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Zucchini V, D'Acapito F, Rapposelli IG, Framarini M, Di Pietrantonio D, Turrini R, Pozzi E, Ercolani G. Impact of RAS, BRAF mutations and microsatellite status in peritoneal metastases from colorectal cancer treated with cytoreduction + HIPEC: scoping review. Int J Hyperthermia 2025; 42:2479527. [PMID: 40101749 DOI: 10.1080/02656736.2025.2479527] [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: 12/12/2024] [Revised: 02/17/2025] [Accepted: 03/10/2025] [Indexed: 03/20/2025] Open
Abstract
BACKGROUND Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has shown survival benefits in select patients with peritoneal metastases (PM) from colorectal cancer (CRC). Molecular alterations, particularly RAS/BRAF mutations and Microsatellite Instability (MSI), play crucial roles in prognostic stratification and treatment planning, influencing both disease-free survival (DFS) and overall survival (OS). This scoping review evaluates the prognostic role of MSI and RAS/BRAF mutations in patients with PM-CRC treated with CRS-HIPEC. DESIGN A literature search was conducted across several databases to identify papers published between 2000 and September 2024. We selected 18 publications that considered DFS and OS as primary or secondary outcomes in patients with RAS/BRAF mutations and MSI following CRS-HIPEC treatment. Studies involving appendiceal cancer, peritoneal disease from non-CRC, pediatric patients, or subjects not treated with CRS-HIPEC were excluded. RESULTS Most studies suggest that RAS and BRAF mutations have a negative influence on survival outcomes. While inconsistencies exist, RAS mutations are generally associated with worse DFS. Specific KRAS subtypes such as KRASMUT2 or KRAS G12V and the BRAF V600 variant correlate with poorer prognosis. MSI status appears to attenuate the adverse effects of RAS/BRAF mutations on survival, although conflicting data persist. CONCLUSION RAS and BRAF mutations correlate with poorer outcomes in PM-CRC, underscoring the need for mutation-informed strategies to refine HIPEC and systemic therapies. Recognizing subtypes may improve patient selection for CRS-HIPEC, optimizing both local disease control and long-term survival. Future research should incorporate these molecular profiles to enhance therapeutic decision-making and better address this challenging condition.
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Affiliation(s)
- Valentina Zucchini
- Department of Medical and Surgical Sciences - DIMEC, Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Fabrizio D'Acapito
- General and Oncologic Department of Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | - Ilario Giovanni Rapposelli
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Massimo Framarini
- General and Oncologic Department of Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | - Daniela Di Pietrantonio
- General and Oncologic Department of Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | - Riccardo Turrini
- Department of Medical and Surgical Sciences - DIMEC, Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Eleonora Pozzi
- Department of Medical and Surgical Sciences - DIMEC, Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Giorgio Ercolani
- Department of Medical and Surgical Sciences - DIMEC, Alma Mater Studiorum - University of Bologna, Bologna, Italy
- General and Oncologic Department of Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
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Núñez JC, Rivera MT, Stevens MA. Adenocarcinoma of the duodenal papilla with synchronous peritoneal metastases-5 years of overall survival: A case report. World J Clin Oncol 2025; 16:103651. [DOI: 10.5306/wjco.v16.i4.103651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 12/20/2024] [Accepted: 02/08/2025] [Indexed: 03/26/2025] Open
Abstract
BACKGROUND Ampullary adenocarcinomas are a rare disease. They can be classified anatomically or according to their histology into intestinal, pancreatobiliary, and mixed subtypes, with different subtypes having distinct prognoses and potential treatments. We report a clinical case of a patient with mixed type adenocarcinoma of the ampulla of Vater, with predominantly intestinal histology, associated with an isolated and synchronous peritoneal carcinomatosis. It is the only case reported in the literature of duodenal ampulla cancer with synchronous peritoneal metastases, with long-term survival.
CASE SUMMARY A 53-year-old male patient with non-insulin-dependent diabetes presented with acute abdominal pain in the right hypochondrium. Images revealed dilatation of the biliary tract and the duct of Wirsung, without a clear obstructive factor. Upper gastrointestinal endoscopy revealed a tumor in the duodenal papilla. Biopsies confirmed an adenocarcinoma. In the first surgical step, a biliodigestive bypass was performed in association with resection of the carcinomatosis. Peritoneal metastases was found during the intraoperative period. Subsequently, chemotherapy with the folinic acid, fluorouracil, and oxaliplatin regimen was administered based on histology, and a favorable response was achieved. After a multidisciplinary discussion, the Whipple procedure was performed. A delayed biopsy showed disease-free margins. The patient achieved 5 years of overall survival in August 2024, and 4 years of disease-free survival in September 2024.
CONCLUSION We conclude that an important value of this work is showing individualized treatment for a patient with cancer.
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Affiliation(s)
- Julio César Núñez
- Department of Surgery, Hospital del Salvador, Santiago 7500922, Región Metropolitana, Chile
- Department of Surgery, Clínica Dávila-Vespucio, Santiago 8241479, Región Metropolitana, Chile
| | - María Teresa Rivera
- Department of Anatomic Pathology, Hospital del Salvador, Santiago 7500922, Región Metropolitana, Chile
| | - Mary Ann Stevens
- Department of Medical Oncology, Hospital del Salvador, Santiago 7500922, Región Metropolitana, Chile
- Department of Medical Oncology, Clínica Alemana, Santiago 7650568, Región Metropolitana, Chile
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D'Acapito F, Framarini M, Di Pietrantonio D, Ercolani G. Personalized treatment selection in colorectal cancer with peritoneal metastasis: Do we need statistically validated indicators or cultural shift? World J Gastrointest Oncol 2025; 17:104110. [DOI: 10.4251/wjgo.v17.i4.104110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 01/03/2025] [Accepted: 01/08/2025] [Indexed: 03/25/2025] Open
Abstract
The study by Wu et al analyzed the correlation between nutritional and inflammatory markers and prognosis in patients with colorectal cancer peritoneal metastasis. The authors propose the neutrophil-to-lymphocyte ratio (NLR) as a predictor of overall survival (OS) and developed a nomogram incorporating NLR, hemoglobin (Hb), and peritoneal cancer index (PCI) to estimate 1- and 2-year survival. Although the nomogram shows high accuracy, the group of patients analyzed is heterogeneous with respect to the surgical treatment received, and no clear definitions are given for normal Hb and there is no reason for choosing a very high PCI (≥ 20). Patient selection for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy requires a multidisciplinary approach. Over-simplification of the selection pathway may deny access to curative treatments to patients who could benefit. While methodologically sound, the study does not consider the effect of treatment received on OS, thus introducing a potential bias.
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Affiliation(s)
- Fabrizio D'Acapito
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forli 47121, Emilia-Romagna, Italy
| | - Massimo Framarini
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forli 47121, Emilia-Romagna, Italy
| | - Daniela Di Pietrantonio
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forli 47121, Emilia-Romagna, Italy
| | - Giorgio Ercolani
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forli 47121, Emilia-Romagna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna 40126, Emilia-Romagna, Italy
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Werba G, Ongchin M. Treatment and Management of Peritoneal Spread from Colorectal Cancer Peritoneal Metastasis. Surg Oncol Clin N Am 2025; 34:211-226. [PMID: 40015800 DOI: 10.1016/j.soc.2024.11.001] [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
Peritoneal metastases from colorectal cancer (PMCRC) present a complex treatment challenge requiring multidisciplinary expertise. Significant controversy exists regarding the optimal management of PMCRC patients. In this article, we seek to review the currently available evidence and discuss key components of patient workup, treatment, and management.
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Affiliation(s)
- Gregor Werba
- Division of Surgical Oncology, Department of Surgery, University of Pittsburgh Medical Center
| | - Melanie Ongchin
- Division of Surgical Oncology, Department of Surgery, University of Pittsburgh Medical Center.
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5
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Deeb AP, Aquina CT. Disparities and Health Care Delivery for Patients with Peritoneal Surface Malignancy. Surg Oncol Clin N Am 2025; 34:287-295. [PMID: 40015805 DOI: 10.1016/j.soc.2024.10.002] [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
Management of peritoneal surface malignancy (PSM) is complex and requires care at a PSM center. Despite the reported benefit of cytoreductive surgery (CRS)/ hyperthermic intraperitoneal chemotherapy (HIPEC) across PSM primaries, the uptake nationwide is low. The reasons are multifaceted and related to factors that disproportionately impact racial and ethnic minorities, rural residents, and other socially vulnerable patient populations. There are significant misperceptions of CRS/HIPEC in the treatment of PSM and the potential benefit for appropriately selected patients. Much work is needed to improve patient and provider education and to expand the reach of expert PSM management to vulnerable patients.
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Affiliation(s)
- Andrew-Paul Deeb
- Surgical Health Outcomes Consortium (SHOC), AdventHealth Digestive Health Institute, Orlando, FL 32804, USA. https://twitter.com/APDEEB
| | - Christopher T Aquina
- Surgical Health Outcomes Consortium (SHOC), AdventHealth Digestive Health Institute, Orlando, FL 32804, USA.
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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.
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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
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Gandawidjaja MH, Eyob B, Chmiel A, Eng OS. The Role of Prophylactic or Adjuvant Hyperthermic Intraperitoneal Therapy in Appendiceal and Colorectal Cancer Peritoneal Metastasis. Surg Oncol Clin N Am 2025; 34:227-240. [PMID: 40015801 DOI: 10.1016/j.soc.2024.12.001] [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
Appendiceal neoplasms and colorectal cancer have a propensity to develop peritoneal metastases. Despite advancements in systemic therapy and surgical management, the development and management of peritoneal metastases remains a challenging problem. Utilization of adjuvant or prophylactic hyperthermic intraperitoneal chemotherapy has been described, with varying quality of data and reported outcomes. The utilization of prophylactic or adjuvant hyperthermic intraperitoneal chemotherapy in patients with appendiceal neoplasms and colorectal cancer remains an active area of exploration.
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Affiliation(s)
- Monique H Gandawidjaja
- Division of Surgical Oncology, Department of Surgery, University of California Irvine, 3800 Chapman Avenue, Suite 6200, Orange, CA 92868, USA
| | - Belain Eyob
- Division of Surgical Oncology, Department of Surgery, University of California Irvine, 3800 Chapman Avenue, Suite 6200, Orange, CA 92868, USA
| | - Abigail Chmiel
- Department of Surgery, Washington University School of Medicine, MSC 8109-29-2300, 4590 Nash Way, Suite 2300, St. Louis, MO 63110, USA
| | - Oliver S Eng
- Division of Surgical Oncology, Department of Surgery, University of California Irvine, 3800 Chapman Avenue, Suite 6200, Orange, CA 92868, USA.
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8
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Mangieri CW, Votanopoulos KI, Shen P, Levine EA. Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) of Extraperitoneal Abdominal Disease, is it Appropriate? Ann Surg Oncol 2025; 32:2893-2902. [PMID: 39904847 PMCID: PMC11882691 DOI: 10.1245/s10434-024-16866-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Accepted: 12/24/2024] [Indexed: 02/06/2025]
Abstract
INTRODUCTION Cytoreductive surgery-hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) candidates often have extraperitoneal abdominal disease. Current expert peritoneal surface malignancy (PSM) guidelines recommend that the presence of extraperitoneal disease is a contraindication to CRS-HIPEC. METHODS We conducted a retrospective review of our institutional appendiceal and colorectal CRS-HIPEC registries. Two study cohorts were constructed: (1) cytoreduction with extraperitoneal abdominal disease, and (2) cytoreductions limited to peritoneal structures alone. The primary study outcome was survival. Subgroup analysis was based on the primary tumor and completeness of cytoreduction. RESULTS Overall, 864 CRS-HIPEC cases were evaluated, consisting of 578 appendiceal primaries and 286 colorectal cancers. The extraperitoneal cohort included 101 patients, with 763 patients in the non-extraperitoneal group. The median follow-up time was 13.18 years. The main analysis showed no significant differences in survival times. For overall survival (OS) there was a mean OS time of 5.87 years and a median OS time of 4.43 years for extraperitoneal cytoreductions compared with a mean of 5.90 years and a median of 4.76 years for non-extraperitoneal cytoreductions (p = 0.955). Five-year OS rates did not differ at 49.1% versus 49.5% (odds ratio [OR] 1.036, 95% confidence interval [CI] 0.671-1.597, p = 0.874). Disease-free survival (DFS) times showed a mean of 4.40 years and a median of 1.93 years for extraperitoneal cases versus a mean of 5.44 years and a median of 3.05 years for non-extraperitoneal cases (p = 0.210). Five-year DFS rates also showed no differences (OR 0.894, 95% CI 0.476-1.681, p = 0.728). No significant differences in progression-free survival (PFS)Pp times (p = 0.061) were reported. Multivariate Cox regression analysis indicated that extraperitoneal CRS was not an independent predictor of OS (hazard ratio [HR] 1.281, 95% CI 0.885-1.854, p = 0.190), DFS (HR 1.087, 95% CI 0.694-1.701, p = 0.716), or PFS (HR 0.650, 95% CI 0.243-1.738). CONCLUSION We conducted the largest analysis evaluating extraperitoneal cytoreductions, with no significant differences in almost all survival outcomes. We propose that the presence of extraperitoneal abdominal disease is not a contraindication to proceeding with CRS-HIPEC.
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Affiliation(s)
- Christopher W Mangieri
- Division of Surgical Oncology, Atrium Wake Forest Baptist Medical Center, Winston-Salem, NC, USA
| | | | - Perry Shen
- Division of Surgical Oncology, Atrium Wake Forest Baptist Medical Center, Winston-Salem, NC, USA
| | - Edward A Levine
- Division of Surgical Oncology, Atrium Wake Forest Baptist Medical Center, Winston-Salem, NC, USA.
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9
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Heslin RT, Whitham ZA, Kim AC. Molecular and Genetic Markers of Peritoneal Metastasis. Surg Oncol Clin N Am 2025; 34:145-154. [PMID: 40015796 DOI: 10.1016/j.soc.2024.12.003] [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
Peritoneal surface malignancies (PSMs) represent a biologically diverse group of cancers that range from primary peritoneal mesothelioma to metastatic gastrointestinal cancers. Because of the heterogenous nature of PSM, there is a large gap in molecular characterization of these cancers. This article reviews the underlying molecular and genetic mechanisms for PSM.
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Affiliation(s)
- Ryan T Heslin
- Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA
| | - Zachary A Whitham
- Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA
| | - Alex C Kim
- Department of Surgical Oncology, UT Southwestern Medical Center, Dallas, TX, USA.
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Vallicelli C, Morezzi D, Perrina D, Fugazzola P, Pinson J, Vigutto G, Ghaly A, Viganò J, Tomasoni M, Ansaloni L, Tuech JJ, Catena F. Colon and rectal peritoneal carcinomatosis: are we mixing apples with oranges? A propensity score-matched analysis. Updates Surg 2025; 77:277-285. [PMID: 39827438 DOI: 10.1007/s13304-025-02104-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Accepted: 01/07/2025] [Indexed: 01/22/2025]
Abstract
Rectal cancer is universally considered a different disease entity as compared to colon cancer, except when dealing with colorectal peritoneal carcinomatosis (PC), in which the two cancers are deemed as the same one. The present study aims to investigate the influence of primary tumor location (colon vs. rectum) on oncologic outcomes in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases. Data from three referral centers undergoing CRS plus HIPEC for PC of colorectal origin were prospectively collected. The primary outcomes were overall survival (OS) and disease-free survival (DFS) according to primary tumor location (colic vs. rectal). Univariate and multivariate analyses were performed using the Cox proportional hazard model first on the total number of patients. Then, a propensity score matching using the nearest-neighbour method with a 1:1 ratio was performed. The study included 167 patients: 126 colic and 41 rectal PC. After propensity score matching, rectal primary tumor location was independently predictive of a lower DFS (HR 1.91; 95%CI 1.06-3.45; p = 0.031) but not of a lower OS (HR 1.12; 95%CI 0.57-2.21; p = 0.73). Post-matching 3-year DFS rates were 49.2% (95%CI 34,3-70,5%) and 19.4% (95%CI 9,4-40,2%) for colic and rectal PC, respectively. The present study shows a significantly worse DFS for rectal cancer PC undergoing CRS and HIPEC compared to colon cancer PC, suggesting a possible need for dedicated pathways for rectal PC patients and posing a question for rectal PC to be considered as a unique disease entity.
