|
1
|
Wiley MB, Bauer J, Alvarez V, Kolics Z, Cheng W, Church DN, Kerr DJ, Kerr RS, Jung B. Activin A affects colorectal cancer progression and immunomodulation in a stage dependent manner. Sci Rep 2025; 15:8509. [PMID: 40075112 PMCID: PMC11903883 DOI: 10.1038/s41598-025-91853-9] [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: 09/10/2024] [Accepted: 02/24/2025] [Indexed: 03/14/2025] Open
Abstract
Advanced colorectal cancer (CRC) continues to present with poor survival and treatment options remain limited. We have shown that increased activin A (activin) expression in the tumor microenvironment (TME) is associated with poor outcome in a cohort of stage III and IV CRC patients. Here, we hypothesized that activin promotes stage specific outcomes in CRC, enhancing metastasis and tolerance in late-stage CRC exclusively. We employed Digital Spatial Profiling (DSP) technology on a cohort of stage II and III CRC patient tissue samples obtained at the time of curative surgery to show that activin co-localization was associated with increased mitogenic signaling, proliferation, and immunosuppression in stage III, but not stage II, CRCs. Furthermore, we found strong linear correlations between markers of immunosuppression and signaling proteins in activin (+) areas, an effect that was not observed in activin (-) areas of tissue. Taken together these data suggest activin exerts pro-metastatic and immunosuppressive effects in stage III, but not stage II, CRC providing an attractive therapeutic target for advanced CRC.
Collapse
Affiliation(s)
- Mark B Wiley
- Department of Medicine, University of Washington College of Medicine, Seattle, WA, 98195, USA
| | - Jessica Bauer
- Department of Medicine, University of Washington College of Medicine, Seattle, WA, 98195, USA
| | - Valentina Alvarez
- Department of Medicine, University of Washington College of Medicine, Seattle, WA, 98195, USA
| | - Zoe Kolics
- Department of Medicine, University of Washington College of Medicine, Seattle, WA, 98195, USA
| | - Wenxuan Cheng
- Department of Medicine, University of Washington College of Medicine, Seattle, WA, 98195, USA
| | - David N Church
- Nuffield Department of Medicine, University of Oxford, Oxford, OX1 4BH, UK
- NIHR Oxford Comprehensive Biomedical Research Center, Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford, OX1 4BH, UK
| | - David J Kerr
- Radcliffe Department of Medicine, University of Oxford, Oxford, OX1 4BH, UK
| | - Rachel S Kerr
- Department of Oncology, University of Oxford, Oxford, OX1 4BH, UK
| | - Barbara Jung
- School of Medicine, University of California, San Diego, San Diego, CA, 92093, USA.
| |
Collapse
|
|
2
|
Ruiz-Grajales ÁE, Correa-Cote JC, Pérez-García YE, Palacios-Fuenmayor LJ, Castrillón-Martínez E. Perfil clínico de pacientes con cáncer colorrectal de aparición temprana y tardía en un centro médico de referencia en Medellín, Colombia: Un análisis comparativo. REVISTA COLOMBIANA DE CIRUGÍA 2024. [DOI: 10.30944/20117582.2576] [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] Open
Abstract
Introducción. La incidencia de cáncer colorrectal (CCR) de aparición temprana (CCR-ATem), definido como CCR en individuos menores de 50 años, está aumentando en todo el mundo. A pesar del incremento en la producción científica internacional sobre CCR-ATem, la investigación es limitada en Colombia. El objetivo de este estudio fue caracterizar clínicamente los adultos con CCR-ATem y CCR de aparición tardía (CCR-ATar, CCR en individuos ≥ 50 años).
Métodos. Estudio observacional, retrospectivo, transversal, en el que se incluyeron los adultos con CCR atendidos en un centro médico de Medellín, Colombia. Los datos se obtuvieron del Registro Institucional de Cáncer. Se establecieron dos grupos de análisis: CCR-ATem y CCR-ATar. Se aplicó la prueba de Chi cuadrado para comparar las variables de interés entre ambos grupos.
Resultados. La muestra incluyó 1,202 pacientes, 53.5 % fueron mujeres (N=643), y la mediana de edad fue de 65 años (rango intercuartil: 55-73). CCR-ATem representó el 15.9 % (N=192). CCR-ATar tuvo más casos de enfermedades cardiometabólicas y tabaquismo (p<0.001). El antecedente familiar de CCR fue proporcionalmente más frecuente en CCR-ATem (7.3 % vs. 3.8 %; p=0.028). Los tumores del colon derecho fueron más frecuentes en CCR-Atar (30.4 % vs. 21.9 %; p=0.041) y los del colon izquierdo en CCR-ATem (30.7 % vs. 23.2 %; p=0.041). Solo un paciente tuvo antecedente de enfermedad inflamatoria intestinal.
Conclusión. CCR-ATem es clínicamente distinto de CCR-ATar con respecto a antecedentes patológicos y toxicológicos, y localización tumoral. Nuestros hallazgos proporcionan información útil para mejorar la toma de decisiones clínicas, particularmente en relación con la edad de inicio en pacientes colombianos con CCR.
Collapse
|
|
3
|
Venegas-Rodríguez JL, Hernández-Sandoval JA, Gutiérrez-Angulo M, Moreno-Ortiz JM, González-Mercado A, Peregrina-Sandoval J, Ramírez-Plascencia HHF, Flores-López BA, Alvizo-Rodríguez CR, Valenzuela-Pérez JA, Cervantes-Ortiz S, Ayala-Madrigal MDLL. KRAS Exon 2 Mutations in Patients with Sporadic Colorectal Cancer: Prevalence Variations in Mexican and Latin American Populations. Cancers (Basel) 2024; 16:2323. [PMID: 39001385 PMCID: PMC11240588 DOI: 10.3390/cancers16132323] [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: 04/13/2024] [Revised: 06/02/2024] [Accepted: 06/21/2024] [Indexed: 07/16/2024] Open
Abstract
We searched for the prevalence of actionable somatic mutations in exon 2 of the KRAS gene in western Mexican patients with CRC. Tumor tissue DNA samples from 150 patients with sporadic CRC recruited at the Civil Hospital of Guadalajara were analyzed. Mutations in exon 2 of the KRAS gene were identified using Sanger sequencing, and the data were analyzed considering clinical-pathological characteristics. Variants in codon 12 (rs121913529 G>A, G>C, and G>T) and codon 13 (rs112445441 G>A) were detected in 26 patients (with a prevalence of 17%). No significant associations were found between these variants and clinical-pathological characteristics (p > 0.05). Furthermore, a comprehensive search was carried out in PubMed/NCBI and Google for the prevalence of KRAS exon 2 mutations in Latin American populations. The 17 studies included 12,604 CRC patients, with an overall prevalence of 30% (95% CI = 0.26-0.35), although the prevalence ranged from 13 to 43% across the different data sources. Determining the variation and frequency of KRAS alleles in CRC patients will enhance their potential to receive targeted treatments and contribute to the understanding of the genomic profile of CRC.
Collapse
Affiliation(s)
- José Luis Venegas-Rodríguez
- Instituto de Genética Humana “Dr. Enrique Corona Rivera”, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico; (J.L.V.-R.); (J.A.H.-S.); (M.G.-A.); (J.M.M.-O.); (A.G.-M.)
