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Xu P, Liu K, Huang S, Lv J, Yan Z, Ge H, Cheng Q, Chen Z, Ji P, Qian Y, Li B, Xu H, Yang L, Xu Z, Zhang D. N 6-methyladenosine-modified MIB1 promotes stemness properties and peritoneal metastasis of gastric cancer cells by ubiquitinating DDX3X. Gastric Cancer 2024; 27:275-291. [PMID: 38252226 DOI: 10.1007/s10120-023-01463-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Accepted: 12/19/2023] [Indexed: 01/23/2024]
Abstract
BACKGROUND Peritoneal metastasis (PM), one of the most typical forms of metastasis in advanced gastric cancer (GC), indicates a poor prognosis. Exploring the potential molecular mechanism of PM is urgently necessary, as it has not been well studied. E3 ubiquitin ligase has been widely established to exert a biological function in various cancers, but its mechanism of action in GC with PM remains unknown. METHODS The effect of MIB1 on PM of GC was confirmed in vitro and in vivo. Co-immunoprecipitation (Co-IP) and mass spectrometry demonstrated the association between MIB1 and DDX3X. Western blot, flow cytometry and immunofluorescence determined that DDX3X was ubiquitylated by MIB1 and promoted stemness. We further confirmed that METTL3 promoted the up-regulation of MIB1 by RNA immunoprecipitation (RIP), luciferase reporter assay and other experiments. RESULTS We observed that the E3 ubiquitin ligase Mind bomb 1 (MIB1) was highly expressed in PMs, and patients with PM with high MIB1 expression showed a worse prognosis than those with low MIB1 expression. Mechanistically, our study demonstrated that the E3 ubiquitin ligase MIB1 promoted epithelial-mesenchymal transition (EMT) progression and stemness in GC cells by degrading DDX3X. In addition, METTL3 mediated m6A modification to stabilize MIB1, which required the m6A reader IGF2BP2. CONCLUSIONS Our study elucidated the specific molecular mechanism by which MIB1 promotes PM of GC, and suggested that targeting the METTL3-MIB1-DDX3X axis may be a promising therapeutic strategy for GC with PM.
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Affiliation(s)
- Peng Xu
- Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Kanghui Liu
- Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Shansong Huang
- Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Jialun Lv
- Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Zhengyuan Yan
- Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
- Department of Surgery, Nanjing Lishui People's Hospital, Nanjing, 211200, China
| | - Han Ge
- Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Quan Cheng
- Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Zetian Chen
- Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Peicheng Ji
- Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Yawei Qian
- Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Bowen Li
- Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Hao Xu
- Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Li Yang
- Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Zekuan Xu
- Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Diancai Zhang
- Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
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Shao S, Yang X, Zhang YN, Wang XJ, Li K, Zhao YL, Mou XZ, Hu PY. Oncolytic Virotherapy in Peritoneal Metastasis Gastric Cancer: The Challenges and Achievements. Front Mol Biosci 2022; 9:835300. [PMID: 35295845 PMCID: PMC8918680 DOI: 10.3389/fmolb.2022.835300] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 02/04/2022] [Indexed: 11/13/2022] Open
Abstract
Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer death globally. Although the mortality rate in some parts of the world, such as East Asia, is still high, new treatments and lifestyle changes have effectively reduced deaths from this type of cancer. One of the main challenges of this type of cancer is its late diagnosis and poor prognosis. GC patients are usually diagnosed in the advanced stages of the disease, which is often associated with peritoneal metastasis (PM) and significantly reduces survival. This type of metastasis in patients with GC poses a serious challenge due to limitations in common therapies such as surgery and tumor resection, as well as failure to respond to systemic chemotherapy. To solve this problem, researchers have used virotherapy such as reovirus-based anticancer therapy in patients with GC along with PM who are resistant to current chemotherapies because this therapeutic approach is able to overcome immune suppression by activating dendritic cells (DCs) and eventually lead to the intrinsic activity of antitumor effector T cells. This review summarizes the immunopathogenesis of peritoneal metastasis of gastric cancer (PMGC) and the details for using virotherapy as an effective anticancer treatment approach, as well as its challenges and opportunities.
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Affiliation(s)
- Su Shao
- Department of General Surgery, Chun’an First People’s Hospital (Zhejiang Provincial People’s Hospital Chun’an Branch), Hangzhou, China
| | - Xue Yang
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital of Hangzhou Medical College), Hangzhou, China
- Clinical Research Institute, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital of Hangzhou Medical College), Hangzhou, China
| | - You-Ni Zhang
- Department of Traumatology, Tiantai People’s Hospital of Zhejiang Province (Tiantai Branch of Zhejiang People’s Hospital), Taizhou, China
| | - Xue-Jun Wang
- Department of General Surgery, Chun’an First People’s Hospital (Zhejiang Provincial People’s Hospital Chun’an Branch), Hangzhou, China
| | - Ke Li
- Guangdong Techpool Bio-pharma Co., Ltd., Guangzhou, China
| | - Ya-Long Zhao
- Guangdong Techpool Bio-pharma Co., Ltd., Guangzhou, China
| | - Xiao-Zhou Mou
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital of Hangzhou Medical College), Hangzhou, China
- Clinical Research Institute, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital of Hangzhou Medical College), Hangzhou, China
- *Correspondence: Xiao-Zhou Mou, ; Pei-Yang Hu,
| | - Pei-Yang Hu
- Department of Traumatology, Tiantai People’s Hospital of Zhejiang Province (Tiantai Branch of Zhejiang People’s Hospital), Taizhou, China
- *Correspondence: Xiao-Zhou Mou, ; Pei-Yang Hu,
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Zeng L, Liao Q, Zeng X, Ye J, Yang X, Zhu S, Tang H, Liu G, Cui W, Ma S, Cui S. Noncoding RNAs and hyperthermic intraperitoneal chemotherapy in advanced gastric cancer. Bioengineered 2022; 13:2623-2638. [PMID: 35089117 PMCID: PMC8973587 DOI: 10.1080/21655979.2021.2021348] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Gastric cancer (GC) is one of the most common malignant tumors globally. About 20-30% of patients with gastric cancer show peritoneal implantation metastasis at the first diagnosis. Peritoneal metastasis is responsible for 70% of deaths of patients with advanced gastric cancer. Although there are many ways to treat advanced gastric cancer, the prognosis of patients with recurrence is unsatisfactory. An auxiliary treatment with hyperthermic intraperitoneal chemotherapy (HIPEC), is an internationally recognized recommended treatment for advanced gastric cancer. A series of clinical trials have shown that HIPEC significantly improves the overall survival of patients with cancer. Compared with the cytoreductive surgery (CRS) alone, HIPEC combined with CRS markedly reduced the rate of peritoneal metastasis in patients with ovarian cancer and colorectal cancer. It has been demonstrated that HIPEC alters transcription of many genes by affecting non-coding RNAs, which may contribute to the suppressive effect of HIPEC on the synthesis of nucleic acids and proteins in cancer cells. This paper reviews the recent advances in understanding the role of non-coding RNAs in tumor invasion and metastasis of advanced gastric cancer. We also consider changes in noncoding RNA levels and other molecules in advanced gastric cancer cases treated with HIPEC. We hope that our review will provide a reference for future research on molecular epidemiology and etiology of advanced gastric cancer and promote precise treatment of this malignancy using HIPEC.
