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Kokkinakis S, Ziogas IA, Llaque Salazar JD, Moris DP, Tsoulfas G. Clinical Prediction Models for Prognosis of Colorectal Liver Metastases: A Comprehensive Review of Regression-Based and Machine Learning Models. Cancers (Basel) 2024; 16:1645. [PMID: 38730597 PMCID: PMC11083016 DOI: 10.3390/cancers16091645] [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: 04/07/2024] [Revised: 04/22/2024] [Accepted: 04/23/2024] [Indexed: 05/13/2024] Open
Abstract
Colorectal liver metastasis (CRLM) is a disease entity that warrants special attention due to its high frequency and potential curability. Identification of "high-risk" patients is increasingly popular for risk stratification and personalization of the management pathway. Traditional regression-based methods have been used to derive prediction models for these patients, and lately, focus has shifted to artificial intelligence-based models, with employment of variable supervised and unsupervised techniques. Multiple endpoints, like overall survival (OS), disease-free survival (DFS) and development or recurrence of postoperative complications have all been used as outcomes in these studies. This review provides an extensive overview of available clinical prediction models focusing on the prognosis of CRLM and highlights the different predictor types incorporated in each model. An overview of the modelling strategies and the outcomes chosen is provided. Specific patient and treatment characteristics included in the models are discussed in detail. Model development and validation methods are presented and critically appraised, and model performance is assessed within a proposed framework.
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Affiliation(s)
- Stamatios Kokkinakis
- Department of General Surgery, School of Medicine, University Hospital of Heraklion, University of Crete, 71500 Heraklion, Greece;
| | - Ioannis A. Ziogas
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; (I.A.Z.); (J.D.L.S.)
| | - Jose D. Llaque Salazar
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; (I.A.Z.); (J.D.L.S.)
| | - Dimitrios P. Moris
- Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA;
| | - Georgios Tsoulfas
- Department of Transplantation Surgery, Centre for Research and Innovation in Solid Organ Transplantation, Aristotle University School of Medicine, 54124 Thessaloniki, Greece
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Ucgul E, Guven DC, Ucgul AN, Ozbay Y, Onur MR, Akin S. Factors Influencing Immunotherapy Outcomes in Cancer: Sarcopenia and Systemic Inflammation. Cancer Control 2024; 31:10732748241302248. [PMID: 39547932 PMCID: PMC11569492 DOI: 10.1177/10732748241302248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 10/15/2024] [Accepted: 11/01/2024] [Indexed: 11/17/2024] Open
Abstract
BACKGROUND Immunotherapy has shown promise in treating various subtypes of metastatic cancers, but many patients are frail and may have compromised immune systems, which can influence treatment outcomes. Sarcopenia, a condition characterized by loss of muscle mass and systemic inflammation, is a potential factor that may negatively impact the response to immunotherapy. However, more data must be collected on the extent of its influence. Therefore, this study aims to investigate the effects of sarcopenia, systemic inflammation, and Eastern Cooperative Oncology Group Performance Status (ECOG PS) on the response to immunotherapy. METHODS We enrolled 100 patients treated with immune checkpoint inhibitors between 2015 and 2021 who underwent computed tomography of the abdomen before the first immunotherapy dose. This study was conducted retrospectively. Gender-specific thresholds were used for the diagnosis of sarcopenia. C-reactive protein (CRP), erythrocyte sedimentation rate, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), albumin, and lactate dehydrogenase (LDH) were used as markers of systemic inflammation. Systemic inflammatory markers and sarcopenia were assessed using univariable and multivariable analyses for overall survival (OS) and progression-free survival (PFS). RESULTS Sarcopenia was found to be a significant prognostic factor associated with poor PFS (HR, 2.33; 95% confidence interval [CI], 1.45-3.74; P < 0.001). In addition, hypoalbuminemia was identified as a significant prognostic factor for predicting OS (HR, 2.10; 95% CI, 1.21-3.66; P = 0.008). CONCLUSIONS Closer monitoring and prevention of sarcopenia may enhance both OS and PFS. Additionally, our composite model may assist oncologists in predicting responses to immunotherapy more accurately. However, further prospective studies are needed to validate these findings.
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Affiliation(s)
- Enes Ucgul
- Division of Endocrinology and Metabolism, Etlik City Hospital, Ankara, Turkey
| | - Deniz Can Guven
- Department of Medical Oncology, Elazığ Fethi Sekin City Hospital, Elazığ, Turkey
| | - Aybala Nur Ucgul
- Department of Radiation Oncology, Gulhane Training and Research Hospital, Ankara, Turkey
| | - Yakup Ozbay
- Department of Radiology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Mehmet Ruhi Onur
- Department of Radiology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Serkan Akin
- Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey
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Plahuta I, Mencinger M, Peruš I, Magdalenić T, Turk Š, Brumec A, Potrč S, Ivanecz A. Ranking as a Procedure for Selecting a Replacement Variable in the Score Predicting the Survival of Patients Treated with Curative Intent for Colorectal Liver Metastases. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:2003. [PMID: 38004052 PMCID: PMC10673064 DOI: 10.3390/medicina59112003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 11/04/2023] [Accepted: 11/13/2023] [Indexed: 11/26/2023]
Abstract
Background and Objectives: The issue of a missing variable precludes the external validation of many prognostic models. For example, the Liverpool score predicts the survival of patients undergoing surgical therapy for colorectal liver metastases, but it includes the neutrophil-lymphocyte ratio, which cannot be measured retrospectively. Materials and Methods: We aimed to find the most appropriate replacement for the neutrophil-lymphocyte ratio. Survival analysis was performed on data representing 632 liver resections for colorectal liver metastases from 2000 to 2020. Variables associated with the Liverpool score, C-reactive protein, albumins, and fibrinogen were ranked. The rankings were performed in four ways: The first two were based on the Kaplan-Meier method (log-rank statistics and the definite integral IS between two survival curves). The next method of ranking was based on univariate and multivariate Cox regression analyses. Results: The ranks were as follows: the radicality of liver resection (rank 1), lymph node infiltration of primary colorectal cancer (rank 2), elevated C-reactive protein (rank 3), the American Society of Anesthesiologists Classification grade (rank 4), the right-sidedness of primary colorectal cancer (rank 5), the multiplicity of colorectal liver metastases (rank 6), the size of colorectal liver metastases (rank 7), albumins (rank 8), and fibrinogen (rank 9). Conclusions: The ranking methodologies resulted in almost the same ranking order of the variables. Elevated C-reactive protein was ranked highly and can be considered a relevant replacement for the neutrophil-lymphocyte ratio in the Liverpool score. These methods are suitable for ranking variables in similar models for medical research.
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Affiliation(s)
- Irena Plahuta
- Clinical Department of Abdominal and General Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia; (I.P.); (T.M.); (Š.T.); (A.B.); (S.P.)
- Department of Surgery, Faculty of Medicine, University of Maribor, Taborska ulica 8, 2000 Maribor, Slovenia
| | - Matej Mencinger
- Faculty of Civil Engineering, Transportation Engineering, and Architecture, University of Maribor, Smetanova ulica 17, 2000 Maribor, Slovenia; (M.M.); (I.P.)
- Institute of Mathematics, Physics and Mechanics, Jadranska 19, 1000 Ljubljana, Slovenia
| | - Iztok Peruš
- Faculty of Civil Engineering, Transportation Engineering, and Architecture, University of Maribor, Smetanova ulica 17, 2000 Maribor, Slovenia; (M.M.); (I.P.)
- Faculty of Natural Science and Engineering, University of Ljubljana, Aškerčeva cesta 12, 1000 Ljubljana, Slovenia
| | - Tomislav Magdalenić
- Clinical Department of Abdominal and General Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia; (I.P.); (T.M.); (Š.T.); (A.B.); (S.P.)
| | - Špela Turk
- Clinical Department of Abdominal and General Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia; (I.P.); (T.M.); (Š.T.); (A.B.); (S.P.)
| | - Aleks Brumec
- Clinical Department of Abdominal and General Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia; (I.P.); (T.M.); (Š.T.); (A.B.); (S.P.)
| | - Stojan Potrč
- Clinical Department of Abdominal and General Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia; (I.P.); (T.M.); (Š.T.); (A.B.); (S.P.)
- Department of Surgery, Faculty of Medicine, University of Maribor, Taborska ulica 8, 2000 Maribor, Slovenia
| | - Arpad Ivanecz
- Clinical Department of Abdominal and General Surgery, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia; (I.P.); (T.M.); (Š.T.); (A.B.); (S.P.)
- Department of Surgery, Faculty of Medicine, University of Maribor, Taborska ulica 8, 2000 Maribor, Slovenia
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Canseco LM, Liu YW, Lu CC, Lee KC, Chen HH, Hu WH, Tsai KL, Yang YH, Wang CC, Hung CH. Survival Evidence of Local Control for Colorectal Cancer Liver Metastases by Hepatectomy and/or Radiofrequency Ablation. Cancers (Basel) 2023; 15:4434. [PMID: 37760404 PMCID: PMC10526261 DOI: 10.3390/cancers15184434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Revised: 09/03/2023] [Accepted: 09/04/2023] [Indexed: 09/29/2023] Open
Abstract
Hepatectomy and/or local ablation therapy have been recommended for colorectal cancer liver metastases (CRLM). However, they still lack strong evidence for their survival benefits, in addition to systemic therapy. This study aims to evaluate the survival evidence of hepatectomy and/or radiofrequency ablation (RFA) therapy in CRLM patients from a large multi-institutional database. A total of 20,251 patients with colorectal cancer, 4521 of whom were with CRLM, were screened for eligibility. Finally, 2612 patients (637 hepatectomy, 93 RFA, 92 combined hepatectomy and RFA, and 1790 non-aggressive treatment) were enrolled. Frequency matching analysis was used to adjust for baseline differences. The 5-year overall survival (OS) was as follows: hepatectomy alone was 47.8%, combined hepatectomy plus RFA was 35.9%, RFA alone was 29.2%, and the non-aggressive treatment group was 7.4%. Kaplan-Meier curves showed that hepatectomy, RFA, and combination were significantly associated with a better OS compared to those without aggressive local therapy (p < 0.001). Multivariate Cox regression analysis showed that male gender (hazard ratio (HR) 0.89; 95% confidence interval (CI), 0.81-0.97; p = 0.011), old age (≥60 years) (HR 1.20; 95% CI, 1.09-1.32; p < 0.001), high CEA level (>5 ng/mL) (HR 2.14; 95% CI, 1.89-2.42; p < 0.001), primary right-sided cancer (HR 1.35; 95% CI, 1.22-1.51; p < 0.001), extrahepatic metastasis (HR 1.46; 95% CI, 1.33-1.60; p < 0.001), systemic therapy (HR 0.7; 95% CI, 0.62-0.79; p < 0.001), and aggressive local therapy (hepatectomy vs. non-local therapy HR 0.22; 95% CI, 0.20-0.26; p < 0.001; RFA vs. non-local therapy HR 0.29; 95% CI, 0.29-0.41; p < 0.001) were independent factors associated with OS. In the frequency matching analysis, patients receiving hepatectomy and/or RFA resulted in a better OS than those without (p < 0.001). In conclusion, aggressive local treatment provides survival advantages over systemic therapy alone among CRLM patients.
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Affiliation(s)
- Lariza Marie Canseco
- Section of Gastroenterology, Department of Internal Medicine, De Los Santos Medical Center, Quezon City 1112, MM, Philippines;
| | - Yueh-Wei Liu
- Liver Transplant Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan; (Y.-W.L.); (C.-C.W.)
| | - Chien-Chang Lu
- Department of Colorectal Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan; (C.-C.L.); (K.-C.L.); (H.-H.C.); (W.-H.H.); (K.-L.T.)
| | - Ko-Chao Lee
- Department of Colorectal Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan; (C.-C.L.); (K.-C.L.); (H.-H.C.); (W.-H.H.); (K.-L.T.)
| | - Hong-Hwa Chen
- Department of Colorectal Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan; (C.-C.L.); (K.-C.L.); (H.-H.C.); (W.-H.H.); (K.-L.T.)
| | - Wan-Hsiang Hu
- Department of Colorectal Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan; (C.-C.L.); (K.-C.L.); (H.-H.C.); (W.-H.H.); (K.-L.T.)
| | - Kai-Lung Tsai
- Department of Colorectal Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan; (C.-C.L.); (K.-C.L.); (H.-H.C.); (W.-H.H.); (K.-L.T.)
| | - Yao-Hsu Yang
- Department of Traditional Chinese Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi 61363, Taiwan;
- Health Information and Epidemiology Laboratory of Chang Gung Memorial Hospital, Chiayi 61363, Taiwan
| | - Chih-Chi Wang
- Liver Transplant Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan; (Y.-W.L.); (C.-C.W.)
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan
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Amygdalos I, Hitpass L, Schmidt F, Josephs G, Bednarsch J, Berres ML, Lüdde T, Olde Damink SWM, Ulmer TF, Neumann UP, Bruners P, Lang SA. Survival after combined resection and ablation is not inferior to that after resection alone, in patients with four or more colorectal liver metastases. Langenbecks Arch Surg 2023; 408:343. [PMID: 37642753 PMCID: PMC10465667 DOI: 10.1007/s00423-023-03082-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Accepted: 08/19/2023] [Indexed: 08/31/2023]
Abstract
PURPOSE Colorectal liver metastases (CRLM) are the predominant factor limiting survival in patients with colorectal cancer. Multimodal treatment strategies are frequently necessary to achieve total tumor elimination. This study examines the efficacy of liver resection combined with local ablative therapy in comparison to liver resection only, in the treatment of patients with ≥ 4 CRLM. METHODS This retrospective cohort study was conducted at the University Hospital RWTH Aachen, Germany. Patients with ≥ 4 CRLM in preoperative imaging, who underwent curative resection between 2010-2021, were included. Recurrent resections and deaths in the early postoperative phase were excluded. Ablation modalities included radiofrequency or microwave ablation, and irreversible electroporation. Differences in overall- (OS) and recurrence-free-survival (RFS) between patients undergoing combined resection-ablation vs. resection only, were examined. RESULTS Of 178 included patients, 46 (27%) underwent combined resection-ablation and 132 (73%) resection only. Apart from increased rates of adjuvant chemotherapy in the first group (44% vs. 25%, p = 0.014), there were no differences in perioperative systemic therapy. Kaplan-Meier and log-rank test analyses showed no statistically significant differences in median OS (36 months for both, p = 0.638) or RFS (9 months for combined resection-ablation vs. 8 months, p = 0.921). Cox regression analysis showed a hazard ratio of 0.891 (p = 0.642) for OS and 0.981 (p = 0.924) for RFS, for patients undergoing resection only. CONCLUSION For patients with ≥ 4 CRLM, combined resection-ablation is a viable option in terms of OS and RFS. Therefore, combined resection-ablation should be considered for complete tumor clearance, in patients with multifocal disease.
