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1
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McQuade C, Renton M, Chouhan A, MacDermott R, O'Brien C. Review of Imaging Peritoneal Disease and Treatment. Can Assoc Radiol J 2025; 76:287-301. [PMID: 39641413 DOI: 10.1177/08465371241296778] [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: 12/07/2024] Open
Abstract
Peritoneal disease can be classified as either benign or malignant in nature. Malignant peritoneal disease can be further considered as either primary or secondary in origin. Primary peritoneal malignancy includes peritoneal mesothelioma, serous carcinoma, and desmoplastic small round cell tumour. Peritoneal carcinomatosis is the most commonly encountered secondary malignant peritoneal disease, typically of ovarian, gastric, colorectal, pancreatic, small bowel neuroendocrine, or breast origin. Others include peritoneal lymphomatosis and sarcomatosis. Benign peritoneal pathology may mimic malignant disease. Differentiating benign from malignant peritoneal pathology can be challenging, but is critical to guide appropriate care and avoid unnecessary intervention. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) offers potentially curative treatment for patients with peritoneal carcinomatosis, pseudomyxoma peritonei, and peritoneal mesothelioma. For such patients, the radiologist provides crucial pre-operative information highlighting sites of disease involvement, particularly for sites which are challenging to assess at laparotomy or laparoscopy, including the hepatic dome, subdiaphragmatic space and mesenteric root. The radiologist is also essential to identify potential contraindications to surgery, as well as interpreting normal post-operative appearances, complications and assessing for disease recurrence.
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Affiliation(s)
- Colin McQuade
- Abdominal Division, Joint Department of Medical Imaging, Toronto, ON, Canada
| | - Mary Renton
- Abdominal Division, Joint Department of Medical Imaging, Toronto, ON, Canada
| | - Ashvina Chouhan
- Abdominal Division, Joint Department of Medical Imaging, Toronto, ON, Canada
| | - Roisin MacDermott
- Abdominal Division, Joint Department of Medical Imaging, Toronto, ON, Canada
| | - Ciara O'Brien
- Abdominal Division, Joint Department of Medical Imaging, Toronto, ON, Canada
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Fan Y, Song S, Pizzi MP, Zou G, Vykoukal JV, Yoshimura K, Jin J, Calin GA, Waters RE, Gan Q, Wang L, Hanash S, Dhar SS, Ajani JA. Exosomal Galectin-3 promotes peritoneal metastases in gastric adenocarcinoma via microenvironment alterations. iScience 2025; 28:111564. [PMID: 39811647 PMCID: PMC11731617 DOI: 10.1016/j.isci.2024.111564] [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: 03/12/2024] [Revised: 06/22/2024] [Accepted: 12/06/2024] [Indexed: 01/16/2025] Open
Abstract
Peritoneal carcinomatosis (PC) in gastric adenocarcinoma (GAC) is the most common metastatic site and leads to a short median survival. Exosomes have been shown to remodel the microenvironment, facilitating tumor metastases. However, the functional component in GAC cell-derived exosomes that remodel the landscape in the peritoneal cavity remains unclear. To address this, we performed in-depth proteomic profiling of ascites-derived exosomes from patients with PC, and we found that Galectin-3 was highly enriched in exosomes derived from malignant ascites. exosomal Galectin-3 was the crucial regulator of PC. Blockage of exosomal Galectin-3 significantly inhibited tumor metastases and prolonged overall survival. Exosomal Galectin-3 activated cancer-associated fibroblasts through integrin α1β1/FAK/Akt/mTOR/CXCL12 signaling. Combined inhibition of the CXCL12-CXCR4 axis and exosomal Galectin-3 enhanced the efficacy of anti-PD-1 immunotherapy, leading to significantly diminished PC progression and durable antitumor responses. These findings provide a rationale for clinical strategy of targeting exosomal Galectin-3 to treat PC.
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Affiliation(s)
- Yibo Fan
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Shumei Song
- Coriell Institute for Medical Research, Camden, NJ 08103, USA
| | - Melissa Pool Pizzi
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Gengyi Zou
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Jody V Vykoukal
- Department of Clinical Cancer Prevention, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Katsuhiro Yoshimura
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan
| | - Jiankang Jin
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - George A Calin
- Department of Translational Molecular Pathology, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Rebecca E Waters
- Department of Pathology, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Qiong Gan
- Department of Pathology, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Linghua Wang
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Samir Hanash
- Department of Clinical Cancer Prevention, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Shilpa S Dhar
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Jaffer A Ajani
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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3
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Khomiak A, Ghaffar S, Rodriguez Franco S, Ziogas IA, Yee EJ, Franklin O, Cumbler E, Chauhan A, McCarter MD, Gleisner AL, Ahrendt S, Del Chiaro M, Schulick RD, Mungo B. Survival Outcomes of Cytoreductive Surgery with HIPEC in Gastric Adenocarcinoma: A National Cancer Database Study. Ann Surg Oncol 2024; 31:8549-8559. [PMID: 39237827 DOI: 10.1245/s10434-024-16142-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 08/19/2024] [Indexed: 09/07/2024]
Abstract
BACKGROUND This study aimed to assess the impact of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) on the survival outcomes for patients with gastric cancer and peritoneal carcinomatosis (PC). METHODS A retrospective analysis of the National Cancer Database from 2004 to 2020 identified patients with topography and histology codes consistent with gastric adenocarcinoma who underwent CRS/HIPEC. The exclusion criteria ruled out known other distant metastasis and missing key data. The study compared the CRS/HIPEC group with patients who had stage IV disease (with the same exclusions for distant metastases) and received systemic chemotherapy but no surgery to the primary site. RESULTS The study included 148 patients who underwent CRS/HIPEC. Their median age was 57 years (interquartile range [IQR], 47-66 years), with 57.4% of the patients identifying as male and 73.6% identifying as white. Most of the CRS/HIPEC patients had locally advanced disease, with 33.8% having pT4 disease and 23% patients having pN3 status. The Charlson-Deyo scores were 0 for 77% and 1 for 16.9% of the patients. The overall survival (OS) among the stage IV patients managed with CRS/HIPEC was significantly longer than for the patients receiving only systemic chemotherapy (median survival, 18.1 vs 9.3 months; p < 0.001), and the 1-year OS was 72.6% versus 38.8% (p < 0.05)). Among the stage IV patients, CRS/HIPEC showed better survival than systemic chemotherapy (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.44-0.73; p < .001) when control was used for the Charlson Deyo score, histology, age, and sex. CONCLUSIONS These results suggest the association of CRS/HIPEC with improved survival for selected patients with gastric adenocarcinoma and peritoneal disease. Some of this difference may have been due to selection bias, but the differences in the survival curves are robust.
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Affiliation(s)
- Andrii Khomiak
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Sumaya Ghaffar
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Salvador Rodriguez Franco
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Ioannis A Ziogas
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Elliott J Yee
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Oskar Franklin
- Department of Diagnostics and Intervention, Surgery, Umeå University, Umeå, Sweden
| | - Ethan Cumbler
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Akshay Chauhan
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Martin D McCarter
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Ana L Gleisner
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Steven Ahrendt
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Richard D Schulick
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Benedetto Mungo
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
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Tang M, Song J, Zhang S, Shu X, Liu S, Ashrafizadeh M, Ertas YN, Zhou Y, Lei M. Innovative theranostic hydrogels for targeted gastrointestinal cancer treatment. J Transl Med 2024; 22:970. [PMID: 39465365 PMCID: PMC11514878 DOI: 10.1186/s12967-024-05749-9] [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: 06/29/2024] [Accepted: 10/08/2024] [Indexed: 10/29/2024] Open
Abstract
Gastrointestinal tumors are the main causes of death among the patients. These tumors are mainly diagnosed in the advanced stages and their response to therapy is unfavorable. In spite of the development of conventional therapeutics including surgery, chemotherapy, radiotherapy and immunotherapy, the treatment of these tumors is still challenging. As a result, the new therapeutics based on (nano)biotechnology have been introduced. Hydrogels are polymeric 3D networks capable of absorbing water to swell with favorable biocompatibility. In spite of application of hydrogels in the treatment of different human diseases, their wide application in cancer therapy has been improved because of their potential in drug and gene delivery, boosting chemotherapy and immunotherapy as well as development of vaccines. The current review focuses on the role of hydrogels in the treatment of gastrointestinal tumors. Hydrogels provide delivery of drugs (both natural or synthetic compounds and their co-delivery) along with gene delivery. Along with delivery, hydrogels stimulate phototherapy (photothermal and photodynamic therapy) in the suppression of these tumors. Besides, the ability of hydrogels for the induction of immune-related cells such as dendritic cells can boost cancer immunotherapy. For more specific cancer therapy, the stimuli-responsive types of hydrogels including thermo- and pH-sensitive hydrogels along with their self-healing ability have improved the site specific drug delivery. Moreover, hydrogels are promising for diagnosis, circulating tumor cell isolation and detection of biomarkers in the gastrointestinal tumors, highlighting their importance in clinic. Hence, hydrogels are diagnostic and therapeutic tools for the gastrointestimal tumors.
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Affiliation(s)
- Min Tang
- Department of Oncology, Chongqing General Hospital, Chongqing University, No.104 Pipa Mountain Main Street, Chongqing, 401120, China
| | - Junzhou Song
- Department of Oncology, BoAo Evergrande International Hospital, Qionghai, 571400, Hainan Province, China
| | - Shuyi Zhang
- Department of Health Management Center, Chongqing General Hospital, Chongqing University, Chongqing, 401120, China
| | - Xiaolei Shu
- Radiation Oncology Center, Chongqing University Cancer Hospital, Chongqing, 400030, China
| | - Shuang Liu
- Department of Ultrasound, Chongqing Health Center for Women and Children, Women and Children's Hospital of Chongqing Medical University, No. 120, Longshan Road, Yubei, Chongqing, 401147, China
| | - Milad Ashrafizadeh
- Department of Radiation Oncology, Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, 250000, Shandong, China.
| | - Yavuz Nuri Ertas
- Department of Biomedical Engineering, Erciyes University, 38039, Kayseri, Türkiye
- Department of Technical Sciences, Western Caspian University, AZ1001, Baku, Azerbaijan
| | - Ya Zhou
- Department of Oncology, Chongqing General Hospital, Chongqing University, No.104 Pipa Mountain Main Street, Chongqing, 401120, China.
| | - Ming Lei
- Department of Nuclear Medicine, Chongqing University FuLing Hospital, Chongqing University, No. 2 Gaosuntang Road, Chongqing, China.
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Bae MI, Jung H, Park EJ, Kwak YL, Song Y. Prognostic Value of the Controlling Nutritional Status (CONUT) Score in Patients Who Underwent Cytoreductive Surgery Combined with Hyperthermic Intraperitoneal Chemotherapy. Cancers (Basel) 2024; 16:2727. [PMID: 39123455 PMCID: PMC11311871 DOI: 10.3390/cancers16152727] [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: 06/12/2024] [Revised: 07/16/2024] [Accepted: 07/29/2024] [Indexed: 08/12/2024] Open
Abstract
The Controlling Nutritional Status (CONUT) score is a novel nutritional index that integrates the serum albumin level, peripheral blood lymphocyte count, and total cholesterol level. This retrospective study explores its prognostic significance in patients undergoing cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). We included 436 patients who underwent CRS-HIPEC, categorized into low (0-3) and high (4-12) CONUT score groups, and performed logistic regression analysis to predict one-year mortality and postoperative morbidity. Our findings revealed that high CONUT scores correlate with increased one-year mortality (47.1% vs. 20.3%, p < 0.001) and morbidity (39.2% vs. 18.2%, p < 0.001) compared to low CONUT scores. Multivariable regression analysis confirmed high CONUT scores as independent predictors of one-year mortality (odds ratio: 2.253, 95% CI: 1.014-5.005, p = 0.046) and postoperative morbidity (odds ratio: 2.201, 95% CI: 1.066-4.547, p = 0.033). These results underscore the CONUT score's effectiveness as an independent marker for evaluating risks associated with CRS-HIPEC, emphasizing its potential to improve risk stratification.
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Affiliation(s)
- Myung Il Bae
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; (M.I.B.)
| | - Hyunjoo Jung
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; (M.I.B.)
| | - Eun Jung Park
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
| | - Young Lan Kwak
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; (M.I.B.)
| | - Young Song
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; (M.I.B.)
- Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
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Min SH, Lee J, Yoo M, Hwang D, Lee E, Kang SH, Lee K, Park YS, Ahn SH, Suh YS, Park DJ, Kim HH. Efficacy of Hyperthermic Pressurized Intraperitoneal Aerosol Chemotherapy in an In Vitro Model Using a Human Gastric Cancer AGS Cell Line and an Abdominal Cavity Model. J Gastric Cancer 2024; 24:246-256. [PMID: 38960884 PMCID: PMC11224724 DOI: 10.5230/jgc.2024.24.e24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 03/30/2024] [Accepted: 04/01/2024] [Indexed: 07/05/2024] Open
Abstract
PURPOSE Peritoneal carcinomatosis (PC) presents a major challenge in the treatment of late-stage, solid tumors, with traditional therapies limited by poor drug penetration. We evaluated a novel hyperthermic pressurized intraperitoneal aerosol chemotherapy (HPIPAC) system using a human abdominal cavity model for its efficacy against AGS gastric cancer cells. MATERIALS AND METHODS A model simulating the human abdominal cavity and AGS gastric cancer cell line cultured dishes were used to assess the efficacy of the HPIPAC system. Cell viability was measured to evaluate the impact of HPIPAC under 6 different conditions: heat alone, PIPAC with paclitaxel (PTX), PTX alone, normal saline (NS) alone, heat with NS, and HPIPAC with PTX. RESULTS Results showed a significant reduction in cell viability with HPIPAC combined with PTX, indicating enhanced cytotoxic effects. Immediately after treatment, the average cell viability was 66.6%, which decreased to 49.2% after 48 hours and to a further 19.6% after 120 hours of incubation, demonstrating the sustained efficacy of the treatment. In contrast, control groups exhibited a recovery in cell viability; heat alone showed cell viability increasing from 90.8% to 94.4%, PIPAC with PTX from 82.7% to 89.7%, PTX only from 73.3% to 74.8%, NS only from 90.9% to 98.3%, and heat with NS from 74.4% to 84.7%. CONCLUSIONS The HPIPAC system with PTX exhibits a promising approach in the treatment of PC in gastric cancer, significantly reducing cell viability. Despite certain limitations, this study highlights the system's potential to enhance treatment outcomes. Future efforts should focus on refining HPIPAC and validating its effectiveness in clinical settings.
