DOI: 10.3390/cancers10110454] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Revised: 10/19/2018] [Accepted: 11/14/2018] [Indexed: 12/13/2022] Open
Abstract
While modified FOLFIRINOX therapy is effective for treating advanced pancreatic cancer, it frequently causes severe neutropenia. The present study investigated the effect of severe neutropenia on clinical outcomes in advanced pancreatic cancer patients who received modified FOLFIRINOX. The study subjects were 51 patients (30 males and 21 females) with advanced pancreatic cancer who received modified FOLFIRINOX (2h bolus injection of oxaliplatin at 85 mg/m², 2 h bolus injection of L-leucovorin at 200 mg/m², 90min bolus injection of irinotecan at 150 mg/m², followed by continuous infusion of 5-fluorouracil for 46 h at 2400 mg/m² without bolus 5-fluorouracil) during the period from January 2014 to May 2018. No patients had prior history of chemotherapy. Adverse events, including neutropenia, were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Median overall survival (OS) was the primary endpoint, while median time to treatment failure (TTF), overall response rate (ORR), and the incidence of other adverse events were secondary endpoints. Severe neutropenia (grade ≥3) occurred in 39 patients (76.4%), and Cox proportional hazard analysis identified high total bilirubin level as a significant risk factor. Median duration of OS was significantly longer in patients with severe neutropenia than in those without it (21.3 months versus 8.9 months, p = 0.020). Moreover, there was a significant correlation between OS and the grade of neutropenia (r = 0.306, p = 0.029). ORR tended to be higher, though not significantly, in patients with severe neutropenia. In contrast, the incidence rates of other adverse events were not different between the two groups. Severe neutropenia is an independent predictor of prognosis in advanced pancreatic cancer patients received modified FOLFIRINOX therapy.
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Inflammation-based prognostic scores in patients with extrahepatic bile duct lesions treated by percutaneous transhepatic biliary stenting combined with 125I seeds intracavitary irradiation. Clin Transl Oncol 2018; 21:665-673. [PMID: 30368724 DOI: 10.1007/s12094-018-1969-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Accepted: 10/16/2018] [Indexed: 12/26/2022]
Abstract
PURPOSE This study aimed at investigating the efficacy of percutaneous transhepatic biliary stenting (PTBS) combined with 125I seeds intracavitary irradiation in the treatment of extrahepatic cholangiocarcinoma (EHC) and to preliminarily explore the prognostic values of inflammation-based scores in these patients. METHODS A total of 113 clinically/pathologically diagnosed cases of EHC who received PTBS combined with 125I seeds implantation were retrospectively analyzed. The postoperative changes of clinical symptoms and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total serum bilirubin (TBIL), direct bilirubin (DBIL), and albumin (ALB) were observed. Preoperative clinical data were extracted to calculate inflammation-based scores, including systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelets-to-lymphocyte ratio (PLR). Kaplan-Meier survival curves and Cox regression analyses were used to evaluate the prognostic significance of inflammation-based scores. RESULTS After operation, clinical symptoms such as jaundice and fever significantly improved in all patients. At 1 month and 3 months postoperatively, serum levels of ALT, AST, ALP, TBIL, and DBIL significantly reduced, and ALB significantly increased, compared with preoperative values. The median survival time of the patients was 12 months and the 1-year survival rate was 56.8%. Univariate analysis revealed that factors related to overall survival were CA19-9, TBIL, ALB, SII, and NLR. Multivariate analysis further identified SII and NLR as independent prognostic models. CONCLUSION The combination of PTBS and 125I seeds intracavitary irradiation is an effective palliative treatment for advanced EHC. Elevated SII and NLR can be used to predict poor survival.
