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Allievi N, Sidhom M, Samuel MV, Tzivanakis A, Dayal S, Cecil T, Mohamed F, Moran B. Survival Analysis and Recurrence Patterns in 555 Patients with Colorectal Peritoneal Metastases Treated by Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy. Ann Surg Oncol 2024; 31:8585-8595. [PMID: 39128977 DOI: 10.1245/s10434-024-15942-1] [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: 04/30/2024] [Accepted: 07/16/2024] [Indexed: 08/13/2024]
Abstract
BACKGROUND The presence at diagnosis, or development of, colorectal peritoneal metastases (CPM) is common in colorectal cancer. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) show promising results in selected patients with CPM. The current study aimed to describe oncologic outcomes of patients with CPM, focusing on recurrence patterns and risk factors for adverse events. METHODS We conducted a retrospective review of patients with CPM treated by CRS and HIPEC at a single institution between 2000 and 2021. RESULTS A total of 555 patients were included, of whom 480 (86.5%) had complete cytoreduction, with a median age of 59 years and median Peritoneal Cancer Index (PCI) of 6. Following complete cytoreduction, 5-year overall survival (OS) and disease-free survival (DFS) were 51% and 31%, respectively. In multivariable Cox regression, PCI >6 (hazard ratio [HR] 2.25), pathological node positivity (pN+; HR 1.94), and perineural invasion (HR 1.85) were associated with decreased OS, while PCI >6, pN+, and previous systemic metastases resulted in reduced DFS. Overall, 284 (62%) patients developed recurrence, of whom 97 (34%) had local recurrence (LR), 100 (35%) had systemic recurrence (SR), and 87 (31%) had combined recurrence (5-year OS: 49.3%, 46%, and 37.4%, respectively). Mutated KRAS (mKRAS) was associated with lower 5-year OS (55.8%) and DFS (27.9%) compared with wild-type KRAS (wtKRAS; 70.7% and 37.6%, respectively). In multivariable analyses, mKRAS was related to decreased OS (HR 1.82), DFS (HR 1.55), and SR (OS 1.89), but not to LR. CONCLUSIONS Complete cytoreduction results in good survival outcomes for patients with CPM. Burden of peritoneal disease and tumor biology are the main predictors of survival. Patients with mKRAS are a high-risk cohort, with increased probability of SR and reduced survival.
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Affiliation(s)
- Niccolo Allievi
- Peritoneal Malignancy Institute, Basingstoke North Hampshire Hospital Foundation Trust, Basingstoke, UK
| | - Mark Sidhom
- Peritoneal Malignancy Institute, Basingstoke North Hampshire Hospital Foundation Trust, Basingstoke, UK
| | - Mark Vasanth Samuel
- Peritoneal Malignancy Institute, Basingstoke North Hampshire Hospital Foundation Trust, Basingstoke, UK
| | - Alexios Tzivanakis
- Peritoneal Malignancy Institute, Basingstoke North Hampshire Hospital Foundation Trust, Basingstoke, UK
| | - Sanjeev Dayal
- Peritoneal Malignancy Institute, Basingstoke North Hampshire Hospital Foundation Trust, Basingstoke, UK
| | - Tom Cecil
- Peritoneal Malignancy Institute, Basingstoke North Hampshire Hospital Foundation Trust, Basingstoke, UK
| | - Faheez Mohamed
- Peritoneal Malignancy Institute, Basingstoke North Hampshire Hospital Foundation Trust, Basingstoke, UK
| | - Brendan Moran
- Peritoneal Malignancy Institute, Basingstoke North Hampshire Hospital Foundation Trust, Basingstoke, UK.
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Larsen SG, Graf W, Larsen RH, Revheim M, Mariathasan AM, Sørensen O, Spasojevic M, Rashid G, Lundstrøm N, Gjertsen TJ, Aksnes A, Bruland ØS. Eighteen-Months Safety and Efficacy Following Intraperitoneal Treatment With 224Radium-Labeled Microparticles After CRS-HIPEC in Patients With Peritoneal Metastasis From Colorectal Cancer. J Surg Oncol 2024; 130:1395-1402. [PMID: 39428687 PMCID: PMC11826020 DOI: 10.1002/jso.27897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Accepted: 08/23/2024] [Indexed: 10/22/2024]
Abstract
BACKGROUND AND OBJECTIVES Peritoneal metastasis from colorectal cancer carries a high risk for relapse after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). A novel alpha-emitting radiopharmaceutical (Radspherin) has been designed to deliver short-range radiation to micrometastases and free-floating tumor cells. METHODS A Phase 1/2a study evaluated the safety, tolerability, and signal of efficacy of escalating doses of Radspherin injected intraperitoneally after CRS-HIPEC. RESULTS Eleven patients received 1-4 MBq (Group 1) whereas 12 patients received 7 MBq; nine patients single dose/three patients split-dose (Group 2). Median age was 66.5 and 61.5 years, and median peritoneal cancer index 6 and 7, respectively. One hundred and seventy-eight adverse events were reported, only seven were deemed related to Radspherin. Thirteen serious adverse events (SAEs) were reported in eight patients and no SAEs were related to Radspherin. At 18-months, none of the 12 patients receiving 7 MBq experienced peritoneal recurrences, however four had non-peritoneal recurrences. Across both groups (n = 22), 41% had recurrent disease, only 14% of them in the peritoneum. CONCLUSIONS Radspherin was well tolerated. At 18 months, median disease-free survival has not been reached, and none of the patients receiving the recommended dose (7 MBq) had peritoneal recurrences. The results are encouraging and warrant further clinical evaluation.
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Affiliation(s)
- S. G. Larsen
- Department of Oncological Surgery, Norwegian Radium HospitalOslo University HospitalOsloNorway
| | - W. Graf
- Department of Surgical SciencesUppsala UniversityUppsalaSweden
- Department of SurgeryUppsala Academic HospitalUppsalaSweden
| | | | - M.‐E. Revheim
- Faculty of Medicine, Institute for Clinical MedicineUniversity of OsloOsloNorway
- The Intervention CentreOslo University HospitalOsloNorway
| | - A. M. Mariathasan
- Department of Oncological Surgery, Norwegian Radium HospitalOslo University HospitalOsloNorway
| | - O. Sørensen
- Department of Oncological Surgery, Norwegian Radium HospitalOslo University HospitalOsloNorway
| | - M. Spasojevic
- Department of Oncological Surgery, Norwegian Radium HospitalOslo University HospitalOsloNorway
| | - G. Rashid
- Department of Radiology, Norwegian Radium HospitalOslo University HospitalOsloNorway
| | - N. Lundstrøm
- Department of Nuclear MedicineUppsala Academic HospitalUppsalaSweden
| | | | | | - Ø. S. Bruland
- Faculty of Medicine, Institute for Clinical MedicineUniversity of OsloOsloNorway
- Department of Oncology, Norwegian Radium HospitalOslo University HospitalOsloNorway
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Pastor-Morate D, Amigo-Morán L, Garranzo-Asensio M, Rejas-González R, Carnicero P, Rodríguez N, Pérez-Robledo JP, Barderas R, Prieto-Nieto I, Domínguez G. ΔNp73 and its effector targets promote colorectal peritoneal carcinosis and predict survival. J Pathol 2024; 263:328-337. [PMID: 38629257 DOI: 10.1002/path.6286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 02/02/2024] [Accepted: 03/20/2024] [Indexed: 06/12/2024]
Abstract
Peritoneal metastasis of colorectal origin appears in ~10-15% of patients at the time of diagnosis and in 30-40% of cases with disease progression. Locoregional spread through the peritoneum is considered stage IVc and is associated with a poor prognosis. The development of a regional therapeutic strategy based on cytoreductive surgery, and hyperthermic intra-abdominal chemotherapy has significantly altered the course of the disease. Although recent evidence supports the benefits of cytoreductive surgery, the benefits of hyperthermic intra-abdominal chemotherapy are, however, still a matter of debate. Understanding the molecular alterations underlying the disease is crucial for developing new therapeutic strategies. Here, we evaluated the involvement in peritoneal dissemination of the oncogenic isoform of TP73, ΔNp73, and its effector targets in in vitro and mouse models, and in 30 patients diagnosed with colorectal peritoneal metastasis. In an orthotopic mouse model, we observed that tumor cells overexpressing ΔNp73 present a higher avidity for the peritoneum and that extracellular vesicles secreted by ΔNp73-upregulating tumor cells enhance their dissemination. In addition, we identified that tumor cells overexpressing ΔNp73 present with dysregulation of genes associated with an epithelial/mesothelial-to-mesenchymal transition (MMT) and that mesothelial cells exposed to the conditioned medium of tumor cells with upregulated ΔNp73 present a mesenchymal phenotype. Lastly, ΔNp73 and its effector target RNAs were dysregulated in our patient series, there were positive correlations between ΔNp73 and its effector targets, and MSN and ITGB4 (ΔNp73 effectors) predicted patient survival. In conclusion, ΔNp73 and its effector targets are involved in the peritoneal dissemination of colorectal cancer and predict patient survival. The promotion of the EMT/MMT and modulation of the adhesion capacity in colorectal cancer cells might be the mechanisms triggered by ΔNp73. Remarkably, ΔNp73 protein is a druggable protein and should be the focus of future studies. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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Affiliation(s)
- Daniel Pastor-Morate
- Department of Medicine, Faculty of Medicine, "Alberto Sols" Biomedical Research Institute, CSIC-UAM and IdiPAZ, Madrid, Spain
| | - Lidia Amigo-Morán
- Department of Medicine, Faculty of Medicine, "Alberto Sols" Biomedical Research Institute, CSIC-UAM and IdiPAZ, Madrid, Spain
| | - María Garranzo-Asensio
- Carlos III Health Institute, Functional Research Unit into Chronic Diseases (UFIEC), Madrid, Spain
| | - Raquel Rejas-González
- Carlos III Health Institute, Functional Research Unit into Chronic Diseases (UFIEC), Madrid, Spain
| | - Patricia Carnicero
- Department of Medicine, Faculty of Medicine, "Alberto Sols" Biomedical Research Institute, CSIC-UAM and IdiPAZ, Madrid, Spain
| | - Nuria Rodríguez
- Department of Medical Oncology, La Paz University Hospital, IdiPAZ-UAM, Madrid, Spain
| | - Juan Pedro Pérez-Robledo
- Peritoneal Carcinosis Unit, Department of General and Gastrointestinal Surgery, La Paz University Hospital, IdiPAZ-UAM, Madrid, Spain
| | - Rodrigo Barderas
- Carlos III Health Institute, Functional Research Unit into Chronic Diseases (UFIEC), Madrid, Spain
| | - Isabel Prieto-Nieto
- Peritoneal Carcinosis Unit, Department of General and Gastrointestinal Surgery, La Paz University Hospital, IdiPAZ-UAM, Madrid, Spain
| | - Gemma Domínguez
- Department of Medicine, Faculty of Medicine, "Alberto Sols" Biomedical Research Institute, CSIC-UAM and IdiPAZ, Madrid, Spain
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Yano H, Gohda Y, Moran BJ, Suda R, Kokudo N. Long-term outcomes and survival analysis of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy in patients with pseudomyxoma peritonei at a newly established peritoneal malignancy centre in Japan. Ann Gastroenterol Surg 2024; 8:701-710. [PMID: 38957568 PMCID: PMC11216784 DOI: 10.1002/ags3.12791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 12/20/2023] [Accepted: 02/26/2024] [Indexed: 07/04/2024] Open
Abstract
Background Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is established in the management of pseudomyxoma peritonei (PMP), selected cases of peritoneal mesothelioma, and resectable colorectal or ovarian peritoneal metastases in Western countries. However, the efficacy and feasibility of these techniques are not well established in the Asian population, and little has been reported on long-term survival outcomes for surgically resected PMP patients. Materials and Methods Retrospective analysis of a prospective database of short- and longer-term outcomes of consecutive patients who underwent CRS and HIPEC for PMP in a newly established peritoneal malignancy unit in Japan between 2010 and 2016. Results A total of 105 patients underwent CRS and HIPEC and 57 maximal tumor debulking (MTD) for pseudomyxoma peritonei. In the CRS group, the primary tumor was appendiceal in 94 patients (90%) followed by ovarian and colorectal. Major postoperative complications occurred in 22/105 patients (21%) with one in-hospital mortality (0.9%). The 5-year overall and disease-free survival rates for the CRS group were 74.2% and 50.1%, respectively. Multivariate analysis revealed unfavorable histology to be the significant predictor of reduced overall and disease-free survival. Completeness of cytoreduction, CA19-9, and CA125 were also associated with disease-free survival. Conclusions This is the first report on long-term outcomes and survival analysis of CRS and HIPEC for PMP in the Asian population. CRS and HIPEC can be conducted with reasonable safety and favorable survival in a new center. Complete tumor removal and histological type are the strongest prognostic factors for both overall and disease-free survival.
