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Noronha V, Patil VM, Menon N, Joshi A, Shah MJ, Singh A, Goud S, Shah S, More S, Nawale K, Nakti D, Yadav A, Jogdhankar S, Kaushal RK, Tiwari VK, Niyogi D, Purandare N, Janu A, Chakrabarty N, Mahajan A, Tibdewal A, Agarwal J, Pawar A, Chowdhury OR, Sharma V, Kapu V, Trikha M, Kumar SV, Kolkur M, Bhagyavant P, Peelay Z, Khedkar R, Jain M, Badwe RA, Prabhash K. Phase III randomized trial comparing neoadjuvant paclitaxel plus platinum with 5-fluorouracil plus platinum in esophageal or gastroesophageal junction squamous cell carcinoma. J Natl Cancer Inst 2025; 117:58-75. [PMID: 39222012 DOI: 10.1093/jnci/djae214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 07/25/2024] [Accepted: 08/27/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND Standard neoadjuvant chemotherapy for locally advanced esophageal or gastroesophageal junction squamous cancer, 5-fluorouracil plus platinum, is toxic and logistically challenging; alternative regimens are needed. METHODS This was a phase III randomized open-label noninferiority trial at Tata Memorial Center, India, in resectable locally advanced esophageal or gastroesophageal junction squamous cancer. Patients were randomly assigned 1:1 to 3 cycles of 3-weekly platinum (cisplatin 75 mg/m2 or carboplatin area under the curve 6) with paclitaxel 175 mg/m2 (day 1) or 5-fluorouracil 1000 mg/m2 continuous infusion (days 1-4), followed by surgery. RESULTS Between August 2014 and June 2022, we enrolled 420 patients; 210 to each arm. Statistically significantly more patients on paclitaxel plus platinum (n =194, 92.3%) received all 3 chemotherapy cycles than on 5-fluorouracil with platinum (n = 170, 85.9%; P = .009). 5-fluorouracil plus platinum caused more grade 3 or higher toxicities (n = 124, 69.7%) than paclitaxel plus platinum (n = 97, 51.9%; P = .001). Surgery was performed in 131 (62.4%) patients on 5-fluorouracil plus platinum vs 139 (66.2%) on paclitaxel plus platinum (P = .415). Paclitaxel plus platinum resulted in higher pathologic primary tumor clearance (n = 33, 25.8%, vs n = 17, 15%; P = .04) and pathologic complete responses in 21.9% compared with 12.4% from 5-fluorouracil plus platinum (P = .053). Median overall survival was 27.5 months (95% confidence interval [CI] = 18.6 to 43.5 months) from paclitaxel plus platinum, which was noninferior to 27.1 months (95% CI = 18.8 to 40.7 months) from 5-fluorouracil plus platinum (hazard ratio [HR] = 0.89, 95% CI = 0.72 to 1.09; P = .346). CONCLUSION Neoadjuvant paclitaxel plus platinum chemotherapy is safer and results in similar R0 resections, higher pathologic tumor clearance and noninferior survival compared with 5-fluorouracil plus platinum. Paclitaxel plus platinum should replace 5-fluorouracil plus platinum as neoadjuvant chemotherapy for resectable locally advanced esophagealor gastroesophageal junction squamous cancer. CLINICAL TRIALS REGISTRY INDIA NUMBER CTRI/2014/04/004516.
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Affiliation(s)
- Vanita Noronha
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Vijay Maruti Patil
- Department of Medical Oncology, PD Hinduja Hospital Medical Research Centre, Mumbai, Khar and Mahim, India
| | - Nandini Menon
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Amit Joshi
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Minit Jalan Shah
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Ajaykumar Singh
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Supriya Goud
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Srushti Shah
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Sucheta More
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Kavita Nawale
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Dipti Nakti
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Akanksha Yadav
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Shweta Jogdhankar
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Rajiv Kumar Kaushal
- Department of Pathology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Virendra Kumar Tiwari
- Department of Surgical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Devayani Niyogi
- Department of Surgical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Nilendu Purandare
- Department of Nuclear Medicine, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Amit Janu
- Department of Radiodiagnosis, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Nivedita Chakrabarty
- Department of Radiodiagnosis, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Abhishek Mahajan
- Department of Imaging, Clatterbridge Cancer Centre National Health Service Foundation Trust, Liverpool, United Kingdom and Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK
| | - Anil Tibdewal
- Department of Radiation Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Jaiprakash Agarwal
- Department of Radiation Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Akash Pawar
- Department of Biostatistics, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Oindrila Roy Chowdhury
- Department of Biostatistics, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Vibhor Sharma
- Department of Medical Oncology, Yatharth Superspeciality Hospital, Noida Extension, Uttar Pradesh, India
| | - Venkatesh Kapu
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Mehak Trikha
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Srigadha Vivek Kumar
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Manali Kolkur
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Priyanka Bhagyavant
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Zoya Peelay
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Rutvij Khedkar
- Department of Pathology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Medha Jain
- Department of Pathology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Rajendra Achyut Badwe
- Department of Surgical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Kumar Prabhash
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
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Makino T, Miyata H, Yasuda T, Kitagawa Y, Muro K, Park JH, Hikichi T, Hasegawa T, Igarashi K, Iguchi M, Masaoka Y, Yano M, Doki Y. A phase 3, randomized, double-blind, multicenter, placebo-controlled study of S-588410, a five-peptide cancer vaccine as an adjuvant therapy after curative resection in patients with esophageal squamous cell carcinoma. Esophagus 2024; 21:447-455. [PMID: 38990441 PMCID: PMC11405444 DOI: 10.1007/s10388-024-01072-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 07/02/2024] [Indexed: 07/12/2024]
Abstract
BACKGROUND S-588410, a cancer peptide vaccine (CPV), comprises five HLA-A*24:02-restricted peptides from five cancer-testis antigens. In a phase 2 study, S-588410 was well-tolerated and exhibited antitumor efficacy in patients with urothelial cancer. Therefore, we aimed to evaluate the efficacy, immune response, and safety of S-588410 in patients with completely resected esophageal squamous cell carcinoma (ESCC). METHODS This phase 3 study involved patients with HLA-A*24:02-positive and lymph node metastasis-positive ESCC who received neoadjuvant therapy followed by curative resection. After randomization, patients were administered S-588410 and placebo (both emulsified with Montanide™ ISA 51VG) subcutaneously. The primary endpoint was relapse-free survival (RFS). The secondary endpoints were overall survival (OS), cytotoxic T-lymphocyte (CTL) induction, and safety. Statistical significance was tested using the one-sided weighted log-rank test with the Fleming-Harrington class of weights. RESULTS A total of 276 patients were randomized (N = 138/group). The median RFS was 84.3 and 84.1 weeks in the S-588410 and placebo groups, respectively (P = 0.8156), whereas the median OS was 236.3 weeks and not reached, respectively (P = 0.6533). CTL induction was observed in 132/134 (98.5%) patients who received S-588410 within 12 weeks. Injection site reactions (137/140 patients [97.9%]) were the most frequent treatment-emergent adverse events in the S-588410 group. Prolonged survival was observed in S-588410-treated patients with upper thoracic ESCC, grade 3 injection-site reactions, or high CTL intensity. CONCLUSIONS S-588410 induced immune response and had acceptable safety but failed to reach the primary endpoint. A high CTL induction rate and intensity may be critical for prolonging survival during future CPV development.
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Affiliation(s)
- Tomoki Makino
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Hiroshi Miyata
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Takushi Yasuda
- Department of Surgery, Kindai University Faculty of Medicine, 377-2, Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan.
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Kei Muro
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan
| | - Jae-Hyun Park
- OncoTherapy Science, Inc., Kawasaki, Kanagawa, Japan
| | - Tetsuro Hikichi
- Laboratory Department, Cancer Precision Medicine, Inc., Kawasaki, Kanagawa, Japan
| | | | | | - Motofumi Iguchi
- Medical Affairs Department, Shionogi & Co., Ltd, Osaka, Japan
| | | | - Masahiko Yano
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
- Kyowakai Hospital, Osaka, Japan
| | - Yuichiro Doki
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
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Wu Y, Liu X, Li H, Wang W, Ye L, Zhou Y, Chen D. D-dimer levels predict the treatment efficacy and prognosis of esophageal squamous cell carcinoma treated with PD-1/PD-L1 inhibitors. Int J Biol Markers 2024; 39:209-216. [PMID: 38887052 DOI: 10.1177/03936155241262045] [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: 06/20/2024]
Abstract
OBJECTIVES This study aimed to explore the value of D-dimer levels in predicting the treatment efficacy and prognosis of advanced esophageal squamous cell carcinoma (ESCC) treated with programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors. METHODS The study retrospectively analyzed 233 ESCC patients who received PD-1/PD-L1 inhibitors. The optimal cut-off values for platelets, fibrinogen, and D-dimer were calculated based on maximally selected rank statistics for patients' overall survival. Univariate and multivariate analyses of progression-free survival and overall survival were conducted by Cox proportional hazards regression model. Subgroup analyses of D-dimer levels in different fibrinogen levels were performed by log-rank test. RESULTS The multivariate Cox regression analyses demonstrated that ESCC patients with D-dimer levels > 236 ng/mL exhibited both poorer progression-free survival (P = 0.004) and overall survival (P < 0.0001) compared to those with low D-dimer levels. The subgroup analyses further indicated that in the group of low fibrinogen levels, the higher D-dimer levels of ESCC patients exhibited significantly shorter progression-free survival (P = 0.0021) and overall survival (P < 0.0001). CONCLUSIONS The study revealed that the D-dimer levels possess predictive value for the treatment efficacy and prognosis of ESCC patients treated with PD-1/PD-L1 inhibitors.
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Affiliation(s)
- Yuchen Wu
- Department of Laboratory Medicine, Zhejiang Cancer Hospital, Hangzhou, China
| | - Xin Liu
- Department of Respiratory, Yichun Central Hospital, Yichun, China
| | - Huihui Li
- Postgraduate Training Base Alliance, Wenzhou Medical University, Wenzhou, China
| | - Wenjing Wang
- Postgraduate Training Base Alliance, Wenzhou Medical University, Wenzhou, China
| | - Lisha Ye
- Postgraduate Training Base Alliance, Wenzhou Medical University, Wenzhou, China
| | - Yun Zhou
- Department of Laboratory Medicine, Zhejiang Cancer Hospital, Hangzhou, China
| | - Da Chen
- Department of Oncological Surgery, Zhejiang Cancer Hospital, Hangzhou, China
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Dellaportas D, Margaris I, Latsonas P, Pikouli A, Vlachos I, Papakonstantinou D, Pararas N, Nastos C, Myoteri D, Pikoulis E. Contemporary Role of Open Left Thoracoabdominal Approach in Esophageal Malignancy Treatment. Cureus 2024; 16:e62922. [PMID: 39040781 PMCID: PMC11262707 DOI: 10.7759/cureus.62922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/22/2024] [Indexed: 07/24/2024] Open
Abstract
INTRODUCTION Despite the widespread use of minimally invasive techniques, open left thoracoabdominal esophagectomy (LTE) can offer excellent visualization and adaptability. The current study aimed to present and evaluate the outcomes related to an open LTE in esophageal malignancy treatment. METHODS A retrospective cohort analysis of data collected from two institutions was performed, including patients with distal esophageal or junctional tumors who underwent open LTE between November 2018 and December 2023. RESULTS Twenty-two patients were included (16 males; mean age 62.8 years). Postoperative complications occurred in eight patients (36%), with pulmonary complications being the most prevalent (seven patients; 32%). One patient experienced a clinical anastomotic leak. No reoperations or escalation to a higher level of care were required. In-hospital and 30-day mortality were zero. Tumor cells were found at the surgical margins in six patients (27%). The mean lymph node yield was 27. During the follow-up period, there were nine deaths and 11 cases of disease recurrence. Isolated locoregional recurrence was seen in five patients (23%). The one-year and two-year overall survival rates were 79% and 47%, respectively. CONCLUSION In selected cases, open LTE remains a valid and safe operation with acceptable morbidity and oncological efficacy.
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Affiliation(s)
- Dionysios Dellaportas
- 3rd Department of Surgery, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, GRC
| | - Ioannis Margaris
- 4th Department of Surgery, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, GRC
| | - Panagiotis Latsonas
- 3rd Department of Surgery, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, GRC
| | - Anastasia Pikouli
- 3rd Department of Surgery, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, GRC
| | - Iakovos Vlachos
- Department of Pathology, Aretaieion University Hospital, National and Kapodistrian University of Athens, Athens, GRC
| | - Dimitrios Papakonstantinou
- 3rd Department of Surgery, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, GRC
| | - Nikolaos Pararas
- 3rd Department of Surgery, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, GRC
| | - Constantinos Nastos
- 3rd Department of Surgery, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, GRC
| | - Despoina Myoteri
- Department of Pathology, Aretaieion University Hospital, National and Kapodistrian University of Athens, Athens, GRC
| | - Emmanuel Pikoulis
- 3rd Department of Surgery, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, GRC
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Ebert MP, Fischbach W, Hollerbach S, Höppner J, Lorenz D, Stahl M, Stuschke M, Pech O, Vanhoefer U, Porschen R. S3-Leitlinie Diagnostik und Therapie der Plattenepithelkarzinome und Adenokarzinome des Ösophagus. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:535-642. [PMID: 38599580 DOI: 10.1055/a-2239-9802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/12/2024]
Affiliation(s)
- Matthias P Ebert
- II. Medizinische Klinik, Medizinische Fakultät Mannheim, Universitätsmedizin, Universität Heidelberg, Mannheim
- DKFZ-Hector Krebsinstitut an der Universitätsmedizin Mannheim, Mannheim
- Molecular Medicine Partnership Unit, EMBL, Heidelberg
| | - Wolfgang Fischbach
- Deutsche Gesellschaft zur Bekämpfung der Krankheiten von Magen, Darm und Leber sowie von Störungen des Stoffwechsels und der Ernährung (Gastro-Liga) e. V., Giessen
| | | | - Jens Höppner
- Klinik für Allgemeine Chirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck
| | - Dietmar Lorenz
- Chirurgische Klinik I, Allgemein-, Viszeral- und Thoraxchirurgie, Klinikum Darmstadt, Darmstadt
| | - Michael Stahl
- Klinik für Internistische Onkologie und onkologische Palliativmedizin, Evang. Huyssensstiftung, Evang. Kliniken Essen-Mitte, Essen
| | - Martin Stuschke
- Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Essen, Essen
| | - Oliver Pech
- Klinik für Gastroenterologie und Interventionelle Endoskopie, Krankenhaus Barmherzige Brüder, Regensburg
| | - Udo Vanhoefer
- Klinik für Hämatologie und Onkologie, Katholisches Marienkrankenhaus, Hamburg
| | - Rainer Porschen
- Gastroenterologische Praxis am Kreiskrankenhaus Osterholz, Osterholz-Scharmbeck
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Liu F, Yang W, He Y, Yang W, Chen L, Xu R, Liu Z, Ke J, Hou B, Zhang L, Lin M, Liang L, Huang Y, Zhang L, Zhang F, Cai F, Xu H, Liu M, Pan Y, Liu Y, He Z, Ke Y. Surgical quality determines the long-term survival superiority of right over left thoracic esophagectomy for localized esophageal squamous cell carcinoma patients: a real-world multicenter study. Int J Surg 2024; 110:675-683. [PMID: 37983771 PMCID: PMC10871567 DOI: 10.1097/js9.0000000000000897] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Accepted: 10/28/2023] [Indexed: 11/22/2023]
Abstract
OBJECTIVE The objective was to compare the long-term overall survival (OS) of right versus left thoracic esophagectomy, and to evaluate whether surgical quality impacts comparison result. BACKGROUND Controversy regarding the optimal thoracic esophagectomy approach persists for esophageal squamous cell carcinoma (ESCC). No study has assessed the effect of surgical quality in comparison between right and left approaches. METHODS The authors consecutively recruited 5556 operable ESCC patients from two high-volume centers in China, of whom 2220 and 3336 received right and left thoracic esophagectomy, respectively. Cumulative sum was used to evaluate the learning curve for operation time of right approach, as the indicator of surgical proficiency. RESULTS With a median follow-up of 83.1 months, right approach, harvesting more lymph nodes, tended to have a better OS than left approach (Mean: 23.8 vs. 16.7 nodes; adjusted hazard ratio (HR)=0.93, 95% CI: 0.85-1.02). Subset analysis by the extent of lymphadenectomy demonstrated that right approach with adequate lymphadenectomy (≥15 nodes) resulted in statistically significant OS benefit compared with left approach (adjusted HR=0.86, 95% CI: 0.77-0.95), but not with limited lymphadenectomy. Subset analysis by surgical proficiency showed that proficient right approach conferred a better OS than left approach (adjusted HR=0.75, 95% CI: 0.64-0.88), but improficient right approach did not have such survival advantage. CONCLUSIONS Surgical quality plays a crucial role in survival comparison between surgical procedures. Right thoracic esophagectomy performed with adequate lymphadenectomy and surgical proficiency, conferring more favorable survival than left approach, should be recommended as the preferred surgical procedure for localized ESCC.
