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Varty GP, Patkar S, Gundavda K, Shah N, Goel M. Optimal treatment strategies for borderline resectable liver metastases from colorectal cancer. J Gastrointest Surg 2025; 29:101868. [PMID: 39448021 DOI: 10.1016/j.gassur.2024.10.023] [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: 04/10/2024] [Revised: 09/24/2024] [Accepted: 10/18/2024] [Indexed: 10/26/2024]
Abstract
BACKGROUND Traditionally, colorectal liver metastases (CRLMs) are divided into "initially resectable" and "initially unresectable." The terminology "borderline resectable" continues to be elusive without any common consensus or definition. This narrative review aims to decode the conundrum of "borderline resectable CRLM (BR-CRLM)" and to discuss optimal treatment strategies. METHODS A comprehensive review was performed using Medline/PubMed and Web of Science databases with a search period ending on January 1, 2024. Using PubMed, the terms "CRLM," "BR-CRLM," and "management of BR-CRLM" were searched. RESULTS The 2016 European Society for Medical Oncology guidelines defined the term "resectability" in CRLM using the "technical (surgical) criteria" and the "oncologically criteria." These 2 criteria form the basis of defining BR-CRLM. Thus, BR-CRLM can be either technically easy but with unfavorable oncologically criteria or technically difficult with favorable oncologically criteria. Although defining BR-CRLM by incorporating both these criteria seems to be the most logical way forward, there is currently a lot of heterogeneity in the literature. It is generally agreed upon that some form of chemotherapy needs to be administered in BR-CRLM before embarking on surgery. Conversion chemotherapy is used in patients with BR-CRLM in which there is a possibility of resection after effective downsizing. Along with improved effective chemotherapy, great strides have been made in pushing the limits of surgery to achieve resectability in this subset of patients. CONCLUSION Advanced surgical techniques and locoregional liver-directed therapies coupled with perioperative chemotherapy with or without targeted therapy have made long-term survival benefit, a reality in patients with BR-CRLM. Thus, the time has come to recognize "BR-CRLM" as a distinct entity.
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Affiliation(s)
- Gurudutt P Varty
- Division of Gastrointestinal and Hepatobiliary Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Shraddha Patkar
- Division of Gastrointestinal and Hepatobiliary Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Kaival Gundavda
- Division of Gastrointestinal and Hepatobiliary Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Niket Shah
- Division of Gastrointestinal and Hepatobiliary Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Mahesh Goel
- Division of Gastrointestinal and Hepatobiliary Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India.
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Piccolo G, Barabino M, Ghilardi G, Masserano R, Lecchi F, Piozzi GN, Bianchi PP. Detection and Real-Time Surgical Assessment of Colorectal Liver Metastases Using Near-Infrared Fluorescence Imaging during Laparoscopic and Robotic-Assisted Resections. Cancers (Basel) 2024; 16:1641. [PMID: 38730593 PMCID: PMC11083015 DOI: 10.3390/cancers16091641] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 04/19/2024] [Accepted: 04/20/2024] [Indexed: 05/13/2024] Open
Abstract
BACKGROUND The European Association of Endoscopic Surgery (EAES) recommends, with strong evidence, the use of indocyanine green (ICG) fluorescence imaging combined with intraoperative ultrasound (IOUS) to improve identification of superficial liver tumors. This study reports the use of ICG for the detection of colorectal liver metastases (CRLMs) during minimally invasive liver resection. METHODS A single-center consecutive series of minimally invasive (laparoscopic and robotic) hepatic resections for CRLMs was prospectively evaluated (April 2019 and October 2023). RESULTS A total of 25 patients were enrolled-11 undergoing laparoscopic and 14 undergoing robotic procedures. The median age was 65 (range 50-85) years. Fifty CRLMs were detected: twenty superficial, eight exophytic, seven shallow (<8 mm from the hepatic surface), and fifteen deep (>10 mm from the hepatic surface) lesions. The detection rates of CRLMs through preoperative imaging, laparoscopic ultrasound (LUS), ICG fluorescence, and combined modalities (ICG and LUS) were 88%, 90%, 68%, and 100%, respectively. ICG fluorescence staining allowed us to detect five small additional superficial lesions (not identified with other preoperative/intraoperative techniques). However, two lesions were false positive fluorescence accumulations. All rim fluorescence pattern lesions were CRLMs. ICG fluorescence was used as a real-time guide to assess surgical margins during parenchymal-sparing liver resections. All patients with integrity of the fluorescent rim around the CRLM displayed a radical resection during histopathological analysis. Four patients (8%) with a protruding rim or residual rim patterns had positive resection margins. CONCLUSIONS ICG fluorescence imaging can be integrated with other conventional intraoperative imaging techniques to optimize intraoperative staging. Rim fluorescence proved to be a valid indicator of the resection margins: by removing the entire fluorescent area, a tumor-negative resection (R0) is achieved.
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Affiliation(s)
- Gaetano Piccolo
- General Surgery Unit, Department of Health Sciences (DISS), San Paolo Hospital, University of Milan, 20142 Milano, Italy; (G.P.); (G.G.); (R.M.); (F.L.); (P.P.B.)
| | - Matteo Barabino
- General Surgery Unit, Department of Health Sciences (DISS), San Paolo Hospital, University of Milan, 20142 Milano, Italy; (G.P.); (G.G.); (R.M.); (F.L.); (P.P.B.)
| | - Giorgio Ghilardi
- General Surgery Unit, Department of Health Sciences (DISS), San Paolo Hospital, University of Milan, 20142 Milano, Italy; (G.P.); (G.G.); (R.M.); (F.L.); (P.P.B.)
| | - Riccardo Masserano
- General Surgery Unit, Department of Health Sciences (DISS), San Paolo Hospital, University of Milan, 20142 Milano, Italy; (G.P.); (G.G.); (R.M.); (F.L.); (P.P.B.)
| | - Francesca Lecchi
- General Surgery Unit, Department of Health Sciences (DISS), San Paolo Hospital, University of Milan, 20142 Milano, Italy; (G.P.); (G.G.); (R.M.); (F.L.); (P.P.B.)
| | - Guglielmo Niccolò Piozzi
- Department of Colorectal Surgery, Portsmouth Hospitals University NHS Trust, Portsmouth PO6 3LY, UK;
| | - Paolo Pietro Bianchi
- General Surgery Unit, Department of Health Sciences (DISS), San Paolo Hospital, University of Milan, 20142 Milano, Italy; (G.P.); (G.G.); (R.M.); (F.L.); (P.P.B.)
