|
1
|
Du XY, Xia RJ, Shen LW, Ma JG, Yao WQ, Xu W, Lin ZP, Ma LB, Niu GQ, Fan RF, Xu SM, Yan L. Quadruple therapy with immunotherapy and chemotherapy as first-line conversion treatment for unresectable advanced gastric adenocarcinoma: A case report. World J Gastrointest Oncol 2025; 17:102258. [DOI: 10.4251/wjgo.v17.i4.102258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 01/20/2025] [Accepted: 02/24/2025] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND The treatment of gastric cancer remains highly challenging, particularly in cases of unresectable locally advanced or metastatic disease. Although chemotherapy and immunotherapy have shown some efficacy in such patients, significant limitations persist in extending survival and enhancing safety. To address these challenges, we designed an innovative first-line quadruple conversion therapy regimen that integrates a programmed cell death protein 1 (PD-1) inhibitor with chemotherapy, and we successfully implemented this therapy regimen in the treatment of a patient with unresectable locally advanced gastric adenocarcinoma.
CASE SUMMARY We report the case of a 55-year-old male who was diagnosed with unresectable locally advanced gastric adenocarcinoma and presented with intermittent epigastric pain and multiple lymph node metastases in the abdominal cavity, with the metastasis being notably large in size. The tumor tissue was negative for human epidermal growth factor receptor 2 by immunohistochemistry. Considering the patient's status, the multidisciplinary team decided to administer sintilimab in combination with albumin-bound paclitaxel (nab-paclitaxel), S-1, and oxaliplatin as a quadruple drug conversion therapy. After 4 cycles of conversion therapy, the patient's epigastric pain was significantly alleviated, his stool color normalized, the volume of the primary tumor and lymph node metastases was markedly reduced, and the tumor marker levels decreased to within the normal range. The patient subsequently underwent laparoscopic total gastrectomy with abdominal lymph node dissection, and postoperative pathological biopsy revealed a pathological complete response and R0 resection, after which the patient recovered to an excellent physical status.
CONCLUSION To the best of our knowledge, this is the first reported case of unresectable locally advanced gastric adenocarcinoma successfully treated with quadruple therapy with a PD-1 inhibitor and chemotherapy as a first-line conversion regimen. This first-line conversion therapy with the quadruple regimen may be effective and safe for unresectable locally advanced gastric adenocarcinoma.
Collapse
Affiliation(s)
- Xiao-Yu Du
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
- Department of Medicine, Northwest Minzu University, Lanzhou 730050, Gansu Province, China
| | - Ren-Jie Xia
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
- Department of Medicine, Northwest Minzu University, Lanzhou 730050, Gansu Province, China
| | - Li-Wen Shen
- Department of Medical Support Center, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Jian-Guo Ma
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
- First School of Clinical Medicine, Gansu University of Chinese Medicine, Lanzhou 730030, Gansu Province, China
| | - Wei-Qing Yao
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
- Department of Medicine, Northwest Minzu University, Lanzhou 730050, Gansu Province, China
| | - Wei Xu
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Zhi-Peng Lin
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Liang-Bin Ma
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Guo-Qiang Niu
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Rui-Fang Fan
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Shu-Mei Xu
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Long Yan
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| |
Collapse
|
|
2
|
Min L, Liu Z, Zhou B, Zhou P, Luo R, Ding Y, Cui Y, Shi Z, Gu Y, Sun Y, Tang Z, Wang X. Transarterial Infusion Chemotherapy and Embolization for Patients With Unresectable Advanced Cancer of Stomach or Gastroesophageal Junction: A Retrospective Study. Cancer Med 2024; 13:e70396. [PMID: 39499047 PMCID: PMC11536461 DOI: 10.1002/cam4.70396] [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: 10/28/2023] [Revised: 06/08/2024] [Accepted: 10/21/2024] [Indexed: 11/07/2024] Open
Abstract
PURPOSE The feasibility of transarterial infusion chemotherapy and embolization (TAICE) in the treatment of advanced gastric cancer remains unclear. This study explored the value of TAICE in patients with unresectable locally advanced or metastatic cancer of stomach or gastroesophageal junction (GEJ). METHODS Patients with unresectable gastric cancer who received TAICE for tumor hemorrhage cessation were enrolled in this retrospective study. TAICE was performed using the Seldinger method. The tumor feeding artery was selected for infusion chemotherapy and then was embolized by microspheres or gelatin sponge. Patients involved in this study received one to four cycles TAICE with one to three drugs in the regimen. The possibility of surgery was evaluated after TAICE. Objective response rate (ORR), disease control rate (DCR), R0 resection rate, pathological complete remission (pCR) rate, major pathological remission (MPR) rate, progression-free survival (PFS), overall survival (OS), and safety were analyzed. RESULTS Between January 2015 and December 2020, a total of 27 patients received a median of 2 (range, 1-4) cycles of TAICE. ORR and DCR were 33.3% and 74.0%, respectively. Eighteen patients received surgery, and 15 of them underwent gastrectomy and D2 lymph node dissection, with an R0 resection rate of 83.3% (15/18). Four (26.7%, 4/15) patients achieved MPR, but none achieved pCR. The median PFS was 19.8 months (95%CI, 12.1-40.0), and the median OS was 36.1 months (95%CI, 21.0-not reached). Patients with gastrectomy had significantly longer PFS (40.0 vs. 9.5 months, p < 0.0001) and OS (not reached vs. 16.6 months, p < 0.0001) than those without gastrectomy. All the TAICE-related adverse events were manageable, with the most common being fatigue (100%), nausea (63.0%), and vomiting (55.6%). No severe surgical complications occurred. CONCLUSION TAICE was well-tolerated and could be a potential therapy to provide opportunity of surgery for patients with unresectable advanced gastric or GEJ cancer.
Collapse
Affiliation(s)
- Lingqiang Min
- Department of Emergency SurgeryZhongshan Hospital, Fudan UniversityShanghaiChina
| | - Zheng Liu
- Shanghai Medical CollegeFudan UniversityShanghaiChina
- Department of Gastrointestinal SurgeryZhongshan Hospital, Fudan UniversityShanghaiChina
| | - Bo Zhou
- Department of Interventional RadiologyZhongshan Hospital, Fudan UniversityShanghaiChina
| | - Peng Zhou
- Department of Gastrointestinal SurgeryZhongshan Hospital, Fudan UniversityShanghaiChina
| | - Rongkui Luo
- Department of PathologyZhongshan Hospital, Fudan UniversityShanghaiChina
| | - Yuqin Ding
- Department of RadiologyZhongshan Hospital, Fudan UniversityShanghaiChina
| | - Yuehong Cui
- Department of Medical OncologyZhongshan Hospital, Fudan UniversityShanghaiChina
| | - Zhongyi Shi
- Department of Gastrointestinal SurgeryZhongshan Hospital, Fudan UniversityShanghaiChina
| | - Yuan Gu
- Department of Gastrointestinal SurgeryZhongshan Hospital, Fudan UniversityShanghaiChina
| | - Yihong Sun
- Department of General SurgeryZhongshan Hospital, Fudan UniversityShanghaiChina
- Gastric Cancer CenterZhongshan Hospital, Fudan UniversityShanghaiChina
| | - Zhaoqing Tang
- Department of Gastrointestinal SurgeryZhongshan Hospital, Fudan UniversityShanghaiChina
- Gastric Cancer CenterZhongshan Hospital, Fudan UniversityShanghaiChina
| | - Xuefei Wang
- Department of Gastrointestinal SurgeryZhongshan Hospital, Fudan UniversityShanghaiChina
- Gastric Cancer CenterZhongshan Hospital, Fudan UniversityShanghaiChina
| |
Collapse
|
|
3
|
Han S, Han S, Qian J, Guo M, Fan J. Analysis of the therapeutic effect and influencing factors on unresectable gastric cancer treated with conversion therapy. Front Oncol 2024; 14:1435398. [PMID: 39540147 PMCID: PMC11557377 DOI: 10.3389/fonc.2024.1435398] [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: 05/20/2024] [Accepted: 10/07/2024] [Indexed: 11/16/2024] Open
Abstract
Background Gastric cancer (GC) is one of the leading causes of cancer-related death in China, and with the extensive development of conversion therapy, the treatment of advanced unresectable gastric cancer (AUGC) patients has ushered in a new dawn. This study aimed to analyze the efficacy of conversion therapy in AUGC patients and explored the relevant factors affecting the efficacy. Method We collected information from GC patients who received conversion therapy from this center and designed a retrospective study. Results We collected relevant clinical data from 160 patients with AUGC. A total of 120 patients who underwent routine R0 resection were identified as conversion cases. A total of 25 patients (15.6%) achieved pCR, 92 patients (57.5%) achieved objective response rate (ORR), 140 patients (87.5%) achieved disease control rate (DCR), and 20 cases (12.5%) observed tumor progression. There were 86 patients who achieved pathological downgrading, with a total downgrading rate of 53.8%. Among the 160 patients, 37 patients (23.1%) had postoperative complications of varying degrees. A total of 72 patients (45.0%) had tumor recurrence/progression at the end of follow-up. The last chemotherapy and surgery (CST) (OR = 1.046, 95% CI 1.013-1.081, p = 0.006), tumor invasion (OR = 32.096, 95% CI 5.091-202.349, p < 0.001), and distant metastasis (OR = 7.050, 95% CI 1.888-26.323, p = 0.004) were independent factors influencing the efficacy of conversion therapy. Conclusion Conversion therapy may have a good therapeutic efficacy for AUGC, and some clinical factors affect the efficacy response.
Collapse
Affiliation(s)
- Saiyi Han
- The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, China
| | - Shaoliang Han
- Department of The Gastrointestinal Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Jun Qian
- The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, China
| | - Mengfu Guo
- The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, China
| | - Jianping Fan
- The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, China
| |
Collapse
|
|
4
|
Tamura T, Kanemasa Y, Nakamura S, Okuya T, Yagi Y, Matsuda S, Murata M, Endo K, Hara K, Okinaga H, Horiguchi SI, Seyama Y, Cho H, Shimoyama T. Management of HER2-positive and microsatellite instability-high advanced gastric cancer: a case report. Int Cancer Conf J 2024; 13:342-347. [PMID: 39398918 PMCID: PMC11464906 DOI: 10.1007/s13691-024-00707-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 07/27/2024] [Indexed: 10/15/2024] Open
Abstract
Chemotherapy for advanced gastric cancer has progressed significantly in the past few decades. Biomarker-specific drugs, including anti-human epidermal growth factor receptor 2 (HER2) drugs for HER2-positive patients and immune checkpoint inhibitors for those with microsatellite instability-high (MSI-H), have become common. However, patients who are positive for HER2 and have MSI-H are extremely rare, and there are no established treatments for these patients. We present the case of a 75-year-old, male patient with gastric cancer with lymph node metastases and liver infiltration. Biomarker analysis revealed HER2 3 + , loss of MLH1, and MSI-H. After three cycles of S-1, oxaliplatin, and trastuzumab, the primary tumor and metastases shrank markedly. He subsequently underwent gastrectomy and hepatectomy as conversion surgery, achieving a pathologically complete response. He has been recurrence-free for seven months postoperatively. The present case demonstrated the efficacy of trastuzumab-containing chemotherapy followed by conversion surgery in a patient with HER2-positive, MSI-H, advanced gastric cancer.
Collapse
Affiliation(s)
- Taichi Tamura
- Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677 Japan
| | - Yusuke Kanemasa
- Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677 Japan
| | - Shohei Nakamura
- Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677 Japan
| | - Toshihiro Okuya
- Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677 Japan
| | - Yu Yagi
- Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677 Japan
| | - Shinichiro Matsuda
- Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677 Japan
| | - Mitsutaka Murata
- Department of Gastric Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Kazuya Endo
- Department of Gastric Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Kentaro Hara
- Department of Gastric Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Hiroko Okinaga
- Department of Hepato-Biliary-Pancreatic Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Shin-ichiro Horiguchi
- Department of Pathology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Yasuji Seyama
- Department of Hepato-Biliary-Pancreatic Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Haruhiko Cho
- Department of Gastric Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Tatsu Shimoyama
- Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677 Japan
| |
Collapse
|
|
5
|
Shinomiya R, Sato Y, Yoshimoto T, Kawaguchi T, Hirao A, Okamoto K, Kawano Y, Sogabe M, Miyamoto H, Takayama T. A case of treatment-resistant advanced gastric cancer with FGFR2 gene alteration successfully treated with pemigatinib. Int Cancer Conf J 2024; 13:240-244. [PMID: 38962030 PMCID: PMC11217231 DOI: 10.1007/s13691-024-00669-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Accepted: 02/17/2024] [Indexed: 07/05/2024] Open
Abstract
Comprehensive genome profiling (CGP) is expected to widen the scope of cancer drug options by identifying the genes involved in carcinogenesis. However, a few patients can access recommended treatments following CGP. Herein, we report a case in which pemigatinib, a selective fibroblast growth factor receptor (FGFR) inhibitor, was used as last-line therapy to treat a patient with advanced gastric cancer exhibiting FGFR2 genomic alterations, as determined by CGP testing. The patient (male, 52 years old) was diagnosed with advanced gastric cancer (cStage IV, cT4aN3M1 [LYM], por, HER2 0, microsatellite stable) and received docetaxel + cisplatin + S-1 (7 cycles), irinotecan + ramucirumab (11 cycles), and nivolumab (3 cycles), but experienced progressive disease (PD). Subsequently, FoundationOne Liquid CDx testing was conducted, revealing FGFR2 rearrangement and amplification; however, no clinical trials on genotype-matched therapies for FGFR2 alterations were available. After three cycles of TAS-102, the patient experienced PD and provided consent for the off-label use of pemigatinib. The Cancer Genomics Medical Committee of our hospital approved the self-funded treatment. The patient had markedly decreased CEA and CA19-9 levels after treatment initiation, but experienced PD after five courses. Over the treatment course, grade 1 hyperphosphatemia and onychomadesis were observed. To the best of our knowledge, this is the first reported case of pemigatinib therapy employed in a patient with advanced gastric cancer exhibiting FGFR2 gene alterations. This case could serve as a notable example of tumor-agnostic therapy to broaden treatment options for gastric cancer patients with rare genetic alterations.
