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Kusamura S, Bhatt A, van Der Speeten K, Kepenekian V, Hübner M, Eveno C, de Hingh I, Delhorme J, Taibi A, Villeneuve L, Dico RL, Moran B, Govaerts K, Zivanovic O, Brennan D, Nadeau C, Van Driel W, Bakrin N, Piso P, Verwaal VJ, González‐Moreno S, Alyami M, Sgarbura O, Rau B, Deraco M, Glehen O. Review of 2022 PSOGI/RENAPE Consensus on HIPEC. J Surg Oncol 2024; 130:1290-1298. [PMID: 39285659 PMCID: PMC11826010 DOI: 10.1002/jso.27885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 08/26/2024] [Indexed: 02/16/2025]
Abstract
The 2022 PSOGI (Peritoneal Surface Oncology Group International) and RENAPE (French Network for Rare Peritoneal Malignancies) consensus on hyperthermic intraperitoneal chemotherapy (HIPEC) was a comprehensive effort aimed at standardizing treatment protocols for various peritoneal malignancies. This initiative is critical due to the wide range of technical variations in HIPEC procedures and the resulting need for standardization to ensure consistent and effective patient care and meaningful audit of multicenter data.
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Affiliation(s)
- Shigeki Kusamura
- PSM Unit, Department of Surgical OncologyFondazione IRCCS Istituto Nazionale dei TumoriMilanItaly
| | - Aditi Bhatt
- Department of Surgical OncologyKD HospitalAhmedabadIndia
| | - Kurt van Der Speeten
- Department of Abdominal and Oncological SurgeryZiekenhuis Oost Limburg (ZOL)GenkBelgium
| | - Vahan Kepenekian
- Department of Oncological SurgeryHôpital Lyon Sud, Hospices Civils de LyonLyonFrance
- CICLYUniversité Claude Bernard Lyon 1LyonFrance
| | - Martin Hübner
- Department of Visceral SurgeryLausanne University Hospital (CHUV), University of Lausanne (UNIL)LausanneSwitzerland
| | - Clarisse Eveno
- Department of Digestive and Oncological SurgeryUniversity Lille, Claude Huriez University HospitalLilleFrance
| | - Ignace de Hingh
- Department of SurgeryCatharina Cancer InstituteEindhovenThe Netherlands
| | - Jean‐Baptiste Delhorme
- Department of General and Digestive SurgeryHautepierre Hospital, Strasbourg University HospitalStrasbourgFrance
| | - Abdelkader Taibi
- Department of Digestive SurgeryDupuytren University HospitalLimogesFrance
- XLIM, UMR 7252CNRSLimogesFrance
| | - Laurent Villeneuve
- Hospices Civils de Lyon, Hôpital Lyon Sud, Service de Recherche et d'Epidémiologie CliniquesPierre‐BéniteFrance
| | - Rea Lo Dico
- Department of General Surgery, Emergency, and New TechnologiesSan Camillo Forlanini HospitalRomeItaly
| | - Brendan Moran
- Peritoneal Malignancy UnitBasingstoke HospitalBasingstokeUK
| | - Kim Govaerts
- Department of Abdominal and Oncological SurgeryZiekenhuis Oost Limburg (ZOL)GenkBelgium
| | - Oliver Zivanovic
- Department of Gynecological OncologyHeidelberg Medizinische KlinikHeidelbergGermany
| | - Donal Brennan
- UCD Gynaecological Oncology GroupUCD School of Medicine, Mater Misericordiae University HospitalDublinIreland
| | - Cedric Nadeau
- Department of Gynecological OncologyClinique du Fief de GrimoirePoitiersCedexFrance
| | - Willemien Van Driel
- Department of Gynecological OncologyNetherlands Cancer InstituteAmsterdamThe Netherlands
| | - Naoual Bakrin
- Department of Surgical OncologyHôpita Lyon Sud, Hospices Civils de LyonLyonFrance
| | - Pompiliu Piso
- Department of General and Visceral SurgeryHospital Barmherzige BrüderRegensburgGermany
| | - Victor J. Verwaal
- Peritoneal Surface Malignancy and HIPEC Skåne University HospitalLunds University SwedenLundsSweden
| | | | - Mohammad Alyami
- Department of General Surgery and Surgical OncologyKing Khalid HospitalNajranSaudi Arabia
| | - Olivia Sgarbura
- Department of Surgical Oncology, Montpellier Cancer InstituteUniversity of MontpellierMontpellierFrance
| | - Beate Rau
- Chirurgische KlinikCampus Charité Mitte, Charité‐UniversitätsmedizinBerlinGermany
| | - Marcello Deraco
- PSM Unit, Department of Surgical OncologyFondazione IRCCS Istituto Nazionale dei TumoriMilanItaly
| | - Olivier Glehen
- Department of Oncological SurgeryHôpital Lyon Sud, Hospices Civils de LyonLyonFrance
- CICLYUniversité Claude Bernard Lyon 1LyonFrance
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Van der Speeten K, Kusamura S, Villeneuve L, Piso P, Verwaal VJ, González-Moreno S, Glehen O. The 2022 PSOGI International Consensus on HIPEC Regimens for Peritoneal Malignancies: HIPEC Technologies. Ann Surg Oncol 2024; 31:7090-7110. [PMID: 39037523 DOI: 10.1245/s10434-024-15513-4] [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: 12/08/2023] [Accepted: 05/09/2024] [Indexed: 07/23/2024]
Abstract
This manuscript reports the results of an international consensus on technologies of hyperthermic intraperitoneal perioperative chemotherapy (HIPEC) performed with the following goals: To provide recommendations for the technological parameters to perform HIPEC. To identify the role of heat and its application forms in treating peritoneal metastases. To provide recommendations regarding the correct dosimetry of intraperitoneal chemotherapy drugs and their carrier solutions. To identify for each intraperitoneal chemotherapy regimen the best dosimetry and fractionation. To identify areas of future research pertaining to HIPEC technology and regimens. This consensus was performed by the Delphi technique and comprised two rounds of voting. In total, 96 of 102 eligible panelists replied to both Delphi rounds (94.1%) with a consensus of 39/51 questions on HIPEC technical aspects. Among the recommendations that met with the strongest consensus were those concerning the dose of HIPEC drug established in mg/m2, a target temperature of at least 42°C, and the use of at least three temperature probes to pursue hyperthermia. Ninety minutes as the ideal HIPEC duration seemed to make consensus. These results should be considered when designing new clinical trials in patients with peritoneal surface malignancies.
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Affiliation(s)
- Kurt Van der Speeten
- Department of Surgical Oncology, Ziekenhuis Oost-Limburg, Genk, Belgium.
- Faculty of Life Sciences, BIOMED Research Institute, University Hasselt, Hasselt, Belgium.
| | - Shigeki Kusamura
- Department of Surgical Oncology, PSM unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Laurent Villeneuve
- Department of Surgical Oncology, Centre Hospitalier Lyon-sud, Lyon, France
| | - Pompiliu Piso
- Department of General and Visceral Surgery, Hospital Barmherzige Brüder, Regensburg, Germany
| | - Vic J Verwaal
- Peritoneal Surface Malignancy and HIPEC Institute for Regional Sundhedforskning, Syddansk University, Odense, Sweden
| | | | - Olivier Glehen
- Department of Surgical Oncology, Centre Hospitalier Lyon-sud, Lyon, France
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Stefano M, Perrina D, Vallicelli C, Ansaloni L, Fugazzola P, Coccolini F, Agnoletti V, Frassineti GL, Passardi A, Tamberi S, Framarini M, Tassinari D, Matteucci L, Sturaro C, Gallo G, Catena F. Prophylaxis and treatment of peritoneal carcinomatosis of gastric origin using hyperthermic intraperitoneal chemotherapy: a systematic review and meta-analysis of randomized trials. J Gastrointest Surg 2024; 28:1185-1193. [PMID: 38599315 DOI: 10.1016/j.gassur.2024.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 03/26/2024] [Accepted: 04/05/2024] [Indexed: 04/12/2024]
Abstract
BACKGROUND Peritoneal carcinomatosis significantly worsens the prognosis of patients with gastric cancer. Cytoreduction + hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results in the prevention and treatment of peritoneal carcinomatosis in advanced gastric cancer (AGC); however, its application remains controversial owing to the variability of the approaches used to perform it and the lack of high-quality evidence. This systematic review and meta-analysis aimed to investigate the role of surgery and HIPEC in the prevention and treatment of peritoneal carcinomatosis of gastric origin. METHODS We conducted a systematic review and meta-analysis of randomized controlled trials comparing surgery + HIPEC vs surgery + chemotherapy for the prophylaxis of peritoneal carcinomatosis and cytoreduction + HIPEC vs chemotherapy or other palliative options for the treatment of peritoneal carcinomatosis. RESULTS Sixteen studies enrolling 1641 patients were included. Surgery + HIPEC significantly improved overall survival in both prophylactic (hazard ratio [HR], 0.56) and therapeutic (HR, 0.57) settings. When surgery + HIPEC was performed with prophylactic intent, the pooled 3-year mortality rate was 32%, whereas for the control group it was 55%. The overall and peritoneal recurrence rates were also reduced (risk ratio [RR], 0.59 and 0.40, respectively). No significant difference was found in morbidity between groups (RR, 0.92). CONCLUSION Based on the current knowledge, HIPEC in AGC seems to be a safe and effective tool for prophylaxis and a promising resource for the treatment of peritoneal carcinomatosis. Regarding the treatment of peritoneal carcinomatosis, the scarcity of large-cohort studies and the heterogeneity of the techniques adopted prevented us from achieving a definitive recommendation.