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Saklani A, Kazi M, Desouza A, Sharma A, Engineer R, Krishnatry R, Gudi S, Ostwal V, Ramaswamy A, Dhanwat A, Bhargava P, Mehta S, Sundaram S, Kale A, Goel M, Patkar S, Vartey G, Kulkarni S, Baheti A, Ankathi S, Haria P, Katdare A, Choudhari A, Ramadwar M, Menon M, Patil P. Tata Memorial Centre Evidence Based Management of Colorectal cancer. Indian J Cancer 2024; 61:S29-S51. [PMID: 38424681 DOI: 10.4103/ijc.ijc_66_24] [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: 01/31/2024] [Accepted: 02/01/2024] [Indexed: 03/02/2024]
Abstract
ABSTRACT This review article examines the evidence-based management of colorectal cancers, focusing on topics characterized by ongoing debates and evolving evidence. To contribute to the scientific discourse, we intentionally exclude subjects with established guidelines, concentrating instead on areas where the current understanding is dynamic. Our analysis encompasses a thorough exploration of critical themes, including the evidence surrounding complete mesocolic excision and D3 lymphadenectomy in colon cancers. Additionally, we delve into the evolving landscape of perioperative chemotherapy in both colon and rectal cancers, considering its nuanced role in the context of contemporary treatment strategies. Advancements in surgical techniques are a pivotal aspect of our discussion, with an emphasis on the utilization of minimally invasive approaches such as laparoscopy and robotic surgery in both colon and rectal cancers, including advanced rectal cases. Moving beyond conventional radical procedures, we scrutinize the feasibility and implications of endoscopic resections for small tumors, explore the paradigm of organ preservation in locally advanced rectal cancers, and assess the utility of total neoadjuvant therapy in the current treatment landscape. Our final segment reviews pivotal trials that have significantly influenced the management of colorectal liver and peritoneal metastasis.
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Affiliation(s)
- Avanish Saklani
- Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, India
- Homi Bhabha National Institute, Mumbai, India
| | - Mufaddal Kazi
- Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, India
- Homi Bhabha National Institute, Mumbai, India
- Department of Surgical Oncology, Advanced Centre of the Treatment, Research, and Education in Cancer, Kharghar, Navi Mumbai, India
| | - Ashwin Desouza
- Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, India
- Homi Bhabha National Institute, Mumbai, India
| | - Ankit Sharma
- Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, India
- Homi Bhabha National Institute, Mumbai, India
- Department of Surgical Oncology, Advanced Centre of the Treatment, Research, and Education in Cancer, Kharghar, Navi Mumbai, India
| | - Reena Engineer
- Homi Bhabha National Institute, Mumbai, India
- Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, India
| | - Rahul Krishnatry
- Homi Bhabha National Institute, Mumbai, India
- Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, India
| | - Shivkumar Gudi
- Homi Bhabha National Institute, Mumbai, India
- Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, India
| | - Vikas Ostwal
- Homi Bhabha National Institute, Mumbai, India
- Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India
| | - Anant Ramaswamy
- Homi Bhabha National Institute, Mumbai, India
- Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India
| | - Aditya Dhanwat
- Homi Bhabha National Institute, Mumbai, India
- Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India
| | - Prabhat Bhargava
- Homi Bhabha National Institute, Mumbai, India
- Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India
| | - Shaesta Mehta
- Homi Bhabha National Institute, Mumbai, India
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Mumbai, India
| | - Sridhar Sundaram
- Homi Bhabha National Institute, Mumbai, India
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Mumbai, India
| | - Aditya Kale
- Homi Bhabha National Institute, Mumbai, India
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Mumbai, India
| | - Mahesh Goel
- Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, India
- Homi Bhabha National Institute, Mumbai, India
| | - Shraddha Patkar
- Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, India
- Homi Bhabha National Institute, Mumbai, India
| | - Gurudutt Vartey
- Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, India
- Homi Bhabha National Institute, Mumbai, India
| | - Suyash Kulkarni
- Homi Bhabha National Institute, Mumbai, India
- Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, India
| | - Akshay Baheti
- Homi Bhabha National Institute, Mumbai, India
- Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, India
| | - Suman Ankathi
- Homi Bhabha National Institute, Mumbai, India
- Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, India
| | - Purvi Haria
- Homi Bhabha National Institute, Mumbai, India
- Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, India
| | - Aparna Katdare
- Homi Bhabha National Institute, Mumbai, India
- Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, India
| | - Amit Choudhari
- Homi Bhabha National Institute, Mumbai, India
- Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, India
| | - Mukta Ramadwar
- Homi Bhabha National Institute, Mumbai, India
- Department of Pathology, Tata Memorial Hospital, Mumbai, India
| | - Munita Menon
- Homi Bhabha National Institute, Mumbai, India
- Department of Pathology, Tata Memorial Hospital, Mumbai, India
| | - Prachi Patil
- Homi Bhabha National Institute, Mumbai, India
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Mumbai, India
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4
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Pham H, Dixon E. Integration of Next-Generation Sequencing in the Surgical Management of Colorectal Liver Metastasis. Ann Surg Oncol 2023; 30:6815-6823. [PMID: 37316745 DOI: 10.1245/s10434-023-13750-7] [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: 05/27/2022] [Accepted: 06/04/2023] [Indexed: 06/16/2023]
Abstract
Hepatic resection remains the treatment of choice for colorectal liver metastases. The advancement of surgical technique and use of perioperative systemic therapy has expanded the number and complexity of patients eligible for surgical resection. In recent years, investigation into gene mutations, such as RAS/RAF pathway, have led to targeted therapies that have significantly improved outcomes. Next-generation sequencing allows analysis of large number of genes that may have potential prognostic relevance in the clinical setting. This review summarizes the current applications of next-generation sequencing technology in metastatic colorectal cancer, focusing on its prognostic implications on patient management.
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Affiliation(s)
- Helen Pham
- Department of Surgery, Faculty of Medicine, University of Calgary, Foothills Medical Centre, Calgary, AB, Canada.
| | - Elijah Dixon
- Department of Surgery, Faculty of Medicine, University of Calgary, Foothills Medical Centre, Calgary, AB, Canada
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Dasari BVM, Raptis D, Syn N, Serrablo A, Ramia JM, Laurenzi A, Sturesson C, Pawlik TM, Siriwardena AK, Lesurtel M. Development and validation of a novel risk score to predict overall survival following surgical clearance of bilobar colorectal liver metastases. BJS Open 2023; 7:zrad085. [PMID: 37738617 PMCID: PMC10516618 DOI: 10.1093/bjsopen/zrad085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 07/11/2023] [Accepted: 07/16/2023] [Indexed: 09/24/2023] Open
Abstract
BACKGROUND Bilobar liver metastases from colorectal cancer pose a challenge for obtaining a satisfactory oncological outcome with an adequate future liver remnant. This study aimed to assess the clinical and pathological determinants of overall survival and recurrence-free survival among patients undergoing surgical clearance of bilobar liver metastases from colorectal cancer. METHODS A retrospective international multicentre study of patients who underwent surgery for bilobar liver metastases from colorectal cancer between January 2012 and December 2018 was conducted. Overall survival and recurrence-free survival at 1, 2, 3 and 5 years after surgery were the primary outcomes evaluated. The secondary outcomes were duration of postoperative hospital stay, and 90-day major morbidity and mortality rates. A prognostic nomogram was developed using covariates selected from a Cox proportional hazards regression model, and internally validated using a 3:1 random partition into derivation and validation cohorts. RESULTS A total of 1236 patients were included from 70 centres. The majority (88 per cent) of the patients had synchronous liver metastases. Overall survival at 1, 2, 3 and 5 years was 86.4 per cent, 67.5 per cent, 52.6 per cent and 33.8 per cent, and the recurrence-free survival rates were 48.7 per cent, 26.6 per cent, 19.2 per cent and 10.5 per cent respectively. A total of 25 per cent of patients had recurrent disease within 6 months. Margin positivity and progressive disease at liver resection were poor prognostic factors, while adjuvant chemotherapy in margin-positive resections improved overall survival. The bilobar liver metastases from colorectal cancer-overall survival nomogram was developed from the derivation cohort based on pre- and postoperative factors. The nomogram's ability to forecast overall survival at 1, 2, 3 and 5 years was subsequently validated on the validation cohort and showed high accuracy (overall C-index = 0.742). CONCLUSION Despite the high recurrence rates, overall survival of patients undergoing surgical resection for bilobar liver metastases from colorectal cancer is encouraging. The novel bilobar liver metastases from colorectal cancer-overall survival nomogram helps in counselling and informed decision-making of patients planned for treatment of bilobar liver metastases from colorectal cancer.
