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Yohanathan L, Chopra A, Simo K, Clancy TE, Khithani A, Anaya DA, Maegawa FA, Sheikh M, Raoof M, Jacobs M, Aleassa E, Boff M, Ferguson B, Tan-Tam C, Winslow E, Qadan M, D’Angelica MI. Assessment and treatment considerations for patients with colorectal liver metastases: AHPBA consensus guideline and update for surgeons. HPB (Oxford) 2025; 27:263-278. [PMID: 39828468 DOI: 10.1016/j.hpb.2024.12.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 11/20/2024] [Accepted: 12/09/2024] [Indexed: 01/22/2025]
Abstract
BACKGROUND Colorectal cancer most commonly metastasizes to the liver. While various treatment strategies have been developed, surgical management of these patients has vital implications on the prognosis and survival of this group of patients. There remains a need for a consensus guideline regarding the surgical evaluation and management of patients with colorectal liver metastases (CRLM). METHODS This review article is a consensus guideline established by the members of the AHPBA Professional Standards Committee, as an amalgamation of existent literature and a guide to surgeons managing this complex disease. RESULTS These guidelines reports the benefits and shortcomings of various diagnostic modalities including imaging and next-generation sequencing in the management of patients with CRLM. While surgery has established survival benefits in patients with resectable disease, this report notes the importance of treatment sequencing with non-surgical modalities as well as between colon and liver resection. Finally, the guidelines address the various treatment modalities for patients with unresectable disease, that may have significant impact on survival. CONCLUSION CRLM is a complex diagnosis which warrants multidisciplinary approach with early surgical involvement in both assessment and management of the disease, to optimize patient outcomes and survival.
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Papakonstantinou M, Fantakis A, Torzilli G, Donadon M, Chatzikomnitsa P, Giakoustidis D, Papadopoulos VN, Giakoustidis A. A Systematic Review of Disappearing Colorectal Liver Metastases: Resection or No Resection? J Clin Med 2025; 14:1147. [PMID: 40004679 PMCID: PMC11856073 DOI: 10.3390/jcm14041147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2025] [Revised: 01/29/2025] [Accepted: 02/07/2025] [Indexed: 02/27/2025] Open
Abstract
Background: Colorectal cancer is the second most common type of cancer and a leading cause of cancer-related deaths worldwide. Approximately 15% of the patients with colorectal cancer will already have liver metastases (CRLMs) at diagnosis. Luckily, the advances in chemotherapy regimens during the past few decades have led to increased rates of disease regression that could even render an originally unresectable disease resectable. In certain patients with CRLMs, the hepatic lesions are missing on preoperative imaging after neoadjuvant chemotherapy. These patients can undergo surgery with or without resection of the sites of the disappearing liver metastases (DLMs). In this systematic review, we assess the recurrence rate of the DLMs that were left unresected as well as the complete pathologic response of those resected. Methods: A literature search was conducted in PubMed for studies including patients with CRLMs who received neoadjuvant chemotherapy and had DLMs in preoperative imaging. Two independent reviewers completed the search according to the PRISMA checklist. Results: Three hundred and twenty-six patients with 1134 DLMs were included in our review. A total of 47 out of 480 DLMs (72.29%) that were removed had viable tumor cells in postoperative histology. One hundred and forty-five tumors could not be identified intraoperatively and were removed based on previous imaging, with thirty (20.69%) of them presenting viable cancer cells. Four hundred and sixty-five lesions could not be identified and were left in place. Of them, 152 (32.69%) developed local recurrence within 5 years. Of note, 34 DLMs could not be categorized as viable or non-viable tumors. Finally, DLMs that were identifiable intraoperatively had a higher possibility of viable tumors compared to non-identifiable ones (72.29% vs. 20.69%, respectively). Conclusions: Disappearing liver metastases that are left unresected have an increased possibility of recurrence. Patients receiving neoadjuvant treatment for CRLMs may have better survival chances after resecting all the DLM sites, either identifiable intraoperatively or not.
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Affiliation(s)
- Menelaos Papakonstantinou
- Aristotle University Surgery Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.P.); (A.F.); (P.C.); (D.G.); (V.N.P.)
| | - Antonios Fantakis
- Aristotle University Surgery Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.P.); (A.F.); (P.C.); (D.G.); (V.N.P.)
| | - Guido Torzilli
- Department of Surgery, Division of Hepatobiliary Surgery & General Surgery, Humanitas Research Hospital, 20089 Rozzano, Italy;
| | - Matteo Donadon
- Surgical Oncology Program, University Maggiore Hospital, University of Piemonte Orientale, 28100 Novara, Italy;
| | - Paraskevi Chatzikomnitsa
- Aristotle University Surgery Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.P.); (A.F.); (P.C.); (D.G.); (V.N.P.)
| | - Dimitrios Giakoustidis
- Aristotle University Surgery Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.P.); (A.F.); (P.C.); (D.G.); (V.N.P.)
| | - Vasileios N. Papadopoulos
- Aristotle University Surgery Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.P.); (A.F.); (P.C.); (D.G.); (V.N.P.)
| | - Alexandros Giakoustidis
- Aristotle University Surgery Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (M.P.); (A.F.); (P.C.); (D.G.); (V.N.P.)
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Davis JMK, Niazi MKK, Ricker AB, Tavolara TE, Robinson JN, Annanurov B, Smith K, Mantha R, Hwang J, Shrestha R, Iannitti DA, Martinie JB, Baker EH, Gurcan MN, Vrochides D. Predicting response to neoadjuvant chemotherapy for colorectal liver metastasis using deep learning on prechemotherapy cross-sectional imaging. J Surg Oncol 2024; 130:93-101. [PMID: 38712939 DOI: 10.1002/jso.27673] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Revised: 04/13/2024] [Accepted: 04/28/2024] [Indexed: 05/08/2024]
Abstract
BACKGROUND AND OBJECTIVES Deep learning models (DLMs) are applied across domains of health sciences to generate meaningful predictions. DLMs make use of neural networks to generate predictions from discrete data inputs. This study employs DLM on prechemotherapy cross-sectional imaging to predict patients' response to neoadjuvant chemotherapy. METHODS Adult patients with colorectal liver metastasis who underwent surgery after neoadjuvant chemotherapy were included. A DLM was trained on computed tomography images using attention-based multiple-instance learning. A logistic regression model incorporating clinical parameters of the Fong clinical risk score was used for comparison. Both model performances were benchmarked against the Response Evaluation Criteria in Solid Tumors criteria. A receiver operating curve was created and resulting area under the curve (AUC) was determined. RESULTS Ninety-five patients were included, with 33,619 images available for study inclusion. Ninety-five percent of patients underwent 5-fluorouracil-based chemotherapy with oxaliplatin and/or irinotecan. Sixty percent of the patients were categorized as chemotherapy responders (30% reduction in tumor diameter). The DLM had an AUC of 0.77. The AUC for the clinical model was 0.41. CONCLUSIONS Image-based DLM for prediction of response to neoadjuvant chemotherapy in patients with colorectal cancer liver metastases was superior to a clinical-based model. These results demonstrate potential to identify nonresponders to chemotherapy and guide select patients toward earlier curative resection.
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Affiliation(s)
- Joshua M K Davis
- Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, North Carolina, USA
| | - Muhammad Khalid Khan Niazi
- Center for Artificial Intelligence Research and the Clinical Image Analysis Lab, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
| | - Ansley B Ricker
- Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, North Carolina, USA
| | - Thomas E Tavolara
- Center for Artificial Intelligence Research and the Clinical Image Analysis Lab, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
| | - Jordan N Robinson
- Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, North Carolina, USA
| | - Bayram Annanurov
- Center for Artificial Intelligence Research and the Clinical Image Analysis Lab, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
| | - Kaylee Smith
- Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, North Carolina, USA
| | - Rohit Mantha
- Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, North Carolina, USA
| | - Jimmy Hwang
- Department of Medical Oncology, Atrium Health Carolinas Medical Center, Levine Cancer Institute, Charlotte, North Carolina, USA
| | - Ruchi Shrestha
- Department of Radiology, Atrium Health, Charlotte, North Carolina, USA
| | - David A Iannitti
- Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, North Carolina, USA
| | - John B Martinie
- Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, North Carolina, USA
| | - Erin H Baker
- Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, North Carolina, USA
| | - Metin N Gurcan
- Center for Artificial Intelligence Research and the Clinical Image Analysis Lab, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
| | - Dionisios Vrochides
- Department of Surgery, Atrium Health Carolinas Medical Center, Charlotte, North Carolina, USA
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Vitello DJ, Merkow RP. The Use of Hepatic Artery Infusion Chemotherapy for Unresectable Colorectal Cancer Liver Metastases. Cancer Treat Res 2024; 192:265-276. [PMID: 39212925 DOI: 10.1007/978-3-031-61238-1_13] [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: 09/04/2024]
Abstract
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in men and women (Siegel et al. in CA Cancer J Clin 72(1):7-33). Over one-half of newly diagnosed individuals will develop liver metastases. Among those with liver-only metastatic disease, only about one in five will be candidates for potentially curable resection.
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Affiliation(s)
- Dominic J Vitello
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Ryan P Merkow
- Department of Surgery, University of Chicago Pritzker School of Medicine, Chicago, IL, USA.
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Takamoto T, Nara S, Ban D, Mizui T, Murase Y, Esaki M, Shimada K, Hashimoto T, Makuuchi M. Objective Definition and Optimized Strategy for "Biologically Borderline Resectable" Colorectal Liver Metastases. World J Surg 2023; 47:2834-2845. [PMID: 37540268 DOI: 10.1007/s00268-023-07133-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/12/2023] [Indexed: 08/05/2023]
Abstract
BACKGROUND The prognostic benefit of preoperative chemotherapy leading to conversion surgery for unresectable colorectal liver metastases (CRLM) is well recognized, while that of neoadjuvant chemotherapy (NAC) compared with upfront surgery (UFS) for resectable CRLM is negligible. This study aims to assess the prognostic benefit and search for optimal indication of NAC for resectable advanced CRLM by establishing an objective definition of biologically borderline resectable (bBR) CRLM. METHODS A bicentric retrospective analysis of patients with CRLM undergoing curative-intent initial liver resection between 2007 and 2021 was performed. An original classification matrix was established, which reassessed technical resectability using virtual hepatectomy and oncological favorability using Beppu's nomogram. Patients with technically resectable but biologically unfavorable CRLM were classified into the bBR group. The propensity score matching analysis using preoperatively available factors was performed to assess long-term outcomes of the bBR-UFS and bBR-NAC groups. RESULTS Of 831 patients reviewed, 240 were categorized into the bBR group: bBR -UFS (n = 139) and bBR-NAC (n = 101). Ten (10%) in the bBR-NAC group (n = 101) experienced biological status change from unfavorable to favorable after NAC (Biological Conversion) and showed significantly longer overall survival (hazard ratio 5.63, 95% confidence interval 1.37-23.1; P = 0.016) than the bBR-UFS group. However, after propensity score matching, no significant difference between the UFS and NAC groups (n = 67 for each) was found in long-term outcomes. CONCLUSIONS NAC for bBR-CRLM did not enhance the prognostic impact of the following liver resection, except for a limited number of optimal candidates experiencing the Biological Conversion.
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Affiliation(s)
- Takeshi Takamoto
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.
| | - Satoshi Nara
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan
| | - Daisuke Ban
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan
| | - Takahiro Mizui
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan
| | - Yoshiki Murase
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan
| | - Minoru Esaki
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan
| | - Kazuaki Shimada
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan
| | - Takuya Hashimoto
- Division of Hepato-Biliary-Pancreatic and Transplantation Surgery, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Masatoshi Makuuchi
- Division of Hepato-Biliary-Pancreatic and Transplantation Surgery, Japanese Red Cross Medical Center, Tokyo, Japan
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Noda T, Takahashi H, Tei M, Nishida N, Hata T, Takeda Y, Ohue M, Wada H, Mizushima T, Asaoka T, Uemura M, Kobayashi S, Murata K, Satoh T, Doki Y, Eguchi H. Clinical outcomes of neoadjuvant chemotherapy for resectable colorectal liver metastasis with intermediate risk of postoperative recurrence: A multi-institutional retrospective study. Ann Gastroenterol Surg 2023; 7:479-490. [PMID: 37152774 PMCID: PMC10154835 DOI: 10.1002/ags3.12631] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 09/30/2022] [Indexed: 05/09/2023] Open
Abstract
Aims Risk-scoring systems for colorectal liver metastasis (CRLM) after hepatectomy allow prognoses to be predicted preoperatively. We investigated the clinical outcomes of neoadjuvant chemotherapy for resectable CRLM according to patient risk status, aiming to determine the subgroup of patients who could benefit from neoadjuvant chemotherapy. Methods In this multi-institutional retrospective analysis, the preoperative risk score was calculated from six previously reported factors: synchronous metastases, primary lymph node positivity, tumor number, largest tumor diameter, extrahepatic metastasis, and the preoperative carbohydrate antigen 19-9 level. Patients were divided into three groups according to their risk scores: low risk (score = 0), intermediate risk (score 1-10), and high risk (score ≥11). Overall and recurrence-free survival curves were calculated using the Kaplan-Meier method. After propensity-score matching in the intermediate-risk group, we compared clinicopathological features and outcomes. Results There were 318 cases, from 20 institutions. The preoperative risk score could be calculated in 277 cases. There were 34, 192, and 51 patients in the low-, intermediate-, and high-risk groups, respectively. Intermediate-risk group patients who received neoadjuvant chemotherapy had significantly better recurrence-free survival than that of patients without neoadjuvant chemotherapy (P = .0453). After propensity-score matching in the intermediate-risk group, the recurrence-free survival rate was better in patients who received neoadjuvant chemotherapy (P = .0261). But the overall survival rate was not improved after the matching. Conclusion Neoadjuvant chemotherapy for resectable CRLM might prolong the recurrence-free survival period for intermediate-risk patients with preoperative risk scores in the range of 1-10, but the overall survival was not improved by neoadjuvant chemotherapy.
