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BACKGROUND: Post-treatment evaluation of patients with rectal cancer (RC) using magnetic resonance imaging (MRI) burdens medical resources, necessitating an exploration of abbreviated protocols. PURPOSE: To evaluate the diagnostic performance of abbreviated MRI (A-MRI) for the post-treatment evaluation of RC patients. MATERIAL AND METHODS: This retrospective study included RC patients who underwent non-contrast rectal MRI and standard liver MRI, as well as abdominal contrast-enhanced computed tomography (CECT) for post-treatment evaluation. A-MRI comprised diffusion-weighted imaging (DWI) and T2-weighted imaging of the upper abdomen and the pelvic cavity. Three radiologists independently reviewed A-MRI, CECT, and standard liver MRI in the detection of viable disease. The diagnostic performances were compared using a reference standard considering all available information, including pathology, FDG-PET, endoscopic results, and clinical follow-up. RESULTS: We included 78 patients (50 men, 28 women; mean age=60.9 ± 10.2 years) and observed viable disease in 34 (43.6%). On a per-patient-basis analysis, A-MRI showed significantly higher sensitivity (95% vs. 81%, P = 0.04) and higher accuracy (93% vs. 82%, P < 0.01), compared to those of CECT, while A-MRI showed comparable sensitivity (91% vs. 91%, P = 0.42) and accuracy (97% vs. 98%, P = 0.06) to that of standard liver MRI. On a per-lesion-based analysis, A-MRI exhibited significantly superior lesion detectability than that of CECT (figure of merit 0.91 vs. 0.77, P < 0.01) and comparable to that of standard liver MRI (figure of merit 0.91 vs. 0.92, P = 0.75). CONCLUSION: A-MRI exhibited higher sensitivity and diagnostic accuracy than those of CECT in the post-treatment evaluation of RC, while it showed comparable performances with standard liver MRI. A-MRI provides diagnostic added value in the follow-up of RC patients.
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Imagen por Resonancia Magnética , Neoplasias del Recto , Sensibilidad y Especificidad , Humanos , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/terapia , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X/métodos , Medios de Contraste , Anciano , Reproducibilidad de los Resultados , Recto/diagnóstico por imagenRESUMEN
BACKGROUND: The antitumor effects of natural killer cells, helper T cells, and cytotoxic T cells after cancer surgery were reported previously. This study hypothesized that propofol-based anesthesia would have fewer harmful effects on immune cells than volatile anesthetics-based anesthesia during colorectal cancer surgery. METHODS: In total, 153 patients undergoing colorectal cancer surgery were randomized and included in the analysis. The primary outcome was the fraction of circulating natural killer cells over time in the propofol and sevoflurane groups. The fractions of circulating natural killer, type 1, type 17 helper T cells, and cytotoxic T cells were investigated. The fractions of CD39 and CD73 expressions on circulating regulatory T cells were investigated, along with the proportions of circulating neutrophils, lymphocytes, and monocytes. RESULTS: The fraction of circulating natural killer cells was not significantly different between the propofol and sevoflurane groups until 24 h postoperatively (20.4 ± 13.4% vs. 20.8 ± 11.3%, 17.9 ± 12.7% vs. 20.7 ± 11.9%, and 18.6 ± 11.6% vs. 21.3 ± 10.8% before anesthesia and after 1 and 24 h after anesthesia, respectively; difference [95% CI], -0.3 [-4.3 to 3.6], -2.8 [-6.8 to 1.1], and -2.6 [-6.2 to 1.0]; P = 0.863, P = 0.136, and P = 0.151 before anesthesia and after 1 and 24 h, respectively). The fractions of circulating type 1 and type 17 helper T cells, cytotoxic T cells, and CD39+ and CD73+ circulating regulatory T cells were not significantly different between the two groups. The neutrophil to lymphocyte ratio in both groups remained within the normal range and was not different between the groups. CONCLUSIONS: Propofol-based anesthesia was not superior to sevoflurane-based anesthesia in terms of alleviating suppression of immune cells including natural killer cells and T lymphocytes during colorectal cancer surgery.
