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Fujitani K, Kurokawa Y, Wada R, Takeno A, Kawabata R, Omori T, Imamura H, Hirao M, Endo S, Kawada J, Moon JH, Takiguchi S, Mori M, Eguchi H, Doki Y. Prospective single-arm multicenter interventional study of surgical resection for liver metastasis from gastric cancer; 3-year overall and recurrence-free survival. Eur J Cancer 2024; 213:115080. [PMID: 39461056 DOI: 10.1016/j.ejca.2024.115080] [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: 06/24/2024] [Revised: 10/08/2024] [Accepted: 10/15/2024] [Indexed: 10/29/2024]
Abstract
OBJECTIVE Potential benefit of surgical resection for liver metastasis from gastric cancer (LMGC) remains controversial because most previous studies were retrospective. We evaluated the outcomes of surgical resection following chemotherapy for LMGC in a prospective single-arm multicenter interventional study. METHODS Patients with synchronous or metachronous LMGC received 2-4 cycles of standard chemotherapy and proceeded to surgical resection if restaging showed a non-progressive disease with a chance of R0 resection. The primary endpoint was 3-year OS of R0 patients, with RFS as secondary. Prognostic factors for R0 patients were evaluated by multivariable Cox regression analysis. RESULTS Seventy patients were enrolled between 2011 and 2019. Two patients were ineligible, and 20 discontinued treatment before surgery. Of the 48 patients eventually undergoing surgery, 43 accomplished R0 resection of the primary and/or metastatic GC, while 1 ended in R2 resection and 4 were considered ineligible. Median and 3-year OS for R0 patients were 39.8 months (95 % confidence interval [CI], 26.9 to not reached) and 58.1 % (95 % CI, 43.1-71.8), respectively, while median and 3-year RFS were 14.9 months (95 % CI 7.9-34.0) and 34.9 % (95 % CI 22.2-50.1), respectively. On multivariable analysis, both multiple liver metastases and positive nodal status (pN1-3) were negatively associated with OS (multiple liver metastases: hazard ratio [HR] 2.71 (95 % CI, 1.16-6.35), P = 0.022; pN1-3: HR 9.11 (95 % CI, 1.22-68.2), P = 0.031). CONCLUSION R0 resection following chemotherapy for LMGC yielded promising survival, with multiple liver metastases and positive nodal status being significant indicators of poor prognosis. CLINICAL TRIAL REGISTRATION NUMBER UMIN 000011445 (https://www.umin.ac.jp/ctr/).
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Affiliation(s)
- Kazumasa Fujitani
- Department of Gastroenterological Surgery, Osaka General Medical Center, Osaka, Japan.
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Ryohei Wada
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Atsushi Takeno
- Department of Surgery, Kansai Rosai Hospital, Amagasaki, Japan
| | | | - Takeshi Omori
- Department of Surgery, Osaka Police Hospital, Osaka, Japan
| | - Hiroshi Imamura
- Department of Surgery, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Motohiro Hirao
- Department of Surgery, Osaka National Hospital, Osaka, Japan
| | - Shunji Endo
- Department of Surgery, Higashi-Osaka Medical Center, Higashi-Osaka, Japan
| | - Junji Kawada
- Department of Surgery, Kaizuka Municipal Hospital, Kaizuka, Japan
| | - Jeong Ho Moon
- Department of Surgery, Osaka 2nd Police Hospital, Osaka, Japan
| | - Shuji Takiguchi
- Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medicine, Nagoya, Japan
| | - Masaki Mori
- Tokai University School of Medicine, Isehara, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
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Takahashi K, Terashima M, Notsu A, Koseki Y, Furukawa K, Fujiya K, Tanizawa Y, Bando E. Surgical treatment for liver metastasis from gastric cancer: A systematic review and meta-analysis of long-term outcomes and prognostic factors. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:108582. [PMID: 39126987 DOI: 10.1016/j.ejso.2024.108582] [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: 01/15/2024] [Revised: 07/18/2024] [Accepted: 08/02/2024] [Indexed: 08/12/2024]
Abstract
Chemotherapy is the mainstay treatment for liver metastasis from gastric cancer. However, some retrospective studies and meta-analyses have indicated the efficacy of hepatectomy, which is an aggressive treatment option. However, the optimal selection criteria for hepatectomy and the role of perioperative chemotherapy remain unclear. Therefore, a meta-analysis of studies on hepatectomy was performed to assess the impact of various factors on overall survival (OS). A systematic review was conducted in accordance with the PRISMA criteria using studies published until 2022. The primary outcome was the hazard ratio (HR) for OS. Comparisons were made between hepatectomy and nonhepatectomy, solitary and multiple metastases, synchronous and metachronous metastases, treatment with and without neoadjuvant chemotherapy, and treatment with and without adjuvant chemotherapy. A total of 50 studies involving 1966 patients who underwent hepatectomy were included in the analysis. The meta-analysis showed a 5-year OS rate of 25 %. A meta-analysis comparing hepatectomy with nonhepatectomy showed an HR of 0.2 for hepatectomy. A meta-analysis comparing solitary and multiple metastases showed a trend toward better OS in patients with solitary metastases (odds ratio [OR]: 0.35). A meta-analysis comparing synchronous and metachronous metastases showed favorable OS for patients with metachronous metastases (OR: 0.66). A meta-analysis comparing neoadjuvant chemotherapy with no neoadjuvant chemotherapy showed no difference in OS. In contrast, a meta-analysis comparing adjuvant chemotherapy with no adjuvant chemotherapy showed better OS for adjuvant chemotherapy (OR: 0.39). This retrospective study indicates that hepatectomy may benefit patients with liver metastases from gastric cancer, particularly those with solitary and metachronous metastases.
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Affiliation(s)
| | | | - Akifumi Notsu
- Clinical Research Center, Shizuoka Cancer Center, Japan
| | - Yusuke Koseki
- Division of Gastric Surgery, Shizuoka Cancer Center, Japan
| | | | - Keiichi Fujiya
- Division of Gastric Surgery, Shizuoka Cancer Center, Japan
| | | | - Etsuro Bando
- Division of Gastric Surgery, Shizuoka Cancer Center, Japan
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Deng Y, Zhao Z, Sheldon M, Zhao Y, Teng H, Martinez C, Zhang J, Lin C, Sun Y, Yao F, Curran MA, Zhu H, Ma L. LIFR regulates cholesterol-driven bidirectional hepatocyte-neutrophil cross-talk to promote liver regeneration. Nat Metab 2024; 6:1756-1774. [PMID: 39147934 PMCID: PMC11498095 DOI: 10.1038/s42255-024-01110-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Accepted: 07/16/2024] [Indexed: 08/17/2024]
Abstract
Liver regeneration is under metabolic and immune regulation. Despite increasing recognition of the involvement of neutrophils in regeneration, it is unclear how the liver signals to the bone marrow to release neutrophils after injury and how reparative neutrophils signal to hepatocytes to reenter the cell cycle. Here we report that loss of the liver tumour suppressor Lifr in mouse hepatocytes impairs, whereas overexpression of leukaemia inhibitory factor receptor (LIFR) promotes liver repair and regeneration after partial hepatectomy or toxic injury. In response to physical or chemical damage to the liver, LIFR from hepatocytes promotes the secretion of cholesterol and CXCL1 in a STAT3-dependent manner, leading to the efflux of bone marrow neutrophils to the circulation and damaged liver. Cholesterol, via its receptor ERRα, stimulates neutrophils to secrete hepatocyte growth factor to accelerate hepatocyte proliferation. Altogether, our findings reveal a LIFR-STAT3-CXCL1-CXCR2 axis and a LIFR-STAT3-cholesterol-ERRα-hepatocyte growth factor axis that form bidirectional hepatocyte-neutrophil cross-talk to repair and regenerate the liver.
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Affiliation(s)
- Yalan Deng
- Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Zilong Zhao
- Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Marisela Sheldon
- Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Yang Zhao
- Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Hongqi Teng
- Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Consuelo Martinez
- Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jie Zhang
- Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Chunru Lin
- Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Yutong Sun
- Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Fan Yao
- Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Hubei Hongshan Laboratory, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, China
| | - Michael A Curran
- Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA
| | - Hao Zhu
- Children's Research Institute, Departments of Pediatrics and Internal Medicine, Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Li Ma
- Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA.
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Hirose Y, Aizawa M, Yabusaki H, Nomura T, Takano K, Kawasaki T, Watanabe G, Shimojima Y, Yuza K, Bamba T, Nakagawa S. Prognostic Role of Preoperative Chemotherapy in Liver-Limited Metastasis from Gastric Cancer. Ann Surg Oncol 2024; 31:4213-4223. [PMID: 38519783 DOI: 10.1245/s10434-024-15224-w] [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: 10/27/2023] [Accepted: 03/09/2024] [Indexed: 03/25/2024]
Abstract
BACKGROUND We investigated the prognostic role of preoperative chemotherapy in patients who underwent hepatectomy for liver-limited metastasis (LLM) from gastric cancer (GC). METHODS A retrospective analysis was conducted for 52 consecutive patients who underwent macroscopically complete (R0 or R1) resection for synchronous or metachronous LLM from GC. RESULTS Of the 52 patients, 18 (35%) received preoperative chemotherapy (PC group), while 34 (65%) underwent upfront surgery (US group). The PC group had a significantly longer overall survival than the US group (cumulative 5-year OS rate: 47.6% vs. 24.8%, p = 0.041). Multivariate analysis of OS revealed that preoperative chemotherapy was an independent favorable prognostic factor (hazard ratio: 0.445, p = 0.036). Patients showing a partial response to preoperative chemotherapy on RECIST had an improved OS compared with those exhibiting stable or progressive disease after preoperative chemotherapy and with US (p = 0.025), even among those with solitary LLM (p = 0.062) and multiple LLM (p = 0.026). At recurrence after hepatectomy for LLM, the PC group had a significantly higher incidence of solitary tumors than the US group (p = 0.043) and had a higher chance to undergo surgical resection for recurrent sites (p = 0.006). CONCLUSIONS Preoperative chemotherapy can be recommended for patients with LLM from GC. The evaluation of the efficacy of preoperative chemotherapy offers additional information to determine the surgical indication for LLM.
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Affiliation(s)
- Yuki Hirose
- Department of Digestive Surgery, Niigata Cancer Center Hospital, Niigata, Japan.
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
| | - Masaki Aizawa
- Department of Digestive Surgery, Niigata Cancer Center Hospital, Niigata, Japan
| | - Hiroshi Yabusaki
- Department of Digestive Surgery, Niigata Cancer Center Hospital, Niigata, Japan
| | - Tatsuya Nomura
- Department of Digestive Surgery, Niigata Cancer Center Hospital, Niigata, Japan
| | - Kabuto Takano
- Department of Digestive Surgery, Niigata Cancer Center Hospital, Niigata, Japan
| | - Takashi Kawasaki
- Department of Pathology, Niigata Cancer Center Hospital, Niigata, Japan
| | - Gen Watanabe
- Department of Pathology, Niigata Cancer Center Hospital, Niigata, Japan
| | - Yukio Shimojima
- Department of Digestive Surgery, Niigata Cancer Center Hospital, Niigata, Japan
| | - Kizuki Yuza
- Department of Digestive Surgery, Niigata Cancer Center Hospital, Niigata, Japan
| | - Takeo Bamba
- Department of Digestive Surgery, Niigata Cancer Center Hospital, Niigata, Japan
| | - Satoru Nakagawa
- Department of Digestive Surgery, Niigata Cancer Center Hospital, Niigata, Japan
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Wang C, Zhang Y, Zhang Y, Li B. A bibliometric analysis of gastric cancer liver metastases: advances in mechanisms of occurrence and treatment options. Int J Surg 2024; 110:01279778-990000000-00950. [PMID: 38215249 PMCID: PMC11020032 DOI: 10.1097/js9.0000000000001068] [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: 09/11/2023] [Accepted: 12/24/2023] [Indexed: 01/14/2024]
Abstract
BACKGROUND Gastric cancer (GC) is the fifth most commonly diagnosed cancer worldwide, and its poor prognosis is predominantly attributed to distant metastasis. Liver is the primary site of GC metastasis. However, there is no universally approved treatment regimen for liver metastasis in GC. The aim of this article is to review the current research status and trends of liver metastasis of gastric cancer worldwide. METHODS We utilized the Web of Science Core Collection database to identify articles on liver metastasis from GC published between 2000 and 2022. We used bibliometric methods to analyze authors, institutions, countries, journals, and references through CiteSpace and VOSviewer. A total of 1,003 articles were included in this study. RESULTS Japan published the most articles in the field, followed by China. Nagoya University is the leading institution in the field of liver metastases in GC. Yasuhiro Kodera from Japan has made significant achievements in this area. We identified Gastric Cancer to be the most influential journal in this field. Using cluster analysis, the keywords were divided into four major clusters:(1) the molecular mechanism of gastric cancer liver metastasis (2) prognosis (3) liver resection (4) chemotherapy. CONCLUSION Our study systematically summarizes the results of gastric cancer liver metastasis research from 2000 to 2022 and describes and predicts research hotspots and trends on a global scale. Research on the molecular mechanisms of gastric cancer liver metastasis will become a hot topic in the future, and the expansion of the surgical treatment scope and the advancement of translational therapy will benefit more patients.