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Affiliation(s)
- Mauro Stefano
- Department of General, Emergency and Trauma Surgery, Bufalini Hospital, Cesena, Italy
| | - Daniele Perrina
- Department of General, Emergency and Trauma Surgery, Bufalini Hospital, Cesena, Italy.
| | - Carlo Vallicelli
- Department of General, Emergency and Trauma Surgery, Bufalini Hospital, Cesena, Italy
| | - Luca Ansaloni
- Department of General, Emergency and Trauma Surgery, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy
| | - Paola Fugazzola
- Department of General, Emergency and Trauma Surgery, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy
| | - Federico Coccolini
- Department of General, Emergency and Trauma Surgery, University Hospital of Pisa, Pisa, Italy
| | - Vanni Agnoletti
- Anesthesia and Intensive Care Unit, Bufalini Hospital, Cesena, Italy
| | - Giovanni Luca Frassineti
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Alessandro Passardi
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Stefano Tamberi
- Department of Medical Oncology, Santa Maria delle Croci Hospital, Ravenna, Italy
| | - Massimo Framarini
- Department of General and Emergency Surgery, Morgagni - Pierantoni Hospital, Forlì, Italy
| | | | - Laura Matteucci
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Chiara Sturaro
- Department of Hospital Pharmaceutical Assistance, Bufalini Hospital, Cesena, Italy
| | - Graziana Gallo
- Department of Pathology, Bufalini Hospital, Cesena, Italy
| | - Fausto Catena
- Department of General, Emergency and Trauma Surgery, Bufalini Hospital, Cesena, Italy
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Jain AJ, Badgwell BD. Current Evidence for the Use of HIPEC and Cytoreductive Surgery in Gastric Cancer Metastatic to the Peritoneum. J Clin Med 2023; 12:6527. [PMID: 37892663 PMCID: PMC10607605 DOI: 10.3390/jcm12206527] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 10/11/2023] [Accepted: 10/12/2023] [Indexed: 10/29/2023] Open
Abstract
Gastric cancer (GCa) is an aggressive malignancy, representing the third leading cause of cancer mortality worldwide. The poor prognosis of GCa can be associated with the prevalence of peritoneal metastasis (PM). Current international and national GCa treatment guidelines only recommend palliative treatment options for patients with PM. Since the 1980s there have been multiple single arm trials, randomized controlled trials, and metanalysis investigating the use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with advanced GCa, with or without PM. Results from these studies have been encouraging, with some large-volume centers even incorporating HIPEC into their treatment algorithms for patients with advanced GCa. Additionally, there are several ongoing trials that, when completed, will increase our understanding of the efficacy of CRS & HIPEC in patients with GCa metastatic to the peritoneum. Herein we review the current evidence, ongoing trials, consensus guidelines, and future considerations regarding the use of CRS & HIPEC in patients suffering from GCa with PM.
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Affiliation(s)
- Anish J. Jain
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Brian D. Badgwell
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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Chidambaram S, Guiral DC, Markar SR. Novel Multi-Modal Therapies and Their Prognostic Potential in Gastric Cancer. Cancers (Basel) 2023; 15:3113. [PMID: 37370723 DOI: 10.3390/cancers15123113] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Revised: 05/22/2023] [Accepted: 06/06/2023] [Indexed: 06/29/2023] Open
Abstract
BACKGROUND Gastric cancer has a poor prognosis and involves metastasis to the peritoneum in over 40% of patients. The optimal treatment modalities have not been established for gastric cancer patients with peritoneal carcinomatosis (GC/PC). Although studies have reported favourable prognostic factors, these have yet to be incorporated into treatment guidelines. Hence, our review aims to appraise the latest diagnostic and treatment developments in managing GC/PC. METHODS A systematic review of the literature was performed using MEDLINE, EMBASE, the Cochrane Review, and Scopus databases. Articles were evaluated for the use of hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurised intraperitoneal aerosolised chemotherapy (PIPAC) in GC/PC. A meta-analysis of studies reporting on overall survival (OS) in HIPEC and comparing the extent of cytoreduction as a prognostic factor was also carried out. RESULTS The database search yielded a total of 2297 studies. Seventeen studies were included in the qualitative and quantitative analyses. Eight studies reported the short-term OS at 1 year as the primary outcome measure, and our analysis showed a significantly higher OS for the HIPEC/CRS cohort compared to the CRS cohort (pooled OR = 0.53; p = 0.0005). This effect persisted longer term at five years as well (pooled OR = 0.52; p < 0.0001). HIPEC and CRS also showed a longer median OS compared to CRS (pooled SMD = 0.61; p < 0.00001). Three studies reporting on PIPAC demonstrated a pooled OS of 10.3 (2.2) months. Prognostic factors for longer OS include a more complete cytoreduction (pooled OR = 5.35; p < 0.00001), which correlated with a peritoneal carcinomatosis index below 7. CONCLUSIONS Novel treatment strategies, such as HIPEC and PIPAC, are promising in the management of GC/PC. Further work is necessary to define their role within the treatment algorithm and identify relevant prognostic factors that will assist patient selection.
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Affiliation(s)
| | - Delia Cortés Guiral
- Surgical Oncology and General Surgery Department, King Khaled Hospital, Najran 66262, Saudi Arabia
| | - Sheraz Rehan Markar
- Department of Molecular Medicine and Surgery, Karolinska Institutet, 17176 Stockholm, Sweden
- Nuffield Department of Surgery, University of Oxford, Oxford OX3 9DU, UK
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Sugarbaker PH, Chang D. Secondary cytoreductive surgery for lymph node positive mucinous appendiceal neoplasms. Surg Oncol 2023; 46:101903. [PMID: 36652898 DOI: 10.1016/j.suronc.2023.101903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 12/15/2022] [Accepted: 01/06/2023] [Indexed: 01/09/2023]
Abstract
BACKGROUND Patients who have surgery for a gastrointestinal cancer routinely have clinical and radiological tests in an effort to detect recurrent disease. If cancer progression is documented, additional surgery performed in a timely manner may prolong survival and help maintain an optimal quality of life. In mucinous appendiceal cancer patients a secondary cytoreductive surgery (SCRS) may be considered if recurrent disease is detected. METHODS In patients with both lymph node metastases and peritoneal metastases from a mucinous appendiceal adenocarcinoma (MACA-LN) who had a prior complete cytoreductive surgery (CRS), the clinical- and treatment-related variables associated with the index CRS and the SCRS were extracted from a database and secured research files. These variables were statistically assessed for their impact on survival. RESULTS Twelve of 39 lymph node positive patients (30.8%) had SCRS. The mean follow-up was 7.6 years and the median survival was 4.5 years. There were 4 males (33%) and median age was 44 years. Significant prognostic variables associated with improved survival with the index CRS by univariant analysis was the use of early postoperative intraperitoneal chemotherapy (EPIC) (p = 0.0469). For the SCRS, no significant prognostic variables, not even completeness of cytoreduction, were discovered. CONCLUSIONS In MACA-LN patients, improved survival with SCRS was shown as compared to patients who recurred but did not undergo SCRS. In this group of patients with an aggressive disease, if SCRS was possible it improved survival with long-term (greater than 5 years) follow-up.
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Affiliation(s)
- Paul H Sugarbaker
- Program in Peritoneal Surface Malignancy, Washington Cancer Institute, Washington, DC, USA.
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Foster JM, Zhang C, Rehman S, Sharma P, Alexander HR. The contemporary management of peritoneal metastasis: A journey from the cold past of treatment futility to a warm present and a bright future. CA Cancer J Clin 2023; 73:49-71. [PMID: 35969103 DOI: 10.3322/caac.21749] [Citation(s) in RCA: 44] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 05/12/2022] [Accepted: 06/15/2022] [Indexed: 01/17/2023] Open
Abstract
Peritoneal metastasis (PM) is often regarded as a less frequent pattern of spread; however, collectively across all spectra of primary tumors, the consequences of PM impact a large population of patients annually. Unlike other modes of metastasis, symptoms at presentation or during the treatment course are common, representing an additional challenge in the management of PM. Early efforts with chemotherapy and incomplete surgical interventions transiently improved symptoms, but durable symptom control and survival extension were rare, which established a perspective of treatment futility for PM through most of the 20th century. Notably, the continued development of better systemic therapy combinations, optimization of cytoreductive surgery (CRS), and rigorous investigation of combining regional therapy-specifically hyperthermic intraperitoneal chemotherapy-with CRS, have resulted in more effective multimodal treatment options for patients with PM. In this article, the authors provide a comprehensive review of the data establishing the contemporary approach for tumors with a high frequency of PM, including appendix, colorectal, mesothelioma, and gastric cancers. The authors also explore the emerging role of adding hyperthermic intraperitoneal chemotherapy to the well established paradigm of CRS and systemic therapy for advanced ovarian cancer, as well as the recent clinical trials identifying the efficacy of poly(adenosine diphosphate ribose) polymerase maintenance therapy. Finally, recent data are included that explore the role of precision medicine technology in PM management that, in the future, may help further improve patient selection, identify the best systemic therapy regimens, detect actionable mutations, and identify new targets for drug development.
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Affiliation(s)
- Jason M Foster
- Division of Surgical Oncology, Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Chunmeng Zhang
- Division of Surgical Oncology, Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Shahyan Rehman
- Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey
| | - Prateek Sharma
- Division of Surgical Oncology, Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, USA
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Di Giorgio A, Gerardi C, Abatini C, Melotti G, Bonavina L, Torri V, Santullo F, Garattini S, De Luca M, Rulli E, Rulli E, Pacelli F, GOETH Investigators. Prophylactic surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC CO2) versus standard surgery for gastric carcinoma at high risk of peritoneal carcinomatosis: short and long-term outcomes (GOETH STUDY)-a collaborative randomized controlled trial by ACOI, FONDAZIONE AIOM, SIC, SICE, and SICO. Trials 2022; 23:969. [PMID: 36457115 PMCID: PMC9714394 DOI: 10.1186/s13063-022-06880-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 11/02/2022] [Indexed: 12/03/2022] Open
Abstract
INTRODUCTION At the time of diagnosis, 15-20% of gastric carcinomas are in stage T4 or T4b. Furthermore, 5-20% of patients undergoing potentially curative surgery suffer from synchronous or metachronous peritoneal metastases. To date, neither surgery nor systemic chemotherapy successfully controls peritoneal dissemination, offering a limited impact on survival. Peritoneal metastases are in fact responsible for death in around 60% of gastric cancer patients. Several Eastern studies in the past have focused on hyperthermic intraperitoneal chemotherapy (HIPEC) as a prophylactic measure in patients with serosal extension, nodal involvement, and positive peritoneal fluid cytology. Therefore, a new multimodal therapeutic strategy based on aggressive surgery plus new locoregional treatment may prolong survival in this particular clinical scenario. METHODS This study compares the efficacy of prophylactic surgery (radical gastric resection, appendectomy, resection of the round ligament of the liver, and bilateral adnexectomy) plus hybrid CO2 HIPEC system versus standard surgery in patients with T3-T4 N0-N + gastric adenocarcinoma. Patients will be randomly assigned (1:1 ratio) to the experimental arm or standard surgery. The primary endpoint is to establish the difference in disease-free survival between the groups. The secondary objective is to compare the safety and tolerability of prophylactic surgery plus HIPEC CO2 versus standard surgery. DISCUSSION Considering the poor prognosis of patients with peritoneal dissemination from gastric cancer, a prophylactic strategy to prevent peritoneal metastases may be beneficial. In patients with gastric cancer at high risk of peritoneal carcinomatosis, we propose aggressive surgical treatment with radical gastrectomy, removal of organs at risk of harbouring tumour cells, and HIPEC. TRIAL REGISTRATION ClinicalTrials.gov NCT03917173. Registered on 16 April 2019. PROTOCOL VERSION v1, March 27, 2019. Protocol number: IRFMN-GCC-7813. EudraCT number: 2019-001478-27.