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Affiliation(s)
- Carlo Vallicelli
- General, Emergency and Trauma Surgery, Maurizio Bufalini Hospital, viale Ghirotti 286, 47521, Cesena, Italy.
| | - Daniele Morezzi
- General, Emergency and Trauma Surgery, Maurizio Bufalini Hospital, viale Ghirotti 286, 47521, Cesena, Italy
- Department of Digestive Surgery, Rouen University Hospital, Rouen, France
| | - Daniele Perrina
- General, Emergency and Trauma Surgery, Maurizio Bufalini Hospital, viale Ghirotti 286, 47521, Cesena, Italy
| | - Paola Fugazzola
- General and Emergency Surgery Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Jean Pinson
- Department of Digestive Surgery, Rouen University Hospital, Rouen, France
| | - Gabriele Vigutto
- General, Emergency and Trauma Surgery, Maurizio Bufalini Hospital, viale Ghirotti 286, 47521, Cesena, Italy
| | - Ahmed Ghaly
- General and Emergency Surgery Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Jacopo Viganò
- General and Emergency Surgery Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Matteo Tomasoni
- General and Emergency Surgery Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Luca Ansaloni
- General and Emergency Surgery Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
- University of Pavia, Pavia, Italy
| | - Jean-Jacques Tuech
- Department of Digestive Surgery, Rouen University Hospital, Rouen, France
| | - Fausto Catena
- General, Emergency and Trauma Surgery, Maurizio Bufalini Hospital, viale Ghirotti 286, 47521, Cesena, Italy
- Alma Mater Studiorum Bologna University, Bologna, Italy
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11
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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.
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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.
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12
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Fauvre A, Ursino C, Garambois V, Culerier E, Milazzo LA, Vezzio-Vié N, Jeanson L, Marchive C, Andrade AF, Combes E, Atis S, Lossaint G, Quenet F, Michaud HA, Khellaf L, Corbeau I, Tosi D, Houede N, Bonnefoy N, Sgarbura O, Gongora C, Faget J. Oxaliplatin, ATR inhibitor and anti-PD-1 antibody combination therapy controls colon carcinoma growth, induces local and systemic changes in the immune compartment, and protects against tumor rechallenge in mice. J Immunother Cancer 2025; 13:e010791. [PMID: 40139833 PMCID: PMC11950992 DOI: 10.1136/jitc-2024-010791] [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: 10/21/2024] [Accepted: 03/01/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is the third most common cancer type and one of the leading causes of cancer-related death worldwide. The treatment of advanced metastatic CRC relies on classical chemotherapy combinations (5-fluorouracil, oxaliplatin or irinotecan). However, their use is limited by the emergence of resistance mechanisms, including to oxaliplatin. In this context, we recently showed that the combination of oxaliplatin and ataxia telangiectasia and Rad3-related protein inhibition (VE-822) is synergistic and may have a potential therapeutic effect in metastatic CRC management. METHODS In this study, we investigated the role of the VE-822+oxaliplatin (Vox) combination on the immune response and its potential synergy with an anti-programmed-cell Death receptor-1 (PD-1) antibody. We used cell lines and organoids from metastatic CRC to investigate in vitro Vox efficacy and orthotopic syngeneic mouse models of metastatic CRC to assess the efficacy of Vox+anti-PD-1 antibody and identify the involved immune cells. RESULTS The Vox+anti-PD-1 antibody combination completely cured tumor-bearing mice and protected them from a rechallenge. Vox was associated with a reduction of tumor-infiltrated neutrophils, CD206+ macrophages and regulatory T cells. Vox also induced a deep depletion of blood neutrophils. The increased bone marrow granulopoiesis failed to compensate for the Vox-mediated mature neutrophil depletion. Neutrophil depletion using a mouse recombinant anti-Ly6G antibody partially mimicked the Vox effect on the tumor microenvironment, but to a lower extent compared with the Vox+anti-PD-1 antibody combination. Vox, but not neutrophil depletion, led to the emergence of an Ly6C+ PD-1+ CD8+ T-cell population in the blood and spleen of tumor-harboring mice. These cells were proliferating, and expressed IFN-γ, CD62L, CXCR3 and Eomes. Moreover, the proportion of tumor antigen-specific T cells and of CD122+ BCL6+ T cells, which shared phenotypic characteristics with stem-like CD8+ T cells, was increased in treated mice. CONCLUSIONS Our work strongly suggests that the Vox+anti-PD-1 antibody combination might significantly improve survival in patients with metastatic and treatment-refractory CRC by acting both on cancer cells and CD8+ T cells.
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Affiliation(s)
- Alexandra Fauvre
- Résistance aux traitements et thérapies innovantes, Institut de Recherche en Cancérologie de Montpellier (IRCM), Université de Montpellier (UM), CNRS, Institut Régional du Cancer de Montpellier (ICM), Montpellier, France
| | - Chiara Ursino
- Immunity and Cancer Team, Institut de Recherche en Cancérologie de Montpellier (IRCM), Université de Montpellier (UM), Institut Régional du Cancer de Montpellier (ICM), Montpellier, France
| | - Veronique Garambois
- Résistance aux traitements et thérapies innovantes, Institut de Recherche en Cancérologie de Montpellier (IRCM), Université de Montpellier (UM), CNRS, Institut Régional du Cancer de Montpellier (ICM), Montpellier, France
| | - Elodie Culerier
- Immunity and Cancer Team, Institut de Recherche en Cancérologie de Montpellier (IRCM), Université de Montpellier (UM), Institut Régional du Cancer de Montpellier (ICM), Montpellier, France
| | - Louis-Antoine Milazzo
- Résistance aux traitements et thérapies innovantes, Institut de Recherche en Cancérologie de Montpellier (IRCM), Université de Montpellier (UM), CNRS, Institut Régional du Cancer de Montpellier (ICM), Montpellier, France
| | - Nadia Vezzio-Vié
- Résistance aux traitements et thérapies innovantes, Institut de Recherche en Cancérologie de Montpellier (IRCM), Université de Montpellier (UM), CNRS, Institut Régional du Cancer de Montpellier (ICM), Montpellier, France
| | - Laura Jeanson
- Résistance aux traitements et thérapies innovantes, Institut de Recherche en Cancérologie de Montpellier (IRCM), Université de Montpellier (UM), CNRS, Institut Régional du Cancer de Montpellier (ICM), Montpellier, France
| | - Candice Marchive
- Résistance aux traitements et thérapies innovantes, Institut de Recherche en Cancérologie de Montpellier (IRCM), Université de Montpellier (UM), CNRS, Institut Régional du Cancer de Montpellier (ICM), Montpellier, France
| | - Augusto Faria Andrade
- McGill University/Research Institute of McGill University, Nada Jabado Lab, Montreal, Quebec, Canada
| | - Eve Combes
- Résistance aux traitements et thérapies innovantes, Institut de Recherche en Cancérologie de Montpellier (IRCM), Université de Montpellier (UM), CNRS, Institut Régional du Cancer de Montpellier (ICM), Montpellier, France
| | - Salima Atis
- Résistance aux traitements et thérapies innovantes, Institut de Recherche en Cancérologie de Montpellier (IRCM), Université de Montpellier (UM), CNRS, Institut Régional du Cancer de Montpellier (ICM), Montpellier, France
| | - Gérald Lossaint
- Institut regional du Cancer de Montpellier, Montpellier, France
| | - François Quenet
- Institut regional du Cancer de Montpellier, Montpellier, France
| | - Henri-Alexandre Michaud
- Immunity and Cancer Team, Institut de Recherche en Cancérologie de Montpellier (IRCM), Université de Montpellier (UM), Institut Régional du Cancer de Montpellier (ICM), Montpellier, France
| | - Lakhdar Khellaf
- Department of Pathology, Montpellier University, Montpellier, France
| | - Ileana Corbeau
- Institut regional du Cancer de Montpellier, Montpellier, France
| | - Diego Tosi
- Medical Oncology Department, Institut régional du Cancer de Montpellier, Montpellier, France
| | - Nadine Houede
- Department of Oncology, University Hospital of Nimes, Nîmes, France
| | - Nathalie Bonnefoy
- Immunity and Cancer Team, Institut de Recherche en Cancérologie de Montpellier (IRCM), Université de Montpellier (UM), Institut Régional du Cancer de Montpellier (ICM), Montpellier, France
| | - Olivia Sgarbura
- Institut regional du Cancer de Montpellier, Montpellier, France
| | - Céline Gongora
- Résistance aux traitements et thérapies innovantes, Institut de Recherche en Cancérologie de Montpellier (IRCM), Université de Montpellier (UM), CNRS, Institut Régional du Cancer de Montpellier (ICM), Montpellier, France
- CNRS, Paris, France
| | - Julien Faget
- Immunity and Cancer Team, Institut de Recherche en Cancérologie de Montpellier (IRCM), Université de Montpellier (UM), Institut Régional du Cancer de Montpellier (ICM), Montpellier, France
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13
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van Gansewinkel EHE, van den Heuvel TBM, van Erning FN, De Hingh IHJT, Bouwense SAW, Simkens GA. Combined peritoneal and liver metastases in colorectal cancer: A Dutch nationwide population-based analysis of incidence, treatment and survival. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109999. [PMID: 40157059 DOI: 10.1016/j.ejso.2025.109999] [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: 02/18/2025] [Accepted: 03/25/2025] [Indexed: 04/01/2025]
Abstract
INTRODUCTION The aim of this study was to determine the incidence, treatment patterns, survival and factors associated with curative treatment in colorectal cancer patients with combined liver and peritoneal metastases using Dutch population-based data. MATERIALS AND METHODS Data from the Netherlands Cancer Registry were used. All patients diagnosed with synchronous isolated peritoneal and liver metastasized colorectal adenocarcinoma between January 1, 2015 and December 31, 2021 were included. Multivariable regression analyses were performed to identify factors associated with receiving curative treatment. Survival rates were calculated for patients undergoing palliative and curative treatment separately. RESULTS Of 14627 patients with colorectal adenocarcinoma in the study period, 927 patients (6.3 %) had isolated liver and peritoneal metastases and were evaluated in this study. Mean age was 66.9 years, non-mucinous and non-signet-ring cell adenocarcinomas were most prevalent (89.0 %) and tumors were mostly located in the colon (92.1 %). Patients were treated with best supportive care (n = 254, 27,4 %), palliative treatment (n = 618, 66,7 %) or curative treatment (n = 55, 5,9 %). Median OS was 1.5 months, 11.3 months, and 32.6 months, respectively. Multivariable analysis showed that younger age (OR 0.95, p < 0.001) and up to 3 liver metastases (OR 0.13, p < 0.001) are positively associated with receiving curative treatment. CONCLUSION This population-based study provides a comprehensive overview of the incidence and treatment of patients with synchronous colorectal liver and peritoneal metastases. It shows that in a highly selected group of patients, curative treatment is associated with better overall survival.
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Affiliation(s)
| | - Teun B M van den Heuvel
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands; Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands; Department of Oncology and Developmental Biology (GROW), Faculty of Health, Medicine and Life Sciences, Maastricht University, P.O. Box 616, MD, 6200, Maastricht, the Netherlands
| | - Felice N van Erning
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands; Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands
| | - Ignace H J T De Hingh
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands; Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands; Department of Oncology and Developmental Biology (GROW), Faculty of Health, Medicine and Life Sciences, Maastricht University, P.O. Box 616, MD, 6200, Maastricht, the Netherlands
| | - Stefan A W Bouwense
- Department of Surgery, Maastricht University Medical Centre, Maastricht, the Netherlands; School of Nutrition and Translation Research in Metabolism (NUTRIM), Faculty of Health, Medicine and Life Sciences, Maastricht University, P.O. Box 616, MD, 6200, Maastricht, the Netherlands
| | - Geert A Simkens
- Department of Surgery, Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands
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14
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Aguirre N, Veach DR, Cercek A, Cheal SM, Larson SM, Nash GM, Cheung NKV. Radioimmunotherapy for peritoneal carcinomatosis: Preclinical proof of concept to clinical translation. Cell Rep Med 2025:102040. [PMID: 40154493 DOI: 10.1016/j.xcrm.2025.102040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 01/09/2025] [Accepted: 03/03/2025] [Indexed: 04/01/2025]
Abstract
Peritoneal carcinomatosis (PC), characterized by the dissemination of metastatic tumor cells throughout the peritoneal cavity from several gastrointestinal and gynecological malignancies, has significantly compromised patient survival. The standard of care is cytoreductive surgery with or without intraperitoneal chemotherapy. However, surgical resection often leaves behind microscopic or clinically occult disease due to the complex anatomy of the peritoneum, where intraperitoneal chemotherapy and systemic chemotherapy have shown limited success. To improve the therapeutic outcome, targeted therapy using radionuclides such as alpha, beta, and Auger emitters delivered by antibodies is actively being investigated. While preclinical murine models of PC have shown the potential of radioimmunotherapy (RIT) using various radioisotopes across a wide spectrum of antigen targets and tumor diagnoses with acceptable toxicities, successful clinical trials are lacking. Here, we retrospectively summarize preclinical and clinical PC studies, consider their translational potential, and examine paths to development that maximize the clinical benefit of RIT in this context.
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Affiliation(s)
- Nicole Aguirre
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
| | - Darren R Veach
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Andrea Cercek
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Sarah M Cheal
- Department of Radiology, Weill Cornell Medicine, New York, NY, USA
| | - Steven M Larson
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Garrett M Nash
- Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Nai-Kong V Cheung
- Pediatric Oncology, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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15
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Pawar A, Kepenekian V, Omar A, Bel N, Villeneuve L, Drevet G, Maury JM, Passot G, Glehen O. Influence of lung metastases on outcomes of curative management of peritoneal metastases from colorectal cancer. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109650. [PMID: 40121748 DOI: 10.1016/j.ejso.2025.109650] [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: 10/28/2024] [Revised: 01/05/2025] [Accepted: 01/29/2025] [Indexed: 03/25/2025]
Abstract
BACKGROUND Traditionally there has been a nihilistic approach towards patients with pulmonary metastases arising from colorectal cancer. However, emerging evidence highlights the benefit of curative intent treatment. Given the established individual roles of pulmonary metastectomy and CRS/HIPEC in the treatment of colorectal pulmonary and peritoneal metastases, respectively, we decided to combine these modalities and determine whether pulmonary metastases really influence the outcomes of curative intent treatment in CRC patients with peritoneal metastases. METHODS This was a retrospective study of a prospectively maintained database of CRC patients with peritoneal metastases undergoing CRS and HIPEC with curative intent from Jan 1, 2005 to Aug 1, 2018. Patients were divided into two groups of without pulmonary metastases and with pulmonary metastases. Patients were followed up for a median 40.8 months. RESULTS Of total 455 patients 19 had pulmonary metastases. The median RFS and OS of all patients was 14.26 months (95 % CI:12.71-16.2) and 56.96 months (95 % CI: 47.73-77.79) respectively. Median RFS and OS of patients with and without pulmonary metastases was 12 & 49.8 months and 14.4 & 57.9 months, respectively. On multivariate analysis, PCI, CC-0 rate, CEA, signet ring histology and retroperitoneal lymph node metastases significantly affected the OS. Presence of pulmonary metastases did not significantly affect the RFS or OS. CONCLUSION There has always been a skepticism in the management CRC with PM and extraperitoneal disease, especially pulmonary metastases with curative intent. Our study demonstrates that CRS and HIPEC improves OS in such patients and pulmonary metastases per se do not influence the outcomes of disease. Nevertheless, further prospective and multi centric studies are required to validate these findings.
