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1
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Jian C, Mou H, Zhang Y, Fan Q, Ou Y. Survival and complications of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in patients with intra-abdominal malignancies: A meta-analysis of randomized controlled trials. Front Pharmacol 2023; 14:1094834. [PMID: 36969856 PMCID: PMC10036049 DOI: 10.3389/fphar.2023.1094834] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Accepted: 02/27/2023] [Indexed: 03/11/2023] Open
Abstract
Background: Peritoneal metastasis (PM) is an advanced stage of intra-abdominal malignancy with a very poor prognosis. In recent years, hyperthermic intraperitoneal chemotherapy (HIPEC) combined with cytoreductive surgery (CRS) has been utilized as an active treatment in the prevention and treatment of PM, with encouraging results. However, compared with CRS alone, the results of the CRS plus HIPEC strategy in the treatment of patients with intra-abdominal malignancies are still controversial. This study sought to determine the impact of HIPEC + CRS on patient survival and adverse events (AEs) by reviewing randomized controlled trials (RCTs) for all types of intra-abdominal malignancies.Methods: A PubMed, Embase, Cochrane Library, Web of Science and Clinical Trials.gov search extracted all RCTs until 12 October 2022, examining the CRS + HIPEC vs. CRS alone strategies in the treatment of various types of intra-abdominal malignancies. The outcomes included overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), progression-free survival (PFS) and AEs. The dichotomous data were pooled and reported as odds ratios (ORs) with 95% confidence intervals (CIs). The survival outcome data were pooled using hazard ratios (HRs) and corresponding 95% CIs. The Cochrane Collaboration’s Risk of Bias Tool was used to assess the risk of bias in the included studies.Results: A total of 12 RCTs were included in this meta-analysis, including 873 patients in the CRS + HIPEC group and 878 patients in the CRS alone group. The studies included 3 (617 patients) on colorectal cancer, 4 (416 patients) on gastric cancer, and 5 (718 patients) on ovarian cancer. Our analysis showed no difference in OS between the CRS + HIPEC and CRS alone groups (HR: 0.79, 95% CI 0.62–1.01). Subgroup analysis showed that CRS + HIPEC improved the OS of gastric cancer patients (HR: 0.49, 95% CI 0.32–0.76) compared with CRS alone. However, CRS + HIPEC did not significantly improve the OS of colorectal cancer (HR: 1.06, 95% CI 0.81–1.38) and ovarian cancer (HR: 0.82, 95% CI 0.62–1.07) patients. In addition, there was no significant difference in DFS/RFS (HR: 0.78, 95% CI 0.57–1.07) or PFS (HR: 1.03, 95% CI 0.77–1.38) between the two groups. Compared with CRS alone, CRS with HIPEC had greater nephrotoxicity (OR: 0.45, 95% CI 0.21–0.98), while other AEs did not differ significantly between the two groups.Conclusion: Our results suggest that CRS + HIPEC may improve OS in gastric cancer patients compared with CRS alone, but we did not observe a benefit for DFS/RFS. For patients with ovarian and colorectal cancers, our results suggest that HIPEC + CRS does not appear to improve survival outcomes. In addition, CRS + HIPEC has higher nephrotoxicity than CRS alone. More evidence from RCTs is needed to evaluate whether the use of CRS + HIPEC is an appropriate option.
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Affiliation(s)
- Changchun Jian
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Orthopedic Laboratory of Chongqing Medical University, Chongqing, China
| | - Hai Mou
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Orthopedic Laboratory of Chongqing Medical University, Chongqing, China
| | - Ye Zhang
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Orthopedic Laboratory of Chongqing Medical University, Chongqing, China
| | - Qingxin Fan
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Orthopedic Laboratory of Chongqing Medical University, Chongqing, China
| | - Yunsheng Ou
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Orthopedic Laboratory of Chongqing Medical University, Chongqing, China
- *Correspondence: Yunsheng Ou,
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Kose S. Role of Computed Tomography in the Evaluation of Peritoneal Carcinomatosis. J Belg Soc Radiol 2023; 107:27. [PMID: 37064170 PMCID: PMC10103720 DOI: 10.5334/jbsr.2921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 02/23/2023] [Indexed: 04/18/2023] Open
Abstract
Peritoneal carcinomatosis (PC) refers to metastatic spread of tumor into the peritoneal cavity. Earlier, PC was thought to be associated with grave clinical outcome. However, various advances in treatment options including cytoreductive surgery and heated intraperitoneal chemotherapy or early post-operative chemotherapy can prolong survival of patients with peritoneal carcinomatosis. These treatment options are associated with high morbidity and mortality. The purpose of this article is to acquaint the radiologist about various appearances of peritoneal carcinomatosis in order to help clinicians in selecting candidates for surgery and avoid unnecessary potentially debilitating surgeries in patients with unresectable PC.
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Affiliation(s)
- Snehal Kose
- All India Institute of Medical Sciences, New Delhi, IN
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3
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Gwee YX, Chia DKA, So J, Ceelen W, Yong WP, Tan P, Ong CAJ, Sundar R. Integration of Genomic Biology Into Therapeutic Strategies of Gastric Cancer Peritoneal Metastasis. J Clin Oncol 2022; 40:2830. [PMID: 35649219 PMCID: PMC9390822 DOI: 10.1200/jco.21.02745] [Citation(s) in RCA: 54] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 01/20/2022] [Accepted: 03/08/2022] [Indexed: 12/13/2022] Open
Abstract
The peritoneum is a common site of metastasis in advanced gastric cancer (GC). Diagnostic laparoscopy is now routinely performed as part of disease staging, leading to an earlier diagnosis of synchronous peritoneal metastasis (PM). The biology of GCPM is unique and aggressive, leading to a dismal prognosis. These tumors tend to be resistant to traditional systemic therapy, and yet, this remains the current standard-of-care recommended by most international clinical guidelines. As this is an area of unmet clinical need, several translational studies and clinical trials have focused on addressing this specific disease state. Advances in genomic sequencing and molecular profiling have revealed several promising therapeutic targets and elucidated novel biology, particularly on the role of the surrounding tumor microenvironment in GCPM. Peritoneal-specific clinical trials are being designed with a combination of locoregional therapeutic strategies with systemic therapy. In this review, we summarize the new knowledge of cancer biology, advances in surgical techniques, and emergence of novel therapies as an integrated strategy emerges to address GCPM as a distinct clinical entity.
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Affiliation(s)
- Yong Xiang Gwee
- Department of Haematology-Oncology, National University Cancer Institute, Singapore
| | - Daryl Kai Ann Chia
- University Surgical Cluster, National University Health System, Singapore
- Division of Surgical Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore
| | - Jimmy So
- University Surgical Cluster, National University Health System, Singapore
- Division of Surgical Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Singapore Gastric Cancer Consortium, Singapore
| | - Wim Ceelen
- Department of GI Surgery, Ghent University Hospital, and Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium
| | - Wei Peng Yong
- Department of Haematology-Oncology, National University Cancer Institute, Singapore
- Singapore Gastric Cancer Consortium, Singapore
- Cancer Science Institute of Singapore, National University of Singapore, Singapore
| | - Patrick Tan
- Singapore Gastric Cancer Consortium, Singapore
- Cancer Science Institute of Singapore, National University of Singapore, Singapore
- Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore
- Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore
- SingHealth/Duke-NUS Institute of Precision Medicine, National Heart Centre Singapore, Singapore
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Chin-Ann Johnny Ong
- Division of Surgery and Surgical Oncology, Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), National Cancer Centre Singapore, Singapore
- Division of Surgery and Surgical Oncology, Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Singapore General Hospital, Singapore
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore
- SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore
- SingHealth Duke-NUS Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore
- Institute of Molecular and Cell Biology, A*STAR Research Entities, Singapore
| | - Raghav Sundar
- Department of Haematology-Oncology, National University Cancer Institute, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Singapore Gastric Cancer Consortium, Singapore
- Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore
- The N.1 Institute for Health, National University of Singapore, Singapore
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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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5
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Khan H, Johnston FM. Current role for cytoreduction and HIPEC for gastric cancer with peritoneal disease. J Surg Oncol 2022; 125:1176-1182. [PMID: 35481913 PMCID: PMC9322542 DOI: 10.1002/jso.26894] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 03/25/2022] [Accepted: 03/25/2022] [Indexed: 12/12/2022]
Abstract
Gastric cancer (GC) is an aggressive malignancy with a high burden of peritoneal disease. Evidence regarding the use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) to improve outcomes has been growing. However, given multiple limitations, there remains a lack of international consensus regarding the optimal treatment paradigm. This review article discusses the burden of peritoneal disease in GC patients and the role of CRS + HIPEC in all treatment intents—curative, prophylactic, and palliative.
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Affiliation(s)
- Hamza Khan
- Department of Surgery, Johns Hopkins University, Baltimore, Maryland, USA
| | - Fabian M Johnston
- Department of Surgery, Johns Hopkins University, Baltimore, Maryland, USA
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Zhang JF, Lv L, Zhao S, Zhou Q, Jiang CG. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Combined with Surgery: A 12-Year Meta-Analysis of this Promising Treatment Strategy for Advanced Gastric Cancer at Different Stages. Ann Surg Oncol 2022; 29:3170-3186. [PMID: 35175455 DOI: 10.1245/s10434-021-11316-z] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 12/28/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND This meta-analysis was designed to systematically assess the effectiveness and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) combined with surgery for different stages of advanced gastric cancer (AGC) during the last 12 years. METHODS The Cochrane Library, PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) were searched online, and papers were retrieved from other sources. Next, randomized controlled trials (RCTs) and high-quality nonrandomized controlled trials (NRCTs) were selected for this analysis. The meta-analysis was conducted with RevMan5.4 software. RESULT The 10 RCTs and 13 NRCTs selected for the study included 1892 patients. The overall survival rates were higher in the HIPEC group at 1 year (risk ratio [RR], 0.52; P = 0.004) and 3 years (RR, 0.63; P < 0.00001) than in the control group for the patients without peritoneal cancer, and the HIPEC group had a significant reduction in the recurrence rate (RR, 0.60; p < 0.00001). Among the patients with peritoneal carcinomatosis (PC), the HIPEC group had significantly higher overall survival rates at 1 year (RR, 0.62; P = 0.00001), 2 years (RR, 0.85; P = 0.002), and 3 years (RR, 0.87; P = 0.0001), with an increase in the overall median survival time of 4.67 months. The two groups showed no statistically significant difference in terms of complications for patients with PC (RR, 1.03; P = 0.93) or without PC (RR, 1.15; P = 0.51). CONCLUSION For local AGC without PC, standard surgery combined with prophylactic HIPEC could prolong survival and reduce the recurrence rate without more complications. The prognosis of this treatment strategy for patients with PC is closely related to patient selection. Complete cytoreduction combined with therapeutic HIPEC could prolong survival.