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Affiliation(s)
- Takehiro Noda
- Department of Gastroenterological Surgery, Graduate School of MedicineOsaka UniversitySuitaJapan
| | - Hidekazu Takahashi
- Department of Gastroenterological Surgery, Graduate School of MedicineOsaka UniversitySuitaJapan
| | | | - Naohiro Nishida
- Department of Medical OncologyOsaka International Cancer InstituteOsakaJapan
| | - Taishi Hata
- Department of SurgeryKansai Rosai HospitalAmagasakiJapan
| | - Yutaka Takeda
- Department of SurgeryKansai Rosai HospitalAmagasakiJapan
| | - Masayuki Ohue
- Department of Gastroenterological SurgeryOsaka International Cancer InstituteOsakaJapan
| | - Hiroshi Wada
- Department of Gastroenterological SurgeryOsaka International Cancer InstituteOsakaJapan
| | | | | | - Mamoru Uemura
- Department of Gastroenterological Surgery, Graduate School of MedicineOsaka UniversitySuitaJapan
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Graduate School of MedicineOsaka UniversitySuitaJapan
| | - Kohei Murata
- Department of SurgeryKansai Rosai HospitalAmagasakiJapan
| | - Taroh Satoh
- Department of Gastroenterological Surgery, Graduate School of MedicineOsaka UniversitySuitaJapan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of MedicineOsaka UniversitySuitaJapan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of MedicineOsaka UniversitySuitaJapan
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7
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Berardi G, Chou J, Gonen M, Balachandran VP, Drebin J, Jarnagin WR, Kingham TP, Soares KC, Wei A, D'Angelica M. A Model to Predict Treatment Failure in Patients Undergoing Upfront Surgery for Resectable Colorectal Liver Metastases. Ann Surg Oncol 2023; 30:2820-2827. [PMID: 36692613 PMCID: PMC10089972 DOI: 10.1245/s10434-023-13113-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 12/07/2022] [Indexed: 01/25/2023]
Abstract
INTRODUCTION Patients who recur in the first year after resection of colorectal liver metastases (CRLM) do poorly. The aim of our study was to predict treatment failure in patients undergoing upfront resection with a nomogram. METHODS Data from patients resected between 1991 and 2019 were randomly split (70:30) into two cohorts. Treatment failure was defined as any recurrence or death within 12 months. A nomogram was constructed using multivariable logistic regression on the training cohort and validated using the testing cohort. RESULTS Overall, 783 patients were included. Primary tumor characteristics included 50% left-sided: 75.2% T3/4 and 56.5% node-positive. The median disease-free interval was 10 months, median number of metastases was 1 (1-50), and with a median size of 3.6 cm (0.2-22); 222 (28.3%) patients recurred within 1 year. Recurrence was mostly extrahepatic with or without liver involvement (150/222, 67.6%). Curative-intent treatment was possible in 37.8% of these patients. Primary location, T-stage and node status, disease-free interval, and number and size of metastases were associated with treatment failure. The area under the curve from the validation of the model was 0.6 (95% confidence interval 0.52-0.68). Patients with a high-risk of treatment failure (≥40%) had a worse survival from the landmark time of 12 months from surgery compared with those with low-risk (2-years: 82% vs. 70%; p = 0.0002). CONCLUSIONS Primary location, T stage, node status, disease-free interval, and number and size of metastases are associated with treatment failure. The survival of patients with a probability of treatment failure ≥40% is unfavorable. Future trials investigating the role of neoadjuvant therapy in these high-risk patients are warranted.
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Affiliation(s)
- Giammauro Berardi
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
| | - Joanne Chou
- Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Mithat Gonen
- Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Vinod P Balachandran
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jeffrey Drebin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - William R Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - T Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Kevin C Soares
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Alice Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Michael D'Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Ghazanfar MA, Abdelhamid A, Aldrighetti L, Sturesson C, Takemura N, Truant S, Fiorentini G, Teh C, Alikhanov R, Ahmed I, Hammond J, Ferrero A, Silva M, Pawlik T, Jones R, Bekheit M. The dilemma of the disappearing colorectal liver metastases: defining international trends in management. HPB (Oxford) 2023; 25:446-453. [PMID: 36775699 DOI: 10.1016/j.hpb.2023.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 12/18/2022] [Accepted: 01/10/2023] [Indexed: 02/14/2023]
Abstract
OBJECTIVE This survey sought to appraise the degree of consistency in the management of disappeared colorectal liver metastases (dCRLM) among liver surgeons in different countries. BACKGROUND Colorectal liver metastases (CRLM) account for half of the deaths secondary to colorectal cancer. Due to the high utilization of chemotherapy before surgery, some or all CRLM can disappear (dCRLM) but management of dCRLMs remains unclear. METHODS Seven simulated scenarios of dCRLM were presented to experienced liver surgeons using an online platform. Treatment decisions were submitted and analysed using the multi-rater kappa method. The effect of the experience, complexity of scenarios, and location and number of dCRLM on treatment decision were analysed. RESULTS Sixty-seven liver surgeons from 25 countries completed the survey. There was no agreement about the therapeutic strategies of dCRLM in all scenarios (kappa 0.12, IQR 0.20-0.32). In scenarios with lower difficulty scores, surgeons tended to offer surgical resection for dCRLM alongside the visible CRLM (vCRLM), however, with poor agreement (kappa 0.32, IQR 0.19-0.51). No agreement was seen for clinical scenario in which all CRLM lesions disappeared (kappa 0.20). CONCLUSION There are clear inconsistencies in the management decisions of dCRLM. Better evidence is required to define optimal management strategies.
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Affiliation(s)
- Mudassar A Ghazanfar
- Institute of Medical Sciences, University of Aberdeen, Scotland, UK; Department of HPB Surgery, NHS Grampian, Scotland, Aberdeen, UK
| | - Amir Abdelhamid
- Institute of Medical Sciences, University of Aberdeen, Scotland, UK; Department of HPB Surgery, NHS Grampian, Scotland, Aberdeen, UK
| | - Luca Aldrighetti
- Hepatobiliary Surgery Division, San Raffaele Hospital, Milan, Italy
| | - Christian Sturesson
- Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Nobuyuki Takemura
- Department of Surgery, National Center for Global Health and Medicine (NCGM), Tokyo, Japan
| | - Stephanie Truant
- Department of Surgery, Centre Hospitalier Régional Universitaire de Lille: Lille, Nord-Pas-de-Calais, Lille, France
| | - Guido Fiorentini
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic Rochester, Rochester, USA
| | - Catherine Teh
- Department of Surgery, Makati Medical Center, Makati Metro Manila, Philippines; Department of Surgery, National Kidney & Transplant Institute, Quezon, Philippines; Department of Surgery, St Luke's Medical Center, Quezon, Philippines
| | - Ruslan Alikhanov
- Moscow Clinical Scientific Center, Department of Liver and Pancreatic Surgery and Transplantation, Russia
| | - Irfan Ahmed
- Institute of Medical Sciences, University of Aberdeen, Scotland, UK; Department of HPB Surgery, NHS Grampian, Scotland, Aberdeen, UK
| | - John Hammond
- Department of HPB and Transplantation, Freeman Hospital, Newcastle Upon Tyne, Newcastle, UK
| | | | - Michael Silva
- Department of Surgery, Oxford University Hospital, Oxford, UK
| | - Timothy Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Ohio, USA
| | - Robert Jones
- Northwest Hepatobiliary Unit, Department of Surgery, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Mohamed Bekheit
- Institute of Medical Sciences, University of Aberdeen, Scotland, UK; Department of HPB Surgery, NHS Grampian, Scotland, Aberdeen, UK; HPB Integrated Center of Care, Elite Integrated Centers of Excellence, Alexandria, Egypt.
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9
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Kuhlmann KF, Tufo A, Kok NF, Gordon-Weeks A, Poston GJ, Diaz Nieto R, Jones R, Fenwick SW, Malik HZ. Disappearing colorectal liver metastases in the era of state-of-the-art triple-modality diagnostic imaging. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:1016-1022. [PMID: 36702715 DOI: 10.1016/j.ejso.2023.01.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 12/19/2022] [Accepted: 01/11/2023] [Indexed: 01/13/2023]
Abstract
INTRODUCTION Systemic therapy can result in disappearance of colorectal liver metastases in up to 40% of patients. This might be an overestimation caused by suboptimal imaging modalities. The aim of this study was to investigate the use of imaging modalities and the incidence, management and outcome of patients with disappearing liver metastases (DLMs). METHODS This was a retrospective study of consecutive patients treated for colorectal liver metastases at a high volume hepatobiliary centre between January 2013 and January 2015 after receiving induction or neoadjuvant systemic therapy. Main outcomes were use of imaging modalities, incidence, management and longterm outcome of patients with DLMs. RESULTS Of 158 patients included, 32 (20%) had 110 DLMs. Most patients (88%) had initial diagnostic imaging with contrast enhanced-CT, primovist-MR and FDG-PET and 94% of patients with DLMs were restaged using primovist-MR. Patients with DLMs had significantly smaller metastases and the median initial size of DLMs was 10 mm (range 5-61). In the per lesion analysis, recurrence after "watch & wait" for DLMs occurred in 36%, while in 19 of 20 resected DLMs no viable tumour cells were found. Median overall (51 vs. 28 months, p < 0.05) and progression free survival (10 vs. 3 months, p = 0.003) were significantly longer for patients with DLMs. CONCLUSION Even state-of-the-art imaging and restaging cannot solve problems associated with DLMs. Regrowth of these lesions occurs in approximately a third of the lesions. Patients with DLMs have better survival.
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Affiliation(s)
- K F Kuhlmann
- Department of Surgical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, the Netherlands; Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom
| | - A Tufo
- Department of General Surgery, Ospedale del Mare, Via Enrico Russo, 80147, Naples, Italy; Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom
| | - N F Kok
- Department of Surgical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, the Netherlands
| | - A Gordon-Weeks
- Nuffield Department of Surgical Sciences, University of Oxford, Old Road, OX3 7BN, United Kingdom
| | - G J Poston
- Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom
| | - R Diaz Nieto
- Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom
| | - R Jones
- Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom
| | - S W Fenwick
- Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom
| | - H Z Malik
- Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom.
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Villard C, Abdelrafee A, Habib M, Ndegwa N, Jorns C, Sparrelid E, Allard MA, Adam R. Prediction of survival in patients with colorectal liver metastases- development and validation of a prognostic score model. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:2432-2439. [PMID: 35786533 DOI: 10.1016/j.ejso.2022.06.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 05/10/2022] [Accepted: 06/17/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Metastatic spread of colorectal cancer to the liver impacts prognosis. Advances in chemotherapy have resulted in increased resectability rates and thereby improved survival in patients with colorectal liver metastases (CRLM). However, criteria are needed to ensure that patients selected for hepatic resection benefit from the invasive therapy. The study aimed to construct a predictive model for overall survival (OS) in patients with CRLM, based on preoperatively available information. METHODS The retrospective cohort study reviewed all patients with CRLM discussed at multidisciplinary team conference at Karolinska University Hospital, Stockholm, Sweden, 2013-2018. Independent prognostic factors for OS were identified, based on which a score model was generated. The model was validated on patients treated for CRLM at Hôpital Universitaire Paul Brousse, Villejuif, France, 2007-2018. Calibration and discrimination methods were used for internal and external validation. RESULTS The Swedish development cohort included 1013 patients, the French validation cohort 391 patients. Poor OS was significantly associated with age>60years (hazard ratio (HR) 3.57 (95%CI 2.18-9.94)), number of CRLM (HR 4.59 (2.83-12.20)), diameter of largest CRLM>5 cm (HR 2.59 (1.74-5.03)), right-sided primary tumour (HR 2.98 (2.00-5.80)), extrahepatic disease (HR 4.14 (2.38-15.87)) and non-resectability (HR 0.77 (0.66-0.90)). The C-statistic for prediction of OS was .74, in the development cohort and 0.69 in the validation cohort. CONCLUSION The presented predictive score model can adequately predict OS for patients at the initial diagnosis of CRLM. The prognostic model could be of clinical value in the management of all patients with CRLM, by predicting individualized survival and thereby facilitating treatment recommendations.
