|
1
|
Holowatyj AN, Overman MJ, Votanopoulos KI, Lowy AM, Wagner P, Washington MK, Eng C, Foo WC, Goldberg RM, Hosseini M, Idrees K, Johnson DB, Shergill A, Ward E, Zachos NC, Shelton D. Defining a 'cells to society' research framework for appendiceal tumours. Nat Rev Cancer 2025; 25:293-315. [PMID: 39979656 DOI: 10.1038/s41568-024-00788-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/12/2024] [Indexed: 02/22/2025]
Abstract
Tumours of the appendix - a vestigial digestive organ attached to the colon - are rare. Although we estimate that around 3,000 new appendiceal cancer cases are diagnosed annually in the USA, the challenges of accurately diagnosing and identifying this tumour type suggest that this number may underestimate true population incidence. In the current absence of disease-specific screening and diagnostic imaging modalities, or well-established risk factors, the incidental discovery of appendix tumours is often prompted by acute presentations mimicking appendicitis or when the tumour has already spread into the abdominal cavity - wherein the potential misclassification of appendiceal tumours as malignancies of the colon and ovaries also increases. Notwithstanding these diagnostic difficulties, our understanding of appendix carcinogenesis has advanced in recent years. However, there persist considerable challenges to accelerating the pace of research discoveries towards the path to improved treatments and cures for patients with this group of orphan malignancies. The premise of this Expert Recommendation article is to discuss the current state of the field, to delineate unique challenges for the study of appendiceal tumours, and to propose key priority research areas that will deliver a more complete picture of appendix carcinogenesis and metastasis. The Appendix Cancer Pseudomyxoma Peritonei (ACPMP) Research Foundation Scientific Think Tank delivered a consensus of core research priorities for appendiceal tumours that are poised to be ground-breaking and transformative for scientific discovery and innovation. On the basis of these six research areas, here, we define the first 'cells to society' research framework for appendix tumours.
Collapse
Affiliation(s)
- Andreana N Holowatyj
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
- Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
- Vanderbilt University School of Medicine, Nashville, TN, USA.
| | - Michael J Overman
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | | | - Andrew M Lowy
- Department of Surgery, Division of Surgical Oncology, Moores Cancer Center, University of California San Diego, La Jolla, CA, USA
| | - Patrick Wagner
- Division of Surgical Oncology, Allegheny Health Network Cancer Institute, Allegheny Health Network, Pittsburgh, PA, USA
| | - Mary K Washington
- Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Cathy Eng
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
| | - Wai Chin Foo
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | | | - Mojgan Hosseini
- Department of Pathology, University of California, San Diego, San Diego, CA, USA
| | - Kamran Idrees
- Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
- Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Douglas B Johnson
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
| | - Ardaman Shergill
- Department of Medicine, University of Chicago Medical Center, Chicago, IL, USA
| | - Erin Ward
- Section of Surgical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
| | - Nicholas C Zachos
- Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
- Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Deborah Shelton
- Appendix Cancer Pseudomyxoma Peritonei (ACPMP) Research Foundation, Springfield, PA, USA
| |
Collapse
|
|
2
|
Sigler GI, Murtha J, Varley PR. Diagnostic Advances and Novel Therapeutics in Peritoneal Metastasis. Surg Oncol Clin N Am 2025; 34:173-194. [PMID: 40015798 DOI: 10.1016/j.soc.2024.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2025]
Abstract
Appropriate assessment of disease burden in patients with peritoneal surface malignancy (PSM) is critical for treatment decision-making, and conventional cross-sectional imaging (computed tomography and/or MRI) often underestimates burden of disease. Advances in imaging for PSM include novel functional imaging modalities that target cells unique to the tumor microenvironment. Novel alternative methods of diagnosis and disease monitoring are also potentially applicable to management of PSM. These include forms of "liquid biopsy" targeting circulating tumor DNA. Novel regional therapies include both new therapeutic agents (immune-based and nanoparticle-based), as well as new methods of delivery such as pressurized intraperitoneal aerosolized chemotherapy.
Collapse
Affiliation(s)
- Gregory I Sigler
- Division of Surgical Oncology, Department of General Surgery, Complex General Surgical Oncology, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Mail Code 7375, Madison, WI 53792, USA
| | - Jacqueline Murtha
- Department of General Surgery, General Surgery, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Mail Code 7375, Madison, WI 53792, USA
| | - Patrick R Varley
- Division of Surgical Oncology, Department of General Surgery, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Mail Code 7375, Madison, WI 53792, USA; William S. Middleton Memorial Veterans Affairs Hospital, Madison, WI, USA.
| |
Collapse
|
|
3
|
Alaswad MM, Arabi TZ, Alshahrani AS, Sabbah BN, Jaamour HW, AlOtry AA, Saleh TW, Alhosainy ZH, Elkordy FH, Elnegali AI, Tlayjeh MH, Kseibi FE, Azzam AZ, Amin TM. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy and intraoperative radiation therapy in the management of gastric cancer: a 10-year single center experience. World J Surg Oncol 2025; 23:62. [PMID: 39987135 PMCID: PMC11846258 DOI: 10.1186/s12957-025-03678-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Accepted: 01/19/2025] [Indexed: 02/24/2025] Open
Abstract
BACKGROUND The rationale behind the use of HIPEC involves targeted elimination of microscopic peritoneal metastasis, a common route for GCa dissemination, thereby improving the overall survival and reducing recurrences. Moreover, the reasoning behind the use of IORT is enhanced loco-regional control and, therefore, reducing recurrence rates. METHODS From February 2013 to June 2023, all GCa patients who underwent HIPEC plus IORT during surgery were included in this study. Median overall survival (OS) and disease-free (DFS) survival were used to evaluate the efficacy of this treatment strategy amongst GCa patients, along with the rate of occurrence and severity of post-operative complications associated with this treatment strategy. RESULTS The median OS and DFS were 63 and 87 months, respectively. More than one-third of the patients in our cohort did not develop any post-operative complications. In patients who developed post-operative complications, the median number of post-operative complications was 1 (IQR 1-2). Most encountered complications were Clavien-Dindo (CD) grade II complications (33.33%) and no in-hospital mortality was observed. CONCLUSIONS This complex, multimodal treatment strategy results in a significantly prolonged OS and DFS when compared to other treatment strategies for gastric cancer patients, with no added morbidity or mortality.
Collapse
Affiliation(s)
- Marwan M Alaswad
- College of Medicine, Alfaisal University, Al Zahrawai Street, Riyadh, Saudi Arabia.
| | - Tarek Z Arabi
- College of Medicine, Alfaisal University, Al Zahrawai Street, Riyadh, Saudi Arabia
| | - Asma S Alshahrani
- Department of Population Health, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
- King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Belal N Sabbah
- College of Medicine, Alfaisal University, Al Zahrawai Street, Riyadh, Saudi Arabia
| | - Heba W Jaamour
- College of Medicine, Alfaisal University, Al Zahrawai Street, Riyadh, Saudi Arabia
| | - Abdullah A AlOtry
- College of Medicine, Alfaisal University, Al Zahrawai Street, Riyadh, Saudi Arabia
| | - Tariq W Saleh
- College of Medicine, Alfaisal University, Al Zahrawai Street, Riyadh, Saudi Arabia
| | - Ziad H Alhosainy
- College of Medicine, Alfaisal University, Al Zahrawai Street, Riyadh, Saudi Arabia
| | - Fadwa H Elkordy
- College of Medicine, Alfaisal University, Al Zahrawai Street, Riyadh, Saudi Arabia
| | - Aya I Elnegali
- College of Medicine, Alfaisal University, Al Zahrawai Street, Riyadh, Saudi Arabia
| | - Mohamed H Tlayjeh
- College of Medicine, Alfaisal University, Al Zahrawai Street, Riyadh, Saudi Arabia
| | - Firas E Kseibi
- College of Medicine, Alfaisal University, Al Zahrawai Street, Riyadh, Saudi Arabia
| | - Ayman Z Azzam
- Department of Surgical Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
- Department of General Surgery, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Tarek M Amin
- Department of Surgical Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| |
Collapse
|
|
4
|
Alaswad M, Arabi TZ, Alhosainy Z, Alammar J, Azzam AZ, Amin TM. Overall survival and prognostic factors associated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy combined with intraoperative radiation therapy in patients with advanced abdominopelvic malignancies: A single center retrospective analysis of 159 patients. J Surg Oncol 2024; 130:1274-1289. [PMID: 39364860 DOI: 10.1002/jso.27791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Accepted: 07/18/2024] [Indexed: 10/05/2024]
Abstract
BACKGROUND AND OBJECTIVES The aim of this study was to look at the overall survival (OS), progression-free survival (PFS), and prognostic factors associated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) combined with intraoperative radiation therapy (IORT). METHODS This study is a single center retrospective study performed on 159 patients who underwent treatment with CRS and HIPEC combined with IORT for abdominopelvic malignancies. OS and PFS were used to evaluate the efficacy of this treatment strategy amongst patients with abdominopelvic malignancies. RESULTS The cohort's median age was 53 years, with a male predominance (58.5%). The median OS was not reached, but the mean OS was 76.87 months. In univariate analysis, several factors, including synchronous organ metastasis, Pathologic Peritoneal Carcinomatosis Index (pPCI) ≥10, increased estimated blood loss, and severe postoperative complications, were associated with worse OS. However, multivariate analysis identified pPCI ≥ 10 as the sole independent predictor of worse OS. The 1- and 3-year survival rates were 83% and 70.4%, respectively. pPCI ≥ 10 and severe postoperative complications were significant predictors of worse survival outcomes. CONCLUSIONS Radical surgery alone is not enough, and CRS combined with HIPEC and IORT, when indicated, was proven to be safe and effective with no added morbidity or mortality.
Collapse
Affiliation(s)
- Marwan Alaswad
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - Tarek Z Arabi
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - Ziad Alhosainy
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - Juman Alammar
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - Ayman Z Azzam
- Department of Surgical Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
- Department of General Surgery, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Tarek M Amin
- Department of Surgical Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| |
Collapse
|
|
5
|
Lario-Perez S, Macia JJ, Lillo-Garcia C, Caravaca I, Lopez-Rodriguez F, Calero A, Tomas-Rodriguez MI, Moya-Martinez A, Arroyo A, Lacueva FJ. Home-Based Trimodal Prehabilitation in Patients with Peritoneal Carcinomatosis Undergoing Cytoreductive Surgery: Effect on Functional Walking Capacity and Skeletal Muscle Mass. Ann Surg Oncol 2024; 31:7133-7141. [PMID: 39012464 DOI: 10.1245/s10434-024-15756-1] [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: 02/28/2024] [Accepted: 06/24/2024] [Indexed: 07/17/2024]
Abstract
BACKGROUND Patients with peritoneal carcinomatosis often suffer from loss of skeletal muscle mass and require extensive surgery. Multimodal prehabilitation may improve physical status but its benefits for these specific patients remain unknown. This study aimed to evaluate the effect of prehabilitation on functional walking capacity and skeletal muscle mass, as well as its association with postoperative complications. PATIENTS AND METHODS A prospective study of patients with peritoneal carcinomatosis following a home-based trimodal prehabilitation program was carried out. Functional walking capacity was assessed with the 6-min walk test (T6MWT), and by the appendicular skeletal muscle index (ASMI) estimated by bioelectrical impedance analysis. Data were collected at the first medical appointment and on the day before surgery. A 90-day postoperative morbidity was registered according to the Clavien-Dindo classification. RESULTS A total of 62 patients were included in the analysis. Women were more prevalent (77.4%) and peritoneal metastasis from ovarian origin accounted for 48.4%. Clavien II-V grades occurred in 30 (57.7%) patients. After prehabilitation, functional walking capacity improved by 42.2 m (39.62-44.72 m) compared with baseline data (p < 0.001), but no improvement was observed in the ASMI (p = 0.301). Patients able to walk at least 360 m after prehabilitation suffered fewer Clavien-Dindo II-V postoperative complications (p = 0.016). A T6MWT of less than 360 m was identified as an independent risk factor in the multivariable analysis (OR 3.99; 1.01-15.79 p = 0.048). CONCLUSIONS This home-based trimodal prehabilitation program improved functional walking capacity but not ASMI scores in patients with peritoneal metastasis before surgery. A T6MWT of less than 360 m was found to be a risk factor for postoperative complications.
Collapse
Affiliation(s)
- S Lario-Perez
- Oncological Abdominal and Pelvic Surgery Unit, General Surgery Department, University General Hospital of Elche, Elche, Spain
| | - J-J Macia
- Oncological Abdominal and Pelvic Surgery Unit, General Surgery Department, University General Hospital of Elche, Elche, Spain
| | - C Lillo-Garcia
- Oncological Abdominal and Pelvic Surgery Unit, General Surgery Department, University General Hospital of Elche, Elche, Spain
| | - I Caravaca
- Oncological Abdominal and Pelvic Surgery Unit, General Surgery Department, University General Hospital of Elche, Elche, Spain
| | - F Lopez-Rodriguez
- Colorectal Unit, General Surgery Department, University General Hospital of Elche, Elche, Spain
- Department of Pathology and Surgery, Miguel Hernández University, San Juan de Alicante, Alicante, Spain
| | - A Calero
- Oncological Abdominal and Pelvic Surgery Unit, General Surgery Department, University General Hospital of Elche, Elche, Spain
- Department of Pathology and Surgery, Miguel Hernández University, San Juan de Alicante, Alicante, Spain
| | - M I Tomas-Rodriguez
- Center for Translational Research in Physiotherapy, Pathology and Surgery Department, Miguel Hernandez University of Elche, Elche, Spain
- Department of Pathology and Surgery, Miguel Hernández University, San Juan de Alicante, Alicante, Spain
| | - A Moya-Martinez
- Statistical Department, FISABIO, University General Hospital of Elche, Elche, Spain
| | - A Arroyo
- Colorectal Unit, General Surgery Department, University General Hospital of Elche, Elche, Spain
- Department of Pathology and Surgery, Miguel Hernández University, San Juan de Alicante, Alicante, Spain
| | - F-J Lacueva
- Oncological Abdominal and Pelvic Surgery Unit, General Surgery Department, University General Hospital of Elche, Elche, Spain.
- Department of Pathology and Surgery, Miguel Hernández University, San Juan de Alicante, Alicante, Spain.
| |
Collapse
|
|
6
|
Perelló-Trias MT, Serrano-Muñoz AJ, Rodríguez-Fernández A, Segura-Sampedro JJ, Ramis JM, Monjo M. Intraperitoneal drug delivery systems for peritoneal carcinomatosis: Bridging the gap between research and clinical implementation. J Control Release 2024; 373:70-92. [PMID: 38986910 DOI: 10.1016/j.jconrel.2024.07.017] [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: 02/29/2024] [Revised: 07/05/2024] [Accepted: 07/06/2024] [Indexed: 07/12/2024]
Abstract
Several abdominal-located cancers develop metastasis within the peritoneum, what is called peritoneal carcinomatosis (PC), constituting a clinical challenge in their therapeutical management, often leading to poor prognoses. Current multidisciplinary strategies, including cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC), demonstrate efficacy but have limitations. In response, alternative strategies are explored in the drug delivery field for intraperitoneal chemotherapy. Controlled drug delivery offers a promising avenue, maintaining localized drug concentrations for optimal PC management. Drug delivery systems (DDS), including hydrogels, implants, nanoparticles, and hybrid systems, show potential for sustained and region-specific drug release. The present review aims to offer an overview of the advances and current designs of DDS for PC chemotherapy administration, focusing on their composition, main characteristics, and principal experimental outcomes, highlighting the importance of biomaterial rationale design and in vitro/vivo models for their testing. Moreover, since clinical data for human subjects are scarce, we offer a critical discussion of the gap between bench and bedside in DDS translation, emphasizing the need for further research.