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Affiliation(s)
- Sa-Hong Min
- Department of Gastrointestinal Surgery, Asan Medical Center, Seoul, Korea
| | - Jieun Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Mira Yoo
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Duyeong Hwang
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Eunju Lee
- Department of Surgery, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, Korea
| | - So Hyun Kang
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Kanghaeng Lee
- Department of Surgery, St. Vincent's Hospital, Suwon, Korea
| | - Young Suk Park
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Sang-Hoon Ahn
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yun-Suhk Suh
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Do Joong Park
- Department of Surgery, Seoul National University Hospital, Seoul, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Hyung-Ho Kim
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
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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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Ho YK, Woo JY, Loke KM, Deng LW, Too HP. Enhanced anti-tumor efficacy with multi-transgene armed mesenchymal stem cells for treating peritoneal carcinomatosis. J Transl Med 2024; 22:463. [PMID: 38750559 PMCID: PMC11097589 DOI: 10.1186/s12967-024-05278-5] [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: 11/08/2023] [Accepted: 05/07/2024] [Indexed: 05/18/2024] Open
Abstract
BACKGROUND Mesenchymal stem cells (MSCs) have garnered significant interest for their tumor-tropic property, making them potential therapeutic delivery vehicles for cancer treatment. We have previously shown the significant anti-tumour activity in mice preclinical models and companion animals with naturally occurring cancers using non-virally engineered MSCs with a therapeutic transgene encoding cytosine deaminase and uracil phosphoribosyl transferase (CDUPRT) and green fluorescent protein (GFP). Clinical studies have shown improved response rate with combinatorial treatment of 5-fluorouracil and Interferon-beta (IFNb) in peritoneal carcinomatosis (PC). However, high systemic toxicities have limited the clinical use of such a regime. METHODS In this study, we evaluated the feasibility of intraperitoneal administration of non-virally engineered MSCs to co-deliver CDUPRT/5-Flucytosine prodrug system and IFNb to potentially enhance the cGAS-STING signalling axis. Here, MSCs were engineered to express CDUPRT or CDUPRT-IFNb. Expression of CDUPRT and IFNb was confirmed by flow cytometry and ELISA, respectively. The anti-cancer efficacy of the engineered MSCs was evaluated in both in vitro and in vivo model. ES2, HT-29 and Colo-205 were cocultured with engineered MSCs at various ratio. The cell viability with or without 5-flucytosine was measured with MTS assay. To further compare the anti-cancer efficacy of the engineered MSCs, peritoneal carcinomatosis mouse model was established by intraperitoneal injection of luciferase expressing ES2 stable cells. The tumour burden was measured through bioluminescence tracking. RESULTS Firstly, there was no changes in phenotypes of MSCs despite high expression of the transgene encoding CDUPRT and IFNb (CDUPRT-IFNb). Transwell migration assays and in-vivo tracking suggested the co-expression of multiple transgenes did not impact migratory capability of the MSCs. The superiority of CDUPRT-IFNb over CDUPRT expressing MSCs was demonstrated in ES2, HT-29 and Colo-205 in-vitro. Similar observations were observed in an intraperitoneal ES2 ovarian cancer xenograft model. The growth of tumor mass was inhibited by ~ 90% and 46% in the mice treated with MSCs expressing CDUPRT-IFNb or CDUPRT, respectively. CONCLUSIONS Taken together, these results established the effectiveness of MSCs co-expressing CDUPRT and IFNb in controlling and targeting PC growth. This study lay the foundation for the development of clinical trial using multigene-armed MSCs for PC.
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Affiliation(s)
- Yoon Khei Ho
- Department of Biochemistry, National University of Singapore, Singapore, 117596, Singapore.
- NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
- AGeM Bio, Singapore, 119276, Singapore.
- Singapore Innovate, Singapore, 059911, Singapore.
| | - Jun Yung Woo
- Department of Biochemistry, National University of Singapore, Singapore, 117596, Singapore
- NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Kin Man Loke
- Department of Biochemistry, National University of Singapore, Singapore, 117596, Singapore
- NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Lih-Wen Deng
- Department of Biochemistry, National University of Singapore, Singapore, 117596, Singapore
- NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Heng-Phon Too
- Department of Biochemistry, National University of Singapore, Singapore, 117596, Singapore
- NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
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9
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Pazir Y, Esmeray A, Caglar U, Erbin A, Ozgor F, Sarilar O, Akbulut F. Comparison of hyperthermic intravesical chemotherapy and Bacillus Calmette-Guerin therapy in high-risk non-muscle invasive bladder cancer: a matched-pair analysis. Int Urol Nephrol 2024; 56:957-963. [PMID: 37880493 DOI: 10.1007/s11255-023-03849-x] [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: 08/13/2023] [Accepted: 10/06/2023] [Indexed: 10/27/2023]
Abstract
PURPOSE To compare adjuvant hyperthermic intravesical chemotherapy (HIVEC) with mitomycin C and standard Bacillus Calmette-Guerin (BCG) therapy in terms of oncological outcomes and adverse events in patients with high-risk non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS The data of patients with high-risk papillary NMIBC treated with adjuvant intravesical BCG instillations or HIVEC in our institution between June 2017 and August 2022 were analyzed retrospectively. Twenty-four patients who received HIVEC were matched 1:1 with patients receiving BCG therapy based on tumor characteristics (tumor stage and grade), age, gender, smoking status, and the number of tumors (single or multiple). HIVEC and standard BCG treatments were compared in terms of recurrence-free survival (RFS), progression-free survival (PFS), and adverse events. RESULTS Forty-eight patients (24 in the BCG group and 24 in the HIVEC group) were included in the study. The median follow-up times of the BCG and HIVEC groups were 32 [interquartile range (IQR): 28.0-47.8] and 28 (IQR: 16.7-41.8) months, respectively (p = 0.11). There was no significant difference between the groups in terms of the 24-month RFS (BCG 83% vs HIVEC 88%, p = 0.64) and the 24-month PFS (BCG 100% vs HIVEC 94%, p = 0.61). Regarding the safety profile, at least one adverse event occurred in 13 (54%) of the patients in the BCG group and 12 (50.0%) of those in the HIVEC group (p = 0.77). CONCLUSION This study demonstrated that HIVEC with mitomycin C has a similar oncological efficacy and safety profile to standard BCG therapy in high-risk NMIBC.
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Affiliation(s)
- Yasar Pazir
- Department of Urology, Haseki Training and Research Hospital, Istanbul, Turkey.
| | - Abdullah Esmeray
- Department of Urology, Haseki Training and Research Hospital, Istanbul, Turkey
| | - Ufuk Caglar
- Department of Urology, Haseki Training and Research Hospital, Istanbul, Turkey
| | - Akif Erbin
- Department of Urology, Haseki Training and Research Hospital, Istanbul, Turkey
| | - Faruk Ozgor
- Department of Urology, Haseki Training and Research Hospital, Istanbul, Turkey
| | - Omer Sarilar
- Department of Urology, Haseki Training and Research Hospital, Istanbul, Turkey
| | - Fatih Akbulut
- Department of Urology, Haseki Training and Research Hospital, Istanbul, Turkey
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10
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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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11
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Yang A, Zhang Z, Chaurasiya S, Park AK, Lu J, Kim SI, Valencia H, Fong Y, Woo Y. Peritoneal-directed chimeric oncolytic virus CF17 prevents malignant ascites and improves survival in gastric cancer peritoneal metastases. Mol Ther Oncolytics 2023; 31:100734. [PMID: 37915757 PMCID: PMC10616379 DOI: 10.1016/j.omto.2023.100734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Accepted: 10/04/2023] [Indexed: 11/03/2023] Open
Abstract
Gastric cancer (GC) peritoneal metastasis (PM) is fatal without effective therapy. We investigated CF17, a new replication-competent chimeric poxvirus, against GC cell lines in vitro and PM in an aggressive GCPM mouse model. We performed viral proliferation and cytotoxicity assays on intestinal-type and diffuse-type human GC cell lines following CF17 treatment. At lower MOIs of 0.01, 0.1, there was >80% killing in most cell lines, while in the more aggressive cell lines, killing was seen at higher MOIs of 1.0 and 10.0. We observed reduced peritoneal tumor burden and prolonged survival with intraperitoneal (i.p.) CF17 treatment in nude mice implanted with the resistant GC cell line. At day 91 after treatment, seven of eight mice were alive in the CF17-treated group vs. one of eight mice in the control group. CF17 treatment inhibited ascites formation (0% vs. 62.5% with PBS). Thus, CF17 efficiently infected, replicated in, and killed GC cells in a dose- and time-dependent manner in vitro. In vivo, i.p. CF17 treatment exhibited robust antitumor activity against an aggressive GCPM model to decrease tumor burden, improve survival, and prevent ascites formation. These preclinical results inform the design of future clinical trials of CF17 for peritoneal-directed therapy in GCPM patients.
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Affiliation(s)
- Annie Yang
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, 1500 E Duarte Road, Duarte, CA, USA
| | - Zhifang Zhang
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, 1500 E Duarte Road, Duarte, CA, USA
| | - Shyambabu Chaurasiya
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, 1500 E Duarte Road, Duarte, CA, USA
| | - Anthony K. Park
- Cancer Immunotherapeutics Program, Beckman Research Institute, City of Hope National Medical Center, 1500 E Duarte Road, Duarte, CA, USA
| | - Jianming Lu
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, 1500 E Duarte Road, Duarte, CA, USA
| | - Sang-In Kim
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, 1500 E Duarte Road, Duarte, CA, USA
| | - Hannah Valencia
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, 1500 E Duarte Road, Duarte, CA, USA
| | - Yuman Fong
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, 1500 E Duarte Road, Duarte, CA, USA
| | - Yanghee Woo
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, 1500 E Duarte Road, Duarte, CA, USA
- Cancer Immunotherapeutics Program, Beckman Research Institute, City of Hope National Medical Center, 1500 E Duarte Road, Duarte, CA, USA
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12
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Chen C, Jung A, Yang A, Monroy I, Zhang Z, Chaurasiya S, Deshpande S, Priceman S, Fong Y, Park AK, Woo Y. Chimeric Antigen Receptor-T Cell and Oncolytic Viral Therapies for Gastric Cancer and Peritoneal Carcinomatosis of Gastric Origin: Path to Improving Combination Strategies. Cancers (Basel) 2023; 15:5661. [PMID: 38067366 PMCID: PMC10705752 DOI: 10.3390/cancers15235661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 11/21/2023] [Accepted: 11/23/2023] [Indexed: 02/12/2024] Open
Abstract
Precision immune oncology capitalizes on identifying and targeting tumor-specific antigens to enhance anti-tumor immunity and improve the treatment outcomes of solid tumors. Gastric cancer (GC) is a molecularly heterogeneous disease where monoclonal antibodies against human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor (VEGF), and programmed cell death 1 (PD-1) combined with systemic chemotherapy have improved survival in patients with unresectable or metastatic GC. However, intratumoral molecular heterogeneity, variable molecular target expression, and loss of target expression have limited antibody use and the durability of response. Often immunogenically "cold" and diffusely spread throughout the peritoneum, GC peritoneal carcinomatosis (PC) is a particularly challenging, treatment-refractory entity for current systemic strategies. More adaptable immunotherapeutic approaches, such as oncolytic viruses (OVs) and chimeric antigen receptor (CAR) T cells, have emerged as promising GC and GCPC treatments that circumvent these challenges. In this study, we provide an up-to-date review of the pre-clinical and clinical efficacy of CAR T cell therapy for key primary antigen targets and provide a translational overview of the types, modifications, and mechanisms for OVs used against GC and GCPC. Finally, we present a novel, summary-based discussion on the potential synergistic interplay between OVs and CAR T cells to treat GCPC.
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Affiliation(s)
- Courtney Chen
- Department of Surgery, City of Hope, Duarte, CA 91010, USA; (C.C.); (A.J.); (A.Y.); (Z.Z.); (S.C.); (S.D.); (Y.F.)
| | - Audrey Jung
- Department of Surgery, City of Hope, Duarte, CA 91010, USA; (C.C.); (A.J.); (A.Y.); (Z.Z.); (S.C.); (S.D.); (Y.F.)
| | - Annie Yang
- Department of Surgery, City of Hope, Duarte, CA 91010, USA; (C.C.); (A.J.); (A.Y.); (Z.Z.); (S.C.); (S.D.); (Y.F.)
| | - Isabel Monroy
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA 91010, USA; (I.M.); (S.P.)
| | - Zhifang Zhang
- Department of Surgery, City of Hope, Duarte, CA 91010, USA; (C.C.); (A.J.); (A.Y.); (Z.Z.); (S.C.); (S.D.); (Y.F.)
| | - Shyambabu Chaurasiya
- Department of Surgery, City of Hope, Duarte, CA 91010, USA; (C.C.); (A.J.); (A.Y.); (Z.Z.); (S.C.); (S.D.); (Y.F.)
| | - Supriya Deshpande
- Department of Surgery, City of Hope, Duarte, CA 91010, USA; (C.C.); (A.J.); (A.Y.); (Z.Z.); (S.C.); (S.D.); (Y.F.)
| | - Saul Priceman
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA 91010, USA; (I.M.); (S.P.)