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Affiliation(s)
- Hideaki Yano
- Department of SurgeryNational Center for Global Health and MedicineTokyoJapan
- Division of Colorectal SurgeryUniversity Hospital SouthamptonSouthamptonUK
| | - Yoshimasa Gohda
- Department of SurgeryNational Center for Global Health and MedicineTokyoJapan
| | - Brendan J. Moran
- Peritoneal Malignancy Institute, North Hampshire HospitalBasingstokeUK
| | | | - Norihiro Kokudo
- Department of SurgeryNational Center for Global Health and MedicineTokyoJapan
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Balachandran R, Thaysen HV, Christensen P, Zachariae R, Iversen LH. Biopsychosocial Late Effects After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastases from Colorectal and Appendiceal Cancer: A National Prospective Cohort Study. Ann Surg Oncol 2024; 31:1959-1969. [PMID: 38127212 PMCID: PMC10838225 DOI: 10.1245/s10434-023-14618-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 11/01/2023] [Indexed: 12/23/2023]
Abstract
BACKGROUND Colorectal cancer with peritoneal metastases can be treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Treatment may result in biopsychosocial late effects (LEs). We explored the frequency and severity of the following biopsychosocial LEs: anxiety, depression, fear of cancer recurrence (FCR), insomnia, fatigue, cognitive impairment, and pain, and evaluated their impact on quality of life (QoL). METHOD This was a national prospective cohort study screening for LEs during the period January 2021-May 2023. Patients completed the following questionnaires: General Anxiety Disorder-7, Patient Health Questionnaire-9, FCR Inventory-Short Form, Insomnia Severity Index, Functional Assessment of Chronic Illness Therapy-Fatigue, cognitive impairment (six items from the European Organisation for Research and Treatment of Cancer Item Library), and the Rectal Cancer Pain Score. Preregistration was completed at ClinicalTrials.gov (NCT04956107). RESULT In total, 99 patients were included. The mean age was 61 years and 57% were women. At 3 months after surgery, the frequent LEs were fatigue (72%), FCR (58%), and pain (48%), and at 12 months after surgery, the frequent LEs were FCR (65%), fatigue (40%), and insomnia (33%). More than half of the patients (54%) reported at least two LEs after 12 months. Patients with moderate-to-severe LEs reported a lower QoL than patients with no/mild LEs. Patients with no/mild LEs had a similar QoL as the Danish norm population. CONCLUSION Biopsychosocial LEs were prevalent. The QoL of patients reporting LEs in the worst severity categories was negatively impacted. Screening and treatment for these LEs should be a focus in cancer survivor follow-up.
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Affiliation(s)
- Rogini Balachandran
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark.
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
- Danish Cancer Society Centre for Research on Survivorship and Late Adverse Effects After Cancer in the Pelvic Organs, Aarhus University Hospital, Aarhus, Denmark.
| | - Henriette Vind Thaysen
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Peter Christensen
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Danish Cancer Society Centre for Research on Survivorship and Late Adverse Effects After Cancer in the Pelvic Organs, Aarhus University Hospital, Aarhus, Denmark
| | - Robert Zachariae
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Danish Cancer Society Centre for Research on Survivorship and Late Adverse Effects After Cancer in the Pelvic Organs, Aarhus University Hospital, Aarhus, Denmark
- Unit for Psychooncology and Health Psychology, Aarhus University Hospital, Aarhus, Denmark
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
- Department of Psychology and Behavioural Sciences, Aarhus University, Aarhus, Denmark
| | - Lene Hjerrild Iversen
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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Shah R, Gangi A. Role of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in the Management of Colorectal Peritoneal Metastases. Clin Colon Rectal Surg 2024; 37:90-95. [PMID: 38322605 PMCID: PMC10843886 DOI: 10.1055/s-0042-1758759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2024]
Abstract
Peritoneal metastases from colon cancer are a particularly challenging disease process given the limited response to systemic chemotherapy. In patients with isolated peritoneal metastases, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy offers a potential treatment option to these patients with limited peritoneal metastases as long as a complete cytoreduction is achieved. Decision about a patient's candidacy for this treatment modality should be undertaken by a multidisciplinary group at expert centers.
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Affiliation(s)
- Rupen Shah
- Division of Surgical Oncology, Henry Ford Cancer Institute/Henry Ford Health, Detroit, Michigan
| | - Alexandra Gangi
- Division of Surgical Oncology, Cedars Sinai Medical Center, Los Angeles, California
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Mizumoto A, Takao N, Imagami T, An B, Oe Y, Togawa T, Yonemura Y. Cytoreductive surgery for synchronous and metachronous colorectal peritoneal dissemination: Japanese P classification and peritoneal cancer index. Ann Gastroenterol Surg 2024; 8:88-97. [PMID: 38250692 PMCID: PMC10797820 DOI: 10.1002/ags3.12721] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 06/25/2023] [Accepted: 07/10/2023] [Indexed: 01/23/2024] Open
Abstract
Aim The outcomes of cytoreductive surgery (CRS) for synchronous and metachronous colorectal peritoneal dissemination were investigated using the Japanese P classification and peritoneal cancer index (PCI). Methods CRS was performed in 111 cases of synchronous peritoneal dissemination and 115 cases of metachronous peritoneal dissemination. The P classification and PCI were determined at the time of laparotomy. Results In the synchronous dissemination group, the 5-year overall survival rates after CRS in P1/P2 and P3 cases were 51% and 13%, respectively. Even for P3, 51% of the patients achieved macroscopic cytoreductive complete resection (CC-0), with a 5-year survival rate of 40%. When P3 cases were classified into PCI 0-9, 10-19, 20-29, and 30-39, CC-0 was achieved in 93%, 70%, 6%, and 0% of the cases, respectively, and the 5-year survival rate of PCI 0-9 was 41%. In the metachronous dissemination group, the 5-year survival rates were 62% for PCI 0-9 and 22% for PCI 10-19; 5-year survival was not observed in patients with a PCI ≥ 20. CC-0 was significantly associated with the postoperative prognosis in both synchronous and metachronous peritoneal dissemination. Conclusion In cases of synchronous dissemination, CRS must be performed for P1 and P2 cases or those with a PCI < 10, while detailed examination using PCI is required for P3 cases. In cases of metachronous dissemination, CRS should be considered when the PCI score is <20.
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Affiliation(s)
- Akiyoshi Mizumoto
- Department of Gastrointestinal Surgery and Peritoneal Dissemination Center, Omi Medical CenterKusatsuJapan
| | - Nobuyuki Takao
- Department of Gastrointestinal Surgery and Peritoneal Dissemination Center, Omi Medical CenterKusatsuJapan
| | - Toru Imagami
- Department of Gastrointestinal Surgery and Peritoneal Dissemination Center, Omi Medical CenterKusatsuJapan
| | - Byonggu An
- Department of Gastrointestinal Surgery and Peritoneal Dissemination Center, Omi Medical CenterKusatsuJapan
| | - Yasumitsu Oe
- Department of Gastrointestinal Surgery and Peritoneal Dissemination Center, Omi Medical CenterKusatsuJapan
| | - Takeshi Togawa
- Department of Gastrointestinal Surgery and Peritoneal Dissemination Center, Omi Medical CenterKusatsuJapan
| | - Yutaka Yonemura
- NPO to support Peritoneal Surface Malignancy TreatmentKyotoJapan
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Winicki NM, Radomski SN, Florissi IS, Cloyd JM, Gutta G, Grotz TE, Scally CP, Fournier KF, Dineen SP, Powers BD, Veerapong J, Baumgartner JM, Clarke CN, Kothari AN, Maduekwe UN, Patel SH, Wilson GC, Schwartz P, Varley PR, Raoof M, Lee B, Malik I, Johnston FM, Greer JB. Neighborhood-Level Socioeconomic Disadvantage Predicts Outcomes in Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Malignancy. Ann Surg Oncol 2023; 30:7840-7847. [PMID: 37620532 PMCID: PMC10592201 DOI: 10.1245/s10434-023-14074-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Accepted: 07/17/2023] [Indexed: 08/26/2023]
Abstract
BACKGROUND Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) improves survival in select patients with peritoneal metastases (PM), but the impact of social determinants of health on CRS/HIPEC outcomes remains unclear. PATIENTS AND METHODS A retrospective review was conducted of a multi-institutional database of patients with PM who underwent CRS/HIPEC in the USA between 2000 and 2017. The area deprivation index (ADI) was linked to the patient's residential address. Patients were categorized as living in low (1-49) or high (50-100) ADI residences, with increasing scores indicating higher socioeconomic disadvantage. The primary outcome was overall survival (OS). Secondary outcomes included perioperative complications, hospital/intensive care unit (ICU) length of stay (LOS), and disease-free survival (DFS). RESULTS Among 1675 patients 1061 (63.3%) resided in low ADI areas and 614 (36.7%) high ADI areas. Appendiceal tumors (n = 1102, 65.8%) and colon cancer (n = 322, 19.2%) were the most common histologies. On multivariate analysis, high ADI was not associated with increased perioperative complications, hospital/ICU LOS, or DFS. High ADI was associated with worse OS (median not reached versus 49 months; 5 year OS 61.0% versus 28.2%, P < 0.0001). On multivariate Cox-regression analysis, high ADI (HR, 2.26; 95% CI 1.13-4.50; P < 0.001), cancer recurrence (HR, 2.26; 95% CI 1.61-3.20; P < 0.0001), increases in peritoneal carcinomatosis index (HR, 1.03; 95% CI 1.01-1.05; P < 0.001), and incomplete cytoreduction (HR, 4.48; 95% CI 3.01-6.53; P < 0.0001) were associated with worse OS. CONCLUSIONS Even after controlling for cancer-specific variables, adverse outcomes persisted in association with neighborhood-level socioeconomic disadvantage. The individual and structural-level factors leading to these cancer disparities warrant further investigation to improve outcomes for all patients with peritoneal malignancies.
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Affiliation(s)
- Nolan M Winicki
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Shannon N Radomski
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Isabella S Florissi
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jordan M Cloyd
- Department of Surgery, The Ohio State University, Columbus, OH, USA
| | - Goutam Gutta
- Department of Surgery, The Ohio State University, Columbus, OH, USA
| | | | - Christopher P Scally
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Keith F Fournier
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Sean P Dineen
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA
| | - Benjamin D Powers
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA
| | - Jula Veerapong
- Department of Surgery, UC San Diego School of Medicine, La Jolla, CA, USA
| | - Joel M Baumgartner
- Department of Surgery, UC San Diego School of Medicine, La Jolla, CA, USA
| | - Callisia N Clarke
- Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Anai N Kothari
- Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Ugwuji N Maduekwe
- 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
| | - Gregory C Wilson
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Patrick Schwartz
- Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA
| | - Patrick R Varley
- Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA
| | - Mustafa Raoof
- Department of Surgery, City of Hope, Duarte, CA, USA
| | - Byrne Lee
- Department of Surgery, Stanford University, Palo Alto, CA, USA
| | - Ibrahim Malik
- Department of Surgery, City of Hope, Duarte, CA, USA
| | - Fabian M Johnston
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jonathan B Greer
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
- Division of Gastrointestinal Surgical Oncology, Peritoneal Surface Malignancy Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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Tan JKT, Wong JSM, Seo CJ, Lim C, Zhu HY, Ong CAJ, Chia CS. Incidence and outcomes of delayed presentation and surgery in peritoneal surface malignancies. Front Oncol 2023; 13:1137785. [PMID: 37324005 PMCID: PMC10265672 DOI: 10.3389/fonc.2023.1137785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Accepted: 05/18/2023] [Indexed: 06/17/2023] Open
Abstract
Background Peritoneal surface malignancies (PSM) present insidiously and often pose diagnostic challenges. There is a paucity of literature quantifying the frequency and extent of therapeutic delays in PSM and its impact on oncological outcomes. Methods A review of a prospectively maintained registry of PSM patients undergoing Cytoreductive Surgery and Hyperthermic Intra-peritoneal Chemotherapy (CRS-HIPEC) was conducted. Causes for treatment delays were identified. We evaluate the impact of delayed presentation and treatment delays on oncological outcomes using Cox proportional hazards models. Results 319 patients underwent CRS-HIPEC over a 6-years duration. 58 patients were eventually included in this study. Mean duration between symptom onset and CRS-HIPEC was 186.0 ± 37.1 days (range 18-1494 days) and mean duration of between patient-reported symptom onset and initial presentation was 56.7 ± 16.8 days. Delayed presentation (> 60 days between symptom onset and presentation) was seen in 20.7% (n=12) of patients and 50.0% (n=29) experienced a significant treatment delay of > 90 days between 1st presentation and CRS-HIPEC. Common causes for treatment delays were healthcare provider-related i.e. delayed or inappropriate referrals (43.1%) and delayed presentation to care (31.0%). Delayed presentation was a significantly associated with poorer disease free survival (DFS) (HR 4.67, 95% CI 1.11-19.69, p=0.036). Conclusion Delayed presentation and treatment delays are common and may have an impact on oncological outcomes. There is an urgent need to improve patient education and streamline healthcare delivery processes in the management of PSM.
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Affiliation(s)
- Jun Kiat Thaddaeus Tan
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, 11 Hospital Crescent, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
| | - Jolene Si Min Wong
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, 11 Hospital Crescent, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- SingHealth Duke-NUS Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
| | - Chin Jin Seo
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, 11 Hospital Crescent, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- SingHealth Duke-NUS Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
| | - Cindy Lim
- Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre Singapore, Singapore, Singapore
| | - Hong-Yuan Zhu
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, 11 Hospital Crescent, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
| | - Chin-Ann Johnny Ong
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, 11 Hospital Crescent, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- SingHealth Duke-NUS Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, 11 Hospital Crescent, Singapore, Singapore
- Institute of Molecular and Cell Biology, A*STAR Research Entitie, Singapore, Singapore
| | - Claramae Shulyn Chia
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, 11 Hospital Crescent, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumors (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- SingHealth Duke-NUS Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
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10
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Hanna DN, Macfie R, Ghani MO, Hermina A, Mina A, Cha DE, Bailey CE, Cohen N, Labow D, Golas B, Sarpel U, Magge D, Idrees K. A total neoadjuvant chemotherapy approach is associated with improved recurrence-free survival in patients with colorectal peritoneal metastases undergoing cytoreductive surgery and HIPEC. J Surg Oncol 2023; 127:442-449. [PMID: 36350108 PMCID: PMC9892314 DOI: 10.1002/jso.27136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Revised: 09/20/2022] [Accepted: 10/24/2022] [Indexed: 11/11/2022]
Abstract
BACKGROUND The primary aim of this study is to evaluate the oncologic outcomes of two popular systemic chemotherapy approaches in patients with colorectal peritoneal metastases (CPM) undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). METHODS We performed a dual-center retrospective review of consecutive patients who underwent CRS-HIPEC for CPM due to high or intermediate-grade colorectal cancer. Patients in the total neoadjuvant therapy (TNT) group received 6 months of preoperative chemotherapy. Patients in the "sandwich" (SAND) chemotherapy group received 3 months of preoperative chemotherapy with a maximum of 3 months of postoperative chemotherapy. RESULTS A total of 34 (43%) patients were included in the TNT group and 45 (57%) patients in the SAND group. The median overall survival (OS) in the TNT and SAND groups were 77 and 61 months, respectively (p = 0.8). Patients in the TNT group had significantly longer recurrence-free survival (RFS) than the SAND group (29 vs. 12 months, p = 0.02). In a multivariable analysis, the TNT approach was independently associated with improved RFS. CONCLUSION In this retrospective study, a TNT approach was associated with improved RFS, but not OS when compared with a SAND approach. Further prospective studies are needed to examine these systemic chemotherapeutic approaches in patients with CPM undergoing CRS-HIPEC.