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Affiliation(s)
- Bobby V M Dasari
- Institute of Immunology and Immunotherapy, University of Birmingham,
Birmingham, UK
- Department of HPB Surgery and Liver Transplantation, Queen Elizabeth
Hospital, Birmingham, UK
| | - Dimitri Raptis
- Department of HPB Surgery and Liver Transplantation, Royal Free
Hospital, London, UK
| | - Nicholas Syn
- Department of HPB Surgery and Liver Transplantation, National University of
Singapore, Singapore
| | - Alejandro Serrablo
- HBP Surgical Division, Miguel Servet University Hospital,
Zaragoza, Spain
| | - Jose Manuel Ramia
- Department of Hepatobiliary Surgery and Liver Transplantation, Hospital
General Universitario de Alicante, Alicante,
Spain
| | - Andrea Laurenzi
- Hepatobiliary Surgery and Organ Transplantation, IRCCS Azienda
Ospedaliero-Universitaria di Bologna, Bologna,
Italy
| | - Christian Sturesson
- Division of Surgery, Department of Clinical Science, Intervention and
Technology (CLINTEC), Karolinska Institutet and Karolinska University
Hospital, Stockholm, Sweden
| | - Timothy M Pawlik
- Division of Surgery, Oncology, and Health Services Management and Policy,
The Ohio State University Wexner Medical Center, Ohio, USA
| | - Ajith K Siriwardena
- Department of Hepatobiliary Surgery, Manchester Royal
Infirmary, Manchester, UK
| | - Mickael Lesurtel
- Department of HPB Surgery & Liver Transplantation, Beaujon
Hospital—University of Paris Cité, Paris,
France
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Hepatectomy versus Chemotherapy for Resectable Colorectal Liver Metastases in Progression after Perioperative Chemotherapy: Expanding the Boundaries of the Curative Intent. Cancers (Basel) 2023; 15:cancers15030783. [PMID: 36765743 PMCID: PMC9913571 DOI: 10.3390/cancers15030783] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 01/23/2023] [Accepted: 01/24/2023] [Indexed: 02/01/2023] Open
Abstract
Disease progression (PD) at neoadjuvant chemotherapy for patients with colorectal liver metastases (CLMs) is considered a contraindication to hepatic resection. Our aim was to estimate the overall survival (OS) in patients undergoing surgery compared with those treated exclusively with chemotherapy in cases of PD. Patients from a single centre with PD were analyzed and subdivided into two groups: hepatectomy (HEP) versus chemotherapy (CHT). An Inverse Probability Weighting (IPW) was run to balance the baseline differences between the two groups. A Cox regression was carried out on identifying factors predicting mortality. From 2010 to 2020, 105 patients in PD to at least one line of chemotherapy were analyzed. Of these, 27 (25.7%) underwent hepatic resection. After a median follow-up of 30 (IQR 14-46) months, 61.9% were dead. The OS values at 1 and 3 years were 54.4 and 10.6% for CHT, and 95 and 46.8% for HEP (p < 0.001). After IPW, two balanced pseudopopulations were obtained: HEP = 85 and CHT = 103. The OS values at 1 and 3 years were 54.4 and 10.6% for CHT, and 97.8 and 49.3% for HEP (HR 0.256, 95%CI: 0.08-0.78, p = 0.033). After IPW, in the multivariate model, surgery resulted in the only protective variable (HR 0.198, 95%CI: 0.08-0.48, p = 0.0016). Our results show that hepatic resection could offer a chance of a longer OS than the prosecution of chemotherapy only in originally resectable patients.
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7
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Famularo S, Milana F, Cimino M, Franchi E, Giuffrida M, Costa G, Procopio F, Donadon M, Torzilli G. Upfront Surgery versus Neoadjuvant Perioperative Chemotherapy for Resectable Colorectal Liver Metastases: A Machine-Learning Decision Tree to Identify the Best Potential Candidates under a Parenchyma-Sparing Policy. Cancers (Basel) 2023; 15:cancers15030613. [PMID: 36765570 PMCID: PMC9913658 DOI: 10.3390/cancers15030613] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Revised: 01/13/2023] [Accepted: 01/17/2023] [Indexed: 01/20/2023] Open
Abstract
Addressing patients to neoadjuvant systemic chemotherapy followed by surgery rather than surgical resection upfront is controversial in the case of resectable colorectal -liver metastases (CLM). The aim of this study was to develop a machine-learning model to identify the best potential candidates for upfront surgery (UPS) versus neoadjuvant perioperative chemotherapy followed by surgery (NEOS). Patients at first liver resection for CLM were consecutively enrolled and collected into two groups, regardless of whether they had UPS or NEOS. An inverse -probability weighting (IPW) was performed to weight baseline differences; survival analyses; and risk predictions were estimated. A mortality risk model was built by Random-Forest (RF) to assess the best -potential treatment (BPT) for each patient. The characteristics of BPT-upfront and BPT-neoadjuvant candidates were automatically identified after developing a classification -and -regression tree (CART). A total of 448 patients were enrolled between 2008 and 2020: 95 UPS and 353 NEOS. After IPW, two balanced pseudo-populations were obtained: UPS = 432 and NEOS = 440. Neoadjuvant therapy did not significantly affect the risk of mortality (HR 1.44, 95% CI: 0.95-2.17, p = 0.07). A mortality prediction model was fitted by RF. The BPT was NEOS for 364 patients and UPS for 84. At CART, planning R1vasc surgery was the main factor determining the best candidates for NEOS and UPS, followed by primitive tumor localization, number of metastases, sex, and pre-operative CEA. Based on these results, a decision three was developed. The proposed treatment algorithm allows for better allocation according to the patient's tailored risk of mortality.
