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Yang JH, Lin WL, Chen WS, Jiang JK, Yang SH, Wang HS, Chang SC, Lan YT, Lin CC, Lin HH, Huang SC, Cheng HH, Yang YW, Lin YZ, Hsu HM, Lin CJ, Teng HW. The survival outcome differs between left-sided colon cancer and middle/low rectal cancer after colorectal hepatic metastasectomy. J Gastrointest Surg 2024; 28:1250-1258. [PMID: 38782088 DOI: 10.1016/j.gassur.2024.05.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 05/15/2024] [Accepted: 05/18/2024] [Indexed: 05/25/2024]
Abstract
BACKGROUND The clinical outcomes between left-sided colon cancer and middle/low rectal cancer seem to be different. This study aimed to examine the effect of primary tumor location regarding the left-sided colon and middle/low rectum on the overall survival (OS) of patients who underwent colorectal hepatic metastasectomy. METHODS Patients who underwent colorectal hepatic metastasectomy were retrospectively enrolled. Patients were classified into 2 groups according to the primary tumor location (left-sided colon and middle/low rectum). Categorical variables were compared using the chi-square test or Fisher exact test, and continuous variables were analyzed using the Student t test. Survival was analyzed using the Kaplan-Meier method and log-rank test. The prognostic factors were analyzed by univariate and multivariate analyses using Cox proportional hazards regression models. RESULTS Overall, 365 patients were enrolled. Patients with left-sided colon cancer had significantly better OS than those with middle/low rectal cancer (hazard ratio [HR], 0.725; P = .018), with median OS estimates of 48 and 38 months, respectively. In the subgroup analysis of RAS mutations, patients with left-sided colon cancer had significantly prolonged OS compared with those with middle/low rectum cancer (HR, 0.608; P = .034), with median OS estimates of 49 and 26 months, respectively. This observation was limited to patients with RAS mutations. CONCLUSION According to our findings, patients with middle/low rectal cancer had poorer survival outcome and should not be categorized together with patients with left-sided colon cancer in terms of OS after colorectal hepatic metastasectomy.
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Affiliation(s)
- Jin-Han Yang
- Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Wen-Ling Lin
- Department of Nursing, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Wei-Shone Chen
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jeng-Kai Jiang
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Shung-Haur Yang
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Surgery, National Yang Ming Chiao Tung University Hospital, Yilan, Taiwan
| | - Huann-Sheng Wang
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Shih-Ching Chang
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yuan-Tzu Lan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chun-Chi Lin
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hung-Hsin Lin
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Sheng-Chieh Huang
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hou-Hsuan Cheng
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Wen Yang
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yu-Zu Lin
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hui-Mei Hsu
- Department of Nursing, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ching-Jui Lin
- Department of Nursing, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hao-Wei Teng
- Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
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Mima K, Hayashi H, Maruno M, Yumoto S, Matsumoto T, Tsukamoto M, Miyata T, Nakagawa S, Nitta H, Imai K, Baba H. Perioperative disabilities in activities of daily living are associated with worse prognosis after hepatectomy for colorectal liver metastasis. HPB (Oxford) 2024; 26:203-211. [PMID: 37770363 DOI: 10.1016/j.hpb.2023.09.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 06/20/2023] [Accepted: 09/11/2023] [Indexed: 09/30/2023]
Abstract
BACKGROUND The number of vulnerable patients with colorectal liver metastasis (CRLM) has increased. This study aimed to clarify the relationship between perioperative activities of daily living (ADL) and clinical outcomes after hepatectomy for CRLM. METHODS Consecutive patients undergoing resection of CRLM from 2004 to 2020 were included. Pre- or postoperative ADL was evaluated according to Barthel index (BI) scores, which range from 0 to 100. Higher scores represent greater level of independence in ADL. Pre- or postoperative BI scores of ≤85 were defined as perioperative disabilities in ADL. Multivariable Cox proportional hazard regression models were utilised to estimate adjusted hazard ratios (HRs) and confidence interval (CI). RESULTS A total of 218 patients were included, 16 (7.3%) revealed preoperative BI scores of ≤85, and 32 (15%) revealed postoperative BI scores of ≤85. In multivariate analyses, the perioperative disabilities in ADL were independently associated with shorter overall survival (HR, 1.96; 95% CI, 1.10-3.31; P = 0.023) and cancer-specific survival (HR, 2.31; 95% CI, 1.29-3.92; P = 0.006). CONCLUSION Perioperative disabilities in ADL were associated with poor prognosis following hepatectomy for CRLM. Improving preoperative vulnerability and preventing functional decline after surgery may provide a favourable prognosis for patients with CRLM.
