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Alvarez-Sarrado E, Frasson M, Sancho-Muriel J, Gomez-Jurado MJ, Cholewa H, Primo-Romaguera V, Millan M, Batista A, Rudenko P, Flor-Lorente B, Garcia-Granero E, Giner F. Peritoneal reflection involvement as a prognostic factor in rectal cancer. Long-term oncological outcomes from a prospective study. Int J Colorectal Dis 2025; 40:114. [PMID: 40347275 PMCID: PMC12065752 DOI: 10.1007/s00384-025-04909-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/02/2025] [Indexed: 05/12/2025]
Abstract
PURPOSE To assess the relevance of peritoneal reflection involvement in long-term oncological outcomes in patients with rectal cancer. METHODS Prospective observational study from a specialized colorectal unit that included a consecutive series of patients undergoing mesorectal excision for rectal cancer. Peritoneal reflection (PR) involvement was evaluated on pathological examination using Shepherd's classification. Overall survival (OS), disease-free survival (DFS), and local recurrence (LR) were assessed. RESULTS One hundred sixty patients were included in the present analysis. Peritoneal involvement was present in 28.2% of the 85 tumors above or at the level of PR. There were no differences in OS, DFS, or LR according to tumor's height location. The 5-year OS, DFS, and LR for tumors involving PR were 58.3%, 61.7%, and 30.3%, respectively. Patients with peritoneal involvement had a higher LR rate (p = 0.02) and shorter OS (p = 0.04). Shepherd's grade 4 peritoneal involvement was an independent risk factor for OS (HR 2.9; 95% CI 1.1-9.5, p = 0.04) and LR (HR 4.2; 95% CI 1.2-16.9, p = 0.04). CONCLUSION After rectal cancer resection, peritoneal involvement is an independent risk factor for local recurrence and poor survival.
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Affiliation(s)
- Eduardo Alvarez-Sarrado
- Department of Colorectal Surgery, University and Polytechnic Hospital La Fe, Av. Fernando Abril Martorell 106, 46026, Valencia, Spain.
| | - Matteo Frasson
- Department of Colorectal Surgery, University and Polytechnic Hospital La Fe, Av. Fernando Abril Martorell 106, 46026, Valencia, Spain
- Department of Surgery, University of Valencia, Valencia, Spain
| | - Jorge Sancho-Muriel
- Department of Colorectal Surgery, University and Polytechnic Hospital La Fe, Av. Fernando Abril Martorell 106, 46026, Valencia, Spain
| | - Maria Jose Gomez-Jurado
- Department of Colorectal Surgery, University and Polytechnic Hospital La Fe, Av. Fernando Abril Martorell 106, 46026, Valencia, Spain
| | - Hanna Cholewa
- Department of Colorectal Surgery, University and Polytechnic Hospital La Fe, Av. Fernando Abril Martorell 106, 46026, Valencia, Spain
| | - Vicent Primo-Romaguera
- Department of Colorectal Surgery, University and Polytechnic Hospital La Fe, Av. Fernando Abril Martorell 106, 46026, Valencia, Spain
| | - Monica Millan
- Department of Colorectal Surgery, University and Polytechnic Hospital La Fe, Av. Fernando Abril Martorell 106, 46026, Valencia, Spain
| | - Adela Batista
- Abdominal Imaging, Department of Radiology, University and Polytechnic Hospital La Fe, Valencia, Spain
| | - Polina Rudenko
- Abdominal Imaging, Department of Radiology, University and Polytechnic Hospital La Fe, Valencia, Spain
| | - Blas Flor-Lorente
- Department of Colorectal Surgery, University and Polytechnic Hospital La Fe, Av. Fernando Abril Martorell 106, 46026, Valencia, Spain
| | - Eduardo Garcia-Granero
- Department of Colorectal Surgery, University and Polytechnic Hospital La Fe, Av. Fernando Abril Martorell 106, 46026, Valencia, Spain
| | - Francisco Giner
- Pathology Department, University of Valencia, Valencia, Spain.
- Pathology Department, University and Polytechnic Hospital La Fe, Av. de Blasco Ibáñez, 13, 46010, València, Spain.
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de'Angelis N, Schena CA, Espin-Basany E, Piccoli M, Alfieri S, Aisoni F, Coccolini F, Frontali A, Kraft M, Lakkis Z, Le Roy B, Luzzi AP, Milone M, Pattacini GC, Pellino G, Petri R, Piozzi GN, Quero G, Ris F, Winter DC, Khan J. Robotic versus laparoscopic right colectomy for nonmetastatic pT4 colon cancer: A European multicentre propensity score-matched analysis. Colorectal Dis 2024; 26:1569-1583. [PMID: 38978153 DOI: 10.1111/codi.17089] [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] [Received: 11/29/2023] [Revised: 04/14/2024] [Accepted: 04/16/2024] [Indexed: 07/10/2024]
Abstract
AIM Minimally invasive surgery has been increasingly adopted for locally advanced colon cancer. However, evidence comparing robotic (RRC) versus laparoscopic right colectomy (LRC) for nonmetastatic pT4 cancers is lacking. METHODS This was a multicentre propensity score-matched (PSM) study of a cohort of consecutive patients with pT4 right colon cancer treated with RRC or LRC. The two surgical approaches were compared in terms of R0, number of lymph nodes harvested, intra- and postoperative complication rates, overall (OS), and disease-free survival (DFS). RESULTS Among a total of 200 patients, 39 RRC were compared with 78 PS-matched LRC patients. The R0 rate was similar between RRC and LRC (92.3% vs. 96.2%, respectively; p = 0.399), as was the odds of retrieving 12 or more lymph nodes (97.4% vs. 96.2%; p = 1). No significant difference was noted for the mean operating time (192.9 min vs. 198.3 min; p = 0.750). However, RRC was associated with fewer conversions to laparotomy (5.1% vs. 20.5%; p = 0.032), less blood loss (36.9 vs. 95.2 mL; p < 0.0001), fewer postoperative complications (17.9% vs. 41%; p = 0.013), a shorter time to flatus (2 vs. 2.8 days; p = 0.009), and a shorter hospital stay (6.4 vs. 9.5 days; p < 0.0001) compared with LRC. These results were confirmed even when converted procedures were excluded from the analysis. The 1-, 3- and 5-year OS (p = 0.757) and DFS (p = 0.321) did not significantly differ between RRC and LRC. CONCLUSION Adequate oncological outcomes are observed for RRC and LRC performed for pT4 right colon cancer. However, RRC is associated with lower conversion rates and improved short-term postoperative outcomes.
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Affiliation(s)
- Nicola de'Angelis
- Unit of Robotic and Minimally Invasive Surgery, Department of Surgery, Ferrara University Hospital, Ferrara, Italy
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
| | - Carlo Alberto Schena
- Unit of Robotic and Minimally Invasive Surgery, Department of Surgery, Ferrara University Hospital, Ferrara, Italy
- Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Eloy Espin-Basany
- Unit of Colorectal Surgery, Department of General and Digestive Surgery, University Hospital Vall d'Hebron-Universitat Autonoma de Barcelona, Barcelona, Spain
| | - Micaela Piccoli
- Unit of General, Emergency Surgery and New Technologies, Ospedale Civile Baggiovara, Azienda Ospedaliero Universitaria Di Modena, Modena, Italy
| | - Sergio Alfieri
- Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Filippo Aisoni
- Unit of General Surgery, Department of Surgery, Ferrara University Hospital, Ferrara, Italy
| | - Federico Coccolini
- General, Emergency and Trauma Surgery Department, Pisa University Hospital, Pisa, Italy
| | - Alice Frontali
- Department of General Surgery, Department of Biomedical and Clinical Sciences 'L. Sacco', University of Milan, ASST Fatebenefratelli Sacco, Milan, Italy
| | - Miquel Kraft
- Unit of Colorectal Surgery, Department of General and Digestive Surgery, University Hospital Vall d'Hebron-Universitat Autonoma de Barcelona, Barcelona, Spain
| | - Zaher Lakkis
- Department of Digestive Surgical Oncology, Liver Transplantation Unit, University Hospital of Besançon, Besançon, France
| | - Bertrand Le Roy
- Department of Digestive and Oncologic Surgery, Hospital Nord, CHU Saint-Etienne, Saint-Etienne, France
| | | | - Marco Milone
- Department of Clinical Medicine and Surgery, "Federico II" University of Naples, Naples, Italy
| | - Gianmaria Casoni Pattacini
- Unit of General, Emergency Surgery and New Technologies, Ospedale Civile Baggiovara, Azienda Ospedaliero Universitaria Di Modena, Modena, Italy
| | - Gianluca Pellino
- Unit of Colorectal Surgery, Department of General and Digestive Surgery, University Hospital Vall d'Hebron-Universitat Autonoma de Barcelona, Barcelona, Spain
| | - Roberto Petri
- General Surgery Department, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy
| | | | - Giuseppe Quero
- Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Frederic Ris
- Division of Abdominal and Transplantation Surgery, Department of Surgery, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland
| | - Des C Winter
- Department of Surgery, St. Vincent's University Hospital, Dublin, Ireland
| | - Jim Khan
- Department of Colorectal Surgery, Portsmouth Hospitals University NHS Trust, Portsmouth, UK
- University of Portsmouth, Portsmouth, UK
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3
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Dai J, Wang KX, Wu LY, Bai XH, Shi HY, Xu Q, Yu J. Development of a Nomogram to Predict Postoperative Peritoneal Metastasis of Colon Cancer. J Comput Assist Tomogr 2023; 47:864-872. [PMID: 37948360 DOI: 10.1097/rct.0000000000001500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/23/2023]
Abstract
OBJECTIVE The aim of this study was to determine the clinicopathological and radiological risk factors for postoperative peritoneal metastasis and develop a prediction model for the early detection of peritoneal metastasis in patients with colon cancer. METHODS We included 174 patients with colon cancer. The clinicopathological and radiological data were retrospectively analyzed. A Cox proportional hazards regression model was used to identify risk factors for postoperative peritoneal metastasis. Based on these risk factors, a nomogram was developed. RESULTS At a median follow-up of 63 months, 43 (24.7%) patients developed peritoneal metastasis. Six independent risk factors (hazards ratio [95% confidence interval]) were identified for postoperative peritoneal metastasis: abdominopelvic fluid (2.12 [1.02-4.40]; P = 0.04), longer maximum tumor length (1.02 [1.00-1.03]; P = 0.02), pN1 (2.50 [1.13-5.56]; P = 0.02), pN2 (4.45 [1.77-11.17]; P = 0.02), nonadenocarcinoma (2.75 [1.18-6.38]; P = 0.02), and preoperative carcinoembryonic antigen levels ≥5 ng/mL (3.08 [1.50-6.30]; P < 0.01). A clinicopathological-radiological model was developed based on these factors. The model showed good discrimination (concordance index, 0.798 [0.723-0.876]; P < 0.001) and was well-calibrated. CONCLUSIONS The developed clinicopathological-radiological nomogram may assist clinicians in identifying patients at high risk of postoperative peritoneal metastasis.