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Affiliation(s)
- A. Di Giorgio
- grid.411075.60000 0004 1760 4193Operational Unit of Peritoneum and Retroperitoneum Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 8, 00168 Rome, Italy
| | - C. Gerardi
- grid.4527.40000000106678902Istituto Di Ricerche Farmacologiche “Mario Negri” IRCCS, Milan, Italy
| | - C. Abatini
- grid.411075.60000 0004 1760 4193Operational Unit of Peritoneum and Retroperitoneum Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 8, 00168 Rome, Italy
| | - G. Melotti
- Associazione Chirurghi Ospedalieri Italiani, ACOI, Rome, Italy
| | - L. Bonavina
- grid.419557.b0000 0004 1766 7370Division of General and Foregut Surgery, Department of Biomedical Sciences for Health, IRCCS Policlinico San Donato and University of Milan, Milan, Italy
| | - V. Torri
- grid.4527.40000000106678902Istituto Di Ricerche Farmacologiche “Mario Negri” IRCCS, Milan, Italy
| | - F. Santullo
- grid.411075.60000 0004 1760 4193Operational Unit of Peritoneum and Retroperitoneum Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 8, 00168 Rome, Italy
| | - S. Garattini
- grid.4527.40000000106678902Istituto Di Ricerche Farmacologiche “Mario Negri” IRCCS, Milan, Italy
| | - M. De Luca
- grid.4527.40000000106678902Istituto Di Ricerche Farmacologiche “Mario Negri” IRCCS, Milan, Italy
| | - Erica Rulli
- grid.4527.40000000106678902Istituto Di Ricerche Farmacologiche “Mario Negri” IRCCS, Milan, Italy
| | - Eliana Rulli
- grid.4527.40000000106678902Istituto Di Ricerche Farmacologiche “Mario Negri” IRCCS, Milan, Italy
| | - F. Pacelli
- grid.411075.60000 0004 1760 4193Operational Unit of Peritoneum and Retroperitoneum Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 8, 00168 Rome, Italy
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Deng H, Li B, Qin X. The short- and long-term survival of hyperthermic intraperitoneal chemotherapy (HIPEC) in the advanced gastric cancer with/without peritoneal carcinomatosis: a systematic review and meta-analysis of randomized controlled trials. Updates Surg 2022; 74:1805-1816. [DOI: 10.1007/s13304-022-01376-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 09/04/2022] [Indexed: 11/27/2022]
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Sugarbaker PH, Chang D. Extent of Disease on Visceral Peritoneal Surfaces of Mucinous Appendiceal Neoplasms Controls Survival. ANNALS OF SURGERY OPEN 2022; 3:e193. [PMID: 37601148 PMCID: PMC10431514 DOI: 10.1097/as9.0000000000000193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 06/28/2022] [Indexed: 11/26/2022] Open
Abstract
Objective To determine causes of treatment failure of low-grade appendiceal mucinous neoplasms (LAMN). Background For 3 decades, LAMN have been treated by cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy. This combined treatment has resulted in a large change in the survival of these patients. Methods A retrospective review of a prospectively maintained database was performed. A restricted cohort of patients with only LAMN histology and complete CRS were included in the statistical analysis. Results Four hundred and fifty patients were available with a median follow-up of 15.3 years (range 10-35 years). The median age was 49.7 and there were 196 males (43.6%). The mean survival was 24.5 years. Extent of parietal peritonectomy, resection of uterus, ovaries and apex of vagina had no impact on survival. Variables that indicated an increased extent of disease on visceral peritoneal surfaces had a significant impact on survival. Early postoperative intraperitoneal chemotherapy with 5-fluorouracil did not augment hyperthermic intraperitoneal chemotherapy (HIPEC). Patients who required reoperation for recurrence or patients with class 4 adverse events had a reduced prognosis. Conclusions The mean survival of LAMN treated by complete CRS and perioperative chemotherapy was 24.5 years. Extent of disease quantitated on visceral peritoneal surfaces by the extent of visceral resections was the variable associated with treatment failure. Peritonectomy plus HIPEC was able to control disease on parietal peritoneal surfaces. Not only a larger extent of disease but also its location on visceral peritoneal surfaces controlled survival.
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Affiliation(s)
- Paul H. Sugarbaker
- From the Washington Cancer Institute, Program in Peritoneal Surface Malignancy Washington, DC
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Sugarbaker PH, Chang D. Secondary cytoreductive surgery for low-grade appendiceal mucinous neoplasms. J Surg Oncol 2022; 126:1451-1461. [PMID: 35975822 DOI: 10.1002/jso.27064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 08/07/2022] [Indexed: 11/09/2022]
Abstract
BACKGROUND In patients with low-grade appendiceal mucinous neoplasms (LAMN), a secondary cytoreductive surgery (SCRS) is often performed if recurrent disease is detected. METHODS In patients with a complete cytoreductive surgery (CRS), the clinical- and treatment-related variables associated with the index CRS and the SCRS were statistically assessed for their impact on overall survival after SCRS. RESULTS Eighty-eight patients of 450 patients (19.6%) had SCRS. The mean survival was 15.3 years for patients requiring SCRS as compared to 24.5 years for the group as a whole. Variables associated with improved survival as a result of the index CRS by multivariant modeling were absence of total gastrectomy (p = 0.0038), moderate peritoneal cancer index of 15-30 (p = 0.0020) and time interval of greater than 36 months from CRS to SCRS (p = 0.0013). Multivariant modeling associated with SCRS were complete CRS (p = 0.0104) and disease progression limited to the abdominal wall (p = 0.0106). Early postoperative intraperitoneal chemotherapy (EPIC) 5-fluorouracil used with CRS improved the outcome with SCRS (p = 0.0095). CONCLUSIONS A requirement for SCRS in 88 patients decreased median survival to 15.3 years as compared to 24.5 years in all 450 LAMN patients (p < 0.0001). Prognostic indicators from both the index CRS and the SCRS had an impact on the outcome of SCRS.
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Affiliation(s)
- Paul H Sugarbaker
- Program in Peritoneal Surface Malignancy, Department of Surgery, MedStar Washington Hospital Center, Washington, District of Columbia, USA
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12
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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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13
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Prophylactic hyperthermic intraperitoneal chemotherapy may benefit the long-term survival of patients after radical gastric cancer surgery. Sci Rep 2022; 12:2583. [PMID: 35173230 PMCID: PMC8850581 DOI: 10.1038/s41598-022-06417-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 01/27/2022] [Indexed: 12/24/2022] Open
Abstract
Hyperthermic intraperitoneal chemotherapy (HIPEC) has been proven to improve the survival rate of gastric cancer and reduce peritoneal recurrence. We aimed to evaluate the effectiveness and safety of prophylactic HIPEC after radical gastric cancer surgery in this study. Researchers searched for studies published in PubMed, Embase, Web of science, Scopus, Cochrane, Clinical key databases and Microsoft Academic databases to identify studies that examine the impact of prophylactic HIPEC on the survival, recurrence and adverse events of patients undergoing radical gastric cancer surgery. RevMan 5.3 was used to analyze the results and risk of bias. The PROSERO registration number is CRD42021262016. This meta-analysis included 22 studies with a total of 2097 patients, 12 of which are RCTs. The results showed that the 1-, 3- and 5-year overall survival rate was significantly favorable to HIPEC (OR 5.10, 2.07, 1.96 respectively). Compared with the control group, the overall recurrence rate and peritoneal recurrence rate of the HIPEC group were significantly lower (OR 0.41, 0.24 respectively). Significantly favorable to the control group in terms of renal dysfunction and pulmonary dysfunction complications (OR 2.44, 6.03 respectively). Regarding the causes of death due to postoperative recurrence: liver recurrence, lymph node and local recurrence and peritoneal recurrence, the overall effect is not significantly different (OR 0.81, 1.19, 0.37 respectively). 1-, 3- and 5-year overall survival follow-up may be incremented by the prophylactic HIPEC, and which reduce the overall recurrence rate and peritoneal recurrence rate. HIPEC may have high-risk of pulmonary dysfunction and renal dysfunction complications. No difference has been found in the deaths due to recurrence after surgery.
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14
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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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15
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Yap DRY, Wong JSM, Tan QX, Tan JWS, Chia CS, Ong CAJ. Effect of HIPEC on Peritoneal Recurrence in Peritoneal Metastasis Treated With Cytoreductive Surgery: A Systematic Review. Front Oncol 2021; 11:795390. [PMID: 34926311 PMCID: PMC8678115 DOI: 10.3389/fonc.2021.795390] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 11/15/2021] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Peritoneal metastasis (PM) is a late-stage manifestation of intra-abdominal malignancies. The current standard of care indicates that cure can only be achieved with cytoreductive surgery (CRS) which is often indicated with concurrent adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC). However, the utility of HIPEC within subsets of PM is not fully understood. We seek to compare the effectiveness of HIPEC in improving peritoneal recurrence rates in PM of different origins. METHODS We conducted a systematic review of trials on the PubMed, EMBASE, and Cochrane databases, last searched in August 2021. Biases were assessed using the Cochrane Collaboration's tool for assessing the risk of bias in randomized trials as well as the Methodological Index for Non-Randomized Studies (MINORS) framework. RESULTS 7 gastric PM studies, 3 ovarian PM studies, and 3 colorectal PM studies were included. Recurrence-free survival was improved in the HIPEC + CRS cohort in 5 gastric trials but only 1 ovarian trial and none of colorectal origin. DISCUSSION Our findings indicate decent effectiveness of HIPEC in gastric PM, but limited utility in ovarian and colorectal PM. Limitations in the current literature are attributed to the paucity of data available, a lack of homogeneity and consideration of novel and personalised treatment regimens. We implore for further studies to be conducted with a focus on patient selection and stratification, and suggest a reframing of approach towards modern molecular and targeted therapeutic options in future studies of HIPEC. SYSTEMATIC REVIEW REGISTRATION https://www.researchregistry.com/browse-the-registry#registryofsystematicreviewsmeta-analyses/registryofsystematicreviewsmeta-analysesdetails/60c1ffff0c1b78001e8efbe3/, identifier reviewregistry1166.