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Affiliation(s)
- Kosuke Mima
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Hiromitsu Hayashi
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Masataka Maruno
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Shinsei Yumoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Takashi Matsumoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Masayo Tsukamoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Tatsunori Miyata
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Shigeki Nakagawa
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Hidetoshi Nitta
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
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Mima K, Hayashi H, Adachi Y, Tajiri T, Ofuchi T, Kanemitsu K, Ogawa D, Yumoto S, Matsumoto T, Itoyama R, Kitano Y, Nakagawa S, Okabe H, Baba H. Patient vulnerability is associated with poor prognosis following upfront hepatectomy for colorectal liver metastasis. Int J Clin Oncol 2024; 29:47-54. [PMID: 37943377 DOI: 10.1007/s10147-023-02429-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 10/10/2023] [Indexed: 11/10/2023]
Abstract
BACKGROUND With the rapid aging of populations worldwide, the number of vulnerable patients with liver metastasis from colorectal cancer has increased. This study aimed to examine the association between vulnerability and clinical outcomes in patients with colorectal liver metastasis (CRLM). METHODS Consecutive 101 patients undergoing upfront hepatectomy for CRLM between 2004 and 2020 were included. The preoperative vulnerability was assessed using the Clinical Frailty Scale (CFS) score ranging from one (very fit) to nine (terminally ill), and frailty was defined as a CFS score of ≥ 4. A multivariable Cox proportional hazard regression model was utilized to investigate associations of frailty with disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS). RESULTS Of the 101 patients, 12 (12%) had frailty. Associations between frailty and surgical outcomes, namely, the incidence of 90-day mortality and postoperative complications, were not statistically significant (P > 0.05). In the multivariable analyses, after adjusting for clinical risk scores calculated using six factors (timing of liver metastasis, primary tumor lymph node status, number of liver tumors, size of the largest tumor, extrahepatic metastatic disease, and carbohydrate antigen 19-9 level) to predict recurrence following hepatectomy for CRLM, preoperative frailty was found to be an independent risk factor for DFS (hazard ratio [HR]:2.37, 95% confidence interval [CI] 1.06-4.72, P = 0.036), OS (HR:4.17, 95% CI 1.43-10.89, P = 0.011), and CSS (HR:3.49, 95% CI 1.09-9.60, P = 0.036). CONCLUSION Preoperative frailty was associated with worse DFS, OS, and CSS after upfront hepatectomy for CRLM. Assessment and improvement of patient vulnerability may provide a favorable prognosis for patients with CRLM.
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Affiliation(s)
- Kosuke Mima
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Hiromitsu Hayashi
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Yuki Adachi
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Takuya Tajiri
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Takashi Ofuchi
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Kosuke Kanemitsu
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Daisuke Ogawa
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Shinsei Yumoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Takashi Matsumoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Rumi Itoyama
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Yuki Kitano
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Shigeki Nakagawa
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Hirohisa Okabe
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan.
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Gholamalizadeh H, Zafari N, Velayati M, Fiuji H, Maftooh M, Ghorbani E, Hassanian SM, Khazaei M, Ferns GA, Nazari E, Avan A. Prognostic value of primary tumor location in colorectal cancer: an updated meta-analysis. Clin Exp Med 2023; 23:4369-4383. [PMID: 37405571 DOI: 10.1007/s10238-023-01120-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 06/12/2023] [Indexed: 07/06/2023]
Abstract
The clinical, histological, and molecular differences between right-sided colon cancer (RCC) and left-sided colon cancer (RCC) have received considerable attention. Over the past decade, many articles have been published concerning the association between primary tumor location (PTL) of colorectal cancer and survival outcomes. Therefore, there is a growing need for an updated meta-analysis integrating the outcomes of recent studies to determine the prognostic role of right vs left-sidedness of PTL in patients with colorectal cancer. We conducted a comprehensive database review using PubMed, SCOPUS, and Cochrane library databases from February 2016 to March 2023 for prospective or retrospective studies reporting data on overall survival (OS) and cancer-specific survival (CSS) of RCC compared with LCC. A total of 60 cohort studies comprising 1,494,445 patients were included in the meta-analysis. We demonstrated that RCC is associated with a significantly increased risk of death compared with LCC by 25% (hazard ratio (HR), 1.25; 95% confidence interval (CI), 1.19-1.31; I2 = 78.4%; Z = 43.68). Results showed that patients with RCC have a worse OS compared with LCC only in advanced stages (Stage III: HR, 1.275; 95% CI 1.16-1.4; P = 0.0002; I2 = 85.8%; Stage IV: HR, 1.34; 95% CI 1.25-1.44; P < 0.0001; I2 = 69.2%) but not in primary stages (Stage I/II: HR, 1.275; 95% CI 1.16-1.4; P = 0.0002; I2 = 85.8%). Moreover, a meta-analysis of 13 studies including 812,644 patients revealed that there is no significant difference in CSS between RCC and LCC (HR, 1.121; 95% CI 0.97-1.3; P = 0.112). Findings from the present meta-analysis highlight the importance of PTL in clinical decision-making for patients with CRC, especially in advanced stages. We provide further evidence supporting the hypothesis that RCC and LCC are distinct disease entities that should be managed differently.