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Affiliation(s)
- Jie Dai
- From the Department of Radiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Gelli M, Desterke C, Bani MA, Boige V, Ferté C, Dartigues P, Job B, Perkins G, Laurent-Puig P, Goéré D, Mathieu JRR, Cartry J, Ducreux M, Jaulin F. Primary Colorectal Tumor Displays Differential Genomic Expression Profiles Associated with Hepatic and Peritoneal Metastases. Cancers (Basel) 2023; 15:4418. [PMID: 37686695 PMCID: PMC10648258 DOI: 10.3390/cancers15174418] [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: 07/15/2023] [Revised: 08/28/2023] [Accepted: 08/31/2023] [Indexed: 09/10/2023] Open
Abstract
BACKGROUND Despite improvements in characterization of CRC heterogeneity, appropriate risk stratification tools are still lacking in clinical practice. This study aimed to elucidate the primary tumor transcriptomic signatures associated with distinct metastatic routes. METHODS Primary tumor specimens obtained from CRC patients with either isolated LM (CRC-Liver) or PM (CRC-Peritoneum) were analyzed by transcriptomic mRNA sequencing, gene set enrichment analyses (GSEA) and immunohistochemistry. We further assessed the clinico-pathological associations and prognostic value of our signature in the COAD-TCGA independent cohort. RESULTS We identified a significantly different distribution of Consensus Molecular Subtypes between CRC-Liver and CRC-peritoneum groups. A transcriptomic signature based on 61 genes discriminated between liver and peritoneal metastatic routes. GSEA showed a higher expression of immune response and epithelial invasion pathways in CRC-Peritoneum samples and activation of proliferation and metabolic pathways in CRC-Liver samples. The biological relevance of RNA-Seq results was validated by the immunohistochemical expression of three significantly differentially expressed genes (ACE2, CLDN18 and DUSP4) in our signature. In silico analysis of the COAD-TCGA showed that the CRC-Peritoneum signature was associated with negative prognostic factors and poor overall and disease-free survivals. CONCLUSIONS CRC primary tumors spreading to the liver and peritoneum display significantly different transcriptomic profiles. The implementation of this signature in clinical practice could contribute to identify new therapeutic targets for stage IV CRC and to define individualized follow-up programs in stage II-III CRC.
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Affiliation(s)
- Maximiliano Gelli
- Université Paris-Saclay, Gustave Roussy, INSERM, Dynamique des Cellules Tumorales (U-1279), F-94805 Villejuif, France; (M.G.); (D.G.); (J.R.R.M.); (J.C.); (M.D.)
- Gustave Roussy, Département de Anesthésie, Chirurgie et Interventionnel, F-94805 Villejuif, France
| | - Christophe Desterke
- Université Paris Saclay, INSERM, Modèles de Cellules Souches Malignes et Thérapeutiques (UMR1310), F-94805 Villejuif, France;
| | - Mohamed Amine Bani
- Gustave Roussy, Département de Biologie et Pathologie Médicale, F-94805 Villejuif, France; (M.A.B.); (P.D.)
- Université Paris-Saclay, CNRS, Inserm, US23, UMS3655, F-94805 Villejuif, France;
| | - Valérie Boige
- Gustave Roussy, Département de Médecine Oncologique, F-94805 Villejuif, France; (V.B.); (C.F.)
| | - Charles Ferté
- Gustave Roussy, Département de Médecine Oncologique, F-94805 Villejuif, France; (V.B.); (C.F.)
| | - Peggy Dartigues
- Gustave Roussy, Département de Biologie et Pathologie Médicale, F-94805 Villejuif, France; (M.A.B.); (P.D.)
| | - Bastien Job
- Université Paris-Saclay, CNRS, Inserm, US23, UMS3655, F-94805 Villejuif, France;
| | - Geraldine Perkins
- Institut du Cancer Paris CARPEM, AP-HP, AP-HP Centre, Department of Hepatogastroenterology and Digestive Oncology, Hôpital Européen Georges Pompidou, 20 Rue Leblanc, F-75015 Paris, France;
| | - Pierre Laurent-Puig
- Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, Centre de Recherche des Cordeliers, INSERM, CNRS, F-75005 Paris, France;
| | - Diane Goéré
- Université Paris-Saclay, Gustave Roussy, INSERM, Dynamique des Cellules Tumorales (U-1279), F-94805 Villejuif, France; (M.G.); (D.G.); (J.R.R.M.); (J.C.); (M.D.)
- Gustave Roussy, Département de Anesthésie, Chirurgie et Interventionnel, F-94805 Villejuif, France
| | - Jacques R. R. Mathieu
- Université Paris-Saclay, Gustave Roussy, INSERM, Dynamique des Cellules Tumorales (U-1279), F-94805 Villejuif, France; (M.G.); (D.G.); (J.R.R.M.); (J.C.); (M.D.)
| | - Jerome Cartry
- Université Paris-Saclay, Gustave Roussy, INSERM, Dynamique des Cellules Tumorales (U-1279), F-94805 Villejuif, France; (M.G.); (D.G.); (J.R.R.M.); (J.C.); (M.D.)
| | - Michel Ducreux
- Université Paris-Saclay, Gustave Roussy, INSERM, Dynamique des Cellules Tumorales (U-1279), F-94805 Villejuif, France; (M.G.); (D.G.); (J.R.R.M.); (J.C.); (M.D.)
- Gustave Roussy, Département de Médecine Oncologique, F-94805 Villejuif, France; (V.B.); (C.F.)
| | - Fanny Jaulin
- Université Paris-Saclay, Gustave Roussy, INSERM, Dynamique des Cellules Tumorales (U-1279), F-94805 Villejuif, France; (M.G.); (D.G.); (J.R.R.M.); (J.C.); (M.D.)
