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Purpose: Matrix metalloproteinase-11 (MMP11), which belongs to the stromelysin subgroup, has been reported to play a role in the progression of colorectal cancer (CRC). However, the significance of MMP11 in the tumor microenvironment, immune/stromal cells, and its mechanism in CRC remain unclear. Methods: The impact of MMP11 knockdown using specific short hairpin RNAs (shRNAs) on the metastasis and invasion of colorectal cancer RKO and SW480 cells was investigated using western blot, quantitative real-time polymerase chain reaction (qRT-PCR), transwell assays, and immunohistochemistry. Results: MMP11 mRNA expression was significantly higher in CRC cells than in normal cells, and its expression was stimulated in CCD-18Co fibroblasts. Additionally, MMP11 expression was found to be higher in individuals aged ≤ 65 years, the T4/T3 group, and Stage III/IV patients. Overall survival (OS) and disease-free survival rates were significantly different between the high and low MMP11 groups. Furthermore, the receiver operating characteristic (ROC) curves for MMP11 at 1-, 3-, and 5-years were 0.450, 0.552, and 0.560, respectively. Moreover, MMP11 promoted the migration and invasion of CRC cells by elevating the expression of Slug protein. Most importantly, MMP11 was positively associated with M0-macrophages and negatively associated with M1-macrophages, NK cells activated, NK cells resting, T cells CD4 memory activated, and T cells follicular helper, indicating the remarkable interactions of MMP11 with tumor immunology. Conclusions: MMP11 plays an important role in colorectal cancer development, and its mechanism in CRC needs to be further explored in the future.
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Movimiento Celular , Neoplasias Colorrectales , Regulación Neoplásica de la Expresión Génica , Metaloproteinasa 11 de la Matriz , Invasividad Neoplásica , Factores de Transcripción de la Familia Snail , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Factores de Transcripción de la Familia Snail/metabolismo , Factores de Transcripción de la Familia Snail/genética , Metaloproteinasa 11 de la Matriz/genética , Metaloproteinasa 11 de la Matriz/metabolismo , Invasividad Neoplásica/genética , Movimiento Celular/genética , Masculino , Línea Celular Tumoral , Femenino , Persona de Mediana Edad , Anciano , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Supervivencia sin EnfermedadRESUMEN
Recent reports have shown that pre-treatment low muscle mass may lead to poorer outcomes for cancer patients. We explored the correlation between Visceral Adipose Tissue (VAT), Subcutaneous Adipose Tissue (SAT), and Muscle Mass (MM) as measured by CT scans, and overall survival (OS) following diagnosis of colorectal cancer (CRC). We conducted a retrospective review of medical records and CT scans of patients diagnosed with CRC between 2007 and 2018. Demographics, pathology, and clinical parameters were collected. Using Image-J software, we measured VAT, SAT, and MM. Survival rates were analyzed using Kaplan-Meier curves, and prognostic factors were assessed using multivariate Cox regression. Analysis included 408 patients with a mean age of 56.9 years and a median follow-up of 93.3 months. Colon and rectum/rectosigmoid colon cancers were equally distributed. The 5-year OS rate was 67.8%. There was no significant difference in OS rates based on SAT or VAT. However, higher MM was associated with a improved 5-year OS rate. Factors such as age, stage, grade, and surgery were also associated to OS rates. These findings suggest that higher muscle mass may lead to better outcomes for CRC patients, highlighting the potential impact of exercise and nutritional interventions on patient outcomes.