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Affiliation(s)
- Simone Famularo
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
- Division of Hepatobiliary Surgery, Department of Surgery, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
- Surgical Data Science Team, Institut de Recherche sur les Cancers de l’Appareil Digestif (IRCAD), 67000 Strasbourg, France
| | - Flavio Milana
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
- Division of Hepatobiliary Surgery, Department of Surgery, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Matteo Cimino
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
| | - Eloisa Franchi
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
| | - Mario Giuffrida
- General Surgery Unit, Department of Medicine and Surgery, University of Parma, 43121 Parma, Italy
| | - Guido Costa
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
- Division of Hepatobiliary Surgery, Department of Surgery, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Fabio Procopio
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
- Division of Hepatobiliary Surgery, Department of Surgery, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
| | - Matteo Donadon
- Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, Italy
- Department of General Surgery, University Maggiore Hospital Della Carità, 28100 Novara, Italy
| | - Guido Torzilli
- Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
- Division of Hepatobiliary Surgery, Department of Surgery, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy
- Correspondence:
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8
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Survival after liver resection and liver transplantation for colorectal liver metastases: a comparative analysis stratified by metabolic tumor volume assessed by 18F-FDG PET/CT. HPB (Oxford) 2022; 24:1055-1062. [PMID: 34924292 DOI: 10.1016/j.hpb.2021.11.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 11/05/2021] [Accepted: 11/29/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Many patients undergoing resection for colorectal liver metastases (CRLM) recur with poor survival. Overall survival (OS) following liver transplantation (LT) for CRLM is reported to be about 80% at 5 years. In this study, survival following resection versus transplantation for CRLM in patients with moderate (6-70 cm3) metabolic tumor volume (MTV) from the preoperative positron emission tomography (PET) was compared. METHODS Disease-free survival (DFS), OS and post recurrence survival (PRS) following resection (n = 18) and LT (n = 12) was compared by using the Kaplan Meier method and log rank test for patients with moderate MTV. RESULTS Patients undergoing LT had unresectable metastases, significantly lower age, higher tumor burden score and number of liver metastases, longer time from diagnosis to surgery, and more patients received neoadjuvant chemotherapy. OS at 5 years was 39% in the resection group and 83% in the LT group (P = 0.012). PRS was significantly improved in patients treated with LT compared to resection with 71% alive at 5 years from recurrence compared to 17% in the resection group (P = 0.017). CONCLUSION LT for selected patients seems to be superior to resection as treatment for CRLM for patients with moderate MTV.
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9
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Burlaka AA, Makhmudov DE, Lisnyi II, Paliichuk AV, Zvirych VV, Lukashenko AV. Parenchyma-sparing strategy and oncological prognosis in patients with colorectal cancer liver metastases. World J Surg Oncol 2022; 20:122. [PMID: 35430799 PMCID: PMC9013456 DOI: 10.1186/s12957-022-02579-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Accepted: 03/22/2022] [Indexed: 12/15/2022] Open
Abstract
Background Preliminary study results demonstrated parenchyma-sparing surgery (PSS) as an effective approach which allowed to remove colorectal cancer (CRC) metastatic lesions within the central liver cites and increased the probability of the liver re-resections. Methods The prospective analysis re-evaluation of the 185 CRC patients surgical treatment has been performed. Results An overall 5-year survival (OS) of the 185 enrolled patients was 43 ± 7%, and the mean and median value for OS was 48.7 ± 1.9% and 55.2 ± 5 (95% CI: 44.4–66.1) months. The 5-year OS for CRC patients whose metastatic lesions were predominantly located within peripheral and central liver segments was 56 ± 8% and 27 ± 9%, respectively (p = 0.08). A 5-year disease-free survival (DFS) rates of patients with peripheral and central liver cites metastatic lesions were 31 ± 7 % and 15 ± 7%, p = 0,12. And the DFS median was 34.2 and 46.5 months for R1v and R0 cohorts, respectively, p = 0.62. Conclusions Parenchyma-sparing surgery should be a priority pathway for complex treatment of patients with deeply located lesions of the right liver lobe. Trial registration The study is registered in https://www.researchregistry.com/browse-the-registry#home/registrationdetails/5ed9f60863e9bf0016624456/, no. 5679.
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10
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Banchini F, Luzietti E, Palmieri G, Bonfili D, Romboli A, Conti L, Capelli P. Laparoscopic Resection of Synchronous Liver Metastasis Involving the Left Hepatic Vein and the Common Trunk Bifurcation: A Strategy of Parenchyma-Sparing Resection with Left Sectionectomy and 4a Subsegmentectomy by Arantius Approach. Healthcare (Basel) 2022; 10:healthcare10030517. [PMID: 35326995 PMCID: PMC8950909 DOI: 10.3390/healthcare10030517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 03/05/2022] [Accepted: 03/09/2022] [Indexed: 11/29/2022] Open
Abstract
When colorectal cancer presents with liver metastasis, hepatic resection remains the most important factor in prolonging survival, and new paradigms have been proposed to augment resectability. An adequate liver remnant and vascularisation are the only limits in complex liver resection, and parenchyma-sparing surgery is a strategy for minimising the complications, preserving liver function, and allowing patients to undergo further liver resection. The laparoscopic approach represents a new challenge, especially when lesions are located in the superior or posterior part of the liver. We discuss the case of an 81-year-old patient with a single synchronous liver metastasis involving the left hepatic vein and leaning into the middle hepatic vein at the common trunk, where we performed a simultaneous laparoscopic colonic resection with a left sectionectomy extended to segment 4a. The strategic approach to the Arantius ligament by joining the left and middle hepatic vein allowed us to avoid a major liver hepatectomy, preserve the liver parenchyma, reduce complications, enhance patient recovery, and perform the entire procedure by laparoscopy. Our example suggests that the Arantius approach to the left hepatic vein and the common trunk could be a feasible approach to consider in laparoscopic surgery for lesions located in their proximity.
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Affiliation(s)
- Filippo Banchini
- Department of General Surgery, Guglielmo da Saliceto Hospital, 29100 Piacenza, Italy; (E.L.); (G.P.); (A.R.); (L.C.); (P.C.)
- Correspondence:
| | - Enrico Luzietti
- Department of General Surgery, Guglielmo da Saliceto Hospital, 29100 Piacenza, Italy; (E.L.); (G.P.); (A.R.); (L.C.); (P.C.)
| | - Gerardo Palmieri
- Department of General Surgery, Guglielmo da Saliceto Hospital, 29100 Piacenza, Italy; (E.L.); (G.P.); (A.R.); (L.C.); (P.C.)
| | - Deborah Bonfili
- Department of General Surgery, Università degli Studi di Parma, 43100 Parma, Italy;
| | - Andrea Romboli
- Department of General Surgery, Guglielmo da Saliceto Hospital, 29100 Piacenza, Italy; (E.L.); (G.P.); (A.R.); (L.C.); (P.C.)
| | - Luigi Conti
- Department of General Surgery, Guglielmo da Saliceto Hospital, 29100 Piacenza, Italy; (E.L.); (G.P.); (A.R.); (L.C.); (P.C.)
| | - Patrizio Capelli
- Department of General Surgery, Guglielmo da Saliceto Hospital, 29100 Piacenza, Italy; (E.L.); (G.P.); (A.R.); (L.C.); (P.C.)
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Lang H, Baumgart J, Roth W, Moehler M, Kloth M. Cancer gene related characterization of patterns and point of recurrence after resection of colorectal liver metastases. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1372. [PMID: 34733924 PMCID: PMC8506541 DOI: 10.21037/atm-21-292] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Accepted: 05/21/2021] [Indexed: 12/16/2022]
Abstract
Background Outcome after resection of CRLM is hampered by a high rate of recurrence. There are little data about the role of cancer related genes and their mutations in this scenario. The aim of our analysis was to assess the predictive power of cancer-related genes and their mutations on risk for and distribution of recurrence and the time of occurrence after resection of colorectal liver metastases (CRLM). Methods We included 130 patients with 167 liver resections. The work-up consisted of the analysis of a total of 720 cancer-related genes by next-generation sequencing (NGS). Results were correlated with the patterns and time of recurrence and survival. Results At the time of analysis, 89/130 patients (68%) had developed recurrence. This included liver only recurrence in 52%, lung only recurrence in 11% and disseminated disease in 37% of cases. In univariate analysis, alterations in the RAS/RAF pathway and in the SMAD family had significant predictive power for the time of recurrence (P<0.0001) whereas single mutations did not reach statistical significance in multivariate analysis. Mutations of PIK3CA were associated with a better prognosis and a later occurrence of relapse. A recurrence risk score (r-RS) based on mutations in these cancer related genes is predictive of the time of recurrence. Conclusions In conclusion, mutations in the RAS/RAF pathway and the SMAD family are risk factors for early recurrence. Mutations of PIK3CA are associated with a lower risk for recurrence after resection of CRLM. Cancer related genes and their mutations do not correlate with patterns of recurrence but are predictive for the timely onset of recurrence.