- Programa de Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
| | - Jesús Arturo Hernández-Sandoval
- Instituto de Genética Humana “Dr. Enrique Corona Rivera”, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico; (J.L.V.-R.); (J.A.H.-S.); (M.G.-A.); (J.M.M.-O.); (A.G.-M.)
- Programa de Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
| | - Melva Gutiérrez-Angulo
- Instituto de Genética Humana “Dr. Enrique Corona Rivera”, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico; (J.L.V.-R.); (J.A.H.-S.); (M.G.-A.); (J.M.M.-O.); (A.G.-M.)
- Programa de Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
- Departamento de Ciencias de la Salud, Centro Universitario de los Altos, Universidad de Guadalajara, Tepatitlán de Morelos 47600, Jalisco, Mexico
| | - José Miguel Moreno-Ortiz
- Instituto de Genética Humana “Dr. Enrique Corona Rivera”, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico; (J.L.V.-R.); (J.A.H.-S.); (M.G.-A.); (J.M.M.-O.); (A.G.-M.)
- Programa de Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
| | - Anahí González-Mercado
- Instituto de Genética Humana “Dr. Enrique Corona Rivera”, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico; (J.L.V.-R.); (J.A.H.-S.); (M.G.-A.); (J.M.M.-O.); (A.G.-M.)
- Programa de Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
| | - Jorge Peregrina-Sandoval
- Departamento de Biología Celular y Molecular, Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Zapopan 44600, Jalisco, Mexico;
| | | | - Beatriz Armida Flores-López
- Departamento de Ciclo de Vida, Facultad de Medicina, Universidad Autónoma de Guadalajara, Zapopan 45129, Jalisco, Mexico;
| | | | - Jesús Alonso Valenzuela-Pérez
- Servicio de Colon y Recto, Hospital Civil “Dr. Juan I. Menchaca”, Guadalajara 44340, Jalisco, Mexico; (J.A.V.-P.); (S.C.-O.)
| | - Sergio Cervantes-Ortiz
- Servicio de Colon y Recto, Hospital Civil “Dr. Juan I. Menchaca”, Guadalajara 44340, Jalisco, Mexico; (J.A.V.-P.); (S.C.-O.)
| | - María de la Luz Ayala-Madrigal
- Instituto de Genética Humana “Dr. Enrique Corona Rivera”, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico; (J.L.V.-R.); (J.A.H.-S.); (M.G.-A.); (J.M.M.-O.); (A.G.-M.)
- Programa de Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
| |
Collapse
|
|
4
|
Oliveira ML, Biggers A, Oddo VM, Yanez B, Booms E, Sharp L, Naylor K, Wolf PG, Tussing-Humphreys L. A Perspective Review on Diet Quality, Excess Adiposity, and Chronic Psychosocial Stress and Implications for Early-Onset Colorectal Cancer. J Nutr 2024; 154:1069-1079. [PMID: 38453027 PMCID: PMC11007745 DOI: 10.1016/j.tjnut.2024.03.002] [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: 01/28/2024] [Revised: 02/23/2024] [Accepted: 03/04/2024] [Indexed: 03/09/2024] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide. Although the overall incidence of CRC has been decreasing over the past 40 y, early-onset colorectal cancer (EOCRC), which is defined as a CRC diagnosis in patients aged >50 y has increased. In this Perspective, we highlight and summarize the association between diet quality and excess adiposity, and EOCRC. We also explore chronic psychosocial stress (CPS), a less investigated modifiable risk factor, and EOCRC. We were able to show that a poor-quality diet, characterized by a high intake of sugary beverages and a Western diet pattern (high intake of red and processed meats, refined grains, and foods with added sugars) can promote risk factors associated with EOCRC development, such as an imbalance in the composition and function of the gut microbiome, presence of chronic inflammation, and insulin resistance. Excess adiposity, particularly obesity onset in early adulthood, is a likely contributor of EOCRC. Although the research is sparse examining CPS and CRC/EOCRC, we describe likely pathways linking CPS to tumorigenesis. Although additional research is needed to understand what factors are driving the uptick in EOCRC, managing body weight, improving diet quality, and mitigating psychosocial stress, may play an important role in reducing an individual's risk of EOCRC.
Collapse
Affiliation(s)
- Manoela Lima Oliveira
- Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL, United States.
| | - Alana Biggers
- College of Medicine, University of Illinois at Chicago, Chicago, IL, United States
| | - Vanessa M Oddo
- Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL, United States
| | - Betina Yanez
- Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
| | - Emily Booms
- Department of Biology, Northeastern Illinois University, Chicago, IL, United States
| | - Lisa Sharp
- Institute for Health Research and Policy, University of Illinois at Chicago, Chicago, IL, United States
| | - Keith Naylor
- College of Medicine, University of Illinois at Chicago, Chicago, IL, United States
| | - Patricia G Wolf
- Department of Nutrition Science, Purdue University, West Lafayette, IN, United States
| | - Lisa Tussing-Humphreys
- Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL, United States
| |
Collapse
|
|
5
|
Ruiz-Grajales ÁE, Orozco-Puerta MM, Zheng S, H de Bock G, Correa-Cote JC, Castrillón-Martínez E. Clinical and pathological differences between early- and late-onset colorectal cancer and determinants of one-year all-cause mortality among advanced-stage patients: a retrospective cohort study in Medellín, Colombia. Cancer Treat Res Commun 2024; 39:100797. [PMID: 38367413 DOI: 10.1016/j.ctarc.2024.100797] [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: 12/14/2023] [Revised: 02/10/2024] [Accepted: 02/14/2024] [Indexed: 02/19/2024]
Abstract
OBJECTIVE To identify the differences between early- (EOCRC) and late-onset colorectal cancer (LOCRC), and to evaluate the determinants of one-year all-cause mortality among advanced-stage patients. METHODS A retrospective cohort study was carried out. CRC patients ≥ 18 years old were included. Chi-Square test was applied to compare both groups. Uni- and multivariate regressions were performed to evaluate the determinants of one-year all-cause mortality in all advanced-stage patients regardless of age of onset. RESULTS A total of 416 patients were enrolled; 53.1 % were female. Ninety cases (21.6 %) had EOCRC and 326 (78.4 %) had LOCRC. EOCRC cases were predominantly sporadic (88.9 %). Histology of carcinoma other than adenocarcinoma (p= 0.044) and rectum tumors (p= 0.039) were more prevalent in EOCRC. LOCRC patients were more likely to have smoking history (p < 0.001) and right colon tumors (p = 0.039). Alcohol consumption history (odds ratio [OR]: 3.375, 95 %CI: 1.022-11.150) and stage IV (OR: 12.632, 95 %CI: 3.506-45.513) were associated with higher one-year all-cause mortality among advanced-stage patients, the opposite was noted with left colon tumors (OR: 0.045, 95 %CI: 0.003-0.588). CONCLUSION EOCRC was predominantly sporadic and had more cases of uncommon histological subtypes and rectal tumors. LOCRC was characterized by a higher prevalence of smoking history. Multivariate regression revealed an association between higher one-year all-cause mortality and alcohol consumption history and stage IV in advanced-stage patients. CRC exhibited differences based on age of onset. The evaluated factors associated with CRC mortality provide valuable insights for healthcare professionals, emphasizing the importance of adequate clinical assessment and early CRC diagnosis.