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Affiliation(s)
- Christina Villard
- Department of Transplantation Surgery, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
| | - Ahmed Abdelrafee
- Gastrointestinal Surgery Center, Department of Surgery, Mansoura University, Mansoura, Egypt
| | - Miriam Habib
- Centre Hépato-Biliaire AP-HP Hôpital Paul Brousse, Equipe Recherche « Chronothérapie, Cancers et Transplantation » Université Paris-Saclay, Villejuif, France
| | - Nelson Ndegwa
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Carl Jorns
- Department of Transplantation Surgery, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Ernesto Sparrelid
- Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; Department of Cancer, Division of Upper GI, Karolinska University Hospital, Stockholm, Sweden
| | - Marc-Antoine Allard
- Centre Hépato-Biliaire AP-HP Hôpital Paul Brousse, Equipe Recherche « Chronothérapie, Cancers et Transplantation » Université Paris-Saclay, Villejuif, France
| | - René Adam
- Centre Hépato-Biliaire AP-HP Hôpital Paul Brousse, Equipe Recherche « Chronothérapie, Cancers et Transplantation » Université Paris-Saclay, Villejuif, France
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11
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Ahmed S, Bosma N, Moser M, Ahmed S, Brunet B, Davies J, Doll C, Dueck DA, Kim CA, Ji S, Le D, Lee-Ying R, Lim H, McGhie JP, Mulder K, Park J, Ravi D, Renouf DJ, Schellenberg D, Wong RPW, Zaidi A. Systemic Therapy and Its Surgical Implications in Patients with Resectable Liver Colorectal Cancer Metastases. A Report from the Western Canadian Gastrointestinal Cancer Consensus Conference. Curr Oncol 2022; 29:1796-1807. [PMID: 35323347 PMCID: PMC8947455 DOI: 10.3390/curroncol29030147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 02/20/2022] [Accepted: 03/04/2022] [Indexed: 11/24/2022] Open
Abstract
The Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) convened virtually on 4 November 2021. The WCGCCC is an interactive multi-disciplinary conference attended by health care professionals, including surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals from across four Western Canadian provinces, British Columbia, Alberta, Saskatchewan, and Manitoba, who are involved in the care of patients with gastrointestinal cancer. They participated in presentation and discussion sessions for the purpose of developing recommendations on the role of systemic therapy and its optimal sequence in patients with resectable metastatic colorectal cancer.
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Affiliation(s)
- Shahid Ahmed
- Saskatoon Cancer Center, Saskatchewan Cancer Agency, 20 Campus Drive, University of Saskatchewan, Saskatoon, SK S7N 4H4, Canada; (B.B.); (D.-A.D.); (D.L.)
| | - Nicholas Bosma
- British Columbia Cancer Agency, Vancouver, BC V5Z 4E6, Canada; (N.B.); (J.D.); (H.L.); (D.J.R.)
| | - Michael Moser
- Department of Surgery, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada;
| | - Shahida Ahmed
- CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada; (S.A.); (C.A.K.); (R.P.W.W.)
| | - Bryan Brunet
- Saskatoon Cancer Center, Saskatchewan Cancer Agency, 20 Campus Drive, University of Saskatchewan, Saskatoon, SK S7N 4H4, Canada; (B.B.); (D.-A.D.); (D.L.)
- Department of Radiation Oncology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada
| | - Janine Davies
- British Columbia Cancer Agency, Vancouver, BC V5Z 4E6, Canada; (N.B.); (J.D.); (H.L.); (D.J.R.)
| | - Corinne Doll
- Arnie Charbonneau Cancer Institute, Alberta Health Service, Calgary, AB T2N 4Z6, Canada; (C.D.); (R.L.-Y.)
| | - Dorie-Anna Dueck
- Saskatoon Cancer Center, Saskatchewan Cancer Agency, 20 Campus Drive, University of Saskatchewan, Saskatoon, SK S7N 4H4, Canada; (B.B.); (D.-A.D.); (D.L.)
- Department of Medical Oncology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada
| | - Christina A. Kim
- CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada; (S.A.); (C.A.K.); (R.P.W.W.)
| | - Shuying Ji
- Shared Health, Winnipeg, MB R3B 2K6, Canada;
| | - Duc Le
- Saskatoon Cancer Center, Saskatchewan Cancer Agency, 20 Campus Drive, University of Saskatchewan, Saskatoon, SK S7N 4H4, Canada; (B.B.); (D.-A.D.); (D.L.)
- Department of Radiation Oncology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada
| | - Richard Lee-Ying
- Arnie Charbonneau Cancer Institute, Alberta Health Service, Calgary, AB T2N 4Z6, Canada; (C.D.); (R.L.-Y.)
| | - Howard Lim
- British Columbia Cancer Agency, Vancouver, BC V5Z 4E6, Canada; (N.B.); (J.D.); (H.L.); (D.J.R.)
| | | | - Karen Mulder
- Cross Cancer Institute, Alberta Health Services, Edmonton, AB T6G 1Z2, Canada;
| | - Jason Park
- Department of Surgery, University of Manitoba, Winnipeg, MB R3T 2N2, Canada;
| | - Deepti Ravi
- Saskatchewan Health Authority, Saskatoon, SK S7K 0M7, Canada;
| | - Daniel J. Renouf
- British Columbia Cancer Agency, Vancouver, BC V5Z 4E6, Canada; (N.B.); (J.D.); (H.L.); (D.J.R.)
| | | | - Ralph P. W. Wong
- CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada; (S.A.); (C.A.K.); (R.P.W.W.)
| | - Adnan Zaidi
- Saskatoon Cancer Center, Saskatchewan Cancer Agency, 20 Campus Drive, University of Saskatchewan, Saskatoon, SK S7N 4H4, Canada; (B.B.); (D.-A.D.); (D.L.)
- Department of Medical Oncology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada
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Fluoreszenzbildgebung mit Indocyaningrün (ICG) in der Chirurgie von kolorektalen Lebermetastasen. COLOPROCTOLOGY 2022. [DOI: 10.1007/s00053-022-00590-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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13
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Matsuhashi N, Tomita H, Tanaka H, Iwata Y, Matsui S, Imai H, Fukada M, Mizutani C, Takahashi T, Yasufuku I, Suetsugu T, Mori R, Tanaka Y, Okumura N, Futamura M, Yoshida K. Evaluation of histopathological heterogeneity of colorectal cancer liver metastasis sites after preoperative chemotherapy. Mol Clin Oncol 2022; 16:61. [PMID: 35127086 PMCID: PMC8771193 DOI: 10.3892/mco.2022.2494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Accepted: 07/14/2021] [Indexed: 11/30/2022] Open
Abstract
Patients with liver metastases from colorectal cancer (CRLMs) frequently receive chemotherapy prior to liver resection. Histopathological assessment of the resected specimen can evaluate the response to chemotherapy. The present study analyzed the association between histopathological changes in the primary site and liver metastases. The present study comprised 45 patients with resectable CRLMs at the Surgical Oncology Department of Gifu University School of Medicine (Gifu, Japan) between January 2006 and August 2015. The study included 24 men and 21 women. The primary colonic tumor was located in the right side in 13 (28.9%) patients and the left side in 32 (71.9%) patients. The present study evaluated patients with metastatic colorectal cancer (31/45) after excluding those in whom histopathological heterogeneity between the primary and liver metastasis changed to grade 3 after chemotherapy. The group that underwent hepatectomy after chemotherapy (n=25) was compared with the group that underwent hepatectomy alone (n=6). In 16 (53.3%) out of 25 patients, histopathological heterogeneity of the liver metastasis was lost (P=0.04). In conclusion, chemotherapy appeared to change histopathological heterogeneity. The present study suggested that the histopathological change of intratumoral heterogeneity is reflected by the response to chemotherapy.
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Affiliation(s)
- Nobuhisa Matsuhashi
- Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan
| | - Hiroyuki Tomita
- Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan
| | - Hidenori Tanaka
- Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan
| | - Yoshinori Iwata
- Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan
| | - Satoshi Matsui
- Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan
| | - Hisashi Imai
- Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan
| | - Masahiro Fukada
- Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan
| | - Chika Mizutani
- Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan
| | - Takao Takahashi
- Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan
| | - Itaru Yasufuku
- Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan
| | - Tomonari Suetsugu
- Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan
| | - Ryutaro Mori
- Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan
| | - Yoshihiro Tanaka
- Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan
| | - Naoki Okumura
- Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan
| | - Manabu Futamura
- Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan
| | - Kazuhiro Yoshida
- Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan
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14
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Prognostic impact of neoadjuvant chemotherapy in patients with synchronous colorectal liver metastasis: A propensity score matching comparative study. Int J Surg 2021; 94:106106. [PMID: 34536602 DOI: 10.1016/j.ijsu.2021.106106] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 08/08/2021] [Accepted: 09/07/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND Synchronous colorectal liver metastasis (SCRLM) is at an advanced tumor stage and requires multidisciplinary treatments. Neoadjuvant chemotherapy (NAC) is thought to be an effective treatment modality, but its prognostic impact is still unclear. MATERIALS AND METHODS Patients with resectable SCRLM presented to eight university hospitals between 2007 and 2017 were retrospectively reviewed. Propensity score matching (PSM) was performed to adjust baseline characteristics between patients who received NAC with those who underwent up-front hepatectomy. The prognostic impact of NAC was then evaluated. RESULTS The cohort comprised of 320 patients: 151 patients received NAC and the remaining 169 patients underwent up-front hepatectomy. After a 1:1 ratio of PSM, 102 patients per group were selected. Within the PSM cohort, 66% patients had multiple liver tumors, with 15% having five or more liver tumors. The median survival (95% confidence interval) periods for patients with and without NAC in the PSM cohort were 88.5 (68.4 - not reached) and 84.2 (52.1 - not reached) months, respectively (P = 0.51). On multivariate analysis, the postoperative events in these patients including operative complications and use of adjuvant chemotherapy after hepatectomy were prognostic factors with hazards (95% confidence interval) being 1.88 (1.18-2.98) and 0.65 (0.42-1.01), respectively. CONCLUSION This PSM study was restricted to patients with SCRLM and relatively advanced tumor stagings. NAC did not show any significant prognostic impact. While operative complications had a significant prognostic impact, use of adjuvant chemotherapy after hepatectomy had only a marginal prognostic impact. Reconsideration of indications for NAC is needed.
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15
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Liu W, Zhang W, Xu Y, Li YH, Xing BC. A Prognostic Scoring System to Predict Survival Outcome of Resectable Colorectal Liver Metastases in this Modern Era. Ann Surg Oncol 2021; 28:7709-7718. [PMID: 34023948 DOI: 10.1245/s10434-021-10143-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 04/10/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND An individualized treatment decision is based on the accurate evaluation of clinical risk factors and prognosis for resectable colorectal liver metastases. The current study aimed to develop an effective nomogram to predict progression-free survival (PFS) and to design a treatment schedule preoperatively. METHODS The study enrolled a primary cohort of 532 patients with resectable colorectal liver metastases (CRLM) who underwent hepatic resection at two institutions and a validation cohort of 237 patients at two additional institutions with resectable CRLM between 1 January 2008 and 31 December 2018. A nomogram was created based on the independent predictors in the multivariable analysis of progression-free survival in the primary cohort. The predictive accuracy and discriminative ability of the nomogram were determined by the concordance index (C-index) and the calibration curve. The score was compared with the current standard Fong score and validated with an external cohort. RESULTS The independent risk factors for CRLM patients identified in the multivariable analysis were tumor larger than 5 cm, more than one tumor, RAS mutation, primary lymph node metastasis, and primary tumor located on the right side. All five factors were considered in the nomogram. The C-index of the nomogram for predicting survival was 0.696. With external validation, the C-index of the nomogram for the prediction of the PFS was 0.682, which demonstrated that this model has a good level of discriminative ability. For high-risk patients (score > 16), neoadjuvant chemotherapy improved PFS and overall survival (OS) after hepatic resection. CONCLUSION The current nomogram demonstrated an accurate performance in predicting PFS for resectable CRLM patients with liver-limited disease. Based on the current nomogram, high-risk patients (nomogram score > 16) might benefit from neoadjuvant chemotherapy.
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Affiliation(s)
- Wei Liu
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Hepatopancreatobiliary Surgery Department I, Beijing Cancer Hospital and Institute, Beijing, People's Republic of China
| | - Wei Zhang
- Department of Colorectal Surgery, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China
| | - Ye Xu
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China
| | - Yu-Hong Li
- Sun Yat-sen University Oncology Hospital, Internal Medicine of Digestive Tumor, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.
| | - Bao-Cai Xing
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Hepatopancreatobiliary Surgery Department I, Beijing Cancer Hospital and Institute, Beijing, People's Republic of China.
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16
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Villard C, Habib M, Nordenvall C, Nilsson PJ, Jorns C, Sparrelid E. Conversion therapy in patients with colorectal liver metastases. Eur J Surg Oncol 2021; 47:2038-2045. [PMID: 33640172 DOI: 10.1016/j.ejso.2021.02.019] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 01/25/2021] [Accepted: 02/16/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The occurrence of colorectal liver metastases (CRLM) impairs prognosis, yet long-term survival can be achieved by enabling liver resection. This study aims to describe factors associated with conversion therapy leading to liver surgery and treatment outcome. METHODS A retrospective cohort study was conducted including all patients with CRLM discussed at multidisciplinary team conference at Karolinska University Hospital, Stockholm, Sweden, from 2013 to 2018. Factors associated with conversion therapy and outcome following conversion therapy were analysed with logistic regression and survival analyses. RESULTS Out of 1023 patients with CRLM, 100 patients (10%) received conversion chemotherapy, out of whom 31 patients (31%) subsequently underwent liver resection. Patients in whom conversion chemotherapy resulted in liver resection were younger (median age 61 vs. 66 years, p = .024), less likely to have a KRAS/NRAS-mutated primary tumours (25% vs. 53%, p = .039) and more likely to have received anti-EGFR agents (32% vs. 4%, p = .001) than patients progressing during conversion chemotherapy. The median OS for patients treated with conversion chemotherapy leading to liver resection was 24 months, compared to 14 months for patients progressing during conversion chemotherapy, p < .001. The OS for patients progressing during conversion chemotherapy was similar to patients given palliative chemotherapy, approximately 13 months. CONCLUSION Conversion therapy offers a survival benefit in selected patients. Despite treatment advances, the majority of patients undergoing conversion chemotherapy never become eligible for curative treatment.