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Affiliation(s)
- Lisi Zeng
- Institute of Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Quanxing Liao
- Department of the Second Area of Gastrointestinal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Xiaohui Zeng
- Institute of Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Jiacai Ye
- Department of Radiotherapy, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Xianzi Yang
- Department of Medical Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Siyu Zhu
- Department of Medical Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Hongsheng Tang
- Department of the Second Area of Gastrointestinal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Gaojie Liu
- Department of the Second Area of Gastrointestinal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Weiwen Cui
- Department of Bioengineering, University of California, Berkeley, California, USA
| | - Shaohua Ma
- Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen, China.,Tsinghua-Berkeley Shenzhen Institute (TBSI), Tsinghua University, Shenzhen, China
| | - Shuzhong Cui
- Department of the Second Area of Gastrointestinal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.,State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China
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Shimura T, Toden S, Kandimalla R, Toiyama Y, Okugawa Y, Kanda M, Baba H, Kodera Y, Kusunoki M, Goel A. Genomewide Expression Profiling Identifies a Novel miRNA-based Signature for the Detection of Peritoneal Metastasis in Patients With Gastric Cancer. Ann Surg 2021; 274:e425-e434. [PMID: 31663973 PMCID: PMC7577555 DOI: 10.1097/sla.0000000000003647] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE This study aimed to conduct a genomewide transcriptomic profiling to develop a microRNA (miRNA)-based signature for the identification of peritoneal metastasis (PM) in patients with gastric cancer (GC). SUMMARY BACKGROUND DATA Even though PM in patients with GC has long been recognized to associate with poor prognosis, currently there is lack of availability of molecular biomarkers for its robust diagnosis. METHODS We performed a systematic biomarker discovery by analyzing miRNA expression profiles in primary tumors from GC patients with and without PM, and subsequently validated the expression of candidate miRNA biomarkers in 3 independent clinical cohorts of 354 patients with advanced GC. RESULTS Five miRNAs (miR-30a-5p, -134-5p, -337-3p, -659-3p, and -3917) were identified during the initial discovery phase; three of which (miR-30a-5p, -659-3p, and -3917) were significantly overexpressed in the primary tumors from PM-positive patients in the testing cohort (P = 0.002, 0.04, and 0.007, respectively), and distinguished patients with versus without peritoneal metastasis with the value of area under the curve (AUC) of 0.82. Furthermore, high expression of these miRNAs also associated with poor prognosis (hazard ratio = 2.18, P = 0.04). The efficacy of the combination miRNA signature was subsequently validated in an independent validation cohort (AUC = 0.74). Finally, our miRNA signature when combined together with the macroscopic Borrmann's type score offered a much superior diagnostic in all 3 cohorts (AUC = 0.87, 0.76, and 0.79, respectively). CONCLUSIONS We have established an miRNA-based signature that have a potential to identify peritoneal metastasis in GC patients.
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Affiliation(s)
- Tadanobu Shimura
- Center for Gastrointestinal Research; Center from Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA
- Department of Molecular Diagnostics, Therapeutics and Translational Medicine, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Shusuke Toden
- Center for Gastrointestinal Research; Center from Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA
- Department of Molecular Diagnostics, Therapeutics and Translational Medicine, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Raju Kandimalla
- Center for Gastrointestinal Research; Center from Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA
- Department of Molecular Diagnostics, Therapeutics and Translational Medicine, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Yuji Toiyama
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Yoshinaga Okugawa
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Mitsuro Kanda
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan
| | - Yasuhiro Kodera
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masato Kusunoki
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Ajay Goel
- Center for Gastrointestinal Research; Center from Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA
- Department of Molecular Diagnostics, Therapeutics and Translational Medicine, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, USA
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The benefits of surgery plus extensive intraoperative peritoneal lavage (EIPL) for patients with gastric cancer compared with surgery alone: a systematic review and meta-analysis. Updates Surg 2021; 74:65-72. [PMID: 34170498 DOI: 10.1007/s13304-021-01120-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 06/20/2021] [Indexed: 12/27/2022]
Abstract
This study aims to synthesize the benefits of surgery plus extensive intraoperative peritoneal lavage (EIPL) for patients with gastric cancer compared with surgery alone. We searched Pubmed, Embase, Web of Science, Cochrane library, ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform (ICTRP) for randomized controlled trials from 2000 to 2021 according to the inclusion and exclusion criteria. The reference lists of studies meeting the criteria were also screened for additional studies. The quality of these studies was assessed by the Cochrane Collaboration Risk of Bias Tool. An inverse-variance random-effects model of DerSimonian and Laird was used to synthesize the HRs and corresponding 95% CIs of short-term outcomes: hospital mortality and postoperative complications. For long-term outcomes (peritoneal recurrence and 3-year or 5-year overall survival rate), narrative synthesis was used. 4 of 43 studies were included for quantitative analysis. For short-term outcomes, the pooled HRs of hospital mortality and postoperative complications are 0.422 (95%CI: 0.037, 4.790) and 0.774 (95%CI: 0.376, 1.592). For long-term outcomes, despite the inconsistent results, patients receiving EPIL did not have reduced peritoneal recurrence and 3-year or 5-year overall survival rate. Compared with surgery alone, surgery plus EIPL does not have more benefits for patients with gastric cancer.
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Kang X, Li W, Liu W, Liang H, Deng J, Wong CC, Zhao S, Kang W, To KF, Chiu PWY, Wang G, Yu J, Ng EKW. LIMK1 promotes peritoneal metastasis of gastric cancer and is a therapeutic target. Oncogene 2021; 40:3422-3433. [PMID: 33883692 PMCID: PMC8116207 DOI: 10.1038/s41388-021-01656-1] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2020] [Revised: 12/06/2020] [Accepted: 01/13/2021] [Indexed: 12/17/2022]
Abstract
Peritoneal metastasis is a common form of metastasis among advanced gastric cancer patients. In this study, we reported the identification of LIM domain kinase 1 (LIMK1) as a promoter of gastric cancer peritoneal metastasis, and its potential to be a therapeutic target of dabrafenib (DAB). Using transcriptomic sequencing of paired gastric cancer peritoneal metastasis, primary tumors, and normal gastric tissues, we first unveiled that LIMK1 is selectively up-regulated in metastatic tumors. Increased LIMK1 in gastric cancer peritoneal metastasis was validated by immunohistochemistry analysis of an independent patient cohort. In vitro functional studies demonstrated that LIMK1 knockout or knockdown significantly inhibited cell migration and invasion of gastric cancer cells. LIMK1 knockout also abrogated peritoneal and liver metastases of gastric cancer cells in nude mice in vivo. Dabrafenib, a small molecule targeting LIMK1, was found to decrease cell migration and invasion of gastric cancer cells in vitro and abolish peritoneal and liver metastasis formation in vivo. Mechanistically, either LIMK1 knockout or Dabrafenib inhibited LIMK1 expression and phosphorylation of its downstream target cofilin. Taken together, our results demonstrated that LIMK1 functions as a metastasis promoter in gastric cancer by inhibiting LIMK1-p-cofilin and that Dabrafenib has the potential to serve as a novel treatment for gastric cancer peritoneal metastasis.
