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Kabagwira J, Fuller RN, Vallejos PA, Sugiono CS, Andrianarijaona VM, Chism JB, O'Leary MP, Molina DC, Langridge W, Senthil M, Wall NR. Amplifying Curcumin's Antitumor Potential: A Heat-Driven Approach for Colorectal Cancer Treatment. Onco Targets Ther 2024; 17:63-78. [PMID: 38313386 PMCID: PMC10838088 DOI: 10.2147/ott.s448024] [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: 11/10/2023] [Accepted: 01/25/2024] [Indexed: 02/06/2024] Open
Abstract
Introduction Peritoneal metastases from colorectal cancer (CRC) present a significant clinical challenge with poor prognosis, often unresponsive to systemic chemotherapy. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment approach for select patients. The use of curcumin, a natural compound with antitumor properties, in HIPEC is of interest due to its lower side effects compared to conventional drugs and potential for increased efficacy through direct delivery to the peritoneal cavity. Methods An in vitro hyperthermic model was developed to simulate clinical HIPEC conditions. Three colon cancer cell lines (SK-CO-1, COLO205, SNU-C1) representing different genetic mutations (p53, KRAS, BRAF) were treated with either curcumin (25 µM) or mitomycin-C (1 µM) for 1, 2, or 3 hours. Post-treatment, cells were incubated at 37°C (normothermia) or 42°C (hyperthermia). Cell viability and proliferation were assessed at 24, 48 and 72 hours post-treatment using Annexin V/PI, MTT assay, trypan blue exclusion, and Hoffman microscopy. Results Hyperthermia significantly enhanced the antitumor efficacy of curcumin, evidenced by a two-fold reduction in cell viability compared to normothermia across all cell lines. In the SNU-C1 cell line, which harbors a p53 mutation, mitomycin-C failed to significantly impact cell viability, unlike curcumin, suggesting mutation-specific differences in treatment response. Discussion The findings indicate that hyperthermia augments the antitumor effects of curcumin in vitro, supporting the hypothesis that curcumin could be a more effective HIPEC agent than traditional drugs like mitomycin-C. Mutation-associated differences in response to treatments were observed, particularly in p53 mutant cells. While further studies are needed, these preliminary results suggest that curcumin in HIPEC could represent a novel therapeutic strategy for CRC patients with peritoneal metastases. This approach may offer improved outcomes with fewer side effects, particularly in genetically distinct CRC subtypes.
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Affiliation(s)
- Janviere Kabagwira
- Department of Basic Science, Division of Biochemistry, Loma Linda University, Loma Linda, CA, USA
- Center for Health Disparities and Molecular Medicine, Loma Linda University, Loma Linda, CA, USA
| | - Ryan N Fuller
- Department of Basic Science, Division of Biochemistry, Loma Linda University, Loma Linda, CA, USA
- Center for Health Disparities and Molecular Medicine, Loma Linda University, Loma Linda, CA, USA
| | - Paul A Vallejos
- Department of Basic Science, Division of Biochemistry, Loma Linda University, Loma Linda, CA, USA
- Center for Health Disparities and Molecular Medicine, Loma Linda University, Loma Linda, CA, USA
| | - Chase S Sugiono
- Department of Basic Science, Division of Biochemistry, Loma Linda University, Loma Linda, CA, USA
| | | | - Jazmine Brianna Chism
- Center for Health Disparities and Molecular Medicine, Loma Linda University, Loma Linda, CA, USA
| | - Michael P O'Leary
- Division of Surgical Oncology, Department of Surgery, Loma Linda University Health, Loma Linda, CA, USA
| | - David Caba Molina
- Division of Surgical Oncology, Department of Surgery, Loma Linda University Health, Loma Linda, CA, USA
| | - William Langridge
- Department of Basic Science, Division of Biochemistry, Loma Linda University, Loma Linda, CA, USA
- Center for Health Disparities and Molecular Medicine, Loma Linda University, Loma Linda, CA, USA
| | - Maheswari Senthil
- Division of Surgical Oncology, Department of Surgery, Irvine Medical Center, University of California, Orange, CA, USA
| | - Nathan R Wall
- Department of Basic Science, Division of Biochemistry, Loma Linda University, Loma Linda, CA, USA
- Center for Health Disparities and Molecular Medicine, Loma Linda University, Loma Linda, CA, USA
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Adam MA, Zhou H, Byrd J, Greenberg AL, Kelly YM, Hall L, Jones HL, Pingpank JF, Lipton ZC, Bartlett DL, Choudry HM. Predicting Severe Complications from Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy: A Data-Driven, Machine Learning Approach to Augment Clinical Judgment. Ann Surg Oncol 2023; 30:5433-5442. [PMID: 37266808 DOI: 10.1245/s10434-023-13657-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 05/02/2023] [Indexed: 06/03/2023]
Abstract
BACKGROUND CRS-HIPEC provides oncologic benefit in well-selected patients with peritoneal carcinomatosis; however, it is a morbid procedure. Decision tools for preoperative patient selection are limited. We developed a risk score to predict severity of 90 day complications for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). PATIENTS AND METHODS Adults who underwent CRS-HIPEC at the University of Pittsburgh Medical Center (March 2001-April 2020) were analyzed as part of this study. Primary endpoint was severe complications within 90 days following CRS-HIPEC, defined using Comprehensive Complication Index (CCI) scores as a dichotomous (determined using restricted cubic splines) and continuous variable. Data were divided into training and test sets. Several machine learning and traditional algorithms were considered. RESULTS For the 1959 CRS-HIPEC procedures included, CCI ranged from 0 to 100 (median 32.0). Adjusted restricted cubic splines model defined severe complications as CCI > 61. A minimum of 20 variables achieved optimal performance of any of the models. Linear regression achieved the highest area under the receiving operator characteristic curve (AUC, 0.74) and outperformed the NSQIP Surgical Risk calculator (AUC 0.80 vs. 0.66). Factors most positively associated with severe complications included peritoneal carcinomatosis index score, symptomatic status, and undergoing pancreatectomy, while American Society of Anesthesiologists 2 class, appendiceal diagnosis, and preoperative albumin were most negatively associated with severe complications. CONCLUSIONS This study refines our ability to predict severe complications within 90 days of discharge from a hospitalization in which CRS-HIPEC was performed. This advancement is timely and relevant given the growing interest in this procedure and may have implications for patient selection, patient and referring provider comfort, and survival.
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Affiliation(s)
| | - Helen Zhou
- Carnegie Mellon University, Pittsburgh, PA, USA
| | | | | | | | - Lauren Hall
- University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Heather L Jones
- University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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Kubi B, Nudotor R, Fackche N, Rowe J, Cloyd JM, Ahmed A, Grotz TE, Fournier K, Dineen S, Veerapong J, Baumgartner JM, Clarke C, Patel SH, Dhar V, Lambert L, Abbott DE, Pokrzywa C, Raoof M, Lee B, Zaidi MY, Maithel SK, Johnston FM, Greer JB. Influence of insurance status on the postoperative outcomes of cytoreductive surgery and HIPEC. J Surg Oncol 2023; 127:706-715. [PMID: 36468401 DOI: 10.1002/jso.27147] [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: 09/23/2022] [Revised: 10/19/2022] [Accepted: 11/09/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is increasingly performed for peritoneal surface malignancies but remains associated with significant morbidity. Scant research is available regarding the impact of insurance status on postoperative outcomes. METHODS Patients undergoing CRS/HIPEC between 2000 and 2017 at 12 participating sites in the US HIPEC Collaborative were identified. Univariate and multivariate analyses were used to compare the baseline characteristics, operative variables, and postoperative outcomes of patients with government, private, or no insurance. RESULTS Among 2268 patients, 699 (30.8%) had government insurance, 1453 (64.0%) had private, and 116 (5.1%) were uninsured. Patients with government insurance were older, more likely to be non-white, and comorbid (p < 0.05). Patients with government (OR: 2.25, CI: 1.50-3.36, p < 0.001) and private (OR: 1.69, CI: 1.15-2.49, p = 0.008) insurance had an increased risk of complications on univariate analysis. There was no independent relationship on multivariate analysis. An American Society of Anesthesiologists score of 3 or 4, peritoneal carcinomatosis index score >15, completeness of cytoreduction score >1, and nonhome discharge were factors independently associated with a postoperative complication. CONCLUSION While there were differences in postoperative outcomes between the three insurance groups on univariate analysis, there was no independent association between insurance status and postoperative complications after CRS/HIPEC.
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Affiliation(s)
- Boateng Kubi
- Department of Surgery, Johns Hopkins University, Baltimore, Maryland, USA
| | - Richard Nudotor
- Department of Surgery, Johns Hopkins University, Baltimore, Maryland, USA
| | - Nadege Fackche
- Department of Surgery, Johns Hopkins University, Baltimore, Maryland, USA
| | - Julian Rowe
- Department of Surgery, Johns Hopkins University, Baltimore, Maryland, USA
| | - Jordan M Cloyd
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Ahmed Ahmed
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Travis E Grotz
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, Minnesota, USA
| | - Keith Fournier
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Sean Dineen
- Department of Gastrointestinal Oncology and Oncologic Sciences, Moffitt Cancer Center, Morsani College of Medicine, Tampa, Florida, USA
| | - Jula Veerapong
- Department of Surgery, Division of Surgical Oncology, University of California, San Diego, California, USA
| | - Joel M Baumgartner
- Department of Surgery, Division of Surgical Oncology, University of California, San Diego, California, USA
| | - Callisia Clarke
- Department of Surgery, Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Sameer H Patel
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Vikrom Dhar
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
| | - Laura Lambert
- Department of Surgery, Division of Surgical Oncology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
| | - Daniel E Abbott
- Department of Surgery, Division of Surgical Oncology, University of Wisconsin, Madison, Wisconsin, USA
| | - Courtney Pokrzywa
- Department of Surgery, Division of Surgical Oncology, University of Wisconsin, Madison, Wisconsin, USA
| | - Mustafa Raoof
- Department of Surgery, Division of Surgical Oncology, City of Hope National Medical Center, Duarte, California, USA
| | - Byrne Lee
- Department of Surgery, Division of Surgical Oncology, City of Hope National Medical Center, Duarte, California, USA
| | - Mohammad Y Zaidi
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
| | - Fabian M Johnston
- Department of Surgery, Johns Hopkins University, Baltimore, Maryland, USA
| | - Jonathan B Greer
- Department of Surgery, Johns Hopkins University, Baltimore, Maryland, USA
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Rouhi AD, Ghanem YK, Hoeltzel GD, Miura JT, Aarons CB, Williams NN, Dumon KR, Karakousis GC. Quality and readability assessment of online patient information on cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. J Surg Oncol 2023; 127:699-705. [PMID: 36394434 DOI: 10.1002/jso.27143] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 10/13/2022] [Accepted: 11/01/2022] [Indexed: 11/19/2022]
Abstract
BACKGROUND AND OBJECTIVES We aim to assess the quality and readability of online information available to patients considering cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). METHODS The top three search engines (Google, Bing, and Yahoo) were searched in March 2022. Websites were classified as academic, hospital-affiliated, foundation/advocacy, commercial, or unspecified. Quality of information was assessed using the JAMA benchmark criteria (0-4) and DISCERN tool (16-80), and the presence of a Health On the Net code (HONcode) seal. Readability was evaluated using the Flesch Reading Ease score. RESULTS Fifty unique websites were included. The average JAMA and DISCERN scores of all websites were 0.72 ± 1.14 and 39.58 ± 13.71, respectively. Foundation/advocacy websites had significantly higher JAMA mean score than commercial (p = 0.044), academic (p < 0.001), and hospital-affiliated websites (p = 0.001). Foundation/advocacy sites had a significantly higher DISCERN mean score than hospital-affiliated (p = 0.035) and academic websites (p = 0.030). The HONcode seal was present in 4 (8%) websites analyzed. Readability was difficult and at the level of college students. CONCLUSIONS The overall quality of patient-oriented online information on CRS-HIPEC is poor and available resources may not be comprehensible to the general public. Patients seeking information on CRS-HIPEC should be directed to sites affiliated with foundation/advocacy organizations.
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Affiliation(s)
- Armaun D Rouhi
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Yazid K Ghanem
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Gerard D Hoeltzel
- Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA
| | - John T Miura
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Cary B Aarons
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Noel N Williams
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Kristoffel R Dumon
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Giorgos C Karakousis
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
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Rubio-López JD, Durán-Martínez M, Moreno-Blázquez A, Rodríguez-Ortiz L, Rufián-Andújar B, Valenzuela-Molina F, Adam ÁC, Sánchez-Hidalgo JM, Rufián-Peña S, Romero-Ruiz A, Briceño-Delgado J, Arjona-Sánchez Á. Intraoperative metabolic changes associated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Langenbecks Arch Surg 2023; 408:34. [PMID: 36648571 PMCID: PMC9845164 DOI: 10.1007/s00423-023-02770-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 12/01/2022] [Indexed: 01/18/2023]
Abstract
BACKGROUND Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) causes considerable hemodynamic, respiratory, and metabolic changes during the perioperative period. OBJECTIVES To evaluate metabolic changes associated with this procedure. Understanding perioperative factors and their association with morbidity may improve the perioperative management of patients undergoing this treatment. METHODS A retrospective review of a prospectively maintained database was performed. All consecutive unselected patients who underwent CRS plus HIPEC between January 2018 and December 2020 (n = 219) were included. RESULTS The mean age was 58 ± 11.7 years and 167 (76.3%) were female. The most frequent histology diagnosis was serous ovarian carcinoma 49.3% (n = 108) and colon carcinoma 36.1% (n = 79). Mean peritoneal cancer index was 14.07 ± 10.47. There were significant variations in pH, lactic acid, sodium, potassium, glycemia, bicarbonate, excess bases, and temperature (p < 0.05) between the pre-HIPEC and post-HIPEC periods. The closed HIPEC technique resulted in higher levels of temperature than the open technique (p < 0.05). Age, potassium level post-HIPEC potassium level, and pre-HIPEC glycemia were identified as prognostic factors for morbidity in multivariate analysis. CONCLUSION The administration of HIPEC after CRS causes significant changes in internal homeostasis. Although the closed technique causes a greater increase in temperature, it is not related to higher morbidity rates. The patient's age, post-HIPEC potassium level, and pre-HIPEC glycemia are predictive factors for morbidity.
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Affiliation(s)
| | - Manuel Durán-Martínez
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital, Menendez Pidal Av. 14004, Cordoba, Spain.
| | - Andrea Moreno-Blázquez
- GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain
| | - Lidia Rodríguez-Ortiz
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital, Menendez Pidal Av. 14004, Cordoba, Spain
- GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain
| | - Blanca Rufián-Andújar
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital, Menendez Pidal Av. 14004, Cordoba, Spain
| | - Francisca Valenzuela-Molina
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital, Menendez Pidal Av. 14004, Cordoba, Spain
| | - Ángela Casado Adam
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital, Menendez Pidal Av. 14004, Cordoba, Spain
- GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain
| | - Juan M Sánchez-Hidalgo
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital, Menendez Pidal Av. 14004, Cordoba, Spain
- GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain
| | - Sebastián Rufián-Peña
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital, Menendez Pidal Av. 14004, Cordoba, Spain
- GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain
| | - Antonio Romero-Ruiz
- GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain
| | - J Briceño-Delgado
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital, Menendez Pidal Av. 14004, Cordoba, Spain
| | - Álvaro Arjona-Sánchez
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital, Menendez Pidal Av. 14004, Cordoba, Spain.
- GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain.
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Vandaele T, Van Slambrouck J, Proesmans V, Clement P, Lambrecht M, Nafteux P, Van Raemdonck D, Ceulemans LJ. Hyperthermic Intrathoracic Chemotherapy (HITHOC) for Pleural Disseminated Thymoma: A Systematic Literature Review. Ann Surg Oncol 2023; 30:543-560. [PMID: 36151429 DOI: 10.1245/s10434-022-12461-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 08/08/2022] [Indexed: 12/13/2022]
Abstract
BACKGROUND Optimal treatment for thymoma with pleural dissemination (TPD) remains unclear. Extended radical resection is the cornerstone for local treatment but the need for pleuro-pneumonectomy is debatable. Cytoreductive surgery with intraoperative hyperthermic intrathoracic chemotherapy (HITHOC) provides an alternative strategy to reduce tumor load and prevent pleural recurrence. OBJECTIVE The aim of this review was to provide an overview of current literature regarding HITHOC for TPD. METHODS A systematic literature review (PRISMA) was performed in the EMBASE, MEDLINE, Cochrane and Web of Science databases, resulting in 154 papers selected for screening (PROSPERO: CRD42020208242). Title, abstract, and full-text screening resulted in 13 papers subjected to structured data extraction and methodological quality assessment. One additional case from our department was included. Inclusion criteria were original research reporting on patients diagnosed with TPD; oncological outcome reporting; intraoperative HITHOC; and papers written in English, Dutch or German. Methodological quality was assessed using the Risk-of-Bias (RoB)-2 Tool and the Newcastle-Ottawa scale. RESULTS HITHOC for TPD was reported in 171 cases. HITHOC-related mortality was absent and morbidity was reported in three cases. Intrathoracic perfusion of a platinum-derivative, often combined with other chemotherapeutic drugs at >40°C for 60 min or longer was always used. Post-HITHOC recurrence was reported in 37/120 cases (31%). In patients with a minimal 1-year follow-up, average time to recurrence was 68.5 months. CONCLUSION Combining cytoreductive surgery and HITHOC is feasible and safe for TPD. The strong heterogeneity in the literature impedes proper outcome analysis. More research is needed to better understand the additional benefit of HITHOC in the TPD setting.
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Affiliation(s)
- Tom Vandaele
- Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium.,Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium
| | - Jan Van Slambrouck
- Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium.,Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium
| | - Viktor Proesmans
- Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Paul Clement
- Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, KU Leuven, Leuven, Belgium.,Laboratory of Experimental Oncology, University Hospitals Leuven, Leuven, Belgium
| | - Maarten Lambrecht
- Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, KU Leuven, Leuven, Belgium.,Laboratory of Experimental Radiotherapy, University Hospitals Leuven, Leuven, Belgium
| | - Philippe Nafteux
- Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium.,Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium
| | - Dirk Van Raemdonck
- Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium.,Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium
| | - Laurens J Ceulemans
- Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium. .,Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium.
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Park EJ, Ahn J, Abuzar SM, Park KS, Hwang SJ, Baik SH. Pharmacologic Effects of Oxaliplatin Instability in Chloride-Containing Carrier Fluids on the Hyperthermic Intraperitoneal Chemotherapy to Treat Colorectal Cancer In Vitro and In Vivo. Ann Surg Oncol 2022; 29:8583-8592. [DOI: 10.1245/s10434-022-12358-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 07/12/2022] [Indexed: 01/05/2023]
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Badran A, Azzam A, Noorelahi M, Alshamsan B, Alkhaldi S, Naguib R, Amin T. Outcomes of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with or without intraoperative radiotherapy for peritoneal carcinomatosis in elderly patients. SURGERY OPEN DIGESTIVE ADVANCE 2022; 6:100051. [DOI: 10.1016/j.soda.2022.100051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/02/2025]
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Parikh MS, Johnson P, Romanes JP, Freitag HE, Spring ME, Garcia-Henriquez N, Monson JRT. Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases: A Systematic Review. Dis Colon Rectum 2022; 65:16-26. [PMID: 34636780 DOI: 10.1097/dcr.0000000000002315] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Combined treatment modality of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is emerging as an alternative option for colorectal peritoneal metastases, but there is ambiguity regarding patient selection, treatment protocols, and efficacy. OBJECTIVE To elaborate on the patient characteristics, hyperthermic intraperitoneal chemotherapy protocol and health outcomes in colorectal peritoneal metastases patients undergoing a combination of hyperthermic intraperitoneal chemotherapy and cytoreductive surgery and provide guidance for future studies. DATA SOURCES A Medline search for English language studies published between 2004 and 2019. STUDY SELECTION Medical subject headings and key terms, including: hyperthermic intraperitoneal chemotherapy, colorectal peritoneal metastases, colorectal cancer and combinations thereof as per guidelines. MAIN OUTCOME MEASURES Overall survival, disease-free survival, and morbidity and mortality rates. RESULTS Of the 26 included studies, 42% were published between 2016 and 2019. More than half of the studies were retrospective in nature and conducted in tertiary specialized centers outside of the United States. The median age range was 44 to 62 years. Mitomycin C-based therapy was seen in 50% of studies. Mean weighted median disease-free survival for 11 studies was 15 months (9 to 36 months). Median OS ranged from 12 to 63 months, with an average of 33.6 months among 20 studies. Overall morbidity varied from 11% to 56%, with a weighted mean of 29% in 18 studies. Mortality ranged from 0 to 34%, with a weighted mean of 4% in 15 studies. LIMITATIONS Despite careful study selection, variability in methodology of the included studies can limit review findings. CONCLUSION Due to study heterogeneity, and a recent large, randomized trial showing no overall benefit, use of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in colorectal peritoneal metastases patients is highly controversial. Further standardized controlled studies can help uniformly define and build consensus among the medical community on patient eligibility and the optimal hyperthermic intraperitoneal chemotherapy techniques. PROSPERO Registered on March 3, 2020, CRD42020146942.
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Affiliation(s)
- Manasi S Parikh
- Center for Colon and Rectal Cancer, Surgical Health Outcomes Consortium, AdventHealth Orlando, Orlando, Florida
| | - Paul Johnson
- Center for Colon and Rectal Cancer, Surgical Health Outcomes Consortium, AdventHealth Orlando, Orlando, Florida
| | | | - Harvey E Freitag
- Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Mary E Spring
- Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, Florida
| | - Norbert Garcia-Henriquez
- Center for Colon and Rectal Cancer, Surgical Health Outcomes Consortium, AdventHealth Orlando, Orlando, Florida
| | - John R T Monson
- Center for Colon and Rectal Cancer, Surgical Health Outcomes Consortium, AdventHealth Orlando, Orlando, Florida
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10
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Sand O, Andersson M, Arakelian E, Cashin P, Semenas E, Graf W. Severe pulmonary complications after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy are common and contribute to decreased overall survival. PLoS One 2021; 16:e0261852. [PMID: 34962947 PMCID: PMC8714091 DOI: 10.1371/journal.pone.0261852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 12/11/2021] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Extensive abdominal surgery is associated with the risk of postoperative pulmonary complications. This study aims to explore the incidence and risk factors for developing postoperative pulmonary complications after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and to analyze how these complications affect overall survival. METHODS Data were collected on 417 patients undergoing surgery between 2007 and2017 at Uppsala University Hospital, Sweden. Postoperative pulmonary complications were graded according to the Clavien-Dindo classification system where Grade ≥ 3 was considered a severe complication. A logistic regression analysis was used to analyze risk factors for postoperative pulmonary complications and a Cox proportional hazards model to assess impact on survival. RESULTS Seventy-two patients (17%) developed severe postoperative pulmonary complications. Risk factors were full thickness diaphragmatic injury and/or diaphragmatic resection [OR 5.393, 95% CI 2.924-9.948, p = < 0.001]. Severe postoperative pulmonary complications, in combination with non-pulmonary complications, contributed to decreased overall survival [HR 2.285, 95% CI 1.232-4.241, p = 0.009]. CONCLUSIONS Severe postoperative pulmonary complications were common and contributed to decreased overall survival. Full thickness diaphragmatic injury and/or diaphragmatic resection were the main risk factors. This finding emphasizes the need for further research on the mechanisms behind pulmonary complications and their association with mortality.
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Affiliation(s)
- Olivia Sand
- Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden
- * E-mail:
| | - Mikael Andersson
- Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden
| | - Erebouni Arakelian
- Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden
| | - Peter Cashin
- Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden
| | - Egidijus Semenas
- Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden
| | - Wilhelm Graf
- Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden
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11
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Ba M, Cui S, Long H, Gong Y, Wu Y, Lin K, Tu Y, Zhang B, Wu W. Safety and Effectiveness of High-Precision Hyperthermic Intraperitoneal Perfusion Chemotherapy in Peritoneal Carcinomatosis: A Real-World Study. Front Oncol 2021; 11:674915. [PMID: 34422631 PMCID: PMC8378327 DOI: 10.3389/fonc.2021.674915] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Accepted: 07/12/2021] [Indexed: 11/19/2022] Open
Abstract
Background Hyperthermic intraperitoneal chemotherapy (HIPEC) has been reported to effectively control peritoneal carcinomatosis (PC) in various patient populations, but there is a lack of real-world data. This study aimed to examine the safety and effectiveness of HIPEC in patients with PC in a real-world setting. Methods This was a retrospective study of patients with PC treated with the high-precision BR-TRG-I type HIPEC device between December 2006 and December 2016. Vital signs during HIPEC and adverse events were recorded. Effectiveness was evaluated by total objective remission rate (ORR), which was based on ascites’ remission 4 weeks after HIPEC. Results A total of 1,200 patients were included. There were 518 males and 682 females, with a mean age of 58.6 ± 6.5 years (range, 32–76 years). Among the patients, 93.6% of the patients (1123/1200) successfully received the three sessions of HIPEC, 158 had massive ascites. The changes of vital signs during HIPEC were within acceptable ranges, and patients only had a transient fever and abdominal distension. Regarding the HIPEC-related complications, hemorrhage was observed in seven (0.6%) patients, anastomotic leakage in four (0.5%), and intestinal obstruction in eight (0.7%). Nine (0.8%, 9/1200) patients had CTCAE grade IV bone marrow suppression, and three (0.3%, 3/1200) patients had severe renal failure (SRF), which were considered to be drug-related. The ORR of malignant ascites was 95.6% (151/158). Conclusion This real-world study strongly suggests that HIPEC was safe in treating PC patients with a low rate of adverse events and leads to benefits in PC patients with massive malignant ascites.
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Affiliation(s)
- Mingchen Ba
- Intracelom Hyperthermic Perfusion Therapy Center, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Shuzhong Cui
- Intracelom Hyperthermic Perfusion Therapy Center, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Hui Long
- Department of Pharmacy, Guangzhou Dermatology Institute, Guangzhou, China
| | - Yuanfeng Gong
- Intracelom Hyperthermic Perfusion Therapy Center, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Yinbing Wu
- Intracelom Hyperthermic Perfusion Therapy Center, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Kunpeng Lin
- Intracelom Hyperthermic Perfusion Therapy Center, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Yinuo Tu
- Intracelom Hyperthermic Perfusion Therapy Center, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Bohuo Zhang
- Intracelom Hyperthermic Perfusion Therapy Center, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Wanbo Wu
- Intracelom Hyperthermic Perfusion Therapy Center, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
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12
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Preclinical In Vivo-Models to Investigate HIPEC; Current Methodologies and Challenges. Cancers (Basel) 2021; 13:cancers13143430. [PMID: 34298644 PMCID: PMC8303745 DOI: 10.3390/cancers13143430] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 07/01/2021] [Accepted: 07/06/2021] [Indexed: 12/23/2022] Open
Abstract
Simple Summary Efficacy of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) depends on patient selection, tumor type, delivery technique, and treatment parameters such as temperature, carrier solution, type of drug, dosage, volume, and treatment duration. Preclinical research offers a powerful tool to investigate the impact of these parameters and to assists in designing potentially more effective treatment protocols and clinical trials. This study aims to review the objectives, methods, and clinical relevance of in vivo preclinical HIPEC studies found in the literature. In total, 60 articles were included in this study. The selected articles were screened on the HIPEC parameters. Recommendations are provided and possible pitfalls are discussed on the choice of type of animal and tumor model per stratified parameters and study goal. The guidelines presented in this paper can improve the clinical relevance and impact of future in vivo HIPEC experiments. Abstract Hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment modality for patients with peritoneal metastasis (PM) of various origins which aims for cure in combination with cytoreductive surgery (CRS). Efficacy of CRS-HIPEC depends on patient selection, tumor type, delivery technique, and treatment parameters such as temperature, carrier solution, type of drug, dosage, volume, and treatment duration. Preclinical research offers a powerful tool to investigate the impact of these parameters and to assist in designing potentially more effective treatment protocols and clinical trials. The different methodologies for peritoneal disease and HIPEC are variable. This study aims to review the objectives, methods, and clinical relevance of in vivo preclinical HIPEC studies found in the literature. In this review, recommendations are provided and possible pitfalls are discussed on the choice of type of animal and tumor model per stratified parameters and study goal. The guidelines presented in this paper can improve the clinical relevance and impact of future in vivo HIPEC experiments.
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13
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The Characteristics of 206 Long-Term Survivors with Peritoneal Metastases from Colorectal Cancer Treated with Curative Intent Surgery: A Multi-Center Cohort from PSOGI. Cancers (Basel) 2021; 13:cancers13122964. [PMID: 34199234 PMCID: PMC8231850 DOI: 10.3390/cancers13122964] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/01/2021] [Accepted: 06/09/2021] [Indexed: 01/04/2023] Open
Abstract
Simple Summary Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy improves survival in selected patients with peritoneal metastases from colorectal cancer (CRC). However, the characteristics of long-term survivors are not well documented. This study set out to investigate the patient characteristics associated with the long-term survival of peritoneal metastases from CRC. We retrospectively analyzed 206 long-term survivors who underwent CRS for peritoneal metastases from CRC. We found that most long-term survivors showed low peritoneal cancer index (PCI), low PCI of small bowel subsets, and complete cytoreduction (CC-0), while some exhibited characteristics considered associated with poor prognosis. Abstract Background: We conducted this study to review the patient characteristics associated with long-term survival in patients with peritoneal metastases from colorectal cancer who underwent cytoreductive surgery (CRS). Methods: We retrospectively investigated patients with peritoneal metastases from CRC treated with curative intent surgery with or without hyperthermic intraperitoneal chemotherapy at 13 institutions worldwide between January 1985 and April 2015 and survived longer than five years after the first CRS for peritoneal metastases. Clinical and oncological features and therapeutic parameters were described and analyzed. Results: Two hundred six long-term survivors were available for study. The median peritoneal cancer index (PCI) of this cohort was 4 (interquartile range (IQR), 2–7), and the median score of the small bowel regions of the PCI (SB-PCI) was 0 (IQR, 0–2). Complete cytoreduction (CC-0) was achieved in 180 (87.4%) patients. Recurrence was observed in 122 (59.2%) patients at a median of 1.8 (IQR, 1.2–2.6) years. Conclusions: While most long-term survivors showed low PCI/SB-PCI and CCR-0, some had characteristics considered associated with poor prognosis. Curative intent treatments may be considered in well-informed and fit patients showing negative factors affecting survival outcome.