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Fawaz J, Pocard M, Liberale G, Eveno C, Malgras B, Sideris L, Hübner M, Sabbagh C, Sgarbura O, Taibi A, Hobeika C. A prediction model to refine the timing of an early second-look laparoscopic exploration in patients with colon cancer at high risk of early peritoneal metastasis recurrence. J Surg Oncol 2023; 128:576-584. [PMID: 37226983 DOI: 10.1002/jso.27359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Revised: 04/28/2023] [Accepted: 05/05/2023] [Indexed: 05/26/2023]
Abstract
BACKGROUND In patients at high risk of peritoneal metastasis (PM) recurrence following surgical treatment of colon cancer (CC), second-look laparoscopic exploration (SLLE) is mandatory; however, the best timing is unknown. We created a tool to refine the timing of early SLLE in patients at high risk of PM recurrence. METHODS This international cohort study included patients who underwent CC surgery between 2009 and 2020. All patients had PM recurrence. Factors associated with PM-free survival (PMFS) were assessed using Cox regression. The primary endpoint was early PM recurrence defined as a PMFS of <6 months. A model (logistic regression) was fitted and corrected using bootstrap. RESULTS In total, 235 patients were included. The median PMFS was 13 (IQR, 8-22) months, and 15.7% of the patients experienced an early PM recurrence. Synchronous limited PM and/or ovarian metastasis (hazard ratio [HR]: 2.50; 95% confidence interval [CI]: [1.66-3.78]; p < 0.001) were associated with a very high-risk status requiring SLLE. T4 (HR: 1.47; 95% CI: [1.03-2.11]; p = 0.036), transverse tumor localization (HR: 0.35; 95% CI: [0.17-0.69]; p = 0.002), emergency surgery (HR: 2.06; 95% CI: [1.36-3.13]; p < 0.001), mucinous subtype (HR: 0.50; 95% CI [0.30, 0.82]; p = 0.006), microsatellite instability (HR: 2.29; 95% CI [1.06, 4.93]; p = 0.036), KRAS mutation (HR: 1.78; 95% CI: [1.24-2.55]; p = 0.002), and complete protocol of adjuvant chemotherapy (HR: 0.93; 95% CI: [0.89-0.96]; p < 0.001) were also prognostic factors for PMFS. Thus, a model was fitted (area under the curve: 0.87; 95% CI: [0.82-0.92]) for prediction, and a cutoff of 150 points was identified to classify patients at high risk of early PM recurrence. CONCLUSION Using a nomogram, eight prognostic factors were identified to select patients at high risk for early PM recurrence objectively. Patients reaching 150 points could benefit from an early SLLE.
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Affiliation(s)
- Jade Fawaz
- Department of Digestive, Hepatobiliary and Liver Transplantation Surgery, Hôpital de la Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris and Sorbonne Université, Paris, France
- Sorbonne University, Paris, France
| | - Marc Pocard
- Department of Digestive, Hepatobiliary and Liver Transplantation Surgery, Hôpital de la Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris and Sorbonne Université, Paris, France
- UMR INSERM 1275 CAP Paris-Tech, Lariboisière Hospital, Université de Paris, Paris, France
| | - Gabriel Liberale
- Department of Surgical Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
| | - Clarisse Eveno
- Department of Digestive and Oncologic Surgery, Claude Huriez University Hospital, Centre Hospitalier Universitaire (CHU), Lille, France
| | - Brice Malgras
- Department of Digestive and Endocrine Surgery, Bégin Military Teaching Hospital, Saint-Mandé, France
| | - Lucas Sideris
- Department of Surgery, Maisonneuve-Rosemont Hospital, University of Montreal, Montreal, Quebec, Canada
| | - Martin Hübner
- Department of Visceral Surgery, Lausanne University Hospital CHUV, Lausanne, Switzerland
| | - Charles Sabbagh
- Department of Digestive Surgery, University Hospital of Amiens Picardie, Jules Verne University of Picardie, Amiens, France
| | - Olivia Sgarbura
- Department of Surgical Oncology, Cancer Institute Montpellier (ICM), University of Montpellier, Montpellier, France
| | - Abdelkader Taibi
- Digestive Surgery Department, Dupuytren Limoges University Hospital, Limoges, France
| | - Christian Hobeika
- Department of Digestive, Hepatobiliary and Liver Transplantation Surgery, Hôpital de la Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris and Sorbonne Université, Paris, France
- UMR INSERM 1275 CAP Paris-Tech, Lariboisière Hospital, Université de Paris, Paris, France
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Ban B, Shang A, Shi J. Development and validation of a nomogram for predicting metachronous peritoneal metastasis in colorectal cancer: A retrospective study. World J Gastrointest Oncol 2023; 15:112-127. [PMID: 36684053 PMCID: PMC9850763 DOI: 10.4251/wjgo.v15.i1.112] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Revised: 11/23/2022] [Accepted: 12/21/2022] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Peritoneal metastasis (PM) after primary surgery for colorectal cancer (CRC) has the worst prognosis. Prediction and early detection of metachronous PM (m-PM) have an important role in improving postoperative prognosis of CRC. However, commonly used imaging methods have limited sensitivity to detect PM early. We aimed to establish a nomogram model to evaluate the individual probability of m-PM to facilitate early interventions for high-risk patients.
AIM To establish and validate a nomogram model for predicting the occurrence of m-PM in CRC within 3 years after surgery.
METHODS We used the clinical data of 878 patients at the Second Hospital of Jilin University, between January 1, 2014 and January 31, 2019. The patients were randomly divided into training and validation cohorts at a ratio of 2:1. The least absolute shrinkage and selection operator (LASSO) regression was performed to identify the variables with nonzero coefficients to predict the risk of m-PM. Multivariate logistic regression was used to verify the selected variables and to develop the predictive nomogram model. Harrell’s concordance index, receiver operating characteristic curve, Brier score, and decision curve analysis (DCA) were used to evaluate discrimination, distinctiveness, validity, and clinical utility of this nomogram model. The model was verified internally using bootstrapping method and verified externally using validation cohort.
RESULTS LASSO regression analysis identified six potential risk factors with nonzero coefficients. Multivariate logistic regression confirmed the risk factors to be independent. Based on the results of two regression analyses, a nomogram model was established. The nomogram included six predictors: Tumor site, histological type, pathological T stage, carbohydrate antigen 125, v-raf murine sarcoma viral oncogene homolog B mutation and microsatellite instability status. The model achieved good predictive accuracy on both the training and validation datasets. The C-index, area under the curve, and Brier scores were 0.796, 0.796 [95% confidence interval (CI) 0.735-0.856], and 0.081 for the training cohort and 0.782, 0.782 (95%CI 0.690-0.874), and 0.089 for the validation cohort, respectively. DCA showed that when the threshold probability was between 0.01 and 0.90, using this model to predict m-PM achieved a net clinical benefit.
CONCLUSION We have established and validated a nomogram model to predict m-PM in patients undergoing curative surgery, which shows good discrimination and high accuracy.
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Affiliation(s)
- Bo Ban
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - An Shang
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Jian Shi
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
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7
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Zwanenburg ES, Gehrels AM, Bastiaenen VP, Aalbers AGJ, Arjona-Sánchez A, Bellato V, van der Bilt JDW, D'Hoore AD, Espinosa-Redondo E, Klaver CEL, Kusters M, Nagtegaal ID, van Ramshorst B, van Santvoort HC, Sica GS, Snaebjornsson P, Wasmann KATGM, de Wilt JHW, Wolthuis AM, Tanis PJ. Metachronous peritoneal metastases in patients with pT4b colon cancer: An international multicenter analysis of intraperitoneal versus retroperitoneal tumor invasion. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:2023-2031. [PMID: 35729015 DOI: 10.1016/j.ejso.2022.05.028] [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: 04/14/2022] [Accepted: 05/27/2022] [Indexed: 11/17/2022]
Abstract
BACKGROUND It was hypothesized that colon cancer with only retroperitoneal invasion is associated with a low risk of peritoneal dissemination. This study aimed to compare the risk of metachronous peritoneal metastases (mPM) between intraperitoneal and retroperitoneal invasion. METHODS In this international, multicenter cohort study, patients with pT4bN0-2M0 colon cancer who underwent curative surgery were categorized as having intraperitoneal invasion (e.g. bladder, small bowel, stomach, omentum, liver, abdominal wall) or retroperitoneal invasion only (e.g. ureter, pancreas, psoas muscle, Gerota's fascia). Primary outcome was 5-year mPM cumulative rate, assessed by Kaplan-Meier analysis. RESULTS Out of 907 patients with pT4N0-2M0 colon cancer, 198 had a documented pT4b category, comprising 170 patients with intraperitoneal invasion only, 12 with combined intra- and retroperitoneal invasion, and 16 patients with retroperitoneal invasion only. At baseline, only R1 resection rate significantly differed: 4/16 for retroperitoneal invasion only versus 8/172 for intra- +/- retroperitoneal invasion (p = 0.010). Overall, 22 patients developed mPM during a median follow-up of 45 months. Two patients with only retroperitoneal invasion developed mPM, both following R1 resection. The overall 5-year mPM cumulative rate was 13% for any intraperitoneal invasion and 14% for retroperitoneal invasion only (Log Rank, p = 0.878), which was 13% and 0%, respectively, in patients who had an R0 resection (Log Rank, p = 0.235). CONCLUSION This study suggests that pT4b colon cancer patients with only retroperitoneal invasion who undergo an R0 resection have a negligible risk of mPM, but this is difficult to prove because of its rarity. This observation might have implications regarding individualized follow-up.