- Cancer Immunotherapeutics Program, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA
| | - Yuman Fong
- Department of Surgery, City of Hope, Duarte, CA 91010, USA; (C.C.); (A.J.); (A.Y.); (Z.Z.); (S.C.); (S.D.); (Y.F.)
| | - Anthony K. Park
- Department of Surgery, City of Hope, Duarte, CA 91010, USA; (C.C.); (A.J.); (A.Y.); (Z.Z.); (S.C.); (S.D.); (Y.F.)
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA 91010, USA; (I.M.); (S.P.)
- Cancer Immunotherapeutics Program, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA
| | - Yanghee Woo
- Department of Surgery, City of Hope, Duarte, CA 91010, USA; (C.C.); (A.J.); (A.Y.); (Z.Z.); (S.C.); (S.D.); (Y.F.)
- Cancer Immunotherapeutics Program, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA
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13
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Song Y, Bae MI, Han DW, Park EJ, Park S, Ham SY. Prognostic role of body composition in peritoneal carcinomatosis patients undergoing cytoreduction and hyperthermic intraperitoneal chemotherapy. World J Surg Oncol 2023; 21:345. [PMID: 37891626 PMCID: PMC10604686 DOI: 10.1186/s12957-023-03233-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 10/19/2023] [Indexed: 10/29/2023] Open
Abstract
BACKGROUND Bioelectric impedance analysis (BIA)-measured body composition and nutritional status have been used as prognostic indicators in various cancer cohorts. This study investigated whether BIA could provide information on prognosis in peritoneal carcinomatosis patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS We retrospectively analyzed the data of 99 patients with preoperative BIA data among those who underwent CRS and HIPEC. The association between BIA-derived parameters and intraoperative peritoneal cancer index (PCI) score was assessed. Predictive analysis for the occurrence of postoperative morbidities including major complications (Clavien-Dindo classification 3-4) and re-admission within 30 days after surgery as well as 1 year mortality was also performed. RESULTS BIA-derived mineral (r = 0.224, p = 0.027), fat (r = - 0.202, p = 0.048), and total body water (TBW)/fat-free mass (FFM) (r = - 0.280, p = 0.005) showed significant associations with intraoperative PCI score. Lower TBW/FFM was an independent predictor of major postoperative complications (OR 0.047, 95% CI 0.003-0.749, p = 0.031) and re-admission (OR 0.094, 95% CI 0.014-0.657, p = 0.017) within 30 days after surgery. Higher fat mass was also independently associated with a higher risk of major postoperative complications (OR 1.120, 95% CI 1.006-1.248, p = 0.039) and re-admission (OR 1.123, 95% CI 1.024-1.230, p = 0.013). Intraoperative PCI score > 20 (OR 4.489, 95% CI 1.191-16.917, p = 0.027) and re-admission within 30 days after surgery (OR 5.269, 95% CI 1.288-21.547, p = 0.021) independently predicted postoperative 1-year mortality. CONCLUSIONS We demonstrate that preoperative BIA-derived TBW/FFM and fat mass were significantly correlated with metastatic extent, assessed by PCI score, in patients with peritoneal carcinomatosis. In addition, BIA-derived TBW/FFM and fat mass showed independent predictability for postoperative 30-day major complications and re-admission in patients undergoing CRS and HIPEC. Our findings suggest that assessment of BIA may improve discrete risk stratification in patients who are planned to receive CRS and HIPEC.
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Affiliation(s)
- Young Song
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, 211 Eonjuro, Gangnam-Gu, 06273, Seoul, Republic of Korea
- Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Myung Il Bae
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, 211 Eonjuro, Gangnam-Gu, 06273, Seoul, Republic of Korea
- Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Dong Woo Han
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, 211 Eonjuro, Gangnam-Gu, 06273, Seoul, Republic of Korea
- Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Eun Jung Park
- Division of Colon and Rectal Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sujung Park
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, 211 Eonjuro, Gangnam-Gu, 06273, Seoul, Republic of Korea
| | - Sung Yeon Ham
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, 211 Eonjuro, Gangnam-Gu, 06273, Seoul, Republic of Korea.
- Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
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14
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Wang R, Song S, Qin J, Yoshimura K, Peng F, Chu Y, Li Y, Fan Y, Jin J, Dang M, Dai E, Pei G, Han G, Hao D, Li Y, Chatterjee D, Harada K, Pizzi MP, Scott AW, Tatlonghari G, Yan X, Xu Z, Hu C, Mo S, Shanbhag N, Lu Y, Sewastjanow-Silva M, Fouad Abdelhakeem AA, Peng G, Hanash SM, Calin GA, Yee C, Mazur P, Marsden AN, Futreal A, Wang Z, Cheng X, Ajani JA, Wang L. Evolution of immune and stromal cell states and ecotypes during gastric adenocarcinoma progression. Cancer Cell 2023; 41:1407-1426.e9. [PMID: 37419119 PMCID: PMC10528152 DOI: 10.1016/j.ccell.2023.06.005] [Citation(s) in RCA: 64] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Revised: 04/10/2023] [Accepted: 06/12/2023] [Indexed: 07/09/2023]
Abstract
Understanding tumor microenvironment (TME) reprogramming in gastric adenocarcinoma (GAC) progression may uncover novel therapeutic targets. Here, we performed single-cell profiling of precancerous lesions, localized and metastatic GACs, identifying alterations in TME cell states and compositions as GAC progresses. Abundant IgA+ plasma cells exist in the premalignant microenvironment, whereas immunosuppressive myeloid and stromal subsets dominate late-stage GACs. We identified six TME ecotypes (EC1-6). EC1 is exclusive to blood, while EC4, EC5, and EC2 are highly enriched in uninvolved tissues, premalignant lesions, and metastases, respectively. EC3 and EC6, two distinct ecotypes in primary GACs, associate with histopathological and genomic characteristics, and survival outcomes. Extensive stromal remodeling occurs in GAC progression. High SDC2 expression in cancer-associated fibroblasts (CAFs) is linked to aggressive phenotypes and poor survival, and SDC2 overexpression in CAFs contributes to tumor growth. Our study provides a high-resolution GAC TME atlas and underscores potential targets for further investigation.
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Affiliation(s)
- Ruiping Wang
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Shumei Song
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Jiangjiang Qin
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China; Institute of Basic Medicine and Cancer, Chinese Academy of Sciences, Hangzhou, Zhejiang 310018, China
| | - Katsuhiro Yoshimura
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Fuduan Peng
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Yanshuo Chu
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Yuan Li
- Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang 110001, China
| | - Yibo Fan
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Jiankang Jin
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Minghao Dang
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Enyu Dai
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Guangsheng Pei
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Guangchun Han
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Dapeng Hao
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Yating Li
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Deyali Chatterjee
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Kazuto Harada
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Melissa Pool Pizzi
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Ailing W Scott
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Ghia Tatlonghari
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Xinmiao Yan
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Zhiyuan Xu
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China
| | - Can Hu
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China
| | - Shaowei Mo
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China
| | - Namita Shanbhag
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Yang Lu
- Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Matheus Sewastjanow-Silva
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Ahmed Adel Fouad Abdelhakeem
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Guang Peng
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Samir M Hanash
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - George A Calin
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Cassian Yee
- Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Pawel Mazur
- Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Autumn N Marsden
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Andrew Futreal
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Zhenning Wang
- Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang 110001, China
| | - Xiangdong Cheng
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China; Institute of Basic Medicine and Cancer, Chinese Academy of Sciences, Hangzhou, Zhejiang 310018, China
| | - Jaffer A Ajani
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
| | - Linghua Wang
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences (GSBS), Houston, TX 77030, USA.
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15
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Wang C, Zhao J, Sun J, Tian C, Dai Z, Liu J, Ji C, Liu D, Wang X, Li H, Sun Y. Intraoperative Pathological Evaluation of Suspicious Peritoneal Nodules for Surgical Decision-making in Gastric Cancer. J Gastrointest Surg 2023; 27:1545-1559. [PMID: 37059962 DOI: 10.1007/s11605-023-05671-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Accepted: 03/21/2023] [Indexed: 04/16/2023]
Abstract
BACKGROUND When frozen pathological results of suspicious peritoneal nodules found in gastric cancer (GC) patients are negative or indeterminant, whether to perform gastrectomy will always be a dilemma for surgeons. This study aimed to facilitate intraoperative surgical decision-making based on frozen section (FS) results and clinicopathological characteristics. METHODS From January 2015 to July 2021, 318 GC patients were enrolled retrospectively. The correlations between frozen and paraffin pathology of peritoneal nodules were examined. Then, predictive factors of positive paraffin section (PS) results were identified, and a nomogram was constructed. The survival significance of gastrectomy was also explored. RESULTS Of 70 FS-negative patients, 59 (84.3%) had concordant negative PS results, while the PS results of 11 (15.7%) were positive. Forty-six (93.9%) and 3 (6.1%) of 49 patients with indeterminant FS results had positive and negative PS results, respectively. The PS results of 95 FS-positive patients were all positive. A nomogram for predicting positive PS results was developed based on Lauren type, nodule distribution, and CA125. Gastrectomy for FS-negative patients improved survival compared to no gastrectomy (HR 0.26, 95% CI 0.11-0.62; P = 0.0012). Survival benefits for gastrectomy vs. no gastrectomy were not demonstrated in patients with indeterminant (HR 0.74, 95% CI 0.27-2.01; P = 0.53) and positive (HR 0.87, 95% CI 0.43-1.74; P = 0.69) FS results. CONCLUSIONS Gastrectomy can be justified for the treatment of operable GC patients with negative frozen pathological results of peritoneal nodules. For patients with positive and indeterminant frozen pathological results, gastrectomy is not recommended unless it is performed as palliative surgery.
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Affiliation(s)
- Chen Wang
- Department of General Surgery, Gastric Cancer Center, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Junjie Zhao
- Department of General Surgery, Gastric Cancer Center, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Jie Sun
- Department of General Surgery, Gastric Cancer Center, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Chenyu Tian
- Department of General Surgery, Gastric Cancer Center, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Zhiqiang Dai
- Department of General Surgery, Zhongshan Hospital, Fudan University (Xiamen Branch), 668 Jinhu Road, Huli District, Xiamen, 361015, Fujian Province, China
| | - Jingdong Liu
- Department of General Surgery, Gastric Cancer Center, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Chengbo Ji
- Department of General Surgery, Gastric Cancer Center, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Dan Liu
- Department of General Surgery, Gastric Cancer Center, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Xuefei Wang
- Department of General Surgery, Gastric Cancer Center, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Haojie Li
- Department of General Surgery, Gastric Cancer Center, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
| | - Yihong Sun
- Department of General Surgery, Gastric Cancer Center, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
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16
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Huang KX, Pan YF, Dai RS, Xu LS, Zhu BW, Zhang XD, Hu YW. A Preliminary Study of Immediate Intraperitoneal Chemotherapy for Stage III Colorectal Cancer. Am J Clin Oncol 2023; 46:193-198. [PMID: 36991528 DOI: 10.1097/coc.0000000000000980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/31/2023]
Abstract
OBJECTIVES Investigate the survival of patients with stage III colorectal cancer (CRC) treated with immediate postoperative intraperitoneal chemotherapy. METHODS The clinical data of 195 patients with stage III CRC admitted to The First Affiliated Hospital of Wenzhou Medical University from June 2017 to June 2018 were retrospectively analyzed. The patients were divided into an observation group and a control group, both groups were treated with the routine laparoscopic radical operation, on the basis of which, the patients in the observation group were treated with intraperitoneal perfusion chemotherapy during the operation. The local recurrence, abdominal cavity metastasis, and liver metastasis were followed up, and the time of disease recurrence and total survival were recorded. RESULTS The survival analysis showed that there was a significant difference in progression-free survival (χ 2 = 5.416, P = 0.020) and overall survival (χ 2 = 4.673, P = 0.031) between the observation group and the control group. CONCLUSIONS During laparoscopic radical resection of CRC, the use of intraperitoneal chemotherapy with raltitrexed can achieve satisfactory results and improve the survival rate of patients with stage III CRC, perioperative use of raltitrexed has been shown to be beneficial in terms of overall survival and progression-free survival.
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Affiliation(s)
- Kai-Xin Huang
- Wenzhou Medical University
- Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University
| | - Yi-Fei Pan
- Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University
| | - Rui-Shuai Dai
- Wenzhou Medical University
- Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University
| | - Ling-Sha Xu
- Wenzhou Medical University
- Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University
| | | | - Xiao-Dong Zhang
- Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University
| | - Yi-Wang Hu
- Wenzhou Medical University
- Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University
- Wenzhou Science and Technology Bureau, Wenzhou, China
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17
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Fan Y, Li Y, Yao X, Jin J, Scott A, Liu B, Wang S, Huo L, Wang Y, Wang R, Pool Pizzi M, Ma L, Shao S, Sewastjanow-Silva M, Waters R, Chatterjee D, Liu B, Shanbhag N, Peng G, Calin GA, Mazur PK, Hanash SM, Ishizawa J, Hirata Y, Nagano O, Wang Z, Wang L, Xian W, McKeon F, Ajani JA, Song S. Epithelial SOX9 drives progression and metastases of gastric adenocarcinoma by promoting immunosuppressive tumour microenvironment. Gut 2023; 72:624-637. [PMID: 36002248 DOI: 10.1136/gutjnl-2021-326581] [Citation(s) in RCA: 40] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Accepted: 08/03/2022] [Indexed: 12/08/2022]
Abstract
OBJECTIVE Many cancers engage embryonic genes for rapid growth and evading the immune system. SOX9 has been upregulated in many tumours, yet the role of SOX9 in mediating immunosuppressive tumour microenvironment is unclear. Here, we aim to dissect the role of SOX9-mediated cancer stemness attributes and immunosuppressive microenvironment in advanced gastric adenocarcinoma (GAC) for novel therapeutic discoveries. METHODS Bulk RNAseq/scRNA-seq, patient-derived cells/models and extensive functional studies were used to identify the expression and functions of SOX9 and its target genes in vitro and in vivo. Immune responses were studied in PBMCs or CD45+ immune cells cocultured with tumour cells with SOX9high or knockout and the KP-Luc2 syngeneic models were used for efficacy of combinations. RESULTS SOX9 is one of the most upregulated SOX genes in GAC and highly expressed in primary and metastatic tissues and associated with poor prognosis. Depletion of SOX9 in patient-derived GAC cells significantly decreased cancer stemness attributes, tumour formation and metastases and consistently increased CD8+ T cell responses when cocultured with PBMCs/CD45+ cells from GAC patients. RNA sequencing identified the leukaemia inhibitory factor (LIF) as the top secreted molecule regulated by SOX9 in tumour cells and was enriched in malignant ascites and mediated SOX9-induced M2 macrophage repolarisation and inhibited T cell function. CONCLUSION Epithelial SOX9 is critical in suppressing CD8+ T cell responses and modified macrophage function in GAC through the paracrine LIF factor. Cotargeting LIF/LIFR and CSF1R has great potential in targeting SOX9-mediated cancer stemness, T cell immunosuppression and metastases suggesting the novel combination therapy against advanced GAC.