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14
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Angeles MA, Martínez-Gómez C, Del M, Migliorelli F, Daix M, Provendier A, Picard M, Ruiz J, Chantalat E, Leray H, Martinez A, Gladieff L, Ferron G. Risk factors for gastric perforation after cytoreductive surgery in patients with peritoneal carcinomatosis: Splenectomy and increased body mass index. PLoS One 2021; 16:e0248205. [PMID: 33661999 PMCID: PMC7932550 DOI: 10.1371/journal.pone.0248205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Accepted: 02/22/2021] [Indexed: 11/18/2022] Open
Abstract
Background Gastric perforation after cytoreductive surgery (CRS) is an infrequent complication. There is lack of evidence regarding the risk factors for this postoperative complication. The aim of this study was to assess the prevalence of postoperative gastric perforation in patients undergoing CRS for peritoneal carcinomatosis (PC) and to evaluate risk factors predisposing to this complication. Methods We designed a unicentric retrospective study to identify all patients who underwent an open upfront or interval CRS after a primary diagnosis of PC of different origins between March 2007 and December 2018 at a French Comprehensive Cancer Center. The main outcome was the occurrence of postoperative gastric perforation. Results Five hundred thirty-three patients underwent a CRS for PC during the study period and 13 (2.4%) presented a postoperative gastric perforation with a mortality rate of 23% (3/13). Neoadjuvant chemotherapy was administered in 283 (53.1%) patients and 99 (18.6%) received hyperthermic intraperitoneal chemotherapy (HIPEC). In the univariate analysis, body mass index (BMI), peritoneal cancer index, splenectomy, distal pancreatectomy, and histology were significantly associated with postoperative gastric perforation. After multivariate analysis, BMI (OR [95%CI] = 1.13 [1.05–1.22], p = 0.002) and splenectomy (OR [95%CI] = 26.65 [1.39–509.67], p = 0.029) remained significantly related to the primary outcome. Conclusions Gastric perforation after CRS is a rare event with a high rate of mortality. While splenectomy and increased BMI are risk factors associated with this complication, HIPEC does not seem to be related. Gastric perforation is probably an ischemic complication due to a multifactorial process. Preventive measures such as preservation of the gastroepiploic arcade and prophylactic suture of the greater gastric curvature require further assessment.
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Affiliation(s)
- Martina Aida Angeles
- Department of Surgical Oncology, Institut Claudius Regaud – Institut Universitaire du Cancer de Toulouse – Oncopole, Toulouse, France
| | - Carlos Martínez-Gómez
- Department of Surgical Oncology, Institut Claudius Regaud – Institut Universitaire du Cancer de Toulouse – Oncopole, Toulouse, France
- INSERM CRCT Team 1, Tumor Immunology and Immunotherapy, Toulouse, France
| | - Mathilde Del
- Department of Surgical Oncology, Institut Claudius Regaud – Institut Universitaire du Cancer de Toulouse – Oncopole, Toulouse, France
| | - Federico Migliorelli
- Department of Gynecology and Obstetrics, Centre Hospitalier Intercommunal des Vallées de l’Ariège, St Jean de Verges, France
| | - Manon Daix
- Department of Surgical Oncology, Institut Claudius Regaud – Institut Universitaire du Cancer de Toulouse – Oncopole, Toulouse, France
| | - Anaïs Provendier
- Department of Surgical Oncology, Institut Claudius Regaud – Institut Universitaire du Cancer de Toulouse – Oncopole, Toulouse, France
| | - Muriel Picard
- Intensive Care Unit, Institut Claudius Regaud – Institut Universitaire du Cancer de Toulouse – Oncopole, Toulouse, France
| | - Jean Ruiz
- Intensive Care Unit, Institut Claudius Regaud – Institut Universitaire du Cancer de Toulouse – Oncopole, Toulouse, France
| | - Elodie Chantalat
- Department of Surgical Oncology, Institut Claudius Regaud – Institut Universitaire du Cancer de Toulouse – Oncopole, Toulouse, France
| | - Hélène Leray
- Department of Surgical Oncology, Institut Claudius Regaud – Institut Universitaire du Cancer de Toulouse – Oncopole, Toulouse, France
| | - Alejandra Martinez
- Department of Surgical Oncology, Institut Claudius Regaud – Institut Universitaire du Cancer de Toulouse – Oncopole, Toulouse, France
- INSERM CRCT Team 1, Tumor Immunology and Immunotherapy, Toulouse, France
| | - Laurence Gladieff
- Department of Medical Oncology, Institut Claudius Regaud – Institut Universitaire du Cancer de Toulouse – Oncopole, Toulouse, France
| | - Gwénaël Ferron
- Department of Surgical Oncology, Institut Claudius Regaud – Institut Universitaire du Cancer de Toulouse – Oncopole, Toulouse, France
- INSERM CRCT Team 19, ONCOSARC – Oncogenesis of sarcomas, Toulouse, France
- * E-mail:
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15
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Turgeon MK, Gamboa AC, Lee RM, Zaidi MY, Kimbrough C, Grotz T, Fournier K, Powers B, Dineen S, Veerapong J, Clarke C, Mogal H, Patel SH, Lambert L, Ronnekleiv-Kelly S, Raoof M, Fackche N, Greer JB, Staley CA, Cloyd JM, Maithel SK, Winer JH. The Intersection of Age and Tumor Biology with Postoperative Outcomes in Patients After Cytoreductive Surgery and HIPEC. Ann Surg Oncol 2020; 27:4894-4907. [PMID: 32378087 PMCID: PMC7644621 DOI: 10.1245/s10434-020-08538-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Indexed: 11/18/2022]
Abstract
BACKGROUND Patient age is a significant factor in preoperative selection for major abdominal surgery. The association of age, tumor biology, and postoperative outcomes in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) remains ill-defined. METHODS Retrospective analysis was performed for patients who underwent a CCR0/1 CRS/HIPEC from the US HIPEC Collaborative Database (2000-2017). Age was categorized into < 65 or ≥ 65 years. Primary outcome was postoperative major complications. Secondary outcomes were non-home discharge (NHD) and readmission. Analysis was stratified by disease histology: non-invasive (appendiceal LAMN/HAMN), and invasive (appendiceal/colorectal adenocarcinoma). RESULTS Of 1090 patients identified, 22% were ≥ 65 (n = 240), 59% were female (n = 646), 25% had non-invasive (n = 276) and 51% had invasive (n = 555) histology. Median PCI was 13 (IQR 7-20). Patients ≥ 65 had a higher rate of major complications (37 vs 26%, p = 0.02), NHD (12 vs 5%, p < 0.01), and readmission (28 vs 22%, p = 0.05), compared to those < 65. For non-invasive histology, age ≥ 65 was not associated with major complications or NHD on multivariable analysis. For invasive histology, when accounting for PCI and CCR, age ≥ 65 was associated with major complications (OR 2.04, 95% CI 1.16-3.59, p = 0.01). When accounting for major complications, age ≥ 65 was associated with NHD (OR 2.54, 95% CI 1.08-5.98, p = 0.03). Age ≥ 65 was not predictive of readmission for any histology when accounting for major complications. CONCLUSIONS Age ≥ 65 years is an independent predictor for postoperative major complications and non-home discharge for invasive histology, but not non-invasive histology. These data inform preoperative counseling, risk stratification, and early discharge planning.
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Affiliation(s)
- Michael K Turgeon
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Adriana C Gamboa
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Rachel M Lee
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Mohammad Y Zaidi
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Charles Kimbrough
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Travis Grotz
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA
| | - Keith Fournier
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Benjamin Powers
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA
- Department of Oncologic Sciences, Morsani College of Medicine, Tampa, FL, USA
| | - Sean Dineen
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA
- Department of Oncologic Sciences, Morsani College of Medicine, Tampa, FL, USA
| | - Jula Veerapong
- Division of Surgical Oncology, Department of Surgery, University of California, San Diego, CA, USA
| | - Callisia Clarke
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Harveshp Mogal
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Sameer H Patel
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Laura Lambert
- Division of Surgical Oncology, Department of Surgery, University of Massachusetts Medical School, Worcester, MA, USA
| | - Sean Ronnekleiv-Kelly
- Division of Surgical Oncology, Department of Surgery, University of Wisconsin, Madison, WI, USA
| | - Mustafa Raoof
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA
| | - Nadege Fackche
- Department of Surgery, Johns Hopkins University, Baltimore, MD, USA
| | - Jonathan B Greer
- Department of Surgery, Johns Hopkins University, Baltimore, MD, USA
| | - Charles A Staley
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Jordan M Cloyd
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Joshua H Winer
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
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16
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Überrück L, Nadiradze G, Yurttas C, Königsrainer A, Königsrainer I, Horvath P. In-Hospital Mortality and Complication Rates According to Health Insurance Data in Patients Undergoing Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface Malignancies in Germany. Ann Surg Oncol 2020; 28:3823-3830. [PMID: 33165722 PMCID: PMC8184558 DOI: 10.1245/s10434-020-09301-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Accepted: 10/15/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND Morbidity and in-hospital mortality rates of patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in Germany are not known. METHODS From 2009 to 2018 all patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in Germany were retrospectively analyzed regarding morbidity and in-hospital mortality rates according to nationwide hospital billing data based on diagnosis-related groups (DRG). The "failure to rescue" (FTR) index, characterizing patients who died after severe but potentially manageable complications, was calculated. RESULTS In total, 8463 patients were included and analyzed. Female sex predominated (1.5:1). Colonic origin of peritoneal metastasis was highest throughout all years, reaching its highest level in 2017 (55%; n = 563) and its lowest level in 2012 (40%; n = 349). Median length of hospital stay reached its maximum in 2017 at 23.9 days and its minimum in 2010 at 22.0 days. Analysis of the total FTR index showed a noticeable improvement over the years, reaching its lowest values in 2017 (9.8%) and 2018 (8.8%). The FTR index for sepsis, peritonitis, and pulmonary complications significantly improved over time. Of the 8463 included patients, 290 died during hospital stay, reflecting an in-hospital mortality rate of 3.4%. CONCLUSION In-hospital mortality after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is reasonably low compared with other surgical procedures. The improvement in the FTR index reflects efforts to centralize treatment at specialized high-volume centers.
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Affiliation(s)
- Lisa Überrück
- Department of General, Visceral and Transplant Surgery, Comprehensive Cancer Center, University of Tübingen, Tübingen, Germany.,National Center for Pleura and Peritoneum, University of Tübingen, Tübingen, Germany
| | - Giorgi Nadiradze
- Department of General, Visceral and Transplant Surgery, Comprehensive Cancer Center, University of Tübingen, Tübingen, Germany.,National Center for Pleura and Peritoneum, University of Tübingen, Tübingen, Germany
| | - Can Yurttas
- Department of General, Visceral and Transplant Surgery, Comprehensive Cancer Center, University of Tübingen, Tübingen, Germany.,National Center for Pleura and Peritoneum, University of Tübingen, Tübingen, Germany
| | - Alfred Königsrainer
- Department of General, Visceral and Transplant Surgery, Comprehensive Cancer Center, University of Tübingen, Tübingen, Germany.,National Center for Pleura and Peritoneum, University of Tübingen, Tübingen, Germany
| | - Ingmar Königsrainer
- Department of General, Visceral and Thoracic Surgery, Feldkirch Academic Teaching Hospital, Feldkirch, Austria
| | - Philipp Horvath
- Department of General, Visceral and Transplant Surgery, Comprehensive Cancer Center, University of Tübingen, Tübingen, Germany. .,National Center for Pleura and Peritoneum, University of Tübingen, Tübingen, Germany.
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17
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Kubi B, Gunn J, Fackche N, Cloyd JM, Abdel-Misih S, Grotz T, Leiting J, Fournier K, Lee AJ, Dineen S, Dessureault S, Veerapong J, Baumgartner JM, Clarke C, Mogal H, Patel SH, Dhar V, Lambert L, Hendrix RJ, Abbott DE, Pokrzywa C, Raoof M, Lee B, Maithel SK, Staley CA, Johnston FM, Wang NY, Greer JB. Predictors of Non-home Discharge after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy. J Surg Res 2020; 255:475-485. [PMID: 32622162 DOI: 10.1016/j.jss.2020.05.085] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Revised: 05/11/2020] [Accepted: 05/24/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND Using a national database of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) recipients, we sought to determine risk factors for nonhome discharge (NHD) in a cohort of patients. METHODS Patients undergoing CRS/HIPEC at any one of 12 participating sites between 2000 and 2017 were identified. Univariate analysis was used to compare the characteristics, operative variables, and postoperative complications of patients discharged home and patients with NHD. Multivariate logistic regression was used to identify independent risk factors of NHD. RESULTS The cohort included 1593 patients, of which 70 (4.4%) had an NHD. The median [range] peritoneal cancer index in our cohort was 14 [0-39]. Significant predictors of NHD identified in our regression analysis were advanced age (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.05-1.12; P < 0.001), an American Society of Anesthesiologists (ASA) score of 4 (OR, 2.87; 95% CI, 1.21-6.83; P = 0.017), appendiceal histology (OR, 3.14; 95% CI 1.57-6.28; P = 0.001), smoking history (OR, 3.22; 95% CI, 1.70-6.12; P < 0.001), postoperative total parenteral nutrition (OR, 3.14; 95% CI, 1.70-5.81; P < 0.001), respiratory complications (OR, 7.40; 95% CI, 3.36-16.31; P < 0.001), wound site infections (OR, 3.12; 95% CI, 1.58-6.17; P = 0.001), preoperative hemoglobin (OR, 0.81; 95% CI, 0.70-0.94; P = 0.006), and total number of complications (OR, 1.41; 95% CI, 1.16-1.73; P < 0.001). CONCLUSIONS Early identification of patients at high risk for NHD after CRS/HIPEC is key for preoperative and postoperative counseling and resource allocation, as well as minimizing hospital-acquired conditions and associated health care costs.
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Affiliation(s)
- Boateng Kubi
- Department of Surgery, Johns Hopkins University, Baltimore, Maryland
| | - Jonathan Gunn
- Department of Surgery, Johns Hopkins University, Baltimore, Maryland
| | - Nadege Fackche
- Department of Surgery, Johns Hopkins University, Baltimore, Maryland
| | - Jordan M Cloyd
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Sherif Abdel-Misih
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Travis Grotz
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, Minnesota
| | - Jennifer Leiting
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, Minnesota
| | - Keith Fournier
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Andrew J Lee
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Sean Dineen
- Department of Gastrointestinal Oncology, Department of Oncologic Sciences, Moffitt Cancer Center, Morsani College of Medicine, Tampa, Florida
| | - Sophie Dessureault
- Department of Gastrointestinal Oncology, Department of Oncologic Sciences, Moffitt Cancer Center, Morsani College of Medicine, Tampa, Florida
| | - Jula Veerapong
- Division of Surgical Oncology, Department of Surgery, University of California- San Diego, San Diego, California
| | - Joel M Baumgartner
- Division of Surgical Oncology, Department of Surgery, University of California- San Diego, San Diego, California
| | - Callisia Clarke
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Harveshp Mogal
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Sameer H Patel
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Vikrom Dhar
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Laura Lambert
- Division of Surgical Oncology, Department of Surgery, University of Massachusetts Medical School, Worcester, Massachusetts
| | - Ryan J Hendrix
- Division of Surgical Oncology, Department of Surgery, University of Massachusetts Medical School, Worcester, Massachusetts
| | - Daniel E Abbott
- Division of Surgical Oncology, Department of Surgery, University of Wisconsin, Madison, Wisconsin
| | - Courtney Pokrzywa
- Division of Surgical Oncology, Department of Surgery, University of Wisconsin, Madison, Wisconsin
| | - Mustafa Raoof
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, Duarte, California
| | - Byrne Lee
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, Duarte, California
| | - Shishir K Maithel
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Charles A Staley
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Fabian M Johnston
- Department of Surgery, Johns Hopkins University, Baltimore, Maryland
| | - Nae-Yuh Wang
- Department of Medicine, Johns Hopkins University, Baltimore, Maryland; Department of Biostatistics and Epidemiology, Bloomberg School of Public Health, Baltimore, Maryland
| | - Jonathan B Greer
- Department of Surgery, Johns Hopkins University, Baltimore, Maryland.
