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Guchelaar NA, de Neijs MJ, Noordman BJ, Graaf HE, van Hellemond IE, van der Sluis PC, Hoop EOD, Lagarde SM, Verhoeven RH, Koolen SL, Luyer MD, de Hingh IH, van Laarhoven HW, Mostert B, Wijnhoven BP, Mathijssen RH. The prognostic value of peritoneal metastases in patients with gastric cancer: a nationwide population-based study. EClinicalMedicine 2025; 81:103109. [PMID: 40026831 PMCID: PMC11872448 DOI: 10.1016/j.eclinm.2025.103109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Revised: 01/14/2025] [Accepted: 01/28/2025] [Indexed: 03/03/2025] Open
Abstract
Background The peritoneum is a common metastatic site in gastric cancer. The prognosis of synchronous peritoneal metastases compared to other metastatic sites in gastric cancer remains understudied. This study aims to evaluate the impact of peritoneal metastases on survival in patients with metastatic gastric cancer. Methods Patients with gastric cancer and synchronous metastases between 2015 and 2020 were identified from the nationwide Netherlands Cancer Registry. Patients were categorized based on the site of metastases. Median overall survival (OS) was calculated for each metastatic site group. Multivariable Cox regression analyses were performed to evaluate the association between patient, tumour, and treatment characteristics, including the impact of systemic therapy, on OS. Findings A total of 4072 patients were included, of whom 1835 (45.1%) had peritoneal metastases. Of these, 58.1% had isolated peritoneal metastases. For patients with metastatic gastric cancer treated with systemic therapy, the median OS was 9.0 months (95% confidence interval (CI): 8.6-9.5), compared to 1.7 months (95% CI: 1.7-1.9) for treatment-naïve patients, who received only palliative care. The survival for patients with isolated peritoneal metastases (4.4 months, 95% CI: 4.0-4.8 months) was similar to those with isolated non-peritoneal metastases (4.6 months, 95% CI: 4.2-5.1 months, adjusted HR: 0.94, 95% CI: 0.86-1.03, p = 0.185). Systemic therapy was associated with comparable survival in patients with peritoneal metastases and those with metastases at other sites. Interpretation This study demonstrates that there is no statistically significant difference in survival between patients with isolated peritoneal metastases and those with isolated non-peritoneal metastases in gastric cancer. Our findings emphasize the unique prognostic landscape for peritoneal metastases in gastric cancer, underscoring the need for disease-specific evaluations, rather than relying on assumptions derived from other cancer types. Funding None.
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Affiliation(s)
- Niels A.D. Guchelaar
- Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, Rotterdam, the Netherlands
| | - Micha J. de Neijs
- Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, Rotterdam, the Netherlands
- Department of Surgery, Division of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Bo J. Noordman
- Department of Surgery, Division of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Heilida E.C. Graaf
- Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, Rotterdam, the Netherlands
| | | | - Pieter C. van der Sluis
- Department of Surgery, Division of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Esther Oomen-de Hoop
- Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, Rotterdam, the Netherlands
| | - Sjoerd M. Lagarde
- Department of Surgery, Division of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Rob H.A. Verhoeven
- Department of Research & Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands
- Cancer Centre Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, the Netherlands
- Department of Medical Oncology, Amsterdam UMC Location University of Amsterdam, Amsterdam, the Netherlands
| | - Stijn L.W. Koolen
- Department of Pharmacy, Erasmus Medical Centre, Rotterdam, the Netherlands
| | - Misha D.P. Luyer
- Department of Surgery, Catharina Cancer Institute, Eindhoven, the Netherlands
| | - Ignace H.J.T. de Hingh
- Department of Surgery, Catharina Cancer Institute, Eindhoven, the Netherlands
- Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands
| | - Hanneke W.M. van Laarhoven
- Cancer Centre Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, the Netherlands
- Department of Medical Oncology, Amsterdam UMC Location University of Amsterdam, Amsterdam, the Netherlands
| | - Bianca Mostert
- Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, Rotterdam, the Netherlands
| | - Bas P.L. Wijnhoven
- Department of Surgery, Division of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Ron H.J. Mathijssen
- Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, Rotterdam, the Netherlands
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Gingrich A, Manguso N, Zuckerman R. Treatment of Gastric Cancer Carcinomatosis. Surg Clin North Am 2025; 105:95-107. [PMID: 39523079 DOI: 10.1016/j.suc.2024.06.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
Patients with gastric cancer peritoneal metastases (GCPM) have Stage IV disease. Systemic therapy is a crucial aspect of their care. Patients with GCPM should have their tumors tested for HER2 and PD-L1 expression and microsatellite instability for potential targeted therapies. If patients with synchronous GCPM have stable disease following neoadjuvant therapy, surgical intervention can be considered. Patients with positive cytology or low-volume peritoneal disease (peritoneal carcinomatosis index [PCI] < 7) may "convert" to negative cytology or resolution of peritoneal metastases following intraperitoneal therapy and may be candidates for subsequent gastrectomy.
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Affiliation(s)
- Alicia Gingrich
- Division of Surgery, Department of Surgical Oncology, MD Anderson Cancer Center, Houston, TX 77025, USA
| | - Nicholas Manguso
- Division of Surgical Oncology, Department of Surgery, University of Nevada Reno/Renown Integrated Health System, 1500 East 2nd Street, Suite 300, Reno, NV 89502, USA
| | - Randall Zuckerman
- Division of Surgical Oncology, Department of Surgery, University of Nevada Reno/Renown Integrated Health System, 1500 East 2nd Street, Suite 300, Reno, NV 89502, USA.
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Krell M, Ranjbar S, Gitlin S, Alvarez Vega DR, Wilson R, Thrasher K, Brown ZJ. Evolution in the Surgical Management of Gastric Cancer Peritoneal Metastases. Cancers (Basel) 2024; 17:100. [PMID: 39796727 PMCID: PMC11719528 DOI: 10.3390/cancers17010100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 12/26/2024] [Accepted: 12/27/2024] [Indexed: 01/13/2025] Open
Abstract
Despite therapeutic treatments and the growing utilization of multimodal therapies, gastric cancer (GC) remains a highly aggressive malignancy with high mortality worldwide. Much of the complexity in treating GC is due to the high incidence of peritoneal metastasis (PM), with mean overall survival typically ranging from 4 to 10 months. With current systemic therapy, targeted therapies, and immunotherapies continuing to remain ineffective for GC/PM, there has been a significant growing interest in intraperitoneal (IP) therapies for the treatment of GC/PM. In this review, we summarize the development of PM and evolving treatment strategies for GC/PM. Furthermore, we explore the various advancements and outcomes of IP therapies, including heated intraperitoneal chemotherapy (HIPEC), neoadjuvant HIPEC, and pressurized intraperitoneal aerosolized chemotherapy (PIPAC).
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Affiliation(s)
| | | | | | | | | | | | - Zachary J. Brown
- Department of Surgery, Division of Surgical Oncology, NYU Langone Health, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA; (M.K.); (S.G.); (D.R.A.V.); (R.W.); (K.T.)
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4
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Wang J, Zhang H, Li J, Ni X, Yan W, Chen Y, Shi T. Exosome-derived proteins in gastric cancer progression, drug resistance, and immune response. Cell Mol Biol Lett 2024; 29:157. [PMID: 39719600 PMCID: PMC11667977 DOI: 10.1186/s11658-024-00676-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 12/09/2024] [Indexed: 12/26/2024] Open
Abstract
Gastric cancer (GC) represents a prevalent malignancy globally, often diagnosed at advanced stages owing to subtle early symptoms, resulting in a poor prognosis. Exosomes are extracellular nano-sized vesicles and are secreted by various cells. Mounting evidence indicates that exosomes contain a wide range of molecules, such as DNA, RNA, lipids, and proteins, and play crucial roles in multiple cancers including GC. Recently, with the rapid development of mass spectrometry-based detection technology, researchers have paid increasing attention to exosomal cargo proteins. In this review, we discussed the origin of exosomes and the diagnostic and prognostic roles of exosomal proteins in GC. Moreover, we summarized the biological functions of exosomal proteins in GC processes, such as proliferation, metastasis, drug resistance, stemness, immune response, angiogenesis, and traditional Chinese medicine therapy. In summary, this review synthesizes current advancements in exosomal proteins associated with GC, offering insights that could pave the way for novel diagnostic and therapeutic strategies for GC in the foreseeable future.
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Affiliation(s)
- Jiayu Wang
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 178 East Ganjiang Road, Suzhou, 215000, China
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Huan Zhang
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 178 East Ganjiang Road, Suzhou, 215000, China
| | - Juntao Li
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Xiangyu Ni
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 178 East Ganjiang Road, Suzhou, 215000, China
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Wenying Yan
- Department of Bioinformatics, School of Biology and Basic Medical Sciences, Suzhou Medical College of Soochow University, 199 Renai Road, Suzhou, 215123, China.
- Center for Systems Biology, Soochow University, Suzhou, China.
- Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development, Suzhou, China.
| | - Yueqiu Chen
- Department of Cardiovascular Surgery of The First Affiliated Hospital and Institute for Cardiovascular Science, Suzhou Medical College of Soochow University, Soochow University, Suzhou, 215007, China.
| | - Tongguo Shi
- Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 178 East Ganjiang Road, Suzhou, 215000, China.
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China.
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Alberto V. ME, Zuluaga D, Winter A, Pratschke J, Rau B, Gül S. Complications After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy - Can We Do Better? J Surg Oncol 2024; 130:1403-1421. [PMID: 39558543 PMCID: PMC11826034 DOI: 10.1002/jso.27988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 08/31/2024] [Indexed: 11/20/2024]
Abstract
The main aim of this review is to analyze postoperative complications after cytoreductive surgery and intraperitoneal chemotherapy. Although the literature in this field is ever growing, reporting on complication is not a given. Nevertheless, some main risk factors such as prior surgery, high tumor burden and the center's expertize have an impact on patient outcomes. Transparency is key, if we want to continue to improve.
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Affiliation(s)
| | - Daniela Zuluaga
- Surgical DepartmentCharité – Universitätsmedizin BerlinBerlinGermany
| | - Axel Winter
- Surgical DepartmentCharité – Universitätsmedizin BerlinBerlinGermany
| | - Johann Pratschke
- Surgical DepartmentCharité – Universitätsmedizin BerlinBerlinGermany
| | - Beate Rau
- Surgical DepartmentCharité – Universitätsmedizin BerlinBerlinGermany
| | - Safak Gül
- Surgical DepartmentCharité – Universitätsmedizin BerlinBerlinGermany
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Carboni F, Corona F, Zazza S. Letter to Editor Regarding Article "Initial Experience Using Laparoscopic HIPEC for Gastric Cancer with Peritoneal Metastasis: Safety and Outcomes". Ann Surg Oncol 2024; 31:6979-6980. [PMID: 39068308 DOI: 10.1245/s10434-024-15865-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 07/08/2024] [Indexed: 07/30/2024]
Affiliation(s)
- Fabio Carboni
- Peritoneal Tumour Unit, IRCCS Regina Elena Cancer Institute, Rome, Italy.
| | - Francesco Corona
- Peritoneal Tumour Unit, IRCCS Regina Elena Cancer Institute, Rome, Italy
| | - Settimio Zazza
- Peritoneal Tumour Unit, IRCCS Regina Elena Cancer Institute, Rome, Italy
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Luksta M, Bausys A, Gendvilaite N, Bickaite K, Rackauskas R, Paskonis M, Luksaite-Lukste R, Ranceva A, Stulpinas R, Brasiuniene B, Baltruskeviciene E, Lachej N, Bausiene J, Poskus T, Bausys R, Tulyte S, Strupas K. Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) for Gastric Cancer Peritoneal Metastases: Results from the Lithuanian PIPAC Program. Cancers (Basel) 2024; 16:2992. [PMID: 39272850 PMCID: PMC11394265 DOI: 10.3390/cancers16172992] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 08/27/2024] [Accepted: 08/27/2024] [Indexed: 09/15/2024] Open
Abstract
BACKGROUND Peritoneal metastases (PM) of gastric cancer (GC) are considered a terminal condition, with reported median survival ranging from 2 to 9 months. Standard treatment typically involves systemic chemotherapy alone or combined with targeted therapy or immunotherapy, though efficacy is limited. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has emerged as a novel technique for treating GC PM, although it remains an experimental treatment under investigation. This study aimed to summarize the outcomes of GC PM treatment with PIPAC from the Lithuanian PIPAC program. METHODS All patients who underwent PIPAC for GC PM at Vilnius University Hospital Santaros Klinikos between 2015 and 2022 were included in this retrospective study. The safety of PIPAC was assessed by postoperative complications according to the Clavien-Dindo classification. Efficacy was evaluated based on the peritoneal carcinomatosis index (PCI), ascites dynamics throughout the treatment, and long-term outcomes. RESULTS In total, 32 patients underwent 71 PIPAC procedures. Intraoperative and postoperative morbidity related to PIPAC occurred after three (4.2%) procedures. Following PIPAC, there was a tendency towards a decrease in median PCI from 10 (Q1 3; Q3 13) to 7 (Q1 2; Q3 12), p = 0.75, and a decrease in median ascites volume from 1300 mL (Q1 500; Q3 3600) at the first PIPAC to 700 mL (Q1 250; Q3 4750) at the last PIPAC, p = 0.56; however, these differences were not statistically significant. The median overall survival after PM diagnosis was 12.5 months (95% CI 10-17), and the median survival after the first PIPAC procedure was 5 months (95% CI 4-10). CONCLUSIONS PIPAC is a safe and feasible treatment option for GC PM; however, well-designed prospective studies are needed to fully assess its efficacy.
