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1
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Blaj S, Häusler S, Piso P. Relevant Ongoing Clinical Trials to Investigate Local-Regional Treatment Strategies for Peritoneal Surface Malignancies. J Surg Oncol 2024; 130:1349-1357. [PMID: 39491890 DOI: 10.1002/jso.27853] [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: 07/05/2024] [Revised: 08/03/2024] [Accepted: 08/19/2024] [Indexed: 11/05/2024]
Abstract
BACKGROUND AND OBJECTIVES The multimodal therapy of peritoneal metastases of common cancers (i.e. colorectal, gastric, and ovarian), including CRS plus HIPEC, is still subject to several clinical studies. METHODS This paper presents the ongoing studies regarding HIPEC, as found on clinicaltrials.gov. The emphasis was set on Phase III recruiting trials, including the newest information from principal investigators who answered the call of the authors. RESULTS Ninety trials have been identified, and the protocols of 15 studies have been presented in detail. CONCLUSIONS There are interesting ongoing trials investigating the role of CRS plus HIPEC.
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Affiliation(s)
- S Blaj
- Department of General and Visceral Surgery, Hospital Barmherzige Brüder, Regensburg, Germany
| | - S Häusler
- Department of Gynaecology and Obstetrics Nathanstift, Hospital Fürth, Germany
| | - P Piso
- Department of General and Visceral Surgery, Hospital Barmherzige Brüder, Regensburg, Germany
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2
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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.
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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
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3
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Zeng L, Huang X, Tian Y, Huang J, Liu H, Wen J, Liu K, Shao Y, Luo J, Tang H, Liao Q, Lei Z, Cui W, Xia Q, Guan T, Li J, Cui S. Tumor Mutational Burden Associated With Response to Hyperthermic Intraperitoneal Chemotherapy. Front Oncol 2022; 12:796263. [PMID: 35350562 PMCID: PMC8958003 DOI: 10.3389/fonc.2022.796263] [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: 10/16/2021] [Accepted: 02/04/2022] [Indexed: 11/13/2022] Open
Abstract
Background Gastric cancer (GC) is one of the most common cancer types, especially in Asian countries. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to improve the progression-free survival among gastric cancer patients with peritoneal metastases; however, not all patients demonstrate response to HIPEC. Methods Biomarkers are needed to select patients for effective treatment of HIPEC. Here, we performed whole-exome sequencing on tumor samples from 18 gastric cancer patients who received HIPEC treatment and assessed the association between genomic mutation features and progression-free survival. Exome sequencing was further conducted on tumor samples from additional 15 gastric cancer patients as a replication study. Results The tumor mutational burden (TMB) was significantly higher in the group of patients with a better response to HIPEC treatment than that of the others. Kaplan–Meier survival curve showed that patients with high TMB had a significantly longer survival time than that in patients with low TMB. This discovery was validated in the replication cohort. Genes bearing mutations recurrently and selectively in patients with better response to HIPEC were found in the two cohorts. Conclusion We found that higher TMB is significantly associated with better response to HIPEC. Our results provide useful hints for prognostic stratification of HIPEC treatment.
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Affiliation(s)
- Lisi Zeng
- Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Xubo Huang
- Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Yun Tian
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Jinxia Huang
- Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Huiyan Liu
- Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Juncai Wen
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Kaihua Liu
- Medical Department, Nanjing Geneseeq Technology Inc., Nanjing, China
| | - Yang Shao
- Medical Department, Nanjing Geneseeq Technology Inc., Nanjing, China
| | - Jiali Luo
- Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Hongsheng Tang
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Quanxing Liao
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Ziying Lei
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Weiwen Cui
- Department of Bioengineering, University of California, Berkeley, Berkeley, CA, United States
| | - Qianghua Xia
- Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Tianpei Guan
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Jin Li
- Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Shuzhong Cui
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.,State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China
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Gronau F, Feldbruegge L, Oberwittler F, Gonzalez-Moreno S, Villeneuve L, Eveno C, Glehen O, Kusamura S, Rau B. HIPEC in Peritoneal Metastasis of Gastric Origin: A Systematic Review of Regimens and Techniques. J Clin Med 2022; 11:jcm11051456. [PMID: 35268546 PMCID: PMC8911234 DOI: 10.3390/jcm11051456] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 03/04/2022] [Accepted: 03/04/2022] [Indexed: 02/06/2023] Open
Abstract
(1) Background: Peritoneal metastasis in gastric cancer is associated with a poor prognosis. Complete cytoreductive surgery including gastrectomy and complete removal of all peritoneal lesions followed by hyperthermic intraperitoneal chemotherapy (HIPEC) achieves promising results. There exists an immersive variety of approaches for HIPEC that makes it difficult to weigh different results obtained in the literature. In order to enable standardization and development of HIPEC, we here present a systematic review of different drug regimens and technical approaches. (2) Methods: PubMed, Embase, and the Cochrane Library were systematically searched on 26 May 2021 using the mesh terms “intraperitoneal chemotherapy AND gastric cancer”. Under consideration of systematic review guidelines, articles reporting on HIPEC in combination with CRS were selected. Data on duration, drugs, dosage, and other application parameters as well as morbidity and long term survival data were extracted for subsequent statistical analysis, tabulation, and descriptive synthesis. We assessed the risk of bias due to inhomogeneity of the patient cohort and incompleteness of report of HIPEC parameters. (3) Results: Out of 1421 screened publications, 42 publications presenting data from 1325 patients met the criteria. Most of the publications were single institutional retrospective cohort studies. The most common HIPEC regimen is performed after gastrointestinal anastomosis and consists of 50–200 mg/m2 cisplatinum and 30–40 mg/m2 mytomycin C at 42–43 °C for 60–90 min in a closed abdomen HIPEC system with three tubes. Almost every study reported incompletely on HIPEC parameters. Lower rates of anastomotic leakage were reported in studies that performed HIPEC after gastrointestinal anastomosis. Studies that performed open HIPEC and integrated a two-drug regimen indicated better overall survival rates. (4) Discussion: This is an exhaustive overview of the use of drug regimens and techniques for HIPEC after CRS for gastric cancer peritoneal metastasis. Other indications and application modes of intraperitoneal chemotherapy such as prophylactic or palliative HIPEC apart from CRS were not addressed. (5) Conclusion: Complete report of HIPEC parameters should be included in every publication. A consensus for dose expression either per BSA or as flat dose is desirable for comparison of the drug regimens. Despite numerous variations, we identified the most common regimens and techniques and their advantages and disadvantages according to the data in the literature. More phase I/II studies are needed to identify the best approach for HIPEC. (6) Other: This review was not supported by third parties.
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Affiliation(s)
- Felix Gronau
- Department of Surgery, Chirurgische Klinik Campus Charité Mitte|Campus Virchow Klinikum, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany; (F.G.); (L.F.); (F.O.)
| | - Linda Feldbruegge
- Department of Surgery, Chirurgische Klinik Campus Charité Mitte|Campus Virchow Klinikum, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany; (F.G.); (L.F.); (F.O.)
| | - Frauke Oberwittler
- Department of Surgery, Chirurgische Klinik Campus Charité Mitte|Campus Virchow Klinikum, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany; (F.G.); (L.F.); (F.O.)
| | | | - Laurent Villeneuve
- Réseau National de Prise en Charge des Tumeurs Rares du Péritoine, French National Registry of Rare Peritoneal Surface Malignancies, 69002 Lyon, France;
| | - Clarisse Eveno
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, 69495 Pierre-Bénite, France; (C.E.); (O.G.)
| | - Olivier Glehen
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, 69495 Pierre-Bénite, France; (C.E.); (O.G.)
| | - Shigeki Kusamura
- Peritoneal Surface Malignancies Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Nazionale Tumori dei Tumori di Milano, 20133 Milano, Italy;
| | - Beate Rau
- Department of Surgery, Chirurgische Klinik Campus Charité Mitte|Campus Virchow Klinikum, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany; (F.G.); (L.F.); (F.O.)
- Correspondence: ; Tel.: +49-30-450-622-214
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Kimura Y, Ohzawa H, Miyato H, Kaneko Y, Saito A, Takahashi K, Tojo M, Yamaguchi H, Kurashina K, Saito S, Hosoya Y, Lefor AK, Sata N, Kitayama J. MiR-29b may suppresses peritoneal metastases through inhibition of the mesothelial-mesenchymal transition (MMT) of human peritoneal mesothelial cells. Sci Rep 2022; 12:205. [PMID: 34997082 PMCID: PMC8742040 DOI: 10.1038/s41598-021-04065-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 11/30/2021] [Indexed: 11/09/2022] Open
Abstract
Peritoneal dissemination is a major metastatic pathway for gastrointestinal and ovarian malignancies. The miR-29b family is downregulated in peritoneal fluids in patients with peritoneal metastases (PM). We examined the effect of miR-29b on mesothelial cells (MC) which play critical a role in the development of PM through mesothelial-mesenchymal transition (MMT). Human peritoneal mesothelial cells (HPMCs) were isolated from surgically resected omental tissue and MMT induced by stimulation with 10 ng/ml TGF-β1. MiR-29b mimics and negative control miR were transfected by lipofection using RNAiMAX and the effects on the MMT evaluated in vitro. HPMC produced substantial amounts of miR-29b which was markedly inhibited by TGF-β1. TGF-β1 stimulation of HPMC induced morphological changes with decreased expression of E-cadherin and calretinin, and increased expression of vimentin and fibronectin. TGF-β1 also enhanced proliferation and migration of HPMC as well as adhesion of tumor cells in a fibronectin dependent manner. However, all events were strongly abrogated by simultaneous transfection of miR-29b. MiR-29b inhibits TGF-β1 induced MMT and replacement of miR-29b in the peritoneal cavity might be effective to prevent development of PM partly through the effects on MC.
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Affiliation(s)
- Yuki Kimura
- Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Hideyuki Ohzawa
- Department of Clinical Oncology, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Hideyo Miyato
- Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Yuki Kaneko
- Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Akira Saito
- Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Kazuya Takahashi
- Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Mineyuki Tojo
- Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Hironori Yamaguchi
- Department of Clinical Oncology, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Kentaro Kurashina
- Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Shin Saito
- Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Yoshinori Hosoya
- Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Alan Kawarai Lefor
- Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Naohiro Sata
- Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Joji Kitayama
- Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan.
- Center for Clinical Research, Jichi Medical University Hospital, Shimotsuke, Tochigi, Japan.
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Mazurek M, Szlendak M, Forma A, Baj J, Maciejewski R, Roviello G, Marano L, Roviello F, Polom K, Sitarz R. Hyperthermic Intraperitoneal Chemotherapy in the Management of Gastric Cancer: A Narrative Review. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:681. [PMID: 35055500 PMCID: PMC8776178 DOI: 10.3390/ijerph19020681] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 01/02/2022] [Accepted: 01/04/2022] [Indexed: 02/05/2023]
Abstract
Gastric cancer (GC) patients with peritoneal metastasis tend to achieve poor clinical outcomes. Until recently, the treatment options were limited mainly to either palliative chemotherapy or radiation therapy in exceptional cases. Currently, these patients benefit from multimodal treatment, such as cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Despite good overall results, this treatment modality is still widely debated. The following study is designed to assess the papers about the possible application and utility of HIPEC in GC. A search in the PubMed, Web of Science, and Scopus databases was performed to assess the papers devoted to the role of HIPEC in GC treatment; a literature search was performed until March 21st; and, finally, 50 studies with a total number of 3946 patients were analyzed. According to the most recent data, it seems to be reasonable to limit the duration of HIPEC to the shortest effective time. Moreover, the drugs used in HIPEC need to have equal concentrations and the same solvent. Perioperative chemotherapy needs to be reported in detail and, furthermore, the term "morbidity" should be defined more clearly by the authors.
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Affiliation(s)
- Marek Mazurek
- Department of Surgical Oncology, Voivodship Hospital in Siedlce, 08-110 Siedlce, Poland;
| | - Małgorzata Szlendak
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (M.S.); (J.B.); (R.M.)
- Department of Oncology, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Alicja Forma
- Department of Forensic Medicine, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Jacek Baj
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (M.S.); (J.B.); (R.M.)
| | - Ryszard Maciejewski
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (M.S.); (J.B.); (R.M.)
| | | | - Luigi Marano
- Department of General Surgery and Surgical Oncology, University of Siena, 53100 Siena, Italy; (L.M.); (F.R.)
| | - Franco Roviello
- Department of General Surgery and Surgical Oncology, University of Siena, 53100 Siena, Italy; (L.M.); (F.R.)
| | - Karol Polom
- Department of Surgical Oncology, Medical University of Gdansk, 80-070 Gdansk, Poland;
| | - Robert Sitarz
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (M.S.); (J.B.); (R.M.)