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Affiliation(s)
- Iakovos Amygdalos
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany.
- Center for Integrated Oncology Aachen, Bonn, Cologne and Düsseldorf (CIO ABCD), Bonn, Germany.
| | - Lea Hitpass
- Center for Integrated Oncology Aachen, Bonn, Cologne and Düsseldorf (CIO ABCD), Bonn, Germany
- Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Aachen, Germany
| | - Felix Schmidt
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany
| | - Gerrit Josephs
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany
| | - Jan Bednarsch
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany
- Center for Integrated Oncology Aachen, Bonn, Cologne and Düsseldorf (CIO ABCD), Bonn, Germany
| | - Marie-Luise Berres
- Center for Integrated Oncology Aachen, Bonn, Cologne and Düsseldorf (CIO ABCD), Bonn, Germany
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany
| | - Tom Lüdde
- Center for Integrated Oncology Aachen, Bonn, Cologne and Düsseldorf (CIO ABCD), Bonn, Germany
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Düsseldorf, Germany
| | - Steven W M Olde Damink
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany
- Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Tom Florian Ulmer
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany
- Center for Integrated Oncology Aachen, Bonn, Cologne and Düsseldorf (CIO ABCD), Bonn, Germany
| | - Ulf P Neumann
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany
- Center for Integrated Oncology Aachen, Bonn, Cologne and Düsseldorf (CIO ABCD), Bonn, Germany
- Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Philipp Bruners
- Center for Integrated Oncology Aachen, Bonn, Cologne and Düsseldorf (CIO ABCD), Bonn, Germany
- Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, Aachen, Germany
| | - Sven Arke Lang
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany
- Center for Integrated Oncology Aachen, Bonn, Cologne and Düsseldorf (CIO ABCD), Bonn, Germany
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Urdaneta Perez M, Morris KT, Stewart K, Sarwar Z, Garwe T. Development of a Risk Score to Predict Post-Discharge Rehabilitation Care After Liver Metastasectomy. J Surg Res 2022; 280:44-49. [PMID: 35961256 DOI: 10.1016/j.jss.2022.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 06/16/2022] [Accepted: 07/06/2022] [Indexed: 10/15/2022]
Abstract
INTRODUCTION Need for discharge to intermediate care (DCIC) can increase length of stay and be a source of stress to patients. Estimating risk of DCIC would allow earlier involvement of case managers, improve length of stay and patient satisfaction by setting realistic expectations. The aim was to use National Surgical Quality Improvement Program dataset to develop a prediction model for DCIC after undergoing liver metastasectomy. METHODS Data were obtained from National Surgical Quality Improvement Program 2011-2018 covering liver metastasectomy. Recursive partitioning narrowed potential predictors and identified thresholds for categorization of continuous variables. Logistic regression identified a predictive model, internally validated by using 200 bootstrap samples with replacement. A risk score was derived using Framingham Study methodology by dividing all regression coefficients by the smallest model coefficient. Receiver operating characteristic analysis identified the score that maximized sensitivity/specificity, defining low/high risk. Finally, recursive partitioning identified categories low/medium/high. RESULTS The most parsimonious model predicting DCIC area under the curve (, 0.722, 95%CI: 0.705-0.739) identified five independent predictors including age >60, procedure type, hypertension requiring medication, albumin <3.5 mg/dL and hematocrit <30%. Internal validation resulted in expected bias-corrected area under the curve of 0.717, 95% CI: 0.698-0.732. The maximum score was 17.9 and 5.8 maximized sensitivity (sn) and specificity (sp) [sn = 81%, sp = 51%) predicting DCIC. Stratified into three groups, a score ≥9.5 identified highest risk (12.8%), ≥4.3 medium (6.1%) and <4.3 lowest risk (1.5%). CONCLUSIONS Determining risk of DCIC benefits shared decision making and patient care. This evidence may enhance discharge planning after liver metastasectomy expediting the process. Age >60 contributed the most weight to the score, but the use of additional variables in three groups allowed further discrimination between patients.
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Sasaki K, Margonis GA, Moro A, Wang J, Wagner D, Gagnière J, Shin JK, D'Silva M, Sahara K, Miyata T, Kusakabe J, Beyer K, Dupré A, Kamphues C, Imai K, Baba H, Endo I, Taura K, Cho JY, Aucejo F, Kornprat P, Kreis ME, Kim JM, Burkhart R, David Kwon CH, Pawlik TM. Nontumor related risk score: A new tool to improve prediction of prognosis after hepatectomy for colorectal liver metastases. Surgery 2022; 171:1580-1587. [PMID: 35221105 DOI: 10.1016/j.surg.2022.01.030] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 01/20/2022] [Accepted: 01/23/2022] [Indexed: 02/06/2023]
Abstract
BACKGROUND Prognostic stratification of patients with colorectal cancer liver metastasis based solely on tumor-related factors has only moderate discriminatory ability. We hypothesized that the inclusion of nontumor related factors can improve prediction of long-term prognosis of patients with colorectal cancer liver metastasis. METHODS Nontumor related laboratory markers were assessed utilizing a training cohort from 2 U.S. institutions (n = 1,205). Factors independently associated with prognosis were used to develop a nontumor related prognostic score. The discriminatory ability, assessed by Harrell's C-statistics (C-index) and net reclassification improvement, was validated and compared with 3 commonly used tumor-related clinical risk scores: Fong clinical risk scores, m-clinical risk scores, and Genetic and Morphological Evaluation (GAME) score in an external validation cohort from 5 Asian (n = 1,307) and 3 European (n = 1,058) institutions. The discriminatory ability of nontumor related prognostic score combined with each of these 3 tumor-related prognostic scores was also estimated. RESULTS Alkaline phosphatase (hazard ratio 1.43; 95% confidence interval, 1.11-1.84), albumin (hazard ratio 0.71; 95% confidence interval, 0.57-0.89), and mean corpuscular volume (hazard ratio 19.0, per log unit; 95% confidence interval, 4.79-75.0) were each independently associated with increased risk of death after resection of colorectal cancer liver metastasis (all P < .05). In turn, alkaline phosphatase, albumin, and mean corpuscular volume were combined to form a nontumor related prognostic score (2.942 × mean corpuscular volume + 0.399 × alkaline phosphatase-0.339 × albumin-12) × 10 (median, 16; range, 1-30). The nontumor related prognostic score had good-to-modest discriminatory ability in the external cohort (C-index = 0.58), which was comparable to the 3 established tumor-related prognostic scores (C-index: Fong clinical risk scores, 0.53, m-clinical risk scores, 0.55, GAME, 0.58). The addition of the nontumor related prognostic score to the tumor-related prognostic scores enhanced the discriminatory ability in the entire study cohort (C-index: nontumor related score+Fong, 0.60, nontumor related score+m-clinical risk scores, 0.61, nontumor related score+GAME, 0.64), as well reclassification improvement (42.5, 42.7%, and 21.2%, respectively). CONCLUSION Nontumor related prognostic information may help improve the prognostic stratification of patients after resection of colorectal cancer liver metastasis. The nontumor related prognostic score may be combined with tumor-related prognostic tools to enhance prognostic stratification of patients with colorectal cancer liver metastasis.
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Affiliation(s)
- Kazunari Sasaki
- Department of Surgery, Stanford University School of Medicine, Stanford, CA.
| | - Georgios Antonios Margonis
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Department of General, Visceral and Vascular Surgery, Charite Campus Benjamin Franklin, Berlin, Germany
| | - Amika Moro
- Department of Surgery, Cleveland Clinic Foundation, Cleveland, OH
| | - Jane Wang
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Doris Wagner
- Department of General Surgery, Medical University of Graz, Graz, Austria
| | - Johan Gagnière
- Service de Chirurgie Digestive, CHU Clermont-Ferrand, Inserm, Université Clermont, Clermont-Ferrand, France
| | - Jung Kyong Shin
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Mizelle D'Silva
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Kota Sahara
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Tatsunori Miyata
- Department of Gastroenterological Surgery, Graduate School of Life Sciences Kumamoto University, Kumamoto, Japan
| | - Jiro Kusakabe
- Department of Surgery, Stanford University School of Medicine, Stanford, CA
| | - Katharina Beyer
- Department of General, Visceral and Vascular Surgery, Charite Campus Benjamin Franklin, Berlin, Germany
| | - Aurélien Dupré
- Service de Chirurgie Digestive, CHU Clermont-Ferrand, Inserm, Université Clermont, Clermont-Ferrand, France
| | - Carsten Kamphues
- Department of General, Visceral and Vascular Surgery, Charite Campus Benjamin Franklin, Berlin, Germany
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Graduate School of Life Sciences Kumamoto University, Kumamoto, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Life Sciences Kumamoto University, Kumamoto, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Kojiro Taura
- Department of Gastroenterological Surgery, Kyoto University Hospital, Kyoto, Japan
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Federico Aucejo
- Department of Surgery, Cleveland Clinic Foundation, Cleveland, OH
| | - Peter Kornprat
- Department of General Surgery, Medical University of Graz, Graz, Austria
| | - Martin E Kreis
- Department of General, Visceral and Vascular Surgery, Charite Campus Benjamin Franklin, Berlin, Germany
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Richard Burkhart
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | | | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH. https://twitter.com/timpawlik
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Peng SH, Mbarak HS, Li YH, Ma C, Shang QL, Chen Z, Bian DJ, Xiao EH. Neoadjuvant intra-arterial versus intravenous chemotherapy in colorectal cancer. Medicine (Baltimore) 2021; 100:e28312. [PMID: 34941125 PMCID: PMC8701446 DOI: 10.1097/md.0000000000028312] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Accepted: 11/24/2021] [Indexed: 01/05/2023] Open
Abstract
To investigate the clinical benefits of transcatheter arterial infusion chemotherapy compared with intravenous chemotherapy in patients with colorectal cancer (CRC).From May 2013 to March 2018, 83 patients (50 men and 33 women) with surgically proven CRC were retrospectively included. Before surgery, 62 patients received conventional systemic chemotherapy, and 21 transcatheter arterial chemotherapy. Basic characteristics, disease control rate (DC), adverse reactions, postoperative complications, and toxicity profiles were collected and compared between the 2 groups.The sigmoid colon (43.37%) was the most common primary tumor location, and the least was the transverse colon (6.02%). Most lesions invaded the subserosa or other structures T3-4 (78.31%), and other lesions invaded the muscular layer T1-2 (21. 69%). The overall DC was 80.65% in the intravenous chemotherapy group and 90.48% in the arterial chemotherapy group (P < .05). Adverse events included myelosuppression and gastrointestinal reactions such as nausea, vomiting, diarrhea, abnormal liver function, and neurotoxicity, which were significantly less common in the intra-arterial group than in the intravenous group (P < .05). Postoperative complications included abdominal infection (11.29% vs 14.29%), intestinal obstruction (6.45% vs 4.76%), anastomotic bleeding (1.61% vs 0.00%), and anastomotic fistula (6.45% vs 4.76%) in the intravenous and intra-arterial groups, respectively (P > .05).Preoperative transcatheter arterial infusion chemotherapy is a safe and effective neoadjuvant chemotherapy measure for CRC with fewer adverse reactions and a higher overall DC.
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BOZBIYIK O, ÇOKER A. Factors affecting survival in liver metastasis of colorectal cancer. EGE TIP DERGISI 2021. [DOI: 10.19161/etd.1036904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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10
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Karami K, Akbari M, Moradi MT, Soleymani B, Fallahi H. Survival prognostic factors in patients with acute myeloid leukemia using machine learning techniques. PLoS One 2021; 16:e0254976. [PMID: 34288963 PMCID: PMC8294525 DOI: 10.1371/journal.pone.0254976] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 07/07/2021] [Indexed: 12/26/2022] Open
Abstract
This paper identifies prognosis factors for survival in patients with acute myeloid leukemia (AML) using machine learning techniques. We have integrated machine learning with feature selection methods and have compared their performances to identify the most suitable factors in assessing the survival of AML patients. Here, six data mining algorithms including Decision Tree, Random Forrest, Logistic Regression, Naive Bayes, W-Bayes Net, and Gradient Boosted Tree (GBT) are employed for the detection model and implemented using the common data mining tool RapidMiner and open-source R package. To improve the predictive ability of our model, a set of features were selected by employing multiple feature selection methods. The accuracy of classification was obtained using 10-fold cross-validation for the various combinations of the feature selection methods and machine learning algorithms. The performance of the models was assessed by various measurement indexes including accuracy, kappa, sensitivity, specificity, positive predictive value, negative predictive value, and area under the ROC curve (AUC). Our results showed that GBT with an accuracy of 85.17%, AUC of 0.930, and the feature selection via the Relief algorithm has the best performance in predicting the survival rate of AML patients.
