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Jung W, Park M, Park SJ, Lee EJ, Kim HS, Kim S, Yoon C. Airborne and surface contamination after rotational intraperitoneal pressurized aerosol chemotherapy using cisplatin. J Gynecol Oncol 2025; 36:e12. [PMID: 38872481 PMCID: PMC11791003 DOI: 10.3802/jgo.2025.36.e12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Revised: 02/13/2024] [Accepted: 04/15/2024] [Indexed: 06/15/2024] Open
Abstract
OBJECTIVE We evaluated the occupational exposure levels of healthcare workers while conducting rotational pressurized intraperitoneal aerosol chemotherapy (RIPAC) using cisplatin in a large animal model. METHODS We performed RIPAC using cisplatin in 6 female pigs and collected surface and air samples during the procedure. Surface samples were obtained from RIPAC devices and personal protective equipment (PPE) by wiping, and air samples were collected around the operating table. All samples were analyzed by inductively coupled plasma-mass spectrometry to detect platinum. RESULTS Among all surface samples (n=44), platinum was detected in 41 samples (93.2%) but not in all air samples (n=16). Among samples collected from RIPAC devices (n=23), minimum and maximum cisplatin levels of 0.08 and 235.09 ng/cm² were detected, mainly because of direct aerosol exposure in the abdominal cavity. Among samples collected from healthcare workers' PPE (n=21), 18 samples (85.7%) showed contamination levels below the detection limit, with a maximum of 0.23 ng/cm². There was no significant contamination among samples collected from masks, shoes, or gloves. CONCLUSION During the RIPAC procedures, there is a potential risk of dermal exposure, as platinum, a surrogate material for cisplatin, was detected at low concentration levels in some surface samples. However, the respiratory exposure risk was not identified, as platinum was not detected in the airborne samples in this study.
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Affiliation(s)
- Wongeon Jung
- Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Korea
| | - Mijin Park
- Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Korea
| | - Soo Jin Park
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Korea
| | - Eun Ji Lee
- Department of Obstetrics and Gynecology, Chung-Ang University Hospital, Seoul, Korea
| | - Hee Seung Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Sunju Kim
- Center for Technology Innovation, Seoul Institute of Technology, Seoul, Korea
| | - Chungsik Yoon
- Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Korea
- Institute of Health and Environment, Seoul National University, Seoul, Korea.
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Hansen PS, Graversen M, Detlefsen S, Ainsworth AP, Fristrup CW, Eckhoff L, Jelin-Klaric M, Mortensen MB. Implementation and evaluation of Pressurized IntraThoracic Aerosol Chemotherapy (PITAC) for the treatment of patients with malignant pleural effusion: study protocol for the Danish phase-I PITAC-OPC5 study. Pleura Peritoneum 2024; 9:141-148. [PMID: 39712295 PMCID: PMC11661466 DOI: 10.1515/pp-2024-0014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Accepted: 10/18/2024] [Indexed: 12/24/2024] Open
Abstract
Objectives Pressurized IntraThoracic Aerosol Chemotherapy (PITAC) is a minimally invasive cancer-directed therapy for patients with malignant pleural effusion (MPE) and/or pleural metastasis (PLM). PITAC is based on Pressurized IntraPeritoneal Aerosol Chemotherapy, which has proven to be safe and feasible. Since 2012, 47 PITACs have been published, and prospective data on feasibility, safety and potential local response are lacking. Methods The prospective, controlled, phase-I study is designed to treat MPE with PITAC. There are no data to support the estimated number of patients needed, but previous experience estimates the non-access rate to 20 %. Twenty eligible patients with MPE will receive two or more PITACs at four-week intervals. During video-assisted thoracoscopy, MPE and/or pleural lavage fluid is evacuated, and the extent of visible PLM is assessed. Pleural biopsies are collected, if possible, for histological response as per Thoracic Regression Grading Score (TRGS). Patients are screened for treatment-related intra- and postoperative complications. The primary outcome is the number of patients with Clavien-Dindo ≥3b or Common Terminology Criteria for Adverse Events≥4 within 30 days. Secondary objectives include PLM-score, TRGS and cytology, length of hospitalization, personnel safety, quality of life, and change in MPE volume. Results PITAC is expected to be safe and feasible for patients and personnel, and achieve positive results in the reduction of MPE volume. Conclusions The results may significantly impact the next clinical, technical, and scientific steps in the implementation of PITAC. Given the suboptimal treatment options for MPE and the seemingly promising results of PITAC, we find the implementation of PITAC ethically reasonable and sound.
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Affiliation(s)
- Pernille Schjødt Hansen
- Odense PIPAC Center (OPC) and Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark
| | - Martin Graversen
- Odense PIPAC Center (OPC) and Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark
- Department of Surgery, HPB and Upper GI Section, Odense University Hospital, Odense, Denmark
| | - Sönke Detlefsen
- Odense PIPAC Center (OPC) and Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark
- Department of Pathology, Odense University Hospital, Odense, Denmark
| | - Alan Patrick Ainsworth
- Odense PIPAC Center (OPC) and Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark
- Department of Surgery, HPB and Upper GI Section, Odense University Hospital, Odense, Denmark
| | - Claus Wilki Fristrup
- Odense PIPAC Center (OPC) and Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark
- Department of Surgery, HPB and Upper GI Section, Odense University Hospital, Odense, Denmark
| | - Lise Eckhoff
- Department of Oncology, Odense University Hospital, Odense, Denmark
| | - Mia Jelin-Klaric
- Department of Oncology, Odense University Hospital, Odense, Denmark
| | - Michael Bau Mortensen
- Odense PIPAC Center (OPC) and Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark
- Department of Surgery, HPB and Upper GI Section, Odense University Hospital, Odense, Denmark
- Faculty of Health Sciences, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
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Li D, Crook C, Chung V, Brar G, Fakih M, Barzi A, Melstrom L, Singh G, Fong Y, Frankel P, Raoof M. Safety of pressurized intraperitoneal aerosolized chemotherapy in biliary cancer patients with peritoneal metastases. Future Oncol 2024; 20:2521-2531. [PMID: 39263892 PMCID: PMC11534098 DOI: 10.1080/14796694.2024.2394013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 08/15/2024] [Indexed: 09/13/2024] Open
Abstract
Biliary tract cancers are a rare diagnosis with a rising incidence. Up to 20% of patients have peritoneal metastases, resulting in symptoms of ascites, abdominal pain and potential bowel obstruction. A standard of care systemic treatment comprises gemcitabine, cisplatin and durvalumab (gem/cis/durva). However, the clinical benefit among patients with peritoneal metastases remains unknown. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) delivers chemotherapy directly to the peritoneal space, which could potentially improve efficacy with minimal systemic toxicity. We describe the design of a Phase I study investigating PIPAC with nab-paclitaxel plus systemic gem/cis/durva among biliary tract cancer patients with peritoneal metastases who have not received prior systemic treatment. The primary end point is safety of PIPAC with nab-paclitaxel in combination with systemic gem/cis/durva.Clinical Trial Registration: NCT05285358 (ClinicalTrials.gov).
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Affiliation(s)
- Daneng Li
- City of Hope Comprehensive Cancer Center, 1500 E Duarte Road, Duarte, CA91010, USA
| | - Christiana Crook
- City of Hope Comprehensive Cancer Center, 1500 E Duarte Road, Duarte, CA91010, USA
| | - Vincent Chung
- City of Hope Comprehensive Cancer Center, 1500 E Duarte Road, Duarte, CA91010, USA
| | - Gagandeep Brar
- City of Hope Comprehensive Cancer Center, 1500 E Duarte Road, Duarte, CA91010, USA
| | - Marwan Fakih
- City of Hope Comprehensive Cancer Center, 1500 E Duarte Road, Duarte, CA91010, USA
| | - Afsaneh Barzi
- City of Hope Comprehensive Cancer Center, 1500 E Duarte Road, Duarte, CA91010, USA
| | - Laleh Melstrom
- City of Hope Comprehensive Cancer Center, 1500 E Duarte Road, Duarte, CA91010, USA
| | - Gagandeep Singh
- City of Hope Comprehensive Cancer Center, 1500 E Duarte Road, Duarte, CA91010, USA
| | - Yuman Fong
- City of Hope Comprehensive Cancer Center, 1500 E Duarte Road, Duarte, CA91010, USA
| | - Paul Frankel
- City of Hope Beckman Research Institute, 1500 E Duarte Road, Duarte, CA91010, USA
| | - Mustafa Raoof
- City of Hope Comprehensive Cancer Center, 1500 E Duarte Road, Duarte, CA91010, USA
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Perrin ML, Bassetti C, Durand Fontanier S, Yardin C, Bardet SM, Taibi A. Effects of HyaRegen gel on tumour proliferation of colorectal peritoneal metastases. PLoS One 2024; 19:e0307965. [PMID: 39255313 PMCID: PMC11386418 DOI: 10.1371/journal.pone.0307965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Accepted: 07/15/2024] [Indexed: 09/12/2024] Open
Abstract
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a valuable therapeutic alternative for patients with peritoneal metastases. PIPAC uses a hyaluronic acid-based gel to reduce surgically induced adhesions. The aim of this study was to evaluate the effects of the hyaluronic acid-based gel on tumor dissemination. First, we explored whether the survival of CT26 luciferase-expressing murine colonic tumor cells was correlated with the dose of HyaRegen® Gel, and we determined the half-maximal inhibitory concentration (the IC50) of the gel. Next, we performed an in vitro study of cell survival rates after gel application on day 0 (D0) and day 1 (D1). Finally, we intraperitoneally administered the gel to mice with immunocompetent BALB/c colonic peritoneal metastases (on D0, D5, D10, D14, and D18). Tumor growth was regularly monitored using a bioluminescence assay (on D11, D17, and D21). After all mice had been sacrificed on D21, the body weights and the volumes of intraperitoneal ascites were measured; the Peritoneal Carcinosis Index (PCI) and Ki-antigen 67 scores were calculated. The IC50 value was 70 μL of gel in a total volume of 100 μL. The cell survival rates on D4 were identical in the control group and the two groups that had been treated with gel on D0 and D1. The bioluminescence levels over time were similar in the gel and control groups. The PCI scores were 35.5 ± 2.89 for the control group and 36 ± 2.45 for the gel group (p = 0.8005). The mean Ki-67 index percentages were 37.28 ±1 1.75 for the control group and 34.03 ± 8.62 for the gel group (p = 0.1971). This in vitro and in vivo study using a mouse model of immunocompetent metastatic peritoneal cancer did not reveal any pro- or anti-tumoral effect of HyaRegen® Gel. These findings indicate that the gel can be used to treat PIPACs with minimal apprehension.
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Affiliation(s)
| | | | - Sylvaine Durand Fontanier
- University Limoges, CNRS, XLIM, UMR 7252, Limoges, France
- Visceral Surgery Department, Dupuytren University Hospital, Limoges, France
| | - Catherine Yardin
- University Limoges, CNRS, XLIM, UMR 7252, Limoges, France
- Cytology and Histology Department, Dupuytren University Hospital, Limoges, France
| | | | - Abdelkader Taibi
- University Limoges, CNRS, XLIM, UMR 7252, Limoges, France
- Visceral Surgery Department, Dupuytren University Hospital, Limoges, France
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Jørgensen MS, Ainsworth AP, Fristrup CW, Mortensen MB, Graversen M. Impact of laparoscopic ultrasound during PIPAC directed treatment of unresectable peritoneal metastasis. Pleura Peritoneum 2024; 9:107-112. [PMID: 39544431 PMCID: PMC11558172 DOI: 10.1515/pp-2024-0007] [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: 05/17/2024] [Accepted: 08/19/2024] [Indexed: 11/17/2024] Open
Abstract
Objectives Laparoscopic ultrasound (LUS) combines both laparoscopy and ultrasound imaging of the peritoneum liver and retroperitoneum. LUS has not been described in treatments with pressurized intraperitoneal aerosol chemotherapy (PIPAC). We present our experience with LUS in patients undergoing PIPAC. Methods Retrospective study of LUS findings from the prospective PIPAC-OPC2 trial. Main outcome was changes in overall treatment strategy due to LUS findings. Results PIPAC-OPC2 included 143 patients of which 33 patients were treated with electrostatic precipitation PIPAC. Nine patients were excluded due to primary non-access. During PIPAC 1, LUS was performed in 112 of 134 (84 %) PIPAC procedures and changed overall treatment strategy in one patient due to detection of multiple liver metastases unseen by baseline CT. During PIPAC 2 and 3 LUS was performed in 59 of 104 (57 %) and 42 of 78 (54 %) PIPAC procedures, respectively. Throughout PIPAC 1-3, LUS also detected pathological lymph nodes in 16 patients, and focal liver lesions in another four patients of uncertain origin. No further examinations were performed in these patients, and the overall treatment strategy was not changed according to the PIPAC-OPC2 protocol. One patient had a splenic capsule rupture related to the LUS itself. This was managed conservatively. Conclusions LUS may be safely performed during PIPAC. However, LUS has limited clinical impact in patients scheduled for PIPAC, and cannot be recommended as a routine procedure when performing PIPAC.
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Affiliation(s)
- Magnus S. Jørgensen
- Odense PIPAC Center, Department of Surgery, Odense University Hospital, Odense, Denmark
| | - Alan P. Ainsworth
- Odense PIPAC Center, Department of Surgery, Odense University Hospital, Odense, Denmark
| | - Claus W. Fristrup
- Odense PIPAC Center, Department of Surgery, Odense University Hospital, Odense, Denmark
| | - Michael B. Mortensen
- Odense PIPAC Center, Department of Surgery, Odense University Hospital, Odense, Denmark
| | - Martin Graversen
- Odense PIPAC Center, Department of Surgery, Odense University Hospital, Odense, Denmark
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Sundar R, Chia DKA, Zhao JJ, Lee ARYB, Kim G, Tan HL, Pang A, Shabbir A, Willaert W, Ma H, Huang KK, Hagihara T, Tan ALK, Ong CAJ, Wong JSM, Seo CJ, Walsh R, Chan G, Cheo SW, Soh CCC, Callebout E, Geboes K, Ng MCH, Lum JHY, Leow WQ, Selvarajan S, Hoorens A, Ang WH, Pang H, Tan P, Yong WP, Chia CSL, Ceelen W, So JBY. Phase I PIANO trial-PIPAC-oxaliplatin and systemic nivolumab combination for gastric cancer peritoneal metastases: clinical and translational outcomes. ESMO Open 2024; 9:103681. [PMID: 39288528 PMCID: PMC11421236 DOI: 10.1016/j.esmoop.2024.103681] [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: 06/12/2024] [Revised: 07/24/2024] [Accepted: 07/26/2024] [Indexed: 09/19/2024] Open
Abstract
INTRODUCTION Pressurized intraperitoneal aerosol chemotherapy-oxaliplatin (PIPAC-OX) induces direct DNA damage and immunogenic cell death in patients with gastric cancer peritoneal metastases (GCPM). Combining PIPAC-OX with immune checkpoint inhibition remains untested. We conducted a phase I first-in-human trial evaluating the safety and efficacy of PIPAC-OX combined with systemic nivolumab (NCT03172416). METHODS Patients with GCPM who experienced disease progression on at least first-line systemic therapy were recruited across three centers in Singapore and Belgium. Patients received PIPAC-OX at 90 mg/m2 every 6 weeks and i.v. nivolumab 240 mg every 2 weeks. Translational studies were carried out on GCPM samples acquired during PIPAC-OX procedures. RESULTS In total, 18 patients with GCPM were prospectively recruited. The PIPAC-OX and nivolumab combination was well tolerated with manageable treatment-related adverse events, although one patient suffered from grade 4 vomiting. At second and third PIPAC-OX, respectively, the median decrease in peritoneal cancer index (PCI) was -5 (interquartile range: -12 to +1) and -7 (interquartile range: -6 to -20) and peritoneal regression grade 1 or 2 was observed in 66.7% (6/9) and 100% (3/3). Translational analyses of 43 GCPM samples revealed enrichment of immune/stromal infiltration and inflammatory signatures in peritoneal tumors after PIPAC-OX and nivolumab. M2 macrophages were reduced in treated peritoneal tumor samples while memory CD4+, CD8+ central memory and naive CD8+ T-cells were increased. CONCLUSIONS The first-in-human trial combining PIPAC-OX and nivolumab demonstrated safety and tolerability, coupled with enhanced T-cell infiltration within peritoneal tumors. This trial sets the stage for future combinations of systemic immunotherapy with locoregional intraperitoneal treatments.