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Affiliation(s)
- Martynas Luksta
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Augustinas Bausys
- Department of Abdominal Surgery and Oncology, National Cancer Institute, 08406 Vilnius, Lithuania
- Laboratory of Experimental Surgery and Oncology, Translational Health Research Institute, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Neda Gendvilaite
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Klaudija Bickaite
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Rokas Rackauskas
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Marius Paskonis
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Raminta Luksaite-Lukste
- Department of Radiology, Nuclear Medicine and Medical Physics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Anastasija Ranceva
- Hematology, Oncology, and Transfusion Medicine Center, Vilnius University Hospital Santaros Klinikos, 08410 Vilnius, Lithuania
| | - Rokas Stulpinas
- National Center of Pathology, Affiliate of Vilnius University Hospital Santaros Klinikos, 08406 Vilnius, Lithuania
| | - Birute Brasiuniene
- Department of Medical Oncology, National Cancer Institute, 08406 Vilnius, Lithuania
- Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Edita Baltruskeviciene
- Department of Medical Oncology, National Cancer Institute, 08406 Vilnius, Lithuania
- Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Nadezda Lachej
- Department of Medical Oncology, National Cancer Institute, 08406 Vilnius, Lithuania
| | - Juste Bausiene
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Tomas Poskus
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
- Laboratory of Experimental Surgery and Oncology, Translational Health Research Institute, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Rimantas Bausys
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
- Department of Abdominal Surgery and Oncology, National Cancer Institute, 08406 Vilnius, Lithuania
| | - Skaiste Tulyte
- Hematology, Oncology, and Transfusion Medicine Center, Vilnius University Hospital Santaros Klinikos, 08410 Vilnius, Lithuania
- Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Kestutis Strupas
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
- Laboratory of Experimental Surgery and Oncology, Translational Health Research Institute, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
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Jin S, Wang Q, Wei Y, Ju Y, Wang K. Patients With Gastric Cancer Who Undergo HIPEC Treatment and Have a Peritoneal Cancer Index of Less Than 12 Can Benefit From Surgery. Am J Ther 2024:00045391-990000000-00208. [PMID: 39167429 DOI: 10.1097/mjt.0000000000001798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/23/2024]
Affiliation(s)
- Shiyang Jin
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
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Wang J, Wang Y, Li J, Ying J, Mu Y, Zhang X, Zhou X, Sun L, Jiang H, Zhuo W, Shen Y, Zhou T, Liu X, Zhou Q. Neutrophil Extracellular Traps-Inhibiting and Fouling-Resistant Polysulfoxides Potently Prevent Postoperative Adhesion, Tumor Recurrence, and Metastasis. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2400894. [PMID: 38636448 DOI: 10.1002/adma.202400894] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 03/19/2024] [Indexed: 04/20/2024]
Abstract
Peritoneal metastasis (PM) is considered one of the most dreaded forms of cancer metastases for both patients and physicians. Aggressive cytoreductive surgery (CRS) is the primary treatment for peritoneal metastasis. Unfortunately, this intensive treatment frequently causes clinical complications, such as postoperative recurrence, metastasis, and adhesion formation. Emerging evidence suggests that neutrophil extracellular traps (NETs) released by inflammatory neutrophils contribute to these complications. Effective NET-targeting strategies thus show considerable potential in counteracting these complications but remain challenging. Here, one type of sulfoxide-containing homopolymer, PMeSEA, with potent fouling-resistant and NET-inhibiting capabilities, is synthesized and screened. Hydrating sulfoxide groups endow PMeSEA with superior nonfouling ability, significantly inhibiting protein/cell adhesion. Besides, the polysulfoxides can be selectively oxidized by ClO- which is required to stabilize the NETs rather than H2O2, and ClO- scavenging effectively inhibits NETs formation without disturbing redox homeostasis in tumor cells and quiescent neutrophils. As a result, PMeSEA potently prevents postoperative adhesions, significantly suppresses peritoneal metastasis, and shows synergetic antitumor activity with chemotherapeutic 5-Fluorouracil. Moreover, coupling CRS with PMeSEA potently inhibits CRS-induced tumor metastatic relapse and postoperative adhesions. Notably, PMeSEA exhibits low in vivo acute and subacute toxicities, implying significant potential for clinical postoperative adjuvant treatment.
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Affiliation(s)
- Jiafeng Wang
- Department of Pharmacology, and Department of Gastroenterology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China
- Department of Cell Biology, and Department of Gastroenterology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China
- Zhejiang Key Laboratory of Smart Biomaterials and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang, 310058, China
| | - Yechun Wang
- Department of Cell Biology, and Department of Gastroenterology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China
| | - Junjun Li
- Department of Cell Biology, and Department of Gastroenterology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China
| | - Jiajia Ying
- Department of Cell Biology, and Department of Gastroenterology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China
| | - Yongli Mu
- Department of Cell Biology, and Department of Gastroenterology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China
| | - Xuanhao Zhang
- Department of Cell Biology, and Department of Gastroenterology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China
| | - Xuefei Zhou
- Department of Cell Biology, and Department of Gastroenterology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China
| | - Leimin Sun
- Department of Cell Biology, and Department of Gastroenterology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China
| | - Haiping Jiang
- Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, China
| | - Wei Zhuo
- Department of Cell Biology, and Department of Gastroenterology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China
- Center for Medical Research and Innovation in Digestive System Tumors, Ministry of Education, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310020, China
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang, 310000, China
| | - Youqing Shen
- Zhejiang Key Laboratory of Smart Biomaterials and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang, 310058, China
| | - Tianhua Zhou
- Department of Cell Biology, and Department of Gastroenterology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China
- Center for Medical Research and Innovation in Digestive System Tumors, Ministry of Education, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310020, China
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang, 310000, China
| | - Xiangrui Liu
- Department of Pharmacology, and Department of Gastroenterology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China
- Zhejiang Key Laboratory of Smart Biomaterials and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang, 310058, China
- Center for Medical Research and Innovation in Digestive System Tumors, Ministry of Education, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310020, China
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang, 310000, China
| | - Quan Zhou
- Department of Cell Biology, and Department of Gastroenterology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China
- Zhejiang Key Laboratory of Smart Biomaterials and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang, 310058, China
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Li AY, Sedighim S, Tajik F, Khan AM, Radhakrishnan VK, Dayyani F, Senthil M. Regional Therapy Approaches for Gastric Cancer with Limited Peritoneal Disease. J Gastrointest Cancer 2024; 55:534-548. [PMID: 38277055 PMCID: PMC11186907 DOI: 10.1007/s12029-023-00994-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/25/2023] [Indexed: 01/27/2024]
Abstract
PURPOSE Despite advances in systemic therapy, outcomes of patients with gastric cancer (GC) peritoneal carcinomatosis (PC) remain poor, in part because of poor penetrance of systemic therapy into peritoneal metastasis due to the plasma-peritoneal barrier and anarchic intra-tumoral circulation. Hence, regional treatment approach with administration of chemotherapy directly into the peritoneal cavity (intraperitoneal, IP) under various conditions, combined with or without cytoreductive surgery (CRS) has remained an area of significant research interest. The purpose of this review is to provide high-level evidence for regional treatment approaches in the management of GCPC with limited peritoneal disease. METHODS A review of the current literature and ongoing clinical trials for regional IP therapies for GCPC was performed. Studies included in this review comprise of phase III randomized controlled trials, non-randomized phase II studies, high-impact retrospective studies, and active ongoing clinical trials for each available IP modality. RESULTS The three common IP approaches are heated intraperitoneal chemotherapy (HIPEC), normothermic intraperitoneal chemotherapy (NIPEC) and more recently introduced, pressurized intraperitoneal aerosolized chemotherapy (PIPAC). These IP approaches have been combined with systemic therapy and/or CRS with varying degrees of promising results, demonstrating evidence of improvements in survival rates and peritoneal disease control. Patient selection, optimization of systemic therapy, and completeness of cytoreduction have emerged as major factors influencing the design of contemporary and ongoing trials. CONCLUSION IP chemotherapy has a clear role in the management of patients with GCPC, and when combined with CRS in appropriately selected patients has the potential to significantly improve survival. Ongoing and upcoming IP therapy clinical trials hold great promise to shape the treatment paradigm for GCPC.
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Affiliation(s)
- Amy Y Li
- Department of Surgery, University of California, Irvine, 3800 Chapman Ave, Ste 7400, 92868, Orange, CA, USA
| | - Shaina Sedighim
- Department of Surgery, University of California, Irvine, 3800 Chapman Ave, Ste 7400, 92868, Orange, CA, USA
| | - Fatemeh Tajik
- Department of Surgery, University of California, Irvine, 3800 Chapman Ave, Ste 7400, 92868, Orange, CA, USA
| | - Aaqil M Khan
- Department of Surgery, University of California, Irvine, 3800 Chapman Ave, Ste 7400, 92868, Orange, CA, USA
| | - Vinodh K Radhakrishnan
- Department of Surgery, University of California, Irvine, 3800 Chapman Ave, Ste 7400, 92868, Orange, CA, USA
| | - Farshid Dayyani
- Department of Medicine, University of California, Irvine, Orange, USA
| | - Maheswari Senthil
- Department of Surgery, University of California, Irvine, 3800 Chapman Ave, Ste 7400, 92868, Orange, CA, USA.
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11
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Langellotti L, Fiorillo C, D’Annibale G, Panza E, Pacelli F, Alfieri S, Di Giorgio A, Santullo F. Efficacy of Cytoreductive Surgery (CRS) + HIPEC in Gastric Cancer with Peritoneal Metastasis: Systematic Review and Meta-Analysis. Cancers (Basel) 2024; 16:1929. [PMID: 38792007 PMCID: PMC11119026 DOI: 10.3390/cancers16101929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 05/11/2024] [Accepted: 05/16/2024] [Indexed: 05/26/2024] Open
Abstract
BACKGROUND Peritoneal carcinomatosis is one of deadliest metastatic patterns of gastric cancer, being associated with a median overall survival (OS) of 4 months. Up to now, palliative systemic chemotherapy (pSC) has been the only recommended treatment. The aim of this study is to evaluate a potential survival benefit after CRS + HIPEC compared to pSC. METHODS A systematic review was conducted according to the PRISMA guidelines in March 2024. Manuscripts reporting patients with peritoneal carcinomatosis from gastric cancer treated with CRS + HIPEC were included. A meta-analysis was performed, comparing the survival results between the CRS + HIPEC and pSC groups, and the primary outcome was the comparison in terms of OS. We performed random-effects meta-analysis of odds ratios (ORs). We assessed heterogeneity using the Q2 statistic. RESULTS Out of the 24 papers included, 1369 patients underwent CRS + HIPEC, with a median OS range of 9.8-28.2 months; and 103 patients underwent pSC, with a median OS range of 4.9-8 months. CRS + HIPEC was associated with significantly increased survival compared to palliative systemic chemotherapy (-1.8954 (95% CI: -2.5761 to -1.2146; p < 0.001). CONCLUSIONS CRS + HIPEC could provide survival advantages in gastric cancer peritoneal metastasis compared to pSC.
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Affiliation(s)
- Lodovica Langellotti
- General Surgery Department, Catholic University of the Sacred Hearth, 00168 Rome, Italy; (L.L.); (G.D.); (E.P.); (F.P.); (S.A.)
| | - Claudio Fiorillo
- Department of Digestive Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of the Sacred Hearth, 00168 Rome, Italy
| | - Giorgio D’Annibale
- General Surgery Department, Catholic University of the Sacred Hearth, 00168 Rome, Italy; (L.L.); (G.D.); (E.P.); (F.P.); (S.A.)
| | - Edoardo Panza
- General Surgery Department, Catholic University of the Sacred Hearth, 00168 Rome, Italy; (L.L.); (G.D.); (E.P.); (F.P.); (S.A.)
| | - Fabio Pacelli
- General Surgery Department, Catholic University of the Sacred Hearth, 00168 Rome, Italy; (L.L.); (G.D.); (E.P.); (F.P.); (S.A.)
- Department of Peritoneum and Retroperitoneum Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of the Sacred Hearth, 00168 Rome, Italy; (A.D.G.); (F.S.)
| | - Sergio Alfieri
- General Surgery Department, Catholic University of the Sacred Hearth, 00168 Rome, Italy; (L.L.); (G.D.); (E.P.); (F.P.); (S.A.)
- Department of Digestive Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of the Sacred Hearth, 00168 Rome, Italy
| | - Andrea Di Giorgio
- Department of Peritoneum and Retroperitoneum Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of the Sacred Hearth, 00168 Rome, Italy; (A.D.G.); (F.S.)
| | - Francesco Santullo
- Department of Peritoneum and Retroperitoneum Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of the Sacred Hearth, 00168 Rome, Italy; (A.D.G.); (F.S.)
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12
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Reese M, Eichelmann AK, Nowacki TM, Pascher A, Sporn JC. The role of cytoreductive surgery and HIPEC for the treatment of primary and secondary peritoneal malignancies-experience from a tertiary care center in Germany. Langenbecks Arch Surg 2024; 409:113. [PMID: 38589714 DOI: 10.1007/s00423-024-03309-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 04/03/2024] [Indexed: 04/10/2024]
Abstract
PURPOSE Peritoneal surface malignancies (PSM) are commonly known to have a dismal prognosis. Over the past decades, novel techniques such as cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC) have been introduced for the treatment of PSM which could improve the overall survival and quality of life of patients with PSM. The decision to proceed with CRS and HIPEC is often challenging due the complexity of the disease, the extent of the procedure, associated side effects, and potential risks. Here, we present our experience with CRS and HIPEC to add to the ongoing discussion about eligibility criteria, technical approach, and expected outcomes and contribute to the evolution of this powerful and promising tool in the multidisciplinary treatment of patients with primary and secondary PSM. METHODS A single-center retrospective chart review was conducted and included a total of 40 patients treated with CRS and HIPEC from April 2020 to September 2022 at the University Hospital Münster Department of Surgery. All patients had histologically confirmed primary or secondary peritoneal malignancies of various primary origins. RESULTS Our study included 22 patients with peritoneal metastases from gastric cancer (55%), 8 with pseudomyxoma peritonei (20%), 4 with mesothelioma of the peritoneum (10%), and 6 patients with PSM originating from other primary tumor locations. Median PCI at time of cytoreduction was 4 (0-25). Completeness of cytoreduction score was 0 in 37 patients (92.5%), 1 in two patients (5%), and 2 in one patient (2.5%). Median overall survival across all patients was 3.69 years. CONCLUSION Complete cytoreduction during CRS and HIPEC can be achieved for patients with low PCI, for patients with high PCI in low-grade malignancies, and even for patients with initially high PCI in high-grade malignancies following a significant reduction of cancer burden due to extensive preoperative treatment with PIPAC and systemic chemotherapy.