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Anestésicos por Inhalación/farmacología , Anestésicos Intravenosos/farmacología , Neoplasias Colorrectales/cirugía , Propofol/farmacología , Sevoflurano/farmacología , Linfocitos T Reguladores/inmunología , Adulto , Anestésicos por Inhalación/inmunología , Anestésicos Intravenosos/inmunología , Neoplasias Colorrectales/inmunología , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Propofol/inmunología , Estudios Prospectivos , Sevoflurano/inmunología , Linfocitos T Reguladores/efectos de los fármacosRESUMEN
The comparison of the genetic profiles between primary and metastatic colorectal cancer (CRC) is needed to enable the discovery of useful therapeutic targets against metastatic CRCs. We performed the targeted next generation sequencing assay of 170 cancer-associated genes for 142 metastatic CRCs, including 95 pairs of primary and metastatic CRCs, to reveal their genomic characteristics and to assess the genetic heterogeneity. The most frequently mutated gene in primary and metastatic CRCs was APC (71% vs. 65%), TP53 (54% vs. 57%), KRAS (45% vs. 44%), PIK3CA (16% vs. 19%), SMAD4 (15% vs. 14%) and FBXW7 (11% vs. 11%). The concordance in the top six frequently mutated genes was 85%, on average. The overall mutation frequencies were consistent with two sets of public data (TCGA and MSKCC). To the author's knowledge, this is the first study to compare the genetic profiles of our cohort with that of the metastatic CRCs from MSKCC. Comparative sequencing analysis between primary and metastatic CRCs revealed a high degree of genetic concordance in the current clinically actionable genes. Therefore, the genetic investigation of archived primary tumor samples with the challenges of obtaining an adequate sample from metastatic sites appears to be sufficient for the application of cancer precision medicine in the metastatic setting.
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Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Proteína de la Poliposis Adenomatosa del Colon/genética , Anciano , Fosfatidilinositol 3-Quinasa Clase I/genética , Estudios de Cohortes , Bases de Datos Genéticas , Proteína 7 que Contiene Repeticiones F-Box-WD/genética , Femenino , Perfil Genético , Genómica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Mutación , Clasificación del Tumor , Metástasis de la Neoplasia/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteína Smad4/genética , Proteína p53 Supresora de Tumor/genéticaRESUMEN
OBJECTIVE: There is limited evidence on the interaction by alcohol dehydrogenase 2 (ADH1B) (rs1229984) and aldehyde dehydrogenase 2 (ALDH2) (rs671) regarding the associations of alcohol and a methyl diet (low folate and high alcohol intake) with cancer risk, partly because of rare polymorphisms in Western populations. DESIGN: In a case-control study, we estimated the ORs and 95 % CIs to evaluate the associations of ADH1B and ALDH2 genotypes with colorectal cancer (CRC) and the joint association between methyl diets and ADH1B and ALDH2 polymorphisms with CRC risk using logistic regression models. SETTING: A hospital-based case-control study. PARTICIPANTS: In total, 1001 CRC cases and 899 cancer-free controls admitted to two university hospitals. RESULTS: We found that alcohol intake increased the risk of CRC; OR (95 % CI) was 2·02 (1·41, 2·87) for ≥60 g/d drinkers compared with non-drinkers (Ptrend < 0·001). The associations for two polymorphisms with CRC were not statistically significant. However, we found a potential interaction of ALDH2 with methyl diets and CRC. We observed a 9·08-fold (95 % CI 1·93, 42·60) higher risk of CRC for low-methyl diets compared with high-methyl diets among individuals with an A allele of ALDH2, but the association was not apparent among those with ALDH2 GG (Pinteraction = 0·02). CONCLUSIONS: Our data support the evidence that gene-methyl diet interactions may be involved in CRC risk in East Asian populations, showing that a low-methyl diet increased the risk of CRC among individuals with an A allele of ALDH2.
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In patients with colorectal cancer (CRC), the BRAF V600E mutation has been reported to be associated with several clinicopathological features and poor survival. However, the prognostic implications of BRAF V600E mutation and the associated clinicopathological characteristics in CRCs remain controversial. Therefore, we reviewed various clinicopathological features, including BRAF status, in 349 primary CRCs and analyzed the relationship between BRAF status and various clinicopathological factors, including overall survival. Similar to previous studies conducted in Eastern countries, the incidence of the BRAF V600E mutation in the current study was relatively low (5.7%). BRAF-mutated CRC exhibits distinct clinicopathological features from wild-type BRAF-expressing cancer independent of the microsatellite instability (MSI) status. This mutation was significantly associated with a proximal tumor location (P = 0.002); mucinous, signet ring cell, and serrated tumor components (P < 0.001, P = 0.003, and P = 0.008, respectively); lymphovascular invasion (P = 0.004); a peritumoral lymphoid reaction (P = 0.009); tumor budding (P = 0.046); and peritoneal seeding (P = 0.012). In conclusion, the incidence of the BRAF V600E mutation was relatively low in this study. BRAF-mutated CRCs exhibited some clinicopathological features which were also frequently observed in MSI-H CRCs, such as a proximal location; mucinous, signet ring cell, and serrated components; and marked peritumoral lymphoid reactions.