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Affiliation(s)
- Hanieh Gholamalizadeh
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Nima Zafari
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahla Velayati
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamid Fiuji
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mina Maftooh
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Elnaz Ghorbani
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Mahdi Hassanian
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Khazaei
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon A Ferns
- Division of Medical Education, Brighton and Sussex Medical School, Falmer, Brighton, Sussex, BN1 9PH, UK
| | - Elham Nazari
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Amir Avan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- College of Medicine, University of Warith Al-Anbiyaa, Karbala, Iraq.
- School of Mechanical, Medical and Process Engineering, Science and Engineering Faculty, Queensland University of Technology, 2 George St, Brisbane, QLD, 4000, Australia.
- Faculty of Health, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia.
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Xu Y, He J, Li W, Zhang W, Liu S, He J, Pan Z, Lu Z, Peng J, Lin J. The Pathologic Complete Response Ratio of Liver Metastases Represents a Valuable Prognostic Indicator. Pathol Oncol Res 2022; 28:1610663. [PMID: 36147656 PMCID: PMC9485473 DOI: 10.3389/pore.2022.1610663] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 08/17/2022] [Indexed: 11/13/2022]
Abstract
Background and Objectives: The aim of this study was to evaluate the role of the pathologic complete response ratio of liver metastases (PCRRLM) in predicting the prognosis and recurrence of colorectal cancer liver metastases (CRLM). Methods: A total of 305 CRLM patients who underwent preoperative chemotherapy followed by hepatectomy were included. PCRRLM was defined as the number of liver metastases exhibiting pathologic complete response (PCR) divided by the number of total resected liver metastases. The Kaplan–Meier method was used to calculate survival, and differences were examined by the log-rank test. Univariate and multivariate analyses were performed to identify the predictors of PCRRLM, recurrence-free survival (RFS) and overall survival (OS). Results: Among the 305 included patients, 44 (14.4%) achieved a PCRRLM ≥0.50 (including PCRRLM = 1), and 261 (85.6%) achieved a PCRRLM <0.50 (including PCRRLM = 0). Patients of an older age (≥55 years old) and those with higher carcinoembryonic antigen (CEA) levels (≥5 ng/ml) were less likely to achieve a PCRRLM ≥0.50. In the multivariate analysis, PCRRLM≥ 0.50 (vs. < 0.50, HR [95% CI]: 0.67 [0.46–0.99], p = 0.043) was associated with better RFS. Positive lymph node status (vs. negative, HR [95% CI]: 1.46 [1.04–2.05], p = 0.028) and TBS ≥5 (vs. < 5, HR [95% CI]: 1.44 [1.02–2.04], p = 0.038) were associated with worse RFS. Conclusion: PCRRLM was significantly associated with long-term RFS after preoperative chemotherapy and CRLM resection. Thus, it may be a valuable indicator of recurrence in CRLM patients.
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Sakamoto Y, Mima K, Ishimoto T, Ogata Y, Imai K, Miyamoto Y, Akiyama T, Daitoku N, Hiyoshi Y, Iwatsuki M, Baba Y, Iwagami S, Yamashita Y, Yoshida N, Komohara Y, Ogino S, Baba H. Relationship between Fusobacterium nucleatum and antitumor immunity in colorectal cancer liver metastasis. Cancer Sci 2021; 112:4470-4477. [PMID: 34464993 PMCID: PMC8586672 DOI: 10.1111/cas.15126] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 08/20/2021] [Accepted: 08/30/2021] [Indexed: 12/31/2022] Open
Abstract
Fusobacterium nucleatum has been detected in 8%-13% of human colorectal cancer, and shown to inhibit immune responses against primary colorectal tumors in animal models. Thus, we hypothesized that the presence of F. nucleatum might be associated with reduced T cell density in colorectal cancer liver metastases (CRLM). We quantified F. nucleatum DNA in 181 CRLM specimens using quantitative PCR assay. The densities of CD8+ T cells, CD33+ cells (marker for myeloid-derived suppressor cells [MDSCs]), and CD163+ cells (marker for tumor-associated macrophages [TAMs]) in CRLM tissue were determined by immunohistochemical staining. Fusobacterium nucleatum was detected in eight (4.4%) of 181 CRLM specimens. Compared with F. nucleatum-negative CRLM, F. nucleatum-positive CRLM showed significantly lower density of CD8+ T cells (P = .033) and higher density of MDSCs (P = .001). The association of F. nucleatum with the density of TAMs was not statistically significant (P = .70). The presence of F. nucleatum is associated with a lower density of CD8+ T cells and a higher density of MDSCs in CRLM tissue. Upon validation, our findings could provide insights to develop strategies that involve targeting microbiota and immune cells for the prevention and treatment of CRLM.