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18
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Ba M, Chen C, Long H, Gong Y, Wu Y, Lin K, Tu Y, Zhang B, Wu W. Cytoreductive surgery and HIPEC for malignant ascites from colorectal cancer - a randomized study. Medicine (Baltimore) 2020; 99:e21546. [PMID: 32872001 PMCID: PMC7437737 DOI: 10.1097/md.0000000000021546] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
INTRODUCTION The efficacy of different timings of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in controlling malignant ascites caused by peritoneal carcinomatosis of colorectal cancer (CRC) is not well defined. The study aims to investigate the clinical efficacy and safety of different timings of CRS with HIPEC for malignant ascites caused by peritoneal carcinomatosis from CRC. MATERIALS AND METHODS This was a preliminary randomized controlled study performed at the Intracelom Hyperthermic Perfusion Therapy Center of the Cancer Hospital of Guangzhou Medical University (China) from December 2008 to December 2016. The patients were randomized to: CRS, followed by HIPEC (CRS+HIPEC; n = 14), and ultrasound-guided HIPEC, followed by CRS 1 to 2 weeks later (HIPEC+ delayed cytoreductive surgery (dCRS) group, n = 14). The endpoints were complete remission rate of ascites, successful complete CRS rate, and overall survival. RESULTS Malignant ascites in all patients showed complete remission; the total effective rate was 100%. Complete CRS was not feasible in any patient. The median follow-up of the 2 groups was 41.9 and 42.3 months in the CRS+HIPEC and HIPEC+dCRS groups, respectively. Overall survival was 14.5 (95%CI: 7-19 months) and 14.3 months (95%CI: 4-21 months) (P > .05). The adverse effects of HIPEC were manageable. CONCLUSIONS CRS+HIPEC and HIPEC+dCRS have the same efficacy in controlling malignant ascites caused by CRC and peritoneal carcinomatosis. The timing of CRS and HIPEC does not prolong the survival of patients with peritoneal carcinomatosis from CRC, even when a complete CRS is not feasible.
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Affiliation(s)
- Mingchen Ba
- Intracelom Hyperthermic Perfusion Therapy Center, Affiliated Cancer Hospital & Institute of Guangzhou Medical University
| | - Cheng Chen
- Intracelom Hyperthermic Perfusion Therapy Center, Affiliated Cancer Hospital & Institute of Guangzhou Medical University
| | - Hui Long
- Department of Pharmacy, Guangzhou Dermatology Institute, Guangzhou, P.R. China
| | - Yuanfeng Gong
- Intracelom Hyperthermic Perfusion Therapy Center, Affiliated Cancer Hospital & Institute of Guangzhou Medical University
| | - Yinbin Wu
- Intracelom Hyperthermic Perfusion Therapy Center, Affiliated Cancer Hospital & Institute of Guangzhou Medical University
| | - Kunpeng Lin
- Intracelom Hyperthermic Perfusion Therapy Center, Affiliated Cancer Hospital & Institute of Guangzhou Medical University
| | - Yinuo Tu
- Intracelom Hyperthermic Perfusion Therapy Center, Affiliated Cancer Hospital & Institute of Guangzhou Medical University
| | - Bohuo Zhang
- Intracelom Hyperthermic Perfusion Therapy Center, Affiliated Cancer Hospital & Institute of Guangzhou Medical University
| | - Wanbo Wu
- Intracelom Hyperthermic Perfusion Therapy Center, Affiliated Cancer Hospital & Institute of Guangzhou Medical University
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19
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Wong EYT, Tan GHC, Kumar M, Teo MCC. Hematological toxicities associated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Asia Pac J Clin Oncol 2020; 16:e38-e46. [DOI: 10.1111/ajco.13275] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Accepted: 10/04/2019] [Indexed: 12/30/2022]
Affiliation(s)
- Evelyn Y. T. Wong
- Division of Surgical OncologyNational Cancer Centre Singapore Singapore
| | - Grace H. C. Tan
- Division of Surgical OncologyNational Cancer Centre Singapore Singapore
| | - Mrinal Kumar
- Division of Surgical OncologyNational Cancer Centre Singapore Singapore
| | - Melissa C. C. Teo
- Division of Surgical OncologyNational Cancer Centre Singapore Singapore
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20
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Wisselink DD, Braakhuis LLF, Gallo G, van Grevenstein WMU, van Dieren S, Kok NFM, de Reuver PR, Tanis PJ, de Hingh IHJT. Systematic review of published literature on oxaliplatin and mitomycin C as chemotherapeutic agents for hyperthermic intraperitoneal chemotherapy in patients with peritoneal metastases from colorectal cancer. Crit Rev Oncol Hematol 2019; 142:119-129. [PMID: 31400583 DOI: 10.1016/j.critrevonc.2019.06.014] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Accepted: 06/28/2019] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND The role of hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin in addition to cytoreductive surgery (CRS) has recently been questioned in peritoneal metastases of colorectal cancer. Whether this applies to all published CRS/HIPEC regimens is unclear. METHODS A systematic literature search identified 46 studies on CRS/HIPEC using either oxaliplatin of mitomycin C with at least one oncological outcome parameter RESULTS: Oxaliplatin and mitomycin C studies were comparable regarding extent of disease, but differed substantially regarding synchronous versus metachronous presentation, application of neo-adjuvant systemic chemotherapy, duration of HIPEC, and completeness of cytoreduction for at least one of the oncological endpoints. Severe postoperative complication rate seemed significantly higher after oxaliplatin-based CRS/HIPEC. CONCLUSION Published cohorts on oxaliplatin-based CRS/HIPEC differed essentially from MMC-based procedures, especially considering the application of oxaliplatin-containing neo-adjuvant systemic therapy and shorter exposure time to intraperitoneal chemotherapy in oxaliplatin studies. No meaningful comparison could be made regarding DFS and OS.
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Affiliation(s)
- Daan D Wisselink
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands.
| | - Linde L F Braakhuis
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands.
| | - Gaetano Gallo
- Department of Medical and Surgical Sciences, Università Magna Graecia di Catanzaro, Viale Europa, 88100 Catanzaro, CZ, Italy.
| | | | - Susan van Dieren
- Clinical Research Unit, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands.
| | - Niels F M Kok
- Department of surgery, Antoni van Leeuwenhoek hospital, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands.
| | - Philip R de Reuver
- Department of surgery, Radboud University Medical Centre, Geert Grooteplein-Zuid 22, 6525 GA Nijmegen, the Netherlands.
| | - Pieter J Tanis
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands.
| | - Ignace H J T de Hingh
- Department of surgery, Catharina hospital, Michelangelolaan 2, 5623 EJ Eindhoven, the Netherlands.
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21
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Ellis RJ, Schlick CJR, Yang AD, Barber EL, Bilimoria KY, Merkow RP. Utilization and Treatment Patterns of Cytoreduction Surgery and Intraperitoneal Chemotherapy in the United States. Ann Surg Oncol 2019; 27:214-221. [PMID: 31187369 DOI: 10.1245/s10434-019-07492-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Indexed: 12/22/2022]
Abstract
INTRODUCTION Cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) is an effective treatment option for selected patients with peritoneal metastases (PM), but national utilization patterns are poorly understood. The objectives of this study were to (1) describe population-based trends in national utilization of CRS/IPC; (2) define the most common indications for the procedure; and (3) characterize the types of hospitals performing the procedure. METHODS The National Inpatient Sample (NIS) was used to identify patients from 2006 to 2015 who underwent CRS/IPC, and to calculate national estimates of procedural frequency and oncologic indication. Hospitals performing CRS/IPC were classified based on size and teaching status. RESULTS The estimated annual number of CRS/IPC cases increased significantly from 189 to 1540 (p < 0.001). Overall, appendiceal cancer was the most common indication (25.7%), followed by ovarian cancer (23.3%), colorectal cancer (22.5%), and unspecified PM (15.0%). Remaining cases (13.5%) were performed for other indications. Most cases were performed in large teaching hospitals (65.9%), compared with smaller teaching hospitals (25.1%), large non-teaching hospitals (5.3%), or small non-teaching hospitals (3.2%). Patients were more likely to undergo CRS/IPC without a diagnosis based on level I evidence (appendiceal, ovarian, or colorectal) at large non-academic hospitals (odds ratio 2.00, 95% confidence interval 1.18-3.38, p = 0.010) compared with large academic hospitals. CONCLUSIONS Utilization of CRS/IPC is increasing steadily in the US, is performed at many types of facilities, and often for a variety of indications that are not supported by high-level evidence. Given associated morbidity of CRS/IPC, a national registry dedicated to cases of IPC is necessary to further evaluate use and outcomes.
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Affiliation(s)
- Ryan J Ellis
- Surgical Outcomes and Quality Improvement Center, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.,Northwestern Institute for Comparative Effectiveness Research in Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine and Northwestern Memorial Hospital, Chicago, IL, USA.,Division of Research and Optimal Patient Care, American College of Surgeons, Chicago, IL, USA
| | - Cary Jo R Schlick
- Surgical Outcomes and Quality Improvement Center, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.,Northwestern Institute for Comparative Effectiveness Research in Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine and Northwestern Memorial Hospital, Chicago, IL, USA
| | - Anthony D Yang
- Surgical Outcomes and Quality Improvement Center, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.,Northwestern Institute for Comparative Effectiveness Research in Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine and Northwestern Memorial Hospital, Chicago, IL, USA
| | - Emma L Barber
- Surgical Outcomes and Quality Improvement Center, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.,Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine and Northwestern Memorial Hospital, Chicago, IL, USA
| | - Karl Y Bilimoria
- Surgical Outcomes and Quality Improvement Center, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.,Northwestern Institute for Comparative Effectiveness Research in Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine and Northwestern Memorial Hospital, Chicago, IL, USA.,Division of Research and Optimal Patient Care, American College of Surgeons, Chicago, IL, USA
| | - Ryan P Merkow
- Surgical Outcomes and Quality Improvement Center, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. .,Northwestern Institute for Comparative Effectiveness Research in Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine and Northwestern Memorial Hospital, Chicago, IL, USA. .,Division of Research and Optimal Patient Care, American College of Surgeons, Chicago, IL, USA.
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22
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Lee JE, Abuzar SM, Seo Y, Han H, Jeon Y, Park EJ, Baik SH, Hwang SJ. Oxaliplatin-loaded chemically cross-linked hydrogels for prevention of postoperative abdominal adhesion and colorectal cancer therapy. Int J Pharm 2019; 565:50-58. [DOI: 10.1016/j.ijpharm.2019.04.065] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 04/17/2019] [Accepted: 04/21/2019] [Indexed: 01/05/2023]
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23
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Foster JM, Sleightholm R, Patel A, Shostrom V, Hall B, Neilsen B, Bartlett D, Smith L. Morbidity and Mortality Rates Following Cytoreductive Surgery Combined With Hyperthermic Intraperitoneal Chemotherapy Compared With Other High-Risk Surgical Oncology Procedures. JAMA Netw Open 2019; 2:e186847. [PMID: 30646202 PMCID: PMC6484874 DOI: 10.1001/jamanetworkopen.2018.6847] [Citation(s) in RCA: 158] [Impact Index Per Article: 26.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
IMPORTANCE Currently, rates of referral of patients with peritoneal metastasis in the United States who qualify for cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) are low, in part because of the misperception of high morbidity and mortality rates. However, patients requiring major gastrointestinal surgical procedures with similar complication rates are routinely referred. OBJECTIVE To evaluate the relative safety of CRS/HIPEC. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of 34 114 patients who underwent CRS/HIPEC, right lobe hepatectomy, trisegmental hepatectomy, pancreaticoduodenectomy, and esophagectomy between January 1, 2005, and December 31, 2015, included in the American College of Surgeons National Surgical Quality Improvement Project (NSQIP) database. Data analysis was performed in 2018. MAIN OUTCOMES AND MEASURES Data from the NSQIP database were used to compare perioperative and 30-day postoperative morbidity and mortality rates of CRS/HIPEC (1822 patients) with other, well-accepted, high-risk surgical oncology procedures: right lobe hepatectomy (5109 patients), trisegmental hepatectomy (2449 patients), pancreaticoduodenectomy (Whipple) (16 793 patients), and esophagectomy (7941 patients). RESULTS For 34 114 patients, median (interquartile range [IQR]) age was 63 (55-71) years and 42% were female. Patients undergoing CRS/HIPEC tended to be younger, with a median age of 57 years, and esophagectomy had the highest median (IQR) American Society of Anesthesiologists classification (3 [3-3]). When compared with CRS/HIPEC, higher complication rates were reported in the following categories: (1) superficial incisional infection in Whipple and esophagectomy (5.4% [95% CI, 4.4%-6.4%] vs 9.7% [95% CI, 9.3%-10.1%] and 7.2% [95% CI, 6.6%-7.8%], respectively; P < .001); (2) deep incisional infection in Whipple (1.7% [95% CI, 1.1%-2.3%] vs 2.7% [95% CI, 2.5%-2.9%]; P < .01); (3) organ space infection in right lobe hepatectomy (7.2% [95% CI, 6.0%-8.4%] vs 9.0% [95% CI, 8.2%-9.8%]; P = .02), trisegmental hepatectomy (12.4% [95% CI, 11.1%-13.7%]; P < .001), and Whipple (12.9% [95% CI, 12.4%-13.4%]; P < .001); and (4) return to the operating room for esophagectomy (6.8% [95% CI, 5.6%-8.0%] vs 14.4% [95% CI, 13.6%-15.2%]; P < .001). Median (IQR) length of hospital stay was lower in CRS/HIPEC (8 [5-11] days) than Whipple (10 [7-15] days) and esophagectomy (10 [8-16] days) (P < .001). Overall 30-day mortality was lower in CRS/HIPEC (1.1%; 95% CI, 0.6%-1.6%) compared with Whipple (2.5%; 95% CI, 2.3%-2.7%), right lobe hepatectomy (2.9%; 95% CI, 2.4%-3.4%), esophagectomy (3.0%; 95% CI, 2.6%-3.4%), and trisegmental hepatectomy (3.9%; 95% CI, 3.1%-4.7%) (P < .001). CONCLUSIONS AND RELEVANCE Comparative analysis revealed CRS/HIPEC to be safe, often safer across the spectrum of NSQIP safety metrics when compared with similar-risk oncologic procedures. Patient selection was important in achieving observed outcomes. High complication rates are a misperception from early CRS/HIPEC experience and should no longer deter referral of patients to experienced centers or impede clinical trial development in the United States.