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Affiliation(s)
- Keyvan Karami
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Department of Animal Science, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Mahboubeh Akbari
- Department of Statistics, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Mohammad-Taher Moradi
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Bijan Soleymani
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
- * E-mail: , (HF); (BS)
| | - Hossein Fallahi
- Department of Biology, School of Sciences, Razi University, Kermanshah, Iran
- * E-mail: , (HF); (BS)
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Shuayb M, Mehedi Hasan M, Hoque MR, Mushtaq Hussain Q, Begum R, Reza MS. Survival and prognostic association in stage IV colorectal cancer patients treated with chemotherapy in Bangladesh. Jpn J Clin Oncol 2021; 51:552-559. [PMID: 33341898 DOI: 10.1093/jjco/hyaa228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 11/03/2020] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE Prognostic factors in colorectal cancer have lesser been evaluated in developing countries. This study aims to determine overall survival and prognostic factors for metastatic colorectal cancer patients who were non-operable and received chemotherapy. METHODS The study retrospectively investigated 67 inoperable metastatic colorectal cancer patients at Square Hospital, Bangladesh. The primary endpoint was overall survival, and the secondary endpoints were prognostic association with factors. Survival probabilities were calculated by non-parametric Kaplan-Meier method and compared by log-rank test. Univariate and multivariable Cox proportional hazard models were implemented to assess the prognostic association. RESULTS Median survival of the entire cohort was 14 months (95% confidence interval: 11-25). In multivariable analysis, two prognostic factors were independently associated with survival: Karnofsky performance status and carcinoembryonic antigen. Patients with Karnofsky performance status <70 had significant higher risk of death than those with Karnofsky performance status ≥70 (adjusted hazard ratio 4.25, 95% confidence interval: 2.15-8.39). Higher risk of death was found to be associated with higher carcinoembryonic antigen: adjusted hazard ratio was 1.72 (95% confidence interval: 0.81-3.68) and 2.96 (95% confidence interval: 1.25-7.01) for patients with carcinoembryonic antigen 10-100 and >100 ng/ml, respectively, while comparing with carcinoembryonic antigen <10 ng/ml. The presence of peritoneal metastasis and grade-III tumour significantly worsened the survival in univariate analysis (hazard ratio 2.46, 95% confidence interval: 1.32-4.57 and hazard ratio 1.74, 95% confidence interval: 1.01-3.03, respectively) but not in multivariable analysis (adjusted hazard ratio 1.92, 95% confidence interval: 0.88-4.18 and adjusted hazard ratio 1.25, 95% confidence interval: 0.66-2.36, respectively). CONCLUSION The study reported survival of stage IV colorectal cancer patients undergo chemotherapy and identified that Karnofsky performance status and carcinoembryonic antigen are the poor prognostic factors to this cohort adjusting for other factors.
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Affiliation(s)
- Md Shuayb
- Square Oncology & Radiotherapy Centre, Square Hospitals Ltd, Dhaka, Bangladesh.,Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada
| | - Md Mehedi Hasan
- Square Oncology & Radiotherapy Centre, Square Hospitals Ltd, Dhaka, Bangladesh
| | - Md Rashedul Hoque
- Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada
| | | | - Rabeya Begum
- Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada
| | - Md Salim Reza
- Square Oncology & Radiotherapy Centre, Square Hospitals Ltd, Dhaka, Bangladesh
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12
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Early Recurrence After Initial Hepatectomy for Colorectal Liver Metastases. Int Surg 2021. [DOI: 10.9738/intsurg-d-17-00018.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Objective
This study investigated the frequency of early recurrence in patients who had undergone hepatectomy for colorectal cancer liver metastasis (CRLM) and assessed the indications for adjuvant chemotherapy in these patients.
Methods
This retrospective analysis included 133 consecutive patients who underwent initial hepatectomy for CRLM between April 2000 and May 2010 and have been followed more than 5 years.
Results
Of the 133 patients, 83 (62%) experienced tumor recurrence, with 14 of the 83 recurrences within 6 months after initial hepatectomy. Overall survival was significantly poorer in patients with recurrences within 6 months than those without any recurrence (P = 0.015). The frequency of adjuvant chemotherapy was significantly lower in patients with recurrences within 6 months than those without recurrences within 6 months. Multivariate analysis showed that H-2 classification was the only independent risk factor for recurrence within 6 months after hepatectomy (P = 0.002). Adjuvant chemotherapy improved prognosis in patients classified as H2.
Conclusions
Patients who experienced tumor recurrence within 6 months after initial hepatectomy for CRLM had a poorer prognosis than patients who experienced recurrence after 6 months. Patients with H2-classification of CRLM should receive preoperative adjuvant chemotherapy.
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13
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Beppu T, Imai K, Honda G, Sakamoto K, Kobayashi S, Endo I, Hasegawa K, Kotake K, Itabashi M, Hashiguchi Y, Kotera Y, Yamaguchi T, Tabuchi K, Kobayashi H, Yamaguchi K, Morita S, Kikuchi K, Miyazaki M, Sugihara K, Yamamoto M, Takahashi K. Proposal of a novel H category-based classification of colorectal liver metastases based on a Japanese nationwide survey. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2021; 28:317-326. [PMID: 33609318 DOI: 10.1002/jhbp.920] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 01/27/2021] [Accepted: 02/18/2021] [Indexed: 11/06/2022]
Abstract
BACKGROUND The conventional H category-based classification for colorectal liver metastases (CRLM) was created by equal weighting of tumor number and tumor size; however, our previous nomogram to predict postoperative disease-free survival demonstrated that CRLM ≥5 as a parameter provided 4.5 times greater impact compared with a largest CRLM size >5 cm. METHODS A total of 3815 patients newly diagnosed with CRLM between 2005 and 2007, including 2220 resectable cases, were investigated. Six groups were created based on largest lesion size (≤ 5 vs >5 cm) and lesion number (1, 2-4, and ≥5). RESULTS The novel (n) H1, nH2, and nH3 categories were defined as solitary lesions with a size ≤5 cm; lesions other than nH1 or nH3; and ≥5 lesions with any lesion size, respectively. In the resectable cohort, the 5-year cumulative overall survival rates were 64.0%, 53.5%, and 42.6% in the nH1, nH2, and nH3 groups, respectively (P < .001), and no significant differences were observed between the conventional H2 and H3 categories. In the overall cohort, the discrimination ability of the two classifications were comparable. CONCLUSION The novel H category-based classification might be beneficial in predicting overall survival in patients with CRLM independent of their resectability.
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Affiliation(s)
- Toru Beppu
- Department of Surgery, Yamaga City Medical Center, Yamaga, Japan
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Goro Honda
- Department of Gastroenterological Surgery, New Tokyo Hospital, Matsudo, Japan
| | - Katsunori Sakamoto
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Toon, Japan
| | - Shin Kobayashi
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Japan
| | | | - Michio Itabashi
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Japan
| | - Yojiro Hashiguchi
- Department of Surgery, Teikyo University Graduate School of Medicine, Itabashi-ku, Japan
| | - Yoshihito Kotera
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Japan
| | - Tatsuro Yamaguchi
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo-ku, Japan
| | - Ken Tabuchi
- Department of Pediatrics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo-ku, Japan
| | | | - Kensei Yamaguchi
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Satoshi Morita
- Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | | | - Masaru Miyazaki
- International University of Health and Welfare, Mita Hospital, Minata-ku, Japan
| | | | - Masakazu Yamamoto
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Japan
| | - Keiichi Takahashi
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo-ku, Japan
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Kamphues C, Andreatos N, Kruppa J, Buettner S, Wang J, Sasaki K, Wagner D, Morioka D, Fitschek F, Løes IM, Imai K, Sun J, Poultsides G, Kaczirek K, Lønning PE, Endo I, Baba H, Kornprat P, Aucejo FN, Wolfgang CL, Kreis ME, Weiss MJ, Margonis GA. The optimal cut-off values for tumor size, number of lesions, and CEA levels in patients with surgically treated colorectal cancer liver metastases: An international, multi-institutional study. J Surg Oncol 2021; 123:939-948. [PMID: 33400818 DOI: 10.1002/jso.26361] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2020] [Revised: 12/18/2020] [Accepted: 12/18/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND OBJECTIVES Despite the long-standing consensus on the importance of tumor size, tumor number and carcinoembryonic antigen (CEA) levels as predictors of long-term outcomes among patients with colorectal liver metastases (CRLM), optimal prognostic cut-offs for these variables have not been established. METHODS Patients who underwent curative-intent resection of CRLM and had available data on at least one of the three variables of interest above were selected from a multi-institutional dataset of patients with known KRAS mutational status. The resulting cohort was randomly split into training and testing datasets and recursive partitioning analysis was employed to determine optimal cut-offs. The concordance probability estimates (CPEs) for these optimal cut offs were calculated and compared to CPEs for the most widely used cut-offs in the surgical literature. RESULTS A total of 1643 patients who met eligibility criteria were identified. Following recursive partitioning analysis in the training dataset, the following cut-offs were identified: 2.95 cm for tumor size, 1.5 for tumor number and 6.15 ng/ml for CEA levels. In the entire dataset, the calculated CPEs for the new tumor size (0.52), tumor number (0.56) and CEA (0.53) cut offs exceeded CPEs for other commonly employed cut-offs. CONCLUSION The current study was able to identify optimal cut-offs for the three most commonly employed prognostic factors in CRLM. While the per variable gains in discriminatory power are modest, these novel cut-offs may help produce appreciable increases in prognostic performance when combined in the context of future risk scores.
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Affiliation(s)
- Carsten Kamphues
- Department of General, Visceral, and Vascular Surgery, Charité, University Medicine, Campus Benjamin Franklin, Berlin, Germany
| | | | - Jochen Kruppa
- Department of General, Visceral, and Vascular Surgery, Charité, University Medicine, Campus Benjamin Franklin, Berlin, Germany
| | - Stefan Buettner
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Jaeyun Wang
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Kazunari Sasaki
- Department of Surgery, Cleveland Clinic, Cleveland, Ohio, USA
| | - Doris Wagner
- Department of General Surgery, Medical University of Graz, Graz, Austria
| | - Daisuke Morioka
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Fabian Fitschek
- Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Inger Marie Løes
- Department of Clinical Science and Oncology, Haukeland University Hospital, University of Bergen, Bergen, Norway
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan
| | - Jinger Sun
- Department of Surgery, Cleveland Clinic, Cleveland, Ohio, USA
| | - George Poultsides
- Department of Surgery, Stanford University School of Medicine, Stanford, California, USA
| | - Klaus Kaczirek
- Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Per Eystein Lønning
- Department of Clinical Science and Oncology, Haukeland University Hospital, University of Bergen, Bergen, Norway
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan
| | - Peter Kornprat
- Department of General Surgery, Medical University of Graz, Graz, Austria
| | | | - Christopher L Wolfgang
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Martin E Kreis
- Department of General, Visceral, and Vascular Surgery, Charité, University Medicine, Campus Benjamin Franklin, Berlin, Germany
| | - Matthew J Weiss
- Department of Surgery, Zucker School of Medicine at Hofstra, Northwell Health Cancer Institute, Lake Success, New York, USA
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15
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Civil O, Okkabaz N, Sahin TT, Tiryaki C, Yazicioglu MB, Kement M. Long-Term Results and Prognostic Significance of Non-ANATOMIC Liver Resection for Colorectal Liver Metastasis: Single Center Experience. Indian J Surg 2020; 82:197-204. [DOI: 10.1007/s12262-019-02041-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 11/28/2019] [Indexed: 02/05/2023] Open
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Duran Derijckere I, Levillain H, Bohlok A, Mathey C, Nezri J, Muteganya R, Trotta N, Lucidi V, Bouazza F, Germanova D, Van Simaeys G, Goldman S, Hendlisz A, Flamen P, Donckier V. The metabolic clinical risk score as a new prognostic model for surgical decision-making in patients with colorectal liver metastases. J Surg Oncol 2020; 121:350-356. [PMID: 31721228 DOI: 10.1002/jso.25763] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 11/04/2019] [Indexed: 01/24/2023]
Abstract
BACKGROUND AND OBJECTIVES Selection for surgery in patients with colorectal liver metastases (CRLM) remains inaccurate. We evaluated if CRLM baseline metabolic characteristics, assessed by [18]F-fluorodeoxyglucose-positron emission tomography/computed tomography (18 FDG-PET/CT), could predict postoperative outcomes. METHODS In a retrospective series of patients undergoing surgery for CRLM, we defined two groups: the long-term survival (LTS) and early relapse (ER) groups, where the postoperative recurrence-free survivals were ≥5 years or <1 year, respectively. We analyzed the patients in whom baseline 18 FDG-PET/CT was available. Clinicopathologic parameters, clinical risk score (CRS), and baseline 18 FDG-PET/CT characteristics were compared between LTS and ER groups. A metabolic CRS (mCRS) was implemented, adding one point to the standard five-point CRS when the highest tumor standardized uptake values (SUVmax )/normal liver mean SUV (SUVmean(liver) ) ratios were >4.3, defining low- and high-risk mCRS by scores of 0 to 2 and 3 to 6, respectively. RESULTS From a series of 450 patients operated for CRLM (mean follow-up of 58 months), we included for analysis 23 and 30 patients in the LTS and ER groups, respectively. Clinicopathologic parameters and CRS were similar in the LTS and ER groups. Median SUVmax /SUVmean(liver) ratios were higher in ER vs LTS patients (4.2 and 2.8, P = .008, respectively). mCRS was increased in ER patients (P = .024); 61% of LTS patients had low-risk mCRS and 73% of the ER patients had high-risk mCRS (P = .023). CONCLUSIONS 18 FDG-PET/CT characteristics combined with traditional CRS may represent a new tool to improve selection for surgery in patients with CRLM.