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Affiliation(s)
| | | | - Ye Zhang
- The First Laboratory of Cancer Institute
| | - Baifeng Li
- Department of Hepatobiliary Surgery, The First Hospital of China Medical University, Shenyang, People’s Republic of China
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Zheng CY, Wu J, Chen CS, Huang ZN, Tang YH, Qiu WW, He QC, Lin GS, Chen QY, Lu J, Wang JB, Lin JX, Cao LL, Lin M, Tu RH, Xie JW, Li P, Huang CM, Zheng YH, Zheng CH. A scoring model for predicting early recurrence of gastric cancer with normal preoperative tumor markers: A multicenter study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:107094. [PMID: 37797381 DOI: 10.1016/j.ejso.2023.107094] [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: 03/20/2023] [Revised: 07/25/2023] [Accepted: 09/22/2023] [Indexed: 10/07/2023]
Abstract
INTRODUCTION Prognostic factors for postoperative early recurrence (ER) of gastric cancer (GC) in patients with normal or abnormal preoperative tumor markers (pre-TMs) remain unclear. MATERIALS AND METHODS 2875 consecutive patients with GC who underwent radical gastrectomy (RG) between January 2010 and December 2016 were enrolled and randomly divided into training and internal validation groups. ER was defined as recurrence within two years of gastrectomy. Normal pre-TMs were defined as CEA≤5 ng/mL and CA199 ≤ 37 U/mL. Least absolute shrinkage selection operator (LASSO) Cox regression analysis was used to screen ER predictors. The scoring model was validated using 546 patients from another hospital. RESULTS A total of 3421 patients were included. Multivariate Cox analysis showed that pre-TMs was an independent prognostic factor for ER. Survival after ER was equally poor in the normal and abnormal pre-TMs groups (P = 0.160). Based on LASSO Cox regression, the ER of patients with abnormal pre-TMs was only associated with the pT and pN stages; however, in patients with normal pre-TMs, it was also associated with tumor size, perineural invasion, and prognostic nutritional index. Scoring model constructed for patients with normal pre-TMs had better predictive performance than TNM staging (concordance-index:0.826 vs. 0.807, P < 0.001) and good reproducibility in both validation sets. Moreover, through risk stratification, the scoring model could not only identify the risk of ER but also distinguish ER patterns and adjuvant chemotherapy benefit subgroups. CONCLUSION pre-TMs is an independent prognostic factor for ER in GC after RG. The established scoring model demonstrates excellent predictive performance and clinical utility.
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Affiliation(s)
- Chang-Yue Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China; Department of Gastrointestinal Surgery, The Affiliated Hospital of Putian University, Putian, China
| | - Ju Wu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China; Department of General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
| | - Chun-Sen Chen
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Ze-Ning Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Yi-Hui Tang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Wen-Wu Qiu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Qi-Chen He
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Guo-Sheng Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Jun Lu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Jia-Bin Wang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Jian-Xian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Long-Long Cao
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Mi Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Ru-Hong Tu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China.
| | - Yu-Hui Zheng
- Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, China.
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China.
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Deng Y, Zhao Z, Sheldon M, Zhao Y, Teng H, Martinez C, Zhang J, Lin C, Sun Y, Yao F, Zhu H, Ma L. LIFR recruits HGF-producing neutrophils to promote liver injury repair and regeneration. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.03.18.533289. [PMID: 36993315 PMCID: PMC10055204 DOI: 10.1101/2023.03.18.533289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/31/2023]
Abstract
The molecular links between tissue repair and tumorigenesis remain elusive. Here, we report that loss of the liver tumor suppressor Lifr in mouse hepatocytes impairs the recruitment and activity of reparative neutrophils, resulting in the inhibition of liver regeneration after partial hepatectomy or toxic injuries. On the other hand, overexpression of LIFR promotes liver repair and regeneration after injury. Interestingly, LIFR deficiency or overexpression does not affect hepatocyte proliferation ex vivo or in vitro . In response to physical or chemical damage to the liver, LIFR from hepatocytes promotes the secretion of the neutrophil chemoattractant CXCL1 (which binds CXCR2 to recruit neutrophils) and cholesterol in a STAT3-dependent manner. Cholesterol, in turn, acts on the recruited neutrophils to secrete hepatocyte growth factor (HGF) to accelerate hepatocyte proliferation and regeneration. Altogether, our findings reveal a LIFR-STAT3- CXCL1-CXCR2 axis and a LIFR-STAT3-cholesterol-HGF axis that mediate hepatic damage- induced crosstalk between hepatocytes and neutrophils to repair and regenerate the liver.
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Al Farai A, Garnier J, Palen A, Ewald J, Delpero JR, Turrini O. Will Patients With Liver Metastasis From Aggressives Cancers Benefit From Surgical Resection? World J Oncol 2022; 13:359-364. [PMID: 36660208 PMCID: PMC9822689 DOI: 10.14740/wjon1516] [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: 07/21/2022] [Accepted: 08/08/2022] [Indexed: 12/26/2022] Open
Abstract
Background We aimed to evaluate the outcomes of resections for liver metastases (LMs) originating from pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), and esophagus/gastric cancers (EGCs), which we label as major killers (MKs; overall survival (OS) under 10%). We hypothesized that LM resection must provide the patient with almost a year of OS postoperatively that is considered beneficial. Methods From January 2005 to December 2020, 23 patients underwent resection for isolated LM from MKs. These patients underwent surgery after a multidisciplinary discussion about their performance status, disease evolution during prolonged medical treatment, and the existence or absence of extrahepatic metastases. Results LM originated from an PDAC, EGC, or NSCLC in 10 patients (43%), nine patients (39%), and four patients (18%), respectively. The median delay between primary cancer and LM diagnoses was 12 months, and the median delay between LM diagnosis and liver resection was 10 months. Most patients, who had objectively responded to medical treatment (57%), had a solitary (61%) and unilobar (70%) LM. Severe morbidity and 90-day mortality rates were 13% and 4.3%, respectively. Margin-free resection was achieved in 16 patients (70%). After liver resection, the median OS was 24 months without a statistical difference when considering the primary tumor site; 1, 3-, and 5-year OS were 70%, 23%, and 23%, respectively. Conclusion Selection based on criteria such as good clinical condition, response to treatment, and long observation period helped identify patients with LM of MKs who seemed to benefit from resection.
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Affiliation(s)
| | - Jonathan Garnier
- Department of Surgery, Institut Paoli-Calmettes, Marseille, France
| | - Anais Palen
- Department of Surgery, Institut Paoli-Calmettes, Marseille, France
| | - Jacques Ewald
- Department of Surgery, Institut Paoli-Calmettes, Marseille, France
| | | | - Olivier Turrini
- Department of Surgery, Aix-Marseille University, Institut Paoli-Calmettes, CRCM, Marseille, France,Corresponding Author: Olivier Turrini, Department of Surgical Oncology, Institut Paoli-Calmettes, 232 Boulevard Sainte Marguerite, 13009 Marseille, France.
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Dong Z, Zhang Y, Geng H, Ni B, Xia X, Zhu C, Liu J, Zhang Z. Development and validation of two nomograms for predicting overall survival and cancer-specific survival in gastric cancer patients with liver metastases: A retrospective cohort study from SEER database. Transl Oncol 2022; 24:101480. [PMID: 35868142 PMCID: PMC9304879 DOI: 10.1016/j.tranon.2022.101480] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 06/04/2022] [Accepted: 07/04/2022] [Indexed: 11/25/2022] Open
Abstract
Nomograms constructed by overall survival and cancer-specific survival can predict more accurately than AJCC stage system for GCLM patients. The study includes the prognostic factor as many as possible and evaluated all of them in the cohort. In our cohort, surgery is a beneficial factor associated with survival. Background Gastric cancer is heterogeneous and aggressive, especially with liver metastasis. This study aims to develop two nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of gastric cancer with liver metastasis (GCLM) patients. Methods From January 2000 to December 2018, a total of 1936 GCLM patients were selected from the Surveillance, Epidemiology, and End Results Program (SEER) database. They were further divided into a training cohort and a validation cohort, with the OS and CSS serving as the study's endpoints. The correlation analyses were used to determine the relationship between the variables. The univariate and multivariate Cox analyses were used to confirm the independent prognostic factors. To discriminate and calibrate the nomogram, calibration curves and the area under the time-dependent receiver operating characteristic curve (time-dependent AUC) were used. DCA curves were used to examine the accuracy and clinical benefits. The clinical utility of the nomogram and the AJCC Stage System was compared using net reclassification improvement (NRI) and integrated differentiation improvement (IDI) (IDI). Finally, the nomogram and the AJCC Stage System risk stratifications were compared. Results There was no collinearity among the variables that were screened. The results of multivariate Cox regression analysis showed that six variables (bone metastasis, lung metastasis, surgery, chemotherapy, grade, age) and five variables (lung metastasis, surgery, chemotherapy, grade, N stage) were identified to establish the nomogram for OS and CSS, respectively. The calibration curves, time-dependent AUC curves, and DCA revealed that both nomograms had pleasant predictive power. Furthermore, NRI and IDI confirmed that the nomogram outperformed the AJCC Stage System. Conclusion Both nomograms had satisfactory accuracy and were validated to assist clinicians in evaluating the prognosis of GCLM patients.
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Affiliation(s)
- Zhongyi Dong
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No.1630 East Road, Pudong New Area, Shanghai 200127, China
| | - Yeqian Zhang
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No.1630 East Road, Pudong New Area, Shanghai 200127, China
| | - Haigang Geng
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No.1630 East Road, Pudong New Area, Shanghai 200127, China
| | - Bo Ni
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No.1630 East Road, Pudong New Area, Shanghai 200127, China
| | - Xiang Xia
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No.1630 East Road, Pudong New Area, Shanghai 200127, China
| | - Chunchao Zhu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No.1630 East Road, Pudong New Area, Shanghai 200127, China
| | - Jiahua Liu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No.1630 East Road, Pudong New Area, Shanghai 200127, China.
| | - Zizhen Zhang
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No.1630 East Road, Pudong New Area, Shanghai 200127, China.
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Li M, Yang B. Long-term outcomes after different treatments for gastric cancer with synchronous liver metastasis: A PRISMA systematic review and network meta-analysis. Medicine (Baltimore) 2022; 101:e29533. [PMID: 35758396 PMCID: PMC9276347 DOI: 10.1097/md.0000000000029533] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Revised: 05/06/2022] [Accepted: 05/06/2022] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND The treatment of gastric cancer (GC) with synchronous liver metastasis is still controversial. This systematic review and network meta-analysis was designed to evaluate the long-term outcomes after different treatments of GC with synchronous liver metastasis. METHODS Several electronic databases were searched to identify eligible studies updated on May 1, 2021. Studies assessing the overall survival (OS) after different treatments (including chemotherapy, interventional therapy, surgical therapy alone and adjunctive therapy after surgery) of GC with synchronous liver metastasis were included. Odds ratios with 95% confidence interval (CI) were calculated for survival variables. RESULTS A total of 15 studies including 4312 patients were included in this network meta-analysis. Adjunctive therapy after surgery performed better than surgery therapy alone (hazard ratio [HR] = 1.23, 95% credible interval [CrI]: 0.69-2.17), chemotherapy (HR = 1.18, 95%CrI: 0.71-1.95), and interventional therapy in terms of 1-year OS (HR = 2.03, 95%CrI: 1.22-3.37). In terms of 3-OS, adjunctive therapy after surgery showed better efficacy than surgery therapy alone (HR = 1.48, 95%CrI: 0.40-5.47), chemotherapy (HR = 1.27, 95%CrI: 0.37-4.35), and interventional therapy (HR = 3.16, 95%CrI: 0.73-13.63). For 5-OS, adjunctive therapy after surgery was superior to surgery therapy alone (HR = 1.74, 95%CrI: 0.08-37.76), chemotherapy (HR = 1.44, 95%CrI: 0.66-3.14), and interventional therapy (HR = 1.46, 95%CrI: 0.06-34.36). There were no statistical inconsistency and small-study effect existed in our network meta-analysis for 1-year, 3-year, or 5-year OS. Cluster ranking analysis performed with surface under the cumulative ranking showed adjuvant therapies after surgery (99.9, 96.7, 90.2) ranking higher than surgery therapy alone, chemotherapy, and interventional therapy for 1-year, 3-year, 5-year OS. CONCLUSION The OS of adjuvant therapy after surgery was better than that of surgery therapy alone, chemotherapy, and interventional therapy. Adjuvant therapy after surgery is the most recommended therapy for people with GC with synchronous liver metastasis.
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Affiliation(s)
- Minghui Li
- Department of General Surgery, Xinhua Hospital Affiliated to Dalian University, Dalian, PR China
| | - Bin Yang
- Department of General Surgery, 967 Hospital of the Joint Service Support Force of PLA, Dalian, PR China
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11
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Goto K, Morimoto M, Osaki M, Tanio A, Izutsu R, Fujiwara Y, Okada F. The impact of AMIGO2 on prognosis and hepatic metastasis in gastric cancer patients. BMC Cancer 2022; 22:280. [PMID: 35296279 PMCID: PMC8925171 DOI: 10.1186/s12885-022-09339-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Accepted: 02/25/2022] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Gastric cancer (GC) is one of the most common malignancies, and the liver is the most common site of hematogenous metastasis of GC. AMIGO2 is a type I transmembrane protein that has been implicated in tumour cell adhesion in adenocarcinomas; however, its importance in GC remains undetermined. METHODS We analyzed AMIGO2 expression by immunohistochemistry using the specific monoclonal antibody for human AMIGO2 in 128 patients who underwent GC surgery to evaluate its relationship between various metastatic and clinical outcomes in GC. RESULTS Immunohistochemistry revealed that AMIGO2 expression was an independent prognostic factor for overall survival, disease-specific survival, and liver metastasis in GC patients. CONCLUSIONS This study showed that AMIGO2 is induced in GC tissues and can mediate hepatic metastasis. Determining AMIGO2 expression in GC will help predict patient prognosis and the incidence of liver metastasis.