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Affiliation(s)
- Xi Kang
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
- Department of Surgery, Hebei Medical University 4th Hospital, Shijiazhuang, China
| | - Weilin Li
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
- Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China
| | - Weixin Liu
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
| | - Han Liang
- Department of Gastroenterology, Tianjin Medical University Cancer Hospital, City Key Laboratory of Tianjin Cancer Center and National Clinical Research Center for Cancer, Tianjin, China
| | - Jingyu Deng
- Department of Gastroenterology, Tianjin Medical University Cancer Hospital, City Key Laboratory of Tianjin Cancer Center and National Clinical Research Center for Cancer, Tianjin, China
| | - Chi Chun Wong
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
| | - Sinan Zhao
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
- Department of Endocrinology, Hebei Medical University 2nd Hospital, Shijiazhuang, China
| | - Wei Kang
- Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China
| | - Ka Fai To
- Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China
| | - Philip Wai Yan Chiu
- Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China
| | - Guiying Wang
- Department of Surgery, Hebei Medical University 4th Hospital, Shijiazhuang, China.
| | - Jun Yu
- Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
| | - Enders Kwok Wai Ng
- Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China.
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Macrì A, Morabito F. The use of intraperitoneal chemotherapy for gastric malignancies. Expert Rev Anticancer Ther 2019; 19:879-888. [PMID: 31544548 DOI: 10.1080/14737140.2019.1671189] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Accepted: 09/19/2019] [Indexed: 12/12/2022]
Abstract
Introduction: Gastric cancer is the fourth/fifth most common malignancy worldwide, with only a quarter of patients achieving a 5-year survival rate. It has been estimated that 15-50% or more of patients have peritoneal disease upon surgical exploration. Until the early 1990s, peritoneal metastasis was considered as terminal stage of the disease; in the late 1990s, selected patients with peritoneal metastasis were recategorized as local disease. Over the past two decades, the treatment of peritoneal involvement has transformed, and cytoreductive surgery plus intraperitoneal therapy have drastically altered the natural course of several malignancies. Areas covered: We performed a review of studies available on PubMed from 1 January 2014 to 31 July 2019 and the analysis of their reference citations. We describe the most current intraperitoneal chemotherapy opportunities in the treatment of gastric cancer: hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC), laparoscopic hyperthermic intraperitoneal chemotherapy (LHIPEC), neoadjuvant intraperitoneal and systemic chemotherapy (NIPS), LHIPEC + NIPS, extensive intraoperative peritoneal lavage (EIPL), early postoperative intraperitoneal chemotherapy (EPIC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC). Expert opinion: Comprehensive treatment consisting of CRS combined with perioperative intraperitoneal/systemic chemotherapy can, today, be considered an effective strategy to improve the long-term survival of gastric cancer patients with peritoneal metastasis.
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Affiliation(s)
- Antonio Macrì
- Peritoneal Surface Malignancy and Soft Tissue Sarcoma Program, Messina University Medical School Hospital , Messina , Italy
| | - Federico Morabito
- Peritoneal Surface Malignancy and Soft Tissue Sarcoma Program, Messina University Medical School Hospital , Messina , Italy
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Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with gastric cancer and peritoneal carcinomatosis. Eur J Surg Oncol 2018; 44:1805-1810. [PMID: 30087071 DOI: 10.1016/j.ejso.2018.06.036] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Revised: 05/23/2018] [Accepted: 06/27/2018] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Gastric Cancer (GC) with Peritoneal Carcinomatosis (PC) has long been regarded as a terminal disease. Over the past two decades, cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has changed the traditional concept of peritoneal metastases from being a systemic disease, to being considered a locoregional dissemination. PATIENTS AND METHODS A prospective study was performed at a high-volume Carcinomatosis Center to evaluate survival, morbi-mortality and prognostic factors for survival in a cohort of patients with GC and PC treated with CRS + HIPEC between June 2006 and December 2016. RESULTS Thirty-five patients were included in the study. Median follow-up was 54 months. Postoperative major complications (>grade IIIa) occurred in 25.7% of patients, including 2 deaths (mortality 5.7%). The median overall survival (OS) was 16 months and the 1-, 3- and 5-year OS rates were 70.8%, 21.3% and 21.3% %, respectively. The median OS for patients with PCI ≤6 was 19 months, in contrast to 12 months for the 19 patients with PCI >6. Three patients were included with only a positive cytology and their median OS was not reached. Perineural invasion was the only factor that had a negative influence in prognosis (HR 18.8) in multivariate analysis. CONCLUSION Although GC with PC still has a poor prognosis, survival has improved in selected patients with CRS + HIPEC and perioperative systemic chemotherapy. Patients with isolated positive cytology or peritoneal carcinomatosis with PCI less than 6 had encouraging survival rates.
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Kitayama J, Ishigami H, Yamaguchi H, Sakuma Y, Horie H, Hosoya Y, Lefor AK, Sata N. Treatment of patients with peritoneal metastases from gastric cancer. Ann Gastroenterol Surg 2018; 2:116-123. [PMID: 29863151 PMCID: PMC5881364 DOI: 10.1002/ags3.12060] [Citation(s) in RCA: 66] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Accepted: 01/14/2018] [Indexed: 12/12/2022] Open
Abstract
Despite recent advances in chemotherapy, outcomes of patients with peritoneal metastases (PM) from gastric cancer are still very poor and standard treatment has not been established. Although oral S‐1 appears to be effective for patients with PM, the effects of systemic chemotherapy are limited. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) yield fewer benefits in patients with PM from gastric cancer than in patients with PM from other malignancies. In comparison, repeated intraperitoneal chemotherapy (RIPEC) with taxanes using an implantable peritoneal access port has a pharmacokinetic advantage for the control of peritoneal lesions and in combination with systemic chemotherapy can result in surprisingly long‐term survival in patients with PM from gastric cancer. Herein, we review the results of recent clinical studies specifically targeting PM from gastric cancer and discuss future prospects for an intraperitoneal approach to the ideal treatment of patients with gastric cancer with peritoneal involvement.
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Affiliation(s)
- Joji Kitayama
- Department of Gastrointestinal Surgery Jichi Medical University Shimotsuke Japan
| | | | - Hironori Yamaguchi
- Department of Gastrointestinal Surgery Jichi Medical University Shimotsuke Japan
| | - Yasunaru Sakuma
- Department of Gastrointestinal Surgery Jichi Medical University Shimotsuke Japan
| | - Hisanaga Horie
- Department of Gastrointestinal Surgery Jichi Medical University Shimotsuke Japan
| | - Yoshinori Hosoya
- Department of Gastrointestinal Surgery Jichi Medical University Shimotsuke Japan
| | - Alan Kawarai Lefor
- Department of Gastrointestinal Surgery Jichi Medical University Shimotsuke Japan
| | - Naohiro Sata
- Department of Gastrointestinal Surgery Jichi Medical University Shimotsuke Japan
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10
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Suh BJ. A Case of Noncuratively Resected Gastric Cancer and Postoperative Chemotherapy with S-1 Monotherapy Resulting in Long-Term Survival for Over 8 Years. Case Rep Oncol 2017; 10:217-225. [PMID: 28611634 PMCID: PMC5465688 DOI: 10.1159/000460290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Accepted: 02/08/2017] [Indexed: 11/19/2022] Open
Abstract
We report the case of a noncuratively resected gastric cancer patient who was successfully treated with S-1 monotherapy, resulting in long-term survival of 96 months. A 72-year-old woman underwent noncurative resection of subtotal gastrectomy for advanced gastric cancer with conglomerated lymph node metastasis and pancreatic invasion. She received chemotherapy with S-1 monotherapy postoperatively. S-1 (100 mg/day) was administered orally after breakfast and dinner for 28 days followed by a 14-day break for a total of 52 months. Regular checkups with esophagogastroduodenoscopy, abdominopelvic computed tomography, and fluorine-18-fluorodeoxyglucose positron emission tomography revealed no evidence of cancer 96 months after the operation. The patient was effectively treated with long-term administration of S-1 after noncurative gastrectomy for advanced gastric cancer.