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Affiliation(s)
- C Villard
- Department of Cancer, Division of Upper GI, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
| | - M Habib
- Centre Hépato-Biliaire AP-HP Hôpital Paul Brousse, Equipe Recherche, Chronothérapie, Cancers et Transplantation, Université Paris-Saclay, Villejuif, France
| | - C Nordenvall
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - P J Nilsson
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - C Jorns
- Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; Department of Transplantation Surgery, Karolinska University, Stockholm, Sweden
| | - E Sparrelid
- Department of Cancer, Division of Upper GI, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
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17
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Ivashchenko OV, Smit JN, Nijkamp J, Ter Beek LC, Rijkhorst EJ, Kok NFM, Ruers TJM, Kuhlmann KFD. Clinical Implementation of In-House Developed MR-Based Patient-Specific 3D Models of Liver Anatomy. Eur Surg Res 2021; 61:143-152. [PMID: 33508828 DOI: 10.1159/000513335] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 11/20/2020] [Indexed: 11/19/2022]
Abstract
Knowledge of patient-specific liver anatomy is key to patient safety during major hepatobiliary surgery. Three-dimensional (3D) models of patient-specific liver anatomy based on diagnostic MRI images can provide essential vascular and biliary anatomical insight during surgery. However, a method for generating these is not yet publicly available. This paper describes how these 3D models of the liver can be generated using open source software, and then subsequently integrated into a sterile surgical environment. The most common image quality aspects that degrade the quality of the 3D models as well possible ways of eliminating these are also discussed. Per patient, a single diagnostic multiphase MRI scan with hepatospecific contrast agent was used for automated segmentation of liver contour, arterial, portal, and venous anatomy, and the biliary tree. Subsequently, lesions were delineated manually. The resulting interactive 3D model could be accessed during surgery on a sterile covered tablet. Up to now, such models have been used in 335 surgical procedures. Their use simplified the surgical treatment of patients with a high number of liver metastases and contributed to the localization of vanished lesions in cases of a radiological complete response to neoadjuvant treatment. They facilitated perioperative verification of the relationship of tumors and the surrounding vascular and biliary anatomy, and eased decision-making before and during surgery.
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Affiliation(s)
- Oleksandra V Ivashchenko
- Department of Surgical Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands, .,Department of Radiology, Leiden University Medical Center, Medical Physics Group, Leiden, The Netherlands,
| | - Jasper N Smit
- Department of Surgical Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Jasper Nijkamp
- Department of Surgical Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Leon C Ter Beek
- Department of Medical Physics and Technology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Erik-Jan Rijkhorst
- Department of Medical Physics and Technology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Niels F M Kok
- Department of Surgical Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Theo J M Ruers
- Department of Surgical Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.,Faculty of Science and Technology (TNW), Nanobiophysics Group (NBP), University of Twente, Enschede, The Netherlands
| | - Koert F D Kuhlmann
- Department of Surgical Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
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18
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De Raffele E, Mirarchi M, Cuicchi D, Lecce F, Casadei R, Ricci C, Selva S, Minni F. Simultaneous colorectal and parenchymal-sparing liver resection for advanced colorectal carcinoma with synchronous liver metastases: Between conventional and mini-invasive approaches. World J Gastroenterol 2020; 26:6529-6555. [PMID: 33268945 PMCID: PMC7673966 DOI: 10.3748/wjg.v26.i42.6529] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Revised: 10/05/2020] [Accepted: 10/26/2020] [Indexed: 02/06/2023] Open
Abstract
The optimal timing of surgery in case of synchronous presentation of colorectal cancer and liver metastases is still under debate. Staged approach, with initial colorectal resection followed by liver resection (LR), or even the reverse, liver-first approach in specific situations, is traditionally preferred. Simultaneous resections, however, represent an appealing strategy, because may have perioperative risks comparable to staged resections in appropriately selected patients, while avoiding a second surgical procedure. In patients with larger or multiple synchronous presentation of colorectal cancer and liver metastases, simultaneous major hepatectomies may determine worse perioperative outcomes, so that parenchymal-sparing LR should represent the most appropriate option whenever feasible. Mini-invasive colorectal surgery has experienced rapid spread in the last decades, while laparoscopic LR has progressed much slower, and is usually reserved for limited tumours in favourable locations. Moreover, mini-invasive parenchymal-sparing LR is more complex, especially for larger or multiple tumours in difficult locations. It remains to be established if simultaneous resections are presently feasible with mini-invasive approaches or if we need further technological advances and surgical expertise, at least for more complex procedures. This review aims to critically analyze the current status and future perspectives of simultaneous resections, and the present role of the available mini-invasive techniques.
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Affiliation(s)
- Emilio De Raffele
- Division of Pancreatic Surgery, Department of Digestive Diseases, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, 40138 Bologna, Italy
| | - Mariateresa Mirarchi
- Dipartimento Strutturale Chirurgico, Ospedale SS Antonio e Margherita, 15057 Tortona (AL), Italy
| | - Dajana Cuicchi
- Surgery of the Alimentary Tract, Department of Digestive Diseases, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, 40138 Bologna, Italy
| | - Ferdinando Lecce
- Surgery of the Alimentary Tract, Department of Digestive Diseases, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, 40138 Bologna, Italy
| | - Riccardo Casadei
- Division of Pancreatic Surgery, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
| | - Claudio Ricci
- Division of Pancreatic Surgery, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
| | - Saverio Selva
- Division of Pancreatic Surgery, Department of Digestive Diseases, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, 40138 Bologna, Italy
| | - Francesco Minni
- Division of Pancreatic Surgery, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
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Martin J, Petrillo A, Smyth EC, Shaida N, Khwaja S, Cheow HK, Duckworth A, Heister P, Praseedom R, Jah A, Balakrishnan A, Harper S, Liau S, Kosmoliaptsis V, Huguet E. Colorectal liver metastases: Current management and future perspectives. World J Clin Oncol 2020; 11:761-808. [PMID: 33200074 PMCID: PMC7643190 DOI: 10.5306/wjco.v11.i10.761] [Citation(s) in RCA: 126] [Impact Index Per Article: 25.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 05/14/2020] [Accepted: 08/31/2020] [Indexed: 02/06/2023] Open
Abstract
The liver is the commonest site of metastatic disease for patients with colorectal cancer, with at least 25% developing colorectal liver metastases (CRLM) during the course of their illness. The management of CRLM has evolved into a complex field requiring input from experienced members of a multi-disciplinary team involving radiology (cross sectional, nuclear medicine and interventional), Oncology, Liver surgery, Colorectal surgery, and Histopathology. Patient management is based on assessment of sophisticated clinical, radiological and biomarker information. Despite incomplete evidence in this very heterogeneous patient group, maximising resection of CRLM using all available techniques remains a key objective and provides the best chance of long-term survival and cure. To this end, liver resection is maximised by the use of downsizing chemotherapy, optimisation of liver remnant by portal vein embolization, associating liver partition and portal vein ligation for staged hepatectomy, and combining resection with ablation, in the context of improvements in the functional assessment of the future remnant liver. Liver resection may safely be carried out laparoscopically or open, and synchronously with, or before, colorectal surgery in selected patients. For unresectable patients, treatment options including systemic chemotherapy, targeted biological agents, intra-arterial infusion or bead delivered chemotherapy, tumour ablation, stereotactic radiotherapy, and selective internal radiotherapy contribute to improve survival and may convert initially unresectable patients to operability. Currently evolving areas include biomarker characterisation of tumours, the development of novel systemic agents targeting specific oncogenic pathways, and the potential re-emergence of radical surgical options such as liver transplantation.
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Affiliation(s)
- Jack Martin
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Angelica Petrillo
- Department of Precision Medicine, Division of Medical Oncology, University of Campania "L. Vanvitelli", Napoli 80131, Italy, & Medical Oncology Unit, Ospedale del Mare, 80147 Napoli Italy
| | - Elizabeth C Smyth
- Department of Oncology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Nadeem Shaida
- Department of Radiology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB22 0QQ, United Kingdom
| | - Samir Khwaja
- Department of Radiology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB22 0QQ, United Kingdom
| | - HK Cheow
- Department of Nuclear Medicine, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Adam Duckworth
- Department of Pathology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Paula Heister
- Department of Pathology, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Raaj Praseedom
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Asif Jah
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Anita Balakrishnan
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Simon Harper
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Siong Liau
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Vasilis Kosmoliaptsis
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Emmanuel Huguet
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
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20
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Quantified MRI and 25OH-VitD3 can be used as effective biomarkers for patients with neoadjuvant chemotherapy-induced liver injury in CRCLM? BMC Cancer 2020; 20:767. [PMID: 32799832 PMCID: PMC7429712 DOI: 10.1186/s12885-020-07282-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Accepted: 08/09/2020] [Indexed: 12/26/2022] Open
Abstract
Background To evaluate proton-density fat-fraction (PDFF) and intravoxel incoherent motion (IVIM) techniques, and human 25-hydroxyvitamin D3 (25OH-VitD3) levels, as potential biomarkers in patients with colorectal cancer with liver metastasis (CRCLM). Changes were compared with those related to chemotherapy-associated steatohepatitis (CASH) and sinusoidal obstruction syndrome (SOS). Methods 63 patients with pathologically confirmed colorectal adenocarcinoma received 4–6 courses of NC before liver resection and underwent magnetic resonance imaging (MRI) with iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantification and IVIM sequences. Blood samples were analyzed using CTCAE. Pathological changes of liver tissues outside the metastases were assessed as the gold standard, and receiver operating characteristic (ROC) curves were analyzed. Results 16 cases had CASH liver injury, 14 cases had SOS changes, and 4 cases had CASH and SOS, and 7 showed no significant changes. Consistency between biochemical indices and pathological findings was poor (kappa = 0.246, p = 0.005). The areas under the ROC curve (AUCs) of ALT, AST, ALP, GGT, and TBIL were 0.571–0.691. AUCs of D, FF, and 25OH-VitD3 exceeded 0.8; when considering these markers together, sensitivity was 85.29% and specificity was 93.13%. ANOVA showed statistically significant differences among D, FF, and 25OH-VitD3 for different grades of liver injury (F = 4.64–26.5, p = 0.000–0.016). Conclusions D, FF, and 25OH-VitD3 are biomarkers for accurate prediction of NC-induced liver injury in patients with CRCLM, while FF and 25OH-VitD3 might be beneficial to distinguish liver injury grades. Trial registration Current Trials was retrospectively registered as ChiCTR1800015242 at Chinese Clinical Trial Registry on March 16, 2018.
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21
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Wang H, Li X, Peng R, Wang Y, Wang J. Stereotactic ablative radiotherapy for colorectal cancer liver metastasis. Semin Cancer Biol 2020; 71:21-32. [PMID: 32629077 DOI: 10.1016/j.semcancer.2020.06.018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 06/23/2020] [Accepted: 06/25/2020] [Indexed: 12/24/2022]
Abstract
Survival improvement of colorectal liver metastasis (CRLM) benefits from systemic therapy and metastasis-directed local therapy. Stereotactic ablative body radiotherapy (SABR), as a new efficient metastasis-directed local therapy with a systematic impact, plays a vital role in CRLM multidisciplinary treatment. SABR leads to a dramatic immunological change in the tumor microenvironment (TME) via differential activation of cytoprotective and cytotoxic pathways in malignant and non-malignant cells, in addition to direct tumor cell death. The synergy of SABR and immunotherapy might increase the abscopal response rate of out-field lesions by targeting different steps of the immune-mediated response, in addition to direct intratumoral cell death. The clinical treatment and efficacy of SABR, its influence on TME, and potential molecular underpinnings of which are the topic of this review.
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Affiliation(s)
- Hao Wang
- Department of Radiation Oncology, Peking University Third Hospital, 49 North Garden Road, Beijing, 100191, China
| | - Xuemin Li
- Department of Radiation Oncology, Peking University Third Hospital, 49 North Garden Road, Beijing, 100191, China
| | - Ran Peng
- Department of Radiation Oncology, Peking University Third Hospital, 49 North Garden Road, Beijing, 100191, China
| | - Yuxia Wang
- Department of Radiation Oncology, Peking University Third Hospital, 49 North Garden Road, Beijing, 100191, China
| | - Junjie Wang
- Department of Radiation Oncology, Peking University Third Hospital, 49 North Garden Road, Beijing, 100191, China.
