|
1
|
Ng D, Cyr D, Khan S, Dossa F, Swallow C, Kazazian K. Molecular mechanisms of metastatic peritoneal dissemination in gastric adenocarcinoma. Cancer Metastasis Rev 2025; 44:50. [PMID: 40317360 PMCID: PMC12049340 DOI: 10.1007/s10555-025-10265-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Accepted: 04/17/2025] [Indexed: 05/07/2025]
Abstract
Peritoneal dissemination portends a dismal prognosis in patients with gastric adenocarcinoma in the context of limited effective treatments. The underlying cellular processes that drive gastric peritoneal carcinomatosis remain unclear, limiting the application of novel targeted therapies. In this comprehensive review, we aimed to identify and summarize all existing context-dependent molecular mechanisms that have been implicated in peritoneal dissemination and peritoneal carcinomatosis establishment from primary gastric adenocarcinoma. We applied a multilevel examination including data from in vivo murine models using human gastric cancer cell lines, in vitro technique-based studies, ex vivo models, and genomic/proteomic and molecular profiling analyses to report on various aspects of gastric cancer peritoneal metastasis biology. Mechanisms promoting peritoneal dissemination were grouped into three main functional categories: (1) intrinsic cancer cell biology, (2) cancer cell-peritoneal surface adhesion, and (3) peritoneal tumor microenvironment. We identified significant overlap among the three categories, indicating a complex interplay between multiple molecular mechanisms. By interrupting these pathways, peritoneal-directed therapies have the potential to improve quality and length of life in patients with high-risk primary gastric cancer.
Collapse
Affiliation(s)
- Deanna Ng
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada
- Institute of Medical Science, University of Toronto, Toronto, Canada
- Department of Surgery, University of Toronto, Toronto, Canada
| | - David Cyr
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada
- Institute of Medical Science, University of Toronto, Toronto, Canada
- Department of Surgery, University of Toronto, Toronto, Canada
| | - Shawn Khan
- Institute of Medical Science, University of Toronto, Toronto, Canada
- Department of Surgery, University of Toronto, Toronto, Canada
| | - Fahima Dossa
- Complex General Surgical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Carol Swallow
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada
- Institute of Medical Science, University of Toronto, Toronto, Canada
- Department of Surgery, University of Toronto, Toronto, Canada
| | - Karineh Kazazian
- Department of Surgery, University of Toronto, Toronto, Canada.
- Department of Surgical Oncology, Toronto General Hospital, University Health Network, 200 Elizabeth Street, 10 Eaton North, Room 219, Toronto, M5G 2 C4, Canada.
| |
Collapse
|
|
2
|
Liu W, Li L, Guo L, Li H, Tang Z, Wang X, Huang L, Sun Y. Dasatinib demonstrates efficacy in organoid derived paclitaxel-resistant Trp53/Cdh1-deficient mouse gastric adenocarcinoma with peritoneal metastasis. CELL REGENERATION (LONDON, ENGLAND) 2025; 14:16. [PMID: 40299206 PMCID: PMC12040775 DOI: 10.1186/s13619-025-00232-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 03/31/2025] [Accepted: 04/02/2025] [Indexed: 04/30/2025]
Abstract
Gastric cancer peritoneal metastasis (GCPM) typically indicates a poor clinical prognosis and is frequently observed in diffuse gastric cancer (GC) patients with CDH1 loss of function. GCPM characterized for its aggressiveness and resistance to chemotherapy, most notably paclitaxel (PTX), poses significant treatment challenges. Previously, no mouse gastric adenocarcinoma (MGA) cell lines with Trp53 (encoding mouse p53) and Cdh1 (encoding mouse E-cadherin) mutations and a high potential for peritoneal metastasis in mice have been established. Here, we derived a mouse GC cell line, called MTC, from subcutaneously transplanted mouse Trp53-/-Cdh1-/- GC organoids. Through matching the short tandem repeat profile of MTC with those in current cell banks, we verified the uniqueness of MTC. Furtherly, we confirmed the features of MTC by detecting the expression of p53, E-cadherin, and pan-CK. After long-term exposure of the original MTC line to PTX, we developed a more aggressive, PTX-resistant cell line, termed MTC-R. Compared with MTC, MTC-R demonstrated enhanced tumorigenicity and high potential for peritoneal metastasis in subcutaneous and intraperitoneal tumour models both in BALB/c nude mice and C57BL/6 J mice. Transcriptome analysis revealed the ECM‒receptor interaction pathway activation during the development of PTX resistance, and dasatinib (DASA) was identified as a potential drug targeting this pathway. DASA showed promise in ameliorating disease progression and improving overall survival in MTC-R GCPM model in C57BL/6 J mice. Overall, we established a novel MGA cell line with Trp53 and Cdh1 mutations and its PTX-resistant variant and demonstrated the efficacy of DASA in treating PTX-resistant GCPM.
Collapse
Affiliation(s)
- Wenshuai Liu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Gastric Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Retroperitoneal Sarcoma Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Lingmeng Li
- Key Laboratory of Systems Biomedicine (Ministry of Education) and Collaborative Innovation Center of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Leilei Guo
- Key Laboratory of Systems Biomedicine (Ministry of Education) and Collaborative Innovation Center of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Haojie Li
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Gastric Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Zhaoqing Tang
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Gastric Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Xuefei Wang
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
- Gastric Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
| | - Liyu Huang
- Key Laboratory of Systems Biomedicine (Ministry of Education) and Collaborative Innovation Center of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
| | - Yihong Sun
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
- Gastric Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
| |
Collapse
|
|
3
|
Gingrich A, Manguso N, Zuckerman R. Treatment of Gastric Cancer Carcinomatosis. Surg Clin North Am 2025; 105:95-107. [PMID: 39523079 DOI: 10.1016/j.suc.2024.06.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
Patients with gastric cancer peritoneal metastases (GCPM) have Stage IV disease. Systemic therapy is a crucial aspect of their care. Patients with GCPM should have their tumors tested for HER2 and PD-L1 expression and microsatellite instability for potential targeted therapies. If patients with synchronous GCPM have stable disease following neoadjuvant therapy, surgical intervention can be considered. Patients with positive cytology or low-volume peritoneal disease (peritoneal carcinomatosis index [PCI] < 7) may "convert" to negative cytology or resolution of peritoneal metastases following intraperitoneal therapy and may be candidates for subsequent gastrectomy.
Collapse
Affiliation(s)
- Alicia Gingrich
- Division of Surgery, Department of Surgical Oncology, MD Anderson Cancer Center, Houston, TX 77025, USA
| | - Nicholas Manguso
- Division of Surgical Oncology, Department of Surgery, University of Nevada Reno/Renown Integrated Health System, 1500 East 2nd Street, Suite 300, Reno, NV 89502, USA
| | - Randall Zuckerman
- Division of Surgical Oncology, Department of Surgery, University of Nevada Reno/Renown Integrated Health System, 1500 East 2nd Street, Suite 300, Reno, NV 89502, USA.
| |
Collapse
|
|
4
|
Dat TQ, Thong DQ, Nguyen DT, Hai NV, Thang NN, Bac NH, Long VD. Effectiveness of conversion surgery in stage IV gastric cancer. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109485. [PMID: 39626330 DOI: 10.1016/j.ejso.2024.109485] [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: 08/11/2024] [Revised: 10/08/2024] [Accepted: 11/21/2024] [Indexed: 01/06/2025]
Abstract
BACKGROUND For patients with stage IV gastric cancer (GC), systemic therapy is often the standard treatment, but the prognosis remains poor. Conversion surgery (CS) has emerged as a potential therapeutic option for selected patients who had certain response to chemotherapy. This study aims to compare the survival outcomes of CS versus continued chemotherapy (CT) in stage IV GC. METHODS We conducted a retrospective cohort study of 52 patients with stage IV gastric adenocarcinoma, from January-2018 to June-2023. Patients were divided into two groups: those who underwent CS (CS group) after a response to chemotherapy and those who continued with systemic chemotherapy (CT group). Baseline characteristics, chemotherapy toxicity, surgical outcomes, and survival data were analyzed and compared. RESULTS Among 52 patients, 26 patients underwent CS, while other 26 continued with CT. The CS group showed a significantly higher 3-year overall survival (OS) rate and median survival time (MST) compared to the CT group (36 % vs. 15 %, HR = 0.39, 95%CI: 0.19-0.79, p = 0.009; 23.4 months vs. 14.7 months, p < 0.001, respectively). Subgroup analysis by Yoshida classification revealed superior survival outcomes for CS in category 3 (MST: 26.1 months vs. 12.6 months, p < 0.001). Multivariate analysis indicated that CS were associated with a longer survival. No major postoperative complications were observed in the CS group. CONCLUSIONS Conversion surgery improved survival outcomes in selected stage IV GC patients compared to systemic chemotherapy alone. CS should be considered as a treatment option for patients who responds to initial chemotherapy, particularly those in Yoshida category 3.
Collapse
Affiliation(s)
- Tran Quang Dat
- Gastro-intestinal Surgery Department, University Medical Center, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Viet Nam
| | - Dang Quang Thong
- Gastro-intestinal Surgery Department, University Medical Center, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Viet Nam
| | - Doan Thuy Nguyen
- Gastro-intestinal Surgery Department, University Medical Center, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Viet Nam
| | - Nguyen Viet Hai
- Gastro-intestinal Surgery Department, University Medical Center, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Viet Nam
| | - Nguyen Nam Thang
- Department of General Surgery, Tay Nguyen Regional General Hospital, Daklak Province, Viet Nam
| | - Nguyen Hoang Bac
- Gastro-intestinal Surgery Department, University Medical Center, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Viet Nam; Department of General Surgery, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Viet Nam
| | - Vo Duy Long
- Gastro-intestinal Surgery Department, University Medical Center, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Viet Nam; Department of General Surgery, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Viet Nam.
| |
Collapse
|
|
5
|
Boshier PR, Tekkis N, Baggaley A, Robb HD, Lafaurie G, Simkens G, Nilsson M, Hanna GB, Petty R. Outcomes of intraperitoneal chemotherapy for the treatment of gastric cancer with peritoneal metastasis: A comprehensive systematic review and meta-analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109499. [PMID: 39644811 DOI: 10.1016/j.ejso.2024.109499] [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: 10/02/2024] [Revised: 11/04/2024] [Accepted: 11/23/2024] [Indexed: 12/09/2024]
Abstract
BACKGROUND Peritoneal metastasis is common in gastric cancer and linked to poor survival. Treatment of peritoneal metastasis with intraperitoneal chemotherapy has become an accepted practice in some centres. This systematic review and meta-analysis intends to provide a comprehensive evaluation of published evidence for the use of intraperitoneal chemotherapy is gastric cancer patients with peritoneal metastasis. METHODS A systematic literature search for studies reporting the use of intraperitoneal chemotherapy for the treatment gastric cancer with macroscopic peritoneal metastasis was performed up until June 2024. Studies were not eligible for inclusion if they described the use of intraperitoneal chemotherapy solely as an adjunct to gastrectomy or cytoreductive surgery. Pooled- and meta-analysis was used to summarise study outcomes. RESULTS Fifty-three studies reporting the outcomes of 2446 gastric cancer patients who received intraperitoneal chemotherapy for the treatment of peritoneal metastasis, were included. Three principal methods of intraperitoneal chemotherapy administration were described: catheter based (normothermic) intraperitoneal chemotherapy (n = 28); pressurised intraperitoneal aerosolised chemotherapy (n = 14), and; hyperthermic intraperitoneal chemotherapy (n = 11). The proportion of patients with complete peritoneal disease regression after receiving intraperitoneal chemotherapy was 27 % (95%CI, 14-41). Median overall survival determined was 16.4 months (95%CI, 14.4-18.4). Meta-analysis of data from eight studies comparing combined intraperitoneal and systemic chemotherapy with systemic chemotherapy alone identified a survival benefit for patients receiving intraperitoneal chemotherapy (Hazard ratio 0.57 [95%CI, 0.48-0.67],P < 0.001). CONCLUSION Despite variation in published treatment approaches and a lack of evidence from well-designed clinical trials, intraperitoneal chemotherapy may be considered safe and in selected circumstances efficacious.
Collapse
Affiliation(s)
- Piers R Boshier
- Department of Surgery and Cancer, Imperial College London, London, UK.
| | - Nicholas Tekkis
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Alice Baggaley
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Henry D Robb
- Department of Surgery and Cancer, Imperial College London, London, UK
| | | | - Geert Simkens
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Magnus Nilsson
- Division of Surgery and Oncology, CLINTEC, Karolinska Institutet, Stokholm, Sweden
| | - George B Hanna
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Russell Petty
- Tayside Medical Science Centre, University of Dundee, Dundee, UK
| |
Collapse
|
|
6
|
Provenzano L, Gwee YX, Conca V, Lonardi S, Bozzarelli S, Tamburini E, Passardi A, Zaniboni A, Tosi F, Aprile G, Nasca V, Boccaccino A, Ambrosini M, Vetere G, Carullo M, Guaglio M, Battaglia L, Zhao JJ, Chia DKA, Yong WP, Tan P, So J, Kim G, Shabbir A, Ong CAJ, Casella F, Cremolini C, Bencivenga M, Sundar R, Pietrantonio F. Unveiling the prognostic significance of malignant ascites in advanced gastrointestinal cancers: a marker of peritoneal carcinomatosis burden. Ther Adv Med Oncol 2024; 16:17588359241289517. [PMID: 39502404 PMCID: PMC11536604 DOI: 10.1177/17588359241289517] [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: 05/25/2024] [Accepted: 09/19/2024] [Indexed: 11/08/2024] Open
Abstract
Background Ascites is common in advanced gastrointestinal cancers with peritoneal metastases (PM) and negatively impacts patient survival. No study to date has specifically evaluated the relationship between ascites, PM and survival outcomes in metastatic colorectal cancer (mCRC) and metastatic gastric cancer (mGC). Objectives This study aims to investigate and elucidate the relationship between malignant ascites, PM and survival outcomes in both mCRC and mGC patients. Design This is a retrospective analysis of prospectively collected clinical trial data of mCRC and mGC patients with PM. Methods We performed two pooled analyses, firstly of two Italian randomized trials enrolling patients with mCRC eligible for systemic therapy (TRIBE2; VALENTINO), and secondly of gastric cancer and peritoneal metastasis (GCPM) patients who underwent bi-directional therapeutic treatment comprising systemic and peritoneal-directed therapies. Results Of 900 mCRC patients, 39 (4.3%) had PM with malignant ascites. Compared to the group without PM, median progression-free and overall survival were significantly inferior in the ascites group (hazard ratio (HR) for progression-free survival (PFS) 1.68, 95% confidence interval (CI): 1.21-2.35, p = 0.007; HR for overall survival (OS) 2.14, 95% CI: 1.57-3.01, p < 0.001), but not in the group of PM without ascites (HR for PFS 1.10, 95% CI: 0.91 - 1.34; HR for OS 1.04, 95% CI: 0.84 - 1.30). Of 170 patients with GCPM, those with ascites had higher median Peritoneal Cancer Index scores (23 vs 9, p < 0.001). Median OS was significantly inferior among those with ascites compared to those without (13.0 vs 21.0 months, HR 1.71, 95% CI: 1.16-2.52, p = 0.007). Conclusion Ascites identifies a subgroup of patients with PM and poor outcomes, for whom tailored research are needed.