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Affiliation(s)
- Mikko Reese
- Department of General, Visceral and Transplant Surgery, University Hospital Münster, Waldeyerstraße 1, 48149, Münster, Germany
| | - Ann-Kathrin Eichelmann
- Department of General, Visceral and Transplant Surgery, University Hospital Münster, Waldeyerstraße 1, 48149, Münster, Germany
| | - Tobias M Nowacki
- Department of Medicine B for Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Münster, Albert-Schweitzer-Campus 1, Münster, 48149, Germany
- Department of Gastroenterology, UKM Marienhospital Steinfurt, Mauritiusstr. 5, Steinfurt, 48565, Germany
| | - Andreas Pascher
- Department of General, Visceral and Transplant Surgery, University Hospital Münster, Waldeyerstraße 1, 48149, Münster, Germany
| | - Judith C Sporn
- Department of General, Visceral and Transplant Surgery, University Hospital Münster, Waldeyerstraße 1, 48149, Münster, Germany.
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13
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Acs M, Piso P, Glockzin G. Peritoneal Metastatic Gastric Cancer: Local Treatment Options and Recommendations. Curr Oncol 2024; 31:1445-1459. [PMID: 38534942 PMCID: PMC10969192 DOI: 10.3390/curroncol31030109] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 02/29/2024] [Accepted: 03/07/2024] [Indexed: 05/26/2024] Open
Abstract
Peritoneal metastasis is a common finding in patients with advanced gastric cancer. Beyond systemic chemotherapy, additive local treatments such as cytoreductive surgery and intraperitoneal chemotherapy are considered an inherent part of different multimodal treatment concepts for selected patients with peritoneal metastatic gastric cancer. This review article discusses the role of cytoreductive surgery (CRS) and intraperitoneal chemotherapy, including HIPEC, NIPS, and PIPAC, as additive therapeutic options with curative and palliative intent.
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Affiliation(s)
- Miklos Acs
- Department of Surgery, University Medical Center Regensburg, 93053 Regensburg, Germany;
| | - Pompiliu Piso
- Department of Surgery, Krankenhaus Barmherzige Brueder Regensburg, 93049 Regensburg, Germany;
| | - Gabriel Glockzin
- Department of Surgery, Muenchen Klinik Bogenhausen, 81925 Munich, Germany
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14
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Van Der Sluis K, Taylor SN, Kodach LL, van Dieren JM, de Hingh IHJT, Wijnhoven BPL, Verhoeven RHA, Vollebergh MA, van Sandick JW. Tumor-positive peritoneal cytology in patients with gastric cancer is associated with poor outcome: A nationwide study. Eur J Cancer 2024; 199:113541. [PMID: 38237371 DOI: 10.1016/j.ejca.2024.113541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 12/14/2023] [Accepted: 01/05/2024] [Indexed: 02/13/2024]
Abstract
BACKGROUND The clinical significance of tumor-positive peritoneal cytology (CYT+) in gastric cancer (GC) patients is unclear. This nationwide cohort study aimed to i) assess the frequency of cytological analysis at staging laparoscopy; ii) determine the prevalence of CYT+GC; and iii) compare overall survival (OS) in CYT+ patients versus those with (PM+) and those without (PM-) macroscopic peritoneal disease. METHODS All patients diagnosed with cT1-4, cN0-2 and M0 or synchronous PM GC between 2016-2021 were identified in the Netherlands Cancer Registry database and linked to the nationwide pathology database. RESULTS A total of 4397 patients was included, of which 40 % underwent cytological assessment following staging laparoscopy (863/1745). The prevalence of CYT+ was 8 %. A total of 69 patients had CYT+(1.6 %), 789 (17.9 %) had PM+ and 3539 (80.5 %) had PM- disease. Hazard ratio for OS in CYT+ versus PM+ was 0.86 (95 %CI 0.64-1.17, p-value=0.338), and in PM- versus PM+0.43 (95 %CI 0.38-0.49, p-value<0.001). No survival difference was found between systemic chemotherapy versus surgical resection in CYT+ patients. DISCUSSION In this nationwide study, OS for gastric cancer patients with CYT+ was equally unfavorable as for those with PM+ and significantly worse as compared to those with PM-. The optimal treatment strategy has yet to be established.
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Affiliation(s)
- Karen Van Der Sluis
- The Netherlands Cancer Institute, Department of Surgical Oncology, Amsterdam, the Netherlands.
| | - Steven N Taylor
- The Netherlands Cancer Institute, Department of Surgical Oncology, Amsterdam, the Netherlands
| | - Liudmila L Kodach
- The Netherlands Cancer Institute, Department of Pathology, Amsterdam, the Netherlands
| | - Jolanda M van Dieren
- The Netherlands Cancer Institute, Department of Gastrointestinal Oncology, Amsterdam, the Netherlands
| | | | - Bas P L Wijnhoven
- Erasmus Medical Centre, Department of Surgery, Rotterdam, the Netherlands
| | - Rob H A Verhoeven
- Netherlands Comprehensive Cancer Organization (IKNL), Department of Research & Development, Utrecht, the Netherlands; Amsterdam UMC location University of Amsterdam, Medical Oncology, Meibergdreef 9, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, the Netherlands
| | - Marieke A Vollebergh
- The Netherlands Cancer Institute, Department of Gastrointestinal Oncology, Amsterdam, the Netherlands
| | - Johanna W van Sandick
- The Netherlands Cancer Institute, Department of Surgical Oncology, Amsterdam, the Netherlands
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15
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Lin T, Chen X, Xu Z, Hu Y, Liu H, Yu J, Li G. Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for gastric cancer with intraoperative detection of limited peritoneal metastasis: a Phase II study of CLASS-05 trial. Gastroenterol Rep (Oxf) 2024; 12:goae001. [PMID: 38390578 PMCID: PMC10882263 DOI: 10.1093/gastro/goae001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 10/05/2023] [Accepted: 12/31/2023] [Indexed: 02/24/2024] Open
Abstract
Background Systemic chemotherapy for gastric cancer with peritoneal metastasis has limited clinical benefit; for those with intraoperative detection of occult peritoneal metastasis, cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is an alternative treatment. However, the feasibility and effects of this modality and criteria for selecting suitable groups remain unclear. This study aimed to explore the safety and efficacy of laparoscopic cytoreductive surgery (L-CRS) followed by HIPEC in gastric cancer with limited peritoneal metastasis, and this study also aimed to determine the optimized cut-off of the peritoneal cancer index. Methods Between March 2017 and November 2019, patients diagnosed with gastric cancer peritoneal metastases by using laparoscopy and the Sugarbaker peritoneal cancer index of ≤12 were eligible for inclusion. All patients received L-CRS (including gastrectomy with D2 lymph node dissection) and resection of visible peritoneal metastasis, followed by post-operative HIPEC, and systemic chemotherapy. The primary end points were median progression-free survival and median survival time, and the secondary outcomes were morbidity and mortality within 30 days after surgery. Results Thirty patients were eligible for analysis, of whom 19 (63.3%) were female, and the overall mean age was 53.0 years. The post-operative morbidity was 20% and the severe complication rate was 10%. The median survival time was 27.0 months with a 2-year overall survival rate of 52.3% and median progression-free survival was 14.0 months with a 2-year progression-free survival of 30.4%. Conclusions L-CRS followed by HIPEC can be safely performed for gastric cancer with limited peritoneal metastasis and potential survival benefits.
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Affiliation(s)
- Tian Lin
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, P. R. China
| | - Xinhua Chen
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, P. R. China
| | - Zhijun Xu
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, P. R. China
| | - Yanfeng Hu
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, P. R. China
| | - Hao Liu
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, P. R. China
| | - Jiang Yu
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, P. R. China
| | - Guoxin Li
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, P. R. China
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16
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Che K, Luo Y, Song X, Yang Z, Wang H, Shi T, Wang Y, Wang X, Wu H, Yu L, Liu B, Wei J. Macrophages reprogramming improves immunotherapy of IL-33 in peritoneal metastasis of gastric cancer. EMBO Mol Med 2024; 16:251-266. [PMID: 38238529 PMCID: PMC10897402 DOI: 10.1038/s44321-023-00012-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Revised: 09/24/2023] [Accepted: 11/20/2023] [Indexed: 02/17/2024] Open
Abstract
Peritoneal metastasis (PM) has a suppressive tumor immune microenvironment (TIME) that limits the effects of immunotherapy. This study aimed to investigate the immunomodulatory effects of intraperitoneal administration of IL-33, a cytokine that is reported to potentiate antitumor immunity and inhibit metastasis. We found survival was significantly prolonged in patients with high IL-33 mRNA expression. In immunocompetent mice, intraperitoneal administration of IL-33 could induce a celiac inflammatory environment, activate immunologic effector cells, and reverse the immunosuppressive tumor microenvironment, which effectively delayed tumor progression and PM of gastric cancer. Mechanistically, IL-33 could induce M2 polarization by activating p38-GATA-binding protein 3 signaling. IL-33 combined with anti-CSF1R or p38 inhibitor to regulate tumor-associated macrophages (TAMs) had a synergistic antitumor effect. Inducing a local inflammatory milieu by IL-33 administration provided a novel approach for treating peritoneal metastasis, which, when combined with TAM reprogramming to reshape TIME, can achieve better treatment efficacy.
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Affiliation(s)
- Keying Che
- Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China
- Tumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Yuting Luo
- Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Xueru Song
- Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Zhe Yang
- Tumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Hanbing Wang
- Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Tao Shi
- Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Yue Wang
- Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Xuan Wang
- Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
- Department of Pathology, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Hongyan Wu
- Department of Pathology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Lixia Yu
- Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Baorui Liu
- Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Jia Wei
- Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
- Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing, China.
- Engineering Research Center of Protein and Peptide Medicine, Ministry of Education, Nanjing, China.
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17
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Pugaev DM, Lyubchenko LN, Ryabov AB, Kaprin AD. Early-onset gasrtric cancer (review). SIBERIAN JOURNAL OF ONCOLOGY 2024; 22:153-171. [DOI: 10.21294/1814-4861-2023-22-6-153-171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Abstract
Objective. Early-onset gastric cancer (EOGC) constitutes a serious medical and social problem. Early-onset gastric cancer accounts for approximately 6% of all malignant epithelial neoplasms.Material and Methods. We reviewed retrospective and prospective randomized trials using Medline and Elibrary databases.Results. The applied significance of the molecular genetic classifications consist in the formation of groups for evaluating prognosis of the disease using multifactorial analysis. This classification indicates that EOGC diagnosed at a locally advanced stage and primary dissemination is most often caused by GS (TCGA) and MSS/EMT(ACRG) subtypes and is characterized by mutations in CDH1, RhoA, CLDN18-ARHGAP genes. These changes are accompanied by the prevalence of diffuse histological type of gastric cancer according to the Lauren classification and ulcerated or infiltrative type according to the Borrmann classification (type III and IV) with the presence of high-grade adenocarcinoma with a signet ring cell component.Conclusion. Considering the aggressiveness of gastric cancer in young patients, who more frequently present with locally advanced and metastatic disease at the time of diagnosis, there is a need for increased cancer alertness among physicians of other specialties, early endoscopic controls to detect cancer at early stages and benefit from both surgical and multimodal treatment.
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Affiliation(s)
- D. M. Pugaev
- Kommunarka Moscow Multidisciplinary Clinical Center, Moscow City Health Department
| | - L. N. Lyubchenko
- N.A. Lopatkin Research Institute of Urology and Interventional Radiology – branch National Medical Research Radiological Centre of the Ministry of Health of the Russia;
National Medical Research Radiological Centre of the Ministry of Health of the Russia
| | - A. B. Ryabov
- P.A. Hertsen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russia;
National Medical Research Radiological Centre of the Ministry of Health of the Russia
| | - A. D. Kaprin
- RUDN University;
P.A. Hertsen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russia;
National Medical Research Radiological Centre of the Ministry of Health of the Russia
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18
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Verbeek JGE, van der Sluis K, Vollebergh MA, van Sandick JW, van Harten WH, Retèl VP. Early Cost-Effectiveness Analysis of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer Patients with Limited Peritoneal Carcinomatosis. PHARMACOECONOMICS - OPEN 2024; 8:119-131. [PMID: 38032438 PMCID: PMC10781926 DOI: 10.1007/s41669-023-00454-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 11/06/2023] [Indexed: 12/01/2023]
Abstract
BACKGROUND Gastric cancer patients with peritoneal carcinomatosis (PC) have a poor prognosis, with a median overall survival of 10 months when treated with systemic chemotherapy only. Cohort studies showed that cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) might improve the prognosis for gastric cancer patients with limited PC. Besides generating trial data on clinical effectiveness, it is crucial to timely collect information on economic aspects to guide the reimbursement decision-making process. No previous data have been published on the cost(-effectiveness) of CRS/HIPEC in this group of patients. Therefore, we performed an early model-based cost-effectiveness analysis of CRS/HIPEC for gastric cancer patients with limited PC in the Dutch setting. METHODS We constructed a two-state (alive-dead) Markov transition model to evaluate costs and clinical outcomes from a Dutch healthcare perspective. Clinical outcomes, transition probabilities and utilities were derived from literature and verified by clinical experts in the field. Costs were measured using two available representative cohorts (2010-2017): one 'systemic chemotherapy only' cohort and one 'CRS/HIPEC' cohort (n = 10 each). Incremental cost-utility ratios (ICURs) were expressed as Euros per quality-adjusted life-year (QALY). We performed probabilistic and deterministic sensitivity, scenario, and value-of-information analyses using a willingness-to-pay (WTP) threshold of €80,000/QALY, which reflects the Dutch norm for severe diseases. RESULTS In the base-case analysis, CRS/HIPEC yielded more QALYs (increment of 0.68) and more costs (increment of €34,706) compared with systemic chemotherapy only, resulting in an ICUR of €50,990/QALY. The probability that CRS/HIPEC was cost effective compared with systemic chemotherapy alone was 64%. To reduce uncertainty, the expected value of perfect information amounted to €4,021,468. The scenario analyses did not alter the results and showed that treatment costs, lifetime health-related quality of life and overall survival had the largest influence on the model. CONCLUSIONS The presented early cost-effectiveness analysis suggests that adding CRS/HIPEC to systemic chemotherapy for gastric cancer patients with limited PC has a good chance of being cost-effectiveness compared with systemic chemotherapy alone when using a WTP of €80,000/QALY. However, there is substantial uncertainty in view of the current available data on effectiveness. Results from the ongoing phase III PERISCOPE II trial are therefore crucial for further decisions on treatment policy and its cost-effectiveness.