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Neoplasias Colorrectales , Humanos , Masculino , Persona de Mediana Edad , Femenino , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Estudios Retrospectivos , Anciano , Pronóstico , Grasa Intraabdominal/patología , Adulto , Centros de Atención Terciaria , Tomografía Computarizada por Rayos X , Tasa de Supervivencia , Grasa Subcutánea/patología , Grasa Subcutánea/diagnóstico por imagen , Estimación de Kaplan-Meier , Músculo Esquelético/patología , Músculo Esquelético/diagnóstico por imagenRESUMEN
Objectives: Treatment of metastatic colorectal cancer (mCRC) includes resection of liver metastases (LM), however, no validated biomarker identifies patients most likely to benefit from this procedure. This meta-analysis aimed to assess the impact of the most relevant molecular alterations in cancer-related genes of CRC (i.e., RAS, BRAF, SMAD4, PIK3CA) as prognostic markers of survival and disease recurrence in patients with mCRC surgically treated by LM resection. Methods: A systematic literature review was performed to identify studies reporting data regarding survival and/or recurrence in patients that underwent complete liver resection for CRC LM, stratified according to RAS, BRAF, PIK3CA, and SMAD4 mutational status. Hazard ratios (HRs) from multivariate analyses were pooled in the meta-analysis and various adjustment strategies for confounding factors were combined. The search was conducted in numerous databases, including MEDLINE (PubMed), Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCO host), and WHO Global Index Medicus, through March 18th, 2022. Meta-analyses, editorials, letters to the editor, case reports, studies on other primary cancers, studies with primary metastatic sites other than the liver, studies lacking specific oncological outcome variables or genetic data, non-English language studies, and studies omitting residual disease data from liver metastasectomy were excluded. The remaining 47 studies were summarized in a descriptive table which outlines the key characteristics of each study and final results were graphically presented. Results: RAS mutation status was negatively associated with overall survival (OS) (HR, 1.68; 95% CI, 1.54-1.84) and recurrence free survival (RFS) (HR, 1.46; 95% CI, 1.33-1.61). A negative association was also found for BRAF regarding OS (HR, 2.64; 95% CI, 2.15-3.24) and RFS (HR, 1.89; 95% CI, 1.32-2.73) and SMAD4 regarding OS (HR, 1.93; 95% CI, 1.56-2.38) and RFS (HR, 1.95; 95% CI, 1.31-2.91). For PIK3CA only three studies were eligible and no significant association with either OS or RFS could be highlighted. Conclusion: RAS, BRAF, and SMAD4 are negatively associated with OS and RFS in patients undergoing curative liver metastasectomy from colorectal cancer. No conclusion can be drawn for PIK3CA due to the limited literature availability. These data support the integration of RAS, BRAF, and SMAD4 mutational status in the surgical decision-making for colorectal liver metastasis. Nevertheless, we have to consider several limitations, the major ones being the pooling of results from studies that evaluated patient outcomes as either disease-free survival (DFS) or RFS; the inclusion of patients with minimal residual disease and unconsidered potential confounding factors, such as variability in resectability definitions, chemotherapy use, and a potential interaction between biological markers and pre- and post-resection pharmacological treatments.
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Neoplasias Colorrectales , Neoplasias Hepáticas , Mutación , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/mortalidad , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/mortalidad , Biomarcadores de Tumor/genética , Pronóstico , Hepatectomía/métodos , Proteínas Proto-Oncogénicas B-raf/genética , Fosfatidilinositol 3-Quinasa Clase I/genética , Proteína Smad4/genética , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugíaRESUMEN
BACKGROUND: The prognostic implications of the RAS status in colorectal cancer liver metastasis (CRLM) remain unclear. This study investigated the prognostic significance of RAS status after curative hepatectomy, focusing on surgical controllability. METHODS: This retrospective study included liver-only CRLM patients who underwent the first hepatectomy between 2015 and 2022 at the National Cancer Center Hospital. Recurrence-free survival (RFS), surgically controllable period (SCP), and overall survival (OS) were compared between RAS wild-type (RAS-wt) and mutant (RAS-mt) patients. Multivariate analyses were conducted to identify independent prognostic factors for each outcome and independent risk factors for less than 1 year SCP. RESULTS: A total of 150 patients were evaluated, comprising 63 patients with RAS-mt status. There was no significant difference in RFS between RAS-mt and RAS-wt (7.00 vs. 8.03 months, p = 0.48). RAS-mt patients exhibited worse SCP (11.80 vs.21.13 months, p < 0.001) and OS (44.03 vs. 70.03 months, p < 0.001) compared to RAS-wt. Multivariate analysis identified RAS-mt as an independent prognostic factor for both OS (hazard ratio [HR]: 3.37, p < 0.001) and SCP (HR: 2.20, p < 0.001), and as an independent risk factor for less than 1 year of SCP (odds ratio, 2.31; p = 0.03). CONCLUSIONS: CRLM with RAS mutations should be considered for strict surgical indications with preoperative chemotherapy and thorough examination, considering the possibility of short SCP.