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Affiliation(s)
- R Sundar
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Haematology-Oncology, National University Cancer Institute, Singapore; Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore; The N.1 Institute for Health, National University of Singapore, Singapore; Singapore Gastric Cancer Consortium, Singapore.
| | - D K A Chia
- Division of Upper Gastrointestinal Surgery, Department of Surgery, National University Hospital, National University Health System, Singapore
| | - J J Zhao
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Haematology-Oncology, National University Cancer Institute, Singapore; Department of Medicine, National University Hospital, Singapore, Singapore
| | - A R Y B Lee
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - G Kim
- Division of Upper Gastrointestinal Surgery, Department of Surgery, National University Hospital, National University Health System, Singapore
| | - H L Tan
- Department of Haematology-Oncology, National University Cancer Institute, Singapore
| | - A Pang
- Division of Upper Gastrointestinal Surgery, Department of Surgery, National University Hospital, National University Health System, Singapore
| | - A Shabbir
- Division of Upper Gastrointestinal Surgery, Department of Surgery, National University Hospital, National University Health System, Singapore
| | - W Willaert
- Department of Gastrointestinal Surgery, Ghent University Hospital, Ghent, Belgium
| | - H Ma
- Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore
| | - K K Huang
- Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore
| | - T Hagihara
- Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore
| | - A L K Tan
- Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore
| | - C-A J Ong
- Singapore Gastric Cancer Consortium, Singapore; Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - J S M Wong
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - C J Seo
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - R Walsh
- Department of Haematology-Oncology, National University Cancer Institute, Singapore
| | - G Chan
- Department of Haematology-Oncology, National University Cancer Institute, Singapore
| | - S W Cheo
- Department of Haematology-Oncology, National University Cancer Institute, Singapore
| | - C C C Soh
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - E Callebout
- Department of Digestive Oncology, Gastroenterology, Ghent University Hospital, Ghent, Belgium
| | - K Geboes
- Department of Gastrointestinal Surgery, Ghent University Hospital, Ghent, Belgium
| | - M C H Ng
- Division of Medical Oncology, National Cancer Centre, Singapore; Duke NUS Medical School, Singapore
| | - J H Y Lum
- Department of Pathology, National University Hospital, Singapore
| | - W Q Leow
- Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore
| | - S Selvarajan
- Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore
| | - A Hoorens
- Department of Pathology, Ghent University Hospital, Ghent, Belgium
| | - W H Ang
- Department of Chemistry, National University of Singapore, Singapore
| | - H Pang
- Department of Chemistry, National University of Singapore, Singapore
| | - P Tan
- Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore; Singapore Gastric Cancer Consortium, Singapore
| | - W P Yong
- Department of Haematology-Oncology, National University Cancer Institute, Singapore; Singapore Gastric Cancer Consortium, Singapore
| | - C S L Chia
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - W Ceelen
- Department of Gastrointestinal Surgery, Ghent University Hospital, Ghent, Belgium
| | - J B Y So
- Singapore Gastric Cancer Consortium, Singapore; Division of Upper Gastrointestinal Surgery, Department of Surgery, National University Hospital, National University Health System, Singapore; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Surgical Oncology, National University Cancer Institute of Singapore (NCIS), Singapore, Singapore.
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Hansen PS, Graversen M, Detlefsen S, Mortensen MB. Review on treatment of pleural metastasis and malignant pleural effusion with Pressurized IntraThoracic Aerosol Chemotherapy (PITAC). Pleura Peritoneum 2024; 9:47-53. [PMID: 38948327 PMCID: PMC11211649 DOI: 10.1515/pp-2023-0048] [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: 11/20/2023] [Accepted: 03/05/2024] [Indexed: 07/02/2024] Open
Abstract
Background Malignant pleural effusion (MPE) is a common and debilitating condition seen in advanced cancer disease, and life-expectancy is short. Symptoms include pain and severe shortness of breath. Current first-line treatment options include pleural drainage using catheters as well as pleurodesis. However, these treatment modalities are often inefficient and patients need repeated procedures. Pressurized IntraThoracic Aerosol Chemotherapy (PITAC) is a minimally invasive procedure, where antineoplastic agents are nebulized under pressure into the pleural space. Content We present the preliminary safety, feasibility, and response assessment data for PITAC based on a comprehensive literature review. Summary Five retrospective studies reported data on 38 PITACs in 21 patients. Data were heterogeneous and incomplete on several important aspects such as procedure, safety, local effect and long-term outcomes. PITAC seems technically feasible with a low risk of complications and may provide some reduction in MPE in selected cases. Outlook PITAC seems feasible, but prospective phase I and II studies are needed to define safety, indications, and efficacy.
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Affiliation(s)
- Pernille Schjødt Hansen
- Odense PIPAC Center (OPC) and Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark
| | - Martin Graversen
- Odense PIPAC Center (OPC) and Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark
- Department of Surgery, HPB and Upper GI Section, Odense University Hospital, Odense, Denmark
| | - Sönke Detlefsen
- Odense PIPAC Center (OPC) and Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark
- Institute of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
- Department of Pathology, Odense University Hospital, Odense, Denmark
| | - Michael Bau Mortensen
- Odense PIPAC Center (OPC) and Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark
- Department of Surgery, HPB and Upper GI Section, Odense University Hospital, Odense, Denmark
- Institute of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
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Chiu CC. Letter to the Editor of Annals of Surgical Oncology Concerning "Safety and Efficacy of Oxaliplatin Pressurized Intraperitoneal Aerosolized Chemotherapy (PIPAC) in Colorectal and Appendiceal Cancer with Peritoneal Metastases: Results of a Multicenter Phase I Trial in the USA". Ann Surg Oncol 2024; 31:2405-2407. [PMID: 37971615 DOI: 10.1245/s10434-023-14595-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Accepted: 09/29/2023] [Indexed: 11/19/2023]
Affiliation(s)
- Chong-Chi Chiu
- Department of General Surgery, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan.
- Department of Medical Education and Research, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan.
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan.
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Taliento C, Restaino S, Scutiero G, Arcieri M, Bernardi G, Martinello R, Driul L, Perrone AM, Fagotti A, Scambia G, Greco P, Vizzielli G. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin in patients with ovarian cancer: A systematic review. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:107250. [PMID: 37951158 DOI: 10.1016/j.ejso.2023.107250] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 10/10/2023] [Accepted: 10/27/2023] [Indexed: 11/13/2023]
Abstract
BACKGROUND PIPAC consists in delivering normothermic chemotherapy solution directly into the peritoneal cavity as an aerosol under pressure. Currently PIPAC is considered as a palliative treatment for patients suffering from non-resectable peritoneal carcinomatosis. We performed a SR to assess tolerance and response of this novel method among patient with OC. METHODS We searched electronic database PubMed, Embase, Web of Science, Clinical Trials.gov. We only included clinical studies reporting PIPAC with cisplatin and doxorubicin in patients with ovarian cancer. RESULTS This systematic review included 4 studies. In 3 studies all patients were pretreated with cytoreductive surgery, in 1 study surgery was performed in 8/34 (23 %) patients. Mean PCI at first PIPAC procedure ranged from 16.3 to 19.6. All studies reported the proportion of patients with ascites at the first PIPAC with a pooled rate of 48,3 %. Pooled rate of CTCAE Grade 3 toxicity calculated on the total number of PIPAC was 6 % and Grade 4 was 0.9 %. One study reported two cases of small bowel perforation related or potentially related to PIPAC. On study reported a cumulative survival after 400 days of 62 % and a mean actuarial survival time of all patients who underwent PIPAC of 442 days. In another study the mean time to progression was 144 days (95 % CI 122-168 days). CONCLUSION This systematic review demonstrated that PIPAC with cisplatin and doxorubicin appear to have a good safety profile with low toxicity and encouraging trend in terms of overall survival.
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Affiliation(s)
- Cristina Taliento
- Department of Medical Sciences, Institute of Obstetrics and Gynecology, University of Ferrara, Italy
| | - Stefano Restaino
- Clinic of Obstetrics and Gynecology, "Santa Maria Della Misericordia" University Hospital, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy
| | - Gennaro Scutiero
- Department of Medical Sciences, Institute of Obstetrics and Gynecology, University of Ferrara, Italy
| | - Martina Arcieri
- Clinic of Obstetrics and Gynecology, "Santa Maria Della Misericordia" University Hospital, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy; Department of Human Pathology of Adult and Childhood "G. Barresi", Unit of Gynecology and Obstetrics, University of Messina, Italy
| | - Giulia Bernardi
- Department of Medical Sciences, Institute of Obstetrics and Gynecology, University of Ferrara, Italy
| | - Ruby Martinello
- Department of Medical Sciences, Institute of Obstetrics and Gynecology, University of Ferrara, Italy
| | - Lorenza Driul
- Clinic of Obstetrics and Gynecology, "Santa Maria Della Misericordia" University Hospital, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy; Department of Medicine, University of Udine, Udine, Italy
| | - Anna Myriam Perrone
- Division of Oncologic Gynecology, Department of Medical and Surgical Sciences (DIMEC), Sant'Orsola-Malpighi Polyclinic Hospital, University of Bologna, Bologna, Italy
| | - Anna Fagotti
- Gynecologic Oncology Unit, Fondazione "Policlinico Universitario A. Gemelli IRCCS, Catholic University of the Sacred Heart, Rome, Italy
| | - Giovanni Scambia
- Gynecologic Oncology Unit, Fondazione "Policlinico Universitario A. Gemelli IRCCS, Catholic University of the Sacred Heart, Rome, Italy
| | - Pantaleo Greco
- Department of Medical Sciences, Institute of Obstetrics and Gynecology, University of Ferrara, Italy
| | - Giuseppe Vizzielli
- Clinic of Obstetrics and Gynecology, "Santa Maria Della Misericordia" University Hospital, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy; Department of Medicine, University of Udine, Udine, Italy.
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10
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Delafoy C, Benoist H, Patin A, Vasseur M, Guillouet S, Eveno C, Guilloit JM, Odou P, Simon N, Saint-Lorant G. Knowledge and practices about safe handling regarding the risk of exposure to antineoplastic drugs for caregivers in compounding units and in operating rooms performing HIPEC/PIPAC. J Oncol Pharm Pract 2023; 29:1628-1636. [PMID: 36514878 DOI: 10.1177/10781552221144303] [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] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Ever since the late 1970s, occupational exposure associated with the handling of antineoplastic drugs (ADs) in the healthcare environment has been highlighted and demonstrated. Contamination was detected in both operating rooms (OR) and compounding units (CU), where healthcare workers handle and are exposed to ADs in different ways. In the OR, the risk of exposure is higher and the staff receives less training in handling ADs than in the CU. This study aimed to assess and compare knowledge and practices about the safe handling of ADs by caregivers working in these two locations, namely the CU and OR. METHODS Two questionnaires (one each for the OR and CU) were created by two investigator pharmacists and were completed during a personal interview of 20 min. The questions were related to the following topics: training, knowledge about occupational exposure and questions related to protective practices. A scoring system was implemented to assess the knowledge and practices of each participant. RESULTS In total, 38 caregivers working in the OR and 39 in the CU were included in our study. Significantly more CU staff had specific initial training (p < 0.001) and ongoing training (p < 0.001) in handling ADs. Concerning the knowledge score, OR caregivers had a significantly lower median score for contamination routes (p < 0.001), contamination surfaces (p < 0.001), existing procedures (p < 0.001) and total knowledge (p < 0.001) than CU caregivers. Concerning protective handling practices of ADs, the two locations had nonsignificantly different median scores (p = 0.892). CONCLUSION This study suggests that there is still room for improvement in terms of knowledge and protection practices when handling ADs. An appropriate and tailored training program should be developed and provided to all caregivers who handle or come in contact with ADs.Clinical trial registrationStudy CONTACT, ref. 19-504.
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Affiliation(s)
- Clémence Delafoy
- Department of Pharmacy, CHU Caen, Caen, France
- UNICAEN, UNIROUEN, ABTE, Centre de Lutte Contre le Cancer F. Baclesse, Normandie University, Caen, France
| | - Hubert Benoist
- Department of Pharmacy, CHU Caen, Caen, France
- UNICAEN, UNIROUEN, ABTE, Centre de Lutte Contre le Cancer F. Baclesse, Normandie University, Caen, France
| | - Alex Patin
- Department of Pharmacy, CHU Caen, Caen, France
| | - Michèle Vasseur
- ULR 7365-GRITA-Groupe de Recherche sur les Formes Injectables et les Technologies Associées, CHU Lille, University of Lille, Lille, France
- Institut of Pharmacy, CHU Lille, Lille, France
| | - Sonia Guillouet
- UNICAEN, CHU de Caen Normandie, Néphrologie, Direction des Soins, Normandie University, Caen, France
| | - Clarisse Eveno
- Department of Digestive Surgery, CHU Lille, Lille, France
| | - Jean-Marc Guilloit
- Department of Surgery, Comprehensive Cancer Center F. Baclesse, Caen, France
| | - Pascal Odou
- ULR 7365-GRITA-Groupe de Recherche sur les Formes Injectables et les Technologies Associées, CHU Lille, University of Lille, Lille, France
- Institut of Pharmacy, CHU Lille, Lille, France
| | - Nicolas Simon
- ULR 7365-GRITA-Groupe de Recherche sur les Formes Injectables et les Technologies Associées, CHU Lille, University of Lille, Lille, France
- Institut of Pharmacy, CHU Lille, Lille, France
| | - Guillaume Saint-Lorant
- Department of Pharmacy, CHU Caen, Caen, France
- UNICAEN, UNIROUEN, ABTE, Centre de Lutte Contre le Cancer F. Baclesse, Normandie University, Caen, France
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11
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Jung W, Park M, Park SJ, Lee EJ, Kim HS, Chung SH, Yoon C. Occupational Exposure during Intraperitoneal Pressurized Aerosol Chemotherapy Using Doxorubicin in a Pig Model. Saf Health Work 2023; 14:237-242. [PMID: 37389318 PMCID: PMC10300457 DOI: 10.1016/j.shaw.2023.04.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 03/17/2023] [Accepted: 04/07/2023] [Indexed: 07/01/2023] Open
Abstract
Background This study evaluated occupational exposure levels of doxorubicin in healthcare workers performing rotational intraperitoneal pressurized aerosol chemotherapy (PIPAC) procedures. Methods All samples were collected during PIPAC procedures applying doxorubicin to an experimental animal model (pigs). All procedures were applied to seven pigs, each for approximately 44 min. Surface samples (n = 51) were obtained from substances contaminating the PIPAC devices, surrounding objects, and protective equipment. Airborne samples were also collected around the operating table (n = 39). All samples were analyzed using ultra-high performance liquid chromatography-mass spectrometry. Results Among the surface samples, doxorubicin was detected in only five samples (9.8%) that were directly exposed to antineoplastic drug aerosols in the abdominal cavity originating from PIPAC devices. The telescopes showed concentrations of 0.48-5.44 ng/cm2 and the trocar showed 0.98 ng/cm2 in the region where the spraying nozzles were inserted. The syringe line connector showed a maximum concentration of 181.07 ng/cm2, following a leakage. Contamination was not detected on the surgeons' gloves or shoes. Objects surrounding the operating table, including tables, operating lights, entrance doors, and trocar holders, were found to be uncontaminated. All air samples collected at locations where healthcare workers performed procedures were found to be uncontaminated. Conclusions Most air and surface samples were uncontaminated or showed very low doxorubicin concentrations during PIPAC procedures. However, there remains a potential for leakage, in which case dermal exposure may occur. Safety protocols related to leakage accidents, selection of appropriate protective equipment, and the use of disposable devices are necessary to prevent occupational exposure.
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Affiliation(s)
- Wongeon Jung
- Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea
| | - Mijin Park
- Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea
- Wonjin Institute for Occupational & Environmental Health, Seoul, Republic of Korea
| | - Soo Jin Park
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Eun Ji Lee
- Department of Obstetrics and Gynecology, Chung-Ang University Hospital, Seoul, Republic of Korea
| | - Hee Seung Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sun Ho Chung
- Bio-Center, Gyeonggido Business & Science Accelerator (GBSA), Suwon, Republic of Korea
| | - Chungsik Yoon
- Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea
- Institute of Health and Environment, Seoul National University, Seoul, Republic of Korea
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12
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Breusa S, Zilio S, Catania G, Bakrin N, Kryza D, Lollo G. Localized chemotherapy approaches and advanced drug delivery strategies: a step forward in the treatment of peritoneal carcinomatosis from ovarian cancer. Front Oncol 2023; 13:1125868. [PMID: 37287910 PMCID: PMC10242058 DOI: 10.3389/fonc.2023.1125868] [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: 12/16/2022] [Accepted: 05/04/2023] [Indexed: 06/09/2023] Open
Abstract
Peritoneal carcinomatosis (PC) is a common outcome of epithelial ovarian carcinoma and is the leading cause of death for these patients. Tumor location, extent, peculiarities of the microenvironment, and the development of drug resistance are the main challenges that need to be addressed to improve therapeutic outcome. The development of new procedures such as HIPEC (Hyperthermic Intraperitoneal Chemotherapy) and PIPAC (Pressurized Intraperitoneal Aerosol Chemotherapy) have enabled locoregional delivery of chemotherapeutics, while the increasingly efficient design and development of advanced drug delivery micro and nanosystems are helping to promote tumor targeting and penetration and to reduce the side effects associated with systemic chemotherapy administration. The possibility of combining drug-loaded carriers with delivery via HIPEC and PIPAC represents a powerful tool to improve treatment efficacy, and this possibility has recently begun to be explored. This review will discuss the latest advances in the treatment of PC derived from ovarian cancer, with a focus on the potential of PIPAC and nanoparticles in terms of their application to develop new therapeutic strategies and future prospects.