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22
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Shur J, Orton M, Connor A, Fischer S, Moulton CA, Gallinger S, Koh DM, Jhaveri KS. A clinical-radiomic model for improved prognostication of surgical candidates with colorectal liver metastases. J Surg Oncol 2020; 121:357-364. [PMID: 31797378 DOI: 10.1002/jso.25783] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Accepted: 11/17/2019] [Indexed: 01/24/2023]
Abstract
BACKGROUND AND OBJECTIVES Colorectal cancer with liver metastases is potentially curable with surgical resection however clinical prognostic factors can insufficiently stratify patients. This study aims to assess whether radiomic features are prognostic and can inform clinical decision making. METHODS This single-site retrospective study included 102 patients who underwent colorectal liver metastases resection with preoperative computed tomography (CT), magnetic resonance imaging (MRI) with gadoxetic acid (EOB) and clinical covariates. A lasso-regularized multivariate Cox proportional hazards model was applied to 114 features (10 clinical, 104 radiomic) to determine association with disease-free survival (DFS). A prognostic index was derived using the significant Cox regression coefficients and their corresponding input features and a threshold was determined to classify patients into high- and low-risk groups, and DFS compared using log-rank tests. RESULTS Four covariates were significantly associated with DFS; bilobar disease (hazard ratio [HR]= 1.56; P = .0043), complete pathological response (HR= 0.67; P = .025), minimum pixel value (HR= 1.66; P = .00016), and small area emphasis (HR= 0.62; P = .0013) from the EOB-MRI data. Radiomic CT features were not prognostic. The prognostic index strongly stratified high- and low-risk prognostic groups (HR = 0.31; P = .00068). CONCLUSION Radiomic MRI features provided meaningful prognostic information above clinical covariates alone. This merits further validation for potential clinical implementation to inform management.
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Affiliation(s)
- Joshua Shur
- Department of Radiology, Royal Marsden Hospital, Sutton, UK
| | - Matthew Orton
- Department of Radiology, Royal Marsden Hospital, Sutton, UK
| | - Ashton Connor
- Department of Surgery, Duke University Hospital, Durham, North Carolina
| | - Sandra Fischer
- Department of Pathology, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Carol-Anne Moulton
- Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Steven Gallinger
- Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Dow-Mu Koh
- Department of Radiology, Royal Marsden Hospital, Sutton, UK
| | - Kartik S Jhaveri
- Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital and Women's College Hospital, University of Toronto, Toronto, Ontario, Canada
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KRAS mutational status impacts pathologic response to pre-hepatectomy chemotherapy: a study from the International Genetic Consortium for Liver Metastases. HPB (Oxford) 2019; 21:1527-1534. [PMID: 30979646 DOI: 10.1016/j.hpb.2019.03.368] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2018] [Revised: 01/08/2019] [Accepted: 03/14/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND A major response to pre-hepatectomy chemotherapy has been associated with improved survival in patients who undergo resection of colorectal liver metastases (CRLM). However, the role of tumor biology, as exemplified by overall and codon-specific KRAS mutational status, in predicting response to chemotherapy is not well defined. METHODS Pathologic response was characterized as minor or major depending on the percentage of remnant viable cells (>50% vs <50%, respectively). Multivariable logistic regression was used to identify factors associated with major response. RESULTS 319 patients met inclusion criteria. 229 patients had a KRAS wild-type (wtKRAS) tumor and 90 harbored KRAS mutations (mutKRAS). A major pathologic response was more commonly noted in patients with wtKRAS compared to mutKRAS (48.5% vs 33.3%, P = 0.01) and wtKRAS status remained independently associated with a major response (P = 0.04). On a codon-specific level, major pathologic response occurred less frequently in those with codon 13 mutations (17.7%) compared to those with codon 12 (35.4%), and other KRAS mutations (33.3%). Importantly, codon 13 mutations were independently associated with minor pathologic response (P = 0.023). CONCLUSIONS Patients with wtKRAS tumors appear to have the highest likelihood of experiencing a major response after preoperative chemotherapy. Future studies in "all-comer" cohorts are needed to confirm these findings and further investigate the response of codon 13 mutations.
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25
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Miyata A, Arita J, Shirata C, Abe S, Akamatsu N, Kaneko J, Kokudo N, Hasegawa K. Quantitative Assessment of the Accuracy of Real-Time Virtual Sonography for Liver Surgery. Surg Innov 2019; 27:60-67. [PMID: 31516065 DOI: 10.1177/1553350619875301] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Background. Real-time virtual sonography (RVS) is a navigation system for liver surgery. In this study, the degree of misalignment of intraoperative RVS images with computed tomographic (CT) images was measured. Methods. Between December 2014 and July 2015, intraoperative RVS was performed in a total of 33 patients undergoing liver surgery. Reconstructed CT images, rendered like intraoperative ultrasonographic (IOUS) images, were adjusted with the IOUS images and visualized side by side. The degree of misalignment between the reconstructed CT images and IOUS images was measured at anterior section, posterior section, and left liver in each patient. Furthermore, the time required for the adjustment was measured as the "adjustment time." Results. The degree of misalignment between the images could potentially be measured for a total of 96 points in the 33 patients. Of these, the actual measurement could not be conducted for 35 points due to poor visualization of the intrahepatic vasculature (n = 20) or to a large misalignment that hampered continuation of further adjustment (n = 15). The median degree of misalignment was 9.8 mm (range = 2.4-37.6 mm) in the right anterior section, 9.8 mm (range = 2.7-71.5 mm) in the right posterior section, and 9.5 mm (range = 0.9-37.6 mm) in the left liver. The median adjustment time was 105 seconds (range = 51-245 seconds). Conclusions. Although some misalignment occurred, it might be acceptable for selected situations. Further investigation is needed to reduce the frequency of adjustment failure.
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Affiliation(s)
- Akinori Miyata
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Junichi Arita
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Chikara Shirata
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Satoru Abe
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Nobuhisa Akamatsu
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Junichi Kaneko
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Norihiro Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.,Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Impact of Genetics on Neoadjuvant Therapy with Complete Pathological Response in Metastatic Colorectal Cancer: Case Report and Review of the Literature. Balkan J Med Genet 2019; 22:75-80. [PMID: 31523624 PMCID: PMC6714337 DOI: 10.2478/bjmg-2019-0004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Treatment of colorectal metastatic cancer is still challenging, despite recent improvements in chemotherapy. A genetic cancer profile, such as the KRAS (Kirsten rat sarcoma) gene status, plays a key role in individualized tailored therapy. Molecular targeted therapy added to neo-adjuvant chemotherapy can achieve a better pathological response and prolong survival. Pathological complete response of colorectal cancer stage IV is rare. A 47-year-old female patient presented with rectal adenocarcinoma and three liver metastases (cT3d/4, N2, Ml). After seven cycles of Bevacizumab and CAPOX in neoadjuvant setting, we noted more than 70.0% regression of metastases and complete regression of the primary tumor. We performed low anterior resection of rectum and synchronous subsegmental resection of S3, because the other two lesions were not detectable. Pathology revealed complete response of the primary and also secondary tumors. After 8 months, diagnostic tests did not show any sign of recurrence and the remaining liver lesions disappeared. Colorectal cancer is a heterogeneous disease and it is necessary to identify patients who are at-risk of recurrence and suitable for neoadjuvant therapy. Genetic biomarkers play an important role in metastatic colorectal cancer treatment. Because of the mutated KRAS gene, Bevacizumab was added to cytotoxic therapy achieving a complete pathological response of primary tumor and metastasis. This case is unique because all reported cases with similar results, described staged surgery and one of reverse staged surgery, but with similar results. This neoadjuvant therapy has extraordinary results for colorectal cancer stage IV and can help disease-free and long-term survival.
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27
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Saad AM, Abdel-Rahman O. Initial systemic chemotherapeutic and targeted therapy strategies for the treatment of colorectal cancer patients with liver metastases. Expert Opin Pharmacother 2019; 20:1767-1775. [PMID: 31314604 DOI: 10.1080/14656566.2019.1642324] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Introduction: The liver is the most common metastatic site in colorectal cancer with more than half the patients developing a liver metastasis either at the time of their diagnosis (synchronous) or later (metachronous). Surgical resection remains the principal curative approach that offers significant survival improvements. However, upfront surgery is only possible in about 10-20% of patients at the time of diagnosis, making the consideration of other treatment modalities essential. Areas covered: In this review, the authors provide an overview of the standard approaches for the initial management of patients with colorectal cancer with liver metastases. They then provide an up-to-date discussion of first-line systemic chemotherapy/targeted therapy options in the contexts of initially resectable and unresectable disease and review toxicities and complications following these options. Expert opinion: Advances in chemotherapeutic agents and biological targeted therapies have improved the prognosis of colorectal cancer with liver metastases. However, there is still no 'single best approach', making further trials necessary to provide more evidence.
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Affiliation(s)
| | - Omar Abdel-Rahman
- Clinical Oncology Department, Ain Shams University , Cairo , Egypt.,Department of Oncology, University of Alberta, Cross Cancer Institute , Edmonton , Alberta , Canada
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28
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El-Said MM, Emile SH. Cellular therapy: A promising tool in the future of colorectal surgery. World J Gastroenterol 2019; 25:1560-1565. [PMID: 30983816 PMCID: PMC6452228 DOI: 10.3748/wjg.v25.i13.1560] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Revised: 02/28/2019] [Accepted: 03/02/2019] [Indexed: 02/06/2023] Open
Abstract
Cellular therapy may be the solution of challenging problems in colorectal surgery such as impaired healing leading to anastomotic leakage and metastatic colorectal cancer (CRC). This review aimed to illustrate the role of cellular therapy in promotion of wound healing and management of metastatic CRC. An organized literature search for the role of cellular therapy in promotion of wound healing and management of metastatic CRC was conducted. Electronic databases including PubMed/Medline, Scopus, and Embase were queried for the search process. Two types of cellular therapy have been recognized, the mesenchymal stem cells (MSCs) and bone marrow-mononuclear cells (BM-MNCs) therapy. These cells have been shown to accelerate and promote healing of various tissue injuries in animal and human studies. In addition, experimental studies have reported that MSCs may help suppress the progression of colon cancer in rat models. This article reviews the possible mechanisms of action and clinical utility of MSCs and BM-MNCs in promotion of healing and suppression of tumor growth in light of the published literature. Cellular therapy has a potentially important role in colorectal surgery, particularly in the promotion of wound healing and management of metastatic CRC. Future directions of cellular therapy in colorectal surgery were explored which may help stimulate futures studies on the role of cellular therapy in colorectal surgery.
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Affiliation(s)
- Mohammed Mohammed El-Said
- Colorectal Surgery Unit, General Surgery Department, Mansoura University Hospitals, Mansoura University, Mansoura 35516, Egypt
| | - Sameh Hany Emile
- Colorectal Surgery Unit, General Surgery Department, Mansoura University Hospitals, Mansoura University, Mansoura 35516, Egypt
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29
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Chow FCL, Chok KSH. Colorectal liver metastases: An update on multidisciplinary approach. World J Hepatol 2019; 11:150-172. [PMID: 30820266 PMCID: PMC6393711 DOI: 10.4254/wjh.v11.i2.150] [Citation(s) in RCA: 138] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2018] [Revised: 11/24/2018] [Accepted: 12/05/2018] [Indexed: 02/06/2023] Open
Abstract
Liver metastasis is the commonest form of distant metastasis in colorectal cancer. Selection criteria for surgery and liver-directed therapies have recently been extended. However, resectability remains poorly defined. Tumour biology is increasingly recognized as an important prognostic factor; hence molecular profiling has a growing role in risk stratification and management planning. Surgical resection is the only treatment modality for curative intent. The most appropriate surgical approach is yet to be established. The primary cancer and the hepatic metastasis can be removed simultaneously or in a two-step approach; these two strategies have comparable long-term outcomes. For patients with a limited future liver remnant, portal vein embolization, combined ablation and resection, and associating liver partition and portal vein ligation for staged hepatectomy have been advocated, and each has their pros and cons. The role of neoadjuvant and adjuvant chemotherapy is still debated. Targeted biological agents and loco-regional therapies (thermal ablation, intra-arterial chemo- or radio-embolization, and stereotactic radiotherapy) further improve the already favourable results. The recent debate about offering liver transplantation to highly selected patients needs validation from large clinical trials. Evidence-based protocols are missing, and therefore optimal management of hepatic metastasis should be personalized and determined by a multi-disciplinary team.
