|
1
|
Yan X, Wang Y, Ma A, Li H. The role of health economic evidence in clinical practice guidelines for colorectal cancer: a comparative analysis across countries. J Comp Eff Res 2025; 14:e240226. [PMID: 39969114 PMCID: PMC11963387 DOI: 10.57264/cer-2024-0226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2024] [Accepted: 01/31/2025] [Indexed: 02/20/2025] Open
Abstract
Aim: Colorectal cancer (CRC) is among the most prevalent malignancies globally and causes massive resource consumption and economic burden. Health economic evidence (HEE) has been used in clinical practice guidelines (CPGs) for cancer to facilitate the rational allocation of health resources. However, in certain guideline development organizations, HEE is not yet utilized as a formal decision-making criterion. This study aimed to compare the discrepancies in the utilization of health economics as evidence in CRC CPGs across different countries and review specific features of economic evidence concerning the guidelines' applicability. Materials & methods: A systematic review was conducted using databases including Medline, Embase, CNKI, WanFang, and other guidelines databases to identify CPGs for CRC published in English or Chinese from January 2017 to September 2023. Data on the incorporation and application of HEE were extracted, and the method and quality of cost-effectiveness analysis (CEA) studies were evaluated. Descriptive analyses were used to summarize the results. Results: Out of 53 CPGs from 14 countries, most originated from the USA (n = 17 of 53 [32%]) and Canada (n = 9 of 53 [17%]). Sixty-eight percent (36/53) considered cost justification, and 57% (30/53) incorporated health economics studies as evidence. The included HEE cited in CPGs ranged from 1990 to 2021 and were not aligned with the countries in which the guidelines were issued. Among these CEA studies, 52% (26/50) were related to screening strategies, and 32% (16/50) pertained to treatment measures. The Markov model was the most frequently used (n = 27 of 50 [54%]). Based on the CHEQUE tool, the methodological quality of these CEA studies was inadequate in areas such as multiple data sources, approaches to select data sources, assessing the quality of data, and relevant equity or distribution. Conclusion: In summary, 57% of guidelines incorporated health economics studies as evidence, with a variation between different countries. The included HEE still had deficiencies in methodology and reporting quality. In the future, it is suggested that health economics research should use a standardized methodology and reporting approach to assist in clinical decision making.
Collapse
Affiliation(s)
- Xiaoyu Yan
- School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China
| | - Yue Wang
- School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China
| | - Aixia Ma
- School of International Pharmaceutical Business & Center for Pharmacoeconomics & Outcomes Research, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China
| | - Hongchao Li
- School of International Pharmaceutical Business & Center for Pharmacoeconomics & Outcomes Research, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China
| |
Collapse
|
|
2
|
Dalmonte S, Cocozza MA, Cuicchi D, Remondini D, Faggioni L, Castellucci P, Farolfi A, Fortunati E, Cappelli A, Biondi R, Cattabriga A, Poggioli G, Fanti S, Castellani G, Coppola F, Curti N. Identification of PET/CT radiomic signature for classification of locally recurrent rectal cancer: A network-based feature selection approach. Heliyon 2025; 11:e41404. [PMID: 39839519 PMCID: PMC11748705 DOI: 10.1016/j.heliyon.2024.e41404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 12/19/2024] [Accepted: 12/19/2024] [Indexed: 01/23/2025] Open
Abstract
Background The modern approach to treating rectal cancer, which involves total mesorectal excision directed by imaging assessments, has significantly enhanced patient outcomes. However, locally recurrent rectal cancer (LRRC) continues to be a significant clinical issue. Identifying LRRC through imaging is complex, due to the mismatch between fibrosis and inflammatory pelvic tissue. This work aimed to develop a machine learning model for predicting LRRC using radiomic features extracted from 18F-FDG Positron Emission Tomography/Computed Tomography (PET/CT). Methods CT and PET images of PET/CT examinations were retrospectively collected from 44 patients, with 29 cases of recurrence (66 %) and 15 cases with no local recurrence (34 %). The whole analysis was conducted separately for CT and PET images to evaluate their different predictive power. Radiomic features were extracted from suspected lesion volumes identified by physicians and the most relevant radiomic features were selected to predict the presence or absence of LRRC. Feature selection was performed using a novel approach derived from gene expression analysis, based on the DNetPRO algorithm. The prediction was done using a Support Vector Classifier (SVC) with a 10-fold cross-validation. The efficiency of the pipeline in predicting LRRC was evaluated according to the sensitivity, specificity, Balanced Accuracy Score (BAS) and Matthews's Correlation Coefficient (MCC). Results CT features were found to be the most predictive, showing a sensitivity of 0.80, a specificity of 0.82, a BAS of 0.81 and an MCC of 0.61. PET features obtained a sensitivity of 0.93, a specificity of 0.61, a BAS of 0.77 and a MCC of 0.52. The combination of PET and CT features obtained a sensitivity of 0.80, a specificity of 0.75, a BAS of 0.77 and a MCC of 0.53. Conclusions To the best of our knowledge, the DNetPRO algorithm was applied for the first time to medical image analysis and proved suitable for the selection of radiomic features with the highest predictive power, a crucial step in a radiomic pipeline. Our results confirmed the efficiency of radiomic features in predicting LRRC, with CT features outperforming PET features in identifying the characteristic texture of LRRC. The combination of both yielded no performance improvement.
Collapse
Affiliation(s)
- Sara Dalmonte
- IRCCS Rizzoli Orthopedic Institute, Medical Technology Laboratory, Bologna, 40138, Italy
- Medical Physics Specialization School, University of Bologna, Bologna, 40127, Italy
| | - Maria Adriana Cocozza
- Department of Radiology, IRCCS Azienda Ospedaliera-Universitaria di Bologna, Bologna, 40138, Italy
| | - Dajana Cuicchi
- Medical and Surgical Department of Digestive, Hepatic and Endocrine-Metabolic Diseases, IRCCS Azienda Ospedaliera-Universitaria di Bologna, Bologna, 40138, Italy
| | - Daniel Remondini
- Department of Physics and Astronomy, University of Bologna, Bologna, 40127, Italy
| | - Lorenzo Faggioni
- Academic Radiology, Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, 56126, Italy
| | - Paolo Castellucci
- Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, 40138, Italy
| | - Andrea Farolfi
- Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, 40138, Italy
| | - Emilia Fortunati
- Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, 40138, Italy
| | - Alberta Cappelli
- Department of Radiology, IRCCS Azienda Ospedaliera-Universitaria di Bologna, Bologna, 40138, Italy
| | - Riccardo Biondi
- IRCCS Institute of Neurological Sciences of Bologna, Data Science and Bioinformatics Laboratory, Bologna, 40139, Italy
| | - Arrigo Cattabriga
- Department of Radiology, IRCCS Azienda Ospedaliera-Universitaria di Bologna, Bologna, 40138, Italy
| | - Gilberto Poggioli
- Medical and Surgical Department of Digestive, Hepatic and Endocrine-Metabolic Diseases, IRCCS Azienda Ospedaliera-Universitaria di Bologna, Bologna, 40138, Italy
| | - Stefano Fanti
- Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, 40138, Italy
| | - Gastone Castellani
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, 40138, Italy
| | - Francesca Coppola
- Department of Radiology, IRCCS Azienda Ospedaliera-Universitaria di Bologna, Bologna, 40138, Italy
- Dipartimento Diagnostica per Immagini AUSL Romagna, UOC Radiologia Faenza, Faenza, 48018, Italy
| | - Nico Curti
- Department of Physics and Astronomy, University of Bologna, Bologna, 40127, Italy
- IRCCS Institute of Neurological Sciences of Bologna, Data Science and Bioinformatics Laboratory, Bologna, 40139, Italy
| |
Collapse
|
|
3
|
Weinberg BA, Murphy CC, Freyer DR, Greathouse KL, Blancato JK, Stoffel EM, Drewes JL, Blaes A, Salsman JM, You YN, Arem H, Mukherji R, Kanth P, Hu X, Fabrizio A, Hartley ML, Giannakis M, Marshall JL. Rethinking the rise of early-onset gastrointestinal cancers: a call to action. JNCI Cancer Spectr 2025; 9:pkaf002. [PMID: 39814070 PMCID: PMC11804804 DOI: 10.1093/jncics/pkaf002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2024] [Accepted: 12/18/2024] [Indexed: 01/18/2025] Open
Abstract
Since the early 1990s, there has been a dramatic rise in gastrointestinal cancers diagnosed in patients under age 50 for reasons that remain poorly understood. The most significant change has been the increase in incidence rates of early-onset colorectal cancer, especially rates of left-sided colon and rectal cancers. Increases in gastric, pancreatic, and other gastrointestinal cancer diagnoses have further contributed to this trend. We formed a multidisciplinary Think Tank to develop a strategic, coordinated approach to studying early-onset gastrointestinal cancers. This area of research is challenging given multifactorial etiologies. We focused on epidemiology and the environment, the microbiome, and survivorship as key pillars to structure a research framework. We advocate a comprehensive strategy to (1) use existing biospecimens, especially those collected longitudinally, with correlation to exposures (the exposome); (2) standardize microbiome specimen collection and analyses of blood, tissue, and stool specimens to minimize contamination and biases; (3) prioritize mechanistic studies to evaluate findings from biomarker studies; and (4) explore the unique survivorship needs of this young population. These recommendations build upon prior efforts with the goal of streamlining research into this important field of study while minimizing redundant efforts. We hope that our findings serve as a clarion call to motivate others to discover why young individuals are being diagnosed with gastrointestinal cancers at such an alarming rate and how to best support those who have been diagnosed.
Collapse
Affiliation(s)
- Benjamin A Weinberg
- Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, United States
| | - Caitlin C Murphy
- Department of Health Promotion & Behavioral Sciences, UTHealth Houston School of Public Health, Houston, TX 77030, United States
| | - David R Freyer
- Departments of Pediatrics, Medicine, and Population & Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90032, United States
- USC Norris Comprehensive Cancer Center and Children’s Hospital Los Angeles, Los Angeles, CA 90089, United States
| | - K Leigh Greathouse
- Department of Human Sciences and Design, Baylor University, Waco, TX 76706, United States
| | - Jan K Blancato
- Department of Oncology, Georgetown University, Washington, DC 20007, United States
| | - Elena M Stoffel
- Department of Internal Medicine, University of Michigan, Rogel Cancer Center, Ann Arbor, MI 48109, United States
| | - Julia L Drewes
- Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
| | - Anne Blaes
- Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, United States
| | - John M Salsman
- Wake Forest University School of Medicine & Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston Salem, NC 27157, United States
| | - Y Nancy You
- Department of Colon and Rectal Surgery, University of Texas MD Anderson Cancer Center, Houston, TX 78701, United States
| | - Hannah Arem
- Healthcare Delivery Research, MedStar Health Research Institute, Washington, DC 20010, United States
| | - Reetu Mukherji
- Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, United States
| | - Priyanka Kanth
- Division of Gastroenterology, MedStar Georgetown University Hospital, Lombardi Comprehensive Cancer Center, Washington, DC 20007, United States
| | - Xin Hu
- Gangarosa Department of Environmental Health, Emory University Rollins School of Public Health, Atlanta, GA 30329, United States
| | - Anne Fabrizio
- Division of Colon & Rectal Surgery, MedStar Georgetown University Hospital, Washington, DC 20007, United States
| | - Marion L Hartley
- Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, United States
| | - Marios Giannakis
- Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, United States
| | - John L Marshall
- Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, United States
| |
Collapse
|
|
4
|
Tong G, Li H, Shen Y, Tan Z, Qian H. The combined evaluation of preoperative serum CEA and postoperative tissue CEA as a prognostic factor in stages 0-IV colorectal cancer: a retrospective cohort study. Front Med (Lausanne) 2025; 11:1447041. [PMID: 39830382 PMCID: PMC11739305 DOI: 10.3389/fmed.2024.1447041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 12/11/2024] [Indexed: 01/22/2025] Open
Abstract
Background The roles of preoperative serum carcinoembryonic antigen (sCEA) and postoperative tissue carcinoembryonic antigen (tCEA) have been extensively studied in isolation in colorectal cancer (CRC). However, the combined role of sCEA and tCEA remains inadequately described. Methods A total of 1,757 retrospective cases of stage 0-IV CRC from January 2006 to January 2016 in our institution were included. Clinicopathological features and follow-up data were collected. Stage 0 was combined with stage I. sCEA levels were classified as normal or high (>10 ng/mL), while tCEA levels were categorised into three grades (+, ++, and +++). This resulted in six combined groups (2 × 3). ANOVA and cross-tabulation were employed to analyse continuous and categorical data, respectively. Univariate and multivariate analyses were conducted using Cox regression. All data were analysed using SPSS 27 and R 4.3.1. Results Some clinicopathologic features differed significantly among the combined CEA test groups (all p < 0.05). The receiver operating characteristic (ROC) curves for sCEA, tCEA, and combined CEA exhibited significant differences in five-year OS with death as the input variable (all p < 0.05). The area under the curve (AUC) for combined CEA was the highest, indicating the value of this study. Cox regression analysis demonstrated that tumour location, T stage, differentiation, chemotherapy, TNM stage, tCEA, and combined CEA were significant in the univariate analysis; however, tCEA was not significant (p = 0.096) in the multivariate analysis among these seven variables. Five-year OS analysis revealed that sCEA, tCEA, and combined CEA were not significant in stages 0 & I-II (all p > 0.05) but were significant in stages III-IV (all p < 0.05), except for tCEA in stage IV (p = 0.24) as per K-M and univariate analysis. No significant difference was observed between sCEA and tCEA (p = 0.55, 0.095), whereas combined CEA demonstrated a significant difference (p < 0.001) in both univariate and multivariate analyses. Conclusion sCEA, tCEA, and combined CEA exhibit prognostic roles in stages III-IV of CRC, with only combined CEA serving as an independent factor in these stages.