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Affiliation(s)
- Silvia Breusa
- Univ Lyon, Université Claude Bernard Lyon 1, Centre National de la Recherche Scientifique (CNRS), LAGEPP Unité Mixte de Recherche (UMR) 5007, Villeurbanne, France
- Apoptosis, Cancer and Development Laboratory- Equipe labellisée ‘La Ligue’, LabEx DEVweCAN, Institut PLAsCAN, Centre de Recherche en Cancérologie de Lyon, Institut national de santé et de la recherche médicale (INSERM) U1052-Centre National de la Recherche Scientifique - Unité Mixte de Recherche (CNRS UMR)5286, Université de Lyon, Centre Léon Bérard, Lyon, France
| | - Serena Zilio
- Univ Lyon, Université Claude Bernard Lyon 1, Centre National de la Recherche Scientifique (CNRS), LAGEPP Unité Mixte de Recherche (UMR) 5007, Villeurbanne, France
- Sociétés d'Accélération du Transfert de Technologies (SATT) Ouest Valorisation, Rennes, France
| | - Giuseppina Catania
- Univ Lyon, Université Claude Bernard Lyon 1, Centre National de la Recherche Scientifique (CNRS), LAGEPP Unité Mixte de Recherche (UMR) 5007, Villeurbanne, France
| | - Naoual Bakrin
- Department of Surgical Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Lyon, France
- Centre pour l'Innovation en Cancérologie de Lyon (CICLY), Claude Bernard University Lyon 1, Lyon, France
| | - David Kryza
- Univ Lyon, Université Claude Bernard Lyon 1, Centre National de la Recherche Scientifique (CNRS), LAGEPP Unité Mixte de Recherche (UMR) 5007, Villeurbanne, France
- Imthernat Plateform, Hospices Civils de Lyon, Lyon, France
| | - Giovanna Lollo
- Univ Lyon, Université Claude Bernard Lyon 1, Centre National de la Recherche Scientifique (CNRS), LAGEPP Unité Mixte de Recherche (UMR) 5007, Villeurbanne, France
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13
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Lang N, Diciola A, Labidi-Galy I, Ris F, Di Marco M, Mach N, Petignat P, Toso C, Undurraga M, Hubner M. Nab-PIPAC: a phase IB study protocol of intraperitoneal cisplatin and nab-paclitaxel administered by pressurised intraperitoneal aerosol chemotherapy (PIPAC) in the treatment of advanced malignancies confined to the peritoneal cavity. BMJ Open 2023; 13:e067691. [PMID: 36604127 PMCID: PMC9827272 DOI: 10.1136/bmjopen-2022-067691] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
INTRODUCTION Intraperitoneal dissemination is a major problem resulting in very poor prognosis and a rapid marked deterioration in the quality of life of patients. Pressurised intraperitoneal aerosol chemotherapy (PIPAC) is an emergent laparoscopic procedure aiming to maximise local efficacy and to reduce systemic side effects. METHODS AND ANALYSIS Nab-PIPAC, a bicentre open-label phase IB, aims to evaluate safety of nab-paclitaxel and cisplatin association using in patients with peritoneal carcinomatosis (PC) of gastric, pancreatic or ovarian origin as ≥1 prior line of systemic therapy. Using a 3+3 design, sequential intraperitoneal laparoscopic application of nab-paclitaxel (7.5, 15, 25, 37.5, 52.5 and 70 mg/m2) and cisplatin (10.5 mg/m2) through a nebuliser to a high-pressure injector at ambient temperature with a maximal upstream pressure of 300 psi. Treatment maintained for 30 min at a pressure of 12 mm Hg and repeated4-6 weeks intervals for three courses total.A total of 6-36 patients are expected, accrual is ongoing. Results are expected in 2024.The primary objective of Nab-PIPAC trial is to assess tolerability and safety of nab-paclitaxel and cisplatin combination administered intraperitoneally by PIPAC in patients with PC of gastric, pancreatic or ovarian origin. This study will determine maximum tolerated dose and provide pharmacokinetic data. ETHIC AND DISSEMINATION Ethical approval was obtained from the ethical committees of Geneva and Vaud (CCER-2018-01327). The study findings will be published in an open-access, peer-reviewed journal and presented at relevant conferences and research meetings. TRIAL REGISTRATION NUMBER NCT04000906.
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Affiliation(s)
- Noemie Lang
- Service d'oncologie, Département d'Oncologie, Hôpitaux Universitaires de Genève, Genève, Switzerland
| | - Antonella Diciola
- Service d'oncologie, Département d'Oncologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
| | - Intidhar Labidi-Galy
- Service d'oncologie, Département d'Oncologie, Hôpitaux Universitaires de Genève, Genève, Switzerland
| | - Frédéric Ris
- Département de Chirurgie, Hôpitaux Universitaires Genève, Genève, Switzerland
| | - Mariagrazia Di Marco
- Service d'oncologie, Département d'Oncologie, Hôpitaux Universitaires de Genève, Genève, Switzerland
| | - Nicolas Mach
- Service d'oncologie, Département d'Oncologie, Hôpitaux Universitaires de Genève, Genève, Switzerland
| | - Patrick Petignat
- Département Gynécologie et Obstétrique, Hôpitaux Universitaires Genève, Genève, Switzerland
| | - Christian Toso
- Département de Chirurgie, Hôpitaux Universitaires Genève, Genève, Switzerland
| | - Manuela Undurraga
- Département Gynécologie et Obstétrique, Hôpitaux Universitaires Genève, Genève, Switzerland
| | - Martin Hubner
- Département de chirurgie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
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14
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Baggaley AE, Lafaurie GBRC, Tate SJ, Boshier PR, Case A, Prosser S, Torkington J, Jones SEF, Gwynne SH, Peters CJ. Pressurized intraperitoneal aerosol chemotherapy (PIPAC): updated systematic review using the IDEAL framework. Br J Surg 2022; 110:10-18. [PMID: 36056893 PMCID: PMC10364525 DOI: 10.1093/bjs/znac284] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 06/28/2022] [Accepted: 07/19/2022] [Indexed: 12/31/2022]
Affiliation(s)
- Alice E Baggaley
- Department of Surgery and Cancer, Imperial College London, St Mary's Hospital, London, UK
| | | | - Sophia J Tate
- Department of Anaesthesia, Swansea Bay University Health Board, Swansea, UK
| | - Piers R Boshier
- Department of Surgery and Cancer, Imperial College London, St Mary's Hospital, London, UK
| | - Amy Case
- Department of Cancer Services, Swansea Bay University Health Board, Swansea, UK
| | - Susan Prosser
- Department of Library Services, Swansea Bay University Health Board, Swansea, UK
| | - Jared Torkington
- Department of Surgery, University Hospital of Wales, Cardiff, UK
| | - Sadie E F Jones
- Department of Obstetrics and Gynaecology, University Hospital of Wales, Cardiff, UK
| | - Sarah H Gwynne
- Department of Cancer Services, Swansea Bay University Health Board, Swansea, UK
| | - Christopher J Peters
- Department of Surgery and Cancer, Imperial College London, St Mary's Hospital, London, UK
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15
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Mangieri CW, Levine EA. Management of peritoneal surface metastases from colorectal cancer: Cytoreductive surgery, hyperthermic intraperitoneal chemotherapy, pressurized intraperitoneal chemotherapy, and beyond. Front Oncol 2022; 12:992030. [PMID: 36425565 PMCID: PMC9679779 DOI: 10.3389/fonc.2022.992030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Accepted: 09/23/2022] [Indexed: 08/30/2023] Open
Abstract
This article provides a contemporary review of the current surgical management of peritoneal surface malignancy (PSM) of colorectal origin. A brief review of the founding history of surgical intervention for PSM is followed by a focused review of the level I evidence, current clinical questions, and evolving advancements. While not intended to address all the facets of PSM, this review aims to provide the reader with the essential knowledge and resources to effectively provide surgical care for carcinomatosis due to colorectal malignancies.
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Affiliation(s)
| | - Edward A. Levine
- Division of Surgical Oncology, Wake Forest Baptist Health Medical Center, Winston-Salem, NC, United States
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16
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Mehta S, Kammar P, Patel A, Goswami G, Shaikh S, Sukumar V, Trivedi E, Bhatt A. Feasibility and Safety of Taxane-PIPAC in Patients with Peritoneal Malignancies-a Retrospective Bi-institutional Study. Indian J Surg Oncol 2022; 14:1-9. [PMID: 36091624 PMCID: PMC9451111 DOI: 10.1007/s13193-022-01641-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Accepted: 08/31/2022] [Indexed: 11/30/2022] Open
Abstract
Taxanes have a favorable pharmacokinetic profile for intraperitoneal application. We report our initial experience with taxane-PIPAC (pressurized intraperitoneal chemotherapy) for unresectable peritoneal metastases from different primary sites in terms of safety, feasibility, response rate, and conversion to resectability. In this retrospective study, PIPAC was performed alone or in combination with systemic chemotherapy. Paclitaxel was used as a single agent, whereas docetaxel was used in combination with cisplatin-adriamycin or oxaliplatin-adriamycin. From December 2019 to December 2021, 47 patients underwent 82 PIPAC procedures (1 PIPAC in 55.3%, 2 in 29.7%, 3 in 14.8%). The most common primary sites were ovarian cancer (31.9%), gastric cancer (23.4%), and colorectal cancer (21.2%). Docetaxel-cisplatin-adriamycin was used in 33 (70.2%) patients, docetaxel-oxaliplatin-adriamycin in 12 (25.5%), and paclitaxel alone in 2 (4.2%) patients. Grade 1-2 complications were observed in 24 (51%) and grade 3-4 complications in 6 (12.7%) patients (8.5% of 82 PIPACs). 16/47 (34.0%) patients had a clinical response to PIPAC. The mean PCI was 25.9 ± 9.2 for the first PIPACs and 22.4 ± 9 for the subsequent PIPACs with an average reduction of 3.6 points [change in PCI ranged from - 14 to + 8]. The PRGS was 1/2 in 4/47 (8.5%) patients (19.0% patients with > 1 PIPAC). A reduction in ascites was observed in 35.4% presenting with ascites. Nine (19.1%) patients had conversion to operability leading to a subsequent cytoreductive surgery in 8 (17%) patients. PIPAC with docetaxel is feasible and safe. The role of PIPAC with both docetaxel and paclitaxel either alone or in combination with other drugs should be investigated in prospective studies.
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Affiliation(s)
- Sanket Mehta
- Department of Surgical Oncology, Saifee Hospital, Mumbai, India
| | - Praveen Kammar
- Department of Surgical Oncology, Saifee Hospital, Mumbai, India
| | - Ankita Patel
- Department of Surgical Oncology, Zydus Hospital, Thaltej, Ahmedabad, 380054 India
| | - Gaurav Goswami
- Department of Radiology, Zydus Hospital, Ahmedabad, India
| | - Sakina Shaikh
- Department of Surgical Oncology, Zydus Hospital, Thaltej, Ahmedabad, 380054 India
| | - Vivek Sukumar
- Department of Surgical Oncology, Saifee Hospital, Mumbai, India
| | - Esha Trivedi
- Department of Surgical Oncology, Saifee Hospital, Mumbai, India
| | - Aditi Bhatt
- Department of Surgical Oncology, Zydus Hospital, Thaltej, Ahmedabad, 380054 India
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17
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Mohammad A, Hor M, Baradeiya AM, Qasim H, Nasr M. Is Pressurized Intraperitoneal Aerosolized Chemotherapy (PIPAC) Effective in Ovarian Cancer With Peritoneal Metastasis? Cureus 2022; 14:e27837. [PMID: 36110443 PMCID: PMC9462586 DOI: 10.7759/cureus.27837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/07/2022] [Indexed: 11/05/2022] Open
Abstract
Ovarian cancer is one of the most common causes of mortality in women and is frequently diagnosed at an advanced stage. Ovarian cancer has a high recurrence rate, with most cases being peritoneal metastasis. The standard treatment of peritoneal metastasis is systemic chemotherapy, but naturally, the peritoneum is poorly vascularized, making this standard of treatment frequently ineffective. Hence, pressurized intraperitoneal aerosol chemotherapy (PIPAC) introduced a new type of intraperitoneal chemotherapy (IPC) in November 2011. Positive feedback on its feasibility, tolerance, and efficacy has encouraged medical communities worldwide to adopt PIPAC as a new drug delivery technique. This study's objective is to review previously conducted research on the efficacy of PIPAC treatment for peritoneal metastasis from ovarian cancer.
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18
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Robella M, Hubner M, Sgarbura O, Reymond M, Khomiakov V, di Giorgio A, Bhatt A, Bakrin N, Willaert W, Alyami M, Teixeira H, Kaprin A, Ferracci F, De Meeus G, Berchialla P, Vaira M, Villeneuve L, Cortés-Guiral D, Nowacki M, So J, Abba J, Afifi A, Mortensen MB, Brandl A, Ceelen W, Coget J, Courvoiser T, de Hingh IH, Delhorme JB, Dumont F, Escayola C, Eveno C, Ezanno AC, Gagnière J, Galindo J, Glatz T, Glehen O, Jäger T, Kepenekian V, Kothonidis K, Lehmann K, Lynch C, Mehta S, Moldovan B, Nissan A, Orry D, Pérez GO, Paquette B, Paskonis M, Piso P, Pocard M, Rau B, Singh S, Somashekhar S, Soravia C, Taibi A, Torkington J, Vizzielli G. Feasibility and safety of PIPAC combined with additional surgical procedures: PLUS study. Eur J Surg Oncol 2022; 48:2212-2217. [DOI: 10.1016/j.ejso.2022.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Revised: 04/04/2022] [Accepted: 05/02/2022] [Indexed: 11/29/2022] Open
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19
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Teixeira Farinha H, Mattille D, Mantziari S, Demartines N, Hübner M. Early postoperative outcomes of staging laparoscopy for peritoneal metastases with or without pressurized intra-peritoneal aerosol chemotherapy (PIPAC). BMC Surg 2022; 22:122. [PMID: 35354404 PMCID: PMC8969273 DOI: 10.1186/s12893-022-01572-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 03/24/2022] [Indexed: 11/12/2022] Open
Abstract
Background Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been introduced for palliative treatment of peritoneal surface malignancies (PSM) and is currently tested also in the neoadjuvant and prophylactic setting. The aim was therefore to compare safety and tolerance of staging laparoscopy with or without PIPAC. Methods This retrospective analysis compared consecutive patients undergoing staging laparoscopy alone for oesogastric cancer with patients having PIPAC for suspected PSM of various origins from January 2015 until January 2020. Safety was assessed by use of the Clavien classification for complications and CTCAE for capturing of adverse events. Pain and nausea were documented by use of a visual analogue scale (VAS: 0–10: maximal intensity). Results Overall, 25 PIPAC procedures were compared to 24 staging laparoscopies. PIPAC procedures took a median of 35 min (IQR: 25–67) longer. Four patients experienced at least one complication in either group (p = 0.741). No differences were noted for postoperative nausea (p = 0.961) and pain levels (p = 0.156). Median hospital stay was 2 (IQR: 1–3) for PIPAC and 1 (IQR: 1–2) for the laparoscopy group (p = 0.104). Conclusions The addition of PIPAC did not jeopardize safety and postoperative outcomes of staging laparoscopy alone. Further studies need to clarify its oncological benefits.
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Affiliation(s)
- Hugo Teixeira Farinha
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Rue du Bugnon, 46, 1005, Lausanne, Switzerland
| | - Daphné Mattille
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Rue du Bugnon, 46, 1005, Lausanne, Switzerland
| | - Styliani Mantziari
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Rue du Bugnon, 46, 1005, Lausanne, Switzerland
| | - Nicolas Demartines
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Rue du Bugnon, 46, 1005, Lausanne, Switzerland
| | - Martin Hübner
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Rue du Bugnon, 46, 1005, Lausanne, Switzerland.
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Horvath P, Yurttas C, Baur I, Steidle C, Reymond MA, Girotti PNC, Königsrainer A, Königsrainer I. Current Medical Care Situation of Patients in Germany Undergoing Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC). Cancers (Basel) 2022; 14:cancers14061443. [PMID: 35326595 PMCID: PMC8946267 DOI: 10.3390/cancers14061443] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 03/02/2022] [Accepted: 03/09/2022] [Indexed: 02/01/2023] Open
Abstract
Objective: Tailored approaches in gastrointestinal oncology have been more frequently introduced in past years and for patients with peritoneal metastases. This article attempts to overview the current strategies in surgical gastrointestinal oncology, with a focus on gastrointestinal peritoneal metastases. Methods: In 2019, all patients undergoing PIPAC therapy in Germany were retrospectively analyzed regarding morbidity and in-hospital mortality rates. Furthermore, patients with chemotherapy-refractory peritoneal metastases from gastric cancer undergoing PIPAC-therapy at our institution were analyzed. Results: In 2019, 534 patients received PIPAC treatment in german hospitals. The in-hospital mortality rate was 0%. In total, 36 patients suffered from postoperative complications (8%). From April 2016 to September 2021, a total of 44 patients underwent 93 PIPAC applications at our institution. The non-access-rate was 0%. The median PRGS was two (range, 1–4). Eleven patients (44%) showed histologically stable disease, whereas six patients (24%) showed histological regression. Median survival, calculated from the date of the first PIPAC application, was 181 days (range, 43–636 days). Conclusions: PIPAC is a safe and feasible procedure with a low in-hospital morbidity and mortality. Furthermore, PIPAC in the palliative and chemorefractory setting and is an appealing approach for patient management in the future.