- Department of Surgical Oncology, St. John’s Cancer Center, 20-090 Lublin, Poland
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Graziosi L, Marino E, Bencivenga M, D’Ignazio A, Solaini L, Ministrini S, Caprioli M, Sacco M, Marrelli D, Mura G, Degiuli M, Morgagni P, Tiberio GAM, De Manzoni G, Roviello F, Donini A. Looking for a strategy in treating peritoneal gastric cancer carcinomatosis: an Italian multicenter Gastric Cancer Research group's analysis. World J Surg Oncol 2021; 19:334. [PMID: 34819103 PMCID: PMC8611869 DOI: 10.1186/s12957-021-02442-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 11/02/2021] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND The present study provides a snapshot of Italian patients with peritoneal metastasis from gastric cancer treated by surgery in Italian centers belonging to the Italian Research Group on Gastric Cancer. Prognostic factors affecting survival in such cohort of patients were evaluated with the final aim to identify patients who may benefit from radical intent surgery. METHODS It is a multicentric retrospective study based on a prospectively collected database including demographics, clinical, surgical, pathological, and follow-up data of patients with gastric cancer and synchronous macroscopic peritoneal metastases. Patients were surgically treated from January 2005 to January 2017. We focused on patients with macroscopic peritoneal carcinomatosis (PC) treated with upfront surgery in order to provide homogeneous evidences. RESULTS Our results show that patients with peritoneal carcinomatosis cannot be considered all lost. Strictly selected cases (R0/R1 and P1 patients) could benefit from an aggressive surgical approach performing an extended lymphadenectomy and HIPEC treatment. CONCLUSION The main result of the study is that GC patients with limited peritoneal involvement can have a survival benefit from a surgery with "radical oncological intent", that means extended lymphadenectomy and R0 resection. The retrospective nature of this study is an important bias, and for this reason, we have started a prospective multicentric study including Italian stage IV patients that hopefully will give us more answers.
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Affiliation(s)
- Luigina Graziosi
- General and Emergency Surgery, Santa Maria della Misericordia Hospital University of Perugia, Perugia, Italy
| | - Elisabetta Marino
- General and Emergency Surgery, Santa Maria della Misericordia Hospital University of Perugia, Perugia, Italy
| | - Maria Bencivenga
- General and Upper GI Surgery Division, University of Verona, Verona, Italy
| | - Alessia D’Ignazio
- Department of Surgery, Policlinico le Scotte, University of Siena, Siena, Italy
| | - Leonardo Solaini
- Department of Surgery, General and Oncologic Surgery, Morgagni-Pierantoni Hospital, Via Forlanini 34, Forlì, Italy
| | - Silvia Ministrini
- Department of Experimental and Clinical Sciences, University of Brescia, Brescia, Italy
| | - Michela Caprioli
- Department of Experimental and Clinical Sciences, University of Brescia, Brescia, Italy
| | - Michele Sacco
- General and Upper GI Surgery Division, University of Verona, Verona, Italy
| | - Daniele Marrelli
- Department of Surgery, Policlinico le Scotte, University of Siena, Siena, Italy
| | - Gianni Mura
- Department of Surgery, Azienda USl Toscana SudEst—Arezzo, Arezzo, Italy
| | - Maurizio Degiuli
- Department of Oncology, Head, Digestive and Surgical Oncology, University of Torino, and San Luigi University Hospital, Orbassano, Italy
| | - Paolo Morgagni
- Department of Surgery, General and Oncologic Surgery, Morgagni-Pierantoni Hospital, Via Forlanini 34, Forlì, Italy
| | | | | | - Franco Roviello
- Department of Surgery, Policlinico le Scotte, University of Siena, Siena, Italy
| | - Annibale Donini
- General and Emergency Surgery, Santa Maria della Misericordia Hospital University of Perugia, Perugia, Italy
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8
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Ji ZH, Zhang Y, Li Y. Intra-operative hyperthermic intraperitoneal chemotherapy for prevention and treatment of peritoneal metastases from gastric cancer: a narrative review. J Gastrointest Oncol 2021; 12:S70-S78. [PMID: 33968427 DOI: 10.21037/jgo-20-262] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Peritoneal metastasis (PM) from gastric cancer (GC) has long been regarded as the terminal disease, lacking of effective treatments. In recent 40 years, cytoreductive surgery (CRS) plus perioperative intraperitoneal chemotherapy, including hyperthermic intraperitoneal chemotherapy (HIPEC), neoadjuvant intraperitoneal and systemic chemotherapy (NIPS), and early post-operative intraperitoneal chemotherapy (EPIC), has been recommended as a preferred treatment option for some selected patients with GCPM. Intraperitoneal free cancer cells were recognized as the pathological cause of PM and the primary target for intraperitoneal chemotherapy. There were a lot of evidence demonstrating that HIPEC could effectively eradiate intraperitoneal free cancer cells and prolong overall survival in GCPM. However, there are still no standard HIPEC protocols. This review summarized the current HIPEC regimens used in GCPM from a literature search, trying to conclude the optimal HIPEC in GCPM, and indicate the future direction of HIPEC study. Moreover, the new data on the exploration of HIPEC in GCPM at Shijitan Hospital, Capital Medical University was shared. In conclusion, there was not enough evidence from publications and our own experience to conclude a recommended HIPEC regimen for GCPM. There is urgent need for standardizing HIPEC protocols worldwide. Accordingly, more international collaborations focusing on pharmacology and HIPEC-related parameters to generate high level evidence are essential.
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Affiliation(s)
- Zhong-He Ji
- Department of Peritoneal Cancer Surgery, Cancer Center of Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Ying Zhang
- Department of Pathology, Cancer Center of Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Yan Li
- Department of Peritoneal Cancer Surgery, Cancer Center of Beijing Shijitan Hospital, Capital Medical University, Beijing, China.,Department of Pathology, Cancer Center of Beijing Shijitan Hospital, Capital Medical University, Beijing, China
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9
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Zhu X, Wu Z, Cao Y, Gao R, Zhang X, Li J. Efficacy and safety of TCM therapies combined with hyperthermic intraperitoneal chemotherapy for peritoneal metastasis of gastric cancer: A protocol for systematic review and meta-analysis. Medicine (Baltimore) 2021; 100:e24337. [PMID: 33530226 PMCID: PMC7850690 DOI: 10.1097/md.0000000000024337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 12/28/2020] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Gastric cancer (GC) has high incidence and mortality worldwide, and peritoneal metastasis is a primary cause of mortality in patients. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a feasible and effective treatment. Traditional Chinese Medicine (TCM) therapies have been combined with HIPEC for certain therapeutic advantages, but there is a lacking of evidence of evidence-based medicine. Therefore, we provide a protocol to evaluate the efficacy and safety of TCM therapies combined with HIPEC in the treatment for peritoneal metastasis of GC. METHODS AND ANALYSIS From inception until December 2020, a systematic and comprehensive literature search will be conducted in both 3 English databases and 4 Chinese databases. Randomized controlled trials (RCTs) will be included related to TCM therapies combined with HIPEC in the treatment for peritoneal metastasis of GC. Two researchers independently conducted data extraction and literature quality evaluation. The methodological qualities, including the risk of bias, will be evaluated using the Cochrane risk of bias assessment tool, while confidence in the cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS This study assessed the efficacy and safety of TCM therapies combined with HIPEC in the treatment of peritoneal metastasis of GC by effective rate, Karnofsky Performance Status (KPS), Carcinoemybryonic Angtigen remission rate, and incidence of adverse reactions etc. CONCLUSIONS This study will provide reliable evidence-based evidence for the clinical application of TCM therapies combined with HIPEC in the treatment for peritoneal metastasis of GC. ETHICS AND DISSEMINATION Ethical approval is not required, as this study is based on the review of published research. This review will be published in a peer-reviewed journal and disseminated both electronically and in print. REGISTRATION NUMBER INPLASY2020120048.
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10
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Laparoscopic Hyperthermic Intraperitoneal Perfusion Chemotherapy for Patients With Malignant Ascites Secondary to Unresectable Gastric Cancer. Surg Laparosc Endosc Percutan Tech 2020; 30:55-61. [PMID: 32004214 DOI: 10.1097/sle.0000000000000380] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND To compare the efficacy of 3 chemotherapeutic combinations for laparoscopic hyperthermic intraperitoneal perfusion chemotherapy (HIPPC) in the treatment of malignant ascites secondary to unresectable gastric cancer (GC). MATERIALS AND METHODS From January 2010 to December 2013, 38 GC patients were randomly divided into 3 groups and treated by laparoscopic HIPPC with 1 of the 3 following chemotherapy combinations: raltitrexed (Ra) with oxaliplatin (L-OHP), Ra with cisplatin (DDP), and Ra with mitomycin C (MMC). Perioperative complications, patients' quality of life, and survival were recorded and compared among the 3 groups. RESULTS The intraoperative course was successful in all patients, and no perioperative death or complication related to laparoscopic HIPPC was documented. The median follow-up period was 9 months and the median survival was 7.5 months for all patients. Patients in the Ra/L-OHP group had a median survival of 8.7 months, the Ra/DDP group had a median survival of 5.6 months, and the Ra/MMC group had a median survival of 7.5 months. Patients' median survival in the Ra/L-OHP group and Ra/MMC group is significantly longer than Ra/DDP group (P<0.05). No significant difference was found in total remission rate of ascites, increase in the Karnofsky performance scale, and incidence rate of port-site metastases among the 3 groups. CONCLUSIONS Laparoscopy-assisted HIPPC provide modest yet encouraging efficacy for malignant ascites secondary to disseminated GC. Our preliminary data indicate that the chemotherapeutical combination of Ra/L-OHP and Ra/MMC might be more beneficial compared with Ra/DDP in terms of patients' survival.
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Yu P, Ye Z, Dai G, Zhang Y, Huang L, Du Y, Cheng X. Neoadjuvant systemic and hyperthermic intraperitoneal chemotherapy combined with cytoreductive surgery for gastric cancer patients with limited peritoneal metastasis: a prospective cohort study. BMC Cancer 2020; 20:1108. [PMID: 33198674 PMCID: PMC7667754 DOI: 10.1186/s12885-020-07601-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Accepted: 10/30/2020] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND There is no currently available treatment for peritoneal metastasis of gastric cancer. This phase II study aimed to evaluate the efficacy and safety of neoadjuvant systemic chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC) combined with cytoreductive surgery (CRS) for the treatment of these patients. METHODS Neoadjuvant chemotherapy comprised two cycles of HIPEC and four cycles of S-1 plus paclitaxel. HIPEC was administered intraperitoneally with paclitaxel (75 mg/m2). For systemic chemotherapy, paclitaxel was administered intravenously(150 mg/m2) on day 1, and S-1 was administered orally(80 mg/m2/day)on days 1-14 of a 3-week cycle. Another two cycles of HIPEC and four cycles of S-1 plus paclitaxel were administered after second diagnostic staging laparoscopy or CRS. The primary endpoints were treatment efficiency and safety; the secondary endpoint was 3-year overall survival (OS). RESULTS A total of 40 patients were enrolled and 38 patients have been analyzed. Of these, 18 (47.4%) patients received neoadjuvant systemic chemotherapy, HIPEC and CRS (conversion therapy group), while 20 patients received only chemotherapy and HIPEC (palliative chemotherapy group). Median OS was markedly improved in the conversion therapy group (21.1 months, 95% confidence interval [CI] 16.7-25.6 months) in comparison with the palliative chemotherapy group(10.8 months, 95%CI 7.3-14.2 months, p = 0.002). After neoadjuvant systemic chemotherapy and HIPEC, a second laparoscopic exploration was performed, and the prognosis of patients with low peritoneal cancer index (PCI) (PCI < 6) was significantly better than that of patients with high PCI (PCI ≥ 6)(20.1 vs.11.3 months, p = 0.006). CONCLUSION Neoadjuvant systemic chemotherapy and HIPEC combined with CRS is safe and feasible, and could potentially improve the prognosis of gastric cancer patients with limited peritoneal metastasis. However, further clinical trials are still warranted. TRIAL REGISTRATION This study has been registered with ClinicalTrials.gov as NCT02549911 . Trial registration date: 15/09/2015.
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Affiliation(s)
- Pengfei Yu
- Department of Gastric Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310022, China
| | - Zeyao Ye
- Department of Gastric Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310022, China
| | - Gaiguo Dai
- Department of Gastric Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310022, China
| | - Yanqiang Zhang
- Department of Gastric Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310022, China
| | - Ling Huang
- Department of Gastric Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310022, China
| | - Yian Du
- Department of Gastric Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310022, China.
| | - Xiangdong Cheng
- Department of Gastric Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310022, China.