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Prognostic stratification of resected pancreatic ductal adenocarcinoma: Past, present, and future. Dig Liver Dis 2018; 50:979-990. [PMID: 30205952 DOI: 10.1016/j.dld.2018.08.009] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Revised: 08/02/2018] [Accepted: 08/02/2018] [Indexed: 02/06/2023]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the digestive cancer with the poorest prognosis, with a 5-year overall survival rate of 7%. Complete surgical resection followed by adjuvant chemotherapy is the only treatment with curative intent. However, many patients with an apparently localized disease who may undergo primary tumor resection already have micro-metastatic disease and will promptly develop metastases. Considering the significant rate of morbidity and mortality upon pancreatic surgery, the pre-operative identification of patients with an aggressive disease is therefore a major clinical issue. Although tumor size, differentiation, margins, and lymph node invasion are the main "classical" prognostic factors, they are not sufficient to fully predict early disease recurrence. In the last decade, multi-omics high-throughput analyses have provided a new insight into PDAC biology and have led to the description of multiple molecular subtypes, with a significant prognostic value for most of them, but that have not yet been transposed to routine clinical practice, mainly due to poor availability of tumor tissue material prior to surgical resection. In this review, we provide an overview of the current status of clinico-pathological and molecular biomarkers (tumor and blood) to predict early recurrence, and their implications for clinical practice and future research development.
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Parente P, Parcesepe P, Covelli C, Olivieri N, Remo A, Pancione M, Latiano TP, Graziano P, Maiello E, Giordano G. Crosstalk between the Tumor Microenvironment and Immune System in Pancreatic Ductal Adenocarcinoma: Potential Targets for New Therapeutic Approaches. Gastroenterol Res Pract 2018; 2018:7530619. [PMID: 30662458 PMCID: PMC6312626 DOI: 10.1155/2018/7530619] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Accepted: 11/04/2018] [Indexed: 02/06/2023] Open
Abstract
Pancreatic ductal adenocarcinoma is a lethal disease for which radical surgery and chemotherapy represent the only curative options for a small proportion of patients. Recently, FOLFIRINOX and nab-paclitaxel plus gemcitabine have improved the survival of metastatic patients but prognosis remains poor. A pancreatic tumor microenvironment is a dynamic milieu of cellular and acellular elements, and it represents one of the major limitations to chemotherapy efficacy. The continued crosstalk between cancer cells and the surrounding microenvironment causes immunosuppression within pancreatic immune infiltrate increasing tumor aggressiveness. Several potential targets have been identified among tumor microenvironment components, and different therapeutic approaches are under investigation. In this article, we provide a qualitative literature review about the crosstalk between the tumor microenvironment components and immune system in pancreatic cancer. Finally, we discuss potential therapeutic strategies targeting the tumor microenvironment and we show the ongoing trials.
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Affiliation(s)
- Paola Parente
- 1Fondazione IRCCS Casa Sollievo della Sofferenza, UO di Anatomia Patologica, Viale Cappuccini 1, 71013 San Giovanni Rotondo, FG, Italy
| | - Pietro Parcesepe
- 2Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, P.le L.A. Scuro 10, 37134 Verona, Italy
| | - Claudia Covelli
- 1Fondazione IRCCS Casa Sollievo della Sofferenza, UO di Anatomia Patologica, Viale Cappuccini 1, 71013 San Giovanni Rotondo, FG, Italy
| | - Nunzio Olivieri
- 3Biology Department, University of Naples Federico II, Via Mezzocannone 8, 80134 Naples, Italy
| | - Andrea Remo
- 4“Mater Salutis” Hospital, ULSS 9, Via C. Gianella 1, 37045 Legnago, Verona, Italy
| | - Massimo Pancione
- 5Department of Sciences and Technologies, University of Sannio, Via Port'Arsa 11, 82100 Benevento, Italy
| | - Tiziana Pia Latiano
- 6Fondazione IRCCS Casa Sollievo della Sofferenza, UO di Oncologia Medica, Viale Cappuccini 1, 71013 San Giovanni Rotondo, FG, Italy
| | - Paolo Graziano
- 1Fondazione IRCCS Casa Sollievo della Sofferenza, UO di Anatomia Patologica, Viale Cappuccini 1, 71013 San Giovanni Rotondo, FG, Italy
| | - Evaristo Maiello
- 6Fondazione IRCCS Casa Sollievo della Sofferenza, UO di Oncologia Medica, Viale Cappuccini 1, 71013 San Giovanni Rotondo, FG, Italy
| | - Guido Giordano
- 6Fondazione IRCCS Casa Sollievo della Sofferenza, UO di Oncologia Medica, Viale Cappuccini 1, 71013 San Giovanni Rotondo, FG, Italy
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