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Affiliation(s)
- Philipp Horvath
- Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Hoppe-Seyler-Str. 3, D-72076 Tübingen, Germany; (P.H.); (C.Y.); (I.B.); (C.S.); (M.A.R.); (A.K.)
| | - Can Yurttas
- Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Hoppe-Seyler-Str. 3, D-72076 Tübingen, Germany; (P.H.); (C.Y.); (I.B.); (C.S.); (M.A.R.); (A.K.)
| | - Isabella Baur
- Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Hoppe-Seyler-Str. 3, D-72076 Tübingen, Germany; (P.H.); (C.Y.); (I.B.); (C.S.); (M.A.R.); (A.K.)
| | - Christoph Steidle
- Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Hoppe-Seyler-Str. 3, D-72076 Tübingen, Germany; (P.H.); (C.Y.); (I.B.); (C.S.); (M.A.R.); (A.K.)
| | - Marc André Reymond
- Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Hoppe-Seyler-Str. 3, D-72076 Tübingen, Germany; (P.H.); (C.Y.); (I.B.); (C.S.); (M.A.R.); (A.K.)
| | - Paolo Nicola Camillo Girotti
- Department of General, Visceral and Thoracic Surgery, Academic Teaching Hospital Feldkirch, Carinagasse 47, 6807 Feldkirch, Austria;
| | - Alfred Königsrainer
- Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Hoppe-Seyler-Str. 3, D-72076 Tübingen, Germany; (P.H.); (C.Y.); (I.B.); (C.S.); (M.A.R.); (A.K.)
| | - Ingmar Königsrainer
- Department of General, Visceral and Thoracic Surgery, Academic Teaching Hospital Feldkirch, Carinagasse 47, 6807 Feldkirch, Austria;
- Correspondence:
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21
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Park SJ, Lee EJ, Seol A, Park S, Ham J, Yim GW, Shim SH, Lim W, Chang SJ, Song G, Park JW, Kim HS. Rotational intraperitoneal pressurized aerosol chemotherapy with paclitaxel and cisplatin: pharmacokinetics, tissue concentrations, and toxicities in a pig model. J Gynecol Oncol 2022; 33:e56. [PMID: 35712969 PMCID: PMC9428304 DOI: 10.3802/jgo.2022.33.e56] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 03/15/2022] [Accepted: 04/17/2022] [Indexed: 11/30/2022] Open
Affiliation(s)
- Soo Jin Park
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Eun Ji Lee
- Department of Obstetrics and Gynecology, Chung-Ang University Hospital, Seoul, Korea
| | - Aeran Seol
- Department of Obstetrics and Gynecology, Korea University College of Medicine, Seoul, Korea
| | - Sunwoo Park
- Department of Plant & Biomaterials science, Gyeongsang National University, Jinju, Korea
| | - Jiyeon Ham
- Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Korea
| | - Ga Won Yim
- Department of Obstetrics and Gynecology, Dongguk University College of Medicine, Goyang, Korea
| | - Seung-Hyuk Shim
- Department of Obstetrics and Gynecology, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Korea
| | - Whasun Lim
- Department of Biological Sciences, Sungkyunkwan University, Suwon, Korea
| | - Suk-Joon Chang
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon, Korea
| | - Gwonhwa Song
- Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Korea
| | - Ji Won Park
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Hee Seung Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
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22
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Girardot-Miglierina A, Clerc D, Alyami M, Villeneuve L, Sgarbura O, Reymond MA, Hübner M. Consensus statement on safety measures for pressurized intraperitoneal aerosol chemotherapy. Pleura Peritoneum 2021; 6:139-149. [PMID: 35071734 PMCID: PMC8719448 DOI: 10.1515/pp-2021-0125] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Accepted: 09/02/2021] [Indexed: 12/18/2022] Open
Abstract
Objectives Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a promising treatment for peritoneal cancer that entails, however, potential risks for the caregivers in the operating room (OR). This study aimed to reach a consensus within the PIPAC community on a comprehensive safety protocol. Methods Active PIPAC centers were invited to participate in a two-round Delphi process on 43 predefined items: concise summaries of the existing evidence were presented together with questions formulated using the population, intervention, comparator, and outcome framework. According to the Grading of Recommendations Assessment, Development, and Evaluation, the strength of recommendation was voted by panelists, accepting a consensus threshold of ≥50% of the agreement for any of the four grading options, or ≥70% in either direction. Results Forty-seven out of 66 invited panelists answered both rounds (response rate 76%). The consensus was reached for 41 out of 43 items (95.3%). Strong and weak recommendations were issued for 30 and 10 items, respectively. A positive consensual recommendation was issued to activate laminar airflow without specific strength, neither strong nor weak. No consensus was reached for systematic glove change for caregivers with a high risk of exposure and filtering facepiece mask class 3 for caregivers with low risk of exposure. Conclusions A high degree of consensus was reached for a comprehensive safety protocol for PIPAC, adapted to the risk of exposure for the different caregivers in the OR. This consensus can serve as a basis for education and help reach a high degree of adherence in daily practice.
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Affiliation(s)
- Arnaud Girardot-Miglierina
- Department of Visceral Surgery , Lausanne University Hospital CHUV, University of Lausanne (UNIL) , Lausanne , Switzerland
| | - Daniel Clerc
- Department of Visceral Surgery , Lausanne University Hospital CHUV, University of Lausanne (UNIL) , Lausanne , Switzerland
| | - Mohammad Alyami
- Department of General Surgery and Surgical Oncology , Oncology Center, King Khalid Hospital , Najran , Saudi Arabia
| | - Laurent Villeneuve
- Department of Public Health , Clinical Research and Epidemiological Unit, Lyon University Hospital , Lyon , France
- University of Lyon , Lyon , France
| | - Olivia Sgarbura
- Department of Surgical Oncology , Cancer Institute Montpellier (ICM) , Montpellier , France
- University of Montpellier , Montpellier , France
- IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier , Montpellier , France
| | - Marc-André Reymond
- Department of General and Transplant Surgery , University Hospital Tübingen and National Center for Pleura and Peritoneum , Tübingen , Germany
| | - Martin Hübner
- Department of Visceral Surgery , Lausanne University Hospital CHUV, University of Lausanne (UNIL) , Lausanne , Switzerland
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23
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Evaluation of the environmental contamination and exposure risk in medical/non-medical staff after oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy. Toxicol Appl Pharmacol 2021; 429:115694. [PMID: 34428445 DOI: 10.1016/j.taap.2021.115694] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 08/11/2021] [Accepted: 08/16/2021] [Indexed: 11/17/2022]
Abstract
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a technique to directly deliver chemotherapeutic drugs in the abdomen for the treatment of peritoneal metastases. Pressurization improves the treatment efficacy but increases the risk of exposure for the medical/non-medical staff who can be exposed by dermal or ocular contact, or inhalation of aerosols containing the cytotoxic drugs. The aim of this study was to evaluate the risk of exposure for the medical/non-medical staff (nurses, surgeons, anaesthesiologists and cleaning personnel; n = 13) during PIPAC with oxaliplatin performed according to the protocol recommended in France. Blood samples were collected 1 h before and immediately after PIPAC, and urine samples 1 h before, and then 3 h and the morning after PIPAC. In the control, non-exposed group (n = 7), only one urine and blood sample were collected. Surface contamination in the operating room was assessed in water- and Surfanios-impregnated wipe samples. The total elemental platinum in each sample was quantified by inductively coupled plasma mass spectrometry, using a method adapted to quantify trace amounts (ng.L-1) in very low volumes (100 μl). No surface contamination was detected. Although 25% of urine samples in the exposed group contained platinum, no statistical difference was observed in urine and plasma samples collected before and after PIPAC and with the control group samples. These findings suggest that the French PIPAC protocol does not increase the risk of exposure to platinum in all staff categories involved. This protocol could be considered in future occupational policies and consensus statements. Trial registration: NCT04014426.
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24
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Raoof M, Malhotra G, Kohut A, O'Leary M, Frankel P, Tran T, Fakih M, Chao J, Lim D, Woo Y, Paz IB, Lew M, Cristea MC, Rodriguez-Rodriguez L, Fong Y, Blakely A, Whelan R, Reymond MA, Merchea A, Dellinger TH. PIPAC for the Treatment of Gynecologic and Gastrointestinal Peritoneal Metastases: Technical and Logistic Considerations of a Phase 1 Trial. Ann Surg Oncol 2021; 29:175-185. [PMID: 34387765 DOI: 10.1245/s10434-021-10505-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Accepted: 07/07/2021] [Indexed: 11/18/2022]
Abstract
BACKGROUND Peritoneal metastases (PM) from ovarian, gastric, appendiceal, or colorectal origin can be treated via cytoreductive surgery with or without the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) for selected patients. Unfortunately, not all patients are candidates for aggressive surgical debulking. For these patients, pressurized intraperitoneal aerosolized chemotherapy (PIPAC) has emerged as an alternative method for intraperitoneal (IP) chemotherapy administration. This report presents the design and implementation of the first phase 1 trial to evaluate the safety and efficacy of PIPAC in the United States. METHODS This is an ongoing prospective phase 1 clinical trial of PIPAC for patients who have histologically confirmed ovarian, uterine, gastric, appendiceal, or colorectal cancer with PM and have progressed to at least one evidence-based chemotherapeutic regimen. The trial has two clinical arms. The patients in arm 1 have gynecologic and gastric malignancies treated with IP cisplatin and doxorubicin, and the arm 2 patients have colorectal and appendiceal malignancies treated with intravenous fluorouracil and leucovorin followed by IP oxaliplatin. All the patients are monitored for dose-limiting toxicities and adverse events. RESULTS Practical and technical considerations for the phase 1 PIPAC trial are presented. These considerations include patient selection, operating room setup, and technical details for successful aerosolized chemotherapy delivery. The phase 1 study results will be reported separately at completion of the trial. CONCLUSIONS The PIPAC treatment is a feasible, minimally invasive approach that permits IP delivery of chemotherapy. Once completed, the ongoing phase 1 trial will help to provide safety and initial efficacy data.
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Affiliation(s)
- Mustafa Raoof
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center (COH), Duarte, CA, USA.
| | - Gautam Malhotra
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center (COH), Duarte, CA, USA
| | - Adrian Kohut
- Division of Gynecologic Oncology, Department of Surgery, City of Hope Comprehensive Cancer Center (COH), Duarte, CA, USA
| | - Michael O'Leary
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center (COH), Duarte, CA, USA
| | - Paul Frankel
- Biostatistics Core, City of Hope Beckman Research Institute, Duarte, CA, USA
| | - Thuy Tran
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center (COH), Duarte, CA, USA
| | - Marwan Fakih
- Department of Medical Oncology, COH, Duarte, CA, USA
| | - Joseph Chao
- Department of Medical Oncology, COH, Duarte, CA, USA
| | - Dean Lim
- Department of Medical Oncology, COH, Duarte, CA, USA
| | - Yanghee Woo
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center (COH), Duarte, CA, USA
| | - Isaac B Paz
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center (COH), Duarte, CA, USA
| | - Michael Lew
- Department of Anesthesiology, COH, Duarte, CA, USA
| | | | - Lorna Rodriguez-Rodriguez
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center (COH), Duarte, CA, USA
| | - Yuman Fong
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center (COH), Duarte, CA, USA
| | | | | | | | | | - Thanh H Dellinger
- Division of Gynecologic Oncology, Department of Surgery, City of Hope Comprehensive Cancer Center (COH), Duarte, CA, USA.
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25
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Račkauskas R, Baušys A, Lukšta M, Jurgaitis J, Paškonis M, Strupas K. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for peritoneal malignancy: initial experience of the first program in the Baltic countries. World J Surg Oncol 2021; 19:236. [PMID: 34376191 PMCID: PMC8356452 DOI: 10.1186/s12957-021-02357-5] [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: 04/22/2021] [Accepted: 08/01/2021] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Peritoneal malignancies include primary and metastatic cancer of the peritoneal cavity. The most common origin for peritoneal metastasis is ovarian, gastric, and colorectal cancers. Irrespective of the origin, peritoneal metastases represent the advanced disease and are associated with poor long-term outcomes. The minimally invasive approach of pressurized intraperitoneal aerosol chemotherapy (PIPAC) allows repeated applications and objective assessment of tumor response by comparing histological samples. This study aimed to investigate the initial experience with PIPAC in the Baltic region. METHODS All patients who underwent PIPAC at Vilnius University Hospital Santaros Klinikos between 2015 and 2020 were included in this retrospective study. The primary outcome of the study was overall survival (OS) in patients with peritoneal carcinomatosis treated by PIPAC. The secondary outcomes included postoperative morbidity; peritoneal carcinomatosis index (PCI) and ascites reduction after treatment by PIPAC. RESULTS In total, 15 patients underwent 34 PIPAC procedures. PIPAC-related intraoperative and postoperative morbidity occurred in 3 (8.8%) of 34 procedures. Following PIPAC, the median PCI decreased from 8 (4; 15) to 5 (1; 16) in GC patients, although, the difference failed for significance, p = 0.581. In OC patients, PCI after PIPAC remained stable. Median overall survival after PIPAC procedure was 25 (95% CI 5-44) months. Ovarian cancer patients (22; 95% CI 12-44 months) had significantly higher OS, compared to gastric cancer patients (8; 95% CI 4-16 months), p = 0.018. CONCLUSIONS PIPAC is safe and feasible for patients with gastric and ovarian cancers peritoneal metastases.
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Affiliation(s)
- Rokas Račkauskas
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
| | - Augustinas Baušys
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | - Martynas Lukšta
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | - Jonas Jurgaitis
- Department of Surgery, University hospital of Klaipeda, Klaipeda, Lithuania
| | - Marius Paškonis
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | - Kęstutis Strupas
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
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26
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Park SJ, Lee EJ, Lee HS, Kim J, Park S, Ham J, Mun J, Paik H, Lim H, Seol A, Yim GW, Shim SH, Kang BC, Chang SJ, Lim W, Song G, Kim JW, Lee N, Park JW, Lee JC, Kim HS. Development of rotational intraperitoneal pressurized aerosol chemotherapy to enhance drug delivery into the peritoneum. Drug Deliv 2021; 28:1179-1187. [PMID: 34121568 PMCID: PMC8204987 DOI: 10.1080/10717544.2021.1937382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
This study aims to evaluate the drug distribution, tissue concentrations, penetration depth, pharmacokinetic properties, and toxicities after rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) in pigs. Because relevant medical devices have not been introduced, we developed our prototype of pressurized intraperitoneal aerosol chemotherapy (PIPAC) and RIPAC by adding a conical pendulum motion device for rotating the nozzle. RIPAC and PIPAC were conducted using 150 ml of 1% methylene blue to evaluate the drug distribution and 3.5 mg of doxorubicin in 50 ml of 0.9% NaCl to evaluate the tissue concentrations and penetration depth, pharmacokinetic properties, and toxicities. All agents were sprayed as aerosols via the nozzle, DreamPen® (Dalim Biotech, Gangwon, South Korea), with a velocity of 5 km/h at a flow rate of 30 ml/min under a pressure of 7 bars, and capnoperitoneum of 12 mmHg was maintained for 30 min. As a result, RIPAC showed a wider distribution and stronger intensity than PIPAC. Compared with PIPAC, RIPAC demonstrated high values of the tissue concentration in the central, right upper, epigastrium, left upper, left lower, right lower, and right flank regions (median, 375.5-2124.9 vs. 161.7-1240 ng/ml; p ≤ .05), and higher values of the depth of concentrated diffusion and depth of maximal diffusion (median, 232.5-392.7 vs. 116.9-240.1 μm; 291.2-551.2 vs. 250.5-362.4 μm; p ≤ .05) in all regions except for bowels. In RIPAC, the pharmacokinetic properties reflected hemodynamic changes during capnoperitoneum, and there were no related toxicities. Conclusively, RIPAC may have the potential to enhance drug delivery into the peritoneum compared to PIPAC.