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Neoplasias Colorrectales , Hepatectomía , Neoplasias Hepáticas , Mutación , Humanos , Estudios Retrospectivos , Masculino , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/mortalidad , Femenino , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidad , Persona de Mediana Edad , Hepatectomía/métodos , Pronóstico , Tasa de Supervivencia , Anciano , Estudios de Seguimiento , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/cirugía , Recurrencia Local de Neoplasia/epidemiología , Adulto , Biomarcadores de Tumor/genéticaRESUMEN
BACKGROUND: Colorectal cancer is the third most common cancer and the second leading cause of cancer death. There are limited therapeutic options for the treatment of locally advanced or metastatic colorectal cancers which fail first-line chemotherapy. Phase I/II studies showed that the combined application of the raltitrexed and irinotecan has significant synergistic effect and acceptable toxicity. However, most of these previous studies have relatively small sample size. METHODS: This is a prospective open-label, single-arm, multi-center, Phase II trial. Brief inclusion criteria: patients were aged 18 to 75 years with locally advanced or metastatic colorectal cancer after failure of 5-FU and oxaliplatin therapy. Enrolled patients received raltitrexed (3 mg/m2, d1) and irinotecan (180 mg/m2, d1) each 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, and the secondary endpoints were disease control rate, objective response rate, overall survival and safety. RESULTS: A total of 108 patients were enrolled between September 2016 and May 2020. The median age was 61 years, ECOG 1 score accounts for 67.6%, the rest were ECOG 0. A total of 502 cycles were completed, with an average of 4.6 cycles and a median of 4 cycles. 108 patients were evaluated, with an objective response rate of 17.6%, and disease control rate of 76.9%. The median follow-up time was 27 months (range:3.1-61.0 m) at data cut-off on March 2023. Median progression-free survival was 4.9 months (95% CI 4.1-5.7) and median overall survival was 13.1 months (95% CI 12.2-15.5). The most common adverse events that were elevated are alanine aminotransferase increased, aspartate aminotransferase increased, fatigue, diarrhoea, neutrocytopenia, thrombocytopenia, hypohemoglobin, and leukocytopenia. Most of the adverse events were Grade I/II, which were relieved after symptomatic treatment, and there were no treatment-related cardiotoxicities and deaths. CONCLUSIONS: The combination of raltitrexed and irinotecan as second-line treatment for mCRC could be a reliable option after failure of standard 5-Fu-first-line chemotherapy in locally advanced or metastatic colorectal cancers, especially for patients with 5-FU intolerance (cardiac events or DPD deficiency patients). TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03053167, registration date was 14/2/2017.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorrectales , Irinotecán , Quinazolinas , Tiofenos , Humanos , Persona de Mediana Edad , Quinazolinas/uso terapéutico , Quinazolinas/efectos adversos , Masculino , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/mortalidad , Irinotecán/uso terapéutico , Irinotecán/administración & dosificación , Anciano , Femenino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Tiofenos/uso terapéutico , Tiofenos/administración & dosificación , Tiofenos/efectos adversos , Estudios Prospectivos , Adulto , Supervivencia sin Progresión , Adulto JovenRESUMEN
MicroRNAs (miRNAs) are a class of small non-coding RNAs that act as important regulators of gene expression, involved in various biological pathways. Aberrant miRNAs expression is associated with the onset and progression of colorectal cancer (CRC). The aim of this study was to investigate the correlation between five miRNAs (miR-29a, miR-101, miR-125b, miR-146a, and miR-155), found to be deregulated in tissue samples of CRC patients, and clinicopathological characteristics and histological markers. Analysis of histological markers was performed by immunohistochemical staining of tumour tissues with Ki-67, p53, CD34, and Bcl-2. Our findings revealed a significant negative correlation between miR-29a expression and Bcl-2 levels. Furthermore, high miR-29a expression was associated with a lower incidence of distant metastasis in CRC patients. We observed negative correlations between miR-101 expression and the number of lymph nodes with metastasis, as well as the size of the largest metastasis; miR-125b expression and lymphovascular invasion; and miR-155 expression and mucus presence. Our survival analysis demonstrated that high miR-29a expression correlated with better progression-free survival of CRC patients, underscoring its potential as a prognostic marker. Our study unveiled intricate relationships between specific miRNA expressions and clinicopathological features in CRC, highlighting the potential utility of miR-29a as a valuable prognostic biomarker.
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Biomarcadores de Tumor , Neoplasias Colorrectales , MicroARNs , Proteínas Proto-Oncogénicas c-bcl-2 , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/mortalidad , Femenino , Masculino , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Persona de Mediana Edad , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Pronóstico , Anciano , Regulación Neoplásica de la Expresión Génica , Adulto , Anciano de 80 o más AñosRESUMEN
Molecular studies have identified various treatment-related prognostic molecules to enhance the effectiveness of colorectal cancer (CRC) treatment and improve survival rates. The expression of cathepsin V in gastrointestinal cancer cells prompted an investigation into its potential as a prognostic indicator for CRC. The evaluation of cathepsin V expression and its clinicopathological significance was conducted through immunohistochemistry in a tissue microarray, encompassing 142 CRC and normal colorectal tissues. Overall and disease-free survival rates, based on cathepsin V expression levels, were assessed using the Kaplan-Meier method and compared utilizing the log-rank test. Univariate and multivariate analyses, employing a Cox proportional hazards model, were performed to identify prognostic factors. Cathepsin V expression exhibited no correlation with age, sex, tumor location, tumor size, or histological grade. However, it was significantly correlated with depth of tumor invasion, regional lymph node (LN) metastasis, distant metastasis, and lymphovascular involvement (all p<0.001). Overall and disease-free survival rates were significantly better with low cathepsin V expression than with high expression (p<0.001). Univariate analysis identified several prognostic factors, including histological grade (low vs. high), tumor size (≤ vs. >5â¯cm), tumor depth (T1 vs. ≥T2), regional LN metastasis, distant metastasis, tumor-node-metastasis (TNM) stage (Stage I vs ≥II), lymphovascular involvement, and cathepsin V expression. Multivariate analysis revealed that tumor depth, distant metastasis, and cathepsin V expression are independent predictors of poor survival. Cathepsin V is frequently expressed in CRC, and its high expression is associated with poor prognosis. Therefore, cathepsin V is a useful prognostic marker for CRC.