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Affiliation(s)
- Ivan Duran Derijckere
- Nuclear Medicine Department, Institut Jules Bordet-Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Hugo Levillain
- Nuclear Medicine Department, Institut Jules Bordet-Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Ali Bohlok
- Surgical Oncology Department, Institut Jules Bordet-Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Celine Mathey
- Nuclear Medicine Department, Hôpital Erasme-Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Jonathan Nezri
- Surgical Oncology Department, Institut Jules Bordet-Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Raoul Muteganya
- Nuclear Medicine Department, Hôpital Erasme-Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Nicola Trotta
- Nuclear Medicine Department, Hôpital Erasme-Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Valerio Lucidi
- Abdominal Surgery Department, Hôpital Erasme-Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Fikri Bouazza
- Surgical Oncology Department, Institut Jules Bordet-Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Desislava Germanova
- Abdominal Surgery Department, Hôpital Erasme-Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Gaetan Van Simaeys
- Nuclear Medicine Department, Hôpital Erasme-Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Serge Goldman
- Nuclear Medicine Department, Hôpital Erasme-Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Alain Hendlisz
- Digestive Oncology Department, Institut Jules Bordet-Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Patrick Flamen
- Nuclear Medicine Department, Institut Jules Bordet-Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Vincent Donckier
- Surgical Oncology Department, Institut Jules Bordet-Université Libre de Bruxelles (ULB), Brussels, Belgium
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18
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Ito T, Sugiura T, Okamura Y, Yamamoto Y, Ashida R, Uesaka K. The impact of posthepatectomy liver failure on long-term survival after hepatectomy for colorectal liver metastasis. HPB (Oxford) 2019; 21:1185-1193. [PMID: 30777694 DOI: 10.1016/j.hpb.2019.01.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2018] [Revised: 01/04/2019] [Accepted: 01/18/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Postoperative complications affect both the short-term and long-term outcomes. The aim of this study was to identify specific prognostic factors among complications after hepatectomy for colorectal liver metastasis (CRLM). METHODS Between 2002 and 2014, 427 patients underwent initial hepatectomy for CRLM. The clinicopathological parameters including postoperative complications were evaluated to identify the prognostic factors for the overall (OS) and relapse-free survival (RFS). RESULTS One hundred and forty-nine patients (34%) developed postoperative complications, including surgical site infection (n = 49, 11.4%), bile leakage (n = 41, 9.6%), posthepatectomy liver failure (PHLF) (n = 26, 6.0%), and pulmonary complication (n = 20, 4.6%). The independent predictors of RFS included primary nodal metastasis, abnormal CA19-9 levels, extrahepatic metastasis, bilateral CRLMs, ≥5 CRLMs, preoperative chemotherapy, lack of adjuvant chemotherapy and PHLF. The 5-year RFS rates in patients with and without PHLF were 8% and 32%, respectively (P < 0.001). The independent prognostic factors for OS included primary nodal metastasis, abnormal CA19-9 levels, extrahepatic metastasis, positive surgical margins, preoperative chemotherapy, lack of adjuvant chemotherapy and PHLF. The 5-year OS rates in patients with and without PHLF were 31% and 63%, respectively (P = 0.004). CONCLUSIONS Among the complications, only PHLF was associated with decreased long-term survival after hepatectomy for CRLM as well as tumor-specific prognostic factors.
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Affiliation(s)
- Takaaki Ito
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
| | - Teiichi Sugiura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan
| | - Yukiyasu Okamura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan
| | - Yusuke Yamamoto
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan
| | - Ryo Ashida
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan
| | - Katsuhiko Uesaka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan
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19
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Ongaro E, Cremolini C, Rossini D, Corti F, Pagani F, Morelli L, Urbani L, Masi G, Sposito C, Filippi B, Borelli B, Zucchelli G, Moretto R, Boccaccino A, Solaini L, de Braud F, Mazzaferro V, Falcone A, Cucchetti A, Pietrantonio F. Clinical and molecular determinants of extrahepatic disease progression in patients with metastatic colorectal cancer with liver-limited metastases deemed initially unresectable. ESMO Open 2019; 4:e000496. [PMID: 31231562 PMCID: PMC6555604 DOI: 10.1136/esmoopen-2019-000496] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2019] [Revised: 02/19/2019] [Accepted: 02/21/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND No tools to predict the probability of extrahepatic disease progression (ePD) of initially unresectable, liver-limited metastatic colorectal cancer (mCRC) are currently available. To estimate the likelihood to develop ePD and to identify clinical and molecular factors that could predict extrahepatic progression-free survival (ePFS), we conducted an observational, retrospective, multicentre cohort study. METHODS We retrospectively identified a cohort of 225 patients with initially unresectable liver-limited disease (LLD), treated from January 2004 to December 2017 with first-line doublets or triplet plus a biological agent at two Italian institutions. RESULTS 173 (77%) patients experienced ePD which occurred within 1, 2 or 3 years from the diagnosis of mCRC in 15%, 49% and 66% of patients, respectively. Globally, 164 (73%) patients underwent a liver resection at some point of their disease history, and 54 (33%) of them underwent a subsequent locoregional treatment. Age > 70 years, locoregional nodal involvement at diagnosis of colorectal cancer and ≥4 liver metastases were significantly associated with higher risk of ePD while liver resections were associated with reduced risk of ePD. In the multivariable model, number of liver metastases (subdistribution HR, SHR 1.63, 95% CI 1.12 to 2.36; p = 0.01) and liver resections (SHR 0.43, 95% CI 0.29 to 0.63; p = 0.001) were still associated with ePD. Number of liver metastases < 4, no nodal involvement at diagnosis and liver resections were also associated with prolonged ePFS. CONCLUSIONS The identified clinical factors could help physicians in personalising the intensity and aggressiveness of liver-directed treatments in patients with mCRC with initially unresectable LLD.
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Affiliation(s)
- Elena Ongaro
- Unit of Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
- Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy
- Department of Oncology, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy
| | - Chiara Cremolini
- Unit of Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
- Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Daniele Rossini
- Unit of Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
- Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Francesca Corti
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Filippo Pagani
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Luca Morelli
- General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
| | - Lucio Urbani
- Department of General Surgery, Liver Metastasis Parenchyma Sparing Surgery Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Gianluca Masi
- Unit of Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
- Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Carlo Sposito
- Department of Gastrointestinal and Hepatobilio-Pancreatic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Beatrice Filippi
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Beatrice Borelli
- Unit of Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
- Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Gemma Zucchelli
- Unit of Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
- Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Roberto Moretto
- Unit of Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
- Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Alessandra Boccaccino
- Unit of Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
- Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Leonardo Solaini
- Department of Medical and Surgical Sciences, DIMEC, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Filippo de Braud
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
- Department of Oncology and Hemato-oncology, Universityof Milan, Milan, Italy
| | - Vincenzo Mazzaferro
- Department of Gastrointestinal and Hepatobilio-Pancreatic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Alfredo Falcone
- Unit of Medical Oncology 2, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
- Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences, DIMEC, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Filippo Pietrantonio
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
- Department of Oncology and Hemato-oncology, Universityof Milan, Milan, Italy
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20
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Afshari K, Chabok A, Naredi P, Smedh K, Nikberg M. Prognostic factors for survival in stage IV rectal cancer: A Swedish nationwide case-control study. Surg Oncol 2019; 29:102-106. [PMID: 31196471 DOI: 10.1016/j.suronc.2019.04.005] [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] [Received: 02/26/2019] [Revised: 04/01/2019] [Accepted: 04/08/2019] [Indexed: 01/28/2023]
Abstract
PURPOSE The aim was to identify patient-, tumor- and treatment-related prognostic factors for five-year survival in rectal cancer patients with synchronous stage IV disease. MATERIAL AND METHODS This nationwide case-control study was based on the Swedish Colorectal Cancer Registry with supplementary information from medical records and the Swedish Inpatient Registry during the period 2000-2008. All resected rectal cancer patients with synchronous metastases that survived more than five years were included as cases. The control group consisted of corresponding patients who lived less than five years, matched in a 1:2 based on gender, age, resection of the rectal tumor, and the study period. RESULTS A total of 405 patients were identified; 99 long-term survivors (LTS) and 182 short-term survivors (STS). Patient-related factors of symptoms and comorbidity did not differ between LTS and STS. Among the treatment-related factors, multiple site metastases (p = 0.007), bilobar liver metastasis (p = 0.002), and increasing number of liver metastasis (p < 0.001) were associated with STS. Prognostic treatment-related factors were preoperative radiotherapy (p = 0.001), metastasectomy (p < 0.001), and radical resection of the primary tumor (p = 0.014). In the multivariable analysis, the single most important factor for becoming a LTS was a metastasectomy (hazard ratio: 8.474, 95% confidence interval: 4.098-17.543). CONCLUSIONS The most important prognostic factor for long-term survival in patients with stage IV rectal cancer was metastasectomy, especially liver surgery. With thorough selection of patients for metastasectomy more patients with metastasized rectal cancer may survive beyond five years.
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Affiliation(s)
- Kevin Afshari
- Colorectal Unit, Department of Surgery and Centre for Clinical Research of Uppsala University, Västmanland's Hospital Västerås, Sweden.
| | - Abbas Chabok
- Colorectal Unit, Department of Surgery and Centre for Clinical Research of Uppsala University, Västmanland's Hospital Västerås, Sweden
| | - Peter Naredi
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden
| | - Kenneth Smedh
- Colorectal Unit, Department of Surgery and Centre for Clinical Research of Uppsala University, Västmanland's Hospital Västerås, Sweden
| | - Maziar Nikberg
- Colorectal Unit, Department of Surgery and Centre for Clinical Research of Uppsala University, Västmanland's Hospital Västerås, Sweden
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21
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Margonis GA, Sasaki K, Gholami S, Kim Y, Andreatos N, Rezaee N, Deshwar A, Buettner S, Allen PJ, Kingham TP, Pawlik TM, He J, Cameron JL, Jarnagin WR, Wolfgang CL, D'Angelica MI, Weiss MJ. Genetic And Morphological Evaluation (GAME) score for patients with colorectal liver metastases. Br J Surg 2018; 105:1210-1220. [PMID: 29691844 DOI: 10.1002/bjs.10838] [Citation(s) in RCA: 126] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Revised: 12/05/2017] [Accepted: 01/15/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND This study sought to develop a clinical risk score for resectable colorectal liver metastasis (CRLM) by combining clinicopathological and clinically available biological indicators, including KRAS. METHODS A cohort of patients who underwent resection for CRLM at the Johns Hopkins Hospital (JHH) was analysed to identify independent predictors of overall survival (OS) that can be assessed before operation; these factors were combined into the Genetic And Morphological Evaluation (GAME) score. The score was compared with the current standard (Fong score) and validated in an external cohort of patients from the Memorial Sloan Kettering Cancer Center (MSKCC). RESULTS Six preoperative predictors of worse OS were identified on multivariable Cox regression analysis in the JHH cohort (502 patients). The GAME score was calculated by allocating points to each patient according to the presence of these predictive factors: KRAS-mutated tumours (1 point); carcinoembryonic antigen level 20 ng/ml or more (1 point), primary tumour lymph node metastasis (1 point); Tumour Burden Score between 3 and 8 (1 point) or 9 and over (2 points); and extrahepatic disease (2 points). The high-risk group in the JHH cohort (GAME score at least 4 points) had a 5-year OS rate of 11 per cent, compared with 73·4 per cent for those in the low-risk group (score 0-1 point). Importantly, in cohorts from both the JHH and MSKCC (747 patients), the discriminatory capacity of the GAME score was superior to that of the Fong score, as demonstrated by the C-index and the Akaike information criterion. CONCLUSION The GAME score is a preoperative prognostic tool that can be used to inform treatment selection.
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Affiliation(s)
- G A Margonis
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - K Sasaki
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - S Gholami
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Y Kim
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - N Andreatos
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - N Rezaee
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - A Deshwar
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - S Buettner
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.,Department of Surgery, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands
| | - P J Allen
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - T P Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - T M Pawlik
- Department of Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - J He
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - J L Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - W R Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - C L Wolfgang
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - M I D'Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - M J Weiss
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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22
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Ushio A, Takauchi K, Kobayashi M, Abe N, Sumida H, Nagata Y, Awai K. [Differentiation between Hepatic Focal Lesions and Heterogenous Physiological Accumulations by Early Delayed Scanning in 18F-FDG PET/CT Examination]. Nihon Hoshasen Gijutsu Gakkai Zasshi 2018; 74:556-562. [PMID: 29925750 DOI: 10.6009/jjrt.2018_jsrt_74.6.556] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
PURPOSE We examined whether early delayed scanning is useful for differentiation of liver lesion and heterogenous physiological accumulation in positron emission tomography (PET) examination. METHODS The subjects of the study were 33 patients with colorectal cancer who underwent PET examination and were added early delayed scanning to distinguish between liver lesions and heterogenous physiological accumulation to conventional early images. We placed same regions of interest (ROI) in the tumor and hepatic parenchyma for early delayed and conventional early images. Then, we measured SUVmax of the ROIs and calculated tumor to liver parenchyma uptake ratio (TLR). In addition, change rates between early and early delayed images were calculated for the SUVmax and TLR. RESULTS The receiver operating characterstic (ROC) analysis result of SUVmax showed the highest SUVmax change rate, and the ROC analysis result of TLR showed the highest early delayed scanning. The SUVmax of the lesions did not change between early scan and early delayed scanning (p=0.98), but it decreased significantly in the normal group (p<0.001). TLR of the lesion group was significantly increased (p<0.001) in early delayed images compared to early scan and TLR significantly decreased in the normal group (p<0.001). The AUC of the ROC curve showed the highest SUVmax change rate (0.99). CONCLUSION Early delayed scanning could distinguish between liver lesions and heterogenous physiological accumulation in colon cancer patients.