Collapse
Affiliation(s)
- Leonardo Provenzano
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Yong Xiang Gwee
- Department of Haematology–Oncology, National University Cancer Institute, Singapore, Singapore
| | - Veronica Conca
- Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy
| | - Sara Lonardi
- Medical Oncology 3 Unit, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Silvia Bozzarelli
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | | | - Alessandro Passardi
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) ‘Dino Amadori’, Meldola, Italy
| | - Alberto Zaniboni
- Unity of Oncology, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy
| | - Federica Tosi
- Department of Hematology, Oncology and Molecular Oncology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
| | - Giuseppe Aprile
- Department of Oncology, San Bortolo General Hospital, Azienda ULSS8, Vicenza, Italy
| | - Vincenzo Nasca
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Alessandra Boccaccino
- Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy
| | - Margherita Ambrosini
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | | | | | - Marcello Guaglio
- Colorectal Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Luigi Battaglia
- Colorectal Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Joseph Jonathan Zhao
- Department of Haematology–Oncology, National University Cancer Institute, Singapore, Singapore
| | - Daryl Kai Ann Chia
- Department of Surgery, University Surgical Cluster, National University Hospital, Singapore, Singapore
| | - Wei Peng Yong
- Department of Haematology–Oncology, National University Cancer Institute, Singapore, Singapore
- Singapore Gastric Cancer Consortium, Singapore, Singapore
- Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
| | - Patrick Tan
- Singapore Gastric Cancer Consortium, Singapore, Singapore
- Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
- Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore, Singapore
- Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore
- SingHealth/Duke-NUS Institute of Precision Medicine, National Heart Centre Singapore, Singapore, Singapore
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Jimmy So
- Department of Surgery, University Surgical Cluster, National University Hospital, Singapore, Singapore
- Singapore Gastric Cancer Consortium, Singapore, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Division of Surgical Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore, Singapore
| | - Guowei Kim
- Department of Surgery, University Surgical Cluster, National University Hospital, Singapore, Singapore
- Division of Surgical Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore, Singapore
| | - Asim Shabbir
- Department of Surgery, University Surgical Cluster, National University Hospital, Singapore, Singapore
- Division of Surgical Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore, Singapore
| | - Chin-Ann Johnny Ong
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | | | - Chiara Cremolini
- Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy
- Unity of Oncology, University Hospital of Pisa, Pisa, Italy
| | - Maria Bencivenga
- The N.1 Institute for Health, National University of Singapore, Singapore, Singapore
- Department of Surgery, Dentistry, Pediatrics and Gynaecology, Upper GI Surgery Unit, University of Verona, Verona, Italy
| | - Raghav Sundar
- Department of Haematology–Oncology, National University Cancer Institute, 1E Kent Ridge Road, Singapore 119228, Singapore
- Singapore Gastric Cancer Consortium, Singapore, Singapore
- Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- The N.1 Institute for Health, National University of Singapore, Singapore, Singapore
| | - Filippo Pietrantonio
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G.Venezian, 1, Milan 20133, Italy
| |
Collapse
|
|
7
|
Kitai T, Yamanaka K. Conversion surgery for gastric cancer with PM. J Surg Oncol 2024; 130:1306-1315. [PMID: 39155703 DOI: 10.1002/jso.27794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Accepted: 07/18/2024] [Indexed: 08/20/2024]
Abstract
It remains unclear whether the application of surgery to gastric cancer with peritoneal carcinomatosis prolongs survival. Twenty studies on conversion surgery were reviewed. Key points were the response to chemotherapy, complete resection, and a low tumor burden at the time of surgery. A bidirectional approach has been developed to increase the response rate. There are two different strategies in surgery. The outcomes of ongoing trials may clarify controversial issues.
Collapse
Affiliation(s)
- Toshiyuki Kitai
- Department of Surgery, Kishiwada Tokushukai Hospital, Kishiwada, Japan
| | - Kenya Yamanaka
- Department of Surgery, Shiga General Hospital, Moriyama, Japan
| |
Collapse
|
|
8
|
Jin S, Wei Y, Wang Q, Ju Y, Wang Z, Cheng Q, Li Z, Liu X, Wang K. Prediction of surgical benefit in gastric cancer patients with peritoneal metastasis treated with hyperthermic intraperitoneal chemotherapy. Updates Surg 2024; 76:2663-2674. [PMID: 39367285 PMCID: PMC11602788 DOI: 10.1007/s13304-024-01989-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Accepted: 09/05/2024] [Indexed: 10/06/2024]
Abstract
The objective is to evaluate whether gastric cancer patients with peritoneal metastasis can benefit from surgery through a comprehensive analysis of different clinical factors and perioperative treatment methods. A total of 135 gastric cancer patients with peritoneal metastasis were treated with Hyperthermic intraperitoneal chemotherapy (HIPEC). Patients were divided into either training group (without surgery, n = 90) or test group (with surgery, n = 45). A nomogram was constructed based on significant prognostic factors. The patients were divided into high- and low-risk groups using a nomogram. Overall survival were then compared according to whether surgery was performed in both groups. Alpha-fetoprotein (AFP), complications, conversion chemotherapy, and postoperative chemotherapy were significantly associated with overall survival (p < 0.05). A nomogram was constructed using the above four factors and validated using the test set. The area under the curve (AUC) of the model was 0.752 (95% CI 0.525-978). In the group that did not undergo surgery, the median survival times for the high-risk and low-risk groups were 7 and 11 months, respectively. In the surgery group, the median survival times for the high-risk and low-risk groups were 11 and 19 months, respectively. The difference was statistically significant (p < 0.0001). The four-factor nomogram can accurately predict high-risk and low-risk populations. Our findings suggest that cytoreductive surgery combined with HIPEC can improve the survival time of patients in both groups.
Collapse
Affiliation(s)
- Shiyang Jin
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, 150081, Heilongjiang, China
| | - Yuzhe Wei
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, 150081, Heilongjiang, China
| | - Qiancheng Wang
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, 150081, Heilongjiang, China
| | - Yuming Ju
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, 150081, Heilongjiang, China
| | - Zeshen Wang
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, 150081, Heilongjiang, China
| | - Qingqing Cheng
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, 150081, Heilongjiang, China
| | - Zhenglong Li
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, 150081, Heilongjiang, China
| | - Xirui Liu
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, 150081, Heilongjiang, China
| | - Kuan Wang
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, 150081, Heilongjiang, China.
| |
Collapse
|
|
9
|
Methasate A, Parakonthun T, Intralawan T, Nampoolsuksan C, Swangsri J. Impact of hyperthermic intraperitoneal chemotherapy on gastric cancer survival: Peritoneal metastasis and cytology perspectives. World J Clin Oncol 2024; 15:840-847. [PMID: 39071459 PMCID: PMC11271738 DOI: 10.5306/wjco.v15.i7.840] [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: 03/12/2024] [Revised: 05/11/2024] [Accepted: 06/03/2024] [Indexed: 07/16/2024] Open
Abstract
BACKGROUND Gastric cancer presenting with peritoneal metastasis is notably associated with diminished survival prospects. The use of cytoreductive surgery in conjunction with hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to increase survival rates in these patients. Despite these advancements, debates persist regarding the magnitude of survival improvement attributed to this treatment modality. The present investigation examined survival outcomes following HIPEC in individuals diagnosed with gastric cancer and peritoneal metastasis, and it took a comparative analysis of patients exhibiting positive and negative cytological findings. AIM To compare the impact of HIPEC on survival in gastric cancer patients with peritoneal metastasis and positive or negative cytology. METHODS Between April 2013 and March 2020, 84 patients with advanced gastric cancer treated at our institution were categorized into three cohorts: HIPEC (20 patients with peritoneal metastasis), cytology-positive (23 patients without peritoneal nodules but with positive wash cytology), and cytology-negative (41 patients with advanced gastric cancer, no peritoneal nodules, and negative wash cytology). The HIPEC cohort underwent gastrectomy with HIPEC, while the cytology-positive and cytology-negative groups received gastrectomy alone. The demographic, pathological, and survival data of the groups were compared. RESULTS The HIPEC cohort-predominantly younger females-exhibited relatively extended surgical durations and high blood loss. Nevertheless, the complication rates were consistent across all three groups. Median survival in the HIPEC group was 20.00 ± 4.89 months, with 1-year, 2-year, and 3-year overall survival rates of 73.90%, 28.70%, and 9.60%, respectively. These figures paralleled the survival rates of the cytology-positive group (52.20% at 1 year, 28.50% at 2 years, and 19.00% at 3 years). Notably, 47% of patients experienced peritoneal recurrence. CONCLUSION HIPEC may offer a modest improvement in short-term survival for patients with gastric cancer and peritoneal metastasis, mirroring the outcomes in cytology-positive patients. However, peritoneal recurrence remained high.
Collapse
Affiliation(s)
- Asada Methasate
- Minimally Invasive Surgery Unit, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
- Upper Gastrointestinal Cancer Center, Siriraj Hospital Mahidol University, Bangkok 10700, Thailand
| | - Thammawat Parakonthun
- Minimally Invasive Surgery Unit, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
- Upper Gastrointestinal Cancer Center, Siriraj Hospital Mahidol University, Bangkok 10700, Thailand
| | - Thita Intralawan
- Minimally Invasive Surgery Unit, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Chawisa Nampoolsuksan
- Minimally Invasive Surgery Unit, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
- Upper Gastrointestinal Cancer Center, Siriraj Hospital Mahidol University, Bangkok 10700, Thailand
| | - Jirawat Swangsri
- Minimally Invasive Surgery Unit, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
- Upper Gastrointestinal Cancer Center, Siriraj Hospital Mahidol University, Bangkok 10700, Thailand
| |
Collapse
|
|
10
|
Meguro Y, Yamaguchi H, Sasanuma H, Shimodaira K, Aoki Y, Chinen T, Morishima K, Miyato H, Miki A, Endo K, Lefor AK, Kitayama J, Sata N. Combined Intraperitoneal Paclitaxel and Systemic Chemotherapy for Patients with Massive Malignant Ascites Secondary to Pancreatic Cancer: A Report of Two Patients. Intern Med 2024; 63:2015-2021. [PMID: 38044154 PMCID: PMC11309862 DOI: 10.2169/internalmedicine.2191-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 10/12/2023] [Indexed: 12/05/2023] Open
Abstract
The prognosis of patients with peritoneal metastases from pancreatic cancer is poor, largely due to massive ascites, which precludes systemic treatment. Two patients with a poor performance status and malignant ascites were treated with cell-free and concentrated ascites reinfusion therapy followed by combined chemotherapy with intraperitoneal paclitaxel, intravenous gemcitabine, and nab-paclitaxel. These patients achieved a survival of 19 and 36 weeks with a relatively good quality of life. Combined intraperitoneal paclitaxel and systemic chemotherapy may provide effective palliative management for some patients with peritoneal metastases from pancreatic cancer.
Collapse
Affiliation(s)
- Yoshiyuki Meguro
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University School of Medicine, Japan
| | - Hironori Yamaguchi
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University School of Medicine, Japan
- Department of Clinical Oncology, Jichi Medical University School of Medicine, Japan
| | - Hideki Sasanuma
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University School of Medicine, Japan
| | - Kentaro Shimodaira
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University School of Medicine, Japan
| | - Yuichi Aoki
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University School of Medicine, Japan
| | - Takashi Chinen
- Department of Clinical Oncology, Jichi Medical University School of Medicine, Japan
| | - Kazue Morishima
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University School of Medicine, Japan
| | - Hideyo Miyato
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University School of Medicine, Japan
- Department of Clinical Oncology, Jichi Medical University School of Medicine, Japan
| | - Atsushi Miki
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University School of Medicine, Japan
| | - Kazuhiro Endo
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University School of Medicine, Japan
| | - Alan Kawarai Lefor
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University School of Medicine, Japan
| | - Joji Kitayama
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University School of Medicine, Japan
| | - Naohiro Sata
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University School of Medicine, Japan
| |
Collapse
|
|
11
|
Cho M, Kim HS, Jung M, Hyung WJ. Perioperative intraperitoneal plus systemic chemotherapy and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for gastric cancer: phase Ib/II single-arm prospective study. J Gastrointest Surg 2024; 28:1095-1103. [PMID: 38705369 DOI: 10.1016/j.gassur.2024.04.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 04/13/2024] [Accepted: 04/27/2024] [Indexed: 05/07/2024]
Abstract
BACKGROUND In gastric cancer, peritoneal metastasis is the most common form of metastasis and leads to dismal prognosis. We aimed to evaluate the safety and efficacy of combining perioperative intraperitoneal (IP) plus systemic chemotherapy, cytoreductive surgery (CRS), and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with gastric cancer with limited peritoneal metastasis or even after reducing peritoneal tumor burden by upfront IP chemotherapy. METHOD Patients were enrolled in phase Ib in a 3 + 3 dose escalation of IP paclitaxel plus a fixed dose of IP cisplatin and oral S-1. In phase II, patients were managed according to the peritoneal cancer index (PCI) by diagnostic laparoscopy. For patients with a PCI of >12, upfront IP and systemic chemotherapy were given. Patients with a PCI of ≤12 or reduced to ≤12 after upfront chemotherapy underwent CRS with HIPEC. The primary endpoints were safety and the recommended phase II dose (RP2D) confirmation for phase Ib and the 1-year overall survival rate for phase II. RESULTS The RP2D was defined as IP 175 mg/m2 paclitaxel and 60 mg/m2 cisplatin and oral 70 mg/m2/day S-1 for 14 days. A total of 22 patients were included. After CRS with HIPEC, there were no grade 3 or higher complications. The median hospital stay was 7 days (range, 6-11). The median overall and progression-free survival were 27.3 months (95% CI, 14.4 to not estimable) and 12.6 months (95% CI, 7.7-14.5), respectively. One-year overall and progression-free survival rates were 81.0% (95% CI, 65.8-99.6) and 54.5% (95% CI, 37.2-79.9), respectively. CONCLUSION A combination of IP plus systemic chemotherapy, CRS, and HIPEC was safe and resulted in good survival outcomes.
Collapse
Affiliation(s)
- Minah Cho
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea; Gastric Cancer Center, Yonsei Cancer Center, Yonsei University Health System, Seoul, Republic of Korea
| | - Hyo Song Kim
- Gastric Cancer Center, Yonsei Cancer Center, Yonsei University Health System, Seoul, Republic of Korea; Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Minkyu Jung
- Gastric Cancer Center, Yonsei Cancer Center, Yonsei University Health System, Seoul, Republic of Korea; Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Woo Jin Hyung
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea; Gastric Cancer Center, Yonsei Cancer Center, Yonsei University Health System, Seoul, Republic of Korea.
| |
Collapse
|
|
12
|
Li AY, Sedighim S, Tajik F, Khan AM, Radhakrishnan VK, Dayyani F, Senthil M. Regional Therapy Approaches for Gastric Cancer with Limited Peritoneal Disease. J Gastrointest Cancer 2024; 55:534-548. [PMID: 38277055 PMCID: PMC11186907 DOI: 10.1007/s12029-023-00994-5] [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] [Accepted: 11/25/2023] [Indexed: 01/27/2024]
Abstract
PURPOSE Despite advances in systemic therapy, outcomes of patients with gastric cancer (GC) peritoneal carcinomatosis (PC) remain poor, in part because of poor penetrance of systemic therapy into peritoneal metastasis due to the plasma-peritoneal barrier and anarchic intra-tumoral circulation. Hence, regional treatment approach with administration of chemotherapy directly into the peritoneal cavity (intraperitoneal, IP) under various conditions, combined with or without cytoreductive surgery (CRS) has remained an area of significant research interest. The purpose of this review is to provide high-level evidence for regional treatment approaches in the management of GCPC with limited peritoneal disease. METHODS A review of the current literature and ongoing clinical trials for regional IP therapies for GCPC was performed. Studies included in this review comprise of phase III randomized controlled trials, non-randomized phase II studies, high-impact retrospective studies, and active ongoing clinical trials for each available IP modality. RESULTS The three common IP approaches are heated intraperitoneal chemotherapy (HIPEC), normothermic intraperitoneal chemotherapy (NIPEC) and more recently introduced, pressurized intraperitoneal aerosolized chemotherapy (PIPAC). These IP approaches have been combined with systemic therapy and/or CRS with varying degrees of promising results, demonstrating evidence of improvements in survival rates and peritoneal disease control. Patient selection, optimization of systemic therapy, and completeness of cytoreduction have emerged as major factors influencing the design of contemporary and ongoing trials. CONCLUSION IP chemotherapy has a clear role in the management of patients with GCPC, and when combined with CRS in appropriately selected patients has the potential to significantly improve survival. Ongoing and upcoming IP therapy clinical trials hold great promise to shape the treatment paradigm for GCPC.