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Affiliation(s)
- Yibo Fan
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Yuan Li
- Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, PR China
| | - Xiaodan Yao
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jiangkang Jin
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ailing Scott
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Bovey Liu
- Department of Biology and Biochemistry, University of Houston, Houston, TX, USA
| | - Shan Wang
- Department of Biology and Biochemistry, University of Houston, Houston, TX, USA
| | - Longfei Huo
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ying Wang
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ruiping Wang
- Departments of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Melissa Pool Pizzi
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Lang Ma
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Shan Shao
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Matheus Sewastjanow-Silva
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Rebecca Waters
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Deyali Chatterjee
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Bin Liu
- Department of Epigenet & Mol Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Namita Shanbhag
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Guang Peng
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - George Adrian Calin
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Pawel Karol Mazur
- Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Samir M Hanash
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jo Ishizawa
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Yuki Hirata
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Osamu Nagano
- Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine Graduate School of Medicine, Tokyo, Japan
| | - Zhenning Wang
- Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, PR China
| | - Linghua Wang
- Departments of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Wa Xian
- Department of Biology and Biochemistry, University of Houston, Houston, TX, USA
| | - Frank McKeon
- Department of Biology and Biochemistry, University of Houston, Houston, TX, USA
| | - Jaffer A Ajani
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Shumei Song
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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18
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Guchelaar NAD, Noordman BJ, Koolen SLW, Mostert B, Madsen EVE, Burger JWA, Brandt-Kerkhof ARM, Creemers GJ, de Hingh IHJT, Luyer M, Bins S, van Meerten E, Lagarde SM, Verhoef C, Wijnhoven BPL, Mathijssen RHJ. Intraperitoneal Chemotherapy for Unresectable Peritoneal Surface Malignancies. Drugs 2023; 83:159-180. [PMID: 36633826 PMCID: PMC9908703 DOI: 10.1007/s40265-022-01828-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/12/2022] [Indexed: 01/13/2023]
Abstract
Malignancies of the peritoneal cavity are associated with a dismal prognosis. Systemic chemotherapy is the gold standard for patients with unresectable peritoneal disease, but its intraperitoneal effect is hampered by the peritoneal-plasma barrier. Intraperitoneal chemotherapy, which is administered repeatedly into the peritoneal cavity through a peritoneal implanted port, could provide a novel treatment modality for this patient population. This review provides a systematic overview of intraperitoneal used drugs, the performed clinical studies so far, and the complications of the peritoneal implemental ports. Several anticancer drugs have been studied for intraperitoneal application, with the taxanes paclitaxel and docetaxel as the most commonly used drug. Repeated intraperitoneal chemotherapy, mostly in combination with systemic chemotherapy, has shown promising results in Phase I and Phase II studies for several tumor types, such as gastric cancer, ovarian cancer, colorectal cancer, and pancreatic cancer. Two Phase III studies for intraperitoneal chemotherapy in gastric cancer have been performed so far, but the results regarding the superiority over standard systemic chemotherapy alone, are contradictory. Pressurized intraperitoneal administration, known as PIPAC, is an alternative way of administering intraperitoneal chemotherapy, and the first prospective studies have shown a tolerable safety profile. Although intraperitoneal chemotherapy might be a standard treatment option for patients with unresectable peritoneal disease, more Phase II and Phase III studies focusing on tolerability profiles, survival rates, and quality of life are warranted in order to establish optimal treatment schedules and to establish a potential role for intraperitoneal chemotherapy in the approach to unresectable peritoneal disease.
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Affiliation(s)
- Niels A. D. Guchelaar
- Department of Medical Oncology, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
| | - Bo J. Noordman
- Department of Surgery, Division of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Stijn L. W. Koolen
- Department of Medical Oncology, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
- Department of Pharmacy, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Bianca Mostert
- Department of Medical Oncology, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
| | - Eva V. E. Madsen
- Department of Surgery, Division of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | | | - Alexandra R. M. Brandt-Kerkhof
- Department of Surgery, Division of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Geert-Jan Creemers
- Department of Medical Oncology, 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
| | - Misha Luyer
- Department of Surgery, Catharina Cancer Institute, Eindhoven, The Netherlands
| | - Sander Bins
- Department of Medical Oncology, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
| | - Esther van Meerten
- Department of Medical Oncology, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
| | - Sjoerd M. Lagarde
- Department of Surgery, Division of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Cornelis Verhoef
- Department of Surgery, Division of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, 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, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
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19
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Pasqual EM, Londero AP, Robella M, Tonello M, Sommariva A, De Simone M, Bacchetti S, Baiocchi G, Asero S, Coccolini F, De Cian F, Guaglio M, Cinquegrana A, Cenzi C, Scaringi S, Macrì A. Repeated Cytoreduction Combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Selected Patients Affected by Peritoneal Metastases: Italian PSM Oncoteam Evidence. Cancers (Basel) 2023; 15:607. [PMID: 36765565 PMCID: PMC9913411 DOI: 10.3390/cancers15030607] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 12/23/2022] [Accepted: 01/16/2023] [Indexed: 01/20/2023] Open
Abstract
The reiteration of surgical cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients affected by recurrent peritoneal metastases is still questioned regarding safety and effectiveness. This study evaluates the safety, efficacy, and associated factors of iterative CRS combined with HIPEC. This multicentric retrospective study collected data from four surgical oncology centers, on iterative HIPEC. We gathered data on patient and cancer characteristics, the peritoneal cancer index (PCI), completeness of cytoreduction (CC), postoperative complications, and overall survival (OS). In the study period, 141 CRS-plus-HIPECs were performed on 65 patients. Nine patients underwent three iterative procedures, and one underwent five. No increased incidence of complications after the second or third procedure was observed. Furthermore, operative time and hospitalization stay were significantly shorter after the second than after the first procedure (p < 0.05). Optimal cytoreduction was achieved in more than 90% of cases in each procedure, whether first, second, or third. A five-year (5 y) OS represented 100% of the cases of diffuse malignant-peritoneal-mesotheliomas, 81.39% of pseudomyxoma peritonei, 34.67% of colorectal cancer (CRC), and 52.50% of ovarian cancer. During the second CRS combined with HIPEC, we observed a lower rate of complete cytoreduction and a non-significantly better survival in cases with complete cytoreduction (5 y-OS CC-0 56.51% vs. 37.82%, p = 0.061). Concomitant hepatic-CRC-metastasis did not compromise the CRS-plus-HIPEC safety and efficacy. This multicentric experience encourages repeated CRS-plus-HIPEC, showing promising results.
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Affiliation(s)
- Enrico Maria Pasqual
- Advanced Surgical Oncology Center, ASUFC, DAME, University of Udine, 33100 Udine, Italy
| | - Ambrogio P. Londero
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Infant Health, University of Genoa, 16132 Genova, Italy
| | | | - Marco Tonello
- Advanced Surgical Oncology Unit, Surgical Oncology of the Esophagus and Digestive Tract, Veneto Institute of Oncology IOV-IRCCS, 35128 Padova, 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 Bacchetti
- Advanced Surgical Oncology Center, ASUFC, DAME, University of Udine, 33100 Udine, Italy
| | - Gianluca Baiocchi
- Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili, 25123 Brescia, Italy
| | - Salvatore Asero
- Soft Tissue U.O. Surgical Oncology-Soft Tissue Tumors, Dipartimento di Oncologia, Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi Catania, 95123 Catania, Italy
| | - Federico Coccolini
- General, Emergency and Trauma Surgery, Pisa University Hospital, 56100 Pisa, Italy
| | - Franco De Cian
- Clinica Chirurgica 1–Ospedale S. Martino, 16132 Genova, Italy
| | - Marcello Guaglio
- Peritoneal Surface Malignancies Unit, Fondazione Istituto Nazionale Tumori IRCCS Milano, 20133 Milano, Italy
| | | | - Carola Cenzi
- Advanced Surgical Oncology Unit, Surgical Oncology of the Esophagus and Digestive Tract, Veneto Institute of Oncology IOV-IRCCS, 35128 Padova, Italy
| | | | - Antonio Macrì
- U.O.C.–P.S.G. con O.B.I. Azienda Ospedaliera Universitaria “G. Martino”, 98125 Messina, Italy
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20
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Badgwell BD. Don't Call It a Comeback-HIPEC for Gastric Cancer. Ann Surg Oncol 2022; 29:7244-7245. [PMID: 35939170 DOI: 10.1245/s10434-022-12383-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 07/29/2022] [Indexed: 11/18/2022]
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21
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Shen C, Lin Y, Guo X, Li Y, Wang D, Du Z, Hu P, Chen X, Zeng X, Lv J, Wu C, Tao K. Comparative Study of the Efficacy and Safety of Radical Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy in Locally Advanced Gastric Cancer: A Propensity Score-Matching Analysis. Ann Surg Oncol 2022; 29:8551-8563. [PMID: 35941344 DOI: 10.1245/s10434-022-12348-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 07/20/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND The effectiveness and safety of preventive hyperthermic intraperitoneal chemotherapy (HIPEC) for gastric cancer (GC) remain controversial. This study aimed to describe the safety and efficacy of radical surgery (RS) with or without HIPEC for patients with locally advanced GC (LAGC). METHODS The study identified 394 patients with LAGC who underwent RS with or without HIPEC in China. RESULTS Of the 394 patients, 146 received RS+HIPEC, and 248 received RS alone. The RS-HIPEC procedure improved the relapse-free survival (RFS) of the GC patients (2-year RFS, 62.9 % vs 37.8 %; χ2 = 4.468; P = 0.035) compared with those who received RS alone. The incidence of postoperative myelosuppression (Z = 4.077; P = 0.043) was higher in the RS+HIPEC group, whereas the incidence of wound complications was lower (Z = 4.077; P = 0.043). In the subgroup analysis, HIPEC improved the OS (2-year OS, 69.9 % vs 40.8 %; χ2 = 5.537; P =0.019) and RFS (2-year RFS, 65.6 % vs 33.3 %; χ2 = 7.380, P = 0.007) of the patients with nerve invasion and the RFS of the patients with vascular invasion (2-year RFS, 60.7 % vs 31.6 %; χ2 = 3.891; P = 0.049). In addition, the prognosis of the patients who underwent HIPEC was better when the tumor diameter was smaller than 5 cm (2-year RFS, 68.6 % vs 37.9 %; χ2 = 3.957; P = 0.047). CONCLUSIONS The RS + HIPEC procedure improved the RFS of the patients with LAGC compared with RS alone, especially the patients with nerve or vascular invasion and the patients with tumor smaller than 5 cm. Moreover, it reduced the incidence of wound complications and did not induce more perioperative complications in addition to myelosuppression.
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Affiliation(s)
- Chu Shen
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei Province, China
| | - Yao Lin
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei Province, China
| | - Xikai Guo
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei Province, China
| | - Yuan Li
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei Province, China
| | - Dianshi Wang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei Province, China
| | - Zhouyuan Du
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei Province, China
| | - Peng Hu
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei Province, China
| | - Xin Chen
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei Province, China
| | - Xinyu Zeng
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei Province, China
| | - Jianbo Lv
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei Province, China
| | - Chuanqing Wu
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei Province, China.
| | - Kaixiong Tao
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei Province, China.
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22
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Badran A, Azzam A, Noorelahi M, Alshamsan B, Alkhaldi S, Naguib R, Amin T. Outcomes of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with or without intraoperative radiotherapy for peritoneal carcinomatosis in elderly patients. SURGERY OPEN DIGESTIVE ADVANCE 2022; 6:100051. [DOI: 10.1016/j.soda.2022.100051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/02/2025]
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23
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Optimization of intraperitoneal aerosolized drug delivery using computational fluid dynamics (CFD) modeling. Sci Rep 2022; 12:6305. [PMID: 35428819 PMCID: PMC9012796 DOI: 10.1038/s41598-022-10369-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 04/04/2022] [Indexed: 01/03/2023] Open
Abstract
Intraperitoneal (IP) aerosolized anticancer drug delivery was recently introduced in the treatment of patients with peritoneal metastases. However, little is known on the effect of treatment parameters on the spatial distribution of the aerosol droplets in the peritoneal cavity. Here, computational fluid dynamics (CFD) modeling was used in conjunction with experimental validation in order to investigate the effect of droplet size, liquid flow rate and viscosity, and the addition of an electrostatic field on the homogeneity of IP aerosol. We found that spatial distribution is optimal with small droplet sizes (1–5 µm). Using the current clinically used technology (droplet size of 30 µm), the optimal spatial distribution of aerosol is obtained with a liquid flow rate of 0.6 mL s−1. Compared to saline, nebulization of higher viscosity liquids results in less homogeneous aerosol distribution. The addition of electrostatic precipitation significantly improves homogeneity of aerosol distribution, but no further improvement is obtained with voltages higher than 6.5 kV. The results of the current study will allow to choose treatment parameters and settings in order to optimize spatial distribution of IP aerosolized drug, with a potential to enhance its anticancer effect.