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Affiliation(s)
- Ajinkya Pawar
- Department of Surgical Oncology, Gujarat Cancer and Research Institute, Ahmedabad, India; Department of General Surgery and Surgical Oncology, Lyon Sud University Hospital, Pierre Benite, France
| | - Vahan Kepenekian
- Department of General Surgery and Surgical Oncology, Lyon Sud University Hospital, Pierre Benite, France; EA 3738 CICLY, Lyon 1 University, Lyon, France.
| | - Alhadeedi Omar
- Department of General Surgery and Surgical Oncology, Lyon Sud University Hospital, Pierre Benite, France; EA 3738 CICLY, Lyon 1 University, Lyon, France
| | - Nicolas Bel
- Department of General Surgery and Surgical Oncology, Lyon Sud University Hospital, Pierre Benite, France
| | | | - Gabrielle Drevet
- EA 3738 CICLY, Lyon 1 University, Lyon, France; Department of Thoracic Surgery, Hospices Civils de Lyon, Lyon, France
| | - Jean Michel Maury
- Department of General Surgery and Surgical Oncology, Lyon Sud University Hospital, Pierre Benite, France; Department of Thoracic Surgery, Hospices Civils de Lyon, Lyon, France
| | - Guillaume Passot
- Department of General Surgery and Surgical Oncology, Lyon Sud University Hospital, Pierre Benite, France; EA 3738 CICLY, Lyon 1 University, Lyon, France
| | - Olivier Glehen
- Department of General Surgery and Surgical Oncology, Lyon Sud University Hospital, Pierre Benite, France; EA 3738 CICLY, Lyon 1 University, Lyon, France
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Chi Y, Lu Y, Wu J, Li G, Li X, Wu Y, Zhao X, Wen J, Sha X, Lu GL, Hu K, Zhang Z. Rational Design of Bioinspired Lipoprotein System to Improve Penetration in Colorectal Peritoneal Metastases. NANO LETTERS 2025. [PMID: 40106687 DOI: 10.1021/acs.nanolett.4c06402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/22/2025]
Abstract
Chemotherapy of lethal colorectal peritoneal metastases (PM) is notoriously challenged by poor drug delivery efficiency in PM tumors. Inspired by the histopathological examinations of PM tumors from colon cancer patients, a C[RGDfK] peptide-modified bioinspired lipoprotein (R-BLP) system was optimized from 8 formulations with profound penetrating ability in PM tumors of colorectal cancers. Then, a chemotherapeutic 7-ethyl-10-hydroxy-camptothecin (SN38)-loaded R-BLP (termed SR-BLP) was designed to promote their penetration in PM tumors and improve the chemotherapeutic efficacy. In CT26-induced PM models, SR-BLP exhibited better penetration profiles in PM tumors over a counterpart liposomal formulation. SR-BLP treatment produced an 80.03% suppression of PM incidence with obvious DNA damage and topoisomerase I (TOP I) downregulation and caused a 1.78-fold prolongation of survival time. Therefore, the histopathological features-inspired R-BLP provides an encouraging tumor-penetrating delivery platform for the effective chemotherapy of colorectal PM.
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Affiliation(s)
- Yifei Chi
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China
| | - Yi Lu
- School of Pharmacy, Key laboratory of smart drug delivery (Ministry of Education) & National key laboratory of complex drug formulations for overcoming delivery barriers, Fudan University, Shanghai 201203, P.R. China
| | - Jingbo Wu
- Department of Pathology, Shanghai Fifth People's Hospital, Fudan University, 801 Heqing Road, Shanghai 200240, P.R. China
| | - Guodong Li
- School of Pharmacy, Key laboratory of smart drug delivery (Ministry of Education) & National key laboratory of complex drug formulations for overcoming delivery barriers, Fudan University, Shanghai 201203, P.R. China
| | - Xianlu Li
- School of Pharmacy, Key laboratory of smart drug delivery (Ministry of Education) & National key laboratory of complex drug formulations for overcoming delivery barriers, Fudan University, Shanghai 201203, P.R. China
| | - Yao Wu
- School of Pharmacy, Key laboratory of smart drug delivery (Ministry of Education) & National key laboratory of complex drug formulations for overcoming delivery barriers, Fudan University, Shanghai 201203, P.R. China
| | - Xiao Zhao
- School of Pharmacy, Key laboratory of smart drug delivery (Ministry of Education) & National key laboratory of complex drug formulations for overcoming delivery barriers, Fudan University, Shanghai 201203, P.R. China
- Department of Pathology, Shanghai Fifth People's Hospital, Fudan University, 801 Heqing Road, Shanghai 200240, P.R. China
| | - Jingyuan Wen
- The University of Auckland, Auckland 1142, New Zealand
| | - Xianyi Sha
- School of Pharmacy, Key laboratory of smart drug delivery (Ministry of Education) & National key laboratory of complex drug formulations for overcoming delivery barriers, Fudan University, Shanghai 201203, P.R. China
| | - Guo-Liang Lu
- The University of Auckland, Auckland 1142, New Zealand
| | - Kaili Hu
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China
| | - Zhiwen Zhang
- School of Pharmacy, Key laboratory of smart drug delivery (Ministry of Education) & National key laboratory of complex drug formulations for overcoming delivery barriers, Fudan University, Shanghai 201203, P.R. China
- Department of Pathology, Shanghai Fifth People's Hospital, Fudan University, 801 Heqing Road, Shanghai 200240, P.R. China
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17
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Gohda Y, Yano H, Suda R, Mirnezami A, Takemura N, Kojima Y, Nagata N, Kawai T, Kokudo N. Repeat Diagnostic Laparoscopy After Chemotherapy is Useful in Patient Selection for Conversion to Cytoreductive Surgery for Initially Unresectable Colorectal and Appendiceal Peritoneal Metastases: A Retrospective Cohort Study. Ann Surg Oncol 2025:10.1245/s10434-025-17106-1. [PMID: 40089619 DOI: 10.1245/s10434-025-17106-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Accepted: 02/17/2025] [Indexed: 03/17/2025]
Abstract
BACKGROUND Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) enable effective management of colorectal and appendiceal peritoneal metastases (CAPM) despite high morbidity. This study aimed to evaluate the role of repeat diagnostic laparoscopy (rDL) after systemic ± intraperitoneal chemotherapy in the management of initially unresectable CAPM. METHODS This retrospective cohort study included 70 consecutive patients with CAPM who underwent initial diagnostic laparoscopy (iDL). Patients with inoperable or equivocal CAPM underwent chemotherapy followed by rDL to assess the treatment response and possibility of conversion to CRS and HIPEC. RESULTS Cytoreductive surgery was deemed feasible for 29 patients and unlikely or equivocal for 41 patients based on iDL. Of the 29 resectable patients, 24 successfully underwent CRS and HIPEC after neoadjuvant chemotherapy. Among the 41 patients initially considered unresectable, 16 were deemed operable based on rDL after chemotherapy, and CRS and HIPEC were achieved for 14 patients (conversion). The median peritoneal cancer index was significantly reduced after chemotherapy for the 14 "conversion" patients, from 16 based on iDL to 11 based on rDL (p < 0.05). The conversion rate was 34% (14/41), with a 5-year survival rate of 14%. Treatment with CRS and HIPEC was achieved for 38 of 45 patients deemed operable based on either iDL or rDL (worst-case estimated positive predictive value, 84%). CONCLUSION Diagnostic laparoscopy is useful in predicting the likelihood of achieving CRS for patients with CAPM. Despite inoperability based on iDL, patients should be considered for rDL after chemotherapy to assess the possibility of conversion to CRS and HIPEC.
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Affiliation(s)
- Yoshimasa Gohda
- Department of Surgery, National Centre for Global Health and Medicine, Tokyo, Japan
| | - Hideaki Yano
- Department of Surgery, National Centre for Global Health and Medicine, Tokyo, Japan.
- Southampton Complex Cancer and Exenteration Team, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
| | - Ryuichiro Suda
- Department of General Surgery, Kimitsu Chuo Hospital, Chiba, Japan
| | - Alex Mirnezami
- Southampton Complex Cancer and Exenteration Team, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Nobuyuki Takemura
- Department of Surgery, National Centre for Global Health and Medicine, Tokyo, Japan
| | - Yasushi Kojima
- Department of Gastroenterology and Hepatology, National Centre for Global Health and Medicine, Tokyo, Japan
| | - Naoyoshi Nagata
- Department of Gastroenterological Endoscopy, Tokyo Medical University, Tokyo, Japan
| | - Takashi Kawai
- Department of Gastroenterological Endoscopy, Tokyo Medical University, Tokyo, Japan
| | - Norihiro Kokudo
- Department of Surgery, National Centre for Global Health and Medicine, Tokyo, Japan
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18
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Kim M, Lee YJ, Seon KE, Kim S, Lee C, Park H, Choi MC, Lee JY. Morbidity and Mortality Outcomes After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Treatment of Ovarian Cancer. J Clin Med 2025; 14:1782. [PMID: 40095895 PMCID: PMC11901296 DOI: 10.3390/jcm14051782] [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: 01/21/2025] [Revised: 02/15/2025] [Accepted: 03/04/2025] [Indexed: 03/19/2025] Open
Abstract
Background/Objectives: Hyperthermic intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery (CRS) has been reported to improve survival in patients with peritoneal carcinomatosis. This study aimed to investigate the morbidity and mortality rates of CRS with HIPEC in patients with ovarian cancers. Methods: We retrospectively reviewed the medical records of patients who underwent CRS with HIPEC for ovarian cancer from January 2013 to July 2021 at two tertiary institutions. The morbidities and mortalities that occurred within 30 days after HIPEC and the clinical and operative factors related to morbidities were investigated. Results: A total of 155 procedures in 151 patients were included in this study. The median age was 55 years and the median score of the peritoneal carcinomatosis index was eight points. Morbidities of grade ≥3 within 30 days of HIPEC occurred in 18 patients (11.6%). The most common severe morbidity was wound infection (3.2%), followed by pleural effusion (1.9%) and postoperative hemorrhage (1.9%). Within the 30-day postoperative period, there were no reported mortality cases. There were statistical differences in age, length of stay, peritoneal carcinomatosis index, bowel resection, operation time, and completeness of cytoreduction between the patients and severe morbidity. However, in the multivariate logistic analysis, none of the factors showed a statistically significant relationship with the occurrence of severe morbidity. Conclusions: The morbidity and mortality rates of CRS with HIPEC in gynecologic cancer patients were relatively low compared to those in previous reports. Further studies about the possible risk factors are needed.
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Affiliation(s)
- Migang Kim
- Comprehensive Gynecologic Cancer Center, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam 13520, Republic of Korea; (M.K.); (C.L.); (H.P.)
| | - Yong Jae Lee
- Department of Obstetrics and Gynecology, Institute of Women’s Life Medical Science, Yonsei University College of Medicine, Seoul 06229, Republic of Korea; (Y.J.L.); (K.E.S.); (S.K.)
| | - Ki Eun Seon
- Department of Obstetrics and Gynecology, Institute of Women’s Life Medical Science, Yonsei University College of Medicine, Seoul 06229, Republic of Korea; (Y.J.L.); (K.E.S.); (S.K.)
| | - Sunghoon Kim
- Department of Obstetrics and Gynecology, Institute of Women’s Life Medical Science, Yonsei University College of Medicine, Seoul 06229, Republic of Korea; (Y.J.L.); (K.E.S.); (S.K.)
| | - Chan Lee
- Comprehensive Gynecologic Cancer Center, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam 13520, Republic of Korea; (M.K.); (C.L.); (H.P.)
| | - Hyun Park
- Comprehensive Gynecologic Cancer Center, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam 13520, Republic of Korea; (M.K.); (C.L.); (H.P.)
| | - Min Chul Choi
- Comprehensive Gynecologic Cancer Center, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam 13520, Republic of Korea; (M.K.); (C.L.); (H.P.)
| | - Jung-Yun Lee
- Department of Obstetrics and Gynecology, Institute of Women’s Life Medical Science, Yonsei University College of Medicine, Seoul 06229, Republic of Korea; (Y.J.L.); (K.E.S.); (S.K.)
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Lei Z, Wang Y, Fang R, Wang K, Tian J, Chen Y, Wang Y, Luo J, He J, Ding B, Yang X, Wang L, Cui S, Tang H. Hyperthermic intraperitoneal chemotherapy after upfront cytoreductive surgery for stage III epithelial ovarian cancer: Follow-up of long-term survival. Acta Obstet Gynecol Scand 2025. [PMID: 40035363 DOI: 10.1111/aogs.15094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 02/14/2025] [Accepted: 02/17/2025] [Indexed: 03/05/2025]
Abstract
INTRODUCTION The survival benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) has been well defined at the time of interval cytoreductive surgery, but the role of HIPEC remains uncertain for patients with newly diagnosed advanced ovarian cancer in the upfront setting. The present study aimed to report the updated long-term survival outcomes after 5 years of follow-up from our previous multicenter retrospective cohort study to compare primary cytoreductive surgery (PCS) plus HIPEC with PCS alone among women with stage III epithelial ovarian cancer. MATERIAL AND METHODS This study was conducted at five high-volume gynecological medical centers in China from January 2010 to May 2017. Eligible patients with complete data were treated with either PCS combined with HIPEC or PCS alone. The 5-year overall survival (OS) rate was updated to compare PCS plus HIPEC with PCS alone. The inverse probability of treatment weighting (IPTW) method based on a propensity score model for each patient was used to control the confounding factors and evaluate the effect of HIPEC. RESULTS Data from 789 patients, a total of 584 eligible stage III epithelial ovarian cancer patients were ultimately included in the analysis (PCS-plus-HIPEC group, n = 425; PCS-alone group, n = 159). After IPTW adjustment, the median OS was 44.5 (95% CI, 40.1-49.1) months in the PCS-plus-HIPEC group and 32.4 (95% CI, 28.8-40.3) months in the PCS-alone group (weighted hazard ratio, 0.74; 95% CI, 0.59-0.93; p = 0.006). At 5 years, the OS rates were 37.9% (95% CI, 33.0%-42.8%) in the PCS-plus-HIPEC group and 26.4% (95% CI, 18.9%-34.6%) in the PCS-alone group (p = 0.007). After stratification into optimal and suboptimal cytoreduction subgroups, patients in the PCS-plus-HIPEC group maintained a greater association with improved OS than those in the PCS-alone group. Among the women who underwent optimal cytoreduction in the PCS-plus-HIPEC group and PCS-alone group, the median OS was 49.9 (95% CI, 45.2-58.4) months and 37.8 (95% CI, 30.5-53.0) months (p = 0.042) while the 5-year OS rate was 43.7% (95% CI, 37.7%-49.6%) and 33.2% (95% CI, 23.3%-43.5%), respectively (p = 0.040). Meanwhile, for those treated with suboptimal cytoreduction subgroup in the PCS-plus-HIPEC and PCS-alone groups, the median OS was 28.4 (95% CI, 22.2-39.9) months and 20.6 (95% CI, 10.6-32.4) months (p = 0.099) while the 5-year OS rate was 22.4% (95% CI, 15.1%-30.5%) and 12.2% (95% CI, 4.4%-24.2%), respectively (p = 0.060). The median follow-up period was 87.2 (95% CI, 85.1-92.7) months. CONCLUSIONS The updated results indicate that the addition of HIPEC is associated with improved long-term survival outcomes beyond 5 years for patients with stage III epithelial ovarian cancer in the upfront setting.
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Affiliation(s)
- Ziying Lei
- Department of Abdominal Surgery, Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, China
| | - Yue Wang
- Department of Gynaecology and Obstetrics, Henan Provincial People's Hospital, Zhengzhou, China
| | - Runya Fang
- Department of Abdominal Surgery, Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, China
| | - Ke Wang
- Department of Gynaecological Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center of Cancer, Tianjin, China
| | - Jun Tian
- Department of Gynaecology and Obstetrics, Huaihe Hospital of Henan University, Kaifeng, China
| | - Yangxiao Chen
- Department of Abdominal Surgery, Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, China
| | - Yingsi Wang
- Department of Abdominal Surgery, Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, China
| | - Jiali Luo
- Department of Abdominal Surgery, Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, China
| | - Jinfu He
- Department of Abdominal Surgery, Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, China
| | - Binghui Ding
- Department of Abdominal Surgery, Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, China
| | - Xianzi Yang
- Department of Abdominal Surgery, Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, China
| | - Li Wang
- Department of Gynaecological Oncology, Affiliated Tumor Hospital of Zhengzhou University, Tumor Hospital of Henan Province, Zhengzhou, China
| | - Shuzhong Cui
- Department of Abdominal Surgery, Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, China
| | - Hongsheng Tang
- Department of Abdominal Surgery, Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, China
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Liu D, Chen Z, Deng W, Lan J, Zhu Y, Wang H, Xu X, Zhang Y, Wu X, Yang K, Cai J. An Organoid Model for the Therapeutic Effect of Hyperthermic Intraperitoneal Chemotherapy for Colorectal Cancer. Ann Surg Oncol 2025; 32:1925-1940. [PMID: 39589577 PMCID: PMC11811434 DOI: 10.1245/s10434-024-16469-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Accepted: 10/23/2024] [Indexed: 11/27/2024]
Abstract
BACKGROUND Consensus regarding the hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer (CRC) regimen remains elusive. In this study, patient-derived tumor organoids from CRC were utilized as a preclinical model for in vitro drug testing of HIPEC regimens commonly used in clinical practice. This approach was used to facilitate the clinical formulation of HIPEC. METHOD Tumor tissues and corresponding clinical data were obtained from patients diagnosed with CRC at the Sixth Affiliated Hospital of Sun Yat-Sen University. Qualified samples were cultured and passaged. We aimed to assess the sensitivity of in vitro hyperthermic perfusion using five different regimens, i.e. mitomycin C, mitomycin C combined with cisplatin, mitomycin C combined with 5-fluorouracil, oxaliplatin, and oxaliplatin combined with 5-fluorouracil. RESULTS Tumor organoids obtained from 46 patients with CRC were cultured, and in vitro hyperthermic perfusion experiments were conducted on 42 organoids using five different regimens. The average inhibition rate of mitomycin C was 85.2% (95% confidence interval [CI] 80.4-89.9%), mitomycin C combined with cisplatin was 85.5% (95% CI 80.2-90.7%), mitomycin C combined with 5-fluorouracil was 65.6% (95% CI 59.6-71.6%), oxaliplatin was 37.9% (95% CI 31.5-44.3%), and oxaliplatin combined with 5-fluorouracil was 40.7% (95% CI 33.9-47.5%). CONCLUSION In vitro hyperthermic perfusion demonstrates that the inhibition rate of mitomycin C, both alone and in combination with cisplatin, surpasses that of the combination of mitomycin C with 5-fluorouracil and oxaliplatin. In clinical practice, the combination of mitomycin C and cisplatin can be regarded as the optimal choice for HIPEC in CRC.