Collapse
Affiliation(s)
- Álvaro Esteban Ruiz-Grajales
- Semillero de Investigación en Salud (SEIS), Facultad de Medicina, Universidad de Antioquia UdeA, Medellín, Colombia.
| | - Manuela María Orozco-Puerta
- Semillero de Investigación en Salud (SEIS), Facultad de Medicina, Universidad de Antioquia UdeA, Medellín, Colombia.
| | - Senshuang Zheng
- Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
| | - Geertruida H de Bock
- Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
| | | | - Esteban Castrillón-Martínez
- Semillero de Investigación en Salud (SEIS), Facultad de Medicina, Universidad de Antioquia UdeA, Medellín, Colombia; Hospital Alma Máter de Antioquia, Medellín, Colombia.
| |
Collapse
|
|
6
|
Wu J, Ma X, Wang X, Zhu G, Wang H, Zhang Y, Li J. Efficacy and Safety of Compound Kushen Injection for Advanced Colorectal Cancer: A Systematic Review and Meta-Analysis of Randomized Clinical Trials with Trial Sequential Analysis. Integr Cancer Ther 2024; 23:15347354241258458. [PMID: 38853681 PMCID: PMC11163932 DOI: 10.1177/15347354241258458] [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: 09/02/2023] [Revised: 04/24/2024] [Accepted: 05/15/2024] [Indexed: 06/11/2024] Open
Abstract
BACKGROUNDS Colorectal cancer (CRC) is one of the common malignant tumors, with a gradually increasing incidence. Due to late detection and poor sensitivity to chemotherapy, it has become a difficult problem in tumor prevention and treatment at present. Exploring or discovering new combinations is a significant strategy for the treatment of CRC. Compound kushen injection (CKI) is a traditional Chinese medicine injection extracted from Sophora flavescens Ait. and Smilax glabra Roxb., which is widely used in the comprehensive treatment of CRC in China. This systematic review is aimed to ascertain the clinical efficacy and safety of CKI combined with chemotherapy in the treatment of advanced CRC based on available data. On this basis, the specific application of CKI in combination with chemotherapy in clinical practice is further discussed. METHODS PubMed, Web of Science, the Cochrane Library, EMBASE, China National Knowledge Infrastructure, Chinese Scientific Journals Database, Wanfang Database, Chinese Biomedicine Database Searches, the Chinese Clinical Trial Registry, and ClinicalTrials.gov were searched systematically, from inception to April 20, 2024. We adopted the ROB2 tool to assess quality of the included trials, Stata 16 for data analysis, and evaluated the publication bias with the funnel plot and Egger's test. The quality of the evidence was justified according to GRADE. We also used trial sequential analysis (TSA) to calculate the final required sample size in this meta-analysis and to verify whether the results present a reliable conclusion. The protocol for this systematic review was registered on PROSPERO (CRD42022380106) and has been published. RESULTS Sixteen trials that examined 1378 patients were included in this study. Meta-analysis revealed that compared with chemotherapy, objective response rate (ORR, RR = 1.30, 95% CI: 1.18-1.44), disease control rate (DCR, RR = 1.08, 95% CI: 1.03-1.13), and KPS score improvement rate were improved (RR = 1.18, 95% CI: 1.07-1.31) by the combination of CKI and chemotherapy in patients with advanced CRC. Additionally, CKI combined with chemotherapy was associated with lower adverse reactions such as leukopenia (RR = 0.74, 95% CI: 0.62-0.87), thrombocytopenia (RR = 0.68, 95% CI: 0.49-0.94), gastrointestinal reactions (RR = 0.72, 95% CI: 0.55-0.94), and liver damage (RR = 0.48, 95% CI: 0.30-0.79), higher CD4+ ratio (MD = 9.70, 95% CI:8.73-10.68) and CD4+/CD8+ ratio (MD = 0.25, 95% CI: 0.22-0.28), and lower CD8+ T cell ratio (MD = -5.25, 95% CI: -5.94 to -4.56). Subgroup analysis demonstrated that ORR and DCR in patients with advanced CRC were improved when CKI combined with FOLFOX and 5Fu + L-OHP. Both 15 and 20 ml/day of CKI combined with FOLFOX provided a significant effect in ORR. Moreover, ORR was improved when the accumulated CKI dose reached 280 ml per course and 420 ml in total. 7 days/course as well as 14 days/course of CKI combined with FOLFOX were effective durations in ORR. As for DCR, 7 days/course of CKI combined with FOLFOX could improve efficacy. Furthermore, CKI + FOLFOX may be useful in ORR and DCR for at least 4 cycles of combination therapies. The TSA showed that firm results in ORR and DCR were established and additional trials were unlikely to change the results. CONCLUSION CKI combined with chemotherapy provides a statistically significant and clinically important effect in the improvement of ORR, DCR, performance status, ADR reduction, and immune function in patients with CRC. However, more rigorously designed, large-scale, and multi-center RCTs are needed in the future.
Collapse
Affiliation(s)
- Jingyuan Wu
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate College, Beijing University of Traditional Chinese Medicine, Beijing, China
| | - Xinyi Ma
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xinmiao Wang
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Guanghui Zhu
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate College, Beijing University of Traditional Chinese Medicine, Beijing, China
| | - Heping Wang
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Ying Zhang
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jie Li
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| |
Collapse
|
|
7
|
Thompson N, Gatenby G, Waddell O, Purcell R, Keenan J, Pearson JF, Frizelle F, Glyn T. Early onset colorectal cancer in Canterbury, New Zealand. ANZ J Surg 2023; 93:2148-2154. [PMID: 36852900 DOI: 10.1111/ans.18357] [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: 01/19/2023] [Revised: 02/11/2023] [Accepted: 02/17/2023] [Indexed: 03/01/2023]
Abstract
BACKGROUND The overall incidence of colorectal cancer is decreasing in much of the world, yet the incidence in those under 50 years of age is increasing (early onset colorectal cancer (EOCRC)). The reasons for this are unclear. This study was undertaken to describe the clinical, pathological and familial characteristics of patients with EOCRC and their oncological outcomes and compare this with previously published data on late onset colorectal cancer (LOCRC). METHODS A retrospective review of all patients diagnosed with EOCRC in Canterbury between 2010 and 2017 was conducted. Data was collected on demographics, family history, treatment, and oncologic outcomes. Kaplan-Meier survival curves were calculated to assess overall survival based on disease stage. RESULTS During the study period (2010-2017) there were 3340 colorectal cancers diagnosed in Canterbury, of which 201 (6%) were in patients under 50 years (range: 17-49). Of these, 87 (43.3%) were female and 125 (62.2%) were aged between 40 and 49 years. 28 (13.9%) were associated with hereditary conditions. Of the 201 patients, 139 (69.2%) had rectal or left-sided cancers. 142 (70.6%) patients presented with either stage 3 or 4 disease and the 5-year overall survival by stage was 79.1% and 14.4%, respectively. CONCLUSION EOCRC is increasing and usually presents as distal left sided cancers, and often at an advanced stage. They do not appear to have the common risk factors of family history or inherited pre-disposition for colorectal cancer. Planning by healthcare providers for this epidemiological change is imperative in investigating symptomatic patients under 50 and optimizing early detection and prevention.