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Affiliation(s)
- Byoung Jo Suh
- Department of Surgery, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea
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Kano K, Aoyama T, Maezawa Y, Nakajima T, Ikeda K, Yamada T, Sato T, Oshima T, Rino Y, Masuda M, Ogata T, Cho H, Yoshikawa T. The survival and prognosticators of peritoneal cytology-positive gastric cancer patients who received upfront gastrectomy and subsequent S-1 chemotherapy. Int J Clin Oncol 2017; 22:887-896. [PMID: 28456896 DOI: 10.1007/s10147-017-1128-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2017] [Accepted: 04/25/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Upfront surgery and subsequent S-1 chemotherapy is frequently selected for peritoneal cytology-positive (CY1) gastric cancer patients without other distant metastases (CY1-only). The objective of this study was to confirm the efficacy of this strategy in clinical practice and to identify the risk factors associated with survival. METHODS Overall survival (OS) and recurrence-free survival (RFS) were examined in 36 CY1-only patients who underwent macroscopic curative resection followed by postoperative S-1 chemotherapy between January 2000 and June 2015. Univariate and multivariate analyses were performed using a Cox proportional hazards model to identify risk factors. RESULTS The median OS was 22.3 months (95% confidence interval 18.7-31.0). When the OS was compared by a log-rank test, significant differences were observed in the status of lymph node metastasis of pathological N3b (pN3b). Moreover, the univariate and multivariate analyses demonstrated that the status of pN3b was a significant independent risk factor for OS and RFS. The median OS in patients with pathological N0-N3a (pN0-N3a) was 31.0 months, while that in patients with pN3b was 18.2 months (P = 0.002). The median RFS in patients with pN0-N3a was 16.4 months, while that in patients with pN3b was 7.9 months (P = 0.007). CONCLUSIONS The present study confirmed the efficacy of postoperative S-1 chemotherapy for CY1-only gastric cancer patients who received upfront surgery. This strategy might be recommended as clinical practice for patients with CY1 disease but a more effective treatment should be established for CY1-positive patients, especially for those who are diagnosed with CY1 and pN3b disease.
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Affiliation(s)
- Kazuki Kano
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Toru Aoyama
- Department of Surgery, Yokohama City University, 3-9, Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
| | - Yukio Maezawa
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Tetsushi Nakajima
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Kosuke Ikeda
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Takanobu Yamada
- Department of Surgery, Yokohama City University, 3-9, Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Tsutomu Sato
- Department of Surgery, Yokohama City University, 3-9, Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Takashi Oshima
- Department of Surgery, Yokohama City University, 3-9, Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Yasushi Rino
- Department of Surgery, Yokohama City University, 3-9, Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Munetaka Masuda
- Department of Surgery, Yokohama City University, 3-9, Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan
| | - Takashi Ogata
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Haruhiko Cho
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Takaki Yoshikawa
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
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The Impact of the Expression Level of Intratumoral Dihydropyrimidine Dehydrogenase on Chemotherapy Sensitivity and Survival of Patients in Gastric Cancer: A Meta-Analysis. DISEASE MARKERS 2017; 2017:9202676. [PMID: 28255193 PMCID: PMC5307138 DOI: 10.1155/2017/9202676] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/15/2016] [Revised: 01/03/2017] [Accepted: 01/12/2017] [Indexed: 01/19/2023]
Abstract
The potential impact that the intratumoral expression level of dihydropyrimidine dehydrogenase (DPD) has on chemotherapy sensitivity and long-term survival for gastric cancer (GC) patients remains controversial; therefore, this study seeks to clarify this issue. Our meta-analysis was performed using Review Manager (RevMan) 5.3 software. In vitro drug sensitivity tests, correlation coefficients between sensitivity to 5-fluorouracil (5-FU), and expression levels of intratumoral DPD were used as effective indexes to analyse. Overall survival (OS) and progression-free survival (PFS) were used as endpoints for patient outcome, and hazard ratios (HRs) and 95% confidence intervals (CIs) were noted as measures of effect. There were 15 eligible studies including 1805 patients for the final analysis. The analysis revealed a statistically significant difference between the expression level of intratumoral DPD activity, DPD mRNA levels, and sensitivity to 5-FU in GC patients, with high expression levels of intratumoral DPD resulting in low sensitivity to 5-FU. However, no matter what therapeutic regimens were used, there was no significant difference for patient outcomes between high and low DPD expression groups, either in OS or in PFS. In conclusion, high levels of intratumoral DPD expression have a negative impact on sensitivity to 5-FU in GC patients, but no prognostic value for long-term survival was uncovered.
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He MM, Zhang DS, Wang F, Wang ZX, Yuan SQ, Wang ZQ, Luo HY, Ren C, Qiu MZ, Jin Y, Wang DS, Chen DL, Zeng ZL, Li YH, He YY, Hao YT, Guo P, Wang FH, Zeng YX, Xu RH. Phase II trial of S-1 plus leucovorin in patients with advanced gastric cancer and clinical prediction by S-1 pharmacogenetic pathway. Cancer Chemother Pharmacol 2016; 79:69-79. [PMID: 27913881 PMCID: PMC5225176 DOI: 10.1007/s00280-016-3209-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Accepted: 11/24/2016] [Indexed: 01/10/2023]
Abstract
Background The first one-arm phase II trial aimed to evaluate and predict efficacy and safety of S-1 plus oral leucovorin (S-1/LV) as first-line chemotherapy for patients with advanced gastric cancer (AGC), using S-1 pharmacogenetic pathway approach. Patients and methods A total of 39 patients orally took S-1 at conventional dose and LV simultaneously at a dose of 25 mg twice daily for a week, within a 2-week cycle. The primary endpoint was overall response rate (ORR), while the secondary endpoints were progression-free survival (PFS), time to failure (TTF), overall survival (OS), disease control rate (DCR), and adverse events (AEs). Peripheral blood was sampled prospectively for baseline expression of dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP), and thymidylate synthase (TS), CYP2A6 gene polymorphisms, and 5-FU pharmacokinetics. Results The ORR and DCR were 41.0 and 76.9%. The median PFS, TTF, and OS were 4.13, 3.70, and 11.40 months. Grade 3–4 AEs occurred in only 13 patients, and grade 4 AEs occurred in only 1 of them. High OPRT/TS and peritoneal metastasis (vs. liver metastasis) independently predicted responding. High OPRT/DPD independently predicted grade 3–4 AEs. High AUC0–24h of 5-FU and metastatic/recurrent sites ≤2 (vs. >3) independently predicted prolonged PFS. Low baseline plasmic DPD independently predicted prolonged OS. Conclusions Two-week, oral S-1/LV regimen demonstrated promising efficacy and safety as first-line chemotherapy for AGC. ClinicalTrials.gov identifier NCT02090153 Electronic supplementary material The online version of this article (doi:10.1007/s00280-016-3209-1) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Ming-Ming He
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, China
| | - Dong-Sheng Zhang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, China
| | - Feng Wang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, China
| | - Zi-Xian Wang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, China
| | - Shu-Qiang Yuan
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, China
| | - Zhi-Qiang Wang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, China
| | - Hui-Yan Luo
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, China
| | - Chao Ren
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, China
| | - Miao-Zhen Qiu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, China
| | - Ying Jin
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, China
| | - De-Shen Wang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, China
| | - Dong-Liang Chen
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, China
| | - Zhao-Lei Zeng
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, China
| | - Yu-Hong Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, China
| | - Yang-Yang He
- Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Yuan-Tao Hao
- Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Pi Guo
- Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Feng-Hua Wang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, China
| | - Yi-Xin Zeng
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, China.,Beijing Hospital, Beijing, China
| | - Rui-Hua Xu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, China.