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Affiliation(s)
- Yuki Sakamoto
- Department of Gastroenterological SurgeryGraduate School of Medical SciencesKumamoto UniversityKumamotoJapan
| | - Kosuke Mima
- Department of Gastroenterological SurgeryGraduate School of Medical SciencesKumamoto UniversityKumamotoJapan
- Department of SurgeryNational Hospital Organization Kumamoto Medical CenterKumamotoJapan
| | - Takatsugu Ishimoto
- Department of Gastroenterological SurgeryGraduate School of Medical SciencesKumamoto UniversityKumamotoJapan
- Gastrointestinal Cancer BiologyInternational Research Center for Medical SciencesKumamoto UniversityKumamotoJapan
| | - Yoko Ogata
- Department of Gastroenterological SurgeryGraduate School of Medical SciencesKumamoto UniversityKumamotoJapan
| | - Katsunori Imai
- Department of Gastroenterological SurgeryGraduate School of Medical SciencesKumamoto UniversityKumamotoJapan
| | - Yuji Miyamoto
- Department of Gastroenterological SurgeryGraduate School of Medical SciencesKumamoto UniversityKumamotoJapan
| | - Takahiko Akiyama
- Department of Gastroenterological SurgeryGraduate School of Medical SciencesKumamoto UniversityKumamotoJapan
| | - Nobuya Daitoku
- Department of Gastroenterological SurgeryGraduate School of Medical SciencesKumamoto UniversityKumamotoJapan
| | - Yukiharu Hiyoshi
- Department of Gastroenterological SurgeryCancer Institute HospitalTokyoJapan
| | - Masaaki Iwatsuki
- Department of Gastroenterological SurgeryGraduate School of Medical SciencesKumamoto UniversityKumamotoJapan
| | - Yoshifumi Baba
- Department of Gastroenterological SurgeryGraduate School of Medical SciencesKumamoto UniversityKumamotoJapan
| | - Shiro Iwagami
- Department of Gastroenterological SurgeryGraduate School of Medical SciencesKumamoto UniversityKumamotoJapan
| | - Yo‐ichi Yamashita
- Department of Gastroenterological SurgeryGraduate School of Medical SciencesKumamoto UniversityKumamotoJapan
| | - Naoya Yoshida
- Department of Gastroenterological SurgeryGraduate School of Medical SciencesKumamoto UniversityKumamotoJapan
- Division of Translational Research and Advanced Treatment Against Gastrointestinal CancerKumamoto UniversityKumamotoJapan
| | - Yoshihiro Komohara
- Department of Cell PathologyGraduate School of Medical SciencesKumamoto UniversityKumamotoJapan
| | - Shuji Ogino
- Program in MPE Molecular Pathological EpidemiologyDepartment of PathologyBrigham and Women's Hospital and Harvard Medical SchoolBostonMassachusettsUSA
- Department of EpidemiologyHarvard T.H. Chan School of Public HealthBostonMassachusettsUSA
- Department of Oncologic PathologyDana‐Farber Cancer InstituteBostonMassachusettsUSA
- Broad Institute of MIT and HarvardCambridgeMassachusettsUSA
- Cancer Immunology and Cancer Epidemiology ProgramsDana‐Farber Harvard Cancer CenterBostonMassachusettsUSA
| | - Hideo Baba
- Department of Gastroenterological SurgeryGraduate School of Medical SciencesKumamoto UniversityKumamotoJapan
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Zhang Y, Ge L, Weng J, Tuo WY, Liu B, Ma SX, Yang KH, Cai H. Neoadjuvant chemotherapy for patients with resectable colorectal cancer liver metastases: A systematic review and meta-analysis. World J Clin Cases 2021; 9:6357-6379. [PMID: 34435001 PMCID: PMC8362587 DOI: 10.12998/wjcc.v9.i22.6357] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 04/14/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND In recent years, neoadjuvant chemotherapy (NAC) has been increasingly used in patients with resectable colorectal liver metastases. However, the efficacy and safety of NAC in the treatment of resectable colorectal liver metastases (CRLM) are still controversial.
AIM To assess the efficacy and application value of NAC in patients with resectable CRLM.
METHODS We searched PubMed, Embase, Web of Science, and the Cochrane Library from inception to December 2020 to collect clinical studies comparing NAC with non-NAC. Data processing and statistical analyses were performed using Stata V.15.0 and Review Manager 5.0 software.
RESULTS In total, 32 studies involving 11236 patients were included in this analysis. We divided the patients into two groups, the NAC group (that received neoadjuvant chemotherapy) and the non-NAC group (that received no neoadjuvant chemotherapy). The meta-analysis outcome showed a statistically significant difference in the 5-year overall survival and 5-year disease-free survival between the two groups. The hazard ratio (HR) and 95% confidence interval (CI) were HR = 0.49, 95%CI: 0.39-0.61, P = 0.000 and HR = 0.48 95%CI: 0.36-0.63, P = 0.000. The duration of surgery in the NAC group was longer than that of the non-NAC group [standardized mean difference (SMD) = 0.41, 95%CI: 0.01-0.82, P = 0.044)]. The meta-analysis showed that the number of liver metastases in the NAC group was significantly higher than that in the non-NAC group (SMD = 0.73, 95%CI: 0.02-1.43, P = 0.043). The lymph node metastasis in the NAC group was significantly higher than that in the non-NAC group (SMD = 1.24, 95%CI: 1.07-1.43, P = 0.004).