Collapse
Affiliation(s)
- Nasya Thompson
- Department of Surgery, University of Otago Christchurch, Christchurch, New Zealand
| | - Grace Gatenby
- Department of Surgery, Te Whatu Ora Health New Zealand Waitaha Canterbury, Christchurch, New Zealand
| | - Oliver Waddell
- Department of Surgery, University of Otago Christchurch, Christchurch, New Zealand
| | - Rachel Purcell
- Department of Surgery, University of Otago Christchurch, Christchurch, New Zealand
| | - Jacqui Keenan
- Department of Surgery, University of Otago Christchurch, Christchurch, New Zealand
| | - John F Pearson
- Biostatistics and Computational Biology Unit, University of Otago Christchurch, Christchurch, New Zealand
| | - Francis Frizelle
- Department of Surgery, University of Otago Christchurch, Christchurch, New Zealand
- Department of Surgery, Te Whatu Ora Health New Zealand Waitaha Canterbury, Christchurch, New Zealand
| | - Tamara Glyn
- Department of Surgery, University of Otago Christchurch, Christchurch, New Zealand
- Department of Surgery, Te Whatu Ora Health New Zealand Waitaha Canterbury, Christchurch, New Zealand
| |
Collapse
|
|
8
|
Calderillo Ruiz G, Lopez Basave H, Vazquez Renteria RS, Castillo Morales A, Guijosa A, Castillo Morales C, Herrera M, Diaz C, Vazquez Cortes E, Ruiz-Garcia E, Munoz Montano WR. The Prognostic Significance of HALP Index for Colon Cancer Patients in a Hispanic-Based Population. JOURNAL OF ONCOLOGY 2022; 2022:4324635. [PMID: 36467502 PMCID: PMC9711950 DOI: 10.1155/2022/4324635] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 10/11/2022] [Accepted: 10/17/2022] [Indexed: 10/04/2023]
Abstract
Background Survival and recurrence rates following locoregional colon cancer surgical resection are highly variable. Currently used tools to assess patient risk are still imperfect. In the present work, we evaluate, for the first time, the prognostic value of the recently developed HALP (hemoglobin, albumin, lymphocyte, and platelet) index in Hispanic colon cancer patients. Patients and Methods. We conducted a retrospective cohort study in Mexican patients with a nonmetastatic colon cancer diagnosis who underwent surgical resection. We determined the preoperative HALP score optimal cut-off value by using the X-tile software. We plotted survival curves using the Kaplan-Meier method and performed a multivariate Cox regression analysis to explore the association of preoperative HALP score with two primary endpoints: overall survival (OS) and disease-free survival (DFS). Results We included 640 patients (49.8% female). The optimal HALP cut-off value was 15.0. A low HALP index was statistically significantly associated with a higher TNM stage. Low HALP score was statistically significantly associated with shorter median OS in the Kaplan-Meier analysis (73.5 vs. 84.8 months) and in the multivariate Cox regression analysis (HR = 1.942, 95% CI = 1.647-2.875). There was no significant association between the HALP score and DFS. Conclusions Our findings show that the HALP index is an independent factor associated with survival in Hispanic patients, despite recurrence. It seems to reflect both the anatomical extent of the disease and traditionally unaccounted nutritional and inflammatory factors that are significant for prognosis.
Collapse
Affiliation(s)
| | - Horacio Lopez Basave
- Gastrointestinal Oncology Unit, Instituto Nacional de Cancerologia, Mexico, Mexico
| | | | | | - Alberto Guijosa
- School of Medicine, Universidad Panamericana, Mexico, Mexico
| | | | - Marytere Herrera
- Gastrointestinal Oncology Unit, Instituto Nacional de Cancerologia, Mexico, Mexico
| | - Consuelo Diaz
- Gastrointestinal Oncology Unit, Instituto Nacional de Cancerologia, Mexico, Mexico
| | | | - Erika Ruiz-Garcia
- Gastrointestinal Oncology Unit, Instituto Nacional de Cancerologia, Mexico, Mexico
| | | |
Collapse
|
|
9
|
Chen D, Zhong X, Lin L, Xie J, Lian Y, Xu L. Comparative efficacy and adverse reactions of apatinib-chemotherapy combinations versus chemotherapy alone for treatment of advanced colorectal cancer: a meta-analysis of randomized controlled trials. Am J Transl Res 2022; 14:6703-6711. [PMID: 36247297 PMCID: PMC9556443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 08/09/2022] [Indexed: 06/16/2023]
Abstract
OBJECTIVE Apatinib mesylate is the first small-molecule anti-angiogenic agent that has been shown to be effective and well-tolerated for treatment of advanced gastric cancer, and has shown encouraging efficacy for treatment of advanced colorectal cancer (CRC). However, previous studies reported diverse efficacy and safety results of apatinib for treatment of advanced CRC. This meta-analysis aimed to compare the efficacy and safety of apatinib plus chemotherapy (trial group) versus chemotherapy alone (control group) for treatment of advanced CRC. METHODS A joint search was performed in electronic databases to retrieve randomized clinical trials (RCTs) reporting the efficacy and adverse reactions of apatinib in the treatment of advanced CRC. The pooled survival, treatment responses, and safety were estimated and compared between the trial and control groups. RESULTS A total of 7 eligible RCTs involving 539 colorectal cancer patients were enrolled. Meta-analysis showed significantly higher overall response rate (risk ratio (RR) = 1.46, P < 0.00001), disease control rate (RR = 1.24, P < 0.00001), complete response (RR = 1.72, P = 0.01), PR (RR = 1.43, P = 0.001), overall survival (mean difference (MD) = 3.89, P = 0.0006), and progression-free survival (MD = 2.94, P < 0.00001) and lower progressive disease (RR = 0.37, P < 0.00001) in the trial group than in the control group; however, there were no significant differences between the two groups in terms of stable disease (RR = 0.89, P = 0.38) or incidence of adverse reactions (RR = 1.01, P = 0.92). CONCLUSION Apatinib plus chemotherapy shows a higher efficacy and comparable safety for treatment of advanced CRC in relative to chemotherapy alone.
Collapse
Affiliation(s)
- Dengsheng Chen
- Department of Pharmacy, Sanming First Hospital, Affiliated Hospital of Fujian Medical UniversitySanming 365000, Fujian Province, China
| | - Xinzhu Zhong
- Department of Pharmacy, Sanming First Hospital, Affiliated Hospital of Fujian Medical UniversitySanming 365000, Fujian Province, China
| | - Lei Lin
- Department of Pharmacy, Sanming First Hospital, Affiliated Hospital of Fujian Medical UniversitySanming 365000, Fujian Province, China
| | - Jiejie Xie
- Department of Pharmacy, Sanming First Hospital, Affiliated Hospital of Fujian Medical UniversitySanming 365000, Fujian Province, China
| | - Yubao Lian
- Department of Infectious Diseases, Sanming First Hospital, Affiliated Hospital of Fujian Medical UniversitySanming 365000, Fujian Province, China
| | - Luning Xu
- Department of Pharmacy, Sanming First Hospital, Affiliated Hospital of Fujian Medical UniversitySanming 365000, Fujian Province, China
| |
Collapse
|
|
10
|
Hoyos-Valdelamar JC, Lora-Acuña LJ, Herrera-Zabaleta LE, Parra-Almeida S, Insignares-Farak Y. Caracterización del cáncer colorrectal en pacientes atendidos en un centro médico del caribe colombiano. REVISTA COLOMBIANA DE CIRUGÍA 2022. [DOI: 10.30944/20117582.2124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Introducción. A nivel mundial el cáncer colorrectal es la tercera causa de malignidad y la segunda causa de mortalidad por cáncer. En Colombia, tiene una prevalencia de 8,3 % dentro de las patologías neoplásicas, ubicándolo en el tercer lugar, después del cáncer de próstata y de mama, lo que lo cataloga como un problema de salud pública, por lo que es de gran importancia mantener datos actualizados acerca de su perfil epidemiológico.