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Affiliation(s)
- Joost G E Verbeek
- Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, P.O. Box 90203, 1006 BE, Amsterdam, The Netherlands
- Department of Health Technology and Services Research, University of Twente, Enschede, The Netherlands
| | - Karen van der Sluis
- Department of Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Marieke A Vollebergh
- Department of Gastrointestinal Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | | | - Wim H van Harten
- Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, P.O. Box 90203, 1006 BE, Amsterdam, The Netherlands
- Department of Health Technology and Services Research, University of Twente, Enschede, The Netherlands
| | - Valesca P Retèl
- Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, P.O. Box 90203, 1006 BE, Amsterdam, The Netherlands.
- Erasmus School of Health Policy and Management, Erasmus University Rotterdam, Rotterdam, The Netherlands.
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19
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Sarvestani AL, Gregory SN, Akmal SR, Hernandez JM, van der Sluis K, van Sandick JW. Gastrectomy + Cytoreductive Surgery + HIPEC for Gastric Cancer with Peritoneal Dissemination (PERISCOPE II). Ann Surg Oncol 2024; 31:28-30. [PMID: 37947975 DOI: 10.1245/s10434-023-14415-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 09/25/2023] [Indexed: 11/12/2023]
Affiliation(s)
- Amber Leila Sarvestani
- Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Stephanie N Gregory
- Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Sarfraz R Akmal
- Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Jonathan M Hernandez
- Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
| | - Karen van der Sluis
- Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
| | - Johanna W van Sandick
- Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
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20
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Guo J, Deng Z, Jin L, Yin S, Xiong Z, Wang C, Chen H, Luo D, Huang D, Peng J, Chen S, Lian L. Prognostic value of hyperthermic intraperitoneal chemotherapy in gastric cancer with synchronous peritoneal metastases: a real-world retrospective study. J Cancer Res Clin Oncol 2023; 149:17881-17896. [PMID: 37947869 DOI: 10.1007/s00432-023-05481-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 10/17/2023] [Indexed: 11/12/2023]
Abstract
PURPOSE Peritoneal metastasis in gastric cancer (GC) is a late-stage condition with a poor prognosis. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a popular treatment for peritoneal metastases. Here, we aim to investigate the real-world application and efficacy of HIPEC alone for GC patients with synchronous peritoneal metastases. METHODS We conducted a retrospective analysis on GC patients with synchronous peritoneal metastasis at the Sixth Affiliated Hospital of Sun Yat-sen University between January 2011 and December 2022. Survival analyses and Cox regression models were performed based on overall survival (OS) and cancer-specific survival (CSS), and subgroup analysis was used to determine the prognostic value of HIPEC across different treatment. RESULTS We enrolled 250 patients, of whom 120 (48%) received HIPEC while 130 (52%) did not. HIPEC showed no survival benefit for GC patients (P = 0.220 for OS and P = 0.370 for CSS). However, subgroup analysis found that HIPEC can only improve OS and CSS when combined with primary tumor resection (P = 0.034 for OS and P = 0.036 for CSS). Moreover, survival analyses also demonstrated that HIPEC independently improved OS (HR for OS = 0.58, 95% CI 0.37-0.92, P = 0.020) and CSS (HR for CSS = 0.58, 95% CI 0.37-0.93, P = 0.024) for patients who underwent primary site resection, but not for those who did not. CONCLUSION HIPEC can improve survival in GC patients with synchronous peritoneal metastases who have primary tumor resection, but not in those without primary tumor resection.
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Affiliation(s)
- Jianping Guo
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, Guangdong, China
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zijian Deng
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, Guangdong, China
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Longyang Jin
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, Guangdong, China
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Shi Yin
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, Guangdong, China
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhizhong Xiong
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, Guangdong, China
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Caiqin Wang
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, Guangdong, China
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Huaxian Chen
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, Guangdong, China
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Dandong Luo
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, Guangdong, China
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Dayin Huang
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, Guangdong, China
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Junsheng Peng
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, Guangdong, China.
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
| | - Shi Chen
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, Guangdong, China.
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
| | - Lei Lian
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, Guangdong, China.
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
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21
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Ho SYA, Tay KV. Systematic review of diagnostic tools for peritoneal metastasis in gastric cancer-staging laparoscopy and its alternatives. World J Gastrointest Surg 2023; 15:2280-2293. [PMID: 37969710 PMCID: PMC10642463 DOI: 10.4240/wjgs.v15.i10.2280] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Revised: 05/16/2023] [Accepted: 06/12/2023] [Indexed: 10/27/2023] Open
Abstract
BACKGROUND Gastric cancer is one of the leading causes of cancer burden and mortality, often resulting in peritoneal metastasis in advanced stages with negative survival outcomes. Staging laparoscopy has become standard practice for suspected cases before a definitive gastrectomy or palliation. This systematic review aims to compare the efficacy of other diagnostic modalities instead of staging laparoscopy as the alternatives are able to reduce cost and invasive staging procedures. Recently, a radiomic model based on computed tomography and positron emission tomography (PET) has also emerged as another method to predict peritoneal metastasis. AIM To determine if the efficacy of computed tomography, magnetic resonance imaging and PET is comparable with staging laparoscopy. METHODS Articles comparing computed tomography, PET, magnetic resonance imaging, and radiomic models based on computed tomography and PET to staging laparoscopies were filtered out from the Cochrane Library, EMBASE, PubMed, Web of Science, and Reference Citations Analysis (https://www.referencecitationanalysis.com/). In the search for studies comparing computed tomography (CT) to staging laparoscopy, five retrospective studies and three prospective studies were found. Similarly, five retrospective studies and two prospective studies were also included for papers comparing CT to PET scans. Only one retrospective study and one prospective study were found to be suitable for papers comparing CT to magnetic resonance imaging scans. RESULTS Staging laparoscopy outperformed computed tomography in all measured aspects, namely sensitivity, specificity, positive predictive value and negative predictive value. Magnetic resonance imaging and PET produced mixed results, with the former shown to be only marginally better than computed tomography. CT performed slightly better than PET in most measured domains, except in specificity and true negative rates. We speculate that this may be due to the limited F-fluorodeoxyglucose uptake in small peritoneal metastases and in linitis plastica. Radiomic modelling, in its current state, shows promise as an alternative for predicting peritoneal metastases. With further research, deep learning and radiomic modelling can be refined and potentially applied as a preoperative diagnostic tool to reduce the need for invasive staging laparoscopy. CONCLUSION Staging laparoscopy was superior in all measured aspects. However, associated risks and costs must be considered. Refinements in radiomic modelling are necessary to establish it as a reliable screening technique.
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Affiliation(s)
| | - Kon Voi Tay
- Upper GI and Bariatric Division, General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
- Upper GI and Bariatric Division, General Surgery, Woodlands Health, Singapore 768024, Singapore
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22
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Schena CA, Laterza V, De Sio D, Quero G, Fiorillo C, Gunawardena G, Strippoli A, Tondolo V, de'Angelis N, Alfieri S, Rosa F. The Role of Staging Laparoscopy for Gastric Cancer Patients: Current Evidence and Future Perspectives. Cancers (Basel) 2023; 15:3425. [PMID: 37444535 DOI: 10.3390/cancers15133425] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Revised: 06/18/2023] [Accepted: 06/27/2023] [Indexed: 07/15/2023] Open
Abstract
A significant proportion of patients diagnosed with gastric cancer is discovered with peritoneal metastases at laparotomy. Despite the continuous improvement in the performance of radiological imaging, the preoperative recognition of such an advanced disease is still challenging during the diagnostic work-up, since the sensitivity of CT scans to peritoneal carcinomatosis is not always adequate. Staging laparoscopy offers the chance to significantly increase the rate of promptly diagnosed peritoneal metastases, thus reducing the number of unnecessary laparotomies and modifying the initial treatment strategy of gastric cancer. The aim of this review was to provide a comprehensive summary of the current literature regarding the role of staging laparoscopy in the management of gastric cancer. Indications, techniques, accuracy, advantages, and limitations of staging laparoscopy and peritoneal cytology were discussed. Furthermore, a focus on current evidence regarding the application of artificial intelligence and image-guided surgery in staging laparoscopy was included in order to provide a picture of the future perspectives of this technique and its integration with modern tools in the preoperative management of gastric cancer.
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Affiliation(s)
- Carlo Alberto Schena
- Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Unit of Colorectal and Digestive Surgery, DIGEST Department, Beaujon University Hospital, AP-HP, University of Paris Cité, Clichy, 92110 Paris, France
| | - Vito Laterza
- Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Davide De Sio
- Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Giuseppe Quero
- Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Department of Digestive Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Claudio Fiorillo
- Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Gayani Gunawardena
- Department of Digestive Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Antonia Strippoli
- Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Vincenzo Tondolo
- Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Nicola de'Angelis
- Unit of Colorectal and Digestive Surgery, DIGEST Department, Beaujon University Hospital, AP-HP, University of Paris Cité, Clichy, 92110 Paris, France
| | - Sergio Alfieri
- Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Department of Digestive Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Fausto Rosa
- Department of Digestive Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
- Emergency and Trauma Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
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23
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Sammartino P, De Manzoni G, Marano L, Marrelli D, Biacchi D, Sommariva A, Scaringi S, Federici O, Guaglio M, Angrisani M, Cardi M, Fassari A, Casella F, Graziosi L, Roviello F. Gastric Cancer (GC) with Peritoneal Metastases (PMs): An Overview of Italian PSM Oncoteam Evidence and Study Purposes. Cancers (Basel) 2023; 15:3137. [PMID: 37370747 PMCID: PMC10296634 DOI: 10.3390/cancers15123137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 04/30/2023] [Accepted: 06/05/2023] [Indexed: 06/29/2023] Open
Abstract
Gastric cancer (GC) continues to be one of the leading types of malignancies worldwide, despite an ongoing decrease in incidence. It is the fifth most frequent type of cancer in the world and the fourth leading cause of cancer death. Peritoneal metastases (PMs) occur in 20-30% of cases during the natural history of the disease. Systemic chemotherapy (SC) is undoubtedly the standard of care for patients with GC and PMs. However, with the development of highly effective regimens (SC combined with intraperitoneal chemotherapy), significant tumor shrinkage has been observed in many patients with synchronous GC and PMs, allowing some to undergo curative resection "conversion surgery" with long-term survival. In recent years, there has been growing interest in intraperitoneal chemotherapy for PMs, because the reduced drug clearance associated with the peritoneal/plasma barrier allows for direct and prolonged drug exposure with less systemic toxicity. These procedures, along with other methods used for peritoneal surface malignancies (PSMs), can be used in GCs with PMs as neoadjuvant chemotherapy or adjuvant treatments after radical surgery or as palliative treatments delivered either laparoscopically or-more recently-as pressurized intraperitoneal aerosol chemotherapy. The great heterogeneity of patients with stage IV gastric cancer did not allow us to carry out a systemic review; therefore, we limited ourselves to providing readers with an overview to clarify the indications and outcomes of integrated treatments for GCs with PMs by analyzing reports from the international clinical literature and the specific experiences of our oncoteam.
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Affiliation(s)
- Paolo Sammartino
- CRS and HIPEC Unit, Pietro Valdoni, Umberto I Policlinico di Roma, 00161 Roma, Italy
| | | | - Luigi Marano
- Department of Medicine, Surgery, and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, 53100 Siena, Italy
| | - Daniele Marrelli
- Department of Medicine, Surgery, and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, 53100 Siena, Italy
| | - Daniele Biacchi
- CRS and HIPEC Unit, Pietro Valdoni, Umberto I Policlinico di Roma, 00161 Roma, Italy
| | - Antonio Sommariva
- Advanced Surgical Oncology Unit, Surgical Oncology of the Esophagus and Digestive Tract, Veneto, Institute of Oncology IOV-IRCCS, 35128 Padova, Italy
| | - Stefano Scaringi
- AOU Careggi, IBD Unit-Chirurgia dell’Apparato Digerente, 50100 Firenze, Italy
| | - Orietta Federici
- Peritoneal Tumors Unit, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy
| | - Marcello Guaglio
- Peritoneal Surface Malignancies Unit, Fondazione Istituto Nazionale Tumori IRCCS Milano, 20133 Milano, Italy
| | - Marco Angrisani
- CRS and HIPEC Unit, Pietro Valdoni, Umberto I Policlinico di Roma, 00161 Roma, Italy
| | - Maurizio Cardi
- CRS and HIPEC Unit, Pietro Valdoni, Umberto I Policlinico di Roma, 00161 Roma, Italy
| | - Alessia Fassari
- CRS and HIPEC Unit, Pietro Valdoni, Umberto I Policlinico di Roma, 00161 Roma, Italy
| | - Francesco Casella
- Upper GI Surgery Division, University of Verona, 37129 Verona, Italy
| | - Luigina Graziosi
- General and Emergency Surgery Department, Santa Maria Della Misericordia Hospital, University of Perugia, 06125 Perugia, Italy
| | - Franco Roviello
- Department of Medicine, Surgery, and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, 53100 Siena, Italy
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24
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Sinukumar S, Kammar P, Ray M, Shaikh S, Patel A, Rajan F, Srinivasan A, Damodaran D, Mehta S, Mahajan V, Deo SVS, Bhatt A. Long-Term Survival in Patients Treated by Cytoreductive Surgery with or Without HIPEC for Peritoneal Surface Malignancies-A report from the Indian HIPEC Registry. Indian J Surg Oncol 2023; 14:198-208. [PMID: 37359912 PMCID: PMC10284732 DOI: 10.1007/s13193-023-01727-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Accepted: 02/24/2023] [Indexed: 03/28/2023] Open
Abstract
A previous report from the Indian HIPEC registry showed acceptable early survival and morbidity in patients undergoing cytoreductive surgery (CRS) + / - hyperthermic intraperitoneal chemotherapy (HIPEC). The goal of this retrospective study was to evaluate the long-term outcomes in these patients. Three hundred seventy-four patients treated from December 2010 to December 2016 and enrolled in the Indian HIPEC registry were included. All patients had completed 5 years from the date of surgery. The 1-, 3-, 5- and 7-year progression-free (PFS) and overall survival (OS) and factors affecting these were evaluated. The histology was epithelial ovarian cancer in 209 (46.5%), pseudomyxoma peritonei (PMP) in 65 (17.3%) and colorectal cancer in 46 (12.9%) patients. The peritoneal cancer index (PCI) was ≥ 15 in 160 (42.8%). A completeness of cytoreduction (CC) score of 0/1 resection was obtained in 83% (CC-0-65%; CC-1-18%). HIPEC was performed in 59.2%. At a median, follow-up of 77 months (6-120 months), 243 (64.9%) patients developed recurrence, and 236 (63%) died of any cause; 138 (36.9%) were lost to follow-up. The median OS was 56 months (95% CI 53.42-61.07), and the median PFS was 28 months (95% CI 37.5-44.4). The 1-, 3-, 5- and 7-year OS was 97.6%, 63%, 37.7% and 24% respectively. The 1-, 3-, 5- and 7-year PFS was 84.8%, 36.5%, 27.3% and 22% respectively. The use of HIPEC (p = 0.03) and PMP of appendiceal origin (p = 0.01) was independent predictors of a longer OS. CRS + / - /HIPEC may achieve long-term survival in patients with PM from different primary sites in the Indian scenario. More prospective studies are needed to confirm these findings and identify factors influencing long-term survival. Supplementary Information The online version contains supplementary material available at 10.1007/s13193-023-01727-7.