CONCLUSION We found that NAC could improve the long-term prognosis of patients with resectable CRLM. At the same time, the NAC group did not increase the risk of any adverse event compared to the non-NAC group.
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Affiliation(s)
- Yue Zhang
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Long Ge
- Evidence Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Jun Weng
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Wen-Yu Tuo
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Bin Liu
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Shi-Xun Ma
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Ke-Hu Yang
- Evidence Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Hui Cai
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
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Treska V, Skala M, Prochazkova K, Svejdova A, Petrakova T, Sebek J, Riha I, Rosendorf J, Polak R, Skalicky T, Liska V. Long-term Results of Surgery for Colorectal Liver Metastases in Terms of Primary Tumour Location and Clinical Risk Factors. In Vivo 2021; 34:2675-2685. [PMID: 32871799 DOI: 10.21873/invivo.12087] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Revised: 04/28/2020] [Accepted: 05/05/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND/AIM The aim of the study was to evaluate the influence of primary tumour location and clinical risk factors for long-term results of surgery for colorectal liver metastases (CLMs). PATIENTS AND METHODS Overall survival (OS) and recurrence-free survival (RFS) were evaluated in 636 patients. Patients were divided by tumour location (right-/left-sided colorectal cancer: RCRC/LCRC; rectal cancer), and age, gender, number and size of CLMs, type of liver surgery and interval from primary operation were evaluated. RESULTS One-, 3- and 5-year OS and RFS were independent of primary tumour location (p<0.59). CLM diameter was negatively associated with OS for the whole cohort (p<0.002), and RCRC (p<0.03) and LCRC (p<0.04) groups, as well as for RFS of those with LCRC (p<0.04). CLM number was negatively associated with RFS for the whole cohort (p<0.0001), RCRC (p<0.02), LCRC (p<0.0001) and RC (p<0.02). Radiofrequency ablation and combined procedures led to worse OS for the whole cohort (p<0.03), and to worse RFS for the whole cohort (p<0.0003) and for those with LCRC (p<0.03). A shorter interval between primary colorectal cancer surgery and CLMs procedure was risky for poor OS and RFS of patients with CLMs from RCRC (p<0.05), LCRC (p<0.05) and RC (p<0.02). CONCLUSION Primary tumour location together with clinical risk factors are important for long-term results of surgery CLMs.
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Affiliation(s)
- Vladislav Treska
- Department of Surgery, University Hospital, School of Medicine in Pilsen, Pilsen, Czech Republic
| | - Martin Skala
- Department of Surgery, University Hospital, School of Medicine in Pilsen, Pilsen, Czech Republic
| | - Kristyna Prochazkova
- Department of Surgery, University Hospital, School of Medicine in Pilsen, Pilsen, Czech Republic
| | - Aneta Svejdova
- Department of Surgery, University Hospital, School of Medicine in Pilsen, Pilsen, Czech Republic
| | - Tereza Petrakova
- Department of Surgery, University Hospital, School of Medicine in Pilsen, Pilsen, Czech Republic
| | - Jakub Sebek
- Department of Surgery, University Hospital, School of Medicine in Pilsen, Pilsen, Czech Republic
| | - Ivan Riha
- Department of Surgery, University Hospital, School of Medicine in Pilsen, Pilsen, Czech Republic
| | - Jachym Rosendorf
- Department of Surgery, University Hospital, School of Medicine in Pilsen, Pilsen, Czech Republic
| | - Robert Polak
- Department of Surgery, University Hospital, School of Medicine in Pilsen, Pilsen, Czech Republic
| | - Tomas Skalicky
- Department of Surgery, University Hospital, School of Medicine in Pilsen, Pilsen, Czech Republic
| | - Vaclav Liska
- Department of Surgery, University Hospital, School of Medicine in Pilsen, Pilsen, Czech Republic
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9
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Gholami S, Stewart S, Kemeny N, Gönen M, Groot Koerkamp B, Cercek A, Kingham P, Balachandran V, Allen P, DeMatteo R, Wei A, Connell L, Drebin J, Jarnagin W, D'Angelica M. Impact of Primary Tumor Laterality on Adjuvant Hepatic Artery Infusion Pump Chemotherapy in Resected Colon Cancer Liver Metastases: Analysis of 487 Patients. Ann Surg Oncol 2020; 28:3685-3694. [PMID: 33230748 DOI: 10.1245/s10434-020-09369-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 10/26/2020] [Indexed: 01/05/2023]
Abstract
BACKGROUND Hepatic artery infusion (HAI) chemotherapy is associated with overall survival (OS) in patients with resected colon cancer liver metastases (CLM). The prognostic impact of primary tumor location in CLM following hepatic resection in patients receiving regional HAI is unknown. This study seeks to investigate the prognostic impact of HAI in relation to laterality in this patient population. METHODS Consecutive patients with resected CLM, with known primary tumor site treated with and without HAI, were reviewed from a prospective institutional database. Correlations between HAI, laterality, other clinicopathological factors, and survival were analyzed, and Cox proportional hazard regression was used to determine whether laterality was an independent prognostic factor. RESULTS From 1993 to 2012, 487 patients [182 with right colon cancer (RCC), 305 with left colon cancer (LCC)] were evaluated with a median follow-up of 6.5 years. Fifty-seven percent (n = 275) received adjuvant HAI. Patients with RCC had inferior 5-year OS compared with LCC (56% vs. 67%, P = 0.01). HAI was associated with improved 5-year OS in both RCC (68% vs. 45%; P < 0.01) and LCC (73% vs. 55%; P < 0.01). On multivariable analysis, HAI remained associated with improved OS (HR 0.52; 95% CI 0.39-0.70; P < 0.01) but primary tumor site did not (HR 0.83; 95% CI 0.63-1.11; P = 0.21). Additional significant prognostic factors on multivariable analysis included age, number of tumors, node-positive primary, positive margins, RAS mutation, two-stage hepatectomy, and extrahepatic disease. Cox proportional hazard regression determined no significant interaction between HAI and laterality on OS [parameter estimate (SEM), 0.12 (0.28); P = 0.67]. CONCLUSIONS Our data show an association of adjuvant HAI and increased OS in patients who underwent curative hepatectomy, irrespective of primary tumor location. Laterality should therefore not impact decision-making when offering adjuvant HAI.