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Affiliation(s)
- Keisuke Goto
- Division of Experimental Pathology, Faculty of Medicine, Tottori University, 86 Nishicho, Yonago, 683-8503, Japan
- Department of Surgery, Division of Gastrointestinal and Pediatric Surgery, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Masaki Morimoto
- Department of Surgery, Division of Gastrointestinal and Pediatric Surgery, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, 683-8504, Japan.
| | - Mitsuhiko Osaki
- Division of Experimental Pathology, Faculty of Medicine, Tottori University, 86 Nishicho, Yonago, 683-8503, Japan
- Chromosome Engineering Research Centre, Tottori University, 86 Nishicho, Yonago, 683-8503, Japan
| | - Akimitsu Tanio
- Department of Surgery, Division of Gastrointestinal and Pediatric Surgery, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Runa Izutsu
- Division of Experimental Pathology, Faculty of Medicine, Tottori University, 86 Nishicho, Yonago, 683-8503, Japan
| | - Yoshiyuki Fujiwara
- Department of Surgery, Division of Gastrointestinal and Pediatric Surgery, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago, 683-8504, Japan
| | - Futoshi Okada
- Division of Experimental Pathology, Faculty of Medicine, Tottori University, 86 Nishicho, Yonago, 683-8503, Japan
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12
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Zhang G, Li Z, Dong J, Zhou W, Zhang Z, Que Z, Zhu X, Xu Y, Cao N, Zhao A. Acacetin inhibits invasion, migration and TGF-β1-induced EMT of gastric cancer cells through the PI3K/Akt/Snail pathway. BMC Complement Med Ther 2022; 22:10. [PMID: 35000605 PMCID: PMC8744305 DOI: 10.1186/s12906-021-03494-w] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 12/21/2021] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Epithelial-to-mesenchymal transition (EMT) is a pivotal cellular phenomenon involved in tumour metastasis and progression. In gastric cancer (GC), EMT is the main reason for recurrence and metastasis in postoperative patients. Acacetin exhibits various biological activities. However, the inhibitory effect of acacetin on EMT in GC is still unknown. Herein, we explored the possible mechanism of acacetin on EMT in GC in vitro and in vivo. METHODS In vitro, MKN45 and MGC803 cells were treated with acacetin, after which cell viability was detected by CCK-8 assays, cell migration and invasion were detected by using Transwell and wound healing assays, and protein expression was analysed by western blots and immunofluorescence staining. In vivo, a peritoneal metastasis model of MKN45 GC cells was used to investigate the effects of acacetin. RESULTS Acacetin inhibited the proliferation, invasion and migration of MKN45 and MGC803 human GC cells by regulating the expression of EMT-related proteins. In TGF-β1-induced EMT models, acacetin reversed the morphological changes from epithelial to mesenchymal cells, and invasion and migration were limited by regulating EMT. In addition, acacetin suppressed the activation of PI3K/Akt signalling and decreased the phosphorylation levels of TGF-β1-treated GC cells. The in vivo experiments demonstrated that acacetin delayed the development of peritoneal metastasis of GC in nude mice. Liver metastasis was restricted by altering the expression of EMT-related proteins. CONCLUSION Our study showed that the invasion, metastasis and TGF-β1-induced EMT of GC are inhibited by acacetin, and the mechanism may involve the suppression of the PI3K/Akt/Snail signalling pathway. Therefore, acacetin is a potential therapeutic reagent for the treatment of GC patients with recurrence and metastasis.
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Affiliation(s)
- Guangtao Zhang
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - Zhaoyan Li
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.,Department of Oncology, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jiahuan Dong
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - Weili Zhou
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - Zhanxia Zhang
- Institute of Traditional Chinese Medicine Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zujun Que
- Institute of Traditional Chinese Medicine Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.,School of Oncology, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xiaohong Zhu
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - Yan Xu
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - Nida Cao
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - Aiguang Zhao
- Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
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13
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Fujitani K, Kurokawa Y, Takeno A, Kawabata R, Omori T, Imamura H, Hirao M, Endo S, Kawada J, Moon JH, Kobayashi N, Takahashi T, Yamasaki M, Takiguchi S, Mori M, Eguchi H, Doki Y. Prospective Multicenter Interventional Study of Surgical Resection for Liver Metastasis from Gastric Cancer: R0 Resection Rate, and Operative Morbidity and Mortality. Ann Surg Oncol 2021; 29:924-932. [PMID: 34480277 DOI: 10.1245/s10434-021-10750-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 08/11/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND The optimal treatment for liver metastasis from gastric cancer (LMGC) remains uncertain. The relevance of surgical resection is controversial. We conducted a prospective multicenter interventional study of surgical resection for LMGC. PATIENTS AND METHODS Patients with synchronous or metachronous LMGC who were surgically fit were registered. The primary endpoint was 3-year overall survival (OS) of patients who underwent R0 resection. Secondary endpoints were R0 resection rate, operative morbidity and mortality, 3-year recurrence-free survival (RFS) of R0 patients, and OS in all registered patients. RESULTS Seventy patients were registered from 24 institutions between December 2011 and November 2019 and received preoperative chemotherapy. Three patients were ineligible, and 19 patients discontinued treatment, with disease progression in 12, adverse events in 4, and consent withdrawal in 3 before surgery. Of the 48 patients eventually undergoing surgery, R0 resection of the primary and/or metastatic GC was accomplished in 43 patients, while 1 patient discontinued treatment for positive peritoneal lavage cytology and 4 patients were considered ineligible based on postoperative pathological findings other than GC. The R0 resection rate of all eligible patients was 68.3% [95% confidence interval (CI) 55.3-79.4%, 43/63 patients], while that of all resected patients was 89.6% (95% CI 77.3-96.5%, 43/48 patients). Postoperative complications were identified in 12 out of 43 patients (27.9%), and Clavien-Dindo grade III or higher complications occurred in seven patients (16.3%). No hospital mortality was observed. CONCLUSIONS R0 resection for LMGC could be performed in approximately two-thirds of all eligible patients, with acceptable surgical morbidity and mortality.
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Affiliation(s)
- Kazumasa Fujitani
- Department of Gastroenterological Surgery, Osaka General Medical Center, Osaka, Japan.
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Atsushi Takeno
- Department of Surgery, Kansai Rosai Hospital, Amagasaki, Japan
| | | | - Takeshi Omori
- Department of Surgery, Osaka Police Hospital, Osaka, Japan
| | - Hiroshi Imamura
- Department of Surgery, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Motohiro Hirao
- Department of Surgery, Osaka National Hospital, Osaka, Japan
| | - Shunji Endo
- Department of Surgery, Higashi-Osaka Medical Center, Higashi-Osaka, Japan
| | - Junji Kawada
- Department of Surgery, Kaizuka Municipal Hospital, Kaizuka, Japan
| | - Jeong Ho Moon
- Department of Surgery, Osaka 2nd Police Hospital, Osaka, Japan
| | - Noboru Kobayashi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Tsuyoshi Takahashi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Makoto Yamasaki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Shuji Takiguchi
- Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medicine, Nagoya, Japan
| | - Masaki Mori
- Department of Surgery and Science, Kyushu University Graduate School of Medicine, Fukuoka, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan
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Granieri S, Altomare M, Bruno F, Paleino S, Bonomi A, Germini A, Facciorusso A, Fagnani D, Bovo G, Cotsoglou C. Surgical treatment of gastric cancer liver metastases: Systematic review and meta-analysis of long-term outcomes and prognostic factors. Crit Rev Oncol Hematol 2021; 163:103313. [PMID: 34044098 DOI: 10.1016/j.critrevonc.2021.103313] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 02/10/2021] [Accepted: 03/29/2021] [Indexed: 12/18/2022] Open
Abstract
The prognosis of patients with metastatic gastric cancer remains dismal, with palliative treatment as standard of care. However, encouraging results have been reported for surgical resection of liver only metastatic gastric cancer in carefully selected patients. A systematic review of articles published from 2000 onwards was conducted according to PRISMA guidelines. Twenty-nine studies were included in qualitative and quantitative analysis. Meta-analysis of proportions pointed out 29.1 % 5ySR (I 2 = 39 %). The pooled weighted median of MSTs was 31.1 months. T stage > 2, metastasis greatest dimension ≥ 5 cm, the presence of multiple metastases and bilobar disease resulted among the strongest predictors of mortality. Funnel plots, Egger's tests, and P-curve analyses failed to show significant publication bias. Based on strict selection criteria and robust statistical analyses, our results show that, in very carefully selected patients without extrahepatic disease, surgical resection with curative intent may significantly improve overall survival.
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Affiliation(s)
- Stefano Granieri
- General Surgery Unit, ASST Vimercate, Via Santi Cosma e Damiano 10, 20871, Vimercate, Italy.
| | - Michele Altomare
- University of Milan, Via Festa del Perdono, 7, 20122, Milan, Italy; Gastrointestinal, Hepato-Pancreatic Surgery and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Via Venezian 1, 20133, Milan, Italy.
| | - Federica Bruno
- General Surgery Unit, ASST Vimercate, Via Santi Cosma e Damiano 10, 20871, Vimercate, Italy.
| | - Sissi Paleino
- General Surgery Unit, ASST Vimercate, Via Santi Cosma e Damiano 10, 20871, Vimercate, Italy; University of Milan, Via Festa del Perdono, 7, 20122, Milan, Italy.
| | - Alessandro Bonomi
- University of Milan, Via Festa del Perdono, 7, 20122, Milan, Italy; General Surgery Unit, ASST Fatebenefratelli-Sacco, Via Giovanni Battista Grassi, 74, 20157, Milan, Italy.
| | - Alessandro Germini
- General Surgery Unit, ASST Vimercate, Via Santi Cosma e Damiano 10, 20871, Vimercate, Italy.
| | - Antonio Facciorusso
- Department of Medical Sciences, Gastroenterology Unit, Ospedali Riuniti di Foggia, Viale Luigi Pinto, 1, 71122, Foggia, Italy.
| | - Daniele Fagnani
- Medical Oncology Unit, ASST Vimercate, Via Santi Cosma e Damiano 10, 20871, Vimercate, Italy.
| | - Giorgio Bovo
- Pathology Unit, ASST Vimercate, Via Santi Cosma e Damiano 10, 20871, Vimercate, Italy.
| | - Christian Cotsoglou
- General Surgery Unit, ASST Vimercate, Via Santi Cosma e Damiano 10, 20871, Vimercate, Italy.
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15
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Marte G, Tufo A, Steccanella F, Marra E, Federico P, Petrillo A, Maida P. Efficacy of Surgery for the Treatment of Gastric Cancer Liver Metastases: A Systematic Review of the Literature and Meta-Analysis of Prognostic Factors. J Clin Med 2021; 10:jcm10051141. [PMID: 33803135 PMCID: PMC7963158 DOI: 10.3390/jcm10051141] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 02/27/2021] [Accepted: 03/01/2021] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND In the last 10 years, the management of patients with gastric cancer liver metastases (GCLM) has changed from chemotherapy alone, towards a multidisciplinary treatment with liver surgery playing a leading role. The aim of this systematic review and meta-analysis is to assess the efficacy of hepatectomy for GCLM and to analyze the impact of related prognostic factors on long-term outcomes. METHODS The databases PubMed (Medline), EMBASE, and Google Scholar were searched for relevant articles from January 2010 to September 2020. We included prospective and retrospective studies that reported the outcomes after hepatectomy for GCLM. A systematic review of the literature and meta-analysis of prognostic factors was performed. RESULTS We included 40 studies, including 1573 participants who underwent hepatic resection for GCLM. Post-operative morbidity and 30-day mortality rates were 24.7% and 1.6%, respectively. One-year, 3-years, and 5-years overall survival (OS) were 72%, 37%, and 26%, respectively. The 1-year, 3-years, and 5-years disease-free survival (DFS) were 44%, 24%, and 22%, respectively. Well-moderately differentiated tumors, pT1-2 and pN0-1 adenocarcinoma, R0 resection, the presence of solitary metastasis, unilobar metastases, metachronous metastasis, and chemotherapy were all strongly positively associated to better OS and DFS. CONCLUSION In the present study, we demonstrated that hepatectomy for GCLM is feasible and provides benefits in terms of long-term survival. Identification of patient subgroups that could benefit from surgical treatment is mandatory in a multidisciplinary setting.
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Affiliation(s)
- Gianpaolo Marte
- Department of General Surgery, Ospedale del Mare, 80147 Naples, Italy; (A.T.); (F.S.); (E.M.); (P.M.)
- Correspondence: ; Tel.: +39-08118775110
| | - Andrea Tufo
- Department of General Surgery, Ospedale del Mare, 80147 Naples, Italy; (A.T.); (F.S.); (E.M.); (P.M.)
| | - Francesca Steccanella
- Department of General Surgery, Ospedale del Mare, 80147 Naples, Italy; (A.T.); (F.S.); (E.M.); (P.M.)
| | - Ester Marra
- Department of General Surgery, Ospedale del Mare, 80147 Naples, Italy; (A.T.); (F.S.); (E.M.); (P.M.)
| | - Piera Federico
- Medical Oncology Unit, Ospedale del Mare, 80147 Naples, Italy; (P.F.); (A.P.)
| | - Angelica Petrillo
- Medical Oncology Unit, Ospedale del Mare, 80147 Naples, Italy; (P.F.); (A.P.)
| | - Pietro Maida
- Department of General Surgery, Ospedale del Mare, 80147 Naples, Italy; (A.T.); (F.S.); (E.M.); (P.M.)
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Ohnuma H, Sato Y, Onoyama N, Hamaguchi K, Hayasaka N, Sato M, Murase K, Takada K, Miyanishi K, Murakami T, Ito T, Nobuoka T, Takemasa I, Kato J. Survival benefit of conversion surgery after intensive chemotherapy for unresectable metastatic gastric cancer: a propensity score-matching analysis. J Cancer Res Clin Oncol 2021; 147:2385-2396. [PMID: 33534051 DOI: 10.1007/s00432-021-03516-7] [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: 10/31/2020] [Accepted: 01/09/2021] [Indexed: 12/23/2022]
Abstract
PURPOSE The clinical benefit of conversion surgery (CS) for unresectable gastric cancer (GC), whereby unresectable GC responds to chemotherapy and subsequently receives curative-intent surgery, remains unclear. Here, we aimed to clarify the clinical value of CS. METHODS In this retrospective cohort study, we analyzed 175 unresectable GC, who received triple combined chemotherapy between 2004 and 2019. We divided patients into two groups: those who underwent CS and those receiving chemotherapy only (CS and C groups, respectively). Propensity score matching was used to minimize confounding bias. RESULTS Of 175 cases, 61 (34.9%) underwent CS. R0 resection was obtained in 85.2%. After matching, 44 pairs were selected; there were no significant differences in baseline covariants. Group CS had a significantly better median overall survival (OS) (18.8 vs. 46.0 months, p < 0.001), and prolonged progression-free survival (7.4 vs. 25.8 months, p < 0.001). Subgroup analysis of OS showed a favorable trend for CS for almost all subgroups. Multivariate analysis revealed that good ECOG performance status and CS were associated with a longer OS. CONCLUSION The survival benefit of CS was consistently demonstrated in the univariate and multivariate analysis, even in the matched cohort. Additional large-scale trials are needed for further validation.
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Affiliation(s)
- Hiroyuki Ohnuma
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Yasushi Sato
- Department of Community Medicine for Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Naoki Onoyama
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Kota Hamaguchi
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Naotaka Hayasaka
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Masanori Sato
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Kazuyuki Murase
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Kohichi Takada
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Koji Miyanishi
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Takeshi Murakami
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Tatsuya Ito
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Takayuki Nobuoka
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Ichiro Takemasa
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Junji Kato
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan.