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Affiliation(s)
- Soo Jin Park
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Eun Ji Lee
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Hee Su Lee
- Interdisciplinary Program in Bioengineering, Seoul National University Graduate School, Seoul, Republic of Korea
| | - Junsik Kim
- Interdisciplinary Program in Bioengineering, Seoul National University Graduate School, Seoul, Republic of Korea
| | - Sunwoo Park
- Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea
| | - Jiyeon Ham
- Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea
| | - Jaehee Mun
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Haerin Paik
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Hyunji Lim
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Aeran Seol
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Ga Won Yim
- Department of Obstetrics and Gynecology, Dongguk University Ilsan Hospital, Goyang, Korea
| | - Seung-Hyuk Shim
- Department of Obstetrics and Gynecology, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea
| | - Beong-Cheol Kang
- Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
| | - Suk Joon Chang
- Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Whasun Lim
- Department of Food and Nutrition, Kookmin University, Seoul, Republic of Korea
| | - Gwonhwa Song
- Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea
| | - Jae-Weon Kim
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Nara Lee
- Department of Obstetrics & Gynecology, CHA Gangnam Medical Center, CHA University, Seoul, Republic of Korea
| | - Ji Won Park
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jung Chan Lee
- Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul, Republic of Korea.,Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University, Seoul, South Korea
| | - Hee Seung Kim
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Republic of Korea
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Roussin F, Taibi A, Canal-Raffin M, Cantournet L, Durand-Fontanier S, Druet-Cabanac M, El Balkhi S, Maillan G. Assessment of workplace environmental contamination and occupational exposure to cisplatin and doxorubicin aerosols during electrostatic pressurized intraperitoneal aerosol chemotherapy. Eur J Surg Oncol 2021; 47:2939-2947. [PMID: 34034944 DOI: 10.1016/j.ejso.2021.05.020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 03/28/2021] [Accepted: 05/07/2021] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Electrostatic precipitation pressurized intraperitoneal aerosol chemotherapy (ePIPAC) is a novel approach for intraperitoneal drug delivery. As ePIPAC using cisplatin and doxorubicin is performed in an operating room, the challenge is to safely deliver the chemotherapeutic aerosol intraperitoneally while preventing exposure to healthcare workers. The objective of this study was to describe cisplatin and doxorubicin workplace environmental contamination and healthcare worker exposure during ePIPAC. METHODS Antineoplastic drugs concentrations of cisplatin and doxorubicin were measured in wipe samples from the operating room, and urine samples were collected from healthcare workers. The air samples were collected in order to detect Cisplatin contamination. Cisplatin was analysed by inductively coupled plasma-mass spectrometry and doxorubicin by ultra-high-performance liquid chromatography coupled with tandem mass spectrometry. RESULTS No trace of cisplatin was found in the air. Cisplatin and doxorubicin were detected on the operating room floor, surfaces, devices and personal protective equipment even after a cleaning protocol. No traces of cisplatin or doxorubicin were found in the urine samples. CONCLUSION In this study, no internal contamination was found in the ePIPAC surgical team even after implementing two successive ePIPAC procedures. These results showed the effectiveness of the individual and collective protective measures applied. However, the cleaning procedure during ePIPAC should be respected to limit environmental exposure to chemotherapy to cisplatin and doxorubicin during ePIPAC.
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Affiliation(s)
- Fanny Roussin
- Pharmacy Department, Dupuytren Limoges University Hospital, France
| | - Abdelkader Taibi
- Digestive Surgery Department, Dupuytren Limoges University Hospital, France; University Limoges, CNRS, XLIM, UMR 7252, F-87000 Limoges, France.
| | - Mireille Canal-Raffin
- INSERM U1219, Université de Bordeaux, 33076, Bordeaux, France; Laboratoire de Pharmacologie Clinique et Toxicologie, CHU de Bordeaux, 33076, Bordeaux, France; University of Bordeaux, 33076, Bordeaux, France
| | | | - Sylvaine Durand-Fontanier
- Digestive Surgery Department, Dupuytren Limoges University Hospital, France; University Limoges, CNRS, XLIM, UMR 7252, F-87000 Limoges, France
| | | | - Souleiman El Balkhi
- Pharmacology-Toxicology and Pharmacovigilance Department, CHU Limoges, France; INSERM, IPPRITT,U1248, F-87000, Limoges, France
| | - Gaëlle Maillan
- Pharmacy Department, Dupuytren Limoges University Hospital, France
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Lurvink RJ, Van der Speeten K, Rovers KP, de Hingh IHJT. The emergence of pressurized intraperitoneal aerosol chemotherapy as a palliative treatment option for patients with diffuse peritoneal metastases: a narrative review. J Gastrointest Oncol 2021; 12:S259-S270. [PMID: 33968442 DOI: 10.21037/jgo-20-497] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an emerging palliative treatment for patients with unresectable peritoneal metastases. Potential advantages of PIPAC over current treatment options are a homogeneous intraperitoneal distribution, low local and systemic toxicity, and enhanced tumour penetration. Given these possible benefits, PIPAC is increasingly implemented in many centres worldwide. Scientific research into PIPAC is currently available from in vitro/in vivo/in animal studies, retrospective cohorts in humans, and phase I and II studies in humans. There are no results from randomised trials comparing PIPAC with conventional treatment, such as palliative systemic therapy. This narrative review aimed to provide an overview of the currently available literature on PIPAC. In general, repetitive PIPAC was feasible and safe for patients and operating room personnel. Primary and secondary non-access rates varied from 0-17% and 0-15%, respectively. Iatrogenic bowel injury was observed in 0-3% of PIPAC procedures. CTCAE grade 1-2 complications were common, mostly consisting of abdominal pain, nausea, vomiting, and fatigue. CTCAE grade 3-4 complications were uncommon, occurring on 0-15% of PIPAC procedures. Post-operative mortality rates of 0-2% were reported. The risk of occupational exposure to cytotoxic drugs was very low when strict safety guidelines were followed. Clinical heterogeneity was high in most studies, since, in general, patients with unresectable peritoneal metastases from a variety of primary tumours were included. Also, patients received either PIPAC monotherapy or PIPAC combined with concomitant systemic therapy, and were able to receive PIPAC in any line of palliative treatment. Since the results were generally not stratified for these three important factors, this severely complicates the interpretation of results. Based on the current literature, PIPAC may be regarded as a promising palliative treatment option in patients with diffuse peritoneal metastases. Initial results show that it is feasible and safe. However, well designed and (ideally) randomized controlled trials are urgently needed to determine the additional value of PIPAC in this setting. Until then, PIPAC should preferably be performed in the setting of clinical trials.
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Affiliation(s)
- Robin J Lurvink
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | | | - Koen P Rovers
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - Ignace H J T de Hingh
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands.,GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands
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Intraperitoneal Chemotherapy for Peritoneal Metastases: Technical Innovations, Preclinical and Clinical Advances and Future Perspectives. BIOLOGY 2021; 10:biology10030225. [PMID: 33804167 PMCID: PMC8001167 DOI: 10.3390/biology10030225] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 03/08/2021] [Accepted: 03/10/2021] [Indexed: 02/07/2023]
Abstract
(1) Background: Tumors of the peritoneal serosa are called peritoneal carcinosis. Their origin may be primary by primitive involvement of the peritoneum (peritoneal pseudomyxoma, peritoneal mesothelioma, etc.). This damage to the peritoneum can also be a consequence of the dissipation of cancers-in particular, digestive (stomach, pancreas, colorectal, appendix) and gynecological (ovaries) ones in the form of metastases. The aim of the treatment is a maximal reduction of the macroscopic disease called "cytoreduction" in combination with hyperthermic intra-abdominal chemotherapy to treat residual microscopic lesions. (2) Methods: In this narrative review, we fundamentally synthetize the evolution of this process over time and its impact on clinical applications. (3) Results: Over the last past decade, different evolutions concerning both delivery modes and conditions concerning hyperthermic intra-abdominal chemotherapy have been realized. (4) Conclusion: The final objective of these evolutions is the improvement of the global and recurrence-free survival of primary and secondary malignant peritoneal pathologies. However, more large randomized controlled trials are needed to demonstrate the efficacy of such treatments with the help of molecular biology and genetics.
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Oh S, Paik H, Park SJ, Lee EJ, Kim HS. Pressurized intraperitoneal aerosol chemotherapy for recurrent ovarian, fallopian or primary peritoneal cancer with peritoneal carcinomatosis: a narrative review. Gland Surg 2021; 10:1244-1251. [PMID: 33842271 DOI: 10.21037/gs-2019-ursoc-12] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
For recurrent ovarian, fallopian or primary peritoneal cancer with peritoneal carcinomatosis (PC), it is challenging to resect tumors completely or to get complete remission by intravenous (IV) chemotherapy, and many patients show the resistance to various chemotherapeutic agents for IV chemotherapy ultimately. As an alternative, pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been introduced for treating the disease, which delivers chemotherapeutic agents as an aerosol form while maintaining high intraperitoneal (IP) pressure. Based on preclinical studies, PIPAC showed better penetration depth and distribution of drugs into the peritoneum in comparison to conventional IP chemotherapy. Tumor regression on histology and peritoneal carcinomatosis index (PCI) has also been shown in relevant studies. In addition, most of the PIPAC procedures were completed successfully with acceptable toxicity due to the use of a low dose of chemotherapeutic agents. For considering these advantages of PIPAC, we review the current status of PIPAC for treating recurrent ovarian, fallopian or primary peritoneal cancer through literature review.
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Affiliation(s)
- Soohyun Oh
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Haerin Paik
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Soo Jin Park
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Eun Ji Lee
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
| | - Hee Seung Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea
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Clerc D, Hübner M, Ashwin KR, Somashekhar SP, Rau B, Ceelen W, Willaert W, Bakrin N, Laplace N, Al Hosni M, Garcia Lozcano EL, Blaj S, Piso P, Di Giorgio A, Vizzelli G, Brigand C, Delhorme JB, Klipfel A, Archid R, Nadiradze G, Reymond MA, Sgarbura O. Current practice and perceptions of safety protocols for the use of intraperitoneal chemotherapy in the operating room: results of the IP-OR international survey. Pleura Peritoneum 2021; 6:39-45. [PMID: 34222648 PMCID: PMC8223803 DOI: 10.1515/pp-2020-0148] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 01/13/2021] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVES To assess the risk perception and the uptake of measures preventing environment-related risks in the operating room (OR) during hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC). METHODS A multicentric, international survey among OR teams in high-volume HIPEC and PIPAC centers: Surgeons (Surg), Scrub nurses (ScrubN), Anesthesiologists (Anest), Anesthesiology nurses (AnesthN), and OR Cleaning staff (CleanS). Scores extended from 0-10 (maximum). RESULTS Ten centers in six countries participated in the study (response rate 100%). Two hundred and eleven responses from 68 Surg (32%), 49 ScrubN (23%), 45 Anest (21%), 31 AnesthN (15%), and 18 CleanS (9%) were gathered. Individual uptake of protection measures was 51.4%, similar among professions and between HIPEC and PIPAC. Perceived levels of protection were 7.57 vs. 7.17 for PIPAC and HIPEC, respectively (p<0.05), with Anesth scoring the lowest (6.81). Perceived contamination risk was 4.19 for HIPEC vs. 3.5 for PIPAC (p<0.01). Information level was lower for CleanS and Anesth for HIPEC and PIPAC procedures compared to all other responders (6.48 vs. 4.86, and 6.48 vs. 5.67, p<0.01). Willingness to obtain more information was 86%, the highest among CleanS (94%). CONCLUSIONS Experience with the current practice of safety protocols was similar during HIPEC and PIPAC. The individual uptake of protection measures was rather low. The safety perception was better for PIPAC, but the perceived level of protection remained relatively low. The willingness to obtain more information was high. Intensified, standardized training of all OR team members involved in HIPEC and PIPAC is meaningful.
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Affiliation(s)
- Daniel Clerc
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Lausanne, Switzerland
| | - Martin Hübner
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Lausanne, Switzerland
| | - K R Ashwin
- Department of Surgical Oncology and Robotic Surgery, Manipal Comprehensive Cancer Centre, Bengaluru, Karnataka, India
| | - S P Somashekhar
- Department of Surgical Oncology and Robotic Surgery, Manipal Comprehensive Cancer Centre, Bengaluru, Karnataka, India
| | - Beate Rau
- Department of Surgery, Campus Virchow-Klinikum and Charité Campus Mitte, Charité-Universitätsmedizin, Berlin, Germany
| | - Wim Ceelen
- Department of Gastrointestinal Surgery, Ghent University Hospital Belgium, Gent, Belgium
| | - Wouter Willaert
- Department of Gastrointestinal Surgery, Ghent University Hospital Belgium, Gent, Belgium
| | - Naoual Bakrin
- Department of Digestive Surgery, Lyon-Sud University Hospital, Lyon, France
| | - Nathalie Laplace
- Department of Digestive Surgery, Lyon-Sud University Hospital, Lyon, France
| | - Mohammed Al Hosni
- Department of Surgical Oncology, Cancer Institute of Montpellier (ICM), Montpellier, France
| | | | - Sebastian Blaj
- Department of General and Visceral Surgery, Krankenhaus Barmherzige Brüder, Regensburg, Germany
| | - Pompiliu Piso
- Department of General and Visceral Surgery, Krankenhaus Barmherzige Brüder, Regensburg, Germany
| | - Andrea Di Giorgio
- Peritoneum and Retroperitoneum Surgical Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - Giuseppe Vizzelli
- Peritoneum and Retroperitoneum Surgical Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - Cécile Brigand
- Department of General and Digestive Surgery, Hautepierre Hospital, Strasbourg University Hospital, Strasbourg, France
| | - Jean-Baptiste Delhorme
- Department of General and Digestive Surgery, Hautepierre Hospital, Strasbourg University Hospital, Strasbourg, France
| | - Amandine Klipfel
- Department of General and Digestive Surgery, Hautepierre Hospital, Strasbourg University Hospital, Strasbourg, France
| | - Rami Archid
- Department of General and Transplant Surgery, University Hospital Tübingen and National Center for Pleura and Peritoneum, Tübingen, Germany
| | - Giorgi Nadiradze
- Department of General and Transplant Surgery, University Hospital Tübingen and National Center for Pleura and Peritoneum, Tübingen, Germany
| | - Marc A Reymond
- Department of General and Transplant Surgery, University Hospital Tübingen and National Center for Pleura and Peritoneum, Tübingen, Germany
| | - Olivia Sgarbura
- Department of Surgical Oncology, Cancer Institute of Montpellier (ICM), Montpellier, France
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Kinoshita J, Yamaguchi T, Moriyama H, Fushida S. Current status of conversion surgery for stage IV gastric cancer. Surg Today 2021; 51:1736-1754. [PMID: 33486610 DOI: 10.1007/s00595-020-02222-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 11/02/2020] [Indexed: 12/23/2022]
Abstract
Palliative chemotherapy with best supportive care is a mainstay for patients with gastric cancer (GC) and distant metastasis. However, with advances in GC chemotherapy, multimodal treatment, including perioperative chemotherapy plus conversion surgery, has attracted attention as a new strategy to improve the outcome of patients with stage IV disease. Conversion surgery is defined as surgical treatment aimed at R0 resection after a good response to induction chemotherapy for tumors originally considered unresectable or marginally resectable for technical and/or oncological reasons. Various biological characteristics differ, depending on each metastatic condition in stage IV GC. The main metastatic pathways of GC can be divided into three categories: lymphatic, hematogenous, and peritoneal. In each category, considerable historical data on conversion surgery have demonstrated the benefits of individualized approaches. However, owing to the diversity of these conditions, a common definition, including the choice of induction chemotherapy, optimal timing of resection, and eligibility for conversion surgery, has not been established among surgical oncologists. Thus, we explore the current and future treatment options by reviewing the literature on this controversial topic comprehensively.
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Affiliation(s)
- Jun Kinoshita
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Takahisa Yamaguchi
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Hideki Moriyama
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Sachio Fushida
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan.
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Taibi A, Teixeira Farinha H, Durand Fontanier S, Sayedalamin Z, Hübner M, Sgarbura O. Pressurized Intraperitoneal Aerosol Chemotherapy Enhanced by Electrostatic Precipitation (ePIPAC) for Patients with Peritoneal Metastases. Ann Surg Oncol 2020; 28:3852-3860. [PMID: 33216263 DOI: 10.1245/s10434-020-09332-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 10/17/2020] [Indexed: 12/22/2022]
Abstract
BACKGROUND Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new mode of intraperitoneal chemotherapy administration that can potentially be improved by the addition of electrostatic precipitation (ePIPAC). This study aimed to describe the procedural details of ePIPAC and to analyze its safety for patients with nonresectable peritoneal metastasis as well as their tolerance and response to this treatment. METHODS This retrospective cohort study included consecutive patients treated with ePIPAC in three centers from April 2019 to April 2020. The toxicities of each patient were assessed using the Common Terminology Criteria for Adverse Events (CTCAE). Complications were documented according to the Clavien classification. Quality of life (QoL) was assessed using EORTC-QLQ-C30, and the peritoneal regression grading score (PRGS) was used to grade histologic responses. Further surrogates for responses were the Peritoneal Cancer Index (PCI), ascites, and symptoms. RESULTS Overall, 69 patients received 147 ePIPACs with oxaliplatin (n = 34) or cisplatin/doxorubicin (n = 35) mainly for colorectal (n = 25), ovarian (n = 14), and gastric (n = 13) primary cancers. Systemic chemotherapy was used in the treatment of 54 patients (76%). The median electrostatic therapy time was 12 min (range 6-30 min). The overall and major CTCAE toxicity rates were respectively 24.6% and 15.9%. The postoperative complications rate according to Clavien classification was 4.7%. The responses of 22 patients who had three or more ePIPAC treatments were evaluated as follows: PCI (16 vs 14; p = 0.4), ascites (320 vs 98 ml; p = 0.1), and PRGS (2.23 vs 1.73; p = 0.15). The complete (PRGS1) and major (PRGS2) histologic responses at the third ePIPAC were respectively 38.5% and 53.8%. Overall QoL was stable during the first ePIPACs. CONCLUSION Repetitive ePIPACs were safe and well tolerated for patients with unresectable peritoneal metastasis.