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Biomarcadores de Tumor , Catepsinas , Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/metabolismo , Femenino , Masculino , Persona de Mediana Edad , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Pronóstico , Anciano , Catepsinas/metabolismo , Catepsinas/análisis , Adulto , Supervivencia sin Enfermedad , Anciano de 80 o más Años , Metástasis Linfática/patología , Cisteína EndopeptidasasRESUMEN
Colorectal cancer (CRC) is a major contributor to global morbidity and mortality, necessitating more effective therapeutic approaches. T cells, prominent in the tumor microenvironment, exert a crucial role in modulating immunotherapeutic responses and clinical outcomes in CRC. This study introduces a pioneering method for characterizing the CRC immune microenvironment using single-cell sequencing data. Unlike previous approaches, which focused on individual T-cell signature genes, we utilized overall infiltration levels of colorectal cancer signature T-cells. Through weighted gene co-expression network analysis, Lasso regression, and StepCox analysis, we developed a prognostic risk model, TRGS (T-cell related genes signatures), based on six T cell-related genes. Multivariate Cox analysis identified TRGS as an independent prognostic factor for CRC, showcasing its superior predictive efficacy compared to existing immune-related prognostic models. Immunoreactivity analysis revealed higher Immunophenoscore and lower Tumor Immune Dysfunction and Exclusion scores in the low-risk group, indicating potential responsiveness to immune checkpoint inhibitor therapy. Additionally, patients in the low-risk group demonstrated heightened sensitivity to 5-fluorouracil-based chemotherapy regimens. In summary, TRGS emerges as a standalone prognostic biomarker for CRC, offering insights to optimize patient responses to immunotherapy and chemotherapy, thereby laying the groundwork for personalized tumor management strategies.
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Neoplasias Colorrectales , RNA-Seq , Análisis de la Célula Individual , Linfocitos T , Microambiente Tumoral , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/mortalidad , Análisis de la Célula Individual/métodos , Pronóstico , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Linfocitos T/inmunología , Linfocitos T/metabolismo , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Femenino , Masculino , Transcriptoma , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismoRESUMEN
Caudal type homeobox transcription factor 2 (CDX2) is a gastrointestinal cancer biomarker that regulates epithelial development and differentiation. Absence or low levels of CDX2 have been associated with poor prognosis and proposed as a chemotherapy response predictor. Tumour tissue samples from 668 patients with stage I-IV colorectal cancer were stained for CDX2 and stratified into two subgroups according to expression levels. Statistical tests were used to evaluate CDX2's relationship with survival and chemotherapy response. Of 646 samples successfully stained, 51 (7.9%) had low CDX2 levels, and 595 (92.1%) had high levels. Low CDX2 staining was associated with poor differentiation and the presence of lymphovascular or perineural invasion and was more common in colon and right-sided tumours. Overall survival (p < 0.001) and disease-free survival (p = 0.009) were reduced in patients with low CDX2 expression. Multivariable analysis validated CDX2 as an independent poor prognostic factor after excluding confounding variables. There was no statistically significant improvement in survival with adjuvant chemotherapy in stage II colon cancer (p = 0.11). In the rectal cohort, there was no relationship between CDX2 levels and therapy response. While confirming the prognostic utility of CDX2 in colorectal cancer, our study highlights that larger studies are required to confirm its utility as a predictive chemotherapy biomarker, especially in left-sided and rectal cancers.
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Biomarcadores de Tumor , Factor de Transcripción CDX2 , Neoplasias Colorrectales , Humanos , Factor de Transcripción CDX2/metabolismo , Factor de Transcripción CDX2/genética , Masculino , Femenino , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/tratamiento farmacológico , Persona de Mediana Edad , Pronóstico , Anciano , Biomarcadores de Tumor/metabolismo , Estadificación de Neoplasias , Adulto , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Quimioterapia AdyuvanteRESUMEN
BACKGROUND: Cancer is a growing public health problem and cancer is linked to vitamin D via several mechanisms. Recent umbrella reviews on the extra-skeletal effects of vitamin D did not turn their attention to cancer. Accordingly, an overview of the current state of research is needed. MATERIALS AND METHODS: An umbrella review was conducted to provide an overview of systematic reviews on the association between vitamin D and incidence or mortality of breast cancer, colorectal cancer, lung cancer, pancreatic cancer, and prostate cancer. RESULTS: Inverse correlations were found between the vitamin D level (measured by circulating 25(OH)D) and mortality for all five types of cancer. For breast cancer, colorectal cancer, lung cancer, and pancreatic cancer, there are also hints of a lower incidence due to higher 25(OH)D levels. CONCLUSION: As most reviews include observational studies, conclusions on causality cannot be made. Methodological differences between the included reviews and different study designs in the individual studies lead to methodological problems. Despite these problems, the review shows inverse correlations between 25(OH)D levels and mortality, and mostly inverse correlations between 25(OH)D levels and incidence.