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Affiliation(s)
- E S Zwanenburg
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - A M Gehrels
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - V P Bastiaenen
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - A G J Aalbers
- Department of Surgery, the Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - A Arjona-Sánchez
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital and GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, (IMIBIC), Cordoba, Spain
| | - V Bellato
- Department of Surgical Science, University Hospital Tor Vergata, Rome, Italy
| | - J D W van der Bilt
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands; Department of Surgery, Flevoziekenhuis, Almere, the Netherlands
| | - A D D'Hoore
- Department of Abdominal Surgery, University Hospital Leuven, Leuven, Belgium
| | - E Espinosa-Redondo
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital and GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, (IMIBIC), Cordoba, Spain
| | - C E L Klaver
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - M Kusters
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - I D Nagtegaal
- Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - B van Ramshorst
- Department of Surgery, St. Antonius Hospital, Nieuwegein, the Netherlands
| | - H C van Santvoort
- Department of Surgery, St. Antonius Hospital, Nieuwegein, the Netherlands
| | - G S Sica
- Department of Surgical Science, University Hospital Tor Vergata, Rome, Italy
| | - P Snaebjornsson
- Department of Pathology, the Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - K A T G M Wasmann
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - J H W de Wilt
- Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - A M Wolthuis
- Department of Abdominal Surgery, University Hospital Leuven, Leuven, Belgium
| | - P J Tanis
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands; Department of Oncological and Gastrointestinal Surgery, Erasmus MC, Rotterdam, the Netherlands.
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8
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Pedrazzani C, Turri G, Marrelli D, Kim HJ, Park EJ, Spolverato G, Foppa C, Spinelli A, Pucciarelli S, Baik SH, Choi GS. Prediction of Metachronous Peritoneal Metastases After Radical Surgery for Colon Cancer: A Scoring System Obtained from an International Multicenter Cohort. Ann Surg Oncol 2022; 29:7896-7906. [PMID: 35789302 PMCID: PMC9550705 DOI: 10.1245/s10434-022-12097-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 06/12/2022] [Indexed: 01/01/2023]
Abstract
Background Since novel strategies for prevention and treatment of metachronous peritoneal metastases (mPM) are under study, it appears crucial to identify their risk factors. Our aim is to establish the incidence of mPM after surgery for colon cancer (CC) and to build a statistical model to predict the risk of recurrence. Patients and Methods Retrospective analysis of consecutive pT3–4 CC operated at five referral centers (2014–2018). Patients who developed mPM were compared with patients who were PM-free at follow-up. A scoring system was built on the basis of a logistic regression model. Results Of the 1423 included patients, 74 (5.2%) developed mPM. Patients in the PM group presented higher preoperative carcinoembryonic antigen (CEA) [median (IQR): 4.5 (2.5–13.0) vs. 2.7 (1.5–5.9), P = 0.001] and CA 19-9 [median (IQR): 17.7 (12.0–37.0) vs. 10.8 (5.0–21.0), P = 0.001], advanced disease (pT4a 42.6% vs. 13.5%; pT4b 16.2% vs. 3.2%; P < 0.001), and negative pathological characteristics. Multivariate logistic regression identified CA 19-9, pT stage, pN stage, extent of lymphadenectomy, and lymphovascular invasion as significant predictors, and individual risk scores were calculated for each patient. The risk of recurrence increased remarkably with score values, and the model demonstrated a high negative predictive value (98.8%) and accuracy (83.9%) for scores below five. Conclusions Besides confirming incidence and risk factors for mPM, our study developed a useful clinical tool for prediction of mPM risk. After external validation, this scoring system may guide personalized decision-making for patients with locally advanced CC. Supplementary Information The online version contains supplementary material available at 10.1245/s10434-022-12097-9.
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Affiliation(s)
- Corrado Pedrazzani
- Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Verona University Hospital, University of Verona, Verona, Italy.
| | - Giulia Turri
- Division of General and Hepatobiliary Surgery, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Verona University Hospital, University of Verona, Verona, Italy
| | - Daniele Marrelli
- Department of Surgery, Policlinico le Scotte, University of Siena, Siena, Italy
| | - Hye Jin Kim
- Colorectal Cancer Centre, Kyungpook National University Medical Centre, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Eun Jung Park
- Division of Colon and Rectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Gaya Spolverato
- General Surgery 3, Department of Surgery, Oncology, and Gastroenterology, University of Padova, Padova, Italy
| | - Caterina Foppa
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.,Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Antonino Spinelli
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.,Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Salvatore Pucciarelli
- General Surgery 3, Department of Surgery, Oncology, and Gastroenterology, University of Padova, Padova, Italy
| | - Seung Hyuk Baik
- Division of Colon and Rectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Gyu Seog Choi
- Colorectal Cancer Centre, Kyungpook National University Medical Centre, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
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9
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Zhang Y, Qin X, Chen W, Liu D, Luo J, Wang H, Wang H. Risk factors for developing peritoneal metastases after curative surgery for colorectal cancer: A systematic review and meta-analysis. Colorectal Dis 2021; 23:2846-2858. [PMID: 34411399 DOI: 10.1111/codi.15880] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Revised: 07/20/2021] [Accepted: 08/16/2021] [Indexed: 01/10/2023]
Abstract
AIM Proactive detection and treatment strategies have achieved encouraging survival outcomes for patients with early peritoneal metastases (PM), but these costly and invasive approaches can only be applied to selected high-risk patients. This meta-analysis aimed to identify the risk factors for metachronous PM after curative surgery for colorectal cancer (CRC). METHOD The study was registered at PROSPERO (CRD42020219187). Databases were searched for studies comparing clinical and histopathological characteristics between patients with metachronous peritoneal metastases from colorectal cancer (pmCRC) and patients without (non-pmCRC). RESULTS Thirty-six studies were included. Metachronous PM were positively associated with perforation (OR 1.920; 95% CI 1.144-3.223; P = 0.014), poor differentiation (OR 2.291; 1.603-3.275; P < 0.001), T4 (OR 2.897; 1.248-6.726; P = 0.013), N1-2 (OR 3.429; 2.684-4.381; P < 0.001), mucinous adenocarcinoma (OR 4.175; 1.798-9.692; P = 0.001), obstruction (OR 4.467; 1.919-10.398; P = 0.001), synchronous ovarian metastases (OR 5.005; 1.140-21.977; P = 0.033), positive peritoneal carcinoembryonic antigen mRNA (OR 9.472; 3.643-24.631; P < 0.001), elevated serum carcinoembryonic antigen (preoperative group, OR 3.545, 1.486-8.459, P = 0.004; postoperative group, OR 13.673, 2.222-84.129, P = 0.005), elevated serum cancer antigen 19-9 (preoperative group, OR 5.281, 2.146-12.994, P < 0.001; postoperative group, OR 18.646, 6.429-54.083, P < 0.001) and positive peritoneal cytology (OR 25.884; 11.372-58.913; P < 0.001). CONCLUSION These evidence-based risk factors are conducive to designing early detection and proactive treatment strategies, enabling precision medicine.
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Affiliation(s)
- Yuanxin Zhang
- Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiusen Qin
- Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wenle Chen
- Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Duo Liu
- Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jian Luo
- Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Huaiming Wang
- Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Hui Wang
- Department of Colorectal Surgery, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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10
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Bastiaenen VP, Aalbers AGJ, Arjona-Sánchez A, Bellato V, van der Bilt JDW, D'Hoore AD, Espinosa-Redondo E, Klaver CEL, Nagtegaal ID, van Ramshorst B, van Santvoort HC, Sica GS, Snaebjornsson P, Wasmann KATGM, de Wilt JHW, Wolthuis AM, Tanis PJ. Risk of metachronous peritoneal metastases in patients with pT4a versus pT4b colon cancer: An international multicentre cohort study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2021; 47:2405-2413. [PMID: 34030920 DOI: 10.1016/j.ejso.2021.05.009] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 04/25/2021] [Accepted: 05/06/2021] [Indexed: 01/01/2023]
Abstract
INTRODUCTION With evolving treatment strategies aiming at prevention or early detection of metachronous peritoneal metastases (PM), identification of high-risk colon cancer patients becomes increasingly important. This study aimed to evaluate differences between pT4a (peritoneal penetration) and pT4b (invasion of other organs/structures) subcategories regarding risk of PM and other oncological outcomes. MATERIALS AND METHODS From eight databases deriving from four countries, patients who underwent curative intent treatment for pT4N0-2M0 primary colon cancer were included. Primary outcome was the 5-year metachronous PM rate assessed by Kaplan-Meier analysis. Independent predictors for metachronous PM were identified by Cox regression analysis. Secondary endpoints included 5-year local and distant recurrence rates, and 5-year disease free and overall survival (DFS, OS). RESULTS In total, 665 patients with pT4a and 187 patients with pT4b colon cancer were included. Median follow-up was 38 months (IQR 23-60). Five-year PM rate was 24.7% and 12.2% for pT4a and pT4b categories, respectively (p = 0.005). Independent predictors for metachronous PM were female sex, right-sided colon cancer, peritumoral abscess, pT4a, pN2, R1 resection, signet ring cell histology and postoperative surgical site infections. Five-year local recurrence rate was 14% in both pT4a and pT4b cancer (p = 0.138). Corresponding five-year distant metastases rates were 35% and 28% (p = 0.138). Five-year DFS and OS were 54% vs. 62% (p = 0.095) and 63% vs. 68% (p = 0.148) for pT4a vs. pT4b categories, respectively. CONCLUSION Patients with pT4a colon cancer have a higher risk of metachronous PM than pT4b patients. This observation has important implications for early detection and future adjuvant treatment strategies.