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Affiliation(s)
| | - Praveen Kammar
- Dept. of Surgical Oncology, Saifee Hospital, Mumbai, India
| | - Mukurdipi Ray
- Dept. of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Sakina Shaikh
- Dept. of Surgical Oncology, Zydus Hospital, Thaltej, Ahmedabad, 380054 India
| | - Ankita Patel
- Dept. of Surgical Oncology, Zydus Hospital, Thaltej, Ahmedabad, 380054 India
| | - Firoz Rajan
- Dept. of Surgical Oncology, Kovai Medical Centre, Coimbatore, India
| | | | | | - Sanket Mehta
- Dept. of Surgical Oncology, Saifee Hospital, Mumbai, India
| | - Vikas Mahajan
- Dept. of Surgical Oncology, Apollo Hospital, Chennai, India
| | | | - Aditi Bhatt
- Dept. of Surgical Oncology, Zydus Hospital, Thaltej, Ahmedabad, 380054 India
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Steinhoff H, Acs M, Blaj S, Dank M, Herold M, Herold Z, Herzberg J, Sanchez-Velazquez P, Strate T, Szasz AM, Piso P. Prolonged hyperthermic intraperitoneal chemotherapy duration with 90 minutes cisplatin might increase overall survival in gastric cancer patients with peritoneal metastases. World J Gastroenterol 2023; 29:2850-2863. [PMID: 37274066 PMCID: PMC10237111 DOI: 10.3748/wjg.v29.i18.2850] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 02/27/2023] [Accepted: 04/10/2023] [Indexed: 05/11/2023] Open
Abstract
BACKGROUND Advanced gastric cancer with synchronous peritoneal metastases (GC-PM) is associated with a poor prognosis. Although cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is a promising approach, only a limited number of Western studies exist.
AIM To investigate the clinicopathological outcomes of patients who underwent CRS-HIPEC for GC-PM.
METHODS A retrospective analysis of patients with GC-PM was conducted. All patients were seen at the Department of General and Visceral Surgery, Hospital Barmherzige Brüder, Regensburg, Germany between January 2011 and July 2021 and underwent CRS-HIPEC. Preoperative laboratory results, the use of neoadjuvant trastuzumab, and the details of CRS-HIPEC, including peritoneal carcinomatosis index, completeness of cytoreduction, and surgical procedures were recorded. Disease-specific (DSS), and overall survival (OS) of patients were calculated.
RESULTS A total of 73 patients were included in the study. Patients treated with neoadjuvant trastuzumab (n = 5) showed longer DSS (P = 0.0482). Higher white blood cell counts (DSS: P = 0.0433) and carcinoembryonic antigen levels (OS and DSS: P < 0.01), and lower hemoglobin (OS and DSS: P < 0.05) and serum total protein (OS: P = 0.0368) levels were associated with shorter survival. Longer HIPEC duration was associated with more advantageous median survival times [60-min (n = 59): 12.86 mo; 90-min (n = 14): 27.30 mo], but without statistical difference. To obtain additional data from this observation, further separation of the study population was performed. First, propensity score-matched patient pairs (n = 14 in each group) were created. Statistically different DSS was found between patient pairs (hazard ratio = 0.2843; 95% confidence interval: 0.1119-0.7222; P = 0.0082). Second, those patients who were treated with trastuzumab and/or had human epidermal growth factor receptor 2 positivity (median survival: 12.68 mo vs 24.02 mo), or had to undergo the procedure before 2016 (median survival: 12.68 mo vs 27.30 mo; P = 0.0493) were removed from the original study population.
CONCLUSION Based on our experience, CRS-HIPEC is a safe and secure method to improve the survival of advanced GC-PM patients. Prolonged HIPEC duration may serve as a good therapy for these patients.
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Affiliation(s)
- Heinrich Steinhoff
- Department of General and Visceral Surgery, Hospital Barmherzige Brüder, Regensburg 93049, Germany
| | - Miklos Acs
- Department of General and Visceral Surgery, Hospital Barmherzige Brüder, Regensburg 93049, Germany
| | - Sebastian Blaj
- Department of General and Visceral Surgery, Hospital Barmherzige Brüder, Regensburg 93049, Germany
| | - Magdolna Dank
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest 1083, Hungary
| | - Magdolna Herold
- Department of Internal Medicine and Hematology, Semmelweis University, Budapest 1088, Hungary
| | - Zoltan Herold
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest 1083, Hungary
| | - Jonas Herzberg
- Department of Surgery, Krankenhaus Reinbek St. Adolf-Stift, Reinbek 21465, Germany
| | | | - Tim Strate
- Department of Surgery, Krankenhaus Reinbek St. Adolf-Stift, Reinbek 21465, Germany
| | - Attila Marcell Szasz
- Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, Budapest 1083, Hungary
| | - Pompiliu Piso
- Department of General and Visceral Surgery, Hospital Barmherzige Brüder, Regensburg 93049, Germany
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26
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Li LM, Feng LY, Liu CC, Huang WP, Yu Y, Cheng PY, Gao JB. Can visceral fat parameters based on computed tomography be used to predict occult peritoneal metastasis in gastric cancer? World J Gastroenterol 2023; 29:2310-2321. [PMID: 37124887 PMCID: PMC10134425 DOI: 10.3748/wjg.v29.i15.2310] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 01/21/2023] [Accepted: 03/20/2023] [Indexed: 04/14/2023] Open
Abstract
BACKGROUND The preoperative prediction of peritoneal metastasis (PM) in gastric cancer would prevent unnecessary surgery and promptly indicate an appropriate treatment plan.
AIM To explore the predictive value of visceral fat (VF) parameters obtained from preoperative computed tomography (CT) images for occult PM and to develop an individualized model for predicting occult PM in patients with gastric carcinoma (GC).
METHODS A total of 128 confirmed GC cases (84 male and 44 female patients) that underwent CT scans were analyzed and categorized into PM-positive (n = 43) and PM-negative (n = 85) groups. The clinical characteristics and VF parameters of two regions of interest (ROIs) were collected. Univariate and stratified analyses based on VF volume were performed to screen for predictive characteristics for occult PM. Prediction models with and without VF parameters were established by multivariable logistic regression analysis.
RESULTS The mean attenuations of VFROI 1 and VFROI 2 varied significantly between the PM-positive and PM-negative groups (P = 0.044 and 0.001, respectively). The areas under the receiver operating characteristic curves (AUCs) of VFROI 1 and VFROI 2 were 0.599 and 0.657, respectively. The mean attenuation of VFROI 2 was included in the final prediction combined model, but not an independent risk factor of PM (P = 0.068). No significant difference was observed between the models with and without mean attenuation of VF (AUC: 0.749 vs 0.730, P = 0.339).
CONCLUSION The mean attenuation of VF is a potential auxiliary parameter for predicting occult PM in patients with GC.
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Affiliation(s)
- Li-Ming Li
- Department of Radiology, Henan Key Laboratory of Imaging Diagnosis and Treatment for Digestive system Tumor, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Lei-Yu Feng
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Chen-Chen Liu
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Wen-Peng Huang
- Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China
| | - Yang Yu
- Beijing Branch, Siemens Healthineers Ltd., Shenyang 110011, Liaoning Province, China
| | - Peng-Yun Cheng
- Beijing Branch, Siemens Healthineers Ltd., Shenyang 110011, Liaoning Province, China
| | - Jian-Bo Gao
- Department of Radiology, Henan Key Laboratory of Imaging Diagnosis and Treatment for Digestive system Tumor, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
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Jusufi M, Piso P, Zorger N. [Peritoneal carcinomatosis secondary to CUP syndrome : Diagnosis and indications for multimodal treatment]. RADIOLOGIE (HEIDELBERG, GERMANY) 2023; 63:371-380. [PMID: 37022459 DOI: 10.1007/s00117-023-01140-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Accepted: 03/13/2023] [Indexed: 04/07/2023]
Abstract
CLINICAL PROBLEM Peritoneal carcinomatosis secondary to cancer of unknown primary (CUP) syndrome is a rare entity for which there are no uniform treatment recommendations or guidelines. The median survival time is 3 months. DIAGNOSIS Computed tomography (CT), magnetic resonance imaging (MRI), and 18F‑FDG positron emission tomography (PET)/CT are valid imaging modalities for the detection of peritoneal carcinomatosis. The sensitivity of all techniques is highest for large, macronodular peritoneal carcinomatosis manifestations. A limitation of all imaging techniques is limited and small-nodular peritoneal carcinomatosis. Also, peritoneal metastasis in the small bowel mesentery or diaphragmatic domes can only be visualized with low sensitivity. Therefore, exploratory laparoscopy should be considered as the next diagnostic step. In half of these cases an unnecessary laparotomy can be avoided, because the laparoscopy revealed diffuse, small-nodule involvement of the small bowel wall and thus an irresectable situation. TREATMENT In selected patients, performing complete cytoreduction followed by hyperthermic intra-abdominal chemotherapy (HIPEC) is a good therapeutic option. Therefore, the identification of the extent of peritoneal tumor manifestation as accurately as possible is important for the definition of the increasingly complex oncological therapy strategies.
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Affiliation(s)
- M Jusufi
- Allgemein- und Viszeralchirurgie, Department für Chirurgie, Klinik für Gastrointestinale und Kolorektale Chirurgie, Asklepios Klinik Barmbek, Rübenkamp 220, 22307, Hamburg, Deutschland.
| | - P Piso
- Allgemein- und Viszeralchirurgie, Krankenhaus Barmherzige Brüder Regensburg, Regensburg, Deutschland
| | - N Zorger
- Radiologie, Neuroradiologie und Nuklearmedizin, Krankenhaus Barmherzige Brüder Regensburg, Regensburg, Deutschland
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Yang A, Zhang Z, Chaurasiya S, Park AK, Jung A, Lu J, Kim SI, Priceman S, Fong Y, Woo Y. Development of the oncolytic virus, CF33, and its derivatives for peritoneal-directed treatment of gastric cancer peritoneal metastases. J Immunother Cancer 2023; 11:e006280. [PMID: 37019471 PMCID: PMC10083877 DOI: 10.1136/jitc-2022-006280] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/09/2023] [Indexed: 04/07/2023] Open
Abstract
BACKGROUND Gastric cancer (GC) that metastasizes to the peritoneum is fatal. CF33 and its genetically modified derivatives show cancer selectivity and oncolytic potency against various solid tumors. CF33-hNIS and CF33-hNIS-antiPDL1 have entered phase I trials for intratumoral and intravenous treatments of unresectable solid tumors (NCT05346484) and triple-negative breast cancer (NCT05081492). Here, we investigated the antitumor activity of CF33-oncolytic viruses (OVs) against GC and CF33-hNIS-antiPDL1 in the intraperitoneal (IP) treatment of GC peritoneal metastases (GCPM). METHODS We infected six human GC cell lines AGS, MKN-45, MKN-74, KATO III, SNU-1, and SNU-16 with CF33, CF33-GFP, or CF33-hNIS-antiPDL1 at various multiplicities of infection (0.01, 0.1, 1.0, and 10.0), and performed viral proliferation and cytotoxicity assays. We used immunofluorescence imaging and flow cytometric analysis to verify virus-encoded gene expression. We evaluated the antitumor activity of CF33-hNIS-antiPDL1 following IP treatment (3×105 pfu × 3 doses) in an SNU-16 human tumor xenograft model using non-invasive bioluminescence imaging. RESULTS CF33-OVs showed dose-dependent infection, replication, and killing of both diffuse and intestinal subtypes of human GC cell lines. Immunofluorescence imaging showed virus-encoded GFP, hNIS, and anti-PD-L1 antibody scFv expression in CF33-OV-infected GC cells. We confirmed GC cell surface PD-L1 blockade by virus-encoded anti-PD-L1 scFv using flow cytometry. In the xenograft model, CF33-hNIS-antiPDL1 (IP; 3×105 pfu × 3 doses) treatment significantly reduced peritoneal tumors (p<0.0001), decreased amount of ascites (62.5% PBS vs 25% CF33-hNIS-antiPDL1) and prolonged animal survival. At day 91, seven out of eight mice were alive in the virus-treated group versus one out of eight in the control group (p<0.01). CONCLUSIONS Our results show that CF33-OVs can deliver functional proteins and demonstrate effective antitumor activity in GCPM models when delivered intraperitoneally. These preclinical results will inform the design of future peritoneal-directed therapy in GCPM patients.