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Affiliation(s)
- Jian-Feng Zhang
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Ling Lv
- Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Shuai Zhao
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Qian Zhou
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Cheng-Gang Jiang
- Department of Surgical Oncology and General Surgery, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
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7
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Zeng L, Liao Q, Zeng X, Ye J, Yang X, Zhu S, Tang H, Liu G, Cui W, Ma S, Cui S. Noncoding RNAs and hyperthermic intraperitoneal chemotherapy in advanced gastric cancer. Bioengineered 2022; 13:2623-2638. [PMID: 35089117 PMCID: PMC8973587 DOI: 10.1080/21655979.2021.2021348] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Gastric cancer (GC) is one of the most common malignant tumors globally. About 20-30% of patients with gastric cancer show peritoneal implantation metastasis at the first diagnosis. Peritoneal metastasis is responsible for 70% of deaths of patients with advanced gastric cancer. Although there are many ways to treat advanced gastric cancer, the prognosis of patients with recurrence is unsatisfactory. An auxiliary treatment with hyperthermic intraperitoneal chemotherapy (HIPEC), is an internationally recognized recommended treatment for advanced gastric cancer. A series of clinical trials have shown that HIPEC significantly improves the overall survival of patients with cancer. Compared with the cytoreductive surgery (CRS) alone, HIPEC combined with CRS markedly reduced the rate of peritoneal metastasis in patients with ovarian cancer and colorectal cancer. It has been demonstrated that HIPEC alters transcription of many genes by affecting non-coding RNAs, which may contribute to the suppressive effect of HIPEC on the synthesis of nucleic acids and proteins in cancer cells. This paper reviews the recent advances in understanding the role of non-coding RNAs in tumor invasion and metastasis of advanced gastric cancer. We also consider changes in noncoding RNA levels and other molecules in advanced gastric cancer cases treated with HIPEC. We hope that our review will provide a reference for future research on molecular epidemiology and etiology of advanced gastric cancer and promote precise treatment of this malignancy using HIPEC.
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Affiliation(s)
- Lisi Zeng
- Institute of Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Quanxing Liao
- Department of the Second Area of Gastrointestinal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Xiaohui Zeng
- Institute of Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Jiacai Ye
- Department of Radiotherapy, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Xianzi Yang
- Department of Medical Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Siyu Zhu
- Department of Medical Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
| | - Hongsheng Tang
- Department of the Second Area of Gastrointestinal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Gaojie Liu
- Department of the Second Area of Gastrointestinal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Weiwen Cui
- Department of Bioengineering, University of California, Berkeley, California, USA
| | - Shaohua Ma
- Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen, China.,Tsinghua-Berkeley Shenzhen Institute (TBSI), Tsinghua University, Shenzhen, China
| | - Shuzhong Cui
- Department of the Second Area of Gastrointestinal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.,State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China
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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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9
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Ong XYS, Sultana R, Tan JWS, Tan QX, Wong JSM, Chia CS, Ong CAJ. The Role of Total Parenteral Nutrition in Patients with Peritoneal Carcinomatosis: A Systematic Review and Meta-Analysis. Cancers (Basel) 2021; 13:4156. [PMID: 34439309 PMCID: PMC8393754 DOI: 10.3390/cancers13164156] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 08/13/2021] [Accepted: 08/16/2021] [Indexed: 01/23/2023] Open
Abstract
Peritoneal carcinomatosis (PC) is often associated with malnutrition and an inability to tolerate enteral feeding. Although total parenteral nutrition (TPN) can be lifesaving for patients with no other means of nutritional support, its use in the management of PC patients remains controversial. Therefore, a systematic review and meta-analysis was performed to evaluate the benefit of TPN on the overall survival of PC patients, in accordance with PRISMA guidelines. A total of 187 articles were screened; 10 were included in this review and eight were included in the meta-analysis. The pooled median overall survival of patients who received TPN was significantly higher than patients who did not receive TPN (p = 0.040). When only high-quality studies were included, a significant survival advantage was observed in PC patients receiving TPN (p < 0.001). Subgroup analysis of patients receiving chemotherapy demonstrated a significant survival benefit (p = 0.008) associated with the use of TPN. In conclusion, TPN may improve survival outcomes in PC patients. However, further studies are needed to conclude more definitively on the effect of TPN.
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Affiliation(s)
- Xing-Yi Sarah Ong
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore 169610, Singapore; (X.-Y.S.O.); (J.W.-S.T.); (Q.X.T.); (J.S.M.W.); (C.S.C.)
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore 169608, Singapore
- Duke-NUS Medical School, Singapore 169857, Singapore;
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore 169610, Singapore
| | | | - Joey Wee-Shan Tan
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore 169610, Singapore; (X.-Y.S.O.); (J.W.-S.T.); (Q.X.T.); (J.S.M.W.); (C.S.C.)
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore 169608, Singapore
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore 169610, Singapore
| | - Qiu Xuan Tan
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore 169610, Singapore; (X.-Y.S.O.); (J.W.-S.T.); (Q.X.T.); (J.S.M.W.); (C.S.C.)
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore 169608, Singapore
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore 169610, Singapore
| | - Jolene Si Min Wong
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore 169610, Singapore; (X.-Y.S.O.); (J.W.-S.T.); (Q.X.T.); (J.S.M.W.); (C.S.C.)
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore 169608, Singapore
| | - Claramae Shulyn Chia
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore 169610, Singapore; (X.-Y.S.O.); (J.W.-S.T.); (Q.X.T.); (J.S.M.W.); (C.S.C.)
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore 169608, Singapore
- SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore
| | - Chin-Ann Johnny Ong
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore 169610, Singapore; (X.-Y.S.O.); (J.W.-S.T.); (Q.X.T.); (J.S.M.W.); (C.S.C.)
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore 169608, Singapore
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore 169610, Singapore
- SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore
- Institute of Molecular and Cell Biology, A*STAR Research Entities, Singapore 138673, Singapore
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10
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Zhang X, Huang H, Yang D, Wang P, Huang X, Hu Z, Zhang Y, Yan R, Zhu Z, Cai Q. Neoadjuvant Intraperitoneal and Systemic Chemotherapy Versus Neoadjuvant Systemic Chemotherapy With Docetaxel, Oxaliplatin, and S-1 for Gastric Cancer With Peritoneal Metastasis: A Propensity Score Matched Analysis. Technol Cancer Res Treat 2021; 20:15330338211036310. [PMID: 34328799 PMCID: PMC8327225 DOI: 10.1177/15330338211036310] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND The optimal treatment for gastric cancer with peritoneal metastasis (GCPM) remains debatable. This study aimed to compare the efficacy and safety of neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) versus neoadjuvant systemic chemotherapy (NSC) for GCPM. METHODS Patients of GCPM received neoadjuvant chemotherapy with docetaxel, oxaliplatin and S-1 between January 2011 and June 2019 were retrospectively evaluated. Propensity score matched (PSM) analysis was carried out to reduce the selection bias. Multivariate Cox regression model was applied to screen the prognostic factors. RESULTS After PSM processing, 71 patients in each group were matched among the 186 GCPM patients included. NIPS yielded a better ascites and cytology response to chemotherapy, higher conversion resection rate and R0 resection rate than NSC. The overall survival (OS) rate in NIPS group was better than that in NSC group. Multivariate analysis revealed that the P stage, ascites response, conversion surgery rate and R0 resection rate were independent prognostic factors. Subgroup analysis indicated that NIPS showed a survival benefit over NSC only in patients with cT3-4a, P1-2, whose cytology turned negative, and who received conversion surgery; while not in patients with cT4b, P0 or P3, whose cytology did not turn negative, or who did not receive conversion surgery. CONCLUSIONS NIPS is a safe and feasible treatment for GCPM, which showed more benefit than NSC.
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Affiliation(s)
- Xin Zhang
- Department of Gastrointestinal Surgery, 56652Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Hejing Huang
- Department of Ultrasound, 56652Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Dejun Yang
- Department of Gastrointestinal Surgery, 56652Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Peng Wang
- Department of Radiology, 56652Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Xin Huang
- Department of Gastrointestinal Surgery, 56652Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Zunqi Hu
- Department of Gastrointestinal Surgery, 56652Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Yu Zhang
- Department of Gastrointestinal Surgery, 56652Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Ronglin Yan
- Department of Gastrointestinal Surgery, 56652Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Zhenxin Zhu
- Department of Gastrointestinal Surgery, 56652Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Qingping Cai
- Department of Gastrointestinal Surgery, 56652Changzheng Hospital, Naval Medical University, Shanghai, China
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11
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Laparoscopic Hyperthermic Intraperitoneal Perfusion Chemotherapy for Patients With Malignant Ascites Secondary to Unresectable Gastric Cancer. Surg Laparosc Endosc Percutan Tech 2020; 30:55-61. [PMID: 32004214 DOI: 10.1097/sle.0000000000000380] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND To compare the efficacy of 3 chemotherapeutic combinations for laparoscopic hyperthermic intraperitoneal perfusion chemotherapy (HIPPC) in the treatment of malignant ascites secondary to unresectable gastric cancer (GC). MATERIALS AND METHODS From January 2010 to December 2013, 38 GC patients were randomly divided into 3 groups and treated by laparoscopic HIPPC with 1 of the 3 following chemotherapy combinations: raltitrexed (Ra) with oxaliplatin (L-OHP), Ra with cisplatin (DDP), and Ra with mitomycin C (MMC). Perioperative complications, patients' quality of life, and survival were recorded and compared among the 3 groups. RESULTS The intraoperative course was successful in all patients, and no perioperative death or complication related to laparoscopic HIPPC was documented. The median follow-up period was 9 months and the median survival was 7.5 months for all patients. Patients in the Ra/L-OHP group had a median survival of 8.7 months, the Ra/DDP group had a median survival of 5.6 months, and the Ra/MMC group had a median survival of 7.5 months. Patients' median survival in the Ra/L-OHP group and Ra/MMC group is significantly longer than Ra/DDP group (P<0.05). No significant difference was found in total remission rate of ascites, increase in the Karnofsky performance scale, and incidence rate of port-site metastases among the 3 groups. CONCLUSIONS Laparoscopy-assisted HIPPC provide modest yet encouraging efficacy for malignant ascites secondary to disseminated GC. Our preliminary data indicate that the chemotherapeutical combination of Ra/L-OHP and Ra/MMC might be more beneficial compared with Ra/DDP in terms of patients' survival.