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24
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Power JW, Dempsey PJ, Yates A, Fenlon H, Mulsow J, Shields C, Cronin CG. Peritoneal malignancy: anatomy, pathophysiology and an update on modern day imaging. Br J Radiol 2022; 95:20210217. [PMID: 34826229 PMCID: PMC9153709 DOI: 10.1259/bjr.20210217] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
With increasing subspecialised experience in radical cytoreductive surgery and intra-abdominal chemotherapy for peritoneal malignancy, outcomes have improved significantly in selected patients. The surgery and the treatment regimens are radical and therefore correct patient selection is critical. The radiologist plays a central role in this process by estimating, as precisely as possible, the pre-treatment disease burden. Because of the nature of the disease process, accurate staging is not an easy task. Tumour deposits may be very small and in locations where they are very difficult to detect. It must be acknowledged that no form of modern day imaging has the capability of detecting the smallest peritoneal nodules, which may only be visible to direct inspection or histopathological evaluation. Nonetheless, it behoves the radiologist to be as exact and precise as possible in the reporting of this disease process. This is both to select patients who are likely to benefit from radical treatment, and just as importantly, to identify patients who are unlikely to achieve adequate cytoreductive outcomes. In this review, we outline the patterns of spread of disease and the anatomic basis for this, as well as the essential aspects of reporting abdominal studies in this patient group. We provide an evidence-based update on the relative strengths and limitations of our available multimodality imaging techniques namely CT, MRI and positron emission tomography/CT.
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Affiliation(s)
- Jack W Power
- University College Dublin (UCD) School of Medicine, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Philip J Dempsey
- University College Dublin (UCD) School of Medicine, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Andrew Yates
- University College Dublin (UCD) School of Medicine, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Helen Fenlon
- University College Dublin (UCD) School of Medicine, Mater Misericordiae University Hospital, Dublin, Ireland
| | | | - Conor Shields
- University College Dublin (UCD) School of Medicine, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Carmel G Cronin
- University College Dublin (UCD) School of Medicine, Mater Misericordiae University Hospital, Dublin, Ireland
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Gronau F, Feldbruegge L, Oberwittler F, Gonzalez-Moreno S, Villeneuve L, Eveno C, Glehen O, Kusamura S, Rau B. HIPEC in Peritoneal Metastasis of Gastric Origin: A Systematic Review of Regimens and Techniques. J Clin Med 2022; 11:jcm11051456. [PMID: 35268546 PMCID: PMC8911234 DOI: 10.3390/jcm11051456] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 03/04/2022] [Accepted: 03/04/2022] [Indexed: 02/06/2023] Open
Abstract
(1) Background: Peritoneal metastasis in gastric cancer is associated with a poor prognosis. Complete cytoreductive surgery including gastrectomy and complete removal of all peritoneal lesions followed by hyperthermic intraperitoneal chemotherapy (HIPEC) achieves promising results. There exists an immersive variety of approaches for HIPEC that makes it difficult to weigh different results obtained in the literature. In order to enable standardization and development of HIPEC, we here present a systematic review of different drug regimens and technical approaches. (2) Methods: PubMed, Embase, and the Cochrane Library were systematically searched on 26 May 2021 using the mesh terms “intraperitoneal chemotherapy AND gastric cancer”. Under consideration of systematic review guidelines, articles reporting on HIPEC in combination with CRS were selected. Data on duration, drugs, dosage, and other application parameters as well as morbidity and long term survival data were extracted for subsequent statistical analysis, tabulation, and descriptive synthesis. We assessed the risk of bias due to inhomogeneity of the patient cohort and incompleteness of report of HIPEC parameters. (3) Results: Out of 1421 screened publications, 42 publications presenting data from 1325 patients met the criteria. Most of the publications were single institutional retrospective cohort studies. The most common HIPEC regimen is performed after gastrointestinal anastomosis and consists of 50–200 mg/m2 cisplatinum and 30–40 mg/m2 mytomycin C at 42–43 °C for 60–90 min in a closed abdomen HIPEC system with three tubes. Almost every study reported incompletely on HIPEC parameters. Lower rates of anastomotic leakage were reported in studies that performed HIPEC after gastrointestinal anastomosis. Studies that performed open HIPEC and integrated a two-drug regimen indicated better overall survival rates. (4) Discussion: This is an exhaustive overview of the use of drug regimens and techniques for HIPEC after CRS for gastric cancer peritoneal metastasis. Other indications and application modes of intraperitoneal chemotherapy such as prophylactic or palliative HIPEC apart from CRS were not addressed. (5) Conclusion: Complete report of HIPEC parameters should be included in every publication. A consensus for dose expression either per BSA or as flat dose is desirable for comparison of the drug regimens. Despite numerous variations, we identified the most common regimens and techniques and their advantages and disadvantages according to the data in the literature. More phase I/II studies are needed to identify the best approach for HIPEC. (6) Other: This review was not supported by third parties.
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Affiliation(s)
- Felix Gronau
- Department of Surgery, Chirurgische Klinik Campus Charité Mitte|Campus Virchow Klinikum, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany; (F.G.); (L.F.); (F.O.)
| | - Linda Feldbruegge
- Department of Surgery, Chirurgische Klinik Campus Charité Mitte|Campus Virchow Klinikum, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany; (F.G.); (L.F.); (F.O.)
| | - Frauke Oberwittler
- Department of Surgery, Chirurgische Klinik Campus Charité Mitte|Campus Virchow Klinikum, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany; (F.G.); (L.F.); (F.O.)
| | | | - Laurent Villeneuve
- Réseau National de Prise en Charge des Tumeurs Rares du Péritoine, French National Registry of Rare Peritoneal Surface Malignancies, 69002 Lyon, France;
| | - Clarisse Eveno
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, 69495 Pierre-Bénite, France; (C.E.); (O.G.)
| | - Olivier Glehen
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, 69495 Pierre-Bénite, France; (C.E.); (O.G.)
| | - Shigeki Kusamura
- Peritoneal Surface Malignancies Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Nazionale Tumori dei Tumori di Milano, 20133 Milano, Italy;
| | - Beate Rau
- Department of Surgery, Chirurgische Klinik Campus Charité Mitte|Campus Virchow Klinikum, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany; (F.G.); (L.F.); (F.O.)
- Correspondence: ; Tel.: +49-30-450-622-214
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Prophylactic hyperthermic intraperitoneal chemotherapy may benefit the long-term survival of patients after radical gastric cancer surgery. Sci Rep 2022; 12:2583. [PMID: 35173230 PMCID: PMC8850581 DOI: 10.1038/s41598-022-06417-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 01/27/2022] [Indexed: 12/24/2022] Open
Abstract
Hyperthermic intraperitoneal chemotherapy (HIPEC) has been proven to improve the survival rate of gastric cancer and reduce peritoneal recurrence. We aimed to evaluate the effectiveness and safety of prophylactic HIPEC after radical gastric cancer surgery in this study. Researchers searched for studies published in PubMed, Embase, Web of science, Scopus, Cochrane, Clinical key databases and Microsoft Academic databases to identify studies that examine the impact of prophylactic HIPEC on the survival, recurrence and adverse events of patients undergoing radical gastric cancer surgery. RevMan 5.3 was used to analyze the results and risk of bias. The PROSERO registration number is CRD42021262016. This meta-analysis included 22 studies with a total of 2097 patients, 12 of which are RCTs. The results showed that the 1-, 3- and 5-year overall survival rate was significantly favorable to HIPEC (OR 5.10, 2.07, 1.96 respectively). Compared with the control group, the overall recurrence rate and peritoneal recurrence rate of the HIPEC group were significantly lower (OR 0.41, 0.24 respectively). Significantly favorable to the control group in terms of renal dysfunction and pulmonary dysfunction complications (OR 2.44, 6.03 respectively). Regarding the causes of death due to postoperative recurrence: liver recurrence, lymph node and local recurrence and peritoneal recurrence, the overall effect is not significantly different (OR 0.81, 1.19, 0.37 respectively). 1-, 3- and 5-year overall survival follow-up may be incremented by the prophylactic HIPEC, and which reduce the overall recurrence rate and peritoneal recurrence rate. HIPEC may have high-risk of pulmonary dysfunction and renal dysfunction complications. No difference has been found in the deaths due to recurrence after surgery.
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Zhan Z, Wang X, Yu J, Zheng J, Zeng Y, Sun M, Peng L, Guo Z, Chen B. Intraperitoneal infusion of recombinant human indentation improves prognosis in gastric cancer ascites. Future Oncol 2022; 18:1259-1271. [PMID: 35114805 DOI: 10.2217/fon-2021-0896] [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] [Indexed: 12/14/2022] Open
Abstract
Objective: To investigate the efficacy and safety of intraperitoneal administration of recombinant human indentation in gastric cancer with malignant ascites. Methods: Clinical data of 90 patients (37 in an Endostar® combined with cisplatin group and 53 in a cisplatin group) were retrospectively analyzed. The primary end point was overall survival, and the secondary end points were objective response rate (ORR), disease control rate (DCR) and so on. Results: Median overall survival was longer in the combination group (9.7 vs 8.1 months; p = 0.01). ORR and DCR were higher in the combination group (ORR: 75.7% vs 54.7%; p = 0.04; DCR: 94.6% vs 75.5%; p = 0.02). There were no significant differences in adverse effects between the two groups. Conclusion: Intraperitoneal administration of recombinant human indentation improved efficacy and survival for gastric cancer with ascites.
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Affiliation(s)
- Zhouwei Zhan
- Department of Medical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian 350014, China
| | - Xiaojie Wang
- Department of Medical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian 350014, China
| | - Jiami Yu
- Department of Medical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian 350014, China
| | - Jingxian Zheng
- Department of Medical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian 350014, China
| | - Yi Zeng
- Department of Gastrointestinal Surgery, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian 350014, China
| | - Mingyao Sun
- Department of Clinical Nutrition, Fujian Provincial Hospital, Fuzhou, Fujian 350001, China
| | - Li Peng
- Department of Diagnostic Radiology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian 350014, China
| | - Zengqing Guo
- Department of Medical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian 350014, China
| | - Bijuan Chen
- Department of Radiotherapy, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian 350014, China
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Merboth F, Garcia S, V Renesse J, Distler M, Welsch T, Weitz J, Stange DE. Comparative Analysis of Postoperative Complications after Cytoreductive Surgery and HIPEC in Gastric Cancer. Oncol Res Treat 2021; 45:45-53. [PMID: 34844244 DOI: 10.1159/000520330] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Accepted: 09/15/2021] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Patients with advanced gastric cancer (AGC) frequently show peritoneal carcinomatosis (PC). PC reduces life expectancy and quality of life. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to improve overall survival. Nevertheless, it has been reported that CRS and HIPEC are accompanied by an increase in postoperative complications. The purpose of this study was to investigate the complications associated with CRS and HIPEC and overall and disease-free survival. METHODS Patients with AGC and PC, who received complete CRS and HIPEC, were included in the HIPEC group (n = 15). Patients with AGC but without PC, who received resection of the primary tumor alone, constituted the control group (n = 43). RESULTS Patients enrolled in the HIPEC group presented with a median PCI of 7. In comparison with the control group, no differences were found in patient characteristics, risk factors, pathological findings, and operative procedures. Twenty-five percentage of the patients in both groups suffered from serious postoperative complications (CDC ≥3a). Surgical and medical complications, rate of reoperation, and mortality did not differ. Also, the recurrence pattern, median survival, and 1- and 2-year survival rates showed no differences. CONCLUSION CRS and HIPEC do not lead to an increased postoperative morbidity and mortality in AGC with PC. Albeit the poorer prognosis of patients with PC, survival of both groups was comparable.
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Affiliation(s)
- Felix Merboth
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany,
| | - Sebastian Garcia
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany
| | - Janusz V Renesse
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany
| | - Marius Distler
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany
| | - Thilo Welsch
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany
| | - Jürgen Weitz
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany
| | - Daniel E Stange
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany
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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; 10:5050. [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.)
| | - 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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Paasch C, De Santo G, Gamal-Eldin HN, Hünerbein M. Repeated cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy in patients with peritoneal carcinomatosis: A retrospective cohort study. Ann Med Surg (Lond) 2021; 70:102824. [PMID: 34584682 PMCID: PMC8453181 DOI: 10.1016/j.amsu.2021.102824] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 09/03/2021] [Accepted: 09/05/2021] [Indexed: 11/17/2022] Open
Abstract
Introduction The prognosis of abdominal cancer with peritoneal carcinomatosis (PC) is poor. In literature, some authors described a repeated Cytoreductive Surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in patients with recurrent PC as feasible for overall survival improvement. Hence, we implemented this approach at our hospital and analyzed our cases. Methods A unicentric retrospective observational study took place at the Helios hospital Berlin-Buch in 2020. The data of individuals who received a HIPEC in the time of 2007-2019 were extracted. The data were entered in the HIPEC database of the German Society of General and Visceral Surgery (StuDoQ|HIPEC, German society for general and visceral surgery). The primary objective was the overall survival after first HIPEC procedure. Results A total of 292 data files from were extracted and 14 patients were identified as eligible for further analysis (7× colorectal, 3x gastric, 1× appendix cancer, 1× cancer of unknown primary, 1× Mesothelioma, 1× Pseudomyxoma peritonei). The mean age was 57 (8) years. The BMI was on average 23.5 (3.5) kg/m2. A total of 8 individuals were female and 6 male (6xASA-Score I, 8xASA-Score II). The initial Peritoneal Cancer Index (PCI) was on average 11.5 (9.1). The average overall survival after 1. HIPEC for colonic cancer was 74 months (n = 3; 43, 70 and 90 month), for gastric cancer 29 months (n = 2; 19 and 39 month) and for mesothelioma 44 months (n = 1). Conclusions Based on our findings Repeated Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy may improve overall survival of selected patients suffering from peritoneal carcinomatosis.