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Affiliation(s)
- Annie Yang
- Department of Surgery, City of Hope National Medical Center, Duarte, California, USA
| | - Zhifang Zhang
- Department of Surgery, City of Hope National Medical Center, Duarte, California, USA
| | - Shyambabu Chaurasiya
- Department of Surgery, City of Hope National Medical Center, Duarte, California, USA
| | - Anthony K Park
- Cancer Immunotherapeutics Program, Beckman Research Institute, City of Hope National Medical Center, Duarte, California, USA
| | - Audrey Jung
- Department of Surgery, City of Hope National Medical Center, Duarte, California, USA
| | - Jianming Lu
- Department of Surgery, City of Hope National Medical Center, Duarte, California, USA
| | - Sang-In Kim
- Department of Surgery, City of Hope National Medical Center, Duarte, California, USA
| | - Saul Priceman
- Cancer Immunotherapeutics Program, Beckman Research Institute, City of Hope National Medical Center, Duarte, California, USA
| | - Yuman Fong
- Department of Surgery, City of Hope National Medical Center, Duarte, California, USA
| | - Yanghee Woo
- Department of Surgery, City of Hope National Medical Center, Duarte, California, USA
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29
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Gastric Cancer with Peritoneal Metastases: Current Status and Prospects for Treatment. Cancers (Basel) 2023; 15:cancers15061777. [PMID: 36980663 PMCID: PMC10046173 DOI: 10.3390/cancers15061777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 03/01/2023] [Accepted: 03/10/2023] [Indexed: 03/17/2023] Open
Abstract
Gastric cancer (GC) has a poor prognostic and only one in four patients will have survived by 5 years after diagnosis. These poor results are due to the fact that most patients are diagnosed in advanced stages; peritoneal metastases (PM) are especially frequent and are difficult to treat. Currently, PM are considered a terminal stage of GC with a poor survival rate and are treated with palliative systemic chemotherapy. Since the beginning of the century, the treatment of PM from different origins has evolved; cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have become the treatment of choice for many malignant diseases that affect the peritoneum. CRS and HIPEC have also been used for patients with GC and PM, achieving survival results that have never been achieved when using systemic chemotherapy alone. The use of HIPEC can even prevent the development of peritoneal recurrences in patients with locally advanced GC as adjuvant therapy, can reduce the volume of peritoneal disease as neoadjuvant therapy, and can control symptoms in a palliative setting. The aim of this review is to collate the current scientific evidence regarding the treatment of PM of GC origin with surgery and intraperitoneal chemotherapy.
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30
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Green BL, Blumenthaler AN, Gamble LA, McDonald JD, Robinson K, Connolly M, Epstein M, Hernandez JM, Blakely AM, Badgwell BD, Davis JL. Cytoreduction and HIPEC for Gastric Carcinomatosis: Multi-institutional Analysis of Two Phase II Clinical Trials. Ann Surg Oncol 2023; 30:1852-1860. [PMID: 36348206 PMCID: PMC10683488 DOI: 10.1245/s10434-022-12761-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 10/24/2022] [Indexed: 11/10/2022]
Abstract
INTRODUCTION There are no approved locoregional therapies for peritoneal carcinomatosis from gastric adenocarcinoma (GA). Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) represents a potential treatment for advanced GA with isolated peritoneal metastasis. PATIENTS AND METHODS Two separate single-institution phase II, single-arm studies evaluating CRS-HIPEC using cisplatin with mitomycin C (NIH: NCT03092518, MDACC: NCT02891447) in patients with GA and confirmed peritoneal metastasis were analyzed. The primary endpoint of each trial was overall survival (OS). Clinical, pathologic, and treatment variables were analyzed for association with outcomes. RESULTS Over 4 years, 41 patients with peritoneal carcinomatosis from GA underwent CRS-HIPEC. All patients had synchronous peritoneal metastasis and received systemic chemotherapy as front-line therapy. A total of 23 patients also received laparoscopic HIPEC prior to open CRS-HIPEC. The majority (63%, n = 26) were male, and median PCI score at CRS-HIPEC was 2. Median OS was 24.9 months from diagnosis and 14.4 months from CRS-HIPEC. Three-year OS was 25% from diagnosis and 22% from CRS-HIPEC. Median RFS was 7.4 months. The rate of 30-day Clavien-Dindo grade ≥ 3 complications was 32%; specifically, the rate of anastomotic leak was 22%. Multivariable analysis identified the number of pathologically positive lymph nodes as an independent predictor of postoperative OS. CONCLUSIONS In patients with gastric adenocarcinoma and isolated peritoneal metastasis treated with CRS-HIPEC, 3-year OS was 22% from CRS-HIPEC, and complications were common. The number of pathologic lymph node metastases was inversely correlated with overall survival. Further investigation of CRS-HIPEC for GA should include patient selection based on response to systemic chemotherapy or incorporate novel intraperitoneal treatment strategies.
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Affiliation(s)
- Benjamin L Green
- Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Alisa N Blumenthaler
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Lauren A Gamble
- Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - James D McDonald
- Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Kristen Robinson
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Maureen Connolly
- Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Monica Epstein
- Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Jonathan M Hernandez
- Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Andrew M Blakely
- Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Brian D Badgwell
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
| | - Jeremy L Davis
- Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
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31
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Surgical Options for Peritoneal Surface Metastases from Digestive Malignancies-A Comprehensive Review. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:medicina59020255. [PMID: 36837456 PMCID: PMC9960111 DOI: 10.3390/medicina59020255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 01/25/2023] [Accepted: 01/25/2023] [Indexed: 01/31/2023]
Abstract
The peritoneum is a common site for the dissemination of digestive malignancies, particularly gastric, colorectal, appendix, or pancreatic cancer. Other tumors such as cholangiocarcinomas, digestive neuroendocrine tumors, or gastrointestinal stromal tumors (GIST) may also associate with peritoneal surface metastases (PSM). Peritoneal dissemination is proven to worsen the prognosis of these patients. Cytoreductive surgery (CRS), along with systemic chemotherapy, have been shown to constitute a survival benefit in selected patients with PSM. Furthermore, the association of CRS with hyperthermic intraperitoneal chemotherapy (HIPEC) seems to significantly improve the prognosis of patients with certain types of digestive malignancies associated with PSM. However, the benefit of CRS with HIPEC is still controversial, especially due to the significant morbidity associated with this procedure. According to the results of the PRODIGE 7 trial, CRS for PSM from colorectal cancer (CRC) achieved overall survival (OS) rates higher than 40 months, but the addition of oxaliplatin-based HIPEC failed to improve the long-term outcomes. Furthermore, the PROPHYLOCHIP and COLOPEC trials failed to demonstrate the effectiveness of oxaliplatin-based HIPEC for preventing peritoneal metastases development in high-risk patients operated for CRC. In this review, we discuss the limitations of these studies and the reasons why these results are not sufficient to refute this technique, until future well-designed trials evaluate the impact of different HIPEC regimens. In contrast, in pseudomyxoma peritonei, CRS plus HIPEC represents the gold standard therapy, which is able to achieve 10-year OS rates ranging between 70 and 80%. For patients with PSM from gastric carcinoma, CRS plus HIPEC achieved median OS rates higher than 40 months after complete cytoreduction in patients with a peritoneal cancer index (PCI) ≤6. However, the data have not yet been validated in randomized clinical trials. In this review, we discuss the controversies regarding the most efficient drugs that should be used for HIPEC and the duration of the procedure. We also discuss the current evidence and controversies related to the benefit of CRS (and HIPEC) in patients with PSM from other digestive malignancies. Although it is a palliative treatment, pressurized intraperitoneal aerosolized chemotherapy (PIPAC) significantly increases OS in patients with unresectable PSM from gastric cancer and represents a promising approach for patients with PSM from other digestive cancers.
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32
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Yin Z, Shi R, Xia X, Li L, Yang Y, Li S, Xu J, Xu Y, Cai X, Wang S, Liu Z, Peng T, Peng Y, Wang H, Ye M, Liu Y, Chen Z, Tan W. An Implantable Magnetic Vascular Scaffold for Circulating Tumor Cell Removal In Vivo. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2022; 34:e2207870. [PMID: 36271719 DOI: 10.1002/adma.202207870] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 10/11/2022] [Indexed: 06/16/2023]
Abstract
An integrated trapped device (ITD) capable of removal of circulating tumor cells (CTCs) can assuage or even prevent metastasis. However, adhesion repertoires are ordinarily neglected in the design of ITDs, possibly leading to the omission of highly metastatic CTC and treatment failure. Here a vascular-like ITD with adhesive sites and wireless magnetothermal response to remove highly metastatic CTC in vivo is presented. Such a vascular-like ITD comprises circumferential well-aligned fibers and artificial adhesion repertoires and is optimized for magnetothermal integration. Continuous and repeated capture in a dynamic environment increases capture efficiency over time. Meanwhile, the heat generation of the ITD leads to the capture of CTC death owing to cell heat sensitivity. Furthermore, the constructed bioinspired ultrastructure of the ITD prevents vascular blockage and induces potential vascular regeneration. Overall, this work defines an extendable strategy for constructing adhesion repertoires against intravascular shear forces, provides a vascular-like ITD for reducing CTC counts, and is expected to alleviate the risk of cancer recurrence.
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Affiliation(s)
- Zhiwei Yin
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, 410082, China
| | - Rui Shi
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, 410082, China
| | - Xin Xia
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, 410082, China
| | - Ling Li
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, 410082, China
- The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, 310022, China
| | - Yanxia Yang
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, 410082, China
| | - Shengkai Li
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, 410082, China
| | - Jieqiong Xu
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, 410082, China
| | - Yiting Xu
- Key Laboratory of Theoretical Organic Chemistry and Function Molecule, Ministry of Education, School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, 411201, China
| | - Xinqi Cai
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, 410082, China
| | - Shen Wang
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, 410082, China
| | - Zhangkun Liu
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, 410082, China
| | - Tianhuan Peng
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, 410082, China
| | - Ying Peng
- NHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, 410008, China
| | - Hua Wang
- Pediatric Research Institute, Hunan Children's Hospital, Changsha, 410007, China
| | - Mao Ye
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, 410082, China
| | - Yanlan Liu
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, 410082, China
| | - Zhuo Chen
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, 410082, China
| | - Weihong Tan
- Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, 410082, China
- The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, 310022, China
- Institute of Molecular Medicine (IMM), Renji Hospital, School of Medicine and College of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China
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Rhode P, Schönherr T, Gockel I. [38/f-Gastric perforation and loss of weight : Preparation for the medical specialist examination: part 27]. CHIRURGIE (HEIDELBERG, GERMANY) 2022; 93:124-128. [PMID: 36427184 DOI: 10.1007/s00104-022-01767-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 10/25/2022] [Indexed: 11/27/2022]
Affiliation(s)
- P Rhode
- Klinik und Poliklinik für Viszeral‑, Transplantations‑, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, AöR, Liebigstr. 20, 04103, Leipzig, Deutschland.
| | - T Schönherr
- Klinik und Poliklinik für Viszeral‑, Transplantations‑, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, AöR, Liebigstr. 20, 04103, Leipzig, Deutschland
| | - I Gockel
- Klinik und Poliklinik für Viszeral‑, Transplantations‑, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, AöR, Liebigstr. 20, 04103, Leipzig, Deutschland
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Li C, Peng X, Peng Z, Yan B. circBGN accelerates gastric cancer cell proliferation and invasion via activating IL6/STAT3 signaling pathway. FASEB J 2022; 36:e22604. [PMID: 36250950 DOI: 10.1096/fj.202200957rr] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 09/20/2022] [Accepted: 09/28/2022] [Indexed: 01/17/2023]
Abstract
Circular RNAs participate in the pathogenesis of various tumors, including gastric cancer (GC). In this study, we investigated the role of circBGN in regulating proliferation and invasion of GC cells and elucidated the mechanism. The expression of circBGN was assessed by quantitative reverse-transcription PCR and in situ hybridization. In addition, loss- and gain-of-function investigations in vitro and in vivo were performed to determine the biological functions of circBGN. Luciferase reporter assays and rescue experiments were applied to investigate the interaction between circBGN and miR-149-5p as well as the relationship between miR-149-5p and IL6. Our results showed that circBGN expression was significantly elevated in GC tissues and cells. Knockdown of circBGN dramatically suppressed GC cell proliferation and invasion in vitro. Xenograft experiments revealed that knockdown of circBGN delayed tumor growth in vivo. Furthermore, circBGN can directly bind to miR-149-5p, thereby preventing miR-149-5p from binding to its target mRNA [IL6 mRNA], thus activating IL6/STAT3 signaling pathway. Rescue assays indicated that circBGN regulates GC cell proliferation and invasion by upregulating miR-149-5p/IL6 axis output. Taken together, our investigation indicates that circBGN supports GC progression by activating IL6/STAT3 signaling pathway, thus pointing to a new possible therapeutic target in GC.
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Affiliation(s)
- Chenghui Li
- Department of General Surgery, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, China
| | - Xiang Peng
- Department of General Surgery, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, China
| | - Zhiyong Peng
- Department of General Surgery, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, China
| | - Bin Yan
- Department of General Surgery, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, China
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35
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MicroRNA-34c-5p exhibits anticancer properties in gastric cancer by targeting MAP2K1 to inhibit cell proliferation, migration, and invasion. BIOMED RESEARCH INTERNATIONAL 2022; 2022:7375661. [PMID: 36203485 PMCID: PMC9532111 DOI: 10.1155/2022/7375661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 08/27/2022] [Indexed: 12/02/2022]
Abstract
Purpose Gastric cancer(GC)is one of the deadliest digestive tract tumors worldwide，existing studies suggest that dysregulated expression of microRNAs (miRNAs) plays an important role in the pathogenesis and progression of GC. This study aimed to investigate the expression, biological function, and downstream mechanism of miR-34c-5p in GC, provide new targets for gastric cancer diagnosis and treatment. Methods The expression of miR-34c-5p in GC tissues and cell lines was examined by RT-qPCR. Cell wound healing, transwell and cell cloning assays were used to detect the effect of miR-34c-5p on the migration and invasion abilities, respectively, of GC cells. Western blot was performed to detect the expression of related proteins. Bioinformatics analysis was used to predict the binding of MAP2K1 to miR-34c-5p and the targeting relationship was confirmed by dual luciferase reporter assay. Results The expression level of miR-34c-5p was significantly decreased in GC tissues and cell lines. miR-34c-5p overexpression inhibited migration, invasion, and colony formation of gastric cancer cells, the related protein E-cadherin expression was significantly increased and N-cadherin, vimentin, and PCNA expression were significantly decreased, while miR-34c-5p knockdown exerted the opposite effects. In addition, the targeting relationship between miR-34c-5p and MAP2K1 was predicted and confirmed, and further confirmed by rescue experiments that MAP2K1 alleviated the inhibitory effect of miR-34c-5p in GC. Conclusion MiR-34c-5p is lowly expressed in GC, and it can target MAP2K1 to exert inhibitory effects on GC proliferation, invasion, and migration. These findings provide a promising biomarker and a potential therapeutic target for gastric cancer.