Collapse
Affiliation(s)
- M Teresa Perelló-Trias
- Cell Therapy and Tissue Engineering Group (TERCIT), Research Institute of Health Sciences (IUNICS), University of the Balearic Islands (UIB), Carretera de Valldemossa, Km 7,5, 07122 Palma, Balearic Islands, Spain; Health Research Institute of the Balearic Islands (IdISBa) - Carretera de Valldemossa, 79. Hospital Universitari Son Espases. Edifici S. 07120 Palma, Balearic Islands, Spain; Department of Fundamental Biology and Health Sciences, University of the Balearic Islands (UIB), Palma, Balearic Islands, Spain
| | - Antonio Jose Serrano-Muñoz
- Cell Therapy and Tissue Engineering Group (TERCIT), Research Institute of Health Sciences (IUNICS), University of the Balearic Islands (UIB), Carretera de Valldemossa, Km 7,5, 07122 Palma, Balearic Islands, Spain; Health Research Institute of the Balearic Islands (IdISBa) - Carretera de Valldemossa, 79. Hospital Universitari Son Espases. Edifici S. 07120 Palma, Balearic Islands, Spain; Department of Fundamental Biology and Health Sciences, University of the Balearic Islands (UIB), Palma, Balearic Islands, Spain
| | - Ana Rodríguez-Fernández
- Cell Therapy and Tissue Engineering Group (TERCIT), Research Institute of Health Sciences (IUNICS), University of the Balearic Islands (UIB), Carretera de Valldemossa, Km 7,5, 07122 Palma, Balearic Islands, Spain; Health Research Institute of the Balearic Islands (IdISBa) - Carretera de Valldemossa, 79. Hospital Universitari Son Espases. Edifici S. 07120 Palma, Balearic Islands, Spain; Department of Fundamental Biology and Health Sciences, University of the Balearic Islands (UIB), Palma, Balearic Islands, Spain
| | - Juan José Segura-Sampedro
- Health Research Institute of the Balearic Islands (IdISBa) - Carretera de Valldemossa, 79. Hospital Universitari Son Espases. Edifici S. 07120 Palma, Balearic Islands, Spain; General & Digestive Surgery Service, Hospital Universitario La Paz, Paseo de la Castellana, 261, Fuencarral-El Pardo, 28046 Madrid, Spain; School of Medicine, University of the Balearic Islands (UIB), Carretera de Valldemossa, km 7,5, 07122 Palma, Balearic Islands, Spain
| | - Joana Maria Ramis
- Cell Therapy and Tissue Engineering Group (TERCIT), Research Institute of Health Sciences (IUNICS), University of the Balearic Islands (UIB), Carretera de Valldemossa, Km 7,5, 07122 Palma, Balearic Islands, Spain; Health Research Institute of the Balearic Islands (IdISBa) - Carretera de Valldemossa, 79. Hospital Universitari Son Espases. Edifici S. 07120 Palma, Balearic Islands, Spain; Department of Fundamental Biology and Health Sciences, University of the Balearic Islands (UIB), Palma, Balearic Islands, Spain.
| | - Marta Monjo
- Cell Therapy and Tissue Engineering Group (TERCIT), Research Institute of Health Sciences (IUNICS), University of the Balearic Islands (UIB), Carretera de Valldemossa, Km 7,5, 07122 Palma, Balearic Islands, Spain; Health Research Institute of the Balearic Islands (IdISBa) - Carretera de Valldemossa, 79. Hospital Universitari Son Espases. Edifici S. 07120 Palma, Balearic Islands, Spain; Department of Fundamental Biology and Health Sciences, University of the Balearic Islands (UIB), Palma, Balearic Islands, Spain.
| |
Collapse
|
|
7
|
Mollaoğlu MC, Karabacak U, Bostancı ME, Seven TE, Karadayı K. Is extereme cytoreductive surgery beneficial to survival ın malignant peritoneal mesothelioma? Acta Chir Belg 2024; 124:281-289. [PMID: 38294331 DOI: 10.1080/00015458.2024.2301806] [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: 04/12/2023] [Accepted: 12/10/2023] [Indexed: 02/01/2024]
Abstract
INTRODUCTION Malign peritoneal mesothelioma (MPM) is an uncommon disease that is difficult to treat. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) are the gold standards for treating MPM. Sometimes extreme cytoreductive surgery (eCRS) is required to achieve complete cytoreduction, which is one of the most important prognostic factors. There is limited information in the literature about the contribution of eCRS in patients with MPM. In this study, we aimed to investigate the impact of eCRS on survival and perioperative outcomes. METHODS The Department of Surgical Oncology at Cumhuriyet University database was retrospectively reviewed for MPM patients who underwent CRS-HIPEC between January 2004 and December 2018. Patients who underwent CRS-HIPEC were divided into eCRS and less extensive CRS (leCRS) groups. A resection of ≥5 organs or ≥3 small bowel anastomoses were defined as eCRS. Both groups were compared regarding survival, demographic information, and perioperative outcomes. RESULTS A total of 31 patients were included. eCRS-HIPEC was used in 15 patients. Complete cytoreduction (CC score 0/1) was achieved in all 31 patients. Compared to leCRS, the eCRS group had a longer median length of stay, longer intensive care unit stay, a higher median peritoneal cancer index (PCI), higher intraoperative blood loss, more frequent occurrence of any complication, and a longer operative time (all p values < 0.001). Clavien Dindo 3-4 complications, ASA, and gender were similar in both groups of patients (p > 0.05). It was found that there was no significant difference between the OS of the eCRS and leCRS groups (37.5 vs. 42.8 months, p = 0.895). CONCLUSIONS Rates of serious complications and morbidity are similar in patients undergoing eCRS compared to leCRS. In patients with high PCI and multiorgan involvement, complete cytoreduction can be achieved by performing eCRS, and survival results equivalent to those with low PCI can be achieved.
Collapse
Affiliation(s)
- Murat Can Mollaoğlu
- Department of Surgical Oncology, Maltepe Medical Park Hospital, İstanbul, Turkey
| | - Ufuk Karabacak
- Department of Surgical Oncology, Sivas Numune Hospital, Sivas, Turkey
| | | | - Turan Eray Seven
- Department of Surgical Oncology, Cumhuriyet University, Sivas, Turkey
| | - Kürşat Karadayı
- Department of Surgical Oncology, Cumhuriyet University, Sivas, Turkey
| |
Collapse
|
|
8
|
Maratta MG, Vitale A, Basso M, Vivolo R, Di Monte E, Biondi A, Di Giorgio A, Rosa F, Tondolo V, Agnes A, Tortora G, Strippoli A, Pozzo C. Benefit of a multimodal approach combining chemotherapy and surgery in oligometastatic gastric cancer: experience from a tertiary referral center. Front Oncol 2024; 14:1343596. [PMID: 38912067 PMCID: PMC11190071 DOI: 10.3389/fonc.2024.1343596] [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: 11/23/2023] [Accepted: 05/17/2024] [Indexed: 06/25/2024] Open
Abstract
Introduction Gastric cancer (GC) is the fourth leading cause of cancer-related death worldwide with limited therapeutic options. The aim of this study was to analyze the value of adding surgery to the first-line treatment in patients with oligometastatic GC (OGC). Methods This retrospective study included patients with OGC who underwent induction chemotherapy followed by surgery of both primary tumor and synchronous metastasis between April 2012 and April 2022. Endpoints were overall survival (OS) and relapse-free survival (RFS) analyzed by the Kaplan-Meier method. Prognostic factors were assessed with the Cox model. Results Data from 39 patients were collected. All cases were referred to our multidisciplinary tumor board (MTB) to evaluate the feasibility of radical surgery. After a median follow-up of 33.6 months (mo.), median OS was 26.6 mo. (95% CI 23.8-29.4) and median RFS was 10.6 mo. (95% CI 6.3-14.8). Pathologic response according to the Mandard criteria (TRG 1-3, not reached versus 20.5 mo. for TRG 4-5; HR 0.23, p=0.019), PS ECOG ≤ 1 (26.7 mo. for PS ≤ 1 versus 11.2 mo. for PS >1; HR 0.3, p=0.022) and a low metastatic burden (26.7 mo. for single site versus 12.9 mo. for ≥2 sites; HR 0.34, p=0.039) were related to good prognosis. No major intraoperative complications nor surgery-related deaths occurred in our series. Discussion A sequential strategy of preoperative chemotherapy and radical surgical excision of both primary tumor and metastases was demonstrated to significantly improve OS and RFS. Multidisciplinary evaluation is mandatory to identify patients who could benefit from this strategy.
Collapse
Affiliation(s)
- Maria Grazia Maratta
- Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Antonio Vitale
- Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Michele Basso
- Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Raffaella Vivolo
- Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Elena Di Monte
- Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Alberto Biondi
- Department of Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Andrea Di Giorgio
- Department of Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Fausto Rosa
- Department of Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Vincenzo Tondolo
- Department of Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Annamaria Agnes
- Department of Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Giampaolo Tortora
- Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Antonia Strippoli
- Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Carmelo Pozzo
- Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| |
Collapse
|
|
9
|
Yrjönen A, Koskenvuo L, Haapamäki C, Lepistö A. Recurrence after cytoreductive surgery and HIPEC for pseudomyxoma peritonei: A single-center retrospective cohort study. Scand J Surg 2024; 113:140-149. [PMID: 37828760 DOI: 10.1177/14574969231200653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2023]
Abstract
BACKGROUND AND AIMS Pseudomyxoma peritonei (PMP) is a rare disease characterized by progressive build-up of mucinous deposits inside the abdominal cavity. The aim of this study was to investigate the effect of disease recurrence on overall survival in patients with PMP after cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS One-hundred thirty-two consecutive PMP patients treated with CRS + HIPEC at Helsinki University Hospital between 2008 and 2017 were included. The impact of clinicopathological and treatment-related characteristics on recurrence and overall survival was evaluated. RESULTS The median follow-up time in the study was 5.04 (range = 0.05-11.60) years. In 121 (91.7%) patients, the disease was classified as low grade and 11 (8.3%) had high-grade disease. In the low-grade group, 26 (21.5%) patients developed a recurrence during follow-up compared to 6 (54.5%) patients in the high-grade group. In the low-grade group, cumulative survival was 98.2%, 91.4%, and 91.4% at 3, 6, and 8 years, respectively. In the high-grade group, cumulative survival was 90.0% and 78.8% at 3 and 6 years, respectively. In patients with recurrent disease, the cumulative survival was 100%, 84.6%, and 84.6% at 3, 6, and 8 years in the low-grade category and 80.0% and 60.0% at 3 and 6 years in the high-grade category, respectively. In the low-grade group, a statistically significant correlation with recurrence but not with overall survival was identified with peritoneal cancer index (PCI), carcinoembryonic antigen (CEA), and the number of affected regions. CONCLUSION The recurrence of low-grade PMP does not significantly affect overall survival of patients. Disease extent may not be a prognostic indicator after curative CRS and HIPEC in low-grade PMP.
Collapse
Affiliation(s)
- Antti Yrjönen
- Jorvi Hospital, Ambulatory Surgery Unit, Karvasmäentie 8, Espoo 02740 Finland
| | - Laura Koskenvuo
- Abdominal Center, Department of Abdominal Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Carola Haapamäki
- Abdominal Center, Department of Abdominal Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Anna Lepistö
- Abdominal Center, Department of Abdominal Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| |
Collapse
|
|
10
|
Herzberg J, Acs M, Guraya SY, Schlitt HJ, Honarpisheh H, Strate T, Piso P. Anastomotic leakage following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal cancer: A clinical cohort study. Surg Oncol 2024; 54:102080. [PMID: 38663060 DOI: 10.1016/j.suronc.2024.102080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Revised: 03/13/2024] [Accepted: 04/15/2024] [Indexed: 05/26/2024]
Abstract
BACKGROUND Extended oncological resections for colorectal cancer surgery are associated with a high rate of complications, especially anastomotic leakage (AL). This study determines the incidence of risk factors for postoperative complications following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer (CRC). METHODS In this cohort study, the clinical data of all patients with CRC, treated with CRS and HIPEC, from 2011 to 2021 was analyzed. We considered patients' characteristics, tumor-specific features, postoperative complications, and hospital stay using Chi-Square-test or Fisher's exact test. The Mann-Whitney-U-test was used to measure the probability of differences between two sets of data. RESULTS Of 1089 HIPEC procedures performed in the study center, 185 patients with CRC and peritoneal metastasis were treated with CRS and HIPEC after formation of at least one anastomosis and therefore included in this study. This included synchronous and metachronous peritoneal metastasis with a mean peritoneal cancer index of 8.67 ± 5.22. In this cohort, AL occurred in 12 (6.5 %) patients. There was no correlation between the number of anastomoses and the occurrence of an AL (p = 0.401). CONCLUSION This study reports a low risk of AL after CRS with HIPEC for CRC, comparable to other published data. If a complete cytoreduction seems possible, the risk of anastomotic leakage should not negatively influence the decision to resect. Further studies on this subject are essential to validate our findings.
Collapse
Affiliation(s)
- Jonas Herzberg
- Department of Surgery - Hospital Reinbek St. Adolf-Stift, Hamburger Strasse 41, 21465, Reinbek, Germany.
| | - Miklos Acs
- Department of General and Visceral Surgery, Hospital Barmherzige Brüder, Regensburg, D-93049, Germany; Department of Surgery, University Hospital, Regensburg, D-93049, Germany
| | - Salman Yousuf Guraya
- Clinical Sciences Department, College of Medicine, University of Sharjah, P. O. Box 27272, Sharjah, United Arab Emirates
| | | | - Human Honarpisheh
- Department of Surgery - Hospital Reinbek St. Adolf-Stift, Hamburger Strasse 41, 21465, Reinbek, Germany
| | - Tim Strate
- Department of Surgery - Hospital Reinbek St. Adolf-Stift, Hamburger Strasse 41, 21465, Reinbek, Germany
| | - Pompiliu Piso
- Department of General and Visceral Surgery, Hospital Barmherzige Brüder, Regensburg, D-93049, Germany
| |
Collapse
|
|
11
|
Ray M, Kumar A, Maranna H. Incidence of incisional hernia in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: an observational clinical study from a tertiary oncology referral care center in India. World J Surg Oncol 2024; 22:132. [PMID: 38760663 PMCID: PMC11100235 DOI: 10.1186/s12957-024-03408-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Accepted: 05/07/2024] [Indexed: 05/19/2024] Open
Abstract
BACKGROUND An incisional hernia (IH) after major abdominal surgery is an unwanted complication particularly following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC). The frequency of IH among patients treated with CRS and HIPEC remains unexpectedly high in various studies. This study aimed to analyze the incidence, determine the factors contributing to the occurrence of IH, and develop methods to reduce the incidence of IH. METHODS We retrospectively analyzed data from a prospectively maintained structured computerized comprehensive database of 360 patients who had undergone CRS and HIPEC after January 2013 and completed two years of follow-up before December 2023. All patients were followed for a minimum period of two years with physical examination and radiological imaging when required and the occurrence of IH was documented. We used SPSS software version 24 to analyze the data using appropriate statistical tests. We set a significance threshold of p < 0.05. RESULTS Within two years of undergoing CRS and HIPEC, 25 patients (6.9%) out of 360 developed IH, indicating an annual incidence rate of 3.5%. The mean duration of hospitalization for the CRS/HIPEC procedure was 8.4 ± 4.13 days. Fifty-two (14.4%) patients experienced early post-operative surgical complications. The development of IH in our series was significantly associated with obesity (76% vs. 8.4%, P = 0.001), the occurrence of early post-operative surgical complications (48% vs. 12%, P = 0.001), mainly category III complications (44% vs. 7.1%), category IV complications (24% vs. 2.9%) according to Clavien-Dindo classification, post neoadjuvant chemotherapy status (72% vs. 87%, P = 0.045) and need for bowel anastomosis (32% vs. 11%, P = 0.002). CONCLUSION The lower incidence of IH following CRS and HIPEC in our patient cohort than in the literature can be attributed to a combination of factors, including the use of meticulous surgical techniques and the use of an abdominal binder postoperatively, particularly in obese patients.
Collapse
Affiliation(s)
- Mukurdipi Ray
- Department of Surgical Oncology, Dr BRA IRCH, AIIMS, New Delhi, 110029, India
| | - Amit Kumar
- Department of Surgical Oncology, Dr BRA IRCH, AIIMS, New Delhi, 110029, India.
| | - Haraesh Maranna
- Department of Surgical Oncology, Dr BRA IRCH, AIIMS, New Delhi, 110029, India
| |
Collapse
|
|
12
|
Sarofim M, Wijayawardana R, Ahmadi N, Barat S, Liauw W, Morris DL. Neoadjuvant chemotherapy does not improve survival for patients with high volume colorectal peritoneal metastases undergoing cytoreductive surgery. World J Surg Oncol 2024; 22:103. [PMID: 38637820 PMCID: PMC11025186 DOI: 10.1186/s12957-024-03392-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 04/16/2024] [Indexed: 04/20/2024] Open
Abstract
BACKGROUND Colorectal peritoneal metastases (CRPM) affects 15% of patients at initial colorectal cancer diagnosis. Neoadjuvant chemotherapy (NAC) prior to cytoreductive surgery (CRS) has been demonstrated to be a safe and feasible option, however there is limited data describing its efficacy in advanced peritoneal disease. This study evaluated the effect of NAC on survival in patients with high volume CRPM undergoing CRS with or without HIPEC. METHODS A retrospective review of all patients who underwent CRS with or without HIPEC for CRPM from 2004 to 2019 at our institution was performed. The cohort was divided based on peritoneal carcinomatosis index (PCI) at surgery: Low Volume (PCI ≤ 16) and High Volume (PCI > 16). RESULTS A total of 326 patients underwent CRS with HIPEC for CRPM. There were 39 patients (12%) with High Volume disease, and 15 of these (38%) received NAC. Patients with High Volume disease had significantly longer operating time, lower likelihood of complete macroscopic cytoreduction (CC-0 score), longer intensive care unit length of stay and longer hospital stay compared to Low Volume disease. In High Volume disease, the NAC group had a significantly shorter median survival of 14.4 months compared to 23.8 months in the non-NAC group (p = 0.046). CONCLUSION Patients with High Volume CRPM achieved good median survival following CRS with HIPEC, which challenges the current PCI threshold for offering CRS. The use of NAC in this cohort did not increase perioperative morbidity but was associated with significantly shorter median survival compared to upfront surgery.
Collapse
Affiliation(s)
- Mina Sarofim
- Liver and Peritonectomy Unit, St George Hospital, Sydney, NSW, Australia.
- School of Medicine, University of New South Wales, Sydney, Australia.