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Nakamichi N, Tsujiura M, Matsui T, Yamamoto T, Yoshioka A, Hiramoto H, Ouchi Y, Ishimoto T, Kosuga T, Mochizuki S, Nakashima S, Bamba M, Masuyama M, Otsuji E. The therapeutic strategy for advanced gastric cancer with pyloric stenosis and liver metastasis; successfully treated by gastro-jejunal bypass and chemotherapy first, followed by curative R0 resection. Surg Case Rep 2021; 7:6. [PMID: 33409765 PMCID: PMC7788145 DOI: 10.1186/s40792-020-00979-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Accepted: 09/18/2020] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND The indication of surgical resection for liver metastasis from gastric cancer (GC) is still limited and controversial because of its more aggressive oncological characteristics than liver metastasis from colorectal cancer. Pyloric stenosis causes an inadequate oral intake and malnutrition in GC patients. We herein report a case of GC with these two factors that was successfully treated by the combination of gastro-jejunal bypass and chemotherapy, followed by curative R0 resection. CASE PRESENTATION A 60-year-old man was diagnosed with type 2 GC with liver metastasis and pyloric stenosis, which was confirmed as the HER2-positive type. He underwent gastrojejunostomy and received capecitabine and cisplatin (XP) + trastuzumab chemotherapy. After three courses of the XP + trastuzumab regimen, shrinkage of the primary lesion and liver metastasis was confirmed and his nutritional parameters markedly improved with a stable oral intake after bypass surgery. He underwent curative R0 resection by distal gastrectomy with D2 lymphadenectomy and partial hepatectomy. Histologically, viable tumor cells were observed in less than one-third of the primary lesion, and only scar tissue without viable cancer cells was noted in the resected liver specimen. His postoperative course was uneventful, and recurrence has not been detected in the 30 months after surgery without adjuvant chemotherapy. CONCLUSION The present case report describes a successful strategy for advanced GC with pyloric stenosis and liver metastasis.
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Affiliation(s)
- Naosuke Nakamichi
- Department of Surgery, Saiseikai Shiga Hospital, 2-4-1 Ohashi, Ritto, Shiga, 520-3046, Japan
| | - Masahiro Tsujiura
- Department of Surgery, Saiseikai Shiga Hospital, 2-4-1 Ohashi, Ritto, Shiga, 520-3046, Japan.
| | - Tomohiro Matsui
- Department of Surgery, Saiseikai Shiga Hospital, 2-4-1 Ohashi, Ritto, Shiga, 520-3046, Japan
| | - Taiga Yamamoto
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Kyoto, 602-8566, Japan
| | - Ayana Yoshioka
- Department of Surgery, Saiseikai Shiga Hospital, 2-4-1 Ohashi, Ritto, Shiga, 520-3046, Japan
| | - Hidekazu Hiramoto
- Department of Surgery, Saiseikai Shiga Hospital, 2-4-1 Ohashi, Ritto, Shiga, 520-3046, Japan
| | - Yoshimi Ouchi
- Department of Surgery, Saiseikai Shiga Hospital, 2-4-1 Ohashi, Ritto, Shiga, 520-3046, Japan
| | - Takeshi Ishimoto
- Department of Surgery, Saiseikai Shiga Hospital, 2-4-1 Ohashi, Ritto, Shiga, 520-3046, Japan
| | - Toshiyuki Kosuga
- Department of Surgery, Saiseikai Shiga Hospital, 2-4-1 Ohashi, Ritto, Shiga, 520-3046, Japan
| | - Satoshi Mochizuki
- Department of Surgery, Saiseikai Shiga Hospital, 2-4-1 Ohashi, Ritto, Shiga, 520-3046, Japan
| | - Susumu Nakashima
- Department of Surgery, Saiseikai Shiga Hospital, 2-4-1 Ohashi, Ritto, Shiga, 520-3046, Japan
| | - Masamichi Bamba
- Department of Diagnostic Pathology, Saiseikai Shiga Hospital, 2-4-1 Ohashi, Ritto, Shiga, 520-3046, Japan
| | - Mamoru Masuyama
- Department of Surgery, Saiseikai Shiga Hospital, 2-4-1 Ohashi, Ritto, Shiga, 520-3046, Japan
| | - Eigo Otsuji
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto, Kyoto, 602-8566, Japan
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Jagric T, Horvat M. Surgical resection of synchronous liver metastases in gastric cancer patients. A propensity score-matched study. Radiol Oncol 2020; 55:57-65. [PMID: 33885239 PMCID: PMC7877268 DOI: 10.2478/raon-2020-0067] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Accepted: 10/15/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND The aim of the study was to determine the value of synchronous liver resection in patients with oligo-metastatic gastric cancer and the prognostic factors in these patients. PATIENTS AND METHODS We compared the results of 21 gastric patients with liver metastases and synchronous liver resection (LMR) to 21 propensity score-matched patients with gastric cancer and liver metastases in whom liver resection was not performed (LM0) and to a propensity score-matched control group of 21 patients without liver metastases and stage III and IV resectable gastric cancer (CG). RESULTS The overall 5-year survival of LMR, LM0 and CG were 14.3%, 0%, and 19%, respectively (p = 0.002). Five-year survival was 47.5% for well-differentiated tumour compared to 0% in patients with moderate or poor tumour differentiation (p = 0.006). In addition, patients with R0 resection and TNM stage N0-1 had a significantly better survival compared to patients with TNM N stage N2-3 (5-year survival: 60% for N0-1 vs. 7.7% for N2-3; p = 0.007). CONCLUSIONS The results presented in the study support synchronous liver resections in gastric patients and provide additional criteria for patient selection.
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Affiliation(s)
- Tomaz Jagric
- Department of General and Abdominal Surgery, University Medical Centre Maribor, MariborSlovenia
| | - Matjaz Horvat
- Faculty of Medicine, University of Maribor, MariborSlovenia
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Yazawa T, Hori T, Yamamoto H, Harada H, Yamamoto M, Yamada M, Tani M, Sato A, Kamada Y, Tani R, Aoyama R, Sasaki Y, Zaima M. Do liver metastases from gastric cancer contraindicate aggressive surgical resection? A 14-year single-center experience. World J Gastrointest Pharmacol Ther 2020; 11:110-122. [PMID: 33251035 PMCID: PMC7667407 DOI: 10.4292/wjgpt.v11.i5.110] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 04/27/2020] [Accepted: 09/01/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Advanced gastric cancer (GC) with liver metastasis is often characterized by multiple and bilobular metastases and may also be associated with extrahepatic metastatic lesions. Hence, many physicians consider that radical surgeries are contraindicated for liver metastases from GC (LMGC). According to the 2017 Japanese treatment guideline for GC, a smaller number of liver metastases without unresectable factors may be an indication for liver resection (LR) with curability. The actual 5-year overall survival (OS) rate ranges from 0 to 0.37. AIM To present the institutional indications for LR for LMGC and identify important factors for prognostic outcomes. METHODS In total, 30 patients underwent LR for LMGC during a 14-year period, and we evaluated the clinical, surgical, and oncological findings. In all patients, radical surgery with intentional lymphadenectomy was performed for the primary GC. The median follow-up duration after the initial LR was 33.7 mo, and three patients with no recurrence died of causes unrelated to the LMGC. The OS and recurrence-free survival rates after the initial LR were assessed. RESULTS Seventeen patients had metachronous LMGC. The initial LR achieved curability in 29 patients. Perioperative chemotherapy was introduced in 23 patients. The median greatest LMGC dimension was 30 mm, and the median number of LMGC was two. Twenty-two patients had unilobular LMGC. The 5-year OS and recurrence-free survival rates were 0.48 and 0.28, respectively. The median survival duration and recurrence-free duration after the initial LR were 16.8 and 8.6 mo, respectively. Twenty-one patients developed recurrence after the initial LR. Additional surgeries for recurrence were performed in nine patients, and these surgeries clearly prolonged the patients' survival. Pathological serosal invasion was an independent predictor of a poor prognostic outcome after the initial LR. Aggressive LR may be indicated for carefully selected patients with LMGC. CONCLUSION Our results of LR for LMGC seem acceptable. Additional surgeries for recurrence after the initial LR might prolong OS. Pathological serosal invasion is important for poor prognostic outcomes.
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Affiliation(s)
- Takefumi Yazawa
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Tomohide Hori
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Hidekazu Yamamoto
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Hideki Harada
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Michihiro Yamamoto
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Masahiro Yamada
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Masaki Tani
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Asahi Sato
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Yasuyuki Kamada
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Ryotaro Tani
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Ryuhei Aoyama
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Yudai Sasaki
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Masazumi Zaima
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
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20
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Uggeri F, Ripamonti L, Pinotti E, Scotti MA, Famularo S, Garancini M, Gianotti L, Braga M, Romano F. Is there a role for treatment-oriented surgery in liver metastases from gastric cancer? World J Clin Oncol 2020; 11:477-494. [PMID: 32821653 PMCID: PMC7407929 DOI: 10.5306/wjco.v11.i7.477] [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: 02/14/2020] [Revised: 06/05/2020] [Accepted: 06/17/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Distant metastases are found in approximately 35% of patients with gastric cancer at their first clinical observation, and of these, 4%-14% involves the liver. Unfortunately, only 0.4%-2.3% of patients with metastatic gastric cancer are eligible for radical surgery. Although surgical resection for gastric cancer metastases is still debated, there have been changes in recent years, although several clinical issues remain to be defined and that must be taken into account before surgery is proposed.
AIM To analyze the clinicopathological factors related to primary gastric tumor and metastases that impact the survival of patients with liver metastatic gastric cancer.
METHODS We performed a systematic review of the literature from 2000 to 2018 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The study protocol was based on identifying studies with clearly defined purpose, eligibility criteria, methodological analysis, and patient outcome.
RESULTS We selected 47 studies pertaining to the purpose of the review, which involved a total of 2304 patients. Median survival was 7-52.3 mo, median disease-free survival was 4.7-18 mo. The 1-, 2-, 3-, and 5-year overall survival (OS) was 33%-90.1%, 10%-60%, 6%-70.4%, and 0%-40.1%, respectively. Only five papers reported the 10-year OS, which was 5.5%–31.5%. The general recurrence rate was between 55.5% and 96%, and that for hepatic recurrence was between 15% and 94%.
CONCLUSION Serous infiltration and lymph node involvement of the primary cancer indicate an unfavorable prognosis, while the presence of single metastasis or ≤ 3 metastases associated with a size of < 5 cm may be considered data that do not contraindicate liver resection.
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Affiliation(s)
- Fabio Uggeri
- School of Medicine and Surgery, University of Milano-Bicocca, Department of Surgery, San Gerardo Hospital, Monza 20900, Italy
| | - Lorenzo Ripamonti
- School of Medicine and Surgery, University of Milano-Bicocca, Department of Surgery, San Gerardo Hospital, Monza 20900, Italy
| | - Enrico Pinotti
- School of Medicine and Surgery, University of Milano-Bicocca, Department of Surgery, San Gerardo Hospital, Monza 20900, Italy
| | | | - Simone Famularo
- School of Medicine and Surgery, University of Milano-Bicocca, Department of Surgery, San Gerardo Hospital, Monza 20900, Italy
| | | | - Luca Gianotti
- School of Medicine and Surgery, University of Milano-Bicocca, Department of Surgery, San Gerardo Hospital, Monza 20900, Italy
| | - Marco Braga
- School of Medicine and Surgery, University of Milano-Bicocca, Department of Surgery, San Gerardo Hospital, Monza 20900, Italy
| | - Fabrizio Romano
- School of Medicine and Surgery, University of Milano-Bicocca, Department of Surgery, San Gerardo Hospital, Monza 20900, Italy
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Baba H, Kanda M, Sawaki K, Umeda S, Miwa T, Shimizu D, Tanaka C, Kobayashi D, Fujiwara M, Kodera Y, Fujii T. PRAME as a Potential Biomarker for Liver Metastasis of Gastric Cancer. Ann Surg Oncol 2020; 27:2071-2080. [DOI: 10.1245/s10434-019-07985-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Indexed: 08/30/2023]
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22
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Qiang W, Shi H, Wu J, Ji M, Wu C. Hepatic Arterial Infusion Combined with Systemic Chemotherapy for Patients with Extensive Liver Metastases from Gastric Cancer. Cancer Manag Res 2020; 12:2911-2916. [PMID: 32425604 PMCID: PMC7196811 DOI: 10.2147/cmar.s245697] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Accepted: 03/31/2020] [Indexed: 12/27/2022] Open
Abstract
Purpose Liver metastases in patients with gastric cancer often indicate poor prognosis. Once liver metastases are extensive, it is difficult to achieve disease control by using systemic chemotherapy alone. The purpose of this study was to evaluate the effect and safety of hepatic arterial infusion (HAI) combined with systemic chemotherapy on extensive liver metastases from gastric cancer. Patients and Methods Between 2012 and 2019, 21 patients with extensive liver metastases from gastric cancer (LMGC) were enrolled in our study. Liver metastases were identified as unresectable and a major factor affecting prognosis mainly based on size and number of intrahepatic lesions. All patients received systemic chemotherapy with S-1 and HAI oxaliplatin plus floxuridine (FUDR). Results Liver metastases in 16 patients (76.2%) were evaluated as H3. The overall response rate was 76.2% (9.5% complete response). Intrahepatic and extrahepatic median progression-free survival times were 9.5 and 5.2 months, respectively. Median survival time (MST) was 12.3 months. All patients did not have the toxicity of grade 4. Grade 3 toxic effects included bone marrow suppression (14.3%) and diarrhea (9.5%). The other treatment-related toxicities were mild and reversible. Conclusion HAI combined with systemic chemotherapy for extensive LMGC seems to be safe and effective, which achieves a high-local response and may contribute to long survival time for patients.