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12
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Yu P, Ye Z, Dai G, Zhang Y, Huang L, Du Y, Cheng X. Neoadjuvant systemic and hyperthermic intraperitoneal chemotherapy combined with cytoreductive surgery for gastric cancer patients with limited peritoneal metastasis: a prospective cohort study. BMC Cancer 2020; 20:1108. [PMID: 33198674 PMCID: PMC7667754 DOI: 10.1186/s12885-020-07601-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Accepted: 10/30/2020] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND There is no currently available treatment for peritoneal metastasis of gastric cancer. This phase II study aimed to evaluate the efficacy and safety of neoadjuvant systemic chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC) combined with cytoreductive surgery (CRS) for the treatment of these patients. METHODS Neoadjuvant chemotherapy comprised two cycles of HIPEC and four cycles of S-1 plus paclitaxel. HIPEC was administered intraperitoneally with paclitaxel (75 mg/m2). For systemic chemotherapy, paclitaxel was administered intravenously(150 mg/m2) on day 1, and S-1 was administered orally(80 mg/m2/day)on days 1-14 of a 3-week cycle. Another two cycles of HIPEC and four cycles of S-1 plus paclitaxel were administered after second diagnostic staging laparoscopy or CRS. The primary endpoints were treatment efficiency and safety; the secondary endpoint was 3-year overall survival (OS). RESULTS A total of 40 patients were enrolled and 38 patients have been analyzed. Of these, 18 (47.4%) patients received neoadjuvant systemic chemotherapy, HIPEC and CRS (conversion therapy group), while 20 patients received only chemotherapy and HIPEC (palliative chemotherapy group). Median OS was markedly improved in the conversion therapy group (21.1 months, 95% confidence interval [CI] 16.7-25.6 months) in comparison with the palliative chemotherapy group(10.8 months, 95%CI 7.3-14.2 months, p = 0.002). After neoadjuvant systemic chemotherapy and HIPEC, a second laparoscopic exploration was performed, and the prognosis of patients with low peritoneal cancer index (PCI) (PCI < 6) was significantly better than that of patients with high PCI (PCI ≥ 6)(20.1 vs.11.3 months, p = 0.006). CONCLUSION Neoadjuvant systemic chemotherapy and HIPEC combined with CRS is safe and feasible, and could potentially improve the prognosis of gastric cancer patients with limited peritoneal metastasis. However, further clinical trials are still warranted. TRIAL REGISTRATION This study has been registered with ClinicalTrials.gov as NCT02549911 . Trial registration date: 15/09/2015.
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Affiliation(s)
- Pengfei Yu
- Department of Gastric Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310022, China
| | - Zeyao Ye
- Department of Gastric Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310022, China
| | - Gaiguo Dai
- Department of Gastric Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310022, China
| | - Yanqiang Zhang
- Department of Gastric Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310022, China
| | - Ling Huang
- Department of Gastric Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310022, China
| | - Yian Du
- Department of Gastric Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310022, China.
| | - Xiangdong Cheng
- Department of Gastric Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310022, China.
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13
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Yarema R, Оhorchak М, Hyrya P, Kovalchuk Y, Safiyan V, Karelin I, Ferneza S, Fetsych M, Matusyak M, Oliynyk Y, Fetsych Т. Gastric cancer with peritoneal metastases: Efficiency of standard treatment methods. World J Gastrointest Oncol 2020; 12:569-581. [PMID: 32461788 PMCID: PMC7235180 DOI: 10.4251/wjgo.v12.i5.569] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Revised: 03/24/2020] [Accepted: 03/28/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Peritoneal metastasis (PM), arising from gastric cancer (GC), is the most common pattern of synchronous and metachronous dissemination and is generally associated with poor prognosis. New therapeutic modalities are being increasingly employed for such patients. AIM To develop more advanced methods, it becomes necessary to study the results of existing standard treatment methods in patients with PM in order to perform a comparative analysis of the strategies. METHODS A retrospective analysis of the efficiency of standard treatment methods (i.e., palliative chemotherapy, palliative gastrectomy, and the best supportive care) was performed on 200 GC patients with synchronous PM. RESULTS The overall survival (OS) rate in 200 GC patients with PM under standard treatment was 5.4 mo. One-year survival occurred in 18.4% of patients. In multivariate analysis, the survival rate was significantly influenced by the following factors: Presence of extraperitoneal metastases, and stage of PM according to both the Japanese Gastric Cancer Association (JGCA) and the peritoneal cancer index (PCI). The median OS and 1-year survival of patients with Р1, P2, and P3 (JGCA) carcinomatosis were 9.8 mo, 6.7 mo, and 4.0 mo, and 47.2%, 18.8%, and 5.1%, respectively. The application of the palliative gastrectomy resulted in an increase in the median OS by up to 17 mo compared to the conservative approach where the value was 8.5 mo (P = 0.05) in patients with Р1 РМ. In patients with Р3, palliative chemotherapy increased the OS by up to 5.6 mo compared to the OS of 3.2 mo (P = 0.0006) for best supportive care. The median OS and 1-year survival of patients with РCI of 1-6, 7-12 and 13+ points were 8.5 mo, 4.2 mo, and 4.1 mo, and 39.8%, 6.7%, and 5.5%, respectively. Palliative gastrectomy increased the median OS to 12.6 mo compared to conservative approach of 8.0 mo (P = 0.03) in patients with РCI of 1-6 points. In patients with РCI 13+ points, only palliative chemotherapy increased the OS to 6.0 mo compared to the OS of 3.4 mo for best supportive care (P = 0.0008). CONCLUSION GC patients with PM are characterized by extremely poor prognoses. Long-term survivors were found in the group with PCI of 1-6 points, and there was no survival difference in groups with PCI 7-12 vs PCI 13+ points. Palliative gastrectomy could prove effective in treating patients with early stage PM. The three standard treatment methods are equally effective for moderate stages of PM. In cases with advanced peritoneal carcinomatosis, a significant increase in prognosis was registered only after treatment with palliative chemotherapy.
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Affiliation(s)
- Roman Yarema
- Department of oncology and Radiology, Danylo Halytsky Lviv National Medical University, Lviv 79010, Ukraine
| | - Мyron Оhorchak
- Department of Abdominal Surgery, Lviv Oncological Regional Treatment and Diagnostic Center, Lviv 79000, Ukraine
| | - Petro Hyrya
- Department of Abdominal Surgery, Lviv Oncological Regional Treatment and Diagnostic Center, Lviv 79000, Ukraine
| | - Yuriy Kovalchuk
- Department of Abdominal Surgery, Lviv Oncological Regional Treatment and Diagnostic Center, Lviv 79000, Ukraine
| | - Victor Safiyan
- Department of Abdominal Surgery, Lviv Oncological Regional Treatment and Diagnostic Center, Lviv 79000, Ukraine
| | - Ivan Karelin
- Department of Abdominal Surgery, Lviv Oncological Regional Treatment and Diagnostic Center, Lviv 79000, Ukraine
| | - Severyn Ferneza
- Department of oncology and Radiology, Danylo Halytsky Lviv National Medical University, Lviv 79010, Ukraine
| | - Markiyan Fetsych
- Department of oncology and Radiology, Danylo Halytsky Lviv National Medical University, Lviv 79010, Ukraine
| | - Myron Matusyak
- Department of Abdominal Surgery, Lviv Oncological Regional Treatment and Diagnostic Center, Lviv 79000, Ukraine
| | - Yuriy Oliynyk
- Department of oncology and Radiology, Danylo Halytsky Lviv National Medical University, Lviv 79010, Ukraine
| | - Тaras Fetsych
- Department of oncology and Radiology, Danylo Halytsky Lviv National Medical University, Lviv 79010, Ukraine
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Fields AC, Lu PW, Li GZ, Welten V, Jolissaint JS, Vierra BM, Saadat LV, Larson AC, Atkinson RB, Melnitchouk N. Current practices and future steps for hyperthermic intraperitoneal chemotherapy. Curr Probl Surg 2020; 57:100727. [PMID: 32151327 DOI: 10.1016/j.cpsurg.2019.100727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Accepted: 12/23/2019] [Indexed: 11/20/2022]
Affiliation(s)
- Adam C Fields
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
| | - Pamela W Lu
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - George Z Li
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Vanessa Welten
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Joshua S Jolissaint
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | | | - Lily V Saadat
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Abby C Larson
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Rachel B Atkinson
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Nelya Melnitchouk
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
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15
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Liu X, Tang M. Effect of early body cavity continuous circulation hyperthermia perfusion chemotherapy combined with systemic chemotherapy (and nursing) on survival rate and serum tumor markers in patients with advanced gastric cancer. EUR J INFLAMM 2020. [DOI: 10.1177/2058739220942339] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
This study was designed to investigate the effects of early coelom continued circulatory hyperthermic perfusion chemotherapy combined with systemic chemotherapy on the survival and serum tumor markers. A total of 128 patients with advanced gastric carcinoma who have received surgical treatments were selected and were randomly divided into study group (receiving early circulatory intraperitoneal hyperthermic perfusion chemotherapy combined with systemic chemotherapy postoperatively) and control group (receiving chemotherapy alone postoperatively), with 64 cases in each. Comparison of serum tumor markers (CA724, CA242), vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), immune function indexes (CD3+, CD4+, CD8+), and 5-year survival rate was assessed. Before treatment, there was no significant difference in the serum tumor markers (CA724 and CA242) as well as the serum VEGF, MMP-2, and MMP-9 levels among the two groups ( P > 0.05). However, the above parameters in the study group were significantly lower than control group 8 weeks after the treatment ( P < 0.05). Before treatment, there was no significant difference in CD3+, CD4+, CD8+ and CD4+/CD8+ between the two groups ( P > 0.05). Eight weeks after the treatment, the CD3+, CD4+ and CD4+/CD8+ in the study group were significantly higher than those in the control group ( P < 0.05), while the CD8+ levels was significantly lower than the latter group ( P < 0.05). The 2-year recurrence rate in the study group was lower than the control group ( P < 0.05). Furthermore, survival rates (1-year, 3-year and 5-year) of the study group were all higher than control group ( P < 0.05). Early circulatory hyperthermia perfusion chemotherapy combined with systemic chemotherapy contributed to the decrease in the serum tumor markers (CA724, CA242) as well as the serum VEGF, MMP-2, and MMP-9 levels, improved the immune functions. This therapeutic regimen prolonged the long-term survival conditions of the patients as well as proved the safety and effectiveness.