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Affiliation(s)
- C Paasch
- University Hospital Brandenburg an der Havel, Brandenburg Medical University, Clinic for General and Visceral Surgery, Hochstraße 29, 14770, Brandenburg an der Havel, Germany
| | - G De Santo
- Department of General Surgery, Oberhavel Kliniken Gransee, Meseberger Weg 12-13, 16775, Gransee, Brandenburg, Germany
| | - H N Gamal-Eldin
- Center of Obesity and Metabolic Surgery, Helios Klinikum Berlin-Buch, Schwanebecker Chaussee 50, 13125, Berlin, Germany
| | - M Hünerbein
- Department of Surgery, Oberhavel Klinik Oranienburg, Robert-Koch-Straße 2-12, 16515, Oranienburg, Germany
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The Anticancer Efficacy of Plasma-Oxidized Saline (POS) in the Ehrlich Ascites Carcinoma Model In Vitro and In Vivo. Biomedicines 2021; 9:biomedicines9080932. [PMID: 34440136 PMCID: PMC8394252 DOI: 10.3390/biomedicines9080932] [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: 06/17/2021] [Revised: 07/20/2021] [Accepted: 07/27/2021] [Indexed: 01/31/2023] Open
Abstract
Cold physical plasma, a partially ionized gas rich in reactive oxygen species (ROS), is receiving increasing interest as a novel anticancer agent via two modes. The first involves its application to cells and tissues directly, while the second uses physical plasma-derived ROS to oxidize liquids. Saline is a clinically accepted liquid, and here we explored the suitability of plasma-oxidized saline (POS) as anticancer agent technology in vitro and in vivo using the Ehrlich Ascites Carcinoma (EAC) model. EAC mainly grows as a suspension in the peritoneal cavity of mice, making this model ideally suited to test POS as a putative agent against peritoneal carcinomatosis frequently observed with colon, pancreas, and ovarium metastasis. Five POS injections led to a reduction of the tumor burden in vivo as well as in a decline of EAC cell growth and an arrest in metabolic activity ex vivo. The treatment was accompanied by a decreased antioxidant capacity of Ehrlich tumor cells and increased lipid oxidation in the ascites supernatants, while no other side effects were observed. Oxaliplatin and hydrogen peroxide were used as controls and mediated better and worse outcomes, respectively, with the former but not the latter inducing profound changes in the inflammatory milieu among 13 different cytokines investigated in ascites fluid. Modulation of inflammation in the POS group was modest but significant. These results promote POS as a promising candidate for targeting peritoneal carcinomatosis and malignant ascites and suggest EAC to be a suitable and convenient model for analyzing innovative POS approaches and combination therapies.
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Hyperthermic Intrathoracic Chemoperfusion for Malignant Pleural Mesothelioma: Systematic Review and Meta-Analysis. Cancers (Basel) 2021; 13:cancers13143637. [PMID: 34298849 PMCID: PMC8307465 DOI: 10.3390/cancers13143637] [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: 06/15/2021] [Revised: 07/07/2021] [Accepted: 07/12/2021] [Indexed: 11/20/2022] Open
Abstract
Simple Summary Treatment of malignant mesothelioma with high-temperature chemotherapeutic instillation of the affected pleural space seems to be advantageous, but higher-quality studies are needed. Abstract Malignant pleural mesothelioma (MPM) is an aggressive malignancy of the pleural lining with exceptionally poor survival. Hyperthermic intrathoracic chemoperfusion (HITHOC) is commonly used with surgery in limited disease. However, data on its effect on survival are limited. In this systematic review and meta-analysis, we analyzed a total of 11 observational articles. HITHOC was compared to control arm that did not receive HITHOC in three studies including 762 patients. The pooled analysis of these studies revealed an SMD of 0.24, with 95% CI of 0.06–0.41 favoring the HITHOC group, reaching statistical significance. The survival effect of HITHOC in epithelioid MPM vs. non-epithelioid MPM was analyzed in four studies. Pooled analysis showed an SMD of 0.79 (95% CI = 0.48–1.10) favoring epithelioid MPM. Based on available data, there seems to be a benefit with HITHOC in regards to overall survival in the treatment of all mesothelioma patients. Multicenter randomized controlled trials are needed to validate and standardize this treatment approach.
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Wu HC, Lin WL, Lin CL, Lin CY, Chen SW, Chen YX, Chen CH, Lee SW, Chen SH, Tsao CJ, Huang WT, Guo HR. Age as a modifier of the effects of chemoradiotherapy with infusional 5-fluorouracil after D2 dissection in gastric cancer. Aging (Albany NY) 2021; 13:17337-17348. [PMID: 34226296 PMCID: PMC8312439 DOI: 10.18632/aging.203223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Accepted: 06/08/2021] [Indexed: 02/01/2023]
Abstract
Adjuvant concurrent chemoradiotherapy (CCRT) is the standard care for patients with resected advanced gastric cancer, but its survival benefits remain undetermined in patients undergoing D2 lymph node dissection (D2 dissection). We evaluated safety and efficacy of adjuvant CCRT with 5-fluorouracil (5-FU) versus chemotherapy alone in 110 gastric cancer patients with D2 dissection treated in Taiwan between January 2009 and January 2013. All the 71 patients receiving adjuvant CCRT were treated with daily infusional 5-FU and radiotherapy. Adjuvant CCRT was associated with higher risks of major hematologic (56.3% vs. 23.8%, p = 0.002) and gastrointestinal (46.9% vs. 14.3%, p = 0.027) toxicities and death (12.5% vs. 0.0%, p = 0.041) in patients above 70 years old, but this was not the case in those ≤70 years of age. Univariate Cox proportional regressions identified adjuvant CCRT as a factor for better overall survival (OS) (hazard ratio [HR]=0.52; 95% confidence interval [CI]: 0.27-0.99) and disease-free survival (DFS) (HR=0.46, 95% CI: 0.24-0.88), but it was not a significant factor for OS or DFS after adjusting for other factors in the multivariate analysis. However, in stratified analyses by age, we found adjuvant CCRT was an independent prognostic factor for better OS (HR=0.07; 95% CI: 0.01-0.38) in patients ≤70 years old, but not in those above 70 years of age. Therefore, it was concluded that age may to be a modifier of the effects of adjuvant CCRT.
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Affiliation(s)
- Hung-Chang Wu
- Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan
| | - Wen-Li Lin
- Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
| | - Chien-Liang Lin
- Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
| | - Cheng-Yao Lin
- Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
- Department of Environmental and Occupational Health, National Cheng Kung University, Tainan, Taiwan
- Department of Senior Welfare and Services, Southern Taiwan University of Science and Technology, Tainan, Taiwan
| | - Shang-Wen Chen
- Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
| | - Yan-Xun Chen
- Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
| | - Chao-Hsun Chen
- Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
| | - Sung-Wei Lee
- Department of Radiation Oncology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
| | - Shang-Hung Chen
- National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
- Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chao-Jung Tsao
- Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
| | - Wen-Tsung Huang
- Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
| | - How-Ran Guo
- Department of Environmental and Occupational Health, National Cheng Kung University, Tainan, Taiwan
- Department of Occupational and Environmental Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
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Abstract
Surgery is an essential component of curative-intent treatment strategies for gastric cancer. However, the care of each patient with gastric cancer must be individualized based on patient and tumor characteristics. It is important that all physicians who will be caring for patient with gastric cancer understand the current best practices of surgical management to provide patients with the highest quality of care. This article aims to provide this information while acknowledging areas of surgical management that are still controversial.
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Affiliation(s)
- Ian Solsky
- Department of Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue Block Building #112, New York, NY 10461, USA
| | - Haejin In
- Department of Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue Block Building #112, New York, NY 10461, USA; Department of Surgery, Albert Einstein College of Medicine, New York, NY, USA; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY, USA.
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Yurttas C, Horvath P, Fischer I, Meisner C, Nadalin S, Königsrainer I, Königsrainer A, Beckert S, Löffler MW. A Prospective, Phase I/II, Open-Label Pilot Trial to Assess the Safety of Hyperthermic Intraperitoneal Chemotherapy After Oncological Resection of Pancreatic Adenocarcinoma. Ann Surg Oncol 2021; 28:9086-9095. [PMID: 34131821 PMCID: PMC8205203 DOI: 10.1245/s10434-021-10187-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 05/01/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is a common fatal disease with unfavorable prognosis, even after oncological resection. To improve survival, adding hyperthermic intraperitoneal chemotherapy (HIPEC) has been suggested. Whether HIPEC entails disproportional short-term mortality is unknown and a prospectively determined adverse events profile is lacking. Since both pancreatic resection and HIPEC may relevantly influence morbidity and mortality, this uncontrolled single-arm, open-label, phase I/II pilot trial was designed to assess the 30-day mortality rate, treatment feasibility, and adverse events connected with HIPEC after oncological pancreatic surgery. METHODS This trial recruited patients scheduled for PDAC resection. A sample size of 16 patients receiving study interventions was estimated to establish a predefined margin of treatment-associated short-term mortality with a power of > 80%. Patients achieving complete macroscopic resection received HIPEC with gemcitabine administered at 1000 mg/m2 body surface area heated to 42 °C for 1 hour. RESULTS Within 30 days after intervention, no patient died or experienced any adverse events higher than grade 3 that were related to HIPEC. Furthermore, treatment-related adverse events were prospectively documented and categorized as expected or unexpected. This trial supports that the actual mortality rate after PDAC resection and HIPEC is below 10%. HIPEC treatment proved feasible in 89% of patients allocated to intervention. Pancreatic fistulas, as key complications after pancreas surgery, occurred in 3/13 patients under risk. CONCLUSION Combined pancreas resection and gemcitabine HIPEC proved feasible and safe, with acceptable morbidity and mortality. Based on these results, further clinical evaluation can be justified. REGISTRATION NUMBER NCT02863471 ( http://www.clinicaltrials.gov ).
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Affiliation(s)
- Can Yurttas
- Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Philipp Horvath
- Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Imma Fischer
- Institute for Clinical Epidemiology and Applied Biometry, University Hospital Tübingen, Tübingen, Germany
| | - Christoph Meisner
- Institute for Clinical Epidemiology and Applied Biometry, University Hospital Tübingen, Tübingen, Germany
| | - Silvio Nadalin
- Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Ingmar Königsrainer
- Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany.,Department of General, Visceral and Thoracic Surgery, Landeskrankenhaus Feldkirch, Feldkirch, Austria
| | - Alfred Königsrainer
- Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany.,German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner Site Tübingen, Tübingen, Germany.,Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany
| | - Stefan Beckert
- Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany.,Department of General and Visceral Surgery, Schwarzwald-Baar Klinikum Villingen-Schwenningen, Villingen-Schwenningen, Germany
| | - Markus W Löffler
- Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany. .,German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner Site Tübingen, Tübingen, Germany. .,Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany. .,Interfaculty Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany. .,Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany.
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Li Z, Redondo Ntutumu JDD, Huang S, Cai Z, Han S, Balde AI, Luo Z, Fang S. Comparison of the outcomes of cytoreductive surgery versus surgery plus hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis: a propensity score matching analysis. Surg Endosc 2021; 35:2789-2796. [PMID: 32632486 DOI: 10.1007/s00464-020-07712-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Accepted: 06/09/2020] [Indexed: 10/23/2022]
Abstract
BACKGROUND Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are effective treatment options for selected patients with peritoneal carcinomatosis (PC). We compared the short-term outcomes of surgery plus HIPEC and CRS alone for PC. METHODS We retrospectively examined patients who underwent CRS-HIPEC for PC at a single center from 2014 to 2019 using the Chinese CRS-HIPEC patient database at our institution. Patients were divided into two groups: surgery plus HIPEC (450) and surgery alone (200). A 1:1 propensity score matching (PSM) analysis was performed. The postoperative outcomes, mortality, and length of hospital stay were compared between the surgery plus HIPEC and CRS alone groups. RESULTS Propensity scoring generated 162 pairs. There was no statistically significant difference in the 30-day mortality rate between the groups (0% vs 0%, P = 1.000), and the morbidity rates were similar in both groups (7.4% vs 8.0%, P = 0.835). The surgery plus HIPEC group had a longer operative time (247.81 ± 64.70 vs 184.55 ± 29.56, P ≤ 0.001) and a slightly longer postoperative hospital stay (14.64 ± 5.24 vs 12.59 ± 3.76, P ≤ 0.001). No other baseline characteristics were significantly different. CONCLUSIONS Surgery plus HIPEC is feasible for select patients and is associated with prolonged surgery times and prolonged hospital stays, and there is no significant difference in mortality rates or postoperative outcomes.