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Affiliation(s)
- David N. Hanna
- Vanderbilt University Medical Center, Section of Surgical Sciences, Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, Nashville, TN
| | - Rebekah Macfie
- Icahn School of Medicine at Mount Sinai University, Department of Surgery, Division of Surgical Oncology, New York City, NY
| | - Muhammad O. Ghani
- Vanderbilt University Medical Center, Section of Surgical Sciences, Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, Nashville, TN
| | - Andrew Hermina
- Vanderbilt University Medical Center, Section of Surgical Sciences, Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, Nashville, TN
| | | | - Da Eun Cha
- Icahn School of Medicine at Mount Sinai University, Department of Surgery, Division of Surgical Oncology, New York City, NY
| | - Christina E. Bailey
- Vanderbilt University Medical Center, Section of Surgical Sciences, Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, Nashville, TN
| | - Noah Cohen
- Icahn School of Medicine at Mount Sinai University, Department of Surgery, Division of Surgical Oncology, New York City, NY
| | - Daniel Labow
- Icahn School of Medicine at Mount Sinai University, Department of Surgery, Division of Surgical Oncology, New York City, NY
| | - Benjamin Golas
- Icahn School of Medicine at Mount Sinai University, Department of Surgery, Division of Surgical Oncology, New York City, NY
| | - Umut Sarpel
- Icahn School of Medicine at Mount Sinai University, Department of Surgery, Division of Surgical Oncology, New York City, NY
| | - Deepa Magge
- Vanderbilt University Medical Center, Section of Surgical Sciences, Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, Nashville, TN
| | - Kamran Idrees
- Vanderbilt University Medical Center, Section of Surgical Sciences, Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, Nashville, TN
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11
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Cytoreductive surgery and intraperitoneal chemotherapy for peritoneal metastasis of colorectal cancer: long-term follow-up results at a single institution in Korea. Int J Colorectal Dis 2023; 38:44. [PMID: 36795220 DOI: 10.1007/s00384-023-04340-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/07/2023] [Indexed: 02/17/2023]
Abstract
PURPOSE This study aimed to examine the 7-year follow-up results of cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) for peritoneal metastasis (PM) of colorectal cancer. METHODS We performed 54 cases of CRS and IPC in 53 patients with PM of colorectal cancer from December 2011 to December 2013. We prospectively collected data and analyzed peritoneal carcinomatosis grade, completeness of cytoreduction, and long-term follow-up (median, 10 [range, 2-92] months) results. RESULTS The mean peritoneal cancer index was 15 (1 ~ 35), and complete cytoreduction was possible in 35 (64.8%) patients. Excluding the four patients who died, 11 (22.4%) out of the 49 patients were alive at the time of the last follow-up, and the overall median survival period was 10.3 months. The overall 2- and 5-year survival rates were 31% and 17%, respectively. Patients with complete cytoreduction had a median survival period of 22.6 months, which was significantly longer than that for patients without complete cytoreduction (3.5 months) (P < 0.001). The 5-year survival rate for patients with complete cytoreduction was 24%, and four patients were still alive without disease. CONCLUSIONS CRS and IPC show a 5-year survival rate of 17% in patients with PM of colorectal cancer. A possibility of long-term survival is observed in a selected group. Multidisciplinary team evaluation for careful patient selection and CRS training program to achieve complete cytoreduction are significantly important factors in improving survival rate.
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12
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Larsen SG, Graf W, Mariathasan AB, Sørensen O, Spasojevic M, Goscinski MA, Selboe S, Lundstrøm N, Holtermann A, Revheim ME, Bruland ØS. First experience with 224Radium-labeled microparticles (Radspherin®) after CRS-HIPEC for peritoneal metastasis in colorectal cancer (a phase 1 study). Front Med (Lausanne) 2023; 10:1070362. [PMID: 36936230 PMCID: PMC10016379 DOI: 10.3389/fmed.2023.1070362] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Accepted: 01/23/2023] [Indexed: 03/05/2023] Open
Abstract
Background Peritoneal metastasis (PM) from colorectal cancer carries a dismal prognosis despite extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). With a median time to recurrence of 11-12 months, there is a need for novel therapies. Radspherin® consists of the α-emitting radionuclide radium-224 (224Ra), which has a half-life of 3.6 days and is adsorbed to a suspension of biodegradable calcium carbonate microparticles that are designed to give short-range radiation to the serosal peritoneal surface linings, killing free-floating and/or tumor cell clusters that remain after CRS-HIPEC. Methods A first-in-human phase 1 study (EudraCT 2018-002803-33) was conducted at two specialized CRS-HIPEC centers. Radspherin® was administered intraperitoneally 2 days after CRS-HIPEC. Dose escalation at increasing activity dose levels of 1-2-4-7-MBq, a split-dose repeated injection, and expansion cohorts were used to evaluate the safety and tolerability of Radspherin®. The aim was to explore the recommended dose and biodistribution using gamma-camera imaging. The results from the planned safety interim analysis after the completion of the dose-limiting toxicity (DLT) period of 30 days are presented. Results Twenty-three patients were enrolled: 14 in the dose escalation cohort, three in the repeated cohort, and six in the expansion cohort. Of the 23 enrolled patients, seven were men and 16 were women with a median age of 64 years (28-78). Twelve patients had synchronous PM stage IV and 11 patients had metachronous PM [primary stage II; (6) and stage III; (5)], with a disease-free interval of 15 months (3-30). The peritoneal cancer index was median 7 (3-19), operation time was 395 min (194-515), and hospital stay was 12 days (7-37). A total of 68 grade 2 adverse events were reported for 17 patients during the first 30 days; most were considered related to CRS and/or HIPEC. Only six of the TEAEs were evaluated as related to Radspherin®. One TEAE, anastomotic leakage, was reported as grade 3. Accordion ≥3 grade events occurred in a total of four of the 23 patients: reoperation due to anastomotic leaks (two) and drained abscesses (two). No DLT was documented at the 7 MBq dose level that was then defined as the recommended dose. The biodistribution of Radspherin® showed a relatively even peritoneal distribution. Conclusion All dose levels of Radspherin® were well tolerated, and DLT was not reached. No deaths occurred, and no serious adverse events were considered related to Radspherin®.Clinical Trial Registration: Clinicaltrials.gov, NCT03732781.
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Affiliation(s)
- Stein Gunnar Larsen
- Department of Gastroenterological Surgery, Section for Surgical Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
- *Correspondence: Stein Gunnar Larsen,
| | - Wilhelm Graf
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
- Uppsala Academic Hospital, Uppsala, Sweden
| | - Anthony Burton Mariathasan
- Department of Gastroenterological Surgery, Section for Surgical Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - Olaf Sørensen
- Department of Gastroenterological Surgery, Section for Surgical Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - Milan Spasojevic
- Department of Gastroenterological Surgery, Section for Surgical Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - Mariusz Adam Goscinski
- Department of Gastroenterological Surgery, Section for Surgical Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - Silje Selboe
- Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway
| | - Nadja Lundstrøm
- Uppsala Academic Hospital, Uppsala, Sweden
- Department of Nuclear Medicine, Uppsala, Sweden
| | - Anne Holtermann
- Department of Gastroenterological Surgery, Section for Surgical Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - Mona-Elisabeth Revheim
- Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway
- Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Øyvind Sverre Bruland
- Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Department of Oncology, Oslo University Hospital, Oslo, Norway
- Oncoinvent AS, Oslo, Norway
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13
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Elgendy H, Iqbal M, Youssef T, Alzahrani A, Rugaan A. Optimizing risk factors influence Intensive Care stay after Hyperthermic Intraperitoneal Chemotherapy? An observational cohort study. Cancer Treat Res Commun 2022; 33:100653. [PMID: 36327575 DOI: 10.1016/j.ctarc.2022.100653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 10/20/2022] [Accepted: 10/25/2022] [Indexed: 11/09/2022]
Abstract
BACKGROUND It may be necessary to admit patients receiving Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to the intensive care unit (ICU). They were required to evaluate the length of ICU stay (LOS) following HIPEC, as well as their survival rates and risk factors that influence LOS. METHODS 74 HIPEC patients were observed after being admitted to the ICU. Their assignments were made based on their LOS at the ICU. Short stay group, patients who stayed in the ICU for three days or less (S-group) and patients who stayed for three days or longer (L-group). RESULTS Survival rates for both groups were comparable. After HIPEC, they exhibited intraoperative hypotension (P = 0.015), hyopthermia (P = 0.014), and hyperglycemia (P = 0.010). Additionally, patients in group L underwent longer surgeries (P = 0.013), lost more blood (P = 0.043), and required more transfusions (P = 0.001). Subjects in group-L had higher SOFA, fentanyl, and vasopressor requirements (all P 0.001), higher ALT and AST levels, disrupted K, lower Na, and higher INR levels (all P 0.001), as well as a higher APACHE II score (P = 0.007). Preoperative BUN had an independent risk factor for LOS of 0.861; (95% CI), (0.742- 0.999); P = 0.048; and crystalloid transfusion had an independent risk factor of 1.000; (95% CI), (0.999- 1.000); P = 0.003. CONCLUSIONS Transfusions of crystalloids and BUN were independent risk factors for extended LOS. ICU LOS had no impact on survival. All measures should be taken to control hemostasis in vulnerable HIPEC participants.
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Affiliation(s)
- Hamed Elgendy
- Department of Anaesthesia, Assiut University Hospitals, Egypt; Department of Anaesthesia, Al Wakrah Hospital, Hamad Medical Corporation, Doha, Qatar.
| | - Masood Iqbal
- Dept. Critical Care Medicine, King Abdullah Medical City, Makkah, Saudi Arabia
| | - Talha Youssef
- Department of Internal Medicine, Nephrology, king Abdul-Aziz Medical City - Ministry of National Guard, Riyadh, Saudi Arabia
| | | | - Asia Rugaan
- Dept. Critical Care Medicine, King Abdullah Medical City, Makkah, Saudi Arabia
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14
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Adamina M, Warlaumont M, Berger MD, Däster S, Delaloye R, Digklia A, Gloor B, Fritsch R, Koeberle D, Koessler T, Lehmann K, Müller P, Peterli R, Ris F, Steffen T, Weisshaupt CS, Hübner M. Comprehensive Treatment Algorithms of the Swiss Peritoneal Cancer Group for Peritoneal Cancer of Gastrointestinal Origin. Cancers (Basel) 2022; 14:4275. [PMID: 36077810 PMCID: PMC9454505 DOI: 10.3390/cancers14174275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 08/26/2022] [Accepted: 08/29/2022] [Indexed: 11/16/2022] Open
Abstract
Peritoneal cancer (PC) is a dire finding, yet in selected patients, long-term survival is possible. Complete cytoreductive surgery (CRS) together with combination immunochemotherapy is essential to achieve cure. Hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC) are increasingly added to the multimodal treatment. The Swiss Peritoneal Cancer Group (SPCG) is an interdisciplinary group of expert clinicians. It has developed comprehensive treatment algorithms for patients with PC from pseudomyxoma peritonei, peritoneal mesothelioma, gastric, and colorectal origin. They include multimodal neoadjuvant treatment, surgical resection, and palliative care. The indication for and results of CRS HIPEC and PIPAC are discussed in light of the current literature. Institutional volume and clinical expertise required to achieve best outcomes are underlined, while inclusion of patients considered for CRS HIPEC and PIPAC in a clinical registry is strongly advised. The present recommendations are in line with current international guidelines and provide the first comprehensive treatment proposal for patients with PC including intraperitoneal chemotherapy. The SPCG comprehensive treatment algorithms provide evidence-based guidance for the multimodal care of patients with PC of gastrointestinal origin that were endorsed by all Swiss clinicians routinely involved in the multimodal care of these challenging patients.
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Affiliation(s)
- Michel Adamina
- Klinik für Viszeral- und Thoraxchirurgie, Kantonsspital Winterthur, 8401 Winterthur, Switzerland
- Faculty of Medicine, University of Basel, 4056 Basel, Switzerland
| | - Maxime Warlaumont
- Chirurgie Digestive et Cancérologique, CHU de Lille, CH de Cambrai, 59000 Lille, France
- Department of Visceral Surgery, Lausanne University Hospital CHUV, University of Lausanne, 1011 Lausanne, Switzerland
| | - Martin D. Berger
- Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
| | - Silvio Däster
- Clarunis, Department of Visceral Surgery, University Centre for Gastrointestinal and Liver Diseases, St. Claraspital and University Hospital Basel, 4031 Basel, Switzerland
| | - Raphaël Delaloye
- Department of Medical Oncology, University Hospital Basel, 4031 Basel, Switzerland
| | - Antonia Digklia
- Department of Oncology, Lausanne University Hospital CHUV, University of Lausanne, 1011 Lausanne, Switzerland
| | - Beat Gloor
- Department of Visceral Surgery and Medicine, Inselspital, University Bern, 3010 Bern, Switzerland
| | - Ralph Fritsch
- Department of Medical Oncology and Hematology, University Hospital Zurich, 8091 Zurich, Switzerland
| | - Dieter Koeberle
- Department of Medical Oncology and Hematology, St. Claraspital, 4002 Basel, Switzerland
- Faculty of Medicine, University of Bern, 3012 Bern, Switzerland
| | - Thibaud Koessler
- Department of Oncology, Geneva University Hospital, 1205 Geneva, Switzerland
| | - Kuno Lehmann
- Department of Surgery and Transplantation, University Hospital Zurich, 8091 Zurich, Switzerland
| | - Phaedra Müller
- Klinik für Viszeral- und Thoraxchirurgie, Kantonsspital Winterthur, 8401 Winterthur, Switzerland
| | - Ralph Peterli
- Clarunis, Department of Visceral Surgery, University Centre for Gastrointestinal and Liver Diseases, St. Claraspital and University Hospital Basel, 4031 Basel, Switzerland
| | - Frédéric Ris
- Division of Digestive Surgery, University Hospitals of Geneva, 1205 Geneva, Switzerland
| | - Thomas Steffen
- Klinik für Allgemein-, Viszeral-, Endokrine und Transplantationschirurgie, Kantonsspital St. Gallen, 9000 St. Gallen, Switzerland
| | | | - Martin Hübner
- Department of Visceral Surgery, Lausanne University Hospital CHUV, University of Lausanne, 1011 Lausanne, Switzerland
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15
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Balachandran R. ASO Author Reflections: Organ-Specific Adverse Effects After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy-A Scoping Review. Ann Surg Oncol 2022; 29:6084-6085. [PMID: 35190947 DOI: 10.1245/s10434-022-11426-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 01/24/2022] [Indexed: 11/18/2022]
Affiliation(s)
- Rogini Balachandran
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark.