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Neoplasias , Vitamina D , Humanos , Vitamina D/sangre , Vitamina D/análogos & derivados , Neoplasias/sangre , Neoplasias/epidemiología , Femenino , Masculino , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/mortalidad , Incidencia , Neoplasias de la Mama/sangre , Neoplasias de la Mama/epidemiología , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/epidemiología , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/epidemiología , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/mortalidad , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/mortalidad , Factores de RiesgoRESUMEN
BACKGROUND: Lymph node ratio (LNR) is suggested to address the shortcomings of using only lymph node yield (LNY) or status in colorectal cancer (CRC) prognosis. This study explores how LNR affects survival in patients with metastatic colorectal cancer (mCRC), seeking to provide clearer insights into its application. METHODS: This observational cohort study investigated stage IV patients with CRC (1995-2021) who underwent an upfront resection of their primary tumour at Concord Hospital, Sydney. Clinicopathological data were extracted from a prospective database, and LNR was calculated both continuously and dichotomously (LNR of 0 and LNR > 0). The primary endpoint was overall survival (OS). The associations between LNR and various clinicopathological variables were tested using regression analyses. Kaplan-Meier and Cox regression analyses estimated OS in univariate and multivariate survival models. RESULTS: A total of 464 patients who underwent a primary CRC resection with clear margins (mean age 68.1 years [SD 13.4]; 58.0% M; colon cancer [n = 339,73.1%]) had AJCC stage IV disease. The median LNR was 0.18 (IQR 0.05-0.42) for colon cancer (CC) resections and 0.21 (IQR 0.09-0.47) for rectal cancer (RC) resections. A total of 84 patients had an LNR = 0 (CC = 66 patients; RC = 18 patients). The 5-year OS for the CC cohort was 10.5% (95% CI 8.7-12.3) and 11.5% (95% CI 8.4-14.6) for RC. Increasing LNR demonstrated a decline in OS in both CC (P < 0.001) and RC (P < 0.001). In patients with non-lymphatic dissemination only (LNR = 0 or N0 status), there was better survival compared with those with lymphatic spread (CC aHR1.50 [1.08-2.07;P = 0.02], RC aHR 2.21 [1.16-4.24;P = 0.02]). CONCLUSIONS: LNR is worthy of consideration in patients with mCRC. An LNR of 0 indicates patients have a better prognosis, underscoring the need for adequate lymphadenectomy to facilitate precise mCRC staging.
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Neoplasias Colorrectales , Índice Ganglionar , Estadificación de Neoplasias , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Pronóstico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/cirugía , Índice Ganglionar/estadística & datos numéricos , Estimación de Kaplan-Meier , Anciano de 80 o más Años , Metástasis Linfática , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Escisión del Ganglio Linfático/estadística & datos numéricosRESUMEN
Colorectal cancer (CRC) is the second leading cause of cancer-related death in Europe. This study aimed to investigate CRC mortality trends in Montenegro from 1990 to 2018 and critically review the impact of preventive activities on cancer suppression in this country. We used the national CRC mortality data categorized by sex and age. Mortality rates were age-standardized according to the World Standard Population. The trends were described using regression techniques. In the period from 1990 to 2018, there was a significant increase in CRC mortality (Pâ <â .05). The death rates and the number of deaths from CRC were constantly increasing for both the overall level and gender, with the mean annual percentage change for the rates respectively average annual percent change (95% confidence interval-CI): 2.6% (1.9-3.2), 2.6% (1.8-3.5); 2.3% (1.3-3.3), and for the number of cases, respectively: 4.2% (3.5-4.9), 4.3% (3.3-5.3), 4.3% (3.2-5.5). The most affected age groups were 65 to 74 years (33%), followed by those aged 75 to 84 years (25%) and the age group 55 to 64 (22%). In Montenegro, CRC mortality trends are increasing among both men and women over the age of 45. Additional research on the risk factors and mechanisms that contribute to the unfavorable trends in CRC mortality in Montenegro is necessary.