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Affiliation(s)
- Fangfang Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Wenlei Yang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Yu He
- Chinese Preventive Medicine Association, Beijing, People's Republic of China
- Department of Non-communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK
| | - Wei Yang
- Cancer Hospital of Shantou University Medical College, Guangdong Province, People's Republic of China
| | - Lei Chen
- Cancer Hospital of Shantou University Medical College, Guangdong Province, People's Republic of China
| | - Ruiping Xu
- Anyang Cancer Hospital, Henan Province, People's Republic of China
| | - Zhen Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Ji Ke
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Bolin Hou
- Linkdoc AI Research (LAIR), Beijing, People's Republic of China
| | - Liqun Zhang
- Cancer Hospital of Shantou University Medical College, Guangdong Province, People's Republic of China
| | - Miaoping Lin
- Cancer Hospital of Shantou University Medical College, Guangdong Province, People's Republic of China
| | - Linlin Liang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Yi Huang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Lixin Zhang
- Anyang Cancer Hospital, Henan Province, People's Republic of China
| | - Fan Zhang
- Cancer Hospital of Shantou University Medical College, Guangdong Province, People's Republic of China
| | - Fen Cai
- Cancer Hospital of Shantou University Medical College, Guangdong Province, People's Republic of China
| | - Huawen Xu
- Cancer Hospital of Shantou University Medical College, Guangdong Province, People's Republic of China
| | - Mengfei Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Yaqi Pan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Ying Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Zhonghu He
- State Key Laboratory of Molecular Oncology, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Yang Ke
- State Key Laboratory of Molecular Oncology, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
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Gao D, Ou J, Tan BG, Yu ZY, Li KY, Li R, Zhang XM, Chen TW, Zhou HY. A novel quantitative model based on gross tumor volume corresponding to anatomical distribution measured with multidetector computed tomography to determine the resectability of non‑distant metastatic esophageal squamous cell carcinoma. Oncol Lett 2023; 26:485. [PMID: 37818136 PMCID: PMC10561156 DOI: 10.3892/ol.2023.14072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 09/12/2023] [Indexed: 10/12/2023] Open
Abstract
It is important to accurately determine the resectability of thoracic esophageal squamous cell carcinoma (ESCC) for treatment decision-making. Previous studies have revealed that the CT-derived gross tumor volume (GTV) is associated with the staging of ESCC. The present study aimed to explore whether the anatomical distribution-based GTV of non-distant metastatic thoracic ESCC measured using multidetector computed tomography (MDCT) could quantitatively determine the resectability. For this purpose, 473 consecutive patients with biopsy-confirmed non-distant metastatic thoracic ESCC who underwent contrast-enhanced CT were randomly divided into a training cohort (TC; 376 patients) and validation cohort (VC; 97 patients). GTV was retrospectively measured using MDCT. Univariate and multivariate analyses were performed to identify the determinants of the resectability of ESCC in the TC. Receiver operating characteristic (ROC) analysis was performed to clarify whether anatomical distribution-based GTV could help quantitatively determinate resectability. Unweighted Cohen's Kappa tests in VC were used to assess the performance of the previous models. Univariate analysis demonstrated that sex, anatomic distribution, cT stage, cN stage and GTV were related to the resectability of ESCC in the TC (all P<0.05). Multivariate analysis revealed that GTV [P<0.001; odds ratio (OR) 1.158] and anatomic distribution (P=0.027; OR, 1.924) were independent determinants of resectability. ROC analysis revealed that the GTV cut-offs for the determination of the resectability of the upper, middle and lower thoracic portions were 23.57, 22.89 and 22.58 cm3, respectively, with areas under the ROC curves of >0.9. Unweighted Cohen's Kappa tests revealed an excellent performance of the ROC models in the upper, middle and lower thoracic portions with Cohen k-values of 0.913, 0.879 and 0.871, respectively. On the whole, the present study demonstrated that GTV and the anatomic distribution of non-distant metastatic thoracic ESCC may be independent determinants of resectability, and anatomical distribution-based GTV can effectively be used to quantitatively determine resectability.
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Affiliation(s)
- Dan Gao
- Medical Imaging Key Laboratory of Sichuan Province, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
- Department of Radiology, Qionglai Medical Center Hospital, Chengdu, Sichuan 611530, P.R. China
| | - Jing Ou
- Medical Imaging Key Laboratory of Sichuan Province, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Bang-Guo Tan
- Department of Radiology, Panzhihua Central Hospital, Panzhihua, Sichuan 617067, P.R. China
| | - Zi-Yi Yu
- Medical Imaging Key Laboratory of Sichuan Province, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Ke-Ying Li
- Medical Imaging Key Laboratory of Sichuan Province, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Rui Li
- Medical Imaging Key Laboratory of Sichuan Province, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Xiao-Ming Zhang
- Medical Imaging Key Laboratory of Sichuan Province, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Tian-Wu Chen
- Medical Imaging Key Laboratory of Sichuan Province, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
- Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China
| | - Hai-Ying Zhou
- Medical Imaging Key Laboratory of Sichuan Province, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
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Abou Chaar MK, Godin A, Harmsen WS, Wzientek C, Saddoughi SA, Hallemeier CL, Cassivi SD, Nichols FC, Reisenauer JS, Shen KR, Tapias LF, Wigle DA, Blackmon SH. Determinants of Long-term Survival Decades After Esophagectomy for Esophageal Cancer. Ann Thorac Surg 2023; 116:1036-1044. [PMID: 37353102 DOI: 10.1016/j.athoracsur.2023.05.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 03/26/2023] [Accepted: 05/01/2023] [Indexed: 06/25/2023]
Abstract
BACKGROUND Long-term survival in esophagectomy patients with esophageal cancer is low due to tumor-related characteristics, with few reports of modifiable variables influencing outcome. We identified determinants of overall survival, time to recurrence, and disease-free survival in this patient cohort. METHODS Adult patients who underwent esophagectomy for primary esophageal cancer from January 5, 2000, through December 30, 2010, at our institution were identified. Univariate Cox models and multivariable logistic regression analyses were used to identify associations between modifiable and unmodifiable patient and clinical variables and outcome of survival for the total cohort and a subgroup with locally advanced disease. RESULTS We identified 870 patients with esophageal cancer who underwent esophagectomy. The median follow-up time was 15 years, and the 15-year overall survival rate was 25.2%, survival free of recurrence was 57.96%, and disease-free survival was 24.21%. Decreased overall survival was associated with the following unmodifiable variables: older age, male sex, active smoking status, history of coronary artery disease, advanced clinical stage, and tumor location. Decreased overall survival was associated with the following modifiable variables: use of neoadjuvant therapy, advanced pathologic stage, resection margin positivity, surgical reintervention, and blood transfusion requirement. The overall survival probability 6 years after esophagectomy was 0.920 (95% CI, 0.895-0.947), and time-to-recurrence probability was 0.988 (95% CI, 0.976-1.000), with a total of 17 recurrences and 201 deaths. CONCLUSIONS Once patients survive 5 years, recurrence is rare. Long-term survival can be achieved in high-volume centers adhering to National Comprehensive Cancer Network guidelines using multidisciplinary care teams that is double what has been previously reported in the literature from national databases.
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Affiliation(s)
- Mohamad K Abou Chaar
- Department of Surgery, Mayo Clinic School of Graduate Medical Education, Mayo Clinic College of Medicine and Science, Rochester, Minnesota
| | - Anny Godin
- Division of Thoracic Surgery, Mayo Clinic, Rochester, Minnesota
| | - William S Harmsen
- Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, Minnesota
| | - Camryn Wzientek
- Division of Thoracic Surgery, Mayo Clinic, Rochester, Minnesota
| | | | | | | | | | | | - K Robert Shen
- Division of Thoracic Surgery, Mayo Clinic, Rochester, Minnesota
| | - Luis F Tapias
- Division of Thoracic Surgery, Mayo Clinic, Rochester, Minnesota
| | - Dennis A Wigle
- Division of Thoracic Surgery, Mayo Clinic, Rochester, Minnesota
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9
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Huang Y, Liu F, Xu R, Zhou F, Yang W, He Y, Liu Z, Hou B, Liang L, Zhang L, Liu M, Pan Y, Liu Y, He Z, Ke Y. Postoperative serum squamous cell carcinoma antigen and carcinoembryonic antigen predict overall survival in surgical patients with esophageal squamous cell carcinoma. Front Oncol 2023; 13:1263990. [PMID: 37810977 PMCID: PMC10556684 DOI: 10.3389/fonc.2023.1263990] [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: 07/20/2023] [Accepted: 09/06/2023] [Indexed: 10/10/2023] Open
Abstract
Background Tumor markers are routinely used in clinical practice. However, for resectable patients with esophageal squamous cell carcinoma (ESCC), they are applied infrequently as their prognostic significance is incompletely understood. Methods This historical cohort study included 2769 patients with resected ESCC from 2011 to 2018 in a high-risk area in northern China. Their clinical data were extracted from the Electronic Medical Record. Survival analysis of eight common tumor markers was performed with multivariable Cox proportional hazards regressions. Results With a median follow-up of 39.5 months, 901 deaths occurred. Among the eight target markers, elevated postoperative serum SCC (Squamous cell carcinoma antigen) and CEA (Carcinoembryonic antigen) predicted poor overall survival (SCC HRadjusted: 2.67, 95% CI: 1.70-4.17; CEA HRadjusted: 2.36, 95% CI: 1.14-4.86). In contrast, preoperative levels were not significantly associated with survival. Stratified analysis also demonstrated poorer survival in seropositive groups of postoperative SCC and CEA within each TNM stage. The above associations were generally robust using different quantiles of concentrations above the upper limit of the clinical normal range as alternative cutoffs. Regarding temporal trends of serum levels, SCC and CEA were similar. Their concentrations fell rapidly after surgery and thereafter remained relatively stable. Conclusion Postoperative serum SCC and CEA levels predict the overall survival of ESCC surgical patients. More importance should be attached to the use of these markers in clinical applications.
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Affiliation(s)
- Yi Huang
- State Key Laboratory of Molecular Oncology, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, China
| | - Fangfang Liu
- State Key Laboratory of Molecular Oncology, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, China
| | | | | | - Wenlei Yang
- State Key Laboratory of Molecular Oncology, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yu He
- Chinese Preventive Medicine Association, Beijing, China
| | - Zhen Liu
- State Key Laboratory of Molecular Oncology, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, China
| | - Bolin Hou
- Linkdoc AI Research (LAIR), Beijing, China
| | - Linlin Liang
- State Key Laboratory of Molecular Oncology, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, China
| | | | - Mengfei Liu
- State Key Laboratory of Molecular Oncology, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yaqi Pan
- State Key Laboratory of Molecular Oncology, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, China
| | - Ying Liu
- State Key Laboratory of Molecular Oncology, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, China
| | - Zhonghu He
- State Key Laboratory of Molecular Oncology, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yang Ke
- State Key Laboratory of Molecular Oncology, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, China
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10
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S3-Leitlinie Diagnostik und Therapie der Plattenepithelkarzinome und Adenokarzinome des Ösophagus. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:e209-e307. [PMID: 37285869 DOI: 10.1055/a-1771-6953] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
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11
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Liu F, Yang W, Yang W, Xu R, Chen L, He Y, Liu Z, Zhou F, Hou B, Zhang L, Zhang L, Zhang F, Cai F, Xu H, Lin M, Liu M, Pan Y, Liu Y, Hu Z, Chen H, He Z, Ke Y. Minimally Invasive or Open Esophagectomy for Treatment of Resectable Esophageal Squamous Cell Carcinoma? Answer From a Real-world Multicenter Study. Ann Surg 2023; 277:e777-e784. [PMID: 35129490 DOI: 10.1097/sla.0000000000005296] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVE To evaluate the long-term and short-term outcomes of MIE compared with OE in localized ESCC patients in real-world settings. BACKGROUND MIE is an alternative to OE, despite the limited evidence regarding its effect on long-term survival. METHODS We recruited 5822 consecutive patients with resectable ESCC in 2 typical high-volume centers in southern and northern China, 1453 of whom underwent MIE. Propensity score-based overlap weighted regression adjusted for multifaceted confounding factors was used to compare outcomes in the MIE and OE groups. RESULTS Five-year OS was 62.7% in the MIE group and 57.7% in the OE group. The overlap weighted Cox regression showed slightly better OS in the MIE group (hazard ratio 0.93, 95% confidence interval: 0.82-1.06). Although duration of surgery was longer and treatment cost higher in the MIE group than in the OE group, the number of lymph nodes harvested was larger, the proportion of intraoperative blood transfusions lower, and postoperative complications less in the MIE group. 30-day (risk ratio [RR] 0.77, 0.381.55) and 90-day (RR 0.79, 0.46-1.35) mortality were lower in the MIE group versus the OE group, although not statistically significant. These findings were consistent across different analytic approaches and subgroups, notably in the subset of ESCC patients with large tumors. CONCLUSIONS MIE can be performed safely with OS comparable to OE for patients with localized ESCC, indicating MIE may be recommended as the primary surgical approach for resectable ESCC in health facilities with requisite technical capacity.