Collapse
Affiliation(s)
- Ryo Shinomiya
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, 3-18-15, Kuramotocho, Tokushima, 770-8503 Japan
| | - Yasushi Sato
- Department of Community Medicine for Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, 3-18-15, Kuramoto-cho, Tokushima, 770-8503 Japan
| | - Takanori Yoshimoto
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, 3-18-15, Kuramotocho, Tokushima, 770-8503 Japan
| | - Tomoyuki Kawaguchi
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, 3-18-15, Kuramotocho, Tokushima, 770-8503 Japan
| | - Akihiro Hirao
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, 3-18-15, Kuramotocho, Tokushima, 770-8503 Japan
| | - Koichi Okamoto
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, 3-18-15, Kuramotocho, Tokushima, 770-8503 Japan
| | - Yutaka Kawano
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, 3-18-15, Kuramotocho, Tokushima, 770-8503 Japan
| | - Masahiro Sogabe
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, 3-18-15, Kuramotocho, Tokushima, 770-8503 Japan
| | - Hiroshi Miyamoto
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, 3-18-15, Kuramotocho, Tokushima, 770-8503 Japan
| | - Tetsuji Takayama
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, 3-18-15, Kuramotocho, Tokushima, 770-8503 Japan
| |
Collapse
|
|
6
|
Yu P, Ding G, Huang X, Wang C, Fang J, Huang L, Ye Z, Xu Q, Wu X, Yan J, Ou Q, Du Y, Cheng X. Genomic and immune microenvironment features influencing chemoimmunotherapy response in gastric cancer with peritoneal metastasis: a retrospective cohort study. Int J Surg 2024; 110:3504-3517. [PMID: 38502852 PMCID: PMC11175815 DOI: 10.1097/js9.0000000000001281] [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: 11/14/2023] [Accepted: 02/22/2024] [Indexed: 03/21/2024]
Abstract
BACKGROUND Patients with peritoneal metastasis (PM) from gastric cancer (GC) exhibit poor prognosis. Chemoimmunotherapy offers promising clinical benefits; however, its efficacy and predictive biomarkers in a conversion therapy setting remain unclear. The authors aimed to retrospectively evaluate chemoimmunotherapy efficacy in a conversion therapy setting for GC patients with PM and establish a prediction model for assessing clinical benefits. MATERIALS AND METHODS A retrospective evaluation of clinical outcomes encompassed 55 GC patients with PM who underwent chemoimmunotherapy in a conversion therapy setting. Baseline PM specimens were collected for genomic and transcriptomic profiling. Clinicopathological factors, gene signatures, and tumor immune microenvironment were evaluated to identify predictive markers and develop a prediction model. RESULTS Chemoimmunotherapy achieved a 41.8% objective response rate and 72.4% R0 resection rate in GC patients with PM. Patients with conversion surgery showed better overall survival (OS) than those without the surgery (median OS: not reached vs 7.82 m, P <0.0001). Responders to chemoimmunotherapy showed higher ERBB2 and ERBB3 mutation frequencies, CTLA4 and HLA-DQB1 expression, and CD8+ T cell infiltration, but lower CDH1 mutation and naïve CD4+ T cell infiltration, compared to nonresponders. A prediction model was established integrating CDH1 and ERBB3 mutations, HLA-DQB1 expression, and naïve CD4+ T cell infiltration (AUC=0.918), which were further tested using an independent external cohort (AUC=0.785). CONCLUSION This exploratory study comprehensively evaluated clinicopathological, genomic, and immune features and developed a novel prediction model, providing a rational basis for the selection of GC patients with PM for chemoimmunotherapy-involved conversion therapy.
Collapse
Affiliation(s)
- Pengfei Yu
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences
| | - Guangyu Ding
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences
| | - Xingmao Huang
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences
| | - Chenxuan Wang
- Medical department, Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, People’s Republic of China
| | - Jingquan Fang
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences
| | - Ling Huang
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences
| | - Zeyao Ye
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences
| | - Qi Xu
- Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang
| | - Xiaoying Wu
- Medical department, Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, People’s Republic of China
| | - Junrong Yan
- Medical department, Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, People’s Republic of China
| | - Qiuxiang Ou
- Medical department, Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, People’s Republic of China
| | - Yian Du
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences
| | - Xiangdong Cheng
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences
| |
Collapse
|
|
7
|
Takeno A, Motoori M, Kishi K, Omori T, Hirao M, Masuzawa T, Fujitani K, Yamamato K, Kurokawa Y, Doki Y. Prognostic factors of conversion surgery for stage IV gastric cancer: A multi-institutional retrospective analysis. Ann Gastroenterol Surg 2024; 8:431-442. [PMID: 38707233 PMCID: PMC11066490 DOI: 10.1002/ags3.12778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 01/06/2024] [Accepted: 01/13/2024] [Indexed: 05/07/2024] Open
Abstract
Background Conversion surgery (CS) is a highly anticipated strategy for stage IV advanced gastric cancer (AGC) with a good response to chemotherapy. However, prognostic factors limiting R0 resection remain unclear. In this multi-institutional study, we investigated the clinical outcomes of CS for stage IV AGC and the prognostic factors of CS-limiting R0 resection and analyzed them according to metastatic patterns. Methods Clinical data on 210 patients who underwent CS for stage IV AGC at six institutions between 2007 and 2017 were retrospectively retrieved. The patient background, preoperative treatment, operative outcomes, and survival times were recorded. Prognostic factors for overall and recurrence-free survival were investigated using univariate and multivariate analyses for patients who underwent R0 resection. Results R0 resection was achieved in 146 (70%) patients. The median survival time was 32 months, and the 3-year survival rate was 45%. Patients who achieved R0 resection had significantly longer survival than those with R1/2 resection (median survival time: 41.5 months vs. 20.7 months). Multivariate analysis identified pathological N positivity for overall and relapse-free survival and pathological T4 for relapse-free survival as significant independent poor prognostic factors of R0 resected patients. There was no significant difference in survival among the peritoneum, liver, and lymph node groups regarding the initial metastatic sites. Conclusions CS with R0 resection for patients with stage IV AGC can lead to longer survival. Patients with pathological T4 and pathological N positivity were eligible for intensive adjuvant therapy after CS with R0 resection.
Collapse
Affiliation(s)
- Atsushi Takeno
- Department of Surgery, National Hospital OrganizationOsaka National HospitalOsakaJapan
| | | | - Kentaro Kishi
- Department of SurgeryOsaka Police HospitalOsakaJapan
| | - Takeshi Omori
- Department of Gastroenterological SurgeryOsaka International Cancer InstituteOsakaJapan
| | - Motohiro Hirao
- Department of Surgery, National Hospital OrganizationOsaka National HospitalOsakaJapan
| | - Toru Masuzawa
- Department of SurgeryKansai Rosai HospitalAmagasakiHyogoJapan
| | | | - Kazuyoshi Yamamato
- Department of Gastroenterological Surgery, Graduate School of MedicineOsaka UniversitySuitaOsakaJapan
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Graduate School of MedicineOsaka UniversitySuitaOsakaJapan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of MedicineOsaka UniversitySuitaOsakaJapan
| |
Collapse
|
|
8
|
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.
Collapse
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
| |
Collapse
|
|
9
|
Ministrini S, Bencivenga M, Filippini F, Mura G, Milandri C, Mazzei MA, Bagnacci G, Berselli M, Monti M, Morgagni P, Solaini L, Marrelli D, Piccioni S, De Pascale S, Graziosi L, Reddavid R, Rosa F, Belluco C, Tiberio G. A pragmatic approach improves the clinical management of stage IV gastric cancer: Comparison between the Meta-Gastro results and the GIRCG's retrospective series. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:107275. [PMID: 37995604 DOI: 10.1016/j.ejso.2023.107275] [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: 08/14/2023] [Revised: 10/29/2023] [Accepted: 11/10/2023] [Indexed: 11/25/2023]
Abstract
INTRODUCTION The Italian Research Group for Gastric Cancer developed a prospective database about stage IV gastric cancer, to evaluate how a pragmatic attitude impacts the management of these patients. MATERIALS AND METHODS We prospectively collected data about metastatic gastric cancer patients thanks to cooperation between radiologists, oncologists and surgeons and we analyzed survival and prognostic factors, comparing the results to those obtained in our retrospective study. RESULTS Three-hundred and eighty-three patients were enrolled from 2018 to September 2022. We observed a higher percentage of laparoscopic exploration with peritoneal lavage in the prospective cohort. In the registry only 3.6 % of patients was submitted to surgery without associated chemotherapy, while in the retrospective population 44.3 % of patients were operated on without any chemotherapy. At univariate and multivariate analyses, the different metastatic sites did not show any survival differences among each other (OS 20.0 vs 16.10 vs 16.7 months for lymphnodal, peritoneal and hepatic metastases, respectively), while the number of metastatic sites and the type of treatment showed a statistical significance (OS 16,7 vs 13,0 vs 4,5 months for 1, 2 and 3 different metastatic sites respectively, p < 0.001; 24,2 vs 12,0 vs 2,5 months for surgery with/without chemotherapy, chemotherapy alone and best supportive treatment respectively, p < 0.001). CONCLUSIONS Our data highlight that the different metastatic sites did not show different survivals, but survival is worse in case of multiple localization. In patients where a curative resection can be achieved, acceptable survival rates are possible. A better diagnostic workup and a more accurate staging impact favorably upon survival.
Collapse
Affiliation(s)
- Silvia Ministrini
- Surgical Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, ASST Spedali Civili of Brescia, 25123, Brescia, Italy.
| | - Maria Bencivenga
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Verona, Italy
| | - Federica Filippini
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Verona, Italy
| | - Gianni Mura
- Department of Surgery, San Donato Hospital, Arezzo, Italy
| | - Carlo Milandri
- Department of Oncology, San Donato Hospital, 52100, Arezzo, Italy
| | - Maria Antonietta Mazzei
- Unit of Diagnostic Imaging, Department of Medical, Surgical and Neuro Sciences and of Radiological Sciences, University of Siena, Azienda Ospedaliero-Universitaria Senese, 53100, Siena, Italy
| | - Giulio Bagnacci
- Unit of Diagnostic Imaging, Department of Medical, Surgical and Neuro Sciences and of Radiological Sciences, University of Siena, Azienda Ospedaliero-Universitaria Senese, 53100, Siena, Italy
| | - Mattia Berselli
- General Surgical Unit I, Department of Surgery, ASST Settelaghi-Varese, Italy
| | - Manlio Monti
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Paolo Morgagni
- General and Oncologic Surgery, "Morgagni-Pierantoni" Hospital, Forlì, Italy
| | - Leonardo Solaini
- General and Oncologic Surgery, "Morgagni-Pierantoni" Hospital, Forlì, Italy
| | - Daniele Marrelli
- Unit of General Surgery and Surgical Oncology, Department of Medicine, Surgery and Neurosciences, University of Siena, Strada delle Scotte, 4, 53100, Siena, Italy
| | - Stefania Piccioni
- Unit of General Surgery and Surgical Oncology, Department of Medicine, Surgery and Neurosciences, University of Siena, Strada delle Scotte, 4, 53100, Siena, Italy
| | - Stefano De Pascale
- Digestive Surgery Unit, European Institute of Oncology IRCCS, 20141, Milan, Italy
| | - Luigina Graziosi
- SC di Chirurgia Generale e d'Urgenza, Azienda Ospedaliera di Perugia, Perugia, Italy
| | - Rossella Reddavid
- University of Turin, Department of Oncology, Division of Surgical Oncology and Digestive Surgery, San Luigi University Hospital, Orbassano, Turin, Italy
| | - Fausto Rosa
- Department of Digestive Surgery, Catholic University, A. Gemelli Hospital, Rome, Italy
| | - Claudio Belluco
- Department of Surgical Oncology, Surgical Oncology Unit, National Cancer institute-Centro di Riferimento Oncologico IRCCS, Aviano, PN, Italy
| | - Guido Tiberio
- Surgical Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, ASST Spedali Civili of Brescia, 25123, Brescia, Italy
| |
Collapse
|
|
10
|
Liang H, Yan X, Li Z, Chen X, Qiu Y, Li F, Wang M, Huang Z, Huang K, Xie Q, Zhang H, Zhong R, Zhao Z, Zou Y, Yu J, Hu Y, Liu H, Li G, Zhao L. Clinical outcomes of conversion surgery following immune checkpoint inhibitors and chemotherapy in stage IV gastric cancer. Int J Surg 2023; 109:4162-4172. [PMID: 37720943 PMCID: PMC10720795 DOI: 10.1097/js9.0000000000000738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 08/24/2023] [Indexed: 09/19/2023]
Abstract
BACKGROUND The clinical benefit of conversion surgery following immunochemotherapy in patients with stage IV gastric cancer (GC) remains uncertain. This study aims to clarify the clinical outcomes of conversion surgery for such patients. METHODS This retrospective cohort study enroled consecutive patients with stage IV GC treated with a combination of immune checkpoint inhibitors and chemotherapy and/or anti-human epidermal growth factor receptor-2 targeted therapy as first-line therapy. Cumulative survival curves were estimated using Kaplan-Meier method. Logistic regression and Cox regression analyses were conducted to identify factors associated with conversion surgery and survival, respectively. RESULTS Among the 136 patients included in the study. The disease control rate was 72.1% (98/136), with objective response rate in 58.8% (80/136) and complete response rate in 5.9% (8/136). Among 98 patients with disease control, 56 patients underwent palliative immunochemotherapy with median progression-free survival (PFS) and overall survival at 9.2 and 16.2 months, respectively; the remaining 42 patients underwent conversion surgery, yielding an unreached median PFS over a 19.0-month median follow-up, accompanied by 1-year overall survival and PFS rates of 96.6% and 89.1%, respectively. The R0 resection rate reached 90.5% (38/42). 7 out of 42 patients achieved pathological complete response, of whom three patients demonstrated human epidermal growth factor receptor-2 positivity. No serious complications leading to death were observed during the perioperative period. Multivariate analysis indicated that programmed death ligand 1 combined positive score greater than or equal to 5 (odds ratio, 0.22; 95% CI, 0.08-0.57; P =0.002) favored successful conversion surgery, while signet ring cell carcinoma (hazard ratio, 6.29; 95% CI, 1.56-25.36; P =0.010) was the poor prognostic factor associated with survival in patients who underwent conversion surgery. CONCLUSIONS Conversion surgery holds the potential for significant survival benefits in stage IV GC patients who have achieved a favourable clinical response to immunochemotherapy. Individuals with signet ring cell carcinoma may experience increased post-conversion surgery recurrence.