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Affiliation(s)
- Xia Liu
- Department of Emergency Abdominal Surgery, The Second Affiliated Hospital, Dalian Medical University, Dalian, P.R. China
| | - Miao Tang
- Department of Critical Medicine, The Second Affiliated Hospital, Dalian Medical University, Dalian, P.R. China
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16
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Beeharry MK, Zhu ZL, Liu WT, Yao XX, Yan M, Zhu ZG. Prophylactic HIPEC with radical D2 gastrectomy improves survival and peritoneal recurrence rates for locally advanced gastric cancer: personal experience from a randomized case control study. BMC Cancer 2019; 19:932. [PMID: 31533660 PMCID: PMC6751672 DOI: 10.1186/s12885-019-6125-z] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2019] [Accepted: 09/03/2019] [Indexed: 02/07/2023] Open
Abstract
Background To investigate the implications of prophylactic intraoperative Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with D2 radical gastrectomy for locally advanced Gastric Cancer (AGC) in a randomized case control study. Method Eighty consecutive patients with locally AGC were randomly separated into 2 groups: HIPEC group (Curative Resection + intraoperative HIPEC with cisplatin 50 mg/m2 at 42.0 ± 1.0 °C for 60 min) and Control group (Curative Resection only). Intraoperative and post-operative events, clinical recovery, morbidity and the disease-free survival (DFS) rates were closely monitored. Results Faster recovery of bowel function (43 ± 5 h vs 68 ± 7, P < 0.05) and shorter postoperative stay (8d vs 14d, P < 0.05) were noted in the HIPEC group. Among the 40 HIPEC group patients, the highest intracranial temperature recorded during the procedure was 38.2 °C but the patient made an eventless recovery. Mild renal dysfunction, hyperbilirubinemia and mild liver dysfunction were recorded in the HIPEC group but their incidences were found to be statistically insignificant when compared with the control group (P > 0.05). The 3 year DFS rate analysis showed that the prophylactic HIPEC group had a higher DFS rate (93% vs 65%, P = 0.0054). The peritoneal recurrence rate was lower in the HIPEC group (3% vs 23%, P < 0.05). Conclusion Prophylactic HIPEC with radical D2 Gastrectomy improves survival and peritoneal recurrence rates for AGC with favorable post-operative recovery at low and acceptable morbidity.
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Affiliation(s)
- Maneesh Kumarsing Beeharry
- Department of Surgery, Ruijin Hospital affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Zheng-Lun Zhu
- Department of Surgery, Ruijin Hospital affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Wen-Tao Liu
- Department of Surgery, Ruijin Hospital affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Xue-Xin Yao
- Department of Surgery, Ruijin Hospital affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
| | - Min Yan
- Department of Surgery, Ruijin Hospital affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Zheng-Gang Zhu
- Department of Surgery, Ruijin Hospital affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
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17
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Yarema R, Mielko J, Fetsych T, Ohorchak M, Skorzewska M, Rawicz‐Pruszyński K, Mashukov A, Maksimovsky V, Jastrzębski T, Polkowski W, Gyrya P, Kovalchuk Y, Safiyan V, Karelin I, Kopetskiy V, Kolesnik O, Kondratskiy Y, Paskonis M. Hyperthermic intraperitoneal chemotherapy (HIPEC) in combined treatment of locally advanced and intraperitonealy disseminated gastric cancer: A retrospective cooperative Central-Eastern European study. Cancer Med 2019; 8:2877-2885. [PMID: 31033239 PMCID: PMC6558472 DOI: 10.1002/cam4.2204] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Accepted: 04/10/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND AND OBJECTIVES Clinical experience in Western Europe suggests that cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are promising methods in the management of gastric cancer (GC) with peritoneal metastases. However, there are almost no data on such treatment results in patient from Central-Eastern European population. METHODS A retrospective cooperative study was performed at 6 Central-Eastern European HIPEC centers. HIPEC was used in 117 patients for the following indications: treatment of GC with limited overt peritoneal metastases (n = 70), adjuvant setting after radical gastrectomy (n = 37) and palliative approach for elimination of severe ascites without gastrectomy (n = 10). RESULTS Postoperative morbidity and mortality rates were 29.1% and 5.1%, respectively. Median overall survival in the groups with therapeutic, adjuvant, and palliative indications was 12.6, 34, and 3.5 months. The only long-term survivors occurred in the group with peritoneal cancer index (PCI) of 0-6 points without survival difference in groups with PCI 7-12 vs PCI 13 or more points. CONCLUSIONS GC patients with limited peritoneal metastases can benefit from CRS + HIPEC. Hyperthermic intraperitoneal chemotherapy could be an effective method of adjuvant treatment of GC with a high risk of intraperitoneal progression. No long-term survival may be expected after palliative approach to HIPEC.
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Affiliation(s)
- Roman Yarema
- Danylo Halytsky Lviv National Medical UniversityLvivUkraine
| | | | - Taras Fetsych
- Danylo Halytsky Lviv National Medical UniversityLvivUkraine
| | - Myron Ohorchak
- Lviv State Oncological Regional Treatment and Diagnostic CenterLvivUkraine
| | | | | | | | | | | | | | - Petro Gyrya
- Lviv State Oncological Regional Treatment and Diagnostic CenterLvivUkraine
| | - Yuriy Kovalchuk
- Lviv State Oncological Regional Treatment and Diagnostic CenterLvivUkraine
| | - Victor Safiyan
- Lviv State Oncological Regional Treatment and Diagnostic CenterLvivUkraine
| | - Ivan Karelin
- Lviv State Oncological Regional Treatment and Diagnostic CenterLvivUkraine
| | | | | | | | - Marius Paskonis
- Vilnius universtiy hospital Santaros klinikosVilniusLithuania
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18
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Chiu CC, Tsao CJ, Wang JJ, Yonemura Y. Can hyperthermic intraperitoneal chemotherapy effectively control gastric cancer-associated peritoneal carcinomatosis? World J Surg Proced 2019; 9:7-11. [DOI: 10.5412/wjsp.v9.i1.7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2018] [Revised: 03/11/2019] [Accepted: 04/19/2019] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer-associated peritoneal carcinomatosis leads to a poor prognosis and low quality of life. The current systemic chemotherapy processes cannot effectively improve survival. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been used as an alternative treatment to control this disease through recurrence prevention, definitive therapeutic modality, and symptom palliation. Although HIPEC has been demonstrated to yield favorable results mainly in some Asian studies, widespread adoption of this treatment is still debatable before larger prospective randomized controlled clinical trials confirm its effectiveness.
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Affiliation(s)
- Chong-Chi Chiu
- Department of General Surgery, Chi Mei Medical Center, Liouying 73657 and Tainan 71004, Taiwan
- Department of Electrical Engineering, Southern Taiwan University of Science and Technology, Tainan 71005, Taiwan
| | - Chao-Jung Tsao
- Department of Oncology, Chi Mei Medical Center, Liouying 73657, Taiwan
| | - Jhi-Joung Wang
- Department of Medical Research, Chi Mei Medical Center, Tainan 71004, Taiwan
- AI Biomed Center, Southern Taiwan University of Science and Technology, Tainan 71005, Taiwan
| | - Yutaka Yonemura
- Peritoneal Surface Malignancy Center, Kishiwada Tokushukai Hospital, Kishiwada, Osaka 596-8522, Japan
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Bai F, Ba F, You Y, Feng Y, Tao W, Wu C, Jiu M, Nie Y. Decreased ST2 expression is associated with gastric cancer progression and pathogenesis. Oncol Lett 2019; 17:5761-5767. [PMID: 31186802 DOI: 10.3892/ol.2019.10223] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 03/14/2019] [Indexed: 01/01/2023] Open
Abstract
Gastric cancer is a type of cancer with increasing incidence and high mortality rates, but molecular biomarkers of diagnostic and therapeutic value are currently lacking. The aim of the present study was to examine the expression pattern of the interleukin 1 receptor-like 1 (ST2) protein and assess its clinicopathological significance in gastric cancer. Western blot analysis of 12 gastric cancer specimens and paired adjacent tissues demonstrated that the protein levels of 2 isoforms of ST2, soluble secreted ST2 and the ST2 variant without the third immunoglobulin motif and splicing in the C-terminal, were markedly decreased in cancer tissues compared with non-cancerous tissues. Immunohistochemical analysis demonstrated that ST2 protein expression was markedly decreased in primary gastric cancer tissues (39.1%, 90/230) compared with adjacent non-cancerous tissues (60.7%, 54/89) (P<0.05). Statistical analysis demonstrated that decreased ST2 expression was significantly associated with advanced tumor node metastasis stage (P<0.001) and tumor differentiation (P<0.001). These data suggest that ST2 protein may be a valuable biomarker of gastric cancer progression and pathogenesis.
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Affiliation(s)
- Feihu Bai
- Department of Gastroenterology, Ningxia Hui Autonomous Region People's Hospital, Yinchuan, Ningxia Hui Autonomous Region 750021, P.R. China
| | - Fangyun Ba
- Department of General Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750001, P.R. China
| | - Yanjie You
- Department of Gastroenterology, Ningxia Hui Autonomous Region People's Hospital, Yinchuan, Ningxia Hui Autonomous Region 750021, P.R. China
| | - Yaning Feng
- Department of Gastroenterology, Ningxia Hui Autonomous Region People's Hospital, Yinchuan, Ningxia Hui Autonomous Region 750021, P.R. China
| | - Wei Tao
- Department of Gastroenterology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750021, P.R. China
| | - Chuanxia Wu
- Department of Gastroenterology, The Second People's Hospital of Linyi, Linyi, Shandong 276000, P.R. China
| | - Mengna Jiu
- Department of Gastroenterology, Ankang Central Hospital, Ankang, Shanxi 725000, P.R. China
| | - Yongzhan Nie
- Department of Gastroenterology, Xijing Hospital of Digestive Diseases, State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xi'an, Shanxi 710000, P.R. China
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Feng Y, Bai F, You Y, Bai F, Wu C, Xin R, Li X, Nie Y. Dysregulated microRNA expression profiles in gastric cancer cells with high peritoneal metastatic potential. Exp Ther Med 2018; 16:4602-4608. [PMID: 30546395 PMCID: PMC6256850 DOI: 10.3892/etm.2018.6783] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2018] [Accepted: 08/14/2018] [Indexed: 12/16/2022] Open
Abstract
Despite significant developments in its clinical treatment, the reported incidence and mortality of gastric cancer have exhibited marked increases. The molecular mechanisms of gastric cancer initiation and progression remain to be fully elucidated. The aim of the present study was to identify novel microRNAs (miRNAs/miRs) with a role in the peritoneal metastasis of gastric cancer by comparing the miRNA expression in the gastric cancer cell line GC9811 with that in its variant GC9811-P, a sub-cell line with a high potential for peritoneal metastasis. A miRNA microarray analysis identified 153 dysregulated miRNAs, including 74 upregulated and 79 downregulated miRNAs. Of these, four significantly upregulated miRNAs (miR-181a-5p, miR-106b-5p, miR-199a-3p and miR-148a-3p) and four downregulated miRNAs (miR-146a-5p, miR-21-5p, miR-222-3p and miR-221-3p) were selected and further confirmed by reverse transcription-quantitative polymerase chain reaction analysis. Furthermore, knockdown of miR-21-5p promoted the migration and invasion of GC9811 cells. Collectively, the results suggested that the miRNA expression profile in GC9811-P vs. GC9811 cells was altered to favor disease progression, and the dysregulated miRNAs, including miR-21-5p, may therefore provide novel biomarkers and potential therapeutic targets for gastric cancer metastasis.