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Affiliation(s)
- Zhou Li
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, No. 253, Industrial Avenue, Haizhu District, Guangzhou, 510282, Guangdong, China.
| | - Juan de Dios Redondo Ntutumu
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, No. 253, Industrial Avenue, Haizhu District, Guangzhou, 510282, Guangdong, China
| | - Shengyi Huang
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, No. 253, Industrial Avenue, Haizhu District, Guangzhou, 510282, Guangdong, China
| | - Zhai Cai
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, No. 253, Industrial Avenue, Haizhu District, Guangzhou, 510282, Guangdong, China
| | - Shuai Han
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, No. 253, Industrial Avenue, Haizhu District, Guangzhou, 510282, Guangdong, China.
| | - A I Balde
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, No. 253, Industrial Avenue, Haizhu District, Guangzhou, 510282, Guangdong, China
| | - Zeyu Luo
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, No. 253, Industrial Avenue, Haizhu District, Guangzhou, 510282, Guangdong, China
| | - Suzhen Fang
- Department of General Surgery, Zhujiang Hospital, Southern Medical University, No. 253, Industrial Avenue, Haizhu District, Guangzhou, 510282, Guangdong, China
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Carino A, Graziosi L, Marchianò S, Biagioli M, Marino E, Sepe V, Zampella A, Distrutti E, Donini A, Fiorucci S. Analysis of Gastric Cancer Transcriptome Allows the Identification of Histotype Specific Molecular Signatures With Prognostic Potential. Front Oncol 2021; 11:663771. [PMID: 34012923 PMCID: PMC8126708 DOI: 10.3389/fonc.2021.663771] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 04/06/2021] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer is the fifth most common malignancy but the third leading cause of cancer-associated mortality worldwide. Therapy for gastric cancer remain largely suboptimal making the identification of novel therapeutic targets an urgent medical need. In the present study we have carried out a high-throughput sequencing of transcriptome expression in patients with gastric cancers. Twenty-four patients, among a series of 53, who underwent an attempt of curative surgery for gastric cancers in a single center, were enrolled. Patients were sub-grouped according to their histopathology into diffuse and intestinal types, and the transcriptome of the two subgroups assessed by RNAseq analysis and compared to the normal gastric mucosa. The results of this investigation demonstrated that the two histopathology phenotypes express two different patterns of gene expression. A total of 2,064 transcripts were differentially expressed between neoplastic and non-neoplastic tissues: 772 were specific for the intestinal type and 407 for the diffuse type. Only 885 transcripts were simultaneously differentially expressed by both tumors. The per pathway analysis demonstrated an enrichment of extracellular matrix and immune dysfunction in the intestinal type including CXCR2, CXCR1, FPR2, CARD14, EFNA2, AQ9, TRIP13, KLK11 and GHRL. At the univariate analysis reduced levels AQP9 was found to be a negative predictor of 4 years survival. In the diffuse type low levels CXCR2 and high levels of CARD14 mRNA were negative predictors of 4 years survival. In summary, we have identified a group of genes differentially regulated in the intestinal and diffuse histotypes of gastric cancers with AQP9, CARD14 and CXCR2 impacting on patients' prognosis, although CXCR2 is the only factor independently impacting overall survival.
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Affiliation(s)
- Adriana Carino
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Luigina Graziosi
- S.C.Gastroenterologia, Azienda Ospedaliera di Perugia, Perugia, Italy
| | - Silvia Marchianò
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Michele Biagioli
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Elisabetta Marino
- S.C.Gastroenterologia, Azienda Ospedaliera di Perugia, Perugia, Italy
| | - Valentina Sepe
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Angela Zampella
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | | | - Annibale Donini
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Stefano Fiorucci
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
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Ray MD, Dhall K. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the management of peritoneal surface malignancies - An evidence-based review. Curr Probl Cancer 2021; 45:100737. [PMID: 34116836 DOI: 10.1016/j.currproblcancer.2021.100737] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 02/27/2021] [Accepted: 03/15/2021] [Indexed: 12/23/2022]
Abstract
BACKGROUND Traditionally, peritoneal surface malignancies (PSM) were considered terminal diseases because of their advanced nature, therefore, systemic chemotherapy was given with palliative intent only. As a result, very poor survival outcomes were observed. But with the introduction of complete Cytoreductive surgery (CRS) and Hyperthermic intraperitoneal chemotherapy (HIPEC), the scenario has changed dramatically. METHODOLOGY An objective electronic database search was performed in Pubmed, NLM Catalog, Google scholar, Bookshelf, and Pubmed Central published in the time period from 2000 till 2020. All the randomized studies were included. In the absence of randomized studies, both prospective and retrospective studies were included. The outcomes of HIPEC were measured in terms of median survival, disease-free survival, overall survival, complications and drug toxicities. RESULTS CRS and HIPEC are considered the standard of care for PMP and MPM even in the absence of level 1 evidence due to lack of an effective alternative treatment. In colorectal and gastric cancer, several phase-three trials are showing overall survival benefit in selected cases while there is a prophylactic and palliative role of HIPEC in gastric cancer. Three reported phase 3 trials showed positive results in ovarian cancer. In peritoneal sarcomatosis, the role of HIPEC is yet to be proven. CONCLUSION The patient selection is the key to the successful outcomes after HIPEC. HIPEC should be performed by the experienced surgeons in specialized centres with a strong critical care and intensive care support to reduce the morbidity and mortality. Ongoing trials and future directions will prove to be an indispensable arm in the oncological armamentarium.
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Affiliation(s)
- Mukur Dipi Ray
- Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Kunal Dhall
- Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India.
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Boerner T, Piso P. A narrative review of intraperitoneal chemotherapy and cytoreductive surgery (CRS) for peritoneal metastases in gastric cancer. J Gastrointest Oncol 2021; 12:S59-S67. [PMID: 33968426 PMCID: PMC8100723 DOI: 10.21037/jgo-20-284] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 08/22/2020] [Indexed: 12/26/2022] Open
Abstract
Peritoneal carcinomatosis of gastric origin is an aggressive tumor entity. Historically it has been considered a terminal disease with no long-term survival, due to limited therapeutic options. However, as a better understanding of tumor biology has evolved in recent years, novel multimodal treatment strategies incorporating intraperitoneal (IP) chemotherapy-hyperthermic intraperitoneal chemotherapy (HIPEC), early postoperative intraperitoneal chemotherapy (EPIC), neoadjuvant intraperitoneal-systemic chemotherapy protocol (NIPS)-and cytoreductive surgery (CRS) have demonstrated promising oncologic outcomes and even long-term survival in selected patients. Most of the studies published to date are retrospective in nature. These studies involve heterogenous patient populations, a wide variety of chemotherapeutic drugs, and show wide variation in outcomes between institutions. Thus, it is difficult to evaluate the results. This review summarizes our current knowledge regarding IP chemotherapy and CRS for peritoneal metastases (PM) in gastric cancer (GC). We describe our institutional treatment regimens. We also provide a brief overview of new, targeted therapies that may show promise in the future.
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Affiliation(s)
- Thomas Boerner
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Pompiliu Piso
- Department of Surgery, Krankenhaus Barmherzige Brüder Regensburg, Regensburg, Germany
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40
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Cowling J, Gorman B, Riaz A, Bundred JR, Kamarajah SK, Evans RPT, Singh P, Griffiths EA. Peri-operative Outcomes and Survival Following Palliative Gastrectomy for Gastric Cancer: a Systematic Review and Meta-analysis. J Gastrointest Cancer 2021; 52:41-56. [PMID: 32959118 PMCID: PMC7900337 DOI: 10.1007/s12029-020-00519-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/09/2020] [Indexed: 02/03/2023]
Abstract
BACKGROUND Many patients with gastric cancer present with late stage disease. Palliative gastrectomy remains a contentious intervention aiming to debulk tumour and prevent or treat complications such as gastric outlet obstruction, perforation and bleeding. METHODS We conducted a systematic review of the literature for all papers describing palliative resections for gastric cancer and reporting peri-operative or survival outcomes. Data from peri-operative and survival outcomes were meta-analysed using random effects modelling. Survival data from patients undergoing palliative resections, non-resective surgery and palliative chemotherapy were also combined. This study was registered with the PROSPERO database (CRD42019159136). RESULTS One hundred and twenty-eight papers which included 58,675 patients contributed data. At 1 year, there was a significantly improved survival in patients who underwent palliative gastrectomy when compared to non-resectional surgery and no treatment. At 2 years following treatment, palliative gastrectomy was associated with significantly improved survival compared to chemotherapy only; however, there was no significant improvement in survival compared to patients who underwent non-resectional surgery after 1 year. Palliative resections were associated with higher rates of overall complications versus non-resectional surgery (OR 2.14; 95% CI, 1.34, 3.46; p < 0.001). However, palliative resections were associated with similar peri-operative mortality rates to non-resectional surgery. CONCLUSION Palliative gastrectomy is associated with a small improvement in survival at 1 year when compared to non-resectional surgery and chemotherapy. However, at 2 and 3 years following treatment, survival benefits are less clear. Any survival benefits come at the expense of increased major and overall complications.
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Affiliation(s)
- Joseph Cowling
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Bethany Gorman
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Afrah Riaz
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - James R Bundred
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
- College of Medical and Dental Sciences, University of Leeds, Leeds, UK
| | - Sivesh K Kamarajah
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
- Department of Upper GI surgery, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS FT, Mindelsohn Way, Birmingham, B15 2TH, UK
| | - Richard P T Evans
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Pritam Singh
- Nottingham Oesophago-Gastric Unit, City Hospital, Hucknall Rd, Nottingham, NG5 1PB, UK
| | - Ewen A Griffiths
- College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
- Department of Upper GI surgery, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS FT, Mindelsohn Way, Birmingham, B15 2TH, UK.
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Gronau F, Jara M, Feldbrügge L, Wolf V, Oeff A, Rau B. [Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer]. Chirurg 2021; 92:522-527. [PMID: 33620502 DOI: 10.1007/s00104-021-01371-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/26/2021] [Indexed: 10/22/2022]
Abstract
BACKGROUND Gastric cancer with peritoneal metastases is associated with an extremely poor prognosis. Developed multimodal treatment concepts, which include a combination of perioperative systemic treatment and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC), show promising results with respect to improvement of the long-term survival. METHODS This article contains a review of the literature of published studies on the topic of gastric cancer and peritoneal metastasis. RESULTS The prognosis of patients with gastric cancer peritoneal carcinomatosis shows an extremely limited median survival of 7 months under palliative second-line systemic treatment. The median survival time increased to 12 months with cytoreductive surgery and in combination with HIPEC showed a positive effect on survival in individual studies. EXPERT OPINION Treatment recommendations for patients with peritoneal metastases of gastric cancer should be carried out by experts in surgical reference centers.
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Affiliation(s)
- Felix Gronau
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow Klinikum, Charité Universitätsmedizin, Berlin, Deutschland
| | - Maximilian Jara
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow Klinikum, Charité Universitätsmedizin, Berlin, Deutschland
| | - Linda Feldbrügge
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow Klinikum, Charité Universitätsmedizin, Berlin, Deutschland
| | - Vincent Wolf
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow Klinikum, Charité Universitätsmedizin, Berlin, Deutschland
| | - Alan Oeff
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow Klinikum, Charité Universitätsmedizin, Berlin, Deutschland
| | - Beate Rau
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow Klinikum, Charité Universitätsmedizin, Berlin, Deutschland. .,Klinik für Chirurgie, Universitätsmedizin Berlin, Charité Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Deutschland.
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42
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Koemans WJ, Houwink A, van der Kaaij RT, Wassenaar ECE, Boerma D, Hahn C, Imhof O, Brandt MG, Ariëns MP, Veenhof AAFA, Hartemink KJ, van Sandick JW. Perioperative Management of Gastric Cancer Patients Treated With (Sub)Total Gastrectomy, Cytoreductive Surgery, and Hyperthermic Intraperitoneal Chemotherapy (HIPEC): Lessons Learned. Ann Surg Oncol 2021; 28:4647-4654. [PMID: 33389293 DOI: 10.1245/s10434-020-09465-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Accepted: 11/25/2020] [Indexed: 11/18/2022]
Abstract
BACKGROUND The PERISCOPE I study was designed to assess the safety and feasibility of (sub)total gastrectomy, cytoreductive surgery (CRS), and hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin and docetaxel for gastric cancer patients who have limited peritoneal dissemination. The current analysis investigated changes in perioperative management together with their impact on postoperative outcomes. METHODS Patients with resectable gastric cancer and limited peritoneal dissemination were administered (sub)total gastrectomy, CRS, and HIPEC with oxaliplatin (460 mg/m2) and docetaxel (escalating scheme: 0, 50, 75 mg/m2). Of the 25 patients who completed the study protocol, 14 were treated in the dose-escalation cohort and 11 were treated in the expansion cohort (to optimize perioperative management). RESULTS A significant proportion of the patients in the dose-escalation cohort (n = 7, 50%) had ileus-related complications. In this cohort, enteral nutrition was started immediately after surgery at 20 ml/h, which was increased on day 1 to meet nutritional needs. In the expansion cohort, enteral nutrition was administered at 10 ml/h until day 3, then restricted to 20 ml/h until day 6, supplemented with total parenteral nutrition to meet nutritional needs. Ileus-related complications occurred for two patients (18%) of the expansion cohort. The intensive care unit (ICU) readmission rate decreased from 50 (n = 7) to 9% (n = 1; p = 0.04). CONCLUSION The implementation of a strict nutritional protocol during the PERISCOPE I study was associated with a decrease in postoperative complications. Based on these results, a perioperative care path was described for the gastric cancer HIPEC patients in the PERISCOPE II study.