Collapse
Affiliation(s)
- Huayuan Liang
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
| | - Xiao Yan
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
| | - Zhiwei Li
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
| | - Xinhua Chen
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
| | - Yaopeng Qiu
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
| | - Fengping Li
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
| | - Minghao Wang
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
| | - Zhicheng Huang
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
| | - Kaihua Huang
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
| | - Qing Xie
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
| | - Huimin Zhang
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
| | - Rou Zhong
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
| | - Zhuoyang Zhao
- Department of Pathology, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Yuan Zou
- Department of Pathology, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Jiang Yu
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
- Multidisciplinary Team of Gastric Tumor , Nanfang Hospital, Southern Medical University
| | - Yanfeng Hu
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
- Multidisciplinary Team of Gastric Tumor , Nanfang Hospital, Southern Medical University
| | - Hao Liu
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
- Multidisciplinary Team of Gastric Tumor , Nanfang Hospital, Southern Medical University
| | - Guoxin Li
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
- Multidisciplinary Team of Gastric Tumor , Nanfang Hospital, Southern Medical University
| | - Liying Zhao
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
- Multidisciplinary Team of Gastric Tumor , Nanfang Hospital, Southern Medical University
| |
Collapse
|
|
11
|
Shin MK, Choi MG, Kim ST, Kang WK, Sohn TS, An JY, Lee JH, Lee JY. The Clinical Implication of Conversion Surgery in Patients with Stage IV Gastric Cancer Who Received Systemic Chemotherapy. Biomedicines 2023; 11:3097. [PMID: 38002099 PMCID: PMC10669208 DOI: 10.3390/biomedicines11113097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Revised: 11/07/2023] [Accepted: 11/14/2023] [Indexed: 11/26/2023] Open
Abstract
With the advances in chemotherapy and immunotherapy, a small subset of patients may be eligible for conversion surgery after achieving tumor regression with chemotherapy. This is a retrospective cohort study of 118 patients with stage IV gastric cancer who received palliative chemotherapy and conversion surgery with a negative resection margin at Samsung Medical Center. Baseline features included comorbidities, body mass index (BMI), carcinoembryonic antigen (CEA) level, primary tumor size, biopsy histology, distant metastatic sites, and molecular markers-HER2, MSI/MMR, PD-L1, and EBV. Post-chemotherapy features included BMI, CEA level, chemotherapy regimen, objective response to chemotherapy, and number of preoperative chemotherapy cycles. Post-operational features included tumor size, histologic differentiation and Lauren's classification, pathologic tumor and nodal stages, invasion of lymphatics/vessels/nerves, peritoneal cytology, and the receipt of postoperative chemotherapy. Of 118 patients, 60 patients received total gastrectomy and 58 patients received subtotal gastrectomy. In all, 21 patients achieved a pathologic complete response, and 97 patients achieved downstaging to yp stage I, II, or III. Before conversion surgery, patients received first-line capecitabine/oxaliplatin (62%), HER2 inhibitors combined with chemotherapy (18%), immune checkpoint inhibitors (15%), and inhibitors of MET or VEGFR2 (5%). In the multivariable analysis, BMI at the time of diagnosis, either HER2 positive, high MSI, or deficient MMR, and the use of targeted agents were significant prognostic factors. Conversion surgery could be considered in patients with stage IV gastric cancer regardless of the initial disease burden. BMI and molecular markers are important prognostic factors that can be used to select candidates.
Collapse
Affiliation(s)
- Min-Kyue Shin
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea (W.-K.K.)
- Department of Digital Health, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul 06355, Republic of Korea
| | - Min-Gew Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
| | - Seung-Tae Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea (W.-K.K.)
| | - Won-Ki Kang
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea (W.-K.K.)
| | - Tae-Sung Sohn
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
| | - Ji-Yeong An
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
| | - Joon-Ho Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
| | - Jee-Yun Lee
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea (W.-K.K.)
| |
Collapse
|
|
12
|
Liu Z, Tian H, Zhu Z. Application of Circulating Tumor Cells and Interleukin-6 in Preoperative Prediction of Peritoneal Metastasis of Advanced Gastric Cancer. J Inflamm Res 2023; 16:3033-3047. [PMID: 37497064 PMCID: PMC10366674 DOI: 10.2147/jir.s414786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Accepted: 06/16/2023] [Indexed: 07/28/2023] Open
Abstract
Background The purpose of this study was to explore the clinical significance of circulating tumor cells (CTCs) and cytokines in peripheral blood in preoperative prediction of peritoneal metastasis (PM) in advanced gastric cancer (AGC). Methods The clinicopathological characteristics of 282 patients with AGC were retrospectively analyzed. The patients were divided into training and validation groups according to the time of receiving treatment. We used univariate analysis and multivariate logistic regression analysis to screen out the independent risk factors of PM in AGC. Then, we incorporated independent risk factors into the nomogram, and evaluated the discriminative ability. Results The levels of CTCs and interleukin-6 (IL-6) of AGC patients with PM were higher than those without PM (P<0.05). Moreover, the levels of CTCs and IL-6 in the occult peritoneal metastasis (OPM) group and the CT-positive PM group were higher than those in the negative PM (P<0.05). Multivariate logistic regression analysis showed that IL-6 > 12.22 pg/mL, CTCs > 4/5mL, CA724 > 6 IU/mL, CA125 > 35 U/mL and tumor size > 5 cm were independent risk factors for PM of AGC. The area under the ROC curve of the nomogram were 0.898 and 0.926 in the training and validation sets, respectively. The clinical decision curve showed that the nomogram had good clinical utility. Conclusion CTCs and IL-6 in peripheral blood are promising biomarkers for predicting the risk of PM in AGC. The nomogram constructed from five risk factors can effectively assess the risk of PM in AGC patients individually.
Collapse
Affiliation(s)
- Zitao Liu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China
| | - Huakai Tian
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China
| | - Zhengming Zhu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China
| |
Collapse
|
|
13
|
Deng YY, Jiang DY, Zhu PF, Lu H, Liu Q, Zhang X, Pan SY, Chen ZL, Yang L. Apatinib combined with SOX regimen for conversion therapy in advanced gastric cancer patients: a retrospective cohort study. World J Surg Oncol 2023; 21:129. [PMID: 37041581 PMCID: PMC10088230 DOI: 10.1186/s12957-023-02973-3] [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: 10/20/2022] [Accepted: 02/27/2023] [Indexed: 04/13/2023] Open
Abstract
BACKGROUND Recently, many studies have shown that the progress of conversion therapy can provide surgical opportunities for patients with advanced gastric cancer (GC) and bring survival benefits. However, the results of the current study show that the regimen used in conversion therapy is still controversial. Apatinib, as the standard third-line treatment for GC, has an inconclusive status in conversion therapy. METHODS This study retrospectively analyzed GC patients admitted to Zhejiang Provincial People's Hospital from June 2016 to November 2019. All patients were pathologically diagnosed, had unresectable factors, and received SOX regimen with or without apatinib as conversion therapy. RESULTS A total of 50 patients were enrolled in the study. Altogether 33 patients (66%) received conversion surgery and 17 patients (34%) received conversion therapy without surgery. The median progression-free survival (PFS) between surgery group and non-surgery group were 21.0 versus 4.0 months (p < 0.0001), and the median overall survival (OS) were 29.0 versus 14.0 months (p < 0.0001). In conversion surgery group, 16 patients (16/33) were treated with SOX plus apatinib, and the R0 resection rate was 81.3%; 17 patients (17/33) were treated with SOX regimen along, and the R0 resection rate was 41.2% (p = 0.032). The PFS in the SOX combined with apatinib group was significantly longer than that of SOX group (25.5 versus 16 months, p = 0.045), and the median OS were 34.0 versus 23.0 months (p = 0.048). The addition of apatinib did not increase the incidence of serious adverse reactions throughout the preoperative therapy period. CONCLUSIONS Patients with advanced inoperable gastric cancer could benefit probably from conversion chemotherapy and subsequence conversion surgery. Apatinib-targeted therapy combined with SOX chemotherapy may be a safe and feasible option for conversion therapy.
Collapse
Affiliation(s)
- Ya-Ya Deng
- Cancer Center, Department of Medical Oncology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China
- The Qingdao University Medical College, Qingdao, Shandong Province, 260075, China
| | - Ding-Yi Jiang
- Cancer Center, Department of Medical Oncology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China
- The Qingdao University Medical College, Qingdao, Shandong Province, 260075, China
| | - Peng-Fei Zhu
- The Qingdao University Medical College, Qingdao, Shandong Province, 260075, China
- Graduate School of Clinical Medicine, Bengbu Medical College, Bengbu, 233000, Anhui Province, China
| | - Hongrui Lu
- The Qingdao University Medical College, Qingdao, Shandong Province, 260075, China
- Graduate School of Clinical Medicine, Bengbu Medical College, Bengbu, 233000, Anhui Province, China
| | - Qian Liu
- The Qingdao University Medical College, Qingdao, Shandong Province, 260075, China
| | - Xinyue Zhang
- Cancer Center, Department of Medical Oncology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China
- The Qingdao University Medical College, Qingdao, Shandong Province, 260075, China
| | - Shuang-Yue Pan
- The Qingdao University Medical College, Qingdao, Shandong Province, 260075, China
- Graduate School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310014, Zhejiang Province, China
| | - Zhe-Ling Chen
- The Qingdao University Medical College, Qingdao, Shandong Province, 260075, China.
| | - Liu Yang
- Cancer Center, Department of Medical Oncology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China.
- The Qingdao University Medical College, Qingdao, Shandong Province, 260075, China.
| |
Collapse
|
|
14
|
Sato Y, Okamoto K, Kida Y, Mitsui Y, Kawano Y, Sogabe M, Miyamoto H, Takayama T. Overview of Chemotherapy for Gastric Cancer. J Clin Med 2023; 12:jcm12041336. [PMID: 36835872 PMCID: PMC9959005 DOI: 10.3390/jcm12041336] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Revised: 01/22/2023] [Accepted: 02/06/2023] [Indexed: 02/11/2023] Open
Abstract
Gastric cancer (GC) is one of the most clinically challenging cancers worldwide. Over the past few years, new molecular-targeted agents and immunotherapy have markedly improved GC prognosis. Human epidermal growth factor receptor 2 (HER2) expression is a key biomarker in first-line chemotherapy for unresectable advanced GC. Further, the addition of trastuzumab to cytotoxic chemotherapy has extended the overall survival of patients with HER2-positive advanced GC. In HER2-negative GC, the combination of nivolumab, an immune checkpoint inhibitor, and a cytotoxic agent has been demonstrated to prolong the overall survival of GC patients. Ramucirumab and trifluridine/tipiracil, which are second- and third-line treatments for GC, and trastuzumab deruxtecan, an antibody-drug conjugate for HER2-positive GC, have been introduced in clinics. New promising molecular-targeted agents are also being developed, and combination therapy comprising immunotherapy and molecular-targeted agents is expected. As the number of available drugs increases, it is important to understand the target biomarkers and drug characteristics and select the optimal therapy for each patient. For resectable disease, differences in the extent of standard lymphadenectomy between Eastern and Western countries have led to different standard treatments: perioperative (neoadjuvant) and adjuvant therapy. This review aimed to summarize recent advances in chemotherapy for advanced GC.
Collapse
Affiliation(s)
- Yasushi Sato
- Department of Community Medicine for Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, Tokushima 770-8503, Japan
- Correspondence: ; Tel.: +81-88-633-7124
| | - Koichi Okamoto
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, Tokushima 770-8503, Japan
| | - Yoshifumi Kida
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, Tokushima 770-8503, Japan
| | - Yasuhiro Mitsui
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, Tokushima 770-8503, Japan
| | - Yutaka Kawano
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, Tokushima 770-8503, Japan
| | - Masahiro Sogabe
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, Tokushima 770-8503, Japan
| | - Hiroshi Miyamoto
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, Tokushima 770-8503, Japan
| | - Tetsuji Takayama
- Department of Gastroenterology and Oncology, Tokushima University Graduate School of Medical Science, Tokushima 770-8503, Japan
| |
Collapse
|
|
15
|
Xiang X, Guo F, Li G, Ma L, Zhu X, Abdulla Z, Li J, Zhang J, Huang M. Efficacy of intra-arterial chemotherapy with sequential anti-PD-1 antibody in unresectable gastric cancer: A retrospective real-world study. Front Oncol 2023; 12:1015962. [PMID: 36686751 PMCID: PMC9849699 DOI: 10.3389/fonc.2022.1015962] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 12/14/2022] [Indexed: 01/06/2023] Open
Abstract
Background The prognosis of unresectable gastric cancer is poor, while the efficacy of anti-PD antibodies has not been evaluated. Methods Patients with unresectable gastric cancer who received intra-arterial chemotherapy (IAC) with sequential anti-PD-1 antibody as induction therapy in Jinling Hospital were retrospectively analyzed. The primary outcome is R0 resection rate. The secondary outcomes include safety, conversion surgery rate, overall survival (OS) and progression free survival (PFS) after postoperative IAC and anti-PD-1 treatments. Meanwhile, Tumor immunity in the microenvironment (TIME) before and after IAC was comprehensively dissected with multiplex immunofluorescence in order to detect possible mechanisms favoring anti-PD-1 treatment response. Results Between May 2019 and October 2020, 36 patients received at least one cycle of IAC with sequential anti-PD-1 antibody in our institution. The objective response was achieved in 28 patients (77.8%). Thirty patients (83.3%) successfully underwent conversion surgery, among which R0 resection was managed in 25/30 patients, and 23.3% (7/30) was assessed as pathological complete remission. During the median follow-up period of 19.7 months, patients who underwent R0 resection displayed superior OS (HR 0.14 [95% CI 0.04-0.50], P < 0.0001) and PFS (HR 0.11 [0.03-0.44], P < 0.0001) than those who did not. Grade 3 adverse events (AEs) were only encountered in 19.4% patients, no grade 4 AEs observed. In TIME analysis, the number of tertiary lymphoid structures (TLSs) (P = 0.004) were greatly induced by IAC, as well as CD8+ T cells (P = 0.011) and PD-1+ cells (P = 0.025). Meanwhile, Tumor associated macrophages shifted towards anti-tumor M1-like subtypes, with CD68+CD163+ M2-like subpopulation significantly decreased (P = 0.04). Conclusion Preoperative IAC with sequential anti-PD-1 antibody exhibited promising clinical benefit for unresectable gastric cancer with remarkable conversion rate and R0 resection rate, and also prolonged survival as postoperative regimen. TIME transformation induced by ICA might mediate the additive effect with the immune checkpoint inhibitor.
Collapse
Affiliation(s)
- Xiaosong Xiang
- Department of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China
| | - Feilong Guo
- Department of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China
| | - Guoli Li
- Department of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China,*Correspondence: Guoli Li,
| | - Long Ma
- Department of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China
| | - Xi Zhu
- Department of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China
| | - Zulpikar Abdulla
- Department of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China
| | - Jiafei Li
- Department of Biostatistics, Columbia University, New York, NY, United States
| | - Junling Zhang
- The Medical Department, 3D Medicines Inc., Shanghai, China
| | - Mengli Huang
- The Medical Department, 3D Medicines Inc., Shanghai, China
| |
Collapse
|
|
16
|
Kano Y, Ichikawa H, Hanyu T, Muneoka Y, Ishikawa T, Aizawa M, Matsuki A, Yabusaki H, Bamba T, Nakagawa S, Kobayashi K, Kuwabara S, Makino S, Kawachi Y, Naito T, Tani T, Hirukawa H, Tada T, Shimada Y, Sakata J, Wakai T. Conversion surgery for stage IV gastric cancer: a multicenter retrospective study. BMC Surg 2022; 22:428. [PMCID: PMC9749226 DOI: 10.1186/s12893-022-01874-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 12/02/2022] [Indexed: 12/15/2022] Open
Abstract
Abstract
Background
Recent improvements in systemic chemotherapy have provided an opportunity for patients with stage IV gastric cancer (GC) to undergo conversion surgery (CS). The aim of this study was to evaluate the long-term outcomes of patients who underwent CS and to elucidate the prognostic factors for CS in stage IV GC.