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Affiliation(s)
- Jason M. Foster
- Department of Surgery, University of Nebraska Medical Center, Omaha
| | | | - Asish Patel
- Department of Surgery, University of Nebraska Medical Center, Omaha
| | - Valerie Shostrom
- Department of Biostatistics, University of Nebraska Medical Center, Omaha
| | - Bradley Hall
- Department of Surgery, University of Nebraska Medical Center, Omaha
| | - Beth Neilsen
- Department of Surgery, University of Nebraska Medical Center, Omaha
| | - David Bartlett
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Lynette Smith
- Department of Biostatistics, University of Nebraska Medical Center, Omaha
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24
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Systematic Review of Variations in Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Peritoneal Metastasis from Colorectal Cancer. J Clin Med 2018; 7:jcm7120567. [PMID: 30572653 PMCID: PMC6306814 DOI: 10.3390/jcm7120567] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Revised: 12/05/2018] [Accepted: 12/10/2018] [Indexed: 02/07/2023] Open
Abstract
Background: Cytoreductive surgery (CRS), followed by hyperthermic intraperitoneal chemotherapy (HIPEC), combines radical surgery with abdominal heated chemotherapy, constituting a multimodal treatment approach. Since clear standards for HIPEC conduct in colorectal carcinoma (CRC) are lacking, we aimed to provide a comprehensive structured survey. Data sources and study eligibility criteria: A systematic literature search was performed in PubMed, with keywords “HIPEC” and “colorectal cancer”, according to established guidelines. Articles were systematically screened, selecting 87 publications complemented by 48 publications identified through extended search for subsequent synthesis and evaluation, extracting inter alia details on used drugs, dosage, temperature, exposure times, and carrier solutions. Results: Compiled publications contained 171 reports on HIPEC conduct foremost with mitomycin C and oxaliplatin, but also other drugs and drug combinations, comprising at least 60 different procedures. We hence provide an overview of interconnections between HIPEC protocols, used drugs and carrier solutions as well as their volumes. In addition, HIPEC temperatures and dosing benchmarks, as well as an estimate of in vivo resulting drug concentrations are demonstrated. Conclusions and implications: Owing to recent developments, HIPEC conduct and practices need to be reassessed. Unfortunately, imprecise and lacking reporting is frequent, which is why minimal information requirements should be established for HIPEC and the introduction of final drug concentrations for comparability reasons seems sensible.
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25
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Ceelen W. HIPEC with oxaliplatin for colorectal peritoneal metastasis: The end of the road? Eur J Surg Oncol 2018; 45:400-402. [PMID: 30392745 DOI: 10.1016/j.ejso.2018.10.542] [Citation(s) in RCA: 70] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2018] [Accepted: 10/30/2018] [Indexed: 12/17/2022] Open
Abstract
In patients with colorectal peritoneal metastases (PM), the use of cytoreductive surgery (CRS) and HIPEC with oxaliplatin (OX) is increasingly used. The results of the recently reported randomized Prodige 7 trial failed to show a difference in overall survival between patients undergoing CRS alone versus CRS combined with HIPEC using high dose OX. The trial was not designed or powered, however, to detect a potentially clinically meaningful benefit in locoregional disease control. Here, I address some potential explanations for the lack of benefit in the Prodige 7 trial, including OX efficacy issues, adverse effects of intraperitoneal high dose glucose, and potential drawbacks of the use of hyperthermia.
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Affiliation(s)
- Wim Ceelen
- Department of GI Surgery and Cancer Research Institute Ghent (CRIG), Ghent University Hospital, B-9000, Ghent, Belgium.
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26
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de Jong LAW, Elekonawo FMK, de Reuver PR, Bremers AJA, de Wilt JHW, Jansman FGA, Ter Heine R, van Erp NP. Hyperthermic intraperitoneal chemotherapy with oxaliplatin for peritoneal carcinomatosis: a clinical pharmacological perspective on a surgical procedure. Br J Clin Pharmacol 2018; 85:47-58. [PMID: 30255585 DOI: 10.1111/bcp.13773] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Revised: 09/17/2018] [Accepted: 09/18/2018] [Indexed: 01/07/2023] Open
Abstract
Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has become the standard of care in the treatment of patients with peritoneal carcinomatosis of colorectal origin. The use of oxaliplatin for HIPEC has gained popularity. Although the HIPEC procedure is adopted throughout the world, major differences exist between treatment protocols regarding the carrier solution, perfusate volume, use of an open or closed technique, duration of the perfusion and application of additional flushing. These differences can influence the pharmacokinetics and pharmacodynamics of oxaliplatin and might thereby have an impact on the efficacy and/or safety of the treatment. Clinicians should be aware of the clinical importance of oxaliplatin pharmacology when performing HIPEC surgery. This review adds new insights into the complex field of the pharmacology of HIPEC and highlights an important worldwide problem: the lack of standardization of the HIPEC procedure.
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Affiliation(s)
- Loek A W de Jong
- Radboudumc, Department of Pharmacy, Radboud Institute for Health Sciences, P.O. Box 9101, 6500, HB, Nijmegen, the Netherlands
| | - Fortuné M K Elekonawo
- Radboudumc, Department of Surgery, Radboud Institute for Health Sciences, P.O. Box 9101, 6500, HB, Nijmegen, the Netherlands
| | - Philip R de Reuver
- Radboudumc, Department of Surgery, Radboud Institute for Health Sciences, P.O. Box 9101, 6500, HB, Nijmegen, the Netherlands
| | - Andre J A Bremers
- Radboudumc, Department of Surgery, Radboud Institute for Health Sciences, P.O. Box 9101, 6500, HB, Nijmegen, the Netherlands
| | - Johannes H W de Wilt
- Radboudumc, Department of Surgery, Radboud Institute for Health Sciences, P.O. Box 9101, 6500, HB, Nijmegen, the Netherlands
| | - Frank G A Jansman
- Department of Clinical Pharmacy, Deventer Teaching Hospital, Nico Bolkesteinlaan 75, 7416 SE, Deventer, the Netherlands.,University of Groningen, Groningen Research Institute of Pharmacy, PharmacoTherapy, -Epidemiology & -Economics, P.O. Box 196, 9700 AD, Groningen, the Netherlands
| | - Rob Ter Heine
- Radboudumc, Department of Pharmacy, Radboud Institute for Health Sciences, P.O. Box 9101, 6500, HB, Nijmegen, the Netherlands
| | - Nielka P van Erp
- Radboudumc, Department of Pharmacy, Radboud Institute for Health Sciences, P.O. Box 9101, 6500, HB, Nijmegen, the Netherlands
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Park EJ, Ahn J, Gwak SW, Park KS, Baik SH, Hwang SJ. Pharmacologic Properties of the Carrier Solutions for Hyperthermic Intraperitoneal Chemotherapy: Comparative Analyses Between Water and Lipid Carrier Solutions in the Rat Model. Ann Surg Oncol 2018; 25:3185-3192. [PMID: 30027459 PMCID: PMC6132421 DOI: 10.1245/s10434-018-6628-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Indexed: 12/28/2022]
Abstract
Background Carrier solutions play an important role in the distribution, plasma absorption, chemical stability, and solubility of anticancer agents during hyperthermic intraperitoneal chemotherapy (HIPEC). In the current study, lipophilic properties of carrier solutions were evaluated to determine whether they improved anticancer drug absorption rates using mitomycin-C (MMC) or oxaliplatin HIPEC as compared to hydrophilic carrier solutions. Methods Sprague-Dawley rats were divided into two groups: MMC and oxaliplatin treatment groups. Each group was then further subdivided by carrier solution: Dianeal® PD-2 peritoneal dialysis solution, 5% dextrose solution and 20% lipid solution (Lipision®). HIPEC was performed over 60 min at 41–42 °C using the anticancer drugs MMC (35 mg/m2) or oxaliplatin (460 mg/m2). The plasma area under the curve (AUC; AUCplasma), peritoneal AUC (AUCperitoneum), and peritoneal/plasma AUC ratios were compared among HIPEC carrier solutions. Results Plasma drug concentrations were significantly different among carrier solutions, varying by time. In contrast, peritoneal drug concentrations did not change with carrier solution. In the MMC group, the peritoneal/plasma AUC ratio of a lipid solution was three times higher than Dianeal® (p < 0.001). In the oxaliplatin group, the peritoneal/plasma AUC ratio was significantly different between carrier solutions (p = 0.046). Although the oxaliplatin AUCperitoneum did not vary (p = 0.941), the AUCplasma of a lipid solution was lower than that of 5% dextrose solution (p = 0.039). Conclusions The lipid carrier solution increases the peritoneal/plasma AUC ratio and decreases plasma absorption rates. However, further study is required before clinical uses, considering its pharmacologic properties and possible risks after HIPEC. Electronic supplementary material The online version of this article (10.1245/s10434-018-6628-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Eun Jung Park
- Division of Colon and Rectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Junhyun Ahn
- Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Korea.,College of Pharmacy, Yonsei University, Incheon, Korea
| | - Sang Won Gwak
- Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Korea.,College of Pharmacy, Yonsei University, Incheon, Korea
| | - Kyung Su Park
- Advanced Analysis Center, Korea Institute of Science and Technology, Seoul, Korea
| | - Seung Hyuk Baik
- Division of Colon and Rectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
| | - Sung-Joo Hwang
- Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Korea. .,College of Pharmacy, Yonsei University, Incheon, Korea.
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28
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Teixeira Farinha H, Grass F, Labgaa I, Pache B, Demartines N, Hübner M. Inflammatory Response and Toxicity After Pressurized IntraPeritoneal Aerosol Chemotherapy. J Cancer 2018; 9:13-20. [PMID: 29290765 PMCID: PMC5743707 DOI: 10.7150/jca.21460] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2017] [Accepted: 10/08/2017] [Indexed: 01/27/2023] Open
Abstract
Background: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is a novel mode of intraperitoneal (IP) drug delivery claiming high IP tissue concentrations with low systemic uptake. The aim was to study inflammatory response and systemic toxicity after PIPAC. Methods: Retrospective monocentric analysis of a consecutive cohort of PIPAC patients between January 2015 and April 2016. Detailed hematological and biochemical analysis was performed the day before surgery and once daily until discharge. Comparative statistics were performed using Mann-Whitney U test and Wilcoxon signed ranked test. Results: Fourty-two consecutive patients underwent a total of 91 PIPAC procedures. Twenty patients received oxaliplatin and 22 cisplatin+doxorubicin (37 vs. 54 procedures). Creatinine, AST and ALT were not significantly altered after PIPAC (p=0.095, p= p=0.153 and p=0.351) and not different between oxaliplatin and cisplatin+doxorubicin regimens (p=0.371, p=0.251 and p=0.288). C-reactive protein (CRP) and procalcitonin (PCT) increased on post-operative day (POD) 2: ∆max 29±5 mg/L (p<0.001) and ∆max 0.05±0.01 μg/L (p=0.005), respectively. Leucocytes increased at POD 1: ∆max 2.2±0.3 G/L (p<0.001). Albumin decreased at POD 2: ∆max -6.0±0.5 g/L (p<0.001). CRP increase correlated positively with Peritoneal Cancer Index (tumor load) (ρ =0.521, p<0.001). Conclusion: PIPAC was followed by a modest and transitory inflammatory response that was commensurate to the disease extent. No hematological, renal or hepatic toxicity was observed even after repetitive administration.
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Affiliation(s)
| | - Fabian Grass
- Department of Visceral Surgery, University Hospital of Lausanne (CHUV), Switzerland
| | - Ismaïl Labgaa
- Department of Visceral Surgery, University Hospital of Lausanne (CHUV), Switzerland
| | - Basile Pache
- Department of Visceral Surgery, University Hospital of Lausanne (CHUV), Switzerland
| | - Nicolas Demartines
- Department of Visceral Surgery, University Hospital of Lausanne (CHUV), Switzerland
| | - Martin Hübner
- Department of Visceral Surgery, University Hospital of Lausanne (CHUV), Switzerland
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van Eden WJ, Kok NFM, Woensdregt K, Huitema ADR, Boot H, Aalbers AGJ. Safety of intraperitoneal Mitomycin C versus intraperitoneal oxaliplatin in patients with peritoneal carcinomatosis of colorectal cancer undergoing cytoreductive surgery and HIPEC. Eur J Surg Oncol 2017; 44:220-227. [PMID: 29258720 DOI: 10.1016/j.ejso.2017.10.216] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2017] [Accepted: 10/21/2017] [Indexed: 10/18/2022] Open
Abstract
BACKGROUND Colorectal peritoneal carcinomatosis (PC) is commonly treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). There is an ongoing international debate about which intraperitoneal chemotherapeutic agent is preferred, Mitomycin C (MMC) or oxaliplatin. We questioned whether the type of chemotherapeutic agent influenced postoperative complication rates or short-term survival. METHODS In this retrospective cohort study patients with colorectal PC who underwent CRS-HIPEC between January 2010 and December 2016 were included. Until March 2014 patients had preferentially been treated with MMC and thereafter with oxaliplatin in an iso-osmotic glucose/electrolyte dialysis (Dianeal®) carrier solution. Main outcomes were postoperative complications, disease free survival (DFS) and overall survival (OS). Survival analyses and multivariable analyses were performed. RESULTS One hundred four patients received MMC and 73 patients oxaliplatin. Postoperative complications did not differ between groups (44.2% (MMC) versus 43.8% (oxaliplatin); P = 0.958). Median DFS was 12.5 months (IQR 6.4-32.4) in the MMC-group and 13.1 months (IQR 6.1-NA) in the oxaliplatin-group (P = 0.669). Median OS was 37.2 months (IQR 17.2-NA) in the MMC-group and 29.4 months (IQR 17.0-NA) in the oxaliplatin-group (P = 0.764). The type of chemotherapeutic agent did not influence OS in multivariable analysis (oxaliplatin versus MMC HR 1.09 (95%CI 0.58-2.06)). The HIPEC-phase was shorter for oxaliplatin (median 32 (IQR 31-34) versus 91 min (IQR 90-92) for MMC (P < 0.001)). CONCLUSION Intraperitoneal oxaliplatin reduced the chemoperfusion time when compared to intraperitoneal MMC without adversely influencing complication rates or short-term survival. It may therefore be the preferential drug in CRS-HIPEC procedures for colorectal PC.