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12
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van der Kaaij RT, Wassenaar ECE, Koemans WJ, Sikorska K, Grootscholten C, Los M, Huitema A, Schellens JHM, Veenhof AAFA, Hartemink KJ, Aalbers AGJ, van Ramshorst B, Boerma D, Boot H, van Sandick JW. Treatment of PERItoneal disease in Stomach Cancer with cytOreductive surgery and hyperthermic intraPEritoneal chemotherapy: PERISCOPE I initial results. Br J Surg 2020; 107:1520-1528. [PMID: 32277764 DOI: 10.1002/bjs.11588] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 02/04/2020] [Accepted: 02/14/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND The role of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer is unknown. This non-randomized dose-finding phase I-II study was designed to assess the safety and feasibility of HIPEC, following systemic chemotherapy, in patients with gastric cancer and limited peritoneal dissemination. The maximum tolerated dose of normothermic intraperitoneal docetaxel in combination with a fixed dose of intraperitoneal oxaliplatin was also explored. METHODS Patients with resectable cT3-cT4a gastric adenocarcinoma with limited peritoneal metastases and/or tumour-positive peritoneal cytology were included. An open HIPEC technique was used with 460 mg/m2 hyperthermic oxaliplatin for 30 min followed by normothermic docetaxel for 90 min in escalating doses (0, 50, 75 mg/m2 ). RESULTS Between 2014 and 2017, 37 patients were included. Of 25 patients who completed the full study protocol, four were treated at dose level 1 (0 mg/m2 docetaxel), six at dose level 2 (50 mg/m2 ) and four at dose level 3 (75 mg/m2 ). At dose level 3, two dose-limiting toxicities occurred, both associated with postoperative ileus. Thereafter, another 11 patients were treated at dose level 2, with no more dose-limiting toxicities. Based on this, the maximum tolerated dose was 50 mg/m2 intraperitoneal docetaxel. Serious adverse events were scored in 17 of 25 patients. The reoperation rate was 16 per cent (4 of 25) and the treatment-related mortality rate was 8 per cent (2 patients, both in dose level 3). CONCLUSION Gastrectomy combined with cytoreductive surgery and HIPEC was feasible using 460 mg/m2 oxaliplatin and 50 mg/m2 normothermic docetaxel.
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Affiliation(s)
| | | | - W J Koemans
- Department of Surgical Oncology, Amsterdam, the Netherlands
| | - K Sikorska
- Department of Biometrics, Amsterdam, the Netherlands
| | - C Grootscholten
- Department of Gastrointestinal Oncology, Amsterdam, the Netherlands
| | - M Los
- Department of Medical Oncology, St Antonius Hospital, Nieuwegein, the Netherlands
| | - A Huitema
- Department of Pharmacy, Amsterdam, the Netherlands
| | - J H M Schellens
- >Department of Clinical Pharmacology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands
| | | | - K J Hartemink
- Department of Surgical Oncology, Amsterdam, the Netherlands
| | - A G J Aalbers
- Department of Surgical Oncology, Amsterdam, the Netherlands
| | | | - D Boerma
- Department of Surgery, Nieuwegein, the Netherlands
| | - H Boot
- Department of Gastrointestinal Oncology, Amsterdam, the Netherlands
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13
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Li XB, Peng KW, Ji ZH, Yu Y, Liu G, Li Y. Prevention of Venous Thromboembolism After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Development of a Physiotherapy Program. Clin Appl Thromb Hemost 2020; 25:1076029619890415. [PMID: 31775523 PMCID: PMC7019383 DOI: 10.1177/1076029619890415] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Background: This study was to assess the risk of venous thromboembolism (VTE) in patients with
peritoneal carcinomatosis (PC) and to evaluate the safety and feasibility of
physiotherapy program to prevent VTE during cytoreductive surgery (CRS) and hyperthermic
intraperitoneal chemotherapy (HIPEC). Methods: For VTE prevention, we developed a systematic physiotherapy program consisting of
active exercises of both arms and legs, and intermittent pneumatic compression device to
massage both legs. This physiotherapy was applied to all patients, and the VTE-related
events were recorded and analyzed. Results: Cytoreductive surgery + HIPEC was performed on 466 patients with PC. All patients had
highest VTE risk, with the median Caprini risk factor score being 11. During the 3-month
observation period, 8 patients had 9 (1.9%) clinically symptomatic VTE events, including
8 (1.7%) deep vein thrombosis and 1 (0.2%) pulmonary embolism. Among those, 5 patients
received pharmacological treatments with low-molecular-weight heparin, and the other 3
received physical exercises only. All these patients recovered well, and there was no
mortality about VTE perioperatively. Conclusions: Patients with PC treated by CRS + HIPEC are at highest risk for VTE. The systematic
physiotherapy program is safe and feasible to prevent VTE post CRS + HIPEC.
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Affiliation(s)
- Xin-Bao Li
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Kai-Wen Peng
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Zhong-He Ji
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Yang Yu
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Gang Liu
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Yan Li
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
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14
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Fields AC, Lu PW, Li GZ, Welten V, Jolissaint JS, Vierra BM, Saadat LV, Larson AC, Atkinson RB, Melnitchouk N. Current practices and future steps for hyperthermic intraperitoneal chemotherapy. Curr Probl Surg 2020; 57:100727. [PMID: 32151327 DOI: 10.1016/j.cpsurg.2019.100727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Accepted: 12/23/2019] [Indexed: 11/20/2022]
Affiliation(s)
- Adam C Fields
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
| | - Pamela W Lu
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - George Z Li
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Vanessa Welten
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Joshua S Jolissaint
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | | | - Lily V Saadat
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Abby C Larson
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Rachel B Atkinson
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Nelya Melnitchouk
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
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15
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Lei Z, Wang J, Li Z, Li B, Luo J, Wang X, Wang J, Ba M, Tang H, He Q, Liao Q, Yang X, Guan T, Liang H, Cui S, On Behalf Of The Chinese Peritoneal Oncology Study Group. Hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis: A multicenter propensity score-matched cohort study. Chin J Cancer Res 2020; 32:794-803. [PMID: 33447001 PMCID: PMC7797229 DOI: 10.21147/j.issn.1000-9604.2020.06.12] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Objective Systemic chemotherapy has limited efficacy in the treatment of peritoneal metastasis (PM) in gastric cancer (GC). Hyperthermic intraperitoneal chemotherapy (HIPEC) combined with complete cytoreductive surgery (CRS) has shown promising outcomes but remains controversial. The present study aimed to evaluate the safety and efficacy of HIPEC without CRS in GC patients with PM. Methods This retrospective propensity score-matched multicenter cohort study included GC patients with PM treated with either chemotherapy alone (Cx group) or with HIPEC combined with chemotherapy (HIPEC-Cx group) in four Chinese high-volume gastric medical centers between 2010 and 2017. The primary outcomes were median survival time (MST) and 3-year overall survival (OS). Propensity score matching was performed to compensate for controlling potential confounding effects and selection bias. Results Of 663 eligible patients, 498 were matched. The MST in the Cx and HIPEC-Cx groups was 10.8 and 15.9 months, respectively [hazard ratio (HR)=0.71, 95% confidence interval (95% CI), 0.58−0.88; P=0.002]. The 3-year OS rate was 10.1% (95% CI, 5.4%−14.8%) and 18.4% (95% CI, 12.3%−24.5%) in the Cx and HIPEC-Cx groups, respectively (P=0.017). The complication rates were comparable. The time to first flatus and length of hospital stay for patients undergoing HIPEC combined with chemotherapy was longer than that of chemotherapy alone (4.6±2.4 dvs. 2.7±1.8 d, P<0.001; 14.2±5.8 dvs. 11.4±7.7 d, P<0.001), respectively. The median follow-up period was 33.2 months.
Conclusions Compared with standard systemic chemotherapy, HIPEC combined with chemotherapy revealed a statistically significant survival benefit for GC patients with PM, without compromising patient safety.
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Affiliation(s)
- Ziying Lei
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Jiahong Wang
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Zhi Li
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Tumor Hospital of Henan Province, Zhengzhou 450008, China
| | - Baozhong Li
- Department of Surgery, Anyang Tumor Hospital, Anyang 455000, China
| | - Jiali Luo
- Department of Oncology, Guangzhou Medical University, Guangzhou 510095, China
| | - Xuejun Wang
- Department of Gastrointestinal Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Jin Wang
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Mingchen Ba
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Hongsheng Tang
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Qingjun He
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Quanxing Liao
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Xiansheng Yang
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Tianpei Guan
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Han Liang
- Department of Gastrointestinal Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Shuzhong Cui
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - On Behalf Of The Chinese Peritoneal Oncology Study Group
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China.,Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Tumor Hospital of Henan Province, Zhengzhou 450008, China.,Department of Surgery, Anyang Tumor Hospital, Anyang 455000, China.,Department of Oncology, Guangzhou Medical University, Guangzhou 510095, China.,Department of Gastrointestinal Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
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16
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Chen X, Liu H, Li G, Yu J. Implications of clinical research on adjuvant chemotherapy for gastric cancer: Where to go next? Chin J Cancer Res 2019; 31:892-900. [PMID: 31949391 PMCID: PMC6955166 DOI: 10.21147/j.issn.1000-9604.2019.06.05] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Accepted: 11/04/2019] [Indexed: 12/18/2022] Open
Abstract
Postoperative adjuvant chemotherapy (ACT) confers superior gastric cancer (GC) survival in the Eastern cohort. However, is the current standard of ACT already excessive, or is it still necessary to increase its intensity for specific subgroups? Tailored ACT strategies for GC depend on gradual exploration by clinical trials in selected patients. Thus, understanding the implications of previous and current research can help us respond wisely and design effective, rational trials, save medical resources and make better decisions in clinical practice. After reviewing and analyzing studies on ACT for GC patients undergoing curative resection, we found that research strategies for conducting "addition" ACT for specific stages of the disease have achieved great progress in making ACT more tailored and personalized in consideration of pathology stages. Furthermore, trials indicate that "addition" ACT strategies for GC patient subgroups based on histological characteristics might be helpful to move toward a more specific tailored and personalized management approach. Designing ACT research focused on different node statuses should also be conducted according to the biological specificity of lymph node (LN) metastasis. Therefore, future trials designed to determine tailored treatment based on histological and biological characteristics for specific subgroups are urgently needed and conducted as the theme of the 2019 American Society of Clinical Oncology (ASCO): Caring for Every Patient, Learning from Every Patient.
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Affiliation(s)
- Xinhua Chen
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Hao Liu
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Guoxin Li
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Jiang Yu
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
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Gamboa AC, Winer JH. Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer. Cancers (Basel) 2019; 11:E1662. [PMID: 31717799 PMCID: PMC6896138 DOI: 10.3390/cancers11111662] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Revised: 10/21/2019] [Accepted: 10/24/2019] [Indexed: 12/24/2022] Open
Abstract
The management of peritoneal metastases from gastric cancer origin has evolved considerably over the last three decades with the establishment of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as efficacious therapies in carefully selected patients. Other approaches such as the use of prophylactic/adjuvant HIPEC in patients who are considered high-risk and those with positive peritoneal cytology will benefit from additional data before being adopted into routine clinical practice. Lastly, there are new and emerging intraperitoneal chemotherapy techniques such as early post-operative intraperitoneal chemotherapy (EPIC) for residual microscopic disease, and pressurized intraperitoneal aerosolized chemotherapy (PIPAC) for patients with advanced unresectable peritoneal carcinomatosis, which are currently under evaluation in clinical trials. The following review outlines the natural history of gastric cancer, currently available neoadjuvant and adjuvant therapies for resectable disease, and existing evidence supporting various approaches to CRS and intraperitoneal chemotherapy.
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Affiliation(s)
- Adriana C. Gamboa
- Division of Surgical Oncology, 1365B Clifton Road NE, Suite B4000, Atlanta, GA 30322, USA;
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18
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Guner A, Yildirim R. Surgical management of metastatic gastric cancer: moving beyond the guidelines. Transl Gastroenterol Hepatol 2019; 4:58. [PMID: 31559339 DOI: 10.21037/tgh.2019.08.03] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Accepted: 08/05/2019] [Indexed: 01/27/2023] Open
Abstract
Despite decreasing incidence, gastric cancer remains a major health problem worldwide and is associated with poor survival. The poor survival is mainly attributed to delayed presentation which may cause local or systemic metastases. The standard of care for patients with metastatic gastric cancer (MGC) is palliative chemotherapy with best supportive care. Although the survival has improved owing to advances in chemotherapeutic agents, it is still unsatisfactory, and some perspective changes are needed in the management of MGC to improve the outcomes. Therefore, various alternative treatment strategies for MGC have formed the most important research topics. Liver-directed treatment (LDT) options such as liver resection, radiofrequency ablation (RFA), microwave ablation (MWA), and hepatic artery infusion chemotherapy (HAIC) have been studied in the management of liver metastasis from gastric cancer (LMGC). Intraperitoneal chemotherapy (IPC) in addition to cytoreductive surgery (CRS) aiming to remove all macroscopic tumor focus resulting from peritoneal dissemination is the treatment option for peritoneal metastasis, while para-aortic lymph node dissection is the treatment option for para-aortic lymph node metastasis which is considered to be M1 disease. Conversion surgery is a novel concept aiming at R0 resection for originally unresectable or marginally resectable tumors after a remarkably good response to the chemotherapy. Large amounts of data in the literature have demonstrated the benefits of individualized approaches such as the combination of systemic and local treatment options in selected patient groups. In this review, we aimed to explore the current and future treatment options by reviewing the literature on this controversial topic.