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Neoplasias Colorrectales/patología , Inestabilidad de Microsatélites , Proteínas Proto-Oncogénicas B-raf/genética , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/mortalidad , Receptores ErbB/metabolismo , Femenino , Fluorouracilo/uso terapéutico , Humanos , Inmunoquímica , Estimación de Kaplan-Meier , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mutación , Compuestos Organoplatinos/uso terapéutico , Pronóstico , Modelos de Riesgos Proporcionales , Proteínas Proto-Oncogénicas B-raf/metabolismo , Análisis de Supervivencia , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Purpose: TNM stage I colorectal cancer (CRC) can recur, although the recurrence rate is low. Few studies have evaluated the risk factors for TNM stage I CRC recurrence. This study aimed to evaluate the TNM stage I CRC recurrence rate, as well as risk factors for recurrence. Methods: In this retrospective study, we reviewed the database of patients who had undergone surgery for TNM stage I CRC between November 2008 and December 2014 without receiving neoadjuvant therapy or transanal excision for rectal cancer. Our analysis included 173 patients. Primary lesions were found in the colon of 133 patients and in the rectum of 40 patients. Results: The CRC recurrence rate was 2.9% (5 out of 173 patients). For colon cancer patients, tumor size was not associated with higher recurrence risk (P = 0.098). However, for rectal cancer patients, both tumor size (≥3 cm) and T stage were associated with higher recurrence risk (P = 0.046 and P = 0.046, respectively). Of the 5 recurrent cases, 1 patient exhibited disease progression despite treatment, 1 patient maintained stable disease status after recurrence treatment, and 3 patients had no evidence of a tumor after recurrence treatment. Conclusion: Our findings suggest that tumor size and T stage are predictors of stage I rectal cancer recurrence, and careful monitoring and follow-up of patients with larger tumors may be warranted.
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BACKGROUND AND OBJECTIVES: Colorectal tumors are often observed with tumor infiltrating lymphocytes, presumably as a host-immune response, and patterns may segregate by types of genomic instability. Microsatellite unstable (MSI) colorectal cancers contain a pronounced lymphocyte reaction that can pathologically identify these tumors. Colorectal tumors with elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) have not been examined for lymphocyte patterns. METHODS: We evaluated a 108-person cohort with 24 adenomas and 84 colorectal cancers for MSI and EMAST. Immunohistochemical detection of CD4+ and CD8+ T cell infiltration were performed. Prognostic relevance was assessed by survival analysis. RESULTS: CD8+ T cell infiltration in the tumor cell nest (p = 0.013) and tumor stroma (p = 0.004) were more prominent in moderately and poorly differentiated adenocarcinoma than in adenoma and well-differentiated adenocarcinoma. CD8+ T cells in the tumor cell nest (p = 0.002) and tumor stroma (p = 0.009) were at higher density in tumors with ulcerating features compared to tumors with a sessile or polypoid appearance. MSI-H tumors showed a higher density of CD8+ T cell infiltrations in tumor cell nests (p = 0.003) and tumor stroma (p = 0.001). EMAST-positive tumors showed a higher density of CD8+ T cell infiltrations than EMAST-negative tumors both in tumor cell nest (p = 0.027) and in tumor stroma (p = 0.003). These changes were not observed with CD4+ T lymphocytes. There was no difference in cancer patient survival based on density of CD8+ cells. CONCLUSIONS: CD8+ T lymphocytes, but not CD4+ cells, were increased in tumor cell nests and the tumor stroma in both MSI and EMAST tumors, and showed higher infiltration in ulcerated tumors. CD8+ T lymphocyte infiltration is associated with both EMAST and MSI patterns, and increases with histological advancement.