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Affiliation(s)
- Ayaka Ushio
- Department of Radiology, Hiroshima University Hospital
| | | | | | - Nobukazu Abe
- Department of Radiology, Hiroshima University Hospital
| | | | - Yasushi Nagata
- Department of Radiation Oncology, Hiroshima University Hospital
| | - Kazuo Awai
- Department of Diagnostic Radiology, Hiroshima University Hospital
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23
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Ma KW, Cheung TT, She WH, Chok KSH, Chan ACY, Dai WC, Lo CM. Risk prediction model for major complication after hepatectomy for malignant tumour - A validated scoring system from a university center. Surg Oncol 2017; 26:446-452. [PMID: 29113664 DOI: 10.1016/j.suronc.2017.08.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2017] [Accepted: 08/29/2017] [Indexed: 01/27/2023]
Abstract
OBJECTIVE To derive and validate a scoring system for major complication after hepatectomy. BACKGROUND Complications after hepatectomy significantly compromise survival outcomes, method to predict such risk is lacking. A reliable scoring system is therefore awaited. METHODS Consecutive adult patients receiving hepatectomy for primary or secondary liver malignancy from 1995 to 2014 were recruited. After randomization, patients were allocated to derivation and validation group respectively. A scoring system predicting occurrence of major complication was developed. RESULTS There were 2613 patients eligible for the study. The overall complication rate for the series was 10%. Impaired performance status (p = 0.014), presence of pre-existing medical illness (p = 0.008), elevated ALP (p = 0.005), urea (p < 0.001), and hypoalbuminemia (p = 0.008), and major hepatectomy (p < 0.001) were found to be independently associated major complications. A score was assigned to each of these factors according to their respective odd ratio. A total score of 0-17 was calculated for all patients. This score was shown to discriminate well with complication rate in both derivation and validation group (c-statistic: 0.71, p < 0.001 and 0.74, p < 0.001 respectively). The complication rate for low (score 0-5), moderate (score 6-10) and high (score 10 or above) risk group were respectively 5%, 16% and 28%. This risk stratification model was tested and confirmed in the validation group using Chi-square goodness-of-fit test (p = 0.864). CONCLUSION A validated risk stratification model provides an accurate and easy-to-use reference tool for patients and clinicians during the informed consent process.
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Affiliation(s)
- Ka Wing Ma
- Department of Surgery, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
| | - Tan To Cheung
- Department of Surgery, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China; State Key Laboratory for Liver Research, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China.
| | - Wong Hoi She
- Department of Surgery, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
| | - Kenneth S H Chok
- Department of Surgery, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
| | - Albert Chi Yan Chan
- Department of Surgery, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
| | - Wing Chiu Dai
- Department of Surgery, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
| | - Chung Mau Lo
- Department of Surgery, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China; State Key Laboratory for Liver Research, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
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24
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Zhang C, Fan HW, Yi WW, Zheng ZQ. Hidden Blood Loss and Its Influential Factors After Laparoscopy-Assisted Gastrectomy for Gastric Cancer. J Laparoendosc Adv Surg Tech A 2017; 28:237-241. [PMID: 29064310 DOI: 10.1089/lap.2017.0468] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
INTRODUCTION Laparoscopy-assisted gastrectomy (LAG) is a minimally invasive procedure for the treatment of gastric cancer. It is generally thought that a minimally invasive technique results in less visible blood loss during the surgery. Nevertheless, a meaningful perioperative hidden blood loss (HBL) is often ignored. In this study, we investigated the amount of HBL and the influential factors after LAG for gastric cancer. METHODS A retrospectively analyzed clinical data of 62 consecutive patients who underwent laparoscopy-assisted total or distal gastrectomy at our center from May 2016 to May 2017. The HBL was calculated according to Gross's and Nadler's formula. The data of patient gender, age, height, weight, body mass index, preoperative and postoperative hematocrit, postoperative drainage, albumin loss, diabetes mellitus, and hypertension were analyzed by multivariate linear regression analysis. The type of surgical reconstruction was analyzed by one-way analysis of variance. The difference between the preoperative blood pressure and postoperative blood pressure was measured by paired sample t-test and boxplot. RESULTS The HBL was 322.2 ± 195.9 mL (64.3% ± 14.1% in total blood loss [TBL]), the TBL was 475.6 ± 222.8 mL, and the hemoglobin (HB) loss was 15.0 ± 8.7 (11.5% ± 6.1% of HB level loss). Multivariate linear regression analysis revealed that gender, hypertension, and albumin loss between preoperation and postoperation are influential factors of HBL in patients after LAG for gastric cancer. Compared to male patients, female patients are positively associated with HBL. CONCLUSION In our study, we found HBL is a significant segment of TBL and is much larger than what we considered previously in LAG for gastric cancer. Gender, hypertension, and albumin loss are significantly correlated with HBL. Therefore, paying attention to HBL is significant for promoting clinical treatment and ensuring patients' safety.
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Affiliation(s)
- Chao Zhang
- 1 Department of General Surgery, The Second Affiliated Hospital of Wenzhou Medical University , Wenzhou, China
| | - Heng-Wei Fan
- 2 Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University , Shanghai, China
| | - Wan-Wan Yi
- 3 Department of Nuclear, Shanghai Tenth People's Hospital, Tongji University , Shanghai, China
| | - Zhi-Qiang Zheng
- 1 Department of General Surgery, The Second Affiliated Hospital of Wenzhou Medical University , Wenzhou, China
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25
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Mahar AL, Compton C, Halabi S, Hess KR, Weiser MR, Groome PA. Personalizing prognosis in colorectal cancer: A systematic review of the quality and nature of clinical prognostic tools for survival outcomes. J Surg Oncol 2017; 116:969-982. [PMID: 28767139 DOI: 10.1002/jso.24774] [Citation(s) in RCA: 101] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2017] [Accepted: 06/16/2017] [Indexed: 12/13/2022]
Abstract
Integrating diverse types of prognostic information into accurate, individualized estimates of outcome in colorectal cancer is challenging. Significant heterogeneity in colorectal cancer prognostication tool quality exists. Methodology is incompletely or inadequately reported. Evaluations of the internal or external validity of the prognostic model are rarely performed. Prognostication tools are important devices for patient management, but tool reliability is compromised by poor quality. Guidance for future development of prognostication tools in colorectal cancer is needed.
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Affiliation(s)
- Alyson L Mahar
- Division of Cancer Care and Epidemiology, Cancer Research Institute, Queen's University, Ontario, Canada
| | - Carolyn Compton
- Professor Life Sciences, Arizona State University and Professor of Laboratory Medicine and Pathology, Mayo Clinic School of Medicine, Rochester, Minnesota.,Chair, Precision Medicine Core, American Joint Committee on Cancer 8th Edition Editorial Board, Rochester, Minnesota
| | - Susan Halabi
- Department of Biostatistics and Bioinformatics, Duke University and Alliance Statistics and Data Center, Durham, North Carolina
| | - Kenneth R Hess
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.,Chair, Evidence-Based Medicine and Statistics Core, AJCC 8th Edition Editorial Board, Rochester, Minnesota
| | | | - Patti A Groome
- Division of Cancer Care and Epidemiology, Cancer Research Institute, Queen's University, Ontario, Canada
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26
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Sasaki K, Margonis GA, Andreatos N, Zhang XF, Buettner S, Wang J, Deshwar A, He J, Wolfgang CL, Weiss M, Pawlik TM. The prognostic utility of the “Tumor Burden Score” based on preoperative radiographic features of colorectal liver metastases. J Surg Oncol 2017; 116:515-523. [DOI: 10.1002/jso.24678] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2017] [Accepted: 04/24/2017] [Indexed: 12/23/2022]
Affiliation(s)
- Kazunari Sasaki
- Department of Surgery; Johns Hopkins University School of Medicine; Baltimore Maryland
| | - Georgios A. Margonis
- Department of Surgery; Johns Hopkins University School of Medicine; Baltimore Maryland
| | - Nikolaos Andreatos
- Department of Surgery; Johns Hopkins University School of Medicine; Baltimore Maryland
| | - Xu-Feng Zhang
- Department of Surgery; Johns Hopkins University School of Medicine; Baltimore Maryland
- Department of Surgery; The Ohio State University Wexner Medical Center; Columbus Ohio
| | - Stefan Buettner
- Department of Surgery; Johns Hopkins University School of Medicine; Baltimore Maryland
| | - Jaeyun Wang
- Department of Surgery; Johns Hopkins University School of Medicine; Baltimore Maryland
| | - Amar Deshwar
- Department of Surgery; Johns Hopkins University School of Medicine; Baltimore Maryland
| | - Jin He
- Department of Surgery; Johns Hopkins University School of Medicine; Baltimore Maryland
| | | | - Matthew Weiss
- Department of Surgery; Johns Hopkins University School of Medicine; Baltimore Maryland
| | - Timothy M. Pawlik
- Department of Surgery; Johns Hopkins University School of Medicine; Baltimore Maryland
- Department of Surgery; The Ohio State University Wexner Medical Center; Columbus Ohio
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27
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Laurent C, Adam JP, Denost Q, Smith D, Saric J, Chiche L. Significance of R1 Resection for Advanced Colorectal Liver Metastases in the Era of Modern Effective Chemotherapy. World J Surg 2016; 40:1191-9. [PMID: 26757718 DOI: 10.1007/s00268-016-3404-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The prognosis impact of positive margins after resection of colorectal liver metastases (CLM) in patients treated with modern effective chemotherapy has not been elucidated. The objective was to compare oncologic outcomes after R0 and R1 resections in the era of modern effective chemotherapy. METHODS Between 1999 and 2010, all consecutive patients undergoing liver resection for CLM were analyzed retrospectively. Patients with extrahepatic metastases, macroscopic residual tumor, treated with combined radiofrequency, or not treated with chemotherapy were excluded. Survival and recurrence after R0 (tumor-free margin >0 mm) and R1 resections were analyzed. RESULTS Among 466 patients undergoing hepatectomy for CLM, 191 were eligible. Of them, 164 (86 %) received preoperative chemotherapy and 105 (55 %) received postoperative chemotherapy. R1 resection (10 %) was comparable in patients treated or not by preoperative chemotherapy. R1 status was associated with more intrahepatic recurrences. Overall survival (OS) (44 vs. 61 %; p = 0.047) and disease-free survival (DFS) (8 vs. 26 %; p = 0.082) were lower in patients after R1 compared to R0 resection (32 months of median follow-up). Preoperative chemotherapy and major hepatectomy were prognostic factors of survival, whereas postoperative chemotherapy was a protective factor from recurrences. In patients treated with preoperative chemotherapy, OS and DFS were similar between R1 and R0 resections (40 vs. 55 %, p = 0.104 and 9 vs. 22 %, p = 0.174, respectively). CONCLUSION In the era of modern effective chemotherapy, R1 resection leads to more intrahepatic recurrences but did not affect OS in selected patient responders to neoadjuvant chemotherapy. Postoperative chemotherapy protects from recurrences whatever the margin resection status.
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Affiliation(s)
- Christophe Laurent
- University of Bordeaux Segalen, 33076, Bordeaux, France. .,Department of Hepatobiliary Surgery, CHU Bordeaux, Saint André Hospital, 1 rue Jean Burguet, 33075, Bordeaux, France.
| | - Jean-Philippe Adam
- University of Bordeaux Segalen, 33076, Bordeaux, France.,Department of Hepatobiliary Surgery, CHU Bordeaux, Saint André Hospital, 1 rue Jean Burguet, 33075, Bordeaux, France
| | - Quentin Denost
- University of Bordeaux Segalen, 33076, Bordeaux, France.,Department of Hepatobiliary Surgery, CHU Bordeaux, Saint André Hospital, 1 rue Jean Burguet, 33075, Bordeaux, France
| | - Denis Smith
- University of Bordeaux Segalen, 33076, Bordeaux, France.,Department of Digestive Oncology, CHU Bordeaux, Saint André Hospital, 33075, Bordeaux, France
| | - Jean Saric
- University of Bordeaux Segalen, 33076, Bordeaux, France.,Department of Hepatobiliary Surgery, CHU Bordeaux, Saint André Hospital, 1 rue Jean Burguet, 33075, Bordeaux, France
| | - Laurence Chiche
- University of Bordeaux Segalen, 33076, Bordeaux, France.,Department of Hepatobiliary Surgery, CHU Bordeaux, Haut-Lévèque Hospital, 33600, Pessac, France
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28
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Zhou XW, Dong H, Yang Y, Luo JW, Wang X, Liu YH, Mao Q. Significance of the prognostic nutritional index in patients with glioblastoma: A retrospective study. Clin Neurol Neurosurg 2016; 151:86-91. [DOI: 10.1016/j.clineuro.2016.10.014] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2016] [Revised: 10/12/2016] [Accepted: 10/21/2016] [Indexed: 12/22/2022]
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29
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Marfà S, Marti J, Reyes A, Casals G, Fernández-Varo G, Carvajal S, García-Valdecasas JC, Fuster J, Jiménez W. Metastatic Tissue Proteomic Profiling Predicts 5-Year Outcomes in Patients with Colorectal Liver Metastases. Transl Oncol 2016; 9:445-452. [PMID: 27751349 PMCID: PMC5067925 DOI: 10.1016/j.tranon.2016.08.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Revised: 08/03/2016] [Accepted: 08/08/2016] [Indexed: 01/05/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common cancers in the developed countries, and nearly 70% of patients with CRC develop colorectal liver metastases (CRLMs). During the last decades, several scores have been proposed to predict recurrence after CRLM resection. However, these risk scoring systems do not accurately reflect the prognosis of these patients. Therefore, this investigation was designed to identify a proteomic profile in human hepatic tumor samples to classify patients with CRLM as “mild” or “severe” based on the 5-year survival. The study was performed on 85 CRLM tumor samples. Firstly, to evaluate any distinct tumor proteomic signatures between mild and severe CRLM patients, a training group of 57 CRLM tumor samples was characterized by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, and a classification and regression tree (CART) analysis was subsequently performed. Finally, 28 CRLM tumor samples were used to confirm and validate the results obtained. Based on all the protein peaks detected in the training group, the CART analysis was generated, and four peaks were considered to be the most relevant to construct a diagnostic algorithm. Indeed, the multivariate model yielded a sensitivity of 85.7% and a specificity of 86.1%, respectively. In addition, the receiver operating characteristic (ROC) curve showed an excellent diagnostic accuracy to discriminate mild from severe CRLM patients (area under the ROC: 0.903). Finally, the validation process yielded a sensitivity and specificity of 68.8% and 83.3%, respectively. We identified a proteomic profile potentially useful to determine the prognosis of CRLM patients based on the 5-year survival.