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Affiliation(s)
- Yaning Feng
- Department of Gastroenterology, Ningxia Hui Autonomous Region People's Hospital, Yinchuan, Ningxia Hui Autonomous Region 750021, P.R. China
| | - Feihu Bai
- Department of Gastroenterology, Ningxia Hui Autonomous Region People's Hospital, Yinchuan, Ningxia Hui Autonomous Region 750021, P.R. China
| | - Yanjie You
- Department of Gastroenterology, Ningxia Hui Autonomous Region People's Hospital, Yinchuan, Ningxia Hui Autonomous Region 750021, P.R. China
| | - Fangyun Bai
- Department of General Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750001, P.R. China
| | - Chuanxia Wu
- Department of Gastroenterology, The Second People's Hospital of Linyi, Linyi, Shandong 276000, P.R. China
| | - Ruijuan Xin
- Department of Gastroenterology, Ningxia Hui Autonomous Region People's Hospital, Yinchuan, Ningxia Hui Autonomous Region 750021, P.R. China
| | - Xue Li
- Department of Gastroenterology, Ningxia Hui Autonomous Region People's Hospital, Yinchuan, Ningxia Hui Autonomous Region 750021, P.R. China
| | - Yongzhan Nie
- Department of Gastroenterology, Xijing Hospital of Digestive Diseases, State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xi'an, Shaanxi 710000, P.R. China
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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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Macrì A, Saladino E. Prophylactic hyperthermic intraperitoneal chemotherapy can be considered in the management of advanced gastric cancer. J Gastrointest Oncol 2016; 7:1017-1018. [PMID: 28078127 PMCID: PMC5177590 DOI: 10.21037/jgo.2016.08.10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2016] [Accepted: 07/06/2016] [Indexed: 11/06/2022] Open
Affiliation(s)
- Antonio Macrì
- Department of Human Pathology, University of Messina, Via Consolare Valeria, 98168 Messina, Italy
| | - Edoardo Saladino
- Cappellani-GIOMI Clinic, V.le Regina Elena, N° 335, 98168 Messina, Italy
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Xin R, Bai F, Feng Y, Jiu M, Liu X, Bai F, Nie Y, Fan D. MicroRNA-214 promotes peritoneal metastasis through regulating PTEN negatively in gastric cancer. Clin Res Hepatol Gastroenterol 2016; 40:748-754. [PMID: 27339596 DOI: 10.1016/j.clinre.2016.05.006] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2015] [Revised: 02/24/2016] [Accepted: 05/03/2016] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND OBJECTIVE We aimed to investigate the effects of microRNA-214 (miR-214) on peritoneal metastasis as well as to elucidate its regulatory mechanism in gastric cancer (GC). METHODS The expression levels of miR-214 in human GC cell lines MKN-28NM, MKN-28M, GC9811 and GC9811-P were analyzed by quantitative real-time PCR. Lentiviral miR-214, lentiviral miR-214 inhibitor, and empty lentiviral vector were transfected to GC cell lines, respectively. The roles of miR-214 in cell invasion, migration, proliferation and colony-forming ability were then analyzed. Besides, the expression levels of PTEN in different transfected cells were determined by western blot analysis. RESULTS We found that miR-214 was up-regulated in GC9811-P cells with high metastatic potential to the peritoneum compared with that in GC9811 cells. In addition, in vitro overexpression of miR-214 promoted cell invasion, migration, proliferation and colony-forming ability of GC9811 cells, while down-regulation of miR-214 had opposite effects in GC9811-P cells. Besides, overexpression of miR-214 in GC9811 cells markedly down-regulated PTEN expression, whereas down-regulation of miR-214 in GC9811-P cells significantly increased PTEN expression. CONCLUSIONS Our findings indicate that miR-214 may promote peritoneal metastasis of GC cells via down-regulation of PTEN, thus leading to the progression of GC.
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Affiliation(s)
- Ruijuan Xin
- Ningxia Hui Autonomous Region People's Hospital, Department of Gastroenterology, Yinchuan, China
| | - Feihu Bai
- Ningxia Hui Autonomous Region People's Hospital, Department of Gastroenterology, Yinchuan, China
| | - Yaning Feng
- Ningxia Hui Autonomous Region People's Hospital, Department of Gastroenterology, Yinchuan, China
| | - Mengna Jiu
- Ningxia Medical University, Yinchuan, China
| | | | - Fangyun Bai
- Affiliated Hospital of Ningxia Medical University, Department of Gastroenterology, Yinchuan, China
| | - Yongzhan Nie
- Xijing Hospital of Digestive Diseases, State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Beilin District, Changlexi Road, 710000 Xi'an, China.
| | - Daiming Fan
- Xijing Hospital of Digestive Diseases, State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Beilin District, Changlexi Road, 710000 Xi'an, China
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Beeharry MK, Liu WT, Yao XX, Yan M, Zhu ZG. A critical analysis of the cytoreductive surgery with hyperthermic intraperitoneal chemotherapy combo in the clinical management of advanced gastric cancer: an effective multimodality approach with scope for improvement. Transl Gastroenterol Hepatol 2016; 1:77. [PMID: 28138643 DOI: 10.21037/tgh.2016.08.05] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2016] [Accepted: 08/22/2016] [Indexed: 12/16/2022] Open
Abstract
Peritoneal carcinomatosis (PC) is manifested in up to 40% of gastric cancer (GC) patients, after which their 5-year survival drops to less than 5%. The currently most acceptable treatment option for advanced GC (AGC) is systemic chemo and radio therapies with however generally very unsatisfying results and this led to a resurgence of interest in regional therapies like cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Small trials have indicated an association with prolonged survival when applying this technique to AGC manifesting with PC. High procedure-related morbidity and mortality associated with the CRS-HIPEC approach have however brought by a polemic on the merits of the latter: with the advent of regulatory approval of more effective as well as novel, more personalized treatment options in AGC, along with advances in tailoring investigational agents specifically for peritoneal delivery, there clearly is a need to outline the appropriate role of CRS-HIPEC in this disease. In a clear objective to improve the therapeutic efficiency of HIPEC, there have been immense developments in the technical aspects of this technology including the use of nanotechnology in more precise drug delivery systems (DDS) or choice of more efficient drugs such as gene-target technology, laparoscopy and so on. Henceforth, in this review, we will be highlighting the past and current status of the CRS + HIPEC procedure, shedding light on the pros and cons in order to boost up the efficiency of this multimodality approach.
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Affiliation(s)
- Maneesh K Beeharry
- Department of Surgery, Rui Jin Hospital, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Wen-Tao Liu
- Department of Surgery, Rui Jin Hospital, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Xue-Xin Yao
- Department of Surgery, Rui Jin Hospital, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Min Yan
- Department of Surgery, Rui Jin Hospital, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Zheng-Gang Zhu
- Department of Surgery, Rui Jin Hospital, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
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25
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Wei J, Wu ND, Liu BR. Regional but fatal: Intraperitoneal metastasis in gastric cancer. World J Gastroenterol 2016; 22:7478-7485. [PMID: 27672270 PMCID: PMC5011663 DOI: 10.3748/wjg.v22.i33.7478] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2016] [Revised: 05/15/2016] [Accepted: 06/15/2016] [Indexed: 02/06/2023] Open
Abstract
Peritoneal carcinomatosis appears to be the most common pattern of metastasis or recurrence and is associated with poor prognosis in gastric cancer patients. Many efforts have been made to improve the survival in patients with peritoneal metastasis. Hyperthermic intraperitoneal chemotherapy remains a widely accepted strategy in the treatment of peritoneal dissemination. Several phase II-III studies confirmed that the combined cytoreducitve surgery and hyperthermic intraperitoneal chemotherapy resulted in longer survival in patients with peritoneal carcinomatosis. In addition, proper selection and effective regional treatment in patients with high risk of peritoneal recurrence after resection will further improve prognosis in local advanced gastric cancer patients.
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26
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Murata S, Yamamoto H, Yamaguchi T, Kaida S, Ishida M, Kodama H, Takebayashi K, Shimizu T, Miyake T, Tani T, Kushima R, Tani M. Viable Cancer Cells in the Remnant Stomach are a Potential Source of Peritoneal Metastasis after Curative Distal Gastrectomy for Gastric Cancer. Ann Surg Oncol 2016; 23:2920-2927. [DOI: 10.1245/s10434-016-5219-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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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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28
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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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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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30
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Seshadri RA, Glehen O. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer. World J Gastroenterol 2016; 22:1114-30. [PMID: 26811651 PMCID: PMC4716024 DOI: 10.3748/wjg.v22.i3.1114] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 09/22/2015] [Accepted: 11/30/2015] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer associated peritoneal carcinomatosis (GCPC) has a poor prognosis with a median survival of less than one year. Systemic chemotherapy including targeted agents has not been found to significantly increase the survival in GCPC. Since recurrent gastric cancer remains confined to the abdominal cavity in many patients, regional therapies like aggressive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been investigated for GCPC. HIPEC has been used for three indications in GC- as an adjuvant therapy after a curative surgery, HIPEC has been shown to improve survival and reduce peritoneal recurrences in many randomised trials in Asian countries; as a definitive treatment in established PC, HIPEC along with CRS is the only therapeutic modality that has resulted in long-term survival in select groups of patients; as a palliative treatment in advanced PC with intractable ascites, HIPEC has been shown to control ascites and reduce the need for frequent paracentesis. While the results of randomised trials of adjuvant HIPEC from western centres are awaited, the role of HIPEC in the treatment of GCPC is still evolving and needs larger studies before it is accepted as a standard of care.
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31
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Ba MC, Long H, Zhang XL, Gong YF, Tang YQ, Wu YB, Yu FH, Cui SZ. Laparoscopic Hyperthermic Intraperitoneal Perfusion Chemotherapy for Patients with Malignant Ascites Secondary to Unresectable Gastric Cancer. J Laparoendosc Adv Surg Tech A 2016; 26:32-9. [PMID: 26779722 DOI: 10.1089/lap.2015.0266] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Affiliation(s)
- Ming-chen Ba
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Hui Long
- Department of Pharmacy, Guangzhou Dermatology Institute, Guangzhou, People's Republic of China
| | - Xiang-Liang Zhang
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Yuan-Feng Gong
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Yun-Qiang Tang
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Yin-Bing Wu
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Fei-Hong Yu
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China
| | - Shu-Zhong Cui
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China
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32
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Canbay E, Torun BC, Torun ES, Yonemura Y. Evolution of management in peritoneal surface malignancies. ULUSAL CERRAHI DERGISI 2015; 32:203-7. [PMID: 27528813 DOI: 10.5152/ucd.2016.3375] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/12/2015] [Accepted: 12/17/2015] [Indexed: 12/29/2022]
Abstract
Management of peritoneal surface malignancies has gradually evolved by the introduction of cytoreductive surgery in combination with intraperitoneal chemotherapy applications. Recently, peritoneal metastases of intraabdominal solid organ tumors and primary peritoneal malignancies such as peritoneal mesothelioma are being treated with this new approach. Selection criteria are important to reduce morbidity and mortality rates of patients who will experience minimal or no benefit from these combined treatment modalities. Management of peritoneal surface malignancies with this current trend is presented in this review.