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Affiliation(s)
- Daniel Ren Yi Yap
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
| | - Jolene Si Min Wong
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- SingHealth Duke-NUS Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
| | - Qiu Xuan Tan
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
| | - Joey Wee-Shan Tan
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
| | - Claramae Shulyn Chia
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- SingHealth Duke-NUS Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
| | - Chin-Ann Johnny Ong
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
- SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- SingHealth Duke-NUS Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- Institute of Molecular and Cell Biology, A*STAR Research Entities, Singapore, Singapore
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16
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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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17
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Granieri S, Bonomi A, Frassini S, Chierici AP, Bruno F, Paleino S, Kusamura S, Germini A, Facciorusso A, Deraco M, Cotsoglou C. Prognostic impact of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer patients: A meta-analysis of randomized controlled trials. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2021; 47:2757-2767. [PMID: 34001385 DOI: 10.1016/j.ejso.2021.05.016] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 04/25/2021] [Accepted: 05/07/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND gastric cancer patients frequently develop peritoneal metastases (PM) with a poor long-term prognosis. A solid body of evidence underlines the beneficial role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on survival, but to date, there is a lack of consensus regarding the optimal strategy in the treatment of locally advanced primary tumors with or without peritoneal metastasis. The present meta-analysis aims to assess the impact of CRS + HIPEC on survival analyzing the results of randomized studies only. METHODS A systematic review of articles was conducted according to PRISMA guidelines. Twelve studies were included in qualitative and quantitative analysis. RESULTS A survival benefit for patients treated with CRS + HIPEC at all time points was highlighted. However, difference in survival was significant at all time points for patients treated for prophylaxis of PM, but no difference was found when considering resection with a curative intent. The 1, 2, 3 and 5-year survival rates (SR) for patients undergoing CRS + HIPEC were 86.9%, 70.5%, 63.7% and 55.7% respectively. CRS + HIPEC for the treatment rather than prophylaxis of PM was the only predictor of a reduced 3y SR. CONCLUSIONS CRS + HIPEC may lead to improved prognosis for patients suffering from locally advanced gastric cancer in both prophylactic and curative settings. However, due to far from negligible postoperative morbidity and mortality rates, a strict patient selection is crucial to achieve the best results. The presence of extraperitoneal disease strongly limits the indication of this kind of surgery.
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Affiliation(s)
- Stefano Granieri
- General Surgery Unit, ASST Vimercate, Via Santi Cosma e Damiano, 10, 20871, Vimercate, Italy.
| | - Alessandro Bonomi
- University of Milan, Via Festa del Perdono, 7, 20122, Milan, Italy; General Surgery Unit, ASST Fatebenefratelli-Sacco, Via Giovanni Battista Grassi, 74, 20157, Milan, Italy.
| | - Simone Frassini
- University of Pavia, Corso Str. Nuova, 65, 27100, Pavia, Italy; General Surgery Unit, Department of Surgery, Fondazione I.R.C.C.S. Policlinico San Matteo, Viale Camillo Golgi, 19, 27100, Pavia, Italy.
| | - Andrea Piero Chierici
- University of Milan, Via Festa del Perdono, 7, 20122, Milan, Italy; General Surgery Unit, ASST Vimercate, Via Santi Cosma e Damiano, 10, 20871, Vimercate, Italy.
| | - Federica Bruno
- General Surgery Unit, ASST Vimercate, Via Santi Cosma e Damiano, 10, 20871, Vimercate, Italy.
| | - Sissi Paleino
- University of Milan, Via Festa del Perdono, 7, 20122, Milan, Italy; General Surgery Unit, ASST Vimercate, Via Santi Cosma e Damiano, 10, 20871, Vimercate, Italy.
| | - Shigeki Kusamura
- Peritoneal Surface Malignancies Unit, Fondazione I.R.C.C.S., Istituto Nazionale Tumori, Via Venezian 1, 20133, Milan, Italy.
| | - Alessandro Germini
- General Surgery Unit, ASST Vimercate, Via Santi Cosma e Damiano, 10, 20871, Vimercate, Italy.
| | - Antonio Facciorusso
- Department of Medical Sciences, Gastroenterology Unit, Ospedali Riuniti di Foggia, Viale Luigi Pinto, 1, 71122, Foggia, Italy.
| | - Marcello Deraco
- Peritoneal Surface Malignancies Unit, Fondazione I.R.C.C.S., Istituto Nazionale Tumori, Via Venezian 1, 20133, Milan, Italy.
| | - Christian Cotsoglou
- General Surgery Unit, ASST Vimercate, Via Santi Cosma e Damiano, 10, 20871, Vimercate, Italy.
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18
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Raoof M, Malhotra G, Kohut A, O'Leary M, Frankel P, Tran T, Fakih M, Chao J, Lim D, Woo Y, Paz IB, Lew M, Cristea MC, Rodriguez-Rodriguez L, Fong Y, Blakely A, Whelan R, Reymond MA, Merchea A, Dellinger TH. PIPAC for the Treatment of Gynecologic and Gastrointestinal Peritoneal Metastases: Technical and Logistic Considerations of a Phase 1 Trial. Ann Surg Oncol 2021; 29:175-185. [PMID: 34387765 DOI: 10.1245/s10434-021-10505-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Accepted: 07/07/2021] [Indexed: 11/18/2022]
Abstract
BACKGROUND Peritoneal metastases (PM) from ovarian, gastric, appendiceal, or colorectal origin can be treated via cytoreductive surgery with or without the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) for selected patients. Unfortunately, not all patients are candidates for aggressive surgical debulking. For these patients, pressurized intraperitoneal aerosolized chemotherapy (PIPAC) has emerged as an alternative method for intraperitoneal (IP) chemotherapy administration. This report presents the design and implementation of the first phase 1 trial to evaluate the safety and efficacy of PIPAC in the United States. METHODS This is an ongoing prospective phase 1 clinical trial of PIPAC for patients who have histologically confirmed ovarian, uterine, gastric, appendiceal, or colorectal cancer with PM and have progressed to at least one evidence-based chemotherapeutic regimen. The trial has two clinical arms. The patients in arm 1 have gynecologic and gastric malignancies treated with IP cisplatin and doxorubicin, and the arm 2 patients have colorectal and appendiceal malignancies treated with intravenous fluorouracil and leucovorin followed by IP oxaliplatin. All the patients are monitored for dose-limiting toxicities and adverse events. RESULTS Practical and technical considerations for the phase 1 PIPAC trial are presented. These considerations include patient selection, operating room setup, and technical details for successful aerosolized chemotherapy delivery. The phase 1 study results will be reported separately at completion of the trial. CONCLUSIONS The PIPAC treatment is a feasible, minimally invasive approach that permits IP delivery of chemotherapy. Once completed, the ongoing phase 1 trial will help to provide safety and initial efficacy data.
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Affiliation(s)
- Mustafa Raoof
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center (COH), Duarte, CA, USA.
| | - Gautam Malhotra
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center (COH), Duarte, CA, USA
| | - Adrian Kohut
- Division of Gynecologic Oncology, Department of Surgery, City of Hope Comprehensive Cancer Center (COH), Duarte, CA, USA
| | - Michael O'Leary
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center (COH), Duarte, CA, USA
| | - Paul Frankel
- Biostatistics Core, City of Hope Beckman Research Institute, Duarte, CA, USA
| | - Thuy Tran
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center (COH), Duarte, CA, USA
| | - Marwan Fakih
- Department of Medical Oncology, COH, Duarte, CA, USA
| | - Joseph Chao
- Department of Medical Oncology, COH, Duarte, CA, USA
| | - Dean Lim
- Department of Medical Oncology, COH, Duarte, CA, USA
| | - Yanghee Woo
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center (COH), Duarte, CA, USA
| | - Isaac B Paz
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center (COH), Duarte, CA, USA
| | - Michael Lew
- Department of Anesthesiology, COH, Duarte, CA, USA
| | | | - Lorna Rodriguez-Rodriguez
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center (COH), Duarte, CA, USA
| | - Yuman Fong
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center (COH), Duarte, CA, USA
| | | | | | | | | | - Thanh H Dellinger
- Division of Gynecologic Oncology, Department of Surgery, City of Hope Comprehensive Cancer Center (COH), Duarte, CA, USA.
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19
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Mishra M, Singh N, Ghatage P. Past, Present, and Future of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Ovarian Cancer. Cureus 2021; 13:e15563. [PMID: 34277186 PMCID: PMC8272440 DOI: 10.7759/cureus.15563] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/10/2021] [Indexed: 11/16/2022] Open
Abstract
Hyperthermic intraperitoneal chemotherapy (HIPEC), along with optimal cytoreductive surgery, has been debated to be a viable option for the treatment of advanced epithelial ovarian cancer with peritoneal carcinomatosis. HIPEC is associated with a direct and improved penetration of chemotherapy drugs into the affected tissue and is associated with fewer systemic side effects. There is no standard protocol for the use of HIPEC in advanced ovarian cancer. Hence, there is controversy over the timing, dose, duration, and efficacy of HIPEC. In this review, the history, technique, current evidence, recommendations, and future directions of HIPEC are discussed.
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Affiliation(s)
- Mona Mishra
- Obstetrics and Gynecology, Maulana Azad Medical College, New Delhi, IND
| | - Nilanchali Singh
- Obstetrics and Gynecology, All India Institute of Medical Sciences, New Delhi, IND
| | - Prafull Ghatage
- Gynecology and Oncology, Tom Baker Cancer Center, Calgary, CAN
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20
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The Role of Hyperthermic Intraperitoneal Chemotherapy for Non-colorectal Peritoneal Surface Malignancies. J Gastrointest Surg 2021; 25:303-318. [PMID: 32808135 DOI: 10.1007/s11605-020-04771-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Accepted: 08/03/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND Peritoneal carcinomatosis, from a variety of gastrointestinal and gynecological malignancies, has been historically challenging to treat and there remains a wide range of biologic aggressiveness in these patients. Malignancies commonly associated with PC include those of colorectal, appendiceal, gastric, ovarian, sarcoma, small intestinal, and primary peritoneal origin among others. Advances in our understanding of this unique disease process have led to significant interest in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) as an emerging treatment option. The goal of CRS-HIPEC is to remove all visible macroscopic disease while preserving organ function, and then treat microscopic disease through perfusion of the peritoneal cavity with heated chemotherapy. PURPOSE Although recent reviews have focused on the management of peritoneal carcinomatosis secondary to colorectal cancer given the publication of several recent randomized controlled trials, the purpose of the current review is to summarize the evidence on CRS-HIPEC for non-colorectal peritoneal surface malignancies, including appendiceal neoplasms, malignant peritoneal mesothelioma, gastric cancer, and ovarian cancer. RESULTS While retrospective studies have clarified the importance of prognostic factors such as the peritoneal carcinomatosis index, completeness of cytoreduction, histopathological characteristics, and lymph node positivity, the lack of convincing level 1 evidence for the use of CRS-HIPEC has led to it remaining a highly controversial topic. CONCLUSION The decision to utilize CRS-HIPEC should involve a multidisciplinary team approach and evaluation of prognostic factors to balance the short-term morbidity of the operation with maximum long-term benefits. Large, multi-institutional groups and ongoing trials hold promise for clarifying the role of CRS-HIPEC in peritoneal surface malignancies.