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Affiliation(s)
- Ali Guner
- Department of General Surgery, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey.,Department of Biostatistics and Medical Informatics, Institute of Medical Science, Karadeniz Technical University, Trabzon, Turkey
| | - Reyyan Yildirim
- Department of General Surgery, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey
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19
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Ji L, Selleck MJ, Morgan JW, Xu J, Babcock BD, Shavlik D, Wall NR, Langridge WH, Lum SS, Garberoglio CA, Reeves ME, Solomon N, Namm JP, Senthil M. Gastric Cancer Peritoneal Carcinomatosis Risk Score. Ann Surg Oncol 2019; 27:240-247. [PMID: 31346896 PMCID: PMC6925067 DOI: 10.1245/s10434-019-07624-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Indexed: 12/24/2022]
Abstract
BACKGROUND Gastric cancer (GC) peritoneal carcinomatosis (PC) is associated with a poor prognosis. Although grade, histology, and stage are associated with PC, the cumulative risk of PC when multiple risk factors are present is unknown. This study aimed to develop a cumulative GCPC risk score based on individual demographic/tumor characteristics. METHODS Patient-level data (2004-2014) from the California Cancer Registry were reviewed by creating a keyword search algorithm to identify patients with gastric PC. Multivariable logistic regression was used to assess demographic/tumor characteristics associated with PC in a randomly selected testing cohort. Scores were assigned to risk factors based on beta coefficients from the logistic regression result, and these scores were applied to the remainder of the subjects (validation cohort). The summed scores of each risk factor formed the total risk score. These were grouped, showing the percentages of patients with PC. RESULTS The study identified 4285 patients with gastric adenocarcinoma (2757 males, 64.3%). The median age of the patients was 67 years (interquartile range [IQR], 20 years). Most of the patients were non-Hispanic white (n = 1748, 40.8%), with proximal (n = 1675, 39.1%) and poorly differentiated (n = 2908, 67.9%) tumors. The characteristics most highly associated with PC were T4 (odds ratio [OR], 3.12; 95% confidence interval [CI], 2.19-4.44), overlapping location (OR 2.27; 95% CI 1.52-3.39), age of 20-40 years (OR 3.42; 95% CI 2.24-5.21), and Hispanic ethnicity (OR 1.86; 95% CI 1.36-2.54). The demographic/tumor characteristics used in the risk score included age, race/ethnicity, T stage, histology, tumor grade, and location. Increasing GCPC score was associated with increasing percentage of patients with PC. CONCLUSION Based on demographic/tumor characteristics in GC, it is possible to distinguish groups with varying odds for PC. Understanding the risk for PC based on the cumulative effect of high-risk features can help clinicians to customize surveillance strategies and can aid in early identification of PC.
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Affiliation(s)
- Liang Ji
- School of Public Health, Loma Linda University, Loma Linda, CA, USA
| | - Matthew J Selleck
- Division of Surgical Oncology, Loma Linda University Health, Loma Linda, CA, USA
| | - John W Morgan
- School of Public Health, Loma Linda University, Loma Linda, CA, USA.,Surveillance, Epidemiology and End Results (SEER) Cancer Registry of Greater California and California Cancer Registry, Sacramento, Loma Linda, CA, USA
| | - Jane Xu
- Division of Biochemistry, School of Medicine, Loma Linda University, Loma Linda, CA, USA
| | - Blake D Babcock
- Division of Surgical Oncology, Loma Linda University Health, Loma Linda, CA, USA
| | - David Shavlik
- School of Public Health, Loma Linda University, Loma Linda, CA, USA
| | - Nathan R Wall
- Division of Biochemistry, School of Medicine, Loma Linda University, Loma Linda, CA, USA
| | - William H Langridge
- Division of Biochemistry, School of Medicine, Loma Linda University, Loma Linda, CA, USA
| | - Sharon S Lum
- Division of Surgical Oncology, Loma Linda University Health, Loma Linda, CA, USA
| | - Carlos A Garberoglio
- Division of Surgical Oncology, Loma Linda University Health, Loma Linda, CA, USA
| | - Mark E Reeves
- Division of Surgical Oncology, Loma Linda University Health, Loma Linda, CA, USA
| | - Naveenraj Solomon
- Division of Surgical Oncology, Loma Linda University Health, Loma Linda, CA, USA
| | - Jukes P Namm
- Division of Surgical Oncology, Loma Linda University Health, Loma Linda, CA, USA
| | - Maheswari Senthil
- Division of Surgical Oncology, Loma Linda University Health, Loma Linda, CA, USA.
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Manzanedo I, Pereira F, Rihuete Caro C, Pérez-Viejo E, Serrano Á, Gutiérrez Calvo A, Regueira FM, Casado-Adam Á, Cascales-Campos PA, Arteaga X, García-Fadrique A, Gómez Sanz R, López García A, Zozaya G, Arjona Á, Gil Martínez J. Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Gastric Cancer with Peritoneal Carcinomatosis: Multicenter Study of Spanish Group of Peritoneal Oncologic Surgery (GECOP). Ann Surg Oncol 2019; 26:2615-2621. [DOI: 10.1245/s10434-019-07450-4] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Indexed: 12/16/2022]
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21
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Zhu BY, Yuan SQ, Nie RC, Li SM, Yang LR, Duan JL, Chen YB, Zhang XS. Prognostic Factors and Recurrence Patterns in T4 Gastric Cancer Patients after Curative Resection. J Cancer 2019; 10:1181-1188. [PMID: 30854127 PMCID: PMC6400673 DOI: 10.7150/jca.28993] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2018] [Accepted: 01/04/2019] [Indexed: 12/26/2022] Open
Abstract
Background: To investigate prognostic factors and recurrence patterns in T4 gastric cancer (GC) patients after curative resection. Methods: Between January 2004 and December 2014, 249 patients with T4 gastric cancer undergoing curative resection were recruited. Patient characteristics, survival, prognostic factors and recurrence patterns were analyzed. Results: Our results showed that the median survival time (MST) for T4 gastric cancer after curative resection was 55.47 months, with 59.47 months for T4a (tumor perforating serosa) and 25.90 months for T4b (tumor invasion of the adjacent structure). Multivariate analysis indicated that age (hazard ratio [HR], 1.86; P = 0.006), location of tumor (HR, 1.25, 0.90 - 5.64; P < 0.001) and intraoperative blood loss (HR, 1.85; P = 0.010) were independent prognostic factors for overall survival (OS). After a median follow-up of 25.87 months, a total of 109 (43.8%) patients suffered from recurrence, and 90 patients had been observed specific recurrence sites, among which peritoneal metastasis was the most common recurrence pattern, 59.0% for T4a and 88.3% for T4b, respectively. Conclusions: For T4 gastric cancer patients after curative resection, older age, gastric cancer of the entire stomach and more intraoperative blood loss were associated with poor OS. The recurrence rate after curative resection for T4 was high, and the most common recurrence pattern was peritoneal metastasis.
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Affiliation(s)
- Bao-Yan Zhu
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Shu-Qiang Yuan
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Run-Cong Nie
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Shu-Man Li
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Li-Rong Yang
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Jin-Ling Duan
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Ying-Bo Chen
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Xiao-Shi Zhang
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
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22
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Fugazzola P, Ansaloni L, Sartelli M, Catena F, Cicuttin E, Leandro G, De' Angelis GL, Gaiani F, Di Mario F, Tomasoni M, Coccolini F. Advanced gastric cancer: the value of surgery. ACTA BIO-MEDICA : ATENEI PARMENSIS 2018; 89:110-116. [PMID: 30561428 PMCID: PMC6502221 DOI: 10.23750/abm.v89i8-s.7897] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Indexed: 02/06/2023]
Abstract
Gastric cancer is a common disease with high mortality. The definition of advanced gastric cancer is still debated. Radical surgery associated to appropriate systemic and intra-abdominal chemotherapy is the gold standard treatment. In presence of peritoneal carcinosis, reaching a complete cytoreduction is the key to achieve long-term survival. Adequate lymphadenectomy is also fundamental. Conversion therapy could be applied to selected IV stage patients. No definitive evidences exist regarding the oncological and surgical superiority of mini-invasive approaches over the classical open techniques.
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Affiliation(s)
- Paola Fugazzola
- Emergency, General and Trauma Surgery dept., Bufalini hospital, Cesena, Italy.
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Dahdaleh FS, Turaga KK. Evolving Treatment Strategies and Outcomes in Advanced Gastric Cancer with Peritoneal Metastasis. Surg Oncol Clin N Am 2018; 27:519-537. [PMID: 29935687 DOI: 10.1016/j.soc.2018.02.006] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Gastric cancer (GC) has a predilection to metastasize to the peritoneum, denoting a poor prognosis. Treatment strategies available for advanced GC have significantly evolved over time and can be categorized into systemic, regional, and surgical. Although systemic therapies have been the mainstay for the treatment of advanced GC, their ability in achieving long-term survival in patients with peritoneal involvement is modest at best. This article describes advances in combined modality treatment of peritoneal metastases, specifically with an emphasis on peritoneal-directed therapies.
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Affiliation(s)
- Fadi S Dahdaleh
- Complex General Surgical Oncology, Section of General Surgery/Surgical Oncology, The University of Chicago Medicine, 5841 South Maryland Avenue, Room S214, MC 5094, Chicago, IL 60637, USA
| | - Kiran K Turaga
- The University of Chicago Medicine, Section of General Surgery/Surgical Oncology, 5841 South Maryland Avenue, Room G207, MC 5094, Chicago, IL 60637, USA.
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24
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Zurleni T, Gjoni E, Altomare M, Rausei S. Conversion surgery for gastric cancer patients: A review. World J Gastrointest Oncol 2018; 10:398-409. [PMID: 30487951 PMCID: PMC6247102 DOI: 10.4251/wjgo.v10.i11.398] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 09/25/2018] [Accepted: 10/07/2018] [Indexed: 02/05/2023] Open
Abstract
Gastric cancer (GC) is the third most common cancer-related cause of death worldwide. In locally advanced tumors, neoadjuvant chemotherapy has recently been introduced in most international Western guidelines. For metastatic and unresectable disease, there is still debate regarding correct management and the role of surgery. The standard approach for stage IV GC is palliative chemotherapy. Over the last decade, an increasing number of M1 patients who responded to palliative regimens of induction chemotherapy have been subsequently undergone surgery with curative intent. The objective of the present review is to analyze the literature regarding this approach, known as “conversion surgery”, which has become one of the most commonly adopted therapeutic options. It is defined as a treatment aiming at an R0 resection after chemotherapy in initially unresectable tumors. The 13 retrospective studies analyzed, with a total of 411 patients treated with conversion therapy, clearly show that even if standardization of unresectable and metastatic criteria, post-chemotherapy resectability evaluation and timing of surgery has not yet been established, an R0 surgery after induction chemotherapy with partial or complete response seems to offer superior survival results than chemotherapy alone. Additional larger sample-size randomized control trials are needed to identify subgroups of well-stratified patients who could benefit from this multimodal approach.
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Affiliation(s)
- Tommaso Zurleni
- Department of Surgery, ASST Valle Olona, Busto Arsizio 21052, Italy
| | - Elson Gjoni
- Department of Surgery, ASST Valle Olona, Busto Arsizio 21052, Italy
| | - Michele Altomare
- Department of Surgery, ASST Valle Olona, Busto Arsizio 21052, Italy
| | - Stefano Rausei
- Department of Surgery, ASST Valle Olona, Gallarate. 21013, Italy
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25
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Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with gastric cancer and peritoneal carcinomatosis. Eur J Surg Oncol 2018; 44:1805-1810. [PMID: 30087071 DOI: 10.1016/j.ejso.2018.06.036] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Revised: 05/23/2018] [Accepted: 06/27/2018] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Gastric Cancer (GC) with Peritoneal Carcinomatosis (PC) has long been regarded as a terminal disease. Over the past two decades, cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has changed the traditional concept of peritoneal metastases from being a systemic disease, to being considered a locoregional dissemination. PATIENTS AND METHODS A prospective study was performed at a high-volume Carcinomatosis Center to evaluate survival, morbi-mortality and prognostic factors for survival in a cohort of patients with GC and PC treated with CRS + HIPEC between June 2006 and December 2016. RESULTS Thirty-five patients were included in the study. Median follow-up was 54 months. Postoperative major complications (>grade IIIa) occurred in 25.7% of patients, including 2 deaths (mortality 5.7%). The median overall survival (OS) was 16 months and the 1-, 3- and 5-year OS rates were 70.8%, 21.3% and 21.3% %, respectively. The median OS for patients with PCI ≤6 was 19 months, in contrast to 12 months for the 19 patients with PCI >6. Three patients were included with only a positive cytology and their median OS was not reached. Perineural invasion was the only factor that had a negative influence in prognosis (HR 18.8) in multivariate analysis. CONCLUSION Although GC with PC still has a poor prognosis, survival has improved in selected patients with CRS + HIPEC and perioperative systemic chemotherapy. Patients with isolated positive cytology or peritoneal carcinomatosis with PCI less than 6 had encouraging survival rates.