Collapse
Affiliation(s)
- Amy Y Li
- Department of Surgery, University of California, Irvine, 3800 Chapman Ave, Ste 7400, 92868, Orange, CA, USA
| | - Shaina Sedighim
- Department of Surgery, University of California, Irvine, 3800 Chapman Ave, Ste 7400, 92868, Orange, CA, USA
| | - Fatemeh Tajik
- Department of Surgery, University of California, Irvine, 3800 Chapman Ave, Ste 7400, 92868, Orange, CA, USA
| | - Aaqil M Khan
- Department of Surgery, University of California, Irvine, 3800 Chapman Ave, Ste 7400, 92868, Orange, CA, USA
| | - Vinodh K Radhakrishnan
- Department of Surgery, University of California, Irvine, 3800 Chapman Ave, Ste 7400, 92868, Orange, CA, USA
| | - Farshid Dayyani
- Department of Medicine, University of California, Irvine, Orange, USA
| | - Maheswari Senthil
- Department of Surgery, University of California, Irvine, 3800 Chapman Ave, Ste 7400, 92868, Orange, CA, USA.
| |
Collapse
|
|
13
|
Yang Z, Lu S, Shi M, Yuan H, Wang Z, Ni Z, He C, Zheng Y, Zhu Z, Liu W, Yao X, Zhang J, Li C, Yan M, Yan C, Zhu Z. Oncological outcomes of conversion therapy in gastric cancer patients with peritoneal metastasis: a large-scale retrospective cohort study. Gastric Cancer 2024; 27:387-399. [PMID: 38143257 PMCID: PMC10896904 DOI: 10.1007/s10120-023-01452-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Accepted: 11/19/2023] [Indexed: 12/26/2023]
Abstract
BACKGROUND Data on the long-term oncological outcomes of patients who undergo conversion surgery (CS) in gastric cancer (GC) patients with peritoneal metastasis (PM) are limited. METHODS GC patients with PM who received intraperitoneal (ip) and systemic chemotherapy between April 2015 and January 2021 were enrolled. Multivariate analysis was performed to identify risk factors associated with survival. Clinicopathological and survival outcomes were compared between those with CS and those without CS (NCS). The paclitaxel (PTX) plus tegafur-gimeracil-oteracil potassium capsules (S-1) (PS) + ip PTX and oxaliplatin plus S-1 (SOX) + ip PTX groups were matched in a 1:1 ratio using propensity score matching. Oncological and survival data were collected and analyzed. RESULTS A total of 540 patients who received ip chemotherapy via subcutaneous port and systemic chemotherapy were analyzed and 268 patients were enrolled, including 113 who underwent CS and 155 who did not. Overall survival (OS) were 27.0 months and 11.8 months in the CS and NCS groups (P < 0.0001), respectively. R0 resection was an independent prognostic factor for patients who underwent CS. The OS of patients with or without ovariectomy was 21.3 or 12.0 months (P < 0.0001). No difference of clinicopathological and survival outcomes was found between the PS + ip PTX and SOX + ip PTX groups. CONCLUSION Conversion therapy is safe and adverse events were manageable. CS improves the survival of GC patients with PM after ip and systemic chemotherapy. R0 is an important prognostic factor. Furthermore, outcomes are comparable between the PS + ip PTX and SOX + ip PTX groups.
Collapse
Affiliation(s)
- Zhongyin Yang
- Shanghai Key Laboratory of Gastric Neoplasms, Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, China
| | - Sheng Lu
- Shanghai Key Laboratory of Gastric Neoplasms, Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, China
| | - Min Shi
- Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hong Yuan
- Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhenqiang Wang
- Shanghai Key Laboratory of Gastric Neoplasms, Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, China
| | - Zhentian Ni
- Shanghai Key Laboratory of Gastric Neoplasms, Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, China
| | - Changyu He
- Shanghai Key Laboratory of Gastric Neoplasms, Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, China
| | - Yanan Zheng
- Shanghai Key Laboratory of Gastric Neoplasms, Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, China
| | - Zhenglun Zhu
- Shanghai Key Laboratory of Gastric Neoplasms, Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, China
| | - Wentao Liu
- Shanghai Key Laboratory of Gastric Neoplasms, Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, China
| | - Xuexin Yao
- Shanghai Key Laboratory of Gastric Neoplasms, Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, China
| | - Jun Zhang
- Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chen Li
- Shanghai Key Laboratory of Gastric Neoplasms, Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, China
| | - Min Yan
- Shanghai Key Laboratory of Gastric Neoplasms, Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, China
| | - Chao Yan
- Shanghai Key Laboratory of Gastric Neoplasms, Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, China.
| | - Zhenggang Zhu
- Shanghai Key Laboratory of Gastric Neoplasms, Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, China
| |
Collapse
|
|
14
|
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
|
|
15
|
Dai W, Chen Y, Xue Y, Wan M, Mao C, Zhang K. Progress in the Treatment of Peritoneal Metastatic Cancer and the Application of Therapeutic Nanoagents. ACS APPLIED BIO MATERIALS 2023; 6:4518-4548. [PMID: 37916787 DOI: 10.1021/acsabm.3c00662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2023]
Abstract
Peritoneal metastatic cancer is a cancer caused by the direct growth of cancer cells from the primary site through the bloodstream, lymph, or peritoneum, which is a difficult part of current clinical treatment. In the abdominal cavity of patients with metastatic peritoneal cancer, there are usually nodules of various sizes and malignant ascites. Among them, nodules of different sizes can obstruct intestinal movement and form intestinal obstruction, while malignant ascites can cause abdominal distension and discomfort, and even cause patients to have difficulty in breathing. The pathology and physiology of peritoneal metastatic cancer are complex and not fully understood. The main hypothesis is "seed" and "soil"; i.e., cells from the primary tumor are shed and implanted in the peritoneal cavity (peritoneal metastasis). In the last two decades, the main treatment modalities used clinically are cytoreductive surgery (CRS), systemic chemotherapy, intraperitoneal chemotherapy, and combined treatment, all of which help to improve patient survival and quality of life (QOL). However, the small-molecule chemotherapeutic drugs used clinically still have problems such as rapid drug metabolism and systemic toxicity. With the rapid development of nanotechnology in recent years, therapeutic nanoagents for the treatment of peritoneal metastatic cancer have been gradually developed, which has improved the therapeutic effect and reduced the systemic toxicity of small-molecule chemotherapeutic drugs to a certain extent. In addition, nanomaterials have been developed not only as therapeutic agents but also as imaging agents to guide peritoneal tumor CRS. In this review, we describe the etiology and pathological features of peritoneal metastatic cancer, discuss in detail the clinical treatments that have been used for peritoneal metastatic cancer, and analyze the advantages and disadvantages of the different clinical treatments and the QOL of the treated patients, followed by a discussion focusing on the progress, obstacles, and challenges in the use of therapeutic nanoagents in peritoneal metastatic cancer. Finally, therapeutic nanoagents and therapeutic tools that may be used in the future for the treatment of peritoneal metastatic cancer are prospected.
Collapse
Affiliation(s)
- Wenjun Dai
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China
| | - Yidan Chen
- Department of Radiation Oncology, Affiliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
| | - Yunxin Xue
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China
| | - Mimi Wan
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China
| | - Chun Mao
- National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China
| | - Ke Zhang
- Department of Radiation Oncology, Affiliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
| |
Collapse
|
|
16
|
Gao H, Ji K, Bao L, Chen H, Lin C, Feng M, Tao L, Wang M. Establishment and verification of prediction model of occult peritoneal metastasis in advanced gastric cancer. World J Surg Oncol 2023; 21:320. [PMID: 37833730 PMCID: PMC10571475 DOI: 10.1186/s12957-023-03188-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 09/17/2023] [Indexed: 10/15/2023] Open
Abstract
BACKGROUND To investigate the risk factors associated with the development of occult peritoneal metastasis in advanced gastric cancer, and establish and externally validate a nomogram for predicting the occurrence of occult peritoneal metastasis in patients with advanced gastric cancer. METHODS A total of 111 patients with advanced gastric cancer who underwent laparoscopic exploration or peritoneal lavage cytology examination at the Affiliated Drum Tower Hospital of Nanjing University Medical School from August 2014 to December 2021 were retrospectively analyzed. The patients diagnosed between 2019 and 2021 were assigned to the training set (n = 64), while those diagnosed between 2014 and 2016 constituted the external validation set (n = 47). In the training set, patients were classified into two groups based on preoperative imaging and postoperative pathological data: the occult peritoneal metastasis group (OPMG) and the peritoneal metastasis negative group (PMNG). In the validation set, patients were classified into the occult peritoneal metastasis group (CY1P0, OPMG) and the peritoneal metastasis negative group (CY0P0, PMNG) based on peritoneal lavage cytology results. A nomogram was constructed using univariate and multivariate analyses. The performance of the nomogram was evaluated using Harrell's C-index, the area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA), and calibration plots. RESULTS This study analyzed 22 potential variables of OPM in 111 gastric cancer patients who underwent laparoscopic exploration or peritoneal lavage cytology examination. Logistic regression analysis results showed that Lauren classification, CLDN18.2 score and CA125 were independent risk factors for OPM in patients with gastric cancer. We developed a simple and easy-to-use prediction nomogram of occult peritoneal metastasis in advanced gastric cancer. This nomogram had an excellent diagnostic performance. The AUC of the bootstrap model in the training set was 0.771 and in the validation set was 0.711. This model showed a good fitting and calibration and positive net benefits in decision curve analysis. CONCLUSION We have developed a prediction nomogram of OPM for gastric cancer. This novel nomogram has the potential to enhance diagnostic accuracy for occult peritoneal metastasis in gastric cancer patients.
Collapse
Affiliation(s)
- Hengfei Gao
- Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China
- Medical School of Nanjing University, Nanjing, China
| | - Kangkang Ji
- Department of Gastrointestinal, Fuyang People's Hospital, Fuyang, China
| | - Linsen Bao
- Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China
- Medical School of Nanjing University, Nanjing, China
| | - Hao Chen
- Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China
- Medical School of Nanjing University, Nanjing, China
| | - Chen Lin
- Department of General Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China
| | - Min Feng
- Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
- Medical School of Nanjing University, Nanjing, China.
| | - Liang Tao
- Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
- Medical School of Nanjing University, Nanjing, China.
| | - Meng Wang
- Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
- Medical School of Nanjing University, Nanjing, China.
| |
Collapse
|
|
17
|
Kang SH, Na HY, Choi Y, Lee E, Yoo M, Hwang D, Min SH, Park YS, Ahn SH, Suh YS, Park DJ, Lee HS, Kim HH. The Shorr Versus Modified Ultrafast Papanicolaou Method for Intraoperative Diagnosis of Peritoneal Washing Cytology in Advanced Gastric Cancer: A Phase II Study. J Gastric Cancer 2023; 23:549-560. [PMID: 37932222 PMCID: PMC10630561 DOI: 10.5230/jgc.2023.23.e34] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Revised: 08/07/2023] [Accepted: 08/14/2023] [Indexed: 11/08/2023] Open
Abstract
PURPOSE According to the American Joint Committee on Cancer cancer staging system, positive peritoneal washing cytology (PWC) indicates stage IV gastric cancer. However, rapid intraoperative diagnosis of PWC has no established reliable method. This study evaluated and compared the diagnostic accuracy of the Shorr and the modified ultrafast Papanicolaou (MUFP) methods for intraoperative PWC. MATERIALS AND METHODS This study included patients with gastric cancer who were clinically diagnosed with stage cT3 or higher. The Shorr and MUFP methods were performed on all PWC specimens, and the results were compared with those of conventional Papanicolaou (PAP) staining with carcinoembryonic antigen immunohistochemistry. Sensitivity, specificity, and partial likelihood tests were used to compare the 2 methods. RESULTS Forty patients underwent intraoperative PWC between November 2019 and August 2021. The average time between specimen reception and slide preparation using Shorr and MUFP methods was 44.4±4.5 minutes, and the average time between specimen reception and pathologic diagnosis was 53.9±8.9 minutes. Eight patients (20.0%) had positive cytology in PAP staining. The Shorr method had a sensitivity of 75.0% and specificity of 93.8%; the MUFP method had 62.5% sensitivity and 100.0% specificity. The area under the curve was 0.844 for Shorr and 0.813 for MUFP. In comparing the C-indices of each method with overall survival, no difference was found among the Shorr, MUFP, and conventional PAP methods. CONCLUSIONS The Shorr and MUFP methods are acceptable for the intraoperative diagnosis of PWC in advanced gastric cancer.
Collapse
Affiliation(s)
- So Hyun Kang
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hee Young Na
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
| | - Younghwa Choi
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Eunju Lee
- Department of Surgery, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, Korea
| | - Mira Yoo
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Duyeong Hwang
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Sa-Hong Min
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young Suk Park
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Sang-Hoon Ahn
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
| | - Yun-Suhk Suh
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Do Joong Park
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
- Department of Surgery, Seoul National University Hospital, Seoul, Korea
| | - Hye Seung Lee
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
- Department of Pathology, Seoul National University Hospital, Seoul, Korea
| | - Hyung-Ho Kim
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| |
Collapse
|
|
18
|
Murono K, Yokoyama Y, Nozawa H, Sasaki K, Emoto S, Matsuzaki H, Kashiwabara K, Ishigami H, Gohda Y, Yamaguchi H, Kitayama J, Ishihara S. Intraperitoneal paclitaxel combined with FOLFOX/CAPOX plus bevacizumab for colorectal cancer with peritoneal carcinomatosis (the iPac-02 trial): study protocol of a single arm, multicenter, phase 2 study. Int J Colorectal Dis 2023; 38:173. [PMID: 37340243 PMCID: PMC10282041 DOI: 10.1007/s00384-023-04434-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/09/2023] [Indexed: 06/22/2023]
Abstract
BACKGROUND The safety of intraperitoneally administrated paclitaxel (op PTX) was demonstrated in the phase I trial of ip PTX combined with conventional systemic chemotherapy for colorectal cancer with peritoneal carcinomatosis. Moreover, the median survival time was 29.3 months, which was longer than that observed in previous studies. Here, we planned the phase II trial of ip PTX: the iPac-02 trial. METHODS This multicenter, open-label, single assignment interventional clinical study includes patients with colorectal cancer with unresectable peritoneal carcinomatosis. FOLFOX-bevacizumab or CAPOX-bevacizumab is administered concomitantly as systemic chemotherapy. PTX 20 mg/m2 is administered weekly through the peritoneal access port in addition to these conventional systemic chemotherapies. The response rate is the primary endpoint. Progression-free survival, overall survival, peritoneal cancer index improvement rate, rate of negative peritoneal lavage cytology, safety, and response rate to peritoneal metastases are the secondary endpoints. A total of 38 patients are included in the study. In the interim analysis, the study will continue to the second stage if at least 4 of the first 14 patients respond to the study treatment. The study has been registered at the Japan Registry of Clinical Trials (jRCT2031220110). RESULTS We previously conducted phase I trial of ip PTX combined with conventional systemic chemotherapy for colorectal cancer with peritoneal carcinomatosis [1]. In the study, three patients underwent mFOLFOX, bevacizumab, and weekly ip PTX, and the other three patients underwent CAPOX, bevacizumab, and weekly ip PTX treatment. The dose of PTX was 20 mg/m [2]. The primary endpoint was the safety of the chemotherapy, and secondary endpoints were response rate, peritoneal cancer index improvement rate, rate of negative peritoneal lavage cytology, progression-free survival, and overall survival. Dose limiting toxicity was not observed, and the adverse events of ip PTX combined with oxaliplatin-based systemic chemotherapy were similar to those described in previous studies using systemic chemotherapy alone [3, 4]. The response rate was 25%, peritoneal cancer index improvement rate was 50%, and cytology in peritoneal lavage turned negative in all the cases. The progression-free survival was 8.8 months (range, 6.8-12 months), and median survival time was 29.3 months [5], which was longer than that observed in previous studies. CONCLUSION Here, we planned the phase II trial of ip paclitaxel combined with conventional chemotherapy for colorectal cancer with peritoneal carcinomatosis: the iPac-02 trial.
Collapse
Affiliation(s)
- Koji Murono
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
| | - Yuichiro Yokoyama
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Hiroaki Nozawa
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Kazuhito Sasaki
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Shigenobu Emoto
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Hiroyuki Matsuzaki
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Kosuke Kashiwabara
- Interfaculty Initiative in Information Studies, Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hironori Ishigami
- Department of Chemotherapy, The University of Tokyo Hospital, Tokyo, Japan
| | - Yoshimasa Gohda
- Department of Gastroenterology and Hepatology, National Center for Global Health and Medicine, Tokyo, Japan
| | - Hironori Yamaguchi
- Department of Clinical Oncology, Jichi Medical University Hospital, Shimotsuke, Japan
| | - Joji Kitayama
- Clinical Research Center, Department of Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Soichiro Ishihara
- Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| |
Collapse
|
|
19
|
Sammartino P, De Manzoni G, Marano L, Marrelli D, Biacchi D, Sommariva A, Scaringi S, Federici O, Guaglio M, Angrisani M, Cardi M, Fassari A, Casella F, Graziosi L, Roviello F. Gastric Cancer (GC) with Peritoneal Metastases (PMs): An Overview of Italian PSM Oncoteam Evidence and Study Purposes. Cancers (Basel) 2023; 15:3137. [PMID: 37370747 PMCID: PMC10296634 DOI: 10.3390/cancers15123137] [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: 03/01/2023] [Revised: 04/30/2023] [Accepted: 06/05/2023] [Indexed: 06/29/2023] Open
Abstract
Gastric cancer (GC) continues to be one of the leading types of malignancies worldwide, despite an ongoing decrease in incidence. It is the fifth most frequent type of cancer in the world and the fourth leading cause of cancer death. Peritoneal metastases (PMs) occur in 20-30% of cases during the natural history of the disease. Systemic chemotherapy (SC) is undoubtedly the standard of care for patients with GC and PMs. However, with the development of highly effective regimens (SC combined with intraperitoneal chemotherapy), significant tumor shrinkage has been observed in many patients with synchronous GC and PMs, allowing some to undergo curative resection "conversion surgery" with long-term survival. In recent years, there has been growing interest in intraperitoneal chemotherapy for PMs, because the reduced drug clearance associated with the peritoneal/plasma barrier allows for direct and prolonged drug exposure with less systemic toxicity. These procedures, along with other methods used for peritoneal surface malignancies (PSMs), can be used in GCs with PMs as neoadjuvant chemotherapy or adjuvant treatments after radical surgery or as palliative treatments delivered either laparoscopically or-more recently-as pressurized intraperitoneal aerosol chemotherapy. The great heterogeneity of patients with stage IV gastric cancer did not allow us to carry out a systemic review; therefore, we limited ourselves to providing readers with an overview to clarify the indications and outcomes of integrated treatments for GCs with PMs by analyzing reports from the international clinical literature and the specific experiences of our oncoteam.