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Affiliation(s)
| | - Kenneth Siu-Ho Chok
- Department of Surgery and State Key Laboratory for Liver Research, the University of Hong Kong, Hong Kong, China
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30
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Tsilimigras DI, Ntanasis-Stathopoulos I, Paredes AZ, Moris D, Gavriatopoulou M, Cloyd JM, Pawlik TM. Disappearing liver metastases: A systematic review of the current evidence. Surg Oncol 2019; 29:7-13. [PMID: 31196496 DOI: 10.1016/j.suronc.2019.02.005] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Accepted: 02/10/2019] [Indexed: 12/14/2022]
Abstract
Advances in systemic chemotherapy have resulted in a significant increase in the reported response rates of colorectal liver metastases (CRLM) over time. Although radiologic response is usually prognostic of favorable outcomes, complete shrinkage of CRLM after chemotherapy, namely "disappearing liver metastases" (DLMs) poses significant therapeutic dilemmas. A systematic review of the literature was conducted to evaluate the existing evidence on the imaging and management of patients with DLMs using the PubMed (Medline), Embase and Cochrane library through December 21st, 2018. The following algorithm was used: "(disappearing OR vanishing OR missing OR (residual tiny)) AND ((liver OR hepatic) AND (metastasis OR metastases OR metastatic OR secondary))." From the 225 records retrieved, 15 studies were finally deemed eligible. A total of 479 patients with DLMs with a median age of 59.5 years (range, 30-83) were identified. Median number of DLM per patient ranged from 1 to 8.8. Median size of LMs prior to chemotherapy was 1.07 cm (range 0.3-3.5). The systemic treatment used to achieve DLMs included systemic chemotherapy alone (only 2 studies) or in combination with targeted agents (11 studies). The median number of chemotherapy cycles in the included studies was 7.8 (range 6-12). Identified factors predisposing to the development of DLM were small size (<2 cm), increased number of treatment cycles, oxaliplatin-based therapy, increased number of CRLM (≥3) and synchronous CRLM. Baseline and preoperative MRI with iv contrast showed the highest sensitivity for DLM detection. Fiducial placement facilitated pre- and intra-operative identification of DLM. Although resection of DLM decreased the local recurrence risk, there was no clearly demonstrated survival benefit after resecting all sites of disappearing lesions. Future randomized clinical trials are highly encouraged to provide strict, evidence-based recommendations for the treatment of patients with DLM.
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Affiliation(s)
- Diamantis I Tsilimigras
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
| | - Ioannis Ntanasis-Stathopoulos
- Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece
| | - Anghela Z Paredes
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
| | - Dimitrios Moris
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
| | - Maria Gavriatopoulou
- Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece
| | - Jordan M Cloyd
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA.
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31
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De Raffele E, Mirarchi M, Cuicchi D, Lecce F, Ricci C, Casadei R, Cola B, Minni F. Simultaneous curative resection of double colorectal carcinoma with synchronous bilobar liver metastases. World J Gastrointest Oncol 2018; 10:293-316. [PMID: 30364774 PMCID: PMC6198303 DOI: 10.4251/wjgo.v10.i10.293] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Revised: 08/05/2018] [Accepted: 08/21/2018] [Indexed: 02/05/2023] Open
Abstract
Synchronous colorectal carcinoma (SCRC) indicates more than one primary colorectal carcinoma (CRC) discovered at the time of initial presentation, accounts for 3.1%-3.9% of CRC, and may occur either in the same or in different colorectal segments. The accurate preoperative diagnosis of SCRC is difficult and diagnostic failures may lead to inappropriate treatment and poorer prognosis. SCRC requires colorectal resections tailored to individual patients, based on the number, location, and stage of the tumours, from conventional or extended hemicolectomies to total colectomy or proctocolectomy, when established predisposing conditions exist. The overall perioperative risks of surgery for SCRC seem to be higher than for solitary CRC. Simultaneous colorectal and liver resection represents an appealing surgical strategy in selected patients with CRC and synchronous liver metastases (CRLM), even though the cumulative risks of the two procedures need to be adequately evaluated. Simultaneous resections have the noticeable advantage of avoiding a second laparotomy, give the opportunity of an earlier initiation of adjuvant therapy, and may significantly reduce the hospital costs. Because an increasing number of recent studies have shown good results, with morbidity, perioperative hospitalization, and mortality rates comparable to staged resections, simultaneous procedures can be selectively proposed even in case of complex colorectal resections, including those for SCRC and rectal cancer. However, in patients with multiple bilobar CRLM, major hepatectomies performed simultaneously with colorectal resection have been associated with significant perioperative risks. Conservative or parenchymal-sparing hepatectomies reduce the extent of hepatectomy while preserving oncological radicality, and may represent the best option for selected patients with multiple CRLM involving both liver lobes. Parenchymal-sparing liver resection, instead of major or two-stage hepatectomy for bilobar disease, seemingly reduces the overall operative risk of candidates to simultaneous colorectal and liver resection, and may represent the most appropriate surgical strategy whenever possible, also for patients with advanced SCRC and multiple bilobar liver metastases.
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Affiliation(s)
- Emilio De Raffele
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Mariateresa Mirarchi
- U.O. di Chirurgia Generale, Dipartimento Strutturale Chirurgico, Ospedale “Antonio e Margherita, ” Tortona (AL) 15057, Italy
| | - Dajana Cuicchi
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Ferdinando Lecce
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Claudio Ricci
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Riccardo Casadei
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Bruno Cola
- Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Alma Mater Studiorum, Policlinico S.Orsola-Malpighi, University of Bologna, Bologna 40138, Italy
| | - Francesco Minni
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
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Peyrat P, Blanc E, Guillermet S, Chen Y, Ferlay C, Perol D, Basso V, Rivoire M, Dupré A. HEPATOFLUO: A prospective monocentric study assessing the benefits of indocyanine green (ICG) fluorescence for hepatic surgery. J Surg Oncol 2018; 117:922-927. [DOI: 10.1002/jso.25011] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Accepted: 01/15/2018] [Indexed: 11/05/2022]
Affiliation(s)
- Patrice Peyrat
- Department of Surgery; Centre Léon Bérard; Lyon France
- Experimental Surgical Unit; Centre Léon Bérard; Lyon France
| | - Ellen Blanc
- Clinical Research and Innovation; Centre Léon Bérard; Lyon France
| | | | - Yao Chen
- Experimental Surgical Unit; Centre Léon Bérard; Lyon France
| | - Céline Ferlay
- Clinical Research and Innovation; Centre Léon Bérard; Lyon France
| | - David Perol
- Clinical Research and Innovation; Centre Léon Bérard; Lyon France
| | - Valéria Basso
- Department of Surgery; Centre Léon Bérard; Lyon France
| | - Michel Rivoire
- Department of Surgery; Centre Léon Bérard; Lyon France
- Experimental Surgical Unit; Centre Léon Bérard; Lyon France
| | - Aurélien Dupré
- Department of Surgery; Centre Léon Bérard; Lyon France
- Experimental Surgical Unit; Centre Léon Bérard; Lyon France
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Liu W, Zhou JG, Sun Y, Zhang L, Xing BC. The role of neoadjuvant chemotherapy for resectable colorectal liver metastases: a systematic review and meta-analysis. Oncotarget 2018; 7:37277-37287. [PMID: 27074564 PMCID: PMC5095075 DOI: 10.18632/oncotarget.8671] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2015] [Accepted: 03/28/2016] [Indexed: 12/17/2022] Open
Abstract
Neoadjuvant chemotherapy is being increasingly accepted as an effective treatment of resectable colorectal liver metastases (CRLM), but it may also damage the hepatic parenchyma. We performed a meta-analysis to compare the outcomes of patients who received neoadjuvant chemotherapy (NEO) prior to hepatic resection with hepatic resection without neoadjuvant chemotherapy (SG). Eligible trials were identified from Embase, PubMed, the Web of Science and the Cochrane library. Hazard ratios (HRs) with a 95% confidence intervals (CIs) were used to measure the pooled effect using a random-effects model. Statistical heterogeneity was detected by I2 test. Sensitivity analyses and publication bias were also assessed. The study outcomes included 3-year, 5-year disease-free and overall survival rate, respectively. Eighteen studies involving 6,254 patients were included. The pooled HRs for 5-year DFS and 5-year OS for NEO in the included studies calculated using the random-effects model were 1.38 (95 % CI; 1.26-1.51, p=0.00; I2=9.6%, p=0.36) and 1.19 (95% CI: 1.02-1.38; p=0.03; I2=49.2%, p=0.03), respectively. For CRLM patients with factors indicating a high risk of recurrence, the pooled HR for 5-year OS of NEO in the included studies calculated using the random-effects model was 0.69 (95% CI: 0.55-0.87; p=0.00; I2=0.0%, p=0.48). These results suggest neoadjuvant chemotherapy improved survival of patients with initially resectable CRLM and a high risk of disease recurrence.
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Affiliation(s)
- Wei Liu
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing , PR China
| | - Jian-Guo Zhou
- Department of Oncology, Affiliated Hospital of Zunyi Medical University, Zunyi Medical University, Zunyi, China
| | - Yi Sun
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing , PR China
| | - Lei Zhang
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing , PR China
| | - Bao-Cai Xing
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing , PR China
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Risk Factors for Unresectable Recurrence After Up-Front Surgery for Colorectal Liver Metastasis. World J Surg 2017; 42:884-891. [DOI: 10.1007/s00268-017-4195-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Park MJ, Hong N, Han K, Kim MJ, Lee YJ, Park YS, Rha SE, Park S, Lee WJ, Park SH, Lee CH, Nam CM, An C, Kim HJ, Kim H, Park MS. Use of Imaging to Predict Complete Response of Colorectal Liver Metastases after Chemotherapy: MR Imaging versus CT Imaging. Radiology 2017; 284:423-431. [DOI: 10.1148/radiol.2017161619] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Min Jung Park
- From the Departments of Radiology (M.J.P., K.H., C.A., H.J.K., H.K., M.S.P.) and Biostatistics (K.H., C.M.N.), Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-Ro, Seodaemun-Gu, Seoul 120-752, Korea; Department of Radiology, Ulsan University College of Medicine, Asan Medical Center, Seoul, Korea (N.H., S.H.P.); Center for Colorectal Cancer, National Cancer Center, Ilsan, Korea (M.J.K.); Department of Radiology, Seoul National University College of Medicine, Bundang Hospital, Bundang,
| | - Nurhee Hong
- From the Departments of Radiology (M.J.P., K.H., C.A., H.J.K., H.K., M.S.P.) and Biostatistics (K.H., C.M.N.), Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-Ro, Seodaemun-Gu, Seoul 120-752, Korea; Department of Radiology, Ulsan University College of Medicine, Asan Medical Center, Seoul, Korea (N.H., S.H.P.); Center for Colorectal Cancer, National Cancer Center, Ilsan, Korea (M.J.K.); Department of Radiology, Seoul National University College of Medicine, Bundang Hospital, Bundang,
| | - Kyunghwa Han
- From the Departments of Radiology (M.J.P., K.H., C.A., H.J.K., H.K., M.S.P.) and Biostatistics (K.H., C.M.N.), Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-Ro, Seodaemun-Gu, Seoul 120-752, Korea; Department of Radiology, Ulsan University College of Medicine, Asan Medical Center, Seoul, Korea (N.H., S.H.P.); Center for Colorectal Cancer, National Cancer Center, Ilsan, Korea (M.J.K.); Department of Radiology, Seoul National University College of Medicine, Bundang Hospital, Bundang,
| | - Min Ju Kim
- From the Departments of Radiology (M.J.P., K.H., C.A., H.J.K., H.K., M.S.P.) and Biostatistics (K.H., C.M.N.), Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-Ro, Seodaemun-Gu, Seoul 120-752, Korea; Department of Radiology, Ulsan University College of Medicine, Asan Medical Center, Seoul, Korea (N.H., S.H.P.); Center for Colorectal Cancer, National Cancer Center, Ilsan, Korea (M.J.K.); Department of Radiology, Seoul National University College of Medicine, Bundang Hospital, Bundang,
| | - Yoon Jin Lee
- From the Departments of Radiology (M.J.P., K.H., C.A., H.J.K., H.K., M.S.P.) and Biostatistics (K.H., C.M.N.), Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-Ro, Seodaemun-Gu, Seoul 120-752, Korea; Department of Radiology, Ulsan University College of Medicine, Asan Medical Center, Seoul, Korea (N.H., S.H.P.); Center for Colorectal Cancer, National Cancer Center, Ilsan, Korea (M.J.K.); Department of Radiology, Seoul National University College of Medicine, Bundang Hospital, Bundang,
| | - Yang Shin Park
- From the Departments of Radiology (M.J.P., K.H., C.A., H.J.K., H.K., M.S.P.) and Biostatistics (K.H., C.M.N.), Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-Ro, Seodaemun-Gu, Seoul 120-752, Korea; Department of Radiology, Ulsan University College of Medicine, Asan Medical Center, Seoul, Korea (N.H., S.H.P.); Center for Colorectal Cancer, National Cancer Center, Ilsan, Korea (M.J.K.); Department of Radiology, Seoul National University College of Medicine, Bundang Hospital, Bundang,