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Affiliation(s)
- Vivian P Bastiaenen
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Centre Amsterdam, Amsterdam, the Netherlands.
| | - Arend G J Aalbers
- Department of Surgery, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
| | - Alvaro Arjona-Sánchez
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital and GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, (IMIBIC), Cordoba, Spain.
| | - Vittoria Bellato
- Department of Surgical Science, University Hospital Tor Vergata, Rome, Italy.
| | - Jarmila D W van der Bilt
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Centre Amsterdam, Amsterdam, the Netherlands; Department of Abdominal Surgery, University Hospital Leuven, Leuven, Belgium.
| | - André D D'Hoore
- Department of Abdominal Surgery, University Hospital Leuven, Leuven, Belgium.
| | - Esther Espinosa-Redondo
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital and GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, (IMIBIC), Cordoba, Spain.
| | - Charlotte E L Klaver
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Centre Amsterdam, Amsterdam, the Netherlands.
| | - Iris D Nagtegaal
- Department of Pathology, Radboud University Medical Centre, Nijmegen, the Netherlands.
| | - Bert van Ramshorst
- Department of Surgery, St. Antonius Hospital, Nieuwegein, the Netherlands.
| | - Hjalmar C van Santvoort
- Department of Surgery, St. Antonius Hospital, Nieuwegein, the Netherlands; Cancer Centre, University Medical Centre Utrecht, Utrecht, the Netherlands.
| | - Giuseppe S Sica
- Department of Surgical Science, University Hospital Tor Vergata, Rome, Italy.
| | - Petur Snaebjornsson
- Department of Pathology, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
| | - Karin A T G M Wasmann
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Centre Amsterdam, Amsterdam, the Netherlands.
| | - Johannes H W de Wilt
- Department of Surgery, Radboud University Medical Centre, Nijmegen, the Netherlands.
| | - Albert M Wolthuis
- Department of Abdominal Surgery, University Hospital Leuven, Leuven, Belgium.
| | - Pieter J Tanis
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Centre Amsterdam, Amsterdam, the Netherlands.
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11
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Tsai TY, You JF, Hsu YJ, Jhuang JR, Chern YJ, Hung HY, Yeh CY, Hsieh PS, Chiang SF, Lai CC, Chiang JM, Tang R, Tsai WS. A Prediction Model for Metachronous Peritoneal Carcinomatosis in Patients with Stage T4 Colon Cancer after Curative Resection. Cancers (Basel) 2021; 13:2808. [PMID: 34200032 PMCID: PMC8200190 DOI: 10.3390/cancers13112808] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 05/30/2021] [Accepted: 06/02/2021] [Indexed: 01/21/2023] Open
Abstract
(1) Background: The aim of this study was to develop a prediction model for assessing individual mPC risk in patients with pT4 colon cancer. Methods: A total of 2003 patients with pT4 colon cancer undergoing R0 resection were categorized into the training or testing set. Based on the training set, 2044 Cox prediction models were developed. Next, models with the maximal C-index and minimal prediction error were selected. The final model was then validated based on the testing set using a time-dependent area under the curve and Brier score, and a scoring system was developed. Patients were stratified into the high- or low-risk group by their risk score, with the cut-off points determined by a classification and regression tree (CART). (2) Results: The five candidate predictors were tumor location, preoperative carcinoembryonic antigen value, histologic type, T stage and nodal stage. Based on the CART, patients were categorized into the low-risk or high-risk groups. The model has high predictive accuracy (prediction error ≤5%) and good discrimination ability (area under the curve >0.7). (3) Conclusions: The prediction model quantifies individual risk and is feasible for selecting patients with pT4 colon cancer who are at high risk of developing mPC.
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Affiliation(s)
- Tzong-Yun Tsai
- Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan; (T.-Y.T.); (J.-F.Y.); (Y.-J.H.); (Y.-J.C.); (H.-Y.H.); (C.-Y.Y.); (P.-S.H.); (S.-F.C.); (C.-C.L.); (J.-M.C.); (R.T.)
- College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan
| | - Jeng-Fu You
- Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan; (T.-Y.T.); (J.-F.Y.); (Y.-J.H.); (Y.-J.C.); (H.-Y.H.); (C.-Y.Y.); (P.-S.H.); (S.-F.C.); (C.-C.L.); (J.-M.C.); (R.T.)
- College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan
| | - Yu-Jen Hsu
- Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan; (T.-Y.T.); (J.-F.Y.); (Y.-J.H.); (Y.-J.C.); (H.-Y.H.); (C.-Y.Y.); (P.-S.H.); (S.-F.C.); (C.-C.L.); (J.-M.C.); (R.T.)
- College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan
| | - Jing-Rong Jhuang
- Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei City 10055, Taiwan;
| | - Yih-Jong Chern
- Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan; (T.-Y.T.); (J.-F.Y.); (Y.-J.H.); (Y.-J.C.); (H.-Y.H.); (C.-Y.Y.); (P.-S.H.); (S.-F.C.); (C.-C.L.); (J.-M.C.); (R.T.)
- College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan
| | - Hsin-Yuan Hung
- Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan; (T.-Y.T.); (J.-F.Y.); (Y.-J.H.); (Y.-J.C.); (H.-Y.H.); (C.-Y.Y.); (P.-S.H.); (S.-F.C.); (C.-C.L.); (J.-M.C.); (R.T.)
- College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan
| | - Chien-Yuh Yeh
- Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan; (T.-Y.T.); (J.-F.Y.); (Y.-J.H.); (Y.-J.C.); (H.-Y.H.); (C.-Y.Y.); (P.-S.H.); (S.-F.C.); (C.-C.L.); (J.-M.C.); (R.T.)
- College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan
| | - Pao-Shiu Hsieh
- Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan; (T.-Y.T.); (J.-F.Y.); (Y.-J.H.); (Y.-J.C.); (H.-Y.H.); (C.-Y.Y.); (P.-S.H.); (S.-F.C.); (C.-C.L.); (J.-M.C.); (R.T.)
- College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan
| | - Sum-Fu Chiang
- Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan; (T.-Y.T.); (J.-F.Y.); (Y.-J.H.); (Y.-J.C.); (H.-Y.H.); (C.-Y.Y.); (P.-S.H.); (S.-F.C.); (C.-C.L.); (J.-M.C.); (R.T.)
- College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan
| | - Cheng-Chou Lai
- Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan; (T.-Y.T.); (J.-F.Y.); (Y.-J.H.); (Y.-J.C.); (H.-Y.H.); (C.-Y.Y.); (P.-S.H.); (S.-F.C.); (C.-C.L.); (J.-M.C.); (R.T.)
- College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan
| | - Jy-Ming Chiang
- Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan; (T.-Y.T.); (J.-F.Y.); (Y.-J.H.); (Y.-J.C.); (H.-Y.H.); (C.-Y.Y.); (P.-S.H.); (S.-F.C.); (C.-C.L.); (J.-M.C.); (R.T.)
- College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan
| | - Reiping Tang
- Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan; (T.-Y.T.); (J.-F.Y.); (Y.-J.H.); (Y.-J.C.); (H.-Y.H.); (C.-Y.Y.); (P.-S.H.); (S.-F.C.); (C.-C.L.); (J.-M.C.); (R.T.)
- College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan
| | - Wen-Sy Tsai
- Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33305, Taiwan; (T.-Y.T.); (J.-F.Y.); (Y.-J.H.); (Y.-J.C.); (H.-Y.H.); (C.-Y.Y.); (P.-S.H.); (S.-F.C.); (C.-C.L.); (J.-M.C.); (R.T.)
- College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan
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12
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Kranenburg O, van der Speeten K, de Hingh I. Peritoneal Metastases From Colorectal Cancer: Defining and Addressing the Challenges. Front Oncol 2021; 11:650098. [PMID: 33816304 PMCID: PMC8010649 DOI: 10.3389/fonc.2021.650098] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 02/15/2021] [Indexed: 12/19/2022] Open
Abstract
The presence of peritoneal metastases (PM) in patients with colorectal cancer (CRC) is associated with an extremely poor prognosis. The diagnosis of PM is challenging, resulting in an underestimation of their true incidence. While surgery can be curative in a small percentage of patients, effective treatment for non-operable PM is lacking, and clinical and pre-clinical studies are relatively sparse. Here we have defined the major clinical challenges in the areas of risk assessment, detection, and treatment. Recent developments in the field include the application of organoid technology, which has generated highly relevant pre-clinical PM models, the application of diffusion-weighted MRI, which has greatly improved PM detection, and the design of small clinical proof-of-concept studies, which allows the efficient testing of new treatment strategies. Together, these developments set the stage for starting to address the clinical challenges. To help structure these efforts, a translational research framework is presented, in which clinical trial design is based on the insight gained from direct tissue analyses and pre-clinical (organoid) models derived from CRC patients with PM. This feed-forward approach, in which a thorough understanding of the disease drives innovation in its clinical management, has the potential to improve outcome in the years to come.