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Affiliation(s)
- Santiago Marfà
- Biochemistry and Molecular Genetics Service, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Josep Marti
- HepatoBilioPancreatic Surgery and Transplant Unit Department of Surgery, ICMDM, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Adalgiza Reyes
- HepatoBilioPancreatic Surgery and Transplant Unit Department of Surgery, ICMDM, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Gregori Casals
- Biochemistry and Molecular Genetics Service, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Guillermo Fernández-Varo
- Biochemistry and Molecular Genetics Service, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biomedicine, University of Barcelona, Barcelona, Spain
| | - Silvia Carvajal
- Biochemistry and Molecular Genetics Service, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - J C García-Valdecasas
- HepatoBilioPancreatic Surgery and Transplant Unit Department of Surgery, ICMDM, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Josep Fuster
- HepatoBilioPancreatic Surgery and Transplant Unit Department of Surgery, ICMDM, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Wladimiro Jiménez
- Biochemistry and Molecular Genetics Service, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biomedicine, University of Barcelona, Barcelona, Spain.
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Kumar R, Dennison AR, Robertson V, Jones MJ, Neal CP, Garcea G. Clinical risk scores in the current era of neoadjuvant chemotherapy for colorectal liver metastases. ANZ J Surg 2016; 88:E16-E20. [PMID: 27621179 DOI: 10.1111/ans.13688] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2016] [Accepted: 05/29/2016] [Indexed: 12/18/2022]
Abstract
BACKGROUND Clinical risk scores (CRS) within the context of neoadjuvant chemotherapy for colorectal liver metastases (CRLM) has not been validated. The predictive value of clinical risk scoring in patients administered neoadjuvant chemotherapy prior to liver surgery for CRLM is evaluated. METHODS A prospective database over a 15-year period (April 1999 to March 2014) was analysed. We identified two groups: A, neoadjuvant chemotherapy prior to CRLM surgery; and B, no neoadjuvant chemotherapy. RESULTS Overall median survival in groups A and B were 36 (2-137) months and 33 (2-137) months. In group A, nodal status, size, number of metastases and carcinoembryonic antigen levels were not found to be independent predictors of overall survival (OS). However, patients with a shorter disease-free interval of less than 12 months had an increased OS (P = 0.0001). Multivariate analysis of high- and low-risk scores compared against survival in group B (P < 0.05) confirms the applicability of the scoring system in traditional settings. CONCLUSION Traditional CRS are not a prognostic predictive tool when applied to patients receiving neoadjuvant chemotherapy for CRLM. Disease-free interval may be one independent variable for use in future risk score systems specifically developed for the neoadjuvant chemotherapy era.
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Affiliation(s)
- Rohan Kumar
- Department of Hepato-Pancreato-Biliary Surgery, University Hospitals of Leicester, Leicester, UK
| | - Ashley R Dennison
- Department of Hepato-Pancreato-Biliary Surgery, University Hospitals of Leicester, Leicester, UK
| | - Vaux Robertson
- Department of Hepato-Pancreato-Biliary Surgery, University Hospitals of Leicester, Leicester, UK
| | - Michael J Jones
- Department of Hepato-Pancreato-Biliary Surgery, University Hospitals of Leicester, Leicester, UK
| | - Christopher P Neal
- Department of Hepato-Pancreato-Biliary Surgery, University Hospitals of Leicester, Leicester, UK
| | - Giuseppe Garcea
- Department of Hepato-Pancreato-Biliary Surgery, University Hospitals of Leicester, Leicester, UK
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31
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Liu BZ, Tao L, Chen YZ, Li XZ, Dong YL, Ma YJ, Li SG, Li F, Zhang WJ. Preoperative Body Mass Index, Blood Albumin and Triglycerides Predict Survival for Patients with Gastric Cancer. PLoS One 2016; 11:e0157401. [PMID: 27309531 PMCID: PMC4911005 DOI: 10.1371/journal.pone.0157401] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2016] [Accepted: 05/27/2016] [Indexed: 02/07/2023] Open
Abstract
Background Gastric cancer (GC) is common and its prognosis is often poor due to difficulties in early diagnosis and optimal treatment strategies. TNM staging system is useful in predicting prognosis but only possible after surgery. Therefore, it is desirable to investigate prognostic factors/markers that may predict prognosis before surgery by which helps appropriate management decisions preoperatively. Methods A total of 320 GC patients were consecutively recruited from 2004 to 2013 and followed up for 127 months (10.6 years) after surgery. These patients’ were examined for body mass index (BMI) and blood levels of albumin, triglyceride, total cholesterol, low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C). Kaplan-Meier method and log rank test were used to analyze long-term survival using the above potential risk markers. We first employed medians of these variables to reveal maximal potentials of the above prognostic predictors. Results Three major findings were obtained: (1) Preoperative BMI was positively correlated with albumin (r = 0.144, P<0.05) and triglyceride (r = 0.365, P<0.01), but negatively correlated with TNM staging (r = -0.265, P<0.05). Preoperative albumin levels were positively correlated with triglyceride (r = 0.173, P<0.05) but again, negatively correlated with TNM staging (r = -0.137, P<0.05); (2) Poor survival was observed in GC patients with lower levels of BMI (P = 0.028), albumin (P = 0.004), and triglyceride (P = 0.043), respectively. Receiver operating characteristic (ROC) curve analyses suggested BMI, albumin and triglyceride to have survival-predictor powers similar to TNM system; and (3) Cox multi-factorial analyses demonstrated that age (P = 0.049), BMI (P = 0.016), cell differentiation (P = 0.001), and TNM staging (P = 0.011) were independent overall survival-predictors for GC patients. Conclusions Preoperative BMI, albumin, and triglyceride levels are capable of predicting survival for GC patients superior to postoperative TNM system in terms of timing for management. As potential survival-predictors, preoperative tests of BMI, albumin and triglyceride, combined with clinical imaging, may help personalized management for GC patients including planning surgical strategy, optimal radio-chemotherapy and appropriate follow-up intervals after surgery.
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Affiliation(s)
- Bin Zheng Liu
- Department of Pathology, the First Affiliated University Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China
- The Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China
| | - Lin Tao
- Department of Pathology, the First Affiliated University Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China
- The Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China
| | - Yun Zhao Chen
- Department of Pathology, the First Affiliated University Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China
- The Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China
| | - Xu Zhe Li
- Department of Pathology, the First Affiliated University Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China
- The Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China
| | - Yu Ling Dong
- Department of Pathology, the First Affiliated University Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China
- The Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China
| | - Ya Jing Ma
- Clinical Laboratory, the First Affiliated University Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China
| | - Shu Gang Li
- Department of Preventive Medicine, Shihezi University School of Medicine, Shihezi, Xinjiang, China
| | - Feng Li
- Department of Pathology, the First Affiliated University Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China
- Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Wen Jie Zhang
- Department of Pathology, the First Affiliated University Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China
- The Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China
- * E-mail:
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Mattar RE, Al-alem F, Simoneau E, Hassanain M. Preoperative selection of patients with colorectal cancer liver metastasis for hepatic resection. World J Gastroenterol 2016; 22:567-581. [PMID: 26811608 PMCID: PMC4716060 DOI: 10.3748/wjg.v22.i2.567] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 09/24/2015] [Accepted: 12/01/2015] [Indexed: 02/06/2023] Open
Abstract
Surgical resection of colorectal liver metastases (CRLM) has a well-documented improvement in survival. To benefit from this intervention, proper selection of patients who would be adequate surgical candidates becomes vital. A combination of imaging techniques may be utilized in the detection of the lesions. The criteria for resection are continuously evolving; currently, the requirements that need be met to undergo resection of CRLM are: the anticipation of attaining a negative margin (R0 resection), whilst maintaining an adequate functioning future liver remnant. The timing of hepatectomy in regards to resection of the primary remains controversial; before, after, or simultaneously. This depends mainly on the tumor burden and symptoms from the primary tumor. The role of chemotherapy differs according to the resectability of the liver lesion(s); no evidence of improved survival was shown in patients with resectable disease who received preoperative chemotherapy. Presence of extrahepatic disease in itself is no longer considered a reason to preclude patients from resection of their CRLM, providing limited extra-hepatic disease, although this currently is an area of active investigations. In conclusion, we review the indications, the adequate selection of patients and perioperative factors to be considered for resection of colorectal liver metastasis.
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Controversies in defining prognostic relevant selection criteria that determine long-term effectiveness of liver resection for noncolorectal nonneuroendocrine liver metastasis. Int J Surg 2015; 24:85-90. [DOI: 10.1016/j.ijsu.2015.11.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2015] [Accepted: 11/04/2015] [Indexed: 12/20/2022]
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Hepatic artery infusion therapy is effective for chemotherapy-resistant liver metastatic colorectal cancer. World J Surg Oncol 2015; 13:296. [PMID: 26452624 PMCID: PMC4600220 DOI: 10.1186/s12957-015-0704-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2015] [Accepted: 09/22/2015] [Indexed: 12/31/2022] Open
Abstract
Background Systemic FOLFOX (folinic acid (leucovorin (LV)), 5-fluorouracil (5-FU), and oxaliplatin), FOLFIRI (LV, 5-FU, and irinotecan), or FOLFOXIRI (5-FU, leucovorin, oxaliplatin, and irinotecan) chemotherapy regimens and additional molecular-target treatments, including anti-vascular endothelial growth factor, anti-epidermal growth factor receptor, and anti-multi-kinase antibodies, have been recommended for unresectable recurrent colorectal cancers. However, no effective treatments are currently available for cases refractory to these therapies. Therefore, the development of alternative therapies is desired. In the present study, we administered and observed the effectiveness of hepatic artery infusion therapy (HAIC) in patients with unresectable liver metastatic colorectal cancers refractory to systemic chemotherapy. In addition, we observed that in an experimental system with anticancer drug-resistant colorectal cancer lines, apoptosis and cell death could be induced by increasing anticancer drug concentrations. Methods The subjects had liver metastatic colorectal cancers that were unresponsive to systemic chemotherapy (FOLFOX/FOLFIRI) or to additional molecular-target therapies for progressive disease. Hepatic infusion tube placement was conducted according to the Seldinger method to insert a catheter with a side hole via the right femoral artery. A coiling procedure was performed to prevent drug influx into the gastroduodenal artery. Ten subjects were selected, and the results were evaluated after HAIC (5-FU and LV administered once weekly). Moreover, anticancer drug-resistant colorectal cancer lines were subsequently prepared to investigate whether increased anticancer drug concentrations could induce apoptosis or cell death. Results Of the 10 subjects, 3 (30 %) showed partial response and 4 (40 %) showed no change according to computed tomography imaging findings obtained after hepatic artery infusion. The disease control rate was 70 %. Eight subjects had improved quality of life. Survival time ranged from 2 to 16 months (median, 9 months). Meanwhile, we found that higher anticancer drug concentrations induced apoptosis and cell death in an anticancer drug-resistant colorectal cancer cell line. Conclusions HAIC was effective in some systemic chemotherapy-resistant colorectal cancers with liver metastases and should be considered as an effective palliative therapy. This supports the finding that apoptosis and cell death could be induced in anticancer drug-resistant colorectal cancer cells in a drug concentration-dependent manner.
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35
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Ayez N, van der Stok EP, de Wilt H, Radema SA, van Hillegersberg R, Roumen RM, Vreugdenhil G, Tanis PJ, Punt CJ, Dejong CH, Jansen RL, Verheul HM, de Jong KP, Hospers GA, Klaase JM, Legdeur MC, van Meerten E, Eskens FA, van der Meer N, van der Holt B, Verhoef C, Grünhagen DJ. Neo-adjuvant chemotherapy followed by surgery versus surgery alone in high-risk patients with resectable colorectal liver metastases: the CHARISMA randomized multicenter clinical trial. BMC Cancer 2015; 15:180. [PMID: 25884448 PMCID: PMC4377036 DOI: 10.1186/s12885-015-1199-8] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Accepted: 03/17/2015] [Indexed: 12/12/2022] Open
Abstract
Background Efforts to improve the outcome of liver surgery by combining curative resection with chemotherapy have failed to demonstrate definite overall survival benefit. This may partly be due to the fact that these studies often involve strict inclusion criteria. Consequently, patients with a high risk profile as characterized by Fong’s Clinical Risk Score (CRS) are often underrepresented in these studies. Conceptually, this group of patients might benefit the most from chemotherapy. The present study evaluates the impact of neo-adjuvant chemotherapy in high-risk patients with primary resectable colorectal liver metastases, without extrahepatic disease. Our hypothesis is that adding neo-adjuvant chemotherapy to surgery will provide an improvement in overall survival (OS) in patients with a high-risk profile. Methods/Design CHARISMA is a multicenter, randomized, phase III clinical trial. Patients will be randomized to either surgery alone (standard treatment, arm A) or to 6 cycles of neo-adjuvant oxaliplatin-based chemotherapy, followed by surgery (arm B). Patients must be ≥ 18 years of age with liver metastases of histologically confirmed primary colorectal carcinoma. Patients with extrahepatic metastases are excluded. Liver metastases must be deemed primarily resectable. Only patients with a CRS of 3–5 are eligible. The primary study endpoint is OS. Secondary endpoints are progression free survival (PFS), quality of life, morbidity of resection, treatment response on neo-adjuvant chemotherapy, and whether CEA levels can predict treatment response. Discussion CHARISMA is a multicenter, randomized, phase III clinical trial that will provide an answer to the question if adding neo-adjuvant chemotherapy to surgery will improve OS in a well-defined high-risk patient group with colorectal liver metastases. Trial registration The CHARISMA is registered at European Union Clinical Trials Register (EudraCT), number: 2013-004952-39, and in the “Netherlands national Trial Register (NTR), number: 4893.