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Affiliation(s)
- Hauke Lang
- Department of General, Visceral and Transplantation Surgery, Universitätsmedizin Mainz, Mainz, Germany
| | - Janine Baumgart
- Department of General, Visceral and Transplantation Surgery, Universitätsmedizin Mainz, Mainz, Germany
| | - Wilfried Roth
- Department of Pathology, Universitätsmedizin Mainz, Mainz, Germany
| | - Markus Moehler
- Department of Gastroenterology and Hepatology, Universitätsmedizin Mainz, Mainz, Germany
| | - Michael Kloth
- Department of Pathology, Universitätsmedizin Mainz, Mainz, Germany
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12
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Schiergens TS, Drefs M, Dörsch M, Kühn F, Albertsmeier M, Niess H, Schoenberg MB, Assenmacher M, Küchenhoff H, Thasler WE, Guba MO, Angele MK, Rentsch M, Werner J, Andrassy J. Prognostic Impact of Pedicle Clamping during Liver Resection for Colorectal Metastases. Cancers (Basel) 2020; 13:E72. [PMID: 33383844 PMCID: PMC7795154 DOI: 10.3390/cancers13010072] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 12/23/2020] [Accepted: 12/24/2020] [Indexed: 12/25/2022] Open
Abstract
Pedicle clamping (PC) during liver resection for colorectal metastases (CRLM) is used to reduce blood loss and allogeneic blood transfusion (ABT). The effect on long-term oncologic outcomes is still under debate. A retrospective analysis of the impact of PC on ABT-demand regarding overall (OS) and recurrence-free survival (RFS) in 336 patients undergoing curative resection for CRLM was carried out. Survival analysis was performed by both univariate and multivariate methods and propensity-score (PS) matching. PC was employed in 75 patients (22%). No increased postoperative morbidity was monitored. While the overall ABT-rate was comparable (35% vs. 37%, p = 0.786), a reduced demand for more than two ABT-units was observed (p = 0.046). PC-patients had better median OS (78 vs. 47 months, p = 0.005) and RFS (36 vs. 23 months, p = 0.006). Multivariate analysis revealed PC as an independent prognostic factor for OS (HR = 0.60; p = 0.009) and RFS (HR = 0.67; p = 0.017). For PC-patients, 1:2 PS-matching (N = 174) showed no differences in the overall ABT-rate compared to no-PC-patients (35% vs. 40%, p = 0.619), but a trend towards reduced transfusion requirement (>2 ABT-units: 9% vs. 21%, p = 0.052; >4 ABT-units: 2% vs. 11%, p = 0.037) and better survival (OS: 78 vs. 44 months, p = 0.088; RFS: 36 vs. 24 months; p = 0.029). Favorable long-term outcomes and lower rates of increased transfusion demand were observed in patients with PC undergoing resection for CRLM. Further prospective evaluation of potential oncologic benefits of PC in these patients may be meaningful.
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Affiliation(s)
- Tobias S. Schiergens
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Munich, Marchioninistr 15, D-81377 Munich, Germany; (M.D.); (M.D.); (F.K.); (M.A.); (H.N.); (M.B.S.); (W.E.T.); (M.O.G.); (M.K.A.); (M.R.); (J.W.); (J.A.)
| | - Moritz Drefs
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Munich, Marchioninistr 15, D-81377 Munich, Germany; (M.D.); (M.D.); (F.K.); (M.A.); (H.N.); (M.B.S.); (W.E.T.); (M.O.G.); (M.K.A.); (M.R.); (J.W.); (J.A.)
| | - Maximilian Dörsch
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Munich, Marchioninistr 15, D-81377 Munich, Germany; (M.D.); (M.D.); (F.K.); (M.A.); (H.N.); (M.B.S.); (W.E.T.); (M.O.G.); (M.K.A.); (M.R.); (J.W.); (J.A.)
| | - Florian Kühn
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Munich, Marchioninistr 15, D-81377 Munich, Germany; (M.D.); (M.D.); (F.K.); (M.A.); (H.N.); (M.B.S.); (W.E.T.); (M.O.G.); (M.K.A.); (M.R.); (J.W.); (J.A.)
| | - Markus Albertsmeier
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Munich, Marchioninistr 15, D-81377 Munich, Germany; (M.D.); (M.D.); (F.K.); (M.A.); (H.N.); (M.B.S.); (W.E.T.); (M.O.G.); (M.K.A.); (M.R.); (J.W.); (J.A.)
| | - Hanno Niess
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Munich, Marchioninistr 15, D-81377 Munich, Germany; (M.D.); (M.D.); (F.K.); (M.A.); (H.N.); (M.B.S.); (W.E.T.); (M.O.G.); (M.K.A.); (M.R.); (J.W.); (J.A.)
| | - Markus B. Schoenberg
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Munich, Marchioninistr 15, D-81377 Munich, Germany; (M.D.); (M.D.); (F.K.); (M.A.); (H.N.); (M.B.S.); (W.E.T.); (M.O.G.); (M.K.A.); (M.R.); (J.W.); (J.A.)
| | - Matthias Assenmacher
- Department of Statistics, Ludwig-Maximilians-University Munich, Akademiestr 1, D-80799 Munich, Germany; (M.A.); (H.K.)
| | - Helmut Küchenhoff
- Department of Statistics, Ludwig-Maximilians-University Munich, Akademiestr 1, D-80799 Munich, Germany; (M.A.); (H.K.)
| | - Wolfgang E. Thasler
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Munich, Marchioninistr 15, D-81377 Munich, Germany; (M.D.); (M.D.); (F.K.); (M.A.); (H.N.); (M.B.S.); (W.E.T.); (M.O.G.); (M.K.A.); (M.R.); (J.W.); (J.A.)
| | - Markus O. Guba
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Munich, Marchioninistr 15, D-81377 Munich, Germany; (M.D.); (M.D.); (F.K.); (M.A.); (H.N.); (M.B.S.); (W.E.T.); (M.O.G.); (M.K.A.); (M.R.); (J.W.); (J.A.)
| | - Martin K. Angele
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Munich, Marchioninistr 15, D-81377 Munich, Germany; (M.D.); (M.D.); (F.K.); (M.A.); (H.N.); (M.B.S.); (W.E.T.); (M.O.G.); (M.K.A.); (M.R.); (J.W.); (J.A.)
| | - Markus Rentsch
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Munich, Marchioninistr 15, D-81377 Munich, Germany; (M.D.); (M.D.); (F.K.); (M.A.); (H.N.); (M.B.S.); (W.E.T.); (M.O.G.); (M.K.A.); (M.R.); (J.W.); (J.A.)
| | - Jens Werner
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Munich, Marchioninistr 15, D-81377 Munich, Germany; (M.D.); (M.D.); (F.K.); (M.A.); (H.N.); (M.B.S.); (W.E.T.); (M.O.G.); (M.K.A.); (M.R.); (J.W.); (J.A.)
| | - Joachim Andrassy
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Munich, Marchioninistr 15, D-81377 Munich, Germany; (M.D.); (M.D.); (F.K.); (M.A.); (H.N.); (M.B.S.); (W.E.T.); (M.O.G.); (M.K.A.); (M.R.); (J.W.); (J.A.)