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Affiliation(s)
- W J van Eden
- Department of Surgical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
| | - N F M Kok
- Department of Surgical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
| | - K Woensdregt
- Department of Surgical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
| | - A D R Huitema
- Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Clinical Pharmacy, University Medical Centre Utrecht, Utrecht, The Netherlands.
| | - H Boot
- Department of Medical Oncology & Gastroenterology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
| | - A G J Aalbers
- Department of Surgical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
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Klaver CEL, Groenen H, Morton DG, Laurberg S, Bemelman WA, Tanis PJ. Recommendations and consensus on the treatment of peritoneal metastases of colorectal origin: a systematic review of national and international guidelines. Colorectal Dis 2017; 19:224-236. [PMID: 28008728 DOI: 10.1111/codi.13593] [Citation(s) in RCA: 76] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2016] [Accepted: 11/01/2016] [Indexed: 12/13/2022]
Abstract
AIM This systematic review aimed to provide an overview of (inter)national guidelines on the treatment of peritoneal metastases of colorectal cancer origin (PMCRC) and to determine the degree of consensus and available evidence with identification of topics for future research. METHOD A systematic search of MEDLINE, Embase, PubMed as well as Tripdatabase, National Guideline Clearinghouse, BMJ Best Practice and Guidelines International Network was performed to identify (inter)national guidelines and consensus statements from oncological or surgical societies on PMCRC. The quality of guidelines was assessed using the AGREE-II score. Topics followed by recommendations were extracted from the guidelines. The recommendations, highest level of supporting evidence and the degree of consensus were determined for each topic. RESULTS Twenty-one guidelines were included, in most (15) of which cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) was recommended in selected patients based on level 1b evidence. Substantial consensus was also reached on the benefit of multidisciplinary team discussion and the achievability of a (near) complete cytoreduction (CC0-1) without supporting evidence. Both evidence and consensus were lacking regarding other aspects including preoperative positron emission tomography/CT, second look surgery in high risk patients, the optimal patient selection for CRS/HIPEC, procedural aspects of HIPEC and (perioperative) systemic therapy. CONCLUSION In currently available guidelines, evidence and consensus on the treatment strategy for PMCRC are lacking. Updates of guidelines are ongoing and future (randomized) clinical trials should contribute to multidisciplinary and international consensus on treatment strategies for PMCRC.
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Affiliation(s)
- C E L Klaver
- Department of Surgery, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - H Groenen
- Department of Surgery, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - D G Morton
- Academic Department of Surgery, University of Birmingham, Edgbaston, Birmingham, UK
| | - S Laurberg
- Department of Surgical Gastroenterology, Aarhus University, Aarhus C, Denmark
| | - W A Bemelman
- Department of Surgery, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - P J Tanis
- Department of Surgery, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
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Gastric perforation following cytoreductive surgery and perioperative intraperitoneal chemotherapy: a case series of six. World J Surg Oncol 2017; 15:44. [PMID: 28187769 PMCID: PMC5303261 DOI: 10.1186/s12957-017-1114-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2016] [Accepted: 02/01/2017] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Incidence of gastric perforation following cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC) is not widely reported. METHODS Suitable patients were identified from our database of 1028 procedures. Relevant information was then gathered via medical records and operation reports for these patients. RESULTS Six patients suffered early postoperative gastric perforation following the procedure (0.58%), all of whom received heated intraoperative intraperitoneal chemotherapy (HIPEC). Surgical exploration revealed protrusion of nasogastric (NG) tube through stomach wall defects which were either located at or near the greater curvature of stomach. These patients were managed successfully with operation, and no mortality was recorded. CONCLUSIONS Gastric perforation following CRS and PIC is most likely the result of a multifactorial process. To reduce the risk of such complication, avoiding nasogastric suction in these patients may prove helpful. Any suspected perforated viscus must be addressed promptly to avoid unwanted morbidity and mortality from the procedure. To our knowledge, conservative management has not been documented to work in this subgroup and surgery remains the mainstay of treatment.
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Leung V, Huo YR, Liauw W, Morris DL. Oxaliplatin versus Mitomycin C for HIPEC in colorectal cancer peritoneal carcinomatosis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2017; 43:144-149. [PMID: 27780675 DOI: 10.1016/j.ejso.2016.09.015] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2016] [Revised: 07/17/2016] [Accepted: 09/21/2016] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Compare long-term outcomes in colorectal cancer (CRC) patients with peritoneal carcinomatosis (PC) treated with peritonectomy/HIPEC using oxaliplatin versus MMC. BACKGROUND Peritonectomy and heated intraperitoneal chemotherapy (HIPEC) greatly improves patient survival in CRC PC. This procedure is not uniform across centres and the optimal choice of HIPEC chemotherapeutic is unclear. Oxaliplatin and Mitomycin C (MMC) are the most commonly used agents and comparative studies have reported varying results. METHOD 201 patients were retrospectively selected from the St George Hospital database, all of which had undergone peritonectomy/HIPEC for CRC PC. Oxaliplatin and MMC were used in 106 and 96 patients, respectively. Each patient's baseline characteristics, operative details, choice of chemotherapeutic agent and survival were noted. RESULTS The two groups did not differ significantly at baseline. Patients receiving oxaliplatin had significantly greater unadjusted median survival compared to MMC (56.0 ± 8.1 vs. 29.0 ± 3.4 months) which translated into a hazards ratio of 0.59 (95% CI 0.37-0.91, p = 0.017). Subgroup analysis further confirmed an advantage with oxaliplatin in females, moderate-well differentiated tumours, tumours without signet ring pathology and PCI 10-15. CONCLUSION Our study suggests oxaliplatin offers a survival advantage over MMC when used for HIPEC in CRC PC. Further studies to understand its efficacy, complications and ideal preparation are required. A Phase III randomised control trial comparing oxaliplatin and MMC would enhance decision-making.
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Affiliation(s)
- V Leung
- University of New South Wales, Kensington, Sydney, NSW, 2052, Australia.
| | - Y R Huo
- University of New South Wales, Kensington, Sydney, NSW, 2052, Australia.
| | - W Liauw
- Department of Surgery, St George Hospital, Gray St Kogarah, Sydney, NSW, 2217, Australia.
| | - D L Morris
- University of New South Wales, Kensington, Sydney, NSW, 2052, Australia; Department of Surgery, St George Hospital, Gray St Kogarah, Sydney, NSW, 2217, Australia.
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Mehta AM, Huitema ADR, Burger JWA, Brandt-Kerkhof ARM, van den Heuvel SF, Verwaal VJ. Standard Clinical Protocol for Bidirectional Hyperthermic Intraperitoneal Chemotherapy (HIPEC): Systemic Leucovorin, 5-Fluorouracil, and Heated Intraperitoneal Oxaliplatin in a Chloride-Containing Carrier Solution. Ann Surg Oncol 2016; 24:990-997. [PMID: 27896510 DOI: 10.1245/s10434-016-5665-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2016] [Indexed: 12/27/2022]
Abstract
BACKGROUND Intraperitoneal chemotherapy has an established role in the treatment of selected patients with colorectal peritoneal metastases. Oxaliplatin is highly suitable as a chemotherapeutic agent for hyperthermic intraperitoneal chemotherapy (HIPEC), but its use to date has been limited because of the morbidity caused by severe electrolyte and glycemic imbalances associated with 5% glucose as its carrier solution. This report provides an overview of the development, rationale, and application of intraperitoneal chemotherapy and the use of various drugs and carrier solutions. A novel, evidence-based protocol for bidirectional oxaliplatin-based HIPEC in a physiologic carrier solution (Dianeal PD4 dextrose 1.36%) is presented, and its impact on electrolyte and glucose levels is demonstrated. METHODS After implementation of the new protocol, the serum electrolyte (sodium, potassium, and chloride) levels, glucose levels, and intravenous insulin requirements were intensively measured in eight consecutive cases immediately before HIPEC (T = 0), immediately after HIPEC (T = 30), 1 h after HIPEC (T = 60), and 3 h after HIPEC (T = 180). RESULTS The median sodium levels were 140 mmol/L at T = 0, 138 mmol/L at T = 30, 140 mmol/L at T = 60, and 140 mmol/L at T = 180. The respective median potassium levels were 4.6, 4.2, 3.7, and 3.9 mmol/L, and the respective median chloride levels were 112, 111, 111, and 112 mmol/L. The respective median glucose levels were 9, 11.5, 10.7, and 8.6 mmol/L. The median insulin requirements were respectively 0.5, 1.5, 1.2, and 0 U/h. None of the patients were diabetic. CONCLUSION Using a novel protocol for bidirectional oxaliplatin-based HIPEC in Dianeal instead of 5% glucose, the observed fluctuations in this study were minimal and not clinically relevant compared with historical values for electrolyte and glycemic changes using 5% glucose as a HIPEC carrier solution. This novel protocol leads to only minimal and clinically irrelevant electrolyte and glycemic disturbances, and its adoption as the standard protocol for oxaliplatin-based HIPEC should be considered.
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Affiliation(s)
- Akash M Mehta
- Department of Surgery, Peritoneal Malignancy Institute, Basingstoke & North Hampshire Hospital, Basingstoke, UK.
| | - Alwin D R Huitema
- Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | | | | | | | - Victor J Verwaal
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark
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Solass W, Horvath P, Struller F, Königsrainer I, Beckert S, Königsrainer A, Weinreich FJ, Schenk M. Functional vascular anatomy of the peritoneum in health and disease. Pleura Peritoneum 2016; 1:145-158. [PMID: 30911618 PMCID: PMC6328070 DOI: 10.1515/pp-2016-0015] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2016] [Accepted: 08/30/2016] [Indexed: 01/28/2023] Open
Abstract
The peritoneum consists of a layer of mesothelial cells on a connective tissue base which is perfused with circulatory and lymphatic vessels. Total effective blood flow to the human peritoneum is estimated between 60 and 100 mL/min, representing 1-2 % of the cardiac outflow. The parietal peritoneum accounts for about 30 % of the peritoneal surface (anterior abdominal wall 4 %) and is vascularized from the circumflex, iliac, lumbar, intercostal, and epigastric arteries, giving rise to a quadrangular network of large, parallel blood vessels and their perpendicular offshoots. Parietal vessels drain into the inferior vena cava. The visceral peritoneum accounts for 70 % of the peritoneal surface and derives its blood supply from the three major arteries that supply the splanchnic organs, celiac and superior and inferior mesenteric. These vessels give rise to smaller arteries that anastomose extensively. The visceral peritoneum drains into the portal vein. Drugs absorbed are subject to first-pass hepatic metabolism. Peritoneal inflammation and cancer invasion induce neoangiogenesis, leading to the development of an important microvascular network. Anatomy of neovessels is abnormal and characterized by large size, varying diameter, convolution and blood extravasation. Neovessels have a defective ultrastructure: formation of large "mother vessels" requires degradation of venular and capillary basement membranes. Mother vessels give birth to numerous "daughter vessels". Diffuse neoangiogenesis can be observed before appearance of macroscopic peritoneal metastasis. Multiplication of the peritoneal capillary surface by neoangiogenesis surface increases the part of cardiac outflow directed to the peritoneum.
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Affiliation(s)
- Wiebke Solass
- Institute of Pathology, Medical School Hannover, Hannover, Germany
| | - Philipp Horvath
- Department of General, Visceral and Transplant Surgery, Eberhard-Karls-Universitat Tubingen Medizinische Fakultat, Tuebingen, Germany
| | - Florian Struller
- Department of General, Visceral and Transplant Surgery, Eberhard-Karls-Universitat Tubingen Medizinische Fakultat, Tuebingen, Germany
| | - Ingmar Königsrainer
- Department of General, Visceral and Transplant Surgery, Eberhard-Karls-Universitat Tubingen Medizinische Fakultat, Tuebingen, Germany
| | - Stefan Beckert
- Department of General, Visceral and Transplant Surgery, Eberhard-Karls-Universitat Tubingen Medizinische Fakultat, Tuebingen, Germany
| | - Alfred Königsrainer
- Department of General, Visceral and Transplant Surgery, Eberhard-Karls-Universitat Tubingen Medizinische Fakultat, Tuebingen, Germany
| | - Frank-Jürgen Weinreich
- Department of General, Visceral and Transplant Surgery, Eberhard-Karls-Universitat Tubingen Medizinische Fakultat, Tuebingen, Germany
| | - Martin Schenk
- Department of General, Visceral and Transplant Surgery, Eberhard-Karls-Universitat Tubingen Medizinische Fakultat, Tuebingen, Germany
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Mistry P, Mohamed F, Dayal S, Cecil TD, Moran BJ. Cytoreductive surgery with intraperitoneal chemotherapy in the management of peritoneal surface malignancy: a pharmacist's perspective. Eur J Hosp Pharm 2016; 23:233-238. [PMID: 31156855 DOI: 10.1136/ejhpharm-2016-000877] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Revised: 03/04/2016] [Accepted: 03/14/2016] [Indexed: 01/04/2023] Open
Abstract
Objectives To explore the use of intraperitoneal chemotherapy in conjunction with cytoreductive surgery for the treatment of peritoneal surface malignancy and highlight the challenges this provides for the hospital pharmacist. Methods A literature search for relevant articles was performed using MEDLINE, PubMed and Cochrane databases. The following keywords and phrases were used: 'hyperthermic intraperitoneal chemotherapy', 'early postoperative intraperitoneal chemotherapy', 'carrier solutions' and 'cytoreductive surgery'. Local experience was also shared, referencing national guidelines and published literature. Results The rationale behind intraperitoneal chemotherapy is to directly administer drugs into the peritoneal cavity and achieve exposure of higher concentrations of cytotoxic agents to tumour nodules within the abdomen and on peritoneal surfaces for a prolonged period of time, without significant systemic toxicity. This has been widely demonstrated in intraoperative and early postoperative settings. Hydrophilic chemotherapy drugs with high molecular weights and permeable to the peritoneum, but slow plasma clearance create high concentrations of the drug in the peritoneal cavity, with lower systemic circulation. Commonly used drugs include mitomycin C, oxaliplatin, cisplatin, doxorubicin and 5-fluorouracil. Newer drugs such as the taxanes and bevacizumab have also shown promise. Heat increases drug penetration into body tissues and destroys tumour cells directly by causing damage to cells that have inherently faulty heat regulation pathways and also increases the cytotoxic effect of selected chemotherapeutic agents. Optimal temperature for hyperthermic intraperitoneal drug administration is between 41 and 43°C in a carrier solution that is compatible with the drug chosen. For early postoperative intraperitoneal chemotherapy high molecular weight starch carrier solutions prolong intraperitoneal dwell time and exposure of drug to tumour cells. Drugs are administered intraoperatively with the abdomen open or closed for between 30 and 120 min depending on the drug chosen and local protocols. Drug doses are traditionally calculated using body surface area. Toxicity such as neutropenia is encountered far less than with systemic chemotherapy. Conclusions This paper discusses the rationale for intraperitoneal drug administration following cytoreductive surgery and describes appropriate drug selection, methods of drug delivery and potential challenges in the use of the intraperitoneal route. It provides evidence and practical guidance for hospital pharmacists who may be involved in the surgical management of peritoneal malignancy particularly in dose calculation, preparation and administration of intraperitoneal chemotherapy.