Métodos. Se realizó un estudio transversal en pacientes con cáncer colorrectal atendidos en el Hospital Universitario del Caribe, Cartagena, Colombia, durante el periodo 2015-2019. Se analizaron las variables sociodemográficas, clínicas, patológicas e histológicas.
Resultados. Se encontraron un total de 268 pacientes atendidos por cáncer colorrectal, con predominio femenino en el (54,5 %) de los casos, y edad promedio de 62 años; con comorbilidades en 48,8 % y sintomatología de dolor abdominal en 56,7 %. El adenocarcinoma se encontró en el 82,1 % de los casos y la intervención más realizada fue la hemicolectomía derecha.
Conclusión. El perfil epidemiológico del cáncer colorrectal encontrado en este estudio concuerda con los hallazgos de la literatura médica mundial, comprometiendo especialmente mujeres en nuestra institución.
Collapse
|
|
11
|
Jung SY, Sobel EM, Pellegrini M, Yu H, Papp JC. Synergistic Effects of Genetic Variants of Glucose Homeostasis and Lifelong Exposures to Cigarette Smoking, Female Hormones, and Dietary Fat Intake on Primary Colorectal Cancer Development in African and Hispanic/Latino American Women. Front Oncol 2021; 11:760243. [PMID: 34692549 PMCID: PMC8529283 DOI: 10.3389/fonc.2021.760243] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 09/22/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Disparities in cancer genomic science exist among racial/ethnic minorities. Particularly, African American (AA) and Hispanic/Latino American (HA) women, the 2 largest minorities, are underrepresented in genetic/genome-wide studies for cancers and their risk factors. We conducted on AA and HA postmenopausal women a genomic study for insulin resistance (IR), the main biologic mechanism underlying colorectal cancer (CRC) carcinogenesis owing to obesity. METHODS With 780 genome-wide IR-specific single-nucleotide polymorphisms (SNPs) among 4,692 AA and 1,986 HA women, we constructed a CRC-risk prediction model. Along with these SNPs, we incorporated CRC-associated lifestyles in the model of each group and detected the topmost influential genetic and lifestyle factors. Further, we estimated the attributable risk of the topmost risk factors shared by the groups to explore potential factors that differentiate CRC risk between these groups. RESULTS In both groups, we detected IR-SNPs in PCSK1 (in AA) and IFT172, GCKR, and NRBP1 (in HA) and risk lifestyles, including long lifetime exposures to cigarette smoking and endogenous female hormones and daily intake of polyunsaturated fatty acids (PFA), as the topmost predictive variables for CRC risk. Combinations of those top genetic- and lifestyle-markers synergistically increased CRC risk. Of those risk factors, dietary PFA intake and long lifetime exposure to female hormones may play a key role in mediating racial disparity of CRC incidence between AA and HA women. CONCLUSIONS Our results may improve CRC risk prediction performance in those medically/scientifically underrepresented groups and lead to the development of genetically informed interventions for cancer prevention and therapeutic effort, thus contributing to reduced cancer disparities in those minority subpopulations.
Collapse
Affiliation(s)
- Su Yon Jung
- Translational Sciences Section, Jonsson Comprehensive Cancer Center, School of Nursing, University of California, Los Angeles, Los Angeles, CA, United States
| | - Eric M. Sobel
- Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States
- Department of Computational Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States
| | - Matteo Pellegrini
- Department of Molecular, Cell and Developmental Biology, Life Sciences Division, University of California, Los Angeles, Los Angeles, CA, United States
| | - Herbert Yu
- Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, United States
| | - Jeanette C. Papp
- Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States
| |
Collapse
|
|
12
|
Done JZ, Fang SH. Young-onset colorectal cancer: A review. World J Gastrointest Oncol 2021; 13:856-866. [PMID: 34457191 PMCID: PMC8371519 DOI: 10.4251/wjgo.v13.i8.856] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 04/30/2021] [Accepted: 07/19/2021] [Indexed: 02/06/2023] Open
Abstract
Despite the general decrease in overall incidence of colorectal cancer since the early 1990s, the incidence of colorectal cancer in patients less than 50 years old has nearly doubled. A systematic review was performed using the PubMed database (2011-2020) and Cochrane Database of Systematic Reviews (2011-2021) to identify studies (published in English) evaluating epidemiologic, clinical, hereditary, and molecular features; as well as evaluation, management, and prognosis of young-onset colorectal cancer patients. Our search yielded a total of 3401 articles, after applying our inclusion criteria. We fully reviewed 94 full-length studies. This systematic review demonstrates the increasing incidence of young-onset colorectal cancer and highlights the importance of being hypervigilant for the differential diagnosis colorectal cancer when evaluating a young adult who presents with gastrointestinal symptoms.
Collapse
Affiliation(s)
- Joy Zhou Done
- Department of Surgery, Johns Hopkins Hospital, Baltimore, MD 21287, United States
| | - Sandy H Fang
- Department of Surgery, Johns Hopkins University School of Medicine, Johns Hopkins Hospital, Baltimore, MD 21287, United States
| |
Collapse
|
|
13
|
Deo SVS, Kumar S, Bhoriwal S, Shukla NK, Sharma A, Thulkar S, Das P, Bhagat P, Dhall K, Pathy S, Mohanti BK. Colorectal Cancers in Low- and Middle-Income Countries-Demographic Pattern and Clinical Profile of 970 Patients Treated at a Tertiary Care Cancer Center in India. JCO Glob Oncol 2021; 7:1110-1115. [PMID: 34236917 PMCID: PMC8457848 DOI: 10.1200/go.21.00111] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
PURPOSE Globally, colorectal cancer (CRC) ranks third in terms of incidence and second in terms of mortality. A relatively low burden of CRC has been reported from low- and middle-income countries (LMIC), and there is a paucity of publications related to CRC from LMIC. PATIENTS AND METHODS A computerized comprehensive structured CRC clinical database was developed. All the patients with histopathologically proven CRC undergoing either curative and palliative multimodality management or surgical interventions between 2000 and 2019 were included in the study. A descriptive analysis of the demographic profile and clinical spectrum was performed. RESULTS A total of 970 patients of CRC were treated between 2000 and 2019. Of these, 401 patients (41.3%) had colon cancer and 569 (58.7%) had rectal cancer. The male-to-female ratio was 1.79:1. The mean age at presentation was 47.7 years. A total of 337 (34.7%) patients qualified as young CRC (≤ 40 years of age at diagnosis). The commonest symptom among patients with colon cancer was abdominal pain; 55.6% of patients had a right-sided primary tumor as compared with 42.2% with left-sided tumors. The commonest symptom among patients with rectal cancer was bleeding per rectum. The predominant location of the tumor was in the lower rectum (58%). Majority of patients with CRC presented with locally advanced stage II and III disease. The most common histologic subtype encountered for both colon and rectal cancers was adenocarcinoma (84.8% and 81.2%, respectively). CONCLUSION This study has revealed certain important findings related to CRC in LMIC including a higher burden of young colorectal cancer, a relatively higher proportion of rectal cancers in comparison with colon cancer, a high percentage of patients with low-rectal cancer, and advanced stage at presentation.