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Affiliation(s)
- Fangfang Liu
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Wenlei Yang
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Wei Yang
- Cancer Hospital of Shantou University Medical College, Guangdong Province, People's Republic of China
| | - Ruiping Xu
- Anyang Cancer Hospital, Henan Province, People's Republic of China
| | - Lei Chen
- Cancer Hospital of Shantou University Medical College, Guangdong Province, People's Republic of China
| | - Yu He
- Department of Non-communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK
| | - Zhen Liu
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Fuyou Zhou
- Anyang Cancer Hospital, Henan Province, People's Republic of China
| | - Bolin Hou
- Linkdoc AI Research (LAIR), Beijing, People's Republic of China
| | - Liqun Zhang
- Cancer Hospital of Shantou University Medical College, Guangdong Province, People's Republic of China
| | - Lixin Zhang
- Anyang Cancer Hospital, Henan Province, People's Republic of China
| | - Fan Zhang
- Cancer Hospital of Shantou University Medical College, Guangdong Province, People's Republic of China
| | - Fen Cai
- Cancer Hospital of Shantou University Medical College, Guangdong Province, People's Republic of China
| | - Huawen Xu
- Cancer Hospital of Shantou University Medical College, Guangdong Province, People's Republic of China
| | - Miaoping Lin
- Cancer Hospital of Shantou University Medical College, Guangdong Province, People's Republic of China
| | - Mengfei Liu
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Yaqi Pan
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Ying Liu
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Zhe Hu
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Huanyu Chen
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Zhonghu He
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Yang Ke
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
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Yang J, Huang A, Yang K, Jiang K. Neoadjuvant chemoradiotherapy plus tislelizumab followed by surgery for esophageal carcinoma (CRISEC study): the protocol of a prospective, single-arm, phase II trial. BMC Cancer 2023; 23:249. [PMID: 36922805 PMCID: PMC10015937 DOI: 10.1186/s12885-023-10687-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Accepted: 02/27/2023] [Indexed: 03/17/2023] Open
Abstract
BACKGROUND The failure rate after neoadjuvant chemoradiotherapy followed by surgery is approximately 34.6%-48% for resectable esophageal carcinoma. Pathologic complete response after neoadjuvant chemoradiotherapy is an important factor in predicting lower recurrence and better survival. Whether the sequential addition of immunotherapy to neoadjuvant chemoradiotherapy will be beneficial to improving the pathologic complete response rate is unknown. METHODS Patients with pathologically confirmed thoracic esophageal squamous cell carcinoma and at clinical T1-2N1-3M0 or T3-4aN0-3M0 (stage II-IVA) according to the eighth edition of American Joint Committee on Cancer staging will be allocated to receive neoadjuvant radiotherapy (41.4 Gy with 23 fractions to planning target volume) with concurrent chemotherapy (albumin-bound paclitaxel, 100 mg/m2, once weekly for five weeks; carboplatin, area under the curve of 2 mg/mL/min, once weekly for five weeks) plus tislelizumab monotherapy sequentially (200 mg every three weeks for three cycles, beginning from the first to the 14th day after the end of radiotherapy). Then, subtotal esophagectomy with two-field lymphadenectomy, including the whole mediastinum and abdomen, will be performed. The primary endpoint for this study is the pathologic complete response rate after neoadjuvant chemoradiotherapy plus tislelizumab. DISCUSSION The optimal timing of the combination of immunotherapy and neoadjuvant chemoradiotherapy in esophageal carcinoma is not determined. The results of this phase II trial will be helpful to clarify the safety and efficacy of the sequential addition of tislelizumab after neoadjuvant chemoradiotherapy for locally advanced resectable esophageal carcinoma. TRIAL REGISTRATION This study was approved on January 26, 2021 and retrospectively registered with ClinicalTrials.gov ( NCT04776590 ) on March 1, 2021.
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Affiliation(s)
- Jinsong Yang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430023, China
| | - Ai Huang
- Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Kunyu Yang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430023, China.
| | - Ke Jiang
- Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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13
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Yang W, Liu F, Xu R, Yang W, He Y, Liu Z, Zhou F, Heng F, Hou B, Zhang L, Chen L, Zhang F, Cai F, Xu H, Lin M, Liu M, Pan Y, Liu Y, Hu Z, Chen H, He Z, Ke Y. Is Adjuvant Therapy a Better Option for Esophageal Squamous Cell Carcinoma Patients Treated With Esophagectomy? A Prognosis Prediction Model Based on Multicenter Real-World Data. Ann Surg 2023; 277:e61-e69. [PMID: 34091512 DOI: 10.1097/sla.0000000000004958] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVE To construct a prediction model for more precise evaluation of prognosis which will allow personalized treatment recommendations for adjuvant therapy in patients following resection of ESCC. BACKGROUND Marked heterogeneity of patient prognosis and limited evidence regarding survival benefit of various adjuvant therapy regimens pose challenges in the clinical treatment of ESCC. METHODS Based on comprehensive clinical data obtained from 4129 consecutive patients with resected ESCC in a high-risk region in China, we identified predictors for overall survival through a 2-phase selection based on Cox proportional hazard regression and minimization of Akaike information criterion. The model was internally validated using bootstrapping and externally validated in 1815 patients from a non-high-risk region in China. RESULTS The final model incorporates 9 variables: age, sex, primary site, T stage, N stage, number of lymph nodes harvested, tumor size, adjuvant treatment, and hemoglobin level. A significant interaction was also observed between N stage and adjuvant treatment. N1+ stage patients were likely to benefit from addition of adjuvant therapy as opposed to surgery alone, but adjuvant therapy did not improve overall survival for N0 stage patients. The C -index of the model was 0.729 in the training cohort, 0.723 after bootstrapping, and 0.695 in the external validation cohort. This model outperformed the seventh edition American Joint Committee on Cancer staging system in prognostic prediction and risk stratification. CONCLUSIONS The prediction model constructed in this study may facilitate precise prediction of survival and inform decision-making about adjuvant therapy according to N stage.
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Affiliation(s)
- Wenlei Yang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Fangfang Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Ruiping Xu
- Anyang Cancer Hospital, Anyang, Henan Province, People's Republic of China
| | - Wei Yang
- Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, People's Republic of China
| | - Yu He
- Department of Non-communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK
| | - Zhen Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Fuyou Zhou
- Anyang Cancer Hospital, Anyang, Henan Province, People's Republic of China
| | - Fanxiu Heng
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of information Technology Service, Peking University Cancer Hospital & institute, Beijing, People's Republic of China
| | - Bolin Hou
- Linkdoc AI Research (LAIR), Beijing, People's Republic of China
| | - Lixin Zhang
- Anyang Cancer Hospital, Anyang, Henan Province, People's Republic of China
| | - Lei Chen
- Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, People's Republic of China
| | - Fan Zhang
- Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, People's Republic of China
| | - Fen Cai
- Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, People's Republic of China
| | - Huawen Xu
- Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, People's Republic of China
| | - Miaoping Lin
- Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, People's Republic of China
| | - Mengfei Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Yaqi Pan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Ying Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Zhe Hu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Huanyu Chen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Zhonghu He
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Yang Ke
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
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Nachiappan M, Kapoor VK. Esophageal Cancer: Whether and What Before or After Surgery? Indian J Surg Oncol 2022; 13:880-887. [PMID: 36687238 PMCID: PMC9845445 DOI: 10.1007/s13193-022-01655-y] [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: 01/07/2022] [Accepted: 09/19/2022] [Indexed: 01/25/2023] Open
Abstract
Esophageal cancer is the eighth most common cancer and the sixth most common cause of cancer-related mortality worldwide. Surgery has been the mainstay of the treatment of esophageal cancer. However, given the dismal survival with surgery alone, other modalities, e.g., chemotherapy (CT) and radiotherapy (RT), have been used for the management of these cancers. This review aims to look at the evolution of multi-modality management of esophageal cancer and tries to answer certain questions pertaining to the management of these cancers.
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Affiliation(s)
- Murugappan Nachiappan
- Department of Surgical Gastroenterology, Sahasra Hospitals, Jayanagar, Bangalore Karnataka, 560082 India
| | - V. K. Kapoor
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Mahatma Gandhi Medical College & Hospital (MGMCH), Jaipur Rajasthan, 302022 India
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15
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Devaud N, Carroll P. Ongoing Controversies in Esophageal Cancer II. Thorac Surg Clin 2022; 32:553-563. [DOI: 10.1016/j.thorsurg.2022.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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16
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Marom G. Esophageal Cancer Staging. Thorac Surg Clin 2022; 32:437-445. [DOI: 10.1016/j.thorsurg.2022.06.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Ahmed OT, Nam GH, Shui Y, Villavicencio J, Vaziri H. Case Series of SMARCA4-Deficient Undifferentiated Esophageal Carcinoma. Cureus 2022; 14:e30874. [DOI: 10.7759/cureus.30874] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/29/2022] [Indexed: 11/06/2022] Open
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18
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Liang L, Liu F, Yang W, Yang W, Chen L, He Y, Liu Z, Zhang L, Zhang F, Cai F, Xu H, Lin M, Liu M, Pan Y, Liu Y, Hu Z, Chen H, He Z, Ke Y. Combined Mean Corpuscular Hemoglobin, Fibrinogen, and Albumin (MF-A) Is a Novel Prognostic Marker in Patients with Resectable Esophageal Squamous Cell Carcinoma. Ann Surg Oncol 2022; 29:5626-5633. [PMID: 35181817 DOI: 10.1245/s10434-022-11415-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Accepted: 01/18/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND The aim was to systematically select blood markers routinely tested in clinical settings, which are independently associated with overall survival (OS) and are able to stratify prognosis of esophageal squamous cell carcinoma (ESCC) patients undergoing esophagectomy. METHODS We selected optimal blood markers for prognostic stratification from 60 candidates in a clinical cohort of 1819 consecutive patients with resectable ESCC in China. Selection was carried out using two-step multivariable Cox proportional hazards regression adjusted for multifaceted confounders. A composite index was developed by multiplying risk factors and dividing them by protective factors. RESULTS With a median follow-up of 48.07 months, 641 deaths occurred in the 1819 patients and the 5-year OS was 56.30%. Two risk factors (mean corpuscular hemoglobin, fibrinogen) and a protective factor (albumin), all dichotomized and assigned values 1 and 2, were used to construct the composite index marker "MF-A". Three risk groups were created based on the MF-A score including low- (0.5), moderate- (1), and high-risk groups (2 and 4). Compared with patients in the low-risk group (1184/1778, 66.59%), those in the moderate- (488, 27.45%), and high-risk (106, 5.96%) groups were at elevated risk of death (adjusted HR: 1.32, 95% CI: 1.11-1.57; adjusted HR: 2.08, 95% CI: 1.56-2.75; Ptrend < 10-7). Within each TNM stage grouping, OS also trended to be significantly worse as the MF-A score increased. CONCLUSIONS "MF-A" is a novel independent predictor which may be used to estimate and stratify prognosis for ESCC patients undergoing esophagectomy.
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Affiliation(s)
- Linlin Liang
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Fangfang Liu
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Wenlei Yang
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Wei Yang
- Cancer Hospital of Shantou University Medical College, Shantou City, People's Republic of China
| | - Lei Chen
- Cancer Hospital of Shantou University Medical College, Shantou City, People's Republic of China
| | - Yu He
- Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK
| | - Zhen Liu
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Liqun Zhang
- Cancer Hospital of Shantou University Medical College, Shantou City, People's Republic of China
| | - Fan Zhang
- Cancer Hospital of Shantou University Medical College, Shantou City, People's Republic of China
| | - Fen Cai
- Cancer Hospital of Shantou University Medical College, Shantou City, People's Republic of China
| | - Huawen Xu
- Cancer Hospital of Shantou University Medical College, Shantou City, People's Republic of China
| | - Miaoping Lin
- Cancer Hospital of Shantou University Medical College, Shantou City, People's Republic of China
| | - Mengfei Liu
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Yaqi Pan
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Ying Liu
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Zhe Hu
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Huanyu Chen
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Zhonghu He
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
| | - Yang Ke
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China
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Unasa H, Hutchinson A, DeSouza S, Poole L, Knudsen C, Hill A, MacCormick AD. Identifying data‐fields for a gastrointestinal cancer clinical quality and safety registry: a systematic literature review. ANZ J Surg 2022; 92:2881-2888. [DOI: 10.1111/ans.17984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 07/05/2022] [Accepted: 07/28/2022] [Indexed: 11/26/2022]
Affiliation(s)
- Hanson Unasa
- Department of Surgery University of Auckland Auckland New Zealand
| | | | - Steve DeSouza
- Department of Surgery University of Auckland Auckland New Zealand
| | - Lydia Poole
- Department of Surgery University of Auckland Auckland New Zealand
| | - Caroline Knudsen
- Department of Surgery University of Auckland Auckland New Zealand
| | - Andrew Hill
- Department of Surgery University of Auckland Auckland New Zealand
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20
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The Clinical Application Value of the Prognostic Nutritional Index for the Overall Survival Prognosis of Patients with Esophageal Cancer: A Robust Real-World Observational Study in China. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:3889588. [PMID: 35872955 PMCID: PMC9300322 DOI: 10.1155/2022/3889588] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 06/27/2022] [Indexed: 12/24/2022]
Abstract
Esophageal cancer is a kind of cancer with high morbidity and mortality, which is accompanied by a profound poor prognosis. A prognostic nutritional index, based on serum albumin levels and peripheral lymphocyte count, has been confirmed to be significantly associated with various cancers. This study was aimed at exploring the prognostic significance of PNI in the overall survival prognosis of patients with esophageal cancer. As a real-world study based on the big database, clinical data of 2661 patients with esophageal cancer were evaluated retrospectively, and the individuals were randomly divided into training and testing cohorts. In these two cohorts, patients are classified into a high-risk group (PNI < 49) and a low-risk group (PNI ≥ 49). Univariate and multivariate analyses were performed to analyze the independent risk factors for the prognosis of esophageal cancer patients by using the Cox proportional hazards regression model. In this study, whether in the training cohort or the testing cohort, according to the univariate analysis, gender, tumor size, tumor grade, T stage, N stage, M stage, TNM stage, and PNI were significantly correlated with overall survival. Furthermore, the multivariate analysis showed that gender, T stage, N stage, M stage, TNM stage, and PNI were independent prognostic risk factors for esophageal cancer. PNI can be regarded as an independent prognostic factor combined with gender, T stage, N stage, M stage, and TNM stage, and it might be a novel reliable biomarker for esophageal cancer.