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Affiliation(s)
- Priya Mistry
- Pharmacy Department, Basingstoke & North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Basingstoke, Hampshire, UK
| | - Faheez Mohamed
- Peritoneal Malignancy Institute, Basingstoke & North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Basingstoke, Hampshire, UK
| | - Sanjeev Dayal
- Peritoneal Malignancy Institute, Basingstoke & North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Basingstoke, Hampshire, UK
| | - Tom D Cecil
- Peritoneal Malignancy Institute, Basingstoke & North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Basingstoke, Hampshire, UK
| | - Brendan J Moran
- Peritoneal Malignancy Institute, Basingstoke & North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Basingstoke, Hampshire, UK
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Trépanier JS, Sidéris L, Lee L, Tremblay JF, Drolet P, Dubé P. Impact of electrocautery and hyperthermic intraperitoneal chemotherapy on intestinal microvasculature in a murine model. Int J Hyperthermia 2016; 32:483-7. [PMID: 27087666 DOI: 10.3109/02656736.2016.1155759] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Electrocautery (EC) is used during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Using a murine model, we studied the effect of HIPEC on small bowel EC lesions and surrounding normal tissues. METHODS Thirty-two rats were divided into five groups: a control group with EC lesions; EC plus intraperitoneal heated 5% dextrose (D5W); EC plus oxaliplatin (OXA, 460 mg/m(2)); EC plus mitomycin C 10 mg/m(2) (MMC10); EC plus MMC 35 mg/m(2) (MMC35). EC lesions and surrounding tissue microvasculature were analysed after intravenous injection of fluorescein. RESULTS In the ileum OXA significantly reduced EC lesions microvasculature compared with the control group; MMC10 caused greater reduction than the control, D5W and MMC35 groups. Surrounding tissue microvasculature was significantly reduced by MMC35 exposure when compared to the control, OXA or MMC10 groups. In the jejunum EC injuries exposed to OXA or MMC10 had significantly reduced microvasculature compared to the control, heated D5W and MMC35 groups. Surrounding tissue microvasculature was significantly reduced by MMC35 exposure when compared to the OXA group. There was no significant microvasculature difference between the EC lesions made before or after HIPEC. CONCLUSION HIPEC with OXA and MMC10 potentiates small bowel wall EC injuries. MMC35 reduces surrounding unharmed tissue microvasculature. There was no effect of hyperthermia alone on microvasculature.
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Affiliation(s)
| | - Lucas Sidéris
- a Maisonneuve-Rosemont Hospital, University of Montreal , Montreal , Quebec , Canada
| | - Lawrence Lee
- b McGill University , Montreal , Quebec , Canada
| | | | - Pierre Drolet
- a Maisonneuve-Rosemont Hospital, University of Montreal , Montreal , Quebec , Canada
| | - Pierre Dubé
- a Maisonneuve-Rosemont Hospital, University of Montreal , Montreal , Quebec , Canada
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Newton AD, Bartlett EK, Karakousis GC. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: a review of factors contributing to morbidity and mortality. J Gastrointest Oncol 2016; 7:99-111. [PMID: 26941988 DOI: 10.3978/j.issn.2078-6891.2015.100] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with prolonged survival for appropriately selected patients with peritoneal dissemination of abdominal malignancies. CRS and HIPEC has been criticized for perceived high rates of morbidity and mortality. Morbidity and mortality rates of CRS and HIPEC, however, do not appear dissimilar to those of other large abdominal surgeries, particularly when relevant patient and operative factors are accounted for. The risk of morbidity and mortality following this surgery for a given individual can be predicted in part by a variety of patient and operative factors. While strong data are lacking, the limited data that exists on the matter suggests that the independent contribution of the heated intraperitoneal chemotherapy to CRS and HIPEC morbidity is relatively small. A more thorough understanding of the patient and operative factors associated with CRS and HIPEC morbidity and mortality, as well as the specific complications related to the intraperitoneal chemotherapy, can better inform clinicians in multidisciplinary teams and patients alike in the decision-making for this surgery.
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Affiliation(s)
- Andrew D Newton
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Edmund K Bartlett
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Giorgos C Karakousis
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
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Charrier T, Passot G, Peron J, Maurice C, Gocevska S, Quénet F, Eveno C, Pocard M, Goere D, Elias D, Ortega-Deballon P, Vaudoyer D, Cotte E, Glehen O. Cytoreductive Surgery Combined with Hyperthermic Intraperitoneal Chemotherapy with Oxaliplatin Increases the Risk of Postoperative Hemorrhagic Complications: Analysis of Predictive Factors. Ann Surg Oncol 2016; 23:2315-22. [PMID: 26920385 DOI: 10.1245/s10434-016-5143-1] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Indexed: 11/18/2022]
Abstract
BACKGROUND Treatment of peritoneal carcinomatosis (PC) using cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is recommended as curative treatment for selected patients. Modalities of HIPEC remain heterogeneous and HIPEC using oxaliplatin (HIPEC-Ox) appears to increase the risk of postoperative hemorrhagic complications (HCs). OBJECTIVE The aim of this study was to assess the risk of HCs after CRS combined with HIPEC-Ox versus other drugs, and to determine predictive factors for HCs after HIPEC-Ox. METHODS Data from 701 patients included in the National French Registry who were treated with CRS and HIPEC at 24 centers between 1998 and 2007 were used to evaluate the incidence of HCs following HIPEC with or without oxaliplatin. Overall, 771 patients treated with HIPEC-Ox at five French specialty centers were then analyzed to determine factors associated with the occurrence of HCs. RESULTS The overall incidence of HCs was 9.8 %. When used with HIPEC, oxaliplatin significantly and independently increased the rate of HCs (15.7 vs. 2.6 % for other drugs; p = 0.004, odds ratio 32.4). Among the 771 patients who underwent HIPEC-Ox, HCs occurred in 14.3 % of patients. The only independent risk factor for HCs was an extended PC with a Peritoneal Cancer Index (PCI) >12 (p = 0.040). CONCLUSION HIPEC-Ox increases the risk of HCs compared with HIPEC with other drugs. The potential oncologic benefit of oxaliplatin and the risk of HCs should be considered in patients with PC who have a high PCI, as well as in at-risk patients.
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Affiliation(s)
- Thibaut Charrier
- Department of General Surgery, Centre Hospitalier Lyon Sud, Pierre Bénite, France.,EMR 3738, Lyon 1 University, Lyon, France
| | - Guillaume Passot
- Department of General Surgery, Centre Hospitalier Lyon Sud, Pierre Bénite, France.,EMR 3738, Lyon 1 University, Lyon, France
| | - Julien Peron
- Department of Biostatistics, UMR 5558, Lyon 1 University, Lyon, France
| | - Christelle Maurice
- Pôle IMER, Unité de Recherche Clinique, Hospices Civils de Lyon, Lyon, France
| | - Sashka Gocevska
- Department of Surgery, Centre Val d'Aurelle, Montpellier, France
| | - François Quénet
- Department of Surgery, Centre Val d'Aurelle, Montpellier, France
| | - Clarisse Eveno
- Department of Surgery, Hôpital Lariboisière, Assistance-Publique, des hôpitaux de Paris, Paris 7 Université Paris Diderot, Paris, France
| | - Marc Pocard
- Department of Surgery, Hôpital Lariboisière, Assistance-Publique, des hôpitaux de Paris, Paris 7 Université Paris Diderot, Paris, France
| | - Diane Goere
- Department of Surgery, Gustave Roussy, Cancer Campus, Grand Paris, Paris, France
| | - Dominique Elias
- Department of Surgery, Gustave Roussy, Cancer Campus, Grand Paris, Paris, France
| | | | - Delphine Vaudoyer
- Department of General Surgery, Centre Hospitalier Lyon Sud, Pierre Bénite, France.,EMR 3738, Lyon 1 University, Lyon, France
| | - Eddy Cotte
- Department of General Surgery, Centre Hospitalier Lyon Sud, Pierre Bénite, France.,EMR 3738, Lyon 1 University, Lyon, France
| | - Olivier Glehen
- Department of General Surgery, Centre Hospitalier Lyon Sud, Pierre Bénite, France. .,EMR 3738, Lyon 1 University, Lyon, France.
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Mehta AM, Van den Hoven JM, Rosing H, Hillebrand MJX, Nuijen B, Huitema ADR, Beijnen JH, Verwaal VJ. Stability of oxaliplatin in chloride-containing carrier solutions used in hyperthermic intraperitoneal chemotherapy. Int J Pharm 2014; 479:23-7. [PMID: 25535649 DOI: 10.1016/j.ijpharm.2014.12.025] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2014] [Accepted: 12/13/2014] [Indexed: 12/24/2022]
Abstract
PURPOSE Oxaliplatin is increasingly becoming the chemotherapeutic drug of choice for the treatment of peritoneal malignancies using cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Oxaliplatin is unstable in chloride-containing media, resulting in the use of 5% dextrose as the carrier solution in these procedures. Exposure of the peritoneum to 5% dextrose during perfusion times varying from 30 min to 90 min is associated with serious hyperglycemias and electrolyte disturbances. This can result in significant postoperative morbidity and mortality. In order to find out whether safer, chloride-containing carrier solutions can be used, we report the results of in-vitro analysis of oxaliplatin stability in both chloride-containing and choride-deficient carrier solutions and discuss the implications for oxaliplatin-based CRS-HIPEC procedures. METHODS 5 mg of oxaliplatin was added to 50 mL of various carrier solutions at 42 °C: 5% dextrose, 0.9% sodium chloride, Ringer lactate, Dianeal(®) PD4 glucose 1.36% solution for peritoneal dialysis and 0.14 M sterile phosphate buffer pH 7.4. Samples were collected at standardized intervals and oxaliplatin concentration was determined using a stability indicating high-performance liquid chromatographic method, coupled to an UV detector (HPLC-UV); oxaliplatin degradation products were identified using HPLC-mass spectometry. RESULTS In 5% dextrose, oxaliplatin concentration remained stable over a 2-hour period. Increasing chloride concentrations were associated with increasing degradation rates; however, this degradation was limited to <10% degradation after 30 min (the standard peritoneal perfusion time in most clinical CRS-HIPEC protocols) and <20% degradation after 120 min at 42 °C. In addition, oxaliplatin degradation was associated with the formation of its active drug form [Pt(dach)Cl2]. CONCLUSIONS The use of chloride-containing carrier solutions for oxaliplatin does not relevantly affect its concentrations under the tested in-vitro conditions. Chloride seems to promote formation of the active cytotoxic drug form of oxaliplatin and therefore could enhance its cytotoxic effect. These data show that more physiological, chloride-containing carrier solutions can be used safely and effectively as a medium for oxaliplatin in CRS-HIPEC procedures.
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Affiliation(s)
- A M Mehta
- Department of Surgical Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
| | - J M Van den Hoven
- Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
| | - H Rosing
- Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
| | - M J X Hillebrand
- Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
| | - B Nuijen
- Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
| | - A D R Huitema
- Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
| | - J H Beijnen
- Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands
| | - V J Verwaal
- Department of Surgical Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
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Desantis M, Bernard JL, Casanova V, Cegarra-Escolano M, Benizri E, Rahili AM, Benchimol D, Bereder JM. Morbidity, mortality, and oncological outcomes of 401 consecutive cytoreductive procedures with hyperthermic intraperitoneal chemotherapy (HIPEC). Langenbecks Arch Surg 2014; 400:37-48. [PMID: 25319432 DOI: 10.1007/s00423-014-1253-z] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2014] [Accepted: 10/02/2014] [Indexed: 01/26/2023]
Abstract
PURPOSE Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are a novel curative treatment option for selected patients with peritoneal carcinomatosis (PC). We aimed to report the mortality rate and the most frequent grade III-IV adverse events and to identify associated prognostic markers. We report oncological outcomes and major prognostic factors influencing overall survival (OS) and disease-free survival. METHODS A total of 401 CRS plus HIPEC procedures were performed on 356 patients. Mortality, grade III-IV adverse events, OS, disease-free survival, and prognostic factors were studied. RESULTS Based on Common Terminology Criteria for Adverse Events (CTCAE of the National Cancer Institute 2006), mortality rate was 1 % and overall rate of morbidity grade III-IV was 12.5 %. In multivariate analysis, only the number of digestive anastomoses (>1) significantly correlated with adverse events with an odds ratio of 2.8 (p = 0.032). OS was related to histological type of PC, with a median survival reaching 47.6 months for PC of ovarian cancer origin, 45.8 months for that of colorectal origin, 64.2 months for peritoneal mesothelioma, and 8.1 months for PC of gastric cancer origin. Over half the patients with pseudomyxoma are still alive. Major prognostic factors influencing survival were histological type, World Health Organization performance status (WHO PS) (hazard ratio (HR) = 3.56), operating time (HR = 0.45), previous chemotherapy (HR = 2.04), number of peritonectomies (HR = 2.03), and completeness of cytoreduction score (HR = 3.12). Disease-free survival across all groups was 16.8 months. CONCLUSION The low mortality rate and 12.5 % grade III-IV morbidity of CRS and HIPEC are acceptable when weighed against overall oncologic survival. This multimodal treatment appears feasible for selected patients and trained centers.
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Affiliation(s)
- Mariangela Desantis
- Department of General Surgery and Gastrointestinal Oncology, Archet 2 CHU Nice, 151 route de St. Antoine de la Ginestière, 06200, Nice, France,
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Huang CQ, Yang XJ, Yu Y, Wu HT, Liu Y, Yonemura Y, Li Y. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival for patients with peritoneal carcinomatosis from colorectal cancer: a phase II study from a Chinese center. PLoS One 2014; 9:e108509. [PMID: 25259574 PMCID: PMC4178169 DOI: 10.1371/journal.pone.0108509] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2014] [Accepted: 08/21/2014] [Indexed: 12/22/2022] Open
Abstract
Background Peritoneal carcinomatosis (PC) is a difficult clinical challenge in colorectal cancer (CRC) because conventional treatment modalities could not produce significant survival benefit, which highlights the acute need for new treatment strategies. Our previous case-control study demonstrated the potential survival advantage of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) over CRS alone. This phase II study was to further investigate the efficacy and adverse events of CRS+HIPEC for Chinese patients with CRC PC. Methods A total of 60 consecutive CRC PC patients underwent 63 procedures consisting of CRS+HIPEC and postoperative chemotherapy, all by a designated team focusing on this combined treatment modality. All the clinico-pathological information was systematically integrated into a prospective database. The primary end point was disease-specific overall survival (OS), and the secondary end points were perioperative safety profiles. Results By the most recent database update, the median follow-up was 29.9 (range 3.5–108.9) months. The peritoneal cancer index (PCI) ≤20 was in 47.0% of patients, complete cytoreductive surgery (CC0-1) was performed in 53.0% of patients. The median OS was 16.0 (95% confidence interval [CI] 12.2–19.8) months, and the 1-, 2-, 3-, and 5-year survival rates were 70.5%, 34.2%, 22.0% and 22.0%, respectively. Mortality and grades 3 to 5 morbidity rates in postoperative 30 days were 0.0% and 30.2%, respectively. Univariate analysis identified 3 parameters with significant effects on OS: PCI ≤20, CC0-1 and adjuvant chemotherapy over 6 cycles. On multivariate analysis, however, only CC0-1 and adjuvant chemotherapy ≥6 cycles were found to be independent factors for OS benefit. Discussion CRS+HIPEC at a specialized treatment center could improve OS for selected CRC PC patients from China, with acceptable perioperative safety.