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Abstract
The peritoneal malignancies span the biologic spectrum of aggressiveness from the indolent growth pattern and superficial nature of well-differentiated mucinous appendiceal adenocarcinoma to the rapidly growing and invasive nature of poorly differentiated signet ring cell adenocarcinomas of the appendix, colon, and stomach. An understanding of the biology, distribution, and volume of disease is critical to appropriately selecting patients for cytoreduction and HIPEC with the goal of long-term survival. Herein the authors discuss appropriate the evaluation and selection of patients for with peritoneal surface malignancies for cytoreduction and HIPEC.
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Affiliation(s)
- Travis E Grotz
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA; Department of Surgical Oncology, MD Anderson Cancer Center, Houston, TX, USA.
| | - Keith F Fournier
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
| | - Paul F Mansfield
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
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27
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Miailhe G, Arfi A, Mirshahi M, Eveno C, Pocard M, Touboul C. A new animal model for hyperthermic intraperitoneal chemotherapy (HIPEC) in tumor-bearing mice in the treatment of peritoneal carcinomatosis of ovarian origin. J Visc Surg 2018; 155:183-189. [PMID: 29108718 DOI: 10.1016/j.jviscsurg.2017.10.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
AIM OF THE STUDY We set out to develop and evaluate the morbidity of a non-invasive hyperthermic intraperitoneal chemotherapy (HIPEC) procedure in mice. HIPEC has been shown to improve overall survival in treating ovarian cancer with peritoneal carcinomatosis. However, related complications, toxicity and the lack of randomized trials limits its widespread use. To improve the surgical technique, there is a need for animal models that allow teams to work on large groups without burdensome logistics. MATERIALS AND METHODS To develop the model, we first determined optimal HIPEC conditions in 20 Black Six mice without carcinomatosis. To evaluate HIPEC morbidity, peritoneal carcinomatosis cells of ovarian origin were injected into the peritoneum of 10 pathogen-free Nude mice. The mice underwent HIPEC 21 days later under general anesthesia. An inflow catheter was introduced into the left hypochondria and an outflow catheter was introduced into the left iliac fossa. Bath infusion was oxaliplatin (920mg/m2) at 43°C for 12minutes. The mice were monitored and sacrificed two weeks after the procedure. RESULTS No deaths were observed during the procedure and infusion was well tolerated throughout the HIPEC. One mouse died the day after the procedure. No major dehydration, hemoperitoneum or evisceration was observed. CONCLUSION This mouse model of closed abdomen HIPEC has limited morbidity and could be a useful model to study HIPEC regimens and its effects on peritoneal carcinomatosis.
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Affiliation(s)
- G Miailhe
- Service de gynécologie obstétrique, hôpital intercommunal de Créteil, université Paris Est, Paris XII, 40, avenue de Verdun, 94000 Créteil, France; UMR Inserm U965, angiogenèse et recherche translationnelle, hôpital Lariboisière, 49, boulevard de la chapelle, 75010 Paris, France
| | - A Arfi
- Service de gynécologie obstétrique, hôpital intercommunal de Créteil, université Paris Est, Paris XII, 40, avenue de Verdun, 94000 Créteil, France; UMR Inserm U965, angiogenèse et recherche translationnelle, hôpital Lariboisière, 49, boulevard de la chapelle, 75010 Paris, France
| | - M Mirshahi
- UMR Inserm U965, angiogenèse et recherche translationnelle, hôpital Lariboisière, 49, boulevard de la chapelle, 75010 Paris, France
| | - C Eveno
- Service de chirurgie digestive et cancérologique, hôpital Lariboisière Fernand-Widal, université Paris VII, 49, boulevard de la chapelle, 75010 Paris, France; UMR Inserm U965, angiogenèse et recherche translationnelle, hôpital Lariboisière, 49, boulevard de la chapelle, 75010 Paris, France
| | - M Pocard
- Service de chirurgie digestive et cancérologique, hôpital Lariboisière Fernand-Widal, université Paris VII, 49, boulevard de la chapelle, 75010 Paris, France; UMR Inserm U965, angiogenèse et recherche translationnelle, hôpital Lariboisière, 49, boulevard de la chapelle, 75010 Paris, France
| | - C Touboul
- Service de gynécologie obstétrique, hôpital intercommunal de Créteil, université Paris Est, Paris XII, 40, avenue de Verdun, 94000 Créteil, France; UMR Inserm U965, angiogenèse et recherche translationnelle, hôpital Lariboisière, 49, boulevard de la chapelle, 75010 Paris, France.
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28
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Ji ZH, Peng KW, Yu Y, Li XB, Yonemura Y, Liu Y, Sugarbaker PH, Li Y. Current status and future prospects of clinical trials on CRS + HIPEC for gastric cancer peritoneal metastases. Int J Hyperthermia 2018; 33:562-570. [PMID: 28124576 DOI: 10.1080/02656736.2017.1283065] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
PURPOSE There is no standard treatment for peritoneal metastases (PM) from gastric cancer (GC). The aim of this review is to evaluate the clinical trials on cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for GC PM. MATERIALS AND METHODS The published clinical trials on CRS + HIPEC for GC PM are critically evaluated, and survival and safety are the primary endpoints. In addition, the registered ongoing clinical trials are summarised. RESULTS The natural course of GC PM is <5 months. CRS + HIPEC could improve the overall survival (OS). In prospective studies, the median OS was 11.0 months in the CRS + HIPEC group vs. 5.4 months in the CRS alone group. In case-control studies, the median OS was 13.3 months in the CRS + HIPEC group vs. 7.9 months in the CRS alone group. In cohort studies, the median OS after CRS + HIPEC was 13.3. The median 1-, 2- and 5-year survival rates after CRS + HIPEC were 50.0%, 35.8% and 13.0%, respectively. There is no statistically significant increase in serious adverse events that are directly attributed to CRS + HIPEC. CONCLUSIONS The combination of CRS and HIPEC is a promising integrated treatment strategy for GC PM that has encouraging initial results, calling for urgent further evaluation of this strategy in randomised control trials (RCTs).
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Affiliation(s)
- Zhong-He Ji
- a Department of Peritoneal Cancer Surgery , Beijing Shijitan Hospital, Capital Medical University , Beijing , China
| | - Kai-Wen Peng
- b Department of Oncology , Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center , Wuhan , China
| | - Yang Yu
- a Department of Peritoneal Cancer Surgery , Beijing Shijitan Hospital, Capital Medical University , Beijing , China
| | - Xin-Bao Li
- a Department of Peritoneal Cancer Surgery , Beijing Shijitan Hospital, Capital Medical University , Beijing , China
| | - Yutaka Yonemura
- c NPO Organization to Support Peritoneal Dissemination Treatment , Kishiwada, Osaka , Japan
| | - Yang Liu
- c NPO Organization to Support Peritoneal Dissemination Treatment , Kishiwada, Osaka , Japan
| | | | - Yan Li
- a Department of Peritoneal Cancer Surgery , Beijing Shijitan Hospital, Capital Medical University , Beijing , China.,b Department of Oncology , Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center , Wuhan , China
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29
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Seshadri RA, Mehta AM. Role of HIPEC in the Prevention of Peritoneal Metastasis from Colorectal, Gastric and Appendiceal Cancer. MANAGEMENT OF PERITONEAL METASTASES- CYTOREDUCTIVE SURGERY, HIPEC AND BEYOND 2018:15-30. [DOI: 10.1007/978-981-10-7053-2_2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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30
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Hsieh MC, Lu CY, Chang WW, Wu SY, Hsiao PK, Liu TJ. Experiences with cytoreduction surgery plus hyperthermic intraperitoneal chemotherapy in Taiwan. Medicine (Baltimore) 2017; 96:e7306. [PMID: 28658135 PMCID: PMC5500057 DOI: 10.1097/md.0000000000007306] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Our hospital was the first institution to offer cytoreduction surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in Taiwan. Therefore, we report our experience and outcomes among patients who underwent HIPEC.Since 2002, 164 eligible patients underwent HIPEC, and we excluded cases of laparoscopic or prophylactic HIPEC. The cases were categorized according to whether they were treated before 2012 (Period 1: 80 cases) or after 2012 (Period 2: 84 cases).The rates of surgical morbidity were 46.3% during Period 1 and 20.2% during Period 2 (P < .01), and the rates of severe complications were 25% during Period 1 and 9.5% during Period 2 (P < .01). The 5-year overall survival rate was 35.8%, with rates of 13.4% for gastric cancer, 27.3% for colon cancer, 70.0% for appendiceal cancer, and 52.4% for ovarian cancer (median follow-up: 34 months). The survival rate was 42.1% when we achieved a cytoreduction score of 0/1, compared with 21.1% in the group with a cytoreduction score of 2/3 (P < .01). Severe complications were associated with a 5-year survival rate of 23.4%, compared with 37.9% among cases without severe complications (P = .01). Complete cytoreduction was achieved in 78.6% of the patients if they underwent their first surgery at our hospital.We have become an experienced hospital for CRS plus HIPEC. Although our complication rate for CRS plus HIPEC was high, it was within the acceptable range. Long-term survival was achieved in a few cases.
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Affiliation(s)
- Mao-Chih Hsieh
- Division of General Surgery, Department of Surgery, Wan Fang Hospital
- Division of General Surgery, Department of Surgery, School of Medicine, College of Medicine
| | - Chang-Yun Lu
- Division of General Surgery, Department of Surgery, Wan Fang Hospital
| | - Wei-Wen Chang
- Division of General Surgery, Department of Surgery, Wan Fang Hospital
| | - Szu-Yuan Wu
- Department of Radiation Oncology, Wan Fang Hospital
- Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University
- Institute of Toxicology, College of Medicine, National Taiwan University, Taipei
- Department of Biotechnology, Hungkuang University, Taichung, Taiwan
| | - Ping-Kun Hsiao
- Division of General Surgery, Department of Surgery, Wan Fang Hospital
| | - Tse-Jia Liu
- Division of General Surgery, Department of Surgery, Wan Fang Hospital
- Division of General Surgery, Department of Surgery, School of Medicine, College of Medicine
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31
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Rau B, Brandl A, Pascher A, Raue W, Sugarbaker P. Oligometastatic Disease in the Peritoneal Space with Gastrointestinal Cancer. Visc Med 2017; 33:42-46. [PMID: 28612016 DOI: 10.1159/000454694] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVES Treatment options for patients with gastrointestinal cancer and oligometastastic disease remain the domain of the medical oncologist. However, in selected cases, attempts to remove or destroy the tumor burden seem appropriate. BACKGROUND DATA During the last decade, the treatment of localized and isolated tumor nodules, such as lung, liver or peritoneal metastasis, has changed. Previously, these patients with metastatic disease only received palliative chemotherapy. Combined treatment approaches and new techniques demonstrate that additional surgery to destroy or remove the metastases seem to be of major benefit to patients. METHODS The recently published important literature regarding peritoneal metastases and oligometastases in gastrointestinal cancer was analyzed. RESULTS The most important factor in the treatment of peritoneal metastases and in cytoreductive surgery is patient selection. Resection of peritoneal metastases should be considered. Hyperthermic intraperitoneal chemotherapy is feasible. However, further results of randomized trials are necessary. Several randomized trials are on the way and will be available in 1-2 years. Systemic chemotherapy alone as an adequate management plan for all sites of metastatic disease is not compatible with a high standard of care. Formulating an optimal plan combining re-operative surgery with regional plus systemic chemotherapy is a necessary task of the multidisciplinary team. CONCLUSIONS In oligometastastic disease of gastrointestinal cancer origin, the selection process is the most important factor for survival. Further studies are needed to determine optimal treatment options.
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Affiliation(s)
- Beate Rau
- Department of General Surgery, Charité - Universitätsmedizin Berlin, Campus Virchow and Mitte, Berlin, Germany, DC, USA
| | - Andreas Brandl
- Department of General Surgery, Charité - Universitätsmedizin Berlin, Campus Virchow and Mitte, Berlin, Germany, DC, USA
| | - Andreas Pascher
- Department of General Surgery, Charité - Universitätsmedizin Berlin, Campus Virchow and Mitte, Berlin, Germany, DC, USA
| | - Wieland Raue
- Department of General Surgery, Charité - Universitätsmedizin Berlin, Campus Virchow and Mitte, Berlin, Germany, DC, USA
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32
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Ellison LM, Man Y, Stojadinovic A, Xin H, Avital I. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in treatment of gastric cancer with peritoneal carcinomatosis. Chin J Cancer Res 2017; 29:86-92. [PMID: 28373757 PMCID: PMC5348479 DOI: 10.21147/j.issn.1000-9604.2017.01.10] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Although gastric cancer with peritoneal carcinomatosis is associated with poor prognosis and is generally treated with palliative systemic therapy, recent studies have shown that cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may prove to be an efficacious treatment option. In addition to reviewing the natural history of gastric cancer with peritoneal carcinomatosis, this mini-review examines literature on the efficacy of CRS and HIPEC as compared to chemotherapy and surgical options. Both randomized and non-randomized studies were summarized with the emphasis focused on overall survival. In summary, CRS and HIPEC are indeed a promising treatment option for gastric cancer with peritoneal carcinomatosis and large randomized clinical trials are warranted.