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
- Danish Cancer Society Centre for Research on Survivorship and Late Adverse Effects After Cancer in the Pelvic Organs, Aarhus, Denmark.
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16
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Management of Peritoneal Disease in Colorectal Cancer. Hematol Oncol Clin North Am 2022; 36:569-582. [DOI: 10.1016/j.hoc.2022.02.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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17
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Larsen SG, Goscinski MA, Dueland S, Steigen SE, Hofsli E, Torgunrud A, Lund-Iversen M, Dagenborg VJ, Flatmark K, Sorbye H. Impact of KRAS, BRAF and microsatellite instability status after cytoreductive surgery and HIPEC in a national cohort of colorectal peritoneal metastasis patients. Br J Cancer 2022; 126:726-735. [PMID: 34887523 PMCID: PMC8888568 DOI: 10.1038/s41416-021-01620-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 10/18/2021] [Accepted: 10/29/2021] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Patients with metastatic colorectal cancer (mCRC) carrying BRAF (mutBRAF) or KRAS mutation (mutKRAS) have an inferior prognosis after liver or lung surgery, whereas the prognostic role in the context of peritoneal metastasis (PM) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been less investigated. METHODS In total, 257 patients with non-appendiceal PM-CRC were included from the Norwegian National Unit for CRS-HIPEC. RESULTS In total, 180 patients received CRS-HIPEC with Mitomycin C, 77 patients received palliative surgery only. In the CRS-HIPEC group, mutBRAF was found in 24.7%, mutKRAS 33.9% and double wild-type 41.4% without differences in survival. MSI was found in 29.3% of mutBRAF cases. Patients with mutBRAF/MSI had superior 5-year survival compared to mutBRAF with MSS (58.3% vs 25.2%, P = 0.022), and better 3-year disease-free survival (DFS) compared to mutKRAS (48.6% vs 17.2%, P = 0.049). Peritoneal Cancer Index and the number of lymph node metastasis were prognostic for OS, and the same two, location and gender prognostic for DFS in multivariate analysis. CONCLUSIONS PM-CRC with CRS-HIPEC patients has a surprisingly high proportion of mutBRAF (24.7%). Survival was similar comparing mutBRAF, mutKRAS and double wild-type cases, whereas a small subgroup with mutBRAF and MSI had better survival. Patients with mutBRAF tumours and limited PM should be considered for CRS-HIPEC.
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Affiliation(s)
- S. G. Larsen
- grid.55325.340000 0004 0389 8485Section for Surgical Oncology, Norwegian Radium Hospital, Department of Gastroenterological Surgery, Oslo University Hospital, Oslo, Norway
| | - M. A. Goscinski
- grid.55325.340000 0004 0389 8485Section for Surgical Oncology, Norwegian Radium Hospital, Department of Gastroenterological Surgery, Oslo University Hospital, Oslo, Norway
| | - S. Dueland
- grid.55325.340000 0004 0389 8485Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - S. E. Steigen
- grid.412244.50000 0004 4689 5540Department of Clinical Pathology, University Hospital of North Norway, Tromsø, Norway
| | - E. Hofsli
- grid.52522.320000 0004 0627 3560The Cancer Clinic, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway ,grid.5947.f0000 0001 1516 2393Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
| | - A. Torgunrud
- grid.5947.f0000 0001 1516 2393Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
| | - M. Lund-Iversen
- grid.5510.10000 0004 1936 8921Department of Clinical Pathology, University of Oslo, Oslo, Norway
| | - V. J. Dagenborg
- grid.55325.340000 0004 0389 8485Section for Surgical Oncology, Norwegian Radium Hospital, Department of Gastroenterological Surgery, Oslo University Hospital, Oslo, Norway
| | - K. Flatmark
- grid.55325.340000 0004 0389 8485Section for Surgical Oncology, Norwegian Radium Hospital, Department of Gastroenterological Surgery, Oslo University Hospital, Oslo, Norway ,grid.55325.340000 0004 0389 8485Department of Tumor Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - H. Sorbye
- grid.7914.b0000 0004 1936 7443Department of Oncology, Haukeland University Hospital and Department of Clinical Science, University of Bergen, Bergen, Norway
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18
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Balachandran R, Mogensen LZ, Christensen P, Thaysen HV, Iversen LH. Organ-Specific Adverse Effects After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy. Ann Surg Oncol 2022; 29:6049-6083. [PMID: 35217973 DOI: 10.1245/s10434-022-11356-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 01/10/2022] [Indexed: 12/15/2022]
Affiliation(s)
- Rogini Balachandran
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark. .,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. .,Danish Cancer Society Centre for Research on Survivorship and Late Adverse Effects after Cancer in the Pelvic Organs, Aarhus, Denmark.
| | | | - Peter Christensen
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,Danish Cancer Society Centre for Research on Survivorship and Late Adverse Effects after Cancer in the Pelvic Organs, Aarhus, Denmark
| | - Henriette Vind Thaysen
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Lene Hjerrild Iversen
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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19
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Lundbech M, Krag AE, Iversen LH, Hvas AM. Postoperative bleeding and venous thromboembolism in colorectal cancer patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: a systematic review and meta-analysis. Int J Colorectal Dis 2022; 37:17-33. [PMID: 34626208 DOI: 10.1007/s00384-021-04021-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/25/2021] [Indexed: 02/04/2023]
Abstract
PURPOSE Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has improved survival for selected patients with peritoneal metastases from colorectal cancer. Previous studies report conflicting rates of postoperative bleeding and venous thromboembolism (VTE) after CRS + HIPEC. The aim of the present study was to systematically review the literature and to estimate the overall 30-day incidence of postoperative bleeding and the overall 90-day incidence of VTE after CRS + HIPEC. METHODS Studies were identified in PubMed, Embase, and Web of Science on 29 April 2021. Data were extracted for a qualitative synthesis and to estimate an overall mean incidence in the meta-analysis. RESULTS Fourteen studies with a total of 3268 patients were included in the systematic review. Postoperative bleeding incidence rates within 30 days ranged from 1.7 to 8.3% with an overall 30-day postoperative bleeding incidence with [95% CI] at 4.2 [2.6;6.2]%. VTE incidence rates within 90 days ranged from 0.2 to 13.6% with an overall 90-day VTE incidence with [95% CI] at 2.7 [1;5.2]% after CRS + HIPEC. CONCLUSION This systematic review and meta-analysis indicate a low risk for postoperative bleeding within 30 days and VTE within 90 days after CRS + HIPEC for peritoneal metastases from colorectal cancer.
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Affiliation(s)
- Mikkel Lundbech
- Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Andreas Engel Krag
- Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.,Department of Plastic and Breast Surgery, Aarhus University Hospital, Aarhus, Denmark
| | - Lene Hjerrild Iversen
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,Department of Surgery, Aarhus University Hospital, Aarhus, Denmark
| | - Anne-Mette Hvas
- Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark. .,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
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20
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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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21
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Jeong SY, Jeon BG, Kim JE, Shin R, Ahn HS, Jin H, Heo SC. Interleukin 10 level in the peritoneal cavity is a prognostic marker for peritoneal recurrence of T4 colorectal cancer. Sci Rep 2021; 11:9212. [PMID: 33911154 PMCID: PMC8080840 DOI: 10.1038/s41598-021-88653-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 04/15/2021] [Indexed: 01/01/2023] Open
Abstract
Peritoneal recurrence (PR) is a major relapse pattern of colorectal cancer (CRC). We investigated whether peritoneal immune cytokines can predict PR. Cytokine concentrations of peritoneal fluid from CRC patients were measured. Patients were grouped according to peritoneal cancer burden (PCB): no tumor cells (≤ pT3), microscopic tumor cells (pT4), or gross tumors (M1c). Cytokine concentrations were compared among the three groups and the associations of those in pT4 patients with and without postoperative PR were assessed. Of the ten cytokines assayed, IL6, IL10, and TGFB1 increased with progression of PCB. Among these, IL10 was a marker of PR in pT4 (N = 61) patients based on ROC curve (p = 0.004). The IL10 cut-off value (14 pg/mL) divided patients into groups with a low (7%, 2 of 29 patients) or high (45%, 16 of 32 patients) 5-year PR (p < 0.001). Multivariable analysis identified high IL10 levels as the independent risk factor for PR. Separation of patients into training and test sets to evaluate the performance of IL10 cut-off model validated this cytokine as a risk factor for PR. Peritoneal IL10 is a prognostic marker of PR in pT4 CRC. Further research is necessary to identify immune response of intraperitoneal CRC growth.
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Affiliation(s)
- Seung-Yong Jeong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Byeong Geon Jeon
- Department of Surgery, Daejin Medical Center Bundang Jesaeng General Hospital, Sungnam-Si, Republic of Korea
| | - Ji-Eun Kim
- Department of Surgery, Seoul National University-Seoul Metropolitan Government (SNU-SMG) Boramae Medical Center, Seoul, Republic of Korea
| | - Rumi Shin
- Department of Surgery, Seoul National University-Seoul Metropolitan Government (SNU-SMG) Boramae Medical Center, Seoul, Republic of Korea
| | - Hye Seong Ahn
- Department of Surgery, Seoul National University-Seoul Metropolitan Government (SNU-SMG) Boramae Medical Center, Seoul, Republic of Korea
| | - Heejin Jin
- Medical Research Collaborating Center, Seoul National University-Seoul Metropolitan Government (SNU-SMG) Boramae Medical Center, Seoul, Republic of Korea
| | - Seung Chul Heo
- Department of Surgery, Seoul National University-Seoul Metropolitan Government (SNU-SMG) Boramae Medical Center, Seoul, Republic of Korea.
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22
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Ramanathan R, Choudry H, Jones H, Girgis M, Gooding W, Kalinski P, Bartlett DL. Phase II Trial of Adjuvant Dendritic Cell Vaccine in Combination with Celecoxib, Interferon-α, and Rintatolimod in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastases. Ann Surg Oncol 2021; 28:4637-4646. [PMID: 33400000 PMCID: PMC7784622 DOI: 10.1245/s10434-020-09464-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 11/25/2020] [Indexed: 01/06/2023]
Abstract
BACKGROUND Peritoneal metastases portend poor prognosis in the setting of standard chemotherapy. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) improves outcomes, but relapse is common. We report a phase II trial evaluating the safety and efficacy of adjuvant αDC1 vaccination with chemokine modulation (CKM) after CRS/HIPEC. METHODS Patients undergoing CRS/HIPEC for appendiceal cancer, colorectal cancer, or peritoneal mesothelioma were enrolled. In addition to standard adjuvant chemotherapy, patients received intranodal and intradermal injections of autologous tumor-loaded αDC1 vaccine. After each vaccine booster, patients received CKM over 4 days, consisting of celecoxib, interferon (IFN)-α, and rintatolimod. RESULTS Forty-six patients underwent CRS/HIPEC followed by αDC1 treatment, including 24 appendiceal primaries, 20 colorectal, and 2 mesotheliomas. DC maturation was successful, with 97% expressing HLA-DR and CD86. Tumor cell recovery from peritoneal tumors was challenging, resulting in only 17% of patients receiving the target dose of αDC1. The αDC1 and CKM regimen was well tolerated. CKM successfully modulated serum inflammatory cytokine and chemokine levels. Median progression-free survival (PFS) for appendiceal primaries was 50.4, 34.2, and 8.9 months for grade 1, 2, and 3 tumors, respectively, while median PFS for colorectal cancer was 20.5 and 8.9 months for moderately and poorly differentiated tumors, respectively. CONCLUSIONS Adjuvant autologous tumor antigen-loaded αDC1 vaccine and CKM is well tolerated. The mucinous nature of peritoneal metastases limits the feasibility of obtaining adequate autologous tumor cells. The improvement in median PFS did not meet our predefined thresholds, leading us to conclude that αDC1 vaccination is not appropriate for patients undergoing CRS/HIPEC for peritoneal metastases.
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Affiliation(s)
- Rajesh Ramanathan
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.,Department of Surgery, Banner MD Anderson Cancer Center, Phoenix, AZ, USA
| | - Haroon Choudry
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Heather Jones
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Mark Girgis
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.,Department of Surgery, UCLA Health, Los Angeles, CA, USA
| | - William Gooding
- Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA
| | - Pawel Kalinski
- Medical Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA
| | - David L Bartlett
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. .,Department of Surgery, AHN Cancer Institute, Pittsburgh, PA, USA.