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21
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Lee YC, Lin CH, Chang WL, Lin WD, Pan JK, Wang WJ, Su BC, Chung HH, Tsai CH, Lin FC, Wang WC, Lu PJ. Concurrent Chemoradiotherapy-Driven Cell Plasticity by miR-200 Family Implicates the Therapeutic Response of Esophageal Squamous Cell Carcinoma. Int J Mol Sci 2022; 23:4367. [PMID: 35457185 PMCID: PMC9030842 DOI: 10.3390/ijms23084367] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 04/09/2022] [Accepted: 04/12/2022] [Indexed: 12/10/2022] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is a common and fatal malignancy with an increasing incidence worldwide. Over the past decade, concurrent chemoradiotherapy (CCRT) with or without surgery is an emerging therapeutic approach for locally advanced ESCC. Unfortunately, many patients exhibit poor response or develop acquired resistance to CCRT. Once resistance occurs, the overall survival rate drops down rapidly and without proper further treatment options, poses a critical clinical challenge for ESCC therapy. Here, we utilized lab-created CCRT-resistant cells as a preclinical study model to investigate the association of chemoradioresistantresistance with miRNA-mediated cell plasticity alteration, and to determine whether reversing EMT status can re-sensitize refractory cancer cells to CCRT response. During the CCRT treatment course, refractory cancer cells adopted the conversion of epithelial to mesenchymal phenotype; additionally, miR-200 family members were found significantly down-regulated in CCRT resistance cells by miRNA microarray screening. Down-regulated miR-200 family in CCRT resistance cells suppressed E-cadherin expression through snail and slug, and accompany with an increase in N-cadherin. Rescuing expressions of miR-200 family members in CCRT resistance cells, particularly in miR-200b and miR-200c, could convert cells to epithelial phenotype by increasing E-cadherin expression and sensitize cells to CCRT treatment. Conversely, the suppression of miR-200b and miR-200c in ESCC cells attenuated E-cadherin, and that converted cells to mesenchymal type by elevating N-cadherin expression, and impaired cell sensitivity to CCRT treatment. Moreover, the results of ESCC specimens staining established the clinical relevance that higher N-cadherin expression levels associate with the poor CCRT response outcome in ESCC patients. Conclusively, miR-200b and miR-200c can modulate the conversion of epithelial-mesenchymal phenotype in ESCC, and thereby altering the response of cells to CCRT treatment. Targeting epithelial-mesenchymal conversion in acquired CCRT resistance may be a potential therapeutic option for ESCC patients.
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Affiliation(s)
- Yu-Cheng Lee
- Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan;
| | - Cheng-Han Lin
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, No. 35 Xiaodong Rd., Tainan 704, Taiwan; (C.-H.L.); (W.-L.C.); (W.-D.L.); (J.-K.P.); (C.-H.T.)
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung 840, Taiwan
| | - Wei-Lun Chang
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, No. 35 Xiaodong Rd., Tainan 704, Taiwan; (C.-H.L.); (W.-L.C.); (W.-D.L.); (J.-K.P.); (C.-H.T.)
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 704, Taiwan
| | - Wen-Der Lin
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, No. 35 Xiaodong Rd., Tainan 704, Taiwan; (C.-H.L.); (W.-L.C.); (W.-D.L.); (J.-K.P.); (C.-H.T.)
| | - Jhih-Kai Pan
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, No. 35 Xiaodong Rd., Tainan 704, Taiwan; (C.-H.L.); (W.-L.C.); (W.-D.L.); (J.-K.P.); (C.-H.T.)
| | - Wei-Jan Wang
- Department of Biological Science and Technology, Research Center for Cancer Biology, China Medical University, Taichung 404, Taiwan;
| | - Bor-Chyuan Su
- Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan;
| | - Hsien-Hui Chung
- Preventive Medicine Program, Center for General Education, Chung Yuan Christian University, Taoyuan City 320, Taiwan;
- Department of Pharmacy and Master Program, College of Pharmacy and Health Care, Tajen University, Pingtung 907, Taiwan
| | - Chen-Hsun Tsai
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, No. 35 Xiaodong Rd., Tainan 704, Taiwan; (C.-H.L.); (W.-L.C.); (W.-D.L.); (J.-K.P.); (C.-H.T.)
| | - Forn-Chia Lin
- Department of Radiation Oncology, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan 704, Taiwan;
| | - Wen-Ching Wang
- Department of Surgery, Chi Mei Medical Center, No. 901, Zhonghua Rd., Yongkang Dist., Tainan 710, Taiwan
| | - Pei-Jung Lu
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, No. 35 Xiaodong Rd., Tainan 704, Taiwan; (C.-H.L.); (W.-L.C.); (W.-D.L.); (J.-K.P.); (C.-H.T.)
- Department of Clinical Medicine Research, National Cheng Kung University Hospital, Tainan 704, Taiwan
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22
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Ma LX, Panov ED, Allen MJ, Darling GE, Yeung JC, Swallow CJ, Brar SS, Wong RK, Veit-Haibach P, Kalimuthu SN, Chen EX, Jang RW, Elimova E. Preoperative and Postoperative Approaches to Gastroesophageal Cancer: What is All the Fuss About. J Natl Compr Canc Netw 2022; 20:193-202. [PMID: 35130503 DOI: 10.6004/jnccn.2021.7118] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 11/30/2021] [Indexed: 11/17/2022]
Abstract
Gastroesophageal cancers carry poor prognoses, and are a leading cause of cancer-related morbidity and mortality worldwide. Even in those with resectable disease, more than half of patients treated with surgery alone experience disease recurrence. Multimodality approaches using preoperative and postoperative chemotherapy and/or radiotherapy have been established, resulting in incremental improvements in outcomes. Globally, there is no standardized approach, and treatment varies with geographic location. The question remains of how to select the optimal perioperative treatment that will maximize benefit for patients while avoiding toxicities from unnecessary therapies. This article reviews currently available evidence supporting preoperative and postoperative therapy in gastroesophageal cancers, with an emphasis on recent practice-changing trials and ongoing areas of investigation, including the role of immune checkpoint inhibition and biomarker-guided treatment.
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Affiliation(s)
- Lucy X Ma
- Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre
| | - Elan D Panov
- Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre
| | - Michael J Allen
- Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre
| | - Gail E Darling
- Division of Thoracic Surgery, Department of Surgery, Toronto General Hospital
| | - Jonathan C Yeung
- Division of Thoracic Surgery, Department of Surgery, Toronto General Hospital
| | - Carol J Swallow
- Department of Surgical Oncology, Princess Margaret Cancer Centre
| | - Savtaj S Brar
- Department of Surgical Oncology, Princess Margaret Cancer Centre
| | - Rebecca K Wong
- Department of Radiation Oncology, Princess Margaret Cancer Centre; and
| | | | - Sangeetha N Kalimuthu
- Department of Pathology, Laboratory Medicine Program, University Health Network, University of Toronto, Toronto, Canada
| | - Eric X Chen
- Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre
| | - Raymond W Jang
- Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre
| | - Elena Elimova
- Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre
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23
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Shim YM, Yun J, Im YH, Lee G, Kang D, Cho J, Kim K, Park SI, Na KJ, Kim SB, Zo JI. The efficacy of adjuvant chemotherapy with capecitabine and cisplatin after surgery in locally advanced esophageal squamous cell carcinoma: a multicenter randomized phase III trial. Dis Esophagus 2022; 35:6307360. [PMID: 34155501 DOI: 10.1093/dote/doab040] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 05/16/2021] [Accepted: 05/30/2021] [Indexed: 12/11/2022]
Abstract
There is limited evidence for the effectiveness of adjuvant chemotherapy in esophageal squamous cell carcinoma (ESCC). This study aimed to assess whether adjuvant capecitabine and cisplatin improve survival compared to surgery alone among patients with locally advanced ESCC. This is a multicenter randomized controlled trial. Patients were eligible if they underwent curative resection for ESCC staged T2-4 or N1 and M0 according to the TNM cancer staging system sixth edition. The intervention group received four cycles of adjuvant chemotherapy (capecitabine: 1,000 mg/m 2 b.i.d for 14 days, and intravenous cisplatin: 75 mg/m2 at day 1, every 3 weeks). A total of 136 patients were randomly assigned to either the adjuvant chemotherapy group (n = 68) or surgery-alone group (n = 68). Seven patients who rejected chemotherapy after randomization were excluded from the final analysis. The cumulative incidence of recurrence within 18 months after surgery was significantly lower in the adjuvant chemotherapy group than in the surgery-alone group (hazard ratio [HR]: 0.49; 95% confidence interval (CI): 0.25-0.95]. However, the 5- and 10-year disease-free survival did not differ between treatment groups (HR: 0.84; 95% CI: 0.53-1.34 and HR: 0.76; 95% CI: 0.50-1.18, respectively). Adjuvant chemotherapy after curative resection in patients with locally advanced ESCC reduced early recurrence but had no statistically significant increase in the long-term disease-free survival. Due to the limited sample size of this study, additional randomized controlled trials with larger sample sizes are necessary.
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Affiliation(s)
- Young Mog Shim
- Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.,Patient-Centered Outcomes Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jeonghee Yun
- Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Young-Hyuck Im
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Genehee Lee
- Patient-Centered Outcomes Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.,Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea
| | - Danbee Kang
- Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea.,Center for Clinical Epidemiology, Samsung Medical Center, Seoul, South Korea
| | - Juhee Cho
- Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea.,Center for Clinical Epidemiology, Samsung Medical Center, Seoul, South Korea.,Departments of Epidemiology and Health, Behavior, and Society, Baltimore, MD, USA
| | - Kwhanmien Kim
- Seoul National University Bundang Hospital and Seoul National University College of Medicine, Seongnam, South Korea
| | - Seung-Il Park
- Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Kook Joo Na
- Department of Thoracic and Cardiovascular Surgery, Chonnam National University Hwasun Hospital, Chonnam National University School of Medicine, Hwasun, South Korea
| | - Sung-Bae Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jae Ill Zo
- Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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24
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Impact of CT-assessed changes in tumor size after neoadjuvant chemotherapy on pathological response and survival of patients with esophageal squamous cell carcinoma. Langenbecks Arch Surg 2022; 407:965-974. [PMID: 34989856 DOI: 10.1007/s00423-022-02430-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 01/01/2022] [Indexed: 12/09/2022]
Abstract
PURPOSE Neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for advanced esophageal squamous cell carcinoma (ESCC) in Japan. Computed tomography (CT) is usually used to assess the therapeutic effect of NAC; however, there are no reliable criteria for predicting pathological response or patient prognosis. METHODS We included 84 patients who underwent esophagectomy between January 2009 and December 2018 and retrospectively reviewed their CT scans performed before and after NAC. The reduction rate of the largest tumor area (TA), long diameter (LD), and short diameter (SD) were measured on a transverse CT image. The pathological response and cutoff values were calculated using the receiver operating characteristic curve, and the most suitable ones for determining the effect were examined. RESULTS The areas under the curve for predicting responders to NAC based on the reduction rate of the TA, LD, and SD were 0.755, 0.761, and 0.781, respectively. The optimal cutoff value of the SD reduction rate for predicting responders to NAC was 22%. An SD reduction ≥ 22% was an independent prognostic factor for overall survival in univariate (p = 0.005, hazard ratio [HR] = 2.755) and multivariate analyses (p = 0.030 HR 2.690). Furthermore, an SD reduction of ≥ 22% was also an independent prognostic factor for relapse-free survival in the univariate (p = 0.007, HR = 2.491) and multivariate analyses (p = 0.007, HR = 0.030). CONCLUSIONS The reduction rate of the tumor SD is a simple predictor of pathological response and patient prognosis.
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25
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Peng Z, Liu XY, Cheng Z, Kai W, Song Z. Comprehensive analysis of a new immune-related prognostic signature for esophageal cancer and its correlation with infiltrating immune cells and target genes. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1576. [PMID: 34790782 PMCID: PMC8576727 DOI: 10.21037/atm-21-4756] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 09/24/2021] [Indexed: 12/24/2022]
Abstract
Background The incidence of esophageal cancer (ESCA) is increasing rapidly, and the 5-year survival rate is less than 20%. This study provides new ideas for clinical treatment by establishing a prognostic signature composed of immune-related genes (IRGs), and fully analyzing its relationship with target genes and the tumor microenvironment (TME). Methods We downloaded the ESCA expression matrix and clinical information from The Cancer Genome Atlas (TCGA) database. Differential expression genes (DEGs) were identified with the edgeR package and crossed with the IRGs we obtained from the ImmPort database to obtain differential IRGs (DEIRGs). The prognostic signature was then obtained through univariate Cox, LASSO-Cox, and multivariate Cox analyses. The receiver operating characteristic (ROC) curve was used to evaluate the prediction effect of the model. The immune cell infiltration abundance obtained by ssGSEA and therapeutic target genes was used to perform sufficient correlation analysis with the obtained prognostic signature and related genes. Results A total of 173 samples were obtained from TCGA database, including 162 tumor and 11 normal samples. The 3,033 differential genes were used to obtain 254 DEIRGs by intersections with 2,483 IRGs (IRGs) obtained from the ImmPort Database. Finally, multivariate Cox regression analysis identified eight prognostic DEIRGs and established a new prognostic signature (HR: 2.49, 95% CI: 1.68–3.67; P<0.001). Based on the expression of the eight genes, the cohort was then divided into high and low risk groups and Kaplan-Meier (K-M) curves were plotted with the log-rank test P<0.0001 and 1-, 3-year area under the curve (AUC) >0.7. The K-M curves grouped according to high and low risks performed well in the two subgroup validation cohorts, with log-rank test P<0.05. There were differences in the degree of infiltration of 16 kinds of immune cells in tumor and normal samples, and the infiltration abundance of 12 kinds of immune cells was different in the high and low-risk groups. Conclusions An effective and validated prognostic signature composed of IRGs was established and had a strong correlation with immune cells and target genes of drug therapy.