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Burlaka AA, Paliichuk AV, Iatsyna OI, Kolesnik ОО. Colorectal cancer liver metastases within the central and peripheral segments: Parenchymal sparing surgery adaptation. Ann Med Surg (Lond) 2020; 58:8-13. [PMID: 32874570 PMCID: PMC7452121 DOI: 10.1016/j.amsu.2020.07.052] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 07/27/2020] [Accepted: 07/30/2020] [Indexed: 02/06/2023] Open
Abstract
Background The debate over the surgical strategy optimization in colorectal cancer patients with liver metastases (mCRC) has been ongoing in the last 20 years. However, parenchyma sparing surgery (PPS) in cases of hard to reach liver cites (HTRLC) remain to be controversial. Methods A prospective analysis of 185 mCRC patients performed who were devided in two groups depending by predominant liver cite localization. Peripherally localized metastases (PLM) (n = 107) (S2, S3, S6, S7, Spiegel lobe and subcapsular area 1-2 cm below the liver surface). Group 2 included those with metastases localized in HTRLC (n = 78) - metastatic lesions of the "right venous core", portal and caval hilum, paracaval part of S1, "deep" parenchyma cites of S5, S8 and S4. Results In 26 (33,3%) and 32 (29,9%) patients of HTRLC and PLM, respectively, performed one liver re-resection (0,62). In HTRLC group 2 and more re-resection were performed in 7 (8,9%) cases while in PLM in 11 (10,3%), p = 0,76. Postoperative major morbidity was 24,4%, 21,8% (p = 0,15) and mortality 8,9%, 4,6% for HTRLC and PLM groups, respectively. R1v principles were implemented in 24 (30,7%) cases with centrally located metastases and in only 6 cases (5.6%) with peripheral localized metastases (p = 0,001). Cumulative 3-year disease-free survival (DSF) for PLM and HTRLC groups was 63% and 41% (p = 0,008). DFS for R1v (n = 24) and R0 (54) cochorts in HTRLC group was 33% and 43%, respeсtively (p = 0,44). Conclusions Principles of the PPS tactic provides an adequate removal of metastatic lesions in hard to reach liver cites allowing to maintain organ functions and increases the feasibility of the repeated liver resections in case of the initial disease progression.
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Affiliation(s)
- A A Burlaka
- Colorectal Cancer Department of National Cancer Institute, Ukraine
| | | | - O I Iatsyna
- Medical Director of National Cancer Institute, Ukraine
| | - О О Kolesnik
- Main Researcher of Colorectal Cancer Department of National Cancer Institute, Ukraine
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Affiliation(s)
- Juan Manuel O'Connor
- GI Clinical Oncology & GI Surgical Oncology, Instituto Alexander Fleming, Av Cramer 1180, Buenos Aires, C1426ANZ, Argentina
| | - Fernando Sanchez Loria
- GI Clinical Oncology & GI Surgical Oncology, Instituto Alexander Fleming, Av Cramer 1180, Buenos Aires, C1426ANZ, Argentina
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15
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Torzilli G, Viganò L, Fontana A, Procopio F, Terrone A, Cimino MM, Donadon M, Del Fabbro D. Oncological outcome of R1 vascular margin for mass-forming cholangiocarcinoma. A single center observational cohort analysis. HPB (Oxford) 2020; 22:570-577. [PMID: 31530450 DOI: 10.1016/j.hpb.2019.08.015] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Revised: 08/20/2019] [Accepted: 08/21/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Recent studies validated the possibility to detach colorectal liver metastases from vessels (R1vasc) featuring R1vasc equivalent to R0 and superior to tumor exposure along the transection plane (R1par). To clarify the outcome of R1 surgery (margin <1 mm) in patients with intrahepatic cholangiocarcinoma (MFCCC), distinguishing R1par and R1vasc resections. METHODS Patients undergoing resection for MFCCC between 2008 and 2016 were considered. Tumor detachment from 1st/2nd-order Glissonean pedicles or hepatic veins was performed in advanced diseases. R0, R1par, and R1vasc were compared. RESULTS The study included 84 resection areas in 59 patients (17 R1vasc). R1vasc group had local recurrence risk similar to R1par group (per-patient analysis 29% vs. 36%; per-resection area analysis 29% vs. 32%), higher than R0 group (3% and 2%, p = 0.003 and p = 0.0003). R1vasc and R1par groups had similar overall and recurrence-free survival (median OS 30 vs. 30 months; RFS 10 vs. 8 months), lower than R0 group (70 and 39 months, p = 0.066 and p = 0.007). CONCLUSION In MFCCC patients, R1vasc resection is not an adequate treatment. Local disease control and survival after R1vasc resection are lower than after R0 resection and similar to R1par resection. R1vasc resection could be exclusively considered to achieve resectability in otherwise unresectable patients.
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Affiliation(s)
- Guido Torzilli
- Division of Hepatobiliary & General Surgery, Department of Surgery, Humanitas Clinical and Research Center - IRCCS, Humanitas University, Via Manzoni 56, 20089, Rozzano, Milan, Italy.
| | - Luca Viganò
- Division of Hepatobiliary & General Surgery, Department of Surgery, Humanitas Clinical and Research Center - IRCCS, Humanitas University, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Andrea Fontana
- Division of Hepatobiliary & General Surgery, Department of Surgery, Humanitas Clinical and Research Center - IRCCS, Humanitas University, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Fabio Procopio
- Division of Hepatobiliary & General Surgery, Department of Surgery, Humanitas Clinical and Research Center - IRCCS, Humanitas University, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Alfonso Terrone
- Division of Hepatobiliary & General Surgery, Department of Surgery, Humanitas Clinical and Research Center - IRCCS, Humanitas University, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Matteo M Cimino
- Division of Hepatobiliary & General Surgery, Department of Surgery, Humanitas Clinical and Research Center - IRCCS, Humanitas University, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Matteo Donadon
- Division of Hepatobiliary & General Surgery, Department of Surgery, Humanitas Clinical and Research Center - IRCCS, Humanitas University, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Daniele Del Fabbro
- Division of Hepatobiliary & General Surgery, Department of Surgery, Humanitas Clinical and Research Center - IRCCS, Humanitas University, Via Manzoni 56, 20089, Rozzano, Milan, Italy
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16
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Extended Molecular Profiling Improves Stratification and Prediction of Survival After Resection of Colorectal Liver Metastases. Ann Surg 2020; 270:799-805. [PMID: 31634180 DOI: 10.1097/sla.0000000000003527] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE The aim of this study was to assess the effect of cancer-related genes and their mutations analyzed by next-generation sequencing (NGS) on the oncological outcome after resection of colorectal liver metastases (CRLM). BACKGROUND Traditional prognostic scores include clinical and pathological parameters of primary tumor and metastases. The modified clinical risk score (m-CS), based on size of metastases, primary tumor nodal status, and RAS mutation status outperformed traditional scores. We hypothesized to further improve the scoring system based on the results of NGS. METHODS Cancer tissues of 139 patients with CRLM were used for NGS. The work-up included the analysis of recurrent somatic mutations and copy number changes of 720 genes. Clinical data were extracted from a prospectively collected institutional liver database. RESULTS Depending on significance, the following cancer-related genes and their alterations (%) were further investigated: APC (86%), TP53 (78%), KRAS (29%), SMAD4 (15%), PIK3CA (14%), BRAF (8%), ERBB2 (6%), SMAD3 (5%), SMAD2 (4%), and NRAS (4%). The most predictive parameters for poor oncological outcome were alterations in the SMAD family (P = 0.0186) and RAS-RAF pathway (P = 0.032). Refining the m-CS by replacing RAS with RAS-RAF pathway and adding SMAD family resulted in an extended clinical risk score which is highly predictive for oncological outcome (P < 0.0001). CONCLUSION In conclusion, mutations of the SMAD family revealed a strong prognostic effect after surgery for CRLM. Integration of alterations of the SMAD family as well as the RAS/RAF pathway resulted in a new, still simple but highly prognostic score.