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Affiliation(s)
- Emel Canbay
- NPO HIPEC Istanbul, Centermed, İstanbul, Turkey; NPO to Support Peritoneal Dissemination Treatment, 1-26 Harukimotomachi, Kishiwada City, Osaka, Japan
| | - Bahar Canbay Torun
- Department of General Surgery, İstanbul University İstanbul School of Medicine, İstanbul, Turkey
| | - Ege Sinan Torun
- Department of Internal Medicine, İstanbul University İstanbul School of Medicine, İstanbul, Turkey
| | - Yutaka Yonemura
- NPO HIPEC Istanbul, Centermed, İstanbul, Turkey; NPO to Support Peritoneal Dissemination Treatment, 1-26 Harukimotomachi, Kishiwada City, Osaka, Japan
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Marrelli D, Polom K, de Manzoni G, Morgagni P, Baiocchi GL, Roviello F. Multimodal treatment of gastric cancer in the west: Where are we going? World J Gastroenterol 2015; 21:7954-7969. [PMID: 26185368 PMCID: PMC4499339 DOI: 10.3748/wjg.v21.i26.7954] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Revised: 03/25/2015] [Accepted: 05/02/2015] [Indexed: 02/06/2023] Open
Abstract
The incidence of gastric cancer (GC) is decreasing worldwide, especially for intestinal histotype of the distal third of the stomach. On the contrary, proximal location and diffuse Lauren histotype have been reported to be generally stable over time. In the west, no clear improvement in long-term results was observed in clinical and population-based studies. Results of treatment in these neoplasms are strictly dependent on tumor stage. Adequate surgery and extended lymphadenectomy are associated with good long-term outcome in early-stage cancer; however, results are still unsatisfactory for advanced stages (III and IV), for which additional treatments could provide a survival benefit. This implies a tailored approach to GC. The aim of this review was to summarize the main multimodal treatment options in advanced resectable GC. Perioperative or postoperative treatments, including chemotherapy, chemoradiotherapy, targeted therapies, and hyperthermic intraperitoneal chemotherapy have been reviewed, and the main ongoing and completed trials have been analyzed. An original tailored multimodal approach to non-cardia GC has been also proposed.
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34
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Montagner IM, Merlo A, Zuccolotto G, Renier D, Campisi M, Pasut G, Zanovello P, Rosato A. Peritoneal tumor carcinomatosis: pharmacological targeting with hyaluronan-based bioconjugates overcomes therapeutic indications of current drugs. PLoS One 2014; 9:e112240. [PMID: 25383653 PMCID: PMC4226476 DOI: 10.1371/journal.pone.0112240] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2014] [Accepted: 10/09/2014] [Indexed: 12/30/2022] Open
Abstract
Peritoneal carcinomatosis still lacks reliable therapeutic options. We aimed at testing a drug delivery strategy allowing a controlled release of cytotoxic molecules and selective targeting of tumor cells. We comparatively assessed the efficacy of a loco-regional intraperitoneal treatment in immunocompromised mice with bioconjugates formed by chemical linking of paclitaxel or SN-38 to hyaluronan, against three models of peritoneal carcinomatosis derived from human colorectal, gastric and esophageal tumor cell xenografts. In vitro, bioconjugates were selectively internalized through mechanisms largely dependent on interaction with the CD44 receptor and caveolin-mediated endocytosis, which led to accumulation of compounds into lysosomes of tumor cells. Moreover, they inhibited tumor growth comparably to free drugs. In vivo, efficacy of bioconjugates or free drugs against luciferase-transduced tumor cells was assessed by bioluminescence optical imaging, and by recording mice survival. The intraperitoneal administration of bioconjugates in tumor-bearing mice exerted overlapping or improved therapeutic efficacy compared with unconjugated drugs. Overall, drug conjugation to hyaluronan significantly improved the profiles of in vivo tolerability and widened the field of application of existing drugs, over their formal approval or current use. Therefore, this approach can be envisaged as a promising therapeutic strategy for loco-regional treatment of peritoneal carcinomatosis.
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Affiliation(s)
| | - Anna Merlo
- Veneto Institute of Oncology IOV - IRCCS, Padua, Italy
| | | | | | | | - Gianfranco Pasut
- Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy
| | - Paola Zanovello
- Veneto Institute of Oncology IOV - IRCCS, Padua, Italy
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Antonio Rosato
- Veneto Institute of Oncology IOV - IRCCS, Padua, Italy
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- * E-mail:
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Cui HB, Ge HE, Bai XY, Zhang W, Zhang YY, Wang J, Li X, Xing LP, Guo SH, Wang ZY. Effect of neoadjuvant chemotherapy combined with hyperthermic intraperitoneal perfusion chemotherapy on advanced gastric cancer. Exp Ther Med 2014; 7:1083-1088. [PMID: 24940391 PMCID: PMC3991504 DOI: 10.3892/etm.2014.1599] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2013] [Accepted: 02/18/2014] [Indexed: 12/23/2022] Open
Abstract
Neoadjuvant and hyperthermic intraperitoneal chemotherapies have been shown to be effective in the treatment of resectable advanced gastric cancer. The aim of the present study was to investigate the clinical efficiency and security of neoadjuvant chemotherapy in combination with hyperthermic intraperitoneal chemotherapy for the treatment of postoperative advanced gastric cancer. A total of 192 patients diagnosed with advanced gastric cancer were randomly divided into the following four groups (n=48 per group): Control, neoadjuvant chemotherapy, hyperthermic intraperitoneal perfusion chemotherapy and joint groups. The joint group received neoadjuvant chemotherapy combined with hyperthermic intraperitoneal perfusion chemotherapy. Complications, adverse reactions, recurrence rates within 2 years and the 1- and 3-year survival rates following surgery were observed. No significant differences were observed in the occurrence rates of I–II degree myelosuppression, III–IV degree myelosuppression, I–II degree nausea or III–IV degree nausea and vomiting among the four groups (P>0.05). The median progression-free survival times were 26, 31, 33 and 28 months in the control, neoadjuvant chemotherapy, hyperthermic intraperitoneal perfusion chemotherapy and joint groups, respectively (P<0.001). Compared with the control group, the recurrence-free 2-year survival rate of the joint group was significantly lower (P=0.04). The difference among the median survival times of the four groups was statistically significant (P=0.001). The 1-year survival rate of the joint group was significantly higher when compared with the control group and the difference was statistically significant (P=0.03). However, no statistically significant difference was identified among the 1-year survival rates of the four groups (P>0.05). Compared with the control group, the 3-year survival rates of the other three groups were significantly higher (P<0.05). Therefore, the results of the present study indicated that neoadjuvant chemotherapy combined with hyperthermic intraperitoneal perfusion chemotherapy for the treatment of advanced gastric cancer is well tolerated and exhibits improved compliance and efficiency.
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Affiliation(s)
- Hai-Bin Cui
- Department of Immunotherapy, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China ; Department of Oncology, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China
| | - Huai-E Ge
- Department of Oncology, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China
| | - Xi-Yong Bai
- Department of Oncology, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China
| | - Wei Zhang
- Department of Oncology, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China
| | - Yuan-Yuan Zhang
- Department of Oncology, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China
| | - Juan Wang
- Department of Immunotherapy, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
| | - Xing Li
- Department of Immunotherapy, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
| | - Lian-Ping Xing
- Department of Pathology, University of Rochester, New York, NY 14642, USA
| | - Sheng-Hu Guo
- Department of Immunotherapy, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
| | - Zhi-Yu Wang
- Department of Immunotherapy, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
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Canbay E, Mizumoto A, Ichinose M, Ishibashi H, Sako S, Hirano M, Takao N, Yonemura Y. Outcome data of patients with peritoneal carcinomatosis from gastric origin treated by a strategy of bidirectional chemotherapy prior to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in a single specialized center in Japan. Ann Surg Oncol 2013; 21:1147-52. [PMID: 24356799 DOI: 10.1245/s10434-013-3443-2] [Citation(s) in RCA: 84] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2013] [Indexed: 12/20/2022]
Abstract
BACKGROUND Management of peritoneal disseminated gastric cancer (GC) remains a challenging problem. The purpose of our study was to evaluate the outcome of bidirectional induction chemotherapy [bidirectional intraperitoneal and systemic induction chemotherapy (BIPSC)] in patients with peritoneal carcinomatosis (PC) arising from GC who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). PATIENTS AND METHODS Overall, 194 patients with PC arising from GC were treated with BIPSC comprising intraperitoneal docetaxel at a dose of 20 mg/m(2) and cisplatin at a dose of 30 mg/m(2) followed by four cycles of oral S-1 at a dose of 60 mg/m(2). CRS and HIPEC were performed in responders to BIPSC. RESULTS Of these 194 patients, 152 (78.3 %) underwent CRS and HIPEC between January 2005 and December 2012. Treatment-related mortality was 3.9 %, and major complications occurred in 23.6 % of patients. The median survival rate was 15.8 months, with 1-, 2-, and 5-year survival rates of 66, 32 and 10.7 %, respectively, in the patients treated with combined treatment. Multivariate analysis identified pathologic response to BIPSC (p = 0.001), low tumor burden [peritoneal cancer index (PCI) ≤ 6] (p = 0.001), and completeness of CRS (CC-0, CC-1) (p = 0.001) as independent predictors for a better prognosis. CONCLUSION As a viable option, BIPSC with CRS and HIPEC for patients with PC arising from GC may be performed safely, with acceptable morbidity and mortality, in a specialized unit. Response to BIPSC, optimal CRS and limited peritoneal dissemination seem to be essential to achieve the best outcomes in these patients.
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Affiliation(s)
- Emel Canbay
- NPO to Support Peritoneal Dissemination Treatment, Department of General Surgery, Tokushu-Kai Hospital, Kishiwada, Osaka, Japan,
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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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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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Kim KW, Chow O, Parikh K, Blank S, Jibara G, Kadri H, Labow DM, Hiotis SP. Peritoneal carcinomatosis in patients with gastric cancer, and the role for surgical resection, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy. Am J Surg 2013; 207:78-83. [PMID: 24157224 DOI: 10.1016/j.amjsurg.2013.04.010] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2012] [Revised: 03/21/2013] [Accepted: 04/24/2013] [Indexed: 01/26/2023]
Abstract
BACKGROUND The aims of this study were to create a model of peritoneal carcinomatosis in patients with gastric cancer and to evaluates outcomes in patients with gastric cancer treated using surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS A single-institution cohort of patients with gastric cancer was analyzed according to the development of gastric cancer with peritoneal carcinomatosis (GCPC). Variables were evaluated using regression analysis. Kaplan-Meier analysis was used to evaluate outcomes after surgical resection, cytoreductive surgery, and HIPEC. RESULTS Age ≤60 years and local tumor stage (T3/T4) were significantly associated with GCPC (odds ratio, 3.95 and 3.94, respectively). Thirty-six-month survival was 57% for patients without peritoneal disease and 39% for patients with GCPC. There was no significant trend of improved survival after surgical management or HIPEC. CONCLUSIONS Age ≤60 years and T3/T4 tumor stage are risk factors for GCPC. Intermediate-term survival of patients with GCPC treated with surgical resection or cytoreductive surgery and HIPEC was not improved, though future research should address the possible benefits of aggressive approaches to the treatment of GCRC.