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Affiliation(s)
- Ninos Ayez
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands.
| | - Eric P van der Stok
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands.
| | - Hans de Wilt
- Department of Surgical Oncology, Radboud University, Nijmegen Medical Center, Nijmegen, The Netherlands.
| | - Sandra A Radema
- Department of Medical Oncology, Radboud University, Nijmegen Medical Center, Nijmegen, The Netherlands.
| | | | - Rudi M Roumen
- Department of Surgery, Máxima Medical Center, Veldhoven, The Netherlands.
| | - Gerard Vreugdenhil
- Department of Medical Oncology, Máxima Medical Center, Veldhoven, The Netherlands.
| | - Pieter J Tanis
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands.
| | - Cornelis J Punt
- Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands.
| | - Cornelis H Dejong
- Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands.
| | - Rob L Jansen
- Department of Medical Oncology, Maastricht University Medical Center, Maastricht, The Netherlands.
| | - Henk M Verheul
- Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
| | - Koert P de Jong
- Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
| | - Geke A Hospers
- Department of Medical Oncology, University Medical Center Groningen, Groningen, The Netherlands.
| | - Joost M Klaase
- Department of Surgery, Medisch Spectrum Twente, Enschede, The Netherlands.
| | - Marie-Cecile Legdeur
- Department of Internal Medicine, Medisch Spectrum Twente, Enschede, The Netherlands.
| | - Esther van Meerten
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
| | - Ferry A Eskens
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
| | - Nelly van der Meer
- Clinical Trial Center, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
| | - Bruno van der Holt
- Clinical Trial Center, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
| | - Cornelis Verhoef
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands.
| | - Dirk J Grünhagen
- Department of Surgical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands.
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Shinto E, Takahashi K, Yamaguchi T, Hashiguchi Y, Kotake K, Itabashi M, Yasuno M, Kanemitsu Y, Nishimura G, Akagi Y, Sato T, Kato T, Matsumoto H, Hase K, Sugihara K. Validation and Modification of the Japanese Classification System for Liver Metastases from Colorectal Cancer: A Multi-institutional Study. Ann Surg Oncol 2015; 22:3888-95. [DOI: 10.1245/s10434-015-4470-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2014] [Indexed: 01/05/2023]
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Nomogram including pretherapeutic parameters for prediction of survival after SIRT of hepatic metastases from colorectal cancer. Eur Radiol 2015; 25:2693-700. [DOI: 10.1007/s00330-015-3658-7] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2015] [Accepted: 02/03/2015] [Indexed: 12/26/2022]
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Stremitzer S, Stift J, Graf A, Singh J, Starlinger P, Gruenberger B, Tamandl D, Gruenberger T. CEA change after neoadjuvant chemotherapy including bevacizumab and clinical outcome in patients undergoing liver resection for colorectal liver metastases. Ann Surg Oncol 2014; 22:1315-23. [PMID: 25323471 DOI: 10.1245/s10434-014-4158-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2014] [Indexed: 01/04/2023]
Abstract
BACKGROUND Liver resection after neoadjuvant chemotherapy offers the chance of cure and long-term survival in patients with resectable colorectal liver metastases (CLM). Currently, there are no established biomarkers that could help identify patients with low risk of recurrence who may benefit most from liver resection in curative intent. To address this issue, the value of carcinoembryonic antigen (CEA) change after neoadjuvant chemotherapy was investigated to predict clinical outcome in this study. METHODS CEA levels before (baseline) and after neoadjuvant chemotherapy including bevacizumab before liver resection were obtained in 154 patients with CLM from a prospectively maintained database. Changes of CEA in percent through neoadjuvant treatment were correlated with recurrence-free survival and overall survival (OS). Patients with normal CEA levels at all times (baseline and follow-up) were excluded from the analyses. RESULTS After exclusion of 15 patients with normal CEA levels at all times, 139 patients were available for analysis. Receiver operating characteristic analyses revealed a CEA change (decrease) cutoff value of 50 %, which significantly separated 88 patients with respect to OS (P = 0.017). Cox regression analyses showed that the change of CEA at a cutoff value of 50 % was predictive for OS (hazard ratio 0.37, P = 0.025) independent from the baseline CEA level, but not for recurrence-free survival. Furthermore, a CEA change of >50 % was associated with a higher radiologic response rate (P = 0.016). CONCLUSIONS CEA change induced through neoadjuvant treatment was associated with radiologic response and OS, and this measure is a promising tool to predict clinical outcome in the future.
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Affiliation(s)
- Stefan Stremitzer
- Department of General Surgery, Medical University Vienna, Vienna, Austria
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Kim KY, Kim NK, Cha IH, Ahn JB, Choi JS, Choi GH, Lim JS, Lee KY, Baik SH, Min BS, Hur H, Roh JK, Shin SJ. Novel methods for clinical risk stratification in patients with colorectal liver metastases. Cancer Res Treat 2014; 47:242-50. [PMID: 25483744 PMCID: PMC4398102 DOI: 10.4143/crt.2014.066] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2014] [Accepted: 04/03/2014] [Indexed: 12/27/2022] Open
Abstract
Purpose Colorectal cancer patients with liver-confined metastases are classified as stage IV, but their prognoses can differ from metastases at other sites. In this study, we suggest a novel method for risk stratification using clinically effective factors. Materials and Methods Data on 566 consecutive patients with colorectal liver metastasis (CLM) between 1989 and 2010 were analyzed. This analysis was based on principal component analysis (PCA). Results The survival rate was affected by carcinoembryonic antigen (CEA) level (p < 0.001; risk ratio, 1.90), distribution of liver metastasis (p=0.014; risk ratio, 1.46), and disease-free interval (DFI; p < 0.001; risk ratio, 1.98). When patients were divided into three groups according to PCA score using significantly affected factors, they showed significantly different survival patterns (p < 0.001). Conclusion The PCA scoring system based on CEA level, distribution of liver metastasis, and DFI may be useful for preoperatively determining prognoses in order to assist in clinical decisionmaking and designing future clinical trials for CLM treatment.
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Affiliation(s)
- Ki-Yeol Kim
- Oral Cancer Research Institute, Seoul, Korea
| | - Nam Kyu Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - In-Ho Cha
- Oral Cancer Research Institute, Seoul, Korea ; Department of Oral and Maxillofacial Surgery, Yonsei University College of Dentistry, Seoul, Korea
| | - Joong Bae Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jin Sub Choi
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Gi-Hong Choi
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Joon Suk Lim
- Department of Diagnostic Radiology, Yonsei University College of Medicine, Seoul, Korea
| | - Kang Young Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Seung Hyuk Baik
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Byung Soh Min
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Hyuk Hur
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Kyung Roh
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Joon Shin
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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Gomez D, Zaitoun AM, De Rosa A, Hossaini S, Beckingham IJ, Brooks A, Cameron IC. Critical review of the prognostic significance of pathological variables in patients undergoing resection for colorectal liver metastases. HPB (Oxford) 2014; 16:836-44. [PMID: 24617566 PMCID: PMC4159457 DOI: 10.1111/hpb.12216] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2013] [Accepted: 12/13/2013] [Indexed: 12/12/2022]
Abstract
OBJECTIVE The aim of this study was to identify prognostic factors, particularly pathological variables, that influence disease-free and overall survival following resection for colorectal liver metastases (CRLM). METHODS Patients undergoing CRLM resection from January 2005 to December 2011 were included. Data analysed included information on demographics, laboratory results, operative findings, histopathological features and survival. RESULTS A total of 259 patients were included. Of these, 138 (53.3%) patients developed recurrent disease, of which 95 died. The median length of follow-up in the remaining patients was 28 months (range: 12-96 months). There were significant associations between recurrence and higher tumour number (P = 0.002), presence of perineural invasion (P = 0.009) and positive margin (R1) resection (P = 0.002). Multivariate analysis showed all three prognostic factors to be independent predictors of disease-free survival. Significantly poorer overall survival after hepatic resection for CRLM was observed in patients undergoing hemi-hepatectomy or more radical resection (P = 0.021), patients with a higher number of tumours (P = 0.024) and patients with perineural invasion (P < 0.001). Multivariate analysis showed perineural invasion to be the only independent predictor of overall survival. CONCLUSIONS The presence of perineural invasion, multiple tumours and an R1 margin were associated with recurrent disease. Perineural invasion was also an independent prognostic factor with respect to overall survival.
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Affiliation(s)
- Dhanwant Gomez
- Department of Hepatobiliary and Pancreatic Surgery, Queen's Medical Centre, Nottingham University Hospitals NHS TrustNottingham, UK
| | - Abed M Zaitoun
- Department of Cellular Pathology, Queen's Medical Centre, Nottingham University Hospitals NHS TrustNottingham, UK
| | - Antonella De Rosa
- Department of Hepatobiliary and Pancreatic Surgery, Queen's Medical Centre, Nottingham University Hospitals NHS TrustNottingham, UK
| | - Sina Hossaini
- Department of Hepatobiliary and Pancreatic Surgery, Queen's Medical Centre, Nottingham University Hospitals NHS TrustNottingham, UK
| | - Ian J Beckingham
- Department of Hepatobiliary and Pancreatic Surgery, Queen's Medical Centre, Nottingham University Hospitals NHS TrustNottingham, UK
| | - Adam Brooks
- Department of Hepatobiliary and Pancreatic Surgery, Queen's Medical Centre, Nottingham University Hospitals NHS TrustNottingham, UK
| | - Iain C Cameron
- Department of Hepatobiliary and Pancreatic Surgery, Queen's Medical Centre, Nottingham University Hospitals NHS TrustNottingham, UK
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Hamilton TD, Leugner D, Kopciuk K, Dixon E, Sutherland FR, Bathe OF. Identification of prognostic inflammatory factors in colorectal liver metastases. BMC Cancer 2014; 14:542. [PMID: 25069793 PMCID: PMC4125702 DOI: 10.1186/1471-2407-14-542] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2013] [Accepted: 07/10/2014] [Indexed: 01/15/2023] Open
Abstract
Background The modified Glasgow Prognostic Score (mGPS) has been reported to be an important prognostic indicator in a number of tumor types, including colorectal cancer (CRC). The features of the inflammatory state thought to accompany elevated C-reactive protein (CRP), a key feature of mGPS, were characterized in patients with colorectal liver metastases. Additional inflammatory mediators that contribute to prognosis were explored. Methods In sera from 69 patients with colorectal liver metastases, a panel of 42 inflammatory mediators were quantified as a function of CRP levels, and as a function of disease-free survival. Multivariate statistical methods were used to determine association of each mediator with elevated CRP and truncated disease-free survival. Results Elevated CRP was confirmed to be a strong predictor of survival (HR 4.00, p = 0.001) and recurrence (HR 3.30, p = 0.002). The inflammatory state associated with elevated CRP was comprised of raised IL-1β, IL-6, IL-12 and IL-15. In addition, elevated IL-8 and PDGF-AB/BB and decreased eotaxin and IP-10 were associated with worse disease-free and overall survival. Conclusions Elevated CRP is associated with a proinflammatory state. The inflammatory state is an important prognostic indicator in CRC liver metastases. The individual contributions of tumor biology and the host to this inflammatory response will require further investigation. Electronic supplementary material The online version of this article (doi:10.1186/1471-2407-14-542) contains supplementary material, which is available to authorized users.
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Affiliation(s)
| | | | | | | | | | - Oliver F Bathe
- Department of Surgery, University of Calgary, Calgary, AB, Canada.
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Macedo FIB, Makarawo T. Colorectal hepatic metastasis: Evolving therapies. World J Hepatol 2014; 6:453-463. [PMID: 25067997 PMCID: PMC4110537 DOI: 10.4254/wjh.v6.i7.453] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2013] [Revised: 02/23/2014] [Accepted: 06/03/2014] [Indexed: 02/06/2023] Open
Abstract
The approach for colorectal hepatic metastasis has advanced tremendously over the past decade. Multidrug chemotherapy regimens have been successfully introduced with improved outcomes. Concurrently, adjunct multimodal therapies have improved survival rates, and increased the number of patients eligible for curative liver resection. Herein, we described major advancements of surgical and oncologic management of such lesions, thereby discussing modern chemotherapeutic regimens, adjunct therapies and surgical aspects of liver resection.
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Roberts KJ, White A, Cockbain A, Hodson J, Hidalgo E, Toogood GJ, Lodge JPA. Performance of prognostic scores in predicting long-term outcome following resection of colorectal liver metastases. Br J Surg 2014; 101:856-66. [PMID: 24817653 DOI: 10.1002/bjs.9471] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/23/2014] [Indexed: 12/20/2022]
Abstract
BACKGROUND Ten-year survival appears to define cure following resection of colorectal liver metastases (CRLMs). Various scores exist to predict outcome at 5 years. This study applied several scores to a patient cohort with 10 years of actual follow-up to assess their performance beyond 5 years. METHODS The study included consecutive patients who underwent liver resection at a single institution between 1992 and 2001. The ability of eight prognostic scoring systems to predict disease-free (DFS) and disease-specific (DSS) survival was analysed using the C-statistic. RESULTS Among 286 patients, the 1-, 3-, 5- and 10-year actual DSS rates were 86.6, 58.3, 39.5 and 24.5 per cent respectively. Seventy patients underwent 105 further resections for recurrent disease, of which 84.8 per cent were within 5 years of follow-up. Analysis of C-statistics showed only one score--the Rees postoperative index--to be a significant predictor of DFS and DSS at all time points. The remaining scores performed less well, and regularly showed no significant improvement in predictive accuracy over what would be expected by chance alone. No score yielded a C-statistic in excess of 0.8 at any time point. CONCLUSION Although available risk scores can predict DFS and DSS, none does so with sufficient discriminatory accuracy to identify all episodes of recurrent disease. A non-negligible proportion of patients develop recurrent disease beyond 5 years of follow-up and so surveillance beyond this point may be advantageous.