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Neoplasias Colorrectales , Mortalidad , Humanos , Montenegro/epidemiología , Neoplasias Colorrectales/mortalidad , Masculino , Femenino , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Mortalidad/tendencias , Factores de Edad , AdultoRESUMEN
BACKGROUND: The incidence and mortality of colorectal cancer were still rising rapidly in many low-income and middle-income countries, which was linked to ongoing societal and economic status. Colorectal cancer is the leading cancer in Ethiopia with relatively lower survival. However, colorectal cancer patients' survival time and predictors have not been well studied in Southern Ethiopia. OBJECTIVE: This study aimed to assess five-year survival and predictors of mortality among colorectal cancer patients at Hawassa Comprehensive Specialized Hospital, Ethiopia. METHOD: Facility-based retrospective cohort study was conducted among 323 patients who visited Hawassa Comprehensive Specialized Hospital from May 1st, 2017 to April 30th, 2022. The Kaplan-Meier survival curve with the Log-rank test was used to estimate the survival time. Bivariable and multivariable Cox proportional hazards regression models were used to determine the net effect of each independent variable on time to death after diagnosis. RESULT: Over the 5-year observation period, the overall mortality rate was 38.5%, with an incidence density of 31 fatalities per 100 person-years observation. Survival at 1, 2, 3, 4, and 5 years was 78%, 53, 32.4%, 23.3%, and 18.7% respectively. The multivariable analysis showed that metastatic disease (AHR = 4.2, CI: 1.5-11.5), baseline carcinoembryonic antigen level ≥5ng/ml (AHR: 2.4, CI: 1.2-5.8), living in rural areas (AHR = 2.2, CI:1.03-4.8) and mucinous carcinoma (AHR = 0.33, CI: 0.13-0.87) were independent predictors of colorectal cancer mortality. CONCLUSION: Overall survival of colorectal cancer patients in the study was low compared to similar studies in developing and developed worlds. A significantly low survival rate was observed for patients with advanced stage, elevated carcinoembryonic antigen levels, and rural residents indicating the key role of early detection and timely initiation of treatment to improve survival and quality of life of patients with colorectal cancer.
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Neoplasias Colorrectales , Humanos , Etiopía/epidemiología , Neoplasias Colorrectales/mortalidad , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Adulto , Estudios de Seguimiento , Tasa de Supervivencia , Estimación de Kaplan-Meier , Modelos de Riesgos Proporcionales , Hospitales Especializados/estadística & datos numéricos , IncidenciaRESUMEN
BACKGROUND: Programmed death-ligand 1 (PD-L1) expression on tumor cells is associated with poor prognosis in several malignancies, while partly contradictory and inconclusive results have been presented for colorectal cancer (CRC). This study aimed to evaluate PD-L1 as a prognostic biomarker in CRC by comparing three different antibody clones. METHODS: Patients surgically treated for CRC between January 1st, 2007, and December 31st, 2015, in Kalmar County, Sweden, were retrospectively included. Tissue microarrays from 862 primary tumors without neoadjuvant treatment were assessed for immunohistochemical expression of PD-L1 in tumor cells (TC) and immune cells (IC) using clones 73-10, SP263, and 22C3. Cox regression proportional hazard models were used to estimate hazard ratios for overall survival (OS) and disease-free interval (DFI) in univariable and multivariable analyses, with 1% and 5% set as cut-offs for positive expression in TC and IC respectively. RESULTS: PD-L1 expression in TC was found in 89 (10%) cases for clone 73-10, 76 (9%) for clone SP263, and 38 (4%) for clone 22C3, while the numbers for IC were 317 (37%) cases for clone 73-10, 264 (31%) for clone SP263, and 89 (10%) for clone 22C3. PD-L1 expression in IC was associated with prolonged OS and DFI in univariable analysis for all three clones. The link to prolonged DFI remained in multivariable analysis for 73-10 and SP263, but only for 73-10 regarding OS. PD-L1 expression in TC was not prognostic of OS in any analysis, while it was associated with prolonged DFI for SP263, and a trend was seen for 73-10. The link to prolonged DFI remained for SP263 and was strengthened for 73-10 in multivariable analysis. CONCLUSIONS: The prognostic value of PD-L1 expression in both IC and TC differs between antibody clones, with 73-10 and SP263 being more reliable for prognostic information than 22C3 in resected CRC.
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Antígeno B7-H1 , Biomarcadores de Tumor , Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/inmunología , Antígeno B7-H1/metabolismo , Masculino , Femenino , Pronóstico , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Biomarcadores de Tumor/metabolismo , Anciano de 80 o más Años , Terapia Neoadyuvante/métodos , Anticuerpos Monoclonales/uso terapéutico , AdultoRESUMEN
PURPOSE: The value of upfront primary tumor resection (PTR) for asymptomatic unresectable metastatic colorectal cancer (mCRC) patients remains contentious. This meta-analysis aimed to assess the prognostic significance of upfront PTR for asymptomatic unresectable mCRC. METHODS: A systematic literature search was performed on June 21st, 2024. To minimize the bias and ensure robust evidence, only randomized controlled trials (RCTs) and case-matched studies (CMS) that compared PTR followed by chemotherapy to chemotherapy alone were included. The primary outcome was overall survival (OS), while cancer-specific survival (CSS) served as the secondary outcome. RESULTS: Eight studies (three RCTs and five CMS) involving 1221 patients were included. Compared to chemotherapy alone, upfront PTR followed by chemotherapy did not improve OS (hazard ratios [HR] 0.91, 95% confidence interval [CI] 0.79-1.04, P = 0.17), but was associated with slightly better CSS (HR 0.59, 95% CI 0.40-0.88, P = 0.009). CONCLUSIONS: The current limited evidence indicates that upfront PTR does not improve OS but may enhance CSS in asymptomatic unresectable mCRC patients. Ongoing trials are expected to provide more reliable evidence on this issue.