Collapse
Affiliation(s)
- Guojun Tong
- Department of Colorectal Surgery, Huzhou Central Hospital, The Affiliated Central Hospital of Huzhou University, Zhejiang, China
- Department of Central Laboratory, Huzhou Central Hospital, The Affiliated Central Hospital of Huzhou University, Zhejiang, China
| | - Hui Li
- Department of General Surgery, Huzhou Central Hospital, The Affiliated Central Hospital of Huzhou University, Zhejiang, China
| | - Yan Shen
- Department of General Surgery, Huzhou Central Hospital, The Affiliated Central Hospital of Huzhou University, Zhejiang, China
| | - Zhenhua Tan
- Department of General Surgery, Huzhou Central Hospital, The Affiliated Central Hospital of Huzhou University, Zhejiang, China
| | - Hai Qian
- Department of General Surgery, Huzhou Central Hospital, The Affiliated Central Hospital of Huzhou University, Zhejiang, China
| |
Collapse
|
|
5
|
Khandalavala B, Carlson S, Elsayed L, Geske J. Physical Activity and Sedentary Behavior in Patients With Breast Cancer: Results of a Single Cohort in the Midwestern United States. Am J Lifestyle Med 2024:15598276241308551. [PMID: 39720786 PMCID: PMC11664562 DOI: 10.1177/15598276241308551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2024] Open
Abstract
Purpose: Physical activity and sedentary behavior have significant prognostic importance in survivors of breast cancer. However, not much is known about physical activity and sedentary behavior in the midwestern United States for patients who have breast cancer. This study provides patient-reported physical activity and sedentary behavior from a cohort of patients from the midwestern United States. Methods: A survey assessed physical activity and sedentary behavior from patients with all types of local or invasive breast cancer and ductal carcinoma in situ (DCIS). Demographic information and characteristics of participants' breast cancer, including time since diagnosis, type of cancer, and remission status were gathered. Results: Data from 108 patients reveal diverse physical activity and sedentary behavior patterns. Seventeen individuals (15.9%) report not engaging in any form of physical activity and only 15.9% report meeting national guideline recommendations of greater than 150 minutes of moderate intensity-equivalent physical activity per week. A wide range of physical activity in minutes was reported across age, time since diagnosis, type of cancer and remission status, none of which was statistically significant. Participants report sitting or reclining an average of 6.1 hours (SD = 3.9) per day during a typical workday and 5.8 hours (SD = 3.8) on a typical non-workday. Conclusions: Our study provides information about physical activity and sedentary behavior in a cohort of midwestern patients with breast cancer and indicates that the majority of the patients could be at high risk for long-term adverse prognosis. Tailored lifestyle programs to enhance physical activity and decrease sedentary behavior are critical to improve outcomes. Our results indicate that clinicians should incorporate healthy lifestyle medicine recommendations for all patients living with breast cancer at any age or time since diagnosis, independent of cancer type or remission status.
Collapse
Affiliation(s)
- Birgit Khandalavala
- University of Nebraska Medical Center & Nebraska Medicine, Omaha, NE, USA (BK)
| | - Sarah Carlson
- University of Nebraska Medical Center, Omaha, NE, USA (SC, JG)
| | - Lina Elsayed
- Clarkson Family Medicine, Nebraska Medicine, Omaha, NE, USA (LE)
| | - Jenenne Geske
- University of Nebraska Medical Center, Omaha, NE, USA (SC, JG)
| |
Collapse
|
|
6
|
Hilty Chu BK, Loria A, Dhimal T, Cai X, Gao S, Li Y, Temple LK, Colugnati F, Cupertino P, Ramsdale EE, Fleming FJ. Challenges of Surveillance in Implementing Nonoperative Management for Rectal Cancer. JAMA Netw Open 2024; 7:e2448682. [PMID: 39625720 PMCID: PMC11615709 DOI: 10.1001/jamanetworkopen.2024.48682] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 10/10/2024] [Indexed: 12/06/2024] Open
Abstract
Importance Close surveillance for detection of local tumor regrowth is critical for patients opting for nonoperative management after neoadjuvant therapy for rectal cancer. However, there are minimal data regarding the feasibility and adherence to National Comprehensive Cancer Network (NCCN) surveillance guidelines for these patients. Objective To determine adherence rates to NCCN-recommended surveillance in patients undergoing nonoperative management for rectal cancer. Design, Setting, and Participants This retrospective cohort study included patients treated at a single academic center (University of Rochester, Rochester, New York) from 2012 to 2023, with analysis completed from March through May 2024. Patients with clinical stage I to III rectal cancer who underwent treatment with neoadjuvant therapy, achieved a clinical complete response (or initially near complete clinical response), and elected for nonoperative management were enrolled. Exposure Achievement of recommended surveillance. Main Outcomes and Measures The primary outcome was adherence to surveillance guidelines for patients undergoing nonoperative management for rectal cancer. Secondary outcomes included assessment of oncologic outcomes stratified by adherence to surveillance. Results Eighty-five patients (54 male [63.5%]; median [IQR] age, 63.0 [54.0-73.0] years) were managed nonoperatively and followed for a median of 4.04 years (95% CI, 3.17-4.58 years). The 5-year overall survival was 82.3% (95% CI, 71.8%-94.5%), the 5-year disease-specific survival was 95.1% (95% CI, 89.6%-100.0%), the rate of local regrowth was 24.7% (21 patients), and the rate of distant metastases was 12.9% (11 patients). Among the 77 patients with more than 6 months of follow-up in their first year of surveillance, only 39.0% of patients (30 patients) achieved NCCN-recommended surveillance in the first year, and this decreased to 15.0% (3 patients) by year 5. However, the time to local regrowth and distant metastasis were similar regardless of the level of surveillance. Conclusions and Relevance In this cohort study of patients with rectal cancer undergoing surveillance after nonoperative management, most did not achieve NCCN-recommended guidelines, although outcomes were not associated with surveillance intensity. This highlights the need for prospective evaluation of a surveillance regimen that is both feasible for patients and health care systems increasingly using nonoperative management. In addition, studies are warranted to explore patient preferences in rectal cancer care and to identify barriers to optimal surveillance.
Collapse
Affiliation(s)
- Bailey K. Hilty Chu
- Surgical Health Outcomes and Reaching for Equity (SHORE), Department of Surgery, University of Rochester Medical Center, Rochester, New York
| | - Anthony Loria
- Surgical Health Outcomes and Reaching for Equity (SHORE), Department of Surgery, University of Rochester Medical Center, Rochester, New York
| | - Totadri Dhimal
- Surgical Health Outcomes and Reaching for Equity (SHORE), Department of Surgery, University of Rochester Medical Center, Rochester, New York
| | - Xueya Cai
- Surgical Health Outcomes and Reaching for Equity (SHORE), Department of Surgery, University of Rochester Medical Center, Rochester, New York
- Department of Biostatistics and Computational Biology, University of Rochester, Rochester, New York
| | - Shan Gao
- Surgical Health Outcomes and Reaching for Equity (SHORE), Department of Surgery, University of Rochester Medical Center, Rochester, New York
- Department of Biostatistics and Computational Biology, University of Rochester, Rochester, New York
| | - Yue Li
- Surgical Health Outcomes and Reaching for Equity (SHORE), Department of Surgery, University of Rochester Medical Center, Rochester, New York
- Department of Public Health Sciences, University of Rochester, Rochester, New York
| | - Larissa K. Temple
- Surgical Health Outcomes and Reaching for Equity (SHORE), Department of Surgery, University of Rochester Medical Center, Rochester, New York
| | - Fernando Colugnati
- School of Medicine, Universidade Federal de Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil
| | - Paula Cupertino
- Surgical Health Outcomes and Reaching for Equity (SHORE), Department of Surgery, University of Rochester Medical Center, Rochester, New York
| | - Erika E. Ramsdale
- James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York
| | - Fergal J. Fleming
- Surgical Health Outcomes and Reaching for Equity (SHORE), Department of Surgery, University of Rochester Medical Center, Rochester, New York
| |
Collapse
|
|
7
|
Zhou Q, Chen X, Zeng B, Zhang M, Guo N, Wu S, Zeng H, Sun F. Circulating tumor DNA as a biomarker of prognosis prediction in colorectal cancer: A systematic review and meta-analysis. JOURNAL OF THE NATIONAL CANCER CENTER 2024. [DOI: 10.1016/j.jncc.2024.05.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2025] Open
|
|
8
|
Turri G, Martinelli L, Rega D, Tamini N, Paiano L, Deidda S, Bao Q, Lorenzon L, De Luca R, Foppa C, Mari V, Taffurelli G, Picciariello A, Marsanic P, Siragusa L, Bagolini F, Nascimbeni R, Rizzo G, Vertaldi S, Zuolo M, Bianchi G, Rorato LM, Reddavid R, Gallo G, Crepaz L, Di Leo A, Trompetto M, Potenza E, Santarelli M, de’Angelis N, Ciarleglio F, Milone M, Coco C, Tiberio GA, Anania G, Sica GS, Muratore A, Altomare DF, Montroni I, De Luca M, Spinelli A, Simone M, Persiani R, Spolverato G, Restivo A, de Manzini N, Braga M, Delrio P, Verlato G, Pedrazzani C. Predictors of Recurrence After Curative Surgery for Stage I Colon Cancer: Retrospective Cohort Analysis of the Italian Society of Surgical Oncology Colorectal Cancer Network Collaborative Group. ANNALS OF SURGERY OPEN 2024; 5:e510. [PMID: 39711675 PMCID: PMC11661724 DOI: 10.1097/as9.0000000000000510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 09/26/2024] [Indexed: 12/24/2024] Open
Abstract
Objective The aim of this study is to provide solid evidence to update the management of stage I colon cancer (CC) after surgery. Background Given the low risk of recurrence of stage I CC, some international guidelines do not recommend intensive follow-up after surgery. However, data on the actual incidence, risk factors, and site of recurrences are scarce. Methods This is a retrospective multicenter cohort study considering patients who underwent surgery at 25 Italian centers between 2010 and 2019, with a minimum follow-up of 24 months. A total of 1883 consecutive adult patients with stage I CC treated with curative surgery were considered, and 1611 fulfilled the inclusion criteria. The primary outcome was the rate of recurrence. Secondary outcomes included survival and risk factors for recurrence. Results Eighty patients developed cancer recurrence (5.0%), of which 90% was systemic relapse. The event was more frequent in pT2 (6.0% vs 3.2%, P = 0.013), male patients (6.1% vs 3.6%, P = 0.021), in the presence of lymphovascular invasion (7.2% vs 3.6%, P = 0.01), and in cases of partial resection (11.1% vs 4.6%, P = 0.011). Also, preoperative carcinoembryonic antigen (P = 0.007) and tumor diameter (P < 0.001) were higher in the group who relapsed. Most patients had isolated cancer recurrence (90%). Recurrences peaked between 10 and 18 months after surgery and declined over time. Adjusted Cox regression analysis identified tumor diameter, carcinoembryonic antigen level, lymphovascular invasion, male gender, and less than 12 analyzed lymph nodes as significant risk factors for worse recurrence-free survival. Conclusions This study showed that a not negligible rate of stage I CC recur after curative surgery. Most relapses occur at a single site within the first 3 years after surgery. This evidence could be used to optimize postoperative follow-up.