Methods
A total of 79 patients who underwent CS with the aim of R0 resection for stage IV GC at six institutions from January 2008 to July 2019 were enrolled. We retrospectively reviewed the clinicopathological data and prognosis.
Results
Of the 79 patients, 23 (31.1%) had initially resectable disease (IR) before chemotherapy, defined as positive for cancer on peritoneal cytology (CY1), resectable hepatic metastasis, or para-aortic lymph node No. 16a2/b1 metastasis. Of the 56 remaining patients with primary unresectable disease, 39 had peritoneal dissemination. R0 resection was accomplished in 63 patients (79.7%). The 3-year OS rates for patients with IR and unresectable disease were 78.3% and 44.5%, respectively. Multivariate analysis showed that IR (P = 0.014) and R0 (P = 0.014) were statistically significant independent prognostic factors for favorable OS. Among patients with peritoneal dissemination alone, OS was significantly better for patients with R0 resection than for patients with R1/2 resection, with the 3-year OS rates of 65.5% and 23.1%, respectively (P = 0.011).
Conclusions
CS is a treatment option for selected patients with stage IV GC. Patients with IR and patients who achieve R0 resection may obtain a survival benefit from CS.
Collapse
|
|
17
|
Two cases of anal squamous cell carcinoma achieving complete response after docetaxel + cisplatin + S-1 (DCS) induction chemotherapy followed by chemoradiation. Clin J Gastroenterol 2022; 16:180-186. [PMID: 36409453 DOI: 10.1007/s12328-022-01736-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Accepted: 11/10/2022] [Indexed: 11/22/2022]
Abstract
Anal squamous cell carcinoma (ASCC) is an uncommon tumor. However, its incidence is increasing worldwide. Surgical resection of locally advanced cases requires permanent anal prosthesis. Thus, chemoradiotherapy (CRT) is preferred as the first-line treatment; however, high local recurrence rate remains an issue. Here, we describe two cases of locally advanced ASCC treated with docetaxel + cisplatin + S-1 (DCS) followed by CRT with S-1 that showed complete response. The two patients, aged 69 and 65 years, were diagnosed with ASCC (cStage IIIB) at our hospital. Due to extensive lymph node metastases, the patients were treated with triple induction chemotherapy (DCS) followed by CRT with S-1. Positron emission tomography/computed tomography performed six months after starting the treatment showed disappearance of tumors, indicating a complete response. The patients continued to receive S-1 for one year and achieved relapse-free long-term survival since the completion of treatment. Therefore, induction chemotherapy with DCS, prior to CRT with S-1 may benefit patients with locally advanced ASCC.
Collapse
|
|
18
|
Shinkai M, Imano M. The clinical effect of conversion surgery for advanced gastric cancer patients with peritoneal metastasis. J Gastrointest Oncol 2022; 13:2169-2177. [PMID: 36388679 PMCID: PMC9660049 DOI: 10.21037/jgo-21-431] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 04/15/2022] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND The prognosis of gastric cancer (GC) patients with peritoneal metastasis (PM) is extremely poor. We developed a new promising regimen combining intraperitoneal (i.p.) paclitaxel (PTX) with systemic PTX and S-1 chemotherapy for GC patients with PM. However, the value of conversion surgery (CS) for GC patients with PM remains unclear. This study aimed to clarify the clinical effect of CS from our updated previous report. METHODS We retrospectively analyzed 50 GC patients, divided into chemotherapy alone (CTx; n=15) and conversion surgery intervention (CSI; n=35) groups. In the CTx group, chemotherapy was continued in responders, while in the CSI group, surgery was performed in chemotherapy-responders. The primary endpoint was overall survival (OS) of the two groups. The secondary endpoint was the safety of CS. RESULTS In the CTx group, 9 of 15 patients (60%) responded to chemotherapy. In the CSI group, PM disappeared in 22 of 35 patients (62.9%), all of whom underwent CS. Post-operative complications occurred in 2 patients (9%) who underwent CS. There were no treatment-related deaths. Regarding OS, there was no significant difference between the two groups [P=0.14; 95% confidence interval (CI), 0.3016-1.197], nor between chemotherapy-responders in the two groups (P=0.059; 95% CI, 0.1473-1.039). However, four patients in the CSI group have survived more than 5 years after CS. CONCLUSIONS CS may be a promising treatment strategy for some GC patients with PM who have responded to chemotherapy.
Collapse
Affiliation(s)
- Masayuki Shinkai
- Department of Surgery, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Motohiro Imano
- Department of Surgery, Faculty of Medicine, Kindai University, Osaka, Japan
| |
Collapse
|
|
19
|
Kinoshita J, Fushida S, Yamaguchi T, Moriyama H, Saito H, Shimada M, Terai S, Okamoto K, Nakamura K, Ninomiya I, Yagi S, Inaki N. Prognostic value of tumor-infiltrating CD163 +macrophage in patients with metastatic gastric cancer undergoing multidisciplinary treatment. BMC Cancer 2022; 22:608. [PMID: 35658848 PMCID: PMC9166590 DOI: 10.1186/s12885-022-09713-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 05/26/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The multidisciplinary treatment including induction chemotherapy plus conversion surgery (CS) has attracted attention as a new strategy to improve the outcome of metastatic gastric cancer (MGC). However, it is unclear which patients achieve a good response to chemotherapy and successful CS. Tumor-infiltrating immune cells (TIICs) have been reported to be both prognostic and predictive biomarkers not only in immunotherapy but also in chemotherapy in many cancer types. However, there have been no reports on the usefulness of TIICs as biomarkers in conversion surgery for MGC. The aim of the present study was to evaluate the association between the TIICs and treatment outcome for the multidisciplinary treatment in MGC. METHODS We retrospectively analyzed 68 MGC patients who received docetaxel plus cisplatin plus S-1 (DCS) therapy between April 2006 and March 2019 in our institute. The number of tumor-infiltrating CD4+, CD8+, Foxp3+lymphocytes, CD68+, CD163+macrophages in pre-treatment endoscopic biopsy samples were evaluated to investigate their predictive value for multidisciplinary treatment. RESULTS Fifty patients underwent CS following DCS therapy (CS group), whereas 18 patients underwent DCS therapy alone (non-CS group). The median survival time (MST) of CS group was 33.3 months, which was significantly longer than the MST of 9.0 months in non-CS group (p < 0.01). The number of CD163+macrophages was extracted as an independent prognostic factor for overall survival in all patients. There were more cases of high infiltration of CD163+macrophages in non-CS group than in CS group. Furthermore, in CS group, pathological responders to DCS therapy showed low infiltration of CD163+ macrophages, and high infiltration of CD8+lymphocyte. CD163 low group showed a significant prolonged survival compared with CD163 high group in patients who underwent CS (p = 0.02). CONCLUSIONS The pre-treatment CD163+macrophages infiltration would be a pivotal biomarker for predicting prognosis and pathological response to multidisciplinary treatment among TIICs in MGC. Thus, for patients with low CD163+macrophage infiltration in pre-treatment biopsy sample, diagnostic imaging should be performed frequently during chemotherapy to avoid missing the optimal timing for CS, and CS should be aggressively considered as a treatment option if curative resection is deemed feasible.
Collapse
Affiliation(s)
- Jun Kinoshita
- Department of Gastrointestinal Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Sachio Fushida
- Department of Gastrointestinal Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan.
| | - Takahisa Yamaguchi
- Department of Gastrointestinal Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Hideki Moriyama
- Department of Gastrointestinal Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Hiroto Saito
- Department of Gastrointestinal Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Mari Shimada
- Department of Gastrointestinal Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Shiro Terai
- Department of Gastrointestinal Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Koichi Okamoto
- Department of Gastrointestinal Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Keishi Nakamura
- Department of Gastrointestinal Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Itasu Ninomiya
- Department of Gastrointestinal Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Shintaro Yagi
- Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Noriyuki Inaki
- Department of Gastrointestinal Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan
| |
Collapse
|
|
20
|
A case of conversion hepatectomy for huge hepatocellular carcinoma with adrenal metastasis and vascular invasion after atezolizumab-bevacizumab treatment. Clin J Gastroenterol 2022; 15:776-783. [PMID: 35585285 DOI: 10.1007/s12328-022-01644-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 05/02/2022] [Indexed: 10/18/2022]
Abstract
We herein report a case of huge hepatocellular carcinoma (HCC) with adrenal metastasis and vascular invasion successfully treated by conversion hepatectomy after atezolizumab-bevacizumab treatment. A 77-year-old male patient with chest pain was admitted. He had a history of HCC treatment; however, the patient stopped receiving follow-up treatment based on his own decision. This time, he visited the emergency department of our hospital for the first time in 5 years. The tumor at the right lobe had grown into a lump with adrenal metastases and was 15 cm in diameter. It had invaded the inferior vena cava. Atezolizumab-bevacizumab treatment was selected for HCC treatment. Before starting treatment, his liver function was preserved (Child-Pugh A5). His alpha fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) levels were 759.0 ng/mL and 5,681 mAU/mL, respectively. Atezolizumab-bevacizumab treatment resulted in a marked decrease in tumor marker levels and tumor staining. After nine courses of atezolizumab-bevacizumab treatment, it became difficult to continue the administration of bevacizumab because of proteinuria. Because the tumor had decreased in size and the tumor markers were in the normal range, we decided to perform conversion hepatectomy. The tumor was completely removed by combined resection of the diaphragm, and pathological analyses showed a complete response to atezolizumab-bevacizumab treatment. No viable tumor cells remained on histological analyses. The patient is doing well without any signs of recurrence at 3 months after conversion surgery.
Collapse
|
|
21
|
Chevallay M, Wassmer CH, Iranmanesh P, Jung MK, Mönig SP. Multimodal treatment in oligometastatic gastric cancer. World J Gastrointest Oncol 2022; 14:434-449. [PMID: 35317315 PMCID: PMC8919006 DOI: 10.4251/wjgo.v14.i2.434] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 08/02/2021] [Accepted: 12/28/2021] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer is generally diagnosed at an advanced stage, especially in countries without screening programs. Previously, the metastatic stage was synonymous with palliative management, and surgical indications were only for symptomatic relief. However, this therapeutic option is associated with poor prognosis. A subgroup of patients with limited metastatic disease could benefit from intensive treatment. A combination of chemotherapy, immunotherapy, and targeted therapy could help either maintain a resectable state for oligometastatic disease or diminish the metastasis size to obtain a complete resection configuration. This latter strategy is known as conversion therapy and has growing evidence with favorable outcomes. Oncosurgical approach of metastatic disease could prolong survival in selected patients. The challenge for the surgeon and oncologist is to identify these specific patients to offer the best multimodal management. We review in this article the actual evidence for the treatment of oligometastatic gastric cancer with curative intent.
Collapse
Affiliation(s)
- Mickael Chevallay
- Division of Digestive Surgery, Geneva University Hospital and Faculty of Medicine, Geneva 1205, Genève, Switzerland
| | - Charles-Henri Wassmer
- Division of Digestive Surgery, Geneva University Hospital and Faculty of Medicine, Geneva 1205, Genève, Switzerland
| | - Pouya Iranmanesh
- Division of Digestive Surgery, Geneva University Hospital and Faculty of Medicine, Geneva 1205, Genève, Switzerland
| | - Minoa K Jung
- Division of Digestive Surgery, Geneva University Hospital and Faculty of Medicine, Geneva 1205, Genève, Switzerland
| | - Stefan P Mönig
- Division of Digestive Surgery, Geneva University Hospital and Faculty of Medicine, Geneva 1205, Genève, Switzerland
| |
Collapse
|
|
22
|
Wang C, Zhang X, Lin S, Yang C, Zhou B, Mi Y, Ye R, Chen Y, Chen W, Lin X, Tan S, Zhou Y, Li W. Superiority of Laparoscopic Gastrojejunostomy Combined With Multimodality Therapy for Gastric Outlet Obstruction Caused by Advanced Gastric Cancer. Front Oncol 2022; 12:814283. [PMID: 35155250 PMCID: PMC8832489 DOI: 10.3389/fonc.2022.814283] [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] [Received: 11/13/2021] [Accepted: 01/10/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Data are limited concerning the survival outcomes of patients with gastric outlet obstruction (GOO) caused by advanced gastric cancers according to laparoscopic gastrojejunostomy (LGJ) combined with multimodality therapy (MMT). Therefore, the purpose of this study was to examine the feasibility and efficacy of these therapies. METHODS This single-centered, retrospective analysis included data of 184 patients with GOO due to advanced gastric cancer (AGC). Treatment models were: laparoscopic gastrojejunostomy combined with multimodality therapy (LGJ+MMT), endoscopic metal stent placement combined with multimodality therapy (EMSP+MMT), and multimodality therapy (MMT). RESULTS Improved oral intake, better nutritional indices, and better response to chemotherapy were observed in the LGJ+MMT group. Subsequent gastrectomy was performed in 43 (61.4%) patients in the LGJ+MMT group, 23 (37.7%) in the EMSP+MMT group, and 11 (20.8%) in the MMT group (P<0.001). LGJ+MMT was associated with better long-term prognosis. As confirmed by propensity scores and multivariate analyses, the 3-year survival rates in the three treatment models were 31.4% with LGJ+MMT, 0% with EMSP+MMT, and 0% with MMT in conversion therapy, and 50.0% with LGJ+MMT, 33.3% with EMSP+MMT, and 23.5% with MMT in NAC. A forest plot revealed that LGJ+MMT was related to a decreased risk of death. CONCLUSIONS LGJ combined with MMT was associated with better nutritional status, higher rates of subsequent gastrectomy, and good prognosis. LGJ combined with MMT may improve the long-term survival of patients with GOO caused by AGC.