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Affiliation(s)
- Sepideh Gholami
- Department of Surgery, UC Davis Cancer Center, Sacramento, CA, USA
| | - Susan Stewart
- Division of Biostatistics, UC Davis Cancer Center, Sacramento, CA, USA
| | - Nancy Kemeny
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Mithat Gönen
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Andrea Cercek
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Vinod Balachandran
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Peter Allen
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Ronald DeMatteo
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Alice Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Louise Connell
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jeffrey Drebin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - William Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Michael D'Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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10
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Sakamoto Y, Mima K, Imai K, Miyamoto Y, Tokunaga R, Akiyama T, Daitoku N, Hiyoshi Y, Iwatsuki M, Nagai Y, Baba Y, Iwagami S, Yamashita YI, Yoshida N, Baba H. Preoperative C-reactive protein-to-albumin ratio and clinical outcomes after resection of colorectal liver metastases. Surg Oncol 2020; 35:243-248. [PMID: 32932221 DOI: 10.1016/j.suronc.2020.09.014] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 08/13/2020] [Accepted: 09/08/2020] [Indexed: 12/16/2022]
Abstract
PURPOSE Accumulating evidence suggests that the inflammatory tumor microenvironment can potentiate tumor progression and metastasis. The C-reactive protein-to-albumin ratio (CAR) is a novel inflammation-based prognostic score. This study was performed to examine the associations of the preoperative CAR with clinical outcomes in patients with colorectal liver metastases (CRLM) after curative resection. METHODS We retrospectively assessed the preoperative CAR in 184 patients who underwent curative resection for CRLM from November 2001 to January 2018 at Kumamoto University (Kumamoto, Japan). The optimal cutoff level of the preoperative CAR was determined by survival classification and regression tree (CART) analysis. We compared clinicopathological factors and prognoses between the high-CAR and low-CAR groups. A Cox proportional hazards model was used to calculate hazard ratios (HRs), controlling for potential confounders. RESULTS A higher preoperative CAR was associated with worse overall survival (OS) (p < 0.0001) and recurrence-free survival (RFS) (p = 0.003). Applying survival CART analysis, the high-CAR group comprised 33 patients (17.9%). In the multivariate analyses, a high CAR was independently associated with shorter OS (HR, 2.82; 95% confidence interval, 1.63-4.72; p = 0.0004) and RFS (HR, 1.62; 95% confidence interval, 1.02-2.49; p = 0.040). A high CAR was associated with a large tumor size, high serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels, high intraoperative blood loss, and more postoperative complications. CONCLUSION A high preoperative CAR is associated with shorter OS and RFS and might serve as a prognostic marker for patients with CRLM after curative resection.
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Affiliation(s)
- Yuki Sakamoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Kosuke Mima
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; Department of Surgery, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yuji Miyamoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Ryuma Tokunaga
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Takahiko Akiyama
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Nobuya Daitoku
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yukiharu Hiyoshi
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Masaaki Iwatsuki
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yohei Nagai
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yoshifumi Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Shiro Iwagami
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yo-Ichi Yamashita
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Naoya Yoshida
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
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11
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Bingham G, Shetye A, Suresh R, Mirnezami R. Impact of primary tumour location on colorectal liver metastases: A systematic review. World J Clin Oncol 2020; 11:294-307. [PMID: 32728532 PMCID: PMC7360521 DOI: 10.5306/wjco.v11.i5.294] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 05/09/2020] [Accepted: 05/14/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is the third most common cause of cancer-related death worldwide. Despite significant advances in screening, surgical management and adjuvant therapies, average 5-year survival seldom exceeds 60% in most developed nations. Metastatic disease represents the primary cause of mortality in patients with CRC, and the liver is the most common location for distant tumour spread. Up to 25% of patients are found to have synchronous liver metastases at the time of diagnosis and a further 30%-40% will develop metachronous disease in the course of follow-up. It has been suggested that primary tumour location [right side versus left side, primary tumour location (PTL)] can influence oncological outcomes in this patient group and that this should be considered in prognostic models and therapeutic decision-making algorithms. This suggestion is not universally accepted and there have been conflicting reports in the literature to date.