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Affiliation(s)
- Weiguang Qiang
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, People's Republic of China
| | - Hongbing Shi
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, People's Republic of China
| | - Jun Wu
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, People's Republic of China
| | - Mei Ji
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, People's Republic of China
| | - Changping Wu
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, People's Republic of China.,Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, People's Republic of China
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23
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Laparoscopic gastrectomy and metastasectomy for stage IV gastric cancer. Surg Endosc 2020; 35:1879-1887. [PMID: 32342215 DOI: 10.1007/s00464-020-07592-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Accepted: 04/22/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND The standard recommended treatment of stage IV gastric cancer is palliative chemotherapy. The aim of this study is to evaluate the role of radical gastrectomy with metastasectomy in these patients, as well as to explore the feasibility and safety of a laparoscopic approach. METHODS 117 consecutive patients with pathologically proven Stage IV gastric cancer who underwent radical gastrectomy with metastasectomy were enrolled in this study. We evaluated short-term and long-term outcomes, comparing laparoscopic surgery with open surgery by propensity score matching. RESULTS The 5-year overall survival rate (OSR) was 23.2% and the median survival time (MST) was 19.8 months. After propensity scoring matching, the 5-year OSR and MST of laparoscopy group was 23.4%, 17.9 months and in the open group, it was 25.0%, 22.8 months (p = 0.882). The complication rate was 5.6% in the laparoscopy group and 23.4% in the open group (p = 0.069). In multivariate analysis, adjuvant chemotherapy, chemotherapy cycle, and postoperative complication were independent prognostic factors of overall survival. CONCLUSIONS Radical gastrectomy with metastasectomy could have a potential role in stage IV gastric cancer. Laparoscopic gastrectomy with metastasectomy in selected stage IV gastric cancer patients is safe and feasible.
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24
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Wang K, Zhang X, Wei J, Xu Y, Liu Q, Xie J, Yuan L, Sun Z, Tan S, Zhang L, Liu B, Yang Y. Hepatic Arterial Infusion Oxaliplatin Plus Oral S-1 Chemotherapy in Gastric Cancer with Unresectable Liver Metastases: A Case Series and Literature Review. Cancer Manag Res 2020; 12:863-870. [PMID: 32104068 PMCID: PMC7012222 DOI: 10.2147/cmar.s233123] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Accepted: 01/10/2020] [Indexed: 12/24/2022] Open
Abstract
Objective The use of hepatic artery infusion (HAI) as a regional therapy against liver metastasis has rarely been reported in gastric cancer. This study aimed to evaluate the efficacy and safety of HAI oxaliplatin plus oral S-1 chemotherapy in first-line palliative therapy for gastric cancer with multiple liver metastases (GCLM). Methods We reviewed the records of five patients with GCLM who received HAI oxaliplatin (70–80 mg/m2 2 hrs d1,15) administered via a port-catheter system and S-1 with oral (35–40 mg/m2 twice daily for d1-14, 28 days for one cycle). Follow-up examination and efficacy evaluation were executed periodically. Results Until the 4th cycle response evaluation, the local effective rate and control rate were 40% and 80%, respectively; only one patient developed progression. HAI chemotherapy had a better local control against liver metastases (median progression-free survival: hepatic, 8.8 months vs. extrahepatic, 6.2 months), accompanied by less systemic toxicity, decreased tumour markers and symptomatic relief. Conclusion HAI oxaliplatin plus oral S-1 chemotherapy can be considered as a new choice of first-line treatment for GCLM, which is also a good approach for controlling extrahepatic lesions with less adverse events.
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Affiliation(s)
- Kangxin Wang
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, People's Republic of China.,Department of Oncology, Nanjing Pukou Central Hospital, Nanjing 211800, People's Republic of China
| | - Xuebin Zhang
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, People's Republic of China
| | - Jia Wei
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, People's Republic of China
| | - Yiwen Xu
- The First Medical School of Nanjing Medical University, Nanjing 210000, People's Republic of China
| | - Qin Liu
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, People's Republic of China
| | - Jiaqi Xie
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, People's Republic of China
| | - Lihua Yuan
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, People's Republic of China
| | - Zhichen Sun
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, People's Republic of China
| | - Siyi Tan
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, People's Republic of China
| | - Lianru Zhang
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, People's Republic of China
| | - Baorui Liu
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, People's Republic of China
| | - Yang Yang
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, People's Republic of China
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Kawahara K, Makino H, Kametaka H, Hoshino I, Fukada T, Seike K, Kawasaki Y, Otsuka M. Outcomes of surgical resection for gastric cancer liver metastases: a retrospective analysis. World J Surg Oncol 2020; 18:41. [PMID: 32093729 PMCID: PMC7038617 DOI: 10.1186/s12957-020-01816-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 02/13/2020] [Indexed: 02/06/2023] Open
Abstract
Background The indications for the surgical treatment of gastric cancer liver metastases (GCLMs) remain controversial. In addition, the outcome of surgery for the treatment of liver metastases of alpha-fetoprotein-producing gastric cancer (AFP-GC) has not yet been reported. We assessed the clinicopathologic features, including AFP-GC, and the surgical results of these patients. Methods This retrospective study analyzed 20 patients who underwent hepatectomy for GCLM at Odawara Municipal Hospital between April 2006 and January 2016. Results The actuarial 1-, 3-, and 5-year overall survival (OS) rates after primary hepatectomy were 80.0%, 55.5%, and 31.7%, respectively, with a median OS of 42 months. Four patients survived for more than 5 years after their final hepatectomy procedures. A multivariate analysis showed multiple metastases in the liver, the elevated level of carbohydrate antigen 19-9 (CA19-9), and an age of less than 70 years to be independently associated with a poor prognosis in terms of OS. No significant differences were noted between the AFP-GC and AFP-negative GC groups. Conclusion Surgical treatment is therefore considered to be a feasible option for GCLM. The findings of the present study showed the number of metastatic liver tumors, the level of CA19-9, and the patient age to be prognostic indicators for the surgical treatment of GCLM.
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Affiliation(s)
- Kenji Kawahara
- Department of Surgery, Odawara Municipal Hospital, 46 Kuno, Odawara City, Kanagawa Prefecture, Japan.
| | - Hironobu Makino
- Department of Surgery, Odawara Municipal Hospital, 46 Kuno, Odawara City, Kanagawa Prefecture, Japan
| | - Hisashi Kametaka
- Department of Surgery, Odawara Municipal Hospital, 46 Kuno, Odawara City, Kanagawa Prefecture, Japan
| | - Isamu Hoshino
- Department of General Surgery, Chiba Cancer Center, 666-2, Nitona-cho, Chuo-ku, Chiba City, Chiba Prefecture, Japan
| | - Tadaomi Fukada
- Department of Surgery, Odawara Municipal Hospital, 46 Kuno, Odawara City, Kanagawa Prefecture, Japan
| | - Kazuhiro Seike
- Department of Surgery, Odawara Municipal Hospital, 46 Kuno, Odawara City, Kanagawa Prefecture, Japan
| | - Yohei Kawasaki
- Biostatistics Section, Clinical Research Center, Chiba University Hospital, 1-8-1, Inohana, Chuo-ku, Chiba City, Chiba Prefecture, Japan
| | - Masayuki Otsuka
- Department f General Surgery, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba City, Chiba Prefecture, Japan
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26
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Zhang K, Chen L. Chinese consensus on the diagnosis and treatment of gastric cancer with liver metastases. Ther Adv Med Oncol 2020; 12:1758835920904803. [PMID: 32127925 PMCID: PMC7036491 DOI: 10.1177/1758835920904803] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Accepted: 01/14/2020] [Indexed: 01/27/2023] Open
Abstract
Background The incidence of gastric cancer with liver metastases (GCLM) is 9.9-18.7%, with a median survival time of 11 months and a 5-year survival rate <20%. Multidisciplinary treatment (MDT) is gradually gaining recognition as the most important method. However, specific treatment plans remain unclear. The aim of study was to provide a consensus to improve the diagnosis and treatment of GCLM. Methods We brought together experts from relevant medical fields across China, including the Chinese Research Hospital Association Digestive Tumor Committee, Chinese Association of Upper Gastrointestinal Surgeons, Chinese Gastric Cancer Association, and the Gastrointestinal Surgical Group of Chinese Surgical Society Affiliated to Chinese Medical Association, to discuss and formulate this consensus. Results A consensus was reached on the diagnosis and treatment of GCLM. Moreover, we have developed a new clinical classification system, the Chinese Type for Gastric Cancer Liver Metastases, based on the likelihood of a surgical treatment being successful. Conclusions The MDT mode should be implemented throughout all treatment of GCLM.A Chinese version of this expert consensus has been published in the Chinese Journal of Practical Surgery (Volume 39, Issue 10, p. 405-411). Written permission was obtained from the Chinese Journal of Practical Surgery to disseminate the expert consensus in English.
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Affiliation(s)
- Kecheng Zhang
- Department of General Surgery, Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Lin Chen
- Department of General Surgery, Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Beijing, 100853, China
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27
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Luo Z, Rong Z, Huang C. Surgery Strategies for Gastric Cancer With Liver Metastasis. Front Oncol 2019; 9:1353. [PMID: 31921626 PMCID: PMC6915096 DOI: 10.3389/fonc.2019.01353] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Accepted: 11/18/2019] [Indexed: 01/27/2023] Open
Abstract
Gastric cancer with liver metastasis is defined as advanced gastric cancer and remains one of the deadliest diseases with poor prognosis. Approximately 4–14% of patients with gastric cancers presented with liver metastases at the initial diagnosis. Owing to its incurability, first-line treatment for gastric cancer with liver metastases is systematic chemotherapy, whereas surgery is usually performed to alleviate severe gastrointestinal symptoms. However, continuously emerging retrospective studies confirmed the role of surgery in gastric cancer with liver metastases and showed significantly improved survival rate in patients assigned to a group of surgery with or without chemotherapy. Therefore, more and more convincing data that resulted from prospective randomized clinical trials is in need to clarify the surgery strategies in patients with gastric cancer with liver metastasis.
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Affiliation(s)
- Zai Luo
- Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zeyin Rong
- Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Chen Huang
- Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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Zhang F, Huang X, Song Y, Gao P, Zhou C, Guo Z, Shi J, Wu Z, Wang Z. Conversion Surgery for Stage IV Gastric Cancer. Front Oncol 2019; 9:1158. [PMID: 31788445 PMCID: PMC6854003 DOI: 10.3389/fonc.2019.01158] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Accepted: 10/17/2019] [Indexed: 12/24/2022] Open
Abstract
The prognosis of stage IV gastric cancer (GC) is poor, with palliative chemotherapy remaining the main therapeutic option. Studies increasingly indicate that patients with unresectable stage IV GC, who undergo gastrectomy with radical intention after responding to several regimens of combined chemotherapy, can achieve good survival outcomes. Thus, surgery aiming at radical resection for unresectable stage IV GC after combined chemotherapy has received increasing attention in recent years. This novel therapeutic strategy was defined as conversion surgery in patients with unresectable stage IV GC and it can associate with significant improved survival when R0 resection can be achieved. Despite the recent advances in conversion surgery for patients with unresectable stage IV GC, selection criteria for combination chemotherapy regimens, indications for conversion surgery, optimal timing to surgery, and postoperative chemotherapy all remain controversial. This article reviews the current state of conversion surgery for unresectable stage IV GC.
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Affiliation(s)
- Fei Zhang
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Xuanzhang Huang
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Yongxi Song
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Peng Gao
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Cen Zhou
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Zhexu Guo
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Jinxin Shi
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Zhonghua Wu
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Zhenning Wang
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
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Gavriilidis P, Roberts KJ, de'Angelis N, Sutcliffe RP. Gastrectomy Alone or in Combination With Hepatic Resection in the Management of Liver Metastases From Gastric Cancer: A Systematic Review Using an Updated and Cumulative Meta-Analysis. J Clin Med Res 2019; 11:600-608. [PMID: 31413772 PMCID: PMC6681857 DOI: 10.14740/jocmr3925] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2019] [Accepted: 07/18/2019] [Indexed: 12/18/2022] Open
Abstract
Background Recent studies have demonstrated that hepatectomy in patients with synchronous hepatic gastric metastases may improve survival in certain patients. This study aimed to evaluate survival benefits of gastrectomy plus hepatectomy versus gastrectomy alone in patients with hepatic gastric metastases. Methods Studies were identified by a systematic search of Embase, PubMed, Cochrane Library, and Google Scholar databases. Traditional and cumulative meta-analyses were used to monitor the evidence over time. Results Eleven studies which included 861 patients compared gastrectomy plus hepatic resection in 349 patients with gastrectomy alone in 512 patients. Overall significantly better survival rates of 1, 2, 3, and 5 years were demonstrated for patients who underwent gastrectomy plus hepatic resection compared to patients who under underwent gastrectomy alone ((hazard ratio (HR) = 0.52 (0.39, 0.69), P < 0.001), (HR = 0.85 (0.74, 0.97), P = 0.01), (HR = 0.80 (0.72, 0.90), P = 0.003), (HR = 0.83 (0.78, 0.90), P < 0.001), respectively). Conclusions Carefully selected patients with hepatic gastric metastases may benefit from hepatic resection.
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Affiliation(s)
- Paschalis Gavriilidis
- Department of Hepato-Biliary-Pancreatic and Oesophago-Gastric Surgery, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London W12 0HS, UK.,Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery, Queen Elizabeth University Hospitals Birmingham, NHS Foundation Trust, B15 2TH, UK
| | - Keith J Roberts
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery, Queen Elizabeth University Hospitals Birmingham, NHS Foundation Trust, B15 2TH, UK
| | - Nicola de'Angelis
- Department of Digestive Surgery, Henri Mondor University Hospital, Creteil 94010, France
| | - Robert P Sutcliffe
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery, Queen Elizabeth University Hospitals Birmingham, NHS Foundation Trust, B15 2TH, UK
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Abstract
Background. Management of gastric cancer (GC) with liver metastases is debated. It is still controversial whether surgical resection provides a survival benefit or not. This systematic review was designed to evaluate the efficacy of hepatectomy for GC liver metastasis. Methods. We searched several electronic databases to identify eligible studies updated on September 2018. Studies assessing the efficacy and safety of hepatectomy versus no hepatectomy were included. Odds ratio (OR) along with 95% confidence interval (95% CI) were utilized for main outcome analysis. Results. In all, 10 studies were included. Patients who underwent hepatectomy had lower 1-year (OR = 0.15, 95% CI = 0.10-0.22, P < .00001), 3-year (OR = 0.16, 95% CI = 0.10-0.27, P < .00001), and 5-year mortality (OR = 0.13, 95% CI = 0.07-0.24, P < .00001) than those without hepatectomy. We also reported favorable survival outcome in patients with metachronous hepatic resection versus synchronous hepatic resection (OR = 2.09, 95% CI = 1.21-3.60, P = .008). However, there was no significant difference between solitary and multiple liver metastases (OR = 0.61, 95% CI = 0.35-1.07, P = .08). Conclusion. The present study demonstrates that hepatic resection in the management of liver metastases of GC can prolong the survival of patients and should be considered a promising treatment for such patients. Furthermore, there are more favorable outcomes in patients with metachronous metastases versus those with synchronous disease. Therefore, metachronous hepatic metastases from GC are not necessarily a contraindication for hepatectomy of the metastatic site.