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Affiliation(s)
- Ki Won Kim
- Department of Surgery, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA
| | - Oliver Chow
- Department of Surgery, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ, USA
| | - Kunal Parikh
- Department of Physical Medicine and Rehabilitation, SUNY Upstate Medical University, Syracuse, NY, USA
| | - Sima Blank
- Department of Surgery, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA
| | - Ghalib Jibara
- Department of Surgery, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA
| | - Hena Kadri
- Department of Surgery, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA
| | - Daniel M Labow
- Department of Surgery, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA
| | - Spiros P Hiotis
- Department of Surgery, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
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40
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Feng Q, Pei W, Zheng ZX, Bi JJ, Yuan XH. Clinicopathologic characteristics and prognostic factors of 63 gastric cancer patients with metachronous ovarian metastasis. Cancer Biol Med 2013. [PMID: 23882423 DOI: 0.7497/j.issn.2095-3941.2013.02.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE This study aims to explore the clinicopathologic characteristics and prognostic factors of gastric cancer patients with metachronous ovarian metastasis. METHODS Clinicopathologic data were collected from 63 post-operative gastric cancer patients with metachronous ovarian metastasis. The patients were admitted to the Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College between January 1999 and December 2011. A log-rank test was conducted for survival analysis. Possible prognostic factors that affect survival were examined by univariate analysis. A Cox regression model was used for multivariate analysis. RESULTS The incidence of ovarian metastasis was 3.4% with a mean age of 45 years. Up to 65.1% of the patients were pre-menopausal. The mean interval between ovarian metastasis and primary cancer was 16 months. Lowly differentiated carcinoma ranked first in the primary gastric cancers. The majority of lesions occurred in the serous membrane (87.3%). The metastatic sites included N2-3 lymph nodes (68.3%), bilateral ovaries (85.7%), and peritoneal membrane (73%). Total resection of metastatic sites was performed (31.7%). The overall median survival was 13.6 months, whereas the overall 1-, 2-, and 3-year survival rates were 52.5%, 22.0%, and 9.8%, respectively. The 5-year survival rate was zero. Univariate analysis showed that the patient prognosis was correlated with metastatic peritoneal seeding, vascular tumor embolus, range of lesion excision, and mode of comprehensive treatment with adjuvant chemotherapy (P<0.05). Multivariate analysis indicated that metastatic peritoneal seeding was an independent prognostic factor for gastric cancer patients with ovarian metastasis (P<0.01). CONCLUSION Effective control of peritoneal seeding-induced metastasis is important for improving the prognosis of gastric cancer patients with ovarian metastasis.
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Affiliation(s)
- Qiang Feng
- Department of Abdominal Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China
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41
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Feng Q, Pei W, Zheng ZX, Bi JJ, Yuan XH. Clinicopathologic characteristics and prognostic factors of 63 gastric cancer patients with metachronous ovarian metastasis. Cancer Biol Med 2013; 10:86-91. [PMID: 23882423 PMCID: PMC3719191 DOI: 10.7497/j.issn.2095-3941.2013.02.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2013] [Accepted: 06/07/2013] [Indexed: 11/25/2022] Open
Abstract
Objective This study aims to explore the clinicopathologic characteristics and prognostic factors of gastric cancer patients with metachronous ovarian metastasis. Methods Clinicopathologic data were collected from 63 post-operative gastric cancer patients with metachronous ovarian metastasis. The patients were admitted to the Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College between January 1999 and December 2011. A log-rank test was conducted for survival analysis. Possible prognostic factors that affect survival were examined by univariate analysis. A Cox regression model was used for multivariate analysis. Results The incidence of ovarian metastasis was 3.4% with a mean age of 45 years. Up to 65.1% of the patients were pre-menopausal. The mean interval between ovarian metastasis and primary cancer was 16 months. Lowly differentiated carcinoma ranked first in the primary gastric cancers. The majority of lesions occurred in the serous membrane (87.3%). The metastatic sites included N2-3 lymph nodes (68.3%), bilateral ovaries (85.7%), and peritoneal membrane (73%). Total resection of metastatic sites was performed (31.7%). The overall median survival was 13.6 months, whereas the overall 1-, 2-, and 3-year survival rates were 52.5%, 22.0%, and 9.8%, respectively. The 5-year survival rate was zero. Univariate analysis showed that the patient prognosis was correlated with metastatic peritoneal seeding, vascular tumor embolus, range of lesion excision, and mode of comprehensive treatment with adjuvant chemotherapy (P<0.05). Multivariate analysis indicated that metastatic peritoneal seeding was an independent prognostic factor for gastric cancer patients with ovarian metastasis (P<0.01). Conclusion Effective control of peritoneal seeding—induced metastasis is important for improving the prognosis of gastric cancer patients with ovarian metastasis.
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Affiliation(s)
- Qiang Feng
- Department of Abdominal Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China
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Hultman B, Lind P, Glimelius B, Sundbom M, Nygren P, Haglund U, Mahteme H. Phase II study of patients with peritoneal carcinomatosis from gastric cancer treated with preoperative systemic chemotherapy followed by peritonectomy and intraperitoneal chemotherapy. Acta Oncol 2013; 52:824-30. [PMID: 22974074 DOI: 10.3109/0284186x.2012.702925] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND The aim was to evaluate the feasibility and the effectiveness of neoadjuvant systemic chemotherapy followed by cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC) in patients with peritoneal carcinomatosis (PC) from gastric cancer. MATERIAL AND METHODS Eighteen patients (median age 57 years, range 38-74) were scheduled for three months' neoadjuvant systemic chemotherapy followed by CRS + HIPEC + EPIC. RESULTS At the time of surgery, the peritoneal tumor burden was extensive with tumor growth on the entire peritoneal cavity. Only eight patients received the entire treatment and OS was 14.3 months (range 6.1-34.3, 95% CI 6.6-20.3). Six patients had macroscopically radical (CC0) surgery and for this subgroup OS was 19.1 months (range 6.1-34.3, 95% CI 6.9-27.1). Postoperative 90-day mortality was 10% (one patient) and the perioperative grades II-IV adverse events (AE) rate was 62.5%. DISCUSSION Neoadjuvant chemotherapy followed by CRS + HIPEC + EPIC does not seem to be associated with prolonged OS in patients with extensive PC growth from gastric cancer unless macroscopically radical surgery is achieved. However, morbidity from this treatment is considerable and it cannot be recommended for routine care until a prospective randomized trial has been performed.
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Affiliation(s)
- Bo Hultman
- Department of Surgical Sciences, Section of Surgery, Uppsala University, Uppsala, Sweden.
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Wei Z, Jiang X, Liu F, Qiao H, Zhou B, Zhai B, Zhang L, Zhang X, Han L, Jiang H, Krissansen GW, Sun X. Downregulation of Skp2 inhibits the growth and metastasis of gastric cancer cells in vitro and in vivo. Tumour Biol 2013; 34:181-192. [PMID: 23229098 DOI: 10.1007/s13277-012-0527-8] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2012] [Accepted: 09/17/2012] [Indexed: 01/14/2023] Open
Abstract
S-phase kinase-associated protein-2 (Skp2) is overexpressed in human cancers and associated with poor prognosis. Skp2 acts as an oncogenic protein by enhancing cancer cell growth and tumor metastasis. The present study has demonstrated that small hairpin RNA (shRNA)-mediated downregulation of Skp2 markedly inhibits the viability, proliferation, colony formation, migration, invasion, and apoptosis of human gastric cancer MGC803 cells, which express a high level of Skp2. In contrast, Skp2 shRNA had only a slight effect on the above properties of BGC823 cells, which express a low level of Skp2. In accord, knockdown of Skp2 suppressed the ability of MGC803 cells to form tumors and to metastasize to the lungs of mice, and the growth of established tumors, by inhibiting cell proliferation and enhancing cell apoptosis. In contrast, overexpression of Skp2 promoted tumorigenesis of BGC823 cells in mice. Skp2 depletion induced cell cycle arrest in the G(1)/S phase by upregulating p27, p21, and p57 and downregulating cyclin E and cyclin-dependent kinase 2. Skp2 depletion also increased caspase-3 activity, impeded the ability of cells to form filopoidia and locomote, upregulated RECK (reversion-inducing cysteine-rich protein with kazal motifs), and downregulated matrix metalloproteinase (MMP)-2 and MMP-9 activity and expression. The results suggest that downregulating Skp2 warrants investigation as a promising strategy to treat gastric cancers that express high levels of Skp2.
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Affiliation(s)
- Zheng Wei
- The Hepatosplenic Surgery Center, Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
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Benizri EI, Bereder JM, Rahili A, Bernard JL, Benchimol D. Ascites and malnutrition are predictive factors for incomplete cytoreductive surgery for peritoneal carcinomatosis from gastric cancer. Am J Surg 2013; 205:668-73. [PMID: 23369310 DOI: 10.1016/j.amjsurg.2012.06.009] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2012] [Revised: 05/03/2012] [Accepted: 06/17/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND Prognosis in peritoneal carcinomatosis from gastric cancer has improved with cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy. The aim of this study was to identify predictive factors for incomplete CS. METHODS Forty-five patients undergoing laparotomy for gastric cancer with peritoneal carcinomatosis were prospectively included from January 2000 to December 2010. In case of optimal CS, patients (n = 14) received hyperthermic intraperitoneal chemotherapy. Otherwise, the laparotomy was closed or a palliative procedure was performed if necessary. All preoperative data were compared between the 2 groups. RESULTS Ascites (hazard ratio, .09; 95% confidence interval, .010-.48; P = .0103) and nutritional status evaluated by the prognostic nutrition index (hazard ratio, .11; 95% confidence interval, .0019-.54; P = .027) were independent predictive factors for incomplete CS. CONCLUSIONS The selection of patients for CS plus hyperthermic intraperitoneal chemotherapy should include the assessment of nutritional status and the detection of an ascites.
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Affiliation(s)
- Emmanuel I Benizri
- Department of General Surgery and Digestive Cancerology, Centre Hospitalier Universitaire de Nice, Hôpital de l'Archet 2, Nice, France.