Collapse
Affiliation(s)
- Paolo Sammartino
- CRS and HIPEC Unit, Pietro Valdoni, Umberto I Policlinico di Roma, 00161 Roma, Italy
| | | | - Luigi Marano
- Department of Medicine, Surgery, and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, 53100 Siena, Italy
| | - Daniele Marrelli
- Department of Medicine, Surgery, and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, 53100 Siena, Italy
| | - Daniele Biacchi
- CRS and HIPEC Unit, Pietro Valdoni, Umberto I Policlinico di Roma, 00161 Roma, Italy
| | - Antonio Sommariva
- Advanced Surgical Oncology Unit, Surgical Oncology of the Esophagus and Digestive Tract, Veneto, Institute of Oncology IOV-IRCCS, 35128 Padova, Italy
| | - Stefano Scaringi
- AOU Careggi, IBD Unit-Chirurgia dell’Apparato Digerente, 50100 Firenze, Italy
| | - Orietta Federici
- Peritoneal Tumors Unit, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy
| | - Marcello Guaglio
- Peritoneal Surface Malignancies Unit, Fondazione Istituto Nazionale Tumori IRCCS Milano, 20133 Milano, Italy
| | - Marco Angrisani
- CRS and HIPEC Unit, Pietro Valdoni, Umberto I Policlinico di Roma, 00161 Roma, Italy
| | - Maurizio Cardi
- CRS and HIPEC Unit, Pietro Valdoni, Umberto I Policlinico di Roma, 00161 Roma, Italy
| | - Alessia Fassari
- CRS and HIPEC Unit, Pietro Valdoni, Umberto I Policlinico di Roma, 00161 Roma, Italy
| | - Francesco Casella
- Upper GI Surgery Division, University of Verona, 37129 Verona, Italy
| | - Luigina Graziosi
- General and Emergency Surgery Department, Santa Maria Della Misericordia Hospital, University of Perugia, 06125 Perugia, Italy
| | - Franco Roviello
- Department of Medicine, Surgery, and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, 53100 Siena, Italy
| |
Collapse
|
|
20
|
Luo J, Jiang L, He C, Shi M, Yang ZY, Shi M, Lu S, Li C, Zhang J, Yan M, Zhu ZG, Yan C. Exosomal hsa-let-7g-3p and hsa-miR-10395-3p derived from peritoneal lavage predict peritoneal metastasis and the efficacy of neoadjuvant intraperitoneal and systemic chemotherapy in patients with gastric cancer. Gastric Cancer 2023; 26:364-378. [PMID: 36738390 DOI: 10.1007/s10120-023-01368-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Accepted: 01/20/2023] [Indexed: 02/05/2023]
Abstract
BACKGROUND The prognosis of advanced gastric cancer (GC) invading the gastric serosa remains poor, mainly owing to high incidence of peritoneal recurrence. Patients with peritoneal metastases are often treated with neoadjuvant intraperitoneal and systemic chemotherapies (NIPS). Good responders to NIPS often undergo conversion gastrectomy. This study aims to explore biomarkers predicting the occurrence of peritoneal metastasis (PM) and evaluating the efficacy of NIPS in GC patients. METHODS We collected six peritoneal lavage (PL) samples from two patients with PM, two without PM, and two with diminished PM after NIPS via intraperitoneal access ports. We equally isolated microRNAs from exosomes derived from PL samples for deep sequencing. Two microRNAs (hsa-let-7g-3p and hsa-miR-10395-3p) were identified, and their expression levels were examined in PL samples of 99 GC patients using qRT-PCR. Moreover, we performed in vivo and in vitro functional assays to investigate effects of these microRNAs on metastasis and chemoresistance of GC cells. RESULTS Exosomal microRNA expression profiling of six PL samples indicated that the microRNA signature in exosomes of PLs from patients with diminished PM was similar to that from patients without PM. Expression levels of hsa-let-7g-3p and hsa-miR-10395-3p were associated with PM. In vivo and in vitro functional assays confirmed that hsa-let-7g-3p and hsa-miR-10395-3p are involved in GC metastasis and chemoresistance. CONCLUSION PL-derived exosomes in GC contain large amounts of microRNAs related to PM. Moreover, hsa-let-7g-3p and hsa-miR-10395-3p could be used as biomarkers predicting PM and NIPS efficacy and are involved in GC metastasis and chemoresistance.
Collapse
Affiliation(s)
- Jiaxin Luo
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China
- Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lingxi Jiang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China
- Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Changyu He
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China
- Shanghai Institute of Digestive Surgery, Shanghai, China
- Shanghai Key Laboratory of Stomach Neoplasm, Shanghai, China
| | - Minmin Shi
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China
- Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhong-Yin Yang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China
- Shanghai Institute of Digestive Surgery, Shanghai, China
- Shanghai Key Laboratory of Stomach Neoplasm, Shanghai, China
| | - Min Shi
- Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Institute of Digestive Surgery, Shanghai, China
- Shanghai Key Laboratory of Stomach Neoplasm, Shanghai, China
| | - Sheng Lu
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China
- Shanghai Institute of Digestive Surgery, Shanghai, China
- Shanghai Key Laboratory of Stomach Neoplasm, Shanghai, China
| | - Chen Li
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China
- Shanghai Institute of Digestive Surgery, Shanghai, China
- Shanghai Key Laboratory of Stomach Neoplasm, Shanghai, China
| | - Jun Zhang
- Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Institute of Digestive Surgery, Shanghai, China
- Shanghai Key Laboratory of Stomach Neoplasm, Shanghai, China
| | - Min Yan
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China
- Shanghai Institute of Digestive Surgery, Shanghai, China
- Shanghai Key Laboratory of Stomach Neoplasm, Shanghai, China
| | - Zheng-Gang Zhu
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China
- Shanghai Institute of Digestive Surgery, Shanghai, China
- Shanghai Key Laboratory of Stomach Neoplasm, Shanghai, China
| | - Chao Yan
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China.
- Shanghai Institute of Digestive Surgery, Shanghai, China.
- Shanghai Key Laboratory of Stomach Neoplasm, Shanghai, China.
| |
Collapse
|
|
21
|
Gwee YX, Chia DKA, So J, Ceelen W, Yong WP, Tan P, Ong CAJ, Sundar R. Integration of Genomic Biology Into Therapeutic Strategies of Gastric Cancer Peritoneal Metastasis. J Clin Oncol 2022; 40:2830. [PMID: 35649219 PMCID: PMC9390822 DOI: 10.1200/jco.21.02745] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 01/20/2022] [Accepted: 03/08/2022] [Indexed: 12/13/2022] Open
Abstract
The peritoneum is a common site of metastasis in advanced gastric cancer (GC). Diagnostic laparoscopy is now routinely performed as part of disease staging, leading to an earlier diagnosis of synchronous peritoneal metastasis (PM). The biology of GCPM is unique and aggressive, leading to a dismal prognosis. These tumors tend to be resistant to traditional systemic therapy, and yet, this remains the current standard-of-care recommended by most international clinical guidelines. As this is an area of unmet clinical need, several translational studies and clinical trials have focused on addressing this specific disease state. Advances in genomic sequencing and molecular profiling have revealed several promising therapeutic targets and elucidated novel biology, particularly on the role of the surrounding tumor microenvironment in GCPM. Peritoneal-specific clinical trials are being designed with a combination of locoregional therapeutic strategies with systemic therapy. In this review, we summarize the new knowledge of cancer biology, advances in surgical techniques, and emergence of novel therapies as an integrated strategy emerges to address GCPM as a distinct clinical entity.
Collapse
Affiliation(s)
- Yong Xiang Gwee
- Department of Haematology-Oncology, National University Cancer Institute, Singapore
| | - Daryl Kai Ann Chia
- University Surgical Cluster, National University Health System, Singapore
- Division of Surgical Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore
| | - Jimmy So
- University Surgical Cluster, National University Health System, Singapore
- Division of Surgical Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Singapore Gastric Cancer Consortium, Singapore
| | - Wim Ceelen
- Department of GI Surgery, Ghent University Hospital, and Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium
| | - Wei Peng Yong
- Department of Haematology-Oncology, National University Cancer Institute, Singapore
- Singapore Gastric Cancer Consortium, Singapore
- Cancer Science Institute of Singapore, National University of Singapore, Singapore
| | - Patrick Tan
- Singapore Gastric Cancer Consortium, Singapore
- Cancer Science Institute of Singapore, National University of Singapore, Singapore
- Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore
- Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore
- SingHealth/Duke-NUS Institute of Precision Medicine, National Heart Centre Singapore, Singapore
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Chin-Ann Johnny Ong
- Division of Surgery and Surgical Oncology, Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), National Cancer Centre Singapore, Singapore
- Division of Surgery and Surgical Oncology, Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Singapore General Hospital, Singapore
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore
- SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore
- SingHealth Duke-NUS Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore
- Institute of Molecular and Cell Biology, A*STAR Research Entities, Singapore
| | - Raghav Sundar
- Department of Haematology-Oncology, National University Cancer Institute, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Singapore Gastric Cancer Consortium, Singapore
- Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore
- The N.1 Institute for Health, National University of Singapore, Singapore
| |
Collapse
|
|
22
|
Yang ZY, Yuan F, Lu S, Xu W, Wu JW, Xi WQ, Shi M, Wang ZQ, Ni ZT, He CY, Yao XX, Zheng YN, Zhu ZL, Liu WT, Zhang J, Zhang H, Li C, Yan C, Yan M, Zhu ZG. Efficacy and Safety of Conversion Therapy by Intraperitoneal and Intravenous Paclitaxel Plus Oral S-1 in Gastric Cancer Patients With Peritoneal Metastasis: A Prospective Phase II Study. Front Oncol 2022; 12:905922. [PMID: 35795055 PMCID: PMC9251062 DOI: 10.3389/fonc.2022.905922] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 05/20/2022] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND Neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) has shown promising results in gastric cancer (GC) with peritoneal metastasis. However, clinical practice experience of NIPS is still lacking in China. In this study, we investigate the efficacy and safety of NIPS in Chinese patients. METHODS Eligible patients received NIPS every 3 weeks. Gastrectomy was performed for patients who met the criteria of conversion surgery. The primary end point was 1-year overall survival (OS) rate. Secondary end points were the response rate, toxic effects, conversion surgery outcomes and median survival time (MST). RESULTS Sixty-seven patients were enrolled. The primary endpoint was achieved with 1-year OS rate reached 67.2% (95% CI, 56.8%-79.4%). Conversion surgery was performed in 42 patients (62.9%), and R0 resection was achieved in 23 patients (54.8%) with the MST of 31.3 months (95% CI, 24.3-38.3). And the MST was 19.3 months (95% CI, 16.4-22.2) for all patients. Toxicity and surgical complications were well-tolerated. Moreover, sex, R0 resection, pathological nodal stage and tumor regression grade (TRG) were independent prognostic factors for patients who underwent conversion surgery. CONCLUSION The NIPS is effective and safe in treating GC patients with peritoneal metastasis. Male patients, patients who underwent R0 resection, patients with ypN0-1 or TRG 1 after conversion surgery are more likely to benefit from the NIPS. CLINICAL TRIAL REGISTRATION http://www.chictr.org.cn/, identifier https://clinicaltrials.gov/ ().
Collapse
Affiliation(s)
- Zhong-Yin Yang
- Department of General Surgery, Gastrointestinal Surgery, Shanghai Key laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Fei Yuan
- Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Sheng Lu
- Department of General Surgery, Gastrointestinal Surgery, Shanghai Key laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wei Xu
- Department of General Surgery, Gastrointestinal Surgery, Shanghai Key laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jun-Wei Wu
- Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wen-Qi Xi
- Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Min Shi
- Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhen-Qiang Wang
- Department of General Surgery, Gastrointestinal Surgery, Shanghai Key laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhen-Tian Ni
- Department of General Surgery, Gastrointestinal Surgery, Shanghai Key laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chang-Yu He
- Department of General Surgery, Gastrointestinal Surgery, Shanghai Key laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xue-Xin Yao
- Department of General Surgery, Gastrointestinal Surgery, Shanghai Key laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ya-Nan Zheng
- Department of General Surgery, Gastrointestinal Surgery, Shanghai Key laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zheng-Lun Zhu
- Department of General Surgery, Gastrointestinal Surgery, Shanghai Key laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wen-Tao Liu
- Department of General Surgery, Gastrointestinal Surgery, Shanghai Key laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jun Zhang
- Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Huan Zhang
- Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chen Li
- Department of General Surgery, Gastrointestinal Surgery, Shanghai Key laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chao Yan
- Department of General Surgery, Gastrointestinal Surgery, Shanghai Key laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Min Yan
- Department of General Surgery, Gastrointestinal Surgery, Shanghai Key laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zheng-Gang Zhu
- Department of General Surgery, Gastrointestinal Surgery, Shanghai Key laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| |
Collapse
|
|
23
|
Prabhu A, Mishra D, Brandl A, Yonemura Y. Gastric Cancer With Peritoneal Metastasis-A Comprehensive Review of Current Intraperitoneal Treatment Modalities. Front Oncol 2022; 12:864647. [PMID: 35719946 PMCID: PMC9204320 DOI: 10.3389/fonc.2022.864647] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 04/22/2022] [Indexed: 12/24/2022] Open
Abstract
The treatment of patients with peritoneal metastasis from gastric cancer continues to evolve. With various forms of intraperitoneal drug delivery available, it is now possible to reach the sites of peritoneal metastases, which were otherwise sub-optimally covered by systemic chemotherapy, owing to the blood peritoneal barrier. We conducted a narrative review based on an extensive literature research, highlighting the current available intraperitoneal treatment options, which resulted in improved survival in well-selected patients of peritoneally metastasized gastric cancer. Intraperitoneal chemotherapy showed promising results in four different treatment modalities: prophylactic, neoadjuvant, adjuvant, and palliative. It is now possible to choose the type of intraperitoneal treatment/s in combination with systemic treatment/s, depending on patients' general condition and peritoneal disease burden, thus providing individualized treatment to these patients. Randomized controlled trials for the different treatment modalities were mainly conducted in Asia and lack further validation in the other parts of the world. Most recent application tools, such as pressurized intraperitoneal aerosol chemotherapy, seem promising and need to pass the ongoing clinical trials.