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Affiliation(s)
- Chao-Qun Huang
- Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, P.R. China
| | - Xiao-Jun Yang
- Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, P.R. China
| | - Yang Yu
- Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, P.R. China
| | - Hai-Tao Wu
- Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, P.R. China
| | - Yang Liu
- Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, P.R. China
- NPO Organization to Support Peritoneal Dissemination Treatment, Osaka, Japan
| | - Yutaka Yonemura
- NPO Organization to Support Peritoneal Dissemination Treatment, Osaka, Japan
| | - Yan Li
- Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, P.R. China
- * E-mail:
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Ba M, Long H, Zhang X, Tang Y, Wu Y, Yu F, Wang S, Cui S. Different sequential approaches of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in treating ovarian cancer with malignant ascites. J Cancer Res Clin Oncol 2014; 140:1497-506. [PMID: 24849730 DOI: 10.1007/s00432-014-1692-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2014] [Accepted: 04/19/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND OBJECTIVES Treatment for malignant ascites in advanced ovarian cancer (OC) patients remains controversial. The objective of this study was to investigate the efficacy of combined continuous circulatory hyperthermic intraperitoneal chemotherapy (HIPEC) preceded or followed by cytoreductive surgery (CRS) for malignant ascites in OC patients. METHODS Female OC patients (n = 32) with malignant ascites were divided based on stable (n = 17) or unstable (n = 15) vital signs. Stable patients were treated with CRS immediately followed by HIPEC (CRS + HIPEC). Unstable patients were treated using B-mode ultrasound-guided HIPEC followed by delayed CRS upon vital sign stability (HIPEC + dCRS). All patients were followed up until death or until December 2012. RESULTS Median follow-up was 29 months. All patients showed ascite regression [objective remission rates (ORR) = 100 %]. Among stable patients, CRS + HIPEC was successful in 14/17 (83.4 %). Among unstable patients, HIPEC + dCRS was successful in 13/15 (86.7 %). Median survival times were 19 and 17 months in the stable and unstable groups, respectively. No significant differences in CRS rates, ascites ORR, Karnofsky performance status scores, or survival rates were observed between groups (P > 0.05). CONCLUSION Cytoreductive surgery with immediate HIPEC and HIPEC with dCRS, determined by vital sign stability, may lead to similar outcomes in OC patients with malignant ascites.
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Affiliation(s)
- Mingchen Ba
- Intracelom Hyperthermic Perfusion Therapy Center, Cancer Hospital of Guangzhou Medical College, Guangzhou, 510095, China,
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Ceelen W, Van Nieuwenhove Y, Putte DV, Pattyn P. Neoadjuvant chemotherapy with bevacizumab may improve outcome after cytoreduction and hyperthermic intraperitoneal chemoperfusion (HIPEC) for colorectal carcinomatosis. Ann Surg Oncol 2014; 21:3023-8. [PMID: 24756812 DOI: 10.1245/s10434-014-3713-7] [Citation(s) in RCA: 71] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2013] [Indexed: 12/14/2022]
Abstract
BACKGROUND In selected patients with colorectal peritoneal carcinomatosis (PC), cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) may improve survival. We aimed to assess whether neoadjuvant chemotherapy with or without bevacizumab is indicated in this patient population. METHODS Colorectal PC patients were treated with CRS and HIPEC using oxaliplatin (200-460 mg/m(2)) or mitomycin C (35 mg/m(2)). Postoperative outcome and long-term survival were prospectively recorded. The impact of clinical variables on overall survival (OS) was assessed using univariate and Cox multivariate analysis. RESULTS Between October 2002 and May 2012, 166 patients were treated with CRS and HIPEC. Neoadjuvant chemotherapy alone was administered to 21 % and neoadjuvant chemotherapy with bevacizumab to 16 % of patients. Postoperative mortality and major morbidity were 2.4 and 35 %, respectively. Half of the patients received adjuvant chemotherapy. After a median follow-up of 18 months, OS was 27 months (95 % confidence interval 20.8-33.2). On univariate analysis, OS was associated with extent of disease (P < 0.001), neoadjuvant chemotherapy with bevacizumab (P = 0.021), completeness of cytoreduction (CC) (P < 0.001), and adjuvant chemotherapy (P = 0.04), but not with primary disease site, synchronous presentation, or chemoperfusion drug. In multivariate Cox regression, independent predictors of OS were CC (hazard ratio 0.29, P < 0.001) and neoadjuvant therapy containing bevacizumab (hazard ratio 0.31, P = 0.019). CONCLUSIONS Long-term OS after CRS and HIPEC for colorectal cancer is associated with CC and neoadjuvant therapy containing bevacizumab. This regimen merits prospective study in patients with resectable PC of colorectal origin.
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Affiliation(s)
- Wim Ceelen
- Department of Surgery, Ghent University Hospital, Ghent, Belgium,
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Hompes D, D'Hoore A, Wolthuis A, Fieuws S, Mirck B, Bruin S, Verwaal V. The use of Oxaliplatin or Mitomycin C in HIPEC treatment for peritoneal carcinomatosis from colorectal cancer: a comparative study. J Surg Oncol 2013; 109:527-32. [PMID: 24375059 DOI: 10.1002/jso.23546] [Citation(s) in RCA: 87] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2013] [Accepted: 12/05/2013] [Indexed: 12/19/2022]
Abstract
BACKGROUND Oxaliplatin and Mitomycin C (MMC) are both suitable as intraperitoneal chemotherapy agents in HIPEC for peritoneal carcinomatosis (PC) of colorectal cancer (CRC). METHODS Patient cohorts from two different HIPEC-centers underwent cytoreductive surgery and HIPEC with Oxaliplatin (39 patients) and MMC (56 patients), respectively. They were compared for toxicity and survival data. The extent of PC was assessed using the Dutch 7-region count. RESULTS The median 7-region count was 4 [range 0-7] for Oxaliplatin-patients versus 2.5 [range 1-6] for MMC-patients (P = 0.004). Median intra-operative blood loss was 650 ml [0-6,000 ml] in Oxaliplatin-patients versus 1,230 ml [range 0-5,300 ml] in MMC-patients (P < 0.001). Only MMC-patients developed neutropenia/leucopenia (26.8%, P < 0.001). After statistical correction for the extent of PC, the overall postoperative complication rate was significantly higher in MMC-patients (OR = 2.68 (95% CI: 1.04-6.91), P = 0.04), with a comparable intra-abdominal complication (IAC) rate (OR = 0.78 (95% CI: 0.30-2.03), P = 0.61), but a tendency towards more extra-abdominal complications (EAC) in MMC-patients (OR = 2.23 (95% CI: 0.91-5.43), P = 0.079). Median follow-up was significantly shorter for Oxaliplatin-patients (2.8 years) than for MMC-patients (5.1 years). Median RFS was 12.2 months [IQR: 7.2-undefined] in the Oxaliplatin-group and 13.8 months [IQR: 7.0-25.8] in the MMC-group (P = 0.87). Median OS is 37.1 months [IQR: 22.4-52.8] for Oxaliplatin-patients and 26.5 months [IQR: 16.9-64.8] for MMC-patients (P = 0.45). Logistic regression analysis (corrected for extent of PC) shows RFS (HR = 1.24 (95% CI: 0.75-2.05), P = 0.39) and OS (HR = 1.37 (95% CI: 0.74-2.54), P = 0.32) are not significantly different. CONCLUSIONS No clear benefit in RFS and OS for HIPEC with Oxaliplatin or MMC could be demonstrated in patients with PC from CRC.
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Affiliation(s)
- D Hompes
- Department of Abdominal Surgery, University Hospitals Gasthuisberg, Leuven, Belgium; Department of Surgical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek-Hospital, Amsterdam, The Netherlands
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Shimizu T, Sonoda H, Murata S, Takebayashi K, Ohta H, Miyake T, Mekata E, Shiomi H, Naka S, Tani T. Hyperthermic intraperitoneal chemotherapy using a combination of mitomycin C,5-fluorouracil, and oxaliplatin in patients at high risk of colorectal peritoneal metastasis: A Phase I clinical study. Eur J Surg Oncol 2013; 40:521-528. [PMID: 24388411 DOI: 10.1016/j.ejso.2013.12.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2013] [Revised: 11/15/2013] [Accepted: 12/05/2013] [Indexed: 01/19/2023] Open
Abstract
INTRODUCTION The drugs and protocols used for hyperthermic intraperitoneal chemotherapy (HIPEC) vary among institutions. Here we show the efficacy of the 3-drug combination of mitomycin C (MMC), 5-fluorouracil (5FU), and oxaliplatin (OHP) in an in vitro simulation of HIPEC and the safety of HIPEC with these drugs during a Phase I study of patients at high risk of developing colorectal peritoneal metastasis. METHODS To simulate HIPEC, we used HCT116 and WiDr cells to assess the growth inhibitory efficacy of MMC 2 μg/mL, 5FU 200 μg/mL, and OHP 40 μg/mL as single drugs or their combination after an exposure time of 30 min at 37 or 42 °C. In addition, nine patients underwent surgical resection of tumors and HIPEC with MMC, 5FU, and an escalating dose of OHP (90/110/130 mg/m²). Dose-limiting toxicity was monitored. RESULTS In the simulation, the 3-drug combination showed marked tumor-suppressive effects compared with those from ten times higher dose of OHP 400 μg/mL, with significant augmentation under hyperthermic conditions. No dose-limiting toxicity occurred in the clinical study. Dose escalation was completed at the final level of OHP. CONCLUSIONS The MMC-5FU-OHP combination showed marked growth inhibition against colorectal cancer cells under hyperthermic conditions in vitro. In the phase I study, the recommended dose of OHP was determined as 130 mg/m² when used with MMC and 5FU; HIPEC using MMC-5FU-OHP appears to be safe and feasible for patients at high risk of colorectal peritoneal metastasis.
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Affiliation(s)
- T Shimizu
- Department of Surgery, Shiga University of Medical Science, Seta-Tsukinowacho, Otsu, Shiga 520-2192, Japan.
| | - H Sonoda
- Department of Surgery, Shiga University of Medical Science, Seta-Tsukinowacho, Otsu, Shiga 520-2192, Japan
| | - S Murata
- Department of Surgery, Shiga University of Medical Science, Seta-Tsukinowacho, Otsu, Shiga 520-2192, Japan
| | - K Takebayashi
- Department of Surgery, Shiga University of Medical Science, Seta-Tsukinowacho, Otsu, Shiga 520-2192, Japan
| | - H Ohta
- Department of Surgery, Shiga University of Medical Science, Seta-Tsukinowacho, Otsu, Shiga 520-2192, Japan
| | - T Miyake
- Department of Surgery, Shiga University of Medical Science, Seta-Tsukinowacho, Otsu, Shiga 520-2192, Japan
| | - E Mekata
- Department of Surgery, Shiga University of Medical Science, Seta-Tsukinowacho, Otsu, Shiga 520-2192, Japan
| | - H Shiomi
- Department of Surgery, Shiga University of Medical Science, Seta-Tsukinowacho, Otsu, Shiga 520-2192, Japan
| | - S Naka
- Department of Surgery, Shiga University of Medical Science, Seta-Tsukinowacho, Otsu, Shiga 520-2192, Japan
| | - T Tani
- Department of Surgery, Shiga University of Medical Science, Seta-Tsukinowacho, Otsu, Shiga 520-2192, Japan
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Coccolini F, Gheza F, Lotti M, Virzì S, Iusco D, Ghermandi C, Melotti R, Baiocchi G, Giulini SM, Ansaloni L, Catena F. Peritoneal carcinomatosis. World J Gastroenterol 2013; 19:6979-6994. [PMID: 24222942 PMCID: PMC3819534 DOI: 10.3748/wjg.v19.i41.6979] [Citation(s) in RCA: 233] [Impact Index Per Article: 19.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2013] [Revised: 09/12/2013] [Accepted: 09/16/2013] [Indexed: 02/06/2023] Open
Abstract
Several gastrointestinal and gynecological malignancies have the potential to disseminate and grow in the peritoneal cavity. The occurrence of peritoneal carcinomatosis (PC) has been shown to significantly decrease overall survival in patients with liver and/or extraperitoneal metastases from gastrointestinal cancer. During the last three decades, the understanding of the biology and pathways of dissemination of tumors with intraperitoneal spread, and the understanding of the protective function of the peritoneal barrier against tumoral seeding, has prompted the concept that PC is a loco-regional disease: in absence of other systemic metastases, multimodal approaches combining aggressive cytoreductive surgery, intraperitoneal hyperthermic chemotherapy and systemic chemotherapy have been proposed and are actually considered promising methods to improve loco-regional control of the disease, and ultimately to increase survival. The aim of this review article is to present the evidence on treatment of PC in different tumors, in order to provide patients with a proper surgical and multidisciplinary treatment focused on optimal control of their locoregional disease.
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Gervais MK, Dubé P, McConnell Y, Drolet P, Mitchell A, Sideris L. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy with oxaliplatin for peritoneal carcinomatosis arising from colorectal cancer. J Surg Oncol 2013; 108:438-43. [PMID: 24018983 DOI: 10.1002/jso.23431] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2013] [Accepted: 08/10/2013] [Indexed: 12/30/2022]
Abstract
BACKGROUND Peritoneal carcinomatosis (PC) from colorectal cancer is associated with a poor prognosis. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) have improved survival compared to systemic chemotherapy. We evaluate the results of this treatment in our institution. METHODS Treatment consisted of complete CRS followed by HIPEC with oxaliplatin (460 mg/m(2) ) in 2 L/m(2) of D5W at 42°C during 30 min. RESULTS From 2004 to 2011, 40 patients with PC from colorectal cancer were included and 25 CRS + HIPEC were performed. Six patients had a negative second-look surgery and nine had unresectable disease. Median follow-up was 22.8 months. Overall 3- and 5-year survival rates for the cohort were 56% and 33%. The 3- and 5-year overall survival rates were 61% and 36% for HIPEC group, 82% and 67% for patients with negative second-look, and 22% and 0% for the unresectable group (P = 0.0087). 3-year disease-free survival for HIPEC group was 22%. Major complication and mortality rate for HIPEC group were 20% and 4%. Peritoneal carcinomatosis index (P = 0.0374) and lymph node status (P = 0.027) were prognostic indicators. CONCLUSIONS CRS + HIPEC with oxaliplatin for PC from colorectal cancer is an effective treatment with encouraging survival results.
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Affiliation(s)
- Mai-Kim Gervais
- Department of Surgery, Hôpital Maisonneuve-Rosemont, University of Montreal, Montréal, Québec, Canada
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Ceelen W, De Somer F, Van Nieuwenhove Y, Vande Putte D, Pattyn P. Effect of perfusion temperature on glucose and electrolyte transport during hyperthermic intraperitoneal chemoperfusion (HIPEC) with oxaliplatin. Eur J Surg Oncol 2013; 39:754-9. [DOI: 10.1016/j.ejso.2012.07.120] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2012] [Revised: 07/13/2012] [Accepted: 07/23/2012] [Indexed: 11/29/2022] Open
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Weber T, Roitman M, Link KH. Current Status of Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy in Patients With Peritoneal Carcinomatosis From Colorectal Cancer. Clin Colorectal Cancer 2012; 11:167-176. [DOI: 10.1016/j.clcc.2012.01.001] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2011] [Revised: 12/14/2011] [Accepted: 01/20/2012] [Indexed: 01/15/2023]
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Helm CW. Current status and future directions of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of ovarian cancer. Surg Oncol Clin N Am 2012; 21:645-63. [PMID: 23021722 DOI: 10.1016/j.soc.2012.07.007] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Epithelial ovarian cancer is a peritoneal surface malignancy that most often presents with spread of disease within the peritoneal cavity. Overall 5-year survival is around 50% and progress in improving outcomes is slow. Among other areas of research, hyperthermic intraperitoneal chemotherapy (HIPEC) provides a promising option. This article reviews the current status of treatment of epithelial ovarian cancer, experience with HIPEC to date, and future directions.
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Affiliation(s)
- C William Helm
- Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Women's Health, Saint Louis University School of Medicine, Suite 290, St Louis, MO 63117, USA.
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