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Araujo RLC, Linhares MM. Pushing the limits of liver surgery for colorectal liver metastases: Current state and future directions. World J Gastrointest Surg 2019; 11:34-40. [PMID: 30842810 PMCID: PMC6397797 DOI: 10.4240/wjgs.v11.i2.34] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2018] [Revised: 01/29/2019] [Accepted: 01/30/2019] [Indexed: 02/06/2023] Open
Abstract
Liver surgery for the treatment of colorectal liver metastases is the standard treatment in a dynamic surgical field with many variables that should be considered in a curative intent scenario. Hepatectomy for colorectal liver metastases has undergone constant changes over the last 30 years, including indications until the need for rescue procedures of recurrent and advanced diseases as well as minimally invasive surgery. These advancements in liver surgery have not only resulted from overall improvements in the surgical field but have also resulted from a better understanding of the biological behavior of the disease, liver regeneration, and homeostasis during and after surgery. Improvements in anesthesiology, intensive care medicine, radiology, and surgical devices have correlated with further advancements of hepatectomies. Moreover, changes are still forthcoming, and both fields of augmented reality and artificial intelligence will likely have future contributions in this field in regard to both diagnoses and the planning of procedures. The aim of this editorial is to emphasize several aspects that have contributed to the paradigm shifts in colorectal liver metastases surgery over the last three decades as well as to discuss the factors concerning patient selection and the technical aspects of liver surgery. Finally, this editorial will highlight the promising new features of this surgery for diagnoses and treatments in this field.
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Affiliation(s)
- Raphael LC Araujo
- Department of Digestive Surgery, Escola Paulista de Medicina - UNIFESP, São Paulo SP 04023-062, Brazil
- Department of Oncology, Americas Medical Service/Brazil, United Health Group, Sao Paulo SP 04023-062, Brazil
- Postgraduation Program, Barretos Cancer Hospital, Barretos, São Paulo SP 04023-062, Brazil
| | - Marcelo M Linhares
- Department of Digestive Surgery, Escola Paulista de Medicina - UNIFESP, São Paulo SP 04023-062, Brazil
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19
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Torzilli G. Minimal Access and Parenchyma Sparing Liver Surgery: Converging or Diverging Concepts? Dig Surg 2018; 35:281-283. [PMID: 29886484 DOI: 10.1159/000486209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Accepted: 12/11/2017] [Indexed: 12/10/2022]
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20
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Vigano L, Darwish SS, Rimassa L, Cimino M, Carnaghi C, Donadon M, Procopio F, Personeni N, Del Fabbro D, Santoro A, Torzilli G. Progression of Colorectal Liver Metastases from the End of Chemotherapy to Resection: A New Contraindication to Surgery? Ann Surg Oncol 2018; 25:1676-1685. [PMID: 29488188 DOI: 10.1245/s10434-018-6387-8] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND Not all patients with resectable colorectal liver metastases (CLM) benefit from liver resection (LR); only patients with disease progression during chemotherapy are excluded from surgery. OBJECTIVE This study was performed to determine whether tumor behavior (stable disease/progression) from the end of chemotherapy to LR impacts prognosis. METHODS Patients undergoing LR after tumor response or stabilization during chemotherapy were considered. Overall, 128 patients who underwent examination by two imaging modalities (computed tomography/magnetic resonance imaging) after chemotherapy with a > 3-week interval between the two imaging modalities were analyzed. Any variation in CLM size was registered. Tumor progression was defined according to the response evaluation criteria in solid tumors (RECIST) criteria. RESULTS Among 128 patients with stable disease or partial response to preoperative chemotherapy, 32 (25%) developed disease progression in the chemotherapy to LR interval, with a disease progression rate of 17% when this interval was < 8 weeks. Survival was lower among patients with progression than those with stable disease [3-year overall survival (OS) 23.0 vs. 52.4%, and recurrence-free survival (RFS) 6.3% vs. 21.6%; p < 0.001]. Survival was extremely poor in patients with early progression (< 8 weeks) (0.0% 2-year OS, 12.5% 6-month RFS). Disease progression in the chemotherapy to LR interval was an independent negative prognostic factor for OS and RFS [hazard ratio 3.144 and 2.350, respectively; p < 0.001]. CONCLUSIONS Early disease progression in the chemotherapy to LR interval occurred in approximately 15% of patients and was associated with extremely poor survival. Even if these data require validation, the risk for early disease progression after chemotherapy should be considered, and, if progression is evident, the indication for surgery should be cautiously evaluated.
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Affiliation(s)
- Luca Vigano
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Clinical and Research Center - IRCCS, Humanitas University, Rozzano, Milan, Italy
| | - Shadya Sara Darwish
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Clinical and Research Center - IRCCS, Humanitas University, Rozzano, Milan, Italy
| | - Lorenza Rimassa
- Medical Oncology and Hematology Unit, Humanitas Clinical and Research Center, Humanitas University, Rozzano, Milan, Italy
| | - Matteo Cimino
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Clinical and Research Center - IRCCS, Humanitas University, Rozzano, Milan, Italy
| | - Carlo Carnaghi
- Medical Oncology and Hematology Unit, Humanitas Clinical and Research Center, Humanitas University, Rozzano, Milan, Italy
| | - Matteo Donadon
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Clinical and Research Center - IRCCS, Humanitas University, Rozzano, Milan, Italy
| | - Fabio Procopio
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Clinical and Research Center - IRCCS, Humanitas University, Rozzano, Milan, Italy
| | - Nicola Personeni
- Medical Oncology and Hematology Unit, Humanitas Clinical and Research Center, Humanitas University, Rozzano, Milan, Italy
| | - Daniele Del Fabbro
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Clinical and Research Center - IRCCS, Humanitas University, Rozzano, Milan, Italy
| | - Armando Santoro
- Medical Oncology and Hematology Unit, Humanitas Clinical and Research Center, Humanitas University, Rozzano, Milan, Italy
| | - Guido Torzilli
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Clinical and Research Center - IRCCS, Humanitas University, Rozzano, Milan, Italy.