- School of Medicine, University of Sydney, Sydney, Australia.
| | - Ruwanthi Wijayawardana
- Liver and Peritonectomy Unit, St George Hospital, Sydney, NSW, Australia
- School of Medicine, University of New South Wales, Sydney, Australia
| | - Nima Ahmadi
- Liver and Peritonectomy Unit, St George Hospital, Sydney, NSW, Australia
- School of Medicine, University of New South Wales, Sydney, Australia
| | - Shoma Barat
- Liver and Peritonectomy Unit, St George Hospital, Sydney, NSW, Australia
- School of Medicine, University of New South Wales, Sydney, Australia
| | - Winston Liauw
- School of Medicine, University of New South Wales, Sydney, Australia
- Cancer Care Centre, St George Hospital, Sydney, NSW, Australia
| | - David L Morris
- Liver and Peritonectomy Unit, St George Hospital, Sydney, NSW, Australia
- School of Medicine, University of New South Wales, Sydney, Australia
| |
Collapse
|
|
13
|
Sarofim M, Wijayawardana R, Ahmadi N, Morris DL. Repeat cytoreductive surgery with HIPEC for colorectal peritoneal metastases: a systematic review. World J Surg Oncol 2024; 22:99. [PMID: 38627808 PMCID: PMC11022433 DOI: 10.1186/s12957-024-03386-6] [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: 02/18/2024] [Accepted: 04/13/2024] [Indexed: 04/19/2024] Open
Abstract
BACKGROUND Colorectal peritoneal metastases (CRPM) are present in 10-20% of patients at the time of their initial cancer diagnosis, and affects over 20% of those who develop colorectal cancer recurrence. Cytoreductive surgery (CRS) with HIPEC is firmly established as the optimal surgical treatment, but there is very little known about the benefit of repeat or iterative CRS. The aim of this review is to provide a systematic evaluation of the perioperative complications, survival outcomes and quality of life in patients undergoing repeat CRS with HIPEC for CRPM. METHODS A systematic review of PubMed, Ovid MEDLINE, EMBASE, Scopus and Cochrane databases was performed to identify all studies that reported outcomes for repeat CRS with or without HIPEC for CRPM. RESULTS Four hundred and ninety-three manuscripts were screened, and 15 retrospective studies were suitable for inclusion. Sample sizes ranged from 2 to 30 participants and comprised a total of 229 patients. HIPEC was used in all studies, but exact rates were not consistently stated. Perioperative morbidity was reported in four studies, between 16.7% and 37.5%. Nine studies reported mortality rate which was consistently 0%. The median overall survival after repeat CRS ranged from 20 to 62.6 months. No studies provided quality of life metrics. CONCLUSION Repeat CRS for CRPM has perioperative morbidity and mortality rates comparable to initial CRS, and offers a potential survival benefit in selected patients. There is however limited high-quality data in the literature.
Collapse
Affiliation(s)
- Mina Sarofim
- Liver and Peritonectomy Unit, St George Hospital, Gray St, Kogarah, NSW, 2217, Australia.
- School of Medicine, University of New South Wales, Sydney, NSW, Australia.
- School of Medicine, University of Sydney, Sydney, NSW, Australia.
| | - Ruwanthi Wijayawardana
- Liver and Peritonectomy Unit, St George Hospital, Gray St, Kogarah, NSW, 2217, Australia
- School of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Nima Ahmadi
- Liver and Peritonectomy Unit, St George Hospital, Gray St, Kogarah, NSW, 2217, Australia
- School of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - David L Morris
- Liver and Peritonectomy Unit, St George Hospital, Gray St, Kogarah, NSW, 2217, Australia
- School of Medicine, University of New South Wales, Sydney, NSW, Australia
| |
Collapse
|
|
14
|
Zohar N, Nevler A, Esquivel J, Yeo CJ, Benvenisti H, Elbaz N, Assaf D, Mor E, Bowne WB. International Expert Consensus on Defining Textbook Oncologic Outcomes in Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastasis. J Am Coll Surg 2024; 238:387-401. [PMID: 38149780 DOI: 10.1097/xcs.0000000000000937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2023]
Abstract
BACKGROUND Textbook oncologic outcome (TOO) is a composite metric shown to correlate with improved survival after curative intent oncologic procedures. Despite increasing use among disciplines in surgical oncology, no consensus exists for its definition in cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). STUDY DESIGN An international consensus-based study employed a Delphi methodology to achieve agreement. Fifty-four senior surgeons from the peritoneal surface malignancies field received a questionnaire comprising TOO parameters divided into 3 surgical domains: operative, short-term, and long-term postoperative outcomes. Two online meetings with participants defined the new criteria. Consensus was achieved when 75% of agreement rate was reached. Clinical data of patients who underwent CRS and HIPEC for colorectal peritoneal metastasis between 2010 and 2022 from 1 designated center (Sheba Medical Center) were collected, the consensus definition applied and outcomes analyzed. RESULTS Thirty-eight surgeons (70%) participated. Expert consensus TOO parameters for colorectal peritoneal metastasis CRS and HIPEC included the absence of unplanned reoperations during 30 days postoperation, absence of severe postoperative complications (Clavien-Dindo ≥III), absence of unplanned readmissions during 30 days postoperation, 90-day postoperative mortality, and absence of contraindications for chemotherapy within 12 weeks from operation, and included the achievement of complete cytoreduction (CC0). The study cohort consisted of 251 patients, and 151 (60%) met TOO criteria. Patients who achieved TOO had significantly better overall survival (median 67.5 months, 95% CI) vs patients who did not achieve TOO (median 44.6 months, 95% CI, p < 0.001) and significantly improved disease-free survival (median, 12 months, 95% CI, vs 9 months, 95% CI, p = 0.01). CONCLUSIONS Achievement of TOO as defined by consensus statement is associated with improved survival.
Collapse
Affiliation(s)
- Nitzan Zohar
- From the Jefferson Pancreas, Biliary and Related Cancer Center, Jefferson Health, Philadelphia, PA (Zohar, Nevler, Yeo, Bowne)
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA (Zohar, Nevler, Yeo, Bowne)
- Department of General and Oncological Surgery-Surgery C, Sheba Medical Center, Tel-Hashomer, Israel (Zohar, Benvenisti, Elbaz, Assaf, Mor)
| | - Avinoam Nevler
- From the Jefferson Pancreas, Biliary and Related Cancer Center, Jefferson Health, Philadelphia, PA (Zohar, Nevler, Yeo, Bowne)
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA (Zohar, Nevler, Yeo, Bowne)
| | | | - Charles J Yeo
- From the Jefferson Pancreas, Biliary and Related Cancer Center, Jefferson Health, Philadelphia, PA (Zohar, Nevler, Yeo, Bowne)
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA (Zohar, Nevler, Yeo, Bowne)
| | - Haggai Benvenisti
- Department of General and Oncological Surgery-Surgery C, Sheba Medical Center, Tel-Hashomer, Israel (Zohar, Benvenisti, Elbaz, Assaf, Mor)
| | - Nadav Elbaz
- Department of General and Oncological Surgery-Surgery C, Sheba Medical Center, Tel-Hashomer, Israel (Zohar, Benvenisti, Elbaz, Assaf, Mor)
| | - Dan Assaf
- Department of General and Oncological Surgery-Surgery C, Sheba Medical Center, Tel-Hashomer, Israel (Zohar, Benvenisti, Elbaz, Assaf, Mor)
| | - Eyal Mor
- Department of General and Oncological Surgery-Surgery C, Sheba Medical Center, Tel-Hashomer, Israel (Zohar, Benvenisti, Elbaz, Assaf, Mor)
| | - Wilbur B Bowne
- From the Jefferson Pancreas, Biliary and Related Cancer Center, Jefferson Health, Philadelphia, PA (Zohar, Nevler, Yeo, Bowne)
- Department of Surgery, Thomas Jefferson University, Philadelphia, PA (Zohar, Nevler, Yeo, Bowne)
| |
Collapse
|
|
15
|
Liberis A, Kyziridis D, Kalakonas A, Tentes AA. Cytoreductive surgery and perioperative intraperitoneal chemotherapy in recurrent ovarian cancer: 18 years of experience. Eur J Obstet Gynecol Reprod Biol 2024; 292:102-106. [PMID: 37992421 DOI: 10.1016/j.ejogrb.2023.11.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 10/30/2023] [Accepted: 11/16/2023] [Indexed: 11/24/2023]
Abstract
AIM To identify the clinical and pathological factors associated with relapse in women who had undergone secondary cytoreductive surgery due to locally advanced recurrent ovarian cancer. METHODS Women with locally advanced recurrent ovarian cancer who had undergone cytoreduction between 2000 and 2018 were included in this study. Demographic, clinical and biochemical intraoperative findings were recorded for each woman. All factors were assessed in order to identify which correlated with the outcomes of interest (i.e. disease relapse, mortality and morbidity). RESULTS In total, 181 women who had undergone secondary cytoreduction were analysed. The hospital mortality rate was 1.7 % (n = 3) and the morbidity rate was 32.1 % (n = 58). Recurrence was recorded in 101 (55.8 %) women. Infiltration of large bowel lymph nodes was a negative prognostic indicator of morbidity (p = 0.029). A prior surgical score of 1 (PSS-1) [odds ratio (OR) 0.465] and complete cytoreduction (OR 0.518) were found to be significant independent predictors for disease relapse. Median overall survival was greater for patients with PSS-1 (151.3 vs 59.4 vs 44.1 months; p = 0.049) and patients with complete cytoreduction (137.6 vs 36.2 vs 10.0 vs 27.4 months; p < 0.001). CONCLUSION Complete cytoreduction and PSS-1 are associated with reduced disease relapse and increased overall survival. Infiltration of large bowel lymph nodes is associated with increased morbidity.
Collapse
Affiliation(s)
- Anastasios Liberis
- Surgical Oncology, Peritoneal Surface Malignancy Programme, Euromedica Kyanous Stavros, Thessaloniki, Greece.
| | - Dimitrios Kyziridis
- Surgical Oncology, Peritoneal Surface Malignancy Programme, Euromedica Kyanous Stavros, Thessaloniki, Greece
| | - Apostolos Kalakonas
- Surgical Oncology, Peritoneal Surface Malignancy Programme, Euromedica Kyanous Stavros, Thessaloniki, Greece
| | - Antonios-Apostolos Tentes
- Surgical Oncology, Peritoneal Surface Malignancy Programme, Euromedica Kyanous Stavros, Thessaloniki, Greece
| |
Collapse
|
|
16
|
Cho HJ, Kim JW, Kim WR. Is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy still beneficial in patients diagnosed with colorectal peritoneal metastasis who underwent palliative chemotherapy? Asian J Surg 2024; 47:296-302. [PMID: 37648541 DOI: 10.1016/j.asjsur.2023.08.135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 07/05/2023] [Accepted: 08/22/2023] [Indexed: 09/01/2023] Open
Abstract
BACKGROUND With a 5-year overall survival of less than 5%, colorectal peritoneal metastasis (CPM) patients are often managed with palliative chemotherapy (CTx). In the past few decades, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been introduced as a possible curative treatment for highly selective CPM patients. We share our experience of CRS and HIPEC given the unique characteristics of the medical system and the benefit of CRS and HIPEC in palliative setting. METHODS From April 2017 to October 2021, CPM patients who underwent CRS and HIPEC were analyzed. Patients were allocated into perioperative and palliative CTx arm based on the duration between initial diagnosis of CPM to undergoing CRS and HIPEC of 6 months. Data including perioperative parameters, postoperative outcomes, and survival were analyzed with a median follow-up of 28.5 months. RESULTS Twenty-six CPM patients underwent CRS and HIPEC. Mean time from diagnosis of CPM to CRS and HIPEC was 5.5 months with 14 patients in the perioperative arm and 12 patients in the palliative arm. Perioperative group showed a longer RFS of 13.5 months compared to 8 months in the palliative group. Median overall survival of palliative group was 41.50 months, and 18 patients among all groups are alive at the time of this report. CONCLUSION CRS and HIPEC could be a treatment option for a carefully selected CPM patients performed by experienced surgeons. Overall survival of 41.50 months in palliative group compared to 16.8 months from conventional systemic CTx supports CRS and HIPEC even in palliative patients.
Collapse
Affiliation(s)
- Hye Jung Cho
- Division of Colorectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jong Woo Kim
- Division of Colorectal Surgery, Department of Surgery, Bundang CHA Medical Center, CHA University College of Medicine, Seongnam, Republic of Korea
| | - Woo Ram Kim
- Division of Colorectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
| |
Collapse
|
|
17
|
Xia W, Geng Y, Hu W. Peritoneal Metastasis: A Dilemma and Challenge in the Treatment of Metastatic Colorectal Cancer. Cancers (Basel) 2023; 15:5641. [PMID: 38067347 PMCID: PMC10705712 DOI: 10.3390/cancers15235641] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 11/07/2023] [Accepted: 11/13/2023] [Indexed: 10/25/2024] Open
Abstract
Peritoneal metastasis (PM) is a common mode of distant metastasis in colorectal cancer (CRC) and has a poorer prognosis compared to other metastatic sites. The formation of PM foci depends on the synergistic effect of multiple molecules and the modulation of various components of the tumor microenvironment. The current treatment of CRC-PM is based on systemic chemotherapy. However, recent developments in local therapeutic modalities, such as cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC), have improved the survival of these patients. This article reviews the research progress on the mechanism, characteristics, diagnosis, and treatment strategies of CRC-PM, and discusses the current challenges, so as to deepen the understanding of CRC-PM among clinicians.
Collapse
Affiliation(s)
- Wei Xia
- Department of Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou 213003, China;
| | - Yiting Geng
- Department of Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou 213003, China;
| | - Wenwei Hu
- Department of Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou 213003, China;
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China
| |
Collapse
|
|
18
|
Gudmundsdottir H, Yonkus JA, Thiels CA, Warner SG, Cleary SP, Kendrick ML, Truty MJ, Grotz TE. Oncologic Outcomes of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Highly Selected Patients with Metastatic Pancreatic Ductal Adenocarcinoma. Ann Surg Oncol 2023; 30:7833-7839. [PMID: 37596449 DOI: 10.1245/s10434-023-14138-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 07/26/2023] [Indexed: 08/20/2023]
Abstract
BACKGROUND Peritoneal metastases (PM) from pancreatic ductal adenocarcinoma (PDAC) are currently treated with palliative systemic chemotherapy alone, with unsatisfactory results. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may provide an oncologic benefit for highly selected patients. PATIENTS AND METHODS Patients with PDAC and isolated PM who completed ≥ 6 months of systemic chemotherapy with objective response between 2017 and 2022 were retrospectively reviewed. All patients met the inclusion/exclusion criteria as per our previously published PDAC CRS/HIPEC protocol. Patients who underwent CRS/HIPEC were compared with matched patients who underwent systemic therapy alone. Overall survival (OS) from diagnosis of PM and progression-free survival (PFS) from CRS/HIPEC was evaluated. RESULTS In total, 61 patients met the inclusion criteria: 38 underwent systemic therapy alone and 23 CRS/HIPEC. There were no differences in baseline prognostic factors, including age, sex, tumor size, tumor location, anatomic resectability, or serum cancer antigen (CA) 19-9 (p > 0.05). Median OS from PM diagnosis in patients who underwent systemic therapy alone was 19 months with 1, 2, and 3 year OS of 81%, 31%, and 8%, respectively. In contrast, median OS from PM diagnosis in patients who underwent CRS/HIPEC was 41 months with improved 1, 2, and 3 year OS of 91%, 66%, and 59%, respectively (p = 0.002). In the 21 patients who achieved complete cytoreduction (CC-0), no adjuvant therapy was administered and the median PFS was 17 months. CONCLUSIONS CRS/HIPEC in highly selected patients with PDAC and PM results in promising oncologic outcomes that are unlikely to be achieved with systemic chemotherapy alone. Further investigation is warranted and ongoing (NCT04858009).
Collapse
Affiliation(s)
| | | | | | | | - Sean P Cleary
- Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | | | - Mark J Truty
- Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | | |
Collapse
|
|
19
|
Sedighim S, Khan A, Li AY, Tajik F, Radhakrishnan VK, Eng O, Turaga K, Senthil M. Adoption of cytoreductive surgery in the management of peritoneal malignancies-Global trends. J Surg Oncol 2023; 128:1021-1031. [PMID: 37818906 DOI: 10.1002/jso.27448] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Accepted: 09/08/2023] [Indexed: 10/13/2023]
Abstract
Cytoreductive surgery (CRS) has now been accepted as an integral component in the management of gastrointestinal and gynecological cancers with peritoneal metastases. Since the adoption of CRS is influenced by access to advanced medical facilities, trained multidisciplinary teams, and funding, there is wide variability in incorporation of CRS into routine clinical practice between high- versus low- and middle-income countries. This review highlights the global trends in the adoption of CRS for peritoneal malignancies with a specific focus on the establishment of CRS programs and barriers to incorporate CRS into routine clinical care in low- and middle-income countries.