Collapse
Affiliation(s)
- Aruna Prabhu
- Department of Surgical Oncology, Thangam Cancer Center, Namakkal, India
| | - Deepti Mishra
- Department of Surgical Oncology, Thangam Cancer Center, Namakkal, India
| | - Andreas Brandl
- Digestive Unit, Champalimaud Foundation, Lisbon, Portugal
- Department of Surgery, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Yutaka Yonemura
- Department of Regional Cancer therapy, Peritoneal Surface Malignancy Centee, Kishiwada Tokushukai Hospital, Kishiwada, Japan
- Japanese/Asian School of Peritoneal Surface Oncology, Osaka, Japan
- Department of Regional Cancer therapy, Peritoneal Surface Malignancy Center, Kusatsu General Hospital, Shiga, Japan
| |
Collapse
|
|
24
|
Tan Y, Chen Q, Pan S, An W, Xu H, Xing Y, Zhang J. LMOD1, an oncogene associated with Lauren classification, regulates the metastasis of gastric cancer cells through the FAK-AKT/mTOR pathway. BMC Cancer 2022; 22:474. [PMID: 35488236 PMCID: PMC9055720 DOI: 10.1186/s12885-022-09541-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 04/11/2022] [Indexed: 11/10/2022] Open
Abstract
Background The Lauren classification of gastric tumors strongly correlates with prognosis. The purpose of this study was to explore the specific molecular mechanism of Lauren classification of gastric cancer and provide a possible theoretical basis for the treatment of gastric cancer. Methods We standardized the gene expression data of five Gene Expression Omnibus gastric cancer databases and constructed a Weighted Co-expression Network Analysis (WGCNA) model based on clinicopathological information. The overall survival (OS) and disease-free survival (DFS) curves were extracted from the Cancer Genome Atlas (TCGA) and GSE62254 databases. Western blotting was used to measure protein expression in cells and tissues. Scratch and transwell experiments were used to test the migration ability of tumor cells. Immunohistochemistry was used to measure tissue protein expression in clinical tissue samples to correlate to survival data. Results The WGCNA model demonstrated that blue cyan was highly correlated with the Lauren classification of the tumor (r = 0.24, P = 7 × 1016). A protein-protein interaction network was used to visualize the genes in the blue cyan module. The OS and PFS TCGA analysis revealed that LMOD1 was a gene of interest. The proportion of diffuse gastric cancer patients with high expression of LMOD1 was significantly higher than that of intestinal type patients. LMOD1 promoted the migration of gastric cancer cells by regulating the FAK-Akt/mTOR pathway in vitro. Additionally, a Gene Set Enrichment Analysis using the TCGA and GSE62254 databases, and western blot data, showed that LMOD1 could promote an epithelial-mesenchymal transition (EMT), thus potentially affecting the occurrence of peritoneal metastasis of gastric cancer. Immunohistochemistry showed that LMOD1 was highly expressed in cancer tissues, and the prognosis of patients with high LMOD1 expression was poor. Conclusion LMOD1 is an oncogene associated with diffuse gastric cancer and can affect the occurrence and development of EMT by regulating the FAK-Akt/mTOR pathway. LMOD1 can therefore promote peritoneal metastasis of gastric cancer cells and can be used as a novel therapeutic target for gastric cancer. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-022-09541-0.
Collapse
Affiliation(s)
- Yuen Tan
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, No 44 of Xiaoheyan Road, Dadong District, Shenyang, 110042, China.,Department of Surgical Oncology, First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, China
| | - Qingchuan Chen
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, China
| | - Siwei Pan
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, China
| | - Wen An
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, China
| | - Huimian Xu
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, China.
| | - Yao Xing
- Department of Cell Biology, Key Laboratory of Cell Biology of Ministry of Public Health, and Key Laboratory of Medical Cell Biology of Ministry of Education, China Medical University, No. 77, Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning, China.
| | - Jianjun Zhang
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, No 44 of Xiaoheyan Road, Dadong District, Shenyang, 110042, China.
| |
Collapse
|
|
25
|
Morgagni P, Solaini L, Saragoni L, Monti M, Valgiusti M, Vittimberga G, Frassineti GL, Framarini M, Ercolani G. Conversion Surgery in Gastric Cancer Carcinomatosis. Front Oncol 2022; 12:852559. [PMID: 35356199 PMCID: PMC8959896 DOI: 10.3389/fonc.2022.852559] [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: 01/11/2022] [Accepted: 02/08/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND After the REGATTA trial, patients with stage IV gastric cancer could only benefit from chemotherapy (CHT). However, some of these patients may respond extraordinarily to palliative chemotherapy, converting their disease to a radically operable stage. We present a single centre experience in treating peritoneal carcinomatosis from gastric cancer. METHODS All patients with stage IV gastric cancer with peritoneal metastases as a single metastatic site operated at a single centre between 2005 and 2020 were included. Cases were grouped according to the treatment received. RESULTS A total of 118 patients were considered, 46 were submitted to palliative gastrectomy (11 were considered M1 because of an unsuspected positive peritoneal cytology), and 20 were submitted to Hyperthermic Intraperitoneal Chemotherapy (HIPEC) because of a <6 Peritoneal Cancer Index (PCI). The median overall survival (OS) after surgery plus HIPEC was 46.7 (95% CI 15.8-64.0). Surgery (without HIPEC) after CHT presented a median OS 14.4 (8.2-26.8) and after upfront surgery 14.7 (10.9-21.1). Patients treated with upfront surgery and considered M1 only because of a positive cytology, had a median OS of 29.2 (25.2-29.2). The OS of patients treated with surgery plus HIPEC were 60.4 months (9.2-60.4) in completely regressed cancer after chemotherapy and 31.2 (15.8-64.0) in those partially regressed (p = 0.742). CONCLUSIONS Conversion surgery for peritoneal carcinomatosis from gastric cancer was associated with long survival and it should always be taken into consideration in this group of patients.
Collapse
Affiliation(s)
- Paolo Morgagni
- General and Oncologic Surgery, “Morgagni-Pierantoni” Hospital, Forlì, Italy
| | - Leonardo Solaini
- General and Oncologic Surgery, “Morgagni-Pierantoni” Hospital, Forlì, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Luca Saragoni
- Pathology Unit, “Morgagni-Pierantoni” Hospital, Forlì, Italy
| | - Manlio Monti
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “DinoAmadori”, Meldola, Italy
| | - Martina Valgiusti
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “DinoAmadori”, Meldola, Italy
| | | | - Giovanni Luca Frassineti
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “DinoAmadori”, Meldola, Italy
| | - Massimo Framarini
- General and Oncologic Surgery, “Morgagni-Pierantoni” Hospital, Forlì, Italy
| | - Giorgio Ercolani
- General and Oncologic Surgery, “Morgagni-Pierantoni” Hospital, Forlì, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| |
Collapse
|
|
26
|
Hyperthermic Intraperitoneal Chemotherapy plus Intravenous Chemotherapy of Paclitaxel with or without Sintilimab in Gastric Cancer: A Comparative Study. JOURNAL OF ONCOLOGY 2022; 2022:3054485. [PMID: 35242186 PMCID: PMC8888085 DOI: 10.1155/2022/3054485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 12/22/2021] [Accepted: 12/28/2021] [Indexed: 11/24/2022]
Abstract
Objective To compare the clinical efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) plus intravenous chemotherapy of paclitaxel with or without sintilimab in peritoneal metastasis of gastric cancer. Methods A total of 120 patients assessed for eligibility with peritoneal metastasis of gastric cancer treated in the oncology department of our hospital from January 2019 to June 2020 were recruited. They were concurrently randomly assigned in a 1 : 1 ratio to receive HIPEC plus sintilimab-paclitaxel intravenous chemotherapy (study group) or plus paclitaxel intravenous chemotherapy only (control group). Results The objective remission rate (ORR) of ascites in the study group was significantly higher than that in the control group. Subgroup analysis showed that an age ≤60 years or well-differentiated tumors were associated with better objective remission. After treatment, significantly higher Karnofsky Performance Status (KPS) scores were observed in the study group versus those of the control group. Adverse events reported were comparable between groups. The study group obtained longer 12-month progression-free survival (PFS) and overall survival (OS) than those of the control group. Conclusion On top of HIPEC, intravenous chemotherapy with sintilimab and paclitaxel constitute an effective alternative for patients with peritoneal metastasis of gastric cancer to enhance ascites remission, ameliorate the quality of life, and prolong survival, versus with paclitaxel alone.
Collapse
|
|
27
|
Lu S, Yang ZY, Yan C, Liu WT, Ni ZT, Yao XX, Hua ZC, Feng RH, Zheng YN, Wang ZQ, Sah BK, Chen MM, Zhu ZL, He CY, Li C, Yan M, Zhu ZG. A phase III trial of neoadjuvant intraperitoneal and systemic chemotherapy for gastric cancer with peritoneal metastasis. Future Oncol 2022; 18:1175-1183. [PMID: 35114800 DOI: 10.2217/fon-2021-1414] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Accepted: 12/08/2021] [Indexed: 02/03/2023] Open
Abstract
Although recent advances in systemic chemotherapy have improved the clinical outcomes of gastric cancer patients with peritoneal metastasis, the peritoneum still represents a common site of treatment failure and disease recurrence. Neoadjuvant intraperitoneal-systemic chemotherapy has been acknowledged as a more aggressive treatment for gastric cancer patients with peritoneal metastasis. In this multicenter phase III randomized controlled trial, 238 patients will be randomly separated into two groups in a 2:1 ratio after laparoscopic exploration. The experimental arm will receive the proposed neoadjuvant intraperitoneal-systemic chemotherapy regimen, whereas the control group will receive a Paclitaxel + S-1 (PS) chemotherapy regimen. The endpoints for the study are overall survival, response rate, gastrectomy radicality rate, progression-free survival and adverse events.
Collapse
Affiliation(s)
- Sheng Lu
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Zhong-Yin Yang
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Chao Yan
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Wen-Tao Liu
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Zhen-Tian Ni
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Xue-Xin Yao
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Zi-Chen Hua
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Run-Hua Feng
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Ya-Nan Zheng
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Zhen-Qiang Wang
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Birendra Kumar Sah
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Ming-Min Chen
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Zheng-Lun Zhu
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Chang-Yu He
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Chen Li
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Min Yan
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Zheng-Gang Zhu
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| |
Collapse
|
|
28
|
Shao S, Yang X, Zhang YN, Wang XJ, Li K, Zhao YL, Mou XZ, Hu PY. Oncolytic Virotherapy in Peritoneal Metastasis Gastric Cancer: The Challenges and Achievements. Front Mol Biosci 2022; 9:835300. [PMID: 35295845 PMCID: PMC8918680 DOI: 10.3389/fmolb.2022.835300] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 02/04/2022] [Indexed: 11/13/2022] Open
Abstract
Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer death globally. Although the mortality rate in some parts of the world, such as East Asia, is still high, new treatments and lifestyle changes have effectively reduced deaths from this type of cancer. One of the main challenges of this type of cancer is its late diagnosis and poor prognosis. GC patients are usually diagnosed in the advanced stages of the disease, which is often associated with peritoneal metastasis (PM) and significantly reduces survival. This type of metastasis in patients with GC poses a serious challenge due to limitations in common therapies such as surgery and tumor resection, as well as failure to respond to systemic chemotherapy. To solve this problem, researchers have used virotherapy such as reovirus-based anticancer therapy in patients with GC along with PM who are resistant to current chemotherapies because this therapeutic approach is able to overcome immune suppression by activating dendritic cells (DCs) and eventually lead to the intrinsic activity of antitumor effector T cells. This review summarizes the immunopathogenesis of peritoneal metastasis of gastric cancer (PMGC) and the details for using virotherapy as an effective anticancer treatment approach, as well as its challenges and opportunities.
Collapse
Affiliation(s)
- Su Shao
- Department of General Surgery, Chun’an First People’s Hospital (Zhejiang Provincial People’s Hospital Chun’an Branch), Hangzhou, China
| | - Xue Yang
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital of Hangzhou Medical College), Hangzhou, China
- Clinical Research Institute, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital of Hangzhou Medical College), Hangzhou, China
| | - You-Ni Zhang
- Department of Traumatology, Tiantai People’s Hospital of Zhejiang Province (Tiantai Branch of Zhejiang People’s Hospital), Taizhou, China
| | - Xue-Jun Wang
- Department of General Surgery, Chun’an First People’s Hospital (Zhejiang Provincial People’s Hospital Chun’an Branch), Hangzhou, China
| | - Ke Li
- Guangdong Techpool Bio-pharma Co., Ltd., Guangzhou, China
| | - Ya-Long Zhao
- Guangdong Techpool Bio-pharma Co., Ltd., Guangzhou, China
| | - Xiao-Zhou Mou
- General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital of Hangzhou Medical College), Hangzhou, China
- Clinical Research Institute, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital of Hangzhou Medical College), Hangzhou, China
- *Correspondence: Xiao-Zhou Mou, ; Pei-Yang Hu,
| | - Pei-Yang Hu
- Department of Traumatology, Tiantai People’s Hospital of Zhejiang Province (Tiantai Branch of Zhejiang People’s Hospital), Taizhou, China
- *Correspondence: Xiao-Zhou Mou, ; Pei-Yang Hu,
| |
Collapse
|
|
29
|
Sun BJ, Lee B. Review of Regional Therapies for Gastric Cancer with Peritoneal Metastases. Cancers (Basel) 2022; 14:cancers14030570. [PMID: 35158837 PMCID: PMC8833629 DOI: 10.3390/cancers14030570] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 01/15/2022] [Accepted: 01/19/2022] [Indexed: 12/20/2022] Open
Abstract
Simple Summary Gastric cancer is usually diagnosed at late stages and is associated with poor five-year survival rates. Metastasis to the peritoneal cavity is common and leads to even worse outcomes. Currently, the mainstay of treatment for metastatic gastric cancer is systemic chemotherapy or supportive care. These recommendations remain despite evidence that suggests systemic therapy has poor penetration into the abdominal cavity, limiting efficacy against peritoneal disease. Newer treatments have been developed to address this problem, specifically regional therapies aimed at delivering chemotherapy directly into the peritoneal cavity to eradicate tumor cells. These novel therapies include hyperthermic intraperitoneal chemotherapy, normothermic intraperitoneal chemotherapy, and pressurized intraperitoneal aerosolized chemotherapy. Regional therapies may also be combined with surgery to remove both macroscopic and microscopic disease. Although more clinical trials are needed to evaluate its efficacy, early studies have shown promising outcomes with intraperitoneal chemotherapy. Abstract Gastric cancer carries a poor prognosis and is a leading cause of cancer-related mortality worldwide. Patients with gastric cancer who develop peritoneal metastases have an even more dismal prognosis, with median survival time measured in months. Since studies have demonstrated that systemic chemotherapy has poor penetration into the peritoneum, multimodal treatment with intraperitoneal chemotherapy has been proposed for the treatment of peritoneal metastases and has become the foundation for newer therapeutic techniques and clinical trials. These include heated intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery (CRS), which involves the application of heated chemotherapy into the abdomen with or without tumor debulking surgery; normothermic intraperitoneal chemotherapy (NIPEC), in which non-heated chemotherapy can be delivered into the abdomen via a peritoneal port allowing for repeat dosing; and pressurized intraperitoneal aerosolized chemotherapy (PIPAC), a newer technique of pressurized and aerosolized chemotherapy delivered into the abdomen during laparoscopy. Early results with intraperitoneal chemotherapy have shown promise in increasing disease-free and overall survival in select patients. Additionally, there may be a palliative effect of these regional therapies. In this review, we explore and summarize these different intraperitoneal chemotherapy treatment regimens for gastric cancer with peritoneal metastases.
Collapse
|
|
30
|
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
|
|
31
|
Shi M, Yang Z, Lu S, Liu W, Ni Z, Yao X, Hua Z, Feng R, Zheng Y, Wang Z, Sah BK, Chen M, Zhu Z, He C, Li C, Zhang J, Yan C, Yan M, Zhu Z. Oxaliplatin plus S-1 with intraperitoneal paclitaxel for the treatment of Chinese advanced gastric cancer with peritoneal metastases. BMC Cancer 2021; 21:1344. [PMID: 34922478 PMCID: PMC8684127 DOI: 10.1186/s12885-021-09027-5] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 11/19/2021] [Indexed: 03/20/2023] Open
Abstract
BACKGROUND In this study, we tried to access the efficacy and safety of oxaliplatin plus S-1 with intraperitoneal paclitaxel (PTX) for the treatment of Chinese advanced gastric cancer with peritoneal metastases. PATIENTS AND METHODS Thirty patients diagnosed with advanced gastric cancer underwent laparoscopic exploration and were enrolled when macroscopic disseminated metastases (P1) were confirmed. PTX was diluted in 1 l of normal saline and IP administered through peritoneal port at an initial dose of 40 mg/m2 over 1 h on day1,8, respectively. Oxaliplatin was administered intravenously at an initial dose of 100 mg/m2 on day1, and S-1 was administered orally at an initial dose of 80 mg/m2 for 14 days followed by 7 days rest, repeated by every 3 weeks. RESULTS Of all these 30 patients, the median number of cycles was 6 (range 2-16) due to the limitation of hematotoxicity and peripheral neuropathy by oxaliplatin. There were 11 (36.7%) patients received conversion surgery. The median progression free survival (PFS) was 6.6 months (95% CI = 4.7-8.5 months) and the median overall survival (OS) was 15.1 months (95% CI = 12.4-17.8 months). The grade 3-4 hematological toxicities were leucopenia (23.3%), neutropenia (23.3%), anemia (16.7%), and thrombocytopenia (20%), respectively. The grade 3-4 non-hematological toxicities were tolerated, most of which were peripheral sensory neuropathy (40%) due to oxaliplatin, diarrhea (20%), nausea and vomiting (26.7%). CONCLUSIONS SOX+ip PTX regimen was effective in advanced gastric cancer with peritoneal metastasis. Survival time was significantly prolonged by conversion surgery. Grade 3-4 toxicities were uncommon. Large scale clinical trial is necessary to get more evidence to identify its efficacy. TRAIL REGISTRATION ChiCTR, ChiCTR-IIR-16009802 . Registered 9 November 2016.