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36
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Adamina M, Warlaumont M, Berger MD, Däster S, Delaloye R, Digklia A, Gloor B, Fritsch R, Koeberle D, Koessler T, Lehmann K, Müller P, Peterli R, Ris F, Steffen T, Weisshaupt CS, Hübner M. Comprehensive Treatment Algorithms of the Swiss Peritoneal Cancer Group for Peritoneal Cancer of Gastrointestinal Origin. Cancers (Basel) 2022; 14:4275. [PMID: 36077810 PMCID: PMC9454505 DOI: 10.3390/cancers14174275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 08/26/2022] [Accepted: 08/29/2022] [Indexed: 11/16/2022] Open
Abstract
Peritoneal cancer (PC) is a dire finding, yet in selected patients, long-term survival is possible. Complete cytoreductive surgery (CRS) together with combination immunochemotherapy is essential to achieve cure. Hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC) are increasingly added to the multimodal treatment. The Swiss Peritoneal Cancer Group (SPCG) is an interdisciplinary group of expert clinicians. It has developed comprehensive treatment algorithms for patients with PC from pseudomyxoma peritonei, peritoneal mesothelioma, gastric, and colorectal origin. They include multimodal neoadjuvant treatment, surgical resection, and palliative care. The indication for and results of CRS HIPEC and PIPAC are discussed in light of the current literature. Institutional volume and clinical expertise required to achieve best outcomes are underlined, while inclusion of patients considered for CRS HIPEC and PIPAC in a clinical registry is strongly advised. The present recommendations are in line with current international guidelines and provide the first comprehensive treatment proposal for patients with PC including intraperitoneal chemotherapy. The SPCG comprehensive treatment algorithms provide evidence-based guidance for the multimodal care of patients with PC of gastrointestinal origin that were endorsed by all Swiss clinicians routinely involved in the multimodal care of these challenging patients.
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Affiliation(s)
- Michel Adamina
- Klinik für Viszeral- und Thoraxchirurgie, Kantonsspital Winterthur, 8401 Winterthur, Switzerland
- Faculty of Medicine, University of Basel, 4056 Basel, Switzerland
| | - Maxime Warlaumont
- Chirurgie Digestive et Cancérologique, CHU de Lille, CH de Cambrai, 59000 Lille, France
- Department of Visceral Surgery, Lausanne University Hospital CHUV, University of Lausanne, 1011 Lausanne, Switzerland
| | - Martin D. Berger
- Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
| | - Silvio Däster
- Clarunis, Department of Visceral Surgery, University Centre for Gastrointestinal and Liver Diseases, St. Claraspital and University Hospital Basel, 4031 Basel, Switzerland
| | - Raphaël Delaloye
- Department of Medical Oncology, University Hospital Basel, 4031 Basel, Switzerland
| | - Antonia Digklia
- Department of Oncology, Lausanne University Hospital CHUV, University of Lausanne, 1011 Lausanne, Switzerland
| | - Beat Gloor
- Department of Visceral Surgery and Medicine, Inselspital, University Bern, 3010 Bern, Switzerland
| | - Ralph Fritsch
- Department of Medical Oncology and Hematology, University Hospital Zurich, 8091 Zurich, Switzerland
| | - Dieter Koeberle
- Department of Medical Oncology and Hematology, St. Claraspital, 4002 Basel, Switzerland
- Faculty of Medicine, University of Bern, 3012 Bern, Switzerland
| | - Thibaud Koessler
- Department of Oncology, Geneva University Hospital, 1205 Geneva, Switzerland
| | - Kuno Lehmann
- Department of Surgery and Transplantation, University Hospital Zurich, 8091 Zurich, Switzerland
| | - Phaedra Müller
- Klinik für Viszeral- und Thoraxchirurgie, Kantonsspital Winterthur, 8401 Winterthur, Switzerland
| | - Ralph Peterli
- Clarunis, Department of Visceral Surgery, University Centre for Gastrointestinal and Liver Diseases, St. Claraspital and University Hospital Basel, 4031 Basel, Switzerland
| | - Frédéric Ris
- Division of Digestive Surgery, University Hospitals of Geneva, 1205 Geneva, Switzerland
| | - Thomas Steffen
- Klinik für Allgemein-, Viszeral-, Endokrine und Transplantationschirurgie, Kantonsspital St. Gallen, 9000 St. Gallen, Switzerland
| | | | - Martin Hübner
- Department of Visceral Surgery, Lausanne University Hospital CHUV, University of Lausanne, 1011 Lausanne, Switzerland
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Ng D, Ali A, Lee K, Eymael D, Abe K, Luu S, Kazazian K, Lu YQ, Brar S, Conner J, Magalhaes M, Swallow CJ. Investigating the mechanisms of peritoneal metastasis in gastric adenocarcinoma using a novel ex vivo peritoneal explant model. Sci Rep 2022; 12:11499. [PMID: 35798764 PMCID: PMC9262973 DOI: 10.1038/s41598-022-13948-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 05/31/2022] [Indexed: 11/09/2022] Open
Abstract
Gastric adenocarcinoma, commonly known as stomach cancer, has a predilection for metastasis to the peritoneum, which portends limited survival. The peritoneal metastatic cascade remains poorly understood, and existing models fail to recapitulate key elements of the interaction between cancer cells and the peritoneal layer. To explore the underlying cellular and molecular mechanisms of peritoneal metastasis, we developed an ex vivo human peritoneal explant model. Fresh peritoneal tissue samples were suspended, mesothelial layer down but without direct contact, above a monolayer of red-fluorescent dye stained AGS human gastric adenocarcinoma cells for 24 h, then washed thoroughly. Implantation of AGS cells within the explanted peritoneum and invasion beyond the mesothelial layer were examined serially using real-time confocal fluorescence microscopy. Histoarchitecture of the explanted peritoneum was preserved over 5 days ex vivo. Both implantation and invasion were suppressed by restoration of functional E-cadherin through stable transfection of AGS cells, demonstrating sensitivity of the model to molecular manipulation. Thus, our ex vivo human peritoneal explant model permits meaningful investigation of the pathways and mechanism that contribute to peritoneal metastasis. The model will facilitate screening of new therapies that target peritoneal dissemination of gastric, ovarian and colorectal cancer.
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Affiliation(s)
- Deanna Ng
- Institute of Medical Science, University of Toronto, Toronto, Canada.,Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.,Department of Surgery, University of Toronto, Toronto, Canada
| | - Aiman Ali
- Faculty of Dentistry, University of Toronto, Toronto, Canada
| | - Kiera Lee
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada
| | - Denise Eymael
- Faculty of Dentistry, University of Toronto, Toronto, Canada
| | - Kento Abe
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada
| | - Shelly Luu
- Institute of Medical Science, University of Toronto, Toronto, Canada.,Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.,Department of Surgical Oncology and Division of General Surgery, Princess Margaret Cancer Centre, University Health Network/Mount Sinai Hospital, 600 University Avenue #1225, Toronto, ON, M5G 1X5, Canada.,Department of Surgery, University of Toronto, Toronto, Canada
| | - Karineh Kazazian
- Institute of Medical Science, University of Toronto, Toronto, Canada.,Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.,Department of Surgical Oncology and Division of General Surgery, Princess Margaret Cancer Centre, University Health Network/Mount Sinai Hospital, 600 University Avenue #1225, Toronto, ON, M5G 1X5, Canada.,Department of Surgery, University of Toronto, Toronto, Canada
| | - Yi Qing Lu
- Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada
| | - Savtaj Brar
- Department of Surgical Oncology and Division of General Surgery, Princess Margaret Cancer Centre, University Health Network/Mount Sinai Hospital, 600 University Avenue #1225, Toronto, ON, M5G 1X5, Canada.,Department of Surgery, University of Toronto, Toronto, Canada
| | - James Conner
- Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada
| | - Marco Magalhaes
- Institute of Medical Science, University of Toronto, Toronto, Canada.,Faculty of Dentistry, University of Toronto, Toronto, Canada
| | - Carol J Swallow
- Institute of Medical Science, University of Toronto, Toronto, Canada. .,Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada. .,Department of Surgical Oncology and Division of General Surgery, Princess Margaret Cancer Centre, University Health Network/Mount Sinai Hospital, 600 University Avenue #1225, Toronto, ON, M5G 1X5, Canada. .,Department of Surgery, University of Toronto, Toronto, Canada.
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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: 21] [Impact Index Per Article: 7.0] [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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Morgagni P, Solaini L, Saragoni L, Monti M, Valgiusti M, Vittimberga G, Frassineti GL, Framarini M, Ercolani G. Conversion Surgery in Gastric Cancer Carcinomatosis. Front Oncol 2022; 12:852559. [PMID: 35356199 PMCID: PMC8959896 DOI: 10.3389/fonc.2022.852559] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 02/08/2022] [Indexed: 11/13/2022] Open
Abstract
Background After the REGATTA trial, patients with stage IV gastric cancer could only benefit from chemotherapy (CHT). However, some of these patients may respond extraordinarily to palliative chemotherapy, converting their disease to a radically operable stage. We present a single centre experience in treating peritoneal carcinomatosis from gastric cancer. Methods All patients with stage IV gastric cancer with peritoneal metastases as a single metastatic site operated at a single centre between 2005 and 2020 were included. Cases were grouped according to the treatment received. Results A total of 118 patients were considered, 46 were submitted to palliative gastrectomy (11 were considered M1 because of an unsuspected positive peritoneal cytology), and 20 were submitted to Hyperthermic Intraperitoneal Chemotherapy (HIPEC) because of a <6 Peritoneal Cancer Index (PCI). The median overall survival (OS) after surgery plus HIPEC was 46.7 (95% CI 15.8-64.0). Surgery (without HIPEC) after CHT presented a median OS 14.4 (8.2-26.8) and after upfront surgery 14.7 (10.9-21.1). Patients treated with upfront surgery and considered M1 only because of a positive cytology, had a median OS of 29.2 (25.2-29.2). The OS of patients treated with surgery plus HIPEC were 60.4 months (9.2-60.4) in completely regressed cancer after chemotherapy and 31.2 (15.8-64.0) in those partially regressed (p = 0.742). Conclusions Conversion surgery for peritoneal carcinomatosis from gastric cancer was associated with long survival and it should always be taken into consideration in this group of patients.
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Affiliation(s)
- Paolo Morgagni
- General and Oncologic Surgery, “Morgagni-Pierantoni” Hospital, Forlì, Italy
| | - Leonardo Solaini
- General and Oncologic Surgery, “Morgagni-Pierantoni” Hospital, Forlì, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Luca Saragoni
- Pathology Unit, “Morgagni-Pierantoni” Hospital, Forlì, Italy
| | - Manlio Monti
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “DinoAmadori”, Meldola, Italy
| | - Martina Valgiusti
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “DinoAmadori”, Meldola, Italy
| | | | - Giovanni Luca Frassineti
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “DinoAmadori”, Meldola, Italy
| | - Massimo Framarini
- General and Oncologic Surgery, “Morgagni-Pierantoni” Hospital, Forlì, Italy
| | - Giorgio Ercolani
- General and Oncologic Surgery, “Morgagni-Pierantoni” Hospital, Forlì, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
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Harada K, Yamashita K, Iwatsuki M, Baba H, Ajani JA. Intraperitoneal therapy for gastric cancer peritoneal carcinomatosis. Expert Rev Clin Pharmacol 2022; 15:43-49. [PMID: 35184625 DOI: 10.1080/17512433.2022.2044790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
INTRODUCTION Gastric adenocarcinoma (GAC) is one of the most aggressive malignancies worldwide and has a poor prognosis. Multidisciplinary therapies are used in its treatment, but the prognosis for GAC patients with peritoneal metastases (PM) remains poor and there is no effective established approach. AREAS COVERED This review summarizes the results of recent clinical studies and recent advances in the management, including surgery, chemotherapy, targeted therapy, and immunotherapy. In this review, keywords were searched in combination with 'peritoneal carcinomatosis' and 'gastric cancer' in PubMed, and then studies that evaluated peritoneal carcinomatosis associated with gastric cancer were identified through reading them. Several studies were quoted at second hand. Despite recent advances in therapeutic approaches such as systemic chemotherapy, immunotherapy, intraperitoneal chemotherapy, debulking surgery, thermal hyperthermic intraperitoneal chemotherapy, pressurized intraperitoneal aerosol chemotherapy, immunotherapy, and best supportive therapy, further studies are necessary. This review also summarizes molecular biology of GAC patients with PM. EXPERT OPINION Each modality is advancing and some have shown therapeutic effects, but none have become standard treatments that exhibit remarkable effects. To improve the prognosis of GAC patients with PM, large-scale clinical trials and further basic research are required.
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Affiliation(s)
- Kazuto Harada
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan
| | - Kohei Yamashita
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.,Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA
| | - Masaaki Iwatsuki
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan
| | - Jaffer A Ajani
- Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA
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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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Sun BJ, Lee B. Review of Regional Therapies for Gastric Cancer with Peritoneal Metastases. Cancers (Basel) 2022; 14:cancers14030570. [PMID: 35158837 PMCID: PMC8833629 DOI: 10.3390/cancers14030570] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 01/15/2022] [Accepted: 01/19/2022] [Indexed: 12/20/2022] Open
Abstract
Simple Summary Gastric cancer is usually diagnosed at late stages and is associated with poor five-year survival rates. Metastasis to the peritoneal cavity is common and leads to even worse outcomes. Currently, the mainstay of treatment for metastatic gastric cancer is systemic chemotherapy or supportive care. These recommendations remain despite evidence that suggests systemic therapy has poor penetration into the abdominal cavity, limiting efficacy against peritoneal disease. Newer treatments have been developed to address this problem, specifically regional therapies aimed at delivering chemotherapy directly into the peritoneal cavity to eradicate tumor cells. These novel therapies include hyperthermic intraperitoneal chemotherapy, normothermic intraperitoneal chemotherapy, and pressurized intraperitoneal aerosolized chemotherapy. Regional therapies may also be combined with surgery to remove both macroscopic and microscopic disease. Although more clinical trials are needed to evaluate its efficacy, early studies have shown promising outcomes with intraperitoneal chemotherapy. Abstract Gastric cancer carries a poor prognosis and is a leading cause of cancer-related mortality worldwide. Patients with gastric cancer who develop peritoneal metastases have an even more dismal prognosis, with median survival time measured in months. Since studies have demonstrated that systemic chemotherapy has poor penetration into the peritoneum, multimodal treatment with intraperitoneal chemotherapy has been proposed for the treatment of peritoneal metastases and has become the foundation for newer therapeutic techniques and clinical trials. These include heated intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery (CRS), which involves the application of heated chemotherapy into the abdomen with or without tumor debulking surgery; normothermic intraperitoneal chemotherapy (NIPEC), in which non-heated chemotherapy can be delivered into the abdomen via a peritoneal port allowing for repeat dosing; and pressurized intraperitoneal aerosolized chemotherapy (PIPAC), a newer technique of pressurized and aerosolized chemotherapy delivered into the abdomen during laparoscopy. Early results with intraperitoneal chemotherapy have shown promise in increasing disease-free and overall survival in select patients. Additionally, there may be a palliative effect of these regional therapies. In this review, we explore and summarize these different intraperitoneal chemotherapy treatment regimens for gastric cancer with peritoneal metastases.