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Affiliation(s)
- Onno Kranenburg
- Department of Surgical Oncology, University Medical Center Utrecht, Utrecht, Netherlands
- Utrecht platform for Organoid Technology, Utrecht University, Utrecht, Netherlands
- *Correspondence: Onno Kranenburg
| | - Kurt van der Speeten
- Department of Surgical Oncology, Faculty of Medicine, Biomedical Research Institute (BIOMED) Research Institute, Hospital Oost-Limburg, Belgium and University Hasselt, Diepenbeek, Belgium
| | - Ignace de Hingh
- Department of Surgery, Research School for Oncology and Developmental Biology, Catharina Hospital Eindhoven, The Netherlands and Maastricht University, Maastricht, Netherlands
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13
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Cortes-Guiral D, Glehen O. Expanding Uses of HIPEC for Locally Advanced Colorectal Cancer: A European Perspective. Clin Colon Rectal Surg 2020; 33:253-257. [PMID: 32968360 DOI: 10.1055/s-0040-1713742] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Locally advanced colorectal cancer is a challenge for surgeons and medical oncologist; 10 to 20% colorectal cancer debut as locally advanced disease, with tumors extending through the colon wall with perforation and/or invasion of adjacent organs or structures. Those locally advanced tumors have a worse prognostic at any stage due not only to systemic dissemination but also in a high percentage of patients, to locoregional recurrence, in fact, peritoneal carcinomatosis of colorectal origin is so predictable that we can assess the risk for each patient according to some histopathological and clinical features: small peritoneal nodules resected in the first surgery (70% probability), ovarian metastases (60%), perforated tumor onset or intraoperative tumor rupture (50%), positive cytology (40%), and pT4/mucinous pT3 up to 40%. Prophylactic or adjuvant hyperthermic intraperitoneal chemotherapy seems to be a promising strategy for patients with advanced colorectal cancer to prevent the development of peritoneal recurrence and improve prognosis of this group of patients.
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Affiliation(s)
- Delia Cortes-Guiral
- General Surgery Department, Principe de Asturias University Hospital, Carretera de Alcala s/n, Alcalá de Henares, Madrid, Spain
| | - Olivier Glehen
- General Surgery Department (Surgical Oncology), Centre Hospitalier Lyon Sud (Hospices Civils de Lyon), Lyon, France
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14
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Abstract
There have been significant developments in the management of advanced and recurrent colorectal cancer in recent decades. 70% of primary colorectal tumours arise in the colon and for patients with stage I-III disease, the standard of care is surgical resection followed by adjuvant therapy where appropriate. Locoregional recurrence (LR) occurs in 4-11.5% of patients following treatment of primary colon cancer with curative intent, and can be categorised as peri-anastomotic, mesenteric/paracolic (nodal), retroperitoneal and peritoneal. Of these, peritoneal recurrence is usually recognised as the most challenging type of recurrence to manage. Patients with isolated peri-anastomotic or limited nodal recurrence in the mesentery or retroperitoneum may be curable by radical salvage surgery, which often requires en bloc multi-visceral resection, while patients with low volume peritoneal metastases may be candidates for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. Ensuring complete resection along embryonic mesocolic planes or en bloc resection of contiguously involved structures are best strategies to reduce the likelihood of local recurrence through a R1 resection margin. The role of complete mesocolic excision (CME) with high vascular ligation has been demonstrated to increase nodal yield and improve overall survival although this is more contentious. In patients with T4a disease and serosal surface involvement, peritoneal recurrence represents the greatest threat. Efforts for early diagnosis of peritoneal recurrence in these patients or prophylactic treatment, while intuitive have not demonstrated the survival benefit that would be expected. Other than locoregional recurrence (LR), systemic recurrence may occur in up to 50% of patients who have undergone curative resection for colorectal cancer. In keeping with portal venous outflow, the most common site of systemic recurrence is the liver. Although previously thought to be a fatal condition, liver resection is now the standard of care where liver metastases can be completely resected with clear margins plus leaving an adequate liver remnant with intact vascular inflow, outflow and biliary drainage. This can usually be achieved in 26-45% of patients presenting with liver metastases. Liver surgeons at the forefront of liver resection have also developed techniques to induce liver hypertrophy so as to improve likelihood of resectability. Even where patients have non-resectable disease, ablative techniques have become increasingly common. Naturally, none of these would be possible without the advent of improved chemotherapeutic and biological options in the field of medical oncology. Pulmonary metastasectomy with curative intent may be possible in a small number (10%) of patients with lung metastases, which is associated with an overall survival of up to 40%. Unlike liver metastases, proportionally less patients with pulmonary metastases will be resectable. For these patients, several ablative options are available. For all patients with recurrent colon cancer, patient selection for radical salvage surgery and decisions surrounding treatment strategy (including use of systemic therapy or ablative procedures) should take place in a multidisciplinary team setting.
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Affiliation(s)
- Kilian G M Brown
- SOuRCe (Surgical Outcomes Research Centre), Royal Prince Alfred Hospital, Sydney, Australia.,RPA Institute of Academic Surgery, Royal Prince Alfred Hospital, Sydney, Australia
| | - Cherry E Koh
- SOuRCe (Surgical Outcomes Research Centre), Royal Prince Alfred Hospital, Sydney, Australia.,RPA Institute of Academic Surgery, Royal Prince Alfred Hospital, Sydney, Australia.,Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney, Australia.,Sydney Medical School, Discipline of Surgery, University of Sydney, Australia
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15
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Baaten ICPA, West NP, Quyn AJ, Seymour MT, Seligmann JF. Colorectal cancer peritoneal metastases: Biology, treatment and next steps. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2020; 46:675-683. [PMID: 31806517 DOI: 10.1016/j.ejso.2019.10.035] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Revised: 10/18/2019] [Accepted: 10/28/2019] [Indexed: 01/22/2023]
Abstract
The presence of peritoneal metastases in patients with advanced colorectal cancer is associated with poor prognosis but the mechanisms for this are unclear. This review summarises the current knowledge of the pathophysiology, clinical features, prevalence, prognosis, and molecular biology of peritoneal metastases and the risk factors for the development of peritoneal metastases following resection of a primary colorectal tumour. Furthermore, the evidence for treatment strategies are described including cytoreductive surgery, hyperthermic intraperitoneal chemotherapy, early post-operative intraperitoneal chemotherapy, sequential post-operative intraperitoneal chemotherapy and emerging novel strategies. Active areas of research should include the identification of individuals at high risk of peritoneal metastases after curative resection of primary tumour, development of a surveillance program for high-risk patients, optimisation of systematic therapies and further investigation of the use of intraperitoneal chemotherapy.
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Affiliation(s)
- Ilona C P A Baaten
- Leeds Institute of Clinical Trial Research, University of Leeds, Leeds, United Kingdom.
| | - Nicholas P West
- Leeds Institute of Medical Research at St. James's, University of Leeds, St James's University Hospital, Beckett Street, Leeds, United Kingdom.
| | - Aaron J Quyn
- Leeds Institute of Medical Research at St. James's, University of Leeds, St James's University Hospital, Beckett Street, Leeds, United Kingdom.
| | - Matthew T Seymour
- Leeds Institute of Medical Research at St. James's, University of Leeds, St James's University Hospital, Beckett Street, Leeds, United Kingdom.
| | - Jenny F Seligmann
- Leeds Institute of Medical Research at St. James's, University of Leeds, St James's University Hospital, Beckett Street, Leeds, United Kingdom.