| | - Sung Eun Rha
- From the Departments of Radiology (M.J.P., K.H., C.A., H.J.K., H.K., M.S.P.) and Biostatistics (K.H., C.M.N.), Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-Ro, Seodaemun-Gu, Seoul 120-752, Korea; Department of Radiology, Ulsan University College of Medicine, Asan Medical Center, Seoul, Korea (N.H., S.H.P.); Center for Colorectal Cancer, National Cancer Center, Ilsan, Korea (M.J.K.); Department of Radiology, Seoul National University College of Medicine, Bundang Hospital, Bundang,
| | - Sumi Park
- From the Departments of Radiology (M.J.P., K.H., C.A., H.J.K., H.K., M.S.P.) and Biostatistics (K.H., C.M.N.), Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-Ro, Seodaemun-Gu, Seoul 120-752, Korea; Department of Radiology, Ulsan University College of Medicine, Asan Medical Center, Seoul, Korea (N.H., S.H.P.); Center for Colorectal Cancer, National Cancer Center, Ilsan, Korea (M.J.K.); Department of Radiology, Seoul National University College of Medicine, Bundang Hospital, Bundang,
| | - Won Jae Lee
- From the Departments of Radiology (M.J.P., K.H., C.A., H.J.K., H.K., M.S.P.) and Biostatistics (K.H., C.M.N.), Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-Ro, Seodaemun-Gu, Seoul 120-752, Korea; Department of Radiology, Ulsan University College of Medicine, Asan Medical Center, Seoul, Korea (N.H., S.H.P.); Center for Colorectal Cancer, National Cancer Center, Ilsan, Korea (M.J.K.); Department of Radiology, Seoul National University College of Medicine, Bundang Hospital, Bundang,
| | - Seong Ho Park
- From the Departments of Radiology (M.J.P., K.H., C.A., H.J.K., H.K., M.S.P.) and Biostatistics (K.H., C.M.N.), Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-Ro, Seodaemun-Gu, Seoul 120-752, Korea; Department of Radiology, Ulsan University College of Medicine, Asan Medical Center, Seoul, Korea (N.H., S.H.P.); Center for Colorectal Cancer, National Cancer Center, Ilsan, Korea (M.J.K.); Department of Radiology, Seoul National University College of Medicine, Bundang Hospital, Bundang,
| | - Chang Hee Lee
- From the Departments of Radiology (M.J.P., K.H., C.A., H.J.K., H.K., M.S.P.) and Biostatistics (K.H., C.M.N.), Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-Ro, Seodaemun-Gu, Seoul 120-752, Korea; Department of Radiology, Ulsan University College of Medicine, Asan Medical Center, Seoul, Korea (N.H., S.H.P.); Center for Colorectal Cancer, National Cancer Center, Ilsan, Korea (M.J.K.); Department of Radiology, Seoul National University College of Medicine, Bundang Hospital, Bundang,
| | - Chung Mo Nam
- From the Departments of Radiology (M.J.P., K.H., C.A., H.J.K., H.K., M.S.P.) and Biostatistics (K.H., C.M.N.), Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-Ro, Seodaemun-Gu, Seoul 120-752, Korea; Department of Radiology, Ulsan University College of Medicine, Asan Medical Center, Seoul, Korea (N.H., S.H.P.); Center for Colorectal Cancer, National Cancer Center, Ilsan, Korea (M.J.K.); Department of Radiology, Seoul National University College of Medicine, Bundang Hospital, Bundang,
| | - Chansik An
- From the Departments of Radiology (M.J.P., K.H., C.A., H.J.K., H.K., M.S.P.) and Biostatistics (K.H., C.M.N.), Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-Ro, Seodaemun-Gu, Seoul 120-752, Korea; Department of Radiology, Ulsan University College of Medicine, Asan Medical Center, Seoul, Korea (N.H., S.H.P.); Center for Colorectal Cancer, National Cancer Center, Ilsan, Korea (M.J.K.); Department of Radiology, Seoul National University College of Medicine, Bundang Hospital, Bundang,
| | - Hye Jin Kim
- From the Departments of Radiology (M.J.P., K.H., C.A., H.J.K., H.K., M.S.P.) and Biostatistics (K.H., C.M.N.), Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-Ro, Seodaemun-Gu, Seoul 120-752, Korea; Department of Radiology, Ulsan University College of Medicine, Asan Medical Center, Seoul, Korea (N.H., S.H.P.); Center for Colorectal Cancer, National Cancer Center, Ilsan, Korea (M.J.K.); Department of Radiology, Seoul National University College of Medicine, Bundang Hospital, Bundang,
| | - Honsoul Kim
- From the Departments of Radiology (M.J.P., K.H., C.A., H.J.K., H.K., M.S.P.) and Biostatistics (K.H., C.M.N.), Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-Ro, Seodaemun-Gu, Seoul 120-752, Korea; Department of Radiology, Ulsan University College of Medicine, Asan Medical Center, Seoul, Korea (N.H., S.H.P.); Center for Colorectal Cancer, National Cancer Center, Ilsan, Korea (M.J.K.); Department of Radiology, Seoul National University College of Medicine, Bundang Hospital, Bundang,
| | - Mi-Suk Park
- From the Departments of Radiology (M.J.P., K.H., C.A., H.J.K., H.K., M.S.P.) and Biostatistics (K.H., C.M.N.), Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-Ro, Seodaemun-Gu, Seoul 120-752, Korea; Department of Radiology, Ulsan University College of Medicine, Asan Medical Center, Seoul, Korea (N.H., S.H.P.); Center for Colorectal Cancer, National Cancer Center, Ilsan, Korea (M.J.K.); Department of Radiology, Seoul National University College of Medicine, Bundang Hospital, Bundang,
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Fiorentini G, Sarti D, Aliberti C, Carandina R, Mambrini A, Guadagni S. Multidisciplinary approach of colorectal cancer liver metastases. World J Clin Oncol 2017; 8:190-202. [PMID: 28638789 PMCID: PMC5465009 DOI: 10.5306/wjco.v8.i3.190] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2017] [Revised: 04/05/2017] [Accepted: 05/05/2017] [Indexed: 02/06/2023] Open
Abstract
Large bowel cancer is a worldwide public health challenge. More than one third of patients present an advanced stage of disease at diagnosis and the liver is the most common site of metastases. Selection criteria for early diagnosis, chemotherapy and surgery have been recently expanded. The definition of resectability remains unclear. The presence of metastases is the most significant prognostic factor. For this reason the surgical resection of hepatic metastases is the leading treatment. The most appropriate resection approach remains to be defined. The two step and simultaneous resection processes of both primary and metastases have comparable survival long-term outcomes. The advent of targeted biological chemotherapeutic agents and the development of loco-regional therapies (chemoembolization, thermal ablation, arterial infusion chemotherapy) contribute to extend favorable results. Standardized evidence-based protocols are missing, hence optimal management of hepatic metastases should be single patient tailored and decided by a multidisciplinary team. This article reviews the outcomes of resection, systemic and loco-regional therapies of liver metastases originating from large bowel cancer.
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Ramaekers P, Ries M, Moonen CT, de Greef M. Improved intercostal HIFU ablation using a phased array transducer based on Fermat's spiral and Voronoi tessellation: A numerical evaluation. Med Phys 2017; 44:1071-1088. [DOI: 10.1002/mp.12082] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2016] [Revised: 11/22/2016] [Accepted: 12/25/2016] [Indexed: 01/25/2023] Open
Affiliation(s)
- Pascal Ramaekers
- Imaging Division; University Medical Center Utrecht; 3508 GA Utrecht The Netherlands
| | - Mario Ries
- Imaging Division; University Medical Center Utrecht; 3508 GA Utrecht The Netherlands
| | - Chrit T.W. Moonen
- Imaging Division; University Medical Center Utrecht; 3508 GA Utrecht The Netherlands
| | - Martijn de Greef
- Imaging Division; University Medical Center Utrecht; 3508 GA Utrecht The Netherlands
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de Jonge J, Olthoff KM. Liver regeneration. BLUMGART'S SURGERY OF THE LIVER, BILIARY TRACT AND PANCREAS, 2-VOLUME SET 2017:93-109.e7. [DOI: 10.1016/b978-0-323-34062-5.00006-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Hong JC, Salama JK. The expanding role of stereotactic body radiation therapy in oligometastatic solid tumors: What do we know and where are we going? Cancer Treat Rev 2017; 52:22-32. [PMID: 27886588 DOI: 10.1016/j.ctrv.2016.11.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Revised: 11/01/2016] [Accepted: 11/03/2016] [Indexed: 02/07/2023]
Abstract
The spectrum hypothesis posits that there are distinct clinical states of metastatic progression. Early data suggest that aggressive treatment of more biologically indolent metastatic disease, characterized by metastases limited in number and destination organ, may offer an opportunity to alter the disease course, potentially allowing for longer survival, delay of systemic therapy, or even cure. The development of stereotactic body radiation therapy (SBRT) has opened new avenues for the treatment of oligometastatic disease. Early data support the use of SBRT for treating oligometastases in a number of organs, with promising rates of treated metastasis control and overall survival. Ongoing investigation is required to definitively establish benefit, determine the appropriate treatment regimen, refine patient selection, and incorporate SBRT with systemic therapies.
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Affiliation(s)
- Julian C Hong
- Department of Radiation Oncology, Duke University, Durham, NC, United States
| | - Joseph K Salama
- Department of Radiation Oncology, Duke University, Durham, NC, United States.
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40
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Kim SS, Song KD, Kim YK, Kim HC, Huh JW, Park YS, Park JO, Kim ST. Disappearing or residual tiny (≤5 mm) colorectal liver metastases after chemotherapy on gadoxetic acid-enhanced liver MRI and diffusion-weighted imaging: Is local treatment required? Eur Radiol 2016; 27:3088-3096. [DOI: 10.1007/s00330-016-4644-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2016] [Revised: 10/03/2016] [Accepted: 10/10/2016] [Indexed: 02/08/2023]
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41
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Araujo RLC, Riechelmann RP, Fong Y. Patient selection for the surgical treatment of resectable colorectal liver metastases. J Surg Oncol 2016; 115:213-220. [PMID: 27778357 DOI: 10.1002/jso.24482] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2016] [Accepted: 09/30/2016] [Indexed: 12/14/2022]
Abstract
Advances in surgery and chemotherapy regimens have increased the long-term survival of patients with colorectal liver metastases (CRLM). Although liver resection remains an essential part of any curative strategy for resectable CRLM, chemotherapy regimens have also improved the long-term outcomes. However, the optimal timing for chemotherapy regimens remains unclear. Thus, this review addressed key points to aid the decision-making process regarding the timing of chemotherapy and surgery for patients with resectable CRLM. J. Surg. Oncol. 2017;115:213-220. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Raphael L C Araujo
- Department of Upper Gastrointestinal and Hepato-Pancreato-Biliary Surgery, Barretos Cancer Hospital, Barretos, São Paulo, Brazil
| | - Rachel P Riechelmann
- Department of Radiology and Oncology, Instituto do Câncer do Estado de São Paulo, University of São Paulo Medical School, São Paulo, Brazil
| | - Yuman Fong
- Department of Surgery, City of Hope National Medical Center, Duarte, California
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Hokuto D, Nomi T, Yamato I, Yasuda S, Obara S, Yoshikawa T, Kawaguchi C, Yamada T, Kanehiro H, Nakajima Y. The prognosis of liver resection for patients with four or more colorectal liver metastases has not improved in the era of modern chemotherapy. J Surg Oncol 2016; 114:959-965. [DOI: 10.1002/jso.24461] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Accepted: 09/07/2016] [Indexed: 01/31/2023]
Affiliation(s)
- Daisuke Hokuto
- Department of Surgery; Nara Medical University; Nara Japan
| | - Takeo Nomi
- Department of Surgery; Nara Medical University; Nara Japan
| | - Ichiro Yamato
- Department of Surgery; Nara Medical University; Nara Japan
| | - Satoshi Yasuda
- Department of Surgery; Nara Medical University; Nara Japan
| | - Shinsaku Obara
- Department of Surgery; Nara Medical University; Nara Japan
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Franklin JM, Sharma RA, Harris AL, Gleeson FV. Imaging oligometastatic cancer before local treatment. Lancet Oncol 2016; 17:e406-14. [PMID: 27599145 DOI: 10.1016/s1470-2045(16)30277-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2016] [Revised: 06/21/2016] [Accepted: 06/23/2016] [Indexed: 12/21/2022]
Abstract
With the advent of novel treatment strategies to help widen the therapeutic window for patients with oligometastatic cancer, improved biomarkers are needed to reliably define patients who can benefit from these treatments. Multimodal imaging is one such option and should be optimised to comprehensively assess metastatic sites, disease burden, and response to neoadjuvant treatment in each disease setting. These features will probably remain important prognostic biomarkers, and are crucial in planning multidisciplinary treatment. There are opportunities to extract additional phenotypic information from conventional imaging, while novel imaging techniques can also reveal specific aspects of tumour biology. Imaging can both characterise and localise the phenotypic heterogeneity of multiple tumour sites. Novel approaches to existing imaging datasets and correlation with tumour biology will be important in realising the potential of imaging to guide treatment in the oligometastatic setting. In this Personal View, we discuss the current status and future directions of imaging before treatment in patients with extracranial oligometastases.