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Affiliation(s)
- W J Koemans
- Department of Surgical Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - A Houwink
- Department of Anesthesiology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.,Department of Intensive Care Medicine, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - R T van der Kaaij
- Department of Surgical Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - E C E Wassenaar
- Department of Dietetics, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - D Boerma
- Department of Dietetics, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - C Hahn
- Department of Anesthesiology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - O Imhof
- Clinical Perfusion, Heartbeat, Eemnes, The Netherlands
| | - M G Brandt
- Department of Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - M P Ariëns
- Department of Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands
| | - A A F A Veenhof
- Department of Surgical Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - K J Hartemink
- Department of Surgical Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - J W van Sandick
- Department of Surgical Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
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Ray MD, Dhall K. Where Does HIPEC Stand: An Evidence Based Review. MULTIDISCIPLINARY APPROACH TO SURGICAL ONCOLOGY PATIENTS 2021:349-358. [DOI: 10.1007/978-981-15-7699-7_44] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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44
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Ajani JA, Xu Y, Huo L, Wang R, Li Y, Wang Y, Pizzi MP, Scott AW, Harada K, Ma L, Yao X, Jin J, Zhao W, Dong X, Badgwell BD, Shanbhag ND, Tatlonghari G, Estrella JS, Roy Chowdhuri S, Kobayashi M, Vykouka JV, Hanash S, Calin GA, Peng G, Lee JS, Johnson RL, Wang Z, Wang L, Song S. YAP1 mediates gastric adenocarcinoma peritoneal metastases that are attenuated by YAP1 inhibition. Gut 2021; 70:55-66. [PMID: 32345613 PMCID: PMC9832914 DOI: 10.1136/gutjnl-2019-319748] [Citation(s) in RCA: 63] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Revised: 03/19/2020] [Accepted: 03/31/2020] [Indexed: 01/14/2023]
Abstract
OBJECTIVE Peritoneal carcinomatosis (PC; malignant ascites or implants) occurs in approximately 45% of advanced gastric adenocarcinoma (GAC) patients and associated with a poor survival. The molecular events leading to PC are unknown. The yes-associated protein 1 (YAP1) oncogene has emerged in many tumour types, but its clinical significance in PC is unclear. Here, we investigated the role of YAP1 in PC and its potential as a therapeutic target. METHODS Patient-derived PC cells, patient-derived xenograft (PDX) and patient-derived orthotopic (PDO) models were used to study the function of YAP1 in vitro and in vivo. Immunofluorescence and immunohistochemical staining, RNA sequencing (RNA-Seq) and single-cell RNA-Seq (sc-RNA-Seq) were used to elucidate the expression of YAP1 and PC cell heterogeneity. LentiCRISPR/Cas9 knockout of YAP1 and a YAP1 inhibitor were used to dissect its role in PC metastases. RESULTS YAP1 was highly upregulated in PC tumour cells, conferred cancer stem cell (CSC) properties and appeared to be a metastatic driver. Dual staining of YAP1/EpCAM and sc-RNA-Seq revealed that PC tumour cells were highly heterogeneous, YAP1high PC cells had CSC-like properties and easily formed PDX/PDO tumours but also formed PC in mice, while genetic knockout YAP1 significantly slowed tumour growth and eliminated PC in PDO model. Additionally, pharmacologic inhibition of YAP1 specifically reduced CSC-like properties and suppressed tumour growth in YAP1high PC cells especially in combination with cytotoxics in vivo PDX model. CONCLUSIONS YAP1 is essential for PC that is attenuated by YAP1 inhibition. Our data provide a strong rationale to target YAP1 in clinic for GAC patients with PC.
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Affiliation(s)
- Jaffer A. Ajani
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.,To whom correspondence should be addressed: Shumei Song, PhD, tel.: 713-834-6144, ,; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. Jaffer A. Ajani, MD, Tel: 713-792-2828, ; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA
| | - Yan Xu
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.,Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, 110001, P.R. China
| | - Longfei Huo
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Ruiping Wang
- Detartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Yuan Li
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.,Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, 110001, P.R. China
| | - Ying Wang
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Melissa Pool Pizzi
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Ailing W. Scott
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Kazuto Harada
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Lang Ma
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Xiaodan Yao
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Jiankang Jin
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Wei Zhao
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Xiaochuan Dong
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Brian D. Badgwell
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Namita D. Shanbhag
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Ghia Tatlonghari
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Jeannelyn S. Estrella
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Sinchita Roy Chowdhuri
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Makoto Kobayashi
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Jody V. Vykouka
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Samir Hanash
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - George A. Calin
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Guang Peng
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Ju-Seog Lee
- Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Randy L. Johnson
- Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Zhenning Wang
- Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, 110001, P.R. China
| | - Linghua Wang
- Detartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Shumei Song
- Department of Gastrointestinal Medical Oncology, UT MD Anderson Cancer Center, Houston, TX, USA
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45
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Abstract
Gastric cancer is still a major cause of death worldwide. While laparoscopic gastrectomy (LG) has gained evidence as a standard treatment for early gastric cancer in the distal stomach, there are still concerns regarding its application for gastric cancer in the upper stomach and advanced gastric cancer. Nevertheless, LG has shown to have faster recovery, shorter hospital stay, less pain, and less blood loss in many retrospective and prospective studies. The application of LG has now extended from conventional radical gastrectomy to novel approaches such as function-preserving gastrectomy and sentinel-node navigated surgery. Studies on the use of laparoscopy in treatment for stage IV gastric cancer are rare, but show that there may be some roles of LG in selected cases. With the development of new laparoscopic tools that augment human ability, the future of LG should move on from proving non-inferiority to demonstrating superiority compared to the traditional open gastrectomy.
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Affiliation(s)
- So Hyun Kang
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea
| | - Hyung-Ho Kim
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea.,Department of Surgery, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
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Rossi SM, Murray T, McDonough L, Kelly H. Loco-regional drug delivery in oncology: current clinical applications and future translational opportunities. Expert Opin Drug Deliv 2020; 18:607-623. [PMID: 33253052 DOI: 10.1080/17425247.2021.1856074] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Introduction: Drug-based treatment regimens for cancer are often associated with off-target toxic side effects and low penetration of the drug at the tumor site leading to patient morbidity and limited efficacy. Loco-regional drug delivery has the potential to increase efficacy while concomitantly reducing toxicity.Areas covered: Clinical applications using loco-regional delivery include intra-arterial drug delivery in retinoblastoma, direct intra-tumoral (IT) injection of ethanol for ablation in hepatocellular carcinoma (HCC) and the use of HIPEC in peritoneal carcinomas. In recent years, there has been a significant increase in both approved products and clinical trials, with a particular emphasis on drug delivery platforms such as drug-eluting beads for HCC and hydrogel platforms for intravesical delivery in bladder cancer.Expert opinion: Development of loco-regional drug-delivery systems has been slow, limited by weak clinical data for early applications and challenges relating to dosing, delivery and retention of drugs at the site of action. However, there is increasing focus on the potential of loco-regional drug delivery when combined with bespoke drug-delivery platforms. With the growth in immunotherapies, the use of IT delivery to drive priming of the anti-tumor response has opened up a new field of opportunity for loco-regional drug delivery.
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Affiliation(s)
- Seona M Rossi
- School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
| | - Timothy Murray
- Department of Radiology, University of British Columbia, Vancouver, British Columbia, Canada
| | - Liam McDonough
- School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
| | - Helena Kelly
- School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
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Blumenthaler AN, Allen CJ, Ikoma N, Blum M, Das P, Minsky BD, Mansfield PF, Ajani JA, Badgwell BD. Laparoscopic HIPEC for Low-Volume Peritoneal Metastasis in Gastric and Gastroesophageal Adenocarcinoma. Ann Surg Oncol 2020; 27:5047-5056. [PMID: 32737700 PMCID: PMC7682939 DOI: 10.1245/s10434-020-08968-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Accepted: 07/21/2020] [Indexed: 11/18/2022]
Abstract
BACKGROUND We seek to determine whether laparoscopic hyperthermic intraperitoneal chemoperfusion (LS-HIPEC) improves overall survival (OS) in patients with gastric and gastroesophageal adenocarcinoma and low-volume peritoneal metastasis compared with standard of care treatment. PATIENTS AND METHODS We reviewed data from a prospectively maintained database of patients with gastric and gastroesophageal adenocarcinoma to identify patients with radiologically occult carcinomatosis or positive peritoneal cytology, no evidence of distant metastasis, and without disease progression during initial chemotherapy or observation. Univariate and multivariable analyses were performed to evaluate the impact of LS-HIPEC on OS. RESULTS We identified 25 patients who underwent LS-HIPEC and 27 treated with a standard of care approach due to patient (33.3%) or provider (51.9%) preference or financial limitations/lack of insurance coverage (14.8%). Resection was ultimately performed in 28% of LS-HIPEC patients and no standard care patients. At a median follow-up of 18.9 months, median OS was 24.7 (IQR 20.8-34.2) months in LS-HIPEC patients and 21.3 (IQR 12.3-23.1) months in standard care patients (p = 0.08). Three-year OS in the LS-HIPEC group was 19.1%, compared with 9.6% (p = 0.08). Patients who underwent resection had a median OS of 25.3 (IQR 22.6-47.1) months compared with 21.3 months in standard care patients (p = 0.05). CONCLUSIONS Neoadjuvant LS-HIPEC for the treatment of low-volume peritoneal disease in gastric and gastroesophageal cancer patients did not significantly improve OS compared with standard care. Multiinstitutional studies are necessary to further elucidate the benefit of LS-HIPEC for this patient population.
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Affiliation(s)
- Alisa N Blumenthaler
- Departments of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Casey J Allen
- Departments of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Naruhiko Ikoma
- Departments of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Mariela Blum
- Departments of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Prajnan Das
- Departments of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Bruce D Minsky
- Departments of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Paul F Mansfield
- Departments of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jaffer A Ajani
- Departments of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Brian D Badgwell
- Departments of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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Wang X, Che X, Yu Y, Cheng Y, Bai M, Yang Z, Guo Q, Xie X, Li D, Guo M, Hou K, Guo W, Qu X, Cao L. Hypoxia-autophagy axis induces VEGFA by peritoneal mesothelial cells to promote gastric cancer peritoneal metastasis through an integrin α5-fibronectin pathway. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2020; 39:221. [PMID: 33081836 PMCID: PMC7576728 DOI: 10.1186/s13046-020-01703-x] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Accepted: 09/07/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND Peritoneal metastasis (PM) is an important pathological process in the progression of gastric cancer (GC). The metastatic potential of tumor and stromal cells is governed by hypoxia, which is a key molecular feature of the tumor microenvironment. Mesothelial cells also participate in this complex and dynamic process. However, the molecular mechanisms underlying the hypoxia-driven mesothelial-tumor interactions that promote peritoneal metastasis of GC remain unclear. METHODS We determined the hypoxic microenvironment in PM of nude mice by immunohistochemical analysis and screened VEGFA by human growth factor array kit. The crosstalk mediated by VEGFA between peritoneal mesothelial cells (PMCs) and GC cells was determined in GC cells incubated with conditioned medium prepared from hypoxia-treated PMCs. The association between VEGFR1 and integrin α5 and fibronectin in GC cells was enriched using Gene Set Enrichment Analysis and KEGG pathway enrichment analysis. In vitro and xenograft mouse models were used to evaluate the impact of VEGFA/VEGFR1 on gastric cancer peritoneal metastasis. Confocal microscopy and immunoprecipitation were performed to determine the effect of hypoxia-induced autophagy. RESULTS Here we report that in the PMCs of the hypoxic microenvironment, SIRT1 is degraded via the autophagic lysosomal pathway, leading to increased acetylation of HIF-1α and secretion of VEGFA. Under hypoxic conditions, VEGFA derived from PMCs acts on VEGFR1 of GC cells, resulting in p-ERK/p-JNK pathway activation, increased integrin α5 and fibronectin expression, and promotion of PM. CONCLUSIONS Our findings have elucidated the mechanisms by which PMCs promote PM in GC in hypoxic environments. This study also provides a theoretical basis for considering autophagic pathways or VEGFA as potential therapeutic targets to treat PM in GC.
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Affiliation(s)
- Xiaoxun Wang
- Institute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, 110001, Liaoning, China
| | - Xiaofang Che
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, 110001, China
| | - Yang Yu
- Institute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, 110001, Liaoning, China
| | - Yu Cheng
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, 110001, China
| | - Ming Bai
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, 110001, China
| | - Zichang Yang
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, 110001, China
| | - Qiqiang Guo
- Institute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, 110001, Liaoning, China
| | - Xiaochen Xie
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, 110001, China
| | - Danni Li
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, 110001, China
| | - Min Guo
- Institute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, 110001, Liaoning, China
| | - Kezuo Hou
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, 110001, China
| | - Wendong Guo
- Institute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, 110001, Liaoning, China
| | - Xiujuan Qu
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001, China. .,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, 110001, China.
| | - Liu Cao
- Institute of Translational Medicine, Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, 110001, Liaoning, China.
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Predicting Peritoneal Dissemination of Gastric Cancer in the Era of Precision Medicine: Molecular Characterization and Biomarkers. Cancers (Basel) 2020; 12:cancers12082236. [PMID: 32785164 PMCID: PMC7547377 DOI: 10.3390/cancers12082236] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Revised: 07/29/2020] [Accepted: 08/05/2020] [Indexed: 12/24/2022] Open
Abstract
Gastric cancer (GC) is a leading cause of worldwide cancer-related death. Being a highly heterogeneous disease, the current treatment of GC has been suboptimal due to the lack of subtype-dependent therapies. Peritoneal dissemination (PD) is a common pattern of GC metastasis associated with poor prognosis. Therefore, it is urgently necessary to identify patients at high risk of PD. PD is found to be associated with Lauren diffuse type GC. Molecular profiling of GC, especially diffuse type GC, has been utilized to identify molecular alterations and has given rise to various molecular classifications, shedding light on the underlying mechanism of PD and enabling identification of patients at higher PD risk. In addition, a series of diagnositc and prognostic biomarkers of PD from serum, peritoneal lavages and primary GCs have been reported. This comprehensive review summarizes findings on the multi-omic characteristics of diffuse type GC, the clinical significance of updating molecular classifications of GC in association with PD risk and research advances in PD-associated biomarkers.
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Initial Single-center Experience of PIPAC in Patients With Unresectable Peritoneal Metastasis. Cir Esp 2020; 99:354-360. [PMID: 32762956 DOI: 10.1016/j.ciresp.2020.06.020] [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: 04/29/2020] [Revised: 06/09/2020] [Accepted: 06/26/2020] [Indexed: 11/23/2022]
Abstract
INTRODUCTION Peritoneal carcinomatosis remains a condition with poor prognosis and limited therapeutic options. Pressurized Intrapertioneal Aerosol Chemotherapy (PIPAC) has been developed as a new tool for delivering intraperitoneal chemotherapy with low morbidity. The aim of this study was to evaluate the initial experience of PIPAC in patients with peritoneal carcinomatosis at our hospital. METHODS A prospective study between January 2019 and February 2020 was carried at a tertiary public hospital. Primary tumor, ascites volume, PCI, chemotherapy regimen, operative time, morbidity, length of hospital stay and mortality were recorded for analysis. RESULTS We analyzed 9 PIPAC procedures performed in 5patients. Median PCI was 27.6 (24-35). Median surgical time was 93minutes (70-125). Only one adverse event occurred out of 9 procedures (Clavien-DindoII). Median length of hospital stay was 2days (1-4). Mortality was 0%. CONCLUSION PIPAC seems to be a feasible and safe procedure to treat peritoneal carcinomatosis, with low morbidity and short hospital stay.
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