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Affiliation(s)
- Zhang Peng
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xin-Yuan Liu
- School of Basic Medical Sciences, Henan University, Kaifeng, China
| | - Zeng Cheng
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Wu Kai
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhao Song
- Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Junttila A, Helminen O, Mrena J, Sihvo E. Exercise capacity in the stair-climbing test predicts outcomes of operable esophageal cancer in minimally invasive era. Eur J Surg Oncol 2021; 48:589-596. [PMID: 34740478 DOI: 10.1016/j.ejso.2021.10.024] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 10/05/2021] [Accepted: 10/25/2021] [Indexed: 12/17/2022] Open
Abstract
INTRODUCTION The risk of complications after esophagectomy highlights the need for careful preoperative assessment. Aim was to assess whether stair-climbing test (SCT) could predict outcomes of patients with operable esophageal cancer in minimally invasive era. MATERIALS AND METHODS Patients with esophageal cancer were evaluated for surgical treatment in Central Finland Central Hospital from 2012 to March 2021. Of evaluated 162 patients, 138 were scheduled to eventually undergo surgery. The exercise capacity was evaluated with symptom limited SCT. Patients were divided into four study groups on intent-to-treat basis: surgery and the SCT >14 m (Group 1), surgery and the SCT <11 m (Group 2), non-surgical therapy and the SCT <11 m (Group 3) and non-surgical therapy and the SCT >14 m (Group 4). Results were adjusted for confounders. RESULTS Major complication rate was 10.1% vs 40.0% between Group 1 and 2 (p = 0.006), and 90-day mortality 0% vs 20.0% (p < 0.001). Overall survival rates in Groups 1-4 at 1-year were 92.3% vs 72.2% vs 46.8% vs 81.8%, at 3-year 68.5% vs 52.7% vs 15.6% vs 27.3% and at 5-year 58.7% vs 39.5% vs 0% vs 0%, respectively (p < 0.001). In adjusted analysis when compared to Group 1, other groups had increased 5-year mortality hazard (Group 2 HR 2.88 (95% CI 1.25-6.63), Group 3 HR 15.6 (95% CI 5.57-43.5) and Group 4 HR 5.35 (95% CI 2.08-13.7)). CONCLUSION Exercise capacity measured with SCT in esophageal cancer patients is a strong predictor of complications and survival, and is a potential parameter to be included in any risk or prognostic models.
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Affiliation(s)
- Anna Junttila
- Department of Surgery, Central Finland Central Hospital, Jyväskylä, Finland.
| | - Olli Helminen
- Department of Surgery, Central Finland Central Hospital, Jyväskylä, Finland; Surgery Research Unit, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
| | - Johanna Mrena
- Department of Surgery, Central Finland Central Hospital, Jyväskylä, Finland
| | - Eero Sihvo
- Department of Surgery, Central Finland Central Hospital, Jyväskylä, Finland
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Squires MH, Gower N, Benbow JH, Donahue EE, Bohl CE, Prabhu RS, Hill JS, Salo JC. PET Imaging and Rate of Pathologic Complete Response in Esophageal Squamous Cell Carcinoma. Ann Surg Oncol 2021; 29:1327-1333. [PMID: 34625880 DOI: 10.1245/s10434-021-10644-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 07/30/2021] [Indexed: 01/03/2023]
Abstract
BACKGROUND For locally advanced esophageal squamous cell carcinoma (ESCC), chemoradiation (ChemoRT) followed by surgery offers the best chance of cure, with a 35-50% pathologic complete response (pCR) rate. Given the morbidity of esophagectomy and the possibility of pCR with ChemoRT, a 'watch and wait' strategy has been proposed, particularly for squamous cell carcinoma. The ability to accurately predict which patients will have pCR from ChemoRT is critical in treatment decision making. This study assessed positron emission tomography (PET) in predicting pCR after neoadjuvant ChemoRT for ESCC. METHODS ESCC patients treated with ChemoRT followed by surgery were identified. Maximum standard uptake value (SUV), metabolic tumor volume, total lesion glycolysis, and first-order textual features of standard deviation, kurtosis and skewness were measured from PET. Univariable and multivariable generalized linear method analyses were performed. A metabolic complete response (mCR) was defined as a post-therapy PET scan with maximum SUV < 4.0. RESULTS Twenty-seven patients underwent ChemoRT followed by surgery, with overall pCR seen in 11 (41%) patients and radiographic mCR seen in 12 (44%) patients. Final pathology for these 12 patients revealed pCR (ypT0N0M0) in 5 (42%) patients and persistent disease in 7 (58%) patients. Univariate analysis did not reveal PET parameters predictive of pCR. CONCLUSION Treatment of ESCC with ChemoRT often results in a robust clinical response. Among patients with an mCR after ChemoRT, disease persistence was found in 58%. The inability of PET to predict pCR is important in the context of a 'watch and wait' strategy for ESCC treated with ChemoRT.
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Affiliation(s)
- M Hart Squires
- Division of Surgical Oncology, Department of Surgery, Carolinas Medical Center, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA
| | - Nicole Gower
- LCI Research Support, Clinical Trials Office, Levine Cancer Institute, Carolinas Medical Center, Atrium Health, Charlotte, NC, USA
| | - Jennifer H Benbow
- LCI Research Support, Clinical Trials Office, Levine Cancer Institute, Carolinas Medical Center, Atrium Health, Charlotte, NC, USA
| | - Erin E Donahue
- Department of Biostatistics, Carolinas Medical Center, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA
| | - Casey E Bohl
- Charlotte Radiology, Atrium Health, Charlotte, NC, USA
| | - Roshan S Prabhu
- Southeast Radiation Oncology Group, Carolinas Medical Center, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA
| | - Joshua S Hill
- Division of Surgical Oncology, Department of Surgery, Carolinas Medical Center, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA
| | - Jonathan C Salo
- Division of Surgical Oncology, Department of Surgery, Carolinas Medical Center, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA.
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Takeda FR, Obregon CDA, Navarro YP, Moura DTH, Ribeiro Jr U, Aissar Sallum RA, Cecconello I. Thoracoscopic esophagectomy is related to better outcomes in early adenocarcinoma of esophagogastric junction tumors. World J Gastrointest Endosc 2021; 13:319-328. [PMID: 34512879 PMCID: PMC8394183 DOI: 10.4253/wjge.v13.i8.319] [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: 02/18/2021] [Revised: 03/21/2021] [Accepted: 07/14/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Thoracoscopic esophagectomy is related to an extended lymphadenectomy, and a high number of retrieved lymph nodes, compared to the transhiatal approach; however, its association with an improvement in overall survival (OS) is debatable.
AIM To compare thoracoscopic esophagectomy with transhiatal esophagectomy in patients with adenocarcinoma of the esophagogastric junction (AEGJ) in terms of survival, number of lymph nodes, and complications.
METHODS In total, 147 patients with AEGJ were selected retrospectively from 2002 to 2019, and divided into Group A for thoracoscopic esophagectomy, and group B for transhiatal esophagectomy. OS, disease-free survival, postoperative complications, and number of nodes, were similarly evaluated.
RESULTS One hundred and thirty (88%) were male; the mean age was 64 years. Group A had a mean age of 61.1 years and group B 65.7 years (P = 0.009). Concerning the extent of lymphadenectomy, group A showed a higher number of retrieved lymph nodes (mean of 31.89 ± 8.2 vs 20.73 ± 7; P < 0.001), with more perioperative complications, such as hoarseness, surgical site infections, and respiratory complications. Although both groups had similar OS rates, subgroup analysis showed better survival of transthoracic esophagectomy in patients with earlier diseases.
CONCLUSION Both methods are safe, having similar morbidity and mortality rates. Transthoracic thoracoscopic esophagectomy allows a more extensive resection of the lymph nodes and may have better oncological outcomes during earlier stages of the disease. Prospective studies are warranted to better evaluate these findings.
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Affiliation(s)
- Flavio Roberto Takeda
- Department of Gastroenterology, University of São Paulo Medical School, São Paulo 05403-000, Brazil
| | | | - Yasmin Peres Navarro
- Department of Gastroenterology, University of São Paulo Medical School, São Paulo 05403-000, Brazil
| | | | - Ulysses Ribeiro Jr
- Department of Gastroenterology, University of São Paulo Medical School, São Paulo 05403-000, Brazil
| | | | - Ivan Cecconello
- Department of Gastroenterology, University of São Paulo Medical School, São Paulo 05403-000, Brazil
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Lu M, Parel JM, Miller D. Interactions between staphylococcal enterotoxins A and D and superantigen-like proteins 1 and 5 for predicting methicillin and multidrug resistance profiles among Staphylococcus aureus ocular isolates. PLoS One 2021; 16:e0254519. [PMID: 34320020 PMCID: PMC8318242 DOI: 10.1371/journal.pone.0254519] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 06/29/2021] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant (MDR) S. aureus strains are well recognized as posing substantial problems in treating ocular infections. S. aureus has a vast array of virulence factors, including superantigens and enterotoxins. Their interactions and ability to signal antibiotics resistance have not been explored. OBJECTIVES To predict the relationship between superantigens and methicillin and multidrug resistance among S. aureus ocular isolates. METHODS We used a DNA microarray to characterize the enterotoxin and superantigen gene profiles of 98 S. aureus isolates collected from common ocular sources. The outcomes contained phenotypic and genotypic expressions of MRSA. We also included the MDR status as an outcome, categorized as resistance to three or more drugs, including oxacillin, penicillin, erythromycin, clindamycin, moxifloxacin, tetracycline, trimethoprim-sulfamethoxazole and gentamicin. We identified gene profiles that predicted each outcome through a classification analysis utilizing Random Forest machine learning techniques. FINDINGS Our machine learning models predicted the outcomes accurately utilizing 67 enterotoxin and superantigen genes. Strong correlates predicting the genotypic expression of MRSA were enterotoxins A, D, J and R and superantigen-like proteins 1, 3, 7 and 10. Among these virulence factors, enterotoxin D and superantigen-like proteins 1, 5 and 10 were also significantly informative for predicting both MDR and MRSA in terms of phenotypic expression. Strong interactions were identified including enterotoxins A (entA) interacting with superantigen-like protein 1 (set6-var1_11), and enterotoxin D (entD) interacting with superantigen-like protein 5 (ssl05/set3_probe 1): MRSA and MDR S. aureus are associated with the presence of both entA and set6-var1_11, or both entD and ssl05/set3_probe 1, while the absence of these genes in pairs indicates non-multidrug-resistant and methicillin-susceptible S. aureus. CONCLUSIONS MRSA and MDR S. aureus show a different spectrum of ocular pathology than their non-resistant counterparts. When assessing the role of enterotoxins in predicting antibiotics resistance, it is critical to consider both main effects and interactions.
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Affiliation(s)
- Min Lu
- Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL, United States of America
| | - Jean-Marie Parel
- Department of Ophthalmology, Ophthalmic Biophysics Center, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, United States of America
| | - Darlene Miller
- Department of Ophthalmology, Ocular Microbiology Laboratory, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, United States of America
- * E-mail:
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Quaas A, Schloesser H, Fuchs H, Zander T, Arolt C, Scheel AH, Rueschoff J, Bruns C, Buettner R, Schroeder W. Improved Tissue Processing in Esophageal Adenocarcinoma After Ivor Lewis Esophagectomy Allows Histological Analysis of All Surgically Removed Lymph Nodes with Significant Effects on Nodal UICC Stages. Ann Surg Oncol 2021; 28:3975-3982. [PMID: 33305335 PMCID: PMC8184552 DOI: 10.1245/s10434-020-09450-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Accepted: 11/16/2020] [Indexed: 01/02/2023]
Abstract
BACKGROUND In esophageal carcinoma, the numbers of metastatic and total removed lymph nodes (LN) are well-established variables of long-term prognosis. The overall rate of retrieved LN depends on neoadjuvant treatment, the extent of surgical lymphadenectomy, and the modality of the pathological workup. The question in this study is whether technically extended histopathological preparation can increase the number of detected (metastatic) LN with an impact on nodal UICC staging. PATIENTS AND METHODS A cohort of 77 patients with esophageal adenocarcinoma was treated with Ivor Lewis esophagectomy including standardized two-field lymphadenectomy. The specimens were grossed, and all manually detectable LN were retrieved. The remaining tissue was completely embedded by the advanced "acetone compression" retrieval technique. The primary outcome parameter was the total number of detected lymph nodes before and after acetone workup. RESULTS A mean number of 23,1 LN was diagnosed after standard manual LN preparation. With complete embedding of the fatty tissue using acetone compression, the number increased to 40.5 lymph nodes (p < 0.0001). The mean number of metastatic LN increased from 3.2 to 4.2 nodal metastases following acetone compression (p < 0.0001). Additional LN metastases which caused a change in the primary (y)pN stage were found in ten patients (13.0%). CONCLUSIONS Advanced lymph node retrieval by acetone compression allows a reliable statement on the real number of removed LN. Results demonstrate an impact on the nodal UICC stage. A future multicenter study will examine the prognostic impact of improved lymph node retrieval on long-term oncologic outcome.
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Affiliation(s)
- A Quaas
- Institute of Pathology, Gastrointestinal Cancer Group Cologne (GCGC), University Hospital Cologne, Cologne, Germany.
| | - H Schloesser
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital Cologne, Cologne, Germany
| | - H Fuchs
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital Cologne, Cologne, Germany
| | - T Zander
- Department of Internal Medicine I, University Hospital Cologne, Cologne, Germany
| | - C Arolt
- Institute of Pathology, Gastrointestinal Cancer Group Cologne (GCGC), University Hospital Cologne, Cologne, Germany
| | - A H Scheel
- Institute of Pathology, Gastrointestinal Cancer Group Cologne (GCGC), University Hospital Cologne, Cologne, Germany
| | - J Rueschoff
- Institute of Pathology, Nordhessen and Targos Molecular Pathology GmbH, Kassel, Germany
| | - C Bruns
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital Cologne, Cologne, Germany
| | - R Buettner
- Institute of Pathology, Gastrointestinal Cancer Group Cologne (GCGC), University Hospital Cologne, Cologne, Germany
| | - W Schroeder
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital Cologne, Cologne, Germany
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Zhang S, Guo J, Zhang H, Li H, Hassan MOO, Zhang L. Metastasis pattern and prognosis in men with esophageal cancer patients: A SEER-based study. Medicine (Baltimore) 2021; 100:e26496. [PMID: 34160464 PMCID: PMC8238299 DOI: 10.1097/md.0000000000026496] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Accepted: 05/30/2021] [Indexed: 01/04/2023] Open
Abstract
Esophageal cancer (EC) is relatively common; at the time of diagnosis, 50% of cases present with distant metastases, and most patients are men. This study aimed to examine and compare the clinicopathological characteristics and metastatic patterns of male EC (MEC) and female EC (FEC). In addition, risk factors associated with MEC prognosis were evaluated.The present study population was extracted from the Surveillance Epidemiology and End Results database. MEC characteristics and factors associated with prognosis were evaluated using descriptive analysis, the Kaplan-Meier method, and the Cox regression model.A total of 12,558 MEC cases were included; among them, 3454 cases had distant organ metastases. Overall, 27.5% of the entire cohort were patients with distant organ metastases. Compared with patients with non-metastatic MEC, patients with metastatic MEC were more likely to be aged ≤60 years, of Black and White race, have a primary lesion in the overlapping esophagus segments, and have a diagnosis of adenocarcinoma of poorly differentiated and undifferentiated grade that was treated with radiotherapy and chemotherapy rather than surgery; moreover, they were also more likely to be married and insured. In addition, patients with MEC were more likely to be aged ≤60 years, White race, and diagnosed with a primary lesion in the lower third of the esophagus and overlapping esophagus segments, and treated without chemotherapy, compared with those with FEC. Patients in the former group were also more likely than those in the latter group to be unmarried and have bone metastasis only and lung metastasis only. Liver, lung, and bone metastases separately, and simultaneous liver and lung metastases were associated with poor survival in MEC patients.Metastatic MEC is associated with clinicopathological characteristics and metastatic patterns different from those associated with non-metastatic MEC and metastatic FEC. Metastatic MEC and FEC patients may have similar prognoses. Distant organ metastasis may be associated with poor prognosis in patients with MEC and FEC.