Collapse
Affiliation(s)
- Min Shi
- Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China
| | - Zhongyin Yang
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China
| | - Sheng Lu
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China
| | - Wentao Liu
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China
| | - Zhentian Ni
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China
| | - Xuexin Yao
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China
| | - Zichen Hua
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China
| | - Runhua Feng
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China
| | - Yanan Zheng
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China
| | - Zhenqiang Wang
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China
| | - Birendra Kumar Sah
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China
| | - Mingmin Chen
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China
| | - Zhenglun Zhu
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China
| | - Changyu He
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China
| | - Chen Li
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China
| | - Jun Zhang
- Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Chao Yan
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China.
| | - Min Yan
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China
| | - Zhenggang Zhu
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China.
| |
Collapse
|
|
32
|
Gertsen EC, Brenkman HJF, van Hillegersberg R, van Sandick JW, van Berge Henegouwen MI, Gisbertz SS, Luyer MDP, Nieuwenhuijzen GAP, van Lanschot JJB, Lagarde SM, Wijnhoven BPL, de Steur WO, Hartgrink HH, Stoot JHMB, Hulsewe KWE, Spillenaar Bilgen EJ, van Det MJ, Kouwenhoven EA, van der Peet DL, Daams F, van Grieken NCT, Heisterkamp J, van Etten B, van den Berg JW, Pierie JP, Eker HH, Thijssen AY, Belt EJT, van Duijvendijk P, Wassenaar E, van Laarhoven HWM, Wevers KP, Hol L, Wessels FJ, Haj Mohammad N, van der Meulen MP, Frederix GWJ, Vegt E, Siersema PD, Ruurda JP. 18F-Fludeoxyglucose-Positron Emission Tomography/Computed Tomography and Laparoscopy for Staging of Locally Advanced Gastric Cancer: A Multicenter Prospective Dutch Cohort Study (PLASTIC). JAMA Surg 2021; 156:e215340. [PMID: 34705049 PMCID: PMC8552113 DOI: 10.1001/jamasurg.2021.5340] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 08/13/2021] [Indexed: 12/24/2022]
Abstract
IMPORTANCE The optimal staging for gastric cancer remains a matter of debate. OBJECTIVE To evaluate the value of 18F-fludeoxyglucose-positron emission tomography with computed tomography (FDG-PET/CT) and staging laparoscopy (SL) in addition to initial staging by means of gastroscopy and CT in patients with locally advanced gastric cancer. DESIGN, SETTING, AND PARTICIPANTS This multicenter prospective, observational cohort study included 394 patients with locally advanced, clinically curable gastric adenocarcinoma (≥cT3 and/or N+, M0 category based on CT) between August 1, 2017, and February 1, 2020. EXPOSURES All patients underwent an FDG-PET/CT and/or SL in addition to initial staging. MAIN OUTCOMES AND MEASURES The primary outcome was the number of patients in whom the intent of treatment changed based on the results of these 2 investigations. Secondary outcomes included diagnostic performance, number of incidental findings on FDG-PET/CT, morbidity and mortality after SL, and diagnostic delay. RESULTS Of the 394 patients included, 256 (65%) were men and mean (SD) age was 67.6 (10.7) years. A total of 382 patients underwent FDG-PET/CT and 357 underwent SL. Treatment intent changed from curative to palliative in 65 patients (16%) based on the additional FDG-PET/CT and SL findings. FDG-PET/CT detected distant metastases in 12 patients (3%), and SL detected peritoneal or locally nonresectable disease in 73 patients (19%), with an overlap of 7 patients (2%). FDG-PET/CT had a sensitivity of 33% (95% CI, 17%-53%) and specificity of 97% (95% CI, 94%-99%) in detecting distant metastases. Secondary findings on FDG/PET were found in 83 of 382 patients (22%), which led to additional examinations in 65 of 394 patients (16%). Staging laparoscopy resulted in a complication requiring reintervention in 3 patients (0.8%) without postoperative mortality. The mean (SD) diagnostic delay was 19 (14) days. CONCLUSIONS AND RELEVANCE This study's findings suggest an apparently limited additional value of FDG-PET/CT; however, SL added considerably to the staging process of locally advanced gastric cancer by detection of peritoneal and nonresectable disease. Therefore, it may be useful to include SL in guidelines for staging advanced gastric cancer, but not FDG-PET/CT.
Collapse
Affiliation(s)
- Emma C. Gertsen
- Department of Surgery, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Hylke J. F. Brenkman
- Department of Surgery, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Richard van Hillegersberg
- Department of Surgery, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Johanna W. van Sandick
- Department of Surgery, the Netherlands Cancer Institute–Antoni van Leeuwenhoek, Amsterdam, the Netherlands
| | - Mark I. van Berge Henegouwen
- Department of Surgery, Amsterdam University Medical Center, location AMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Suzanne S. Gisbertz
- Department of Surgery, Amsterdam University Medical Center, location AMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Misha D. P. Luyer
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | | | | | - Sjoerd M. Lagarde
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, the Netherlands
| | - Bas P. L. Wijnhoven
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, the Netherlands
| | - Wobbe O. de Steur
- Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
| | - Henk H. Hartgrink
- Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
| | | | | | | | - Marc J. van Det
- Department of Surgery, ZGT hospital, Almelo, the Netherlands
| | | | - Donald L. van der Peet
- Department of Surgery, Amsterdam University Medical Center, location VUmc, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Freek Daams
- Department of Surgery, Amsterdam University Medical Center, location VUmc, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Nicole C. T. van Grieken
- Department of Pathology, Amsterdam University Medical Center, location VUmc, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Joos Heisterkamp
- Department of Surgery, Elisabeth Twee-Steden Hospital, Tilburg, the Netherlands
| | - Boudewijn van Etten
- Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Jan Willem van den Berg
- Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Jean Pierre Pierie
- Department of Surgery, Medical Center Leeuwarden, Leeuwarden, the Netherlands
| | - Hasan H. Eker
- Department of Surgery, Medical Center Leeuwarden, Leeuwarden, the Netherlands
| | - Annemieke Y. Thijssen
- Department of Gastroenterology, Albert Schweitzer Hospital, Dordrecht, the Netherlands
| | - Eric J. T. Belt
- Department of Surgery, Albert Schweitzer Hospital, Dordrecht, the Netherlands
| | | | - Eelco Wassenaar
- Department of Surgery, Gelre Ziekenhuizen, Apeldoorn, the Netherlands
| | - Hanneke W. M. van Laarhoven
- Prospective Observational Cohort Study of Oesophageal-Gastric Cancer Patients (POCOP) of the Dutch Upper GI Cancer Group, Amsterdam, the Netherlands
- Department of Medical Oncology, Amsterdam University Medical Center, location AMC, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Kevin P. Wevers
- Department of Surgery, Isala Ziekenhuis, Zwolle, the Netherlands
| | - Lieke Hol
- Department of Gastroenterology, Maasstad Ziekenhuis, Rotterdam, the Netherlands
| | - Frank J. Wessels
- Department of Radiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Nadia Haj Mohammad
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Miriam P. van der Meulen
- Julius Center for Health Sciences and Primary Care, Utrecht University, Utrecht, the Netherlands
| | - Geert W. J. Frederix
- Julius Center for Health Sciences and Primary Care, Utrecht University, Utrecht, the Netherlands
| | - Erik Vegt
- Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Peter D. Siersema
- Department of Gastroenterology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Jelle P. Ruurda
- Department of Surgery, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| |
Collapse
|
|
33
|
Marano L, Marrelli D, Sammartino P, Biacchi D, Graziosi L, Marino E, Coccolini F, Fugazzola P, Valle M, Federici O, Baratti D, Deraco M, Di Giorgio A, Macrì A, Pasqual EM, Framarini M, Vaira M, Roviello F. Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer with Synchronous Peritoneal Metastases: Multicenter Study of 'Italian Peritoneal Surface Malignancies Oncoteam-S.I.C.O.'. Ann Surg Oncol 2021; 28:9060-9070. [PMID: 34057569 PMCID: PMC8590997 DOI: 10.1245/s10434-021-10157-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 04/29/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND The development of multimodality treatment, including cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC), has led to promising results in selected patients with peritoneal disease of gastric origin. The aim of this study was to investigate the short- and long-term outcomes of CRS/HIPEC in the treatment of synchronous peritoneal metastasis in gastric cancer. METHODS The Italian Peritoneal Surface Malignancies Oncoteam-S.I.C.O. retrospective registry included patients with synchronous peritoneal malignancy from gastric cancer submitted to gastrectomy with CRS and HIPEC between 2005 and 2018 from 11 high-volume, specialized centers. RESULTS A total of 91 patients with a median age of 58 years (range 26-75) were enrolled. The median overall survival (OS) time for the whole group of patients was 20.2 months (95% confidence interval [CI] 11.8-28.5] and the median recurrence-free survival (RFS) was 7.3 months (95% CI 4-10.6). The completeness of cytoreduction score (CCS) of 0 and Peritoneal Cancer Index (PCI) score of ≤ 6 groups showed a significantly better long-term survival (median OS 40.7 and 44.3 months, respectively) compared with the incomplete resected groups (median OS 10.7 months, p = 0.003) and PCI score of > 6 group (median OS 13.4 months, p = 0.005). A significant difference was observed in the survival rate according to neoadjuvant treatment (untreated patients: 10.7 months, 95% CI 5.1-16.2; treated patients: 35.3 months, 95% CI 2.8-67.8; p = 0.022). CONCLUSIONS In referral centers, CRS and HIPEC after neoadjuvant treatment significantly improved survival in selected patients. Patients with a PCI score ≤ 6, complete cytoreduction, negative nodal involvements, and negative cytology had encouraging results, showing a clinically meaningful survival.
Collapse
Affiliation(s)
- Luigi Marano
- Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Siena, Italy.
| | - Daniele Marrelli
- Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Siena, Italy
| | - Paolo Sammartino
- Cytoreductive Surgery and HIPEC Unit, Department of Surgery "Pietro Valdoni", Sapienza University of Rome, Rome, Italy
| | - Daniele Biacchi
- Cytoreductive Surgery and HIPEC Unit, Department of Surgery "Pietro Valdoni", Sapienza University of Rome, Rome, Italy
| | - Luigina Graziosi
- General and Emergency Surgery, University of Perugia, Perugia, Italy
| | - Elisabetta Marino
- General and Emergency Surgery, University of Perugia, Perugia, Italy
| | - Federico Coccolini
- General, Emergency and Trauma Surgery Department, Bufalini Hospital, Cesena, Italy
- General, Emergency and Trauma Surgery Department, Pisa University Hospital, Pisa, Italy
| | - Paola Fugazzola
- General, Emergency and Trauma Surgery Department, Bufalini Hospital, Cesena, Italy
| | - Mario Valle
- Department of Digestive Surgery, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Orietta Federici
- Department of Digestive Surgery, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Dario Baratti
- Fondazione IRCCS Istituto Nazionale Dei Tumori di Milano, Peritoneal Surface Malignancies Unit, Milan, Italy
| | - Marcello Deraco
- Fondazione IRCCS Istituto Nazionale Dei Tumori di Milano, Peritoneal Surface Malignancies Unit, Milan, Italy
| | - Andrea Di Giorgio
- Surgical Unit of Peritoneum and Retroperitoneum, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Antonio Macrì
- Peritoneal Surface Malignancy and Soft Tissue Sarcoma Program, Messina University Medical School Hospital, Messina, Italy
| | - Enrico Maria Pasqual
- Department of Medical Area, University of Udine, Santa Maria della Misericordia University Hospital Udine, Udine, Italy
| | | | - Marco Vaira
- Candiolo Cancer Institute, Unit of Surgical Oncology, FPO-IRCCS, Candiolo, Italy
| | - Franco Roviello
- Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Siena, Italy
| |
Collapse
|
|
34
|
Ishigami H, Tsuji Y, Shinohara H, Kodera Y, Kanda M, Yabusaki H, Ito S, Imano M, Yamashita H, Hidemura A, Yamaguchi H, Fukagawa T, Oba K, Kitayama J, Seto Y. Intraperitoneal Chemotherapy as Adjuvant or Perioperative Chemotherapy for Patients with Type 4 Scirrhous Gastric Cancer: PHOENIX-GC2 Trial. J Clin Med 2021; 10:jcm10235666. [PMID: 34884367 PMCID: PMC8658657 DOI: 10.3390/jcm10235666] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 11/26/2021] [Accepted: 11/29/2021] [Indexed: 12/20/2022] Open
Abstract
The prognosis of patients with type 4 scirrhous gastric cancer remains poor due to a high risk of peritoneal metastasis. We have previously developed combined chemotherapy regimens of intraperitoneal (IP) paclitaxel (PTX) and systemic chemotherapy, and promising clinical efficacy was reported in gastric cancer with peritoneal metastasis. Herein, a randomized, phase III study is proposed to verify the efficacy of IP PTX to prevent peritoneal recurrence. Gastric cancer patients with type 4 tumors and without apparent distant metastasis, including peritoneal metastasis, will be randomized for standard systemic chemotherapy or combined IP and systemic chemotherapy based on peritoneal lavage cytology findings. Those with negative peritoneal cytology will receive radical gastrectomy and adjuvant chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). Those with positive peritoneal cytology will receive three courses of S-1 plus oxaliplatin (control arm), or S-1 plus oxaliplatin and IP PTX (experimental arm). Subsequently, they undergo gastrectomy and receive postoperative chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). The primary endpoint is disease free survival after a 3-year follow-up period. Secondary endpoints are overall survival, survival without peritoneal metastasis, safety, completion rate, curative resection rate, and histological response of preoperative chemotherapy. A total of 300 patients are to be enrolled.
Collapse
Affiliation(s)
- Hironori Ishigami
- Department of Chemotherapy, The University of Tokyo Hospital, Tokyo 113-8655, Japan
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan;
- Correspondence: ; Tel.: +81-3-3815-5411
| | - Yasushi Tsuji
- Department of Medical Oncology, Tonan Hospital, Sapporo 060-0004, Japan;
| | - Hisashi Shinohara
- Department of Gastroenterological Surgery, Division of Upper GI, Hyogo College of Medicine, Nishinomiya 663-8507, Japan;
| | - Yasuhiro Kodera
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; (Y.K.); (M.K.)
| | - Mitsuro Kanda
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; (Y.K.); (M.K.)
| | - Hiroshi Yabusaki
- Department of Gastroenterological Surgery, Niigata Cancer Center Hospital, Niigata 951-8566, Japan;
| | - Seiji Ito
- Department of Gastrointestinal Surgery, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan;
| | - Motohiro Imano
- Department of Surgery, Kindai University Faculty of Medicine, Osakasayama 589-8511, Japan;
| | - Hiroharu Yamashita
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo 101-8309, Japan;
| | - Akio Hidemura
- Department of Surgery, Kanto Rosai Hospital, Kawasaki 211-8510, Japan;
| | - Hironori Yamaguchi
- Department of Clinical Oncology, Jichi Medical University Hospital, Shimotsuke 329-0498, Japan;
| | - Takeo Fukagawa
- Department of Surgery, Teikyo University School of Medicine, Tokyo 173-8605, Japan;
| | - Koji Oba
- Interfaculty Initiative in Information Studies, Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan;
| | - Joji Kitayama
- Clinical Research Center, Department of Surgery, Jichi Medical University, Shimotsuke 329-0498, Japan;
| | - Yasuyuki Seto
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan;
| |
Collapse
|
|
35
|
Shimura T, Toden S, Kandimalla R, Toiyama Y, Okugawa Y, Kanda M, Baba H, Kodera Y, Kusunoki M, Goel A. Genomewide Expression Profiling Identifies a Novel miRNA-based Signature for the Detection of Peritoneal Metastasis in Patients With Gastric Cancer. Ann Surg 2021; 274:e425-e434. [PMID: 31663973 PMCID: PMC7577555 DOI: 10.1097/sla.0000000000003647] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE This study aimed to conduct a genomewide transcriptomic profiling to develop a microRNA (miRNA)-based signature for the identification of peritoneal metastasis (PM) in patients with gastric cancer (GC). SUMMARY BACKGROUND DATA Even though PM in patients with GC has long been recognized to associate with poor prognosis, currently there is lack of availability of molecular biomarkers for its robust diagnosis. METHODS We performed a systematic biomarker discovery by analyzing miRNA expression profiles in primary tumors from GC patients with and without PM, and subsequently validated the expression of candidate miRNA biomarkers in 3 independent clinical cohorts of 354 patients with advanced GC. RESULTS Five miRNAs (miR-30a-5p, -134-5p, -337-3p, -659-3p, and -3917) were identified during the initial discovery phase; three of which (miR-30a-5p, -659-3p, and -3917) were significantly overexpressed in the primary tumors from PM-positive patients in the testing cohort (P = 0.002, 0.04, and 0.007, respectively), and distinguished patients with versus without peritoneal metastasis with the value of area under the curve (AUC) of 0.82. Furthermore, high expression of these miRNAs also associated with poor prognosis (hazard ratio = 2.18, P = 0.04). The efficacy of the combination miRNA signature was subsequently validated in an independent validation cohort (AUC = 0.74). Finally, our miRNA signature when combined together with the macroscopic Borrmann's type score offered a much superior diagnostic in all 3 cohorts (AUC = 0.87, 0.76, and 0.79, respectively). CONCLUSIONS We have established an miRNA-based signature that have a potential to identify peritoneal metastasis in GC patients.