Collapse
Affiliation(s)
- Shaina Sedighim
- Department of Surgery, University of California, Irvine, California, USA
| | - Aaqil Khan
- Department of Surgery, University of California, Irvine, California, USA
- School of Medicine, University of California, Irvine, California, USA
| | - Amy Y Li
- Division of Surgical Oncology, Department of Surgery, University of California Irvine Medical Center, Orange, California, USA
| | - Fatemeh Tajik
- Department of Surgery, University of California, Irvine, California, USA
| | | | - Oliver Eng
- Division of Surgical Oncology, Department of Surgery, University of California Irvine Medical Center, Orange, California, USA
| | - Kiran Turaga
- Division of Surgical Oncology, Yale School of Medicine, New Haven, Connecticut, USA
| | - Maheswari Senthil
- Department of Surgery, University of California, Irvine, California, USA
- Division of Surgical Oncology, Department of Surgery, University of California Irvine Medical Center, Orange, California, USA
| |
Collapse
|
|
20
|
Intraperitoneal chemotherapy for primary gastric cancer. Cochrane Database Syst Rev 2023; 2023:CD015698. [PMCID: PMC10521024 DOI: 10.1002/14651858.cd015698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/29/2024]
Abstract
This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the benefits and harms of intraperitoneal chemotherapy (IPC) in people with primary gastric cancer, with or without peritoneal metastasis.
Collapse
|
|
21
|
Stokkel LE, van Rossum HH, van de Kamp MW, Boellaard TN, Bekers EM, Kok NFM, van Rhijn BWG, Mertens LS. Clinical value of preoperative serum tumor markers CEA, CA19-9, CA125, and CA15-3 in surgically treated urachal cancer. Urol Oncol 2023; 41:326.e17-326.e24. [PMID: 36813613 DOI: 10.1016/j.urolonc.2023.01.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 12/20/2022] [Accepted: 01/27/2023] [Indexed: 02/23/2023]
Abstract
INTRODUCTION Urachal adenocarcinoma (UrAC) is a very rare malignancy with a poor prognosis. The role of preoperative serum tumor markers (STMs) in UrAC is unknown. The aim of this study was to assess the clinical value of elevated STMs including carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), cancer antigen 125 (CA125), and cancer antigen 15-3 (CA15-3) in surgically treated UrAC, and to evaluate their prognostic significance. METHODS This was a retrospective study of consecutive patients with histopathologically confirmed UrAC who underwent surgical treatment at a single tertiary hospital. Blood levels of CEA, CA19-9, CA125, and CA15-3 were determined before surgery. The proportion of patients with elevated STMs was calculated, as well as the association between elevated STMs and clinicopathological characteristics, recurrence-free survival and disease-specific survival. RESULTS Of the 50 patients included; CEA, CA 19-9, CA125, and CA15-3 were elevated in 40%, 25%, 26%, and 6% respectively. Elevated CEA was associated with higher pT-stage (odds ratio [OR] 3.3 [95% confidence interval 1.0-11.1], P = 0.003), higher Sheldon stage (OR 6.9 [95% CI 0.8-60.4], P = 0.01), male sex (OR 4.7 [95% CI 1.2-18.3], P = 0.01), and the presence of peritoneal metastases at the time of diagnosis (OR 3.5 [95% CI 0.9-14.2], P = 0.04). Elevated CA19-9 was associated with signet-cell component (OR 1.7 [95% CI 0.9-3.3], P = 0.03) and elevated CA125 was associated with peritoneal metastases at the time of diagnosis (OR 6.0 [95% CI 1.2-30.6], P = 0.04). Elevated STMs before surgery were not associated with recurrence-free survival and/or disease-specific survival. CONCLUSION A subset of patients with surgically treated UrAC has elevated STMs preoperatively. CEA was most frequently (40%) elevated and correlated with unfavorable tumor characteristics. However, STM levels did not correlate with prognostic outcomes.
Collapse
Affiliation(s)
- Laura E Stokkel
- Department of Urology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Huub H van Rossum
- Department of Analytical Chemistry, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Maaike W van de Kamp
- Department of Urology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Thierry N Boellaard
- Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Elise M Bekers
- Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Niels F M Kok
- Department of Surgical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Bas W G van Rhijn
- Department of Urology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Urology, Caritas St. Josef Medical Centre, University of Regensburg, Regensburg, Germany
| | - Laura S Mertens
- Department of Urology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
| |
Collapse
|
|
22
|
Schena CA, Laterza V, De Sio D, Quero G, Fiorillo C, Gunawardena G, Strippoli A, Tondolo V, de'Angelis N, Alfieri S, Rosa F. The Role of Staging Laparoscopy for Gastric Cancer Patients: Current Evidence and Future Perspectives. Cancers (Basel) 2023; 15:3425. [PMID: 37444535 DOI: 10.3390/cancers15133425] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Revised: 06/18/2023] [Accepted: 06/27/2023] [Indexed: 07/15/2023] Open
Abstract
A significant proportion of patients diagnosed with gastric cancer is discovered with peritoneal metastases at laparotomy. Despite the continuous improvement in the performance of radiological imaging, the preoperative recognition of such an advanced disease is still challenging during the diagnostic work-up, since the sensitivity of CT scans to peritoneal carcinomatosis is not always adequate. Staging laparoscopy offers the chance to significantly increase the rate of promptly diagnosed peritoneal metastases, thus reducing the number of unnecessary laparotomies and modifying the initial treatment strategy of gastric cancer. The aim of this review was to provide a comprehensive summary of the current literature regarding the role of staging laparoscopy in the management of gastric cancer. Indications, techniques, accuracy, advantages, and limitations of staging laparoscopy and peritoneal cytology were discussed. Furthermore, a focus on current evidence regarding the application of artificial intelligence and image-guided surgery in staging laparoscopy was included in order to provide a picture of the future perspectives of this technique and its integration with modern tools in the preoperative management of gastric cancer.
Collapse
Affiliation(s)
- Carlo Alberto Schena
- Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Unit of Colorectal and Digestive Surgery, DIGEST Department, Beaujon University Hospital, AP-HP, University of Paris Cité, Clichy, 92110 Paris, France
| | - Vito Laterza
- Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Davide De Sio
- Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Giuseppe Quero
- Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Department of Digestive Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Claudio Fiorillo
- Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Gayani Gunawardena
- Department of Digestive Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Antonia Strippoli
- Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Vincenzo Tondolo
- Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Nicola de'Angelis
- Unit of Colorectal and Digestive Surgery, DIGEST Department, Beaujon University Hospital, AP-HP, University of Paris Cité, Clichy, 92110 Paris, France
| | - Sergio Alfieri
- Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Department of Digestive Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Fausto Rosa
- Department of Digestive Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
- Emergency and Trauma Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| |
Collapse
|
|
23
|
Kammar P, Garach N, Bhatt A, Anam J, Maniar V, Gore A, Mehta S. High-Risk Peritoneal Mesothelioma: Does Metronomic Chemotherapy Have a Role? Indian J Surg Oncol 2023; 14:181-188. [PMID: 37359939 PMCID: PMC10284749 DOI: 10.1007/s13193-022-01691-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 12/13/2022] [Indexed: 01/06/2023] Open
Abstract
Objective To evaluate the feasibility, tolerance, and efficacy of OMCT (oral metronomic chemotherapy) after CRS + HIPEC for peritoneal mesothelioma in patients with poor prognostic factors: PCI > 20, incomplete CRS, poor performance status, or progression on systemic chemotherapy. Methods A retrospective analysis of patients undergoing CRS + HIPEC for peritoneal mesothelioma and receiving OMCT for poor risk factors. Results Sixteen patients underwent CRS + HIPEC between 2013 and 2017. The median PCI was 31.5. Complete cytoreduction (CC-0/1) was obtained in 8 patients (50%). All 16 received HIPEC except one patient with baseline renal dysfunction.Thirteen patients had PCI > 20 where only 5 had CC-0/1. Of 8 suboptimal cytoreduction (CC-2/3), 7 received OMCT (6 for progression on chemotherapy and one for mixed histology). Three patients had PCI < 20 and all had CC-0/1 clearance. Only one received OMCT for progression on adjuvant chemotherapy. Patients receiving OMCT for progression on adjuvant chemotherapy (ACT) were in poor PS.The median follow-up was 13.4 months. Five are alive with the disease (three are on OMCT). Six are alive without disease (2 are on OMCT). The mean OS was 24.3 months and the mean DFS was 18 months. Outcomes were similar between CC-0/1 and CC-2/3 groups, OMCT vs no OMCT groups.All patients receiving OMCT for progression on neoadjuvant chemotherapy had better survival (alive at 12, 20, 32, 36 months) compared to those receiving OMCT for progression on the ACT (p = 0.012). Conclusion OMCT is a good alternative in high-volume peritoneal mesothelioma with incomplete cytoreduction and progression on chemotherapy. OMCT may improve outcomes in these scenarios when started early.
Collapse
Affiliation(s)
- Praveen Kammar
- Department of Surgical Oncology, Saifee Hospital, Mumbai, India
| | - Niharika Garach
- Department of Surgical Oncology, Holy Family Hospital, Mumbai, India
| | - Aditi Bhatt
- Department of Gynaecological and GI Oncology, Zydus Hospital, Ahemdabad, India
| | - Jay Anam
- Department of Surgical Oncology, Saifee Hospital, Mumbai, India
| | - Vashisth Maniar
- Department of Medical Oncology, Saifee Hospital, Mumbai, India
| | - Adwaita Gore
- Department of Medical Oncology, Prince Aly Khan Hospital, Mumbai, India
| | - Sanket Mehta
- Peritoneal Surface Oncology, Saifee Hospital, Mumbai, India
| |
Collapse
|
|
24
|
Byrwa DJ, Twist CJ, Skitzki J, Repasky E, Ham PB, Gupta A. A Review of the Use of Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Malignancy in Pediatric Patients. Cancers (Basel) 2023; 15:2815. [PMID: 37345152 DOI: 10.3390/cancers15102815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 05/12/2023] [Accepted: 05/15/2023] [Indexed: 06/23/2023] Open
Abstract
Hyperthermic intraperitoneal chemotherapy (HIPEC) can directly target microscopic peritoneal disease, has achieved regular consideration in the treatment of several adult cancer types, and is more recently being studied in pediatrics. This review paper provides an overview of the use of this modality in pediatrics in order to identify medication choice, discuss post-operative morbidity and mortality, and evaluate impact on overall survival. Four databases were searched including Scopus, PubMed, Embase, and CINAHL and ultimately 37 papers documenting the use of this modality comprising 264 pediatric patients were included. Malignancies treated include desmoplastic small round cell tumor, rhabdomyosarcoma, angiosarcoma, colorectal carcinoma, and mesothelioma, with several rarer tumor types. Cisplatin was the most commonly used drug for HIPEC at varying concentrations for 30-90 min in duration at temperatures of approximately 41-42 °C. Reported toxicities were generally self-limited and there was no post-operative mortality. The impact on overall survival versus systemic chemotherapy and debulking surgery is uncertain due to lack of clinical trials and very small sample size across tumor subsets and the overall pediatric population. The relationship between degree of tumor burden and extent of surgical debulking needs to be further clarified. Future directions include prospective clinical trials, establishment of patient databases to facilitate standardization of HIPEC in pediatric patients, and additional approaches to optimize HIPEC.
Collapse
Affiliation(s)
- David J Byrwa
- Department of Pediatrics, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY 14203, USA
| | - Clare J Twist
- Department of Pediatrics, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY 14203, USA
- Division of Pediatric Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA
| | - Joseph Skitzki
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA
- Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA
| | - Elizabeth Repasky
- Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA
| | - P Ben Ham
- Department of Surgery, Division of Pediatric Surgery, John R Oishei Children's Hospital, Buffalo, NY 14203, USA
| | - Ajay Gupta
- Department of Pediatrics, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY 14203, USA
- Division of Pediatric Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA
| |
Collapse
|
|
25
|
Erstad DJ, Robinson KA, Beaty K, Rafeeq S, Chiang YJ, Raghav K, Shen JP, Overman MJ, Foo WC, Taggart MW, Mansfield PF, Royal RE, Fournier KF, Scally CP. Prognostic significance of acellular mucin in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for appendiceal neoplasms. Langenbecks Arch Surg 2023; 408:110. [PMID: 36853519 DOI: 10.1007/s00423-022-02732-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Accepted: 10/15/2022] [Indexed: 03/01/2023]
Abstract
INTRODUCTION Appendiceal neoplasms have a propensity for peritoneal dissemination. The standard of care for select individuals is CRS/HIPEC. In the current 8th AJCC Staging system, a finding of only intraperitoneal acellular mucin (M1a) is classified as Stage IVa. There is concern that the current AJCC system may over-stage patients. METHODS This was a single-institution retrospective review of 164 cases of mucinous appendiceal neoplasm. Patients undergoing CRS/HIPEC with M1a disease were compared to patients with peritoneal deposits containing tumor cells (well-differentiated adenocarcinoma; low-grade mucinous carcinoma peritonei-M1b,G1). Overall and recurrence-free survival were assessed. RESULTS Median age was 51 years, 70% were female, and 75% White. Sixty-four patients had M1a disease and 100 M1b,G1 disease. M1a disease had a lower median PCI score (11 vs. 20, p = .0001) and a higher rate of complete CRS (62% vs. 50%, p = .021). Median follow-up was 7.6 years (IQR 5.6-10.5 years). For M1a disease, there were no recurrences and only one patient died during the study interval. In comparison, for M1b disease, 66/100 (66%) recurred with a 5-year RFS of 40.5% (HR 8.0, 95% CI 4.9-15.1, p < .0001), and 31/100 (31%) died with a 5-year OS of 84.8% (HR 4.5, 95% CI 2.2-9.2, p < .0001). CONCLUSIONS Acellular mucin (M1a disease) after CRS/HIPEC for appendiceal neoplasm is associated with longer OS and RFS compared to M1b, G1 disease. Current AJCC staging does not accurately reflect the differing outcomes of these two patient populations. The presence of acellular mucin in the peritoneal cavity should not be perceived as a metastatic equivalent.
Collapse
Affiliation(s)
- Derek J Erstad
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1484, Houston, TX, 77030-4009, USA.
| | - Kristen A Robinson
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1484, Houston, TX, 77030-4009, USA
| | - Karen Beaty
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1484, Houston, TX, 77030-4009, USA
| | - Safia Rafeeq
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1484, Houston, TX, 77030-4009, USA
| | - Yi-Ju Chiang
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1484, Houston, TX, 77030-4009, USA
| | - Kanwal Raghav
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - John P Shen
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Michael J Overman
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Wai Chin Foo
- Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Melissa W Taggart
- Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Paul F Mansfield
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1484, Houston, TX, 77030-4009, USA
| | - Richard E Royal
- Department of Surgery, Maine Medical Center, Portland, MN, USA
| | - Keith F Fournier
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1484, Houston, TX, 77030-4009, USA
| | - Christopher P Scally
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1484, Houston, TX, 77030-4009, USA
| |
Collapse
|
|
26
|
Sommariva A, Valle M, Gelmini R, Tonello M, Carboni F, De Manzoni G, Sorrentino L, Pasqual EM, Bacchetti S, Sassaroli C, Di Giorgio A, Framarini M, Marrelli D, Casella F, Federici O. Laparoscopic Cytoreduction Combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Peritoneal Surface Malignancies (PSM): Italian PSM Oncoteam Evidence and Literature Review. Cancers (Basel) 2022; 15:cancers15010279. [PMID: 36612274 PMCID: PMC9818987 DOI: 10.3390/cancers15010279] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 12/29/2022] [Accepted: 12/29/2022] [Indexed: 01/03/2023] Open
Abstract
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has gained increasing acceptance in clinical practice. Performing CRS and HIPEC laparoscopically represents a challenging and intriguing technical evolution. However, the experiences are limited, and the evidence is low. This retrospective analysis was performed on patients treated with laparoscopic CRS-HIPEC within the Italian Peritoneal Surface Malignancies Oncoteam. Clinical, perioperative, and follow-up data were extracted and collected on prospectively maintained databases. We added a systematic review according to the PRISMA method for English-language articles through April 2022 using the keywords laparoscopic, hyperthermic, HIPEC, and chemotherapy. From 2016 to 2022, fourteen patients were treated with Lap-CRS-HIPEC with curative intent within the Italian centers. No conversion to open was observed. The median duration of surgery was 487.5 min. The median Peritoneal Cancer Index (PCI) was 3, and complete cytoreduction was achieved in all patients. Two patients (14.3%) had major postoperative complications, one requiring reintervention. After a median follow-up of 16.9 months, eleven patients were alive without disease (78.6%), two patients developed recurrence (14.3%), and one patient died for unrelated causes (7.1%). The literature review confirmed these results. In conclusion, current evidence shows that Lap-CRS-HIPEC is feasible, safe, and associated with a favorable outcome in selected patients. An accurate patient selection will continue to be paramount in choosing this treatment.