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Affiliation(s)
- Jun-Kai Cui
- Department of Hepatobiliary Surgery, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, China
| | - Mei Liu
- Department of Intensive Care Unit, Wuhan No. 1 Hospital, Wuhan, China
| | - Xiao-Ke Shang
- Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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31
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Li Q, Xu X, Su D, Zhou T, Wang G, Li Z. Long-term survival of an elderly patient with advanced gastric cancer after combination therapy: a case report and literature review. BMC Cancer 2019; 19:459. [PMID: 31096933 PMCID: PMC6524267 DOI: 10.1186/s12885-019-5683-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2018] [Accepted: 05/08/2019] [Indexed: 12/18/2022] Open
Abstract
Background Gastric cancer ranks the fifth most common cancer, and the third leading cause of cancer-related deaths worldwide. Gastric cancer with liver metastasis (GCLM) has devastating prognosis, however, optimal treatment of GCLM, especially in elderly patients, has yet to be clarified. Case presentation A 75-year-old man was diagnosed with advanced gastric cancer (GC), presenting with acute gastrointestinal bleeding and synchronous metastatic lesion in liver. Based on multidisciplinary team (MDT)‘s decision, this patient underwent distal palliative gastrectomy with R1 margin. Histopathological diagnosis was stage IV gastric adenocarcinoma (pT3N2M1), HER2 negative. The patient was treated with chemotherapy and argon-helium cryoablation of liver and lung metastases.HER-2 gene amplification was identified in peripheral blood at later stage of therapy. The patient had been followed-up for 39 months, in sharp contrast to a median survival time of 13.8 months for majority of advanced GC. Conclusions Palliative distal gastrectomy in combination with chemotherapy and cryoablation significantly prolongs overall survival of an elderly patient with GCLM. Electronic supplementary material The online version of this article (10.1186/s12885-019-5683-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Qingwei Li
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150000, China
| | - Xuejun Xu
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150000, China
| | - Dan Su
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150000, China
| | - Tianshuo Zhou
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150000, China
| | - Guangyu Wang
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150000, China
| | - Zhiwei Li
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150000, China.
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32
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Chen W, Yu J, Zhang Y, Wang W, Yu W, Shi X, Xu Z, Liu H. First-line application of apatinib combined with S-1 based on peripheral circulating tumor cell screening to treat advanced gastric adenocarcinoma: a case report. ANNALS OF TRANSLATIONAL MEDICINE 2019; 7:181. [PMID: 31168462 DOI: 10.21037/atm.2019.03.68] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Apatinib mesylate, a small-molecule tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptor-2 (VEGFR-2), has been recommended as a third-line class A agent for patients with advanced gastric adenocarcinoma in China since April 2018. Thus far, there is no case report on the combined use of apatinib and S-1 as the first-line treatment option for metastatic gastric cancer (GC) patients based on peripheral circulating tumor cell (pCTC) monitoring. We present a unique case in which liver metastases originating from GC gradually shrank and disappeared in the presence of pCTC-positive disease after treatment with apatinib for 17 months. More surprisingly, the pCTCs became negative after the addition of S-1 halfway through treatment. A 71-year-old Chinese man who underwent gastroscopic biopsy and laparoscopy was diagnosed with gastric adenocarcinoma with multiple liver metastases. The pathological stage was T4NxM1. The patient obtained clinical benefit from first-line apatinib within 4 weeks. After developing grade 2 hand-foot syndrome, the patient began to take S-1 alone. When the condition was significantly relieved, the elderly patient continued to take apatinib combined with S-1 and achieved satisfactory therapeutic results. Many studies suggest that the prognosis of this type of GC is grim. However, apatinib increased the overall survival (OS) duration of the patient to 34 months. We hypothesize that combining apatinib with S-1 as a first-line therapeutic option for pCTC-positive advanced GC is feasible.
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Affiliation(s)
- Weikai Chen
- Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou 730000, China.,Department of General Surgery, No. 940 Hospital of Chinese People's Liberation Army Joint Logistic Support Force, Lanzhou 730050, China
| | - Jianping Yu
- Department of General Surgery, No. 940 Hospital of Chinese People's Liberation Army Joint Logistic Support Force, Lanzhou 730050, China
| | - Yanan Zhang
- Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou 730000, China.,Department of General Surgery, No. 940 Hospital of Chinese People's Liberation Army Joint Logistic Support Force, Lanzhou 730050, China
| | - Wenjie Wang
- Second Clinical Medical College, Lanzhou University, Lanzhou 730030, China
| | - Wenwen Yu
- Department of General Surgery, No. 940 Hospital of Chinese People's Liberation Army Joint Logistic Support Force, Lanzhou 730050, China
| | - Xin Shi
- Department of General Surgery, No. 940 Hospital of Chinese People's Liberation Army Joint Logistic Support Force, Lanzhou 730050, China
| | - Zipeng Xu
- Second Clinical Medical College, Lanzhou University, Lanzhou 730030, China
| | - Hongbin Liu
- Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou 730000, China.,Department of General Surgery, No. 940 Hospital of Chinese People's Liberation Army Joint Logistic Support Force, Lanzhou 730050, China.,Second Clinical Medical College, Lanzhou University, Lanzhou 730030, China
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Zurleni T, Gjoni E, Altomare M, Rausei S. Conversion surgery for gastric cancer patients: A review. World J Gastrointest Oncol 2018; 10:398-409. [PMID: 30487951 PMCID: PMC6247102 DOI: 10.4251/wjgo.v10.i11.398] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 09/25/2018] [Accepted: 10/07/2018] [Indexed: 02/05/2023] Open
Abstract
Gastric cancer (GC) is the third most common cancer-related cause of death worldwide. In locally advanced tumors, neoadjuvant chemotherapy has recently been introduced in most international Western guidelines. For metastatic and unresectable disease, there is still debate regarding correct management and the role of surgery. The standard approach for stage IV GC is palliative chemotherapy. Over the last decade, an increasing number of M1 patients who responded to palliative regimens of induction chemotherapy have been subsequently undergone surgery with curative intent. The objective of the present review is to analyze the literature regarding this approach, known as “conversion surgery”, which has become one of the most commonly adopted therapeutic options. It is defined as a treatment aiming at an R0 resection after chemotherapy in initially unresectable tumors. The 13 retrospective studies analyzed, with a total of 411 patients treated with conversion therapy, clearly show that even if standardization of unresectable and metastatic criteria, post-chemotherapy resectability evaluation and timing of surgery has not yet been established, an R0 surgery after induction chemotherapy with partial or complete response seems to offer superior survival results than chemotherapy alone. Additional larger sample-size randomized control trials are needed to identify subgroups of well-stratified patients who could benefit from this multimodal approach.
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Affiliation(s)
- Tommaso Zurleni
- Department of Surgery, ASST Valle Olona, Busto Arsizio 21052, Italy
| | - Elson Gjoni
- Department of Surgery, ASST Valle Olona, Busto Arsizio 21052, Italy
| | - Michele Altomare
- Department of Surgery, ASST Valle Olona, Busto Arsizio 21052, Italy
| | - Stefano Rausei
- Department of Surgery, ASST Valle Olona, Gallarate. 21013, Italy
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34
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Wang W, Jin J, Dai F, Long Z, Liu X, Cai H, Zhou Y, Chen Z, Huang H. Interleukin-15 suppresses gastric cancer liver metastases by enhancing natural killer cell activity in a murine model. Oncol Lett 2018; 16:4839-4846. [PMID: 30250549 PMCID: PMC6144747 DOI: 10.3892/ol.2018.9303] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2015] [Accepted: 04/28/2017] [Indexed: 12/12/2022] Open
Abstract
Interleukin (IL)-15 is a promising cytokine for cancer immunotherapy as it is a critical factor for the proliferation and activation of natural killer (NK) cells. Previous studies have suggested critical roles of IL-15 in tumor invasion and metastasis. However, the association between IL-15 and liver metastasis of gastric cancer (LMGC) remains unknown. The present study investigated the therapeutic efficacy of recombinant mouse IL-15 (rmIL-15) in murine LMGC models, in which stable green fluorescent protein (GFP)-expressing MKN45 cells (MKN45-GFP cells) were injected into the spleen parenchyma of mice for liver metastasis. At different treatments (high dose group: 2.5 µg of rmIL-15; low dose group: 0.2 µg of rmIL-15; control group: PBS), it was found that rmIL-15 decreased the formation of liver metastasis sites. Additionally, this treatment lead to improved survival of mice following tumor cell transplantation. Treatment with a high dose of rmIL-15 provided greater therapeutic efficacy by prolonged survival of the mice compared with low dose group and control group. It was found that NK cells isolated from the liver that received the high dose of rmIL-15 showed stronger cytotoxic activity compared with the other two groups on the target cells. These findings hold significant importance for the use of IL-15 as a potential adjuvant/therapeutic for liver metastasis from gastric cancer.
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Affiliation(s)
- Wei Wang
- Department of Gastric Cancer and Soft Tissue Sarcoma, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.,Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226000, P.R. China
| | - Jiejie Jin
- Department of Gastric Cancer and Soft Tissue Sarcoma, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
| | - Faxiang Dai
- Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226000, P.R. China
| | - Ziwen Long
- Department of Gastric Cancer and Soft Tissue Sarcoma, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
| | - Xiaowen Liu
- Department of Gastric Cancer and Soft Tissue Sarcoma, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
| | - Hong Cai
- Department of Gastric Cancer and Soft Tissue Sarcoma, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
| | - Ye Zhou
- Department of Gastric Cancer and Soft Tissue Sarcoma, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
| | - Zhong Chen
- Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226000, P.R. China
| | - Hua Huang
- Department of Gastric Cancer and Soft Tissue Sarcoma, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
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35
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Carmona-Bayonas A, Jiménez-Fonseca P, Echavarria I, Sánchez Cánovas M, Aguado G, Gallego J, Custodio A, Hernández R, Viudez A, Cano JM, Martínez de Castro E, Macías I, Martín Carnicero A, Garrido M, Mangas M, Álvarez Manceñido F, Visa L, Azkarate A, Ramchandani A, Fernández Montes A, Longo F, Sánchez A, Pimentel P, Limón ML, Arias D, Cacho Lavin D, Sánchez Bayona R, Cerdá P, García Alfonso P. Surgery for metastases for esophageal-gastric cancer in the real world: Data from the AGAMENON national registry. Eur J Surg Oncol 2018; 44:1191-1198. [DOI: 10.1016/j.ejso.2018.03.019] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2018] [Revised: 03/16/2018] [Accepted: 03/22/2018] [Indexed: 12/19/2022] Open
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36
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Xiao Y, Zhang B, Wu Y. Prognostic analysis and liver metastases relevant factors after gastric and hepatic surgical treatment in gastric cancer patients with metachronous liver metastases: a population-based study. Ir J Med Sci 2018; 188:415-424. [PMID: 30062399 DOI: 10.1007/s11845-018-1864-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Accepted: 07/09/2018] [Indexed: 01/20/2023]
Abstract
BACKGROUND The prognosis for patients with liver metastases from gastric cancer is very poor. Nevertheless, standard therapeutic strategies have not been established yet. The impact of hepatic surgical treatment on survival of patients with metachronous liver metastases from gastric cancer still remains controversial. METHODS We conducted a retrospective analysis on records of 436 patients who received radical gastrectomy (with D2 lymphadenectomy, regardless of hepatic surgical treatment) for gastric cancer with metachronous (≥ 3 months after gastrectomy) liver metastases in our center between 2001 and 2016. All patients were followed until 2017/10/31 or withdrawn from the follow-up because of death. RESULTS The median interval for non-hepatic metastases of the 436 patients who underwent radical gastrectomy is 14 months. T (P = 0.041), N (P = 0.023) and lymphovascular invasion (P < 0.001) were independent predictors affecting liver metastases-free interval. The overall survival rates for the 436 patients were 44.5, 29.7, 16.3, and 16.3% at 1, 2, 3, and 5 years respectively since treatment of hepatic metastases, with a median survival time of 11 months. N (P = 0.025), extent of liver metastases (H) (H2 vs. H1, P = 0.036; H3 vs. H1, P < 0.001), and treatment of liver metastatic lesions (P < 0.001) were significant independent prognostic factors for survival after presence of liver metastases. Among H1 and H2 patients, median survival in hepatic surgical treatment group was significantly longer than that in systemic chemotherapy alone group (25 vs. 11 months, P = 0.015). CONCLUSIONS Liver examinations should be performed during the first 2 years after gastric surgery and continued for 5 years for high-risk patients. Active therapeutic strategies may prolong patients' survival compared with supportive treatment alone. Patients with H1, H2 metachronous liver metastases may be considered appropriate candidates for hepatic surgical treatment before embarking on systemic chemotherapy alone. TRIAL REGISTRATION ISRCTN Registry (Retrospectively registered; Reference number: 35067; Date: 02/04/2018).
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Affiliation(s)
- Yibin Xiao
- Department of Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China
| | - Bo Zhang
- Department of Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China
| | - Yulian Wu
- Department of Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
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37
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Ministrini S, Solaini L, Cipollari C, Sofia S, Marino E, D'Ignazio A, Bencivenga M, Tiberio GAM. Surgical treatment of hepatic metastases from gastric cancer. Updates Surg 2018; 70:273-278. [PMID: 29845462 DOI: 10.1007/s13304-018-0536-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2018] [Accepted: 05/13/2018] [Indexed: 12/15/2022]
Abstract
The purpose of the study was to investigate the clinical factors influencing the prognosis of patients submitted to hepatectomy for metastases from gastric cancer and their clinical role. We conducted a retrospective multicentre review. We evaluated how survival from surgery was influenced by patient-related, tumour-related and treatment-related prognostic factors. We analysed data on 144 patients submitted to hepatectomy for metastases from gastric cancer, in the synchronous and metachronous setting. In 117 cases, an R0 resection was achieved, while in 27 an R + hepatic resection was performed. Chemotherapy was administered to 55 patients. Surgical mortality was 2.1% and morbidity 21.5%. One-, 3-, and 5-year OS rates after surgery were 49.9, 19.4 and 11.6%, respectively, with a median OS of 12.0 months. T4 gastric cancer, H3 hepatic involvement, non-curative resection, recurrence after surgery, and abstention from chemotherapy were associated with a worse prognosis. Factor T and H displayed a clear (p < 0.001) cumulative effect. Our data show that R0 resection must be pursued whenever possible. The treatment of T4 gastric cancer with hepatic bilateral and diffuse metastasis (H3) should be considered carefully or it should be probably avoided. Finally, a multimodal treatment associating surgery and chemotherapy offers the best survival results.