Collapse
Affiliation(s)
- S V S Deo
- Department of Surgical Oncology, Dr BRAIRCH, All India Institute of Medical Sciences, New Delhi, India
| | - Sunil Kumar
- Department of Surgical Oncology, Dr BRAIRCH, All India Institute of Medical Sciences, New Delhi, India
| | - Sandeep Bhoriwal
- Department of Surgical Oncology, Dr BRAIRCH, All India Institute of Medical Sciences, New Delhi, India
| | - N K Shukla
- Department of Surgical Oncology, Dr BRAIRCH, All India Institute of Medical Sciences, New Delhi, India
| | - Atul Sharma
- Department of Medical Oncology, Dr BRAIRCH, All India Institute of Medical Sciences, New Delhi, India
| | - Sanjay Thulkar
- Department of Radio-Diagnosis, Dr BRAIRCH, All India Institute of Medical Sciences, New Delhi, India
| | - Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Prakash Bhagat
- Department of Surgical Oncology, Dr BRAIRCH, All India Institute of Medical Sciences, New Delhi, India
| | - Kunal Dhall
- Department of Surgical Oncology, Dr BRAIRCH, All India Institute of Medical Sciences, New Delhi, India
| | - Sushmita Pathy
- Department of Radiation Oncology, Dr BRAIRCH, All India Institute of Medical Sciences, New Delhi, India
| | - B K Mohanti
- Department of Radiation Oncology, Dr BRAIRCH, All India Institute of Medical Sciences, New Delhi, India
| |
Collapse
|
|
14
|
Optimal Allocation of Chemotherapy Schemes for Metastatic Colon Cancer in Colombia. Value Health Reg Issues 2021; 26:105-112. [PMID: 34166882 DOI: 10.1016/j.vhri.2021.01.006] [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: 06/30/2020] [Revised: 12/10/2020] [Accepted: 01/16/2021] [Indexed: 11/22/2022]
Abstract
OBJECTIVES This study aims to determine the optimal proportion for different chemotherapy schemes in patients with metastatic colorectal cancer who have undergone surgical resection in Colombia. METHODS A linear programming model was used to quantify the optimal proportion of the chemotherapy schemes that maximize quality-adjusted life-years (QALYs). The model was evaluated in 6 different scenarios using parametric and dynamic optimization with different budget restriction constraints. The results were compared to the current mixture of schemes used in our country. RESULTS The results show that 63%, 37%, and 0.8% of the population should receive the FOLFOXIRI scheme (fluorouracil + leucovorin + oxaliplatin + irinotecan), FOLFIRI (irinotecan + leucovorin + fluorouracil), and FOLFIRI plus cetuximab, respectively. With these proportions, 8734 QALYs and universal coverage of the population are obtained. In an optimistic scenario (high QALYs, low costs, and budget of $40 million), the entire population should receive the FOLFIRI scheme. A pessimistic scenario (low QALYs, high costs, and budget of $15 million) would benefit only 46% of the population with the fluorouracil plus leucovorin scheme. In the other 3 scenarios with higher budget constraints, 52%, 69%, and 86% of the population should receive FOLFIRI, respectively. Dynamic optimization revealed that FOLFIRI and FOLFOX (oxaliplatin + leucovorin + fluorouracil) schemes are more likely to generate higher QALYs with lower costs and a limited budget. CONCLUSIONS The current use of chemotherapy schemes is not optimal. An increasing proportion of FOLFIRI, FOLFOX, and FOLFOXIRI should be used more often as schemes to treat metastatic colorectal cancer in Colombia.
Collapse
|
|
15
|
Kabel AM, Ashour AM, Ali DA, Arab HH. The immunomodulatory effects of topiramate on azoxymethane-induced colon carcinogenesis in rats: The role of the inflammatory cascade, vascular endothelial growth factor, AKT/mTOR/MAP kinase signaling and the apoptotic markers. Int Immunopharmacol 2021; 98:107830. [PMID: 34118646 DOI: 10.1016/j.intimp.2021.107830] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 05/08/2021] [Accepted: 05/25/2021] [Indexed: 11/27/2022]
Abstract
BACKGROUND Colon cancer is a malignant condition that affects the lower gastrointestinal tract and has unfavorable prognosis. Its mechanisms range from enhanced production of reactive oxygen species, inflammatory changes in the colon microenvironment and affection of the apoptotic pathways. Due to the high incidence of resistance of colon cancer to the traditional chemotherapeutic agents, a need for finding safe/effective agents that can attenuate the malignant changes had emerged. OBJECTIVE To investigate the possible immunomodulatory and antitumor effects of topiramate on azoxymethane-induced colon cancer in rats. METHODOLOGY Fifty male Wistar rats were randomized into five equal groups as follows: Control; azoxymethane-induced colon cancer; azoxymethane + methyl cellulose; azoxymethane + topiramate small dose; and azoxymethane + topiramate large dose. The body weight gain, serum carcinoembryonic antigen (CEA), tissue antioxidant status, proinflammatory cytokines, vascular endothelial growth factor (VEGF), Nrf2/HO-1 content, p-AKT, mTOR, p38 MAP kinase, caspase 9, nerve growth factor beta and beclin-1 were measured. Also, parts of the colon had undergone histopathological and immunohistochemical evaluation. KEY FINDINGS Topiramate improved the body weight gain, decreased serum CEA, augmented the antioxidant defenses in the colonic tissues with significant amelioration of the inflammatory changes, decline in tissue VEGF and p-AKT/mTOR/MAP kinase signaling and increased Nrf2/HO-1 content in a dose-dependent manner when compared to rats treated with azoxymethane alone. In addition, topiramate, in a dose-dependent manner, significantly enhanced apoptosis and improved the histopathological picture in comparison to animals treated with azoxymethane alone. CONCLUSION Taking these findings together, topiramate might serve as a new effective adjuvant line of treatment of colon cancer.
Collapse
Affiliation(s)
- Ahmed M Kabel
- Pharmacology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt.
| | - Ahmed M Ashour
- Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al Qura University, P.O. Box 13578, Makkah 21955, Saudi Arabia
| | - Dina A Ali
- Clinical Pathology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt
| | - Hany H Arab
- Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
| |
Collapse
|
|
16
|
Alvarez K, Cassana A, De La Fuente M, Canales T, Abedrapo M, López-Köstner F. Clinical, Pathological and Molecular Characteristics of Chilean Patients with Early-, Intermediate- and Late-Onset Colorectal Cancer. Cells 2021; 10:cells10030631. [PMID: 33809084 PMCID: PMC7999342 DOI: 10.3390/cells10030631] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 03/03/2021] [Accepted: 03/10/2021] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) is the second most frequent neoplasm in Chile and its mortality rate is rising in all ages. However, studies characterizing CRC according to the age of onset are still lacking. This study aimed to identify clinical, pathological, and molecular features of CRC in Chilean patients according to the age of diagnosis: early- (≤50 years; EOCRC), intermediate- (51–69 years; IOCRC), and late-onset (≥70 years; LOCRC). The study included 426 CRC patients from Clinica Las Condes, between 2007 and 2019. A chi-square test was applied to explore associations between age of onset and clinicopathological characteristics. Body Mass Index (BMI) differences according to age of diagnosis was evaluated through t-test. Overall (OS) and cancer-specific survival (CSS) were estimated by the Kaplan–Meier method. We found significant differences between the age of onset, and gender, BMI, family history of cancer, TNM Classification of Malignant Tumors stage, OS, and CSS. EOCRC category was characterized by a family history of cancer, left-sided tumors with a more advanced stage of the disease but better survival at 10 years, and lower microsatellite instability (MSI), with predominant germline mutations. IOCRC has shown clinical similarities with the EOCRC and molecular similarities to the LOCRC, which agrees with other reports.