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Affiliation(s)
- Shengqiang Zhang
- Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin
| | - Jida Guo
- Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin
| | - Hongyan Zhang
- Department of Physiology and Neurobiology, Mudanjiang Medical University, Mudanjiang, China
| | - Huawei Li
- Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin
| | - Mohamed Osman Omar Hassan
- Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin
- Department of Cardiothoracic Surgery, Qena University Hospitals, Qena Faculty of Medicine, South Valley University, Qena, Egypt
| | - Linyou Zhang
- Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin
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Deng X, He W, Jiang Y, Deng S, Mao T, Leng X, Luo Q, Zheng K, Han Y. The impact of adjuvant therapy on survival for node-negative esophageal squamous cell carcinoma: a propensity score-matched analysis. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:998. [PMID: 34277798 PMCID: PMC8267332 DOI: 10.21037/atm-21-2539] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 06/16/2021] [Indexed: 11/06/2022]
Abstract
Background At present, the primary treatment of esophageal cancer is surgery-based comprehensive treatment, including adjuvant therapy such as chemotherapy and/or radiotherapy. However, the role of adjuvant therapy for esophageal squamous cell carcinoma (ESCC) with pathologically node-negative (pN0) disease is controversial. This study aimed to evaluate the impact of postoperative adjuvant therapy on survival in patients with pN0 ESCC. Methods Patients with ESCC who underwent R0 esophagectomy in the Department of Thoracic Surgery of Sichuan Cancer Hospital from January 2008 to December 2013 were enrolled. Patients were divided into two groups: a surgery alone (Group S) group or a surgery + adjuvant therapy (Group S + A) group. The primary outcomes were overall survival (OS) and disease-free survival (DFS), and every consecutive case was followed up until death or the last follow-up. Results A total of 387 patients with ESCC patients who had pN0 were enrolled in the study. After propensity score matching (PSM), each group consisted of 150 patients. In the overall cohort, the 5-year OS (75.6% vs. 69.7%; P=0.004) and 5-year DFS (64.9% vs. 48.2%; P=0.003) rates were higher in Group S + A than in Group S. In the matched samples, the same outcomes were observed (5-year OS: 75.6% vs. 69.7%, P=0.026; 5-year DFS: 67.6% vs. 69.6%, P=0.036). Multivariate regression analysis indicated that postoperative chemotherapy was associated with longer OS [hazard ratio (HR): 0.622, 95% confidence interval (CI): 0.416-0.928; P=0.02] and DFS (HR: 0.571, 95% CI: 0.390-0.836; P=0.004); in contrast, T3 stage tumors (HR: 1.953, 95% CI: 1.238-3.082; P=0.004) and <15 lymph node dissections (HR: 1.81; 95% CI: 1.238-2.648; P = 0.002) were found to be independent risk factors for pN0 ESCC. Conclusions Adjuvant therapy, especially chemotherapy, prolonged OS and DFS for patients with ESCC who had pN0 disease. Fewer lymph node dissections and T3 stage tumors were independent risk factors for OS and DFS.
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Affiliation(s)
- Xuyang Deng
- School of Medicine, Southwest Medical University, Luzhou, China
| | - Wenwu He
- Department of Thoracic Surgery, Sichuan Cancer Hospital & Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, China
| | - Yingchun Jiang
- Department of Thoracic Surgery, Sichuan Cancer Hospital & Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, China
| | - Sijie Deng
- Department of Endocrinology, People's Hospital of Deyang City, Deyang, China
| | - Tianqin Mao
- School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, China
| | - Xuefeng Leng
- Department of Thoracic Surgery, Sichuan Cancer Hospital & Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, China
| | - Qiyu Luo
- School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, China
| | - Kai Zheng
- School of Medicine, Southwest Medical University, Luzhou, China
| | - Yongtao Han
- School of Medicine, Southwest Medical University, Luzhou, China.,Department of Thoracic Surgery, Sichuan Cancer Hospital & Research Institute, School of Medicine, University of Electronic Science and Technology of China (UESTC), Chengdu, China
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Turgeman I, Ben-Aharon I. Evolving treatment paradigms in esophageal cancer. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:903. [PMID: 34164537 PMCID: PMC8184467 DOI: 10.21037/atm.2020.03.110] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Accepted: 02/28/2020] [Indexed: 12/23/2022]
Abstract
A heterogenous disease with a dismal prognosis, esophageal cancer poses a major health challenge worldwide. In recent years, the treatment landscape for esophageal adenocarcinoma and squamous cell carcinoma (SCC) has undergone major evolution, with the elucidation of underlying biologic pathways and predispositions. Neoadjuvant chemoradiation has emerged as a leading approach for the management of locoregional esophageal cancer, while perioperative chemotherapy has shown promising outcomes specifically in adenocarcinoma of the lower esophagus and gastroesophageal junction (GEJ). Studies also explore the implementation of chemoradiation in various sequential preoperative strategies, as well as in the adjuvant setting. Definitive chemoradiation is considered a valid alternative for non-surgical candidates with SCC. Clinical trials currently evaluating the potential benefits of different approaches may shed light on existing controversies regarding optimal management of locoregional disease. For patients with metastatic cancer, chemotherapy remains the backbone of antineoplastic treatment alongside palliative care, moreover the discovery of novel biological targets has led to the initiation of targeted and immune therapy for specific subpopulations. Taken together, an era of burgeoning clinical trials and changing paradigms has evolved in esophageal oncology. Multidisciplinary collaboration is key to effective combination and sequencing of treatment modalities tailored per patient and per tumor histology. This work aims to provide a comprehensive overview of state-of-the-art oncological management of esophageal cancer, with consideration of new challenges and obstacles to be overcome.
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Affiliation(s)
- Ilit Turgeman
- Division of Oncology, Rambam Health Care Campus, Haifa, Israel
| | - Irit Ben-Aharon
- Division of Oncology, Rambam Health Care Campus, Haifa, Israel
- Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
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Junttila A, Väyrynen JP, Ahtiainen M, Kuopio T, Mrena J, Sihvo E, Helminen O. Immune cell score, PD-L1 expression and prognosis in esophageal cancer. Acta Oncol 2021; 60:544-548. [PMID: 33438497 DOI: 10.1080/0284186x.2020.1868571] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Affiliation(s)
- Anna Junttila
- Department of Surgery, Central Finland Central Hospital, Jyväskylä, Finland
| | - Juha P. Väyrynen
- Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland
| | - Maarit Ahtiainen
- Department of Education and Research, Central Finland Health Care District, Jyväskylä, Finland
| | - Teijo Kuopio
- Department of Education and Research, Central Finland Health Care District, Jyväskylä, Finland
- Department of Pathology, Central Finland Central Hospital, Jyväskylä, Finland
- Department of Biological and Environmental Science, University of Jyväskylä, Jyväskylä, Finland
| | - Johanna Mrena
- Department of Surgery, Central Finland Central Hospital, Jyväskylä, Finland
| | - Eero Sihvo
- Department of Surgery, Central Finland Central Hospital, Jyväskylä, Finland
| | - Olli Helminen
- Department of Surgery, Central Finland Central Hospital, Jyväskylä, Finland
- Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland
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Proposed Modification of the pN2 Classification of the 8th Edition AJCC Staging System for Esophageal Squamous Cell Carcinoma: A Preliminary Study Based on the Chinese Population. JOURNAL OF ONCOLOGY 2021; 2021:8871884. [PMID: 33777143 PMCID: PMC7972858 DOI: 10.1155/2021/8871884] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 01/24/2021] [Accepted: 02/08/2021] [Indexed: 11/17/2022]
Abstract
Objective To evaluate the efficacy of the nodal staging of the 8th edition AJCC staging system for esophageal squamous cell carcinoma (ESCC) and propose a modification of the current pN2 classification. Methods 1188 patients who underwent esophagectomy for ESCC at Sun Yat-sen University Cancer Center in Guangzhou (Guangdong, China) between January 2005 and June 2010 were reviewed. We used the X-tile software to determine the optimal cutoff points. Kaplan–Meier method and log-rank test were used to compare the differences of survival. Multivariate Cox regression analysis was performed for the factors that were statistically significant in univariate analysis. Result In multivariate Cox regression analysis, alcohol consumption, pT status, and pN status were independent prognostic factors for overall survival (OS) according to the current pN classifications. And the observed 5-year OS rates for groups pN0, pN1, pN2, pN3 were 66.7%, 45.0%, 31.5%, and 21.5%, respectively (P<0.001). Based on the above results, the current pN2 classification was further subdivided as pN2a [3 metastatic lymph nodes (LNs)] and pN2b (4−6 metastatic LNs) groups. The 5-year OS rates for groups pN0, pN1, pN2a, pN2b, and pN3 were 66.7%, 45.0%, 37.7%, 26.3% and 21.5%, respectively (P<0.001). The rate of 5-year disease-free survival (DFS) was 60.0% for patients with pN0, compared with 36.8%, 29.3%, 20.8%, and 14.3% for those with pN1, pN2a, pN2b, and pN3, respectively (P<0.001).The current pN2 classification should be subdivided as pN2a (3 metastatic LNs) and pN2b (4–6 metastatic LNs) groups. The modified pN2 classification could better discriminate the survival differences between patients with 3–6 metastatic LNs for ESCC in the Chinese population.
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Litle VR. Commentary: POEM: Provision of effective management (through collaboration). J Thorac Cardiovasc Surg 2021; 163:520-521. [PMID: 33781595 DOI: 10.1016/j.jtcvs.2021.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 02/28/2021] [Accepted: 03/02/2021] [Indexed: 11/28/2022]
Affiliation(s)
- Virginia R Litle
- Division of Thoracic Surgery, Department of Surgery, Boston University School of Medicine, Boston, Mass.
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de Nucci G, Petrone MC, Imperatore N, Asti E, Rossi G, Manes G, Vecchi M, Pastorelli L, Bonavina L, Arcidiacono PG. Staging esophageal cancer: low EUS accuracy in t2n0 patients. Endosc Int Open 2021; 9:E313-E318. [PMID: 33655027 PMCID: PMC7892275 DOI: 10.1055/a-1336-2505] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 10/14/2020] [Indexed: 12/23/2022] Open
Abstract
Background and study aims Esophageal cancer (EC) is one of the most lethal malignancies worldwide. Staging of EC is performed with computed tomography (CT), positron-emission tomography (PET), and endoscopic ultrasonography (EUS). Patient management mostly depends on lymph node status. Compared to histopathology, the accuracy of EUS for T and N parameters is about 85 % and 75 %, respectively. Errors in staging may change prognosis. The aim of this study was to assess the role of EUS in T2-N0 EC considering the experience of two high-volume digestive endoscopic centers. Methods Two prospectively collected databases were queried to identify all patients with EC, staged as cT2N0 by EUS, with no distant metastases at CT/PET scan and who underwent transthoracic esophagectomy. Preoperative EUS staging (cTNM) was compared to histopathology of the surgical specimen (pTNM) to evaluate accuracy. Results Of 729 consecutive patients with EC between January 2011 and September 2018, 72 (49 men) had cT2N0 disease. CT and PET scans confirmed the absence of distant metastasis. In 43 of 72 patients (60 %), the evaluation was correct, 23 of 72 (31,7 %) were understaged, and six of 72 patients (8,3 %) were overstaged. Among the understaged patients, eight were understaged by tumor depth (35 %), seven by nodal involvement (30 %), and eight by both (35 %). All six patients who were overstaged had T1b-N0 disease. EUS accuracy was 77 % in staging for tumor depth and 82 % in staging for nodal metastases. The positive predictive value (PPV) for cT2N0 EC was 60 % (43 pT2N0 /72 cT2N). Conclusions The accuracy of EUS staging of T2N0 EC is low, with only 60 % of patients undergoing appropriate therapy based on histopathology.
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Affiliation(s)
- Germana de Nucci
- Gastroenterology and Endoscopy Unit, ASST Rhodense, Garbagnate Milanese-Milan, Italy
| | - Maria Chiara Petrone
- Bilio-pancreatic Endoscopy and Endoscopic Ultrasound Unit, San Raffaele Hospital, Milan, Italy
| | | | - Emanuele Asti
- Division of General and Foregut Surgery, IRCCS Policlinico San Donato, University of Milano, Milan, Italy
| | - Gemma Rossi
- Bilio-pancreatic Endoscopy and Endoscopic Ultrasound Unit, San Raffaele Hospital, Milan, Italy
| | - Giampiero Manes
- Gastroenterology and Endoscopy Unit, ASST Rhodense, Garbagnate Milanese-Milan, Italy
| | - Maurizio Vecchi
- Gastroenterology and Endoscopy Unit, Ca Granda Policlinic Major Hospital, Milan, Italy
| | - Luca Pastorelli
- Gastroenterology Unit, IRCCS Policlinico San Donato and Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
| | - Luigi Bonavina
- Division of General and Foregut Surgery, IRCCS Policlinico San Donato, University of Milano, Milan, Italy
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Guo J, Zhang S, Li H, Hassan MOO, Lu T, Zhao J, Zhang L. Lung Metastases in Newly Diagnosed Esophageal Cancer: A Population-Based Study. Front Oncol 2021; 11:603953. [PMID: 33718154 PMCID: PMC7947855 DOI: 10.3389/fonc.2021.603953] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 01/11/2021] [Indexed: 12/16/2022] Open
Abstract
Background Esophageal cancer is one of the most common cancer types, with its most common distant metastatic site being the lung. Currently, population-based data regarding the proportion and prognosis of patients with esophageal cancer with lung metastases (ECLM) at the time of diagnosis is insufficient. Therefore, we aimed to determine the proportion of patients with ECLM at diagnosis, as well as to investigate the prognostic parameters of ECLM. Methods This population-based observational study obtained data from the Surveillance, Epidemiology, and End Results (SEER) database registered between 2010 and 2016. Multivariable logistic regression was performed to identify predictors of the presence of ECLM at diagnosis. Multivariable Cox regression and competing risk analysis were used to assess prognostic factors in patients with ECLM. Median survival was estimated using Kaplan–Meier curves. Results Of 10,965 patients diagnosed with esophageal cancer between 2010 and 2016, 713 (6.50%) presented with initial lung metastasis at diagnosis. Lung metastasis represented 27.15% of all cases with metastatic disease to any distant site. Considering all patients with esophageal cancer, multivariable logistic regression indicated that pathology grade, pathology type, T staging, N staging, race, and number of extrapulmonary metastatic sites were predictive factors for the occurrence of lung metastases at diagnosis. The median survival time of patients with ECLM was 4.0 months. Patients receiving chemotherapy or chemoradiotherapy had the longest median overall survival, 7.0 months. Multivariable Cox regression indicated that age, histology type, T2 staging, number of extrapulmonary metastatic sites, and treatment (chemotherapy, radiotherapy, or chemoradiotherapy) were independent predictors for overall survival (OS). Multivariable competing risk analysis determined that age, number of extrapulmonary metastatic sites, and treatment were independent predictors for esophageal cancer-specific survival (CSS). Conclusion The findings of this study may provide important information for the early diagnosis of ECLM, as well as aid physicians in choosing appropriate treatment regimens for these patients.