Collapse
Affiliation(s)
- Antonio Sommariva
- Advanced Surgical Oncology Unit, Unit of Surgical Oncology of the Esophagus and Digestive Tract, Veneto Institute of Oncology IOV-IRCCS, 35128 Padova, Italy
- Correspondence: ; Tel.: +39-423-421306
| | - Mario Valle
- Peritoneal Tumours Unit, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy
| | - Roberta Gelmini
- SC Chirurgia Generale d’Urgenza ed Oncologica, AOU Policlinico di Modena, 41125 Modena, Italy
| | - Marco Tonello
- Advanced Surgical Oncology Unit, Unit of Surgical Oncology of the Esophagus and Digestive Tract, Veneto Institute of Oncology IOV-IRCCS, 35128 Padova, Italy
| | - Fabio Carboni
- Peritoneal Tumours Unit, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy
| | | | - Lorena Sorrentino
- SC Chirurgia Generale d’Urgenza ed Oncologica, AOU Policlinico di Modena, 41125 Modena, Italy
| | - Enrico Maria Pasqual
- AOUD Center Advanced Surgical Oncology, DAME University of Udine, 33100 Udine, Italy
| | - Stefano Bacchetti
- AOUD Center Advanced Surgical Oncology, DAME University of Udine, 33100 Udine, Italy
| | - Cinzia Sassaroli
- Colorectal Surgical Oncology, Abdominal Oncology Department, “Fondazione Giovanni Pascale” IRCCS, 80131 Naples, Italy
| | - Andrea Di Giorgio
- Surgical Unit of Peritoneum and Retroperitoneum, Fondazione Policlinico Universitario A. Gemelli—IRCCS, 00168 Rome, Italy
| | - Massimo Framarini
- Surgery and Advanced Oncological Therapy Unit, Ospedale “GB.Morgagni-L.Pierantoni”—AUSL Forlì, 47121 Forlì, Italy
| | - Daniele Marrelli
- Department of Medicine, Surgery, and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, 53100 Siena, Italy
| | - Francesco Casella
- Upper GI Surgery Division, University of Verona, 37134 Verona, Italy
| | - Orietta Federici
- Peritoneal Tumours Unit, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy
| |
Collapse
|
|
27
|
Marrelli D, Ansaloni L, Federici O, Asero S, Carbone L, Marano L, Baiocchi G, Vaira M, Coccolini F, Di Giorgio A, Framarini M, Gelmini R, Palopoli C, Accarpio F, Fagotti A. Cytoreductive Surgery (CRS) and HIPEC for Advanced Ovarian Cancer with Peritoneal Metastases: Italian PSM Oncoteam Evidence and Study Purposes. Cancers (Basel) 2022; 14:6010. [PMID: 36497490 PMCID: PMC9740463 DOI: 10.3390/cancers14236010] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Revised: 11/25/2022] [Accepted: 12/01/2022] [Indexed: 12/12/2022] Open
Abstract
Ovarian cancer is the eighth most common neoplasm in women with a high mortality rate mainly due to a marked propensity for peritoneal spread directly at diagnosis, as well as tumor recurrence after radical surgical treatment. Treatments for peritoneal metastases have to be designed from a patient's perspective and focus on meaningful measures of benefit. Hyperthermic intraperitoneal chemotherapy (HIPEC), a strategy combining maximal cytoreductive surgery with regional chemotherapy, has been proposed to treat advanced ovarian cancer. Preliminary results to date have shown promising results, with improved survival outcomes and tumor regression. As knowledge about the disease process increases, practice guidelines will continue to evolve. In this review, we have reported a broad overview of advanced ovarian cancer management, and an update of the current evidence. The future perspectives of the Italian Society of Surgical Oncology (SICO) are discussed conclusively.
Collapse
Affiliation(s)
- Daniele Marrelli
- Unit of General Surgery and Surgical Oncology, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy
| | - Luca Ansaloni
- Unit of General Surgery San Matteo Hospital, 27100 Pavia, Italy
| | - Orietta Federici
- Surgical Oncology, Peritoneum and Abdomen Pathologies, National Cancer Institute Regina Elena, 00144 Rome, Italy
| | - Salvatore Asero
- Unit of Surgical Oncology, Soft Tissue Tumors, Department of Oncology, Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi, 95123 Catania, Italy
| | - Ludovico Carbone
- Unit of General Surgery and Surgical Oncology, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy
| | - Luigi Marano
- Unit of General Surgery and Surgical Oncology, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy
| | - Gianluca Baiocchi
- Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili, 25123 Brescia, Italy
| | - Marco Vaira
- Candiolo Cancer Institute, FPO–IRCCS, Candiolo, 10060 Torino, Italy
| | - Federico Coccolini
- General, Emergency and Trauma Surgery, Pisa University Hospital, 56122 Pisa, Italy
| | - Andrea Di Giorgio
- Surgical Unit of Peritoneum and Retroperitoneum, Fondazione Policlinico Universitario A. Gemelli–IRCCS, 00168 Rome, Italy
| | - Massimo Framarini
- Surgery and Advanced Oncological Therapy Unit, Ospedale GB. Morgagni-L. Pierantoni, AUSL Forlì, 47121 Forlì-Cesena, Italy
| | - Roberta Gelmini
- Unit of Emergency General Surgery and Surgical Oncology, AOU Policlinico di Modena, 41125 Modena, Italy
| | - Carmen Palopoli
- Unit of PSG and OBI, Azienda Ospedaliera Universitaria G. Martino, 98124 Messina, Italy
| | - Fabio Accarpio
- CRS and HIPEC Unit, Pietro Valdoni, Umberto I Policlinico di Roma, 00161 Roma, Italy
| | - Anna Fagotti
- Unit of Ovarian Carcinoma, Fondazione Policlinico Universitario A. Gemelli–IRCCS, 00168 Rome, Italy
| |
Collapse
|
|
28
|
Turner KM, Morris MC, Delman AM, Hanseman D, Johnston FM, Greer J, Walle KV, Abbott DE, Raoof M, Grotz TE, Fournier K, Dineen S, Veerapong J, Maduekwe U, Kothari A, Staley CA, Maithel SK, Lambert LA, Kim AC, Cloyd JM, Wilson GC, Sussman JJ, Ahmad SA, Patel SH. Do Lymph Node Metastases Matter in Appendiceal Cancer with Peritoneal Carcinomatosis? A US HIPEC Collaborative Study. J Gastrointest Surg 2022; 26:2569-2578. [PMID: 36258061 DOI: 10.1007/s11605-022-05489-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 09/17/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND Whether formal regional lymph node (LN) evaluation is necessary for patients with appendiceal adenocarcinoma (AA) who have peritoneal metastases is unclear. The aim of this study was to evaluate the prognostic value of LN metastases on survival in patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). METHODS A retrospective analysis of the US HIPEC collaborative, a multi-institutional consortium comprising 12 high-volume centers, was performed to identify patients with AA who underwent CRS-HIPEC with adequate LN sampling (≥ 12 LNs). RESULTS Two hundred-fifty patients with AA who underwent CRS-HIPEC were included. Outcomes were compared between LN - and LN + disease. Baseline patient characteristics between groups were similar, with most patients undergoing complete cytoreduction (0/1: 86.0% vs. 76.8%, p = 0.08), respectively. More adverse tumor factors were found in patients with LN + disease, including poor differentiation, signet ring cells, and lymphovascular invasion. Multivariate analysis of overall survival (OS) found LN + disease was independently associated with worse OS (HR: 2.82 95%CI: 1.25-6.34, p = 0.01), even after correction for receipt of systemic therapy. On Kaplan-Meier analysis, median OS was lower in patients with LN + disease (25.9 months vs. 91.4 months, p < 0.01). LN + disease remained associated with poor OS following propensity score matching (HR: 4.98 95%CI: 1.72-14.40, p < 0.01) and in patients with PCI ≥ 20 (HR: 3.68 95%CI: 1.54-8.80, p < 0.01). CONCLUSIONS In this large multi-institutional study of patients with AA undergoing CRS-HIPEC, LN status remained associated with worse OS even in the setting of advanced peritoneal carcinomatosis. Formal LN evaluation should be performed for most patients with AA undergoing CRS-HIPEC.
Collapse
Affiliation(s)
- Kevin M Turner
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Mackenzie C Morris
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Aaron M Delman
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Dennis Hanseman
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | | | - Jonathan Greer
- Department of Surgery, Johns Hopkins University, Baltimore, MD, USA
| | - Kara Vande Walle
- Department of Surgery, Division of Surgical Oncology, University of Wisconsin, Madison, WI, USA
| | - Daniel E Abbott
- Department of Surgery, Division of Surgical Oncology, University of Wisconsin, Madison, WI, USA
| | - Mustafa Raoof
- Department of Surgery, Division of Surgical Oncology, City of Hope National Medical Center, Duarte, CA, USA
| | - Travis E Grotz
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA
| | - Keith Fournier
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Sean Dineen
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Morsani College of Medicine, Tampa, FL, USA
| | - Jula Veerapong
- Department of Surgery, Division of Surgical Oncology, University of California, San Diego, San Diego, CA, USA
| | - Ugwuji Maduekwe
- Department of Surgery, Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Anai Kothari
- Department of Surgery, Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Charles A Staley
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Laura A Lambert
- Peritoneal Surface Malignancy Program Section of Surgical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
| | - Alex C Kim
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Jordan M Cloyd
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Gregory C Wilson
- Department of Surgery, Division of Surgical Oncology, University of Cincinnati College of Medicine, Medical Science Building, 231 Albert Sabin Way, Cincinnati, OH, 45267-0558, USA
| | - Jeffrey J Sussman
- Department of Surgery, Division of Surgical Oncology, University of Cincinnati College of Medicine, Medical Science Building, 231 Albert Sabin Way, Cincinnati, OH, 45267-0558, USA
| | - Syed A Ahmad
- Department of Surgery, Division of Surgical Oncology, University of Cincinnati College of Medicine, Medical Science Building, 231 Albert Sabin Way, Cincinnati, OH, 45267-0558, USA
| | - Sameer H Patel
- Department of Surgery, Division of Surgical Oncology, University of Cincinnati College of Medicine, Medical Science Building, 231 Albert Sabin Way, Cincinnati, OH, 45267-0558, USA.
| |
Collapse
|
|
29
|
Rieser C, Phelos H, Zureikat A, Pingpank J, Ongchin M, Lee A, Brown J, Choudry MH, Hoehn RS. Socioeconomic Barriers to CRS HIPEC for Appendiceal Cancer within a Regional Academic Hospital System. Ann Surg Oncol 2022; 29:6593-6602. [PMID: 35639293 PMCID: PMC9547669 DOI: 10.1245/s10434-022-11949-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 05/12/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Appendiceal cancer with peritoneal metastases (ACPM) is a complex disease requiring multidisciplinary care. Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion (CRS HIPEC) can significantly improve survival but requires evaluation by a surgical oncologist and significant treatment endurance. The impacts of socioeconomic status (SES) and other social determinants of health on rates of surgical evaluation and treatment have not been examined. METHODS We conducted a retrospective cohort study examining all patients with ACPM from 2010 to 2018 in a regional healthcare system. Patient characteristics, oncologic details, treatment strategies, and survival were examined. The primary outcomes of interest were referral to Surgical Oncology, receipt of CRS HIPEC, and survival. RESULTS Of 194 patients identified, 94% had synchronous ACPM. The majority of patients (95%) were referred to surgical oncology. Advanced age was the only predictor of nonreferral (p < 0.001). A total of 147 patients (76%) ultimately underwent CRS HIPEC. After adjusting for medical and tumor characteristics, CRS HIPEC was less likely for patients who were unmarried [odds ratio (OR) 0.253, p = 0.004] or of low SES (OR 0.372, p = 0.03). On subanalysis of patients undergoing CRS HIPEC, median overall survival was worse for patients of low SES [51 months versus not reached (NR), p = 0.05], and this disparity persisted on multivariate analysis [hazard ratio (HR) = 2.278, p = 0.001]. CONCLUSIONS This analysis is the first to evaluate barriers to CRS HIPEC for ACPM. While most patients were evaluated by a multidisciplinary team, nonmedical factors may play a role in the treatment received and ultimate outcomes. Addressing these disparities is crucial for ensuring equitable outcomes and improving patient care.
Collapse
Affiliation(s)
- Caroline Rieser
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Heather Phelos
- Division of Trauma and Acute Care Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Amer Zureikat
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - James Pingpank
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Melanie Ongchin
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Andrew Lee
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Joshua Brown
- Division of Trauma and Acute Care Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - M Haroon Choudry
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Richard S Hoehn
- Division of Surgical Oncology, University Hospitals, Cleveland, OH, USA.
| |
Collapse
|
|
30
|
Bjersand K, Blom K, Poromaa IS, Stålberg K, Lejon AM, Bäckman F, Nyberg Å, Andersson C, Larsson R, Nygren P. Ex vivo assessment of cancer drug sensitivity in epithelial ovarian cancer and its association with histopathological type, treatment history and clinical outcome. Int J Oncol 2022; 61:128. [PMID: 36082820 PMCID: PMC9477110 DOI: 10.3892/ijo.2022.5418] [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: 03/14/2022] [Accepted: 07/04/2022] [Indexed: 12/01/2022] Open
Abstract
Epithelial ovarian cancer (EOC) is divided into type I and type II based on histopathological features. Type I is clinically more indolent, but also less sensitive to chemotherapy, compared with type II. The basis for this difference is not fully clarified. The present study investigated the pattern of drug activity in type I and type II EOC for standard cytotoxic drugs and recently introduced tyrosine kinase inhibitors (TKIs), and assessed the association with treatment history and clinical outcome. Isolated EOC tumor cells obtained at surgery were investigated for their sensitivity to seven standard cytotoxic drugs and nine TKIs using a short-term fluorescent microculture cytotoxicity assay (FMCA). Drug activity was compared with respect to EOC subtype, preoperative chemotherapy, cross-resistance and association with progression-free survival (PFS). Out of 128 EOC samples, 120 samples, including 21 type I and 99 type II, were successfully analyzed using FMCA. Patients with EOC type I had a significantly longer PFS time than patients with EOC type II (P=0.01). In line with clinical experience, EOC type I samples were generally more resistant than type II samples to both standard cytotoxic drugs and the TKIs, reaching statistical significance for cisplatin (P=0.03) and dasatinib (P=0.002). A similar pattern was noted in samples from patients treated with chemotherapy prior to surgery compared with treatment-naive samples, reaching statistical significance for fluorouracil, irinotecan, dasatinib and nintedanib (all P<0.05). PFS time gradually shortened with increasing degree of drug resistance. Cross-resistance between drugs was in most cases statistically significant yet moderate in degree (r<0.5). The clinically observed relative drug resistance of EOC type I, as well as in patients previously treated, is at least partly due to mechanisms in the tumor cells. These mechanisms seemingly also encompass kinase inhibitors. Ex vivo assessment of drug activity is suggested to have a role in the optimization of drug therapy in EOC.
Collapse
Affiliation(s)
- Kathrine Bjersand
- Department of Women's and Children's Health, Uppsala University, S‑751 85 Uppsala, Sweden
| | - Kristin Blom
- Department of Medical Sciences, Uppsala University, S‑751 85 Uppsala, Sweden
| | | | - Karin Stålberg
- Department of Women's and Children's Health, Uppsala University, S‑751 85 Uppsala, Sweden
| | - Ann-Marie Lejon
- Department of Women's and Children's Health, Uppsala University, S‑751 85 Uppsala, Sweden
| | - Fatma Bäckman
- Department of Medical Sciences, Örebro University Hospital, S‑701 85 Örebro, Sweden
| | - Åsa Nyberg
- Department of Gynecology, Falun Hospital, S‑791 31 Falun, Sweden
| | - Claes Andersson
- Department of Medical Sciences, Uppsala University, S‑751 85 Uppsala, Sweden
| | - Rolf Larsson
- Department of Medical Sciences, Uppsala University, S‑751 85 Uppsala, Sweden
| | - Peter Nygren
- Department of Immunology, Genetics and Pathology, Uppsala University, S‑751 85 Uppsala, Sweden
| |
Collapse
|
|
31
|
Turner KM, Morris MC, Sohal D, Sussman JJ, Wilson GC, Ahmad SA, Patel SH. Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases: A Summary of Key Clinical Trials. J Clin Med 2022; 11:jcm11123406. [PMID: 35743476 PMCID: PMC9225119 DOI: 10.3390/jcm11123406] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Revised: 06/02/2022] [Accepted: 06/12/2022] [Indexed: 01/27/2023] Open
Abstract
The peritoneal cavity is a common site of metastatic spread from colorectal cancer (CRC). Patients with peritoneal metastases (PM) often have aggressive underlying tumor biology and poor survival. While only a minority of patients with CRC have potentially resectable disease, the high overall incidence of CRC makes management of PM a common clinical problem. In this population, cytoreductive surgery (CRS)-hyperthermic intraperitoneal chemotherapy (HIPEC) is the only effective therapy for appropriately selected patients. In this narrative review, we summarize the existing literature on CRS-HIPEC in colorectal PM. Recent prospective clinical trials have shown conflicting evidence regarding the benefit of HIPEC perfusion in addition to CRS. Current strategies to prevent PM in those at high-risk have been shown to be ineffective. Herein we will provide a framework for clinicians to understand and apply these data to treat this complex disease presentation.
Collapse
Affiliation(s)
- Kevin M. Turner
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0558, USA; (K.M.T.); (M.C.M.)
| | - Mackenzie C. Morris
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0558, USA; (K.M.T.); (M.C.M.)
| | - Davendra Sohal
- Department of Internal Medicine, Division of Hematology & Oncology, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0558, USA;
| | - Jeffrey J. Sussman
- Department of Surgery, Division of Surgical Oncology, University of Cincinnati College of Medicine, 231 Albert Sabin Way (ML 0558), Cincinnati, OH 45267-0558, USA; (J.J.S.); (G.C.W.); (S.A.A.)
| | - Gregory C. Wilson
- Department of Surgery, Division of Surgical Oncology, University of Cincinnati College of Medicine, 231 Albert Sabin Way (ML 0558), Cincinnati, OH 45267-0558, USA; (J.J.S.); (G.C.W.); (S.A.A.)
| | - Syed A. Ahmad
- Department of Surgery, Division of Surgical Oncology, University of Cincinnati College of Medicine, 231 Albert Sabin Way (ML 0558), Cincinnati, OH 45267-0558, USA; (J.J.S.); (G.C.W.); (S.A.A.)
| | - Sameer H. Patel
- Department of Surgery, Division of Surgical Oncology, University of Cincinnati College of Medicine, 231 Albert Sabin Way (ML 0558), Cincinnati, OH 45267-0558, USA; (J.J.S.); (G.C.W.); (S.A.A.)