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Affiliation(s)
- Duo Liu
- Department of Colorectal Surgery, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Medical Innovation Technology Transformation Center of Shenzhen Second People's Hospital, Shenzhen University, Shenzhen, China
| | - Zexin Chen
- Guangdong Research Center of Organoid Engineering and Technology, Accurate International Biotechnology Co. Ltd., Guangzhou, China
| | - Weihao Deng
- Department of Pathology, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Jianqiang Lan
- Guangdong Research Center of Organoid Engineering and Technology, Accurate International Biotechnology Co. Ltd., Guangzhou, China
| | - Yu Zhu
- Guangdong Research Center of Organoid Engineering and Technology, Accurate International Biotechnology Co. Ltd., Guangzhou, China
| | - Huaiming Wang
- Department of Colorectal Surgery, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Xing Xu
- Department of Breast and Thyroid Surgery, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Medical Innovation Technology Transformation Center of Shenzhen Second People's Hospital, Shenzhen University, Shenzhen, China
| | - Yuanxin Zhang
- Department of Colorectal Surgery, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Xiangwei Wu
- Qiantang Biotechnology Co. Ltd., Suzhou, China
| | - Keli Yang
- Department of Colorectal Surgery, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
| | - Jian Cai
- Department of Colorectal Surgery, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Medical Innovation Technology Transformation Center of Shenzhen Second People's Hospital, Shenzhen University, Shenzhen, China.
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Madonia D, Cashin P, Graf W, Ghanipour L. Appendiceal adenocarcinoma-patterns of tumor spread and prognosis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:108755. [PMID: 39443251 DOI: 10.1016/j.ejso.2024.108755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 09/20/2024] [Accepted: 10/09/2024] [Indexed: 10/25/2024]
Abstract
INTRODUCTION Appendiceal adenocarcinoma represents a diagnostic and therapeutic challenge since it is prone to early lymphatic and peritoneal spread. We aimed to analyze the proportion of lymph node metastases in completion right hemicolectomy specimens, risk factors for peritoneal metastases (PM), and prognosis after definitive treatment. METHODS Ninety-three patients with appendiceal adenocarcinoma scheduled for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) in Uppsala 2004-2020 were identified from a prospectively maintained registry. Risk factors for PM were assessed based on the presence (CT + group, n = 55) or absence (CT - group, n = 37) of visible PM at baseline CT scan. Prognostic factors were analyzed based on the actual presence (PM group, n = 66) or absence (no PM group, n = 27) of PM. RESULTS The median age was 60 (26-78). Forty-eight patients were women. Resection of PM at initial surgery indicated an 80 % risk of finding PM at a follow-up exploration. R1 appendectomy and perforated appendix had a similar risk for PM (24 %,26 %) which increased to 38 % if both were present. Regional lymph node metastases occurred in 31 % in the CT + group vs. 14 % in the CT - group (p = 0.005) and was associated with poor survival HR 5.16 (1.49-17.81). The 5-year OS and DFS rates were 54 % and 29 % in the PM group. CONCLUSIONS Patients with certain risk factors have a high likelihood of PM despite a normal CT scan, which justifies selective exploration at a HIPEC center. Regional lymph node spread supports the current practice of completion right hemicolectomy and is a significant prognostic factor.
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Affiliation(s)
- D Madonia
- Department of Surgical Sciences, Uppsala University, Sweden.
| | - P Cashin
- Department of Surgical Sciences, Uppsala University, Sweden
| | - W Graf
- Department of Surgical Sciences, Uppsala University, Sweden
| | - L Ghanipour
- Department of Surgical Sciences, Uppsala University, Sweden
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Alexander HR. Invited Commentary: Ten-Year Outcome of a Randomized Trial: Cytoreduction and HIPEC with Mitomycin C Versus Oxaliplatin for Appendiceal Neoplasm with Peritoneal Dissemination, by Levine et al. Ann Surg Oncol 2025; 32:1420-1421. [PMID: 39694999 DOI: 10.1245/s10434-024-16716-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Accepted: 12/01/2024] [Indexed: 12/20/2024]
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Khorfan R, Sedighim S, Caba-Molina D, Tran TB, Senthil M, O'Leary MP, Eng OS. National Trends and Outcomes in Cytoreductive Surgery for Colorectal Cancer with Peritoneal Metastases Before and After PRODIGE 7. Ann Surg Oncol 2025; 32:1422-1424. [PMID: 39572498 DOI: 10.1245/s10434-024-16539-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Accepted: 11/04/2024] [Indexed: 02/12/2025]
Affiliation(s)
- Rhami Khorfan
- Division of Surgical Oncology, Department of Surgery, Loma Linda University School of Medicine, Loma Linda, CA, USA
| | - Shaina Sedighim
- Division of Surgical Oncology, Department of Surgery, University of California-Irvine, Orange, CA, USA
| | - David Caba-Molina
- Division of Surgical Oncology, Department of Surgery, Loma Linda University School of Medicine, Loma Linda, CA, USA
| | - Thuy B Tran
- Division of Surgical Oncology, Department of Surgery, University of California-Irvine, Orange, CA, USA
| | - Maheswari Senthil
- Division of Surgical Oncology, Department of Surgery, University of California-Irvine, Orange, CA, USA
| | - Michael P O'Leary
- Division of Surgical Oncology, Department of Surgery, University of California-Irvine, Orange, CA, USA
| | - Oliver S Eng
- Division of Surgical Oncology, Department of Surgery, University of California-Irvine, Orange, CA, USA.
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Carrion-Alvarez L, Primavesi F, Søreide K, Sochorova D, Diaz-Nieto R, Dopazo C, Serrablo A, Edhemovic I, Stättner S. Liver metastases from colorectal cancer: A joint ESSO-EAHPBA-UEMS core curriculum collaboration. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109728. [PMID: 40023020 DOI: 10.1016/j.ejso.2025.109728] [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: 02/18/2025] [Revised: 02/22/2025] [Accepted: 02/24/2025] [Indexed: 03/04/2025]
Abstract
Colorectal liver metastases (CRLM) are a major indication for liver surgery in Europe, highlighting the need for standardized knowledge and training in surgical oncology. The European Society of Surgical Oncology (ESSO) has updated its core curriculum to provide a structured framework for education. Previous publications have addressed pancreatic, hepatocellular, and biliary tract cancers to support candidates preparing for the European Board of Surgery Qualification (EBSQ) exams in Surgical Oncology and Hepato-Pancreato-Biliary Surgery. However, a dedicated guide for CRLM remains absent. This article aims to fill that gap by offering a structured reference on CRLM, covering epidemiology, staging, genetics, and diagnosis of metastatic colorectal cancer. It also outlines multidisciplinary treatment strategies, including systemic, surgical, interventional, and palliative approaches. A structured literature review was conducted using PubMed to identify the most updated (inter)national management guidelines, prioritizing recent multicentre studies, systematic reviews, and meta-analyses published from January 2020 to January 2025. By bridging the gap between the ESSO core curriculum and detailed subspecialty training, this guide provides an essential resource for hepatobiliary surgeons and surgical oncologists. It serves as a valuable tool for those preparing for board examinations while promoting a standardized approach to CRLM education and management across Europe.
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Affiliation(s)
- Lucia Carrion-Alvarez
- HPB Unit, General Surgery Department, Fuenlabrada University Hospital, Madrid, Spain.
| | - Florian Primavesi
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria.
| | - Kjetil Søreide
- Department of Gastrointestinal Surgery, HPB Unit, Stavanger University Hospital, Stavanger, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway; Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Dana Sochorova
- Department of Surgery, Tomas Bata Hospital Zlin, Czech Republic
| | - Rafael Diaz-Nieto
- Hepatobiliary Surgery Unit, Liverpool University Hospital, Liverpool, UK
| | - Cristina Dopazo
- Department of HPB Surgery and Transplants, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autónoma de Barcelona, Barcelona, Spain
| | | | - Ibrahim Edhemovic
- Department of Surgical Oncology, Institute of Oncology, Ljubljana, Slovenia; Faculty of Medicine Ljubljana, University of Ljubljana, Ljubljana, Slovenia
| | - Stefan Stättner
- Johannes Kepler University Linz, Kepler University Hospital GmbH, Department of General and Visceral Surgery, Hepatobiliary Unit, Krankenhausstrasse 9, 4021, Linz, Austria
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Yurttas C, Kalmbach S, Ansorge E, Bezmawi M, Blumenstock G, Löffler MW, Mihaljevic AL, Ernst C, Holderried M. [Is cytoreductive surgery with HIPEC adequately funded?]. CHIRURGIE (HEIDELBERG, GERMANY) 2025:10.1007/s00104-025-02246-7. [PMID: 39971798 DOI: 10.1007/s00104-025-02246-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/16/2025] [Indexed: 02/21/2025]
Abstract
BACKGROUND Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a treatment concept for highly selected patients with peritoneal metastases and primary tumors (PMT). A challenge from the perspective of hospitals is the cost intensity of this promising multimodal treatment option. RESEARCH QUESTION Which factors influence the cost and revenue structure of CRS/HIPEC treatment in the current diagnosis-related group (DRG) system according to § 17b of the German Hospital Financing Act (KHG)? MATERIAL AND METHODS The database for this analysis was constituted by all patients treated with combined CRS/HIPEC at a certified tumor center between 2017 and 2021. The statistical analysis performed was descriptive, using two-sample and multisample comparisons (ANOVA) as well as linear correlation and regression analyses. RESULTS The total length of hospitalization for 173 patients was on average 16.1 days and the average length of stay in the intensive care unit was 2.2 days. Postoperative complications occurred in 110 (63.6%) patients. The average DRG revenue obtained was € 21,658.48. The total costs for the combined CRS/HIPC treatment amounted to an average of € 23,764.77 and were therefore on average € 2106.29 (8.86%) higher than the DRG revenue granted for the treatment. The length of stay in the intensive care unit and the total length of hospitalization correlated positively with the treatment costs and DRG revenue. DISCUSSION This study presents key factors influencing the cost and revenue structure of CRS/HIPEC and illustrates that this promising surgical treatment approach is relevantly underfunded by the German DRG system. A reform of the current DRG system with special consideration of highly complex oncological treatment concepts is therefore recommended.
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Affiliation(s)
- Can Yurttas
- Klinik für Allgemeine, Viszeral- und Transplantationschirurgie, Universitätsklinikum Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Deutschland.
| | - Sarah Kalmbach
- Klinik für Allgemeine, Viszeral- und Transplantationschirurgie, Universitätsklinikum Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Deutschland
| | - Emilia Ansorge
- Klinik für Allgemeine, Viszeral- und Transplantationschirurgie, Universitätsklinikum Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Deutschland
| | - Mohamed Bezmawi
- Klinik für Allgemeine, Viszeral- und Transplantationschirurgie, Universitätsklinikum Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Deutschland
| | - Gunnar Blumenstock
- Institut für klinische Epidemiologie und angewandte Biometrie, Universitätsklinikum Tübingen, Silcherstraße 5, 72076, Tübingen, Deutschland
| | - Markus W Löffler
- Klinik für Allgemeine, Viszeral- und Transplantationschirurgie, Universitätsklinikum Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Deutschland
- Institut für klinische und experimentelle Transfusionsmedizin, Medizinische Fakultät Tübingen, Otfried-Müller-Str. 4/1, 72076, Tübingen, Deutschland
| | - André L Mihaljevic
- Klinik für Allgemeine, Viszeral- und Transplantationschirurgie, Universitätsklinikum Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Deutschland
| | - Christian Ernst
- Institut Health Care & Public Management, Lehrstuhl für Ökonomik und Management sozialer Dienstleistungen, Universität Hohenheim, Fruwirthstraße 48, 70599, Stuttgart, Deutschland
| | - Martin Holderried
- Institut Health Care & Public Management, Lehrstuhl für Ökonomik und Management sozialer Dienstleistungen, Universität Hohenheim, Fruwirthstraße 48, 70599, Stuttgart, Deutschland
- Zentralbereich Medizin: Struktur‑, Prozess- und Qualitätsmanagement, Universitätsklinikum Tübingen, Hoppe-Seyler-Straße 6, 72076, Tübingen, Deutschland
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Tang J, Liao L, Xiao B, Sui Q, Zheng M, Jiang W, Han K, Kong L, Pan Z, Ding P. Efficacy and safety of subtotal pelvic peritonectomy for colorectal cancer patients with peritoneal metastasis confined to the pelvic cavity. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109703. [PMID: 40022888 DOI: 10.1016/j.ejso.2025.109703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 12/21/2024] [Accepted: 02/12/2025] [Indexed: 03/04/2025]
Abstract
BACKGROUND Cytoreductive surgery has shown survival benefits for colorectal cancer (CRC) patients with peritoneal metastasis. However, the optimal extent of peritonectomy remains controversial in cases of limited peritoneal metastases. This study modified selective pelvic peritonectomy (SPP) into subtotal pelvic peritonectomy (STPP) for metastasis confined to pelvic cavity, and aimed to evaluate its feasibility, safety, and impact on survival outcomes. MATERIALS AND METHODS CRC patients with limited peritoneal metastasis confined to the pelvic cavity who underwent CC0 (no macroscopic residual cancer remained) resection were included from a prospectively collected database. Surgical complications, disease-free survival (DFS), and overall survival (OS) were analyzed. RESULTS A total of 67 patients were included (26 in the STPP group and 41 in the SPP group). Clinically, STPP was found to be feasible and without increased surgical complications or mortality rates. At a median follow-up of 33.9 months, the 3-year DFS was 65.9 % and 30.7 % in STPP and SPP groups, respectively (P= 0.002). The 3-year OS was 84.1 % and 68.5 % in STPP and SPP groups, respectively (P= 0.006). Moreover, STTP was independently associated with improved DFS (HR = 0.351, 95 % CI 0.165-0.745, P= 0.006) and OS (HR = 0.324, 95 % CI 0.116-0.902, P=0.032). Female gender was also independently associated with poor DFS (HR = 2.146, 95 % CI 1.078-4.271, P= 0.031). Among 24 female patients with remaining ovaries, 9 (37.5 %) cases developed metachronous ovarian metastasis, and of these 6 underwent a second operation. CONCLUSIONS Subtotal pelvic peritonectomy is associated with promising long-term outcomes in CRC patients with peritoneal metastasis confined to the pelvic cavity. Prophylactic bilateral oophorectomy should be strongly considered during cytoreductive surgery.
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Affiliation(s)
- Jinghua Tang
- Departments of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong, 510060, PR China
| | - Leen Liao
- Departments of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong, 510060, PR China
| | - Binyi Xiao
- Departments of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong, 510060, PR China
| | - Qiaoqi Sui
- Departments of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong, 510060, PR China
| | - Muxu Zheng
- Departments of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong, 510060, PR China
| | - Wu Jiang
- Departments of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong, 510060, PR China
| | - Kai Han
- Departments of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong, 510060, PR China
| | - Lingheng Kong
- Departments of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong, 510060, PR China
| | - Zhizhong Pan
- Departments of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong, 510060, PR China.
| | - Peirong Ding
- Departments of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong, 510060, PR China.