Collapse
Affiliation(s)
- Karin Alvarez
- Oncology Center, Clinica Universidad de Los Andes, Santiago 7620157, Chile;
| | - Alessandra Cassana
- Joint Doctoral Degree Program in Medical Sciences, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile;
- Coloproctology Unit, Clinica Las Condes, Santiago 7591047, Chile;
| | | | - Tamara Canales
- Cancer Institute, Clinica Las Condes, Santiago 7591047, Chile;
| | - Mario Abedrapo
- Coloproctology Unit, Clinica Las Condes, Santiago 7591047, Chile;
- Faculty of Medicine, Universidad de Chile, Santiago 8320000, Chile
| | - Francisco López-Köstner
- Oncology Center, Clinica Universidad de Los Andes, Santiago 7620157, Chile;
- Faculty of Medicine, Universidad de Chile, Santiago 8320000, Chile
- Correspondence:
| |
Collapse
|
|
17
|
Maldonado Cañón K, Carmona Gómez EA. Adenocarcinoma de colon sigmoide metastásico en paciente joven, presentación atípica: reporte de caso. REVISTA COLOMBIANA DE CIRUGÍA 2021. [DOI: 10.30944/20117582.494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
El adenocarcinoma colorrectal es la tercera causa de muerte por cáncer en mujeres y la cuarta en hombres a nivel mundial. Se diagnostica en su mayoría en pacientes mayores a los 50 años, siendo la edad media al momento del diagnóstico los 72 años. A pesar eso, se estima que en los próximos años aumentará la incidencia en personas jóvenes y de mediana edad. Debido a esta proyección y considerando que la ausencia de signos y síntomas específicos no permite un diagnóstico oportuno, se hacen necesarias la sensibilización clínica y un alto índice de sospecha en las presentaciones atípicas. Se presenta el caso de una paciente joven que consulta por un cuadro de un mes de síntomas respiratorios quien, después de tratamiento antibiótico, antiviral e inmunomodulador sistémico, presenta sepsis de origen abdominal por peritonitis de cuatro cuadrantes secundaria a perforación de colon sigmoide debida a adenocarcinoma bien diferenciado, metastásico a pulmón, que la llevó a la muerte.
Collapse
|
|
18
|
Basendowah M, Alshaynawi S, Madani TA, Alabdulqader MH, Hakami M. Positron Emission Tomography With Fluorodeoxyglucose Incidental Detection of Colon Cancer in a Patient's Follow-Up for Nasopharyngeal Carcinoma During the COVID-19 Pandemic: A Case Report. Cureus 2020; 12:e9939. [PMID: 32968599 PMCID: PMC7505672 DOI: 10.7759/cureus.9939] [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] [Indexed: 11/05/2022] Open
Abstract
Colorectal cancer (CRC) is a type of widespread, deadly malignancy that took thousands of lives around the globe. In the last two decades, CRC represented the most common cancer among men and ranked third among women in Saudi Arabia. Positron emission tomography with fluorodeoxyglucose (FDG-PET), can incidentally detect malignancy, as in our case, FDG-PET disclosed high abnormal FDG far away from the first primary malignancy. The current case is of a 65-year-old female who was following up on her nasopharyngeal carcinoma (first primary). During her last management, FDG-PET was requested to find any FDG uptake in the nasopharyngeal region; stunning FDG uptake was incidentally found at the ascending colon diagnosed as early-stage (pT2N0) colon cancer. Colonoscopy was done and India Ink was injected to facilitate localizing the mass during the laparoscopic removal of the tumor, which was delayed due to the pandemic of COVID-19. This took place in March 2020 at King Abdul-Aziz University Hospital in Jeddah.
Collapse
Affiliation(s)
| | | | - Turki A Madani
- Surgery, King Abdulaziz University Hospital, Jeddah, SAU
| | - Mutaz H Alabdulqader
- Family Medicine, King Abdulaziz Medical City, National Guard Hospital - Health Affairs, Jeddah, SAU
| | | |
Collapse
|
|
19
|
Carvalho MR, Reis RL, Oliveira JM. Dendrimer nanoparticles for colorectal cancer applications. J Mater Chem B 2020; 8:1128-1138. [PMID: 31971528 DOI: 10.1039/c9tb02289a] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Cancer nanotechnology is a prolific field of research, where nanotools are employed to diagnose and treat cancer with unprecedented precision. Targeted drug delivery is fundamental for more efficient cancer treatments. For this, nanoparticles have been extensively used during the past few years in order to improve the specificity, selectivity and controlled release of drug delivery. It holds potential in minimizing systemic toxicity through the development of functionalized particles for targeted treatment. Among all the type of nanoparticles, dendrimers display several advantages, which make them ideal candidates for improved and targeted drug delivery in cancer research. Dendrimers can transport large amounts of drug into specific areas. In addition, they can be employed for monitoring the progress of the treatment process, with an unprecedented theranostic capability. Special emphasis is given to colorectal cancer and to the preferred employed strategies for producing drug-loaded/functionalized NPs for cancer therapy in the past few years.
Collapse
Affiliation(s)
- M R Carvalho
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal. and ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal and The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Guimarães, Portugal
| | - R L Reis
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal. and ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal and The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Guimarães, Portugal
| | - J M Oliveira
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal. and ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal and The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Guimarães, Portugal
| |
Collapse
|
|
20
|
Fleitas-Kanonnikoff T, Martinez‐Ciarpaglini C, Ayala J, Gauna C, Denis R, Yoffe I, Sforza S, Martínez MT, Pomata A, Ibarrola‐Villava M, Arevshatyan S, Burriel V, Boscá D, Pastor O, Ferrer‐Martinez A, Carrasco F, Mongort C, Navarro S, Ribas G, Cervantes A. Molecular profile in Paraguayan colorectal cancer patients, towards to a precision medicine strategy. Cancer Med 2019; 8:3120-3130. [PMID: 31059199 PMCID: PMC6558499 DOI: 10.1002/cam4.2191] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Revised: 04/08/2019] [Accepted: 04/09/2019] [Indexed: 12/24/2022] Open
Abstract
Somatic mutation analysis and evaluation of microsatellite instability (MSI) have become mandatory for selecting personalized therapy strategies for advanced colorectal cancer and are not available as routine methods in Paraguay. The aims of this study were to analyze the molecular profile as well as the microsatellite status in a series of advanced colorectal patients from two public hospitals from Paraguay, to introduce these methodologies in the routine practice to guide the therapeutic decisions. Thirty‐six patients diagnosed with advanced colorectal cancer from two referent public hospitals from Paraguay were recruited from May 2017 to February 2018. Sequenom Mass spectrometry, Oncocarta Panel V.1 was applied to analyze the mutational profile from formalin‐fixed paraffin‐embedded samples. The microsatellite status was tested by immunohistochemistry (IHC). The mean age of the patients was 52 years with a range from 20 to 74 years. Eighty‐three percent of the patients included in the study have advanced‐stage tumors at the moment of the diagnosis. Sixteen patients (44.4%) were wild‐type for all the oncogene regions analyzed with the Oncocarta panel. Thirty‐two hot‐spot pathogenic variants on seven oncogenes, among 20 patients (55.6%), were identified, including KRAS, NRAS, BRAF, PI3KCA, FGFR, epidermal growth factor receptor, and PDGFRA. Moreover, 14 (38.8%) of these patients presented pathogenic variants in KRAS/NRAS or BRAF genes that have implications in the clinical practice decisions. Five patients (14%) presented MSI. The IHC study for microsatellite status and the molecular profile analysis through Sequenom mass spectrometry are feasible and useful methods, due to identify those patient candidates for targeted therapies and for the budgetary calculations of the National Health Plans.