- Correspondence: ; Tel.: +1-516-558-6018; Fax: +1-513-584-0459
| |
Collapse
|
|
32
|
Badran A, Azzam A, Noorelahi M, Alshamsan B, Alkhaldi S, Naguib R, Amin T. Outcomes of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with or without intraoperative radiotherapy for peritoneal carcinomatosis in elderly patients. SURGERY OPEN DIGESTIVE ADVANCE 2022; 6:100051. [DOI: 10.1016/j.soda.2022.100051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/02/2025]
|
|
33
|
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]
|
|
34
|
Wong JSM, Tan GHC, Cheok SHX, Ong CAJ, Chia CS, Teo MCC. Implications of peritoneal cancer index distribution on patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Pleura Peritoneum 2022; 7:95-102. [PMID: 35812008 PMCID: PMC9166179 DOI: 10.1515/pp-2021-0150] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Accepted: 03/23/2022] [Indexed: 11/25/2022] Open
Abstract
Objectives Peritoneal cancer index (PCI) score is a common prognostication tool in peritoneal metastases (PM). We hypothesize that the distribution of PCI score and involvement of specific regions affects survival and morbidity outcomes. Methods Data was collected from a prospective database of patients who underwent CRS and HIPEC for PM at the National Cancer Centre Singapore. We evaluate the relationship between PCI, PCI distribution, and survival and morbidity outcomes. Results One hundred and fifty-two patients underwent CRS and HIPEC with a median PCI score of nine (range 0–31). Median overall survival (OS) and progression free survival (PFS) were 43 and 17 months, respectively. Region six (pelvis) was most commonly involved and had the highest frequency of heavy disease burden. Presence of PM in the lower abdomen, flanks, and small bowel were associated with poorer OS (p=0.01, 0.03, <0.001) and PFS (p=0.04, 0.02, <0.001). Involvement of porta hepatitis predicted poorer OS but not PFS (p=0.03). Involvement of the gastric antrum resulted in higher rates of postoperative complications. Conclusions The pattern of PCI distribution may be associated with varying survival and morbidity outcomes.
Collapse
Affiliation(s)
- Jolene Si Min Wong
- Department of Sarcoma , Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore , Singapore , Singapore
- Department of Sarcoma , Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital , Singapore , Singapore
- SingHealth Duke-NUS Surgery Academic Medical Program, Duke-NUS Medical School , Singapore , Singapore
- SingHealth Duke-NUS Oncology Academic Medical Program, Duke-NUS Medical School , Singapore , Singapore
| | - Grace Hwei Ching Tan
- Department of Sarcoma , Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore , Singapore , Singapore
- Department of Sarcoma , Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital , Singapore , Singapore
| | - Sabrina Hui Xian Cheok
- Department of Sarcoma , Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore , Singapore , Singapore
- Department of Sarcoma , Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital , Singapore , Singapore
| | - Chin-Ann Johnny Ong
- Department of Sarcoma , Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore , Singapore , Singapore
- Department of Sarcoma , Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital , Singapore , Singapore
- SingHealth Duke-NUS Surgery Academic Medical Program, Duke-NUS Medical School , Singapore , Singapore
- SingHealth Duke-NUS Oncology Academic Medical Program, Duke-NUS Medical School , Singapore , Singapore
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore , Singapore , Singapore
| | - Claramae Shulyn Chia
- Department of Sarcoma , Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore , Singapore , Singapore
- Department of Sarcoma , Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital , Singapore , Singapore
- SingHealth Duke-NUS Surgery Academic Medical Program, Duke-NUS Medical School , Singapore , Singapore
- SingHealth Duke-NUS Oncology Academic Medical Program, Duke-NUS Medical School , Singapore , Singapore
| | - Melissa Ching Ching Teo
- Department of Sarcoma , Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore , Singapore , Singapore
- Department of Sarcoma , Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital , Singapore , Singapore
- SingHealth Duke-NUS Surgery Academic Medical Program, Duke-NUS Medical School , Singapore , Singapore
- SingHealth Duke-NUS Oncology Academic Medical Program, Duke-NUS Medical School , Singapore , Singapore
| |
Collapse
|
|
35
|
Rieser CJ, Alvikas J, Phelos H, Hall LB, Zureikat AH, Lee A, Ongchin M, Holtzman MP, Pingpank JF, Bartlett DL, Choudry MHA. Failure to Thrive Following Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy: Causes and Consequences. Ann Surg Oncol 2022; 29:2630-2639. [PMID: 34988834 DOI: 10.1245/s10434-021-11100-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 11/01/2021] [Indexed: 11/18/2022]
Abstract
BACKGROUND Failure to thrive (FTT) is a complex syndrome of nutritional failure and functional decline. Readmission for FTT following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS HIPEC) is common but underexamined. This study aims to determine features, risk factors, and prognostic significance of FTT following CRS HIPEC. PATIENTS AND METHODS We reviewed patients who underwent CRS HIPEC from 2010 to 2018 at our institution. Patients were categorized into no readmission, FTT readmission, and other readmission. FTT was determined by coding and chart review. We compared baseline characteristics, oncologic data, perioperative outcomes, and survival among the three cohorts. RESULTS Of 1068 discharges examined, 379 patients (36%) were readmitted within 90 days, of which 134 (12.5%) were labeled as FTT. Patients with FTT readmission had worse preoperative functional status, higher rates of malnutrition, more complex resections, longer hospital stays, and more postoperative complications (all p < 0.001). Ostomy creation [relative risk ratio (RRR) 4.06], in-hospital venous thromboembolism (VTE), discharge to nursing home (RRR 2.48), pre-CRS HIPEC chemotherapy (RRR 1.98), older age (RRR 1.84), and female gender (RRR 1.69) were all independent predictors for FTT readmission on multinomial regression (all p < 0.01). FTT readmission was associated with worse median overall survival on multivariate analysis [hazard ratio (HR) 1.60, p < 0.001] after controlling for oncologic, perioperative, and baseline factors. CONCLUSIONS FTT is common following CRS HIPEC and appears to be associated with baseline patient characteristics, operative burden, and postoperative complications. Perioperative strategies for improving nutrition and activity, along with early recognition and intervention in FTT may improve patient outcomes.
Collapse
Affiliation(s)
- Caroline J Rieser
- Division of Surgical Oncology, Koch Regional Perfusion Center, University of Pittsburgh, Pittsburgh, PA, USA.
| | - Jurgis Alvikas
- Division of Surgical Oncology, Koch Regional Perfusion Center, University of Pittsburgh, Pittsburgh, PA, USA
| | - Heather Phelos
- Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA
| | - Lauren B Hall
- Division of Surgical Oncology, Koch Regional Perfusion Center, University of Pittsburgh, Pittsburgh, PA, USA
| | - Amer H Zureikat
- Division of Surgical Oncology, Koch Regional Perfusion Center, University of Pittsburgh, Pittsburgh, PA, USA
| | - Andrew Lee
- Division of Surgical Oncology, Koch Regional Perfusion Center, University of Pittsburgh, Pittsburgh, PA, USA
| | - Melanie Ongchin
- Division of Surgical Oncology, Koch Regional Perfusion Center, University of Pittsburgh, Pittsburgh, PA, USA
| | - Matthew P Holtzman
- Division of Surgical Oncology, Koch Regional Perfusion Center, University of Pittsburgh, Pittsburgh, PA, USA
| | - James F Pingpank
- Division of Surgical Oncology, Koch Regional Perfusion Center, University of Pittsburgh, Pittsburgh, PA, USA
| | - David L Bartlett
- AHN Cancer Institute, Allegheny Health Network, Pittsburgh, PA, USA
| | - M Haroon A Choudry
- Division of Surgical Oncology, Koch Regional Perfusion Center, University of Pittsburgh, Pittsburgh, PA, USA
| |
Collapse
|
|
36
|
The role of computed tomography in the assessment of tumour extent and the risk of residual disease after upfront surgery in advanced ovarian cancer (AOC). Arch Gynecol Obstet 2022; 306:1235-1243. [PMID: 35235024 PMCID: PMC9470643 DOI: 10.1007/s00404-022-06466-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Accepted: 02/15/2022] [Indexed: 11/28/2022]
Abstract
Purpose Epithelial ovarian cancer is usually diagnosed in the advanced stages. To choose the best therapeutic approach, an accurate preoperative assessment of the tumour extent is crucial. This study aimed to determine whether the peritoneal cancer index (PCI), the amount of ascites, and the presence of cardiophrenic nodes (CPLNs) visualized by computed tomography (CT) can assess the tumour extent (S-PCI) and residual disease (RD) for advanced ovarian cancer (AOC) patients treated with upfront surgery. Methods In total, 118 AOC cases were included between January 2016 and December 2018 at Skåne University Hospital, Lund, Sweden. Linear regression and interclass correlation (ICC) analyses were used to determine the relationship between CT-PCI and S-PCI. The patients were stratified in complete cytoreductive surgery (CCS) with no RD or to non-CCS with RD of any size. The amount of ascites on CT (CT-ascites), CA-125 and the presence of radiological enlarged CPLNs (CT-CPLN) were analysed to evaluate their impact on estimating RD. Results CT-PCI correlated well with S-PCI (0.397; 95% CI 0.252–0.541; p < 0.001). The risk of RD was also related to CT-PCI (OR 1.069 (1.009–1.131), p < 0.023) with a cut-off of 21 for CT-PCI (0.715, p = 0.000). The sensitivity, specificity, positive predictive value and negative predictive value were 58.5, 70.3, 52.2 and 75.4%, respectively. CT-ascites above 1000 ml predicted RD (OR 3.510 (1.298–9.491) p < 0.013). Conclusion CT is a reliable tool to assess the extent of the disease in advanced ovarian cancer. Higher CT-PCI scores and large volumes of ascites estimated on CT predicted RD of any size.
Collapse
|
|
37
|
Nizam W, Fackche N, Pessoa B, Kubi B, Cloyd JM, Grotz T, Fournier K, Dineen S, Veerapong J, Baumgartner JM, Clarke C, Patel SH, Wilson GC, Lambert L, Abbott DE, Vande Walle KA, Lee B, Raoof M, Maithel SK, Russell MC, Zaidi MY, Johnston FM, Greer JB. Prognostic Significance of Preoperative Tumor Markers in Pseudomyxoma Peritonei from Low-Grade Appendiceal Mucinous Neoplasm: a Study from the US HIPEC Collaborative. J Gastrointest Surg 2022; 26:414-424. [PMID: 34506026 DOI: 10.1007/s11605-021-05075-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 04/07/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND Tumor markers are commonly utilized in the diagnostic evaluation, treatment decision making, and surveillance of appendiceal tumors. In this study, we aimed to determine the prognostic significance of elevated preoperative tumor markers in patients with pseudomyxoma peritonei secondary to low-grade appendiceal mucinous neoplasm who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. METHODS Using a multi-institutional database, eligible patients with measured preoperative tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), or cancer antigen 125 (CA-125)] were identified. Univariate and multivariate Cox-proportional hazards regression analysis assessed relationships between normal and elevated serum tumor markers with progression-free and overall survival in the context of multiple clinicopathologic variables. RESULTS zTwo hundred and sixty-four patients met criteria. CEA was the most commonly measured tumor marker (97%). Patients who had any elevated tumor marker had a higher peritoneal carcinomatosis index (PCI) as compared to those with normal range markers. Elevated CEA and CA 19-9 levels were individually associated with longer inpatient length of stay, requirement for intraoperative transfusion, and incomplete cytoreduction. Utilization of neoadjuvant chemotherapy, increased PCI score, elevated CA 19-9 (p = 0.007), and CA-125 levels (p = 0.01) were predictive of decreased progression-free survival on univariate analysis. However, in a multivariate model, only elevated PCI was a statistically significant predictor of progression-free survival. CONCLUSION Elevated preoperative tumor markers indicate a higher burden of disease but are not independently associated with survival in this retrospective multi-institutional cohort. Further prospective studies are needed to clarify the utility of these markers in this patient population.
Collapse
Affiliation(s)
- Wasay Nizam
- Department of Surgery, Johns Hopkins University, 600 N. Wolfe Street/Blalock 609, Baltimore, MD, 21287, USA
| | - Nadege Fackche
- Department of Surgery, Johns Hopkins University, 600 N. Wolfe Street/Blalock 609, Baltimore, MD, 21287, USA
| | - Bernardo Pessoa
- Department of Surgery, Johns Hopkins University, 600 N. Wolfe Street/Blalock 609, Baltimore, MD, 21287, USA
| | - Boateng Kubi
- Department of Surgery, Johns Hopkins University, 600 N. Wolfe Street/Blalock 609, Baltimore, MD, 21287, USA
| | - Jordan M Cloyd
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Travis Grotz
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA
| | - Keith Fournier
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Sean Dineen
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Department of Oncologic Sciences, Morsani College of Medicine, Tampa, FL, USA
| | - Jula Veerapong
- Division of Surgical Oncology, Department of Surgery, University of California, San Diego, CA, USA
| | - Joel M Baumgartner
- Division of Surgical Oncology, Department of Surgery, University of California, San Diego, CA, USA
| | - Callisia Clarke
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Wauwatosa, 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
| | - Laura Lambert
- Division of Surgical Oncology, Department of Surgery, University of Massachusetts Medical School, Worcester, MA, USA
| | - Daniel E Abbott
- Division of Surgical Oncology, Department of Surgery, University of Wisconsin, Madison, WI, USA
| | - Kara A Vande Walle
- Division of Surgical Oncology, Department of Surgery, University of Wisconsin, Madison, WI, USA
| | - Byrne Lee
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, Duarte, USA
| | - Mustafa Raoof
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, Duarte, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, USA
| | - Maria C Russell
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, USA
| | - Mohammad Y Zaidi
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, USA
| | - Fabian M Johnston
- Department of Surgery, Johns Hopkins University, 600 N. Wolfe Street/Blalock 609, Baltimore, MD, 21287, USA
| | - Jonathan B Greer
- Department of Surgery, Johns Hopkins University, 600 N. Wolfe Street/Blalock 609, Baltimore, MD, 21287, USA.
| |
Collapse
|
|
38
|
Rosa F, Galiandro F, Ricci R, Di Miceli D, Quero G, Fiorillo C, Cina C, Alfieri S. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases: analysis of short- and long-term outcomes. Langenbecks Arch Surg 2021; 406:2797-2805. [PMID: 34661754 PMCID: PMC8803682 DOI: 10.1007/s00423-021-02353-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 10/08/2021] [Indexed: 12/13/2022]
Abstract
Background Peritoneal metastases carry the worst prognosis among all sites of colorectal cancer (CRC) metastases. In recent years, the advent of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has improved survival for selected patients with limited peritoneal involvement. We report the evolution of CRS and HIPEC for colorectal peritoneal metastases at a tertiary referral center over a 10-year period. Methods Patients with colorectal peritoneal metastases undergoing CRS and HIPEC were included and retrospectively analyzed at a tertiary referral center from January 2006 to December 2015. Main outcomes included evaluation of grade III/IV complications, mortality rate, overall and disease-free survival, and prognostic factors influencing survival on a Cox multivariate analysis. Results Sixty-seven CRSs were performed on 67 patients during this time for colorectal peritoneal metastases. The median patient age was 57 years with 55.2% being female. The median peritoneal carcinomatosis index (PCI) was 7, with complete cytoreduction achieved in 65 (97%) cases. Grade > 2 complications occurred in 6 cases (8.9%) with no mortality. The median overall survival for the entire cohort was 41 months, with a 3-year overall survival of 43%. In case of complete cytoreduction, median overall and disease-free survival were 57 months and 36 months respectively, with a 3-year disease-free survival of 62%. Complete cytoreduction and nonmucinous histology were key factors independently associated with improved overall survival. Conclusions CRS and HIPEC for limited peritoneal metastases from CRC are safe and effective, with acceptable morbidity. In selected patients, it offers a highly favorable long-term outcomes.
Collapse
Affiliation(s)
- Fausto Rosa
- Department of Digestive Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy.