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Neoplasias Colorrectales , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/cirugía , Enfermedades Asintomáticas , Estudios de Casos y Controles , PronósticoRESUMEN
Colorectal cancer (CRC) is a common malignant tumor associated with high morbidity and mortality. Despite an increase in early screening and treatment options, people with CRC still have a poor prognosis and a low 5-year survival rate. Therefore, mining more therapeutic targets and developing means of early diagnosis and determining prognosis are now imperative in the clinical treatment of CRC. Ferroptosis is a recently identified type of regulated cell death (RCD) characterized, which is identified by the accumulation of iron-dependent lipid peroxidation, thereby causing membrane damage and cell death. Recent studies have shown that ferroptosis is associated with tumors, including CRC, and can be involved in CRC progression; however, the underlying mechanisms are complex and heterogeneous and have not been thoroughly summarized. Therefore, this study reviewed the roles of ferroptosis in CRC progression to target ferroptosis-related factors for CRC treatment. The significance of ferroptosis-related biomarkers and genes in the early diagnosis and prognosis of CRC was also investigated. Furthermore, the limitations of ferroptosis studies in the current treatment of CRC, as well as future research perspectives, are discussed.
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Neoplasias Colorrectales , Ferroptosis , Humanos , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/mortalidad , Peroxidación de Lípido , Pronóstico , Animales , Biomarcadores de Tumor/metabolismoRESUMEN
In Europe, CRC is the second most common cause of cancer death, and surgery remains the mainstay curative treatment. Age and frailty are associated with an increased risk of postoperative morbidity and 1-year mortality. Chronological age is not sufficient to assess the risk of postoperative complications. The CGA has been developed to better identify frail patients. Geriatric co-management have been developed to optimize the post-operative outcomes. We analyzed the real-life of geriatric co-management within an ERAS program on surgical outcomes at 90 days and oncologic outcomes at 1 year in patients aged 70 years or older after surgery for CRC. This was a retrospective study based on a prospective cohort. Fifty-one patients with a G8 score ≤ 14 were referred to geriatricians for preoperative CGA (Frail Group). They were compared with 151 patients with a G8 score ≥ 15 (Robust Group). In the Frail Group, patients were significantly older with more comorbidities than the patients in the Robust Group. Oncologic characteristics, treatments and global post-operative outcomes were comparable between the two groups. One year after surgery mortality and recurrence rates were similar between the two groups. Our study suggests that geriatric co-management is feasible and contributes to the reduction of postoperative morbimortality. Moreover, performing the CGA after G8 score screening and completion of geriatric interventions resulted in similar 90-day postoperative outcomes, in frail patients than in robust patients. Our results confirmed the benefit of geriatric co-management, involving G8 screening, CGA, and ERAS, for frail older patients undergoing surgery for CRC.
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Neoplasias Colorrectales , Anciano Frágil , Fragilidad , Evaluación Geriátrica , Complicaciones Posoperatorias , Humanos , Anciano , Masculino , Femenino , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/mortalidad , Anciano de 80 o más Años , Evaluación Geriátrica/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/mortalidad , Estudios RetrospectivosRESUMEN
The overall prognosis for colorectal cancer (CRC) remains challenging as the survival time varies widely, even in patients with the same stage of disease. Recent studies suggest prognostic relevance of the novel markers of systemic inflammation, the systemic immune-inflammation index (SII), and the systemic inflammation response index (SIRI). We conducted a comprehensive meta-analysis to assess the prognostic significance of the SII and the SIRI in CRC. We searched the relevant literature for observational studies, and random effects models were employed to conduct a statistical analysis using the metaanalysisonline.com platform. Pooled effect sizes were reported with hazard ratios (HRs) and corresponding 95% confidence intervals (CI). Data from 29 studies published between 2016 and 2024, comprising 10,091 participants, were included in our meta-analysis on SII. CRC patients with high SII levels had worse disease outcomes, which were associated with poor OS (HR: 1.75; 95% CI: 1.4-2.19) and poor PFS/DFS/RFS (HR: 1.25; 95% CI: 1.18-1.33). This increased risk of worse OS was present irrespective of the treatment strategy, sample size (<220 and ≥220), and cutoff used to define high and low SII (<550 and ≥550) groups. Based on data from five studies comprising 2362 participants, we found a strong association between the high SIRI and worse OS (HR: 2.65; 95% CI: 1.6-4.38) and DFS/RFS (HR: 2.04; 95% CI: 1.42-2.93). According to our results, both the SII and SIRI hold great promise as prognostic markers in CRC. Further validations are needed for their age- and stage-specific utility in the clinical routine.