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Coccolini F, Catena F, Glehen O, Yonemura Y, Sugarbaker PH, Piso P, Ceresoli M, Montori G, Ansaloni L. Effect of intraperitoneal chemotherapy and peritoneal lavage in positive peritoneal cytology in gastric cancer. Systematic review and meta-analysis. Eur J Surg Oncol 2016; 42:1261-7. [PMID: 27134147 DOI: 10.1016/j.ejso.2016.03.035] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2016] [Revised: 03/20/2016] [Accepted: 03/31/2016] [Indexed: 12/17/2022] Open
Abstract
INTRODUCTION The most common cause of tumour progression in advanced gastric cancer is peritoneal carcinosis (PC). The necessity to increase the survival in advanced diseases suggested to deliver the chemotherapy directly in the peritoneal cavity also in Cy+/PC- and to experiment the effect of massive peritoneal lavage to wash out the tumour cells. The aim of this study is to investigate the gain in term of survival and peritoneal recurrence rate of the intraperitoneal chemotherapy and/or peritoneal lavage in patients with Cy+/PC-. MATERIAL AND METHODS A systematic review with meta-analysis of trials about the effect of intraperitoneal chemotherapy (IPC) and/or peritoneal lavage (PL) on positive cytology in gastric cancer without carcinosis. RESULTS Three trials have been included (164 patients: 76 received surgery alone, 51 surgery + IPC and 37 surgery + IPC + PL). Two- and five-years survival is increased by IPC (RR = 1.62, RR = 3.10). 2 and 5 years survival is further increased by IPC + PL (RR = 2.33, RR = 6.19). Peritoneal recurrence is reduced by IPC (OR = 0.45) and by IPC + PL (OR = 0.13). CONCLUSIONS Two- and five-years overall survival in patients with free cancer cells without carcinosis is incremented by intraperitoneal chemotherapy. Peritoneal lavage further increases these survival rates and also it further decreases the peritoneal recurrence rate.
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Affiliation(s)
- F Coccolini
- General Surgery Department, Papa Giovanni XXIII Hospital, Bergamo, Italy.
| | - F Catena
- General Surgery Department, Ospedale Maggiore, Parma, Italy
| | - O Glehen
- General Surgery Department, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon and EMR 3738, Université Lyon 1, France
| | - Y Yonemura
- General Surgery Department, Kusatsu General Hospital, Yabase 1660, Japan
| | | | - P Piso
- Surgery Department, University of Regensburg, Regensburg D-93053, Germany
| | - M Ceresoli
- General Surgery Department, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - G Montori
- General Surgery Department, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - L Ansaloni
- General Surgery Department, Papa Giovanni XXIII Hospital, Bergamo, Italy
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15
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Tang R, Jiang M, Liang L, Xiong D, Dang Y, Chen G. Long Noncoding RNA MALAT-1 Can Predict Poor Prognosis: A Meta-Analysis. Med Sci Monit 2016; 22:302-9. [PMID: 26821178 PMCID: PMC4737057 DOI: 10.12659/msm.895171] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Background MALAT-1 is a highly conserved nuclear long non-coding RNA (lncRNA). The overexpression of MALAT-1 has been reported in several types of cancers. This meta-analysis was conducted to further investigate its potential role as a prognostic indicator in various cancers. Material/Methods The meta-analysis was performed by use of systematic search terms in 13 databases for qualified papers on prognosis in cancer from inception to June 30, 2015. The combined hazard ratios (HRs) with 95% confidence interval (95% CI) were computed to demonstrate the effect of MALAT-1 on prognosis of cancers. Results A total of 590 papers were initially identified, and 17 studies were finally included in this paper. Meta-analysis was accomplished with a total of 1626 patients. Combined HRs and 95% CI were calculated by fixed-effects or random-effects models. The quality assessment of included studies was performed by the Newcastle-Ottawa scale (NOS). High expression of MALAT-1 was found to be an indicator of poor prognosis in overall survival (OS) (HR=1.84, 95% CI: 1.27–2.67) and disease-free survival (DFS) (HR=2.37, 95% CI: 1.55–3.62). In subgroups, the associations between MALAT-1 and survival were also apparent, for instance, in country subgroup: China (HR=1.85, 95% CI: 1.14–2.99). Conclusions The overexpression of MALAT-1 may be a potential prognostic indicator for various human cancers.
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Affiliation(s)
- Ruixue Tang
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang, China (mainland)
| | - Mengtong Jiang
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang, China (mainland)
| | - Lu Liang
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang, China (mainland)
| | - Dandan Xiong
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang, China (mainland)
| | - Yiwu Dang
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang, China (mainland)
| | - Gang Chen
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang, China (mainland)
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16
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Seshadri RA, Glehen O. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer. World J Gastroenterol 2016; 22:1114-30. [PMID: 26811651 PMCID: PMC4716024 DOI: 10.3748/wjg.v22.i3.1114] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 09/22/2015] [Accepted: 11/30/2015] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer associated peritoneal carcinomatosis (GCPC) has a poor prognosis with a median survival of less than one year. Systemic chemotherapy including targeted agents has not been found to significantly increase the survival in GCPC. Since recurrent gastric cancer remains confined to the abdominal cavity in many patients, regional therapies like aggressive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been investigated for GCPC. HIPEC has been used for three indications in GC- as an adjuvant therapy after a curative surgery, HIPEC has been shown to improve survival and reduce peritoneal recurrences in many randomised trials in Asian countries; as a definitive treatment in established PC, HIPEC along with CRS is the only therapeutic modality that has resulted in long-term survival in select groups of patients; as a palliative treatment in advanced PC with intractable ascites, HIPEC has been shown to control ascites and reduce the need for frequent paracentesis. While the results of randomised trials of adjuvant HIPEC from western centres are awaited, the role of HIPEC in the treatment of GCPC is still evolving and needs larger studies before it is accepted as a standard of care.