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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: 18] [Impact Index Per Article: 3.6] [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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Reutovich MY, Krasko OV, Sukonko OG. Hyperthermic intraperitoneal chemotherapy in serosa-invasive gastric cancer patients. Eur J Surg Oncol 2019; 45:2405-2411. [PMID: 31387756 DOI: 10.1016/j.ejso.2019.07.030] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Revised: 06/17/2019] [Accepted: 07/29/2019] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Evaluation of hyperthermic intraperitoneal chemotherapy (HIPEC) in reducing metachronous peritoneal metastases (MPM) risks in patients with resectable serosa-invasive gastric cancer. MATERIALS & METHODS Between 2008 and 2016, 154 patients with gastric cancer (stage IIB-IIIC) were randomly assigned to two groups: 76 patients underwent HIPEC (cisplatin 50 mg/m2 + doxorubicin 50 mg/m2, 42 °C, 1 h) combined with radical surgery (HIPEC group) and 78 patients underwent only radical surgery (control group). RESULTS Evaluation of HIPEC toxicity showed neither toxic complications of IV-V degree nor haematological toxicity (according to CTCAE v. 4.03). There was no significant difference in the rate of complications between the two groups (p = 0.254). There was a more frequent disease progression in the control group than in the HIPEC group: 42/55 patients (76.4%) vs. 36/68 patients (52.9%), respectively (p = 0.009). At the same time a significant decrease in the rate of MPM was observed after HIPEC administration as compared with surgery alone - 16/68 (12.8%) vs. 39/55 (27.6%) (p < 0.001). 3-year progression-free survival was 47% (95% CI 36-61)) in the HIPEC group and 27% (95% CI 17-43) in the control group - p = 0.0024. The N-stage, HIPEC procedure, type of surgery and interaction between HIPEC treatment and age were independent prognostic factors. CONCLUSIONS HIPEC appears to be helpful in improving treatment results in radically operated gastric cancer patients.
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Affiliation(s)
- M Yu Reutovich
- Gastroesophageal Pathology Departement, N.N. Alexandrov National Cancer Center, Minsk, Belarus.
| | - O V Krasko
- United Institute of Informatics Problems, National Academy of Sciences, Minsk, Belarus
| | - O G Sukonko
- Gastroesophageal Pathology Departement, N.N. Alexandrov National Cancer Center, Minsk, Belarus
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23
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Sugarbaker PH. Prevention and Treatment of Peritoneal Metastases: a Comprehensive Review. Indian J Surg Oncol 2019; 10:3-23. [PMID: 30948866 PMCID: PMC6414583 DOI: 10.1007/s13193-018-0856-1] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Accepted: 12/04/2018] [Indexed: 02/06/2023] Open
Abstract
Peritoneal metastases may occur from a majority of cancers that occur within the abdomen or pelvis. When cancer spread to the peritoneal surfaces is documented, a decision regarding palliation versus an aggressive approach using cytoreductive surgery (CRS) and hyperthermic perioperative intraperitoneal chemotherapy (HIPEC) must be made. This decision is dependent on a well-defined group of prognostic indicators. In addition to treatment, prevention of peritoneal metastases may be an option. The clinical and pathologic features of a primary cancer can be used to select perioperative treatments that may prevent cancer cells within the abdomen and pelvis from progressing to established peritoneal metastases. In some clinical situations with appendiceal and colorectal cancers, the clinical or histopathologic features may indicate that second-look surgery plus perioperative chemotherapy should occur. Peritoneal metastases should always be considered by the multidisciplinary team for treatment or prevention.
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Affiliation(s)
- Paul H. Sugarbaker
- Center for Gastrointestinal Malignancies, MedStar Washington Hospital Center, 106 Irving St., NW, Suite 3900, Washington, DC 20010 USA
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24
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Abstract
Peritoneal malignancies may result in a widespread disease process, peritoneal carcinomatosis (PC), which has significant morbidity and mortality for patients afflicted by this disease. Dissemination into the peritoneum and throughout the abdomen can be due to a primary peritoneal cancer or other primary malignancies that have metastasized, including (but not limited to) colorectal cancer, gastric cancer, pancreatic cancer, appendiceal cancer, ovarian cancer, and mesothelioma. Patients with gastrointestinal (GI) or gynecologic malignancies with peritoneal carcinomatosis may have dismal survival due to a high disease burden within the abdominal cavity. Some studies suggest the average survival for patients with peritoneal carcinomatosis of colorectal origin is 18–48 months, for high-grade appendiceal adenocarcinoma 12–36 months, and for low-grade appendiceal neoplasms >60 months. As the understanding of peritoneal malignancies and peritoneal carcinomatosis evolved, it may now be acceptable to treat this as locoregional disease.
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Affiliation(s)
- Suayib Yalcin
- Department of Medical Oncology, Hacettepe University Institute of Cancer, Sihhiye, Ankara Turkey
| | - Philip A. Philip
- Department of Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI USA
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25
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Bartlett DL. Current Management and Future Opportunities for Peritoneal Metastases. Ann Surg Oncol 2018; 25:2132-2134. [PMID: 29948419 DOI: 10.1245/s10434-018-6520-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Indexed: 01/08/2023]
Affiliation(s)
- David L Bartlett
- University of Pittsburgh, UPMC Health System, Pittsburgh, PA, USA.
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26
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Abstract
PURPOSE OF REVIEW Peritoneal metastases may occur from a majority of cancers that occur within the abdomen or pelvis. When cancer spread to the peritoneal surfaces is documented, a decision regarding palliation vs. an aggressive approach using cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy must be made. The perioperative chemotherapy may be hyperthermic intraperitoneal chemotherapy (HIPEC) administered in the operating room or early postoperative intraperitoneal chemotherapy (EPIC) administered in the first 4 or 5 postoperative days. RECENT FINDINGS This decision is dependent on a well-defined group of prognostic indicators. In addition to treatment, the clinical and pathologic features of a primary cancer can be used to select perioperative treatments that may prevent cancer cells within the abdomen and pelvis from progressing to established peritoneal metastases. In some clinical situations with appendiceal and colorectal cancers, the clinical or histopathologic features may indicate that second-look surgery plus perioperative chemotherapy should occur. Peritoneal metastases should always be considered for treatment or prevention.
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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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He Z, Zhao TT, Xu HM, Wang ZN, Xu YY, Song YX, Ni ZR, Xu H, Yin SC, Liu XY, Miao ZF. Efficacy and safety of intraperitoneal chemotherapy in patients with advanced gastric cancer: a cumulative meta-analysis of randomized controlled trials. Oncotarget 2017; 8:81125-81136. [PMID: 29113372 PMCID: PMC5655267 DOI: 10.18632/oncotarget.20818] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Accepted: 08/23/2017] [Indexed: 01/04/2023] Open
Abstract
Even when a curative gastrectomy is conducted, the majority of advanced gastric cancer patients with invasion die due to peritoneal recurrence. We performed electronic searches to identify randomized controlled trials published through April 2017 evaluating the effect of intraperitoneal chemotherapy (IPC) on survival rates. We included 23 trials reporting data on 2,767 patients with advanced gastric cancer. Overall, we noted that patients who received IPC had a significantly increased 1-year survival rate, and the treatment effect of IPC on 1-year survival was most prominent in studies conducted in Japan or those with a mean age of less than 60 years. IPC was also associated with an increased incidence of 2-year survival rate, but it was not seen to have this effect in studies conducted in China or Australia or with a mean age greater than 60 years. Similarly, IPC associated with a significantly increased 3-year survival rate, but this difference was not detected in studies conducted in Austria or with a mean age greater than 60 years. IPC has no significant effect on the 5-year survival rate. Finally, IPC was associated with a lower risk of recurrence in patients with advanced gastric cancer. The findings of this study suggest that gastric cancer patients who receive IPC associate with increased 1-year, 2-year, and 3-year survival rates, but this does not extend out to a 5-year survival rate. IPC is also shown to play a protective role against the risk of recurrence in patients with advanced gastric cancer.
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Affiliation(s)
- Zheng He
- Department of Radiation Oncology, First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Ting-Ting Zhao
- Department of Breast Surgery, First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Hui-Mian Xu
- Department of Surgical Oncology, First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Zhen-Ning Wang
- Department of Surgical Oncology, First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Ying-Ying Xu
- Department of Breast Surgery, First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Yong-Xi Song
- Department of Surgical Oncology, First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Zhong-Ran Ni
- Department of Surgical Oncology, First Hospital of China Medical University, Shenyang, Liaoning Province, China.,School of Life Science, University of Technology Sydney, Ultimo, New South Wales, Australia
| | - Hao Xu
- Department of Medical Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Song-Cheng Yin
- Department of Surgical Oncology, First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Xing-Yu Liu
- Department of Surgical Oncology, First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Zhi-Feng Miao
- Department of Surgical Oncology, First Hospital of China Medical University, Shenyang, Liaoning Province, China
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29
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Desiderio J, Chao J, Melstrom L, Warner S, Tozzi F, Fong Y, Parisi A, Woo Y. The 30-year experience-A meta-analysis of randomised and high-quality non-randomised studies of hyperthermic intraperitoneal chemotherapy in the treatment of gastric cancer. Eur J Cancer 2017; 79:1-14. [PMID: 28456089 DOI: 10.1016/j.ejca.2017.03.030] [Citation(s) in RCA: 152] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Revised: 03/09/2017] [Accepted: 03/26/2017] [Indexed: 02/07/2023]
Abstract
IMPORTANCE Hyperthermic intraperitoneal chemotherapy (HIPEC) has been used within various multimodality strategies for the prevention and treatment of gastric cancer peritoneal carcinomatosis. OBJECTIVE To systematically evaluate the role of HIPEC in gastric cancer and clarify its effectiveness at different stages of peritoneal disease progression. DATA SOURCES Medline and Embase databases between January 1, 1985 and June 1, 2016. STUDY SELECTION Randomised control trials and high-quality non-randomised control trials selected on a validated tool (methodological index for non-randomised studies) comparing HIPEC and standard oncological management for the treatment of advanced stage gastric cancer with and without peritoneal carcinomatosis were considered. DATA EXTRACTION AND SYNTHESIS A random-effects network meta-analysis. MAIN OUTCOMES AND MEASURES The primary outcomes were overall survival and disease recurrence. Secondary outcomes were overall complications, type of complications, and sites of recurrence. RESULTS A total of 11 RCTs and 21 non-randomised control trials (2520 patients) were included. For patients without the presence of peritoneal carcinomatosis (PC), the overall survival rates between the HIPEC and control groups at 3 or 5 years resulted in favour of the HIPEC group (risk ratio [RR] = 0.82, P = 0.01). No difference in the 3-year overall survival (RR = 0.99, P = 0.85) in but a prolonged median survival of 4 months in favour of the HIPEC group (WMD = 4.04, P < 0.001) was seen in patients with PC. HIPEC was associated with significantly higher risk of complications for both patients with PC (RR = 2.15, P < 0.01) and without (RR = 2.17, P < 0.01). This increased risk in the HIPEC group was related to systemic drugs toxicity. Anastomotic leakage rates were found to be similar between groups. CONCLUSIONS Our study demonstrates a survival advantage of the use of HIPEC as a prophylactic strategy and suggests that patients whose disease burden is limited to positive cytology and limited nodal involvement may benefit the most from HIPEC. For patients with extensive carcinomatosis, the completeness of cytoreductive surgery is a critical prognostic factor for survival. Future RCTs should better define patient selection criteria.