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Mazurek M, Szlendak M, Forma A, Baj J, Maciejewski R, Roviello G, Marano L, Roviello F, Polom K, Sitarz R. Hyperthermic Intraperitoneal Chemotherapy in the Management of Gastric Cancer: A Narrative Review. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:681. [PMID: 35055500 PMCID: PMC8776178 DOI: 10.3390/ijerph19020681] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 01/02/2022] [Accepted: 01/04/2022] [Indexed: 02/05/2023]
Abstract
Gastric cancer (GC) patients with peritoneal metastasis tend to achieve poor clinical outcomes. Until recently, the treatment options were limited mainly to either palliative chemotherapy or radiation therapy in exceptional cases. Currently, these patients benefit from multimodal treatment, such as cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Despite good overall results, this treatment modality is still widely debated. The following study is designed to assess the papers about the possible application and utility of HIPEC in GC. A search in the PubMed, Web of Science, and Scopus databases was performed to assess the papers devoted to the role of HIPEC in GC treatment; a literature search was performed until March 21st; and, finally, 50 studies with a total number of 3946 patients were analyzed. According to the most recent data, it seems to be reasonable to limit the duration of HIPEC to the shortest effective time. Moreover, the drugs used in HIPEC need to have equal concentrations and the same solvent. Perioperative chemotherapy needs to be reported in detail and, furthermore, the term "morbidity" should be defined more clearly by the authors.
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Affiliation(s)
- Marek Mazurek
- Department of Surgical Oncology, Voivodship Hospital in Siedlce, 08-110 Siedlce, Poland;
| | - Małgorzata Szlendak
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (M.S.); (J.B.); (R.M.)
- Department of Oncology, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Alicja Forma
- Department of Forensic Medicine, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Jacek Baj
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (M.S.); (J.B.); (R.M.)
| | - Ryszard Maciejewski
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (M.S.); (J.B.); (R.M.)
| | | | - Luigi Marano
- Department of General Surgery and Surgical Oncology, University of Siena, 53100 Siena, Italy; (L.M.); (F.R.)
| | - Franco Roviello
- Department of General Surgery and Surgical Oncology, University of Siena, 53100 Siena, Italy; (L.M.); (F.R.)
| | - Karol Polom
- Department of Surgical Oncology, Medical University of Gdansk, 80-070 Gdansk, Poland;
| | - Robert Sitarz
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (M.S.); (J.B.); (R.M.)
- Department of Surgical Oncology, St. John’s Cancer Center, 20-090 Lublin, Poland
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Hou S, Wang J, Li W, Hao X, Hang Q. Roles of Integrins in Gastrointestinal Cancer Metastasis. Front Mol Biosci 2021; 8:708779. [PMID: 34869579 PMCID: PMC8634653 DOI: 10.3389/fmolb.2021.708779] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 10/08/2021] [Indexed: 12/12/2022] Open
Abstract
Integrins are a large family of heterodimeric transmembrane receptors which mediate cell adhesion and transmit signals to the cell interior. The mechanistic roles of integrins have long been an enigma in cancer, given its complexity in regulating different cellular behaviors. Recently, however, increasing research is providing new insights into its function and the underlying mechanisms, which collectively include the influences of altered integrin expression on the aberrant signaling pathways and cancer progression. Many studies have also demonstrated the potentiality of integrins as therapeutic targets in cancer treatment. In this review, we have summarized these recent reports and put a particular emphasis on the dysregulated expression of integrins and how they regulate related signaling pathways to facilitate the metastatic progression of gastrointestinal cancer, including gastric cancer (GC) and colorectal cancer (CRC), which will address the crucial roles of integrins in gastrointestinal cancer.
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Affiliation(s)
- Sicong Hou
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Jiaxin Wang
- Department of Clinical Medicine, Medical College, Yangzhou University, Yangzhou, China
| | - Wenqian Li
- Department of Clinical Medicine, Medical College, Yangzhou University, Yangzhou, China
| | - Xin Hao
- Department of Clinical Medicine, Medical College, Yangzhou University, Yangzhou, China
| | - Qinglei Hang
- Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
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Yap DRY, Wong JSM, Tan QX, Tan JWS, Chia CS, Ong CAJ. Effect of HIPEC on Peritoneal Recurrence in Peritoneal Metastasis Treated With Cytoreductive Surgery: A Systematic Review. Front Oncol 2021; 11:795390. [PMID: 34926311 PMCID: PMC8678115 DOI: 10.3389/fonc.2021.795390] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 11/15/2021] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Peritoneal metastasis (PM) is a late-stage manifestation of intra-abdominal malignancies. The current standard of care indicates that cure can only be achieved with cytoreductive surgery (CRS) which is often indicated with concurrent adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC). However, the utility of HIPEC within subsets of PM is not fully understood. We seek to compare the effectiveness of HIPEC in improving peritoneal recurrence rates in PM of different origins. METHODS We conducted a systematic review of trials on the PubMed, EMBASE, and Cochrane databases, last searched in August 2021. Biases were assessed using the Cochrane Collaboration's tool for assessing the risk of bias in randomized trials as well as the Methodological Index for Non-Randomized Studies (MINORS) framework. RESULTS 7 gastric PM studies, 3 ovarian PM studies, and 3 colorectal PM studies were included. Recurrence-free survival was improved in the HIPEC + CRS cohort in 5 gastric trials but only 1 ovarian trial and none of colorectal origin. DISCUSSION Our findings indicate decent effectiveness of HIPEC in gastric PM, but limited utility in ovarian and colorectal PM. Limitations in the current literature are attributed to the paucity of data available, a lack of homogeneity and consideration of novel and personalised treatment regimens. We implore for further studies to be conducted with a focus on patient selection and stratification, and suggest a reframing of approach towards modern molecular and targeted therapeutic options in future studies of HIPEC. SYSTEMATIC REVIEW REGISTRATION https://www.researchregistry.com/browse-the-registry#registryofsystematicreviewsmeta-analyses/registryofsystematicreviewsmeta-analysesdetails/60c1ffff0c1b78001e8efbe3/, identifier reviewregistry1166.
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Affiliation(s)
- Daniel Ren Yi Yap
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
| | - Jolene Si Min Wong
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- SingHealth Duke-NUS Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
| | - Qiu Xuan Tan
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
| | - Joey Wee-Shan Tan
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
| | - Claramae Shulyn Chia
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- SingHealth Duke-NUS Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
| | - Chin-Ann Johnny Ong
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
- SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- SingHealth Duke-NUS Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- Institute of Molecular and Cell Biology, A*STAR Research Entities, Singapore, Singapore
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Zhu M, Zhang N, Ma J, He S. Integration of exosomal miR-106a and mesothelial cells facilitates gastric cancer peritoneal dissemination. Cell Signal 2021; 91:110230. [DOI: 10.1016/j.cellsig.2021.110230] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 12/20/2021] [Accepted: 12/21/2021] [Indexed: 12/24/2022]
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Bausys A, Gricius Z, Aniukstyte L, Luksta M, Bickaite K, Bausys R, Strupas K. Current treatment strategies for patients with only peritoneal cytology positive stage IV gastric cancer. World J Clin Cases 2021; 9:9711-9721. [PMID: 34877310 PMCID: PMC8610919 DOI: 10.12998/wjcc.v9.i32.9711] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 07/28/2021] [Accepted: 09/16/2021] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) is one of the most common malignancies worldwide and surgery remains the only potentially curative treatment option for it. Although a significant proportion of GC patients are found with distant metastases already at the initial diagnosis. Peritoneal dissemination is the most common site of metastases. Positive peritoneal cytology (Cy1) is associated with poor long-term outcomes; thus, these patients are considered as stage IV even if macroscopic carcinomatosis is absent. Currently, there is no clear evidence for the most optimal treatment for this distinct subpopulation of the stage IV cohort. Available strategies vary from palliative chemotherapy to upfront gastrectomy. This comprehensive review summarized current evidence of different treatment strategies for Cy1 GC including roles of surgery, systemic and intraperitoneal chemotherapy.
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Affiliation(s)
- Augustinas Bausys
- Department of Abdominal Surgery and Oncology, National Cancer Institute, Vilnius 08406, Lithuania
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 03101, Lithuania
| | - Zilvinas Gricius
- Faculty of Medicine, Vilnius University, Vilnius 08406, Lithuania
| | - Laura Aniukstyte
- Faculty of Medicine, Vilnius University, Vilnius 08406, Lithuania
| | - Martynas Luksta
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 03101, Lithuania
| | | | - Rimantas Bausys
- Department of Abdominal Surgery and Oncology, National Cancer Institute, Vilnius 08406, Lithuania
| | - Kestutis Strupas
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Vilnius University, Vilnius 03101, Lithuania
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Qian S, Villarejo-Campos P, García-Olmo D. The Role of CAR-T Cells in Peritoneal Carcinomatosis from Gastric Cancer: Rationale, Experimental Work, and Clinical Applications. J Clin Med 2021; 10:jcm10215050. [PMID: 34768570 PMCID: PMC8584918 DOI: 10.3390/jcm10215050] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 10/23/2021] [Accepted: 10/26/2021] [Indexed: 12/24/2022] Open
Abstract
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have shown poor effectiveness in treating peritoneal carcinomatosis (PC) of gastric origin with a high tumor burden (high peritoneal cancer index), though there are scarce therapy alternatives that are able to improve survival. In experimental studies, chimeric antigen receptor-T (CAR-T) cell therapy has shown encouraging results in gastric cancer and is currently being evaluated in several clinical trials. Regarding PC, CAR-T cell therapy has also proven useful in experimental studies, especially when administered intraperitoneally, as this route improves cell distribution and lifespan. Although these results need to be supported by ongoing clinical trials, CAR-T cells are a promising new therapeutic approach to peritoneal metastases from gastric cancer. In this review, we summarize the current evidence of the use of CAR-T cells in gastric cancer and PC of gastric origin.
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Affiliation(s)
- Siyuan Qian
- Department of Surgery, Fundación Jimenez Diaz University Hospital, Avda. Reyes Católicos, 2, 28040 Madrid, Spain; (S.Q.); (D.G.-O.)
| | - Pedro Villarejo-Campos
- Department of Surgery, Fundación Jimenez Diaz University Hospital, Avda. Reyes Católicos, 2, 28040 Madrid, Spain; (S.Q.); (D.G.-O.)
- Correspondence: ; Tel.: +34-91-550-48-00 (ext. 2781)
| | - Damián García-Olmo
- Department of Surgery, Fundación Jimenez Diaz University Hospital, Avda. Reyes Católicos, 2, 28040 Madrid, Spain; (S.Q.); (D.G.-O.)
- Department of Surgery, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo s/n, 28034 Madrid, Spain
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Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal metastasis of non-primary origin. Langenbecks Arch Surg 2021; 406:2817-2825. [PMID: 34686891 DOI: 10.1007/s00423-021-02354-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Accepted: 10/10/2021] [Indexed: 12/19/2022]
Abstract
PURPOSE The objective of this study was to analyze the role of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy that has developed in the treatment of patients with peritoneal metastasis of non-primary origin. METHODS Patients who underwent treatment for secondary gastrointestinal and ovarian malignancies over a 20-year period were reviewed. Survival curves were estimated by the Kaplan-Meier product limit method and the log-rank test was used to assess differences between subgroups. RESULTS The study included 293 patients. The most common histology was ovarian cancer (56.3%). Median PCI was 16 and CC0-1 resection was obtained in 88.1% of cases. Grade III and IV complications occurred in 12 patients (4.1%) and 47 patients (16%), respectively. The 30- and 60-day mortality rate was 1.3% (4 patients) and 2.4% (7 patients). Five-year OS was 21.7%, 73.6%, 42.1%, and 0 for colorectal, appendiceal, ovarian, and gastric cancer (p = < 0.0001), respectively, whereas 5-year DFS was 12.4%, 48.4%, 24.3%, and 0 (p = < 0.0001), respectively. Survival outcomes were significantly higher for CC0 in each subgroup of patients. CONCLUSION Despite being a complex procedure, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy should be considered a safe treatment with acceptable postoperative morbidity and mortality rates, if performed in high-volume centers. Good survival outcomes have been increasingly obtained in selected patients with peritoneal metastasis of non-primary origin.
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Laparoscopic Heated Intraperitoneal Chemotherapy in the Treatment of Carcinomatosis of Gastric Adenocarcinoma Origin. J Clin Med 2021; 10:jcm10204757. [PMID: 34682880 PMCID: PMC8539356 DOI: 10.3390/jcm10204757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 10/09/2021] [Accepted: 10/15/2021] [Indexed: 11/30/2022] Open
Abstract
The use of heated intraperitoneal chemotherapy (HIPEC) in conjunction with cytoreductive surgery has been gaining increasing traction in treating gastric adenocarcinoma with metastasis to the peritoneum in recent years. The addition of laparoscopic HIPEC (LS-HIPEC) to these treatment algorithms has increased the flexibility and adaptability of HIPEC integrating into treatment sequencing, allowing for iterative protocols of LS-HIPEC prior to cytoreduction as neoadjuvant treatment, as well as in the palliation of patients with unresectable disease and uncontrolled ascites. As the use of HIPEC in gastric adenocarcinoma continues to be refined, LS-HIPEC algorithms should continue to be considered and utilized both in curative treatment algorithms as well as in patients in the palliative setting. Given that LS-HIPEC remains a relatively nascent treatment modality, we advocate for its use in the setting of a clinical trial when feasible.
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