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Torzilli G, Viganò L, Cimino M, Imai K, Vibert E, Donadon M, Mansour D, Castaing D, Adam R. Is Enhanced One-Stage Hepatectomy a Safe and Feasible Alternative to the Two-Stage Hepatectomy in the Setting of Multiple Bilobar Colorectal Liver Metastases? A Comparative Analysis between Two Pioneering Centers. Dig Surg 2018; 35:323-332. [PMID: 29439275 DOI: 10.1159/000486210] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2017] [Accepted: 12/10/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND Two-stage hepatectomy (TSH) is the present standard for multiple bilobar colorectal metastases (CLM). As alternative, ultrasound-guided one-stage hepatectomy (E-OSH) has been proposed even for deep-located nodules to compare TSH and E-OSH. METHODS All consecutive TSH at the Paul Brousse Hospital and E-OSH at the Humanitas Research Hospital were considered. The inclusion criteria were ≥6 CLM, ≥3 CLM in the left liver, and ≥1 lesion with vascular contact. A total of 74 TSH and 35 E-OSH were compared. RESULTS The 2 groups had similar characteristics. Drop-out rate of TSH was 40.5%. In comparison with the cumulated hepatectomies of TSH, E-OSH had lower blood loss (500 vs. 1,100 mL, p = 0.009), overall morbidity (37.1 vs. 70.5%, p = 0.003), severe morbidity (14.3 vs. 36.4%, p = 0.04), and liver-specific morbidity (22.9 vs. 40.9%, p = 0.02). R0 resection rate was similar between groups. E-OSH and completed TSH had similar overall survival (5-year 38.2 vs. 31.8%), recurrence-free survival (3-year 17.6 vs. 17.7%), and recurrence sites. CONCLUSIONS E-OSH is a safe alternative to TSH for multiple bilobar deep-located CLM. Whenever feasible, E-OSH should even be considered the preferred option because it has excellent safety and oncological outcomes equivalent to completed TSH, without the drop-out risk.
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Affiliation(s)
- Guido Torzilli
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas University, School of Medicine, Humanitas Research Hospital, Milan, Italy
| | - Luca Viganò
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas University, School of Medicine, Humanitas Research Hospital, Milan, Italy
| | - Matteo Cimino
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas University, School of Medicine, Humanitas Research Hospital, Milan, Italy
| | - Katsunori Imai
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, University of Paris, Paris, France
| | - Eric Vibert
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, University of Paris, Paris, France
| | - Matteo Donadon
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas University, School of Medicine, Humanitas Research Hospital, Milan, Italy
| | - Doaa Mansour
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas University, School of Medicine, Humanitas Research Hospital, Milan, Italy
| | - Denis Castaing
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, University of Paris, Paris, France
| | - Ren Adam
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, University of Paris, Paris, France
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22
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Klar E, Büchler MW, Lang H, Lordick F, Mittler J, Mizuno T, Torzilli G, Ulrich A, Vauthey JN. Oligometastases of Gastrointestinal Cancer Origin. Visc Med 2017; 33:76-81. [PMID: 28612021 DOI: 10.1159/000463468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Affiliation(s)
- Ernst Klar
- Department of General, Thoracic, Vascular and Transplantation Surgery, University of Rostock, Rostock, Germany, Rozzano (Milan), Italy
| | - Markus W Büchler
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany, Rozzano (Milan), Italy
| | - Hauke Lang
- Department of General, Visceral and Transplant Surgery, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany, Rozzano (Milan), Italy
| | - Florian Lordick
- University Cancer Center Leipzig (UCCL), University Hospital Leipzig, Leipzig, Germany, Rozzano (Milan), Italy
| | - Jens Mittler
- Department of General, Visceral and Transplant Surgery, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany, Rozzano (Milan), Italy
| | - Takashi Mizuno
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, Rozzano (Milan), Italy
| | - Guido Torzilli
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas University and Humanitas Research Hospital, Rozzano (Milan), Italy
| | - Alexis Ulrich
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany, Rozzano (Milan), Italy
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, Rozzano (Milan), Italy
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Torzilli G, Adam R, Viganò L, Imai K, Goransky J, Fontana A, Toso C, Majno P, de Santibañes E. Surgery of Colorectal Liver Metastases: Pushing the Limits. Liver Cancer 2016; 6:80-89. [PMID: 27995092 PMCID: PMC5159716 DOI: 10.1159/000449495] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND The recent advent of more effective chemotherapy and the development of surgical procedures have expanded the pool of resectable patients with colorectal liver metastases (CLM). Two-stage hepatectomy (TSH), associated liver partition and portal vein ligation for staged hepatectomy (ALPPS), and ultrasound-guided enhanced one-stage hepatectomy (e-OSH) are the surgical solutions proposed for these patients, but the range of indications for these procedures vary from institution to institution. SUMMARY The advantages and disadvantages of each approach are herein discussed. Patients who drop out between the staged operations of TSH limit its success rate, although predictive scores may help with patient selection and thereby optimize the results. Safety and oncological suitability are concerns to be addressed when considering ALPPS. These concerns notwithstanding, ALPPS has introduced an innovative concept in surgery: the monosegmental remnant liver. Studies involving e-OSH have proven the oncological suitability of tumor exposure once the CLM is detached from major intrahepatic vessels. This finding could expand the indications for e-OSH, although the technical challenges that it entails limit its spread among the surgical community. The liver-first approach involves the clearance of tumors from the liver before the colorectal primary is tackled. This approach fully justifies the complexity of e-OSH. KEY MESSAGES Predictive scores limiting the interstage dropout of TSH, partial and monosegmental ALPPS, and R1 vascular e-OSH justified by solid long-term results represent new insights that could help refne the patient assignment to each of these approaches. Additionally, liver transplantation is an emerging treatment for CLM that should be taken into account.
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Affiliation(s)
- Guido Torzilli
- Department of Surgery, Division of Hepatobiliary and General Surgery, Humanitas University, Hu-manitas Clinical and Research Hospital, Rozzano, Italy,*Guido Torzilli, MD, PhD Department of Surgery, Division of Hepatobiliary and General Surgery, Humanitas University, Humanitas Clinical and Research Hospital, Via Manzoni, 56, IT–20089, Rozzano, Milano (Italy), Tel. +39 02 8224 4769, E-Mail
| | - René Adam
- Centre Hépato-Biliaire, AP-HP, Hôpital Universitaire Paul Brousse, Villejuif, France
| | - Luca Viganò
- Department of Surgery, Division of Hepatobiliary and General Surgery, Humanitas University, Hu-manitas Clinical and Research Hospital, Rozzano, Italy
| | - Katsunori Imai
- Centre Hépato-Biliaire, AP-HP, Hôpital Universitaire Paul Brousse, Villejuif, France
| | - Jeremias Goransky
- Department of General Surgery, Division of Hepatobiliary and Pancreatic Surgery, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Andrea Fontana
- Department of Surgery, Division of Hepatobiliary and General Surgery, Humanitas University, Hu-manitas Clinical and Research Hospital, Rozzano, Italy
| | - Christian Toso
- Department of Visceral and Transplantation Surgery, University Hospitals of Geneva, Geneva, Switzerland
| | - Pietro Majno
- Department of Visceral and Transplantation Surgery, University Hospitals of Geneva, Geneva, Switzerland
| | - Eduardo de Santibañes
- Department of General Surgery, Division of Hepatobiliary and Pancreatic Surgery, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
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