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Affiliation(s)
- Jida Guo
- Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Shengqiang Zhang
- Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Huawei Li
- Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Mohamed Osman Omar Hassan
- Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Tong Lu
- Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Jiaying Zhao
- Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Linyou Zhang
- Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
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Wang T, Wu Y, Zhou H, Wu C, Zhang X, Chen Y, Zhao D. Development and validation of a novel competing risk model for predicting survival of esophagogastric junction adenocarcinoma: a SEER population-based study and external validation. BMC Gastroenterol 2021; 21:38. [PMID: 33499821 PMCID: PMC7836166 DOI: 10.1186/s12876-021-01618-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Accepted: 01/17/2021] [Indexed: 12/16/2022] Open
Abstract
Background Adenocarcinoma in Esophagogastric Junction (AEG) is a severe gastrointestinal malignancy with a unique clinicopathological feature. Hence, we aimed to develop a competing risk nomogram for predicting survival for AEG patients and compared it with new 8th traditional tumor-node-metastasis (TNM) staging system. Methods Based on data from the Surveillance, Epidemiology, and End Results (SEER) database of AEG patients between 2004 and 2010, we used univariate and multivariate analysis to filter clinical factors and then built a competing risk nomogram to predict AEG cause-specific survival. We then measured the clinical accuracy by comparing them to the 8th TNM stage with a Receiver Operating Characteristic (ROC) curve, Brier score, and Decision Curve Analysis (DCA). External validation was performed in 273 patients from China National Cancer Center. Results A total of 1755 patients were included in this study. The nomogram was based on five variables: Number of examined lymph nodes, grade, invasion, metastatic LNs, and age. The results of the nomogram was greater than traditional TNM staging with ROC curve (1-year AUC: 0.747 vs. 0.641, 3-year AUC: 0.761 vs. 0.679, 5-year AUC: 0.759 vs. 0.682, 7-year AUC: 0.749 vs. 0.673, P < 0.001), Brier score (3-year: 0.198 vs. 0.217, P = 0.012; 5-year: 0.198 vs. 0.216, P = 0.008; 7-year: 0.199 vs. 0.215, P = 0.014) and DCA. In external validation, the nomogram also showed better diagnostic value than traditional TNM staging and great prediction accuracy. Conclusion We developed and validated a novel nomogram and risk stratification system integrating clinicopathological characteristics for AEG patients. The model showed superior prediction ability for AEG patients than traditional TNM classification.
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Affiliation(s)
- Tongbo Wang
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 PanjiayuanNanli, Chaoyang District, Beijing, 100021, China
| | - Yan Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Hong Zhou
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 PanjiayuanNanli, Chaoyang District, Beijing, 100021, China
| | - Chaorui Wu
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 PanjiayuanNanli, Chaoyang District, Beijing, 100021, China
| | - Xiaojie Zhang
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 PanjiayuanNanli, Chaoyang District, Beijing, 100021, China
| | - Yingtai Chen
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 PanjiayuanNanli, Chaoyang District, Beijing, 100021, China.
| | - Dongbing Zhao
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 PanjiayuanNanli, Chaoyang District, Beijing, 100021, China.
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Xia X, Liu Z, Cai B, Di X, Sun X, Ge X. A comparison between raltitrexed plus cisplatin and docetaxel plus cisplatin in concurrent chemoradiation for non-surgical esophageal squamous cell carcinoma. Cancer Radiother 2021; 25:39-44. [PMID: 33419607 DOI: 10.1016/j.canrad.2020.06.029] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 05/29/2020] [Accepted: 06/07/2020] [Indexed: 01/04/2023]
Abstract
PURPOSE Chemoradiotherapy (CRT) is considered as a standard treatment for unresectable and inoperable esophageal cancer (EC) patients. However, no consensus has been reached regarding the optimal synchronous chemotherapy regimen and the best combination of radiotherapy and chemotherapy. The aim of this study was to evaluate the efficacy and toxicity of raltitrexed plus cisplatin and docetaxel plus cisplatin to find a safe and effective concurrent chemotherapy schedule. PATIENTS AND METHODS Our retrospective study included 151 EC patients treated with raltitrexed and cisplatin (RP) (n=90) or docetaxel and cisplatin (DP) (n=61) from 2011 till 2018. Survival outcomes and treatment related toxicity were analyzed between the two groups. RESULTS PFS and OS were 18 and 34 months in the RP group, while 13 and 20 months in the DP group (P=0.118 and P=0.270). The 1-, 2-, 3-year survival rates of the RP group were 71.1, 55.4 and 46.4%. For the DP group, these were 63.9, 44.3 and 37.6%, respectively. Compared with DP group, RP group received a superior CR rate (68.9% versus 52.5%, P=0.041). There was a trend that the total number of toxic reactions in RP group was lower than that in DP group (P=0.058). CONCLUSIONS Even RP and DP groups have the similar survival outcomes and toxicity, raltitrexed/cisplatin get a higher complete response rate. Our study suggests that raltitrexed combined with cisplatin is a safe and effective concurrent chemotherapy regimen and it might be used as an alternative for cisplatin/5-FU and cisplatin/docetaxel in CCRT for EC patients.
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Affiliation(s)
- X Xia
- Department of Radiation Oncology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, 300, Guangzhou Road, Nanjing, Jiangsu, China
| | - Z Liu
- Department of Radiation Oncology, school of Nanjing Medical University, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, 300, Guangzhou Road, Nanjing, Jiangsu, China
| | - B Cai
- Department of Medicine Research, Chinese Academy of Medical Sciences & Peking Union Medical College Hospital of Skin Diseases and Institute of Dermatology, 12, Jiangwang Temple Street, Nanjing, Jiangsu, China
| | - X Di
- Department of Radiation Oncology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, 300, Guangzhou Road, Nanjing, Jiangsu, China
| | - X Sun
- Department of Radiation Oncology, school of Nanjing Medical University, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, 300, Guangzhou Road, Nanjing, Jiangsu, China.
| | - X Ge
- Department of Radiation Oncology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, 300, Guangzhou Road, Nanjing, Jiangsu, China.
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Yin J, Dong L, Zhao J, Wang H, Li J, Yu A, Chen W, Wei W. Composition and consistence of the bacterial microbiome in upper, middle and lower esophagus before and after Lugol's iodine staining in the esophagus cancer screening. Scand J Gastroenterol 2020; 55:1467-1474. [PMID: 33169656 DOI: 10.1080/00365521.2020.1839961] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Esophageal bacteria, as the integral composition of human ecosystem, have been reported to be associated with esophageal lesions. However, few studies focus on microbial compositions in different esophageal segments, especially after Lugol's iodine staining (LIS) in the endoscopic examination for the screening of esophageal cancer. We aim to investigate the composition of the bacterial microbiome in upper, middle and lower esophagus and if LIS would affect the detection of bacteria. METHODS A total of 141 fasting samples including the upper, middle and lower esophagus from 27 participants were collected by brushing the mucosal surface of the esophagus before (Eso) and after (Lug) LIS. Bacterial V3-V4 region of 16S rRNA gene was amplified and sequenced by Illumina's sequencing platform. RESULTS The top six abundant bacterial phyla taxa among three locations from both Eso and Lug groups were Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria and TM7. In terms of genera, the bacterium in three locations from two groups was all characterized by a highest relative abundance of Streptococcus. Bacteria diversity and the relative abundance between Eso and Lug were comparable (p > .05). Bacteria diversity was consistent in different esophageal locations within the individual. CONCLUSION The bacterial microbiome in healthy esophagus are highly diverse and consistent even among three physiological sites at all clades. Lugol's iodine staining would not change local microenvironment in term of microbial composition. These findings provide an essential baseline for future studies investigating local and systemic bacterial microbiome and esophageal diseases.
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Affiliation(s)
- Jian Yin
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Li Dong
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Institutes of Biomedical Sciences, Shanxi University, Taiyuan, China
| | - Jing Zhao
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,School of Public Health, Peking Union Medical College, Beijing, China
| | - Hairui Wang
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Shenzhen Center for Disease Control and Prevention, Shenzhen, China
| | - Juxiao Li
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Aisong Yu
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wen Chen
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wenqiang Wei
- Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Söderström HK, Räsänen J, Saarnio J, Toikkanen V, Tyrväinen T, Rantanen T, Valtola A, Ohtonen P, Pääaho M, Kokkola A, Kallio R, Karttunen TJ, Pohjanen VM, Ristimäki A, Laine S, Sihvo E, Kauppila JH. Cohort profile: a nationwide population-based retrospective assessment of oesophageal cancer in the Finnish National Esophago-Gastric Cancer Cohort (FINEGO). BMJ Open 2020; 10:e039575. [PMID: 33055119 PMCID: PMC7559040 DOI: 10.1136/bmjopen-2020-039575] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Revised: 09/02/2020] [Accepted: 09/22/2020] [Indexed: 02/06/2023] Open
Abstract
PURPOSE The Finnish National Esophago-Gastric Cancer Cohort (FINEGO) was established to combine the available registry data with detailed patient information to form a comprehensive, retrospective, population-based research platform of surgically treated oesophageal and gastric cancer in Finland. This cohort profile describes the 2045 surgically treated patients with oesophageal cancer included in the FINEGO cohort. PARTICIPANTS Registry data were collected from the National Cancer, Patient, Education and Death Registries from 1 January 1987 to 31 December 2016. All patients over 18 years of age, who had either curative surgery, palliative surgery or salvage surgery for primary cancer in the oesophagus are included in this study. FINDINGS TO DATE 2045 patients had surgery for oesophageal cancer in the selected time period. 67.2% were man, and the majority had only minor comorbidities. The proportions of adenocarcinomas and squamous cell carcinomas were 43.1% and 44.4%, respectively, and 12.5% had other or missing histology. Only about 23% of patients received neoadjuvant therapy. Oesophagectomy was the treatment of choice and most patients were treated at low-volume centres, but median annual hospital volume increased over time. Median overall survival was 23 months, 5-year survival for all patients in the cohort was 32.9% and cancer-specific survival was 36.5%. FUTURE PLANS Even though Finland only has a population of 5.5 million, surgery for oesophageal carcinoma has not been centralised and therefore previously reported results have mostly been small, single-centre cohorts. Because of FINEGO, we now have a population-based, unselected cohort of surgically treated patients, enabling research on national trends over time regarding oesophageal cancer, including patient characteristics, tumour histology, stage and neoadjuvant treatment, surgical techniques, hospital volumes and patient mortality. Data collection is ongoing, and the cohort will be expanded to include more detailed data from patient records and national biobanks.
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Affiliation(s)
- Henna K Söderström
- Department of General Thoracic and Oesophageal Surgery, Heart and Lung Centre, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Jari Räsänen
- Department of General Thoracic and Oesophageal Surgery, Heart and Lung Centre, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Juha Saarnio
- Surgery Research Unit, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
| | - Vesa Toikkanen
- Department of Cardiothoracic Surgery, Heart Center, Tampere University Hospital and University of Tampere, Tampere, Finland
| | - Tuula Tyrväinen
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland
| | - Tuomo Rantanen
- Department of Surgery, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
| | - Antti Valtola
- Department of Surgery, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
| | - Pasi Ohtonen
- Surgery Research Unit, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
| | - Minna Pääaho
- Surgery Research Unit, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
| | - Arto Kokkola
- Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Raija Kallio
- Department of Oncology and Haematology, Oulu University Hospital, Oulu, Finland
| | - Tuomo J Karttunen
- Cancer and Translational Medicine Research Unit, Medical Research Center, University of Oulu and Oulu University Hospital, Oulu, Finland
| | - Vesa-Matti Pohjanen
- Cancer and Translational Medicine Research Unit, Medical Research Center, University of Oulu and Oulu University Hospital, Oulu, Finland
| | - Ari Ristimäki
- Department of Pathology, HUSLAB, HUS Diagnostic Center, Helsinki, Finland
- Applied Tumour Genomics Research Program, Research Programs Unit, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Simo Laine
- The Division of Digestive Surgery and Urology, Turku University Hospital, Turku, Finland
| | - Eero Sihvo
- Department of Surgery, Central Finland Central Hospital, Jyväskylä, Finland
| | - Joonas H Kauppila
- Surgery Research Unit, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
- Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
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Askari A, Munster AB, Jambulingam P, Riaz A. Critical number of lymph node involvement in esophageal and gastric cancer and its impact on long-term survival-A single-center 8-year study. J Surg Oncol 2020; 122:1364-1372. [PMID: 32803769 DOI: 10.1002/jso.26145] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 07/22/2020] [Indexed: 12/25/2022]
Abstract
BACKGROUND Nodal disease in esophageal and gastric cancer is associated with poor survival. OBJECTIVES To determine the critical level of lymph node involvement where survival becomes significantly compromised. METHODS Survival analyses using multivariable Cox regression and receiver operator characteristics (ROC) were undertaken to determine what number of positive lymph nodes were most sensitive and specific in predicting survival. RESULTS A total of 317 patients underwent esophagectomy (n = 190, 59.9%) and gastrectomy (n = 127, 40.1%) for adenocarcinoma. At multivariable analyses, four nodes positivity (irrespective of T-category) was associated with nearly a fivefold increased risk of mortality when compared to node-negative patients (hazard ratio [HR], 4.9; interquartile range 2.0-11.5; P < .001). A positive ratio of up to 50.0% was not associated with worse survival than having four nodes positive (HR, 4.6; 95% confidence interval, 2.6-8.1; P < .001). ROC analysis demonstrated four lymph nodes positive to have a sensitivity of 80.5%, a specificity of 60.1%, and an accuracy of 77.8 (P < .001). CONCLUSION The absolute number of nodes positive for cancer is more important than the proportion of positive nodes in predicting survival in esophageal/gastric cancer. Four positive lymph nodes are associated with a fivefold increase in mortality. Beyond this, increasing numbers of positive lymph nodes make no appreciable difference to survival.