Collapse
Affiliation(s)
- Chuandong Wang
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.,Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, China
| | - Xiaojuan Zhang
- Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, China.,Department of Radiology, 900th Hospital Logistic Support Forces of PLA, Fuzhou, China
| | - Shengtao Lin
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.,Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, China
| | - Changshun Yang
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.,Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, China
| | - BiaoHuan Zhou
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.,Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, China
| | - Yulong Mi
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.,Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, China
| | - Rong Ye
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.,Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, China
| | - Yifan Chen
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.,Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, China
| | - Weijie Chen
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.,Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, China
| | - Xiaojun Lin
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.,Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, China
| | - Song Tan
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.,Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, China
| | - Yuhang Zhou
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.,Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, China
| | - Weihua Li
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.,Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, China
| |
Collapse
|
|
23
|
Xie QY, Liu HY, Guo ZY, Wu YP, He GL, Cai L, Pan MX, Fu SJ. Case Report: One-Year Delay in the Effect of Conversion Surgery Therapy for Advanced Hepatocellular Carcinoma After Systemic Therapy. Front Mol Biosci 2022; 8:810251. [PMID: 35187075 PMCID: PMC8855209 DOI: 10.3389/fmolb.2021.810251] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Accepted: 12/13/2021] [Indexed: 11/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most commonly diagnosed malignancy and the third leading cause of cancer-related deaths worldwide. A 58-year-old man visited his local hospital due to abdominal discomfort and was diagnosed with lung metastasis. After admission to our hospital in April 2020, he received two cycles of transcatheter arterial embolization (TAE), hepatic arterial infusion chemotherapy (HAIC-Folfox), sorafenib, and camrelizumab every 3 weeks. Due to the end of HAIC treatment, he underwent drug-eluting transcatheter arterial chemoembolization (dTACE) once, sorafenib, and camrelizumab. However, because of worsening liver function, we interrupted TACE and only gave sorafenib and camrelizumab in August 2020. Although he received systemic therapy, the tumors still rapidly progressed and we considered the possibility of tumor resistance. Subsequently, regorafenib was given. In September, the patient underwent conventional TACE (cTACE) once, regorafenib, and camrelizumab. After half a year of comprehensive treatment, the treatment effect was not satisfactory, and he returned to the local hospital to received regorafenib every day and camrelizumab once every 3 weeks. The patient found that the tumor and lung metastasis had shrunk significantly after 1 year of the initial diagnosis, then he was admitted to our hospital and received surgery treatment, and now he has survived disease-free for 6 months.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | - Shun-Jun Fu
- *Correspondence: Ming-Xin Pan, ; Shun-Jun Fu,
| |
Collapse
|
|
24
|
Shinkai M, Imano M, Hiraki Y, Momose K, Kato H, Shiraishi O, Yasuda A, Tsubaki M, Nishida S, Yasuda T. Efficacy of conversion surgery after a single intraperitoneal administration of paclitaxel and systemic chemotherapy for gastric cancer with peritoneal metastasis. Langenbecks Arch Surg 2022; 407:975-983. [PMID: 34988644 DOI: 10.1007/s00423-021-02410-7] [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: 07/16/2021] [Accepted: 12/13/2021] [Indexed: 11/29/2022]
Abstract
PURPOSE The prognosis of gastric cancer patients with peritoneal metastasis (PM) remains dismal with standard systemic chemotherapy. Intraperitoneal (i.p.) chemotherapy with paclitaxel (PTX) has local effects on intra-abdominal cancer cells. According to this phenomenon, we have developed regimens combining single i.p. PTX administration with systemic chemotherapy. This treatment strategy is very promising; however, the effect of "conversion surgery" in patients responding to this chemotherapy is unclear. Therefore, we performed a retrospective study to evaluate the safety and efficacy of conversion surgery for gastric cancer patients with PM. METHODS We enrolled 52 gastric cancer patients with PM who were treated with single i.p. PTX plus systemic chemotherapy between 2005 and 2015. Conversion surgery was performed where PM was eliminated by combination chemotherapy. RESULTS Among 52 gastric cancer patients, the disappearance of PM was confirmed in 33 patients (63.5%). Gastrectomy with D2 lymph node dissection was performed in all these patients. Histological response of grade ≥ 1b was achieved in 13 patients (39%). Clavien-Dindo grade II postoperative complications occurred in three patients (9%). There were no treatment-related deaths. The median survival time and 1-, 3-, and 5-year overall survival rates of the 33 patients who underwent conversion surgery were 30.7 months and 78.8%, 36.3%, and 24.2%, respectively, and those of the 19 patients who did not undergo surgery were 12.5 months and 52.6%, 5.2%, and 0%, respectively. CONCLUSION Conversion surgery is safe and may prolong survival for gastric cancer patients with PM who have responded to single i.p. PTX plus systemic chemotherapy.
Collapse
Affiliation(s)
- Masayuki Shinkai
- Department of Surgery, Faculty of Medicine, Kindai University, 377-2 Ohno-Higashi, Osakasayama, Osaka, 587-8511, Japan
| | - Motohiro Imano
- Department of Surgery, Faculty of Medicine, Kindai University, 377-2 Ohno-Higashi, Osakasayama, Osaka, 587-8511, Japan.
| | - Yoko Hiraki
- Department of Surgery, Faculty of Medicine, Kindai University, 377-2 Ohno-Higashi, Osakasayama, Osaka, 587-8511, Japan
| | - Kota Momose
- Department of Surgery, Faculty of Medicine, Kindai University, 377-2 Ohno-Higashi, Osakasayama, Osaka, 587-8511, Japan
| | - Hiroaki Kato
- Department of Surgery, Faculty of Medicine, Kindai University, 377-2 Ohno-Higashi, Osakasayama, Osaka, 587-8511, Japan
| | - Osamu Shiraishi
- Department of Surgery, Faculty of Medicine, Kindai University, 377-2 Ohno-Higashi, Osakasayama, Osaka, 587-8511, Japan
| | - Atsushi Yasuda
- Department of Surgery, Faculty of Medicine, Kindai University, 377-2 Ohno-Higashi, Osakasayama, Osaka, 587-8511, Japan
| | - Masanobu Tsubaki
- Division of Pharmacotherapy, Faculty of Pharmacy, Kindai University, Higashiosaka, Japan
| | - Shozo Nishida
- Division of Pharmacotherapy, Faculty of Pharmacy, Kindai University, Higashiosaka, Japan
| | - Takushi Yasuda
- Department of Surgery, Faculty of Medicine, Kindai University, 377-2 Ohno-Higashi, Osakasayama, Osaka, 587-8511, Japan
| |
Collapse
|
|
25
|
Abstract
The prognosis of advanced gastric cancer (AGC) is extremely poor, and the therapeutic effect of traditional palliative chemotherapy is far from satisfactory. To overcome this bottleneck, palliative surgery resection, perioperative chemotherapy combined with surgical resection, hyperthermic intraperitoneal chemotherapy (HIPEC), pressurized intraperitoneal aerosol chemotherapy (PIPAC), radiation therapy, molecular-targeted therapy have been explored in AGC. Although considerable progress has been achieved, there is still no overwhelming therapeutic method. Due to the high heterogeneity of AGC, it is particularly vital to reshaped the paradigm of gastric cancer therapy according to the characteristics of clinical classifications and molecular subtypes.
Collapse
Affiliation(s)
- Tao Li
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yufang He
- The First Clinical Medical School, Southern Medical University, Guangzhou, Guangdong, China
| | - Qinglei Zhong
- The First Clinical Medical School, Southern Medical University, Guangzhou, Guangdong, China
| | - Jiang Yu
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xinhua Chen
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| |
Collapse
|
|
26
|
Naganuma A, Suzuki Y, Hoshino T, Yasuoka H, Tamura Y, Naruse H, Tanaka H, Hirai K, Sakamoto I, Ogawa T, Hatanaka T, Kakizaki S. A case of conversion hepatectomy for huge ruptured hepatocellular carcinoma after transarterial embolization and lenvatinib therapy. Clin J Gastroenterol 2021; 15:177-184. [PMID: 34811701 DOI: 10.1007/s12328-021-01558-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 11/10/2021] [Indexed: 12/09/2022]
Abstract
We herein report a successfully treated case of huge ruptured hepatocellular carcinoma (HCC) by conversion hepatectomy after transarterial embolization (TAE) and lenvatinib therapy. A 33-year-old male patient with right hypochondralgia and liver tumor was referred to our hospital. He had a history of surgery for heart malformation. The tumor at the right lobe was 15 cm in diameter with bloody ascites. Right atrial thrombus 4.5 cm in diameter and marked cardiac dilatation were observed. TAE with ethanol suspended in lipiodol and gelatin sponge achieved hemostasis of the ruptured HCC. Although viable HCC remained after TAE, surgical treatment was abandoned because of abdominal wall invasion and his heart function. Lenvatinib and rivaroxaban were then initiated for HCC and atrial thrombus, respectively. Lenvatinib treatment resulted in a reduction in tumor marker levels and the tumor size. First, we planned conversion hepatectomy after 5 months of lenvatinib. However, recurrence of atrial thrombus prompted us to put off the surgery, and lenvatinib was re-administered. After improvement of atrial thrombus, we finally performed conversion hepatectomy 10 months after starting lenvatinib administration. The tumor was completely removed by combined resection of the diaphragm, and the patient has been doing well without any signs of recurrence.
Collapse
Affiliation(s)
- Atsushi Naganuma
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Yuhei Suzuki
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Takashi Hoshino
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Hidetoshi Yasuoka
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Yuki Tamura
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Hiroaki Naruse
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Hiroshi Tanaka
- Department of Surgery, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Keitaro Hirai
- Department of Surgery, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Ichiro Sakamoto
- Department of Surgery, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Tetsushi Ogawa
- Department of Surgery, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Takeshi Hatanaka
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, 564-1 Kamishindenmachi, Maebashi, Gunma, 371-0821, Japan
| | - Satoru Kakizaki
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan. .,Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan.
| |
Collapse
|
|
27
|
Jian D, Qian C, Wang D, Ma Q, Wang L, Li C, Xu M, Dai N, Chen Q, He J, Zhang H, Yuan M, Chen R, Chao R, Feng Y. Conversion therapy with tislelizumab for high microsatellite instability, unresectable stage III gastric cancer: a case report. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1489. [PMID: 34734041 PMCID: PMC8506721 DOI: 10.21037/atm-21-4295] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 09/18/2021] [Indexed: 12/20/2022]
Abstract
Gastric cancer (GC) is the fifth-highest ranked cancer for incidence and second for mortality from cancer worldwide. Conversion therapy has recently emerged as an alternative therapy for advanced/metastatic GC patients who are unable to undergo surgical resection at the time of diagnosis. Herein, we present the case of a patient with unresectable stage III GC of high microsatellite instability (MSI), high tumor mutation burden (TMB), and Epstein-Barr virus (EBV) positive. The patient received conversion therapy involving a combination of chemotherapy and immunotherapy regimens. After 3 courses of chemotherapy combined with tislelizumab, the patient underwent laparoscopic radical total gastrectomy. The pathological examination demonstrated that there was no cancerous tissue at the proximal or distal end of the tumor and no lymph node metastases in the lesser or greater curvature, indicating a pathologic complete response. Thereafter, the patient continued tislelizumab treatment to prevent postoperative carcinoma recurrence and metastasis, and to improve prognosis. In conclusion, our study confirmed that chemotherapy combined with immunotherapy is a promising conversion therapy for GC patients with locally unresectable lesions or distant lymph node metastasis, and these findings warrant large-scale clinical studies. This report highlights the clinical importance of next-generation sequencing technology in investigating therapeutic strategy to provide the maximal clinical benefit for patients with GC.
Collapse
Affiliation(s)
- Dan Jian
- Cancer Center, Daping Hospital, Army Medical University, Chongqing, China
| | - Chengyuan Qian
- Cancer Center, Daping Hospital, Army Medical University, Chongqing, China
| | - Dong Wang
- Cancer Center, Daping Hospital, Army Medical University, Chongqing, China
| | - Qiang Ma
- Department of Pathology, Daping Hospital, Army Medical University, Chongqing, China
| | - Li Wang
- Department of Gastric & Colorectal Surgery, Daping Hospital, Army Medical University, Chongqing, China
| | - Chunxue Li
- Department of Gastric & Colorectal Surgery, Daping Hospital, Army Medical University, Chongqing, China
| | - Mingfang Xu
- Cancer Center, Daping Hospital, Army Medical University, Chongqing, China
| | - Nan Dai
- Cancer Center, Daping Hospital, Army Medical University, Chongqing, China
| | - Qian Chen
- Cancer Center, Daping Hospital, Army Medical University, Chongqing, China
| | - Juan He
- Cancer Center, Daping Hospital, Army Medical University, Chongqing, China
| | | | | | | | - Rui Chao
- Department of Orthopaedic Surgery, Chongqing Emergency Medical Center, The Fourth People's Hospital of Chongqing, Chongqing University Central Hospital, Chongqing, China
| | - Yan Feng
- Cancer Center, Daping Hospital, Army Medical University, Chongqing, China
| |
Collapse
|
|
28
|
Wang C, Lin S, Zhang X, Li W. Laparoscopic gastrojejunostomy versus endoscopic stenting combined with conversion therapy for gastric outlet obstruction. Scand J Gastroenterol 2021; 56:1248-1254. [PMID: 34314303 DOI: 10.1080/00365521.2021.1956581] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE There have been no studies comparing laparoscopic gastrojejunostomy (LGJ) and endoscopic metal stent placement (EMSP) combined with conversion therapy for gastric outlet obstruction (GOO) due to incurable advanced gastric cancer (GC). Therefore, the present study examined the short- and long-term outcomes and compared their therapeutic effects. METHODS We retrospectively evaluated the clinical outcomes of 94 patients with GOO due to incurable advanced GC. Patients were assigned to the LGJ (n = 48) or EMSP (n = 46) groups. Multivariate analyses were conducted to identify the factors associated with overall survival. A propensity score-matched analysis was performed to avoid confounding bias. RESULTS Compared to the EMSP group, patients in the LGJ group had fewer postoperative complications, better nutritional and inflammatory status, and a lower positive rate of tumor markers (p < .05). Conversion surgery was performed in 23 and 11 patients in the LGJ and EMSP groups, respectively. The median survival time (MST) in the LGJ group was 13.2 months, compared to 6.8 months for the EMSP group (p < .0001). Propensity score analyses confirmed this result. The MST of patients receiving conversion surgery was significantly better than that of patients without surgery in both the LGJ and EMSP groups (LGJ group: 38.3 months versus 7.6 months; EMSP group: 19.2 months versus 5.3 months, respectively, p < .0001). Multivariate analysis identified treatment selection and conversion surgery as independent prognostic factors for overall survival. CONCLUSION LGJ is an effective and feasible alternative to conversion therapy in terms of short- and long-term outcomes.