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Affiliation(s)
- Jacopo Desiderio
- Department of Surgery, City of Hope National Medical Centre, Duarte, CA, USA; Department of Digestive Surgery, St. Mary's Hospital, University of Perugia, Terni, Italy
| | - Joseph Chao
- Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Centre, Duarte, CA, USA
| | - Laleh Melstrom
- Department of Surgery, City of Hope National Medical Centre, Duarte, CA, USA
| | - Susanne Warner
- Department of Surgery, City of Hope National Medical Centre, Duarte, CA, USA
| | - Federico Tozzi
- Department of Surgery, City of Hope National Medical Centre, Duarte, CA, USA
| | - Yuman Fong
- Department of Surgery, City of Hope National Medical Centre, Duarte, CA, USA
| | - Amilcare Parisi
- Department of Digestive Surgery, St. Mary's Hospital, University of Perugia, Terni, Italy
| | - Yanghee Woo
- Department of Surgery, City of Hope National Medical Centre, Duarte, CA, USA.
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30
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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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31
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Flessner MF. Pharmacokinetic problems in peritoneal drug administration: an update after 20 years. Pleura Peritoneum 2016; 1:183-191. [PMID: 30911622 DOI: 10.1515/pp-2016-0022] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Accepted: 11/29/2016] [Indexed: 12/14/2022] Open
Abstract
Intraperitoneal chemotherapy has demonstrated significant pharmacologic and clinical advantage over traditional intravenous administration for cancers that are restricted to the peritoneal cavity. The combination of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) has become the standard technique used to fight ovarian and gastrointestinal cancers in many centers. However, challenges remain for HIPEC to contact the entire peritoneal surface, penetrate the tumor tissue, and transport to the lymphatics and other metastatic sites. New innovations in delivery technique, such as heated aerosol, and in delivery molecules, such as microparticles, nanoparticles, nanogels, and tumor-penetrating peptides are being tested in animal models and will likely soon be in human trials. Improvements in overall care, such as the recent clinical trial of an oral agent for maintenance therapy in ovarian carcinoma, will continue in this field for the next 20 years.
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32
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Feingold PL, Kwong MLM, Davis JL, Rudloff U. Adjuvant intraperitoneal chemotherapy for the treatment of gastric cancer at risk for peritoneal carcinomatosis: A systematic review. J Surg Oncol 2016; 115:192-201. [PMID: 27878811 DOI: 10.1002/jso.24476] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2016] [Accepted: 10/02/2016] [Indexed: 12/29/2022]
Abstract
The peritoneal surface is a frequent site of recurrence following surgery for gastric cancer. A systematic review and random effect analysis was undertaken to analyze current literature regarding the role of adjuvant intraperitoneal chemotherapy in gastric cancer. While pooled analysis supports the use of adjuvant IP chemotherapy in resectable gastric cancer, maximal benefit occured with intra-operative delivery, and possibly the use of MMC. J. Surg. Oncol. 2017;115:192-201. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Paul L Feingold
- Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Mei Li M Kwong
- Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Jeremy L Davis
- Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Udo Rudloff
- Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
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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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Smyth EC, Verheij M, Allum W, Cunningham D, Cervantes A, Arnold D. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2016; 27:v38-v49. [PMID: 27664260 DOI: 10.1093/annonc/mdw350] [Citation(s) in RCA: 1111] [Impact Index Per Article: 123.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Affiliation(s)
- E C Smyth
- Department of Gastrointestinal Oncology, Royal Marsden Hospital, London and Surrey, UK
| | - M Verheij
- Department of Radiation Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - W Allum
- Department of Surgery, Royal Marsden Hospital, London and Surrey
| | - D Cunningham
- Department of Medicine, Royal Marsden Hospital, London and Surrey, UK
| | - A Cervantes
- Medical Oncology Department, INCLIVA University of Valencia, Valencia, Spain
| | - D Arnold
- Instituto CUF de Oncologia (I.C.O.), Lisbon, Portugal
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Coccolini F, Celotti A, Ceresoli M, Montori G, Marini M, Catena F, Ansaloni L. Hyperthermic intraperitoneal chemotherapy (HIPEC) and neoadjuvant chemotherapy as prophylaxis of peritoneal carcinosis from advanced gastric cancer-effects on overall and disease free survival. J Gastrointest Oncol 2016; 7:523-9. [PMID: 27563441 DOI: 10.21037/jgo.2016.06.05] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND The possibility to enlarge criteria for intra-peritoneal chemotherapy (IPC) to all patients at high-risk to develop peritoneal carcinosis (i.e., with serosal invasion) is still discussed. METHODS Retrospective case-control study. Three-groups: advanced-gastric-cancer (AGC) (pT4) without proven carcinosis: prophylactic group (PG), those with PC: treatment group (TG), AGC (pT3-pT4) operated without hyperthermic intraperitoneal chemotherapy (HIPEC), surgery alone group (SG T3, SG T4). RESULTS Forty four patients. 26 (59.1%) were male. Sixteen (36%) patients underwent 16 HIPEC: 6 (38%) had AGC (pT4) without PC (PG), 10 (62%) had carcinosis (TG), 28 were operated without HIPEC (SG T3, SG T4). The mean disease free survival (DFS): TG: 7.7 months, SG T4: 21.6 months, SG T3: 27.7 months, PG: 34.5 months. DFS was significantly different for TG (P=0.03, P=0.021, P=0.013 respectively). The mean OS TG: 10 months, SG T4: 27.1 months, SG T3: 28.2 months, PG: 34.6 months. OS was significantly different for TG (P=0.04, P=0.04, P=0.045 respectively). Severe complication rate: TG: 60%, PG: 16.7%, SG T3: 7.7% and SG T4: 25% (P=0.035). Length-of-stay differs significantly (P=0.003); overall length-of-stay: 19.41 days [standard deviation (SD) ±15.03]; TG: 33.01 (SD ±23.08), PG: 20.17 (SD ±6.21), SG T3: 11.33 (SD ±3.22), SG T4: 15.36 (SD ±5.48). CONCLUSIONS Prophylactic intraperitoneal chemotherapy associated to neoadjuvant chemotherapy increases the DFS and OS in patients with AGC without carcinosis. More data are needed in order to confirm these results.
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Affiliation(s)
- Federico Coccolini
- General Surgery Department, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Andrea Celotti
- General Surgery Department, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Marco Ceresoli
- General Surgery Department, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Giulia Montori
- General Surgery Department, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Michele Marini
- General Surgery Department, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Fausto Catena
- General and Emergency surgery, Parma Maggiore Hospital, Parma, Italy
| | - Luca Ansaloni
- General Surgery Department, Papa Giovanni XXIII Hospital, Bergamo, Italy
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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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37
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Neuwirth MG, Alexander HR, Karakousis GC. Then and now: cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC), a historical perspective. J Gastrointest Oncol 2016; 7:18-28. [PMID: 26941981 DOI: 10.3978/j.issn.2078-6891.2015.106] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
The management of peritoneal carcinomatosis, once considered a condition with few therapeutic options, has undergone dramatic change with the advancement of surgical techniques and systemic cancer therapy. Cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) administration, in particular, has significantly impacted the prospect of improving outcomes for this debilitating presentation of malignancy in selected patients. This regional surgical therapy itself has undergone many stages of evolution through its original conception nearly a century ago. Progressive changes in this field have included refinements and ongoing standardization in technique, development of a common language to describe tumor burden and extent of resection, better selection of chemotherapeutics based on tumor histology, reduction of surgical morbidity and mortality, and an improved understanding of factors for appropriate patient selection, to list but a few examples. CRS/HIPEC continues to play an important role in the management of select patients with carcinomatosis of certain tumor histology and its role will no doubt continue to be redefined as new therapies emerge.
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Affiliation(s)
- Madalyn G Neuwirth
- 1 Department of General Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA ; 2 Department of Surgery, University of Maryland, Maryland, MD 20742, USA
| | - H Richard Alexander
- 1 Department of General Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA ; 2 Department of Surgery, University of Maryland, Maryland, MD 20742, USA
| | - Giorgos C Karakousis
- 1 Department of General Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA ; 2 Department of Surgery, University of Maryland, Maryland, MD 20742, USA
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38
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Feingold PL, Kwong MLM, Sabesan A, Sorber R, Rudloff U. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for gastric cancer and other less common disease histologies: is it time? J Gastrointest Oncol 2016; 7:87-98. [PMID: 26941987 DOI: 10.3978/j.issn.2078-6891.2015.098] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer is the fourth most commonly diagnosed cancer worldwide, and once spread to the peritoneum, has a 5-year survival of less than 5%. Recent years have demonstrated advances in the use of cytoreductive surgery (CRS) in combination with heated intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal carcinomatosis due to various malignancies. The frequent desmoplastic stroma and poor vascularization impeding drug delivery particularly in the diffuse form of gastric cancer is thought to provide a sound rationale for a regionalized treatment approach in this disease. Here, we seek to review the available data to define the role of CRS and HIPEC in gastric cancer metastatic to the peritoneal surface, and furthermore, analyze the use of CRS and HIPEC in malignancies less commonly treated with the regionalized perfusion approach.