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Chen D, Ma Y, Li J, Wen L, Liu L, Zhang G, Hu H, Huang C, Yao X. Risk factors for postoperative acute kidney injury after cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: a meta-analysis and systematic review. World J Surg Oncol 2025; 23:40. [PMID: 39905442 DOI: 10.1186/s12957-025-03657-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Accepted: 01/07/2025] [Indexed: 02/06/2025] Open
Abstract
BACKGROUND Acute kidney injury after CRS + HIPEC is a serious postoperative complication, but only a few studies have reported its postoperative risk factors. In addition, there are large discrepancies in the results of available observational studies. METHODS We searched The Cochrane Library, Embase, Web of Science,and PubMed to identify observational studies reporting risk factors for AKI after CRS + HIPEC. A meta-analysis was performed to investigate the effect of various preoperative and intraoperative risk factors on AKI after CRS + HIPEC. RESULTS A total of 7 studies were included in this study, comprising 1550 patients who developed AKI after CRS + HIPEC. The results of meta-analysis showed that the significant preoperative risk factors were age, sex, BMI, eGFR, Hb, PCI, diabetes mellitus, and hypertension. IO cisplatin, IO SBP < 100 was identified as an intraoperative risk factor, whereas IO mitomycin emerged as a protective factor for postoperative AKI. In addition, the risk of postoperative AKI varied by primary tumor site, with Appendix being less prone to AKI, while mesothelioma and ovarian, two sites with a greatly elevated risk of postoperative AKI. CONCLUSIONS This meta-analysis identified a number of risk factors for postoperative AKI after CRS + HIPEC. By identifying these risk factors, it is more beneficial for clinicians to perform early preoperative interventions and select the most appropriate treatment strategy for their patients, thus minimizing the risk of postoperative AKI. TRIAL REGISTRATION PROSPERO CRD42024585269.
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Affiliation(s)
- Dengzhuo Chen
- Gannan Medical University, Ganzhou, China
- Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital, Ganzhou, China
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China
| | - Yongli Ma
- Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital, Ganzhou, China
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China
| | - Jinghui Li
- Gannan Medical University, Ganzhou, China
- Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital, Ganzhou, China
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China
| | - Liang Wen
- Gannan Medical University, Ganzhou, China
- Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital, Ganzhou, China
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China
| | - Linfeng Liu
- Gannan Medical University, Ganzhou, China
- Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital, Ganzhou, China
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China
| | - Guosheng Zhang
- Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital, Ganzhou, China
| | - Hongkai Hu
- Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital, Ganzhou, China.
| | - Chengzhi Huang
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
| | - Xueqing Yao
- Gannan Medical University, Ganzhou, China.
- Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital, Ganzhou, China.
- Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
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Brière R, Simard AJ, Rouleau-Fournier F, Letarte F, Drolet S, Brind'Amour A. Perioperative management and survival outcomes following cytoreductive surgery in patients with peritoneal metastases from rectal cancer: A scoping review. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109498. [PMID: 39615297 DOI: 10.1016/j.ejso.2024.109498] [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: 06/13/2024] [Revised: 11/02/2024] [Accepted: 11/23/2024] [Indexed: 01/03/2025]
Abstract
BACKGROUND Patients with rectal cancer and peritoneal metastases (PM) may have a worse prognosis and benefit from a different management than patients with colon cancer. METHODS A systematic literature search of MEDLINE (PubMed) and EMBASE databases was performed to identify all reported patients with rectal cancer and PM treated with cytoreductive surgery (CRS), with or without hyperthermic intraperitoneal chemotherapy (HIPEC), to investigate the proper selection criteria for this population, the optimal perioperative management, and highlight its specific oncological outcomes. RESULTS Twenty studies reporting on 285 patients were identified. Median age varied from 28 to 63 years, and 57.5 % of patients had synchronous disease. The use of neoadjuvant treatment was frequent, but regimens were heterogenous, consisting of radiotherapy alone, chemoradiotherapy or systemic chemotherapy. Thirty-two percent did not receive any neoadjuvant treatment. Most patients (85.6 %) received HIPEC after CRS, with mitomycin C being the most used drug. Complete cytoreduction was performed in 90.1 % of patients. Data on stoma creation and management were poorly reported. Severe complications occurred in 32.2 % of patients. Median disease-free survival ranged from 6 to 22 months, and median overall survival varied from 7 to 53.2 months. CONCLUSION This scoping review highlights the paucity of data available regarding the management of patients with rectal cancer and PM. It also emphasizes different issues and dilemmas regarding this specific population, especially on the use of neoadjuvant treatment, the role of HIPEC after CRS and stoma management.
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Affiliation(s)
- Raphaëlle Brière
- Department of Surgery, CHU de Québec - Université Laval, Quebec, Canada.
| | - Anne-Julie Simard
- Department of Surgery, CHU de Québec - Université Laval, Quebec, Canada.
| | | | - François Letarte
- Department of Surgery, CHU de Québec - Université Laval, Quebec, Canada.
| | - Sébastien Drolet
- Department of Surgery, CHU de Québec - Université Laval, Quebec, Canada.
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Piercey O, Chantrill L, Hsu H, Ma B, Price T, Tan IB, Teng H, Tie J, Desai J. Expert consensus on the optimal management of BRAF V600E-mutant metastatic colorectal cancer in the Asia-Pacific region. Asia Pac J Clin Oncol 2025; 21:31-45. [PMID: 39456063 PMCID: PMC11733838 DOI: 10.1111/ajco.14132] [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: 05/15/2024] [Revised: 09/14/2024] [Accepted: 10/09/2024] [Indexed: 10/28/2024]
Abstract
The burden of colorectal cancer (CRC) is high in the Asia-Pacific region, and several countries in this region have among the highest and/or fastest growing rates of CRC in the world. A significant proportion of patients will present with or develop metastatic CRC (mCRC), and BRAFV600E-mutant mCRC represents a particularly aggressive phenotype that is less responsive to standard chemotherapies. In light of recent therapeutic advances, an Asia-Pacific expert consensus panel was convened to develop evidence-based recommendations for the diagnosis, treatment, and management of patients with BRAFV600E-mutant mCRC. The expert panel comprised nine medical oncologists from Australia, Hong Kong, Singapore, and Taiwan (the authors), who met to review current literature and develop eight consensus statements that describe the optimal management of BRAFV600E-mutant mCRC in the Asia-Pacific region. As agreed by the expert panel, the consensus statements recommend molecular testing at diagnosis to guide individualized treatment decisions, propose optimal treatment pathways according to microsatellite stability status, advocate for more frequent monitoring of BRAFV600E-mutant mCRC, and discuss local treatment strategies for oligometastatic disease. Together, these expert consensus statements are intended to optimize treatment and improve outcomes for patients with BRAFV600E-mutant mCRC in the Asia-Pacific region.
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Affiliation(s)
| | - Lorraine Chantrill
- Illawarra Shoalhaven Local Health DistrictIllawarraNew South WalesAustralia
- Faculty of Science, Medicine and HealthUniversity of WollongongWollongongNew South WalesAustralia
| | - Hung‐Chih Hsu
- Division of Hematology OncologyChang Gung Memorial HospitalNew TaipeiTaiwan
- College of MedicineChang Gung UniversityTaoyuanTaiwan
| | - Brigette Ma
- State Key Laboratory of Translational Oncology, Sir YK Pao Centre for Cancer, Department of Clinical Oncology, Hong Kong Cancer InstituteThe Chinese University of Hong KongHong Kong SARChina
| | - Timothy Price
- The Queen Elizabeth HospitalAdelaideSouth AustraliaAustralia
| | - Iain Beehuat Tan
- Division of Medical OncologyNational Cancer Centre SingaporeSingaporeSingapore
| | - Hao‐Wei Teng
- Department of OncologyTaipei Veterans General HospitalTaipeiTaiwan
| | - Jeanne Tie
- Peter MacCallum Cancer CentreMelbourneVictoriaAustralia
- Sir Peter MacCallum Department of OncologyThe University of MelbourneMelbourneVictoriaAustralia
| | - Jayesh Desai
- Peter MacCallum Cancer CentreMelbourneVictoriaAustralia
- Sir Peter MacCallum Department of OncologyThe University of MelbourneMelbourneVictoriaAustralia
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Aguirre N, Chung SK, Foote MB, Shia J, Vakiani E, Gowda T, Paty PB, Weiser MR, Garcia-Aguilar J, Karagkounis G, Cercek A, Nash GM. Predictors of Recurrence in Nonmetastatic Appendiceal Epithelial Cancers: An Updated Single-Center Experience Over 25 Years. Ann Surg Oncol 2025; 32:695-702. [PMID: 39604747 PMCID: PMC11813631 DOI: 10.1245/s10434-024-16366-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Accepted: 10/01/2024] [Indexed: 11/29/2024]
Abstract
BACKGROUND Appendiceal epithelial tumors are rare and encompass a broad set of adenocarcinoma histologies, including mucinous (mAC), colonic-type (cAC), and goblet cell (GCA) adenocarcinomas. It has previously been reported that nodal disease predicted recurrence in patients with nonmetastatic appendiceal adenocarcinomas, supporting diagnostic laparoscopy with right hemicolectomy for staging and assessment for risk of recurrence. In this update, we sought to identify predictors of nodal disease on initial diagnostic pathology in nonmetastatic adenocarcinomas. METHODS Patients with nonmetastatic appendiceal adenocarcinoma at a single institution from 1994 to 2020 were included. Clinicopathologic characteristics that predict recurrence and lymph node metastasis were analyzed. Workup included staging laparoscopy with right hemicolectomy, seriel imaging and biochemical monitoring. RESULTS A total of 147 patients with mAC (18%), cAC (22%), and GCAs (59%) were included. After median follow-up of 53 months, 23 (16%) patients recurred, most commonly in the peritoneal cavity (17/23, 74%). Recurrence rates were higher among node-positive patients (59% vs. 5%, P < 0.001). Nodal disease was more common in mAC (27%) and cAC (37%) than in GCA (11%); however, adenocarcinoma grade was not associated with nodal involvement. CONCLUSIONS Nodal metastasis was more common in mAC and cAC compared with GCA and was the only significant predictor of recurrence in appendix cancer.
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Affiliation(s)
- Nicole Aguirre
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Sebastian K Chung
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Michael B Foote
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jinru Shia
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Efsevia Vakiani
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Tina Gowda
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Philip B Paty
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Martin R Weiser
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Julio Garcia-Aguilar
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Georgios Karagkounis
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Andrea Cercek
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Garrett M Nash
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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Müller C, Macher-Beer A, Birnleitner H, Rainer M, Sachet M, Oehler R, Bachleitner-Hofmann T. Effect of systemic FOLFOXIRI plus bevacizumab treatment of colorectal peritoneal metastasis on local and systemic immune cells. Surgery 2025; 178:108868. [PMID: 39472264 DOI: 10.1016/j.surg.2024.09.025] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Revised: 08/30/2024] [Accepted: 09/18/2024] [Indexed: 01/11/2025]
Abstract
AIM The immune system plays a crucial role in the outcome of colorectal cancer. Systemic chemotherapies modulate the immune cell composition. Little is known about these changes in peritoneal metastasized colorectal cancer. Thus, we aimed to characterize local and systemic immune cells in the course of systemic chemotherapy. METHODS We included in total 20 patients with peritoneal metastasized colorectal cancer in our exploratory study. Initially, we investigated the peripheral blood cell distributions before and after systemic chemotherapy in a set of 11 retrospectively collected samples. Then, a prospective clinical cohort was set up to evaluate local and systemic immune cell distribution in detail (n = 9). Tumor tissue, peritoneal fluid, and peripheral blood were collected. The main immune cell subtypes were characterized using flow cytometry and immunohistochemistry, respectively. RESULTS Neutrophils and the neutrophil-to-lymphocyte ratio significantly declined in response to systemic chemotherapy while circulating T cells increased (CD8+P = .015, CD4+P = .041). In peritoneal fluid, we observed a decrease of CD25+/FOXP3+/CD4+ regulatory T cells (P = .049) without loss of their ability to produce interferon gamma. T-cell infiltration in the tumor microenvironment showed a considerable variability between patients. However, the number of tumor-infiltrating CD8+ lymphocytes was not significantly changed by the application of systemic chemotherapy. Neither tumor cells nor lymphocytes or macrophages showed noteworthy expression of PD1 or PD-L1. CONCLUSION Our data show that immune cell distribution after systemic chemotherapy changes in peripheral blood. Interestingly, in peritoneal fluid only the inhibitory Treg population decreased and local T cells within peritoneal metastases remain unaffected. These data indicate little to no effect of systemic chemotherapy on the local immune system, supporting the need for new therapeutic options.
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Affiliation(s)
- Catharina Müller
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Austria.
| | | | - Hanna Birnleitner
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Austria
| | - Marlene Rainer
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Austria
| | - Monika Sachet
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Austria
| | - Rudolf Oehler
- Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Austria
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Aguirre-Allende I, Pereira-Pérez F, Manzanedo-Romero I, Fernandez-Briones P, Muñoz-Martín M, Serrano-Moral Á, Perez-Viejo E. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: A pragmatic comparison of oncological outcomes in synchronous versus metachronous disease. Surg Oncol 2025; 58:102183. [PMID: 39778343 DOI: 10.1016/j.suronc.2024.102183] [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: 04/27/2024] [Revised: 11/24/2024] [Accepted: 12/18/2024] [Indexed: 01/11/2025]
Abstract
BACKGROUND disease burden (PCI), completeness of cytoreduction or histological features, are known to influence survival after CRS-HIPEC for colorectal peritoneal metastases (CPM). However, there is still debate about influence of CPM onset. The aim of this study is to determine the impact of CPM onset on oncological outcomes after CRS-HIPEC. METHODS all patients with CPM scheduled for CRS-HIPEC at one reference center between December 2007 and September 2022 were included. s-PM were defined as those diagnosed at primary disease treatment; m-PM were considered those diagnosed during follow-up. Survival outcomes and recurrence rates were compared using a pragmatic analysis. RESULTS 125 patients with s-CPM and 170 patients with m-CPM were analyzed. Median follow-up was 58.6 and 50.6 months in s-CPM and m-CPM groups(p = 0.11). Complete cytoreduction (CCS-0/-1) rates were comparable: 84 % s-CPM vs. 88.2 % m-CPM(p = 0.190). Overall survival (OS) was significantly shorter in s-CPM: 24.7 vs. 46.6 months (p = 0.024). Conversely, median disease-free survival was similar in both groups, 10 months vs. 11 months(p = 0.155). Patients in the s-CPM group presented more pN+(p = 0.001), higher histologic grade(p = 0.007) and PCI(p = 0.04), and higher rate of concurrent liver metastases(p = 0.004). RAS/BRAF gene mutations and microsatellite instability did not differ significantly. Perioperative chemotherapy regimens and tolerance were also similar. CONCLUSIONS despite s-CPM being associated with impaired OS after CRS-HIPEC, the onset of PM was not found to be an independent determinant for survival. High-risk molecular and histological features strongly influence oncological outcomes after CRS-HIPEC. This is valuable data that could aid in preoperative patient selection process for CRS-HIPEC.
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Affiliation(s)
- Ignacio Aguirre-Allende
- Hepatobiliary and Peritoneal Surface Malignancies Unit. General and Digestive Surgery Department, Donostia University Hospital-IHO Donostialdea, IIS Biodonostia, Spain.
| | - Fernando Pereira-Pérez
- Peritoneal Surface Malignancies Unit, General and Digestive Surgery Department, Fuenlabrada University Hospital, Madrid, Spain
| | - Israel Manzanedo-Romero
- Peritoneal Surface Malignancies Unit, General and Digestive Surgery Department, Fuenlabrada University Hospital, Madrid, Spain
| | - Paula Fernandez-Briones
- Peritoneal Surface Malignancies Unit, General and Digestive Surgery Department, Fuenlabrada University Hospital, Madrid, Spain
| | - María Muñoz-Martín
- Peritoneal Surface Malignancies Unit, General and Digestive Surgery Department, Fuenlabrada University Hospital, Madrid, Spain
| | - Ángel Serrano-Moral
- Peritoneal Surface Malignancies Unit, General and Digestive Surgery Department, Fuenlabrada University Hospital, Madrid, Spain
| | - Estibalitz Perez-Viejo
- Peritoneal Surface Malignancies Unit, General and Digestive Surgery Department, Fuenlabrada University Hospital, Madrid, Spain
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Sato K, Matsui S, Chiba T, Noguchi T, Sakamoto T, Mukai T, Yamaguchi T, Akiyoshi T, Fukunaga Y. Prognostic Impact of Potentially Curative Resection for Synchronous Peritoneal Carcinomatosis with Lavage Cytology Positivity in Colorectal Cancer: A Retrospective Observational Study. J Anus Rectum Colon 2025; 9:52-60. [PMID: 39882235 PMCID: PMC11772798 DOI: 10.23922/jarc.2024-079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 09/09/2024] [Indexed: 01/31/2025] Open
Abstract
Objectives Although curative resection for synchronous peritoneal carcinomatosis has been reported to improve prognosis, cases with positive intraoperative lavage cytology have not been reported. In this study, we investigated the prognostic value of potentially curative resection based on colorectal cancer and lavage cytology positivity in patients with synchronous peritoneal carcinomatosis. Methods We retrospectively evaluated 72 patients who underwent intraoperative lavage cytology and one-stage potentially curative resection of primary and metastatic lesions (lavage cytology-positive, n = 21; lavage cytology-negative, n = 51) between July 2004 and December 2019. We compared the 5-year overall survival and 3-year recurrence rates between the lavage cytology-positive and lavage cytology-negative groups. Results No significant differences were observed in the 5-year overall survival (48.2% vs. 45.5%, P = 0.924) or 3-year recurrence rates (74.5% vs. 62%, P = 0.143) between the two groups. Univariate analysis for 3-year recurrence revealed that lavage cytology-positive status was not an explanatory variable (hazard ratio: 1.552, 95% confidence interval: 0.83-2.902, P = 0.169). Multivariate analysis identified colon cancer as an independent risk factor of recurrence. Conclusions In resectable cases, the resection of synchronous peritoneal carcinomatosis from colorectal cancer can be considered even if intraoperative lavage cytology is positive.