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Affiliation(s)
- James M Franklin
- Department of Radiology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Department of Oncology, University of Oxford, UK.
| | | | - Adrian L Harris
- Department of Oncology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Department of Oncology, University of Oxford, UK
| | - Fergus V Gleeson
- Department of Radiology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Department of Oncology, University of Oxford, UK
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Dervenis C, Xynos E, Sotiropoulos G, Gouvas N, Boukovinas I, Agalianos C, Androulakis N, Athanasiadis A, Christodoulou C, Chrysou E, Emmanouilidis C, Georgiou P, Karachaliou N, Katopodi O, Kountourakis P, Kyriazanos I, Makatsoris T, Papakostas P, Papamichael D, Pechlivanides G, Pentheroudakis G, Pilpilidis I, Sgouros J, Tekkis P, Triantopoulou C, Tzardi M, Vassiliou V, Vini L, Xynogalos S, Ziras N, Souglakos J. Clinical practice guidelines for the management of metastatic colorectal cancer: a consensus statement of the Hellenic Society of Medical Oncologists (HeSMO). Ann Gastroenterol 2016; 29:390-416. [PMID: 27708505 PMCID: PMC5049546 DOI: 10.20524/aog.2016.0050] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Accepted: 03/10/2016] [Indexed: 12/12/2022] Open
Abstract
There is discrepancy and failure to adhere to current international guidelines for the management of metastatic colorectal cancer (CRC) in hospitals in Greece and Cyprus. The aim of the present document is to provide a consensus on the multidisciplinary management of metastastic CRC, considering both special characteristics of our Healthcare System and international guidelines. Following discussion and online communication among the members of an executive team chosen by the Hellenic Society of Medical Oncology (HeSMO), a consensus for metastastic CRC disease was developed. Statements were subjected to the Delphi methodology on two voting rounds by invited multidisciplinary international experts on CRC. Statements reaching level of agreement by ≥80% were considered as having achieved large consensus, whereas statements reaching 60-80% moderate consensus. One hundred and nine statements were developed. Ninety experts voted for those statements. The median rate of abstain per statement was 18.5% (range: 0-54%). In the end of the process, all statements achieved a large consensus. The importance of centralization, care by a multidisciplinary team, adherence to guidelines, and personalization is emphasized. R0 resection is the only intervention that may offer substantial improvement in the oncological outcomes.
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Affiliation(s)
- Christos Dervenis
- General Surgery, "Konstantopouleio" Hospital of Athens, Greece (Christos Dervenis)
| | - Evaghelos Xynos
- General Surgery, "InterClinic" Hospital of Heraklion, Greece (Evangelos Xynos)
| | | | - Nikolaos Gouvas
- General Surgery, "METROPOLITAN" Hospital of Piraeus, Greece (Nikolaos Gouvas)
| | - Ioannis Boukovinas
- Medical Oncology, "Bioclinic" of Thessaloniki, Greece (Ioannis Boukovinas)
| | - Christos Agalianos
- General Surgery, Athens Naval & Veterans Hospital, Greece (Christos Agalianos, Ioannis Kyriazanos, George Pechlivanides)
| | - Nikolaos Androulakis
- Medical Oncology, "Venizeleion" Hospital of Heraklion, Greece (Nikolaos Androulakis)
| | | | | | - Evangelia Chrysou
- Radiology, University Hospital of Heraklion, Greece (Evangelia Chrysou)
| | - Christos Emmanouilidis
- Medical Oncology, "Interbalkan" Medical Center, Thessaloniki, Greece (Christos Emmanoulidis)
| | - Panagiotis Georgiou
- Colorectal Surgery, Chelsea and Westminster NHS Foundation Trust, London, UK (Panagiotis Georgiou, Paris Tekkis)
| | - Niki Karachaliou
- Medical Oncology, Dexeus University Institut, Barcelona, Spain (Niki Carachaliou)
| | - Ourania Katopodi
- Medical Oncology, "Iaso" General Hospital, Athens, Greece (Ourania Katopoidi)
| | - Panteleimon Kountourakis
- Medical Oncology, Oncology Center of Bank of Cyprus, Nicosia, Cyprus (Pandelis Kountourakis, Demetris Papamichael)
| | - Ioannis Kyriazanos
- General Surgery, Athens Naval & Veterans Hospital, Greece (Christos Agalianos, Ioannis Kyriazanos, George Pechlivanides)
| | - Thomas Makatsoris
- Medical Oncology, University Hospital of Patras, Greece (Thomas Makatsoris)
| | - Pavlos Papakostas
- Medical Oncology, "Ippokrateion" Hospital of Athens, Greece (Pavlos Papakostas)
| | - Demetris Papamichael
- Medical Oncology, Oncology Center of Bank of Cyprus, Nicosia, Cyprus (Pandelis Kountourakis, Demetris Papamichael)
| | - George Pechlivanides
- General Surgery, Athens Naval & Veterans Hospital, Greece (Christos Agalianos, Ioannis Kyriazanos, George Pechlivanides)
| | | | - Ioannis Pilpilidis
- Gastroenterology, "Theageneion" Cancer Hospital, Thessaloniki, Greece (Ioannis Pilpilidis)
| | - Joseph Sgouros
- Medical Oncology, "Agioi Anargyroi" Hospital of Athens, Greece (Joseph Sgouros)
| | - Paris Tekkis
- Colorectal Surgery, Chelsea and Westminster NHS Foundation Trust, London, UK (Panagiotis Georgiou, Paris Tekkis)
| | | | - Maria Tzardi
- Pathology, University Hospital of Heraklion, Greece (Maria Tzardi)
| | - Vassilis Vassiliou
- Radiation Oncology, Oncology Center of Bank of Cyprus, Nicosia, Cyprus (Vassilis Vassiliou)
| | - Louiza Vini
- Radiation Oncology, "Iatriko" Center of Athens, Greece (Lousa Vini)
| | - Spyridon Xynogalos
- Medical Oncology, "George Gennimatas" General Hospital, Athens, Greece (Spyridon Xynogalos)
| | - Nikolaos Ziras
- Medical Oncology, "Metaxas" Cancer Hospital, Piraeus, Greece (Nikolaos Ziras)
| | - John Souglakos
- Medical Oncology, University Hospital of Heraklion, Greece (John Souglakos)
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Kuhlmann K, van Hilst J, Fisher S, Poston G. Management of disappearing colorectal liver metastases. Eur J Surg Oncol 2016; 42:1798-1805. [PMID: 27260846 DOI: 10.1016/j.ejso.2016.05.005] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Revised: 04/17/2016] [Accepted: 05/05/2016] [Indexed: 01/18/2023] Open
Abstract
The development of new potent systemic treatment modalities has led to a significant increase in survival of patients with colorectal liver metastases. In the neo-adjuvant setting, these modalities can be used for patient selection, down staging, and conversion from non-resectable to resectable liver metastases. In addition, complete radiological disappearance of metastases can occur, the phenomenon of disappearing liver metastases. Because only a small percentage of these patients (0-8%) have a complete radiological response of all liver metastases, most patients will undergo surgery. At laparotomy, local residual disease at the site of the disappeared metastasis is still found in 11-67%, which highlights the influence of the imaging modalities used at (re)staging. When the region of the disappeared liver metastasis was resected, microscopically residual disease was found in up to 80% of the specimens. Alternatively, conservative management of radiologically disappeared liver metastases resulted in 19-74% local recurrence, mostly within two years. Obviously, these studies are highly dependent on the quality of the imaging modalities utilised. Most studies employed CT as the modality of choice, while MRI and PET was only used in selective series. Overall, the phenomenon of disappearing liver metastases seems to be a radiological rather than an actual biological occurrence, because the rates of macroscopic and microscopic residual disease are high as well as the local recurrence rates. Therefore, the disappeared metastases still require an aggressive surgical approach and standard (re)staging imaging modalities should include at least CT and MRI.
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Affiliation(s)
- K Kuhlmann
- Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom.
| | - J van Hilst
- Department of Surgery, Academic Medical Center, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands
| | - S Fisher
- Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom
| | - G Poston
- Liver Surgery Unit, Aintree University Hospital NHS Trust, Lower Lane, Liverpool, L9 7AL, United Kingdom
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46
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Molecular markers of prognosis and therapeutic targets in metastatic colorectal cancer. Surg Oncol 2016; 25:190-9. [PMID: 27566022 DOI: 10.1016/j.suronc.2016.05.018] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Accepted: 05/19/2016] [Indexed: 12/18/2022]
Abstract
Metastatic disease ultimately occurs in approximately 50-70% of patients presenting with colorectal cancer. In patients with advanced disease, there is significant variability in individual patient outcomes. To improve understanding of tumor behavior, markers such as KRAS and BRAF mutation status are increasingly utilized. Additionally, newer surrogates of tumor biology, such as telomerase activity and the prevalence of circulating tumor cells and circulating tumor DNA, have generated increasing interest due to clinical potential. While the extent to which these newer markers can predict outcome and guide therapy is yet to be determined, KRAS mutation status is currently used to guide systemic therapy in selected patients. Furthermore, advances in our understanding of various tumorigenic pathways (such as the mitogen activated protein kinase pathway) have enabled newer targeted agents, including BRAF inhibitors. Interestingly, although inhibition of BRAF in patients has not translated into improved outcomes, characterization of BRAF mutations led to an association with microsatellite instability. A unique histologic characteristic of certain tumors in patients with microsatellite instability is the infiltration by lymphocytes at the tumor-stromal interface. This feature highlights the biology of the tumor in its microenvironment and underlies the efficacy of the programmed-death inhibitor, pembrolizumab, in patients with microsatellite unstable metastatic colorectal cancer. With an increasing number of prognostic markers and therapeutic options in metastatic colorectal cancer, the multidisciplinary approach becomes critical for appropriate treatment decisions.
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Lemke J, Cammerer G, Ganser J, Scheele J, Xu P, Sander S, Henne-Bruns D, Kornmann M. Survival and Prognostic Factors of Colorectal Liver Metastases After Surgical and Nonsurgical Treatment. Clin Colorectal Cancer 2016; 15:e183-e192. [PMID: 27269232 DOI: 10.1016/j.clcc.2016.04.007] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2015] [Revised: 04/04/2016] [Accepted: 04/27/2016] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Colorectal cancer is one leading cause of cancer-related death worldwide, and distant metastases determine an unfavorable prognosis. Surgical resection of colorectal liver metastases (CRLM) improves survival and provides the chance for cure. The aim of this study was to prospectively analyze the outcome of patients with CRLM in a population-based manner, and thereby, to compare the prognosis of patients undergoing resection with those receiving nonsurgical treatment. Moreover, we set out to identify and confirm important prognostic factors after resection of CRLM. PATIENTS AND METHODS We analyzed the outcome of 506 patients diagnosed with CRLM in our institution from 1996 to 2011. Survival and the impact of clinical and pathologic factors were analyzed by univariate analysis. Important independent prognostic factors were analyzed by multivariate analysis. RESULTS The 5-year overall survival rate (5y-OSR) for patients receiving resection of CRLM (n = 152) was 46% (95% confidence interval (CI), 37%-54%) compared with a 5y-OSR of 6% (95% CI, 4%-9%) for patients treated nonsurgically (n = 354). There was no perioperative mortality. Multivariate analysis revealed, among other factors, good performance status of the patient (low American Society of Anesthesiologists score), the absence of extrahepatic metastases, < 5 metastatic lesions, and a tumor-free resection margin (R0) as important, independent prognostic factors. Importantly, repeated hepatic resections of CRLM performed in 13 patients were associated with an excellent outcome (5y-OSR, 47%; 95% CI, 17%-72%). CONCLUSION Surgical resection, which can be performed with tolerable site-effects, is the first choice for patients diagnosed with metachronous and synchronous CRLM. Of note, repeated resections should be advised in recurrent intrahepatic colorectal cancer whenever possible.
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Affiliation(s)
- Johannes Lemke
- Clinic of General and Visceral Surgery, University of Ulm, Ulm, Germany
| | - Gregor Cammerer
- Clinic of General and Visceral Surgery, University of Ulm, Ulm, Germany
| | - Johannes Ganser
- Clinic of General and Visceral Surgery, University of Ulm, Ulm, Germany
| | - Jan Scheele
- Clinic of General and Visceral Surgery, University of Ulm, Ulm, Germany
| | - Pengfei Xu
- Clinic of General and Visceral Surgery, University of Ulm, Ulm, Germany
| | - Silvia Sander
- Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany
| | - Doris Henne-Bruns
- Clinic of General and Visceral Surgery, University of Ulm, Ulm, Germany
| | - Marko Kornmann
- Clinic of General and Visceral Surgery, University of Ulm, Ulm, Germany.
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Wilson A, Ronnekliev-Kelly S, Winner M, Pawlik TM. Liver-Directed Therapy in Metastatic Colorectal Cancer. CURRENT COLORECTAL CANCER REPORTS 2016. [DOI: 10.1007/s11888-016-0311-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Qadan M, D'Angelica MI. Complex Surgical Strategies to Improve Resectability in Borderline-Resectable Disease. CURRENT COLORECTAL CANCER REPORTS 2015; 11:369-377. [PMID: 28090195 DOI: 10.1007/s11888-015-0290-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Colorectal cancer is the third most common malignancy in the USA and continues to pose a significant epidemiologic problem, despite major advances in the treatment of patients with advanced disease. Up to 50 % of patients will develop metastatic disease at some point during the course of their disease, with the liver being the most common site of metastatic disease. In this review, we address the relatively poorly defined entity of borderline-resectable colorectal liver metastases. The workup and staging of borderline-resectable disease are discussed. We then discuss management strategies, including surgical techniques and medical therapies, which are currently utilized in order to improve resectability.
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Affiliation(s)
- Motaz Qadan
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C898, New York, NY 10065, USA
| | - Michael I D'Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, C898, New York, NY 10065, USA
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de Greef M, Schubert G, Wijlemans JW, Koskela J, Bartels LW, Moonen CTW, Ries M. Intercostal high intensity focused ultrasound for liver ablation: The influence of beam shaping on sonication efficacy and near-field risks. Med Phys 2015; 42:4685-97. [DOI: 10.1118/1.4925056] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
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