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Borda F, Borda A, Jiménez J, Zozaya JM, Prieto C, Gómez M, Urman J, Ibáñez B. Valor predictivo de la hipoalbuminemia pre-tratamiento sobre el pronóstico del cáncer colorrectal resecado. GASTROENTEROLOGIA Y HEPATOLOGIA 2014; 37:289-95. [DOI: 10.1016/j.gastrohep.2013.12.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 12/16/2013] [Accepted: 12/19/2013] [Indexed: 12/11/2022]
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Fontana R, Herman P, Pugliese V, Perini MV, Coelho FF, Cecconello I. Surgical outcomes and prognostic factors in patients with synchronous colorectal liver metastases. ARQUIVOS DE GASTROENTEROLOGIA 2014; 51:4-9. [PMID: 24760056 DOI: 10.1590/s0004-28032014000100002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/24/2013] [Accepted: 10/25/2013] [Indexed: 02/06/2023]
Abstract
CONTEXT Colorectal cancer is the second most prevalent cancer worldwide, and the liver is the most common site of metastases. Surgical resection of colorectal liver metastases provides the sole possibility of cure and the best odds of long-term survival. Objectives To describe surgical outcomes and identify features associated with disease prognosis in patients submitted to synchronous colorectal cancer liver metastasis resection. METHODS Retrospective study of 59 patients who underwent surgery for synchronous colorectal cancer liver metastasis. Actuarial survival and disease-free survival were assessed, depending on the prognostic variable of interest. RESULTS Postoperative mortality and morbidity rates were 3.38% and 30.50% respectively. Five-year disease-free survival was estimated at 23.96%, and 5-year overall survival, at 38.45%. Carcinoembryonic antigen levels ≥ 50 ng/mL and presence of three or more liver metastasis were limiting factors for disease-free survival, but did not affect late survival. No patient with liver metastases and extrahepatic disease had disease-free interval longer than 20 months, but this had no significance or impact on long-term survival. None of the prognostic factors assessed had an impact on late survival, although no patients with more than three liver metastases survived beyond 40 months. CONCLUSIONS Although Carcinoembryonic antigen levels and number of metastases are prognostic factors that limit disease-free survival, they had no impact on 5-year survival and, therefore, should not determine exclusion from surgical treatment. Resection is the best treatment option for synchronous colorectal liver metastases, and even for patients with multiple metastases, large tumors and extrahepatic disease, it can provide long-term survival rates over 38%.
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Affiliation(s)
- Rafael Fontana
- Universidade de Caxias do Sul, Faculdade de Medicina, Caxias do Sul, RS, Brasil
| | | | - Vincenzo Pugliese
- Universidade de São Paulo, Faculdade de Medicina, Departmento de Gastroenterologia, São Paulo, SP, Brasil
| | - Marcos Vinicius Perini
- Universidade de São Paulo, Faculdade de Medicina, Departmento de Gastroenterologia, São Paulo, SP, Brasil
| | | | - Ivan Cecconello
- Universidade de São Paulo, Faculdade de Medicina, Departmento de Gastroenterologia, São Paulo, SP, Brasil
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Tan MCB, Butte JM, Gonen M, Kemeny N, Fong Y, Allen PJ, Kingham TP, DeMatteo RP, Jarnagin WR, D'Angelica MI. Prognostic significance of early recurrence: a conditional survival analysis in patients with resected colorectal liver metastasis. HPB (Oxford) 2013; 15:803-13. [PMID: 23782400 PMCID: PMC3791120 DOI: 10.1111/hpb.12136] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2013] [Accepted: 04/29/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND For patients undergoing liver resection for colorectal metastases, specific clinico-pathological variables have been shown to be prognostic at baseline. This study analyses how the prognostic capability of these variables changes in a conditional survival model. METHODS Retrospective review of a prospectively maintained database of patients who underwent an R0 resection of colorectal liver metastases from 1994 to 2004 at a single institution. RESULTS In total, 807 patients were identified, with an 87-month median follow-up for survivors. Five- and 10-year disease-specific survivals (DSS) were 68% and 55%, respectively. The probability of further survival increased as the survival time increased. For 3-year survivors (n = 504), DSS were no longer significantly different between patients with a low (0-2) or high (3-5) clinical risk score (CRS, P = 0.19). On multivariate analysis, independent predictors of DSS for 3-year survivors were recurrence within the first 3 years after a liver resection, a pre-operative carcinoembryonic antigen (CEA) >200 ng/ml and disease-free interval <12 months prior to the diagnosis of liver metastasis. However, for those patients who were recurrence free at 1 year, no clinico-pathological variables retained prognostic significance. DISCUSSION After 3 years of DSS and 1 year of recurrence-free survival, baseline clinico-pathological variables have a limited ability to predict future survival. Early post-operative recurrence appears to be the most useful single clinical feature in estimating conditional DSS.
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Affiliation(s)
- Marcus CB Tan
- Department of Surgery, Memorial Sloan-Kettering Cancer CenterNew York, NY, USA
| | - Jean M Butte
- Department of Surgery, Memorial Sloan-Kettering Cancer CenterNew York, NY, USA
| | - Mithat Gonen
- Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer CenterNew York, NY, USA
| | - Nancy Kemeny
- Department of Medicine, Memorial Sloan-Kettering Cancer CenterNew York, NY, USA
| | - Yuman Fong
- Department of Surgery, Memorial Sloan-Kettering Cancer CenterNew York, NY, USA
| | - Peter J Allen
- Department of Surgery, Memorial Sloan-Kettering Cancer CenterNew York, NY, USA
| | - T Peter Kingham
- Department of Surgery, Memorial Sloan-Kettering Cancer CenterNew York, NY, USA
| | - Ronald P DeMatteo
- Department of Surgery, Memorial Sloan-Kettering Cancer CenterNew York, NY, USA
| | - William R Jarnagin
- Department of Surgery, Memorial Sloan-Kettering Cancer CenterNew York, NY, USA
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Ribero D, Viganò L, Amisano M, Capussotti L. Prognostic factors after resection of colorectal liver metastases: from morphology to biology. Future Oncol 2013; 9:45-57. [PMID: 23252563 DOI: 10.2217/fon.12.159] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Despite improved overall survival rates after potentially curative liver resection (~50-58% at 5 years), almost half of patients experience disease recurrence highlighting the need for a precise definition of outcomes to stratify patients for clinical trials and to guide treatment decisions. In the past, several factors, such as an advanced primary T stage, the primary N+ status, a large tumor size, multiple tumors, a disease-free interval of <12 months, an elevated carcinoembryonic antigen level, the presence of an extrahepatic disease, and the margin width (<1 cm) and status (positive), have been recognized to predict poor outcomes, but most of them lack the sensitivity for accurate individual prognostication. Thus, in recent years, new factors, such as response to chemotherapy, either clinical or pathological, that more closely reflect tumor biology have been established and adopted in the clinical practice. Similarly, biomarkers of poor prognosis, especially mutations in KRAS and BRAF and the expression of thymidylate synthase, have been studied, yielding promising results. However, robust evidence of their prognostic utility awaits prospective validation.
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Affiliation(s)
- Dario Ribero
- Department of General Surgery & Surgical Oncology, Ospedale Mauriziano Umberto I, Torino, Italy
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Pre-operative hypoalbuminaemia predicts poor overall survival in rectal cancer: a retrospective cohort analysis. BMC Clin Pathol 2013; 13:12. [PMID: 23590192 PMCID: PMC3637439 DOI: 10.1186/1472-6890-13-12] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2012] [Accepted: 04/11/2013] [Indexed: 12/12/2022] Open
Abstract
Background Serum albumin is a marker of nutrition and inflammation. It has recently emerged as a predictor of outcome after surgery for rectal cancer. Our aim was to evaluate if pre-operative serum albumin would predict survival after resection for rectal cancer. Method 226 Patients with rectal cancer of all stages undergoing resection with curative intent were studied. Kaplan-Meier curves analysed survival based on a pre-operative albumin level of <35 g/L vs. >35 g/L. We sought for significant associations of survival with age, sex, stage, tumour site, use of neoadjuvant chemoradiation, microscopic positive resection margins, differentiation, angio, peri-neural, and lymphovascular invasion using individual variable analysis. Multifactorial analysis was performed using type III analysis with Weibull hazard model and Cox-proportional hazard model. Significance was assigned to a P value <0.05. Results Of 226 patients (median age- 59 years; range 19 – 88, Male - 54%), forty five (20%) had an albumin level < 35 g/L and was associated with a poor overall survival (P = 0.02). Mean survival in months for <35 g/L vs. >35 g/L was 64.7 (SE - 9.3) vs. 95.8 (SE – 7.0) and 5 year overall survival rates were 49% and 69%. Individual variable analysis revealed age, circumferential margin, stage, perineural, lympho-vascular and angio invasion to be also significant. With multifactorial analysis hypoalbuminaemia (HR = 0.58; 95% CI: 0.35 - 0.95, P = 0.03), advanced stage (HR = 2.0; 95% CI: 1.26 - 3.23, P < 0.01) and positive circumferential margin (HR = 2.2; 95% CI: 1.26 - 3.89, P < 0.01) remained significant. Conclusion Preoperative hypoalbuminaemia is an independent risk factor for poor overall survival in rectal cancer. Advanced tumour stage and circumferential margin positivity were the other associations with poor survival.
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Mavros MN, de Jong M, Dogeas E, Hyder O, Pawlik TM. Impact of complications on long-term survival after resection of colorectal liver metastases. Br J Surg 2013; 100:711-8. [DOI: 10.1002/bjs.9060] [Citation(s) in RCA: 115] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/29/2012] [Indexed: 12/13/2022]
Abstract
Abstract
Background
Postoperative complications may have an adverse effect not only on short-term but also long-term outcome among patients having surgery for cancer. A retrospective series of patients who had surgery for colorectal liver metastases (CLM) was used to assess this association.
Methods
Patients who had surgery with curative intent for CLM from 2000 to 2009 were included. The impact of postoperative complications, patient characteristics, disease stage and treatment on long-term survival was analysed using multivariable Cox regression models.
Results
A total of 251 patients were included. The median age was 58 (interquartile range 51–68) years and there were 87 women (34·7 per cent). A minor or major postoperative complication developed in 41 and 14 patients respectively, and five patients (2·0 per cent) died after surgery. The 5-year recurrence-free (RFS) and overall survival rates were 19·5 and 41·9 per cent respectively. Multivariable analysis revealed that postoperative complications independently predicted shorter RFS (hazard ratio (HR) 2·36, 95 per cent confidence interval 1·56 to 3·58) and overall survival (HR 2·34, 1·46 to 3·74). Other independent predictors of shorter RFS and overall survival included lymph node metastasis, concomitant extrahepatic disease, a serum carcinoembryonic antigen level of at least 100 ng/dl, and the use of radiofrequency ablation (RFS only). The severity of complications also correlated with RFS (P = 0·006) and overall survival (P = 0·001).
Conclusion
Postoperative complications were independently associated with decreased long-term survival after surgery for CLM with curative intent. The prevention and management of postoperative adverse events may be important oncologically.
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Affiliation(s)
- M N Mavros
- Department of Surgery, Johns Hopkins University School of Medicine, Blalock 688, 600 North Wolfe Street, Baltimore, Maryland 21287, USA
| | - M de Jong
- Department of Surgery, Johns Hopkins University School of Medicine, Blalock 688, 600 North Wolfe Street, Baltimore, Maryland 21287, USA
| | - E Dogeas
- Department of Surgery, Johns Hopkins University School of Medicine, Blalock 688, 600 North Wolfe Street, Baltimore, Maryland 21287, USA
| | - O Hyder
- Department of Surgery, Johns Hopkins University School of Medicine, Blalock 688, 600 North Wolfe Street, Baltimore, Maryland 21287, USA
| | - T M Pawlik
- Department of Surgery, Johns Hopkins University School of Medicine, Blalock 688, 600 North Wolfe Street, Baltimore, Maryland 21287, USA
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López-Gómez M, Cejas P, Merino M, Fernández-Luengas D, Casado E, Feliu J. Management of colorectal cancer patients after resection of liver metastases: can we offer a tailored treatment? Clin Transl Oncol 2012; 14:641-58. [PMID: 22911546 DOI: 10.1007/s12094-012-0853-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2012] [Accepted: 06/11/2012] [Indexed: 01/10/2023]
Abstract
Surgical resection remains the only option of cure for patients with colorectal liver metastases, and no patient should be precluded from surgery. There is much controversy not only regarding the most appropriate therapeutic approach in the neoadjuvant setting but also after surgery is performed. Many patients will experience early relapses but others will be long survivors. We need to establish reliable prognostic and predictive factors to offer a tailored treatment. Several prognostic factors after metastasectomy have been identified: high C-reactive protein levels, a high neutrophil-lymphocyte ratio, elevated neutrophil count and low serum albumin are related to a worst outcome. Elevated CEA and Ki 67 levels, intrahepatic and perihepatic lymph node invasion are also some of the markers related to a worst outcome. In contrast, the administration of preoperative chemotherapy has been associated with a better prognosis after hepatectomy. The administration of adjuvant chemotherapy should be done taking in consideration these factors. Regarding predictive factors, determination of ERCC1, TS, TP and DPD and UGT1 polymorphisms assessment could be considered prior to chemotherapy administration. This would avoid treatment related toxicities and increase this population quality of life.
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Affiliation(s)
- Miriam López-Gómez
- Clinical Oncology Department, Infanta Sofía University Hospital, Paseo de Europa 34, San Sebastián de los Reyes, 28702, Madrid, Spain.
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