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Affiliation(s)
- Alan Askari
- Department of Surgery, West Hertfordshire Hospitals NHS Trust, Watford, UK
| | - Alex B Munster
- Department of Surgery, West Hertfordshire Hospitals NHS Trust, Watford, UK
| | | | - Amjid Riaz
- Department of Surgery, West Hertfordshire Hospitals NHS Trust, Watford, UK
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Xu QL, Li H, Zhu YJ, Xu G. The treatments and postoperative complications of esophageal cancer: a review. J Cardiothorac Surg 2020; 15:163. [PMID: 32631428 PMCID: PMC7336460 DOI: 10.1186/s13019-020-01202-2] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Accepted: 06/22/2020] [Indexed: 12/24/2022] Open
Abstract
Abstract Esophageal cancer is still one of the most common cancers in the world. We review the appropriate treatments at different stages of esophageal cancer and also analyze the advantages and disadvantages of these treatments. The prognosis and recovery of different treatment regimens are further discussed. In particular, post-operative complications are the major causes of high mortality derived from the esophageal cancer. Therefore, we particularly discuss the main complications resulting in high mortality after surgery of esophageal cancer, and summarize their risk factors and treatment options. Background As the common cancer, the complications of esophageal cancer after surgery have been not obtained systematic treatment strategy, focusing on treatment regimens based on the different stages of esophageal cancers. Methods and overview This paper systematically summarizes the appropriate treatment strategies for different stages of esophageal cancers, and their advantages and disadvantages. We particularly focus on the postoperative survival rate of patients and postoperative complications, and discuss the causes of high mortality risk factors after surgery. The risk factors of death and corresponding treatment methods are further summarized in this study. Conclusion Postoperative complications is the main cause responsible for the hard cure of esophageal cancers. The existing literatures indicate that postoperative anastomotic fistula is one of the most important complications leading to death, while it has not received much attention yet. We suggest that anastomotic fistula should be detected and dealt with early by summarizing these literatures. It is, therefore, necessary to develop a set of methods to predict or check anastomotic fistula in advance.
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Affiliation(s)
- Qi-Liang Xu
- Department of Cardiothoracic Surgery, Heze Municipal Hospital, Heze, 274031, Shandong, China
| | - Hua Li
- Department of Information, Heze Municipal Hospital, Heze, 274031, Shandong, China
| | - Ye-Jing Zhu
- Department of Clinical Pharmacy, Heze Municipal Hospital, Heze, 274031, Shandong, China
| | - Geng Xu
- Department of Cardiothoracic Surgery, Heze Municipal Hospital, Heze, 274031, Shandong, China.
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Udagawa H. Past, present, and future of three-field lymphadenectomy for thoracic esophageal cancer. Ann Gastroenterol Surg 2020; 4:324-330. [PMID: 32724875 PMCID: PMC7382429 DOI: 10.1002/ags3.12338] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 02/28/2020] [Accepted: 03/22/2020] [Indexed: 12/14/2022] Open
Abstract
In spite of repeated appeal of the effectiveness of three-field lymphadenectomy (3FL) by Japanese esophageal surgeons, it has not been accepted worldwide as a standard therapeutic measure for thoracic esophageal cancer. In this review, a concise summary of the history of 3FL, its present position, and its future perspective is discussed. Although a lack of randomized controlled trial (RCT) is one of the largest criticisms of 3FL, it seems difficult to make 3FL world-standard even if a RCT with a positive result was made. The essence of 3FL has revealed the fact that bilateral cervical paraesophageal nodes and nodes in the bilateral supraclavicular fossae are regional nodes of thoracic esophageal cancer. To let the world admit this essence should be the real endpoint of "3FL issue" without RCT. In the era of new modalities, Japanese surgeons should be free from the idea that 3FL is indispensable though the essence of 3FL should remain.
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Affiliation(s)
- Harushi Udagawa
- Toranomon Hospital KajigayaKawasaki CityJapan
- Okinaka Memorial Institute for Medical ResearchTokyoJapan
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Tozburun S. Superficial photothermal laser ablation of ex vivo sheep esophagus using a cone-shaped optical fiber tip. JOURNAL OF BIOPHOTONICS 2020; 13:e201960116. [PMID: 32134552 DOI: 10.1002/jbio.201960116] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 02/28/2020] [Accepted: 02/29/2020] [Indexed: 06/10/2023]
Abstract
Superficial photothermal laser ablation (SPLA) may be useful as a therapeutic approach producing a depth of injury that is sufficient to eliminate mucosal lesion but not deep enough to induce thermal effects in deeper tissue layers. The purpose of this preliminary study is twofold: (a) to describe design steps of a fiber probe capable of delivering a tightly focused laser beam, including Monte-Carlo-based simulations, and (b) to complete the initial testing of the probe in a sheep esophagus model, ex vivo. The cone-shaped (tapered) fiber tip was obtained by chemical etching of the optical fiber. A 1505 nm diode laser providing power up to 500 mW was operated in continuous wave. The successful SPLA of the sheep mucosa layer was demonstrated for various speed-power combinations, including 300 mW laser power at a surface scanning rate of 0.5 mm/s and 450 mW laser power at a surface scanning rate of 2.0 mm/s. Upon further development, this probe may be useful for endoscopic photothermal laser ablation of the mucosa layer using relatively low laser power.
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Affiliation(s)
- Serhat Tozburun
- Izmir Biomedicine and Genome Center, Izmir, Turkey
- Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir, Turkey
- Department of Biophysics, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey
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Griffin N, Rowe CW, Gao F, Jobling P, Wills V, Walker MM, Faulkner S, Hondermarck H. Clinicopathological Significance of Nerves in Esophageal Cancer. THE AMERICAN JOURNAL OF PATHOLOGY 2020; 190:1921-1930. [PMID: 32479822 DOI: 10.1016/j.ajpath.2020.05.012] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 05/08/2020] [Accepted: 05/18/2020] [Indexed: 02/07/2023]
Abstract
Nerves are emerging promoters of cancer progression, but the innervation of esophageal cancer and its clinicopathologic significance remain unclear. In this study, nerves were analyzed by immunohistochemistry in a cohort of 260 esophageal cancers, including 40 matched lymph node metastases and 137 normal adjacent esophageal tissues. Nerves were detected in 38% of esophageal cancers and were more associated with squamous cell carcinomas (P = 0.04). The surrounding or invasion of nerves by cancer cells (perineural invasion) was detected in 12% of esophageal cancers and was associated with reduced survival (P = 0.04). Nerves were found to express the following receptors for nerve growth factor (NGF): neurotrophic receptor tyrosine kinase 1 and nerve growth factor receptor. An association was suggested between high production of NGF by cancer cells and the presence of nerves (P = 0.02). In vitro, NGF production in esophageal cancer cells was shown by Western blot, and esophageal cancer cells were able to induce neurite outgrowth in the PC12 neuronal cells. The neurotrophic activity of esophageal cancer cells was inhibited by anti-NGF blocking antibodies. Together, these data suggest that innervation is a feature in esophageal cancers that may be driven by cancer cell-released NGF.
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Affiliation(s)
- Nathan Griffin
- Faculty of Health and Medicine, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute, University of Newcastle, New Lambton, Australia
| | - Christopher W Rowe
- Hunter Medical Research Institute, University of Newcastle, New Lambton, Australia; Faculty of Health and Medicine, School of Medicine and Public Health, University of Newcastle, Callaghan, Australia
| | - Fangfang Gao
- Faculty of Health and Medicine, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute, University of Newcastle, New Lambton, Australia
| | - Phillip Jobling
- Faculty of Health and Medicine, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute, University of Newcastle, New Lambton, Australia
| | - Vanessa Wills
- Faculty of Health and Medicine, School of Medicine and Public Health, University of Newcastle, Callaghan, Australia; Department of Surgery, John Hunter Hospital, Newcastle, New South Wales, Australia
| | - Marjorie M Walker
- Hunter Medical Research Institute, University of Newcastle, New Lambton, Australia; Faculty of Health and Medicine, School of Medicine and Public Health, University of Newcastle, Callaghan, Australia
| | - Sam Faulkner
- Faculty of Health and Medicine, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute, University of Newcastle, New Lambton, Australia
| | - Hubert Hondermarck
- Faculty of Health and Medicine, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute, University of Newcastle, New Lambton, Australia.
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Kong L, Lu X, Chen X, Wu Y, Zhang Y, Shi H, Li J. Qigesan inhibits esophageal cancer cell invasion and migration by inhibiting Gas6/Axl-induced epithelial-mesenchymal transition. Aging (Albany NY) 2020; 12:9714-9725. [PMID: 32432570 PMCID: PMC7288918 DOI: 10.18632/aging.103238] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Accepted: 03/31/2020] [Indexed: 12/14/2022]
Abstract
Qigesan (QGS) has been used to effectively treat esophageal cancer (EC) for decades in China, but the mechanism by which it suppresses EC metastasis remains unknown. In this study, we examined the effects of QGS on EC cell mobility. Using immunohistochemistry and immunofluorescence, expression of Gas6 and Axl, which promote tumor cell migration and invasion, was examined in carcinoma tissues and adjacent normal tissues from EC patients. Levels of Gas6, Axl, and the Gas6/Axl complex were also examined in ECA109 and TE13 EC cells treated with QGS. In addition, immunofluorescent staining and quantitative protein analysis were used to examine E-cadherin, N-cadherin, and Snail levels in ECA109 and TE13 EC cells after QSG administration, and cell mobility was assessed. The results demonstrated that levels of Gas6 and Axl expression are higher in EC tissues than in adjacent normal tissues. Moreover, QGS decreased Gas6/Axl levels, increased E-cadherin expression, decreased Snail and N-cadherin expression, and inhibited epithelial-mesenchymal transition (EMT) in EC cells. QGS thus suppresses EMT in EC by inhibiting Gas6/Axl binding.
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Affiliation(s)
- Lingyu Kong
- College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, Hebei, China
| | - Xin Lu
- Department of Clinical Laboratory, Tangshan Maternal and Children Hospital, Tangshan 063000, Hebei, China
| | - Xuanyu Chen
- College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, Hebei, China
| | - Yunyan Wu
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei, China
| | - Yushuang Zhang
- Department of Traditional Chinese Medicine, Tumor Hospital of Hebei Province, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei, China
| | - Huijuan Shi
- Department of Traditional Chinese Medicine, Tumor Hospital of Hebei Province, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei, China
| | - Jing Li
- College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang 050017, Hebei, China,Department of Traditional Chinese Medicine, Tumor Hospital of Hebei Province, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei, China
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Yuan Y, Ma G, Hu X, Huang Q. Evaluating the eighth edition TNM staging system for esophageal cancer among patients receiving neoadjuvant therapy: A SEER study. Cancer Med 2020; 9:4648-4655. [PMID: 32391623 PMCID: PMC7333840 DOI: 10.1002/cam4.2997] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 01/12/2020] [Accepted: 02/19/2020] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND The evaluation of the eighth edition of ypTNM staging system for patients with esophageal cancer was limited in the setting of neoadjuvant therapy. METHODS A total of 2324 patients with esophageal cancer receiving radio(chemo)therapy prior to surgery from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2013 were eligible for the analysis. Kaplan-Meier method and Cox proportional hazards models were used to estimate overall survivals. RESULTS Among patients with preoperative therapy, both the seventh edition TNM grouping and the eighth edition ypTNM grouping could significantly stratify the overall survival (both log-rank P < .001). There was not significant difference in the C-index of the seventh edition TNM grouping (0.575; 95%CI, 0.558-0.593) and the eighth edition ypTNM grouping (0.569; 95%CI, 0.551-0.587) (P = .098). In multivariable Cox analysis, ypN category was the strongest predictor of overall survival (P < .001), followed by tumor grade (HR, 1.33; 95%CI, 1.12-1.56; P = .001). The combination of ypT, ypN, and ypG categories yielded significantly higher C-index (0.591; 95%CI, 0.573-0.609) than that of the seventh edition TNM staging (P = .024). CONCLUSION Tumor grade remained an independent predictor of overall survival in the setting of neoadjuvant therapy, and could improve the performance of ypTNM staging system.
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Affiliation(s)
- Yonggang Yuan
- Department of Thoracic Surgery, Qilu Hospital of Shandong University(Qingdao), Qingdao, P.R. China
| | - Ge Ma
- Department of Respiratory Medicine, Yidu Central Hospital of Weifang, Weifang, China
| | - Xuelei Hu
- Department of Thoracic Surgery, Qilu Hospital of Shandong University(Qingdao), Qingdao, P.R. China
| | - Qingyuan Huang
- Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China
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Kong J, Wang W. A Systemic Review on the Regulatory Roles of miR-34a in Gastrointestinal Cancer. Onco Targets Ther 2020; 13:2855-2872. [PMID: 32308419 PMCID: PMC7138617 DOI: 10.2147/ott.s234549] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Accepted: 12/22/2019] [Indexed: 12/12/2022] Open
Abstract
MicroRNAs (miRNAs) are a class of endogenous non-coding single-stranded small-molecule RNAs that regulate gene expression by repressing target messenger RNA (mRNA) translation or degrading mRNA. miR-34a is one of the most important miRNAs participating in various physiological and pathological processes. miR-34a is abnormally expressed in a variety of tumors. The roles of miR-34a in gastrointestinal cancer (GIC) draw lots of attention. Numerous studies have demonstrated that dysregulated miR-34a is closely related to the proliferation, differentiation, migration, and invasion of tumor cells, as well as the diagnosis, prognosis, treatment, and chemo-resistance of tumors. Thus, we systematically reviewed the abnormal expression and regulatory roles of miR-34a in GICs including esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), hepatocellular carcinoma (HCC), pancreatic cancer (PC), and gallbladder cancer (GBC). It may provide a profile of versatile roles of miR-34a in GICs.
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Affiliation(s)
- Jiehong Kong
- Center for Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China
| | - Weipeng Wang
- Center for Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China
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