AIM To provide a comprehensive summary of the available evidence regarding the impact of PTL on oncological outcomes in patients with colorectal cancer liver metastases (CRCLM).
METHODS MEDLINE, EMBASE and COCHRANE were searched for relevant publications using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. Data on oncological outcomes was then extracted from full text articles that met the predefined inclusion criteria.
RESULTS A total of 41 studies were identified that met predefined inclusion criteria for this review. In 21 out of 38 studies that provided data on overall survival, a statistically significant improvement in overall survival was reported in patients with left sided primary tumours. These studies included a total of 13897 patients compared with 4306 patients in the studies that did not show a significant difference. Eight studies noted a similar trend towards improved disease-free or progression-free survival. Several authors observed distinct patterns of relapse after treatment of hepatic metastases according to PTL; for example hepatic recurrence after treatment of CRCLM appears to occur more aggressively with right-sided CRC.
CONCLUSION Taken together, the findings of the present review indicate that PTL may have a role as an independent prognostic factor when determining treatment and disease surveillance strategies in CRC. The mechanisms responsible for this variation remain poorly understood, but are likely to relate to molecular, histological and embryological differences, as well as inherent differences in therapeutic sensitivity.
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Affiliation(s)
- George Bingham
- Department of General Surgery, St. Thomas’s Hospital, Lambeth, London SE1 7EH, United Kingdom
| | - Alysha Shetye
- Department of Colorectal Surgery, Royal Free Hospital, Hampstead, London NW3 2QG, United Kingdom
| | - Reena Suresh
- Department of General Surgery, St. Thomas’s Hospital, Lambeth, London SE1 7EH, United Kingdom
| | - Reza Mirnezami
- Department of Colorectal Surgery, Royal Free Hospital, Hampstead, London NW3 2QG, United Kingdom
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12
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Wang XY, Zhang R, Wang Z, Geng Y, Lin J, Ma K, Zuo JL, Lu L, Zhang JB, Zhu WW, Chen JH. Meta-analysis of the association between primary tumour location and prognosis after surgical resection of colorectal liver metastases. Br J Surg 2019; 106:1747-1760. [PMID: 31386192 DOI: 10.1002/bjs.11289] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2019] [Revised: 05/14/2019] [Accepted: 05/28/2019] [Indexed: 12/24/2022]
Abstract
BACKGROUND Primary tumour location is emerging as an important prognostic factor in localized and metastatic colorectal cancers. However, its prognostic role in colorectal liver metastasis (CRLM) after hepatectomy remains controversial. A systematic review and meta-analysis was undertaken to evaluate its prognostic value. METHODS References were identified through searches of PubMed, Embase, Web of Science and the Cochrane Library comparing overall or disease-free survival after hepatic resection between patients with CRLM originating from right- or left-sided colorectal cancers. Data were pooled using hazard ratios (HRs) and 95 per cent confidence intervals according to a random-effects model. Meta-regression and subgroup analyses were conducted to assess the effect of underlying confounding factors on HR estimates and to adjust for this. RESULTS The final analysis included 21 953 patients from 45 study cohorts. Compared with left-sided primary tumour location, right-sided location was associated with worse overall survival (HR 1·39, 95 per cent c.i. 1·28 to 1·51; P < 0·001; prediction interval 1·00 to 1·93), and also tended to have a negative impact on disease-free survival (HR 1·18, 1·06 to 1·32; P = 0·004; prediction interval 0·79 to 1·75). Subgroup analysis showed that the negative effect of right-sided primary tumour location on overall survival was more prominent in the non-Asian population (HR 1·47, 1·33 to 1·62) than the Asian population (HR 1·18, 1·05 to 1·32) (P for interaction <0·01). CONCLUSION This study demonstrated a prognostic role for primary tumour location in patients with CRLM receiving hepatectomy, especially regarding overall survival. Adding primary tumour location may provide important optimization of prognosis prediction models for CRLM in current use.