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Phase II study of single intraperitoneal chemotherapy followed by systemic chemotherapy for gastric cancer with peritoneal metastasis. J Gastrointest Surg 2012; 16:2190-6. [PMID: 23099736 DOI: 10.1007/s11605-012-2059-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2012] [Accepted: 10/12/2012] [Indexed: 01/31/2023]
Abstract
BACKGROUND We conducted a phase II study involving a single administration of intraperitoneal chemotherapy with paclitaxel followed by sequential systemic chemotherapy with S-1+ paclitaxel for advanced gastric cancer patients with peritoneal metastasis. METHODS Gastric cancer patients with peritoneal metastasis were enrolled. Paclitaxel (80 mg/m(2)) was administered intraperitoneally at staging laparoscopy. Within 7 days, patients received systemic chemotherapy with S-1 (80 mg/m(2)/day on days 1-14) plus paclitaxel (50 mg/m(2) on days 1 and 8), followed by 7-days rest. The responders to this chemotherapy underwent second-look laparoscopy, and gastrectomy with D2 lymph node dissection was performed in patients when the disappearance of peritoneal metastasis had been confirmed. The primary endpoint of the study was overall survival rate. RESULTS Thirty-five patients were enrolled. All patients were confirmed as having localized peritoneal metastasis by staging laparoscopy. Eventually, gastrectomy was performed in 22 patients. The median survival time of the total patient population and those patients in which gastrectomy was performed was 21.3 and 29.8 months, respectively. The overall response rate was 65.7 % for all patients. The frequent grade 3/4 toxic effects included neutropenia and leukopenia. CONCLUSIONS Sequential intraperitoneal and intravenous paclitaxel plus S-1 was well tolerated in gastric cancer patients with peritoneal metastasis.
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Kusamura S, Baratti D, Virzì S, Bonomi S, Iusco DR, Grassi A, Hutanu I, Deraco M. Learning curve for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal surface malignancies: analysis of two centres. J Surg Oncol 2012; 107:312-9. [PMID: 22926536 DOI: 10.1002/jso.23231] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2012] [Accepted: 07/10/2012] [Indexed: 12/27/2022]
Abstract
BACKGROUND We assessed the learning curve (LC) of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in treating peritoneal surface malignancies (PSM) in two centers and evaluated in which extent surgical tutoring could abbreviate the learning process. METHODS Six hundred and forty-one cases submitted to CRS using peritonectomy procedures and HIPEC were considered. After having overcome its own LC, the NCI of Milan has provided technical assistance to Bentivoglio's centre for the development of a new PSM program since 2003. The risk-adjusted sequential probability ratio test (RA-SPRT) was employed to assess the LC of the two centers. Outcomes were incomplete cytoreduction, G3-5 morbidity (NCI-CTCAE.v3) and procedure-related mortality (PRM). RESULTS Rates of incomplete cytoreduction, G3-5 morbidity, and PRM were 8.4%, 30.1%, and 3.9%, respectively, in the entire series. The breaking points of the LC concerning incomplete cytoreduction, G3-5 morbidity, and PRM were achieved at 141, 158, and 144 cases, in the Milan's experience, and at 126, 134, and 60 cases in the Bentivoglio's experience. CONCLUSIONS Surgical tutoring could substantially shorten the steep LC associated with CRS and HIPEC. Our data should be confirmed by further studies on LC focusing oncological outcomes. Other factors that could influence the length of learning process should be identified.
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Affiliation(s)
- Shigeki Kusamura
- Peritoneal Surface Malignancy Program, Department of Surgery, National Cancer Institute, Milan, Italy
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Sun X, Zhang X, He C, Qiao H, Jiang X, Jiang H, Sun X. ABT-737 Synergizes with Arsenic Trioxide to Induce Apoptosis of Gastric Carcinoma Cells In Vitro and In Vivo. J Int Med Res 2012; 40:1251-64. [PMID: 22971477 DOI: 10.1177/147323001204000404] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
OBJECTIVE: This study investigated the potential synergistic effects of two inducers of apoptosis: the small molecule ABT-737 and arsenic trioxide (ATO). METHODS: Human gastric carcinoma cell lines SGC-7901 and MGC-803 were used to determine the effects of ABT-737 and ATO (alone or in combination) on cell proliferation and apoptosis in vitro. In vivo effects of these drugs were investigated in SGC-7901 solid tumours, grown in immunodeficient mice. RESULTS: ABT-737 and ATO inhibited proliferation and induced apoptosis in SGC-7901 and MGC-803 cells in concentration- and time-dependent manners, and showed a synergistic effect. ABT-737 disturbed the binding of B cell lymphoma (Bcl)-2 homologous antagonist killer and Bcl-extra large; ATO downregulated myeloid cell leukaemia (Mcl)-1 protein and upregulated Mcl-1short, the short splicing variant. ABT-737 and ATO significantly suppressed SGC-7901 xenograft growth, synergistically inhibited tumour growth and induced apoptosis in vivo. CONCLUSIONS: This study provides preclinical evidence that ABT-737 and ATO synergize to induce apoptosis of gastric carcinoma cells, suggesting that further investigation of these agents (as potential treatments for gastric cancer) is warranted.
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Affiliation(s)
- Xp Sun
- Department of General Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - X Zhang
- Department of General Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - C He
- Department of General Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - H Qiao
- Department of General Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - X Jiang
- Department of General Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - H Jiang
- Department of General Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - X Sun
- Department of General Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, China
- Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
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Role of vascular endothelial growth factor (VEGF) and VEGF-R genotyping in guiding the metastatic process in pT4a resected gastric cancer patients. PLoS One 2012; 7:e38192. [PMID: 22808003 PMCID: PMC3392267 DOI: 10.1371/journal.pone.0038192] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2012] [Accepted: 05/01/2012] [Indexed: 12/20/2022] Open
Abstract
In radically resected gastric cancer the possibility to predict the site of relapse could be clinically relevant for the selection of post-surgical management. We previously showed that specific tumour integrins genotypes are independently associated with either peritoneal or hematogenous metastases (ITGA and ITGV). Recently VEGF and VEGF-R polymorphisms have been demonstrated to potentially affect tumour angiogenesis and the metastatic process in gastric cancer. We then investigated the role of VEGFs and VEGF-R genotyping in determining either peritoneal carcinosis or hematogenous metastases in radically resected gastric cancer patients. Tumour genotyping for integrins (ITGA and ITGV) was also performed according to our previous findings. Genotyping for VEGF-A, VEGF-C, VEGFR-1,2,3 and ITGA and ITGV was carried out on pT4a radically resected gastric tumours recurring with either peritoneal-only carcinosis or hematogenous metastases. 101 patients fulfilled the inclusion criteria: 57 with peritoneal carcinomatosis only and 44 with hematogenous spread only. At multivariate analysis, intestinal histology and the AC genotype of rs699947 (VEGFA) showed to independently correlate with hematogenous metastases (p = 0.0008 and 0.008 respectively), whereas diffuse histology and the AA genotype of rs2269772 (ITGA) independently correlated with peritoneal-only diffusion (p = <0.0001 and 0.03 respectively). Our results seem to indicate that combining information from genotyping of rs699947 (VEGFA, AC), rs2269772 (ITGA, AA) and tumour histology could allow clinicians to individuate gastric cancer at high risk for recurrence either with peritoneal or hematogenous metastases. The selection tool deriving from this analysis may allow an optimal use of the available treatment strategies in these patients.
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Brücher BLDM, Piso P, Verwaal V, Esquivel J, Derraco M, Yonemura Y, Gonzalez-Moreno S, Pelz J, Königsrainer A, Ströhlein M, Levine EA, Morris D, Bartlett D, Glehen O, Garofalo A, Nissan A. Peritoneal carcinomatosis: cytoreductive surgery and HIPEC--overview and basics. Cancer Invest 2012; 30:209-24. [PMID: 22360361 DOI: 10.3109/07357907.2012.654871] [Citation(s) in RCA: 76] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Tumor involvement of the peritoneum-peritoneal carcinomatosis-is a heterogeneous form of cancer that had been generally regarded as a sign of systemic tumor disease and as a terminal condition. The multimodal treatment approach for patients with peritoneal carcinomatosis, which had been conceived and developed, consists of what is known as cytoreductive surgery, followed by hyperthermic intraperitoneal chemotherapy (HIPEC). Depending on the tumor mass as assessed intraoperatively and the histopathological differentiation, patients who undergo cytoreductive surgery and HIPEC have a significant survival benefit. Mean increases in the survival period ranging from six months to up to four years have now been reported. In view of the substantial logistic effort and the extent of the surgery involved, this treatment approach represents a major challenge both for patients and for surgical oncologists, as well as for the members of the overall interdisciplinary structure required, which includes oncology, anesthesiology and intensive care, psycho-oncology, and patient management. The surgical procedures alone may take 8-14 hr. The present paper provides an overview of the basis for the approach and the use of specialized classifications and quantitative prognostic indicators.
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Affiliation(s)
- Björn L D M Brücher
- Surgical Oncology, Department of Surgery, Tübingen Comprehensive Cancer Center, University of Tübingen, Germany.
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50
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Hultman B, Lundkvist J, Glimelius B, Nygren P, Mahteme H. Costs and clinical outcome of neoadjuvant systemic chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from gastric cancer. Acta Oncol 2012; 51:112-21. [PMID: 22070666 DOI: 10.3109/0284186x.2011.594809] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND The costs for loco-regional treatment of peritoneal carcinomatosis from gastric cancer are not well investigated. The aims of this study were to evaluate the costs and clinical outcome of systemic chemotherapy followed by cytoreductive surgery and intraperitoneal chemotherapy compared to systemic chemotherapy only in patients with peritoneal carcinomatosis from gastric cancer. MATERIAL AND METHODS Ten patients were scheduled for systemic chemotherapy followed by loco-regional treatment. A reference group of 10 matched control patients treated with systemic chemotherapy only were used and both groups were evaluated with respect to clinical outcome and cost. RESULTS The mean overall cost in the loco-regional group was $145,700 (range $49,900-$487,800) and $59,300 (range $23,000-$94,800) for the control group. The mean overall survival for the loco-regional group was 17.4 months (range 6.0-34.3), and 11.1 months (range 0.1-24.2) for the systemic chemotherapy only group. The gain in life-years was 0.52 and in quality-adjusted life-years 0.49, leading to incremental cost per life-year and quality-adjusted life-years gained of $166,716 and $175,164, for loco-regional group compared to systemic chemotherapy. DISCUSSION Treatment of peritoneal carcinomatosis from gastric cancer is costly irrespective of treatment modality. If the survival benefit from adding loco-regional treatment to systemic chemotherapy indicated from this comparison is true, the incremental cost is considered high.
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Affiliation(s)
- Bo Hultman
- Department of Surgical Sciences, Section of Surgery, Uppsala University, Sweden.
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