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23
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Brown KGM, Ansari N, Solomon MJ, Austin KKS, Hamilton AER, Young CJ. Pelvic exenteration combined with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for advanced primary or recurrent colorectal cancer with peritoneal metastases. Colorectal Dis 2021; 23:186-191. [PMID: 32978813 DOI: 10.1111/codi.15378] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 07/25/2020] [Accepted: 09/10/2020] [Indexed: 02/06/2023]
Abstract
AIM The aim was to report early outcomes of six patients who underwent combined pelvic exenteration (PE), cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced or recurrent colorectal cancer with colorectal peritoneal metastases at a single centre. The literature contains limited data on the safety and oncological outcomes of patients who undergo this combined procedure. METHODS Six patients who underwent combined PE, CRS and HIPEC at Royal Prince Alfred Hospital, Sydney, between January 2017 and February 2020 were identified and included. Data were extracted from prospectively maintained databases. RESULTS Three patients underwent surgery for advanced primary rectal cancer, while two patients had recurrent sigmoid cancer and one had recurrent rectal cancer. All patients had synchronous peritoneal metastases. Two patients required total PE and two patients had a central (bladder-sparing) PE. The median peritoneal carcinomatosis index was 6 (range 3-12) and all patients underwent a complete cytoreduction. The median operating time was 702 min (range 485-900) and the median blood loss was 1650 ml (range 700-12,000). The median length of intensive care unit and hospital stay was 4.5 and 25 days, respectively. There was no inpatient, 30-day or 90-day mortality. Three patients (50%) experienced a major (Clavien-Dindo III/IV) complication. At a median follow-up of 11.5 months (range 2-18 months), two patients died with recurrent disease, one patient was alive with recurrence, while three patients remain alive and disease-free. Of the three patients who developed recurrent disease, one had isolated pelvic recurrence, one had pelvic and peritoneal recurrences and one had bone metastases. CONCLUSION Early results from this initial experience with simultaneous PE, CRS and HIPEC suggest that this combined procedure is safe and feasible; however, the long-term oncological and quality of life outcomes require further investigation.
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Affiliation(s)
- Kilian G M Brown
- Surgical Outcomes Research Centre (SOuRCe), Sydney, New South Wales, Australia.,The Institute of Academic Surgery at RPA, Sydney, New South Wales, Australia.,Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
| | - Nabila Ansari
- Surgical Outcomes Research Centre (SOuRCe), Sydney, New South Wales, Australia.,The Institute of Academic Surgery at RPA, Sydney, New South Wales, Australia.,Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
| | - Michael J Solomon
- Surgical Outcomes Research Centre (SOuRCe), Sydney, New South Wales, Australia.,The Institute of Academic Surgery at RPA, Sydney, New South Wales, Australia.,Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.,University of Sydney, Sydney, New South Wales, Australia
| | - Kirk K S Austin
- Surgical Outcomes Research Centre (SOuRCe), Sydney, New South Wales, Australia.,The Institute of Academic Surgery at RPA, Sydney, New South Wales, Australia.,Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
| | - Auerilius E R Hamilton
- Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
| | - Christopher J Young
- The Institute of Academic Surgery at RPA, Sydney, New South Wales, Australia.,Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.,University of Sydney, Sydney, New South Wales, Australia
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24
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Hallam S, Stockton J, Bryer C, Whalley C, Pestinger V, Youssef H, Beggs AD. The transition from primary colorectal cancer to isolated peritoneal malignancy is associated with an increased tumour mutational burden. Sci Rep 2020; 10:18900. [PMID: 33144643 PMCID: PMC7641117 DOI: 10.1038/s41598-020-75844-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Accepted: 10/13/2020] [Indexed: 12/31/2022] Open
Abstract
Colorectal Peritoneal metastases (CPM) develop in 15% of colorectal cancers. Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS & HIPEC) is the current standard of care in selected patients with limited resectable CPM. Despite selection using known prognostic factors survival is varied and morbidity and mortality are relatively high. There is a need to improve patient selection and a paucity of research concerning the biology of isolated CPM. We aimed to determine the biology associated with transition from primary CRC to CPM and of patients with CPM not responding to treatment with CRS & HIPEC, to identify those suitable for treatment with CRS & HIPEC and to identify targets for existing repurposed or novel treatment strategies. A cohort of patients with CPM treated with CRS & HIPEC was recruited and divided according to prognosis. Molecular profiling of the transcriptome (n = 25), epigenome (n = 24) and genome (n = 21) of CPM and matched primary CRC was performed. CPM were characterised by frequent Wnt/ β catenin negative regulator mutations, TET2 mutations, mismatch repair mutations and high tumour mutational burden. Here we show the molecular features associated with CPM development and associated with not responding to CRS & HIPEC. Potential applications include improving patient selection for treatment with CRS & HIPEC and in future research into novel and personalised treatments targeting the molecular features identified here.
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Affiliation(s)
- Sally Hallam
- Surgical Research Laboratory, Institute of Cancer and Genomic Science, University of Birmingham, Birmingham, B15 2TT, UK
| | - Joanne Stockton
- Surgical Research Laboratory, Institute of Cancer and Genomic Science, University of Birmingham, Birmingham, B15 2TT, UK
| | - Claire Bryer
- Surgical Research Laboratory, Institute of Cancer and Genomic Science, University of Birmingham, Birmingham, B15 2TT, UK
| | - Celina Whalley
- Surgical Research Laboratory, Institute of Cancer and Genomic Science, University of Birmingham, Birmingham, B15 2TT, UK
| | - Valerie Pestinger
- Surgical Research Laboratory, Institute of Cancer and Genomic Science, University of Birmingham, Birmingham, B15 2TT, UK
| | - Haney Youssef
- Surgical Research Laboratory, Institute of Cancer and Genomic Science, University of Birmingham, Birmingham, B15 2TT, UK
| | - Andrew D Beggs
- Surgical Research Laboratory, Institute of Cancer and Genomic Science, University of Birmingham, Birmingham, B15 2TT, UK.
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25
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Yano H. Cytoreductive Surgery Combined with Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastasis from Colorectal Cancer. Clin Colon Rectal Surg 2020; 33:372-376. [PMID: 33162842 DOI: 10.1055/s-0040-1714242] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Peritoneal metastasis from colorectal cancer (PM-CRC) is used to be considered a systemic and fatal condition; however, it has been growingly accepted that PM-CRC can still be local disease rather than systemic disease as analogous to liver or lung metastasis. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is now considered an optimal treatment for PM-CRC with accumulating evidence. There is a good reason that CRS + HIPEC, widely accepted as a standard of care for pseudomyxoma peritonei (PMP), could be a viable option for PM-CRC given a similarity between PM-CRC and PMP. Recent years have also seen that modern systemic chemotherapy with or without molecular targeted agents can be effective for PM-CRC. It is possible that neoadjuvant or adjuvant chemotherapy combined with CRS + HIPEC could further improve outcomes. Patient selection, utilizing modern images and increasingly laparoscopy, is crucial. Particularly, diagnostic laparoscopy is likely to play a significant role in predicting the likelihood of achieving complete cytoreduction and assessing the peritoneal cancer index score.
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Affiliation(s)
- Hideaki Yano
- Consultant General and Colorectal Surgeon, University Hospital Southampton, Southampton, Hampshire, United Kingdom
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26
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Sluiter NR, van der Bilt JD, Croll DMR, Vriens MR, de Hingh IHJT, Hemmer P, Aalbers AGJ, Bremers AJA, Ceelen W, D'Hoore A, Schoonmade LJ, Coupé V, Verheul H, Kazemier G, Tuynman JB. Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Versus Surgery Without HIPEC for Goblet-Cell Carcinoids and Mixed Adenoneuroendocrine Carcinomas: Propensity Score-Matched Analysis of Centers in the Netherlands and Belgium. Clin Colorectal Cancer 2020; 19:e87-e99. [PMID: 32651131 DOI: 10.1016/j.clcc.2020.01.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Revised: 07/22/2019] [Accepted: 01/06/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND The value of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneally metastasized goblet-cell carcinoids (GCCs) and mixed adenoneuroendocrine carcinomas (MANECs) is currently unclear. We compared outcomes of CRS-HIPEC to surgery alone for peritoneally metastasized GCCs and MANECs. PATIENTS AND METHODS Two cohorts were obtained from the Netherlands Cancer Registry (n = 569): patients with peritoneally metastasized GCCs and MANECs treated with CRS-HIPEC in Dutch and Belgian centers (n = 45), and patients treated with surgery alone. Primary outcome was overall survival (OS). Secondary outcomes were morbidity and hospital mortality. After propensity score matching, OS was compared in univariate and multivariate analyses. A systematic literature review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines from database inception to June 25, 2018. RESULTS After matching for sex, tumor stage, lymph node stage, and liver metastases, CRS-HIPEC was associated with improved median OS in the combined GCC and MANEC group and the separate GCC subgroup in univariate (GCC + MANEC: 39 vs. 12 months, P < .001; GCC: 39 vs. 12 months, P = .017) and multivariate analysis (GCC + MANEC: hazard ratio 4.27, 95% confidence interval 1.88-9.66, P = .001; GCC: hazard ratio 2.77, 95% confidence interval 1.06-7.26, P = .038). Acceptable grade III-IV morbidity (17.5%) and mortality (0) were seen after CRS-HIPEC. The literature review supported these findings. CONCLUSION CRS-HIPEC is associated with substantial survival benefit in patients with peritoneally metastasized GCCs and MANECs compared to surgery alone and is a safe treatment option. These data support centralized care of GCC and MANEC patients with peritoneal spread in expert centers offering CRS-HIPEC.
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Affiliation(s)
- Nina R Sluiter
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
| | | | - Dorothée M R Croll
- Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Menno R Vriens
- Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
| | | | - Patrick Hemmer
- Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
| | - Arend G J Aalbers
- Department of Surgery, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Andreas J A Bremers
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Wim Ceelen
- Department of Surgery, University Hospital Ghent, Gent, Belgium
| | - Andre D'Hoore
- Department of Surgery, University Hospital Leuven, Leuven, Belgium
| | - Linda J Schoonmade
- Medical Library, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Veerle Coupé
- Department of Epidemiology and Biostatistics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Henk Verheul
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Geert Kazemier
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Jurriaan B Tuynman
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
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27
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Leigh N, Solomon D, Pletcher E, Labow DM, Magge DR, Sarpel U, Golas BJ. The importance of primary tumor origin in gastrointestinal malignancies undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. World J Surg Oncol 2020; 18:182. [PMID: 32703239 PMCID: PMC7379772 DOI: 10.1186/s12957-020-01938-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Accepted: 06/29/2020] [Indexed: 12/14/2022] Open
Abstract
Background Appendiceal and colorectal cancers with peritoneal carcinomatosis (PC) can derive benefit from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). However, its role in gastric and small bowel malignancies remains undefined. Methods We retrospectively analyzed 251 gastrointestinal adenocarcinomas with PC which underwent CRS/HIPEC at our institution from 2007 to 2017. We compared outcomes of gastric, small bowel, appendiceal, and colorectal cohorts. Results Thirty-one gastric, 8 small bowel, 91 appendiceal, and 121 colorectal cohorts were included. More gastric cancers (90%) received neoadjuvant chemotherapy than any other cohort, p = 0.002. Although colorectal had the lowest peritoneal cancer index (PCI) (9) and appendiceal the highest (16), all cohorts underwent similar rates of organ resection and complete cytoreduction. Length of stay (p = 0.005) and major perioperative morbidity (Clavien III/IV, p = 0.011) were significantly higher in gastric and small bowel. Median overall survival (OS, p < 0.001) was significantly shorter in gastric (13 months) and small bowel (9 months) than in appendiceal (33 months) and colorectal (42 months) cohorts. On multivariate analysis, complete cytoreduction and PCI score were significant predictors of OS, p < 0.05. Conclusions Primary tumor origin significantly affects outcomes after CRS/HIPEC for gastrointestinal malignancies. Though there was a survival benefit in appendiceal and colorectal, gastric and small bowel survival was comparable to systemic chemotherapy.
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Affiliation(s)
- Natasha Leigh
- Division of Surgical Oncology, Icahn School of Medicine at Mount Sinai St. Luke's West Hospital, 425 West 59th Street, Suite 7B, New York, NY, 10019, USA.
| | - Daniel Solomon
- Division of Surgical Oncology, Icahn School of Medicine at Mount Sinai St. Luke's West Hospital, 425 West 59th Street, Suite 7B, New York, NY, 10019, USA
| | - Eric Pletcher
- Division of Surgical Oncology, Icahn School of Medicine at Mount Sinai St. Luke's West Hospital, 425 West 59th Street, Suite 7B, New York, NY, 10019, USA
| | - Daniel M Labow
- Division of Surgical Oncology, Icahn School of Medicine at Mount Sinai St. Luke's West Hospital, 425 West 59th Street, Suite 7B, New York, NY, 10019, USA
| | - Deepa R Magge
- Division of Surgical Oncology, Icahn School of Medicine at Mount Sinai St. Luke's West Hospital, 425 West 59th Street, Suite 7B, New York, NY, 10019, USA
| | - Umut Sarpel
- Division of Surgical Oncology, Icahn School of Medicine at Mount Sinai St. Luke's West Hospital, 425 West 59th Street, Suite 7B, New York, NY, 10019, USA
| | - Benjamin J Golas
- Division of Surgical Oncology, Icahn School of Medicine at Mount Sinai St. Luke's West Hospital, 425 West 59th Street, Suite 7B, New York, NY, 10019, USA
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28
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Leigh N, Solomon D, Pletcher E, Labow DM, Magge DR, Sarpel U, Golas BJ. Is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy indicated in hepatobiliary malignancies? World J Surg Oncol 2020; 18:124. [PMID: 32527272 PMCID: PMC7291534 DOI: 10.1186/s12957-020-01898-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Accepted: 05/28/2020] [Indexed: 02/06/2023] Open
Abstract
Background Hepatopancreaticobiliary malignancies with peritoneal carcinomatosis exhibit poor survival with current therapies: hepatocellular carcinoma 11 months with sorafenib, and pancreaticobiliary 9–14 months with systemic chemotherapy. However, limited data exist on the utility of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in these patients. Methods We retrospectively reviewed our institutional hepatopancreaticobiliary malignancies with peritoneal carcinomatosis which underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy from 2007 to 2017 and analyzed perioperative and oncologic outcomes. Results Seventeen patients were included: 9 hepatocellular carcinoma, 8 pancreaticobiliary (4 cholangiocarcinoma, 3 gallbladder, 1 pancreatic). Peritoneal cancer index, number of organs resected, completeness of cytoreduction, and 30-day morbidity were equivalent. Hepatocellular carcinoma received significantly less neoadjuvant therapy (11%, p = 0.008), though adjuvant therapy rates were similar. At a median follow-up of 15 months, progression-free survival was similar amongst all cohorts. However, overall survival was longer in hepatocellular carcinoma (42 months vs. cholangiocarcinoma 19 months, gallbladder 8 months, pancreatic 15 months, p = 0.206) with 59% 3-year overall survival (vs. 0% cholangiocarcinoma, 0% gallbladder, 0% pancreatic). Conclusions Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy may offer a survival benefit in select hepatocellular carcinoma patients with peritoneal carcinomatosis, though has dubious utility in pancreaticobiliary malignancies.