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Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Linfocitos Infiltrantes de Tumor/patología , Inestabilidad de Microsatélites , Repeticiones de Microsatélite/genética , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenoma/genética , Adenoma/patología , Relación CD4-CD8 , Linfocitos T CD4-Positivos/patología , Linfocitos T CD8-positivos/patología , Diferenciación Celular , Estudios de Cohortes , Humanos , Estudios RetrospectivosRESUMEN
BACKGROUND: An objective method for determining the location of the cancer with respect to peritoneal reflection would be helpful to decide the treatment modality for rectal cancer. This study was designed to evaluate the accuracy and usefulness of rectal MRI to determine spatial relations between the peritoneal reflection and rectal cancer and to compare these with operative findings. PATIENTS AND METHODS: Patients that underwent a rectal cancer operation after a rectal MRI check between November 2008 and June 2010 were considered for the study. The patients that received preoperative concurrent chemoradiation or trans-anal local excision were excluded. RESULTS: Fifty-four patients constituted the study cohort. By comparing surgical and radiologic findings, the accuracy for predicting tumour location in relation to the peritoneal reflection by rectal MRI in all patients was 90.7%. In terms of tumour location in relation to peritoneal reflection, the accuracy of rectal MRI was 93.5% in patients with a tumour located above the peritoneal reflection, 90.0% in patients with a tumour located on the peritoneal reflection, and 84.6% in patients with a tumour located below the peritoneal reflection (p=0.061). When the cohort was subdivided by gender, body mass index (BMI), operative findings, or tumour size, no significant difference was observed among subgroups. CONCLUSIONS: Rectal MRI could be a useful tool for evaluating the relation between rectal cancer and peritoneal reflection especially when tumour size is less than 8cm. Rectal MRI can provide information regarding the location of rectal cancer in relation to the peritoneal reflection for treatment planning purposes.
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BACKGROUND & AIMS: Elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) occurs during microsatellite instability (MSI) that is not associated with major defects in DNA mismatch repair (MMR) but rather the reduced (heterogenous) expression of the MMR protein hMSH3; it occurs in sporadic colorectal tumors. We examined the timing of development of EMAST during progression of colorectal neoplasias and looked for correlations between EMAST and clinical and pathology features of tumors. METHODS: We evaluated tumor samples from a cohort of patients that had 24 adenomas and 84 colorectal cancers. EMAST were analyzed after DNA microdissection of matched normal and tumor samples using the polymorphic tetranucleotide microsatellite markers MYCL1, D9S242, D20S85, D8S321, and D20S82; data were compared with clinical and pathology findings. Traditional MSI analysis was performed and hMSH3 expression was measured. RESULTS: Moderately differentiated adenocarcinomas and poorly differentiated adenocarcinomas had higher frequencies of EMAST (56.9% and 40.0%, respectively) than well-differentiated adenocarcinomas (12.5%) or adenomas (33.3%) (P = .040). In endoscopic analysis, ulcerated tumors had a higher frequency of EMAST (52.3%) than flat (44.0%) or protruded tumors (20.0%) (P = .049). In quantification, all tumors with >3 tetranucleotide defects lost MSH3 (>75% of cells); nuclear heterogeneity of hMSH3 occurred more frequently in EMAST-positive (40.0%) than in EMAST-negative tumors (13.2%) (P = .010). CONCLUSIONS: EMAST is acquired during progression of adenoma and well-differentiated carcinomas to moderately and poorly differentiated carcinomas; it correlates with nuclear heterogeneity for hMSH3. Loss of hMSH3 corresponds with multiple tetranucleotide frameshifts. The association between EMAST and ulcerated tumors might result from increased inflammation.