- Università Cattolica del Sacro Cuore, Rome, Italy.
| | - Federica Galiandro
- Department of Digestive Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy
| | - Riccardo Ricci
- Università Cattolica del Sacro Cuore, Rome, Italy
- Department of Pathology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | | | - Giuseppe Quero
- Department of Digestive Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy
| | - Claudio Fiorillo
- Department of Digestive Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy
| | - Caterina Cina
- Department of Digestive Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy
| | - Sergio Alfieri
- Department of Digestive Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy
- Università Cattolica del Sacro Cuore, Rome, Italy
| |
Collapse
|
|
39
|
Kurreck A, Gronau F, Alberto Vilchez ME, Abels W, Enghard P, Brandl A, Francis R, Föhre B, Lojewski C, Pratschke J, Thuss-Patience P, Modest D, Rau B, Feldbrügge L. Sodium Thiosulfate Reduces Acute Kidney Injury in Patients Undergoing Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy with Cisplatin: A Single-Center Observational Study. Ann Surg Oncol 2021; 29:152-162. [PMID: 34350529 PMCID: PMC8677645 DOI: 10.1245/s10434-021-10508-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Accepted: 07/07/2021] [Indexed: 12/31/2022]
Abstract
Background Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) represents a multimodal treatment concept for patients with peritoneal surface malignancies. The use of intraperitoneal cisplatin (CDDP) is associated with a risk of acute kidney injury (AKI). The aim of this study is to evaluate the protective effect of perioperative sodium thiosulfate (STS) administration on kidney function in patients undergoing CRS and CDDP-based HIPEC. Patients and Methods We retrospectively analyzed clinical data of all patients who underwent CRS and CDDP-based HIPEC at our hospital between March 2017 and August 2020. Patients were stratified according to the use of sodium thiosulfate (STS vs. no STS). We compared kidney function and clinical outcome parameters between both groups and determined risk factors for postoperative AKI on univariate and multivariate analysis. AKI was classified according to acute kidney injury network (AKIN) criteria. Results Of 238 patients who underwent CRS and CDDP-based HIPEC, 46 patients received STS and 192 patients did not. There were no significant differences in baseline characteristics. In patients who received STS, a lower incidence (6.5% vs. 30.7%; p = 0.001) and severity of AKI (p = 0.009) were observed. On multivariate analysis, the use of STS (OR 0.089, p = 0.001) remained an independent kidney-protective factor, while arterial hypertension (OR 5.283, p < 0.001) and elevated preoperative urea serum level (OR 5.278, p = 0.032) were predictors for postoperative AKI. Conclusions The present data suggest that STS protects patients from AKI caused by CRS and CDDP-based HIPEC. Further prospective studies are needed to validate the benefit of STS among kidney-protective strategies. Supplementary Information The online version contains supplementary material available at 10.1245/s10434-021-10508-x.
Collapse
Affiliation(s)
- Annika Kurreck
- Department of Hematology, Oncology and Tumorimmunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Felix Gronau
- Department of Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Miguel Enrique Alberto Vilchez
- Department of Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Wiltrud Abels
- Department of Anesthesiology and Operative Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Philipp Enghard
- Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Andreas Brandl
- Digestive Unit, Champalimaud Foundation, Lisbon, Portugal
| | - Roland Francis
- Department of Anesthesiology and Operative Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Bettina Föhre
- Department of Anesthesiology and Operative Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Christian Lojewski
- Department of Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Johann Pratschke
- Department of Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Peter Thuss-Patience
- Department of Hematology, Oncology and Tumorimmunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Dominik Modest
- Department of Hematology, Oncology and Tumorimmunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Beate Rau
- Department of Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
| | - Linda Feldbrügge
- Department of Surgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| |
Collapse
|
|
40
|
McCarthy B, Singh R, Levi-Polyachenko N. Oxaliplatin-resistant colorectal cancer models for nanoparticle hyperthermia. Int J Hyperthermia 2021; 38:152-164. [PMID: 33576281 DOI: 10.1080/02656736.2021.1876253] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
INTRODUCTION Metastatic colorectal cancer (CRC) is complicated by chemotherapy-resistant cell populations. Oxaliplatin is used in heated intraperitoneal hyperthermic chemoperfusion (HIPEC) for treatment of disseminated CRC. Photothermal nanoparticles can provide focal heating to improve the response of CRC cells to oxaliplatin, by confining heating near individual cells. Reduction in cellular luciferase signal may allow single-cell-resolution recording of thermal dosimetry. METHODS Oxaliplatin resistant (OxR) variants of luciferase-expressing CT26.WT-Fluc-Neo CRC cells were developed and their sensitivity to hyperthermia was evaluated. Polymer-based photothermal nanoparticles were developed, characterized and used to explore their potential for imparting a thermal dose to improve cell response to oxaliplatin. A correlation of thermal dose to intracellular luciferase activity was established using quantitative luminescence monitoring and microscopy. RESULTS Luciferase-based monitoring of thermal dose within CT26 cell lines was validated within the ranges of 0.04-8.33 CEM43 for parental cells and 0.05-9.74 CEM43 for OxR CT26 cells. This was further confirmed using nanoparticle-induced hyperthermia, where the single-cell resolution of the thermal dose can be achieved. The nanoparticles enhance cell killing of resistant cells when combined with oxaliplatin and stimulated to generate heat. CONCLUSION Nanoparticle-based hyperthermia is effective for augmenting chemotherapy and can be coupled with reductions in CT26 luciferase expression to monitor thermal dose at single-cell resolution. The development of OxR CT26.WT-Fluc-Neo CRC cells sets the stage for pre-clinical evaluations to measure nanoparticle-induced hyperthermia to augment chemotherapy (Nano-HIPEC) in a chemotherapy-resistant model of disseminated CRC.
Collapse
Affiliation(s)
- Bryce McCarthy
- Department of Plastic and Reconstructive Surgery Research, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Ravi Singh
- Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Nicole Levi-Polyachenko
- Department of Plastic and Reconstructive Surgery Research, Wake Forest School of Medicine, Winston-Salem, NC, USA
| |
Collapse
|
|
41
|
Deo S, Ray M, Bansal B, Bhoriwal S, Bhatnagar S, Garg R, Gupta N, Sharma A, Kumar L, Thulkar S, Dhamija E, Mathur S, Das P. Feasibility and outcomes of cytoreductive surgery and HIPEC for peritoneal surface malignancies in low- and middle-income countries: a single-center experience of 232 cases. World J Surg Oncol 2021; 19:164. [PMID: 34090452 PMCID: PMC8180169 DOI: 10.1186/s12957-021-02276-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 05/27/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has recently emerged as a viable management option for peritoneal surface malignancy (PSM). CRS and HIPEC is a complex, multidisciplinary and resource-intensive surgical procedure. It has a steep learning curve and is associated with significant morbidity and mortality. The expertise is mostly limited to few dedicated high-volume centers located in developed countries. We present a single institutional experience of 232 cases of CRS and HIPEC performed at a tertiary care cancer center in a low- and middle-income country (LMIC). METHODS A multidisciplinary PSM program was initiated in 2015 at a high-volume public-sector tertiary care cancer center in North India catering largely to patients belonging to low- and middle-income groups. Perioperative protocols were developed, and a prospective structured database was created to capture data. All patients undergoing CRS and HIPEC between January 2015 and December 2020 were identified, and the data was retrospectively analyzed for clinical spectrum, surgical details, and perioperative morbidity and mortality. RESULTS Two hundred and thirty-two patients underwent CRS and HIPEC during the study period. Epithelial ovarian carcinoma (56.5%) was the most common malignancy treated, followed by pseudomyxoma peritonei (18.5%), colorectal carcinoma (13.4%), and malignant mesothelioma (5.6%). Optimal CRS could be achieved in 94.4% of patients. Cisplatin and mitomycin were the most common drugs used for HIPEC. A total of 28.0% of patients had morbidity including deep vein thrombosis, subacute intestinal obstruction, sepsis, burst abdomen, lymphocele, urinoma, acute renal failure, and enterocutaneous fistula. The overall treatment-related mortality was 3.5%. CONCLUSIONS Results of the current study indicate that it is feasible to establish a successful CRS and HIPEC program for PSM in government-funded hospitals in LMIC facing resource constraints. The most common indication for CRS and HIPEC were carcinoma of the ovary followed by pseudomyxoma peritonei and colorectal carcinoma. Overall morbidity and mortality in the current series are comparable to global standards, reported from high-income countries. A protocol-based multidisciplinary team approach, optimal patient selection, and surgical expertise can help achieve optimal outcomes in government-funded hospitals in LMIC.
Collapse
Affiliation(s)
- Suryanarayana Deo
- Department of Surgical Oncology, Dr. BRA-IRCH, AIIMS, New Delhi, 110029, India.
| | - Mukurdipi Ray
- Department of Surgical Oncology, Dr. BRA-IRCH, AIIMS, New Delhi, 110029, India
| | - Babul Bansal
- Department of Surgical Oncology, Dr. BRA-IRCH, AIIMS, New Delhi, 110029, India
| | - Sandeep Bhoriwal
- Department of Surgical Oncology, Dr. BRA-IRCH, AIIMS, New Delhi, 110029, India
| | - Sushma Bhatnagar
- Department of Onco-anesthesia & Palliative Medicine, BRA-IRCH, AIIMS, New Delhi, India
| | - Rakesh Garg
- Department of Onco-anesthesia & Palliative Medicine, BRA-IRCH, AIIMS, New Delhi, India
| | - Nishkarsh Gupta
- Department of Onco-anesthesia & Palliative Medicine, BRA-IRCH, AIIMS, New Delhi, India
| | - Atul Sharma
- Department of Medical Oncology, BRA-IRCH, AIIMS, New Delhi, India
| | - Lalit Kumar
- Department of Medical Oncology, BRA-IRCH, AIIMS, New Delhi, India
| | - Sanjay Thulkar
- Department of Radiodiagnosis, BRA-IRCH, AIIMS, New Delhi, India
| | - Ekta Dhamija
- Department of Radiodiagnosis, BRA-IRCH, AIIMS, New Delhi, India
| | | | | |
Collapse
|
|
42
|
Mikkelsen MS, Petersen LK, Blaakaer J, Marinovskij E, Rosenkilde M, Andersen G, Bouchelouche K, Iversen LH. Assessment of peritoneal metastases with DW-MRI, CT, and FDG PET/CT before cytoreductive surgery for advanced stage epithelial ovarian cancer. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2021; 47:2134-2141. [PMID: 33812768 DOI: 10.1016/j.ejso.2021.03.239] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 03/04/2021] [Accepted: 03/11/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND Preoperative assessment of peritoneal metastases is an important factor for treatment planning and selection of candidates for cytoreductive surgery (CRS) in primary advanced stage (FIGO stages III-IV) epithelial ovarian cancer (EOC). The primary aim was to evaluate the efficacy of DW-MRI, CT, and FDG PET/CT used for preoperative assessment of peritoneal cancer index (PCI). MATERIAL AND METHODS In this prospective observational cohort study, 50 advanced stage EOC patients were examined with DW-MRI and FDG PET/CT with contrast enhanced CT as part of the diagnostic program. All patients were deemed amenable for upfront CRS. Imaging PCI was determined for DW-MRI, CT, and FDG PET/CT by separate readers blinded to the surgical findings. The primary outcome was agreement between the imaging PCI and PCI determined at surgical exploration (the reference standard) evaluated with Bland-Altman statistics. RESULTS The median surgical PCI was 18 (range: 3-32). For all three imaging modalities, the imaging PCI most often underestimated the surgical PCI. The mean differences between the surgical PCI and the imaging PCI were 4.2 (95% CI: 2.6-5.8) for CT, 4.4 (95% CI: 2.9-5.8) for DW-MRI, and 5.3 (95% CI: 3.6-7.0) for FDG PET/CT, and no overall statistically significant differences were found between the imaging modalities (DW-MRI - CT, p = 0.83; DW-MRI - FDG PET/CT, p = 0.24; CT - FDG PET/CT, p = 0.06). CONCLUSION Neither DW-MRI nor CT nor FDG PET/CT was superior in preoperative assessment of the surgical PCI in patients scheduled for upfront CRS for advanced stage EOC.
Collapse
Affiliation(s)
- Mette Schou Mikkelsen
- Department of Gynecology and Obstetrics, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.
| | - Lone Kjeld Petersen
- Open Patient Explorative Data Network, Department of Clinical Research, University of Southern Denmark, J.B. Winsløws Vej 9 a, 3. Etage, 5000, Odense C, Denmark; Department of Clinical Research, University of Southern Denmark, J.B. Winsløvs Vej 15, 5000, Odense C, Denmark; Department of Gynecology and Obstetrics, Odense University Hospital, J. B. Winsløws Vej 4, 5000, Odense, Denmark
| | - Jan Blaakaer
- Department of Clinical Research, University of Southern Denmark, J.B. Winsløvs Vej 15, 5000, Odense C, Denmark; Department of Gynecology and Obstetrics, Odense University Hospital, J. B. Winsløws Vej 4, 5000, Odense, Denmark
| | - Edvard Marinovskij
- Department of Radiology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark
| | - Mona Rosenkilde
- Department of Radiology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark
| | - Gratien Andersen
- Department of Radiology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark
| | - Kirsten Bouchelouche
- Department of Nuclear Medicine & PET Center, Aarhus University Hospital, Palle Juul-Jensens Boulevard 165, 8200, Aarhus N, Denmark
| | - Lene Hjerrild Iversen
- Department of Surgery, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark; Department of Clinical Medicine, Aarhus University, Palle Juul-Jensens Boulevard 82, 8200, Aarhus N, Denmark
| |
Collapse
|
|
43
|
Survival advantage of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer: experience from a Western tertiary referral center. Langenbecks Arch Surg 2021; 406:1847-1857. [PMID: 33704561 PMCID: PMC8481141 DOI: 10.1007/s00423-021-02102-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 01/21/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Selection criteria and prognostic factors for patients with advanced gastric cancer (AGC) undergoing cytoreductive surgery (CRS) plus hyperthermic intra-operative peritoneal chemotherapy (HIPEC) have not been well defined, and the literature data are not homogeneous. The aim of this study was to compare prognostic factors influencing overall (OS) and disease-free survival (DFS) in a population of patients affected by AGC with surgery alone and surgery plus HIPEC, both with curative (PCI, peritoneal carcinomatosis index > 1) and prophylactic (PCI = 0) intent. METHODS A retrospective analysis of a prospectively collected database was conducted in patients affected by AGC from January 2006 to December 2015. Uni- and multivariate analyses of prognostic factors were performed. RESULTS A total of 85 patients with AGC were analyzed. A 5-year OS for surgery alone, CRS plus curative HIPEC, and surgery plus prophylactic HIPEC groups was 9%, 27% and 33%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p = 0.05), curative HIPEC vs surgery alone group (p = 0.03), and curative vs prophylactic HIPEC (p = 0.04). A 5-year DFS for surgery alone, CRS + curative HIPEC, and surgery + prophylactic HIPEC groups was 9%, 20%, and 30%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p < 0.0001), curative HIPEC vs surgery alone group (p = 0.008), and curative vs prophylactic HIPEC (p = 0.05). CONCLUSIONS Patients with AGC undergoing surgery plus HIPEC had a better OS and DFS with respect to patients treated with surgery alone.
Collapse
|
|
44
|
Rieser CJ, Hoehn RS, Zenati M, Hall LB, Kang E, Zureikat AH, Lee A, Ongchin M, Holtzman MP, Pingpank JF, Bartlett DL, Choudry MHA. Impact of Socioeconomic Status on Presentation and Outcomes in Colorectal Peritoneal Metastases Following Cytoreduction and Chemoperfusion: Persistent Inequalities in Outcomes at a High-Volume Center. Ann Surg Oncol 2021; 28:3522-3531. [PMID: 33687614 PMCID: PMC8184539 DOI: 10.1245/s10434-021-09627-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 12/06/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion (CRS HIPEC) can offer significant survival advantage for select patients with colorectal peritoneal metastases (CRPM). Low socioeconomic status (SES) is implicated in disparities in access to care. We analyze the impact of SES on postoperative outcomes and survival at a high-volume tertiary CRS HIPEC center. PATIENTS AND METHODS We conducted a retrospective cohort study examining patients who underwent CRS HIPEC for CRPM from 2000 to 2018. Patients were grouped according to SES. Baseline characteristics, perioperative outcomes, and survival were examined between groups. RESULTS A total of 226 patients were analyzed, 107 (47%) low-SES and 119 (53%) high-SES patients. High-SES patients were younger (52 vs. 58 years, p = 0.01) and more likely to be White (95.0% vs. 91.6%, p = 0.06) and privately insured (83% vs. 57%, p < 0.001). They traveled significantly further for treatment and had lower burden of comorbidities and frailty (p = 0.01). Low-SES patients more often presented with synchronous peritoneal metastases (48% vs. 35%, p = 0.05). Following CRS HIPEC, low-SES patients had longer length of stay and higher burden of postoperative complications, 90-day readmission, and 30-day mortality. Median overall survival following CRS HIPEC was worse for low-SES patients (17.8 vs. 32.4 months, p = 0.02). This disparity persisted on multivariate survival analysis (low SES: HR = 1.46, p = 0.03). CONCLUSIONS Despite improving therapies for CRPM, low-SES patients remain at a significant disadvantage. Even patients who overcome barriers to care experience worse short- and long-term outcomes. Improving access and addressing these disparities is crucial to ensure equitable outcomes and improve patient care.