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17
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Okugawa Y, Toiyama Y, Hur K, Toden S, Saigusa S, Tanaka K, Inoue Y, Mohri Y, Kusunoki M, Boland CR, Goel A. Metastasis-associated long non-coding RNA drives gastric cancer development and promotes peritoneal metastasis. Carcinogenesis 2014; 35:2731-9. [PMID: 25280565 DOI: 10.1093/carcin/bgu200] [Citation(s) in RCA: 224] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The prognosis of gastric cancer (GC) patients with peritoneal dissemination remains poor, and a better understanding of the underlying mechanisms is critical for the development of new treatments that will improve survival in these patients. This study aimed to clarify the clinical and biological role of two key metastasis-associated long non-coding RNAs (lncRNAs) in GC. We analyzed the expression levels of two lncRNAs-Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) and HOX-Antisense Intergenic RNA (HOTAIR)-by real-time reverse transcription PCR in 300 gastric tissues (150 GC and 150 adjacent normal mucosa), and in seven GC cell lines. Functional characterization for the role of HOTAIR in GC was performed by small interfering RNA (siRNA) knockdown, followed by series of in-vitro and in-vivo experiments. Expression of both lncRNAs was significantly higher in cancerous tissues than in corresponding normal mucosa, and higher expression of these lncRNAs significantly correlated with peritoneal metastasis in GC patients. In addition, elevated HOTAIR expression emerged both as an independent prognostic and risk factor for peritoneal dissemination. SiRNA knockdown of HOTAIR in GC cells significantly inhibited cell proliferation, migration and invasion, but concurrently enhanced the anoikis rate in transfected cells. In an in vivo assay, HOTAIR siRNA-transfected MKN45 cells injected into nude mice inhibited the growth of xenograft tumors and peritoneal metastasis compared with controls. Our data provide novel evidence for the biological and clinical significance of HOTAIR expression as a potential biomarker for identifying patients with peritoneal metastasis, and as a novel therapeutic target in patients with gastric neoplasia.
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Affiliation(s)
- Yoshinaga Okugawa
- Gastrointestinal Cancer Research Laboratory, Division of Gastroenterology, Department of Internal Medicine, Charles A. Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, 3500 Gaston Avenue, Suite H-250, Dallas, TX 75246, USA and
| | - Yuji Toiyama
- Gastrointestinal Cancer Research Laboratory, Division of Gastroenterology, Department of Internal Medicine, Charles A. Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, 3500 Gaston Avenue, Suite H-250, Dallas, TX 75246, USA and Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan
| | - Keun Hur
- Gastrointestinal Cancer Research Laboratory, Division of Gastroenterology, Department of Internal Medicine, Charles A. Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, 3500 Gaston Avenue, Suite H-250, Dallas, TX 75246, USA and
| | - Shusuke Toden
- Gastrointestinal Cancer Research Laboratory, Division of Gastroenterology, Department of Internal Medicine, Charles A. Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, 3500 Gaston Avenue, Suite H-250, Dallas, TX 75246, USA and
| | - Susumu Saigusa
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan
| | - Koji Tanaka
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan
| | - Yasuhiro Inoue
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan
| | - Yasuhiko Mohri
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan
| | - Masato Kusunoki
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan
| | - C Richard Boland
- Gastrointestinal Cancer Research Laboratory, Division of Gastroenterology, Department of Internal Medicine, Charles A. Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, 3500 Gaston Avenue, Suite H-250, Dallas, TX 75246, USA and
| | - Ajay Goel
- Gastrointestinal Cancer Research Laboratory, Division of Gastroenterology, Department of Internal Medicine, Charles A. Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, 3500 Gaston Avenue, Suite H-250, Dallas, TX 75246, USA and
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18
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Kikuchi H, Kamiya K, Hiramatsu Y, Miyazaki S, Yamamoto M, Ohta M, Baba S, Konno H. Laparoscopic narrow-band imaging for the diagnosis of peritoneal metastasis in gastric cancer. Ann Surg Oncol 2014; 21:3954-62. [PMID: 24859934 DOI: 10.1245/s10434-014-3781-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2013] [Indexed: 12/20/2022]
Abstract
BACKGROUND Staging laparoscopy (SL) is often used to diagnose peritoneal metastasis in patients with advanced gastric cancer, but accurate detection of metastasis can be difficult. We evaluated the usefulness of laparoscopic narrow-band imaging (NBI) versus conventional laparoscopic white-light imaging (WLI) for the diagnosis of peritoneal metastasis. METHODS We excised 37 white nodules from the parietal peritoneum of 26 patients with gastric cancer and suspected peritoneal metastasis. The WLI and NBI findings were compared with the pathological findings. All the peritoneal lesions examined were observed as white nodules on WLI. Intranodular vessels were evaluated by WLI and NBI for (1) vessel dilatation, (2) vessel tortuousness, (3) vessel heterogeneity, and (4) brown spots. RESULTS Each individual abnormal finding had a diagnostic accuracy of less than 79 % with or without NBI. Detection of any one abnormal finding had a sensitivity, specificity, and accuracy of 47.8, 85.7, and 62.2 %, respectively, on WLI and 91.3, 71.4, and 83.8 %, respectively, on NBI, for detection of peritoneal metastasis. Detection of any one abnormal finding on NBI plus clear demarcation of the nodule on WLI had a sensitivity of 91.3 %, specificity of 92.9 %, and accuracy of 91.9 % for detection of peritoneal metastasis. Pathological examination showed that a brown spot detected on NBI correlated with dilated vessels around cancer cells. Vascular endothelial growth factor was expressed in 76.2 % of peritoneal metastases. CONCLUSIONS NBI was more sensitive for the detection of dilated vessels than WLI. NBI could be a useful tool for the diagnosis of peritoneal metastasis during SL.
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Affiliation(s)
- Hirotoshi Kikuchi
- Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan,
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19
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Sato D, Kogashiwa Y, Tsukahara K, Yamauchi K, Kohno N. Phase I study of nedaplatin prior to S-1 in patients with locally advanced head and neck squamous cell carcinoma. Chemotherapy 2014; 59:314-8. [PMID: 24480865 DOI: 10.1159/000357469] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2013] [Accepted: 11/20/2013] [Indexed: 11/19/2022]
Abstract
BACKGROUND We previously reported on the regimen of S-1 plus nedaplatin (NDP), with S-1 was administered orally for 14 days and NDP intravenously on day 8. The maximum tolerated dose (MTD) of NDP was determined to be 90 mg/m². The main toxicities were neutropenia and thrombocytopenia. This result was tolerated, but we believe there is a more effective and tolerable regimen. Thus, we investigated the S-1 regimen administered orally for 14 days, and NDP intravenously on day 1 in patients with locally advanced head and neck squamous cell carcinoma. PATIENTS AND METHODS Oral administration of S-1 (days 1-14) and intravenous NDP (day 1) were tested for patients with advance head and neck cancer in a phase I setting. The dose of S-1 was fixed and the dose of NDP was escalated from 70 mg/m², with an increase of 10 mg/m² per step, to find the MTD. RESULTS A total of 15 patients were registered. The MTD of NDP was determined to be 100 mg/m². The main toxicities were neutropenia and thrombocytopenia. The response rate (RR) was 57.1%. CONCLUSIONS The recommended dose of NDP for a phase II study was determined to be 100 mg/m². We concluded that our regimen was well tolerated and that the RR was acceptable.