Collapse
Affiliation(s)
- Chuandong Wang
- Shengli Clinical Medical College, Fujian Medical University, Fuzhou, China.,Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, China
| | - Shengtao Lin
- Shengli Clinical Medical College, Fujian Medical University, Fuzhou, China.,Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, China
| | - Xiaojuan Zhang
- Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, China.,Department of Radiology, 900th Hospital Logistic Support Forces of PLA, Fuzhou, China
| | - Weihua Li
- Shengli Clinical Medical College, Fujian Medical University, Fuzhou, China.,Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, China
| |
Collapse
|
|
29
|
Wang C, Lin S, Zhang X, Yang C, Li W. Laparoscopic Gastrojejunostomy with Conversion Therapy in Gastric Outlet Obstruction Caused by Incurable Advanced Gastric Cancer. Cancer Manag Res 2021; 13:6847-6857. [PMID: 34512024 PMCID: PMC8420554 DOI: 10.2147/cmar.s322569] [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: 06/01/2021] [Accepted: 08/14/2021] [Indexed: 12/27/2022] Open
Abstract
Purpose The benefits of laparoscopic gastrojejunostomy (LGJ) combined with conversion therapy for malignant gastric outlet obstruction (GOO) caused by incurable advanced gastric cancer (AGC) are unclear. This study aimed to examine the feasibility and efficacy of LGJ followed by enteral nutrition and conversion therapy in malignant GOO. Patients and Methods The clinical outcomes for 66 patients with GOO due to incurable AGC were retrospectively evaluated. The patients were classified into multimodal therapy (LGJ, enteral nutrition, and chemotherapy, n = 35) and chemotherapy alone (n = 31) groups. Conversion surgery was defined as surgery aimed at R0 resection in initially incurable tumours. Results Compared to the chemotherapy group, multimodal therapy patients had improved oral intake, more chemotherapy cycles, better nutritional indices, less sarcopenia, and improved quality of life (QOL) post-treatment. Conversion surgery was performed in 17 multimodal therapy patients, with no perioperative mortality, and R0 resection achieved in 15 patients (88.2%). The median survival time of multimodal therapy patients was 16.7 months, compared to 4.5 months for chemotherapy patients. Multimodal therapy patients with conversion surgery had significantly longer overall survival than those without surgery (44.2 vs 8.5 months, respectively, P< 0.001). Multivariate analysis identified multimodal therapy and improved or stable QOL as independent prognostic factors. Conclusion Multimodal therapy was associated with better nutritional and metabolic status, a safely induced high conversion surgery rate with a high R0 resection rate, and a good prognosis. LGJ with enteral nutrition and conversion therapy may improve long-term survival in obstructive incurable AGC.
Collapse
Affiliation(s)
- Chuandong Wang
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, People's Republic of China.,Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, 350001, People's Republic of China
| | - Shengtao Lin
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, People's Republic of China.,Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, 350001, People's Republic of China
| | - Xiaojuan Zhang
- Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, 350001, People's Republic of China.,Department of Radiology, 900th Hospital Logistic Support Forces of PLA, Fuzhou, 350001, People's Republic of China
| | - Changshun Yang
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, People's Republic of China.,Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, 350001, People's Republic of China
| | - Weihua Li
- Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350001, People's Republic of China
| |
Collapse
|
|
30
|
Namikawa T, Marui A, Yokota K, Fujieda Y, Munekage M, Uemura S, Maeda H, Kitagawa H, Kobayashi M, Hanazaki K. Successful Conversion Surgery for Advanced Gastric Cancer With Multiple Liver Metastases Following Ramucirumab Plus Paclitaxel Combination Treatment. In Vivo 2021; 35:2929-2935. [PMID: 34410989 PMCID: PMC8408704 DOI: 10.21873/invivo.12584] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 06/11/2021] [Accepted: 06/15/2021] [Indexed: 02/07/2023]
Abstract
AIM To present the case of a patient with unresectable gastric cancer showing a remarkable effect by second-line drug treatment with ramucirumab plus paclitaxel and conversion surgery. CASE REPORT A 68-year-old woman who was diagnosed with gastric cancer was referred to us. Esophagogastroduodenoscopy showed an ulcerated lesion with an irregular nodulated border in the lower third of the stomach, and histology of biopsied specimens indicated a poorly differentiated adenocarcinoma. Enhanced computed tomography revealed extensive invasion of the liver, and the patients was treated using S-1 plus oxaliplatin as first-line chemotherapy. Because she developed liver metastases, the treatment regimen was changed to ramucirumab plus paclitaxel as the second-line treatment. After four cycles of weekly paclitaxel with ramucirumab treatment, the liver metastases had completely disappeared. Because no other metastatic lesions in other organs were detected, we performed total gastrectomy with D2 lymphadenectomy. The macroscopic findings of the surgically resected specimen revealed an ulcerated lesion with an irregularly modulated lesion measuring 9.5×4.5 cm. Pathological analysis demonstrated a poorly differentiated adenocarcinoma in the stomach, with invasion to the liver through the serosal layer, and seven lymph node metastases. The postoperative course was unremarkable, and she received ramucirumab in combination with paclitaxel treatment. However, liver metastasis appeared at 4 months after the operation, for which she was treated with irinotecan. Although the patient continued to receive irinotecan chemotherapy for 10 months, her general condition gradually deteriorated, and she was started on best supportive care 13 months after conversion surgery. CONCLUSION Conversion surgery may prolong survival not only through first-line but also second-line treatments in selected patients with unresectable advanced gastric cancer; however, assessments of additional cases and further studies are required to establish this treatment strategy.
Collapse
Affiliation(s)
| | - Akira Marui
- Department of Surgery, Kochi Medical School, Kochi, Japan
| | | | - Yuki Fujieda
- Department of Surgery, Kochi Medical School, Kochi, Japan
| | | | - Sunao Uemura
- Department of Surgery, Kochi Medical School, Kochi, Japan
| | | | | | - Michiya Kobayashi
- Department of Human Health and Medical Sciences, Kochi Medical School, Kochi, Japan
| | | |
Collapse
|
|
31
|
Retrospective evaluation of the effect of Ninjin'yoeito in hepatocellular carcinoma patients treated with lenvatinib. Surg Today 2021; 52:441-448. [PMID: 34417867 DOI: 10.1007/s00595-021-02358-7] [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: 02/26/2021] [Accepted: 06/15/2021] [Indexed: 02/08/2023]
Abstract
PURPOSES Lenvatinib (LEN) is a molecular-target drug, used for unresectable hepatocellular carcinoma (HCC). It is associated with adverse events (AEs), including hypertension, proteinuria, fatigue, and anorexia, which may force dose reduction or discontinuation. Ninjin'yoeito (NYT) is a Chinese-Japanese herbal compound that can effectively treat fatigue and anorexia, and which has been used for chronic liver diseases. NYT reduces AEs and improves the liver function in patients treated with sorafenib but its effect on LEN is unclear. METHODS The present study included 46 patients (male, n = 32; female, n = 14) who received LEN for HCC at our hospital. Their median age was 70 years (range 36-88 years), and their median body weight was 61.5 kg (range 38.4-97.0 kg). Patients were divided into two groups, depending on whether they received NYT medication. Their AEs and liver function were examined one month after starting LEN. RESULTS The NYT group suffered less fatigue (63.6% vs. 11.4%, P = 0.0014) and showed elevated aspartate aminotransferase levels (45.5% vs. 14.3%, P = 0.0433) in comparison to the non-NYT group. The non-NYT group also showed a significantly exacerbated albumin-bilirubin (ALBI) grade (P = 0.0342) and ALBI score (average change: + 0.232, P = 0.0001) at 1 month in comparison to baseline. CONCLUSION NYT apparently suppressed LEN-induced fatigue and helped maintain liver function in patients with HCC.
Collapse
|
|
32
|
Short-term survival and safety of apatinib combined with oxaliplatin and S-1 in the conversion therapy of unresectable gastric cancer. BMC Cancer 2021; 21:702. [PMID: 34126957 PMCID: PMC8204414 DOI: 10.1186/s12885-021-08459-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 06/07/2021] [Indexed: 02/03/2023] Open
Abstract
Background We conducted a single-arm phase II trial to investigate the short-term efficacy and safety of apatinib combined with oxaliplatin and S-1 in the treatment of unresectable gastric cancer. Patients and methods Previously untreated patients with unresectable HER-2-negative advanced gastric cancer were selected. All the patients received six cycles of S-1 and oxaliplatin and five cycles of apatinib, which were administered at intervals of three weeks. The surgery was performed after six cycles of drug treatment. The primary endpoints were radical resection (R0) rate and safety. This study was registered with the China Trial Register, number ChiCTR-ONC-17010430 (01/12/2016–01/12/2022). Results A total of 39 patients were enrolled. Efficacy evaluation was feasible for 37 patients. One patient achieved complete response (CR, 2.7%), 26 patients achieved partial response (PR, 70.3%), three patients had stable disease (SD, 8.1%) and seven patients had progressive disease (PD, 18.9%). The objective response rate (ORR) was 73.0% and the disease control rate (DCR) was 81.1%. 22 patients underwent surgery, among which 14 patients underwent radical resection (R0), with a R0 resection rate of 63.6%. The 1-year survival rate of the surgical group (22 patients) was 71.1% and the 2-year survival rate was 41.1%. The median survival time was 21 months. The incidence of adverse events (AEs) was 100%. Leucopenia (65.3%) and granulocytopenia (69.2%) were the most common hematological AEs. The most common non-hematological AEs were fatigue (51.3%) and oral mucositis (35.9%). Conclusion Apatinib combined with oxaliplatin and S-1 showed good short-term survival and acceptable safety in the conversion therapy of unresectable gastric cancer.
Collapse
|
|
33
|
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.
Collapse
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.)
| |
Collapse
|
|
34
|
Impact of Palliative Gastrectomy in Patients with Incurable Gastric Cancer. ACTA ACUST UNITED AC 2021; 57:medicina57030198. [PMID: 33652574 PMCID: PMC7996496 DOI: 10.3390/medicina57030198] [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: 01/16/2021] [Revised: 02/09/2021] [Accepted: 02/23/2021] [Indexed: 11/28/2022]
Abstract
Background and Objectives: The prognosis of metastatic or unresectable gastric cancer is dismal, and the benefits of the palliative resection of primary tumors with noncurative intent remain controversial. This study aimed to evaluate the impact of palliative gastrectomy (PG) on overall survival in gastric cancer patients. Materials and Methods: One hundred forty-eight gastric cancer patients who underwent PG or a nonresection (NR) procedure between January 2011 and 2017 were retrospectively reviewed to select and analyze clinicopathological factors that affected prognosis. Results: Fifty-five patients underwent primary tumor resection with palliative intent, and 93 underwent NR procedures owing to the presence of metastatic or unresectable disease. The PG group was younger and more female dominant. In the PG group, R1 and R2 resection were performed in two patients (3.6%) and 53 patients (96.4%), respectively. The PG group had a significantly longer median overall survival than the NR group (28.4 vs. 7.7 months, p < 0.001). Multivariate analyses revealed that the overall survival was significantly better after palliative resection (hazard ratio (HR), 0.169; 95% confidence interval (CI), 0.088–0.324; p < 0.001) in patients with American Society of Anesthesiologists Physical Status (ASA) scores ≤1 (HR, 0.506; 95% CI, 0.291–0.878; p = 0.015) and those who received postoperative chemotherapy (HR, 0.487; 95% CI, 0.296–0.799; p = 0.004). Among the patients undergoing palliative resection, the presence of <15 positive lymph nodes was the only significant predictor of better overall survival (HR, 0.329; 95% CI, 0.121–0.895; p = 0.030). Conclusions: PG might lead to the prolonged survival of certain patients with incurable gastric cancer, particularly those with less-extensive lymph-node metastasis.
Collapse
|
|
35
|
Kinoshita J, Yamaguchi T, Moriyama H, Fushida S. Current status of conversion surgery for stage IV gastric cancer. Surg Today 2021; 51:1736-1754. [PMID: 33486610 DOI: 10.1007/s00595-020-02222-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 11/02/2020] [Indexed: 12/23/2022]
Abstract
Palliative chemotherapy with best supportive care is a mainstay for patients with gastric cancer (GC) and distant metastasis. However, with advances in GC chemotherapy, multimodal treatment, including perioperative chemotherapy plus conversion surgery, has attracted attention as a new strategy to improve the outcome of patients with stage IV disease. Conversion surgery is defined as surgical treatment aimed at R0 resection after a good response to induction chemotherapy for tumors originally considered unresectable or marginally resectable for technical and/or oncological reasons. Various biological characteristics differ, depending on each metastatic condition in stage IV GC. The main metastatic pathways of GC can be divided into three categories: lymphatic, hematogenous, and peritoneal. In each category, considerable historical data on conversion surgery have demonstrated the benefits of individualized approaches. However, owing to the diversity of these conditions, a common definition, including the choice of induction chemotherapy, optimal timing of resection, and eligibility for conversion surgery, has not been established among surgical oncologists. Thus, we explore the current and future treatment options by reviewing the literature on this controversial topic comprehensively.
Collapse
Affiliation(s)
- Jun Kinoshita
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Takahisa Yamaguchi
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Hideki Moriyama
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Sachio Fushida
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan.
| |
Collapse
|
|
36
|
Tomonari T, Sato Y, Tanaka H, Tanaka T, Taniguchi T, Sogabe M, Okamoto K, Miyamoto H, Muguruma N, Saito Y, Imura S, Bando Y, Shimada M, Takayama T. Conversion therapy for unresectable hepatocellular carcinoma after lenvatinib: Three case reports. Medicine (Baltimore) 2020; 99:e22782. [PMID: 33080748 PMCID: PMC7571946 DOI: 10.1097/md.0000000000022782] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Lenvatinib (LEN) is a novel potent multi-tyrosine kinase inhibitor, approved as first-line treatment for unresectable hepatocellular carcinoma (HCC). Considering its high objective response rate, LEN therapy could be expected to achieve downstaging of tumors and lead to conversion therapy with hepatectomy or ablation. However, the feasibility of conversion therapy after LEN treatment in unresectable HCC remains largely unknown. PATIENT CONCERNS Here, we reported 3 cases of unresectable HCC: case 1, a 69-year-old man diagnosed with ruptured HCC; case 2, a 72-year-old woman with nonalcoholic steatohepatitis-based HCC; and case 3, a 73-year-old man with a history of alcoholic cirrhosis-based HCC. DIAGNOSIS In all cases, cirrhosis was classified as Child-Pugh 5 and modified albumin-bilirubin grade 1 or 2a. HCC was diagnosed as Barcelona Clinic Liver Cancer (BCLC) stage B. INTERVENTIONS In all cases, LEN was initiated after conventional-transcatheter arterial embolization enforcement, while maintaining liver function. OUTCOMES In all cases, the main tumor size decreased after 6 months of LEN treatment and no satellite nodes were detected, indicating downstaging of HCC to BCLC stage A. Subsequently, conversion hepatectomy or ablation was performed. After successful conversion therapy, the general condition of the patients was good, without tumor recurrence during the observation period (median 10 months). LESSONS This study demonstrated that LEN enables downstaging of HCC and thus represents a bridge to successful surgery or ablation therapy. In particular, LEN treatment may facilitate the possibility for conversion therapy of initially unresectable HCC, while maintaining the hepatic functional reserve.