Collapse
Affiliation(s)
- Tadanobu Shimura
- Center for Gastrointestinal Research; Center from Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA
- Department of Molecular Diagnostics, Therapeutics and Translational Medicine, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Shusuke Toden
- Center for Gastrointestinal Research; Center from Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA
- Department of Molecular Diagnostics, Therapeutics and Translational Medicine, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Raju Kandimalla
- Center for Gastrointestinal Research; Center from Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA
- Department of Molecular Diagnostics, Therapeutics and Translational Medicine, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Yuji Toiyama
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Yoshinaga Okugawa
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Mitsuro Kanda
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan
| | - Yasuhiro Kodera
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masato Kusunoki
- Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan
| | - Ajay Goel
- Center for Gastrointestinal Research; Center from Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA
- Department of Molecular Diagnostics, Therapeutics and Translational Medicine, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| |
Collapse
|
|
36
|
Zhang X, Huang H, Yang D, Wang P, Huang X, Hu Z, Zhang Y, Yan R, Zhu Z, Cai Q. Neoadjuvant Intraperitoneal and Systemic Chemotherapy Versus Neoadjuvant Systemic Chemotherapy With Docetaxel, Oxaliplatin, and S-1 for Gastric Cancer With Peritoneal Metastasis: A Propensity Score Matched Analysis. Technol Cancer Res Treat 2021; 20:15330338211036310. [PMID: 34328799 PMCID: PMC8327225 DOI: 10.1177/15330338211036310] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND The optimal treatment for gastric cancer with peritoneal metastasis (GCPM) remains debatable. This study aimed to compare the efficacy and safety of neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) versus neoadjuvant systemic chemotherapy (NSC) for GCPM. METHODS Patients of GCPM received neoadjuvant chemotherapy with docetaxel, oxaliplatin and S-1 between January 2011 and June 2019 were retrospectively evaluated. Propensity score matched (PSM) analysis was carried out to reduce the selection bias. Multivariate Cox regression model was applied to screen the prognostic factors. RESULTS After PSM processing, 71 patients in each group were matched among the 186 GCPM patients included. NIPS yielded a better ascites and cytology response to chemotherapy, higher conversion resection rate and R0 resection rate than NSC. The overall survival (OS) rate in NIPS group was better than that in NSC group. Multivariate analysis revealed that the P stage, ascites response, conversion surgery rate and R0 resection rate were independent prognostic factors. Subgroup analysis indicated that NIPS showed a survival benefit over NSC only in patients with cT3-4a, P1-2, whose cytology turned negative, and who received conversion surgery; while not in patients with cT4b, P0 or P3, whose cytology did not turn negative, or who did not receive conversion surgery. CONCLUSIONS NIPS is a safe and feasible treatment for GCPM, which showed more benefit than NSC.
Collapse
Affiliation(s)
- Xin Zhang
- Department of Gastrointestinal Surgery, 56652Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Hejing Huang
- Department of Ultrasound, 56652Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Dejun Yang
- Department of Gastrointestinal Surgery, 56652Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Peng Wang
- Department of Radiology, 56652Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Xin Huang
- Department of Gastrointestinal Surgery, 56652Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Zunqi Hu
- Department of Gastrointestinal Surgery, 56652Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Yu Zhang
- Department of Gastrointestinal Surgery, 56652Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Ronglin Yan
- Department of Gastrointestinal Surgery, 56652Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Zhenxin Zhu
- Department of Gastrointestinal Surgery, 56652Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Qingping Cai
- Department of Gastrointestinal Surgery, 56652Changzheng Hospital, Naval Medical University, Shanghai, China
| |
Collapse
|
|
37
|
Jeong O, Jung MR, Kang JH. Treatment Modality Based Survival in Gastric Carcinoma Patients with Stand-Alone Peritoneal Metastasis: a Case-Control Study. J Gastric Cancer 2021; 21:122-131. [PMID: 34234974 PMCID: PMC8255297 DOI: 10.5230/jgc.2021.21.e12] [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: 02/27/2021] [Revised: 04/07/2021] [Accepted: 05/09/2021] [Indexed: 12/24/2022] Open
Abstract
Purpose To date, there are no promising treatments for gastric carcinoma with peritoneal metastasis. Some researchers have suggested a survival benefit of gastrectomy in select patients. This study investigated the survival of gastric carcinoma patients with stand-alone peritoneal metastasis according to the type of treatment modality. Materials and Methods We reviewed the data of 132 patients with gastric carcinoma and stand-alone peritoneal metastasis. We performed gastrectomy when the primary tumor was deemed resectable and systemic chemotherapy was administered. We analyzed patient survival according to the type of treatment, and the prognostic value of gastrectomy was evaluated in univariate and multivariate models. Results Among all patients, 70 underwent gastrectomy plus chemotherapy, 20 underwent gastrectomy alone, 36 underwent chemotherapy alone, and 6 received supportive care. The median patient survival was 13 months. Patients who underwent gastrectomy had significantly longer survival than those who did not undergo gastrectomy (14 vs. 8 months, P<0.001). Patients who received chemotherapy showed significantly longer survival than those who did not (13 vs. 7 months, P=0.032). Patients who underwent gastrectomy plus chemotherapy showed better survival than those who underwent other treatments. In multivariate analysis, gastrectomy was found to be an independent prognostic factor (hazard ratio, 0.52; 95% confidence interval, 0.33–0.82) in addition to chemotherapy. Conclusions Our study showed that patients who underwent gastrectomy plus chemotherapy had the best survival. Although the survival benefit of gastrectomy remains uncertain, it is a favorable prognostic indicator in patients with stand-alone peritoneal metastasis.
Collapse
Affiliation(s)
- Oh Jeong
- Division of Gastroenterologic Surgery, Chonnam National University Hwasun Hospital, Hwasun, Korea.,Department of Surgery, Chonnam National University Medical School, Hwasun, Korea
| | - Mi Ran Jung
- Division of Gastroenterologic Surgery, Chonnam National University Hwasun Hospital, Hwasun, Korea.,Department of Surgery, Chonnam National University Medical School, Hwasun, Korea
| | - Ji Hoon Kang
- Division of Gastroenterologic Surgery, Chonnam National University Hwasun Hospital, Hwasun, Korea.,Department of Surgery, Chonnam National University Medical School, Hwasun, Korea
| |
Collapse
|
|
38
|
Joshi SS, Badgwell BD. Current treatment and recent progress in gastric cancer. CA Cancer J Clin 2021; 71:264-279. [PMID: 33592120 PMCID: PMC9927927 DOI: 10.3322/caac.21657] [Citation(s) in RCA: 1033] [Impact Index Per Article: 258.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Revised: 12/08/2020] [Accepted: 12/09/2020] [Indexed: 12/15/2022] Open
Abstract
Gastric cancer is not a top-10 malignancy in the United States but represents one of the most common causes of cancer death worldwide. Biological differences between tumors from Eastern and Western countries add to the complexity of identifying standard-of-care therapy based on international trials. Systemic chemotherapy, radiotherapy, surgery, immunotherapy, and targeted therapy all have proven efficacy in gastric adenocarcinoma; therefore, multidisciplinary treatment is paramount to treatment selection. Triplet chemotherapy for resectable gastric cancer is now accepted and could represent a plateau of standard cytotoxic chemotherapy for localized disease. Classification of gastric cancer based on molecular subtypes is providing an opportunity for personalized therapy. Biomarkers, in particular microsatellite instability (MSI), programmed cell death ligand 1 (PD-L1), human epidermal growth factor receptor 2 (HER2), tumor mutation burden, and Epstein-Barr virus, are increasingly driving systemic therapy approaches and allowing for the identification of populations most likely to benefit from immunotherapy and targeted therapy. Significant research opportunities remain for the less differentiated histologic subtypes of gastric adenocarcinoma and those without markers of immunotherapy activity.
Collapse
Affiliation(s)
- Smita S Joshi
- Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Brian D Badgwell
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| |
Collapse
|
|
39
|
Brandl A, Prabhu A. Intraperitoneal chemotherapy in the treatment of gastric cancer peritoneal metastases: an overview of common therapeutic regimens. J Gastrointest Oncol 2021; 12:S32-S44. [PMID: 33968424 DOI: 10.21037/jgo-2020-04] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Peritoneal metastasis (PM) have an incidence of 10-20% in patients with gastric cancer (GC), and even up to 40% in patients with UICC Stage III GC. Due to the aggressive characteristic of adenocarcinoma of the stomach, GC is the third leading cause of cancer deaths worldwide. For GC with PM, the treatment of choice is according to national and international guidelines systemic chemotherapy, combined with biologic therapy against specific receptor antigen in with overexpression, such as HER-2. Multimodal treatment regimens including intraperitoneal application of chemotherapy and cytoreductive surgery (CRS) have been investigated and established all over the world. Driven by pharmacological studies and thoughts considering the increased benefits of cytotoxic agents used in the abdominal cavity, several drugs and drug combinations are widely used. In order to standardize treatment protocols, it is crucial to differentiate between normothermic and hyperthermic intraperitoneal chemotherapy (NIPEC, HIPEC). The requirements of an ideal cytotoxic drug different obviously dependent on its application method. Because of their high molecular weight and lipophilic structure, taxanes, such as paclitaxel or docetaxel have a long intraperitoneal retention time and are commonly used in NIPEC, while platin derivates, such as carboplatin or oxaliplatin are known for their synergistic effect to heat and are chosen in HIPEC. This review aims to explore and summarize different intraperitoneal treatment regimens strictly evaluated by supporting evidence in an effort to consolidate many regimens to a few evidence-based treatment protocols that deserve further investigation and distribution. This analysis included all studies focusing on intraperitoneal chemotherapy: Phase II, Phase III trials and non-randomized retrospective trials of larger cohorts of patients with GC and established PM or risk of PM. Interestingly, the protocols for NIPEC are quite uniform, with less variation between the therapeutic components in contrast to the different HIPEC protocols. This difference might be explained by the divergent evolution of NIPEC and HIPEC, as the former exclusively originated in Japan, while HIPEC experienced a more multicentric evolution and distribution in the United States, Asia, Europe, and worldwide utilization today.
Collapse
Affiliation(s)
- Andreas Brandl
- Digestive Unit, Champalimaud Foundation, Lisbon, Portugal
| | - Aruna Prabhu
- Department of Surgical Oncology, Thangam Cancer Center, Namakkal, Tamil Nadu, India
| |
Collapse
|
|
40
|
Canbay E, Canbay Torun B, Cosarcan K, Altunal C, Gurbuz B, Bilgic C, Sezgin C, Kaban KK, Yilmaz S, Yazici Z. Surgery with hyperthermic intraperitoneal chemotherapy after response to induction chemotherapy in patients with peritoneal metastasis of gastric cancer. J Gastrointest Oncol 2021; 12:S47-S56. [PMID: 33968425 DOI: 10.21037/jgo-20-121] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background Gastric cancer (GC) with peritoneal metastases (PM) has a dismal prognosis and to date only a few management options have been reported. Of those, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) after induction bidirectional intraperitoneal and systemic chemotherapy (BIPSC) appear as a promising treatment option for these patients. Outcome data including safety and efficacy of CRS with radical Gastrectomy and HIPEC after response to combination of laparoscopic HIPEC (LHIPEC) with BIPSC as an induction therapy in patients with PM of GC was evaluated in this retrospective observational study. Methods Diagnostic Laparoscopy was performed in 53 patients with PM of GC who admitted to the Center for Treatment of Peritoneal Surface Malignancies, Istanbul, between 2013 and 2016. Peritoneal cancer index (PCI), ascites status and cytology were determined. The patients underwent LHIPEC and then, BIPSC induction chemotherapy using intraperitoneal docetaxel (30 mg/m2) and cisplatin (30 mg/m2) and intravenous Docetaxel/Cisplatin/5-Fluorouracil (DCF) for 3 cycles. In selected patients, CRS with radical gastrectomy and HIPEC were performed after the response to induction therapy. BIPSC was continued for 3 more cycles with a dose reduction in an adjuvant setting. Results All LHIPEC procedures were uneventful with Grade 1-2 side effects (11/53, 20,8%). As a response to induction chemotherapy PCI was reduced from 19.6±8 (range, 6-39) to 13.6±9.8 (range, 1-39) (P<0.001). Ascites was detected in 55% (29 out of 53) and cytology was positive in 51% (27 out of 53) of the patients before induction chemotherapy. Ascites was completely abolished and all cytology became negative. Then, 34 of 53 (64.15%) patients underwent CRS with radical gastrectomy and HIPEC. CC0/1 resection was achieved in 22 (64.70%) of patients (P<0.05). The median survival time was 18.9±13.4 (95% CI: 15.2-22.6 months. Combined surgery and HIPEC related mortality occurred in 1 out of 34 patients (2.9%) due to developed diffuse intravascular coagulation at postoperative day 2. Grade 2 operative complications included biliary fistula in one, and duodenal stump leakage in two patients (8.7%). All of the fistula closed with conservative management. The median survival time was 18.9±13.4 months and the median progression-free survival time was 15.6±12.9 with 1-, 2-, and 5-year survival rates of 82.4%, 59% and 17.6% in patients with PM of GC. Multivariate analysis identified high peritoneal cancer index (P=0.000) and complete resection (P<0.05) as independent predictors for better progression-free and overall survival. Conclusions The best outcomes can be expected with optimal cytoreduction and limited peritoneal dissemination in response to induction chemotherapy. Knowledgeable selection of patients with PM of GC is essential to perform surgery with HIPEC safely with acceptable mortality and morbidity.
Collapse
Affiliation(s)
- Emel Canbay
- Department of General Surgery, NPO Center for Peritoneal Surface Malignancies, Istanbul, Turkey
| | - Bahar Canbay Torun
- Department of General Surgery, Istanbul Haseki Education & Research Hospital, Istanbul, Turkey
| | - Kaan Cosarcan
- Department of Anesthesiology, American Hospital, Istanbul, Turkey
| | - Cetin Altunal
- Department of General Surgery, NPO Center for Peritoneal Surface Malignancies, Istanbul, Turkey
| | - Bulent Gurbuz
- Department of General Surgery, American Hospital, Istanbul, Turkey
| | - Cagri Bilgic
- Department of General Surgery, American Hospital, Istanbul, Turkey
| | - Canfeza Sezgin
- Department of Medical Oncology, American Hospital, Istanbul, Turkey
| | - Kerim Kim Kaban
- Department of Medical Oncology, Faculty of Medicine, Biruni University, Istanbul, Turkey
| | - Serpil Yilmaz
- Department of Pathology, American Hospital, Istanbul, Turkey
| | - Zeliha Yazici
- Department of Pharmacology, Faculty of Medicine, Biruni University, Istanbul, Turkey
| |
Collapse
|
|
41
|
Kang WZ, Zhong YX, Ma FH, Tian YT. Progress and controversy in treatment of gastric cancer patients with positive peritoneal lavage cytology. Shijie Huaren Xiaohua Zazhi 2021; 29:269-273. [DOI: 10.11569/wcjd.v29.i6.269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Wen-Zhe Kang
- 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
| | - Yu-Xin Zhong
- 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
| | - Fu-Hai Ma
- 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
| | - 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
| |
Collapse
|
|
42
|
Parray A, Gupta V, Chaudhari VA, Shrikhande SV, Bhandare MS. Role of intraperitoneal chemotherapy in gastric cancer. SURGERY IN PRACTICE AND SCIENCE 2021. [DOI: 10.1016/j.sipas.2020.100025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
|
|
43
|
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
|
|
44
|
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: 23] [Impact Index Per Article: 5.8] [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
|
|
45
|
Kang WZ, Zhong YX, Ma FH, Xue LY, Xiong JP, Ma S, Li Y, Xie YB, Quan X, Tian YT. Survival outcomes and prognostic indicators for gastric cancer patients with positive peritoneal wash cytology but no peritoneal metastasis after radical gastrectomy. World J Gastrointest Oncol 2021; 13:24-36. [PMID: 33510847 PMCID: PMC7805269 DOI: 10.4251/wjgo.v13.i1.24] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 11/03/2020] [Accepted: 11/29/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Positive peritoneal wash cytology with no peritoneal metastasis (CY1P0) is a special type of distant gastric cancer metastasis, which describes a patient with positive peritoneal lavage cytology, but no definitive peritoneal metastasis, and there are no widely accepted treatment guidelines. We enrolled 48 primary CY1P0 gastric cancer patients treated by radical gastrectomy in this study. Our study illustrated the efficacy of radical gastrectomy for CY1P0 gastric cancer patients, and suggested that the pathological N factor and vascular invasion were significant independent risk factors for overall survival (OS). AIM To assess the survival of CY1P0 gastric cancer patient post-radical gastrectomy, and to identify factors associated with long-term prognosis. METHODS Our study included 48 patients with primary CY1P0 gastric cancer who had radical gastrectomies at the Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China between 2013 and 2018. R0 resection was achieved in all 48 patients. Twelve patients received neoadjuvant chemotherapy. Thirty patients received adjuvant chemotherapy and four received adjuvant chemoradiotherapy. OS statistics were available for 48 patients. Follow-up continued through March 2020. Univariate and multivariate analyses were performed using a Cox proportional hazards model to identify prognostic factors. RESULTS Median OS was 22.0 mo (95% confidence interval: 13.366-30.634 mo) post-surgery. Univariate analyses demonstrated that tumor site (P = 0.021), pathological N factor (P = 0.001), pathological T factor (P = 0.028), vascular invasion (P = 0.046), and the level of CA199 prior to initiating therapy (P = 0.002) were significant risk factors for OS. Multivariate analyses demonstrated that pathological N factor (P = 0.001) and vascular invasion (P = 0.031) were significant independent risk factors for OS. CONCLUSION This study suggested that radical gastrectomy may be efficient for CY1P0 gastric cancer patient post-radical gastrectomy and the pathological N factor and vascular invasion are significant independent risk factors for OS.