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Neoplasias Colorrectales , Inflamación , Humanos , Biomarcadores de Tumor , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/diagnóstico , Inflamación/inmunología , PronósticoRESUMEN
BACKGROUND: The controlled nutritional status score (CONUT) and handgrip strength (HGS) were both predictive indexes for the prognosis of cancers. However, the combination of CONUT and HGS for predicting the prognosis of gastrointestinal cancer had not been developed. This study aimed to explore the combination of CONUT and HGS as the potential predictive prognosis in patients with gastric and colorectal cancer. METHODS: A cohort study was conducted with gastric and colorectal cancer patients in multicenter in China. Based on the optimal HGS cutoff value for different sex, the HGS cutoff value was determined. The patients were divided into high and low HGS groups based on their HGS scores. A CONUT score of 4 or less was defined as a low CONUT, whereas scores higher than 4 were defined as high CONUT. The Kaplan-Meier method was used to create survival curves, and the log-rank test was used to compare time-event relationships between groups. A Cox proportional hazard regression model was used to determine independent risk factors for overall survival (OS). RESULTS: A total 2177 gastric and colorectal patients were enrolled in this study, in which 1391 (63.9%) were men (mean [SD] age, 66.11 [11.60] years). Multivariate analysis revealed that patients with high HGS had a lower risk of death than those with low HGS (hazard ratio [HR],0.87; 95% confidence interval [CI], 0.753-1.006, P = 0.06), while high CONUT had a higher risk of death than those with low CONUT (HR, 1.476; 95% CI, 1.227-1.777, P < 0.001). Patients with both low HGS and high CONUT had 1.712 fold increased risk of death (HR, 1.712; 95% CI, 1.364-2.15, P < 0.001). Moreover, cancer type and sex were stratified and found that patients with high CONUT and low HGS had lower survival rate than those with low CONUT and high HGS in both gastric or colorectal cancer, and both male and female. CONCLUSION: A combination of low HGS and high CONUT was associated with poor prognosis in patients with gastrointestinal cancer, which could probably predict the prognosis of gastrointestinal cancer more accurate than HGS or CONUT alone.
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Neoplasias Gastrointestinales , Fuerza de la Mano , Estado Nutricional , Humanos , Masculino , Femenino , Anciano , Fuerza de la Mano/fisiología , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/fisiopatología , Pronóstico , Persona de Mediana Edad , China/epidemiología , Estudios de Cohortes , Evaluación Nutricional , Factores de Riesgo , Modelos de Riesgos Proporcionales , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/fisiopatología , Estimación de Kaplan-Meier , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/fisiopatologíaRESUMEN
INTRODUCTION: Age and comorbidity are considered the strongest predictors for adverse events after colorectal cancer (CRC) surgery. We aimed to study the interaction of age and comorbidity and to gain better insight in options to improve care for the growing group of older patients. MATERIALS AND METHODS: We included all patients ≥70 years undergoing elective surgery for non-metastatic CRC between 2011 and 2019 in the Netherlands. Baseline characteristics, surgical and non-surgical complications, readmission, and short-term mortality were collected from the Dutch Colorectal Audit (DCRA). The cohort was stratified by 70-79, 80-89, and ≥ 90 years. Comorbidity prevalence and postoperative outcomes were determined per age group. We analyzed the interaction (age-group*comorbidity) with all outcomes using multivariate logistic regression analysis. Age-stratified analysis was indicated if the interaction was significant. RESULTS: We included 25,727 patients of 70-79 years, 12,198 patients of 80-89 years, and 713 of ≥90 years. Non-surgical complications and mortality increased with older age, while surgical complications significantly decreased. However, the association of a Charlson Comorbidity Index (CCI) score ≥ 3, cardiovascular, and cardiopulmonary disease with adverse postoperative outcome decreased with older age. For example, the odds ratio (OR) of a CCI score ≥ 3 for non-surgical complications was 1.79 (confidence interval [CI] 95% 1.66-1.94), 1.50 (CI 95% 1.36-1.65), and 1.21 (CI 95% 0.80-1.81) for, respectively, 70-79, 80-89, and ≥ 90 years. DISCUSSION: The rate of non-surgical complications after CRC surgery increased with older age, although older age itself became less associated with comorbidity. Perhaps risk assessment in the oldest patients should shift towards other predictors, such as frailty.