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Affiliation(s)
- Natasha Leigh
- Division of Surgical Oncology, Icahn School of Medicine at Mount Sinai St. Luke's West Hospital, 425 West 59th Street, Suite 7B, New York, NY, 10019, USA.
| | - Daniel Solomon
- Division of Surgical Oncology, Icahn School of Medicine at Mount Sinai St. Luke's West Hospital, 425 West 59th Street, Suite 7B, New York, NY, 10019, USA
| | - Eric Pletcher
- Division of Surgical Oncology, Icahn School of Medicine at Mount Sinai St. Luke's West Hospital, 425 West 59th Street, Suite 7B, New York, NY, 10019, USA
| | - Daniel M Labow
- Division of Surgical Oncology, Icahn School of Medicine at Mount Sinai St. Luke's West Hospital, 425 West 59th Street, Suite 7B, New York, NY, 10019, USA
| | - Deepa R Magge
- Division of Surgical Oncology, Icahn School of Medicine at Mount Sinai St. Luke's West Hospital, 425 West 59th Street, Suite 7B, New York, NY, 10019, USA
| | - Umut Sarpel
- Division of Surgical Oncology, Icahn School of Medicine at Mount Sinai St. Luke's West Hospital, 425 West 59th Street, Suite 7B, New York, NY, 10019, USA
| | - Benjamin J Golas
- Division of Surgical Oncology, Icahn School of Medicine at Mount Sinai St. Luke's West Hospital, 425 West 59th Street, Suite 7B, New York, NY, 10019, USA
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29
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Beagan JJ, Sluiter NR, Bach S, Eijk PP, Vlek SL, Heideman DAM, Kusters M, Pegtel DM, Kazemier G, van Grieken NCT, Ylstra B, Tuynman JB. Circulating Tumor DNA as a Preoperative Marker of Recurrence in Patients with Peritoneal Metastases of Colorectal Cancer: A Clinical Feasibility Study. J Clin Med 2020; 9:jcm9061738. [PMID: 32512811 PMCID: PMC7357031 DOI: 10.3390/jcm9061738] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 05/29/2020] [Accepted: 06/01/2020] [Indexed: 12/13/2022] Open
Abstract
Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) may be curative for colorectal cancer patients with peritoneal metastases (PMs) but it has a high rate of morbidity. Accurate preoperative patient selection is therefore imperative, but is constrained by the limitations of current imaging techniques. In this pilot study, we explored the feasibility of circulating tumor (ct) DNA analysis to select patients for CRS-HIPEC. Thirty patients eligible for CRS-HIPEC provided blood samples preoperatively and during follow-up if the procedure was completed. Targeted Next-Generation Sequencing (NGS) of DNA from PMs was used to identify bespoke mutations that were subsequently tested in corresponding plasma cell-free (cf) DNA samples using droplet digital (dd) PCR. CtDNA was detected preoperatively in cfDNA samples from 33% of patients and was associated with a reduced disease-free survival (DFS) after CRS-HIPEC (median 6.0 months vs median not reached, p = 0.016). This association could indicate the presence of undiagnosed systemic metastases or an increased metastatic potential of the tumors. We demonstrate the feasibility of ctDNA to serve as a preoperative marker of recurrence in patients with PMs of colorectal cancer using a highly sensitive technique. A more appropriate treatment for patients with preoperative ctDNA detection may be systemic chemotherapy in addition to, or instead of, CRS-HIPEC.
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Affiliation(s)
- Jamie J. Beagan
- Department of Pathology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (J.J.B.); (P.P.E.); (D.A.M.H.); (D.M.P.); (N.C.T.v.G.)
| | - Nina R. Sluiter
- Department of Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (N.R.S.); (S.B.); (S.L.V.); (M.K.); (G.K.); (J.B.T.)
| | - Sander Bach
- Department of Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (N.R.S.); (S.B.); (S.L.V.); (M.K.); (G.K.); (J.B.T.)
| | - Paul P. Eijk
- Department of Pathology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (J.J.B.); (P.P.E.); (D.A.M.H.); (D.M.P.); (N.C.T.v.G.)
| | - Stijn L. Vlek
- Department of Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (N.R.S.); (S.B.); (S.L.V.); (M.K.); (G.K.); (J.B.T.)
| | - Daniëlle A. M. Heideman
- Department of Pathology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (J.J.B.); (P.P.E.); (D.A.M.H.); (D.M.P.); (N.C.T.v.G.)
| | - Miranda Kusters
- Department of Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (N.R.S.); (S.B.); (S.L.V.); (M.K.); (G.K.); (J.B.T.)
| | - D. Michiel Pegtel
- Department of Pathology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (J.J.B.); (P.P.E.); (D.A.M.H.); (D.M.P.); (N.C.T.v.G.)
| | - Geert Kazemier
- Department of Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (N.R.S.); (S.B.); (S.L.V.); (M.K.); (G.K.); (J.B.T.)
| | - Nicole C. T. van Grieken
- Department of Pathology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (J.J.B.); (P.P.E.); (D.A.M.H.); (D.M.P.); (N.C.T.v.G.)
| | - Bauke Ylstra
- Department of Pathology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (J.J.B.); (P.P.E.); (D.A.M.H.); (D.M.P.); (N.C.T.v.G.)
- Correspondence: ; Tel.: +31-(0)20-4442-495
| | - Jurriaan B. Tuynman
- Department of Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; (N.R.S.); (S.B.); (S.L.V.); (M.K.); (G.K.); (J.B.T.)
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Tan G, Wong J. Surgical management and hyperthermic intraperitoneal chemotherapy for locally advanced colorectal cancer. J Gastrointest Oncol 2020; 11:508-512. [PMID: 32655929 DOI: 10.21037/jgo.2019.12.10] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Locally advanced colorectal cancers (CRC) pose several management challenges, including local recurrence and the development of peritoneal metastases (PM). These recurrences are associated with a poor prognosis and onerous complications. In selected patients with PM, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) have shown to confer survival benefit. However, its effectiveness depends on the disease extent and this combined treatment is associated with significant morbidity. Additionally, early detection of PM is difficult even with state-of-the-art imaging techniques. Due to the high-risk of developing PM, locally advanced CRC are currently being investigated in several trials, including adjuvant HIPEC in an attempt to reduce the risk of PM. This review article sets out to examine the current data available on this topic, in an attempt to determine the suitability and effectiveness of HIPEC in the management of locally advanced CRC.
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Affiliation(s)
- Grace Tan
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery & Surgical Oncology, National Cancer Centre Singapore and Singapore General Hospital, Singapore, Singapore
| | - Jolene Wong
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery & Surgical Oncology, National Cancer Centre Singapore and Singapore General Hospital, Singapore, Singapore
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Impact of Neoadjuvant Chemotherapy on the Outcomes of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases: A Multi-Institutional Retrospective Review. J Clin Med 2020; 9:jcm9030748. [PMID: 32164300 PMCID: PMC7141272 DOI: 10.3390/jcm9030748] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 03/03/2020] [Accepted: 03/04/2020] [Indexed: 12/13/2022] Open
Abstract
Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with improved survival for patients with colorectal peritoneal metastases (CR-PM). However, the role of neoadjuvant chemotherapy (NAC) prior to CRS-HIPEC is poorly understood. A retrospective review of adult patients with CR-PM who underwent CRS+/-HIPEC from 2000–2017 was performed. Among 298 patients who underwent CRS+/-HIPEC, 196 (65.8%) received NAC while 102 (34.2%) underwent surgery first (SF). Patients who received NAC had lower peritoneal cancer index score (12.1 + 7.9 vs. 14.3 + 8.5, p = 0.034). There was no significant difference in grade III/IV complications (22.4% vs. 16.7%, p = 0.650), readmission (32.3% vs. 23.5%, p = 0.114), or 30-day mortality (1.5% vs. 2.9%, p = 0.411) between groups. NAC patients experienced longer overall survival (OS) (median 32.7 vs. 22.0 months, p = 0.044) but similar recurrence-free survival (RFS) (median 13.8 vs. 13.0 months, p = 0.456). After controlling for confounding factors, NAC was not independently associated with improved OS (OR 0.80) or RFS (OR 1.04). Among patients who underwent CRS+/-HIPEC for CR-PM, the use of NAC was associated with improved OS that did not persist on multivariable analysis. However, NAC prior to CRS+/-HIPEC was a safe and feasible strategy for CR-PM, which may aid in the appropriate selection of patients for aggressive cytoreductive surgery.
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Thangudu S, Kalluru P, Vankayala R. Preparation, Cytotoxicity, and In Vitro Bioimaging of Water Soluble and Highly Fluorescent Palladium Nanoclusters. Bioengineering (Basel) 2020; 7:bioengineering7010020. [PMID: 32098070 PMCID: PMC7175340 DOI: 10.3390/bioengineering7010020] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 02/11/2020] [Accepted: 02/18/2020] [Indexed: 01/16/2023] Open
Abstract
Fluorescent probes offer great potential to identify and treat surgical tumors by clinicians. To this end, several molecular probes were examined as in vitro and in vivo bioimaging probes. However, due to their ultra-low extinction coefficients as well as photobleaching problems, conventional molecular probes limit its practical utility. To address the above mentioned challenges, metal nanoclusters (MNCs) can serve as an excellent alternative with many unique features such as higher molar extinction coefficients/light absorbing capabilities, good photostability and appreciable fluorescence quantum yields. Herein, we reported a green synthesis of water soluble palladium nanoclusters (Pd NCs) and characterized them by using various spectroscopic and microscopic characterization techniques. These nanoclusters showed excellent photophysical properties with the characteristic emission peak centered at 500 nm under 420 nm photoexcitation wavelength. In vitro cytotoxicity studies in human cervical cancer cells (HeLa) cells reveal that Pd NCs exhibited good biocompatibility with an IC50 value of >100 µg/mL and also showed excellent co-localization and distribution throughout the cytoplasm region with a significant fraction translocating into cell nucleus. We foresee that Pd NCs will carry huge potential to serve as a new generation bioimaging nanoprobe owing to its smaller size, minimal cytotoxicity, nucleus translocation capability and good cell labelling properties.
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Affiliation(s)
- Suresh Thangudu
- Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan;
| | - Poliraju Kalluru
- Department of Chemistry, University of Calgary, Calgary, AB T2N 1N4, Canada;
| | - Raviraj Vankayala
- Department of Bioscience and Bioengineering, Indian Institute of Technology Jodhpur, Jodhpur, Rajasthan 342037, India
- Correspondence:
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Wong JSM, Tan GHC, Chia CS, Ong J, Ng WY, Teo MCC. The importance of synchronicity in the management of colorectal peritoneal metastases with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. World J Surg Oncol 2020; 18:10. [PMID: 31931817 PMCID: PMC6958608 DOI: 10.1186/s12957-020-1784-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Accepted: 01/05/2020] [Indexed: 12/11/2022] Open
Abstract
Background Colorectal peritoneal metastases (CPM) occur in up to 13% of patients with colorectal cancer, presenting either synchronously or metachronously. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) have been increasingly utilised for selected CPM patients with favourable outcomes, though its benefits may differ for synchronous (s-CPM) and metachronous CPM (m-CPM). Methods A retrospective analysis of CPM patients treated with CRS and HIPEC at the National Cancer Centre Singapore over 15 years was performed. In the s-CPM group, CPM was diagnosed at primary presentation with CRS and HIPEC performed at the time of or within 6 months from primary surgery. In the m-CPM group, patients developed CPM > 6 months after primary curative surgery. Results One hundred two patients with CPM were treated with CRS and HIPEC. Twenty (19.6%) patients had s-CPM and 82 (80.4%) had m-CPM. Recurrences occurred in 45% of s-CPM and in 54% of m-CPM (p = 0.619). Median overall survival was significantly prolonged in patients with m-CPM (45.2 versus 26.9 months, p = 0.025). In a subset of m-CPM patients with limited PCI in whom ICU stay was not required, a survival advantage was seen (p = 0.031). Conclusion A survival advantage was seen a subset of m-CPM patients, possibly representing differences in disease biology.
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Affiliation(s)
- Jolene Si Min Wong
- Division of Surgical Oncology, National Cancer Centre Singapore, 9 Hospital Drive, Singapore, 169610, Singapore
| | - Grace Hwei Ching Tan
- Division of Surgical Oncology, National Cancer Centre Singapore, 9 Hospital Drive, Singapore, 169610, Singapore.
| | - Claramae Shulyn Chia
- Division of Surgical Oncology, National Cancer Centre Singapore, 9 Hospital Drive, Singapore, 169610, Singapore
| | - Johnny Ong
- Division of Surgical Oncology, National Cancer Centre Singapore, 9 Hospital Drive, Singapore, 169610, Singapore
| | - Wai Yee Ng
- Division of Surgical Oncology, National Cancer Centre Singapore, 9 Hospital Drive, Singapore, 169610, Singapore
| | - Melissa Ching Ching Teo
- Division of Surgical Oncology, National Cancer Centre Singapore, 9 Hospital Drive, Singapore, 169610, Singapore
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High-grade complication is associated with poor overall survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Int J Clin Oncol 2020; 25:984-994. [PMID: 31915944 DOI: 10.1007/s10147-019-01609-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2019] [Accepted: 12/21/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly used in peritoneal carcinomatosis (PC) management. This modality is criticized for its high morbidity and mortality. We evaluate the morbidity and mortality of patients undergoing this procedure in our institution. METHODS A review of our institution's database was performed. All patients who underwent CRS/HIPEC between July 2011 and March 2018 were divided into three groups: no, low-grade, and high-grade complications. Prognostic factors were determined with Cox regression, while morbidity risk factors were analyzed using multinomial logistic regression. RESULTS 225 consecutive patients underwent CRS/HIPEC. The most common primary cancer types were colorectal (35.1%), appendiceal (25.8%), and ovarian (22.2%). Median age was 55 years old (range 14-77), and patients were typically female (68.0%). 38.7% developed low-grade complications and 14.7% had high-grade complications. No 30-day mortality was observed. Different tumor origins are associated with significant differences in overall survival (p < 0.001). Patients without complications had significantly better survival than those with high-grade complications (HR 0.35, 95% CI 0.15-0.81, p < 0.001). Males were more likely to develop low-grade complications (OR 3.30, 95% CI 1.31-8.30, p = 0.011). Intra-operative blood loss was associated with greater odds of developing any post-operative complications (OR 1.001, 95% CI 1.0003-1.002, p = 0.007; and OR 1.002, 95% CI 1.001-1.002, p < 0.001, for low and high grade, respectively). CONCLUSION Presence of high-grade complication was associated with poorer survival in patients after CRS/HIPEC. Pre-operative careful assessment of patients is pivotal to ensure favorable patient outcome following this complex procedure.