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Affiliation(s)
- Kentaro Sato
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Shimpei Matsui
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Tomohiro Chiba
- Department of Cytology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Tatsuki Noguchi
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takashi Sakamoto
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Toshiki Mukai
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Tomohiro Yamaguchi
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takashi Akiyoshi
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yosuke Fukunaga
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
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Namakshenas P, Crezee J, Tuynman JB, Tanis PJ, Oei AL, Kok HP. Computational Evaluation of Improved HIPEC Drug Delivery Kinetics via Bevacizumab-Induced Vascular Normalization. Pharmaceutics 2025; 17:155. [PMID: 40006522 PMCID: PMC11859678 DOI: 10.3390/pharmaceutics17020155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 01/17/2025] [Accepted: 01/20/2025] [Indexed: 02/27/2025] Open
Abstract
Background: Oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) using the original 30 min protocol has shown limited benefits in patients with peritoneal metastasis of colorectal cancer (PMCRC), likely due to the short duration, which limits drug penetration into tumor nodules. Bevacizumab, an antiangiogenic antibody that modifies the tumor microenvironment, may improve drug delivery during HIPEC. This in silico study evaluates the availability of oxaliplatin within tumor nodules when HIPEC is performed after bevacizumab treatment. Methods: Using a computational fluid dynamics (CFD) model of HIPEC, the temperature and oxaliplatin distribution within the rat abdomen were calculated, followed by a model of drug transport within tumor nodules located at various sites in the peritoneum. The vascular normalization effect of the bevacizumab treatment was incorporated by adjusting the biophysical parameters of the tumor nodules. The effective penetration depth values, including the thermal enhancement ratio of cytotoxicity, were then compared between HIPEC alone and HIPEC combined with the bevacizumab treatment. Results: After bevacizumab treatments at doses of 0.5 mg/kg and 5 mg/kg, the oxaliplatin availability increased by up to 20% and 45% when HIPEC was performed during the vascular normalization phase, with the penetration depth increasing by 1.5-fold and 2.3-fold, respectively. Tumors with lower collagen densities and larger vascular pore sizes showed higher oxaliplatin enhancement after the combined treatment. Bevacizumab also enabled a reduction in the oxaliplatin dose (up to half at 5 mg/kg bevacizumab) while maintaining effective drug levels in the tumor nodules, potentially reducing systemic toxicity. Conclusions: These findings suggest that administering oxaliplatin-based HIPEC during bevacizumab-induced vascular normalization could significantly improve drug penetration and enhance treatment efficacy.
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Affiliation(s)
- Pouya Namakshenas
- Department of Radiation Oncology, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (J.C.); (A.L.O.); (H.P.K.)
- Cancer Center Amsterdam, Cancer Biology and Immunology, 1105 AZ Amsterdam, The Netherlands
- Cancer Center Amsterdam, Treatment and Quality of Life, 1105 AZ Amsterdam, The Netherlands; (J.B.T.); (P.J.T.)
| | - Johannes Crezee
- Department of Radiation Oncology, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (J.C.); (A.L.O.); (H.P.K.)
- Cancer Center Amsterdam, Cancer Biology and Immunology, 1105 AZ Amsterdam, The Netherlands
- Cancer Center Amsterdam, Treatment and Quality of Life, 1105 AZ Amsterdam, The Netherlands; (J.B.T.); (P.J.T.)
| | - Jurriaan B. Tuynman
- Cancer Center Amsterdam, Treatment and Quality of Life, 1105 AZ Amsterdam, The Netherlands; (J.B.T.); (P.J.T.)
- Department of Surgery, Amsterdam UMC Location Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
| | - Pieter J. Tanis
- Cancer Center Amsterdam, Treatment and Quality of Life, 1105 AZ Amsterdam, The Netherlands; (J.B.T.); (P.J.T.)
- Department of Surgery, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands
| | - Arlene L. Oei
- Department of Radiation Oncology, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (J.C.); (A.L.O.); (H.P.K.)
- Cancer Center Amsterdam, Cancer Biology and Immunology, 1105 AZ Amsterdam, The Netherlands
- Laboratory for Experimental Oncology and Radiobiology (LEXOR), 1105 AZ Amsterdam, The Netherlands
| | - H. Petra Kok
- Department of Radiation Oncology, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (J.C.); (A.L.O.); (H.P.K.)
- Cancer Center Amsterdam, Cancer Biology and Immunology, 1105 AZ Amsterdam, The Netherlands
- Cancer Center Amsterdam, Treatment and Quality of Life, 1105 AZ Amsterdam, The Netherlands; (J.B.T.); (P.J.T.)
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Zhang Y, Jin Z, Wang Z, Yan L, Liu A, Li F, Li Y, Zhang Y. Trends in Colorectal Cancer Peritoneal Metastases Research: A Comprehensive Bibliometric Analysis. J Gastrointest Cancer 2025; 56:51. [PMID: 39847239 DOI: 10.1007/s12029-025-01176-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/11/2025] [Indexed: 01/24/2025]
Abstract
BACKGROUND Colorectal cancer (CRC) stands as the third most prevalent malignancy globally and is recognized as the second leading cause of cancer-related mortality. Notably, nearly 50% of individuals diagnosed with CRC ultimately develop metastatic disease, with the peritoneum emerging as the second most frequent site for metastatic spread. Recent advancements in therapeutic frameworks have enhanced both survival rates and quality of life metrics for patients afflicted with colorectal cancer peritoneal metastases (CRCPM). OBJECTIVE This study endeavors to facilitate an in-depth review of the current scientific landscape surrounding CRCPM, ultimately aiming to delineate future avenues for investigative research in this realm. METHODS Employing R software through the Bibliometrix package, alongside analytical tools such as CiteSpace and VOSviewer, we performed a comprehensive bibliometric analysis. This enabled us to assess pivotal keywords, prominent authors, influential countries, notable institutions, relevant literature, and key journals pertinent to the field of CRCPM research. RESULTS Our findings illustrate a significant uptick in the volume of publications addressing CRCPM, with the USA leading in overall contribution, complemented by substantial input from distinguished scholars in the Netherlands and France. The author Ignace H. J. T. de Hingh emerged as the most prolific contributor. Current research endeavors have predominantly focused on the characterization of primary malignancies with peritoneal metastases, therapeutic interventions for CRCPM, and the orchestration of clinical trials. CONCLUSION This analysis culminates in a systematic encapsulation of the prevailing research findings concerning CRCPM, underscoring current hotspots and predicting future trends within the global research spectrum. The exploration of treatment modalities for CRCPM remains vibrant, and ongoing multicenter clinical trials are anticipated to further enrich our understanding and management of this challenging clinical issue.
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Affiliation(s)
- Yuzhe Zhang
- The First Laboratory of Cancer Institute, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Zi Jin
- Nuclear Medicine Department, Shenyang Fifth People's Hospital, Shenyang, 110001, China
| | - Zhongqing Wang
- Department of Information Center, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Lirong Yan
- The First Laboratory of Cancer Institute, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Aoran Liu
- The First Laboratory of Cancer Institute, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Fang Li
- The First Laboratory of Cancer Institute, The First Hospital of China Medical University, Shenyang, 110001, China
| | - Yanke Li
- Department of Anorectal Surgery, The First Hospital of China Medical University, Shenyang, 110001, China.
| | - Ye Zhang
- The First Laboratory of Cancer Institute, The First Hospital of China Medical University, Shenyang, 110001, China.
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Morera-Ocon FJ, Navarro-Campoy C, Guastella T, Landete-Molina F. Controversies around the treatment of peritoneal metastases of colorectal cancer. World J Gastrointest Oncol 2025; 17:100199. [PMID: 39817141 PMCID: PMC11664603 DOI: 10.4251/wjgo.v17.i1.100199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 10/24/2024] [Accepted: 11/07/2024] [Indexed: 12/12/2024] Open
Abstract
In this editorial we examine the article by Wu et al published in the World Journal of Gastrointestinal Oncology. Surgical resection for peritoneal metastases from colorectal cancer (CRC) has been gradually accepted in the medical oncology community. A randomized trial (PRODIGE 7) on cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) failed to prove any benefit of oxaliplatin in the overall survival of patients with peritoneal metastases from colorectal origin. Nevertheless, isolated systemic chemotherapy for CRC stage IV has demonstrated a reduced response in peritoneal metastases than that obtained in other metastatic sites such as the liver. Another tool is required in those patients to achieve more local control of the disease. Surgical groups in peritoneal surgery continue to use HIPEC in their procedures, using other agents than oxaliplatin for peritoneal cavity infusion, such as mitomycin C. These patients present with complex surgical issues to manage, and consequently a large burden of complications has to be anticipated. Therefore, identifying patients who will benefit from CRS with or without HIPEC would be of great interest.
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Affiliation(s)
| | - Clara Navarro-Campoy
- Department of Gynecology and Obstetrics, Hospital 9 Octubre, Valencia 46015, Spain
| | - Ticiano Guastella
- Department of Pathology, Hospital General de Requena, Requena 46340, Spain
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Rijsemus CJV, Kok NFM, Aalbers AGJ, Grotenhuis BA, Berardi E, Snaebjornsson P, Lambregts DMJ, Beets-Tan RGH, Lahaye MJ. Can surgeons predict the extent of abdominal surgery based on MRI findings in CRS-HIPEC candidates with colorectal cancer? EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109583. [PMID: 40157179 DOI: 10.1016/j.ejso.2025.109583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 12/12/2024] [Accepted: 01/03/2025] [Indexed: 04/01/2025]
Abstract
INTRODUCTION Diffusion-weighted MRI (DW-MRI) is a promising tool for selecting patients with colorectal peritoneal metastases for cytoreductive surgery (CRS). This study investigated whether surgeons can predict the extent of CRS based on preoperative MRI findings. METHODS This single-centre retrospective study included patients who underwent CRS-HIPEC after preoperative MRI. An expert abdominal radiologist showed MR images to three experienced surgeons, who independently predicted the probability of achieving a complete resection by scoring which of 29 anatomical structures would be resected during CRS-HIPEC. Other predictions were surgery duration, number of anastomoses and CRS-HIPEC resulting in a stoma. Predictions were confirmed using surgical reports and histopathology. RESULTS Data from 29 patients were analyzed. The median surgical PCI was 6 [range 0-19]. Complete resection was achieved in all patients with a total of 216 structures resected. All three surgeons had a negative predicting value (NPV) above 75% for most anatomical structures, and a positive predicting value (PPV) ranging from moderate (50%-75%) to good (>75%). The PPV for CRS-HIPEC resulting in a stoma ranged between 71% and 100%, and for colon anastomoses between 57% and 77%. The ICC indicated good to excellent (≥0.75) agreement among surgeons' predictions for most structures. CONCLUSION Based on DW-MRI, the abdominal radiologist and surgeon are good at predicting the extent of the cytoreductive surgical procedure. Surgeons can use MRI findings for surgical planning and patient expectation management. However, adhesions and fibrosis interpreted as possible tumors during surgery and not clearly depicted small metastases on MRI can lead to more resections than anticipated.
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Affiliation(s)
- C J V Rijsemus
- Dept. of Radiology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, the Netherlands; Dept. of Surgery, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, the Netherlands; GROW School for Oncology and Developmental Biology - University of Maastricht, Maastricht, the Netherlands.
| | - N F M Kok
- Dept. of Surgery, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, the Netherlands
| | - A G J Aalbers
- Dept. of Surgery, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, the Netherlands
| | - B A Grotenhuis
- Dept. of Surgery, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, the Netherlands
| | - E Berardi
- Dept. of Radiology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, the Netherlands
| | - P Snaebjornsson
- Dept. of Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, the Netherlands
| | - D M J Lambregts
- Dept. of Radiology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, the Netherlands
| | - R G H Beets-Tan
- Dept. of Radiology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, the Netherlands; GROW School for Oncology and Developmental Biology - University of Maastricht, Maastricht, the Netherlands; Faculty of Healyth Sciences, University of Southeren Denmark, Denmark
| | - M J Lahaye
- Dept. of Radiology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, the Netherlands
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Jo JW, Suh JW, Lee SC, Namgung H, Park DG. Current status of postoperative morbidity following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal cancer with peritoneal metastasis: a prospective single-center observational study. Ann Surg Treat Res 2025; 108:12-19. [PMID: 39823036 PMCID: PMC11735167 DOI: 10.4174/astr.2025.108.1.12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 10/29/2024] [Accepted: 11/06/2024] [Indexed: 01/19/2025] Open
Abstract
Purpose This study aimed to evaluate current morbidity rates following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colorectal cancer and peritoneal metastasis. Methods A total of 42 patients who underwent CRS and HIPEC for colorectal cancer with peritoneal metastasis at a single tertiary referral center between January 2022 and December 2022 were included. Perioperative outcomes and postoperative complications were prospectively assessed. Results The mean peritoneal cancer index (PCI) was 16.0. The distribution of PCI scores was as follows: <10, 33.3%; 10-19, 26.2%; and ≥ 20, 40.5%. Completeness of the cytoreduction (CCR) scores were as follows: 57.1% of patients achieved CCR-0, 16.7% achieved CCR-1, 7.1% achieved CCR-2, and 19.0% achieved CCR-3. The mean operation time was 9.1 hours, and the median hospital stay was 17.0 days. Postoperative complications occurred within 30 days in 47.6% of cases and between 30 and 60 days in 11.9% of cases. Reoperation within 30 days was required in 5 cases, and 1 patient died within 30 days. The most common complications were pleural effusion (5 patients), anastomosis site leakage (3 patients), and pneumonia (3 patients). Patients with higher PCI scores were more likely to experience complications (P = 0.038). Conclusion Although CRS and HIPEC are still associated with high morbidity and mortality compared to other colorectal surgeries, outcomes have improved with increased experience. These results suggest that the procedure is becoming a more acceptable treatment option over time.
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Affiliation(s)
- Jae Won Jo
- Department of Surgery, Dankook University College of Medicine, Cheonan, Korea
| | - Jung Wook Suh
- Department of Surgery, Dankook University College of Medicine, Cheonan, Korea
| | - Sung Chul Lee
- Department of Surgery, Dankook University College of Medicine, Cheonan, Korea
| | - Hwan Namgung
- Department of Surgery, Dankook University College of Medicine, Cheonan, Korea
| | - Dong-Guk Park
- Department of Surgery, Dankook University College of Medicine, Cheonan, Korea
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Sourrouille I, Pastier C, Gelli M, Benhaïm L, Cattan P, Ducreux M, Aparicio T, Goéré D. Results of complete cytoreductive strategy in patients with peritoneal metastases of colorectal origin with or without extraperitoneal metastases: A bicentric analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:108788. [PMID: 39531916 DOI: 10.1016/j.ejso.2024.108788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 10/03/2024] [Accepted: 10/24/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Increased survival can be achieved in patients with colorectal cancer peritoneal metastases (CRPM) treated with cytoreductive surgery. The benefit of this strategy remains uncertain when CRPM are associated with extraperitoneal metastases (EPM). The aim of this study was to compare short- and long-term outcomes of patients treated with CRS for CRPM, with or without EPM. METHODS This study included 413 consecutive patients who underwent CRS for CRPM: 120 with EPM (EPM+) and 293 without (EPM-). Patients with isolated ovarian metastases were included in EPM-group (n = 83). RESULTS EPM were mainly located to the liver (66 %,n = 79), retroperitoneal lymph nodes (33 %,n = 40); less frequently to the spleen (9 %,n = 12), lung (9 %,n = 10) or pleura (1 %,n = 1). Ovarian metastases were present in 126 patients (83 in EMP-, 43 in EPM+). Peritoneal carcinomatosis index (PCI) was similar in EPM- (8 [4-14]) and EPM+ (8 [3-13],p = 0.335) groups, as postoperative mortality (3 % vs 3 %,p = 1) and major morbidity rates (28 % vs 35 %,p = 0.223). Median overall survival (mOS) and disease-free survival were significantly higher in the EPM-group (58m vs 39m, and 16m vs 10m,p = 0.003). We highlighted 3 prognostic groups 1) EPM-with PCI<10 (mOS 93m), 2) EPM+ with PCI<10 (mOS 57m), 3) EPM-with 10 15 regardless EPM (mOS 26m, p < 0.001). CONCLUSION Complete cytoreductive surgery seems to be feasible in patients with EPM, without increase in postoperative morbidity and mortality compared to patients without EPM. This strategy provides prolonged survival in selected patients with limited peritoneal metastases from colorectal cancer.