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Affiliation(s)
- Lynne M Ellison
- Bon Secours Cancer Institute, Bon Secours Health System, Richmond, VA 23226, USA
| | - Yangao Man
- Bon Secours Cancer Institute, Bon Secours Health System, Richmond, VA 23226, USA
| | | | - Hongwu Xin
- Laboratory of Oncology, the First People's Hospital of Jingzhou City, the First Hospital and Clinical Medical School of Yangtze University, Jingzhou 434008, China; Laboratory of Oncology, Center for Molecular Medicine, Medical School, Yangtze University, Jingzhou 434023, China
| | - Itzhak Avital
- Bon Secours Cancer Institute, Bon Secours Health System, Richmond, VA 23226, USA
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33
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Ji ZH, Peng KW, Li Y. Intraperitoneal free cancer cells in gastric cancer: pathology of peritoneal carcinomatosis and rationale for intraperitoneal chemotherapy/hyperthermic intraperitoneal chemotherapy in gastric cancer. Transl Gastroenterol Hepatol 2016; 1:69. [PMID: 28138635 DOI: 10.21037/tgh.2016.08.03] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2016] [Accepted: 08/15/2016] [Indexed: 12/19/2022] Open
Abstract
Peritoneal carcinomatosis (PC) is one of the most common causes of death in gastric cancer patients. Intraperitoneal free cancer cells (IFCCs) play a very important role in forming PC, but the administration of intraperitoneal chemotherapy (IPC) and/or hyperthermic intraperitoneal chemotherapy (HIPEC) could be an effective treatment for IFCCs. This review focuses on the origin of IFCCs, the mechanism of PC formatting, the rationale of IPC/HIPEC, and the current clinical trials on IPC/HIPEC to treat advanced gastric cancer patients.
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Affiliation(s)
- Zhong-He Ji
- Department of Peritoneal Cancer Surgery, Cancer Center of Beijing Shijitan Hospital affiliated to the Capital Medical University, Beijing 100038, China
| | - Kai-Wen Peng
- Department of Peritoneal Cancer Surgery, Cancer Center of Beijing Shijitan Hospital affiliated to the Capital Medical University, Beijing 100038, China
| | - Yan Li
- Department of Peritoneal Cancer Surgery, Cancer Center of Beijing Shijitan Hospital affiliated to the Capital Medical University, Beijing 100038, China
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34
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Li Y, Zhou YF, Liang H, Wang HQ, Hao JH, Zhu ZG, Wan DS, Qin LX, Cui SZ, Ji JF, Xu HM, Wei SZ, Xu HB, Suo T, Yang SJ, Xie CH, Yang XJ, Yang GL. Chinese expert consensus on cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignancies. World J Gastroenterol 2016; 22:6906-6916. [PMID: 27570426 PMCID: PMC4974588 DOI: 10.3748/wjg.v22.i30.6906] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2016] [Revised: 04/02/2016] [Accepted: 06/13/2016] [Indexed: 02/07/2023] Open
Abstract
Locoregional spread of abdominopelvic malignant tumors frequently results in peritoneal carcinomatosis (PC). The prognosis of PC patients treated by conventional systemic chemotherapy is poor, with a median survival of < 6 mo. However, over the past three decades, an integrated treatment strategy of cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) has been developed by the pioneering oncologists, with proved efficacy and safety in selected patients. Supported by several lines of clinical evidence from phases I, II and III clinical trials, CRS + HIPEC has been regarded as the standard treatment for selected patients with PC in many established cancer centers worldwide. In China, an expert consensus on CRS + HIPEC has been reached by the leading surgical and medical oncologists, under the framework of the China Anti-Cancer Association. This expert consensus has summarized the progress in PC clinical studies and systematically evaluated the CRS + HIPEC procedures in China as well as across the world, so as to lay the foundation for formulating PC treatment guidelines specific to the national conditions of China.
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Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy with lobaplatin and docetaxel to treat synchronous peritoneal carcinomatosis from gastric cancer: Results from a Chinese center. Eur J Surg Oncol 2016; 42:1024-34. [DOI: 10.1016/j.ejso.2016.04.053] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Revised: 04/05/2016] [Accepted: 04/18/2016] [Indexed: 12/29/2022] Open
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Yuan M, Wang Z, Hu G, Yang Y, Lv W, Lu F, Zhong H. A retrospective analysis of hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis. Mol Clin Oncol 2016; 5:395-399. [PMID: 27446587 DOI: 10.3892/mco.2016.918] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2016] [Accepted: 05/25/2016] [Indexed: 12/17/2022] Open
Abstract
Peritoneal metastasis (PM) is a poor prognostic factor in patients with gastric cancer. The aim of this study was to evaluate the efficacy and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with advanced gastric cancer with PM by retrospective analysis. A total of 54 gastric cancer patients with positive ascitic fluid cytology were included in this study: 23 patients were treated with systemic chemotherapy combined with HIPEC (HIPEC+ group) and 31 received systemic chemotherapy alone (HIPEC- group). The patients were divided into 4 categories according to the changes of ascites, namely disappear, decrease, stable and increase. The disappear + decrease rate in the HIPEC+ group was 82.60%, which was statistically significantly superior to that of the HIPEC- group (54.80%). The disappear + decrease + stable rate was 95.70% in the HIPEC+ group and 74.20% in the HIPEC- group, but the difference was not statistically significant. In 33 patients with complete survival data, including 12 from the HIPEC+ and 21 from the HIPEC- group, the median progression-free survival was 164 and 129 days, respectively, and the median overall survival (OS) was 494 and 223 days, respectively. In patients with ascites disappear/decrease/stable, the OS appeared to be better compared with that in patients with ascites increase, but the difference was not statistically significant. Further analysis revealed that patients with controlled disease (complete response + partial response + stable disease) may have a better OS compared with patients with progressive disease, with a statistically significant difference. The toxicities were well tolerated in both groups. Therefore, HIPEC was found to improve survival in advanced gastric cancer patients with PM, but the difference was not statistically significant, which may be attributed to the small number of cases. Further studies with larger samples are required to confirm our data.
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Affiliation(s)
- Meiqin Yuan
- Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
| | - Zeng Wang
- Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
| | - Guinv Hu
- Department of Surgical Oncology, Dongyang People's Hospital, Dongyang, Zhejiang 322100, P.R. China
| | - Yunshan Yang
- Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
| | - Wangxia Lv
- Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
| | - Fangxiao Lu
- Department of Radiology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
| | - Haijun Zhong
- Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
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Chia CS, Seshadri RA, Kepenekian V, Vaudoyer D, Passot G, Glehen O. Survival outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from gastric cancer: a systematic review. Pleura Peritoneum 2016; 1:67-77. [PMID: 30911610 PMCID: PMC6386497 DOI: 10.1515/pp-2016-0010] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2016] [Accepted: 05/08/2016] [Indexed: 02/07/2023] Open
Abstract
Background: The current treatment of choice for peritoneal carcinomatosis from gastric cancer is systemic chemotherapy. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a new aggressive form of loco-regional treatment that is currently being used in pseudomyxoma peritoneii, peritoneal mesothelioma and peritoneal carcinomatosis from colorectal cancer. It is still under investigation for its use in gastric cancer. Methods: The literature between 1970 and 2016 was surveyed systematically through a review of published studies on the treatment outcomes of CRS and HIPEC for peritoneal carcinomatosis from gastric cancer. Results: Seventeen studies were included in this review. The median survival for all patients ranged from 6.6 to 15.8 months. The 5-years overall survival ranged from 6 to 31%. For patients with complete cytoreduction, the median survival was 11.2 to 43.4 months and the 5-years overall survival was 13 % to 23%. Important prognostic factors were found to be a low peritoneal carcarcinomatosis index (PCI) score and the completeness of cytoreduction. Conclusion: The current evidence suggests that CRS and HIPEC has a role to play in the treatment of peritoneal carcinomatosis from gastric cancer. Long term survival has been shown for a select group of patients. However, further studies are needed to validate these results.
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Kitayama J, Yamaguchi H, Ishigami H, Matsuzaki K, Sata N. Intraperitoneal Mesenchymal Cells Promote the Development of Peritoneal Metastasis Partly by Supporting Long Migration of Disseminated Tumor Cells. PLoS One 2016; 11:e0154542. [PMID: 27136922 PMCID: PMC4854412 DOI: 10.1371/journal.pone.0154542] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Accepted: 04/14/2016] [Indexed: 11/18/2022] Open
Abstract
The human peritoneal cavity contains a small number of free cells of mesenchymal cell lineage. Intraperitoneal mesenchymal cells (PMC) play supportive roles in metastasis formation on the peritoneum. In this study, we found that PMC, when co-cultuerd with human gastric cancer cells, MKN45, enhanced the proliferation of MKN45 when cultured at low, but not high, cellular density. Also, PMC suppressed apoptotic cell death of MKN45 only under low density culture conditions. Time-lapse videoanalysis clearly demonstrated that PMC randomly migrated more vigorously than did MKN45, and strongly enhanced the migration behavior of co-cultured MKN45. In fact, the majority of MKN45 migrated together in direct physical contact with PMC, and the sum of migration lengths from original position of co-cultured MKN45 for 48 hours was approximately 10 times longer than that of MKN45 cultured alone. Our data suggest that enhanced migration can increase the chance of direct contact or positional proximity among sparcely distributed MKN45, which may bring survival advantages to tumor cells. This may be one of the important mechanisms of peritoneal metastasis, since only a small number of tumor cells are considered to be disseminated in the early step of metastasis formation on the peritoneum.
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Affiliation(s)
- Joji Kitayama
- Department of Gastrointestinal Surgery, Jichi Medical University, Tochigi, Japan
- * E-mail:
| | - Hironori Yamaguchi
- Department of Gastrointestinal Surgery, Jichi Medical University, Tochigi, Japan
| | | | | | - Naohiro Sata
- Department of Gastrointestinal Surgery, Jichi Medical University, Tochigi, Japan
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Men HT, Gou HF, Liu JY, Li Q, Luo DEY, Bi F, Qiu M. Prognostic factors of intraperitoneal chemotherapy for peritoneal carcinomatosis of gastric cancer: A retrospective study from a single center. Oncol Lett 2016; 11:3501-3507. [PMID: 27123142 DOI: 10.3892/ol.2016.4403] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2015] [Accepted: 11/20/2015] [Indexed: 02/05/2023] Open
Abstract
Peritoneal carcinomatosis (PC) of gastric origin is currently recognized as a terminal disease with a poor prognosis. Advancements in novel therapeutic approaches, including intraperitoneal chemotherapy (IPC), have recently been made and it is believed that this may have contributed to the improved survival observed in patients with PC. The present study aimed to investigate overall survival (OS) and the associated prognostic factors in patients with PC of gastric origin who underwent IPC. A total of 57 patients were studied, with a median age of 51 years. The median follow-up time was 12.4 months. PC was diagnosed in all patients with gastric cancer. The median survival time of all patients was 10.1 months, whilst the OS rate at 1, 2 and 3 years was observed to be 46, 19 and 12%, respectively. Symptomatic ascites and a signet ring cell (SRC) histopathological type were demonstrated to signify a poor prognosis. Complete resection of all gross disease (CCR-0) and an increased number of cycles of systemic chemotherapy were independent factors that were observed to correlate with increased OS. The most common morbidities of grade 3/4 adverse effects were bone marrow suppression, nausea or vomiting, and diarrhea. In conclusion, IPC is an important treatment option for patients with PC that has originated from gastric cancer. Symptomatic ascites and SRC adenocarcinoma serve as negative clinicopathological prognostic factors, whilst CCR-0 and increased systemic chemotherapy cycles (≥4 cycles) may prove to be an important therapeutic option for PC patients.