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Larentzakis A, O'Dwyer ST, Becker J, Shuweihdi F, Aziz O, Selvasekar CR, Fulford P, Renehan AG, Wilson M. Referral pathways and outcome of patients with colorectal peritoneal metastasis (CRPM). Eur J Surg Oncol 2019; 45:2310-2315. [DOI: 10.1016/j.ejso.2019.07.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2019] [Revised: 05/27/2019] [Accepted: 07/03/2019] [Indexed: 12/25/2022] Open
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Mikkelsen MS, Christiansen T, Petersen LK, Blaakaer J, Iversen LH. Morbidity after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with carboplatin used for ovarian, tubal, and primary peritoneal cancer. J Surg Oncol 2019; 120:550-557. [PMID: 31267569 DOI: 10.1002/jso.25603] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Accepted: 06/07/2019] [Indexed: 01/08/2023]
Abstract
BACKGROUND AND OBJECTIVES Hypertherm intraperitoneal chemotherapy (HIPEC) is increasingly used in the treatment of ovarian, tubal, and primary peritoneal cancer (OC). The aim was to evaluate short-term morbidity of cytoreductive surgery (CRS) and carboplatin HIPEC. METHODS Prospective feasibility study performed from January 2016 to December 2017. Twenty-five patients with primary OC (FIGO III-IV) received upfront or interval CRS combined with carboplatin HIPEC at dose 800 mg/m 2 . Primary outcome measurements: grade 3 to 5 adverse events within 30 days according to Common Terminology Criteria for Adverse Events. Secondary outcome measurements: reoperation rate, length of hospital stay, readmission rate, and time from surgery to systemic chemotherapy administration. RESULTS No deaths (grade 5) or grade 4 adverse events were observed. Eleven patients (44.0%) experienced at least one grade 3 adverse event, the most common being an infection (28.0%) and neutropenia (12.0%). The reoperation rate was 8.0%. The median hospital stay was 14 days (range 9-25 days), and five patients (25.0%) were readmitted within 30 days after surgery. Median time from surgery to the administration of the first dose of systemic chemotherapy was 41 days (range 24-81 days). CONCLUSION Our small-scale prospective study supports that CRS and carboplatin HIPEC used for primary advanced-stage OC is feasible with acceptable morbidity.
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Affiliation(s)
- Mette Schou Mikkelsen
- Department of Gynecology and Obstetrics, Aarhus University Hospital, Aarhus, Denmark
| | - Thora Christiansen
- Department of Gynecology and Obstetrics, Aarhus University Hospital, Aarhus, Denmark
| | - Lone Kjeld Petersen
- Department of Gynecology and Obstetrics, Odense University Hospital, Odense, Denmark
| | - Jan Blaakaer
- Department of Gynecology and Obstetrics, Odense University Hospital, Odense, Denmark
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Steffen T, Putora PM, Hübner M, Gloor B, Lehmann K, Kettelhack C, Adamina M, Peterli R, Schmidt J, Ris F, Glatzer M. Diagnostic Nodes of Patient Selection for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Among Colorectal Cancer Patients: A Swiss National Multicenter Survey. Clin Colorectal Cancer 2019; 18:e335-e342. [PMID: 31371166 DOI: 10.1016/j.clcc.2019.06.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 06/03/2019] [Accepted: 06/17/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND The management of patients with colorectal cancer (CRC) with peritoneal metastases is challenging, and the roles of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are unclear and debated among experts. MATERIALS AND METHODS The experts of the Swiss Peritoneal Cancer Group were contacted and agreed to participate in this analysis. Experts from 9 centers in Switzerland provided their decision algorithms for CRS/HIPEC for patients with or at high risk for peritoneal metastases from CRC. Their responses were converted into decision trees on the basis of objective consensus methodology. The decision trees were used as a basis to identify consensus and discrepancies. RESULTS The final treatment algorithms included a total of 5 decision criteria (age, Peritoneal Cancer Index [PCI], extraperitoneal metastases, Peritoneal Surface Disease Severity Score, and various risk factors [RF]) and 2 treatment options (HIPEC, yes or no). HIPEC was never recommended for patients without peritoneal metastases in the absence of RF for peritoneal metastases. For patients with a PCI ≤15 without organ metastases, all centers recommended CRS/HIPEC. There was also a consensus not to perform CRS/HIPEC in elderly patients (80 years and older), those with a PCI >20, and those with unresectable metastases. For patients with a PCI = 16 to 20, there was no consensus. CONCLUSION Multiple decision criteria relevant to all participating centers were identified. Because patient selection for CRS/HIPEC remains difficult, uniform criteria for the term "high risk" for peritoneal metastases and systemic metastases are helpful. Future trials and guidelines should take these criteria into account.
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Affiliation(s)
- Thomas Steffen
- Department of Surgery, Kantonsspital St Gallen, St Gallen, Switzerland.
| | - Paul Martin Putora
- Department of Radiation Oncology, Kantonsspital St Gallen, St Gallen, Switzerland; Department of Radiation Oncology, University of Bern, Bern, Switzerland
| | - Martin Hübner
- Department of Visceral Surgery, Lausanne University Hospital, Lausanne, Switzerland
| | - Beat Gloor
- Department of Surgery, Inselspital, University Hospital of Bern, Bern, Switzerland
| | - Kuno Lehmann
- Department of Surgery and Transplantation, University Hospital of Zürich, Zürich, Switzerland
| | | | - Michel Adamina
- Department of Surgery, Kantonsspital Winterthur, Winterthur, Switzerland
| | - Ralph Peterli
- Department of Surgery, St Claraspital, Basel, Switzerland
| | - Jan Schmidt
- Department of Surgery, Klinik Hirslanden, Zürich, Switzerland
| | - Frédéric Ris
- Department of Surgery, University Hospital of Geneva, Geneva, Switzerland
| | - Markus Glatzer
- Department of Radiation Oncology, Kantonsspital St Gallen, St Gallen, Switzerland
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Leigh NL, Solomon D, Feingold D, Magge DR, Golas BJ, Sarpel U, Labow DM. Improved Survival with Experience: A 10-Year Learning Curve in Hyperthermic Intraperitoneal Chemotherapy and Cytoreductive Surgery. Ann Surg Oncol 2019; 27:222-231. [DOI: 10.1245/s10434-019-07518-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2018] [Indexed: 12/21/2022]
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Arjona-Sanchez A, Rodriguez-Ortiz L, Baratti D, Schneider MA, Gutiérrez-Calvo A, García-Fadrique A, Tuynman JB, Cascales-Campos PA, Martín VC, Morales R, Salti GI, Arteaga X, Pacheco D, Alonso-Gomez J, Yalkin O, Villarejo-Campos P, Sanchez-Hidalgo JM, Casado-Adam A, Cosano-Alvarez A, Rufian-Peña S, Briceño J. RAS Mutation Decreases Overall Survival After Optimal Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy of Colorectal Peritoneal Metastasis: A Modification Proposal of the Peritoneal Surface Disease Severity Score. Ann Surg Oncol 2019; 26:2595-2604. [PMID: 31111351 DOI: 10.1245/s10434-019-07378-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Indexed: 11/18/2022]
Abstract
BACKGROUND Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are currently the most accepted treatment for peritoneal metastases from colorectal cancer. Restrictive selection criteria are essential to obtain the best survival benefits for this complex procedure. The most widespread score for patient selection, the peritoneal surface disease severity score (PSDSS), does not include current biological factors that are known to influence on prognosis. We investigated the impact of including RAS mutational status in the selection criteria for these patients. METHODS We studied the risk factors for survival by multivariate analysis using a prospective database of consecutive patients with carcinomatosis from colorectal origin treated by CRS and HIPEC in our unit from 2009 to 2017. The risk factors obtained were validated in a multicentre, international cohort, including a total of 520 patients from 15 different reference units. RESULTS A total of 77 patients were selected for local análisis. Only RAS mutational status (HR: 2.024; p = 0.045) and PSDSS stage (HR: 2.90; p = 0.009) were shown to be independent factors for overall survival. Early PSDSS stages I and II associated to RAS mutations impaired their overall survival with no significant differences with PSDSS stage III overall survival (p > 0.05). These results were supported by the international multicentre validation. CONCLUSIONS By including RAS mutational status, we propose an updated RAS-PSDSS score that outperforms PSDSS alone providing a quick and feasible preoperative assessment of the expected overall survival for patients with carcinomatosis from colorectal origin undergone to CRS + HIPEC.
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Affiliation(s)
- A Arjona-Sanchez
- Oncologic and Pancreatic Surgery Unit, University Hospital Reina Sofıa, Córdoba, Spain. .,Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, University Hospital Reina Sofıa, Córdoba, Spain.
| | - L Rodriguez-Ortiz
- Oncologic and Pancreatic Surgery Unit, University Hospital Reina Sofıa, Córdoba, Spain
| | - D Baratti
- Peritoneal Surface Malignancy Program, Department of Surgery, Fondazione IRCCS Instituto Nazionale Tumori, Milan, Italy
| | - M A Schneider
- Department of Surgery and Transplantation, University Hospital of Zurich, Zurich, Switzerland
| | - A Gutiérrez-Calvo
- Surgery Department, Unit of Peritoneal Oncologic Surgery, Hospital Príncipe de Asturias, Alcalá de Henares, Madrid, Spain
| | - A García-Fadrique
- Department of Surgery, Instituto Valenciano de Oncología, Valencia, Spain
| | - J B Tuynman
- Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
| | - P A Cascales-Campos
- Departamento De Cirugía General, Unidad De Cirugía De La Carcinomatosis Peritoneal, Virgen De La Arrixaca University Hospital, Murcia, Spain
| | - V Concepción Martín
- Unit of Peritoneal Oncologic Surgery and Colorectal Surgery, Hospital University Nuestra Señora de la Candelaria, Tenerife, Spain
| | - R Morales
- Unit of Oncologic and Pancreatic Surgery, Hospital Son Spaces, Palma de Mallorca, Spain
| | - G I Salti
- Division of Surgical Oncology, The University of Illinois at Chicago Hospital and Health Sciences System, Chicago, IL, USA
| | - X Arteaga
- Department of Surgery, Donostia Hospital, San Sebastián, Spain
| | - D Pacheco
- Gastroenterology Service, Liver Transplantation Unit, Rio Hortega Hospital, Valladolid, Spain
| | - J Alonso-Gomez
- Department of Surgery, H.U. Gran Canaria Dr. Negrín, Canarias, Spain
| | - O Yalkin
- Department of Surgical Oncology, Ankara University Faculty of Medicine, Ankara, Turkey
| | - P Villarejo-Campos
- Department of Surgical Oncology, University Hospital Ciudad Real, Ciudad Real, Spain
| | - J M Sanchez-Hidalgo
- Oncologic and Pancreatic Surgery Unit, University Hospital Reina Sofıa, Córdoba, Spain.,Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, University Hospital Reina Sofıa, Córdoba, Spain
| | - A Casado-Adam
- Oncologic and Pancreatic Surgery Unit, University Hospital Reina Sofıa, Córdoba, Spain.,Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, University Hospital Reina Sofıa, Córdoba, Spain
| | - A Cosano-Alvarez
- Oncologic and Pancreatic Surgery Unit, University Hospital Reina Sofıa, Córdoba, Spain
| | - S Rufian-Peña
- Oncologic and Pancreatic Surgery Unit, University Hospital Reina Sofıa, Córdoba, Spain.,Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, University Hospital Reina Sofıa, Córdoba, Spain
| | - J Briceño
- Oncologic and Pancreatic Surgery Unit, University Hospital Reina Sofıa, Córdoba, Spain.,Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, University Hospital Reina Sofıa, Córdoba, Spain
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Paredes AZ, Abdel-Misih S, Schmidt C, Dillhoff ME, Pawlik TM, Cloyd JM. Predictors of Readmission After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy. J Surg Res 2019; 234:103-109. [DOI: 10.1016/j.jss.2018.09.022] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Revised: 08/03/2018] [Accepted: 09/07/2018] [Indexed: 12/17/2022]
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Mahmoud AM, Ismail YM, Hussien A, Debaky Y, Ahmed IS, Mikhael HSW, Moneer M. Peritoneal carcinomatosis in colorectal cancer: Defining predictive factors for successful cytoreductive surgery and hyperthermic intraperitoneal chemotherapy – A pilot study. J Egypt Natl Canc Inst 2018; 30:143-150. [DOI: 10.1016/j.jnci.2018.10.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Revised: 10/29/2018] [Accepted: 10/31/2018] [Indexed: 01/18/2023] Open
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Flanagan M, Solon J, Chang K, Deady S, Moran B, Cahill R, Shields C, Mulsow J. Peritoneal metastases from extra-abdominal cancer – A population-based study. Eur J Surg Oncol 2018; 44:1811-1817. [DOI: 10.1016/j.ejso.2018.07.049] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Revised: 05/10/2018] [Accepted: 07/02/2018] [Indexed: 01/30/2023] Open
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Implications of Stoma Formation as Part of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy. World J Surg 2018; 42:2036-2042. [PMID: 29302727 DOI: 10.1007/s00268-017-4450-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Formation of protective stoma as part of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) may be an effective tool in reducing anastomotic leak incidence. Our aim was to evaluate the incidence and implications of stoma formation during CRS-HIPEC and to examine whether a creation of protective stoma reduces the postoperative morbidity. METHODS A cohort retrospective analysis of all CRS-HIPEC procedures performed between 2004 and 2016 was conducted. Predicting factors for stoma formation were assessed by comparing all patients who underwent stoma formation to those who did not; both groups were then restricted to cases with ≥2 bowel anastomoses and compared in terms of perioperative outcomes in order to determine whether protective stoma confers a morbidity benefit. RESULTS One hundred and ninety-nine CRS-HIPEC procedures were performed on 186 patients. Thirty-four patients (17%) underwent stoma formation, 24 of them as protective stoma. Formation of a stoma was correlated with higher peritoneal carcinomatosis index score (13.6 ± 8 vs. 9.5 ± 7.7, p = 0.007), larger number of organs resected (p < 0.001), greater number of anastomoses (p < 0.001), prolonged operative time (8.1 ± 2.7 vs. 6.6 ± 2.2 h, p = 0.002), and prolonged hospital stay (12 vs. 8.5 days, p = 0.001). In procedures requiring ≥2 anastomoses, formation of protective stoma reduced the anastomotic leak rate (6 vs. 37%, p = 0.025), the morbidity rate (6 vs. 41%, p = 0.017), and reoperation rate (0 vs. 28%, p = 0.03). Overall, 15 patients (44%) underwent stoma reversal, 3 of whom had a complication treated non-operatively. CONCLUSIONS Protective stoma should be considered in extensive CRS-HIPEC procedures requiring two or more bowel anastomoses in order to reduce the postoperative morbidity rate.