Collapse
Affiliation(s)
- Tania Fleitas-Kanonnikoff
- Department of Medical OncologyCIBERONCBiomedical Research Institute INCLIVAUniversity of ValenciaValenciaSpain
| | | | - Josefina Ayala
- Department of Medical OncologyInstituto Nacional del Cáncer (INCAN)CapiatáParaguay
| | - Cinthia Gauna
- Department of Medical OncologyInstituto Nacional del Cáncer (INCAN)CapiatáParaguay
| | - Rita Denis
- Department of Medical OncologyHospital de Clínicas (HC)Universidad Nacional de AsunciónSan LorenzoParaguay
| | - Ita Yoffe
- Department of Medical OncologyHospital de Clínicas (HC)Universidad Nacional de AsunciónSan LorenzoParaguay
| | - Silvia Sforza
- Department of Medical OncologyInstituto Nacional del Cáncer (INCAN)CapiatáParaguay
| | | | - Alicia Pomata
- Department of PathologyInstituto Nacional del Cáncer (INCAN)CapiatáParaguay
| | - Maider Ibarrola‐Villava
- Department of Medical OncologyCIBERONCBiomedical Research Institute INCLIVAUniversity of ValenciaValenciaSpain
| | | | | | | | - Oscar Pastor
- Gembiosoft‐Universidad Politécnica de ValenciaValenciaSpain
| | - Ana Ferrer‐Martinez
- Department of Medical OncologyCIBERONCBiomedical Research Institute INCLIVAUniversity of ValenciaValenciaSpain
| | - Francisca Carrasco
- Department of Medical OncologyCIBERONCBiomedical Research Institute INCLIVAUniversity of ValenciaValenciaSpain
| | - Cristina Mongort
- Department of PathologyCIBERONCBiomedical Research Institute INCLIVAUniversity of ValenciaValenciaSpain
| | - Samuel Navarro
- Department of PathologyCIBERONCBiomedical Research Institute INCLIVAUniversity of ValenciaValenciaSpain
| | - Gloria Ribas
- Department of Medical OncologyCIBERONCBiomedical Research Institute INCLIVAUniversity of ValenciaValenciaSpain
| | - Andres Cervantes
- Department of Medical OncologyCIBERONCBiomedical Research Institute INCLIVAUniversity of ValenciaValenciaSpain
| |
Collapse
|
|
21
|
Campo-Sánchez S, Camargo-Trillos J, Calle-Ramírez J, Gómez-Wolff L, Sánchez-Patiño L, García-García H. Colorectal cancer survival at an oncologic center in Colombia. A historic cohort study. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2019. [DOI: 10.1016/j.rgmxen.2018.07.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
|
|
22
|
Zhang Q, Berger FG, Love B, Banister CE, Murphy EA, Hofseth LJ. Maternal stress and early-onset colorectal cancer. Med Hypotheses 2018; 121:152-159. [PMID: 30396471 DOI: 10.1016/j.mehy.2018.09.035] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Revised: 09/10/2018] [Accepted: 09/20/2018] [Indexed: 02/07/2023]
Abstract
Early-onset colorectal cancer (EOCRC) is defined as colorectal cancer (CRC) diagnosed before the age of 50. Alarmingly, there has been a significant increase in EOCRC diagnoses' worldwide over the past several decades. Emerging data suggest EOCRCs have distinguishing clinical, pathological, biological and molecular features; and thus, are a fundamentally different subtype of CRCs. Unfortunately, there is no simple explanation for the causes of EOCRC. Scientifically rigorous studies are needed to determine what may be driving the challenging epidemiology of EOCRC. We contend here that a reasonable hypothesis is that prenatal risk factors such as maternal stress and associated sleeping disorders influence offspring epigenetic make-up, and shape immune system and gut health contributing to an increased risk for EOCRC.
Collapse
Affiliation(s)
- Qi Zhang
- Department of Drug Discovery and Biomedical Science, College of Pharmacy, University of South Carolina, Columbia, SC, USA
| | - Franklin G Berger
- Department of Biology, College of Arts and Sciences, University of South Carolina, Columbia, SC, USA
| | - Bryan Love
- Department of Clinical Pharmacy & Outcomes Sciences, College of Pharmacy, University of South Carolina, Columbia, SC, USA
| | - Carolyn E Banister
- Department of Drug Discovery and Biomedical Science, College of Pharmacy, University of South Carolina, Columbia, SC, USA
| | - Elizabeth A Murphy
- Department of Pathology, Microbiology and Immunology, University of South Carolina, Columbia, SC, USA
| | - Lorne J Hofseth
- Department of Drug Discovery and Biomedical Science, College of Pharmacy, University of South Carolina, Columbia, SC, USA.
| |
Collapse
|
|
23
|
Colorectal cancer survival at an oncologic center in Colombia. A historic cohort study. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2018; 84:174-184. [PMID: 29884570 DOI: 10.1016/j.rgmx.2018.04.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Revised: 03/20/2018] [Accepted: 04/19/2018] [Indexed: 01/18/2023]
Abstract
INTRODUCTION AND AIMS In Colombia, cancer of the colon is the third most frequent cancer in relation to incidence and mortality. Five-year survival depends on stage at diagnosis, albeit that rate is not known for the country. The aim of the present study was to characterize the overall survival and disease-free survival rates in an adult population with colorectal cancer treated at an oncology center in Medellín, Colombia. MATERIALS AND METHODS A retrospective cohort study was conducted. The case records of patients with a histologic diagnosis of colorectal cancer, seen within the time frame of 2011 and 2015, were reviewed. The overall survival and disease-free survival curves were calculated using the Kaplan-Meier method. RESULTS A total of 824 (54.9%) patients with cancer of the colon and 676 (45.1%) with cancer of the rectum were treated. Mean patient age was 63.3 years, female sex predominated (56.3%), and 98.1% of the tumors were adenocarcinomas. The majority of the lesions were stage iii (31.9% in the colon and 35.5% in the rectum) at the time of diagnosis. Surgery was the most frequent treatment in the colon (85.2%) and radiotherapy was the most frequent in the rectum (75.4%). Overall survival at the median follow-up (27.3 months) was 66.7% for cancer of the colon and 63.9% for cancer of the rectum. Disease-free survival at the median follow-up (18.6 months in colon and 14.9 in rectum) was 72.5 and 68.9%, respectively. CONCLUSIONS The clinical characteristics and treatment of patients were similar to those found in other studies. Two-year survival was higher than in other Colombian reports and 5-year survival was lower than that observed in developed countries.
Collapse
|