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Affiliation(s)
- Hai-Tao Men
- Division of Abdominal Cancer, Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China; Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Yuanjiagang, Yuzhong 400016, P.R. China
| | - Hong-Feng Gou
- Division of Abdominal Cancer, Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Ji-Yan Liu
- Division of Abdominal Cancer, Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Qiu Li
- Division of Abdominal Cancer, Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - DE-Yun Luo
- Division of Abdominal Cancer, Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Feng Bi
- Division of Abdominal Cancer, Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Meng Qiu
- Division of Abdominal Cancer, Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China
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Sun JH, Ji ZH, Yu Y, Wu HT, Huang CQ, Zhang Q, Yang XJ, Yonemura Y, Li Y. Cytoreductive Surgery plus Hyperthermic Intraperitoneal Chemotherapy to Treat Advanced/Recurrent Epithelial Ovarian Cancer: Results from a Retrospective Study on Prospectively Established Database. Transl Oncol 2016; 9:130-138. [PMID: 27084429 PMCID: PMC4833965 DOI: 10.1016/j.tranon.2016.02.002] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2015] [Revised: 02/14/2016] [Accepted: 02/24/2016] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Despite the best standard treatment, optimal cytoreductive surgery (CRS) and platinum/taxane-based chemotherapy, prognosis of advanced epithelial ovarian carcinoma (EOC) remains poor. Recently, CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC) has been developed to treat peritoneal carcinomatosis (PC). This study was to evaluate the efficacy and safety of CRS+HIPEC to treat PC from advanced/recurrent EOC. METHODS Forty-six PC patients from advanced EOC (group A) or recurrent EOC (group B) were treated by 50 CRS+HIPEC procedures. The primary endpoints were progression-free survival (PFS) and overall survival (OS); the secondary endpoints were safety profiles. RESULTS The median OS was 74.0 months [95% confidence interval (CI) 8.5-139.5] for group A versus 57.5 months (95% CI 29.8-85.2) for group B (P = .68). The median PFS was not reached for group A versus 8.5 months (95% CI 0-17.5) for group B (P = .034). Better median OS correlated with peritoneal cancer index (PCI) < 20 (76.6 months for PCI ≤ 20 group vs 38.5 months for PCI > 20 group, P = .01), complete cyroreduction (residual disease ≤ 2.5 mm) [79.5 months for completeness of cytoreduction (CC) score 0-1 vs 24.3 months for CC 2-3, P = .00], and sensitivity to platinum (65.3 months for platinum-sensitive group vs 20.0 for platinum-resistant group, P = .05). Serious adverse events occurred in five patients (10.0%). Multivariate analysis identified CC score as the only independent factor for better survival. CONCLUSION For advanced/recurrent EOC, CRS+HIPEC could improve OS with acceptable safety.
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Affiliation(s)
- Jian-Hua Sun
- Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan, 430071, P. R. China; Department of Gastrointestinal Surgery, Enshi Autonomous Prefecture Hospital, Enshi, Hubei, 445000, P. R. China
| | - Zhong-He Ji
- Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan, 430071, P. R. China
| | - Yang Yu
- Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan, 430071, P. R. China
| | - Hai-Tao Wu
- Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan, 430071, P. R. China
| | - Chao-Qun Huang
- Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan, 430071, P. R. China
| | - Qian Zhang
- Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan, 430071, P. R. China
| | - Xiao-Jun Yang
- Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan, 430071, P. R. China
| | - Yutaka Yonemura
- NPO Organization to Support Peritoneal Dissemination Treatment, Osaka, Japan
| | - Yan Li
- Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan, 430071, P. R. China; Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital Affiliated to the Capital Medical University, Beijing, 100038, P. R. China.
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Yonemura Y, Canbay E, Li Y, Coccolini F, Glehen O, Sugarbaker PH, Morris D, Moran B, Gonzaletz-Moreno S, Deraco M, Piso P, Elias D, Batlett D, Ishibashi H, Mizumoto A, Verwaal V, Mahtem H. A comprehensive treatment for peritoneal metastases from gastric cancer with curative intent. Eur J Surg Oncol 2016; 42:1123-31. [PMID: 27160355 DOI: 10.1016/j.ejso.2016.03.016] [Citation(s) in RCA: 79] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2016] [Revised: 03/12/2016] [Accepted: 03/16/2016] [Indexed: 12/29/2022] Open
Abstract
Recently, Peritoneal Surface Oncology Group International (PSOGI) developed a novel comprehensive treatment consisting of cytoreductive surgery (CRS) and perioperative chemotherapy (POC) for the treatment of peritoneal metastases (PM) from gastric cancer with curative intent. This article reviews the results of this treatment and verifies its indication. In this strategy, peritoneal cancer index (PCI) is determined by laparoscopy, and a peritoneal port is placed. Neoadjuvant bidirectional intraperitoneal/systemic chemotherapy (NIPS) is performed for 3 cycles, and then laparotomy is performed. Cytoreductive surgery with peritonectomy procedures and hyperthermic intraperitoneal chemoperfusion (HIPEC) are performed. Multivariate analyses showed that completeness of cytoreduction, pathologic response to NIPS and PCI level and cytologic status after NIPS, as independent prognostic factors. PCI less than cut-off level after NIPS, negative cytology after NIPS, and positive response to NIPS were identified as the indications for comprehensive treatment. Patients who hold these criteria should be considered as the candidates for CRS and HIPEC.
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Affiliation(s)
- Y Yonemura
- Peritoneal Surface Malignancy Center, Kishiwada Tokushukai Hospital, Kusatsu General Hospital, Kishiwada, Shiga, Japan; NPO to Support Peritoneal Surface Malignancy Treatment, Oosaka, 600 8189, Japan.
| | - E Canbay
- NPO to Support Peritoneal Surface Malignancy Treatment, Oosaka, 600 8189, Japan
| | - Y Li
- Department of Peritoneal Surface Oncology, Beijin Shijitan Hospital of Capital Medical University, Beijin, 100038, China
| | - F Coccolini
- General Surgery Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - O Glehen
- Dēpartement de Chirurgie Gēnerale, Centre Hospitalier Lyon-Sud Hospices Civils de Lyon, Universitē Lyon, 69495, France
| | - P H Sugarbaker
- Center of Gastrointestinal Malignancies, Program in Peritoneal Surface Malignancies, MedStar Washington Hospital Center, Washington, DC, 20010, USA
| | - D Morris
- Department of Surgery, St George Hospital, University of New South Wales, Australia
| | - B Moran
- Peritoneal Malignancy Institute Basingstoke, Hampshire Hospitals Foundation Trust, Adelmaston Road, Basingstoke RG24 9NA, UK
| | - S Gonzaletz-Moreno
- Department of Surgical Oncology, Peritoneal Surface Oncology Program, MD Anderson Cancer Center, Madrid, Spain
| | - M Deraco
- National Cancer Institute of Milan, Italy
| | - P Piso
- Krankenhaus Barmherzige Brieder, Teaching Hospital of the University of Regensburg, Regensburg, Germany
| | - D Elias
- Département de Chirurgie Générale, Institut Gustave Roussy, Villejuif, Cedex, France
| | - D Batlett
- Division of Surgical Oncology, Hillman Cancer Center, 5115 Centre Ave, Pittsburgh, PA, 15232, USA
| | - H Ishibashi
- Peritoneal Surface Malignancy Center, Kishiwada Tokushukai Hospital, Kusatsu General Hospital, Kishiwada, Shiga, Japan
| | - A Mizumoto
- Peritoneal Surface Malignancy Center, Kishiwada Tokushukai Hospital, Kusatsu General Hospital, Kishiwada, Shiga, Japan
| | - V Verwaal
- Oncologisch GE Chirurg, Catharina, Ziekenhuis Eindhoven, The Netherlands
| | - H Mahtem
- Department of Surgical Sciences, Uppsala University, Övriga Samarbeten, Akademiska Sjukhuset, Ing 70 1 Tr, 751 85, Uppsala, Sweden
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Wu Y, Pan M, Cui S, Ba M, Chen Z, Ruan Q. Efficacy and safety of ultrasound-guided continuous hyperthermic intraperitoneal perfusion chemotherapy for the treatment of malignant ascites: a midterm study of 36 patients. Onco Targets Ther 2016; 9:403-7. [PMID: 26855589 PMCID: PMC4725693 DOI: 10.2147/ott.s85564] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
Abstract
Background This study aimed to evaluate the efficacy and safety of ultrasound-guided continuous hyperthermic intraperitoneal perfusion chemotherapy (CHIPC) for the treatment of malignant ascites (MA). Methods Between July 2011 and June 2013, 36 MA patients were prospectively and consecutively hospitalized for three cycles of elective CHIPC under ultrasound guidance, maintained at a constant flow rate of 400–600 mL/min normal saline containing 5-fluorouracil plus mitomycin or carboplatin and at a constant temperature of 43°C±0.2°C, for 90 minutes. Main outcome measures were ascites resolution, Karnofsky performance status (KPS), and serum tumor biomarkers at 2 weeks after the last cycle of CHIPC. All the patients underwent uneventful CHIPC as scheduled, and vital signs remained stable over CHIPC. Results At 2 weeks after the last cycle of CHIPC, MA completely and partially resolved in 26 (72.2%) patients and eight (22.2%) patients, respectively; mean KPS score increased from pretreatment 61±9 to posttreatment 76±9 (P<0.001), and serum carcinoembryonic antigen and carbohydrate antigens 12-5 and 19-9 significantly decreased (all P<0.01). Conclusion The current study indicated that ultrasound-guided CHIPC is an effective and safe palliative treatment modality for MA with respect to MA resolution, patient’s general well-being, and systemic disease control. The long-term benefit of CHIPC on overall survival remains to be investigated in MA patients.
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Affiliation(s)
- Yinbing Wu
- Second Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou Medical University, Guangzhou, People's Republic of China; Treatment Center of Body Cavitary Thermo-Perfusion, Cancer Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Mingxin Pan
- Second Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Shuzhong Cui
- Treatment Center of Body Cavitary Thermo-Perfusion, Cancer Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Mingchen Ba
- Treatment Center of Body Cavitary Thermo-Perfusion, Cancer Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Zulong Chen
- Treatment Center of Body Cavitary Thermo-Perfusion, Cancer Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Qiang Ruan
- Treatment Center of Body Cavitary Thermo-Perfusion, Cancer Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, People's Republic of China
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Ji Z, Sun J, Wu H, Zhang Q, Peng K, Li Y. Assessment of Hyperthermic Intraperitoneal Chemotherapy to Eradicate Intraperitoneal Free Cancer Cells. Transl Oncol 2016; 9:18-24. [PMID: 26947877 PMCID: PMC4800055 DOI: 10.1016/j.tranon.2015.11.015] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2015] [Accepted: 11/20/2015] [Indexed: 02/09/2023] Open
Abstract
OBJECTIVE: To assess the effect of hyperthermic intraperitoneal chemotherapy (HIPEC) to eradicate intraperitoneal free cancer cells and to explore the feasibility of cytological cure for peritoneal carcinomatosis (PC). METHODS: The peritoneal lavage fluid (or ascites) from 50 PC patients was collected before and after intraoperative HIPEC, respectively, for conventional cytology test, and conventional and real-time quantitative reverse transcript polymerase chain reaction detecting carcinoembryonic antigen (CEA) mRNA and cytokeratin-20 (CK20) mRNA. The blood samples 3 days before and 7 days after intraoperative HIPEC were also collected for detecting the serum tumor markers, including CEA, carbohydrate antigen (CA) 125, and CA19-9. RESULTS: The positive rate of conventional cytology test before HIPEC versus after HIPEC was100.0% versus 22.0% (P = .000). The positive rates of CEA mRNA and CK20 mRNA before HIPEC versus after HIPEC were 100.0% versus 86.0% (P = .012) and 100.0% versus 96.0% (P = .495), respectively. Moreover, after HIPEC, 18 (36.0%) patients had a decline in CEA mRNA (P = .000), and 17 (34.0%) patients had a decline in CK20 mRNA (P = .000). The positive rates of serum CEA, CA125, and CA199 before HIPEC versus after HIPEC were 52.0% versus 28.0% (P = .014), 52.0% versus 44.0% (P = .423), and 40.0% versus 28.0% (P = .205), respectively. CONCLUSION: HIPEC could effectively eradicate intraperitoneal free cancer cells and partially achieve cytological cure for PC.
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Affiliation(s)
- Zhonghe Ji
- Department of Peritoneal Cancer Surgery, Cancer Center of Beijing Shijitan Hospital, The Capital Medical University, Beijing, 100038, China; Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan, 430071, China
| | - Jianhua Sun
- Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan, 430071, China
| | - Haitao Wu
- Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan, 430071, China
| | - Qian Zhang
- Department of Peritoneal Cancer Surgery, Cancer Center of Beijing Shijitan Hospital, The Capital Medical University, Beijing, 100038, China; Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan, 430071, China
| | - Kaiwen Peng
- Department of Peritoneal Cancer Surgery, Cancer Center of Beijing Shijitan Hospital, The Capital Medical University, Beijing, 100038, China; Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan, 430071, China
| | - Yan Li
- Department of Peritoneal Cancer Surgery, Cancer Center of Beijing Shijitan Hospital, The Capital Medical University, Beijing, 100038, China; Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan, 430071, China.