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Sluiter NR, Tuynman JB. ASO Author Reflections: Toward Improved Selection of Patients for Cytoreduction and HIPEC: Identification of Prognostic Factors for Patients with Colorectal Peritoneal Metastases. Ann Surg Oncol 2018; 25:840-841. [PMID: 30302638 PMCID: PMC6329718 DOI: 10.1245/s10434-018-6842-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2018] [Indexed: 11/28/2022]
Affiliation(s)
- Nina R Sluiter
- Department of Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
| | - Jurriaan B Tuynman
- Department of Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
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Harji DP, Vallance A, Selgimann J, Bach S, Mohamed F, Brown J, Fearnhead N. A systematic analysis highlighting deficiencies in reported outcomes for patients with stage IV colorectal cancer undergoing palliative resection of the primary tumour. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2018; 44:1469-1478. [PMID: 30007475 DOI: 10.1016/j.ejso.2018.06.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2018] [Revised: 05/24/2018] [Accepted: 06/11/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Management of the primary tumour in the presence of unresectable metastatic colorectal cancer (mCRC) is controversial. The role of primary tumour resection (PTR) has been investigated by a number of retrospective cohort studies, with a number on going randomised controlled trials. The aim of this study was to identify the clinical and patient-reported outcomes currently reported in studies that evaluate the role of PTR in mCRC. METHODS Literature searches were performed in MEDLINE (via OvidSP) (1966-June 2017), EMBASE (via OvidSP) and the Cochrane Library using terms related to colorectal cancer and primary tumour resection. All studies documenting outcomes following palliative PTR were included. Eligible articles were assessed using the Risk of Bias In Non-Randomised Studies of Intervention (ROBINS-I) tool. RESULTS Of 11,209 studies screened, 59 non-randomised studies reporting outcomes on 331,157 patients were included. Patient characteristics regarding performance status and co-morbidity were recorded in 26 (44.1%) and 17 (28.8%) studies. The chemotherapy regime used was reported in 27 (45.8%) studies. The operative setting and the operative approach was reported in 42 (71%) and 14 (23.7%) studies. Post-operative mortality and morbidity were reported in 33 (55.9%) and 35 (59.3%) studies. Overall survival was reported in 49 (83.1%) studies, with 5 different definitions identified. Quality of life was only reported in 1 (1.7%) study. CONCLUSION This study demonstrates significant heterogeneity in the selection and definition of outcomes reported following PTR in mCRC. There is significant heterogeneity with a significant under-reporting of important outcomes such as treatment related adverse events and patient reported outcomes.
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Affiliation(s)
- Deena P Harji
- Newcastle Centre of Bowel Disease, Royal Victoria Infirmary, Newcastle upon Tyne, UK; Clinical Trials Research Unit, University of Leeds, UK.
| | - Abigail Vallance
- Clinical Effectiveness Unit, Royal College of Surgeons, London, UK
| | - Jenny Selgimann
- Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK
| | - Simon Bach
- Department of Surgery, University Hospitals Birmingham, Birmingham, UK
| | - Faheez Mohamed
- Peritoneal Malignancy Institute, North Hampshire Hospital, Hampshire Hospital Foundation Trust, Basingstoke, UK
| | - Julia Brown
- Clinical Trials Research Unit, University of Leeds, UK
| | - Nicola Fearnhead
- Department of Colorectal Surgery, Addenbrooke's Hospital, Cambridge, UK
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46
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Brandl A, Pratschke J, Rau B. Chirurgisch-onkologische Therapie primärer und sekundärer peritonealer Neoplasien. Eur Surg 2018. [DOI: 10.1007/s10353-018-0553-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Metastatic Colorectal Cancer to the Peritoneum: Current Treatment Options. Curr Treat Options Oncol 2018; 19:49. [DOI: 10.1007/s11864-018-0563-8] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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48
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Lorimier G, Seegers V, Coudert M, Dupoiron D, Thibaudeau E, Pouplin L, Lebrec N, Dubois PY, Dumont F, Guérin-Meyer V, Capitain O, Campone M, Wernert R. Prolonged perioperative thoracic epidural analgesia may improve survival after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: A comparative study. Eur J Surg Oncol 2018; 44:1824-1831. [PMID: 30213715 DOI: 10.1016/j.ejso.2018.08.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Revised: 08/16/2018] [Accepted: 08/22/2018] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVE To assess the effectiveness of prolonged perioperative thoracic epidural analgesia (PEA) on long term survival of patients who underwent a complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases (CPM). BACKGROUND Grade III-IV morbidity affects long term outcomes after CRS and HIPEC. As compared with opioid administered via patient-controlled analgesia (PCA), PEA reduces morbidity. METHOD From 2005 to 2016, 150 patients underwent CRS plus HIPEC with or without prolonged PEA. Clinical data and outcomes collected from prospective database were analyzed. Survival was assessed in terms of analgesic method using Kaplan-Meier plots and a propensity score. RESULTS Patients 'characteristics of 59 patients in PCA group were comparable to those of 91 patients in PEA group, except for age, ASA score and fluid requirements, significantly more important in PEA group. Grade III-IV morbidity was 62.7% in PCA group compared with 36.3% in PEA group (p = 0.0015). Median overall survival (OS) of PEA group was 54.7 months compared to 39.5 months in PCA group (p = 0.0078). When adjusted on the covariates, using the propensity score, the PEA significantly improves OS [HR 0.40 (95% CI: 0.28-0.56)] (p < 0.0001) and disease free survival (DFS) [HR 0.61 (95% CI: 0.45-0.81] (p < 0.0007) CONCLUSIONS: In this retrospective study of patients who underwent a complete CRS and HIPEC for colorectal peritoneal metastases, the perioperative thoracic epidural analgesia prolonged for over 72 h reduced significantly the grade III-IV morbidity and may improve OS and DFS.
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Affiliation(s)
- Gérard Lorimier
- Department of Surgical Oncology, Integrated Center of Oncology, Angers, France
| | - Valérie Seegers
- Department of Clinical Research, Integrated Center of Oncology, Angers, France.
| | - Marie Coudert
- Department of Medical Oncology, Integrated Center of Oncology, Angers, France
| | - Denis Dupoiron
- Department of Anesthesiology, Integrated Center of Oncology, Angers, France
| | - Emilie Thibaudeau
- Department of Surgical Oncology, Integrated Center of Oncology, Nantes, France
| | - Luc Pouplin
- Department of Anesthesiology, Integrated Center of Oncology, Nantes, France
| | - Nathalie Lebrec
- Department of Anesthesiology, Integrated Center of Oncology, Angers, France
| | - Pierre Yves Dubois
- Department of Anesthesiology, Integrated Center of Oncology, Angers, France
| | - Frédéric Dumont
- Department of Surgical Oncology, Integrated Center of Oncology, Nantes, France
| | | | - Olivier Capitain
- Department of Medical Oncology, Integrated Center of Oncology, Angers, France
| | - Mario Campone
- Department of Medical Oncology, Integrated Center of Oncology, Angers, France
| | - Romuald Wernert
- Department of Surgical Oncology, Integrated Center of Oncology, Angers, France
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Guerrero W, Munene G, Dickson PV, Stiles ZE, Mays J, Davidoff AM, Glazer ES, Shibata D, Deneve JL. Outcome and factors associated with aborted cytoreduction for peritoneal carcinomatosis. J Gastrointest Oncol 2018; 9:664-673. [PMID: 30151262 DOI: 10.21037/jgo.2018.04.05] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) offers a potential cure for peritoneal carcinomatosis (PC), whereas aborted cytoreduction is associated with a poor outcome. We evaluate factors associated with aborted CRS procedures. Methods An IRB approved retrospective review was performed from 12/2011 to 2/2016. Clinicopathologic variables and outcomes are described. Results Seventy-four patients underwent attempted CRS/HIPEC which was completed in 51 (69%) and aborted in 23 (31%). There was no difference in age, race, gender or prior treatment between groups. Patients who underwent aborted procedures had a higher peritoneal cancer index (PCI, 26.1±9.9 vs. 16.2±10.5, P=0.001). Overall survival (OS) was significantly improved for patients who underwent completed CRS/HIPEC (41.0±10.4 vs. 6.0±2.3 months, P<0.0001). Patients with an appendiceal and colorectal primary who underwent CRS/HIPEC had a significantly better outcome (median not reached vs. 6±5.4 months, P<0.0001, and 28.0±7.5 vs. 8.0±4.0 months, P<0.0001, respectively). Colorectal pathology (P=0.014) and PCI score (<0.0001) were independent predictors of aborted CRS procedures. Conclusions One-third of patients with PC had significant disease which prevented successful completion of CRS/HIPEC. PCI and colorectal primary tumor pathology were associated with a greater likelihood of aborted CRS procedures.
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Affiliation(s)
- Whitney Guerrero
- Department of Surgery, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Gitonga Munene
- Western Michigan University, Homer Stryker School of Medicine, West Michigan Cancer Center, Kalamazoo, MI, USA
| | - Paxton V Dickson
- Department of Surgery, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Zachary E Stiles
- Department of Surgery, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Johnathan Mays
- College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Andrew M Davidoff
- Department of Surgery, St Jude Children's Research Hospital, Memphis, TN, USA
| | - Evan S Glazer
- Department of Surgery, University of Tennessee Health Science Center, Memphis, TN, USA
| | - David Shibata
- Department of Surgery, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Jeremiah L Deneve
- Department of Surgery, University of Tennessee Health Science Center, Memphis, TN, USA
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50
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Bignell MB, Mehta AM, Alves S, Chandrakumaran K, Dayal SP, Mohamed F, Cecil TD, Moran BJ. Impact of ovarian metastases on survival in patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignancy originating from appendiceal and colorectal cancer. Colorectal Dis 2018; 20:704-710. [PMID: 29502336 DOI: 10.1111/codi.14057] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2017] [Accepted: 02/20/2018] [Indexed: 12/24/2022]
Abstract
AIM Ovarian metastases from gastrointestinal tract malignancies have been considered an ominous finding with poor prognosis. The aim of this project was to determine the impact on survival, and potential cure, when cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are combined to treat peritoneal malignancy in women with Krukenberg tumours. METHOD A retrospective analysis of prospectively collected data between January 2010 and July 2015. Female patients undergoing complete CRS (macroscopic tumour removal) and HIPEC for pseudomyxoma peritonei (PMP) of appendiceal origin, or colorectal peritoneal metastases (CPM) were included. Survival was estimated using the Kaplan-Meier method and survival rates compared using the log-rank test. RESULTS In total, 889 patients underwent surgery for peritoneal malignancy, of whom 551 were female. Of these, 504/551 (91%) underwent complete CRS and HIPEC. Overall, 405/504 (80%) had at least one involved ovary removed either during CRS and HIPEC or at their index prereferral operation. Three hundred and fifty-two patients (87%) had an appendiceal tumour and 53 (13%) had CPM. At a median follow up of 40 months, overall survival (OS) did not differ significantly between patients with or without ovarian involvement in women with a primary low-grade appendiceal tumour or CPM. In women with high-grade primary appendiceal pathology, OS was significantly lower in patients with ovarian metastases compared with those without ovarian involvement. CONCLUSION Women with ovarian metastases from low-grade appendiceal tumours or colorectal cancer treated with CRS and HIPEC have similar survival rates to patients without ovarian metastases. Long-term survival and cure is feasible in patients amenable to complete tumour removal.
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Affiliation(s)
- M B Bignell
- Peritoneal Malignancy Institute, Basingstoke amd North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Basingstoke, UK
| | - A M Mehta
- Peritoneal Malignancy Institute, Basingstoke amd North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Basingstoke, UK
| | - S Alves
- Peritoneal Malignancy Institute, Basingstoke amd North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Basingstoke, UK
| | - K Chandrakumaran
- Peritoneal Malignancy Institute, Basingstoke amd North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Basingstoke, UK
| | - S P Dayal
- Peritoneal Malignancy Institute, Basingstoke amd North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Basingstoke, UK
| | - F Mohamed
- Peritoneal Malignancy Institute, Basingstoke amd North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Basingstoke, UK
| | - T D Cecil
- Peritoneal Malignancy Institute, Basingstoke amd North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Basingstoke, UK
| | - B J Moran
- Peritoneal Malignancy Institute, Basingstoke amd North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Basingstoke, UK
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