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Affiliation(s)
| | - Clément Pastier
- Department of Surgical Oncology, Hopital Saint Louis, Paris, France
| | | | - Léonor Benhaïm
- Department of Surgical Oncology, Gustave Roussy, Villejuif, France
| | - Pierre Cattan
- Department of Surgical Oncology, Hopital Saint Louis, Paris, France
| | - Michel Ducreux
- Department of Medical Oncology, Gustave Roussy, Villejuif, France
| | - Thomas Aparicio
- Department of Medical Oncology, Hopital Saint Louis, Paris, France
| | - Diane Goéré
- Department of Surgical Oncology, Hopital Saint Louis, Paris, France.
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Kappen J, Abdel-Rahman O. Advances in pharmacotherapy for the treatment of peritoneal metastases from colorectal cancer. Expert Opin Pharmacother 2025; 26:17-30. [PMID: 39604139 DOI: 10.1080/14656566.2024.2435946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 11/26/2024] [Indexed: 11/29/2024]
Abstract
INTRODUCTION Patients with peritoneal metastasis (PM) from colorectal cancer (CRC) typically have a poor prognosis with historically few treatment options. Cytoreductive surgery (CRS) is the mainstay of treatment to remove macrometastases into the peritoneum, but residual micrometastases are often left behind. Systemic chemotherapy remains a cornerstone of treatment for micrometastases, but intraperitoneal therapy offers advantages including higher local dose concentration with fewer systemic side effects from treatment. AREAS COVERED This review covers advancements in the routes and types of pharmacotherapies for PM in CRC. EXPERT OPINION More evidence is needed to justify HIPEC with CRS as the standard of care treatment modality for patients with resectable PM in CRC. New therapies such as oncolytic viruses, biologics, and small-molecule inhibitors may become additional treatment modalities for PM.
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Affiliation(s)
- Janson Kappen
- Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Omar Abdel-Rahman
- Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada
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Tidadini F, Arvieux C, Glehen O, Sourrouille I, Marchal F, Abba J, Malgras B, Quesada JL, Pocard M, Ezanno AC. Repeat Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Using Open and Closed Abdomen Techniques for Colorectal Peritoneal Metastases and Peritoneal Pseudomyxoma Recurrences: Results from Six French Expert Centers. Ann Surg Oncol 2025; 32:209-220. [PMID: 39496899 DOI: 10.1245/s10434-024-16407-1] [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: 08/09/2024] [Accepted: 10/07/2024] [Indexed: 11/06/2024]
Abstract
BACKGROUND Standard treatment for resectable peritoneal metastases (PM) combines cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC); however, the rate of recurrence remains high and repeat CRS/HIPEC may be considered in well-selected patients. We describe our postoperative and oncological outcomes. METHODS Between 1994 and 2024, data from 132 repeat CRS/HIPEC procedures were analyzed in this retrospective multicenter study. Morbimortality, overall survival (OS) and recurrence-free survival (RFS) were evaluated for colorectal peritoneal metastases (CRPM) and peritoneal pseudomyxoma (PMP). RESULTS Overall, 63 patients, including 55 patients with CRPM (87.3%) and 8 patients with PMP (12.7%), underwent CRS/HIPEC. Of these patients, 58 (92%) underwent CRS/HIPEC twice, 4 (6.3%) underwent CRS/HIPEC three times, and 1 (1.6%) underwent CRS/HIPEC four times. Peritoneal Carcinomatosis Index (PCI) score, operating room occupancy, complication and readmission rates at day 90, and length of intensive care unit and hospital stay were similar between the initial and first repeat CRS/HIPEC procedures. No 90-day postoperative mortality occurred. For CRPM, the median OS was 82.3, 53.9, and 74.5 months from the initial, first, and second repeat CRS/HIPEC procedures, respectively, with a median RFS of 22.0, 36.9, and 13.2 months, respectively. For PMP, after a median follow-up of 70.8 and 39.3 months from the initial and first repeat CRS/HIPEC procedures, respectively, all patients were alive, with a median RFS of 22.4 and 39.4 months, respectively. Multivariate analysis shown that no factor was significantly related to severe complications (Dindo-Clavien 3-4) or OS. CONCLUSIONS In selected patients with CRPM and PMP, CRS/HIPEC shows comparable results between the initial and repeat procedures in terms of postoperative outcomes, and appears to improve survival, especially for PMP. Repeat CRS/HIPEC is an option to be considered in patients presenting with CRPM or PMP.
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Affiliation(s)
- Fatah Tidadini
- Department of Digestive and Emergency Surgery, Grenoble-Alpes University Hospital, Grenoble, France.
- Lyon Center for lnnovation in Cancer, Lyon 1 University, Lyon, France.
| | - Catherine Arvieux
- Department of Digestive and Emergency Surgery, Grenoble-Alpes University Hospital, Grenoble, France
- Lyon Center for lnnovation in Cancer, Lyon 1 University, Lyon, France
| | - Olivier Glehen
- Lyon Center for lnnovation in Cancer, Lyon 1 University, Lyon, France
- Surgical Department, Lyon Sud University Hospital, Lyon, France
| | - Isabelle Sourrouille
- Department of Surgical Oncology, Gustave Roussy Cancer Center, Villejuif, France
| | - Frédéric Marchal
- Department of Digestive Surgery, Institut de Cancérologie de Lorraine, Vandoeuvre-les-Nancy, France
| | - Julio Abba
- Department of Digestive and Emergency Surgery, Grenoble-Alpes University Hospital, Grenoble, France
| | - Brice Malgras
- Department of Digestive Surgery, Begin Military Teaching Hospital, Saint Mandé, France
| | - Jean-Louis Quesada
- Department of Digestive and Emergency Surgery, Grenoble-Alpes University Hospital, Grenoble, France
| | - Marc Pocard
- Department of Digestive Surgery, La Pitié Salpêtrière Hospital, Paris, France
- INSERM, U965 CART Unit, Paris, France
| | - Anne-Cécile Ezanno
- Department of Digestive Surgery, Begin Military Teaching Hospital, Saint Mandé, France.
- INSERM, Univ Rennes, OSS (Oncogenesis, Stress, Signaling) Laboratory, UMR_S 1242, Rennes, France.
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Krell M, Ranjbar S, Gitlin S, Alvarez Vega DR, Wilson R, Thrasher K, Brown ZJ. Evolution in the Surgical Management of Gastric Cancer Peritoneal Metastases. Cancers (Basel) 2024; 17:100. [PMID: 39796727 PMCID: PMC11719528 DOI: 10.3390/cancers17010100] [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: 12/02/2024] [Revised: 12/26/2024] [Accepted: 12/27/2024] [Indexed: 01/13/2025] Open
Abstract
Despite therapeutic treatments and the growing utilization of multimodal therapies, gastric cancer (GC) remains a highly aggressive malignancy with high mortality worldwide. Much of the complexity in treating GC is due to the high incidence of peritoneal metastasis (PM), with mean overall survival typically ranging from 4 to 10 months. With current systemic therapy, targeted therapies, and immunotherapies continuing to remain ineffective for GC/PM, there has been a significant growing interest in intraperitoneal (IP) therapies for the treatment of GC/PM. In this review, we summarize the development of PM and evolving treatment strategies for GC/PM. Furthermore, we explore the various advancements and outcomes of IP therapies, including heated intraperitoneal chemotherapy (HIPEC), neoadjuvant HIPEC, and pressurized intraperitoneal aerosolized chemotherapy (PIPAC).
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Affiliation(s)
| | | | | | | | | | | | - Zachary J. Brown
- Department of Surgery, Division of Surgical Oncology, NYU Langone Health, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA; (M.K.); (S.G.); (D.R.A.V.); (R.W.); (K.T.)
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Brown ZJ, Krell M, Gitlin S, Ranjbar S, Vega DA, Pawlik TM. Prospects of the surgical management of colorectal peritoneal metastasis. J Gastrointest Surg 2024; 29:101940. [PMID: 39746646 DOI: 10.1016/j.gassur.2024.101940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 12/26/2024] [Accepted: 12/28/2024] [Indexed: 01/04/2025]
Abstract
BACKGROUND Colorectal cancer (CRC) is a common malignancy with the propensity to metastasize. Common sites of metastasis include the liver, lungs, and peritoneum, with peritoneal metastases (PMs) having the worst prognosis. Unfortunately, systemic chemotherapy is often less effective in the treatment of PMs. Therefore, removal of all visible tumor via cytoreductive surgery along with intraperitoneal (IP) therapies has been used. METHODS A comprehensive review of the literature was conducted using MEDLINE/PubMed and Web of Science with an end date of September 1, 2024, regarding cytoreductive surgery and heated IP chemotherapy for CRC PMs. RESULTS Recent studies have called into question the utility of IP chemotherapy in the treatment of CRC PMs. However, regardless of IP chemotherapy, cytoreductive surgery has demonstrated an additional survival benefit for patients with PM secondary to CRC. DISCUSSION This study reviews the pathophysiology of CRC PM, the current treatment paradigms, and a pathway for improving outcomes in patients with CRC PM.
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Affiliation(s)
- Zachary J Brown
- Division of Surgical Oncology, Department of Surgery, New York University Grossman Long Island School of Medicine, New York University Langone Health, Mineola, NY, United States.
| | - Matthew Krell
- Division of Surgical Oncology, Department of Surgery, New York University Grossman Long Island School of Medicine, New York University Langone Health, Mineola, NY, United States
| | - Saige Gitlin
- Division of Surgical Oncology, Department of Surgery, New York University Grossman Long Island School of Medicine, New York University Langone Health, Mineola, NY, United States
| | - Suedeh Ranjbar
- Division of Surgical Oncology, Department of Surgery, New York University Grossman Long Island School of Medicine, New York University Langone Health, Mineola, NY, United States
| | - Diego Alvarez Vega
- Division of Surgical Oncology, Department of Surgery, New York University Grossman Long Island School of Medicine, New York University Langone Health, Mineola, NY, United States
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, Wexner Medical Center and James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States
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Zoń A, Bednarek IA. Hyperthermia Potentiates the Effectiveness of Anticancer Drugs-Cisplatin and Tamoxifen on Ovarian Cancer Cells In Vitro. Int J Mol Sci 2024; 25:13664. [PMID: 39769428 PMCID: PMC11728268 DOI: 10.3390/ijms252413664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Revised: 12/18/2024] [Accepted: 12/18/2024] [Indexed: 01/16/2025] Open
Abstract
Ovarian cancer is one of the most prevalent cancers among women. Due to the frequent problems during treatment, such as relapses or the development of resistance to treatment, new methods of treating this disease are being sought. A special attention is directed towards the combination therapies combining several different anticancer agents. The aim of the following study was to examine the effect of combination therapy with mild hyperthermia (temperatures of 39 °C and 40 °C) and anticancer drugs-cisplatin and tamoxifen-on the SKOV-3 ovarian cancer cell line in vitro. Furthermore, the study also assessed the effect of moderate hyperthermia on the anticancer effectiveness of both of these drugs. The cytotoxic effect of the therapy was assessed using MTT assay and fluorescent acridine orange staining. Changes in the expression of genes involved in apoptosis processes were evaluated using RT-qPCR. It has been shown that the use of combination therapy leads to a significant increase in apoptosis processes in SKOV-3 ovarian cancer cells and, consequently, to a decrease in their viability. At the molecular level, mild hyperthermia leads primarily to a decrease in the expression of anti-apoptotic genes, and also, to a small extent, to an increase in the expression of proapoptotic genes. The results also indicate that moderate hyperthermia has a positive effect on the cytotoxic efficacy of both cisplatin and tamoxifen on ovarian cancer cells. This suggests that hyperthermia could be a potential component in combination therapy for ovarian cancer.
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Affiliation(s)
- Aleksandra Zoń
- Department of Biotechnology and Genetic Engineering, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jedności 8, 41-200 Sosnowiec, Poland
| | - Ilona Anna Bednarek
- Department of Biotechnology and Genetic Engineering, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jedności 8, 41-200 Sosnowiec, Poland
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Aulicino M, Santullo F, D’Annibale G, Abatini C, Attalla El Halabieh M, Orsini C, Barberis L, D’Agostino L, Tersigni I, Pacelli F, Lodoli C, Di Giorgio A, Ferracci F, Pacelli F. Efficacy and Insights from an Extensive Series of Cytoreductive Surgery for Peritoneal Neoplasms: A High-Volume Single-Center Experience. Cancers (Basel) 2024; 16:4229. [PMID: 39766128 PMCID: PMC11726991 DOI: 10.3390/cancers16244229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 12/13/2024] [Accepted: 12/17/2024] [Indexed: 01/15/2025] Open
Abstract
Background: Advances in cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC) have improved outcomes for selected patients with peritoneal surface malignancies (PSMs). Methods: This retrospective study analyzed 743 PSM patients treated at Fondazione Policlinico Universitario Agostino Gemelli from January 2016 to February 2024. The primary aim was to assess median overall survival (mOS), median disease-free survival (mDFS), and median progression-free survival (mPFS) stratified by tumor origin. Secondary outcomes examined the role of diagnostic laparoscopy in the management of PSMs and intra- and postoperative complications' rates. Results: A total of 1113 procedures were performed: 389 CRS, 370 PIPAC, and 354 diagnostic laparoscopies. Colorectal cancer was the predominant indication for CRS (52.4%), with a mOS of 52 months and mDFS of 22 months. Patients affected by gastric cancer undergoing CRS had a mOS of 18 months and a mDFS of 13 months, while PIPAC yielded a mOS of 9 months and a mPFS of 4 months. Among patients with pseudomyxoma peritonei undergoing CRS, the 5-year DFS rate was 64.1%, and OS rate was 89%. Patients affected by mesothelioma and treated with CRS exhibited a median OS of 43 months and a DFS of 26 months. Pancreatic and hepatobiliary cancers were treated with PIPAC, with a respective mOS of 12 and 8 months. Postoperative complications occurred in 12.6% of CRS, 3.2% of PIPAC, and 1.7% of diagnostic laparoscopies. High peritoneal cancer index (PCI), gastric resection, and blood loss over 500 mL were identified as risk factors for major complications in a multivariate analysis. Conclusions: Developing a highly experienced multidisciplinary team is crucial for delivering tailored treatment strategies which aim to achieve optimal oncological outcomes while preserving patients' quality of life.
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Affiliation(s)
- Matteo Aulicino
- General Surgery Department, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (M.A.); (C.O.); (L.B.); (L.D.); (I.T.); (F.F.); (F.P.)
| | - Francesco Santullo
- Surgical Unit of Peritoneum and Retroperitoneum Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (C.A.); (M.A.E.H.); (C.L.); (A.D.G.)
| | - Giorgio D’Annibale
- General Surgery Department, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (M.A.); (C.O.); (L.B.); (L.D.); (I.T.); (F.F.); (F.P.)
| | - Carlo Abatini
- Surgical Unit of Peritoneum and Retroperitoneum Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (C.A.); (M.A.E.H.); (C.L.); (A.D.G.)
| | - Miriam Attalla El Halabieh
- Surgical Unit of Peritoneum and Retroperitoneum Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (C.A.); (M.A.E.H.); (C.L.); (A.D.G.)
| | - Cecilia Orsini
- General Surgery Department, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (M.A.); (C.O.); (L.B.); (L.D.); (I.T.); (F.F.); (F.P.)
| | - Lorenzo Barberis
- General Surgery Department, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (M.A.); (C.O.); (L.B.); (L.D.); (I.T.); (F.F.); (F.P.)
| | - Luca D’Agostino
- General Surgery Department, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (M.A.); (C.O.); (L.B.); (L.D.); (I.T.); (F.F.); (F.P.)
| | - Ilaria Tersigni
- General Surgery Department, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (M.A.); (C.O.); (L.B.); (L.D.); (I.T.); (F.F.); (F.P.)
| | - Fiammetta Pacelli
- Department of Surgical and Medical Sciences and Translational Medicine, Sant ’Andrea University Hospital, Sapienza University of Rome, 00185 Rome, Italy;
| | - Claudio Lodoli
- Surgical Unit of Peritoneum and Retroperitoneum Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (C.A.); (M.A.E.H.); (C.L.); (A.D.G.)
| | - Andrea Di Giorgio
- Surgical Unit of Peritoneum and Retroperitoneum Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (C.A.); (M.A.E.H.); (C.L.); (A.D.G.)
| | - Federica Ferracci
- General Surgery Department, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (M.A.); (C.O.); (L.B.); (L.D.); (I.T.); (F.F.); (F.P.)