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Affiliation(s)
- Dai Sato
- Department of Otolaryngology, Head and Neck Surgery, Kyorin University School of Medicine, Tokyo, Japan
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Shirao K, Boku N, Yamada Y, Yamaguchi K, Doi T, Goto M, Nasu J, Denda T, Hamamoto Y, Takashima A, Fukuda H, Ohtsu A. Randomized Phase III study of 5-fluorouracil continuous infusion vs. sequential methotrexate and 5-fluorouracil therapy in far advanced gastric cancer with peritoneal metastasis (JCOG0106). Jpn J Clin Oncol 2013; 43:972-80. [PMID: 24014884 DOI: 10.1093/jjco/hyt114] [Citation(s) in RCA: 89] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
OBJECTIVE Owing to the risks of serious and sustained toxicity, anticancer drugs such as cisplatin and irinotecan cannot be readily administered to patients with gastric cancer and severe peritoneal metastasis. Therefore, a standard chemotherapy regimen has yet to be established for these types of patients. This randomized study investigated the utility of sequential methotrexate and 5-fluorouracil therapy vs. 5-fluorouracil continuous infusion for gastric cancer with peritoneal metastasis. METHODS Eligible patients had radiologically confirmed peritoneal metastasis with intestinal stenosis, peritoneal tumor or ascites. Treatment with 5-fluorouracil continuous infusion (800 mg/m(2)/day, ci, d1-5, q4w) or methotrexate and 5-fluorouracil therapy (methotrexate, 100 mg/m(2), bolus infusion, followed 3 h later by 5-fluorouracil, 600 mg/m(2), bolus infusion, with leucovorin rescue, q1w) was continued until disease progression or unacceptable toxicity. The projected sample size was 236, providing 80% power to detect a 40% increase in median overall survival in methotrexate and 5-fluorouracil therapy with a one-sided α of 0.05. RESULTS All 237 randomized patients were included in the primary analysis. The methotrexate and 5-fluorouracil therapy arm was not superior to the 5-fluorouracil continuous infusion arm (median survival time, 9.4 months in the 5-fluorouracil continuous infusion arm, 10.6 months in the methotrexate and 5-fluorouracil therapy arm; hazard ratio, 0.94; 95% confidence interval, 0.72-1.22; one-sided P = 0.31). Frequencies of Grade 3 or higher neutropenia, Grade 3 or higher anorexia and treatment-related deaths were 0.9, 27.4 and 1.7%, respectively, in the 5-fluorouracil continuous infusion arm, and 31.9, 33.6 and 0.9%, respectively, in the methotrexate and 5-fluorouracil therapy arm. CONCLUSIONS Methotrexate and 5-fluorouracil therapy is not suitable for use as standard therapy for advanced gastric cancer with peritoneal metastasis.
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Affiliation(s)
- Kuniaki Shirao
- *Department of Medical Oncology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu City, Oita 879-5593, Japan.
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Hu HB, Kuang L, Zeng XM, Li B, Liu EY, Zhong MZ. Predictive value of thymidylate synthase expression in gastric cancer: a systematic review with meta-analysis. Asian Pac J Cancer Prev 2012; 13:261-7. [PMID: 22502681 DOI: 10.7314/apjcp.2012.13.1.261] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
PURPOSE The relationship between thymidylate synthase (TS) expression and outcomes in gastric cancer (GC) patients remains controversial, although most studies reported poor survival and reduced response to fluoropyrimidine were related to high TS in tumors. We carried out a systematic review of the literature with meta-analysis to estimate the predictive value of TS expression from published studies. METHODS We identified 24 studies analysing the outcome data in gastric cancer stratified by TS expression. Effect measures of outcome were hazard ratios (HRs) for overall survival (OS) and event-free survival (EFS), or the odds ratio (OR) for overall response rate (ORR). HRs and ORs from these eligible studies were pooled using random-effects meta- analysis. RESULTS Fifteen studies investigated outcomes in a total of 844 patients with advanced GC, and nine studies investigated outcomes in a total of 1,235 patients with localized GC undergoing adjuvant therapy. Meta- analysis of estimates showed high TS expression was significantly associated with poor OS in the advanced setting (HR: 1.43, 95%CI: 1.08 - 1.90), and poor EFS in the adjuvant setting (HR: 1.53, 95%CI: 1.01 - 2.32). Subgroup analysis demonstrated TS expression to have even greater value in predicting OS, EFS and ORR in advanced GC patients treated with fluoropyrimidine monotherapy (HR for OS: 2.32, 95%CI: 1.53 - 3.50; HR for EFS: 1.76, 95%CI: 1.19 - 2.60; OR for ORR: 0.32, 95%CI: 0.11 - 0.95). CONCLUSION High levels of TS expression were associated with a poorer OS for advanced GC patients compared with low levels. In the adjuvant setting, high TS expression was also associated with a worse EFS. Additional studies with consistent methodology are needed to define the precise predictive value of TS.
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Affiliation(s)
- Hua-Bin Hu
- Department of Oncology, Xiangya Hospital of Central South University, Changsha, China
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A proposal of a practical and optimal prophylactic strategy for peritoneal recurrence. JOURNAL OF ONCOLOGY 2012; 2012:340380. [PMID: 22481921 PMCID: PMC3306955 DOI: 10.1155/2012/340380] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/14/2011] [Accepted: 11/04/2011] [Indexed: 12/27/2022]
Abstract
Peritoneal metastasis, which often arises in patients with advanced gastric cancer, is well known as a miserable and ill-fated disease. Once peritoneal metastasis is formed, it is extremely difficult to defeat. We advocated EIPL (extensive intraoperative peritoneal lavage) as a useful and practical adjuvant surgical technique for those gastric cancer patients who are likely to suffer from peritoneal recurrence. In this paper, we review the effect of EIPL therapy on prevention of peritoneal recurrence on patients with peritoneal free cancer cells without overt peritoneal metastasis (CY+/P−) through the prospective randomized study, and we verified its potential as an optimal and standard prophylactic therapeutic strategy for peritoneal recurrence.
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Fujiwara Y, Takiguchi S, Nakajima K, Miyata H, Yamasaki M, Kurokawa Y, Mori M, Doki Y. Intraperitoneal docetaxel combined with S-1 for advanced gastric cancer with peritoneal dissemination. J Surg Oncol 2011; 105:38-42. [DOI: 10.1002/jso.22057] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2011] [Accepted: 07/18/2011] [Indexed: 01/19/2023]
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Izuishi K, Haba R, Kushida Y, Kadota K, Takebayashi R, Sano T, Usuki H, Hossain MA, Mori H, Masaki T, Suzuki Y. S-1 and the treatment of gastric cancer with peritoneal dissemination. Exp Ther Med 2011; 2:985-990. [PMID: 22977609 DOI: 10.3892/etm.2011.290] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2011] [Accepted: 06/14/2011] [Indexed: 12/18/2022] Open
Abstract
Peritoneal dissemination is the most common metastatic pattern of gastric cancer. We frequently face the necessity for gastrectomy in the event of gastric stenosis or gastric bleeding. However, the indication for palliative gastrectomy and the effectiveness of palliative chemotherapy are not clear. We retrospectively evaluated the prognostic factors after palliative gastrectomy in 121 gastric cancer patients with peritoneal dissemination. The expression of orotate phosphoribosyl transferase (OPRT) was examined immunohistochemically. The median survival time of all patients after palliative gastrectomy was 8.8 months. In the multivariate analyses, we adjusted the data of 82 patients without liver metastases for the background of 5-fluouracil (5-FU)-based chemotherapy regimen. The analysis revealed that the degree of peritoneal dissemination (multiple vs. a few metastases or cytology-positive; P= 0.01) and chemotherapy (S-1 vs. other 5-FU; P=0.01) were independent predictors of survival. Particularly, S-1 treatment was associated with a more favorable prognosis of the patients with high levels of OPRT expression compared to that of the patients with low expression. Patients with peritoneal dissemination are considered as terminal and inoperable. However, S-1 treatment may improve the survival after palliative gastrectomy in patients selected according to the degree of peritoneal dissemination and high OPRT expression.