Collapse
Affiliation(s)
- Giulia Turri
- From the Chirurgia Generale ed Epatobiliare, Azienda Ospedaliera Universitaria Integrata di Verona, Università degli Studi di Verona, Verona, Italy
| | - Luigi Martinelli
- Department of Diagnostic and Public Health, University of Verona, Verona, Italy
| | - Daniela Rega
- Colorectal Surgical Oncology, Abdominal Oncology Department, Istituto Nazionale per lo Studio e la Cura dei Tumori, “Fondazione G. Pascale” IRCSS, Naples, Italy
| | - Nicolò Tamini
- Chirurgia Generale, IRCCS San Gerardo Monza, Università Milano Bicocca, Milano, Italy
| | - Lucia Paiano
- UCO Clinica Chirurgica, Università di Trieste, Trieste, Italy
| | - Simona Deidda
- UOC Chirurgia Coloproctologica, AOU Cagliari, Cagliari, Italy
| | - QuocRiccardo Bao
- Chirurgia Generale 3, Azienda Ospedaliera Universitaria Integrata di Padova, Padova, Italy
| | - Laura Lorenzon
- UOC Chirurgia Generale 1, Fondazione Policlinico Universitario Agostino Gemelli – IRCCS, Roma, Italy
| | - Raffaele De Luca
- Department of Surgical Oncology, IRCCS Istituto Tumori “Giovanni Paolo II”, Bari, Italy
| | - Caterina Foppa
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Valentina Mari
- Chirurgia Generale, Ospedale Santa Maria della Misericordia, Rovigo, Italy
| | | | | | - Patrizia Marsanic
- S.C. Chirurgia, Ospedale E. Agnelli, ASL TO 3, Presidio Pinerolo, Italy
| | - Leandro Siragusa
- Minimally Invasive and Gastrointestinal Surgery Unit, Department of General Surgery, University of Rome Tor Vergata, Rome, Italy
| | - Francesco Bagolini
- Chirurgia 1, Ospedale di Cona, Azienda Ospedaliera Universitaria Integrata di Ferrara, Ferrara, Italy
| | - Riccardo Nascimbeni
- Clinica Chirurgica, Dipartimento di Scienze Cliniche e Sperimentali, Università degli Studi di Brescia, Brescia, Italy
| | - Gianluca Rizzo
- UOC Chirurgia Digestiva e del Colon-Retto - Ospedale Isola Tiberina Gemelli Isola, Roma, Italy
| | - Sara Vertaldi
- Chirurgia Endoscopica, AOUI Federico II Napoli, Napoli, Italy
| | - Michele Zuolo
- APSS, Azienda Provinciale per i Servizi Sanitari, UO di Chirurgia Generale, Ospedale Valli del Noce, Trento, Italy
| | - Giorgio Bianchi
- Unit of Digestive and HPB Surgery, Henri Mordor University Hospital, Paris, France
| | - Lisa Marie Rorato
- Chirurgia d’Urgenza e PS 3, AOU Città della Salute e della Scienza, Torino, Italy
| | - Rossella Reddavid
- Division of Surgical Oncology and Digestive Surgery, Department of Oncology, University of Turin, San Luigi University Hospital, Turin, Italy
| | - Gaetano Gallo
- Unità di Chirurgia Colorettale, Clinica Santa Rita, Vercelli, Italy
- Department of Surgery, Sapienza University of Rome, Rome, Italy
| | - Lorenzo Crepaz
- Chirurgia Generale e Mininvasiva, Ospedale San Camillo, Trento, Italy
| | - Alberto Di Leo
- Chirurgia Generale e Mininvasiva, Ospedale San Camillo, Trento, Italy
| | - Mario Trompetto
- Unità di Chirurgia Colorettale, Clinica Santa Rita, Vercelli, Italy
| | - Enrico Potenza
- Division of Surgical Oncology and Digestive Surgery, Department of Oncology, University of Turin, San Luigi University Hospital, Turin, Italy
| | - Mauro Santarelli
- Chirurgia d’Urgenza e PS 3, AOU Città della Salute e della Scienza, Torino, Italy
| | - Nicola de’Angelis
- Unit of Digestive and HPB Surgery, Henri Mordor University Hospital, Paris, France
| | - Francesco Ciarleglio
- APSS, Azienda Provinciale per i Servizi Sanitari, UO di Chirurgia Generale, Ospedale Valli del Noce, Trento, Italy
| | - Marco Milone
- Chirurgia Endoscopica, AOUI Federico II Napoli, Napoli, Italy
| | - Claudio Coco
- Chirurgia Generale 2, Fondazione Policlinico Universitario “A.Gemelli”, IRCCS Roma, Italy
| | - Guido Alberto Tiberio
- Clinica Chirurgica, Dipartimento di Scienze Cliniche e Sperimentali, Università degli Studi di Brescia, Brescia, Italy
| | - Gabriele Anania
- Chirurgia 1, Ospedale di Cona, Azienda Ospedaliera Universitaria Integrata di Ferrara, Ferrara, Italy
| | - Giuseppe S. Sica
- Minimally Invasive and Gastrointestinal Surgery Unit, Department of General Surgery, University of Rome Tor Vergata, Rome, Italy
| | - Andrea Muratore
- S.C. Chirurgia, Ospedale E. Agnelli, ASL TO 3, Presidio Pinerolo, Italy
| | - Donato Francesco Altomare
- Dipartimento di Medicina di Precisione e Rigenerativa e Polo Jonico (DiMePRE-J), Università degli Studi Aldo Moro di Bari, Bari, Italy
| | - Isacco Montroni
- Chirurgia Colorettale, Ospedale Santa Maria delle Croci, Ravenna, Italy
| | - Maurizio De Luca
- Chirurgia Generale, Ospedale Santa Maria della Misericordia, Rovigo, Italy
| | - Antonino Spinelli
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Michele Simone
- Department of Surgical Oncology, IRCCS Istituto Tumori “Giovanni Paolo II”, Bari, Italy
| | - Roberto Persiani
- UOC Chirurgia Generale 1, Fondazione Policlinico Universitario Agostino Gemelli – IRCCS, Roma, Italy
| | - Gaya Spolverato
- Chirurgia Generale 3, Azienda Ospedaliera Universitaria Integrata di Padova, Padova, Italy
| | - Angelo Restivo
- UOC Chirurgia Coloproctologica, AOU Cagliari, Cagliari, Italy
| | | | - Marco Braga
- Chirurgia Generale, IRCCS San Gerardo Monza, Università Milano Bicocca, Milano, Italy
| | - Paolo Delrio
- Colorectal Surgical Oncology, Abdominal Oncology Department, Istituto Nazionale per lo Studio e la Cura dei Tumori, “Fondazione G. Pascale” IRCSS, Naples, Italy
| | - Giuseppe Verlato
- Department of Diagnostic and Public Health, University of Verona, Verona, Italy
| | - Corrado Pedrazzani
- From the Chirurgia Generale ed Epatobiliare, Azienda Ospedaliera Universitaria Integrata di Verona, Università degli Studi di Verona, Verona, Italy
| |
Collapse
|
|
9
|
Gielen AHC. Guideline for the assessment and management of gastrointestinal symptoms following colorectal surgery-A UEG/ESCP/EAES/ESPCG/ESPEN/ESNM/ESSO collaboration. Part I-Sequelae to oncological diseases. United European Gastroenterol J 2024; 12:1489-1506. [PMID: 39576262 DOI: 10.1002/ueg2.12658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2024] Open
Affiliation(s)
- Anke H C Gielen
- Department of Surgery, Maastricht University (Maastricht University, Including Maastricht UMC+), Maastricht, The Netherlands
- School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands
| |
Collapse
|
|
10
|
Luo S, Xu J, Mo C, Gong W, Li C, Hou X, Ou M. High-throughput sequencing reveals twelve cell death pattern prognostic target genes as potential drug-response-associated genes in the treatment of colorectal cancer cells with palmatine hydrochloride. ONCOLOGIE 2024. [DOI: 10.1515/oncologie-2024-0378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Abstract
Objectives
Palmatine Hydrochloride (PaH), an isoquinoline alkaloid from Phellodendron amurense and Coptis chinensis, has analgesic, anti-inflammatory, and anticancer properties. This study aimed to assess PaH’s effectiveness against SW480 colorectal cancer (CRC) cells and explore its molecular mechanisms.
Methods
PaH’s effects on SW480 CRC cells were evaluated using MTT assays for proliferation, scratch assays for migration, and flow cytometry for apoptosis. Differentially expressed genes (DEGs) were identified through high-throughput sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses assessed DEG roles. Prognostic significance related to programmed cell death (PCD) was analyzed using R-Package with TCGA data. RT-qPCR validated key genes identified.
Results
PaH significantly inhibited SW480 cell growth, invasion, and apoptosis. The MTT assay showed inhibition rates increased from 5.49 % at 25 μg/mL to 52.48 % at 400 μg/mL. Scratch assays indicated reduced cell invasion over 24, 48, and 72 h. Apoptosis rose from 12.36 % in controls to 45.54 % at 400 μg/mL. Sequencing identified 3,385 significant DEGs, primarily in cancer pathways (p=0.004). Among 35 PCD-related DEGs, Lasso Cox regression highlighted 12 key genes, including TERT, TGFBR1, WNT4, and TP53. RT-qPCR confirmed TERT and TGFBR1 downregulation (0.614-fold, p=0.008; 0.41-fold, p<0.001) and TP53 and WNT4 upregulation (5.634-fold, p<0.001; 5.124-fold, p=0.002).
Conclusions
PaH inhibits CRC cell proliferation, migration, and invasion by modulating key PCD genes, suggesting its potential as a CRC therapeutic agent.
Collapse
Affiliation(s)
- Sha Luo
- Laboratory Center, Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders , The Second Affiliated Hospital of Guilin Medical University , Guilin, 541199 , China
- Laboratory Center, Guangxi Key Laboratory of Metabolic Reprogramming and Intelligent Medical Engineering for Chronic Diseases , The Second Affiliated Hospital of Guilin Medical University , Guilin, 541199 , China
| | - Jiajun Xu
- Laboratory Center, Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders , The Second Affiliated Hospital of Guilin Medical University , Guilin, 541199 , China
- Laboratory Center, Guangxi Key Laboratory of Metabolic Reprogramming and Intelligent Medical Engineering for Chronic Diseases , The Second Affiliated Hospital of Guilin Medical University , Guilin, 541199 , China
| | - Chune Mo
- Laboratory Center, Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders , The Second Affiliated Hospital of Guilin Medical University , Guilin, 541199 , China
- Laboratory Center, Guangxi Key Laboratory of Metabolic Reprogramming and Intelligent Medical Engineering for Chronic Diseases , The Second Affiliated Hospital of Guilin Medical University , Guilin, 541199 , China
| | - Weiwei Gong
- Laboratory Center, Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders , The Second Affiliated Hospital of Guilin Medical University , Guilin, 541199 , China
- Laboratory Center, Guangxi Key Laboratory of Metabolic Reprogramming and Intelligent Medical Engineering for Chronic Diseases , The Second Affiliated Hospital of Guilin Medical University , Guilin, 541199 , China
| | - Chunhong Li
- Laboratory Center, Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders , The Second Affiliated Hospital of Guilin Medical University , Guilin, 541199 , China
- Laboratory Center, Guangxi Key Laboratory of Metabolic Reprogramming and Intelligent Medical Engineering for Chronic Diseases , The Second Affiliated Hospital of Guilin Medical University , Guilin, 541199 , China
| | - Xianliang Hou
- Laboratory Center, Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders , The Second Affiliated Hospital of Guilin Medical University , Guilin, 541199 , China
- Laboratory Center, Guangxi Key Laboratory of Metabolic Reprogramming and Intelligent Medical Engineering for Chronic Diseases , The Second Affiliated Hospital of Guilin Medical University , Guilin, 541199 , China
| | - Minglin Ou
- Laboratory Center, Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders , The Second Affiliated Hospital of Guilin Medical University , Guilin, 541199 , China
- Laboratory Center, Guangxi Key Laboratory of Metabolic Reprogramming and Intelligent Medical Engineering for Chronic Diseases , The Second Affiliated Hospital of Guilin Medical University , Guilin, 541199 , China
| |
Collapse
|
|
11
|
Goldstein DA, Tschernichovsky R, Razi T, Filosof K, Menashe I, Arbel R, Netzer D. Choosing Wisely in oncology: are guidelines effective at preventing unnecessary diagnostics? The example of surveillance positron emission tomography for patients with localised colorectal cancer. BMJ ONCOLOGY 2024; 3:e000391. [PMID: 39886174 PMCID: PMC11347680 DOI: 10.1136/bmjonc-2024-000391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Accepted: 07/22/2024] [Indexed: 02/01/2025]
Abstract
Objective Healthcare overuse is a major challenge for healthcare systems and patients worldwide. Professional guidelines such as the 'Choosing Wisely' guidelines have attempted to reduce specific examples of overuse. We examined the use of surveillance positron emission tomography CT (PETCT) in patients with colorectal cancer (CRC) treated with curative intent. Methods and analysis We used the large Clalit Health Services dataset in Israel to identify patients with CRC who received adjuvant chemotherapy between January 2017 and December 2021. We examined the number of PETCTs performed for each patient. Results We included 1799 patients in our study cohort. We distinguished localised from metastatic cases based on specific drugs administered or not administered during the follow-up period (ie, biologics). For the entire cohort, the median number of PETCTs performed per patient over the study period was 3364 (20.2%) patients underwent a single PETCT, 946 (52.6%) patients underwent ≥2 PETCTs and 25 patients underwent ≥10 PETCTs. If none or a single PETCT is considered 'guideline-concordant' during diagnosis and treatment of localised CRC, 69% of 4231 PETCTs performed were 'guideline-discordant'. Conclusion Despite the professional guidelines recommending against routine PETCT to monitor for recurrence following curative-intent treatment of CRC, there remains a large volume of guideline-discordant PETCTs, constituting healthcare overuse of an expensive diagnostic procedure.