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Seshadri RA, Glehen O. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer. World J Gastroenterol 2016; 22:1114-30. [PMID: 26811651 PMCID: PMC4716024 DOI: 10.3748/wjg.v22.i3.1114] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 09/22/2015] [Accepted: 11/30/2015] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer associated peritoneal carcinomatosis (GCPC) has a poor prognosis with a median survival of less than one year. Systemic chemotherapy including targeted agents has not been found to significantly increase the survival in GCPC. Since recurrent gastric cancer remains confined to the abdominal cavity in many patients, regional therapies like aggressive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been investigated for GCPC. HIPEC has been used for three indications in GC- as an adjuvant therapy after a curative surgery, HIPEC has been shown to improve survival and reduce peritoneal recurrences in many randomised trials in Asian countries; as a definitive treatment in established PC, HIPEC along with CRS is the only therapeutic modality that has resulted in long-term survival in select groups of patients; as a palliative treatment in advanced PC with intractable ascites, HIPEC has been shown to control ascites and reduce the need for frequent paracentesis. While the results of randomised trials of adjuvant HIPEC from western centres are awaited, the role of HIPEC in the treatment of GCPC is still evolving and needs larger studies before it is accepted as a standard of care.
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Coccolini F, Montori G, Ceresoli M, Cima S, Valli MC, Nita GE, Heyer A, Catena F, Ansaloni L. Advanced gastric cancer: What we know and what we still have to learn. World J Gastroenterol 2016; 22:1139-1159. [PMID: 26811653 PMCID: PMC4716026 DOI: 10.3748/wjg.v22.i3.1139] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2015] [Revised: 09/25/2015] [Accepted: 11/24/2015] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer is a common neoplastic disease and, more precisely, is the third leading cause of cancer death in the world, with differences amongst geographic areas. The definition of advanced gastric cancer is still debated. Different stadiating systems lead to slightly different stadiation of the disease, thus leading to variations between the single countries in the treatment and outcomes. In the present review all the possibilities of treatment for advanced gastric cancer have been analyzed. Surgery, the cornerstone of treatment for advanced gastric cancer, is analyzed first, followed by an investigation of the different forms and drugs of chemotherapy and radiotherapy. New frontiers in treatment suggest the growing consideration for intraperitoneal administration of chemotherapeutics and combination of traditional drugs with new ones. Moreover, the necessity to prevent the relapse of the disease leads to the consideration of administering intraperitoneal chemotherapy earlier in the therapeutical algorithm.
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46
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Chia CS, You B, Decullier E, Vaudoyer D, Lorimier G, Abboud K, Bereder JM, Arvieux C, Boschetti G, Glehen O. Patients with Peritoneal Carcinomatosis from Gastric Cancer Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Is Cure a Possibility? Ann Surg Oncol 2016; 23:1971-9. [PMID: 26753751 DOI: 10.1245/s10434-015-5081-3] [Citation(s) in RCA: 116] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2015] [Indexed: 12/14/2022]
Abstract
BACKGROUND Peritoneal carcinomatosis is an increasingly common finding in gastric carcinoma. Previously, patients were treated as terminal, and median survival was poor. The use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in this context is still highly debatable. OBJECTIVE The aim of this study was to evaluate the long-term outcomes associated with CRS and HIPEC, and define prognostic factors for cure, if possible. PATIENTS AND METHODS All patients with gastric carcinomatosis from five French institutions who underwent combined complete CRS and HIPEC and had a minimum follow-up of 5 years were included in this study. Cure was defined as a disease-free interval of more than 5 years from the last treatment until the last follow-up. RESULTS Of the 81 patients who underwent CRS and HIPEC from 1989 to 2009, 59 had a completeness of cytoreduction score (CCS) of 0 (complete macroscopic resection), and the median Peritoneal Cancer Index (PCI) score was 6. Mitomycin C was the most commonly used drug during HIPEC (88 %). The 5-year overall survival (OS) rate was 18 %, with nine patients still disease-free at 5 years, for a cure rate of 11 %. All 'cured' patients had a PCI score below 7 and a CCS of 0. Factors associated with improved OS on multivariate analysis were synchronous resection (p = 0.02), a lower PCI score (p = 0.12), and the CCS (p = 0.09). CONCLUSION The cure rate of 11 % for patients with gastric carcinomatosis who are deemed terminal emphasizes that CRS and HIPEC should be considered in highly selected patients (low disease extent and complete CRS).
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Affiliation(s)
- C S Chia
- Hospices Civils de Lyon, Department of General and Oncologic Surgery, Cancer Institute, Pierre Bénite, France.
| | - B You
- Hospices Civils de Lyon, Department of Oncology, Cancer Institute of HCL, Pierre Bénite, France.,Université Lyon 1, Research Unit EMR 3738, Lyon, France
| | - E Decullier
- Hospices Civils de Lyon, Pôle Information Médicale Evaluation Recherche, Unité de Recherche Clinique, Lyon, France.,Université de Lyon, RECIF, EA Santé Individu Société 4129, Lyon, France.,Université Lyon 1, Lyon, France
| | - D Vaudoyer
- Hospices Civils de Lyon, Department of General and Oncologic Surgery, Cancer Institute, Pierre Bénite, France
| | - G Lorimier
- Service de Chirurgie Digestive et Cancérologique, Centre P. Papin, Angers, France
| | - K Abboud
- Service de Chirurgie Générale, Hopital Nord, St Etienne, France.,Université Lyon 1, Research Unit EMR 3738, Lyon, France
| | - J-M Bereder
- Service de Chirurgie Générale et Cancérologie Digestive, CHU L'Archet II, Nice, France
| | - C Arvieux
- Service de Chirurgie Digestive, CHU A. Michallon, Grenoble, France.,Université Lyon 1, Research Unit EMR 3738, Lyon, France
| | - G Boschetti
- Department of Hepatogastroenterology, Cancer Institute of HCL, Lyon Sud, Pierre Bénite, France
| | - O Glehen
- Hospices Civils de Lyon, Department of General and Oncologic Surgery, Cancer Institute, Pierre Bénite, France.,Université Lyon 1, Research Unit EMR 3738, Lyon, France.,Surgical Oncology Department, CHRU Lyon Sud, Pierre Bénite, Cedex, France
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Ba MC, Long H, Zhang XL, Gong YF, Tang YQ, Wu YB, Yu FH, Cui SZ. Laparoscopic Hyperthermic Intraperitoneal Perfusion Chemotherapy for Patients with Malignant Ascites Secondary to Unresectable Gastric Cancer. J Laparoendosc Adv Surg Tech A 2016; 26:32-9. [PMID: 26779722 DOI: 10.1089/lap.2015.0266] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Affiliation(s)
- Ming-chen Ba
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Hui Long
- Department of Pharmacy, Guangzhou Dermatology Institute, Guangzhou, People's Republic of China
| | - Xiang-Liang Zhang
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Yuan-Feng Gong
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Yun-Qiang Tang
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Yin-Bing Wu
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Fei-Hong Yu
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Shu-Zhong Cui
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China
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48
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Maeda H, Kobayashi M, Sakamoto J. Evaluation and treatment of malignant ascites secondary to gastric cancer. World J Gastroenterol 2015; 21:10936-10947. [PMID: 26494952 PMCID: PMC4607895 DOI: 10.3748/wjg.v21.i39.10936] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2015] [Revised: 07/26/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023] Open
Abstract
Malignant ascites affects approximately 10% of patients with gastric cancer (GC), and poses significant difficulties for both patients and clinicians. In addition to the dismal general condition of affected patients and the diversity of associated complications such as jaundice and ileus, problems in assessing scattered tumors have hampered the expansion of clinical trials for this condition. However, the accumulation of reported studies is starting to indicate that the weak response to treatment in GC patients with malignant ascites is more relevant to their poor prognosis rather than to the ascites volume at diagnosis. Therefore, precise assessment of initial state of ascites, repetitive evaluation of treatment efficacy, selection of suitable treatment, and swift transition to other treatment options as needed are paramount to maximizing patient benefit. Accurately determining ascites volume is the crucial first step in clinically treating a patient with malignant ascites. Ultrasonography is commonly used to identify the existence of ascites, and several methods have been proposed to estimate ascites volume. Reportedly, the sum of the depth of ascites at five points (named “five-point method”) on three panels of computed tomography images is well correlated to the actual ascites volume and/or abdominal girth. This method is already suited to repetitive assessment due to its convenience compared to the conventional volume rendering method. Meanwhile, a new concept, “Clinical Benefit Response in GC (CBR-GC)”, was recently introduced to measure the efficacy of chemotherapy for malignant ascites of GC. CBR-GC is a simple and reliable patient-oriented evaluation system based on changes in performance status and ascites, and is expected to become an important clinical endpoint in future clinical trials. The principal of treatment for GC patients with ascites is palliation and prevention of ascites-related symptoms. The treatment options are various, including a standard treatment based on the available guidelines, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC), laparoscopic HIPEC alone, intravenous chemotherapy, intraperitoneal chemotherapy, and molecular targeting therapy. Although each treatment option is valid, further research is imperative to establish the optimal choice for each patient.
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Yonemura Y, Canbay E, Endou Y, Ishibashi H, Mizumoto A, Li Y, Liu Y, Takeshita K, Ichinose M, Takao N, Saitou T, Noguchi K, Hirano M, Glehen O, Brűcher B, Sugarbaker PH. Comprehensive treatment for the peritoneal metastasis from gastric cancer. World J Surg Proced 2015; 5:187-197. [DOI: 10.5412/wjsp.v5.i2.187] [Citation(s) in RCA: 5] [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: 07/13/2014] [Revised: 10/05/2014] [Accepted: 03/18/2015] [Indexed: 02/06/2023] Open
Abstract
Recently, a novel comprehensive treatment consisting of cytoreductive surgery (CRS) and perioperative chemotherapy (POC) was developed for the treatment of peritoneal metastasis (PM) with a curative intent. In the treatment, the macroscopic disease is completely removed by the peritonectomy techniques in combination with POC. This article reviews the results of the comprehensive treatment for PM from gastric cancer, and verifies the effects of CRS and POC, including neoadjuvant chemotherapy (NAC) and hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC). Completeness of cytoreduction, peritoneal carcinomatosis index (PCI) less than the threshold levels after NAC, absence of ascites, cytologic status, pathologic response after NAC are the independent prognostic factors. Among these prognostic factors, PCI threshold level is the most valuable independent prognostic factor. After staging laparoscopy, patients with PM from gastric cancer are recommended to treat with NAC before CRS. After NAC, indication for CRS is determined by laparoscopy. The indications of the comprehensive treatment are patients with PCI less than the threshold levels, negative cytology, and responders after NAC. Patients satisfy these factors are the candidates for the CRS and HIPEC.
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Mei LJ, Wang LW, Huang CQ, Yang XJ, Li Y. Oral gastrografin radiography for the evaluation of the functional impact of peritoneal carcinomatosis: Correlation with clinicopathological findings. Mol Clin Oncol 2015; 3:979-986. [PMID: 26623037 DOI: 10.3892/mco.2015.573] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Accepted: 04/15/2015] [Indexed: 02/06/2023] Open
Abstract
This study was conducted to evaluate the functional impact of peritoneal carcinomatosis (PC) on the gastrointestinal system by oral gastrografin radiography (OGR). OGR was performed on 105 patients with PC from abdominal malignancies. The OGR characteristics were analyzed and compared with intraoperative observations. OGR provided real-time dynamic information on the functional impacts of PC. The OGR findings were normal in 9 (8.6%) and abnormal in 96 (91.4%) cases. In terms of frequency, 33 cases (31.4%) exhibited mild intestinal aggregation and flattening of the intestinal mucosa; 29 cases (27.6%) exhibited limited intestinal invasion, marginally stenotic small bowel and mucosal deformities; 26 cases (24.8%) exhibited only mild mesenteric contracture and mild slowing of gastrointestinal peristalsis; 5 cases (4.8%) exhibited obvious mesenteric contracture, ball-like changes, fixed position and disappearance of the intestinal mucosa; 2 cases (1.9%) exhibited complete pyloric obstruction; and 1 case (0.9%) exhibited duodenal obstruction. Gastric PC was associated with a higher percentage of stomach filling defects and small intestinal aggregates compared with PC from other malignancies (P<0.01 for both). In 87 cases, the ORG findings were in accordance with the intraoperative findings (κ=0.726, P<0.001), whereas 17 cases (16.2%) were underestimated and 1 (0.9%) was overestimated by OGR. This study indicated that OGR may be a useful technique for the evaluation of the functional impacts of PC on the gastrointestinal system and may help optimize the selection of patients for treatment.
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Affiliation(s)
- Lie-Jun Mei
- Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China ; Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Lin-Wei Wang
- Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China ; Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan, Hubei 430071, P.R. China
| | - Chao-Qun Huang
- Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China ; Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan, Hubei 430071, P.R. China
| | - Xiao-Jun Yang
- Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China ; Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan, Hubei 430071, P.R. China
| | - Yan Li
- Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China ; Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan, Hubei 430071, P.R. China
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