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Affiliation(s)
- X-Y Wang
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.,Institutes of Cancer Metastasis, Fudan University, Shanghai, China
| | - R Zhang
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.,Institutes of Cancer Metastasis, Fudan University, Shanghai, China
| | - Z Wang
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.,Institutes of Cancer Metastasis, Fudan University, Shanghai, China
| | - Y Geng
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.,Institutes of Cancer Metastasis, Fudan University, Shanghai, China
| | - J Lin
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.,Institutes of Cancer Metastasis, Fudan University, Shanghai, China
| | - K Ma
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.,Institutes of Cancer Metastasis, Fudan University, Shanghai, China
| | - J-L Zuo
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.,Institutes of Cancer Metastasis, Fudan University, Shanghai, China
| | - L Lu
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.,Institutes of Cancer Metastasis, Fudan University, Shanghai, China
| | - J-B Zhang
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - W-W Zhu
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.,Institutes of Cancer Metastasis, Fudan University, Shanghai, China
| | - J-H Chen
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.,Institutes of Cancer Metastasis, Fudan University, Shanghai, China
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13
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Gasser E, Braunwarth E, Riedmann M, Cardini B, Fadinger N, Presl J, Klieser E, Ellmerer P, Dupré A, Imai K, Malik H, Baba H, Ulmer H, Schneeberger S, Öfner D, Dinnewitzer A, Stättner S, Primavesi F. Primary tumour location affects survival after resection of colorectal liver metastases: A two-institutional cohort study with international validation, systematic meta-analysis and a clinical risk score. PLoS One 2019; 14:e0217411. [PMID: 31150437 PMCID: PMC6544347 DOI: 10.1371/journal.pone.0217411] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Accepted: 05/10/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Colorectal cancer (CRC) represents a major cause for cancer death and every third patient develops liver metastases (CRLM). Several factors including number and size of metastases and primary tumour lymph-node status have been linked to survival. The primary tumour location along the colo-rectum continuum (sidedness) was analysed in first-line chemotherapy trials, where right-sided CRCs showed decreased survival. This association has not yet been clearly established in patients undergoing resection for CRLM. METHODS Clinicopathological differences in CRLM resections according to sidedness in two Austrian centres (2003-2016) are described and survival is compared through Kaplan-Meier and multivariable analysis. A risk-score is presented with time-dependent receiver operating curve analysis and international validation in two major hepatobiliary centres. Furthermore, a systematic meta-analysis of studies on primary tumour location and survival after CRLM resection was performed. RESULTS 259 patients underwent hepatectomy. Right-sided CRC patients (n = 59) more often had positive primary tumour lymph-nodes (76.3%/61.3%;p = 0.043) and RAS-mutations (60%/34.9%;p = 0.036). The median overall and disease-free survival was 33.5 and 9.1 months in right-sided versus 55.5 (p = 0.051) and 12.1 months (p = 0.078) in left-sided patients. In multivariable analysis nodal-status (HR 1.52), right-sidedness (HR 1.53), extrahepatic disease (HR 1.71) and bilobar hepatic involvement (HR 1.41) were significantly associated with overall survival. Sidedness was not independently associated with disease-free survival (HR 1.33; p = 0.099). A clinical risk score including right-sidedness, nodal-positivity and extrahepatic involvement significantly predicted overall (p = 0.005) and disease-free survival (p = 0.027), which was confirmed by international validation in 527 patients (p = 0.001 and p = 0.011). Meta-analysis including 10 studies (n = 4312) showed a significant association of right-sidedness with overall survival after resection (HR 1.55;p<0.001). There was no significant association with disease-free survival (HR 1.22;p = 0.077), except when rectal-cancers were excluded (HR 1.39;p = 0.006). CONCLUSIONS Patients with liver metastases from right-sided CRC experience worse survival after hepatic resection. Sidedness is a simple yet effective factor to predict outcome.
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Affiliation(s)
- Elisabeth Gasser
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Eva Braunwarth
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Marina Riedmann
- Department of Medical Statistics, Informatics and Health Economics, Medical University of Innsbruck, Innsbruck, Austria
| | - Benno Cardini
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Nikolaus Fadinger
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Jaroslav Presl
- Department of Surgery, Paracelsus Medical University, Salzburg, Austria
| | - Eckhard Klieser
- Institute of Pathology, Paracelsus Medical University, Salzburg, Austria
| | - Philipp Ellmerer
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| | - Aurélien Dupré
- Liverpool Hepatobiliary Centre, Aintree University Hospital, Liverpool, United Kingdom
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Kumamoto University, Kumamoto, Japan
| | - Hassan Malik
- Liverpool Hepatobiliary Centre, Aintree University Hospital, Liverpool, United Kingdom
| | - Hideo Baba
- Department of Gastroenterological Surgery, Kumamoto University, Kumamoto, Japan
| | - Hanno Ulmer
- Department of Medical Statistics, Informatics and Health Economics, Medical University of Innsbruck, Innsbruck, Austria
| | - Stefan Schneeberger
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Dietmar Öfner
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
- Department of Surgery, Paracelsus Medical University, Salzburg, Austria
| | - Adam Dinnewitzer
- Department of Surgery, Paracelsus Medical University, Salzburg, Austria
| | - Stefan Stättner
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
- Department of Surgery, Paracelsus Medical University, Salzburg, Austria
| | - Florian Primavesi
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
- Department of Surgery, Paracelsus Medical University, Salzburg, Austria
- * E-mail:
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