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Affiliation(s)
- Paul L Feingold
- Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Mei Li M Kwong
- Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Arvind Sabesan
- Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Rebecca Sorber
- Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Udo Rudloff
- Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
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39
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The Role of Hyperthermic Intraperitoneal Chemotherapy in Gastric Cancer. Indian J Surg Oncol 2016; 7:198-207. [PMID: 27065710 DOI: 10.1007/s13193-016-0502-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2016] [Accepted: 01/28/2016] [Indexed: 12/26/2022] Open
Abstract
Peritoneal metastasis, either synchronous or metachronous, is commonly seen in gastric cancer. It is associated with a poor prognosis, with a median survival of less than one year. The outcomes are not significantly improved by the use of systemic chemotherapy. We review the relevant literature on the role of HIPEC in gastric cancer. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been used in three situations in gastric cancer. Besides its role as a definitive treatment in patients with established peritoneal metastasis (PM), it has been used as a prophylaxis against peritoneal recurrence after curative surgery and also as a palliative treatment in advanced peritoneal metastasis with intractable ascites. While prophylactic HIPEC has been shown to reduce peritoneal recurrence and improve survival in many randomised trials, palliative HIPEC can reduce the need for frequent paracentesis. Although CRS with HIPEC has shown promise in increasing the survival of selected patients with established PM from gastric cancer, larger studies are needed before this can be accepted as a standard of care.
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40
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Braam HJ, Schellens JH, Boot H, van Sandick JW, Knibbe CA, Boerma D, van Ramshorst B. Selection of chemotherapy for hyperthermic intraperitoneal use in gastric cancer. Crit Rev Oncol Hematol 2015; 95:282-96. [PMID: 25921419 DOI: 10.1016/j.critrevonc.2015.04.004] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2014] [Revised: 01/22/2015] [Accepted: 04/07/2015] [Indexed: 12/21/2022] Open
Abstract
PURPOSE Several studies have shown the potential benefit of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer patients. At present the most effective chemotherapeutic regime in HIPEC for gastric cancer is unknown. The aim of this review was to provide a comprehensive overview of chemotherapeutic agents used for HIPEC in gastric cancer. METHODS A literature search was conducted using the PubMed database to identify studies on chemotherapy used for HIPEC in gastric cancer patients. RESULTS AND CONCLUSION The chemotherapeutic regime of choice in HIPEC for gastric cancer has yet to be determined. The wide variety in studies and study parameters, such as chemotherapeutic agents, dosage, patient characteristics, temperature of perfusate, duration of perfusion, carrier solutions, intraperitoneal pressure and open or closed perfusion techniques, warrant more experimental and clinical studies to determine the optimal treatment schedule. A combination of drugs probably results in a more effective treatment.
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Affiliation(s)
- H J Braam
- Department of Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands.
| | - J H Schellens
- Division of Clinical Pharmacology, Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Science Faculty, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
| | - H Boot
- Division of Gastroenterology and Hepatology, Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - J W van Sandick
- Department of Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - C A Knibbe
- Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands; Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - D Boerma
- Department of Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - B van Ramshorst
- Department of Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands
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41
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Randle RW, Votanopoulos KI, Shen P, Levine EA, Stewart JH. Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy. Surg Oncol 2015. [DOI: 10.1007/978-1-4939-1423-4_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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42
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VILLA AF, EL BALKHI S, ABOURA R, SAGEOT H, HASNI-PICHARD H, POCARD M, ELIAS D, JOLY N, PAYEN D, BLOT F, POUPON J, GARNIER R. Evaluation of oxaliplatin exposure of healthcare workers during heated intraperitoneal perioperative chemotherapy (HIPEC). INDUSTRIAL HEALTH 2014; 53:28-37. [PMID: 25327298 PMCID: PMC4331192 DOI: 10.2486/indhealth.2014-0025] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/22/2014] [Accepted: 08/28/2014] [Indexed: 06/04/2023]
Abstract
The aim of this study was to evaluate air and surface contaminations, and internal contamination of healthcare workers during open-abdomen HIPEC using oxaliplatin. Platinum (Pt) was measured in urine of exposed workers and in multiple air and surface samples. Three successive HIPEC procedures were investigated in each of the two hospitals participating in the study. Analysis of air samples did not detect any oxaliplatin contamination. Heavy contamination of the operating table, the floor at the surgeon's feet, and the surgeon's overshoes were observed. Hand contamination was observed in surgeons using double gloves for intra-abdominal chemotherapy administration, but not in those using three sets of gloves. Pt was not detected in urine samples obtained after HIPEC (<5 ng/L). The main risk of HIPEC is related to direct or indirect skin exposure and can be prevented by correct use of adapted protective equipment.
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Affiliation(s)
- Antoine F. VILLA
- Poison Centre, Occupational and Environmental Unit, Fernand
Widal Hospital, France
| | | | - Radia ABOURA
- Toxicology Laboratory, Lariboisière Hospital, France
| | | | | | - Marc POCARD
- Department of Digestive Diseases, Lariboisiere Hospital,
France
- University Paris Diderot, France
| | - Dominique ELIAS
- Department of Surgical Oncology, Institut Gustave Roussy
Cancer Center, France
| | - Nathalie JOLY
- Occupational Medicine, Institut Gustave Roussy Cancer Center,
France
| | - Didier PAYEN
- Department of Anesthesiology and Critical Care, Lariboisiere
Hospital, France
- University Paris Diderot, France
| | - François BLOT
- Intensive Care Unit, Institut Gustave Roussy Cancer Center,
France
| | - Joel POUPON
- Toxicology Laboratory, Lariboisière Hospital, France
| | - Robert GARNIER
- Poison Centre, Occupational and Environmental Unit, Fernand
Widal Hospital, France
- University Paris Diderot, France
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43
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Ahmed S, Stewart JH, Shen P, Votanopoulos KI, Levine EA. Outcomes with cytoreductive surgery and HIPEC for peritoneal metastasis. J Surg Oncol 2014; 110:575-84. [DOI: 10.1002/jso.23749] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2014] [Accepted: 07/16/2014] [Indexed: 12/17/2022]
Affiliation(s)
- Shuja Ahmed
- Surgical Oncology Service; Department of General Surgery; Wake Forest Baptist Medical Center; Winston Salem North Carolina
| | - John H. Stewart
- Surgical Oncology Service; Department of General Surgery; Wake Forest Baptist Medical Center; Winston Salem North Carolina
| | - Perry Shen
- Surgical Oncology Service; Department of General Surgery; Wake Forest Baptist Medical Center; Winston Salem North Carolina
| | - Konstantinos I. Votanopoulos
- Surgical Oncology Service; Department of General Surgery; Wake Forest Baptist Medical Center; Winston Salem North Carolina
| | - Edward A. Levine
- Surgical Oncology Service; Department of General Surgery; Wake Forest Baptist Medical Center; Winston Salem North Carolina
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44
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Giuliani A, Miccini M, Basso L. Extent of lymphadenectomy and perioperative therapies: Two open issues in gastric cancer. World J Gastroenterol 2014; 20:3889-3904. [PMID: 24744579 PMCID: PMC3983445 DOI: 10.3748/wjg.v20.i14.3889] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2013] [Revised: 11/23/2013] [Accepted: 03/05/2014] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer is one of the leading causes of death for cancer worldwide, although geographical variations in incidence exist. Over the last decades, its incidence and mortality have gradually decreased in Western countries, while these have increased, or remained stable, in the other world regions. Gastric cancer is often diagnosed at an advanced stage, with the only notable exception of Japan, where nationwide screening programs are enforced, due to local high incidence. Curative- intent surgery (i.e., gastrectomy, total or partial, and lymphadenectomy) remains the cornerstone of treatment of gastric cancer. Much has been debated about the extent of lymph node dissection and, although it is a valuable contribution to staging and cure, operative treatment only represents one aspect of overall effective management, as the risk of both locoregional and distant recurrences are high, and bear a poor prognosis. As a matter of fact, surgery, as a single modality treatment, has probably achieved its maximum efficacy for local control and survival, while other accompanying nonsurgical treatment modalities have to be taken into account, although their role is still the subject of considerable debate. The authors in this review present an update on the outcome of treatment of gastric cancer in relation to the extent of lymphadenectomy and of various nonsurgical preoperative, intraoperative, and postoperative strategies.
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45
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Magge D, Zenati M, Mavanur A, Winer J, Ramalingam L, Jones H, Zureikat A, Holtzman M, Lee K, Ahrendt S, Pingpank J, Zeh HJ, Bartlett DL, Choudry HA. Aggressive locoregional surgical therapy for gastric peritoneal carcinomatosis. Ann Surg Oncol 2013; 21:1448-55. [PMID: 24197761 DOI: 10.1245/s10434-013-3327-5] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2013] [Indexed: 12/13/2022]
Abstract
BACKGROUND Peritoneal carcinomatosis from gastric cancer (GPC) responds poorly to systemic chemotherapy. Limited published data demonstrate improved outcomes after aggressive locoregional therapies. We assessed the efficacy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) in GPC. METHODS We prospectively analyzed 23 patients with GPC undergoing CRS/HIPEC between 2001 and 2010. Kaplan-Meier survival curves and multivariate Cox regression models identified prognostic factors affecting oncologic outcomes. RESULTS CRS/HIPEC was performed for synchronous GPC in 20 patients and metachronous GPC in 3 patients. Adequate CRS was achieved in 22 patients (CC-0 = 17; CC-1 = 5) and median peritoneal cancer index was 10.5. Most patients received preoperative chemotherapy (83 %) and total gastrectomy (78 %). Pathology revealed diffuse histology (65 %), signet cells (65 %) and LN involvement (64 %). Major postoperative morbidity occurred in 12 patients, with 1 in-hospital mortality at postoperative day 66. With median follow-up of 52 months, median overall survival (OS) was 9.5 months (95 % confidence interval 4.7-17.3), with 1- and 3- year OS rates of 50 and 18 %. Median progression-free survival (PFS) was 6.8 months (95 % confidence interval 3.9-14.6). In a multivariate Cox regression model, male gender [hazard ratio (HR) 6.3], LN involvement (HR 1.2), residual tumor nodules (HR 2.4), and >2 anastomoses (HR 2.8) were joint significant predictors of poor OS (χ (2) = 18.2, p = 0.001), while signet cells (HR 8.9), anastomoses >2 (HR 5.5), and male gender (HR 2.4) were joint significant predictors of poor progression (χ (2) = 16.3, p = 0.001). CONCLUSIONS Aggressive CRS/HIPEC for GPC may confer a survival benefit in select patients with limited lymph node involvement and completely resectable disease requiring less extensive visceral resections.