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Affiliation(s)
- Silvia Ministrini
- General Surgery, University of Brescia, piazzale Spedali Civili, 1, 25123, Brescia, Italy.
| | | | | | - Silvia Sofia
- General Surgery, University of Torino, Turin, Italy
| | | | | | | | - Guido A M Tiberio
- General Surgery, University of Brescia, piazzale Spedali Civili, 1, 25123, Brescia, Italy
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38
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Montagnani F, Crivelli F, Aprile G, Vivaldi C, Pecora I, De Vivo R, Clerico MA, Fornaro L. Long-term survival after liver metastasectomy in gastric cancer: Systematic review and meta-analysis of prognostic factors. Cancer Treat Rev 2018; 69:11-20. [PMID: 29860024 DOI: 10.1016/j.ctrv.2018.05.010] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2018] [Revised: 05/15/2018] [Accepted: 05/16/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Despite the amelioration of systemic therapy, overall survival (OS) of metastatic gastric cancer (GC) patients remains poor. Liver is a common metastatic site and retrospective series suggest a potential OS benefit from hepatectomy, with interesting 5-year (5 y) and 10-year (10 y) OS rates in selected patients. We aim to evaluate the impact of liver resection and related prognostic factors on long-term outcome in this setting. METHODS We searched Pubmed, EMBASE, and Abstracts/posters from international meetings since 1990. Data were extracted from publish papers. Random effects models meta-analyses and meta-regression models were built to assess 5yOS and the impact of different prognostic factor. Heterogeneity was assessed using between study variance, I2 and Cochran's Q. Funnel plot were used to assess small study bias. RESULTS Thirty-three observational studies (for a total of 1304 patients) were included. Our analysis demonstrates a 5yOS rate of 22% (95%CI: 18-26%) and 10yOS rate of 11% (95%CI: 7-18%) among patients undergoing radical hepatectomy. A favorable effect on OS was shown by several factors linked to primary cancer (lower T and N stage, no lympho-vascular or serosal invasion) and burden of hepatic disease (≤3 metastases, unilobar involvement, greatest lesion < 5 cm, negative resection margins). Moreover, lower CEA and CA19.9 levels and post-resection chemotherapy were associated with improved OS. CONCLUSIONS Surgical resection of liver metastases from GC seems associated with a significant chance of 5yOS and 10yOS and compares favourably with results of medical treatment alone. Prospective evaluation of this approach and validation of adequate selection criteria are needed.
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Affiliation(s)
- Francesco Montagnani
- Department of Oncology, Azienda Sanitaria locale di Biella, Ponderano (BI), Italy.
| | | | - Giuseppe Aprile
- Department of Oncology, Ospedale San Bortolo, Azienda ULSS8 Berica - Distretto Est, Vicenza, Italy
| | - Caterina Vivaldi
- Unit of Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Irene Pecora
- Unit of Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Rocco De Vivo
- Department of Oncology, Ospedale San Bortolo, Azienda ULSS8 Berica - Distretto Est, Vicenza, Italy
| | | | - Lorenzo Fornaro
- Unit of Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
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Sisic L, Strowitzki MJ, Blank S, Nienhueser H, Dorr S, Haag GM, Jäger D, Ott K, Büchler MW, Ulrich A, Schmidt T. Postoperative follow-up programs improve survival in curatively resected gastric and junctional cancer patients: a propensity score matched analysis. Gastric Cancer 2018; 21:552-568. [PMID: 28741059 DOI: 10.1007/s10120-017-0751-4] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2017] [Accepted: 07/15/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND To date there is no evidence that more intensive follow-up after surgery for esophagogastric adenocarcinoma translates into improved survival. This study aimed to evaluate the impact of standardized surveillance by a specialized center after resection on survival. METHODS Data of 587 patients were analyzed who underwent curative surgery for esophagogastric adenocarcinoma in our institution. Based on their postoperative surveillance, patients were assigned to either standardized follow-up (SFU) by the National Center for Tumor Diseases (SFU group) or individual follow-up by other physicians (non-SFU group). Propensity score matching (PSM) was performed to compensate for heterogeneity between groups. Groups were compared regarding clinicopathological findings, recurrence, and impact on survival before and after PSM. RESULTS Of 587 patients, 32.7% were in the SFU and 67.3% in the non-SFU group. Recurrence occurred in 39.4% of patients and 92.6% within the first 3 years; 73.6% were treated, and of those 17.1% underwent resection. In recurrent patients overall and post-recurrence survival (OS/PRS) was influenced by diagnostic tools (p < 0.05), treatment (p ≤ 0.001), and resection of recurrence (p ≤ 0.001). Standardized follow-up significantly improved OS (84.9 vs. 38.4 months, p = 0.040) in matched analysis and was an independent positive predictor of OS before and after PSM (p = 0.034/0.013, respectively). CONCLUSION After PSM, standardized follow-up by a specialized center significantly improved OS. Cross-sectional imaging and treatment of recurrence were associated with better outcome. Regular follow-up by cross-sectional imaging especially during the first 3 years should be recommended by national guidelines, since early detection might help select patients for treatment of recurrence and even resection in few designated cases.
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Affiliation(s)
- Leila Sisic
- Department of Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Moritz J Strowitzki
- Department of Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Susanne Blank
- Department of Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Henrik Nienhueser
- Department of Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Sara Dorr
- Department of Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Georg Martin Haag
- Department of Medical Oncology, National Center for Tumor Diseases (NCT), University Hospital Heidelberg, 69120, Heidelberg, Germany
| | - Dirk Jäger
- Department of Medical Oncology, National Center for Tumor Diseases (NCT), University Hospital Heidelberg, 69120, Heidelberg, Germany
| | - Katja Ott
- Department of Surgery, RoMed Hospital Rosenheim, 83022, Rosenheim, Germany
| | - Markus W Büchler
- Department of Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Alexis Ulrich
- Department of Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Thomas Schmidt
- Department of Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.
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CT-guided percutaneous cryoablation for palliative therapy of gastric cancer liver metastases. Cryobiology 2018; 82:43-48. [PMID: 29679550 DOI: 10.1016/j.cryobiol.2018.04.010] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2017] [Revised: 03/17/2018] [Accepted: 04/13/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Liver metastases occur in approximately 4%-14% of gastric cancer patients and are associated with high mortality. However, no standardized treatment approach is available for these patients. We aimed to assess the clinical outcomes of patients with gastric cancer liver metastases (GCLM) who underwent percutaneous cryoablation. METHODS We retrospectively enrolled 19 patients with 27 metastatic hepatic tumors who underwent cryoablation for liver metastases after gastrectomy for primary gastric cancer. Complications, overall survival (OS), local tumor progression-free survival (PFS), recurrence rates, and quality of life were assessed. RESULTS After cryoablation therapy, the median OS for all 19 patients was 16.0 months (range, 5-50 months), and the 1-, 2-, and 3-year OS rates were 78.9%, 43.4%, and 21.7%, respectively. The median local tumor PFS was 8.0 months (range, 3-24 months), and the local tumor PFS rates at 6 and 12 months were 59.2% and 23.2%, respectively. Overall, patients' quality of life improved after cryoablation therapy (P < 0.05). Complications in this study were mild; no severe complications caused by technique were detected. CONCLUSIONS Cryoablation provided good local control, improved patients' quality of life and had a low complication rate. Our research showed that cryoablation may be an effective palliative treatment for GCLM.
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Role of hepatectomy in gastric cancer with multiple liver-limited metastases. Gastric Cancer 2018; 21:338-344. [PMID: 28577228 DOI: 10.1007/s10120-017-0730-9] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Accepted: 05/25/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Several studies have demonstrated the benefit of hepatectomy for treating gastric cancer (GC) with liver-limited metastases (LLM). The survival benefit of hepatectomy compared with that of systemic chemotherapy is unknown, particularly in patients with multiple LLM. This study investigated the survival benefit of hepatectomy compared with that of systemic chemotherapy administered to patients with GC with multiple LLM. METHODS We retrospectively reviewed the data of consecutive patients with GC with two or three LLM who underwent hepatectomy or received systemic chemotherapy as initial treatment at the Shizuoka Cancer Center between December 2004 and December 2015. RESULTS Nine of 24 patients who met the inclusion criteria underwent hepatectomy, and 15 received chemotherapy. In the hepatectomy group, all patients achieved R0 resection and none died during hospitalization. Three patients received adjuvant chemotherapy. Disease recurred in eight patients (88.9%). In the chemotherapy group, three patients underwent hepatectomy following initial chemotherapy and did not experience recurrence or death during follow-up. Median follow-up was 47.9 months and median overall survival (OS) was 38.1 and 24.8 months in the chemotherapy and hepatectomy groups, respectively. Multivariate analysis of OS, including initial treatment, revealed that unilobar liver metastasis was the only independent favorable prognostic factor. CONCLUSIONS Although hepatectomy for patients with GC with multiple LLM is not recommended as the initial therapy, it prolonged the survival of patients with tumors controlled using systemic chemotherapy.
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Ryu T, Takami Y, Wada Y, Tateishi M, Matsushima H, Yoshitomi M, Saitsu H. Oncological outcomes after hepatic resection and/or surgical microwave ablation for liver metastasis from gastric cancer. Asian J Surg 2017; 42:100-105. [PMID: 29254868 DOI: 10.1016/j.asjsur.2017.09.005] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2017] [Revised: 09/20/2017] [Accepted: 09/30/2017] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Indications and efficacy of surgical treatment for liver metastases from gastric cancer (LMGCs) remain controversial. This retrospective study was designed to clarify the benefits of surgical treatment and identify prognostic factors. METHODS Between December 1997 and December 2015, 34 consecutive patients underwent hepatic resection and surgical microwave ablation for synchronous or metachronous LMGCs at our institution. We analyzed their cumulative overall survival (OS) and recurrence-free survival (RFS) rates and clinical parameters to identify predictors of prognosis. RESULTS Of the 34 patients, 14 underwent hepatic resection, 13 underwent surgical microwave ablation, and 7 underwent hepatic resection combined with surgical microwave ablation. Their OS rates were 1-year: 84.4%, 3-year: 38.6%, and 5-year: 34.7%; and their RFS rates were 1-year: 38.5%, 3-year: 28.0%, and 5-year: 28.0%. OS did not significantly vary among the surgical procedures. In multivariable analysis, positive of both CEA and CA19-9 were independent predictors of poor survival (hazard ratio [HR] 4.51; P = 0.049) and early recurrence (HR 5.70; P = 0.047). CONCLUSIONS Both hepatic resection and surgical microwave ablation for LMGCs are effective and can improve survival in selected patients.
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Affiliation(s)
- Tomoki Ryu
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
| | - Yuko Takami
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Yoshiyuki Wada
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Masaki Tateishi
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Hajime Matsushima
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Munehiro Yoshitomi
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Hideki Saitsu
- Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
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Minimally invasive surgery as a treatment option for gastric cancer with liver metastasis: a comparison with open surgery. Surg Endosc 2017; 32:1422-1433. [PMID: 29075971 DOI: 10.1007/s00464-017-5826-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2017] [Accepted: 08/11/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND As minimally invasive techniques advances, minimally invasive surgery (MIS) has emerged as an alternative modality for advanced gastric cancer. In this study, we compared the short- and long-term surgical outcomes of MIS and conventional open surgery for gastric cancer liver metastasis (GCLM) in terms of safety, feasibility, and efficacy. METHODS This retrospective study used data from a prospective database at the Chinese People's Liberation Army General Hospital. From January 2006 to June 2016, 53 gastric cancer patients with synchronous liver metastasis accepted radical gastrectomy combined with either or both hepatectomy and radiofrequency ablation for liver metastases. The 53 patients enrolled in the study were divided into two groups: a conventional open surgery group (n = 42) and an MIS group (n = 11). Propensity score matching (PSM) analysis was performed to overcome possible bias. RESULTS With PSM performed at a 1:3 ratio, 11 patients who received MIS were compared with 33 open surgery cases. Mean operation time was significantly longer for the MIS group compared with the open surgery group (301 vs. 236 min, P = 0.032), while the open surgery group had a larger estimated blood loss than the MIS group (421 vs. 196 ml, P = 0.019). Time to first flatus and postoperative complications, including Clavien-Dindo classification, were similar in the two groups. However, patients undergoing MIS had a significantly shorter time to first sips of water (P = 0.020) and soft diet (P = 0.020) compared with open surgery counterparts. Long-term outcomes were comparable between groups (P = 0.090) after adjustment by PSM analysis. CONCLUSIONS MIS achieved superior short-term outcomes and comparable long-term outcomes compared with open surgery in GCLM patients. For experienced surgeons, both laparoscopic and robotic methods of MIS are reasonable approaches for the management of highly selected GCLM patients.
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Intensified neoadjuvant multimodal approach in synchronous liver metastases from gastric cancer: a single institutional experience. Clin Transl Oncol 2017; 20:658-665. [PMID: 29043568 DOI: 10.1007/s12094-017-1767-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Accepted: 10/07/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Synchronous liver metastases (LM) from gastric (GC) or esophagogastric junction (EGJ) adenocarcinoma are a rare events. Several trials have evaluated the role of liver surgery in this setting, but the impact of preoperative therapy remains undetermined. METHODS Patients with synchronous LM from GC/EGJ adenocarcinoma who achieved disease control after induction chemotherapy (ICT) and were subsequently scheduled to chemoradiotherapy (CRT) to the primary tumor and surgery assessment were retrospectively analyzed. Pathological response, patterns of relapse, progression-free survival (PFS), and overall survival (OS) were calculated. From July 2002 to September 2012, 16 patients fulfilling the inclusion criteria were identified. RESULTS Primary tumor site was GC (nine patients) or EGJ (seven patients). LM were considered technically unresectable in nine patients. Radiological response to the whole neoadjuvant program was achieved in 13 patients. Eight patients underwent surgical resection of the primary tumor; in five of these LM were resected. A complete pathological response in the primary or in the LM was found in four and three patients, respectively. The most frequent site of relapse/progression was systemic (eight patients). Local and liver-only relapses were observed in two patients each. After a median follow-up of 91 months, the median OS and PFS were 23.0 (95% CI 13.2-32.8) and 17.0 months (95% CI 11.7-22.3). 5-year actuarial PFS is 17.6%. CONCLUSION Our results suggest that an intensified approach using ICT followed by CRT in synchronous LM from GC/EGJ adenocarcinoma is feasible and may translate into prolonged survival times in selected patients.