- Surgical Unit of Peritoneum and Retroperitoneum Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (C.A.); (M.A.E.H.); (C.L.); (A.D.G.)
| | - Fabio Pacelli
- General Surgery Department, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (M.A.); (C.O.); (L.B.); (L.D.); (I.T.); (F.F.); (F.P.)
- Surgical Unit of Peritoneum and Retroperitoneum Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (C.A.); (M.A.E.H.); (C.L.); (A.D.G.)
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46
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Manoğlu B, Sökmen S, Egeli T, Derici ZS, Ağalar C, Aksoy SÖ. Prognostic Value of Immune Scoring System for Colorectal Cancer Patients with Peritoneal Metastasis. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:2070. [PMID: 39768948 PMCID: PMC11678378 DOI: 10.3390/medicina60122070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/02/2024] [Revised: 11/21/2024] [Accepted: 12/03/2024] [Indexed: 01/04/2025]
Abstract
Background and Objectives: There is no reliable immune scoring system that can help us predict the postoperative outcomes of colorectal cancer patients with peritoneal metastases after cytoreductive surgery. In this cohort, the aims were (1) to evaluate the postoperative morbidity, mortality and surgical oncological outcomes in colorectal cancer patients with peritoneal metastasis; (2) to compare oncological and postoperative outcomes of colon cancer patients with peritoneal metastasis and rectal cancer patients with peritoneal metastasis; and (3) to assess the prognostic value of the modified Glasgow Prognostic Score (mGPS) and the CRP-albumin ratio (CAR). Materials and Methods: A prospectively maintained database of 258 patients who underwent cytoreductive surgery for peritoneal metastases of colorectal origin between 2007 and 2024 was analyzed. According to the anatomical location of the primary tumor, two different groups were created: rectum cancer patients with peritoneal metastasis (Group A) and colon cancer patients with peritoneal metastasis (Group B). All standard clinico-pathological characteristics, operative findings, morbi-mortality results, and final oncologic outcomes were compared between Groups A and B. We evaluated whether CAR and mGPS could predict postoperative morbi-mortality and overall survival in the two groups or not. Results: No significant difference was detected between Groups A and B in terms of clinical-demographic characteristics. In both groups, the preoperative mGPS and CAR values were statistically significantly higher in those who developed postoperative high-grade complications (C-D grade III/IV) (p < 0.001) and those who died perioperatively (p = 0.001 and p = 0.002). Conclusions: In multivariate Cox analysis, the CAR was found to be an independent prognostic factor for overall survival in this cohort. CAR and mGPS predicted high-grade complications and postoperative mortality in both groups.
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Affiliation(s)
- Berke Manoğlu
- Peritoneal Surface Malignancy Center, Department of Surgery, Dokuz Eylul University Faculty of Medicine, 35340 Balcova, Turkey; (S.S.); (T.E.); (Z.S.D.); (C.A.); (S.Ö.A.)
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Zhou H, Wang H, Yi S, Yu S. Effectiveness of hyperthermic intraperitoneal chemotherapy during primary curative resection for colorectal carcinoma. Int J Colorectal Dis 2024; 39:197. [PMID: 39643725 PMCID: PMC11624244 DOI: 10.1007/s00384-024-04774-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/26/2024] [Indexed: 12/09/2024]
Abstract
PURPOSE Peritoneal metastasis (PM) is the life-threatening cause of colorectal cancer patients (CRC). Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) plus cytoreductive surgery exhibited promising effects in preventing recurrence and increasing the survival of CRC patients. However, the outcomes of HIPEC on treating advanced CRC with risk of PM are still controversial. Here, we retrospectively examined the impact of HIPEC on preventing PM and its overall effects on patients with locally advanced CRC who underwent primary curative resection at our center. METHODS We retrospectively analyzed 45 patients diagnosed with locally advanced colorectal cancer (CRC) who underwent primary curative laparoscopic surgery with proactive hyperthermic intraperitoneal chemotherapy (HIPEC), in conjunction with adjuvant systemic chemotherapy at our center between 2019 and 2022. An additional 55 patients with locally advanced CRC who underwent similar surgery and received adjuvant systemic chemotherapy but did not undergo HIPEC during the same period were selected as the control group. Disease-free survival (DFS), overall survival (OS), and PM incidence were compared between patients with and without HIPEC. RESULTS AND CONCLUSIONS The cumulative PM incidence was 2.2% in the HIPEC group and 14.5% in the control group(P = 0.0347). No significant adverse effects were observed in the HIPEC group. Furthermore, Kaplan-Meier survival analysis showed that the HIPEC correlated to better DFS [hazard ratio (HR) 0.4670, 95% confidence interval (CI) 0.2305-0.9462; P = 0.0345] and extended the overall survival of CRC patients [hazard ratio (HR) 0.3978, 95% confidence interval (CI) 0.1684-0.9395; P = 0.0355]. Therefore, our data supports that adjuvant HIPEC can prevent peritoneal failure in CRC patients and improve both PFS and OS survival following primary curative resection.
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Affiliation(s)
- Hongwei Zhou
- Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan Province, China
| | - Hui Wang
- Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan Province, China
| | - Shijie Yi
- Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan Province, China
| | - Shiyao Yu
- Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan Province, China.
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48
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Patel S, Sheshadri RA, Saklani A, Sp S, Kumar R, Singh S, Sukumar V, Bhatt A. INDEPSO-ISPSM Consensus on Peritoneal Malignancies: Management of Colorectal Peritoneal Metastases. JCO Glob Oncol 2024; 10:e2400306. [PMID: 39637347 DOI: 10.1200/go-24-00306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Accepted: 10/15/2024] [Indexed: 12/07/2024] Open
Abstract
PURPOSE This manuscript reports the results of the Indian Network for Development of Peritoneal Surface Oncology and Indian Society of Peritoneal Surface Malignancies (INDEPSO-ISPSM) consensus that aimed to provide recommendations for some important aspects management of patients with colorectal peritoneal metastases (CPM) and address some issues unique to India. METHODS The modified Delphi technique was used with two rounds of voting. There were 29 questions on nine main topics-the role of cytoreductive surgery (CRS), patient selection for CRS, preoperative workup, role of systemic chemotherapy (SC), CPM with other visceral metastases, molecular profile, hyperthermic intraperitoneal chemotherapy (HIPEC) and other modalities of intraperitoneal chemotherapy (IPC), prophylactic/preventive strategies, and surveillances after CRS. A consensus was achieved if anyone option received >70 votes (strong consensus >90%). RESULTS Forty-eight surgical (n = 41) and gastrointestinal (n = 7) oncologists were invited; 44 agreed to participate. The response rate was 95.4% (42/44) in round 1 and 93.1% (41/44) in round 2. Overall, a consensus was achieved on 23/29 (79.3%) questions (strong consensus on 6/29 [20.6%]). The panel strongly recommended considering surgery for limited CPM with limited liver metastases (92.5%), not altering the surgical approach in patients with KRAS mutations (91.67%), and limiting the use of IPC for unresectable CPM outside clinical trials (95%). Adjuvant SC was recommended for all patients undergoing CRS (89.47%). CRS is a therapeutic option for selected patients with CPM including those with metachronous CPM (79.49) and signet ring cell cancers (76.92%). HIPEC was recommended outside clinical trials only for patients with peritoneal cancer index 11-15(80%). CONCLUSION The panel recommended CRS for most indications but was very selective in recommending HIPEC and IPC outside clinical trials. These recommendations should be a useful resource in clinical decision making for clinicians treating CPM in India and regions with a similar sociodemographic background.
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Affiliation(s)
- Swapnil Patel
- Department of Surgical Oncology, Upkar Hospital and Cancer Institute, Varanasi, India
| | | | - Avanish Saklani
- Department of Colorectal Surgery and GI Surgery, Tata Memorial Hospital, Mumbai, India
| | - Somashekhar Sp
- Department of Surgical Oncology, Aster International Institute of Oncology, Bangalore, India
| | - Rohit Kumar
- Department of Surgical Oncology, Aster International Institute of Oncology, Bangalore, India
| | - Shivendra Singh
- Department of GI and HPB Surgery, Rajiv Gandhi Cancer Institute, New Delhi, India
| | - Vivek Sukumar
- Department of Surgical Oncology, Specialty Surgical Oncology, Mumbai, India
| | - Aditi Bhatt
- Department of Surgical Oncology, Shalby Cancer and Research Institute, Ahmedabad, India
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49
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Blaj S, Leebmann H, Babucke M, Acs M, Piso P. Peritoneal Carcinomatosis in Colorectal Cancer: Review and Update of Current Clinical Data. Clin Colorectal Cancer 2024; 23:309-317. [PMID: 38879377 DOI: 10.1016/j.clcc.2024.05.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 05/14/2024] [Accepted: 05/15/2024] [Indexed: 12/01/2024]
Abstract
The peritoneal metastasized colorectal cancer (pmCRC) represents a serious health problem worldwide with a special emphasis in the developed countries. Several guidelines recognize the role of multimodal therapy consisting of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of pmCRC. New data suggests that some other factors, eg, tumor biology, immune profile, neoadjuvant chemotherapy may play a predictive role for the oncological outcome of these patients.
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Affiliation(s)
- S Blaj
- Clinic for General and Visceral Surgery, Hospital Barmherzige Brüder Regensburg, Germany.
| | - H Leebmann
- Clinic for General and Visceral Surgery, Hospital Barmherzige Brüder Regensburg, Germany
| | - M Babucke
- Clinic for General and Visceral Surgery, Hospital Barmherzige Brüder Regensburg, Germany
| | - M Acs
- Clinic for Surgery, University Hospital Regensburg, Germany
| | - P Piso
- Clinic for General and Visceral Surgery, Hospital Barmherzige Brüder Regensburg, Germany
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50
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Bhatt A, Villeneuve L, Sardi A, Souadka A, Buseck A, Moran BJ, Khannousi BE, de Pedro CG, Baratti D, Biacchi D, Morris D, Labow D, Levine EA, Mohamed F, Adeleke G, Goswami G, Bonnefoy I, Perry KC, Votanopoulos KI, Parikh L, Deraco M, Alyami M, Cohen N, Benzerdjeb N, Shah N, Bahaoui NE, Khajoueinejad N, Rousset P, Shen P, Barat S, Stanford S, Khouchoua S, Troob S, Shaikh S, Sarpel U, Gushchin V, Samuel VM, Kepenekian V, Sammartino P, Glehen O. Correlation of Morphological Appearance of Peritoneal Lesions at Laparotomy and Disease at Pathological Assessment in Patients Undergoing Cytoreductive Surgery for Peritoneal Malignancy: Results of Phase I of the PRECINCT Study in 707 Patients. Ann Surg Oncol 2024; 31:8560-8571. [PMID: 39187665 PMCID: PMC11549162 DOI: 10.1245/s10434-024-16035-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 08/01/2024] [Indexed: 08/28/2024]
Abstract
BACKGROUND The PRECINCT (Pattern of peritoneal dissemination and REsponse to systemic Chemotherapy IN Common and uncommon peritoneal Tumors) is a prospective, multicenter, observational study. This report from phase I of PRECINCT outlines variations in recording the surgical peritoneal cancer index (sPCI) at experienced peritoneal malignancy centers and the incidence of pathologically confirmed disease in morphologically different peritoneal lesions (PL). METHODS The sPCI was recorded in a prespecified format that included the morphological appearance of PL. Six prespecified morphological terms were provided. The surgical and pathological findings were compared. RESULTS From September 2020 to December 2021, 707 patients were enrolled at 10 centers. The morphological details are routinely recorded at two centers, structure bearing the largest nodule, and exact size of the largest tumor deposit in each region at four centers each. The most common morphological terms used were normal peritoneum in 3091 (45.3%), tumor nodules in 2607 (38.2%) and confluent disease in 786 (11.5%) regions. The incidence of pathologically confirmed disease was significantly higher in 'tumor nodules' with a lesion score of 2/3 compared with a lesion score of 1 (63.1% vs. 31.5%; p < 0.001). In patients receiving neoadjuvant chemotherapy, the incidence of pathologically confirmed disease did not differ significantly from those undergoing upfront surgery [751 (47.7%) and 532 (51.4%) respectively; p = 0.069]. CONCLUSIONS The sPCI was recorded with heterogeneity at different centers. The incidence of pathologically confirmed disease was 49.2% in 'tumor nodules'. Frozen section could be used more liberally for these lesions to aid clinical decisions. A large-scale study involving pictorial depiction of different morphological appearances and correlation with pathological findings is indicated.
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Affiliation(s)
- Aditi Bhatt
- Department of Surgical Oncology, Zydus Hospital, Ahmedabad, India
| | - Laurent Villeneuve
- Department of Clinical Research, Centre-Hospitalier Lyon-sud, Lyon, France
| | - Armando Sardi
- Department of Surgical Oncology, Mercy Medical Centre, Baltimore, MD, USA
| | - Amine Souadka
- Department of Surgical Oncology, National Cancer Institute, Rabat, Morocco
| | - Alison Buseck
- Department of Surgical Oncology, Mercy Medical Centre, Baltimore, MD, USA
| | - Brendan J Moran
- Department of Surgical Oncology, Peritoneal Malignancy Institute, Basingstoke, UK
| | | | | | - Dario Baratti
- Department of Surgical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Danielle Biacchi
- Department of Surgical Oncology, Sapienza University of Rome, Rome, Italy
| | - David Morris
- Department of Surgical Oncology, St. George Hospital, Sydney, NSW, Australia
| | - Daniel Labow
- Department of Surgical Oncology, Mount Sinai Hospital, New York, NY, USA
| | - Edward A Levine
- Section of Surgical Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Faheez Mohamed
- Department of Surgical Oncology, Peritoneal Malignancy Institute, Basingstoke, UK
| | - Gbadebo Adeleke
- Department of Pathology, Peritoneal Malignancy Institute, Basingstoke, UK
| | - Gaurav Goswami
- Department of Radiology, Zydus Hospital, Ahmedabad, India
| | - Isabelle Bonnefoy
- Department of Clinical Research, Centre-Hospitalier Lyon-sud, Lyon, France
| | | | | | - Loma Parikh
- Department of Pathology, Zydus Hospital, Ahmedabad, India
| | - Marcello Deraco
- Department of Surgical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Mohammad Alyami
- Department of Surgical Oncology, King Khaled Hospital, Najran, Saudi Arabia
| | - Noah Cohen
- Department of Surgical Oncology, Mount Sinai Hospital, New York, NY, USA
| | - Nazim Benzerdjeb
- Department of Pathology, Centre Hospitalier Lyon-sud, Lyon, France
| | - Nehal Shah
- Department of Pathology, National Cancer Institute, Rabat, Morocco
| | - Nezha El Bahaoui
- Department of Surgical Oncology, National Cancer Institute, Rabat, Morocco
| | | | - Pascal Rousset
- Department of Radiology, Centre Hospitalier Lyon-sud, Lyon, France
| | - Perry Shen
- Section of Surgical Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Shoma Barat
- Department of Surgical Oncology, St. George Hospital, Sydney, NSW, Australia
| | - Sophia Stanford
- Department of Clinical Research, Peritoneal Malignancy Institute, Basingstoke, UK
| | - Selma Khouchoua
- Department of Radiology, National Cancer Institute, Rabat, Morocco
| | - Samantha Troob
- Department of Surgical Oncology, Mount Sinai Hospital, New York, NY, USA
| | - Sakina Shaikh
- Department of Surgical Oncology, Zydus Hospital, Ahmedabad, India
| | - Umut Sarpel
- Department of Surgical Oncology, Mount Sinai Hospital, New York, NY, USA
| | - Vadim Gushchin
- Department of Surgical Oncology, Mercy Medical Centre, Baltimore, MD, USA
| | - Vasanth Mark Samuel
- Department of Surgical Oncology, Peritoneal Malignancy Institute, Basingstoke, UK
| | - Vahan Kepenekian
- Department of Surgical Oncology, Centre Hospitalier Lyon-sud, Lyon, Pierre Bénite, France
| | - Paolo Sammartino
- Department of Surgical Oncology, Sapienza University of Rome, Rome, Italy
| | - Olivier Glehen
- Department of Surgical Oncology, Centre Hospitalier Lyon-sud, Lyon, Pierre Bénite, France.
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