Collapse
Affiliation(s)
- Tetsu Tomonari
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School
| | - Yasushi Sato
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School
| | - Hironori Tanaka
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School
| | - Takahiro Tanaka
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School
| | - Tatsuya Taniguchi
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School
| | - Masahiro Sogabe
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School
| | - Koichi Okamoto
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School
| | - Hiroshi Miyamoto
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School
| | - Naoki Muguruma
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School
| | - Yu Saito
- Department of Digestive and Transplant Surgery, Tokushima University
| | - Satoru Imura
- Department of Digestive and Transplant Surgery, Tokushima University
| | - Yoshimi Bando
- Molecular and Environmental Pathology, University of Tokushima Graduate School, Tokushima, Japan
| | - Mitsuo Shimada
- Department of Digestive and Transplant Surgery, Tokushima University
| | - Tetsuji Takayama
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School
| |
Collapse
|
|
37
|
Zhang X, Huang H, Wei Z, Zhu Z, Yang D, Fu H, Xu J, Hu Z, Zhang Y, You Q, Huang X, Yan R, Wang W, Cai Q. Comparison of Docetaxel + Oxaliplatin + S-1 vs Oxalipatin + S-1 as Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer: A Propensity Score Matched Analysis. Cancer Manag Res 2020; 12:6641-6653. [PMID: 32801898 PMCID: PMC7398747 DOI: 10.2147/cmar.s258360] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 07/03/2020] [Indexed: 12/24/2022] Open
Abstract
Background What is the optimal neoadjuvant chemotherapy (NAC) regimen for locally advanced gastric cancer (LAGC) remains debatable. The objective of this study was to compare the efficacy of docetaxel+oxaliplatin+S-1 (DOS) vs oxaliplatin+S-1 (SOX) as NAC for LAGC. Methods Data of 248 LAGC patients who received either DOS or SOX as NAC in our hospital between January 2010 and January 2018 were reviewed retrospectively. Propensity score matched (PSM) analysis was applied to minimize the selection bias in both groups. Prognostic factors were screened by univariate and multivariate Cox regression analyses. Results Of the 248 LAGC patients included, 180 patients were subjected to the PSM analysis. Patients in DOS group showed a better tumor response to NAC, higher radical resection rate and R0 resection rate than those in SOX group. The overall survival (OS) rate in DOS group was better than that in SOX group, although the overall incidence of Grade 3/4 NAC-related toxicity in DOS group was higher, as represented by leukopenia and neutropenia. Multivariate analysis revealed that the NAC regimen, cTNM stage and the R0 resection rate were independent prognostic factors. In addition, patients with TLND less than 16 population showed a worse OS rate. Subgroup analysis indicated that patients benefited from the addition of docetaxel regardless of the clinical T stage, but those with high clinical N stages (N2-3) did not. Conclusion DOS is a safe and feasible NAC regimen for LAGC, which is worth popularizing in clinical practice.
Collapse
Affiliation(s)
- Xin Zhang
- Department of Gastrointestinal Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China
| | - Hejing Huang
- Department of Ultrasound, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China
| | - Ziran Wei
- Department of Gastrointestinal Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China
| | - Zhenxin Zhu
- Department of Gastrointestinal Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China
| | - Dejun Yang
- Department of Gastrointestinal Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China
| | - Hongbing Fu
- Department of Gastrointestinal Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China
| | - Jiapeng Xu
- Department of Gastrointestinal Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China
| | - Zunqi Hu
- Department of Gastrointestinal Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China
| | - Yu Zhang
- Department of Gastrointestinal Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China
| | - Qing You
- Department of Gastrointestinal Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China
| | - Xin Huang
- Department of Gastrointestinal Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China
| | - Ronglin Yan
- Department of Gastrointestinal Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China
| | - Weimin Wang
- Department of Gastrointestinal Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China
| | - Qingping Cai
- Department of Gastrointestinal Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China
| |
Collapse
|
|
38
|
Jiang D, Xu Y, Chen Y, Jiang J, Wang M, Yang M, Chen Z, Yang L. Apatinib Combined With SOX Regimen in Conversion Treatment of Advanced Gastric Cancer: A Case Series and Literature Review. Front Pharmacol 2020; 11:1027. [PMID: 32765260 PMCID: PMC7381218 DOI: 10.3389/fphar.2020.01027] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Accepted: 06/24/2020] [Indexed: 12/30/2022] Open
Abstract
Gastric cancer is a common digestive tract tumor and the second most prevalent cancer. The prognosis of advanced gastric cancer is poor. Conversion therapy can reduce tumor burden, downgrade tumor, and increase the possibility of complete resection, thus prolonging the survival time of patients with gastric cancer. In conversion therapy, chemotherapy and targeted therapy are the main methods of medical treatment, which can control tumor growth and recurrence. As an antiangiogenic targeted drug, apatinib is widely used in the third-line treatment of advanced gastric cancer. Recent studies have shown that it may be of great help in rapid reduction of tumor stage and improvement of prognosis in conversion therapy. This study reported three cases of gastric cancer complicated with multiple abdominal and retroperitoneal lymph node metastases. After receiving apatinib combined with SOX regimen for four cycles, computed tomography showed that the focus and lymph node metastasis were reduced after treatment, and primary tumors were resected. Postoperative pathology result showed that the patients got R0 resection. After radical surgery, the maintenance therapy including apatinib was given. The progression-free survival time was more than 10 months. Apatinib combined with SOX regimen as a conversion therapy for advanced gastric adenocarcinoma increases the possibility of successful surgical resection, which might prolong the survival time of patients.
Collapse
Affiliation(s)
- Dingyi Jiang
- Department of Medical Oncology, The Qingdao University Medical College, Qingdao, China
| | - Yunyun Xu
- Department of Medical Oncology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China
| | - Yunwang Chen
- Department of Medical Oncology, The Qingdao University Medical College, Qingdao, China
| | - Jiahong Jiang
- Department of Medical Oncology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China
| | - Mingxing Wang
- Department of Medical Oncology, Bengbu Medical College, Bengbu, China
| | - Min Yang
- Department of Medical Oncology, The Qingdao University Medical College, Qingdao, China
| | - Zheling Chen
- Department of Medical Oncology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China
| | - Liu Yang
- Department of Medical Oncology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China
| |
Collapse
|
|
39
|
Abstract
INTRODUCTION Proactive palliative care can effectively relieve symptoms early and effectively as well as improve the quality of life of patients with gastric adenocarcinoma (GAC). AREAS COVERED The review summarizes palliative care for GAC. GAC caused specific symptoms, such as malignant gastric outlet obstruction (GOO), bleeding, weight loss, and/or ascites, therefore, these symptoms must be addressed specifically. EXPERT OPINION Palliative care should start early to control general symptoms, thus may improve the patient's condition to make the patient eligible for anti-cancer treatment. As some stage IV GAC patients can now live longer, palliative interventions become more important. A multimodality interdisciplinary approach is strongly encouraged.
Collapse
|
|
40
|
Jeong GS, Lee IS, Park YS, Kim BS, Yoo MW, Yook JH, Kim BS. Advantages of ypTNM Staging in Post-surgical Prognosis for Initially Unresectable or Stage IV Gastric Cancers. J Gastric Cancer 2020; 20:233-244. [PMID: 33024580 PMCID: PMC7521980 DOI: 10.5230/jgc.2020.20.e20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Revised: 04/16/2020] [Accepted: 05/01/2020] [Indexed: 11/29/2022] Open
Abstract
Purpose For unresectable or initially metastatic gastric cancer, conversion surgery (CVS), after systemic chemotherapy, has received attention as a treatment strategy. This study evaluated the prognostic value of ypTNM stage and the oncologic outcomes in patients receiving CVS. Materials and Methods A retrospective review of clinicopathologic findings and oncologic outcomes of 116 patients who underwent CVS with curative intent, after combination chemotherapy, between January 2000 and December 2015, has been reported here. Results Twenty-six patients (22.4%) underwent combined resection of another organ and 12 patients received para-aortic lymphadenectomy (10.3%). Pathologic complete remission (CR) was confirmed in 11 cases (9.5%). The median overall survival (OS) and disease-free survival (DFS) times were 35.0 and 21.3 months, respectively. In multivariate analysis, ypTNM stage was the sole independent prognostic factor for DFS (P=0.042). Tumors invading an adjacent organ or involving distant lymph nodes showed better survival than those with peritoneal seeding or solid organ metastasis (P=0.084). Kaplan-Meier curves showed that the 3-year OS rate of patients with pathologic CR and those with CR of the primary tumor but residual node metastasis was 81.8% and 80.0%, respectively. OS was 65.8% for stage 1 patients, 49.8% for those at stage 2, and 36.3% for those at stage 3. Conclusions The ypTNM staging is a significant prognostic factor in patients who underwent CVS for localized unresectable or stage IV gastric cancers. Patients with locally advanced but unresectable lesions or with tumors with distant nodal metastasis may be good candidates for CVS.
Collapse
Affiliation(s)
- Gyu-Seong Jeong
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - In-Seob Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-Soo Park
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Beom-Su Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Moon-Won Yoo
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeong-Hwan Yook
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Byung-Sik Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| |
Collapse
|
|
41
|
Nakagawa T, Sato Y, Tanahashi T, Mitsui Y, Kida Y, Fujino Y, Hirata M, Kitamura S, Miyamoto H, Okamoto K, Muguruma N, Bando Y, Takayama T. JMJD2A sensitizes gastric cancer to chemotherapy by cooperating with CCDC8. Gastric Cancer 2020; 23:426-436. [PMID: 31677131 DOI: 10.1007/s10120-019-01024-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Accepted: 10/14/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Jumonji domain-containing protein 2A (JMJD2A) of the JMJD2 family of histone lysine demethylases has been implicated in tumorigenesis. However, its expression and role in gastric cancer (GC) drug resistance remain unknown. Here, we investigated the role of JMJD2A in GC chemotherapeutic susceptibility and its clinical relevance in GC. METHODS We selected 12 relevant genes from previously identified gene signatures that can predict GC susceptibility to docetaxel, cisplatin, and S-1 (DCS) therapy. Each gene was knocked down using siRNA in GC cell lines, and cell viability assays were performed. JMJD2A expression in GC cell lines and tissues was assessed using qRT-PCR and immunohistochemistry, respectively. A JMJD2A downstream target related to drug susceptibility was examined using whole-gene expression array and immunoprecipitation. RESULTS Among the 12 candidate genes, down-regulation of JMJD2A showed the maximum effect on GC susceptibility to anti-cancer drugs and increased the IC50 values for 5-FU, cisplatin, and docetaxel 15.3-, 2.7-, and 4.0-fold, respectively. JMJD2A was universally expressed in 12 GC cell lines, and its overexpression in GC tissue was positively correlated with tumor regression in 34 DCS-treated patients. A whole-gene expression array of JMJD2A-knockdown GC cells demonstrated a significant decrease in the expression of pro-apoptotic coiled-coil domain containing 8 (CCDC8), a downstream target of JMJD2A. Direct interaction between CCDC8 and JMJD2A was verified using immunoprecipitation. CCDC8 inhibition restored drug resistance to docetaxel, cisplatin, and S-1. CONCLUSIONS Our results indicate that JMJD2A is a novel epigenetic factor affecting GC chemotherapeutic susceptibility, and JMJD2A/CCDC8 is a potential GC therapeutic target.
Collapse
Affiliation(s)
- Tadahiko Nakagawa
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan.,Department of Health and Nutrition, Faculty of Nursing and Nutrition, The University of Shimane, Shimane, 693-8550, Japan
| | - Yasushi Sato
- Department of Community Medicine for Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School of Biomedical Sciences, Tokushima, 770-8503, Japan.
| | - Toshihito Tanahashi
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan
| | - Yasuhiro Mitsui
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan
| | - Yoshifumi Kida
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan
| | - Yasuteru Fujino
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan
| | - Misato Hirata
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan
| | - Shinji Kitamura
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan
| | - Hiroshi Miyamoto
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan
| | - Koichi Okamoto
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan
| | - Naoki Muguruma
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan
| | - Yoshimi Bando
- Division of Pathology, Tokushima University Hospital, Tokushima, 770-8503, Japan
| | - Tetsuji Takayama
- Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan
| |
Collapse
|
|
42
|
Wang D, Li W, Yin L, Du Y, Zhang S, Suo J. Association of serum levels of deoxyribose 1-phosphate and S-lactoylglutathione with neoadjuvant chemotherapy sensitivity in patients with gastric cancer: A metabolomics study. Oncol Lett 2020; 19:2231-2242. [PMID: 32194721 PMCID: PMC7039117 DOI: 10.3892/ol.2020.11350] [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: 03/23/2019] [Accepted: 01/07/2020] [Indexed: 12/15/2022] Open
Abstract
The present study screened serum samples from patients with advanced-stage gastric cancer and known sensitivities to neoadjuvant chemotherapy, in order to identify metabolites that may serve as potential biomarkers for chemotherapy sensitivity. A total of 47 patients with stage III (T4b) or IV gastric cancer, including 31 in the training group and 16 in a validation group, were classified based on their responses to conversion therapy consisting of oxaliplatin, tegafur and continuous hyperthermic peritoneal perfusion with cisplatin. Serum samples were analyzed by liquid chromatography-mass spectrometry to obtain a metabolite profile of each patient. Patients who were responsive and non-responsive to neoadjuvant chemotherapy exhibited significant differences in serum levels of deoxyribose 1-phosphate, S-lactoylglutathione, lysophosphatidylcholine (16:0) and O-arachidonoyl ethanolamine. Logistic regression analysis indicated that deoxyribose 1-phosphate and S-lactoylglutathione were independently associated with chemosensitivity. Serum levels of deoxyribose 1-phosphate and S-lactoylglutathione were independently associated with the sensitivity of gastric cancer to neoadjuvant chemotherapy, therefore, serving as potential predictors of patient response.