Collapse
Affiliation(s)
- Daniel A Goldstein
- Rabin Medical Center, Petah Tikva, Israel
- Tel Aviv University, Tel Aviv, Israel
- Clalit Health Services, Tel Aviv, Israel
| | - Roi Tschernichovsky
- Rabin Medical Center, Petah Tikva, Israel
- Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
| | - Talish Razi
- Clalit Health Service, Tel Aviv, Israel
- Department of Epidemiology, Biostatistics and Health Community Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | | | - Idan Menashe
- Department of Epidemiology, Biostatistics and Health Community Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Ronen Arbel
- Clalit Health Service, Tel Aviv, Israel
- Sapir College, Hof Ashkelon, Israel
| | | |
Collapse
|
|
12
|
Ivatury SJ, Suwanabol PA, Roo ACD. Shared Decision-Making, Sphincter Preservation, and Rectal Cancer Treatment: Identifying and Executing What Matters Most to Patients. Clin Colon Rectal Surg 2024; 37:256-265. [PMID: 38882940 PMCID: PMC11178388 DOI: 10.1055/s-0043-1770720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/18/2024]
Abstract
Rectal cancer treatment often encompasses multiple steps and options, with benefits and risks that vary based on the individual. Additionally, patients facing rectal cancer often have preferences regarding overall quality of life, which includes bowel function, sphincter preservation, and ostomies. This article reviews these data in the context of shared decision-making approaches in an effort to better inform patients deliberating treatment options for rectal cancer.
Collapse
Affiliation(s)
- Srinivas Joga Ivatury
- Department of Surgery and Perioperative Care, University of Texas at Austin Dell Medical School, Austin, Texas
| | | | - Ana C. De Roo
- Department of Surgery, Section of Colon and Rectal Surgery, Washington University School of Medicine, St Louis, Missouri
| |
Collapse
|
|
13
|
Emile SH, Wignakumar A. Non-operative management of rectal cancer: Highlighting the controversies. World J Gastrointest Surg 2024; 16:1501-1506. [PMID: 38983314 PMCID: PMC11230012 DOI: 10.4240/wjgs.v16.i6.1501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 04/18/2024] [Accepted: 04/23/2024] [Indexed: 06/27/2024] Open
Abstract
There remains much ambiguity on what non-operative management (NOM) of rectal cancer truly entails in terms of the methods to be adopted and the best algorithm to follow. This is clearly shown by the discordance between various national and international guidelines on NOM of rectal cancer. The main aim of the NOM strategy is organ preservation and avoiding unnecessary surgical intervention, which carries its own risk of morbidity. A highly specific and sensitive surveillance program must be devised to avoid patients undergoing unnecessary surgical interventions. In many studies, NOM, often interchangeably called the Watch and Wait strategy, has been shown as a promising treatment option when undertaken in the appropriate patient population, where a clinical complete response is achieved. However, there are no clear guidelines on patient selection for NOM along with the optimal method of surveillance.
Collapse
Affiliation(s)
- Sameh Hany Emile
- Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, FL 33331, United States
| | - Anjelli Wignakumar
- Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, FL 33331, United States
| |
Collapse
|
|
14
|
Tsai KY, Huang PS, Chu PY, Nguyen TNA, Hung HY, Hsieh CH, Wu MH. Current Applications and Future Directions of Circulating Tumor Cells in Colorectal Cancer Recurrence. Cancers (Basel) 2024; 16:2316. [PMID: 39001379 PMCID: PMC11240518 DOI: 10.3390/cancers16132316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 06/19/2024] [Accepted: 06/21/2024] [Indexed: 07/16/2024] Open
Abstract
The ability to predict or detect colorectal cancer (CRC) recurrence early after surgery enables physicians to apply appropriate treatment plans and different follow-up strategies to improve patient survival. Overall, 30-50% of CRC patients experience cancer recurrence after radical surgery, but current surveillance tools have limitations in the precise and early detection of cancer recurrence. Circulating tumor cells (CTCs) are cancer cells that detach from the primary tumor and enter the bloodstream. These can provide real-time information on disease status. CTCs might become novel markers for predicting CRC recurrence and, more importantly, for making decisions about additional adjuvant chemotherapy. In this review, the clinical application of CTCs as a therapeutic marker for stage II CRC is described. It then discusses the utility of CTCs for monitoring cancer recurrence in advanced rectal cancer patients who undergo neoadjuvant chemoradiotherapy. Finally, it discusses the roles of CTC subtypes and CTCs combined with clinicopathological factors in establishing a multimarker model for predicting CRC recurrence.
Collapse
Affiliation(s)
- Kun-Yu Tsai
- Division of Colon and Rectal Surgery, New Taipei Municipal TuCheng Hospital, New Taipei City 23652, Taiwan
| | - Po-Shuan Huang
- Graduate Institute of Biomedical Engineering, Chang Gung University, Taoyuan City 33302, Taiwan
| | - Po-Yu Chu
- Graduate Institute of Biomedical Engineering, Chang Gung University, Taoyuan City 33302, Taiwan
| | - Thi Ngoc Anh Nguyen
- Graduate Institute of Biomedical Engineering, Chang Gung University, Taoyuan City 33302, Taiwan
| | - Hsin-Yuan Hung
- Division of Colon and Rectal Surgery, New Taipei Municipal TuCheng Hospital, New Taipei City 23652, Taiwan
- College of Medicine, Chang Gung University, Taoyuan City 33302, Taiwan
| | - Chia-Hsun Hsieh
- College of Medicine, Chang Gung University, Taoyuan City 33302, Taiwan
- Division of Hematology and Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33302, Taiwan
- Division of Hematology and Oncology, Department of Internal Medicine, New Taipei Municipal Hospital, New Taipei City 23652, Taiwan
| | - Min-Hsien Wu
- Graduate Institute of Biomedical Engineering, Chang Gung University, Taoyuan City 33302, Taiwan
- Division of Hematology and Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan City 33302, Taiwan
- Division of Hematology and Oncology, Department of Internal Medicine, New Taipei Municipal Hospital, New Taipei City 23652, Taiwan
- Department of Biomedical Engineering, Chang Gung University, Taoyuan City 33302, Taiwan
| |
Collapse
|
|
15
|
He S, Zhang J, Wang R, Li L, Sun W, Wang J, Deng Y, Liang W, Dou R. Long-term Changes in Low Anterior Resection Syndrome in Survivors of Rectal Cancer: Longitudinal Follow-up of a Randomized Controlled Trial. Dis Colon Rectum 2024; 67:834-840. [PMID: 38426539 DOI: 10.1097/dcr.0000000000003262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/02/2024]
Abstract
BACKGROUND Postoperative bowel dysfunction, also known as low anterior resection syndrome, is common in rectal cancer survivors and significantly impacts quality of life. Although long-term longitudinal follow-up is lacking, improvement of the syndrome is commonly believed to happen only within the first 2 years. OBJECTIVE This study aimed to depict the longitudinal evolvement of low anterior resection syndrome beyond 3 years and explore factors associated with changes. DESIGN Longitudinal long-term follow-ups were performed for the single center with the largest cohort within the multicenter FOWARC randomized controlled trial. SETTING A quaternary referral center. PATIENTS Individuals diagnosed with rectal cancer who received long-course neoadjuvant chemotherapy or chemoradiotherapy, followed by sphincter-preserving radical proctectomy. MAIN OUTCOME MEASUREMENTS Change of low anterior resection syndrome score and stoma status. RESULTS Of the 220 patients responding to the first follow-up at a median of 39 months, 178 (80.9%) responded to the second follow-up after a median of 83 months. During this interval, the mean low anterior resection syndrome score improved from 29.5 (95% CI, 28.3-30.7) to 18.6 (95% CI, 16.6-20.6). Fifty-six (31.5%) patients reported improvement from major to no/minor severity, and 6 (3.4%) patients had new stomas because of severe bowel dysfunction. Neoadjuvant radiotherapy ( p = 0.016) was independently and negatively associated with improvement of the score. LIMITATIONS Loss of follow-up during the long-term follow-ups. CONCLUSIONS Most rectal cancer survivors with low anterior resection syndrome continued to improve beyond 3 years after proctectomy. Neoadjuvant radiotherapy was negatively associated with long-term improvement of low anterior resection syndrome. See Video Abstract . CAMBIO A LARGO PLAZO DEL SNDROME DE RESECCIN ANTERIOR BAJA EN SUPERVIVIENTES DE CNCER DE RECTO SEGUIMIENTO LONGITUDINAL DE UN ENSAYO CONTROLADO ALEATORIO ANTECEDENTES:La disfunción intestinal posoperatoria, también conocida como síndrome de resección anterior baja, es común en los sobrevivientes de cáncer de recto y afecta significativamente la calidad de vida. Aunque falta un seguimiento longitudinal a largo plazo, comúnmente se cree que la mejoría del síndrome ocurre sólo dentro de los primeros dos años.OBJETIVO:Este estudio tiene como objetivo representar la evolución longitudinal del síndrome de resección anterior baja más allá de los 3 años y explora los factores asociados con el cambio.DISEÑO:Se realizaron seguimientos longitudinales a largo plazo para el único centro con la cohorte más grande dentro del ensayo controlado aleatorio multicéntrico FOWARC.AJUSTE:Un centro de referencia cuaternario.PACIENTES:Individuos diagnosticados con cáncer de recto que recibieron quimioterapia neoadyuvante de larga duración o quimiorradioterapia, seguida de proctectomía radical con preservación del esfínter.PRINCIPALES MEDICIONES DE RESULTADO:Cambio en la puntuación del síndrome de resección anterior baja y el estado del estoma.RESULTADOS:De los 220 pacientes que respondieron al primer seguimiento con una mediana de 39 meses, 178 (80,9%) respondieron al segundo seguimiento después de una mediana de 83 meses. Durante el intervalo, la puntuación media del síndrome de resección anterior baja mejoró de 29,5 (intervalo de confianza [IC] del 95%: 28,3-30,7) a 18,6 (IC del 95%: 16,6-20,6). 56 (31,5%) pacientes informaron una mejoría de mayor a ninguna gravedad, y 6 (3,4%) pacientes tuvieron un nuevo estoma debido a una disfunción intestinal grave. La radiación neoadyuvante (p = 0,016) se asoció de forma independiente y negativa con la mejora de la puntuación.LIMITACIONES:Pérdida de seguimiento durante los seguimientos a largo plazo.CONCLUSIÓN:La mayoría de los sobrevivientes de cáncer de recto con síndrome de resección anterior baja continuaron mejorando más allá de los 3 años después de la proctectomía. La radiación neoadyuvante se asoció negativamente con la mejora a largo plazo del síndrome de resección anterior baja. (Traducción-Dr Yolanda Colorado ).
Collapse
Affiliation(s)
- Siqi He
- Department of Gastrointestinal Surgery, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People's Republic of China
- Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
| | - Jinquan Zhang
- Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
| | - Runxian Wang
- Department of Gastrointestinal Surgery, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People's Republic of China
| | - Li Li
- Pelvic Floor Center, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
| | - Weipeng Sun
- Department of Colorectal Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Jianping Wang
- Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
| | - Yanhong Deng
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
- Department of Medical Oncology, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
| | - Weiwen Liang
- Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
| | - Ruoxu Dou
- Department of Gastrointestinal Surgery, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People's Republic of China
- Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
| |
Collapse
|
|
16
|
Nyström K, Olsson L. A systematic review of population-based studies on metachronous metastases of colorectal cancer. World J Surg 2024; 48:1521-1533. [PMID: 38747538 DOI: 10.1002/wjs.12204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 04/22/2024] [Indexed: 06/13/2024]
Abstract
BACKGROUND The occurrence of metachronous metastases (MM) of colorectal (CRC), colon (CC), and rectal (RC) cancer of population-based studies has not been compiled in a systematic review previously. METHODS MEDLINE, Embase, and Cochrane Library were searched for primary studies of any design from inception until January 2021 and updated in August 2023 (CRD42021261648). The PRISMA guidelines were adopted, and the Newcastle-Ottawa Quality Assessment Scale used for risk of bias assessment. Outcomes on overall and organ-specific MM were extracted. A narrative analysis followed. RESULTS Out of 2143 unique hits, 162 publications were read in full-text and 37 population-based cohort studies published in 1981-2022 were included. Ten studies adopted time-dependent analyses; eight were registry-based and seven had a low risk of bias. Three studies reported 5-year recurrence rate of MM overall of stages I-III; for CRC, it was 20.5%, for CC, it was 18% and 25.6%, and for RC, it was 23%. Four studies reported 5-year recurrence rate of organ-specific MM of stages I-III-for CRC, it was 2.2% and 5.5% for peritoneal metastases and 5.8% for lung metastases and for CC 4.5% for peritoneal metastases. Twenty-seven studies reported proportions of patients diagnosed with MM, but data on the length of follow-up was incomplete and varied widely. Proportions of patients with CRC stages I-III that developed MM overall was 14.4%-26.1% in 10 studies. In relation to the enrollment period, a downward trend may be discernible. CONCLUSION Studies adopting a more appropriate analysis were highly heterogeneous, whereas uncertain data of partly inadequate studies may indicate that MM are overall declining.