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Affiliation(s)
- Deepa Magge
- Division of Surgical Oncology, University of Pittsburgh, Pittsburgh, PA, USA
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Coccolini F, Gheza F, Lotti M, Virzì S, Iusco D, Ghermandi C, Melotti R, Baiocchi G, Giulini SM, Ansaloni L, Catena F. Peritoneal carcinomatosis. World J Gastroenterol 2013; 19:6979-6994. [PMID: 24222942 PMCID: PMC3819534 DOI: 10.3748/wjg.v19.i41.6979] [Citation(s) in RCA: 233] [Impact Index Per Article: 19.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2013] [Revised: 09/12/2013] [Accepted: 09/16/2013] [Indexed: 02/06/2023] Open
Abstract
Several gastrointestinal and gynecological malignancies have the potential to disseminate and grow in the peritoneal cavity. The occurrence of peritoneal carcinomatosis (PC) has been shown to significantly decrease overall survival in patients with liver and/or extraperitoneal metastases from gastrointestinal cancer. During the last three decades, the understanding of the biology and pathways of dissemination of tumors with intraperitoneal spread, and the understanding of the protective function of the peritoneal barrier against tumoral seeding, has prompted the concept that PC is a loco-regional disease: in absence of other systemic metastases, multimodal approaches combining aggressive cytoreductive surgery, intraperitoneal hyperthermic chemotherapy and systemic chemotherapy have been proposed and are actually considered promising methods to improve loco-regional control of the disease, and ultimately to increase survival. The aim of this review article is to present the evidence on treatment of PC in different tumors, in order to provide patients with a proper surgical and multidisciplinary treatment focused on optimal control of their locoregional disease.
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47
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Coccolini F, Cotte E, Glehen O, Lotti M, Poiasina E, Catena F, Yonemura Y, Ansaloni L. Intraperitoneal chemotherapy in advanced gastric cancer. Meta-analysis of randomized trials. Eur J Surg Oncol 2013; 40:12-26. [PMID: 24290371 DOI: 10.1016/j.ejso.2013.10.019] [Citation(s) in RCA: 179] [Impact Index Per Article: 14.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2013] [Revised: 10/20/2013] [Accepted: 10/23/2013] [Indexed: 12/15/2022] Open
Abstract
INTRODUCTION An important component of treatment failure in gastric cancer (GC) is cancer dissemination within the peritoneal cavity and nodal metastasis. Intraperitoneal chemotherapy (IPC) is considered to give a fundamental contribute in treating advanced GC. The purpose of the study is to investigate the effects of IPC in patients with advanced GC. MATERIAL AND METHODS A systematic review with meta-analysis of randomized controlled trials (RCTs) of IPC + surgery vs. control in patients with advanced GC was performed. RESULTS Twenty prospective RCTs have been included (2145 patients: 1152 into surgery + IPC arm and 993 into control arm). Surgery + IPC improves: 1, 2 and 3-year mortality (OR = 0.31, 0.27, 0.29 respectively), 2 and 3-year mortality in patients with loco-regional nodal metastasis (OR = 0.28, 0.16 respectively), 1 and 2-year mortality rate in patients with serosal infiltration (OR = 0.33, 0.27 respectively). Morbidity rate was increased by surgery + IPC (OR = 1.82). The overall recurrence and the peritoneal recurrence rates were improved by surgery + IPC (OR = 0.46 and 0.47 respectively). There was no statistically significant difference in lymph-nodal recurrence rate. The rate of haematogenous metastasis was improved by surgery + IPC (OR = 0.63). CONCLUSIONS 1, 2 and 3-year overall survival is incremented by the IPC. No differences have been found at 5-year in overall survival rate. 2 and 3-year mortality rates in patients with nodal invasion and 1 and 2-year mortality rates in patients with serosal infiltration are improved by the use of IPC. IPC has positive effect on peritoneal recurrence and distant metastasis. Morbidity rate is incremented by IPC. Loco-regional lymph-nodes invasion in patients affected by advanced gastric cancer is not a contraindication to IPC.
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Affiliation(s)
- F Coccolini
- General Surgery Dept., Papa Giovanni XXIII Hospital, Bergamo, Italy; General Surgery Dept., Centre Hospitalier Lyon Sud, Hospices Civils de Lyon and EMR 3738, Université Lyon 1, France.
| | - E Cotte
- General Surgery Dept., Centre Hospitalier Lyon Sud, Hospices Civils de Lyon and EMR 3738, Université Lyon 1, France
| | - O Glehen
- General Surgery Dept., Centre Hospitalier Lyon Sud, Hospices Civils de Lyon and EMR 3738, Université Lyon 1, France
| | - M Lotti
- General Surgery Dept., Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - E Poiasina
- General Surgery Dept., Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - F Catena
- General Surgery Dept., Ospedale Maggiore, Parma, Italy
| | - Y Yonemura
- General Surgery Dept., Kusatsu General Hospital, Yabase 1660, Japan
| | - L Ansaloni
- General Surgery Dept., Papa Giovanni XXIII Hospital, Bergamo, Italy
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48
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Roviello F, Caruso S, Neri A, Marrelli D. Treatment and prevention of peritoneal carcinomatosis from gastric cancer by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: overview and rationale. Eur J Surg Oncol 2013; 39:1309-16. [PMID: 24183797 DOI: 10.1016/j.ejso.2013.10.010] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2013] [Revised: 09/19/2013] [Accepted: 10/09/2013] [Indexed: 12/24/2022] Open
Abstract
Peritoneal carcinomatosis (PC) from gastric cancer is a condition with a very bleak prognosis. Most authors consider it to be a terminal disease and recommend palliative therapy only. Multimodal therapeutic approaches to PC have emerged in the last decades, combining cytoreductive surgery (CRS) and peritonectomy procedures with perioperative intraperitoneal chemotherapy (IPEC), including hyperthermic intraperitoneal chemotherapy (HIPEC) and/or early postoperative intraperitoneal chemotherapy (EPIC). We reviewed the pertinent literature concerning the HIPEC modality both for the treatment of established PC and the prevention of peritoneal recurrence after potentially curative gastric cancer (GC) surgery. Basically, the two procedures relate to different aspects of GC and they are not comparable, since the latter has been used as an adjuvant when PC is still not macroscopically evident and the former has been exclusively used in advanced gastric cancer stages with peritoneal dissemination. Data supporting beneficial effects once gastric PC is already manifest is scarce and limited to few centres with specific experience in this field. Conversely, with regards to the peritoneal perfusion for preventing PC in high risk gastric cancer patients, there are phase III trials and meta-analysis which support beneficial effects resulting from the HIPEC procedure. To offer a baseline guide, we summarized the actual status and general outcome obtained by this multimodal technique, in association or not with CRS as treatment of advanced GC.
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Affiliation(s)
- F Roviello
- Department of Human Pathology and Oncology, Section of General Surgery and Surgical Oncology, University of Siena, Viale Bracci-Policlinico "Le Scotte", 53100 Siena, Italy
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49
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Mi DH, Li Z, Yang KH, Cao N, Lethaby A, Tian JH, Santesso N, Ma B, Chen YL, Liu YL. Surgery combined with intraoperative hyperthermic intraperitoneal chemotherapy (IHIC) for gastric cancer: a systematic review and meta-analysis of randomised controlled trials. Int J Hyperthermia 2013; 29:156-67. [PMID: 23418917 DOI: 10.3109/02656736.2013.768359] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Adjuvant intraoperative hyperthermic intraperitoneal chemotherapy (IHIC) is a therapy which combines thermotherapy and intraperitoneal chemotherapy. It is theoretically powerful for patients with advanced gastric cancer (AGC), but is there evident advantage in clinical practice? We need evidence to guide our decision-making. OBJECTIVES Meta-analysis was performed to assess the effectiveness and safety of adjuvant intraoperative hyperthermic intraperitoneal chemotherapy (IHIC) for patients with resectable locally advanced gastric cancer, and to provide the reference for clinical practice and study. METHODS We searched the Cochrane Library, PubMed, Embase, Web of Science and Chinese databases (Chinese BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI) and Wanfang) electronically and also retrieved papers from other sources (tracing related references and communication with other authors). All relevant randomised controlled trials (RCTs) were collected to compare surgery combined with IHIC to surgery without IHIC for AGC. There were no language restrictions. After independent quality assessment and data extraction by two reviewers, meta-analysis was conducted by RevMan 5.1 software. RESULTS 16 RCTs involving 1,906 patients were included. Compared with surgery alone, combination therapy (surgery plus IHIC) was associated with a significant improvement in survival rate at 1 year (hazard ratio (HR) = 2.99; 95% confidence interval (CI) = 2.21 to 4.05; p < 0.00001), 2 years (HR = 2.43; 95%CI = 1.81 to 3.26; p < 0.00001), 3 years (HR = 2.63; 95%CI = 2.17 to 3.20; p < 0.00001), 5 years (HR = 2.49; 95%CI = 1.97 to 3.14; p < 0.00001), and 9 years (HR = 2.14; 95%CI = 1.38 to 3.32; p = 0.0007). Compared with surgery alone, combination therapy was associated with a significant reduction in recurrence rate at 2 years (RR = 0.42; 95%CI = 0.29 to 0.61; p < 0.00001), 3 years (RR = 0.35; 95%CI = 0.24 to 0.51; p < 0.00001) and 5 years (RR = 0.47; 95%CI = 0.39 to 0.56; p < 0.00001). IHIC was not found to be associated with higher risks of anastomotic leakage, ileus, bowel perforation, myelosuppression, gastrointestinal reaction and hypohepatia, but it increased the incidence of abdominal pain (RR = 21.46; 95%CI = 5.24 to 87.78; p < 0.00001). CONCLUSIONS Compared with surgery alone, surgery combined with IHIC can improve survival rate and reduce the recurrence rate, with acceptable safety. However, safety outcomes should be further evaluated by larger samples and high quality studies. Additionally, hyperthermia for the intraperitoneal chemotherapy needs more clinical research.
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Affiliation(s)
- Deng-Hai Mi
- Evidence-Based Medicine Centre of Lanzhou University, Lanzhou, Gansu Province, China
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Romano F, Uggeri F, Nespoli L, Gianotti L, Garancini M, Maternini M, Nespoli A, Uggeri F. Gastric Cancer Immunotherapy: An Overview. ACTA ACUST UNITED AC 2013. [DOI: 10.4236/jct.2013.45116] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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