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Okabe H, Ueda S, Obama K, Hosogi H, Sakai Y. Induction chemotherapy with S-1 plus cisplatin followed by surgery for treatment of gastric cancer with peritoneal dissemination. Ann Surg Oncol 2009; 16:3227-36. [PMID: 19777180 DOI: 10.1245/s10434-009-0706-z] [Citation(s) in RCA: 96] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2009] [Accepted: 07/22/2009] [Indexed: 12/28/2022]
Abstract
BACKGROUND The prognosis of gastric cancer patients with peritoneal dissemination is poor. Recently, chemotherapy with S-1 plus cisplatin has been shown to be highly effective for advanced gastric cancer. METHODS In 41 patients diagnosed with either macro- or microscopic peritoneal dissemination by staging laparoscopy, and receiving induction chemotherapy with S-1 plus cisplatin between August 2002 and February 2008, response of peritoneal lesions to the induction chemotherapy and the outcome of the following surgery were retrospectively evaluated. RESULTS Of 41 patients identified, 38 patients (93%) completed two cycles. Among grade 3 or 4 adverse effects, neutropenia was most frequently observed (9 patients; 22%). After chemotherapy, 32 patients (78%) underwent surgery and R0 resection was accomplished in 22 patients. Although objective response by Response Evaluation Criteria in Solid Tumors (RECIST) was recorded in only four patients (10%), peritoneal dissemination disappeared in 19 patients (46%). Patients with limited peritoneal metastasis, negative peritoneal cytology, or response of the primary lesion were more likely to exhibit disappearance of the peritoneal dissemination. Median survival time of all patients was 20.4 months. Patients with R0 resection had median survival time of 43.2 months, which was significantly longer than for those with noncurative resection (12.6 months) or without surgery (10.3 months). CONCLUSIONS Limited peritoneal dissemination of gastric origin is highly sensitive to induction chemotherapy with S-1 plus cisplatin. Resection after disappearance of peritoneal metastasis could cure some patients.
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Affiliation(s)
- Hiroshi Okabe
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
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Kuramoto M, Shimada S, Ikeshima S, Matsuo A, Yagi Y, Matsuda M, Yonemura Y, Baba H. Extensive intraoperative peritoneal lavage as a standard prophylactic strategy for peritoneal recurrence in patients with gastric carcinoma. Ann Surg 2009; 250:242-6. [PMID: 19638909 DOI: 10.1097/sla.0b013e3181b0c80e] [Citation(s) in RCA: 184] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE This prospective randomized multicenter study aims to evaluate the efficacy of extensive intraoperative peritoneal lavage followed by intraperitoneal chemotherapy (EIPL-IPC) on the overall 5-year survival of advanced gastric cancer patients with intraperitoneal free cancer cells without overt peritoneal metastasis (CY+/P-). The study also aims to determine the merit and reliability of EIPL-IPC therapy as a prophylactic strategy for peritoneal metastasis. SUMMARY BACKGROUND DATA Although the prognosis of advanced gastric cancer patients with CY+/P- is extremely poor, a suitable standard regimen for treating such patients has not yet been established. METHODS A total of 88 patients with CY+/P- from 1522 patients with advanced gastric cancer at multicenters were enrolled in this study and were randomly allocated to 3 groups: surgery alone group, surgery plus intraperitoneal chemotherapy (IPC) group, and surgery plus EIPL and IPC (EIPL-IPC) group. Prognostic significance of EIPL-IPC therapy was evaluated by Kaplan-Meier curves, and its value as an independent prognostic factor was assessed by univariate and multivariate analyses. RESULTS The overall 5-year survival rate of the patients with EIPL-IPC was 43.8%, and this data were significantly better than that of the IPC group (4.6%, P < 0.0001) and the surgery alone group (0%, P < 0.0001). Among various recurrent patterns, the EIPL-IPC group had a significantly lower incidence of peritoneal recurrence than both of the other groups (P < 0.0001). Univariate and multivariate analyses revealed that EIPL was the most significant impact factor. CONCLUSIONS The present study clearly revealed that EIPL-IPC therapy significantly improved the 5-year survival span of advanced gastric cancer patients with CY+/P-. Thus, EIPL-IPC therapy is strongly recommended as a standard prophylactic strategy for peritoneal dissemination.
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Affiliation(s)
- Masafumi Kuramoto
- Department of Surgery, Yatsushiro Social Insurance General Hospital, Kumamoto, Japan
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Sadahiro S, Suzuki T, Maeda Y, Ishikawa K, Tanaka Y, Yasuda S, Kamijo A, Makuuchi H, Murayama C. Dihydropyrimidine dehydrogenase activity during long-term adjuvant treatment with oral uracil and tegafur for colorectal cancer. Chemotherapy 2007; 53:442-5. [PMID: 17952005 DOI: 10.1159/000110016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2006] [Accepted: 12/07/2006] [Indexed: 11/19/2022]
Abstract
BACKGROUND Dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme for the degradation of 5-fluorouracil. The effect of long-term treatment with oral fluoropyrimidines on DPD activity has not been investigated. This study was conducted to examine changes in DPD activity in peripheral mononuclear cells (PMNC) during long-term treatment with oral uracil and tegafur (UFT) for colorectal cancer. METHODS UFT was administered for 5 consecutive days and not administered the next 2 days for 6 months after surgery. PMNC-DPD activity was measured before and 1, 2, 4 and 6 months after starting UFT administration. RESULTS In 70 eligible patients, there were no significant variations of PMNC-DPD activity during postoperative administration of UFT for 6 months. Grade 2 or higher adverse events were observed in significantly more patients with low DPD than with high DPD activity (p = 0.018). CONCLUSION There were no significant variations of PMNC-DPD activity during the postoperative administration of UFT for 6 months. Low PMNC-DPD activity before UFT treatment was considered to be a predicting factor for toxicity.
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Affiliation(s)
- Sotaro Sadahiro
- Department of Surgery, Tokai University School of Medicine, Isehara, Japan.
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Maruta F, Ishizone S, Hiraguri M, Fujimori Y, Shimizu F, Kumeda S, Miyagawa S. A clinical study of docetaxel with or without 5'DFUR as a second-line chemotherapy for advanced gastric cancer. Med Oncol 2007; 24:71-5. [PMID: 17673814 DOI: 10.1007/bf02685905] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2006] [Revised: 11/30/1999] [Accepted: 08/30/2006] [Indexed: 11/25/2022]
Abstract
We conducted a clinical pilot study to evaluate the efficacy and safety of the combination of docetaxel and 5'DFUR as a second-line chemotherapy for gastric cancer. Twenty-four patients were divided into two groups by simple randomization: group A (60 mg/m2 of docetaxel, every 3 wk) and group B (regimen A + 600 mg/body of 5'DFUR). The response rate was 17% and 42% in group A and B, respectively (p < 0.05). The MST from the start of the first-line was 17 mo in group B. The major adverse event was leukopenia in both groups.
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Affiliation(s)
- Fukuto Maruta
- Department of Surgery, Shinshu University School of Medicine, Japan.
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