Collapse
Affiliation(s)
- Karin Nyström
- Faculty of Medicine and Health, Örebro University, Örebro, Sweden
- Department of Oncology, Örebro University Hospital, Örebro, Sweden
| | - Louise Olsson
- Faculty of Medicine and Health, Örebro University, Örebro, Sweden
- Centre for Assessment of Medical Technology, Örebro University Hospital, Örebro, Sweden
| |
Collapse
|
|
17
|
Takayama Y, Tsukamoto S, Kudose Y, Takamizawa Y, Moritani K, Esaki M, Kanemitsu Y, Igarashi A. Cost-effectiveness of surveillance intervals after curative resection of colorectal cancer. Jpn J Clin Oncol 2024; 54:637-646. [PMID: 38376792 DOI: 10.1093/jjco/hyae018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Accepted: 01/25/2024] [Indexed: 02/21/2024] Open
Abstract
BACKGROUND Major guidelines consistently recommend 5 years of postoperative surveillance for patients with colorectal cancer. However, they differ in their recommendations for examination intervals and whether they should vary according to disease stage. Furthermore, there are no reports on the cost-effectiveness of the different surveillance schedules. The objective of this study is to identify the most cost-effective surveillance intervals after curative resection of colorectal cancer. METHODS A total of 3701 patients who underwent curative surgery for colorectal cancer at the National Cancer Center Hospital were included. A cost-effectiveness analysis was conducted for the five surveillance strategies with reference to the guidelines. Expected medical costs and quality-adjusted life years after colorectal cancer resection were calculated using a state-transition model by Monte Carlo simulation. The incremental cost-effectiveness ratio per quality-adjusted life years gained was calculated for each strategy, with a maximum acceptable value of 43 500-52 200 USD (5-6 million JPY). RESULTS Stages I, II and III included 1316, 1082 and 1303 patients, respectively, with 45, 140 and 338 relapsed cases. For patients with stage I disease, strategy 4 (incremental cost-effectiveness ratio $26 555/quality-adjusted life year) was considered to be the most cost-effective, while strategies 3 ($83 071/quality-adjusted life year) and 2 ($289 642/quality-adjusted life year) exceeded the threshold value. In stages II and III, the incremental cost-effectiveness ratio for strategy 3 was the most cost-effective option, with an incremental cost-effectiveness ratio of $18 358-22 230/quality-adjusted life year. CONCLUSIONS In stage I, the cost-effectiveness of intensive surveillance is very poor and strategy 4 is the most cost-effective. Strategy 3 is the most cost-effective in stages II and III.
Collapse
Affiliation(s)
- Yuji Takayama
- Department of Colorectal Surgery, National Cancer Center, Tokyo, Japan
| | | | - Yozo Kudose
- Department of Colorectal Surgery, National Cancer Center, Tokyo, Japan
| | | | - Konosuke Moritani
- Department of Colorectal Surgery, National Cancer Center, Tokyo, Japan
| | - Minoru Esaki
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center, Tokyo, Japan
| | | | - Ataru Igarashi
- Department of Health Economics and Outcomes Research, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
| |
Collapse
|
|
18
|
Wehrle CJ, Woo K, Chang J, Gamaleldin M, DeHaan R, Dahdaleh F, Felder S, Rosen DR, Champagne B, Steele SR, Naffouje SA. Impact of neoadjuvant therapy on nodal harvest in clinical stage III rectal cancer: Establishing optimum cut-offs by disease response. J Surg Oncol 2024; 129:945-952. [PMID: 38221655 DOI: 10.1002/jso.27586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 12/19/2023] [Accepted: 12/29/2023] [Indexed: 01/16/2024]
Abstract
INTRODUCTION A minimum lymph node harvest (LNH) of 12 is the current standard for appropriate nodal staging in resectable rectal cancer. However, the rise of neoadjuvant chemoradiation (NCRT) and total neoadjuvant therapy (TNT) has been associated with decreasing number of LNH. We hypothesize that as tumor response to neoadjuvant therapy increases, the optimum for LNH to achieve appropriate nodal staging should decrease. METHODS Patients with clinical stage III rectal adenocarcinoma who underwent NCRT/TNT followed by resection were identified from the National Cancer Database. A JoinPoint regression analysis was used to determine the LNH for each tumor regression grade (TRG) category beyond which the rate of positive nodes does not significantly change. RESULTS Thirteen thousand four hundred and twenty-six patients met inclusion criteria. Of these, 2406 (17.9%) achieved TRG 0 or ypT0 and 8210 (61.2%) achieved ypN0. Collectively, 2043 patients (15.2%) were reported to have a pathologic complete response (ypT0 ypN0). Positive pathologic nodes were found in 15%, 23%, 31%, 54%, and 53% as ypT stage increased from ypT0 to ypT4, respectively. Similarly, ypN+ rates were 15%, 36%, 41%, and 55% in TRG 0-3. No JoinPoint was identified for TRG 0, whereas inflection points were found at 6-10 nodes for TRG1 (p = 0.002) and TRG 2 (p = 0.016), and at 11-15 nodes for TRG 3. CONCLUSION The benchmark of retrieving 12 nodes in resectable stage III rectal cancer is not consistently achieved after NCRT/TNT. We demonstrate that the LNH requirement to establish accurate pathologic nodal staging can vary depending on the tumor response to neoadjuvant therapies.
Collapse
Affiliation(s)
- Chase J Wehrle
- Cleveland Clinic, Digestive Diseases and Surgery and Institute, General Surgery, Cleveland, Ohio, USA
| | - Kimberly Woo
- Cleveland Clinic, Digestive Diseases and Surgery and Institute, General Surgery, Cleveland, Ohio, USA
| | - Jenny Chang
- Cleveland Clinic, Digestive Diseases and Surgery and Institute, General Surgery, Cleveland, Ohio, USA
| | - Maysoon Gamaleldin
- Cleveland Clinic, Digestive Diseases and Surgery and Institute, General Surgery, Cleveland, Ohio, USA
| | - Reece DeHaan
- Cleveland Clinic, Digestive Diseases and Surgery and Institute, General Surgery, Cleveland, Ohio, USA
| | - Fadi Dahdaleh
- Department of Surgical Oncology, Edward-Elmhurst Health, Elmhurst, Illinois, USA
| | - Seth Felder
- Moffitt Cancer Center, GI Oncology Program, Tampa, Florida, USA
| | - David R Rosen
- Cleveland Clinic Digestive Diseases and Surgery and Institute, Colorectal Surgery, Cleveland, Ohio, USA
| | - Bradley Champagne
- Cleveland Clinic Digestive Diseases and Surgery and Institute, Colorectal Surgery, Cleveland, Ohio, USA
| | - Scott R Steele
- Cleveland Clinic Digestive Diseases and Surgery and Institute, Colorectal Surgery, Cleveland, Ohio, USA
| | - Samer A Naffouje
- Cleveland Clinic, Digestive Diseases and Surgery and Institute, General Surgery, Cleveland, Ohio, USA
| |
Collapse
|
|
19
|
Liu J, Tan F, Zhang Y, Zhou P, Qian Q, He Q, Xu J. Application Value of High-Quality Nursing in Operating Room in Rectal Cancer Operation and its Influence on Postoperative Rehabilitation. Surg Innov 2024:15533506231221895. [PMID: 38468453 DOI: 10.1177/15533506231221895] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/13/2024]
Abstract
OBJECTIVE To study the value of high-quality care in operating room during operation of patients with rectal cancer and the effect of this nursing model on postoperative rehabilitation. METHODS This study recruited 72 patients with rectal cancer, including 36 in the control group and 36 in the observation group. Patients in the control group received routine care, and those in the observation group received high-quality care in operating room. RESULTS The anxiety score (5.50 ± .77 vs 10. 08 ± 1.13), stress score (6.97 ± .60 vs 8.61 ± .99), and depression score (4.02 ± .65 vs 5.50 ± .91) in the observation group were less than the control group after treatment (P < .05). The measured values of diastolic blood pressure (73.19 ± 1.96 vs 86.13 ± 2.0), systolic blood pressure (121.08 ± 1.62 vs 130.63 ± 2.84), heart rate (73.05 ± 1.63 vs 87.11 ± 2.91) and adrenaline E(E) (58.40 ± 3.02 vs 61.42 ± 3.86) in the observation group were less than the control group after treatment (P < .05). The cooperation degree (94.44 vs 75.00) in the observation group was greater than the control group, but the operation time (308.47 ± 9.92 vs 339.47 ± 12.70), postoperative intestinal function recovery time (16.30 ± 1.14 vs 30.94 ± 2.10) and length of stay (10.47 ± 1.85 vs 13.33 ± 1.95) were all shorter than the control group (P < .05). The nasopharyngeal temperature in the observation group was greater than the control group at 30 minutes during operation (36.16 ± .50 vs 35.19 ± .40) and after operation, and fear score (2.22 ± .42 vs 3.63 ± .72) was less than the control group (P < .05). CONCLUSION The application of high-quality care in the operating room during rectal cancer surgery has a significantly good clinical outcome.
Collapse
Affiliation(s)
- Juan Liu
- Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Feng Tan
- Department of Infection Management, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Yihui Zhang
- Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Ping Zhou
- Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Qian Qian
- Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Qiaofang He
- Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Jingpin Xu
- Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| |
Collapse
|
|
20
|
Pinheiro M, Moreira DN, Ghidini M. Colon and rectal cancer: An emergent public health problem. World J Gastroenterol 2024; 30:644-651. [PMID: 38515957 PMCID: PMC10950624 DOI: 10.3748/wjg.v30.i7.644] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Revised: 12/22/2023] [Accepted: 01/22/2024] [Indexed: 02/21/2024] Open
Abstract
Colorectal cancer ranks third globally, with a high mortality rate. In the United States, and different countries in Europe, organized population screenings exist and include people between 50 and 74 years of age. These screenings have allowed an early diagnosis and consequently an improvement in health indicators. Colon and rectal cancer (CRC) is a disease of particular interest due to the high global burden associated with it and the role attributed to prevention and early diagnosis in reducing morbidity and mortality. This study is a review of CRC pathology and includes the most recent scientific evidence regarding this pathology, as well as a diagnosis of the epidemiological situation of CRC. Finally, the recommendation from a public health perspective will be discussed in detail taking into account the context and the most current recommendations.
Collapse
Affiliation(s)
- Marina Pinheiro
- LAQV, REQUIMTE, Department of Chemistry, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
- Unidade de Saúde Pública, Unidade Local de Saúde Barcelos/Esposende, Barcelinhos 4755-069, Braga, Portugal
| | - David Nascimento Moreira
- Unidade de Saúde Pública, Unidade Local de Saúde Barcelos/Esposende, Barcelinhos 4755-069, Braga, Portugal
| | - Michele Ghidini
- Medical Oncology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan 20122, Italy
| |
Collapse
|
|
21
|
Lim DYZ, Tan YB, Koh JTE, Tung JYM, Sng GGR, Tan DMY, Tan CK. ChatGPT on guidelines: Providing contextual knowledge to GPT allows it to provide advice on appropriate colonoscopy intervals. J Gastroenterol Hepatol 2024; 39:81-106. [PMID: 37855067 DOI: 10.1111/jgh.16375] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 09/06/2023] [Accepted: 09/22/2023] [Indexed: 10/20/2023]
Abstract
BACKGROUND AND AIM Colonoscopy is commonly used in screening and surveillance for colorectal cancer. Multiple different guidelines provide recommendations on the interval between colonoscopies. This can be challenging for non-specialist healthcare providers to navigate. Large language models like ChatGPT are a potential tool for parsing patient histories and providing advice. However, the standard GPT model is not designed for medical use and can hallucinate. One way to overcome these challenges is to provide contextual information with medical guidelines to help the model respond accurately to queries. Our study compares the standard GPT4 against a contextualized model provided with relevant screening guidelines. We evaluated whether the models could provide correct advice for screening and surveillance intervals for colonoscopy. METHODS Relevant guidelines pertaining to colorectal cancer screening and surveillance were formulated into a knowledge base for GPT. We tested 62 example case scenarios (three times each) on standard GPT4 and on a contextualized model with the knowledge base. RESULTS The contextualized GPT4 model outperformed the standard GPT4 in all domains. No high-risk features were missed, and only two cases had hallucination of additional high-risk features. A correct interval to colonoscopy was provided in the majority of cases. Guidelines were appropriately cited in almost all cases. CONCLUSIONS A contextualized GPT4 model could identify high-risk features and quote appropriate guidelines without significant hallucination. It gave a correct interval to the next colonoscopy in the majority of cases. This provides proof of concept that ChatGPT with appropriate refinement can serve as an accurate physician assistant.