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Affiliation(s)
- Abdelkader Taibi
- Digestive Surgery Department, Visceral Surgery Department, Dupuytren Limoges University Hospital, Limoges, France. .,CNRS, XLIM, UMR 7252, University Limoges, 87000, Limoges, France.
| | - Hugo Teixeira Farinha
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Lausanne, Switzerland
| | - Sylvaine Durand Fontanier
- Digestive Surgery Department, Visceral Surgery Department, Dupuytren Limoges University Hospital, Limoges, France.,CNRS, XLIM, UMR 7252, University Limoges, 87000, Limoges, France
| | - Zaid Sayedalamin
- Surgical Oncology Department, Montpellier Cancer Institute (ICM), University of Montpellier, Montpellier, France
| | - Martin Hübner
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Lausanne, Switzerland
| | - Olivia Sgarbura
- Surgical Oncology Department, Montpellier Cancer Institute (ICM), University of Montpellier, Montpellier, France
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Drevet G, Maury JM, Bakrin N, Tronc F. Technique of pressurized intrathoracic aerosol chemotherapy (PITAC) for malignant pleural effusion. Pleura Peritoneum 2020; 5:20200129. [PMID: 33575461 PMCID: PMC7823156 DOI: 10.1515/pp-2020-0129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Accepted: 10/21/2020] [Indexed: 11/17/2022] Open
Abstract
Objectives Malignant pleural effusion (MPE) is a devastating evolution of several malignancies. Pressurized intrathoracic aerosol chemotherapy (PITAC) might be a novel therapy option in MPE. Methods PITAC is considered for patients with MPE with a performance status <2 and without other metastatic sites. General anesthesia is administered and a double-lumen bronchial tube is inserted. The patient is placed in a lateral decubitus position, and the operation is performed after ipsilateral lung exclusion. Two 12-mm balloon trocars are inserted—one in the seventh intercostal space in the mid-axillary line and one in the fifth intercostal space in the anterior axillary line. Extent of pleural disease and volume of MPE are documented. MPE is removed and parietal pleural biopsy are performed. An intrathoracic pressure of 12 mmHg CO2 is established, and a combination of Cisplatin (10.5 mg/m2 in a total volume of 150 cc NaCl 0.9%) and Doxorubicin (2.1 mg/m2 in a total volume of 50 cc NaCl 0.9%) are aerosolized via nebulizer in the pleural cavity. Vital signs and nebulization are remote-controlled. After 30 min, the remaining toxic aerosol is exhausted using a closed surgical smoke evacuation system. A 24Fr chest tube is inserted in postero-apical position with continuous negative pressure of 20 cm H2O. When needed, PITAC may be repeated every six weeks in alternate with systemic chemotherapy. Results In our hands, the technique above has shown to be feasible and safe. Conclusions Further studies are needed to assess the potential symptomatic and oncological benefits of PITAC in MPE.
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Affiliation(s)
- Gabrielle Drevet
- Department of Thoracic Surgery, Lung and Heart-Lung Transplantation, Louis Pradel Hospital, Hospices Civils de Lyon, Lyon, France
| | - Jean-Michel Maury
- Department of Thoracic Surgery, Lung and Heart-Lung Transplantation, Louis Pradel Hospital, Hospices Civils de Lyon, Lyon, France.,Viral Infection and Comparative Pathology (IVPC), UMR 754, Claude Bernard Lyon 1 University, Lyon, France
| | - Naoual Bakrin
- Department of General Surgery and Surgical Oncology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France.,EMR 3738 Lyon Sud Charles Mérieux Faculty, Claude Bernard University Lyon 1, Oullins, France
| | - François Tronc
- Department of Thoracic Surgery, Lung and Heart-Lung Transplantation, Louis Pradel Hospital, Hospices Civils de Lyon, Lyon, France
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Current practice of pressurized intraperitoneal aerosol chemotherapy (PIPAC): Still standardized or on the verge of diversification? Eur J Surg Oncol 2020; 47:149-156. [PMID: 32900609 DOI: 10.1016/j.ejso.2020.08.020] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2020] [Revised: 07/20/2020] [Accepted: 08/20/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND PIPAC is a new treatment modality for peritoneal cancer which has been practiced and evaluated until very recently by few academic centers in a highly standardized manner. Encouraging oncological outcomes and the safety profile have led to widespread adoption. The aim of this study was to assess current PIPAC practice in terms of technique, treatment and safety protocol, and indications. METHODS A standardized survey with 82 closed-ended questions was sent online to active PIPAC centers which were identified by help of PIPAC training centers and the regional distributors of the PIPAC-specific nebulizer. The survey inquired about center demographics (n = 8), technique (n = 34), treatment and safety protocol (n = 34), and indications (n = 6). RESULTS Overall, 62 out of 66 contacted PIPAC centers answered the survey (response rate 93%). 27 centers had performed >60 PIPAC procedures. A consensus higher than 70% was reached for 37 items (50%), and higher than 80% for 28 items (37.8%). The topics with the highest degree of consensus were safety and installation issues (93.5% and 80.65%) while chemotherapy and response evaluation were the least consensual topics (63.7 and 59.6%). The attitudes were not influenced by volume, PIPAC starting year, type of activity, or presence of peritoneal metastases program. CONCLUSION Homogeneous treatment standards of new techniques are important to guarantee safe implementation and practice but also to allow comparison between cohorts and multi-center analysis of merged data including registries. Efforts to avoid diversification of PIPAC practice include regular update of the PIPAC training curriculum, targeted research and a consensus statement.
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Takahara N, Nakai Y, Ishigami H, Saito K, Sato T, Hakuta R, Ishigaki K, Saito T, Hamada T, Mizuno S, Kogure H, Yamashita H, Isayama H, Seto Y, Koike K. A phase I study of intraperitoneal paclitaxel combined with gemcitabine plus nab-paclitaxel for pancreatic cancer with peritoneal metastasis. Invest New Drugs 2020; 39:175-181. [PMID: 32772340 DOI: 10.1007/s10637-020-00982-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 08/03/2020] [Indexed: 10/23/2022]
Abstract
PURPOSE A phase I study of intraperitoneal paclitaxel (ip PTX) combined with gemcitabine (GEM) plus nab-paclitaxel (nab-PTX) (GnP) was conducted to determine the maximum tolerated dose (MTD) and the recommended dose (RD) in pancreatic cancer patients with peritoneal metastasis in first-line setting. METHODS Based on the 3 + 3 dose-escalation model, ip PTX, GEM and nab-PTX were administered at doses of 20 or 30 mg/m2, 800 or 1000 mg/m2 and 100 or 125 mg/m2 (level 1, 2 and 3, respectively) on days 1, 8 and 15 in 4-week cycles. Dose-limiting toxicity (DLT) defined as severe adverse events was evaluated during the first cycle of the treatment. Safety and preliminary efficacy were also investigated. RESULTS In total, 12 patients were enrolled. While 2 of the first 6 patients enrolled at level 1 experienced DLTs (grade 3 ip port dysfunction and grade 3 pneumonia), no DLT was observed in the next 6 patients enrolled at level 2 and 3. Therefore, we did not reach the MTD and the RD was determined to be level 3 (ip PTX of 30 mg/m2, GEM of 1000 mg/m2, and nab-PTX of 125 mg/m2). The major grade 3/4 adverse events included neutropenia (58%), anemia (33%), and ip port dysfunction (25%). The response rate was 25% and the median PFS was 5.4 (95% confidence interval; 2.4-16.0). The cytological status in peritoneal lavage turned negative in 8 patients (67%). CONCLUSIONS Ip PTX combined with GnP was feasible and potentially effective in pancreatic cancer with peritoneal metastasis as a first-line treatment deserved further evaluations.
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Affiliation(s)
- Naminatsu Takahara
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yousuke Nakai
- Department of Endoscopy and Endoscopic Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
| | - Hironori Ishigami
- Department of Chemotherapy, The University of Tokyo Hospital, Tokyo, Japan
| | - Kei Saito
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tatsuya Sato
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryunosuke Hakuta
- Department of Endoscopy and Endoscopic Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Kazunaga Ishigaki
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tomotaka Saito
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tsuyoshi Hamada
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Suguru Mizuno
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hirofumi Kogure
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroharu Yamashita
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroyuki Isayama
- Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan
| | - Yasuyuki Seto
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Rouche A, Hübner M, Grass F, Pache B, Demartines N, Blanc C. Anaesthesia in a Toxic Environment: Pressurised Intraperitoneal Aerosol Chemotherapy: A Retrospective Analysis. Turk J Anaesthesiol Reanim 2020; 48:273-279. [PMID: 32864641 PMCID: PMC7434348 DOI: 10.5152/tjar.2019.15493] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2019] [Accepted: 08/27/2019] [Indexed: 11/22/2022] Open
Abstract
OBJECTIVE Pressurised intraperitoneal aerosol chemotherapy (PIPAC) is a new type of intraperitoneal chemotherapy for peritoneal carcinosis via minimally invasive surgery. This technique's specificity is the remote application of the therapy because of the potential risk of exposure to toxic products. The present paper summarises the important aspects of PIPAC and analyses the anaesthetic outcomes. METHODS This retrospective study included all patients undergoing PIPAC treatment between January 2015 and February 2018. Data on protocol adherence and perioperative anaesthetic complications and postoperative nausea and vomiting (PONV) and pain levels (visual analogue scale 0-10) from recovery room to 72 h were analysed. RESULTS The overall analysis included 193 PIPAC procedures on 87 patients. Protocol adherence was high as regards the use of propofol (100%), rocuronium (98%), antiemetic prophylaxis (99%) and lidocaine intravenous (i.v.) (87%). No accidental exposure to chemotherapy occurred during the study period. Of the 87 patients, 6.3% suffered delayed recovery, 58% due to hypothermia and 42% due to excessive sedation or curarisation. In the recovery room, 16% of patients suffered moderate to severe pain, requiring >8 mg of morphine i.v., with average doses of 13.7 mg. Median postoperative pain scores were 1 and 3 at 12 h and 0 and 0 at 72 h at rest and mobilisation, respectively. PONV was observed in <10% of patients during the first 12 h, but in 40% at 72 h. CONCLUSION A dedicated anaesthetic protocol and intraoperative safety checklist facilitates safe, well-tolerated anaesthesia for PIPAC treatments.
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Affiliation(s)
- Amir Rouche
- Department of Anaesthesiology, Lausanne University Hospital (CHUV), Lausanne, Switzerland
| | - Martin Hübner
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), Lausanne, Switzerland
| | - Fabian Grass
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), Lausanne, Switzerland
| | - Basile Pache
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), Lausanne, Switzerland
| | - Nicolas Demartines
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), Lausanne, Switzerland
| | - Catherine Blanc
- Department of Anaesthesiology, Lausanne University Hospital (CHUV), Lausanne, Switzerland
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Di Giorgio A, Sgarbura O, Rotolo S, Schena CA, Bagalà C, Inzani F, Russo A, Chiantera V, Pacelli F. Pressurized intraperitoneal aerosol chemotherapy with cisplatin and doxorubicin or oxaliplatin for peritoneal metastasis from pancreatic adenocarcinoma and cholangiocarcinoma. Ther Adv Med Oncol 2020; 12:1758835920940887. [PMID: 32782488 PMCID: PMC7383654 DOI: 10.1177/1758835920940887] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Accepted: 06/15/2020] [Indexed: 02/06/2023] Open
Abstract
Background Systemic chemotherapy for pancreatic adenocarcinoma (PDAC) and cholangiocarcinoma (CC) with peritoneal metastases (PM) is affected by several pharmacological shortcomings and low clinical efficacy. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is expected to maximize exposure of peritoneal nodules to antiblastic agents. This study aims to evaluate safety and efficacy of PIPAC for PM of PDAC and CC origin. Methods This is a retrospective analysis of consecutive PDAC and CC cases with PM treated with PIPAC at two European referral centers for peritoneal disease. We prospectively recorded from August 2016 to May 2019 demographic, clinical, surgical, and oncological data. We performed a feasibility and safety assessment and an efficacy analysis based on clinical and pathological regression. Results Twenty patients with PM from PDAC (14) and CC (six) underwent 45 PIPAC administrations. Cisplatin-doxorubicin or oxaliplatin were administered to eight and 12 patients, respectively. We experienced one intraoperative complication (small bowel perforation) and 18 grade 1-2 postoperative adverse events according to Common Terminology Criteria for Adverse Events version 4.0. A pathological regression was recorded in 50% of patients (62% in the cisplatin-doxorubicin cohort and 42% in the oxaliplatin one). Median survival from the first PIPAC was 9.7 and 10.9 months for PDAC and CC, respectively. Conclusion PIPAC resulted feasible and safe without relevant toxicity issues, with both cisplatin-doxorubicin and oxaliplatin. The pathological response observed supports the evidence of antitumoral activity. Despite the study limitations, these outcomes are encouraging, recommending PIPAC in prospective, controlled trials in the palliative setting or the first line chemotherapy for PM from PDAC and CC.
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Affiliation(s)
- Andrea Di Giorgio
- Foundation Policlinico Universitario A. Gemelli - IRCCS, Peritoneum and Retroperitoneum Surgery, Roma, Lazio, Italy
| | - Olivia Sgarbura
- Department of Surgical Oncology, Montpellier Cancer Institute, Montpellier, Languedoc-Roussillon, France
| | - Stefano Rotolo
- Department of Surgical, Oncological and Oral Sciences (Di.Chir.On.S.), University of Palermo, Via del Vespro, 129, Palermo, 90127, Sicilia, Italy
| | - Carlo Alberto Schena
- Foundation Policlinico Universitario A. Gemelli - IRCCS, General Surgery Unit, Roma, Lazio, Italy
| | - Cinzia Bagalà
- Foundation Policlinico Universitario A. Gemelli - IRCCS, Division of Medical Oncology, Roma, Lazio, Italy
| | - Frediano Inzani
- Foundation Policlinico Universitario A. Gemelli - IRCCS, Anatomic Pathology Unit, Roma, Lazio, Italy
| | - Andrea Russo
- Foundation Policlinico Universitario A. Gemelli - IRCCS, Institute of Intensive Care Medicine and Anesthesiology, Roma, Lazio, Italy
| | - Vito Chiantera
- Division of Gynecologic Oncology, University of Palermo, Palermo, Sicilia, Italy
| | - Fabio Pacelli
- Foundation Policlinico Universitario A. Gemelli - IRCCS, Peritoneum and Retroperitoneum Surgery, Roma, Lazio, Italy
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Alyami M, Hübner M, Grass F, Bakrin N, Villeneuve L, Laplace N, Passot G, Glehen O, Kepenekian V. Pressurised intraperitoneal aerosol chemotherapy: rationale, evidence, and potential indications. Lancet Oncol 2020; 20:e368-e377. [PMID: 31267971 DOI: 10.1016/s1470-2045(19)30318-3] [Citation(s) in RCA: 196] [Impact Index Per Article: 39.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 04/18/2019] [Accepted: 04/23/2019] [Indexed: 02/06/2023]
Abstract
Pressurised intraperitoneal aerosol chemotherapy (PIPAC) was introduced as a new treatment for patients with peritoneal metastases in November, 2011. Reports of its feasibility, tolerance, and efficacy have encouraged centres worldwide to adopt PIPAC as a novel drug delivery technique. In this Review, we detail the technique and rationale of PIPAC and critically assess its evidence and potential indications. A systematic search was done to identify all relevant literature on PIPAC published between Jan 1, 2011, and Jan 31, 2019. A total of 106 articles or reports on PIPAC were identified, and 45 clinical studies on 1810 PIPAC procedures in 838 patients were included for analysis. Repeated PIPAC delivery was feasible in 64% of patients with few intraoperative and postoperative surgical complications (3% for each in prospective studies). Adverse events (Common Terminology Criteria for Adverse Events greater than grade 2) occurred after 12-15% of procedures, and commonly included bowel obstruction, bleeding, and abdominal pain. Repeated PIPAC did not have a negative effect on quality of life. Using PIPAC, an objective clinical response of 62-88% was reported for patients with ovarian cancer (median survival of 11-14 months), 50-91% for gastric cancer (median survival of 8-15 months), 71-86% for colorectal cancer (median survival of 16 months), and 67-75% (median survival of 27 months) for peritoneal mesothelioma. From our findings, PIPAC has been shown to be feasible and safe. Data on objective response and quality of life were encouraging. Therefore, PIPAC can be considered as a treatment option for refractory, isolated peritoneal metastasis of various origins. However, its use in further indications needs to be validated by prospective studies.