Collapse
Affiliation(s)
- Daguang Wang
- Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Wei Li
- Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Lei Yin
- Research Institute of Translational Medicine, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Yechao Du
- Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Shaopeng Zhang
- Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Jian Suo
- Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.,Jilin Province Key Laboratory of Bioinformatics for Gastrointestinal Tumor, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| |
Collapse
|
|
43
|
Wang Z, Chen JQ, Liu JL, Tian L. Issues on peritoneal metastasis of gastric cancer: an update. World J Surg Oncol 2019; 17:215. [PMID: 31829265 PMCID: PMC6907197 DOI: 10.1186/s12957-019-1761-y] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2019] [Accepted: 11/26/2019] [Indexed: 12/19/2022] Open
Abstract
Background Peritoneal metastasis (PM) is one of the most common forms of metastasis with a very poor prognosis in patients with gastric cancer (GC). The mechanisms, diagnosis, and management of PM remain controversial. Main body Stephen Paget’s “seed-and-soil” hypothesis gives us an illustration of the mechanisms of PM. Recently, hematogenous metastasis and exosomes from GC are identified as novel mechanisms for PM. Diagnostic accuracy of conventional imaging modalities for PM is not satisfactory, but texture analysis may be a useful adjunct for the prediction of PM. Biological markers in peritoneal washings are helpful in identifying patients at high risk of PM, but many limitations remain to be overcome. Response of PM from systemic chemotherapy alone is very limited. However, conversion therapy is confirmed to be safe and able to prolong the survival of GC patients with PM. As an important part of conversion therapy, intraperitoneal chemotherapy with taxanes has become an ideal approach with several advantages. Additionally, gastrectomy should be considered in patients who would tolerate surgery if a remarkable response to chemotherapy was observed. Conclusion Texture analysis is a reliable adjunct for the prediction of PM, and conversion therapy provides a new choice for GC patients with PM. The underlying mechanisms and new biological markers for GC patients with PM should be the direction of future studies. Furthermore, significant aspects of conversion therapy, such as timing and method of the operation, and the indications remain to be clarified.
Collapse
Affiliation(s)
- Zhen Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi Zhuang Autonomous Region, China.
| | - Jun-Qiang Chen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi Zhuang Autonomous Region, China.
| | - Jin-Lu Liu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi Zhuang Autonomous Region, China
| | - Lei Tian
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi Zhuang Autonomous Region, China
| |
Collapse
|
|
44
|
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.
Collapse
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
| |
Collapse
|
|
45
|
Conversion gastrectomy for stage IV unresectable gastric cancer: a GIRCG retrospective cohort study. Gastric Cancer 2019; 22:1285-1293. [PMID: 31065878 DOI: 10.1007/s10120-019-00968-2] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Accepted: 04/25/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND The aim of this study is to report the experience with conversion surgery from six Gruppo Italiano Ricerca Cancro Gastrico (GIRCG) centers, focusing our analysis on factors affecting survival and the risk of recurrence. METHODS A retrospective, multicenter cohort study was performed in patients who had undergone conversion gastrectomy between 2005 and 2017. Data were extracted from a GIRCG database including all metastatic gastric cancer patients submitted to surgery. Only stage IV unresectable tumors/metastases which became resectable after chemotherapy were included in this analysis. RESULTS Forty-five resected M1 patients were included in the analysis. Reasons for being deemed unresectable at diagnosis were peritoneal involvement (PCI > 6) (n = 38, 84.4%), distant metastatic nodes (n = 3, 6.6%) and extensive liver involvement (n = 4, 8.8%). Median follow-up was 25 months (IQR 9-50). Median overall survival from surgery was 15 months and 1-, 3- and 5-year survivals were 57.2, 36.1 and 24%, respectively. Median progression-free survival was 12 months with 1- and 3-year survival of 46.4 and 33.9%, respectively. At cox regression analysis the only independent prognostic factor for OS was the presence of more than one type of metastasis (HR 4.41, 95% CI 1.72-11.3, p = 0.002). A positive microscopic resection margin was the only risk factor for recurrence (HR 5.72, 95% CI 1.04-31.4, p = 0.045). CONCLUSIONS Unresectable stage IV GC patients could benefit from radical surgery after chemotherapy and achieve long survivals. The main prognostic factor for these patients was the presence of more than one type of extra-gastric metastatic involvement.
Collapse
|
|
46
|
Zhang P, Li S, Chen Z, Lu Y, Zhang H. LncRNA SNHG8 promotes proliferation and invasion of gastric cancer cells by targeting the miR-491/PDGFRA axis. Hum Cell 2019; 33:123-130. [DOI: 10.1007/s13577-019-00290-0] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Accepted: 10/04/2019] [Indexed: 12/24/2022]
|
|
47
|
Wang T, Wang N, Ren H, Zhou H, Zhou A, Jin J, Chen Y, Zhao D. Long-term Results of Conversion Therapy for Initially Unresectable Gastric Cancer: Analysis of 122 Patients at the National Cancer Center in China. J Cancer 2019; 10:5975-5985. [PMID: 31762807 PMCID: PMC6856572 DOI: 10.7150/jca.35527] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2019] [Accepted: 08/18/2019] [Indexed: 02/07/2023] Open
Abstract
Purpose: To assess the long-term survival and prognostic factors of conversion therapy in patients with initially unresectable gastric cancer. Patients and methods: We conducted a retrospective study of clinicopathological and survival data of 122 consecutive patients who were diagnosed with initially unresectable gastric cancer and underwent the conversion surgery after systemic chemotherapy at the China National Cancer Center between May 2006 and May 2017. Results: For all the 122 patients, the 3- and 5-year overall survival (OS) rates from the date of chemotherapy initiation were 61.0% and 52.0%, respectively, with a median OS of 63.6 months. During follow-up, the recurrence was observed in 49 (40.1%) patients who underwent conversion surgery. According to the multivariate COX regression analysis, receipt of postoperative adjuvant chemotherapy (POAC) was the only significant independent predictor of a favorable OS (HR 0.40; 95% CI 0.18-0.85, P=0.017). Log-rank analysis showed that POAC group experienced a survival advantage in terms of PFS when compared with observation group (HR 0.53, 95%CI 0.31-0.92, P=0.009). Conclusions: Conversion therapy may provide long-term survival for patients with initially unresectable gastric cancer. Postoperative adjuvant chemotherapy might be recommended for patients who underwent conversion therapy.
Collapse
Affiliation(s)
- Tongbo Wang
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Nianchang Wang
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Hu Ren
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Hong Zhou
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Aiping Zhou
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jing Jin
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yingtai Chen
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Dongbing Zhao
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| |
Collapse
|
|
48
|
Sato S, Kunisaki C, Tanaka Y, Sato K, Miyamoto H, Yukawa N, Kosaka T, Akiyama H, Endo I, Misumi T. Curative-Intent Surgery for Stage IV Advanced Gastric Cancer: Who Can Undergo Surgery and What Are the Prognostic Factors for Long-Term Survival? Ann Surg Oncol 2019; 26:4452-4463. [PMID: 31529308 DOI: 10.1245/s10434-019-07790-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND A retrospective study was performed to evaluate the predictive factors for performing curative-intent surgery and prognostic factors for long-term survival of patients undergoing surgery for stage IV gastric cancer. PATIENTS AND METHODS Between 2001 and 2017, 271 patients with stage IV gastric cancer with distant metastasis who underwent systemic chemotherapy were enrolled. Logistic regression analysis was performed to evaluate predictive factors for curative-intent surgery. Cox proportional hazards regression model was applied for patients who were subsequently treated with curative-intent surgery to identify prognostic factors for long-term survival. RESULTS Curative-intent surgery was performed in 48 patients (17.7%). Median survival time was significantly longer in the surgery group than in the nonsurgery group (53 vs. 11 months, p < 0.0001). R0 resection was performed in 35 patients (72.9%). The three-year overall survival (OS) rates of the R0, R1, and R2 surgery groups were 75.4%, 33.3%, and 25.0%, respectively (p = 0.0002). Logistic regression analysis revealed that lymphogenous distant metastasis alone (odds ratio = 3.276, p = 0.004), positive lavage cytology alone (6.394, 0.014), doublet or triplet chemotherapy (4.064, 0.034), and high Glasgow prognostic score (0.276, 0.001) were independent predictive factors for performing curative-intent surgery. Among patients undergoing surgery, the Cox proportional hazards regression model for OS showed that R0 surgery was an independent prognostic factor for favorable OS (hazard ratio 0.188, p = 0.022). CONCLUSIONS Patients with lymphogenous distant metastasis alone, P0CY1 alone, good immunonutritional status, and doublet/triplet chemotherapy are candidates for performing effective curative-intent surgery. R0 surgery is crucial for improving long-term survival after surgery.
Collapse
Affiliation(s)
- Sho Sato
- Department of Surgery, Gastroenterological Center, Yokohama City University, Yokohama City, Kanagawa, Japan.,Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama City, Kanagawa, Japan
| | - Chikara Kunisaki
- Department of Surgery, Gastroenterological Center, Yokohama City University, Yokohama City, Kanagawa, Japan.
| | - Yusaku Tanaka
- Department of Surgery, Gastroenterological Center, Yokohama City University, Yokohama City, Kanagawa, Japan
| | - Kei Sato
- Department of Surgery, Gastroenterological Center, Yokohama City University, Yokohama City, Kanagawa, Japan
| | - Hiroshi Miyamoto
- Department of Surgery, Gastroenterological Center, Yokohama City University, Yokohama City, Kanagawa, Japan
| | - Norio Yukawa
- Department of Surgery, Gastroenterological Center, Yokohama City University, Yokohama City, Kanagawa, Japan
| | - Takashi Kosaka
- Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama City, Kanagawa, Japan
| | - Hirotoshi Akiyama
- Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama City, Kanagawa, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama City, Kanagawa, Japan
| | - Toshihiro Misumi
- Department of Biostatistics, School of Medicine, Yokohama City University, Yokohama City, Kanagawa, Japan
| |
Collapse
|
|
49
|
Nakamura M, Ojima T, Nakamori M, Katsuda M, Tsuji T, Hayata K, Kato T, Yamaue H. Conversion Surgery for Gastric Cancer with Peritoneal Metastasis Based on the Diagnosis of Second-Look Staging Laparoscopy. J Gastrointest Surg 2019; 23:1758-1766. [PMID: 30264385 DOI: 10.1007/s11605-018-3983-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Accepted: 09/17/2018] [Indexed: 01/31/2023]
Abstract
BACKGROUND Patients with positive peritoneal cytology (CY1) or peritoneal dissemination (P1) have significantly poor prognosis. We performed pre-therapeutic staging laparoscopy (SL) to diagnose peritoneal metastasis for patients with advanced gastric cancer. When peritoneal metastasis disappears by chemotherapy for patients with CY1 or P1, we have intention to perform conversion surgery (CS). This study aims to clarify the clinical significance of CS for such patients. METHODS We retrospectively analyzed clinical outcomes of 115 patients with advanced gastric cancer (large type 3, type 4, serosa-invasion) who underwent SL between 2005 and 2014. Disappearance of peritoneal metastasis was confirmed by second-look SL. RESULTS CY0P0, CY1P0, and P1 were found in 56, 26, and 33 patients, respectively. In patients with CY1P0, 12 patients (66.7%) underwent CS (R0) as peritoneal cytology turned negative. All cases received S-1-based regimens, with median five treatment courses. The survival of patients with CS was significantly longer than those without CS (median survival time (MST); 41 vs. 11 months, respectively, P < 0.001). We observed no difference in overall survival between patients who underwent CS and patients with CY0P0 at the first SL (P = 0.913). All patients with P1 received chemotherapy. As peritoneal metastasis of five patients (15.2%) disappeared by chemotherapy, those patients underwent the CS (R0). The survival of patients who underwent CS was significantly longer than those who did not (MST; 31 vs. 10 months, respectively, P = 0.034). CONCLUSION This study suggests that conversion surgery contributes to improvement in survival of patients with peritoneal metastasis.
Collapse
Affiliation(s)
- Masaki Nakamura
- Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8510, Japan
| | - Toshiyasu Ojima
- Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8510, Japan
| | - Mikihito Nakamori
- Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8510, Japan
| | - Masahiro Katsuda
- Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8510, Japan
| | - Toshiaki Tsuji
- Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8510, Japan
| | - Keiji Hayata
- Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8510, Japan
| | - Tomoya Kato
- Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8510, Japan
| | - Hiroki Yamaue
- Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8510, Japan.
| |
Collapse
|
|
50
|
Zheng XH, Zhang W, Yang L, Du CX, Li N, Xing GS, Tian YT, Xie YB. Role of D2 gastrectomy in gastric cancer with clinical para-aortic lymph node metastasis. World J Gastroenterol 2019; 25:2338-2353. [PMID: 31148905 PMCID: PMC6529887 DOI: 10.3748/wjg.v25.i19.2338] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Revised: 04/17/2019] [Accepted: 04/29/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Owing to the technical difficulty of pathological diagnosis, imaging is still the most commonly used method for clinical diagnosis of para-aortic lymph node metastasis (PALM) and evaluation of therapeutic effects in gastric cancer, which leads to inevitable false-positive findings in imaging. Patients with clinical PALM may have entirely different pathological stages (stage IV or not), which require completely different treatment strategies. There is no consensus on whether surgical intervention should be implemented for this group of patients. In particular, the value of D2 gastrectomy in a multidisciplinary treatment (MDT) approach for advanced gastric cancer with clinical PALM remains unknown.
AIM To investigate the value of D2 gastrectomy in a MDT approach for gastric cancer patients with clinical PALM.
METHODS In this real-world study, clinico-pathological data of all gastric cancer patients treated at the Cancer Hospital, Chinese Academy of Medical Sciences between 2011 and 2016 were reviewed to identify those with clinically enlarged PALM. All the clinico-pathological data were prospectively documented in the patient medical record. For all the gastric cancer patients with advanced stage disease, especially those with suspicious distant metastasis, the treatment methods were determined by a multidisciplinary team.
RESULTS In total, 48 of 7077 primary gastric cancer patients were diagnosed as having clinical PALM without other distant metastases. All 48 patients received chemotherapy as the initial treatment. Complete or partial response was observed in 39.6% (19/48) of patients in overall and 52.1% (25/48) of patients in the primary tumor. Complete response of PALM was observed in 50.0% (24/48) of patients. After chemotherapy, 45.8% (22/48) of patients received D2 gastrectomy, and 12.5% (6/48) of patients received additional radiotherapy. The postoperative major complication rate and mortality were 27.3% (6/22) and 4.5% (1/22), respectively. The median overall survival and progression-free survival of all the patients were 18.9 and 12.1 mo, respectively. The median overall survival of patients who underwent surgical resection or not was 50.7 and 12.8 mo, respectively. The 3-year and 5-year survival rates were 56.8% and 47.3%, respectively, for patients who underwent D2 resection. Limited PALM and complete response of PALM after chemotherapy were identified as favorable factors for D2 gastrectomy.
CONCLUSION For gastric cancer patients with radiologically suspicious PALM that responds well to chemotherapy, D2 gastrectomy could be a safe and effective treatment and should be adopted in a MDT approach for gastric cancer with clinical PALM.
Collapse
Affiliation(s)
- Xiao-Hao Zheng
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Wen Zhang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Lin Yang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Chun-Xia Du
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ning Li
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Gu-Sheng Xing
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yan-Tao Tian
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yi-Bin Xie
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| |
Collapse
|