Collapse
Affiliation(s)
- Daniel Yan Zheng Lim
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
- Medicine Academic Clininical Programme, Duke-NUS Medical School, Singapore, Singapore
| | - Yu Bin Tan
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - Jonathan Tian En Koh
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | | | | | - Damien Meng Yew Tan
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
- Medicine Academic Clininical Programme, Duke-NUS Medical School, Singapore, Singapore
| | - Chee-Kiat Tan
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
- Medicine Academic Clininical Programme, Duke-NUS Medical School, Singapore, Singapore
| |
Collapse
|
|
22
|
Langenfeld SJ, Davis BR, Vogel JD, Davids JS, Temple LKF, Cologne KG, Hendren S, Hunt S, Garcia Aguilar J, Feingold DL, Lightner AL, Paquette IM. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Rectal Cancer 2023 Supplement. Dis Colon Rectum 2024; 67:18-31. [PMID: 37647138 DOI: 10.1097/dcr.0000000000003057] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
Affiliation(s)
- Sean J Langenfeld
- Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska
| | - Bradley R Davis
- Department of Surgery, Carolinas Medical Center, Charlotte, North Carolina
| | - Jon D Vogel
- Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado
| | | | - Larissa K F Temple
- Colorectal Surgery Division, Department of Surgery, University of Rochester Medical Center, Rochester, New York
| | - Kyle G Cologne
- Department of Surgery, Division of Colorectal Surgery, University of Southern California, Los Angeles, California
| | - Samantha Hendren
- Division of Colon and Rectal Surgery, Department of Surgery, University of Michigan, Michigan Medicine, Ann Arbor, Michigan
| | - Steven Hunt
- Department of Surgery, Section of Colon and Rectal Surgery, Washington University School of Medicine, St. Louis, Missouri
| | - Julio Garcia Aguilar
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Daniel L Feingold
- Department of Surgery, Rutgers University, New Brunswick, New Jersey
| | - Amy L Lightner
- Department of Colon and Rectal Surgery, Cleveland Clinic, Cleveland, Ohio
| | - Ian M Paquette
- Department of Surgery, Division of Colon and Rectal Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio
| |
Collapse
|
|
23
|
Vitello DJ, Merkow RP. The Use of Hepatic Artery Infusion Chemotherapy for Unresectable Colorectal Cancer Liver Metastases. Cancer Treat Res 2024; 192:265-276. [PMID: 39212925 DOI: 10.1007/978-3-031-61238-1_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in men and women (Siegel et al. in CA Cancer J Clin 72(1):7-33). Over one-half of newly diagnosed individuals will develop liver metastases. Among those with liver-only metastatic disease, only about one in five will be candidates for potentially curable resection.
Collapse
Affiliation(s)
- Dominic J Vitello
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Ryan P Merkow
- Department of Surgery, University of Chicago Pritzker School of Medicine, Chicago, IL, USA.
| |
Collapse
|
|
24
|
Nakashima Y, Fudeyasu K, Kataoka Y, Taito S, Ariie T, Mikami Y. Efficacy of Pelvic Floor Muscle Training for Postoperative Patients With Rectal Cancer: A Systematic Review and Meta-Analysis. Cureus 2023; 15:e50287. [PMID: 38205462 PMCID: PMC10776499 DOI: 10.7759/cureus.50287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/08/2023] [Indexed: 01/12/2024] Open
Abstract
This study aimed to assess the effectiveness of pelvic floor muscle training (PFMT) for fecal incontinence (FI) and health-related quality of life (HR-QOL) after colorectal cancer surgery. This systematic review (SR) and meta-analysis included randomized controlled trials (RCTs) that examined the effects of PFMT after colorectal cancer surgery, which were extracted from several databases in January 2023. The primary outcomes were FI (Wexner scores), HR-QOL, and adverse events. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence (CoE). A total of seven RCTs were included. Our SR results suggested that PFMT showed little to no difference in FI (mean difference 0.62 higher; 95% CI: -1.26 to 2.5, low CoE) and adverse events (risk ratio 5.78; 95% CI: 0.28-117.22, low CoE). Two adverse events occurred in the PFMT group (anastomotic stenosis, suboptimal use of laxatives) and were not observed in controls. HR-QOL was measured in two RCTs using 12-item Short Form Survey (SF-12) and fecal incontinence quality of life (FIQL). Two RCTs found no trend toward a positive impact on HR-QOL. Higher quality RCTs on colorectal cancer after surgery are required. Furthermore, extending the duration of the PFMT intervention may be necessary to ensure its success.
Collapse
Affiliation(s)
- Yuki Nakashima
- Division of Rehabilitation, Department of Clinical Practice and Support, Hiroshima University Hospital, Hiroshima, JPN
- Department of Systematic Reviewers, Scientific Research WorkS Peer Support Group (SRWS-PSG), Osaka, JPN
| | - Kenichi Fudeyasu
- Division of Rehabilitation, Department of Clinical Practice and Support, Hiroshima University Hospital, Hiroshima, JPN
| | - Yuki Kataoka
- Department of Systematic Reviewers, Scientific Research WorkS Peer Support Group (SRWS-PSG), Osaka, JPN
- Department of Internal Medicine, Kyoto Min-iren Asukai Hospital, Kyoto, JPN
- Section of Clinical Epidemiology, Department of Community Medicine, Kyoto University Graduate School of Medicine, Kyoto, JPN
- Department of Healthcare Epidemiology, School of Public Health, Kyoto University Graduate School of Medicine, Kyoto, JPN
| | - Shunsuke Taito
- Division of Rehabilitation, Department of Clinical Practice and Support, Hiroshima University Hospital, Hiroshima, JPN
- Department of Systematic Reviewers, Scientific Research WorkS Peer Support Group (SRWS-PSG), Osaka, JPN
| | - Takashi Ariie
- Department of Systematic Reviewers, Scientific Research WorkS Peer Support Group (SRWS-PSG), Osaka, JPN
- Department of Physical Therapy, School of Health Sciences at Fukuoka, International University of Health and Welfare, Fukuoka, JPN
| | - Yukio Mikami
- Department of Rehabilitation Medicine, Hiroshima University Hospital, Hiroshima, JPN
| |
Collapse
|
|
25
|
Yagi S, Takahashi M, Tsuji T, Yanagibashi S, Higashihara T, Ohtsuka H, Hayashi T, Takuma K, Morita Y, Nakazono A, Okada H, Ohtsuka M. Two cases of colorectal liver metastasis with residual liver recurrence after a long recurrence-free survival period. Surg Case Rep 2023; 9:202. [PMID: 37987931 PMCID: PMC10663427 DOI: 10.1186/s40792-023-01779-5] [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: 09/13/2023] [Accepted: 11/07/2023] [Indexed: 11/22/2023] Open
Abstract
BACKGROUND The rate of residual liver recurrence after the resection of colorectal liver metastases is high, and most cases recur within 5 years of the initial hepatectomy. Here, we report two cases of residual liver recurrence after radical resection of colorectal liver metastases after a long recurrence-free survival period. CASE PRESENTATION Case 1 involved a 62-year-old woman treated for ascending colon cancer in April 2011 who underwent right hepatectomy for synchronous colorectal liver metastasis in April 2012. However, in September 2021, computed tomography revealed residual recurrence in the lateral segment of the liver, and a lateral segmentectomy of the liver was performed. In Case 2, a 52-year-old man treated for cecal cancer in July 2002 underwent lateral segmentectomy of the liver for metachronous colorectal liver metastasis in October 2006. Subsequently, there was no recurrence; however, computed tomography showed residual liver recurrence in the right lobe of the liver in October 2021, and an expanded posterior hepatic segmentectomy was performed. Histopathological findings in both cases were consistent with colorectal liver metastases. CONCLUSIONS We encountered two cases in which residual liver recurrence was observed after a long period of recurrence-free survival. Although rare, there have been a few cases of late recurrence of liver metastases after radical resection of cancer liver metastases.
Collapse
Affiliation(s)
- Shotaro Yagi
- Department of Surgery, Tokyo Metropolitan Tama Medical Center, 2-8-29, Musashidai Fuchu-Shi, Tokyo, 183-8524, Japan
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Makoto Takahashi
- Department of Surgery, Tokyo Metropolitan Tama Medical Center, 2-8-29, Musashidai Fuchu-Shi, Tokyo, 183-8524, Japan.
| | - Taiki Tsuji
- Department of Surgery, Tokyo Metropolitan Tama Medical Center, 2-8-29, Musashidai Fuchu-Shi, Tokyo, 183-8524, Japan
| | - Susumu Yanagibashi
- Department of Surgery, Tokyo Metropolitan Tama Medical Center, 2-8-29, Musashidai Fuchu-Shi, Tokyo, 183-8524, Japan
| | - Taku Higashihara
- Department of Surgery, Tokyo Metropolitan Tama Medical Center, 2-8-29, Musashidai Fuchu-Shi, Tokyo, 183-8524, Japan
| | - Hideo Ohtsuka
- Department of Surgery, Tokyo Metropolitan Tama Medical Center, 2-8-29, Musashidai Fuchu-Shi, Tokyo, 183-8524, Japan
| | - Tatsuya Hayashi
- Department of Surgery, Tokyo Metropolitan Tama Medical Center, 2-8-29, Musashidai Fuchu-Shi, Tokyo, 183-8524, Japan
| | - Kunio Takuma
- Department of Surgery, Tokyo Metropolitan Tama Medical Center, 2-8-29, Musashidai Fuchu-Shi, Tokyo, 183-8524, Japan
| | - Yasuhiro Morita
- Department of Surgery, Tokyo Metropolitan Tama Medical Center, 2-8-29, Musashidai Fuchu-Shi, Tokyo, 183-8524, Japan
| | - Ayano Nakazono
- Department of Gastroenterology, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan
| | - Haruka Okada
- Department of Pathology, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan
| | - Masayuki Ohtsuka
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| |
Collapse
|
|
26
|
Karim S, Doll CM, Dingley B, Merchant SJ, de Moraes FY, Booth CM. The Choosing Wisely Oncology Canada Cancer List: An Update. J Cancer Policy 2023; 37:100431. [PMID: 37391095 DOI: 10.1016/j.jcpo.2023.100431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Accepted: 06/22/2023] [Indexed: 07/02/2023]
Abstract
BACKGROUND Choosing Wisely (CW) Canada is a national campaign to identify unnecessary or harmful services that are frequently used in Canada. The original CW Oncology Canada Cancer list was developed in 2014. A CW Oncology Canada working group was established to review new evidence and guidelines and to update the current CW Oncology Canada Cancer List. METHODS Between January and March 2022, we conducted a survey of members of the Canadian Association of Medical Oncology (CAMO), Canadian Association of Radiation Oncology (CARO) and the Canadian Society of Surgical Oncology (CSSO). We took the feedback from the survey, including potential new recommendations as well as those that were thought to be no longer relevant and up to date, and conducted a literature review with the assistance of the Canadian Agency for Drugs and Technology in Health (CADTH). The final updated list of recommendations was made by the CW Oncology Canada working group based on a consensus process. RESULTS We reviewed two potential recommendations to add and two potential recommendations to remove from the existing CW Oncology Canada Cancer List. The recommendation "Do not prescribe whole brain radiation over stereotactic radiosurgery for patient with limited brain metastases (≤4 lesions)" was supported by several evidence-based guidelines with the strength of recommendations ranging from strong to moderate and the quality of evidence ranging from level 1 to level 3. After reviewing the evidence, the working group felt that the other potential recommendation to add and the two potential recommendations to remove did not have sufficient strength and quality of evidence at this time to be added or removed from the list. CONCLUSION The updated Choosing Wisely Oncology Canada Cancer List consists of 11 items that oncologists should question in the treatment of patients with cancer. This list can be used to design specific interventions to reduce low value care.