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Affiliation(s)
- Mohammad Alyami
- Department of General Surgery and Surgical Oncology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France; Department of General Surgery and Surgical Oncology, Oncology Center, King Khalid Hospital, Najran, Saudi Arabia.
| | - Martin Hübner
- Department of Visceral Surgery, Lausanne University Hospital, University of Lausanne, Switzerland
| | - Fabian Grass
- Department of Visceral Surgery, Lausanne University Hospital, University of Lausanne, Switzerland; Department of Surgery, Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, MN, USA
| | - Naoual Bakrin
- Department of General Surgery and Surgical Oncology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France; EMR 3738 Lyon Sud Charles Mérieux Faculty, Claude Bernard University Lyon 1, Oullins, France
| | - Laurent Villeneuve
- Department of Public Health, Clinical Research and Epidemiology, Hospices Civils de Lyon, Lyon, France
| | - Nathalie Laplace
- Department of General Surgery and Surgical Oncology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France; EMR 3738 Lyon Sud Charles Mérieux Faculty, Claude Bernard University Lyon 1, Oullins, France
| | - Guillaume Passot
- Department of General Surgery and Surgical Oncology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France; EMR 3738 Lyon Sud Charles Mérieux Faculty, Claude Bernard University Lyon 1, Oullins, France
| | - Olivier Glehen
- Department of General Surgery and Surgical Oncology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France; EMR 3738 Lyon Sud Charles Mérieux Faculty, Claude Bernard University Lyon 1, Oullins, France
| | - Vahan Kepenekian
- Department of General Surgery and Surgical Oncology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France; EMR 3738 Lyon Sud Charles Mérieux Faculty, Claude Bernard University Lyon 1, Oullins, France
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Alyami M, Bonnot PE, Mercier F, Laplace N, Villeneuve L, Passot G, Bakrin N, Kepenekian V, Glehen O. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for unresectable peritoneal metastasis from gastric cancer. Eur J Surg Oncol 2020; 47:123-127. [PMID: 32561204 DOI: 10.1016/j.ejso.2020.05.021] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Revised: 05/09/2020] [Accepted: 05/25/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND PIPAC is a recent approach with promising results for patients with peritoneal metastasis (PM). We aimed to evaluate survival and postoperative outcome of patients with unresectable PM from gastric origin treated with chemotherapy and PIPAC. METHODS A retrospective analysis of a prospective maintained PIPAC database was queried for all patients diagnosed with unresectable PM from gastric cancer who underwent PIPAC before 2018. PIPAC with Cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 were given for 30 min at 6-week intervals. Outcome criteria were overall survival and adverse events according to (CTCAE) version4.0. RESULTS One hundred Sixty-three PIPAC were done in 42 consecutive patients. Twenty-two (52%) of the patients were female. Signet-ring cells were observed in 33/42 patients (78.6%). At the first PIPAC, median age was 51.5 years (32-74). Median PCI was 17 (1-39). Twenty (47.6%) patients underwent more than 2 lines of pre-PIPAC chemotherapy. All patients had systemic chemotherapy alternating with PIPAC. Median consecutive PIPAC procedures were 3 (1-12). Overall and major complications (CTCAE - III, IV) occurred in 10 (6.1%) and 5 procedures (3.1%), respectively. Two patients (4.7%) died within 30 days of a PIPAC procedure, one related to small bowel obstruction and a pulmonary embolism for the other. Overall Survival was 19.1 months. Six (14.3%) patients became resectable during treatment and underwent curative intent CRS and HIPEC. CONCLUSIONS PIPAC with low-dose cisplatin and doxorubicin is safe and feasible in association with systemic chemotherapy for gastric PM. Survival data are encouraging and justify further clinical studies in this indication.
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Affiliation(s)
- Mohammad Alyami
- Department of General Surgery & Surgical Oncology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre, Bénite, France; EMR 3738, Lyon 1 University, Lyon, France; Department of General Surgery and Surgical Oncology, Oncology Center, King Khalid Hospital, Najran, Saudi Arabia.
| | - Pierre-Emmanuel Bonnot
- Department of General Surgery & Surgical Oncology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre, Bénite, France; EMR 3738, Lyon 1 University, Lyon, France
| | - Frederic Mercier
- Department of General Surgery & Surgical Oncology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre, Bénite, France; Department of Surgical Oncology, Centre Hospitalo-Universitaire de Montreal, Montreal, Canada
| | - Nathalie Laplace
- Department of General Surgery & Surgical Oncology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre, Bénite, France; EMR 3738, Lyon 1 University, Lyon, France
| | - Laurent Villeneuve
- Department of General Surgery & Surgical Oncology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre, Bénite, France; EMR 3738, Lyon 1 University, Lyon, France
| | - Guillaume Passot
- Department of General Surgery & Surgical Oncology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre, Bénite, France; EMR 3738, Lyon 1 University, Lyon, France
| | - Naoual Bakrin
- Department of General Surgery & Surgical Oncology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre, Bénite, France; EMR 3738, Lyon 1 University, Lyon, France
| | - Vahan Kepenekian
- Department of General Surgery & Surgical Oncology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre, Bénite, France; EMR 3738, Lyon 1 University, Lyon, France
| | - Olivier Glehen
- Department of General Surgery & Surgical Oncology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre, Bénite, France; EMR 3738, Lyon 1 University, Lyon, France
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Wexner SD, Cortés‐Guiral D, Gilshtein H, Kent I, Reymond MA. COVID-19: impact on colorectal surgery. Colorectal Dis 2020; 22:635-640. [PMID: 32359223 PMCID: PMC7267609 DOI: 10.1111/codi.15112] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 04/26/2020] [Accepted: 04/30/2020] [Indexed: 12/12/2022]
Abstract
AIM The rapid spread of the COVID-19 pandemic has created unprecedented challenges for the medical and surgical healthcare systems. With the ongoing need for urgent and emergency colorectal surgery, including surgery for colorectal cancer, several questions pertaining to operating room (OR) utilization and techniques needed to be rapidly addressed. METHOD This manuscript discusses knowledge related to the critical considerations of patient and caregiver safety relating to personal protective equipment (PPE) and the operating room environment. RESULTS During the COVID-19 pandemic, additional personal protective equipment (PPE) may be required contingent upon local availability of COVID-19 testing and the incidence of known COVID-19 infection in the respective community. In addition to standard COVID-19 PPE precautions, a negative-pressure environment, including an OR, has been recommended, especially for the performance of aerosol-generating procedures (AGPs). Hospital spaces ranging from patient wards to ORs to endoscopy rooms have been successfully converted from standard positive-pressure to negative-pressure spaces. Another important consideration is the method of surgical access; specifically, minimally invasive surgery with pneumoperitoneum is an AGP and thus must be carefully considered. Current debate centres around whether it should be avoided in patients known to be infected with SARS-CoV-2 or whether it can be performed under precautions with safety measures in place to minimize exposure to aerosolized virus particles. Several important lessons learned from pressurized intraperitoneal aerosolized chemotherapy procedures are demonstrated to help improve our understanding and management. CONCLUSION This paper evaluates the issues surrounding these challenges including the OR environment and AGPs which are germane to surgical practices around the world. Although there is no single universally agreed upon set of answers, we have presented what we think is a balanced cogent description of logical safe approaches to colorectal surgery during the COVID-19 pandemic.
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Affiliation(s)
- S. D. Wexner
- Department of Colorectal SurgeryCleveland Clinic FloridaWestonFloridaUSA
| | - D. Cortés‐Guiral
- Department of Colorectal SurgeryKing Khalid HospitalNejranSaudi Arabia
| | - H. Gilshtein
- Department of Colorectal SurgeryCleveland Clinic FloridaWestonFloridaUSA
| | - I. Kent
- Department of Colorectal SurgeryCleveland Clinic FloridaWestonFloridaUSA
| | - M. A. Reymond
- Department of General and Transplant SurgeryNational Center for Pleura and Peritoneum (NCPP)TübingenGermany
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Alyami M, Sgarbura O, Khomyakov V, Horvath P, Vizzielli G, So J, Torrent J, Delgadillo X, Martin D, Ceelen W, Reymond M, Pocard M, Hübner M. Standardizing training for Pressurized Intraperitoneal Aerosol Chemotherapy. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2020; 46:2270-2275. [PMID: 32561205 DOI: 10.1016/j.ejso.2020.05.007] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2020] [Revised: 04/28/2020] [Accepted: 05/08/2020] [Indexed: 11/28/2022]
Abstract
BACKGROUND PIPAC is a novel mode of intraperitoneal drug delivery for patients with peritoneal cancer (PC). PIPAC is a safe treatment with promising oncological results. Therefore, a structured training program is needed to maintain high standards and to guarantee safe implementation. METHODS An international panel of PIPAC experts created by means of a consensus meeting a structured 2-day training course including essential theoretical content and practical exercises. For every module, learning objectives were defined and structured presentations were elaborated. This structured PIPAC training program was then tested in five courses. RESULTS The panel consisted of 12 experts from 11 different centres totalling a cumulative experience of 23 PIPAC courses and 1880 PIPAC procedures. The final program was approved by all members of the panel and includes 12 theoretical units (45 min each) and 6 practical units including dry-lab and live surgeries. The panel finalized and approved 21 structured presentations including the latest evidence on PIPAC and covering all mandatory topics. These were organized in 8 modules with clear learning objectives to be tested by 12 multiple-choice questions. Lastly, a structured quantifiable (Likert scale 1-5) course evaluation was created. The new course was successfully tested in five courses with 85 participants. Mean overall satisfaction with the content was rated at 4.79 (±0.5) with at 4.71 (±0.5) and at 4.61 (±0.7), respectively for course length and the balance between theory and practice. CONCLUSIONS The proposed PIPAC training program contains essential theoretical background and practical training enabling the participants to safely implement PIPAC.
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Affiliation(s)
- Mohammad Alyami
- Department of General Surgery and Surgical Oncology, Oncology Center, King Khalid Hospital, Najran, Saudi Arabia.
| | - Olivia Sgarbura
- Department of Surgical Oncology, Cancer Institute in Montpellier, France
| | - Vladimir Khomyakov
- Moscow Research Oncological Institute n.a. P.A. Herzen, Thoracoabdominal, Moscow, Russian Federation
| | | | | | - Jimmy So
- National University Hospital, Singapore
| | - Juan Torrent
- QTI Comprehensive Cancer Center, Barcelona, Spain
| | | | - David Martin
- Department of Visceral Surgery, Lausanne University Hospital CHUV, University of Lausanne (UNIL), Switzerland
| | | | | | - Marc Pocard
- Université de Paris, UMR 1275 CAP Paris-Tech, F-75010, Paris, France; Service de Chirurgie Digestive et Cancérologie Hôpital Lariboisière, 2 rue Ambroise Paré, F-75010, Paris, France
| | - Martin Hübner
- Department of Visceral Surgery, Lausanne University Hospital CHUV, University of Lausanne (UNIL), Switzerland
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Mowbray NG, Ansell J, Horwood J, Cornish J, Rizkallah P, Parker A, Wall P, Spinelli A, Torkington J. Safe management of surgical smoke in the age of COVID-19. Br J Surg 2020; 107:1406-1413. [PMID: 32363596 PMCID: PMC7267397 DOI: 10.1002/bjs.11679] [Citation(s) in RCA: 137] [Impact Index Per Article: 27.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 04/09/2020] [Indexed: 12/21/2022]
Abstract
Background The COVID-19 global pandemic has resulted in a plethora of guidance and opinion from surgical societies. A controversial area concerns the safety of surgically created smoke and the perceived potential higher risk in laparoscopic surgery. Methods The limited published evidence was analysed in combination with expert opinion. A review was undertaken of the novel coronavirus with regards to its hazards within surgical smoke and the procedures that could mitigate the potential risks to healthcare staff. Results Using existing knowledge of surgical smoke, a theoretical risk of virus transmission exists. Best practice should consider the operating room set-up, patient movement and operating theatre equipment when producing a COVID-19 operating protocol. The choice of energy device can affect the smoke produced, and surgeons should manage the pneumoperitoneum meticulously during laparoscopic surgery. Devices to remove surgical smoke, including extractors, filters and non-filter devices, are discussed in detail. Conclusion There is not enough evidence to quantify the risks of COVID-19 transmission in surgical smoke. However, steps can be undertaken to manage the potential hazards. The advantages of minimally invasive surgery may not need to be sacrificed in the current crisis.
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Affiliation(s)
- N G Mowbray
- Department of General Surgery, University Hospital of Wales, Cardiff, UK
| | - J Ansell
- Department of General Surgery, University Hospital of Wales, Cardiff, UK
| | - J Horwood
- Department of General Surgery, University Hospital of Wales, Cardiff, UK
| | - J Cornish
- Department of General Surgery, University Hospital of Wales, Cardiff, UK
| | - P Rizkallah
- School of Medicine, Cardiff University, Cardiff, UK
| | - A Parker
- School of Medicine, Cardiff University, Cardiff, UK
| | - P Wall
- Isca Healthcare Research, Caerleon, UK
| | - A Spinelli
- Department of General and Minimally Invasive Surgery, Istituto Clinico Humanitas, Rozzano, Italy
| | - J Torkington
- Department of General Surgery, University Hospital of Wales, Cardiff, UK
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Tate SJ, Torkington J. Pressurized intraperitoneal aerosol chemotherapy: a review of the introduction of a new surgical technology using the IDEAL framework. BJS Open 2020; 4:206-215. [PMID: 31957257 PMCID: PMC7093779 DOI: 10.1002/bjs5.50257] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 12/06/2019] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The IDEAL (Idea, Development, Evaluation, Assessment, Long-term study) framework is a scheme of investigation for innovative surgical therapeutic interventions. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a procedure based on laparoscopy to deliver intraperitoneal chemotherapy for peritoneal metastases, introduced in 2011. The aim of this article was to review literature on PIPAC and assess whether development of the technique has followed the IDEAL framework. METHODS A search of MEDLINE and Embase was carried out to identify scientific reports on PIPAC published between January 2000 and February 2019. The studies were categorized according to the IDEAL stages. RESULTS Eighty-six original research papers on PIPAC were identified. There were 23 stage 0, 18 stage 1, 25 stage 2a and six stage 2b studies. Protocol papers for stage 1, 2b and 3 studies, and trial registrations for stage 2a studies, were also identified. The number of centres publishing reports and the number of publications has increased each year. Overall, there has been progression through the IDEAL stages; however, about 60 per cent of clinical reports published in 2018 were stage 1 Idea-type studies. CONCLUSION Since its introduction, studies investigating PIPAC have progressed in line with the IDEAL framework. However, the majority of studies reported recently were stage 0 and 1 studies.
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Affiliation(s)
- S. J. Tate
- Department of General SurgeryUniversity Hospital of WalesCardiffUK
- Division of Cancer and GeneticsCardiff University School of MedicineCardiffUK
| | - J. Torkington
- Department of General SurgeryUniversity Hospital of WalesCardiffUK
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Lee HS, Kim J, Lee EJ, Park SJ, Mun J, Paik H, Oh SH, Park S, Ryu S, Lim W, Song G, Kim HS, Lee JC. Evaluation of a Novel Prototype for Pressurized Intraperitoneal Aerosol Chemotherapy. Cancers (Basel) 2020; 12:cancers12030633. [PMID: 32182896 PMCID: PMC7139407 DOI: 10.3390/cancers12030633] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 03/05/2020] [Accepted: 03/06/2020] [Indexed: 11/16/2022] Open
Abstract
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been suggested as an alternative option for treating peritoneal carcinomatosis (PC). Even with its clinical advantages, the current PIPAC system still suffers from limitations regarding drug distribution area and penetration depth. Thus, we evaluated the new PIPAC system using a novel prototype, and compared its performance to the results from previous studies related with the current MIP® indirectly because the system is currently not available for purchase in the market. The developed prototype includes a syringe pump, a nozzle, and controllers. Drug distribution was conducted using a methylene blue solution for performance test. For penetration depth evaluation, an ex-vivo experiment was performed with porcine tissues in a 3.5 L plastic box. Doxorubicin was sprayed using the novel prototype, and its penetration depth was investigated by confocal laser scanning microscopy. The experiment was repeated with varying nozzle levels from the bottom. The novel prototype sprays approximately 30 μm drug droplets at a flow rate of 30 mL/min with 7 bars of pressure. The average diameter of sprayed region with concentrated dye was 18.5 ± 1.2 cm, which was comparable to that of the current MIP® (about 10 cm). The depth of concentrated diffusion (DCD) did not differ among varying nozzle levels, whereas the depth of maximal diffusion (DMD) decreased with increasing distance between the prototype and the bottom (mean values, 515.3 μm at 2 cm; 437.6 μm at 4 cm; 363.2 μm at 8 cm), which was comparable to those of the current MIP® (about 350–500 μm). We developed a novel prototype that generate small droplets for drug aerosolization and that have a comparably wide sprayed area and depth of penetration to the current MIP® at a lower pressure.