Collapse
Affiliation(s)
- Wen-Zhe Kang
- 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
| | - Yu-Xin Zhong
- 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
| | - Fu-Hai Ma
- 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
| | - Li-Yan Xue
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Bejing 100021, China
| | - Jian-Ping Xiong
- 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
| | - Shuai Ma
- 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
| | - Yang Li
- 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
| | - Xu Quan
- 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
| | - 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
| |
Collapse
|
|
46
|
Badgwell B, Ikoma N, Murphy MB, Wang X, Estrella J, Roy-Chowdhuri S, Das P, Minsky BD, Lano E, Song S, Mansfield P, Ajani J. A Phase II Trial of Cytoreduction, Gastrectomy, and Hyperthermic Intraperitoneal Perfusion with Chemotherapy for Patients with Gastric Cancer and Carcinomatosis or Positive Cytology. Ann Surg Oncol 2021; 28:258-264. [PMID: 32556731 DOI: 10.1245/s10434-020-08739-5] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND Current national guidelines do not include hyperthermic intraperitoneal chemoperfusion (HIPEC) as treatment for gastric cancer, and there are no completed clinical trials of cytoreduction, gastrectomy, and HIPEC from the US. METHODS Patients with gastric adenocarcinoma and positive peritoneal cytology or carcinomatosis who had completed systemic chemotherapy and laparoscopic HIPEC underwent cytoreduction, gastrectomy, and HIPEC with 30 mg mitomycin C and 200 mg cisplatin. The primary endpoint was overall survival (OS), with a secondary endpoint of postoperative complications (NCT02891447). RESULTS We enrolled 20 patients from September 2016 to March 2019. Six patients had positive cytology only and 14 had carcinomatosis. All patients were treated with systemic chemotherapy with a median of eight cycles (range 5-11 cycles) and at least one laparoscopic HIPEC. The median peritoneal carcinomatosis index at cytoreduction/gastrectomy/HIPEC was 2 (range 0-13). After surgery, the 90-day morbidity and mortality rates were 70% and 0%, respectively. Median length of hospital stay was 13 days (range 7-23 days); median follow-up was 33.5 months; median OS from the date of diagnosis of metastatic disease was 24.2 months; and median OS from the date of cytoreduction, gastrectomy, and HIPEC was 16.1 months. 1-, 2-, and 3-year OS rates from the diagnosis of metastatic disease were 90%, 50%, and 28%, respectively. CONCLUSIONS Survival rates for patients with gastric adenocarcinoma and peritoneal disease treated with cytoreduction, gastrectomy, and HIPEC are encouraging; our early results are similar to those of recent prospective registry studies. Multi-institutional and cooperative group trials should be supported to confirm survival and safety outcomes.
Collapse
Affiliation(s)
- Brian Badgwell
- Department of Surgical Oncology, Unit 1484, MD Anderson Cancer Center, Houston, TX, USA.
| | - Naruhiko Ikoma
- Department of Surgical Oncology, Unit 1484, MD Anderson Cancer Center, Houston, TX, USA
| | - Mariela Blum Murphy
- Department of Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA
| | - Xuemei Wang
- Department of Biostatistics, MD Anderson Cancer Center, Houston, TX, USA
| | | | | | - Prajnan Das
- Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA
| | - Bruce D Minsky
- Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA
| | - Elizabeth Lano
- Department of Diagnostic Imaging, MD Anderson Cancer Center, Houston, TX, USA
| | - Shumei Song
- Department of Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA
| | - Paul Mansfield
- Department of Surgical Oncology, Unit 1484, MD Anderson Cancer Center, Houston, TX, USA
| | - Jaffer Ajani
- Department of Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA
| |
Collapse
|
|
47
|
Saito S, Yamaguchi H, Ohzawa H, Miyato H, Kanamaru R, Kurashina K, Hosoya Y, Lefor AK, Sata N, Kitayama J. Intraperitoneal Administration of Paclitaxel Combined with S-1 Plus Oxaliplatin as Induction Therapy for Patients with Advanced Gastric Cancer with Peritoneal Metastases. Ann Surg Oncol 2020; 28:3863-3870. [PMID: 33270170 PMCID: PMC8184712 DOI: 10.1245/s10434-020-09388-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Accepted: 11/04/2020] [Indexed: 12/27/2022]
Abstract
Background Intraperitoneal (IP) administration of paclitaxel (PTX) has a great pharmacokinetic advantage to control peritoneal lesions and can be combined with various systemic chemotherapies. In this study, we evaluate the efficacy and tolerability of a combination of IP-PTX and systemic S-1/oxaliplatin (SOX) for induction chemotherapy for patients with peritoneal metastases (PM) from gastric cancer (GC). Patients and Methods Patients with GC who were diagnosed as macroscopic PM (P1) or positive peritoneal cytology (CY1) by staging laparoscopy between 2016 and 2019 were enrolled. PTX was IP administered at 40 mg/m2 on days 1 and 8. Oxaliplatin was IV administered at 100 mg/m2 on day 1, and S-1 was administered at 80 mg/m2/day for 14 consecutive days, repeated every 21 days. Survival time and toxicities were retrospectively explored. Results Forty-four patients received SOX + IP-PTX with a median (range) of 16 (1–48) courses, although oxaliplatin was suspended due to the hematotoxicity or intolerable peripheral neuropathy in many patients. The 1-year overall survival (OS) rate was 79.5% (95% CI 64.4–88.8%) with median survival time of 25.8 months. Gastrectomy was performed in 20 (45%) patients who showed macroscopic shrinkage of PM with a 1-year OS rate of 100% (95% CI 69.5–100%). Grade 2 and 3 histological responses was achieved in four (20%) and one (5%) patients. Grade 3/4 toxicities included neutropenia (11%), leukopenia (39%), and anemia (14%). There were no treatment-related deaths. Conclusions Combination chemotherapy using SOX + IP-PTX regimen is highly effective and recommended as induction chemotherapy for patients with PM from GC.
Collapse
Affiliation(s)
- Shin Saito
- Department of Gastrointestinal Surgery, Jichi Medical University, Tochigi, Japan
| | | | - Hideyuki Ohzawa
- Department of Chemotherapy, Jichi Medical University, Tochigi, Japan
| | - Hideyo Miyato
- Department of Gastrointestinal Surgery, Jichi Medical University, Tochigi, Japan
| | - Rihito Kanamaru
- Department of Gastrointestinal Surgery, Jichi Medical University, Tochigi, Japan
| | - Kentaro Kurashina
- Department of Gastrointestinal Surgery, Jichi Medical University, Tochigi, Japan
| | - Yoshinori Hosoya
- Department of Gastrointestinal Surgery, Jichi Medical University, Tochigi, Japan
| | - Alan Kawarai Lefor
- Department of Gastrointestinal Surgery, Jichi Medical University, Tochigi, Japan
| | - Naohiro Sata
- Department of Gastrointestinal Surgery, Jichi Medical University, Tochigi, Japan
| | - Joji Kitayama
- Department of Gastrointestinal Surgery, Jichi Medical University, Tochigi, Japan.
| |
Collapse
|
|
48
|
Brandl A, Yonemura Y, Glehen O, Sugarbaker P, Rau B. Long term survival in patients with peritoneal metastasised gastric cancer treated with cytoreductive surgery and HIPEC: A multi-institutional cohort from PSOGI. Eur J Surg Oncol 2020; 47:172-180. [PMID: 33071173 DOI: 10.1016/j.ejso.2020.10.006] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 08/21/2020] [Accepted: 10/05/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Peritoneal metastasis (PM) of gastric cancer (GC) is relatively common (17%) and is associated with poor survival. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is still controversially discussed, as it has proven an increase in survival in selected patients, but only a small subgroup reached long-term survival. The aim of this study was to collect and analyse a worldwide cohort of patients treated with CRS and HIPEC with long-term survival in order to explore relevant patient characteristics. METHODS We conducted a questionnaire, which was distributed to all collaborators of the Peritoneal Surface Oncology Group International (PSOGI). Inclusion criteria were: histopathologic proven PM of GC, treated with CRS and HIPEC, and overall survival >5 years. Patient, tumour, and therapeutic details were collected and analysed. RESULTS From an analysis of 448 patients treated between 1994 and 2014, a total of 28 patients with a mean age of 53.0 years and mean PCI of 3.3 were included. The overall median survival was 11.0 years (min 5.0; max 27.9). The predictors completeness of cytoreduction (CC-0) and PCI<6 were present in 22/28 patients. 12/28 patients developed at a median of 9.6 years tumour recurrence, and was associated with inferior median overall survival compared to patients without recurrence (8.8 years vs. not reached; p = 0.002). CONCLUSIONS Long-term survival and even cure are possible in patients with PM of GC treated with CRS and HIPEC. Completeness of cytoreduction and low PCI seemed to be crucial. Further studies are needed in order to improve existing selection criteria.
Collapse
Affiliation(s)
- Andreas Brandl
- Department of Surgery, Campus Virchow-Klinikum and Charité Campus Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany; Digestive Unit, Champalimaud Foundation, Lisbon, Portugal
| | - Yutaka Yonemura
- Department of Regional Cancer Therapy, Peritoneal Surface Malignancy Center, Kishiwada Tokushukai Hospital, Kishiwada, Japan
| | - Olivier Glehen
- Department of Surgical Oncology, Centre Hospitalier Lyon-Sud, Lyon, France
| | - Paul Sugarbaker
- Program in Peritoneal Surface Oncology, Washington Cancer Institute, Washington, DC, USA
| | - Beate Rau
- Department of Surgery, Campus Virchow-Klinikum and Charité Campus Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany.
| |
Collapse
|
|
49
|
Ishikawa W, Kikuchi S, Ogawa T, Tabuchi M, Tazawa H, Kuroda S, Noma K, Nishizaki M, Kagawa S, Urata Y, Fujiwara T. Boosting Replication and Penetration of Oncolytic Adenovirus by Paclitaxel Eradicate Peritoneal Metastasis of Gastric Cancer. MOLECULAR THERAPY-ONCOLYTICS 2020; 18:262-271. [PMID: 32728614 PMCID: PMC7378855 DOI: 10.1016/j.omto.2020.06.021] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 06/22/2020] [Indexed: 02/07/2023]
Abstract
Peritoneal metastasis is the most frequent form of distant metastasis and recurrence in gastric cancer, and the prognosis is extremely poor due to the resistance of systemic chemotherapy. Here, we demonstrate that intraperitoneal (i.p.) administration of a green fluorescence protein (GFP)-expressing attenuated adenovirus with oncolytic potency (OBP-401) synergistically suppressed the peritoneal metastasis of gastric cancer in combination with paclitaxel (PTX). OBP-401 synergistically suppressed the viability of human gastric cancer cells in combination with PTX. PTX enhanced the antitumor effect of OBP-401 due to enhanced viral replication in cancer cells. The combination therapy increased induction of mitotic catastrophe, resulting in accelerated autophagy and apoptosis. Peritoneally disseminated nodules were selectively visualized as GFP-positive spots by i.p. administration of OBP-401 in an orthotopic human gastric cancer peritoneal dissemination model. PTX enhanced the deep penetration of OBP-401 into the disseminated nodules. Moreover, a non-invasive in vivo imaging system demonstrated that the combination therapy of i.p. OBP-401 administration with PTX significantly inhibited growth of peritoneal metastatic tumors and the amount of malignant ascites. i.p. virotherapy with PTX may be a promising treatment strategy for the peritoneal metastasis of gastric cancer.
Collapse
Affiliation(s)
- Wataru Ishikawa
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
| | - Satoru Kikuchi
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
- Corresponding author: Satoru Kikuchi, Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
| | - Toshihiro Ogawa
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
| | - Motoyasu Tabuchi
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
| | - Hiroshi Tazawa
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
- Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama 700-8558, Japan
| | - Shinji Kuroda
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
- Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama 700-8558, Japan
| | - Kazuhiro Noma
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
| | - Masahiko Nishizaki
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
| | - Shunsuke Kagawa
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
| | - Yasuo Urata
- Oncolys BioPharma, Inc., Tokyo 106-0032, Japan
| | - Toshiyoshi Fujiwara
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
| |
Collapse
|
|
50
|
Chia DKA, So JBY. Recent Advances in Intra-peritoneal Chemotherapy for Gastric Cancer. J Gastric Cancer 2020; 20:115-126. [PMID: 32595996 PMCID: PMC7311211 DOI: 10.5230/jgc.2020.20.e15] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2020] [Revised: 03/09/2020] [Accepted: 03/20/2020] [Indexed: 12/21/2022] Open
Abstract
Peritoneal metastasis (PM) frequently occurs in patients with gastric cancer (GC) and confers a dismal prognosis despite advances in systemic chemotherapy. While systemic chemotherapy has poor peritoneal penetration, intraperitoneal (IP) chemotherapy remains sequestered, resulting in high peritoneal drug concentrations with less systemic side-effects. The first application of IP treatment was hyperthermic intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery (CRS) for gastric cancer peritoneal metastasis (GCPM); but was associated with an increased morbidity and mortality rate without significantly improving overall survival (OS). While CRS confers limited benefit, the potential role of prophylactic HIPEC and laparoscopic neoadjuvant HIPEC are currently being evaluated. Combination systemic and IP chemotherapy (SIPC) gained popularity in the 1990s, since it provided the benefits of IP treatment while reducing surgical morbidity, demonstrating promising early results in multiple Phase II trials. Unfortunately, these findings were not confirmed in the recent PHOENIX-GC randomized controlled trial; therefore, the appropriate treatment for GCPM remains controversial. Small observational studies from Japan and Singapore have reported successful downstaging of PM in GC patients receiving SIPC who subsequently underwent conversion gastrectomy with a median OS of 21.6–34.6 months. Recently, the most significant development in IP-directed therapy is pressurized IP aerosol chemotherapy (PIPAC). Given that aerosol chemotherapy achieves a wider distribution and deeper penetration, the outcomes of multiple ongoing trials assessing its efficacy are eagerly awaited. Indeed, IP-directed therapy has evolved rapidly in the last 3 decades, with an encouraging trend toward improved outcomes in GCPM, and may offer some hope for an otherwise fatal disease.
Collapse
Affiliation(s)
- Daryl K A Chia
- Department of Surgery, University Surgical Cluster, National University Health System, Singapore
| | - Jimmy B Y So
- Department of Surgery, University Surgical Cluster, National University Health System, Singapore.,Division of General Surgery (Upper Gastrointestinal Surgery), Department of Surgery, University Surgical Cluster, National University Health System, Singapore.,Division of Surgical Oncology, National University Cancer Institute, Singapore
| |
Collapse
|