Collapse
Affiliation(s)
- Safiya Karim
- Department of Oncology, University of Calgary, Calgary, AB, Canada.
| | - Corinne M Doll
- Department of Oncology, University of Calgary, Calgary, AB, Canada
| | | | - Shaila J Merchant
- Department of Oncology, Queen's University, Kingston, ON, Canada; Division of Cancer Care and Epidemiology, Queen's University Cancer Research Institute, Kingston, ON, Canada
| | - Fabio Ynoe de Moraes
- Department of Oncology, Queen's University, Kingston, ON, Canada; Division of Cancer Care and Epidemiology, Queen's University Cancer Research Institute, Kingston, ON, Canada
| | - Christopher M Booth
- Department of Oncology, Queen's University, Kingston, ON, Canada; Division of Cancer Care and Epidemiology, Queen's University Cancer Research Institute, Kingston, ON, Canada
| |
Collapse
|
|
27
|
Ding PQ, Au F, Cheung WY, Heitman SJ, Lee-Ying R. Cost-Effectiveness of Surveillance after Metastasectomy of Stage IV Colorectal Cancer. Cancers (Basel) 2023; 15:4121. [PMID: 37627149 PMCID: PMC10452589 DOI: 10.3390/cancers15164121] [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: 07/25/2023] [Revised: 08/10/2023] [Accepted: 08/14/2023] [Indexed: 08/27/2023] Open
Abstract
Surveillance of stage IV colorectal cancer (CRC) after curative-intent metastasectomy can be effective for detecting asymptomatic recurrence. Guidelines for various forms of surveillance exist but are supported by limited evidence. We aimed to determine the most cost-effective strategy for surveillance following curative-intent metastasectomy of stage IV CRC. We performed a decision analysis to compare four active surveillance strategies involving clinic visits and investigations elicited from National Comprehensive Cancer Network (NCCN) recommendations. Markov model inputs included data from a population-based cohort and literature-derived costs, utilities, and probabilities. The primary outcomes were costs (2021 Canadian dollars) and quality-adjusted life years (QALYs) gained. Over a 10-year base-case time horizon, surveillance with follow-ups every 12 months for 5 years was most economically favourable at a willingness-to-pay threshold of CAD 50,000 per QALY. These patterns were generally robust in the sensitivity analysis. A more intensive surveillance strategy was only favourable with a much higher willingness-to-pay threshold of approximately CAD 425,000 per QALY, with follow-ups every 3 months for 2 years then every 12 months for 3 additional years. Our findings are consistent with NCCN guidelines and justify the need for additional research to determine the impact of surveillance on CRC outcomes.
Collapse
Affiliation(s)
- Philip Q. Ding
- Oncology Outcomes Program, Department of Oncology, University of Calgary, Calgary, AB T2N 4Z6, Canada
- Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada
| | - Flora Au
- Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada
| | - Winson Y. Cheung
- Oncology Outcomes Program, Department of Oncology, University of Calgary, Calgary, AB T2N 4Z6, Canada
- Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N2, Canada
| | - Steven J. Heitman
- Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada
| | - Richard Lee-Ying
- Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N2, Canada
| |
Collapse
|
|
28
|
Huisman JF, Dang H, Moons LMG, Backes Y, Dik VK, Groen JN, Ter Borg F, van Bergeijk JD, Geesing JMJ, Spanier BWM, Terhaar Sive Droste JS, Overwater A, van Lelyveld N, Kessels K, Lacle MM, Offerhaus GJA, Brohet RM, Knijn N, Vleggaar FP, van Westreenen HL, de Vos Tot Nederveen Cappel WH, Boonstra JJ. Diagnostic value of radiological staging and surveillance for T1 colorectal carcinomas: A multicenter cohort study. United European Gastroenterol J 2023. [PMID: 37300377 DOI: 10.1002/ueg2.12403] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 04/19/2023] [Indexed: 06/12/2023] Open
Abstract
BACKGROUND The role of radiological staging and surveillance imaging is under debate for T1 colorectal cancer (CRC) as the risk of distant metastases is low and imaging may lead to the detection of incidental findings. OBJECTIVE The aim of this study was to evaluate the yield of radiological staging and surveillance imaging for T1 CRC. METHODS In this retrospective multicenter cohort study, all patients of 10 Dutch hospitals with histologically proven T1 CRC who underwent radiological staging in the period 2000-2014 were included. Clinical characteristics, pathological, endoscopic, surgical and imaging reports at baseline and during follow-up were recorded and analyzed. Patients were classified as high-risk T1 CRC if at least one of the histological risk factors (lymphovascular invasion, poor tumor differentiation, deep submucosal invasion or positive resection margins) was present and as low-risk when all risk factors were absent. RESULTS Of the 628 included patients, 3 (0.5%) had synchronous distant metastases, 13 (2.1%) malignant incidental findings and 129 (20.5%) benign incidental findings at baseline staging. Radiological surveillance was performed among 336 (53.5%) patients. The 5-year cumulative incidence of distant recurrence, malignant and benign incidental findings were 2.4% (95% confidence interval (CI): 1.1%-5.4%), 2.5% (95% CI: 0.6%-10.4%) and 18.3% (95% CI: 13.4%-24.7%), respectively. No distant metastatic events occurred among low-risk T1 CRC patients. CONCLUSION The risk of synchronous distant metastases and distant recurrence in T1 CRC is low, while there is a substantial risk of detecting incidental findings. Radiological staging seems unnecessary prior to local excision of suspected T1 CRC and after local excision of low-risk T1 CRC. Radiological surveillance should not be performed in patients with low-risk T1 CRC.
Collapse
Affiliation(s)
- Jelle F Huisman
- Department of Gastroenterology and Hepatology, Isala, Zwolle, the Netherlands
| | - Hao Dang
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands
| | - Leon M G Moons
- Department. of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Yara Backes
- Department. of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Vincent K Dik
- Department of Gastroenterology and Hepatology, Medisch Centrum Leeuwarden, Leeuwarden, the Netherlands
| | - John N Groen
- Department of Gastroenterology and Hepatology, Sint Jansdal, Harderwijk, the Netherlands
| | - Frank Ter Borg
- Department of Gastroenterology and Hepatology, Deventer Hospital, Deventer, the Netherlands
| | - Jeroen D van Bergeijk
- Department of Gastroenterology and Hepatology, Gelderse Vallei Hospital, Ede, the Netherlands
| | - Joost M J Geesing
- Department of Gastroenterology and Hepatology, Diakonessenhuis, Utrecht, the Netherlands
| | - B W Marcel Spanier
- Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, the Netherlands
| | | | - Anouk Overwater
- Department of Gastroenterology and Hepatology, Sint Antonius Hospital, Nieuwegein, the Netherlands
| | - Niels van Lelyveld
- Department of Gastroenterology and Hepatology, Sint Antonius Hospital, Nieuwegein, the Netherlands
| | - Koen Kessels
- Department of Gastroenterology and Hepatology, Sint Antonius Hospital, Nieuwegein, the Netherlands
| | - Miangela M Lacle
- Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - G Johan A Offerhaus
- Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Richard M Brohet
- Departmentof Epidemiology and Statistics, Isala, Zwolle, the Netherlands
| | - Nikki Knijn
- Department of Pathology-DNA, Rijnstate Hospital, Arnhem, the Netherlands
| | - Frank P Vleggaar
- Department. of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands
| | | | | | - Jurjen J Boonstra
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands
| |
Collapse
|
|
29
|
Aldilaijan AF, Kim YI, Kim CW, Yoon YS, Park IJ, Lim SB, Kim J, Ro JS, Kim JC. Clinical implication of tissue carcinoembryonic antigen expression in association with serum carcinoembryonic antigen in colorectal cancer. Sci Rep 2023; 13:7616. [PMID: 37165043 PMCID: PMC10172318 DOI: 10.1038/s41598-023-34855-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Accepted: 05/09/2023] [Indexed: 05/12/2023] Open
Abstract
This study aimed to evaluate the prognostic significance of carcinoembryonic antigen (CEA) expression in tumor tissues of patients with colorectal cancer (CRC). The cohort included 7,412 patients with CRC from January 2010 to December 2015. Survival outcomes were assessed based on tissue CEA (t-CEA) patterns and intensities. Three-year (76.7% versus 81.3%) and 5-year (71.7% versus 77.6%, p < 0.001) disease-free survival (DFS) rates were significantly (p < 0.001) poorer in patients with a diffuse-cytoplasmic pattern than an apicoluminal pattern. Three-year (79% versus 86.6%) and 5-year (74.6% versus 84.7%) DFS rates were also significantly (p < 0.001) poorer in patients with high than low t-CEA intensity. Three-year (84.6% versus 88.4%) and 5-year (77.3% versus 82.6%) overall survival (OS) rates were significantly (p < 0.001) poorer in patients with diffuse-cytoplasmic than apicoluminal pattern of CEA expression, and both 3-year (86.7% versus 91.2%) and 5-year (80.1% versus 87.7%) OS rates were significantly (p < 0.001) poorer in patients with high than low t-CEA intensity. Multivariate analyses showed that high-intensity t-CEA was independently associated with DFS (p = 0.02; hazard ratio [HR] = 1.233) and OS (p = 0.032; HR = 1.228). Therefore, high-intensity t-CEA is a significant prognostic factor in CRC, independent of serum CEA (s-CEA), and can complement s-CEA in predicting survival outcomes after CRC resection.
Collapse
Affiliation(s)
- Abdulmohsin Fawzi Aldilaijan
- Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea
| | - Young Il Kim
- Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea
| | - Chan Wook Kim
- Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea.
| | - Yong Sik Yoon
- Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea
| | - In Ja Park
- Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea
| | - Seok-Byung Lim
- Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea
| | - Jihun Kim
- Department of Pathology, Institute of Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jun-Soo Ro
- Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jin Cheon Kim
- Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea
| |
Collapse
|
|
30
|
Stage IV Colorectal Cancer Management and Treatment. J Clin Med 2023; 12:jcm12052072. [PMID: 36902858 PMCID: PMC10004676 DOI: 10.3390/jcm12052072] [Citation(s) in RCA: 40] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 03/02/2023] [Accepted: 03/04/2023] [Indexed: 03/08/2023] Open
Abstract
(1) Background: Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related mortality worldwide. Up to 50% of patients with CRC develop metastatic CRC (mCRC). Surgical and systemic therapy advances can now offer significant survival advantages. Understanding the evolving treatment options is essential for decreasing mCRC mortality. We aim to summarize current evidence and guidelines regarding the management of mCRC to provide utility when making a treatment plan for the heterogenous spectrum of mCRC. (2) Methods: A comprehensive literature search of PubMed and current guidelines written by major cancer and surgical societies were reviewed. The references of the included studies were screened to identify additional studies that were incorporated as appropriate. (3) Results: The standard of care for mCRC primarily consists of surgical resection and systemic therapy. Complete resection of liver, lung, and peritoneal metastases is associated with better disease control and survival. Systemic therapy now includes chemotherapy, targeted therapy, and immunotherapy options that can be tailored by molecular profiling. Differences between colon and rectal metastasis management exist between major guidelines. (4) Conclusions: With the advances in surgical and systemic therapy, as well as a better understanding of tumor biology and the importance of molecular profiling, more patients can anticipate prolonged survival. We provide a summary of available evidence for the management of mCRC, highlighting the similarities and presenting the difference in available literature. Ultimately, a multidisciplinary evaluation of patients with mCRC is crucial to selecting the appropriate pathway.
Collapse
|
|
31
|
Radiomic Features from Post-Operative 18F-FDG PET/CT and CT Imaging Associated with Locally Recurrent Rectal Cancer: Preliminary Findings. J Clin Med 2023; 12:jcm12052058. [PMID: 36902845 PMCID: PMC10004457 DOI: 10.3390/jcm12052058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 03/03/2023] [Accepted: 03/03/2023] [Indexed: 03/08/2023] Open
Abstract
Locally Recurrent Rectal Cancer (LRRC) remains a major clinical concern; it rapidly invades pelvic organs and nerve roots, causing severe symptoms. Curative-intent salvage therapy offers the only potential for cure but it has a higher chance of success when LRRC is diagnosed at an early stage. Imaging diagnosis of LRRC is very challenging due to fibrosis and inflammatory pelvic tissue, which can mislead even the most expert reader. This study exploited a radiomic analysis to enrich, through quantitative features, the characterization of tissue properties, thus favoring an accurate detection of LRRC by Computed Tomography (CT) and 18F-FDG-Positron Emission Tomography/CT (PET/CT). Of 563 eligible patients undergoing radical resection (R0) of primary RC, 57 patients with suspected LRRC were included, 33 of which were histologically confirmed. After manually segmenting suspected LRRC in CT and PET/CT, 144 Radiomic Features (RFs) were generated, and RFs were investigated for univariate significant discriminations (Wilcoxon rank-sum test, p < 0.050) of LRRC from NO LRRC. Five RFs in PET/CT (p < 0.017) and two in CT (p < 0.022) enabled, individually, a clear distinction of the groups, and one RF was shared by PET/CT and CT. As well as confirming the potential role of radiomics to advance LRRC diagnosis, the aforementioned shared RF describes LRRC as tissues having high local inhomogeneity due to the evolving tissue's properties.