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Affiliation(s)
- Hee Su Lee
- Interdisciplinary Program in Bioengineering, Seoul National University Graduate School, Seoul 08826, Republic of Korea; (H.S.L.); (J.K.)
| | - Junsik Kim
- Interdisciplinary Program in Bioengineering, Seoul National University Graduate School, Seoul 08826, Republic of Korea; (H.S.L.); (J.K.)
| | - Eun Ji Lee
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul 03080, Republic of Korea; (E.J.L.); (S.J.P.); (J.M.); (H.P.); (S.H.O.)
| | - Soo Jin Park
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul 03080, Republic of Korea; (E.J.L.); (S.J.P.); (J.M.); (H.P.); (S.H.O.)
| | - Jaehee Mun
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul 03080, Republic of Korea; (E.J.L.); (S.J.P.); (J.M.); (H.P.); (S.H.O.)
| | - Haerin Paik
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul 03080, Republic of Korea; (E.J.L.); (S.J.P.); (J.M.); (H.P.); (S.H.O.)
| | - Soo Hyun Oh
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul 03080, Republic of Korea; (E.J.L.); (S.J.P.); (J.M.); (H.P.); (S.H.O.)
| | - Sunwoo Park
- Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea; (S.P.); (S.R.); (G.S.)
| | - Soomin Ryu
- Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea; (S.P.); (S.R.); (G.S.)
| | - Whasun Lim
- Department of Food and Nutrition, Kookmin University, Seoul 02707, Republic of Korea;
| | - Gwonhwa Song
- Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea; (S.P.); (S.R.); (G.S.)
| | - Hee Seung Kim
- Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul 03080, Republic of Korea; (E.J.L.); (S.J.P.); (J.M.); (H.P.); (S.H.O.)
- Correspondence: (H.S.K.); (J.C.L.); Tel.: +82-2-740-8573 (J.C.L.)
| | - Jung Chan Lee
- Department of Biomedical Engineering, College of Medicine and Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University, Seoul 03080, Republic of Korea
- Correspondence: (H.S.K.); (J.C.L.); Tel.: +82-2-740-8573 (J.C.L.)
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Pressurized Intraperitoneal Aerosol Chemotherapy, a Palliative Treatment Approach for Patients With Peritoneal Carcinomatosis: Description of Method and Systematic Review of Literature. Dis Colon Rectum 2020; 63:242-255. [PMID: 31914116 DOI: 10.1097/dcr.0000000000001565] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Peritoneal metastases arise in patients with a variety of primary cancers, and are associated with a poor prognosis. Systemic chemotherapy is the mainstay of treatment; however, the morbidity is considerable and the survival benefit is modest. Cytoreductive surgery and heated intraperitoneal chemotherapy is a potentially curative treatment available to a minority of patients; however, most develop recurrent disease. A novel palliative treatment for peritoneal metastases, pressurized intraperitoneal aerosol chemotherapy, has recently been introduced. Pressurized intraperitoneal aerosol chemotherapy utilizes an aerosol of chemotherapy in carbon dioxide gas. It is instilled into the abdomen under pressure via laparoscopic ports. No cytoreduction is performed. Pressurized intraperitoneal aerosol chemotherapy can be repeated at 6-week intervals. Oxaliplatin or cis-platinum and doxorubicin have been used to date. OBJECTIVE This study aims to systematically review and evaluate the method, and the preclinical and early clinical results of pressurized intraperitoneal aerosol chemotherapy. DATA SOURCES Medline and the Cochrane Library were the data sources for the study. STUDY SELECTION Peer-reviewed series of greater than 10 patients, with sufficient patient data, through April 2019, were selected. INTERVENTION Patients with peritoneal metastases underwent pressurized intraperitoneal aerosol chemotherapy. MAIN OUTCOME MEASURES Patient dropout, histologic tumor response, adverse events, and 30-day mortality were the primary outcomes measured. RESULTS A total of 921 patients with peritoneal metastases were brought to the operating room for pressurized intraperitoneal aerosol chemotherapy. The number of pressurized intraperitoneal aerosol chemotherapy treatments administered was as follows: 1 treatment, 862 (94%); 2 treatments, 645 (70%); and 3 treatments, 390 patients (42%). Initial laparoscopic access was not possible in 59 patients (6.4%). Common Terminology Criteria for Adverse Events grade 3 or higher were noted in 13.7% of the patients who, collectively, underwent a total of 2116 treatments. The 30-day mortality was 2.4% (22/921). LIMITATIONS This study was limited by the heterogeneity of reported data and primary tumor types and by the lack of long-term survival data. CONCLUSIONS Early clinical results are encouraging, but tumor-specific, prospective, randomized trials are needed to compare pressurized intraperitoneal aerosol chemotherapy to systemic chemotherapy. This method has yet to be introduced to the United States. It is another therapeutic option for patients with peritoneal metastases and will broaden the patient base for future clinical trials.
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Intraperitoneal aerosolized drug delivery: Technology, recent developments, and future outlook. Adv Drug Deliv Rev 2020; 160:105-114. [PMID: 33132169 DOI: 10.1016/j.addr.2020.10.015] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 09/28/2020] [Accepted: 10/22/2020] [Indexed: 12/11/2022]
Abstract
Current therapies for patients with peritoneal metastases (PM) are only moderately effective. Recently, a novel locoregional treatment method for PM was introduced, consisting of a combination of laparoscopy with intraperitoneal (IP) delivery of anticancer agents as an aerosol. This 'pressurized intraperitoneal aerosol chemotherapy' (PIPAC) may enhance tissue drug penetration by the elevated IP pressure during CO2 capnoperitoneum. Also, repeated PIPAC cycles allow to accurately stage peritoneal disease and verify histological response to treatment. This review provides an overview of the rationale, indications, and currently used technology for therapeutic IP nebulization, and discusses the basic mechanisms governing aerosol particle transport and peritoneal deposition. We discuss early clinical results in patients with advanced, irresectable PM and highlight the potential of electrostatic aerosol precipitation. Finally, we discuss promising novel approaches, including nebulization of nanoparticles and prolonged release formulations.
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Solanki SL, Mukherjee S, Agarwal V, Thota RS, Balakrishnan K, Shah SB, Desai N, Garg R, Ambulkar RP, Bhorkar NM, Patro V, Sinukumar S, Venketeswaran MV, Joshi MP, Chikkalingegowda RH, Gottumukkala V, Owusu-Agyemang P, Saklani AP, Mehta SS, Seshadri RA, Bell JC, Bhatnagar S, Divatia JV. Society of Onco-Anaesthesia and Perioperative Care consensus guidelines for perioperative management of patients for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Indian J Anaesth 2019; 63:972-987. [PMID: 31879421 PMCID: PMC6921319 DOI: 10.4103/ija.ija_765_19] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 10/28/2019] [Accepted: 11/18/2019] [Indexed: 02/07/2023] Open
Abstract
Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for primary peritoneal malignancies or peritoneal spread of malignant neoplasm is being done at many centres worldwide. Perioperative management is challenging with varied haemodynamic and temperature instabilities, and the literature is scarce in many aspects of its perioperative management. There is a need to have coalition of the existing evidence and experts' consensus opinion for better perioperative management. The purpose of this consensus practice guideline is to provide consensus for best practice pattern based on the best available evidence by the expert committee of the Society of Onco-Anaesthesia and Perioperative Care comprising perioperative physicians for better perioperative management of patients of CRS-HIPEC.
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Affiliation(s)
- Sohan Lal Solanki
- Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
- Address for correspondence: Dr. Sohan Lal Solanki, Department of Anaesthesiology, Critical Care and Pain, 2nd Floor, Main Building, Tata Memorial Hospital, Mumbai - 400 012, Maharashtra, India. E-mail:
| | - Sudipta Mukherjee
- Department of Anaesthesiology, Critical Care Medicine and Pain, Tata Medical Center, Kolkata, West Bengal, India
| | - Vandana Agarwal
- Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Raghu S Thota
- Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Kalpana Balakrishnan
- Department of Anaesthesia, Pain and Palliative Care, Cancer Institute, Chennai, Tamil Nadu, India
| | - Shagun Bhatia Shah
- Department of Anaesthesiology and Critical Care, Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India
| | - Neha Desai
- Department of Anaesthesiology, Critical Care Medicine and Pain, Tata Medical Center, Kolkata, West Bengal, India
| | - Rakesh Garg
- Department of Onco-Anaesthesiology and Palliative Medicine, Dr BRAIRCH, All India Institute of Medical Sciences, New Delhi, India
| | - Reshma P Ambulkar
- Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | | | - Viplab Patro
- Department of Anaesthesiology, Critical Care Medicine and Pain, Tata Medical Center, Kolkata, West Bengal, India
| | - Snita Sinukumar
- Surgical Oncology, Jehangir Hospital, Pune, Maharashtra, India
| | | | - Malini P Joshi
- Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | | | - Vijaya Gottumukkala
- Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Pascal Owusu-Agyemang
- Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Avanish P Saklani
- Gastro-Intestinal Services, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Sanket Sharad Mehta
- Department of Surgical Oncology, Saifee Hospital, Mumbai, Maharashtra, India
| | | | - John C Bell
- Anaesthetics and Intensive Care Medicine, Peritoneal Malignancy Institute, Hampshire Hospitals NHS FT, Basingstoke, United Kingdom
| | - Sushma Bhatnagar
- Department of Onco-Anaesthesiology and Palliative Medicine, Dr BRAIRCH, All India Institute of Medical Sciences, New Delhi, India
| | - Jigeeshu V Divatia
- Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
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Tavernier C, Passot G, Vassal O, Allaouchiche B, Decullier E, Bakrin N, Alyami M, Davigo A, Bonnet JM, Louzier V, Paquet C, Glehen O, Kepenekian V. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) might increase the risk of anastomotic leakage compared to HIPEC: an experimental study. Surg Endosc 2019; 34:2939-2946. [PMID: 31456025 DOI: 10.1007/s00464-019-07076-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Accepted: 08/19/2019] [Indexed: 01/06/2023]
Abstract
BACKGROUND Pressurized intraperitoneal aerosol chemotherapy (PIPAC) and hyperthermic intraperitoneal chemotherapy (HIPEC) are technics proposed to treat patients with peritoneal carcinomatosis, in different settings. There is some concern about an over-risk of anastomotic leakage (AL) with PIPAC jeopardizing a combination with cytoreductive surgery. This study used a healthy swine model to compare the postoperative AL rate between PIPAC and HIPEC with digestive resection and to analyze macrocirculation and microcirculation parameters. METHODS Segmental colonic resection with a handsewn anastomosis was performed on 16 healthy pigs; 8 pigs had a PIPAC procedure with 7.5 mg/m2 cisplatin (PIPAC group), and 8 pigs had a closed HIPEC procedure with 70 mg/m2 cisplatin and 42 °C as the target intraperitoneal temperature (HIPEC group). Pigs were kept alive for 8 days, then sacrificed and autopsied to look for AL, which was defined as local abscess or digestive fluid leakage when pressure was applied to the anastomosis. Food intake, weight, and core temperature were monitored postoperatively. Macrocirculation (heart rate, systolic blood pressure) and microcirculation parameters (percentage of perfused vessels, perfused vessels density, DeBacker score) were evaluated intraoperatively at five timepoints. Results were compared between pigs with AL and those without. RESULTS The HIPEC group had no AL, but 3 of 8 pigs (37.5%) had AL in the PIPAC group (p = 0.20). Heart rate and core temperature showed perioperative increases in the HIPEC group. Intraoperatively, heart rate was higher in the HIPEC group at the two last timepoints (123 vs. 93 bpm, p = 0.031, and 110 vs. 85 bpm, p = 0.010, at timepoints 3 and 4, respectively). Other macrocirculatory and microcirculatory parameters showed no significant differences. CONCLUSION In this healthy swine model, PIPAC might have increased AL incidence compared to HIPEC. This potential over-risk did not seem to be related to changes in the microcirculation. PIPAC should probably not be used with digestive resection and should be avoided in cases of perioperative serosal injury.
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Affiliation(s)
- Clément Tavernier
- Department of Digestive Surgery, Lyon-Sud University Hospital, Lyon, France
- EMR 3738, Lyon 1 University, Lyon, France
| | - Guillaume Passot
- Department of Digestive Surgery, Lyon-Sud University Hospital, Lyon, France
- EMR 3738, Lyon 1 University, Lyon, France
| | - Oliva Vassal
- Department of Intensive Care, Lyon-Sud University Hospital, Lyon, France
| | - Bernard Allaouchiche
- Department of Intensive Care, Lyon-Sud University Hospital, Lyon, France
- University of Lyon, VetAgro Sup, APCSe, Marcy l'Étoile, France
| | | | - Naoual Bakrin
- Department of Digestive Surgery, Lyon-Sud University Hospital, Lyon, France
- EMR 3738, Lyon 1 University, Lyon, France
| | - Mohammad Alyami
- Department of Digestive Surgery, Lyon-Sud University Hospital, Lyon, France
- EMR 3738, Lyon 1 University, Lyon, France
| | - Axel Davigo
- Department of Digestive Surgery, Lyon-Sud University Hospital, Lyon, France
- EMR 3738, Lyon 1 University, Lyon, France
| | | | - Vanessa Louzier
- University of Lyon, VetAgro Sup, APCSe, Marcy l'Étoile, France
| | | | - Olivier Glehen
- Department of Digestive Surgery, Lyon-Sud University Hospital, Lyon, France
- EMR 3738, Lyon 1 University, Lyon, France
| | - Vahan Kepenekian
- Department of Digestive Surgery, Lyon-Sud University Hospital, Lyon, France.
- EMR 3738, Lyon 1 University, Lyon, France.
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50
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Jansen-Winkeln B, Thieme R, Haase L, Niebisch S, Pommer C, Lyros O, Zimmer J, Lordick F, Remane Y, Frontini R, Gockel I. [Perioperative safety of intraperitoneal aerosol chemotherapy : Analysis of our first 111 pressurized intraperitoneal aerosol chemotherapy (PIPAC) procedures]. Chirurg 2019; 90:137-145. [PMID: 29947920 DOI: 10.1007/s00104-018-0667-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
BACKGROUND Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new tool in the treatment of patients with peritoneal carcinomatosis. The aerosol containing chemotherapeutic drugs is administered laparoscopically into the abdominal cavity to achieve a local treatment effect. This can be carried out in combination with systemic chemotherapy. MATERIAL AND METHODS Within the framework of a register study, we prospectively documented and evaluated the data of our first 111 PIPAC procedures. The analysis focused on perioperative patient safety and safety at the workplace. Perioperative clinical patient data were analyzed and the platinum concentration in the operating room was checked by wipe samples. RESULTS A total of 62 patients were scheduled for PIPAC and 121 operations were carried out. In 9 procedures a secure access to the abdomen could not be found and 54 patients received 111 PIPAC treatments. One patient died as a result of intestinal perforation, six bowel lesions were treated immediately and healed without further complications. A further patient developed a postoperative renal failure. Otherwise, there was no major complications and no cases of toxicity. CONCLUSION The PIPAC procedure can be used as a supplement to systemic drug treatment for peritoneal carcinomatosis. An exact selection of suitable patients is important. The PIPAC is a low-risk procedure when performed under strict inclusion criteria and under standardized conditions, for the patients and also the surgical staff.
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Affiliation(s)
- B Jansen-Winkeln
- Klinik und Poliklinik für Viszeral‑, Transplantations‑, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, AöR, Liebigstr. 20, 04103, Leipzig, Deutschland.
| | - R Thieme
- Klinik und Poliklinik für Viszeral‑, Transplantations‑, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, AöR, Liebigstr. 20, 04103, Leipzig, Deutschland
| | - L Haase
- Klinik und Poliklinik für Viszeral‑, Transplantations‑, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, AöR, Liebigstr. 20, 04103, Leipzig, Deutschland
| | - S Niebisch
- Klinik und Poliklinik für Viszeral‑, Transplantations‑, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, AöR, Liebigstr. 20, 04103, Leipzig, Deutschland
| | - C Pommer
- Klinik und Poliklinik für Viszeral‑, Transplantations‑, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, AöR, Liebigstr. 20, 04103, Leipzig, Deutschland
| | - O Lyros
- Klinik und Poliklinik für Viszeral‑, Transplantations‑, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, AöR, Liebigstr. 20, 04103, Leipzig, Deutschland
| | - J Zimmer
- Apotheke, Universitätsklinikum Leipzig, AöR, Liebigstr. 20, 04103, Leipzig, Deutschland
| | - F Lordick
- Universitäres Krebszentrum Leipzig (UCCL), Universitätsklinikum Leipzig, AöR, Liebigstr. 20, 04103, Leipzig, Deutschland
| | - Y Remane
- Apotheke, Universitätsklinikum Leipzig, AöR, Liebigstr. 20, 04103, Leipzig, Deutschland
| | - R Frontini
- Apotheke, Universitätsklinikum Leipzig, AöR, Liebigstr. 20, 04103, Leipzig, Deutschland
| | - I Gockel
- Klinik und Poliklinik für Viszeral‑, Transplantations‑, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, AöR, Liebigstr. 20, 04103, Leipzig, Deutschland
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