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Fukami Y, Kaneoka Y, Maeda A, Takayama Y, Takahashi T, Uji M, Kumada T. Adjuvant hepatic artery infusion chemotherapy after hemihepatectomy for gastric cancer liver metastases. Int J Surg 2017; 46:79-84. [PMID: 28882769 DOI: 10.1016/j.ijsu.2017.08.578] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Revised: 08/05/2017] [Accepted: 08/16/2017] [Indexed: 12/24/2022]
Abstract
BACKGROUND The most frequent pattern of recurrence is remnant liver after hepatectomy for gastric cancer liver metastases (GLM). The evidence of adjuvant hepatic artery infusion chemotherapy (HAIC) after hepatectomy for GLM is lacking. The aim of this study was to evaluate the efficacy of adjuvant HAIC after hemihepatectomy for GLM. METHODS Between 2001 and 2012, 14 patients who underwent hemihepatectomy for GLM were included in this study. Adjuvant HAIC to the remnant hemiliver was the FEM regimen (333 mg/m2 5-fluorouracil each week, 30 mg/m2 epirubicin once every 4 weeks, and 2.7 mg/m2 mitomycin-C once every 2 weeks) and was administered for 6 months after hemihepatectomy. Clinicopathological prognostic factors for survival were analyzed using a prospectively collected database. RESULTS Nine patients had solitary GLM, and 5 patients had multiple GLM before surgery. The median period from hemihepatectomy to HAIC was 30 days. The 6-month HAIC completion rate was 79% (n = 11/14). Reasons of HAIC failure included liver dysfunction (n = 1), catheter infection (n = 1), and development of multiple recurrence (n = 1). The median follow-up was 29 (range 8-166) months. Recurrences were detected in 8 patients (57%). The site of recurrences included lung (n = 1), lymph nodes (n = 1), peritoneal dissemination (n = 1), brain (n = 1), pleural (n = 1), and multiple sites (n = 3). The overall 5-year survival rate was 43%. The pathological T4 classification and the preoperative CEA ≥5 ng/mL were significant prognostic factors for overall survival. CONCLUSIONS Adjuvant HAIC after hemihepatectomy for GLM prevents remnant liver recurrence and may contribute to long-term survival.
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Affiliation(s)
- Yasuyuki Fukami
- Department of Surgery, Ogaki Municipal Hospital, Gifu, Japan.
| | - Yuji Kaneoka
- Department of Surgery, Ogaki Municipal Hospital, Gifu, Japan
| | - Atsuyuki Maeda
- Department of Surgery, Ogaki Municipal Hospital, Gifu, Japan
| | - Yuichi Takayama
- Department of Surgery, Ogaki Municipal Hospital, Gifu, Japan
| | | | - Masahito Uji
- Department of Surgery, Ogaki Municipal Hospital, Gifu, Japan
| | - Takashi Kumada
- Department of Gastroenterology, Ogaki Municipal Hospital, Gifu, Japan
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Kataoka K, Kinoshita T, Moehler M, Mauer M, Shitara K, Wagner AD, Schrauwen S, Yoshikawa T, Roviello F, Tokunaga M, Boku N, Ducreux M, Terashima M, Lordick F. Current management of liver metastases from gastric cancer: what is common practice? New challenge of EORTC and JCOG. Gastric Cancer 2017; 20:904-912. [PMID: 28150070 DOI: 10.1007/s10120-017-0696-7] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Accepted: 01/18/2017] [Indexed: 02/07/2023]
Abstract
The role of multidisciplinary treatment including surgery for liver metastases from gastric cancer (LMGC) is controversial. Studies to answer this clinical question are increasing in number, but all published data thus far are based on retrospective analyses with limited sample sizes. Thus, the European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Tract Cancer Group (GITCG) and the Japan Clinical Oncology Group (JCOG) Stomach Cancer Study Group (SCSG) initiated a collaboration to develop an optimal treatment strategy for LMGC. Before planning a prospective study, a questionnaire was sent out to the network members of both groups in June 2016 to clarify current common practice in each region. Sixty-seven sites from 17 countries in the EORTC network and 55 sites from Japan responded. According to the survey, for patients with resectable LMGC without extrahepatic metastases, preoperative chemotherapy followed by resection of both primary (if still in place) and liver lesions was the preferred option for both the synchronous and the metachronous setting. For patients with unresectable LMGC, most of the sites recommended chemotherapy only. In this article, the detailed results of this survey are reported, shedding light on current community practice, and a joint EORTC-JCOG strategy of investigation is delineated.
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Affiliation(s)
- Kozo Kataoka
- European Organisation for Research and Treatment of Cancer (EORTC) Headquarters, Avenue E, Mounier 83/11, 1200, Brussels, Belgium.
| | - Takahiro Kinoshita
- Department of Gastric Surgery Division, National Cancer Center Hospital East, Chiba, Japan
| | - Markus Moehler
- First Department of Internal Medicine, Johannes Gutenberg-University of Mainz, Mainz, Germany
| | - Murielle Mauer
- European Organisation for Research and Treatment of Cancer (EORTC) Headquarters, Avenue E, Mounier 83/11, 1200, Brussels, Belgium
| | - Kohei Shitara
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, National Cancer Center Hospital East, Chiba, Japan
| | | | - Stefanie Schrauwen
- European Organisation for Research and Treatment of Cancer (EORTC) Headquarters, Avenue E, Mounier 83/11, 1200, Brussels, Belgium
| | - Takaki Yoshikawa
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Franco Roviello
- General Surgery and Surgical Oncology Department, University of Siena, Siena, Italy
| | - Masanori Tokunaga
- Division of Gastric Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Narikazu Boku
- Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan
| | - Michel Ducreux
- Department of Medical Oncology, Gustave Roussy, Villejuif, France
| | | | - Florian Lordick
- University Cancer Center Leipzig (UCCL), University Hospital Leipzig, Liebigstr. 20, 04103, Leipzig, Germany.
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Influence of Surgical Resection of Hepatic Metastases From Gastric Adenocarcinoma on Long-term Survival: Systematic Review and Pooled Analysis. Ann Surg 2017; 263:1092-101. [PMID: 26797324 DOI: 10.1097/sla.0000000000001542] [Citation(s) in RCA: 118] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES The objectives of this systematic review and pooled analysis were to examine long-term survival, morbidity, and mortality following surgical resection of gastric cancer hepatic metastases and to identify prognostic factors that improve survival. BACKGROUND Patients with hepatic metastases from gastric cancer are traditionally treated with palliative chemotherapy. METHODS A systematic literature search was undertaken (1990 to 2015). Publications were included if they studied more than 10 patients undergoing hepatectomy for hepatic metastasis from gastric adenocarcinoma in the absence of peritoneal disease or other distant organ involvement. The primary outcome was the hazard ratio (HR) for overall survival. The influence of liver metastasis related factors; multiple vs single and metachronous vs synchronous upon survival was also assessed. RESULTS The median number of resections for the 39 studies included was 21 (range 10 to 64). Procedures were associated with a median 30-day morbidity of 24% (0% to 47%) and mortality of 0% (0% to 30%). The median 1-year, 3-year, and 5-year survival were 68%, 31%, and 27%, respectively. Survival was improved in Far Eastern compared with Western studies; 1-year (73% vs 59%), 3-year (34% vs 24.5%), and 5-year (27.3% vs 16.5%). Surgical resection of hepatic metastases was associated with a significantly improved overall survival (HR = 0.50; P < 0.001). Meta-analysis confirmed the additional survival benefit of solitary compared with multiple hepatic metastases (odds ratio = 0.31; P = 0.011). CONCLUSIONS The observed improved survival rates following the resection of hepatic metastasis from gastric adenocarcinoma in selected patients merit a prospective study to formally address the survival benefits and the influence on quality of life of such approach.
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Conversion therapy for inoperable advanced gastric cancer patients by docetaxel, cisplatin, and S-1 (DCS) chemotherapy: a multi-institutional retrospective study. Gastric Cancer 2017; 20:517-526. [PMID: 27553665 DOI: 10.1007/s10120-016-0633-1] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Accepted: 08/08/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND Conversion therapy is an option for unresectable metastatic gastric cancer when distant metastases are controlled by chemotherapy; however, the feasibility and efficacy remain unclear. This study aimed to assess the feasibility and efficacy of conversion therapy in patients with initially unresectable gastric cancer treated with docetaxel, cisplatin, and S-1 (DCS) chemotherapy by evaluating clinical outcomes. METHODS One hundred unresectable metastatic gastric cancer patients, enrolled in three DCS chemotherapy clinical trials, were retrospectively evaluated. The patients received oral S-1 (40 mg/m2 b.i.d.) on days 1-14 and intravenous cisplatin (60 mg/m2) and docetaxel (50-60 mg/m2) on day 8 every 3 weeks. Conversion therapy was defined when the patients could undergo R0 resection post-DCS chemotherapy and were able to tolerate curative surgery. RESULTS Conversion therapy was achieved in 33/100 patients, with no perioperative mortality. Twenty-eight of the 33 patients (84.8 %) achieved R0 resection, and 78.8 % were defined as histological chemotherapeutic responders. The median overall survival (OS) of patients who underwent conversion therapy was 47.8 months (95 % CI 28.0-88.5 months). Patients who underwent R0 resection had significantly longer OS than those who underwent R1 and R2 resections (P = 0.0002). Of the patients with primarily unresectable metastases, 10 % lived >5 years. Among patients who underwent conversion therapy, multivariate analysis showed that the pathological response was a significant independent predictor for OS. CONCLUSIONS DCS safely induced a high conversion rate, with very high R0 and pathological response rates, and was associated with a good prognosis; these findings warrant further prospective investigations.
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Fukumitsu N, Okumura T, Takizawa D, Numajiri H, Ohnishi K, Mizumoto M, Aihara T, Ishikawa H, Tsuboi K, Sakurai H. Proton beam therapy for liver metastases from gastric cancer. JOURNAL OF RADIATION RESEARCH 2017; 58:357-362. [PMID: 27974509 PMCID: PMC5440857 DOI: 10.1093/jrr/rrw102] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/10/2016] [Revised: 04/28/2016] [Indexed: 05/31/2023]
Abstract
Liver metastases from gastric cancer (LMGC) is a non-curable, fatal disease with a 5-year survival rate of <10%. Although various local treatments have been applied, their clinical utility has not been established. The purpose of this study was to investigate the safety and effectiveness of proton beam therapy (PBT) for the treatment of patients with LMGC. A total of nine patients (seven men, two women; aged 56-78 years) with LMGC who received PBT between 2002 and 2012 were retrospectively reviewed. Patients who had tumors confined to the liver were investigated, and patients who had extrahepatic tumors were excluded. Six of the patients had solitary tumors, and three patients had multiple tumors. The total irradiation dose was 64-77 Gy relative biological effectiveness (RBE), and three patients received concurrent chemotherapy. The overall and progression-free survival (OS and PFS) rates, local control (LC) rate, and adverse effects were investigated. All patients completed treatment without interruption, and late adverse effects of higher than Grade 3 were not observed. The OS rates at 1, 3 and 5 years were 100%, 78% and 56%, respectively (median, 5.5 years); the PFS rates were 67%, 40% and 40% (median, 2.6 years); and the LC rates were 89%, 71% and 71%. PBT was demonstrated to be a safe treatment, and the OS and PFS rates were not inferior to those for other types of local treatment. Therefore, PBT should be considered as an effective local treatment option for patients with LMGC.
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Affiliation(s)
- Nobuyoshi Fukumitsu
- Proton Medical Research Center, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8575, Japan
| | - Toshiyuki Okumura
- Proton Medical Research Center, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8575, Japan
| | - Daichi Takizawa
- Proton Medical Research Center, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8575, Japan
| | - Haruko Numajiri
- Proton Medical Research Center, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8575, Japan
| | - Kayoko Ohnishi
- Proton Medical Research Center, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8575, Japan
| | - Masashi Mizumoto
- Proton Medical Research Center, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8575, Japan
| | - Teruhito Aihara
- Proton Medical Research Center, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8575, Japan
| | - Hitoshi Ishikawa
- Proton Medical Research Center, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8575, Japan
| | - Koji Tsuboi
- Proton Medical Research Center, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8575, Japan
| | - Hideyuki Sakurai
- Proton Medical Research Center, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8575, Japan
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Surgical resection for hepatic metastasis from gastric cancer: a multi- institution study. Oncotarget 2017; 8:71147-71153. [PMID: 29050350 PMCID: PMC5642625 DOI: 10.18632/oncotarget.16705] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2017] [Accepted: 03/21/2017] [Indexed: 02/07/2023] Open
Abstract
Background The beneficial effect of surgical resection for hepatic metastasis from gastric cancer (HMGC) remains elusive. This study was conducted to analyze surgical outcomes of HMGC and determine the prognostic factors associated with survival. Results The in-hospital mortality rate was zero, and the overall morbidity rate was 56%. The overall 1-, 3-, and 5-year survival rate after surgery was 87.5%, 47.6%, and 21.7%, respectively, with a median survival time of 34.0 months. Multiple liver metastases (hazard ratio [HR] =1.998; 95% confidence interval [CI] = 1.248-3.198; P = 0.004) and ≥ T3 stage of the primary gastric cancer (HR = 2.065; 95% CI = 1.201–3.549; P = 0.009) were independent prognostic determinants in the multivariate analysis. Materials and Methods Data on surgical resection of 96 patients with HMGC at six institutions in China were analysed retrospectively. Prognostic factors were assessed by multiple stepwise regression analysis using the Cox model. Conclusions Surgical resection for HMGC is feasible and beneficial to long-term survival in selected patients.
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