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16
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Veld JV, Wisselink DD, Amelung FJ, Consten ECJ, de Wilt JHW, de Hingh I, Bemelman WA, van Hooft JE, Tanis PJ. Synchronous and Metachronous Peritoneal Metastases in Patients with Left-Sided Obstructive Colon Cancer. Ann Surg Oncol 2020; 27:2762-2773. [PMID: 32170481 PMCID: PMC7334250 DOI: 10.1245/s10434-020-08327-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Indexed: 12/17/2022]
Abstract
Background Controversy exists on emergency setting as a risk factor for peritoneal metastases (PM) in colon cancer patients. Data in patients with obstruction are scarce. The aim of this study was to determine the incidence of synchronous and metachronous PM, risk factors for the development of metachronous PM, and prognostic implications within a large nationwide cohort of left-sided obstructive colon cancer (LSOCC). Methods Patients with LSOCC treated between 2009 and 2016 were selected from the Dutch ColoRectal Audit. Additional treatment and long-term outcome data were retrospectively collected from original patient files in 75 hospitals in 2017. Results In total, 3038 patients with confirmed obstruction and without perforation were included. Synchronous PM (at diagnosis or < 30 days postoperatively) were diagnosed in 148/2976 evaluable patients (5.0%), and 3-year cumulative metachronous PM rate was 9.9%. Multivariable Cox regression analyses revealed pT4 stage (HR 1.782, 95% CI 1.191–2.668) and pN2 stage (HR 2.101, 95% CI 1.208–3.653) of the primary tumor to be independent risk factors for the development of metachronous PM. Median overall survival in patients with or without synchronous PM was 20 and 63 months (p < 0.001) and 3-year overall survival of patients that did or did not develop metachronous PM was 48.1% and 77.0%, respectively (p < 0.001). Conclusion This population based study revealed a 5.0% incidence of synchronous peritoneal metastases in patients who underwent resection of left-sided obstructive colon cancer. The subsequent 3-year cumulative metachronous PM rate was 9.9%, with advanced tumor and nodal stage as independent risk factors for the development of PM. Electronic supplementary material The online version of this article (10.1245/s10434-020-08327-7) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Joyce Valerie Veld
- Department of Surgery, Amsterdam University Medical Centers, University of Amsterdam, Cancer Centre Amsterdam, Amsterdam, The Netherlands.,Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Cancer Centre Amsterdam, Amsterdam, The Netherlands
| | - Daniel Derk Wisselink
- Department of Surgery, Amsterdam University Medical Centers, University of Amsterdam, Cancer Centre Amsterdam, Amsterdam, The Netherlands
| | - Femke Julie Amelung
- Department of Surgery, Meander Medical Center, Amersfoort, The Netherlands.,Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Esther Catharina Josephina Consten
- Department of Surgery, Meander Medical Center, Amersfoort, The Netherlands.,Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
| | | | - Ignace de Hingh
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
| | - Wilhelmus Adrianus Bemelman
- Department of Surgery, Amsterdam University Medical Centers, University of Amsterdam, Cancer Centre Amsterdam, Amsterdam, The Netherlands
| | - Jeanin Elise van Hooft
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Cancer Centre Amsterdam, Amsterdam, The Netherlands
| | - Pieter Job Tanis
- Department of Surgery, Amsterdam University Medical Centers, University of Amsterdam, Cancer Centre Amsterdam, Amsterdam, The Netherlands.
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17
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Graversen M, Detlefsen S, Fristrup C, Pfeiffer P, Mortensen MB. Adjuvant Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) in resected high-risk colon cancer patients - study protocol for the PIPAC-OPC3 Trial. A prospective, controlled phase 2 Study. Pleura Peritoneum 2018; 3:20180107. [PMID: 30911655 PMCID: PMC6404996 DOI: 10.1515/pp-2018-0107] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2018] [Accepted: 05/07/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Peritoneal metastasis (PM) is the second most common site of recurrence in colon cancer (CC) patients and accounts for approximately one-third of all recurrences. Patients with T4 or intraperitoneal perforated colon cancers have an increased risk of developing PM, and since manifest PM is difficult to treat, high-risk patients should be offered prophylactic treatment. Here, we propose a study of adjuvant oxaliplatin administered as pressurized intraperitoneal aerosol chemotherapy (PIPAC OX) in patients with high-risk colon cancer (T4, perforated tumors, ovarian metastasis). METHODS PIPAC-OPC3 CC is a non-randomized, non-blinded phase 2 cohort study designed to treat high-risk colon cancer patients with adjuvant PIPAC-directed therapy. Based on an expected 90 % peritoneal recurrence-free survival with adjuvant PIPAC against the estimated 75 % without, 60 patients are needed (α: 0.05, power: 0.8). Eligible patients will receive two PIPAC treatments with oxaliplatin (92 mg/m2) at 4-6 week intervals. During laparoscopy, the peritoneum is biopsied at two locations, and peritoneal lavage with 500 mL of saline and laparoscopic ultrasound is performed. The patients are screened for adverse medical events and surgery-related complications after each PIPAC procedure. After the second PIPAC procedure, the patients will be examined in the outpatient clinic and followed with CT scans 12, 24 and 36 months after resection. The primary outcome of the PIPAC-OPC3 CC trial is to evaluate if PIPAC-directed adjuvant therapy can reduce the risk of PM. Secondary outcomes include the number of conversions from positive to negative peritoneal lavage cytology after one PIPAC procedure, completion rate of two adjuvant PIPAC treatments, toxicity and complication rate and recurrence-free and overall survival rates after 1, 3 and 5 years. RESULTS It is expected that PIPAC-directed adjuvant therapy can provide an absolute risk reduction of 15 % regarding the development of PM in high-risk colon cancer patients, and that this may result in increased survival rates. We expect that free intraperitoneal tumor cells (FITC) may be detected by peritoneal lavage performed just prior to the administration of PIPAC-directed therapy, and that this treatment may convert FITC-positive patients to a FITC-negative status. CONCLUSIONS This study may provide important knowledge to be used in designing additional studies on PIPAC in the adjuvant setting of other primary cancers. TRIAL REGISTRATION ClinicalTrials.gov Identifier NCT03280511 (2017-09-12). European Clinical Trials Database (EudraCT) 2017-002637-37.
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Affiliation(s)
- Martin Graversen
- Odense PIPAC Center (OPC) and Odense Pancreas Center (OPAC), Department of Oncology, Odense University Hospital, Odense C 5000, Denmark
| | - Sönke Detlefsen
- Odense PIPAC Center (OPC) and Odense Pancreas Center (OPAC), Department of Pathology, Odense University Hospital, Odense, Denmark
| | - Claus Fristrup
- Odense PIPAC Center (OPC) and Odense Pancreas Center (OPAC), Department of Oncology, Odense University Hospital, Odense, Denmark
| | - Per Pfeiffer
- Odense PIPAC Center (OPC) and Odense Pancreas Center (OPAC), Department of Oncology, Odense University Hospital, Odense, Denmark
| | - Michael Bau Mortensen
- Odense PIPAC Center (OPC) and Odense Pancreas Center (OPAC), HPB and Upper GI Section, Department of Surgery, Odense University Hospital, Odense, Denmark
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18
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Honoré C, Gelli M, Francoual J, Benhaim L, Elias D, Goéré D. Ninety percent of the adverse outcomes occur in 10% of patients: can we identify the populations at high risk of developing peritoneal metastases after curative surgery for colorectal cancer? Int J Hyperthermia 2018; 33:505-510. [PMID: 28540831 DOI: 10.1080/02656736.2017.1306119] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Peritoneal metastases (PM) occur in 3.4-6.3% after curative surgery for non-metastatic colorectal cancer. Systematic "2nd look" surgery helps overcoming the diagnostic problem but can be only proposed to selected patients. The aim of this study was to update the knowledge on risk factors of developing PM after curative surgery for colorectal cancer. METHODS A systematic review of the literature published between 2011 and 2016 was made, searching for all clinical studies reporting the incidence of recurrent PM after curative surgery for colorectal cancer and factors associated with the primary tumour that were likely to influence this recurrence rate. RESULTS Seven new clinical studies were considered informative for risk factors and added to the 16 reviewed in 2013. Even if the level of evidence was low, data suggested rates of recurrent PM at 1 year between 54% and 71% after completely resected synchronous PM, between 62% and 71% after resection of isolated synchronous ovarian metastases, of 27% after surgery for a perforated primary tumour, of 16% after surgery for a pT4 tumour, and between 11% and 36% after surgery for a mucinous histological subtype. No new risk factor was identified. CONCLUSIONS Evidence regarding the incidence of recurrent PM after curative surgery for colorectal cancer is poor. Situations at higher risk of recurrent PM are synchronous PM, synchronous isolated ovarian metastases, perforated primary tumour with serosa invasion and mucinous histological subtype.