Collapse
Affiliation(s)
- Caroline J Rieser
- Division of Surgical Oncology, Koch Regional Perfusion Center, University of Pittsburgh, UPMC Cancer Pavilion, Pittsburgh, PA, USA.
| | - Richard S Hoehn
- Division of Surgical Oncology, Koch Regional Perfusion Center, University of Pittsburgh, UPMC Cancer Pavilion, Pittsburgh, PA, USA
| | - Mazen Zenati
- Division of Surgical Oncology, Koch Regional Perfusion Center, University of Pittsburgh, UPMC Cancer Pavilion, Pittsburgh, PA, USA
| | - Lauren B Hall
- Division of Surgical Oncology, Koch Regional Perfusion Center, University of Pittsburgh, UPMC Cancer Pavilion, Pittsburgh, PA, USA
| | - Eliza Kang
- Division of Surgical Oncology, Koch Regional Perfusion Center, University of Pittsburgh, UPMC Cancer Pavilion, Pittsburgh, PA, USA
| | - Amer H Zureikat
- Division of Surgical Oncology, Koch Regional Perfusion Center, University of Pittsburgh, UPMC Cancer Pavilion, Pittsburgh, PA, USA
| | - Andrew Lee
- Division of Surgical Oncology, Koch Regional Perfusion Center, University of Pittsburgh, UPMC Cancer Pavilion, Pittsburgh, PA, USA
| | - Melanie Ongchin
- Division of Surgical Oncology, Koch Regional Perfusion Center, University of Pittsburgh, UPMC Cancer Pavilion, Pittsburgh, PA, USA
| | - Matthew P Holtzman
- Division of Surgical Oncology, Koch Regional Perfusion Center, University of Pittsburgh, UPMC Cancer Pavilion, Pittsburgh, PA, USA
| | - James F Pingpank
- Division of Surgical Oncology, Koch Regional Perfusion Center, University of Pittsburgh, UPMC Cancer Pavilion, Pittsburgh, PA, USA
| | - David L Bartlett
- AHN Cancer Institute, Allegheny Health Network, Pittsburgh, PA, USA
| | - M Haroon A Choudry
- Division of Surgical Oncology, Koch Regional Perfusion Center, University of Pittsburgh, UPMC Cancer Pavilion, Pittsburgh, PA, USA
| |
Collapse
|
|
45
|
Rosa F, Galiandro F, Ricci R, Di Miceli D, Longo F, Quero G, Tortorelli AP, Alfieri S. Survival advantage of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer: experience from a Western tertiary referral center. Langenbecks Arch Surg 2021; 406:1071-1080. [PMID: 33611693 PMCID: PMC8208915 DOI: 10.1007/s00423-021-02137-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 02/15/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Selection criteria and prognostic factors for patients with advanced gastric cancer (AGC) undergoing cytoreductive surgery (CRS) plus hyperthermic intra-operative peritoneal chemotherapy (HIPEC) have not been well defined and the literature data are not homogeneous. The aim of this study was to compare prognostic factors influencing overall (OS) and disease-free survival (DFS) in a population of patients affected by AGC with surgery alone and surgery plus HIPEC, both with curative (PCI, Peritoneal Carcinomatosis Index >1) and prophylactic (PCI=0) intent. METHODS A retrospective analysis of a prospectively collected database was conducted in patients affected by AGC from January 2006 to December 2015. Uni- and multivariate analyses of prognostic factors were performed. RESULTS A total of 85 patients with AGC were analyzed. Five-year OS for surgery alone, CRS plus curative HIPEC, and surgery plus prophylactic HIPEC groups was 9%, 27%, and 33%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p = 0.05), curative HIPEC vs surgery alone group (p = 0.03), and curative vs prophylactic HIPEC (p = 0.04). Five-year DFS for surgery alone, CRS + curative HIPEC, and surgery + prophylactic HIPEC groups was 9%, 20%, and 30%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p < 0.0001), curative HIPEC vs surgery alone group (p = 0.008), and curative vs prophylactic HIPEC (p = 0.05). CONCLUSIONS Patients with AGC undergoing surgery plus HIPEC had a better OS and DFS with respect to patients treated with surgery alone.
Collapse
Affiliation(s)
- Fausto Rosa
- Digestive Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy. .,Università Cattolica del Sacro Cuore, Rome, Italy.
| | - Federica Galiandro
- Digestive Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy
| | - Riccardo Ricci
- Università Cattolica del Sacro Cuore, Rome, Italy.,Pathology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | | | - Fabio Longo
- Digestive Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy
| | - Giuseppe Quero
- Digestive Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy
| | - Antonio Pio Tortorelli
- Digestive Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy
| | - Sergio Alfieri
- Digestive Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy.,Università Cattolica del Sacro Cuore, Rome, Italy
| |
Collapse
|
|
46
|
Lee JL, Kim M, Kim J, Kim CW, Ha YJ, Kim SY, Cho DH, Kim JC. Evaluation of the significance of pseudomyxoma peritonei patients based on the Peritoneal Surface Oncology Group International (PSOGI) classification. Asian J Surg 2021; 44:848-853. [PMID: 33622598 DOI: 10.1016/j.asjsur.2021.01.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 12/21/2020] [Accepted: 01/04/2021] [Indexed: 11/28/2022] Open
Abstract
BACKGROUND Pseudomyxoma peritonei (PMP) is a rare disease characterized by mucinous ascites and deposits on the peritoneal surfaces. The study aimed to assess PMP patients according to the Peritoneal Surface Oncology Group International (PSOGI) classification, as a part of standardization of this rare disease. METHODS This retrospective study analyzed PMP patients who underwent surgery between January 2007 and December 2017. All histologic slides were re-evaluated and the clinical data were collected. According to the PSOGI, PMP was retrospectively classified into three categories: low-grade (LG-PMP), high-grade (HG-PMP), and signet-ring cells (SRC-PMP). The extent of peritoneal involvement was quantified by the peritoneal cancer index (PCI). The completeness of cytoreduction (CCR) was dichotomized as complete or incomplete. RESULTS Fifty-seven patients were included in this study, consisted of 39 patients with LG-PMP (74.0%), 14 with HG-PMP (20.8%), and 4 with SRC-PMP (5.2%). There was no operative mortality and major complications occurred in 24 patients (31.2%). The 5-year overall survival was 56.2% ± 8.1% for LG-PMP, 37.5% ± 12.1% for HG-PMP, and 25.0% ± 21.7% for SRC-PMP. Concerning CCR, the 5-year overall (complete: 59.5% ± 8.4% vs. incomplete: 12.7% ± 8.1%, p = 0.001) and disease-free survival (complete: 38.6% ± 8.9% vs. incomplete: 7.7% ± 6.8%, p = 0.001) were significantly different. In a multivariable analysis, PSOGI classification and CCR independently correlated with survival (p = 0.011 and 0.018, respectively). CONCLUSIONS The PSOGI classification provides prognostic stratification, hopefully requiring further validation including every single case of PMP established as a standard criteria.
Collapse
Affiliation(s)
- Jong Lyul Lee
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea; Institute of Innovative Cancer Research, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Meejeong Kim
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Jihun Kim
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Chan Wook Kim
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea; Institute of Innovative Cancer Research, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Ye Jin Ha
- Institute of Innovative Cancer Research, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Seon-Young Kim
- Medical Genomics Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon, South Korea
| | - Dong-Hyung Cho
- School of Life Science, Kyungpook National University, Daegu, South Korea
| | - Jin Cheon Kim
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea; Institute of Innovative Cancer Research, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.
| |
Collapse
|
|
47
|
McCarthy B, Cudykier A, Singh R, Levi-Polyachenko N, Soker S. Semiconducting polymer nanoparticles for photothermal ablation of colorectal cancer organoids. Sci Rep 2021; 11:1532. [PMID: 33452397 PMCID: PMC7810691 DOI: 10.1038/s41598-021-81122-w] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Accepted: 12/14/2020] [Indexed: 12/22/2022] Open
Abstract
Colorectal cancer (CRC) treatment is currently hindered by micrometastatic relapse that cannot be removed completely during surgery and is often chemotherapy resistant. Targeted theranostic nanoparticles (NPs) that can produce heat for ablation and enable tumor visualization via their fluorescence offer advantages for detection and treatment of disseminated small nodules. A major hurdle in clinical translation of nanoparticles is their interaction with the 3D tumor microenvironment. To address this problem tumor organoid technology was used to evaluate the ablative potential of CD44-targeted polymer nanoparticles using hyaluronic acid (HA) as the targeting agent and coating it onto hybrid donor acceptor polymer particles (HDAPPs) to form HA-HDAPPs. Additionally, nanoparticles composed from only the photothermal polymer, poly[4,4-bis(2-ethylhexyl)-cyclopenta[2,1-b;3,4-b']dithiophene-2,6-diyl-alt-2,1,3-benzoselenadiazole-4,7-diyl] (PCPDTBSe), were also coated with HA, to form HA-BSe NPs, and evaluated in 3D. Monitoring of nanoparticle transport in 3D organoids revealed uniform diffusion of non-targeted HDAPPs in comparison to attenuated diffusion of HA-HDAPPs due to nanoparticle-matrix interactions. Computational diffusion profiles suggested that HA-HDAPPs transport may not be accounted for by diffusion alone, which is indicative of nanoparticle/cell matrix interactions. Photothermal activation revealed that only HA-BSe NPs were able to significantly reduce tumor cell viability in the organoids. Despite limited transport of the CD44-targeted theranostic nanoparticles, their targeted retention provides increased heat for enhanced photothermal ablation in 3D, which is beneficial for assessing nanoparticle therapies prior to in vivo testing.
Collapse
Affiliation(s)
- Bryce McCarthy
- Department of Plastic and Reconstructive Surgery Research, Wake Forest School of Medicine, Winston Salem, NC, USA
- Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston Salem, NC, USA
| | - Amit Cudykier
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston Salem, NC, USA
| | - Ravi Singh
- Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, USA
- Comprehensive Cancer Center at Wake Forest Baptist Medical, Medical Center Boulevard, Winston Salem, NC, USA
| | - Nicole Levi-Polyachenko
- Department of Plastic and Reconstructive Surgery Research, Wake Forest School of Medicine, Winston Salem, NC, USA.
- Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA.
- Comprehensive Cancer Center at Wake Forest Baptist Medical, Medical Center Boulevard, Winston Salem, NC, USA.
| | - Shay Soker
- Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA.
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston Salem, NC, USA.
- Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
- Comprehensive Cancer Center at Wake Forest Baptist Medical, Medical Center Boulevard, Winston Salem, NC, USA.
| |
Collapse
|
|
48
|
Roife D, Powers BD, Zaidi MY, Staley CA, Cloyd JM, Ahmed A, Grotz T, Leiting J, Fournier K, Lee AJ, Veerapong J, Baumgartner JM, Clarke C, Patel SH, Hendrix RJ, Lambert L, Abbott DE, Pokrzywa C, Lee B, Blakely A, Greer J, Johnston FM, Laskowitz D, Dessureault S, Dineen SP. CRS/HIPEC with Major Organ Resection in Peritoneal Mesothelioma Does not Impact Major Complications or Overall Survival: A Retrospective Cohort Study of the US HIPEC Collaborative. Ann Surg Oncol 2020; 27:4996-5004. [PMID: 33073341 DOI: 10.1245/s10434-020-09232-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 09/23/2020] [Indexed: 11/18/2022]
Abstract
INTRODUCTION CRS/HIPEC is thought to confer a survival advantage for patients with malignant peritoneal mesothelioma (MPM). However, the impact of nonperitoneal organ resection is not clearly defined. We evaluated the impact of major organ resection (MOR) on postoperative outcomes and overall survival (OS). PATIENTS AND METHODS The US HIPEC collaborative database (2000-2017) was reviewed for MPM patients who underwent CRS/HIPEC. MOR was defined as total or partial resection of diaphragm, stomach, spleen, pancreas, small bowel, colon, rectum, kidney, ureter, bladder, and/or uterus. MOR was categorized as 0, 1, or 2+ organs. RESULTS A total of 174 patients were identified. Median PCI was 16 (3-39). The distribution of patients with MOR-0, MOR-1, and MOR-2+ was 94, 45, and 35 patients, respectively. MOR-1 and MOR-2+ groups had a higher frequency of any complication compared with MOR-0 (57.8%, 74.3%, and 48.9%, respectively, p = 0.035), but Clavien 3/4 complications were similar. Median length of stay was slightly higher in the MOR-1 and MOR-2+ groups (10 and 11 days) compared with the MOR-0 cohort (9 days, p = 0.005). Incomplete cytoreduction, ASA class 4, and male gender were associated with increased mortality on unadjusted analysis; however, their impact on OS was attenuated on multivariable analysis. MOR was not associated with OS based on these data (MOR-1: HR 1.67, 95% CI 0.59-4.74; MOR-2+ : HR 0.77, 95% CI 0.22-2.69). CONCLUSIONS MOR was not associated with an increase in major complications or worse OS in patients undergoing CRS/HIPEC for MPM and should be considered, if necessary, to achieve complete cytoreduction for MPM patients.
Collapse
Affiliation(s)
- David Roife
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, USA
- Department of Oncologic Sciences, University of South Florida, Morsani College of Medicine, Tampa, USA
| | - Benjamin D Powers
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, USA
- Department of Oncologic Sciences, University of South Florida, Morsani College of Medicine, Tampa, USA
| | - Mohammad Y Zaidi
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, USA
| | - Charles A Staley
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, USA
| | - Jordan M Cloyd
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, USA
| | - Ahmed Ahmed
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, USA
| | - Travis Grotz
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, USA
| | - Jennifer Leiting
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, USA
| | - Keith Fournier
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, USA
| | - Andrew J Lee
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, USA
| | - Jula Veerapong
- Division of Surgical Oncology, Department of Surgery, University of California, San Diego, USA
| | - Joel M Baumgartner
- Division of Surgical Oncology, Department of Surgery, University of California, San Diego, USA
| | - Callisia Clarke
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, USA
| | - Sameer H Patel
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, USA
| | - Ryan J Hendrix
- Division of Surgical Oncology, Department of Surgery, University of Massachusetts Medical School, Worcester, USA
| | - Laura Lambert
- Department of Surgery, Huntsman Cancer Institute, University of Utah, Salt Lake City, USA
| | - Daniel E Abbott
- Division of Surgical Oncology, Department of Surgery, University of Wisconsin, Madison, USA
| | - Courtney Pokrzywa
- Division of Surgical Oncology, Department of Surgery, University of Wisconsin, Madison, USA
| | - Byrne Lee
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, Duarte, USA
| | - Andrew Blakely
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, Duarte, USA
| | - Jonathan Greer
- Department of Surgery, Johns Hopkins University, Baltimore, MD, USA
| | | | - Danielle Laskowitz
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, USA
| | - Sophie Dessureault
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, USA
- Department of Oncologic Sciences, University of South Florida, Morsani College of Medicine, Tampa, USA
| | - Sean P Dineen
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, USA.
- Department of Oncologic Sciences, University of South Florida, Morsani College of Medicine, Tampa, USA.
| |
Collapse
|
|
49
|
Mikkelsen MS, Blaakaer J, Petersen LK, Schleiss LG, Iversen LH. Pharmacokinetics and toxicity of carboplatin used for hyperthermic intraperitoneal chemotherapy (HIPEC) in treatment of epithelial ovarian cancer. Pleura Peritoneum 2020; 5:20200137. [PMID: 33575463 PMCID: PMC7829861 DOI: 10.1515/pp-2020-0137] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 08/06/2020] [Indexed: 12/03/2022] Open
Abstract
Objectives Carboplatin is frequently used in various doses for hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of epithelial ovarian cancer (EOC) although its pharmacokinetics, including focus on the perfusion time, has not been evaluated when used in modern era cytoreductive surgery (CRS). The aim was to evaluate the pharmacokinetics and hematological toxicity of carboplatin used for HIPEC with a perfusion time of 90 min. Methods Fifteen patients with stage III–IV primary EOC received CRS and 90 min of HIPEC with carboplatin at dose 800 mg/m2. For the pharmacokinetic analysis, perfusate and blood samples were obtained during HIPEC and up to 48 h after HIPEC (blood only). Hematological toxicity within 30 days was graded according to Common Terminology Criteria for Adverse Events. Severe toxicity (grades 3–5) is reported. Results Mean maximum concentration of carboplatin was 12 times higher in perfusate than plasma (mean CmaxPF=348 µg/mL (range: 279–595 µg/mL) versus mean CmaxPL=29 µg/mL (range: 21–39 µg/mL)). Mean terminal half-life of carboplatin in perfusate was 104 min (range: 63–190 min) and mean intraperitoneal-to-plasma area under the concentration-time curve (AUC) ratio was 12.3 (range: 7.4–17.2). Two patients (13%) had grade 3 neutropenia within 30 days. No grade 4–5 hematological toxicities were identified. Conclusions Carboplatin has a favorable pharmacokinetic profile for 90 min HIPEC administration, and the hematological toxicity was acceptable at dose 800 mg/m2. Large interindividual differences were found in the pharmacokinetic parameters, making risk of systemic exposure difficult to predict.
Collapse
Affiliation(s)
- Mette Schou Mikkelsen
- Department of Gynecology and Obstetrics, Aarhus University Hospital, Aarhus, Denmark
| | - Jan Blaakaer
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark.,Department of Gynecology and Obstetrics, Odense University Hospital, Odense, Denmark
| | - Lone Kjeld Petersen
- Open Patient Explorative Data Network, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.,Department of Gynecology and Obstetrics, Odense University Hospital, Odense, Denmark
| | | | | |
Collapse
|
|
50
|
Prospective Comparative Analysis of Total Versus Involved Field Parietal Peritonectomy During Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) for Peritoneal Surface Malignancies from Colorectal Cancer. Indian J Surg 2020. [DOI: 10.1007/s12262-019-02017-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
|