Collapse
|
|
32
|
Lauretta A, Montori G, Guerrini GP. Surveillance strategies following curative resection and non-operative approach of rectal cancer: How and how long? Review of current recommendations. World J Gastrointest Surg 2023; 15:177-192. [PMID: 36896297 PMCID: PMC9988648 DOI: 10.4240/wjgs.v15.i2.177] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 12/30/2022] [Accepted: 01/18/2023] [Indexed: 02/27/2023] Open
Abstract
Different follow-up strategies are available for patients with rectal cancer following curative treatment. A combination of biochemical testing and imaging investigation, associated with physical examination are commonly used. However, there is currently no consensus about the types of tests to perform, the timing of the testing, and even the need for follow-up at all has been questioned. The aim of this study was to review the evidence of the impact of different follow-up tests and programs in patients with non-metastatic disease after definitive treatment of the primary. A literature review was performed of studies published on MEDLINE, EMBASE, the Cochrane Library and Web of Science up to November 2022. Current published guidelines from the most authoritative specialty societies were also reviewed. According to the follow-up strategies available, the office visit is not efficient but represents the only way to maintain direct contact with the patient and is recommended by all authoritative specialty societies. In colorectal cancer surveillance, carcinoembryonic antigen represents the only established tumor marker. Abdominal and chest computed tomography scan is recommended considering that the liver and lungs are the most common sites of recurrence. Since local relapse in rectal cancer is higher than in colon cancer, endoscopic surveillance is mandatory. Different follow-up regimens have been published but randomized comparisons and meta-analyses do not allow to determine whether intensive or less intensive follow-up had any significant influence on survival and recurrence detection rate. The available data do not allow the drawing of final conclusions on the ideal surveillance methods and the frequency with which they should be applied. It is very useful and urgent for clinicians to identify a cost-effective strategy that allows early identification of recurrence with a special focus for high-risk patients and patients undergoing a “watch and wait” approach.
Collapse
Affiliation(s)
- Andrea Lauretta
- Department of Surgical Oncology, Centro di Riferimento Oncologico di Aviano IRCCS, Aviano 33081, Italy
| | - Giulia Montori
- Department of General Surgery, Vittorio Veneto Hospital, ULSS 2 Marca Trevigiana, Vittorio Veneto 31029, Italy
| | - Gian Piero Guerrini
- Hepato-Pancreato-Biliary Surgical Oncology and Liver Transplantation Unit, Policlinico-AUO Modena, Modena 41124, Italy
| |
Collapse
|
|
33
|
A multi-modal study examining long-term bowel, urinary, and sexual function after rectal cancer surgery. Am J Surg 2022; 224:562-568. [DOI: 10.1016/j.amjsurg.2022.02.046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 02/16/2022] [Indexed: 11/19/2022]
|
|
34
|
An Evidence-Based Guideline for Surveillance of Patients after Curative Treatment for Colon and Rectal Cancer. Curr Oncol 2022; 29:724-740. [PMID: 35200561 PMCID: PMC8870404 DOI: 10.3390/curroncol29020062] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 01/24/2022] [Accepted: 01/28/2022] [Indexed: 11/16/2022] Open
Abstract
Objective: To provide recommendations for a surveillance regimen that leads to the largest overall survival benefit for patients after curative treatment for Stage I–IV colon and rectal cancer. Methods: Consistent with the Program in Evidence-Based Care’s standard approach, guideline databases, i.e., MEDLINE, EMBASE, PubMed, Cochrane Library, and PROSPERO, were systematically searched. Then, we drafted recommendations and methodology experts performed an internal review of the resulting draft recommendations, which was followed by an external review by targeted experts and intended users. Results: Four systematic reviews and two randomized controlled trials were identified that provided evidence for recommendations. Conclusions: For patients with stage I–III colon cancer, a medical history and physical examination should be performed every six months for three years; computed tomography (CT) of the chest-abdomen-pelvis (CT CAP) should be performed at one and three years, or one CT CAP could be performed at 18 months; the use of carcinoembryonic antigen (CEA) is optional if CT imaging is being performed; and surveillance colonoscopy should be performed one year after the initial surgery. The frequency of subsequent surveillance colonoscopy should be dictated by previous findings, but generally, colonoscopies should be performed every five years if the findings are normal. There was insufficient evidence to support these recommendations for patients with rectal cancer, Stage IV colon cancer, and patients over the age of 75 years. Patients should be informed of current recommendations and the treating physician should discuss the specific risks and benefits of each recommendation with their patients.
Collapse
|
|
35
|
McGowan EM, Lin Y, Chen S. Targeting Chronic Inflammation of the Digestive System in Cancer Prevention: Modulators of the Bioactive Sphingolipid Sphingosine-1-Phosphate Pathway. Cancers (Basel) 2022; 14:cancers14030535. [PMID: 35158806 PMCID: PMC8833440 DOI: 10.3390/cancers14030535] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 01/15/2022] [Accepted: 01/18/2022] [Indexed: 01/04/2023] Open
Abstract
Incidence of gastrointestinal (GI) cancers is increasing, and late-stage diagnosis makes these cancers difficult to treat. Chronic and low-grade inflammation are recognized risks for most GI cancers. The GI mucosal immune system maintains healthy homeostasis and signalling molecules made from saturated fats, bioactive sphingolipids, play essential roles in healthy GI immunity. Sphingosine-1-phosphate (S1P), a bioactive sphingolipid, is a key mediator in a balanced GI immune response. Disruption in the S1P pathway underlies systemic chronic metabolic inflammatory disorders, including diabetes and GI cancers, providing a strong rationale for using modulators of the S1P pathway to treat pathological inflammation. Here, we discuss the effects of bioactive sphingolipids in immune homeostasis with a focus on S1P in chronic low-grade inflammation associated with increased risk of GI carcinogenesis. Contemporary information on S1P signalling involvement in cancers of the digestive system, from top to bottom, is reviewed. Further, we discuss the use of novel S1P receptor modulators currently in clinical trials and their potential as first-line drugs in the clinic for chronic inflammatory diseases. Recently, ozanimod (ZeposiaTM) and etrasimod have been approved for clinical use to treat ulcerative colitis and eosinophilic oesophagitis, respectively, which may have longer term benefits in reducing risk of GI cancers.
Collapse
Affiliation(s)
- Eileen M. McGowan
- Central Laboratory, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China; (Y.L.); (S.C.)
- Guangdong Provincial Engineering Research Center for Esophageal Cancer Precise Therapy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China
- School of Life Sciences, University of Technology Sydney, Broadway, Sydney, NSW 2007, Australia
- Correspondence: ; Tel.: +86-614-0581-4048
| | - Yiguang Lin
- Central Laboratory, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China; (Y.L.); (S.C.)
- Guangdong Provincial Engineering Research Center for Esophageal Cancer Precise Therapy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China
- School of Life Sciences, University of Technology Sydney, Broadway, Sydney, NSW 2007, Australia
| | - Size Chen
- Central Laboratory, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China; (Y.L.); (S.C.)
- Guangdong Provincial Engineering Research Center for Esophageal Cancer Precise Therapy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China
| |
Collapse
|
|
36
|
Whelan S, Burneikis D, Kalady MF. Rectal cancer: Maximizing local control and minimizing toxicity. J Surg Oncol 2021; 125:46-54. [PMID: 34897711 DOI: 10.1002/jso.26743] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Accepted: 10/11/2021] [Indexed: 12/31/2022]
Abstract
Adoption of multimodality treatment approach for rectal cancer has resulted in significant improvements in oncologic outcomes. The roles of chemotherapy, radiation, and surgery in rectal cancer treatment are continuously evolving with the goal of achieving the best possible oncologic and functional outcome while minimizing treatment toxicity. The aim of this review is to summarize the most recent trials focusing on organ-sparing treatment strategies and the optimal selection of patients for neoadjuvant radiation therapy.
Collapse
Affiliation(s)
- Sean Whelan
- Department of Surgery, Division of Colon and Rectal Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Dominykas Burneikis
- Department of Surgery, Division of Colon and Rectal Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Matthew F Kalady
- Department of Surgery, Division of Colon and Rectal Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| |
Collapse
|
|
37
|
Abstract
CASE SUMMARY A 59-year-old previously healthy, asymptomatic man initially presented for his first screening colonoscopy. At this time, a friable, partially obstructing tumor was encountered in his proximal rectum. Final workup demonstrated a mrT2N1M0 upper rectal cancer. The patient went on to successfully complete total neoadjuvant chemoradiation therapy and was taken to the operating room for an uncomplicated robotic-assisted low anterior resection with primary anastomosis. His final pathology revealed an ypT2N1M0 rectal cancer, and he was subsequently followed in surveillance per National Comprehensive Cancer Network guidelines. At long-term follow-up visits he continued to report significant depressive symptoms and functional impairment. Despite aggressive medical management with fiber supplementation and antidiarrheal medications, the patient continued to struggle with bowel movement frequency and urgency. He reported having 4 to 6 clustered bowel movements during the day and 1 to 2 stools at night that significantly limited his ability to perform normal day-to-day activities.
Collapse
Affiliation(s)
- Robert D Shaw
- Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
| | | |
Collapse
|
|
38
|
Dou R, He S, Deng Y, Wang J. Comparison of guidelines on rectal cancer: exception proves the rule? Gastroenterol Rep (Oxf) 2021; 9:290-298. [PMID: 34567560 PMCID: PMC8460091 DOI: 10.1093/gastro/goab034] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/14/2021] [Accepted: 07/07/2021] [Indexed: 12/19/2022] Open
Abstract
The standard of care for early or locally advanced rectal cancer is promoted by multiple clinical practice guidelines globally, but the considerable differences between the guidelines may cause confusion. We compared the latest updated clinical practice guidelines from five professional societies/authorities: National Comprehensive Cancer Network, American Society of Colorectal Surgeons, European Society of Medical Oncology, Chinese National Health Commission, and Chinese Society of Clinical Oncology. Key evidence is discussed for a better understanding of some seemingly contradictory recommendations.
Collapse
Affiliation(s)
- Ruoxu Dou
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Siqi He
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Yanhong Deng
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.,Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Jianping Wang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.,Department of Gastrointestinal Surgery, Foresea Life Insurance Guangzhou General Hospital, Guangzhou, Guangdong, P. R. China
| |
Collapse
|
|
39
|
Kim JC, Ha YJ, Park IJ, Kim CW, Yoon YS, Lee JL, Tak KH, Cho DH, Park SH, Kim SK, Kim SY, Kim YS. Tumor immune microenvironment of primary colorectal adenocarcinomas metastasizing to the liver or lungs. J Surg Oncol 2021; 124:1136-1145. [PMID: 34351649 DOI: 10.1002/jso.26631] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 07/19/2021] [Accepted: 07/27/2021] [Indexed: 12/21/2022]
Abstract
BACKGROUND Because of the heterogeneity of metastatic colorectal cancer (mCRC), a genome-wide analysis was performed to characterize the tumor immune microenvironment (TIME). METHODS RNA-seq analysis of 62 primary CRCs without and 63 with systemic metastasis (SM- and SM+ groups) was conducted, and the data were used in a training set after adjustment by propensity score matching. Samples were further subdivided into those with hepatic metastasis (CHM subgroup), pulmonary metastasis (CPM subgroup), or concurrent CHM and CPM (concurrent group). Validation was done by quantitative reverse-transcription polymerase chain reaction using another 40 primary CRC samples. RESULTS Compared with the CHM or CPM subgroups, the concurrent group showed upregulated in inflammatory or immune processes, cytokine secretion, and myeloid leukocyte migration. Nine candidate genes were selected: SM-specific IDO1, JAM3, and PDE2A; CHM- or CPM-specific BIRC7; CPM-specific HISI1H2BK, and both SM-specific and CHM- or CPM-specific EPHB6, LPL, THBD, and PPBP. In a validation set of primary CRCs, JAM3 and IDO1 (p = 0.044 and p = 0.036, respectively) were confirmed to show significant upregulation and downregulation, respectively, in the SM+ group, whereas HIST1H2BK (p = 0.017) was significantly upregulated in the CPM subgroup. CONCLUSIONS Our findings indicate that a host-suppressive TIME is established in the primary tumor of mCRC and identify immune-related site-specific markers of mCRC.
Collapse
Affiliation(s)
- Jin C Kim
- Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.,Laboratory of Cancer Biology and Genetics, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea
| | - Ye J Ha
- Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.,Laboratory of Cancer Biology and Genetics, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea
| | - In J Park
- Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.,Laboratory of Cancer Biology and Genetics, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea
| | - Chan W Kim
- Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.,Laboratory of Cancer Biology and Genetics, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea
| | - Yong S Yoon
- Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.,Laboratory of Cancer Biology and Genetics, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea
| | - Jong L Lee
- Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.,Laboratory of Cancer Biology and Genetics, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea
| | - Ka H Tak
- Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.,Laboratory of Cancer Biology and Genetics, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea
| | - Dong-Hyung Cho
- School of Life Sciences, Graduate School, Kyungpook National University, Daegu, Korea
| | - Seong H Park
- Genome Editing Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Korea
| | - Seon-Kyu Kim
- Genome Editing Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Korea
| | - Seon-Young Kim
- Genome Editing Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Korea
| | - Yong S Kim
- Genome Editing Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Korea
| |
Collapse
|