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Affiliation(s)
- Charles Honoré
- a Department of Surgical Oncology , Gustave Roussy , Cancer Campus , Villejuif , France
| | - Maximiliano Gelli
- a Department of Surgical Oncology , Gustave Roussy , Cancer Campus , Villejuif , France
| | - Julie Francoual
- a Department of Surgical Oncology , Gustave Roussy , Cancer Campus , Villejuif , France
| | - Léonor Benhaim
- a Department of Surgical Oncology , Gustave Roussy , Cancer Campus , Villejuif , France
| | - Dominique Elias
- a Department of Surgical Oncology , Gustave Roussy , Cancer Campus , Villejuif , France
| | - Diane Goéré
- a Department of Surgical Oncology , Gustave Roussy , Cancer Campus , Villejuif , France
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19
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Kyang LS, Valle SJ, Alzahrani NA, Morris DL. Prevention of peritoneal recurrence in high-risk colorectal cancer and evidence of T4 status as a potential risk factor. ANZ J Surg 2018; 88:975-981. [PMID: 29510456 DOI: 10.1111/ans.14428] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2017] [Revised: 01/03/2018] [Accepted: 01/13/2018] [Indexed: 01/13/2023]
Affiliation(s)
- Lee Shyang Kyang
- Department of Surgery, St George Hospital; The University of New South Wales; Sydney New South Wales Australia
| | - Sarah J. Valle
- Department of Surgery, St George Hospital; The University of New South Wales; Sydney New South Wales Australia
| | - Nayef A. Alzahrani
- Department of Surgery, St George Hospital; The University of New South Wales; Sydney New South Wales Australia
- College of Medicine; Al Imam Muhammad Ibn Saud Islamic University (IMSIU); Riyadh Saudi Arabia
| | - David L. Morris
- Department of Surgery, St George Hospital; The University of New South Wales; Sydney New South Wales Australia
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20
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Nagata H, Ishihara S, Oba K, Tanaka T, Hata K, Kawai K, Nozawa H. Development and Validation of a Prediction Model for Postoperative Peritoneal Metastasis After Curative Resection of Colon Cancer. Ann Surg Oncol 2018; 25:1366-1373. [PMID: 29508182 DOI: 10.1245/s10434-018-6403-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Indexed: 01/02/2023]
Abstract
BACKGROUND Detection of peritoneal metastasis remains challenging due to the limited sensitivity of current examination methods. This study aimed to establish a prediction model for estimating the individual risk of postoperative peritoneal metastasis from colon cancer to facilitate early interventions for high-risk patients. METHODS This study investigated 1720 patients with stages 1-3 colon cancer who underwent curative resection at the University of Tokyo Hospital between 1997 and 2015. The data for the patients were retrospectively retrieved from their medical records. The risk score was developed using the elastic net techniques in a derivation cohort (973 patients treated in 1997-2009) and validated in a validation cohort (747 patients treated in 2010-2015). RESULTS The factors selected using the elastic net approaches included the T stage, N stage, number of examined lymph nodes, preoperative carcinoembryonic antigen level, large bowel obstruction, and anastomotic leakage. The model had good discrimination (c-index, 0.85) and was well-calibrated after application of the bootstrap resampling method. Discrimination and calibration were favorable in external validation (c-index, 0.83). The model presented a clear stratification of patients' risk for postoperative peritoneal recurrence, and decision curve analysis showed its net benefit across a wide range of threshold probabilities. CONCLUSIONS This study established and validated a prediction model that can aid clinicians in optimizing postoperative surveillance and therapeutic strategies according to the individual patient risk of peritoneal recurrence.
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Affiliation(s)
- Hiroshi Nagata
- Department of Surgical Oncology, Faculty of Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
| | - Soichiro Ishihara
- Surgery Department, Sanno Hospital, International University of Health and Welfare, Tokyo, Japan
| | - Koji Oba
- Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.,Interfaculty Initiative in Information Studies, The University of Tokyo, Tokyo, Japan
| | - Toshiaki Tanaka
- Department of Surgical Oncology, Faculty of Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Keisuke Hata
- Department of Surgical Oncology, Faculty of Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazushige Kawai
- Department of Surgical Oncology, Faculty of Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroaki Nozawa
- Department of Surgical Oncology, Faculty of Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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21
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Prognostic value of radiologically enlarged lymph nodes in patients with metastatic colorectal cancer: Subgroup findings of the randomized, open-label FIRE-3/AIO KRK0306 trial. Eur J Radiol 2018; 100:124-129. [PMID: 29496069 DOI: 10.1016/j.ejrad.2018.01.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Revised: 01/03/2018] [Accepted: 01/05/2018] [Indexed: 01/13/2023]
Abstract
PURPOSE To determine the prognostic impact of radiologically enlarged lymph nodes ≥ 10 mm on the survival of patients with metastatic colorectal cancer. MATERIALS AND METHODS The prospective, randomized, open-label FIRE-3/AIO KRK0306 trial evaluated the first-line therapy of patients with KRAS exon 2 wild-type metastatic colorectal cancer with fluorouracil, folinic acid and irinotecan plus either cetuximab or bevacizumab. In the RAS wild-type population (n = 400), adequately evaluable baseline computed tomographies (n = 339) were reviewed for enlarged regional and distant lymph nodes. Their prognostic relevance was retrospectively analyzed in uni- and multivariable Cox proportional hazard regressions. RESULTS Median overall survival was 21.7 months in patients with enlarged lymph nodes and 33.2 months in patients without (hazard rate ratio [HR] = 1.61, 95% confidence interval [CI], 1.23-2.09; P < 0.001). This was confirmed in multivariable analysis (HR = 1.37, 95% CI, 1.02-1.83; P = 0.036). Progression-free survival of patients with enlarged lymph nodes showed a consistent but insignificant trend (9.9 vs. 11.1 months; HR = 1.23, 95% CI, 0.98-1.54; P = 0.072). Enlarged lymph nodes were also associated with BRAF-mutations (P = 0.004). CONCLUSION The presence of radiologically enlarged lymph nodes in baseline staging has a negative prognostic value beyond established and potential prognostic parameters.
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22
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Cortes-Guiral D, Elias D, Cascales-Campos PA, Badía Yébenes A, Guijo Castellano I, León Carbonero AI, Martín Valadés JI, Garcia-Foncillas J, Garcia-Olmo D. Second-look surgery plus hyperthermic intraperitoneal chemotherapy for patients with colorectal cancer at high risk of peritoneal carcinomatosis: Does it really save lives? World J Gastroenterol 2017; 23:377-381. [PMID: 28210074 PMCID: PMC5291843 DOI: 10.3748/wjg.v23.i3.377] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2016] [Revised: 11/02/2016] [Accepted: 11/16/2016] [Indexed: 02/06/2023] Open
Abstract
The treatment of peritoneal carcinomatosis (PC) of colorectal origin with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) has a 5-year recurrence-free or cure rate of at least 16%, so it is no longer labeled as a fatal disease, and offers prolonged survival for patients with a low peritoneal carcinomatosis index. Metachronous PC of colorectal origin is so predictable that there is a model which has been used to successfully determine the individual risk of each patient. Patients at risk are clearly identified; those with the highest risk have small peritoneal nodules present in the first surgery (70% probability of developing PC), ovarian metastases (60%), perforated tumor onset or intraoperative tumor rupture (50%). Current clinical, biological and imaging techniques still lack sufficient sensitivity to diagnose PC in its initial stages, when CRS plus HIPEC has a greater impact and a higher cure rate. Second-look surgery with HIPEC or prophylactic HIPEC at the time of the first intervention have been proposed as means of preventing and/or anticipating clinical or radiological relapse in at-risk patients. Both techniques have shown a significant decrease in peritoneal relapses and should be considered essential weapons in the management of colorectal cancer.
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23
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Gelli M, Huguenin JF, Cerebelli C, Benhaim L, Honoré C, Elias D, Goéré D. Strategies to prevent peritoneal carcinomatosis arising from colorectal cancer. Future Oncol 2017; 13:907-918. [PMID: 28052691 DOI: 10.2217/fon-2016-0389] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
In the last decades, cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy became a curative option for peritoneal metastases in selected patients, otherwise considered for palliative therapy alone. Better knowledge of physiopathology of peritoneal spread and identification of predictive factors for peritoneal relapse prompted specialized centers to investigate the role of a 'proactive approach' in order to early detect peritoneal metastasis. These encouraging data could justify an active attitude in selected patients at high risk of peritoneal recurrence after curative resection of primary tumor. Selection criteria and the timing of complementary hyperthermic intraperitoneal chemotherapy remain important points of discussion. In this article, we will discuss treatment principles and future perspectives to early treat and, if possible, to prevent peritoneal dissemination after curative treatment of colorectal cancer.
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Affiliation(s)
- Maximiliano Gelli
- Department of Surgical Oncology, Gustave Roussy, Université Paris-Saclay, F-94805 Villejuif, France
| | - Janina Fl Huguenin
- Department of Surgical Oncology, Gustave Roussy, Université Paris-Saclay, F-94805 Villejuif, France
| | - Cecilia Cerebelli
- Department of Surgical Oncology, Gustave Roussy, Université Paris-Saclay, F-94805 Villejuif, France
| | - Léonor Benhaim
- Department of Surgical Oncology, Gustave Roussy, Université Paris-Saclay, F-94805 Villejuif, France
| | - Charles Honoré
- Department of Surgical Oncology, Gustave Roussy, Université Paris-Saclay, F-94805 Villejuif, France
| | - Dominique Elias
- Department of Surgical Oncology, Gustave Roussy, Université Paris-Saclay, F-94805 Villejuif, France
| | - Diane Goéré
- Department of Surgical Oncology, Gustave Roussy, Université Paris-Saclay, F-94805 Villejuif, France
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