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Neoplasias Colorrectales/genética , ADN de Neoplasias/genética , Proteínas de Unión al ADN/genética , Regulación Neoplásica de la Expresión Génica , Repeticiones de Microsatélite/genética , Disparidad de Par Base , Colonoscopía , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Proteínas de Unión al ADN/metabolismo , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Proteína 3 Homóloga de MutS , Reacción en Cadena de la PolimerasaRESUMEN
PURPOSE: We aimed to investigate whether adjuvant oxaliplatin-based chemotherapy after treatment for hepatic metastasis affects recurrence or survival and to determine the risk factors for recurrence or survival. METHODS: Forty-six patients who underwent curative treatment for hepatic metastasis from colorectal cancer between July 2009 and December 2017 were included from a retrospectively collected patient database. Curative resection included hepatic resection, radiofrequency ablation (RFA), or a combination of both, followed by adjuvant chemotherapy with oxaliplatin-based chemotherapy. RESULTS: Thirty-seven patients (80.4%) had colon cancer and 9 (19.6%) had rectal cancer. Twenty-six patients (56.5%) underwent hepatic resection, 7 (15.2%) RFA, and 13 (28.3%) hepatic resection and RFA. Thirty-two patients (69.6%) underwent chemotherapy after hepatic treatment. The recurrence incidence was 50% in the non-chemotherapy group and 46.9% in the chemotherapy group (P > 0.999). The incidence of death was 7.1% in the non-chemotherapy group and 18.8% in the chemotherapy group (P = 0.657). The recurrence risk factors were N stage (N0 vs. N2; P = 0.013, P = 0.005) and bilobed hepatic metastasis (P = 0.027, P = 0.009) in the univariate and multivariate analyses, respectively. However, chemotherapy after hepatic treatment was not a risk factor for disease-free survival (DFS) or overall survival (OS) in the univariate and multivariate analyses (P = 0.656 and P = 0.414, respectively; P = 0.510 and P = 0.459, respectively). CONCLUSION: Oxaliplatin-based adjuvant chemotherapy after colorectal hepatic metastasis treatment did not affect the DFS or OS. The N stage of the primary tumor and bilobed hepatic metastasis are risk factors for recurrence and death.
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KRAS mutation is frequently identified in advanced colorectal carcinoma (CRC); however, its prognostic significance and the associated histological features have remained to be clarified. In the present study, the precise histological results and prognostic value of KRAS-mutated CRCs were investigated in patients from South Korea. A retrospective review of the results from KRAS mutation testing, as well as evaluation of the histology of 310 cases of CRC at various stages, were performed. Cross-tabulation and survival analysis were performed according to the KRAS status. Patients with KRAS mutation more frequently exhibited serrated and papillary architectures (P=0.009 and P=0.014, respectively). KRAS mutation was an independent unfavorable prognostic factor for overall survival (OS) according to multivariate analysis (P=0.001), whereas no association was observed with disease-free survival (DFS) (P=0.611). Of note, in the subgroup of KRAS-mutated carcinomas, the presence of a solid component on histology was associated with less favorable OS (P=0.032). Furthermore, among the wild type cases, patients with a micropapillary component had a worse OS than those who did not (P=0.018). However, no subgroup or specific histological features were associated with DFS. In summary, KRAS-mutated CRCs had a moderate association with particular histological features, and according to the KRAS mutational status, there was a certain degree of association between histology and prognosis.
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INTRODUCTION: Periorbital metastasis of colorectal cancer is rare. Therefore, herein, we report a patient with rectal cancer who presented with periorbital metastasis without any systemic metastasis. PATIENT CONCERNS: The patient was a 57-year-old man who had a painless nodule on his left eyelid. DIAGNOSIS: The patient presented with loose and frequent stools and was diagnosed with rectal adenocarcinoma via colonoscopic biopsy at the local clinic. Curative resection (low anterior resection with temporary ileostomy formation) was performed 4 weeks after completing chemoradiotherapy. The final TNM stage was yp stage T2N0M0. Eight months after the diagnosis of rectal cancer, a protruding lesion was noticed on the patient's left eyelid. Histologic evaluation of the nodule revealed metastatic adenocarcinoma of rectal cancer. INTERVENTIONS: The patient received neoadjuvant chemoradiotherapy and curative resection for rectal cancer. After excision of the periorbital nodule, he received 5 cycles of chemotherapy. OUTCOMES: The patient underwent regular follow-up because he was not able to endure chemotherapy; no recurrence has been observed 21 months after the diagnosis of rectal cancer. Histologic examination revealed metastatic adenocarcinoma of rectal cancer on the patient's left eyelid. However, consecutive imaging studies revealed no other metastatic lesions. Finally, the patient was diagnosed with a solitary periorbital metastasis of rectal cancer. CONCLUSION: This case report helps in understanding the course of progression from rectal cancer to periorbital metastasis.
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Adenocarcinoma/patología , Neoplasias Orbitales/secundario , Neoplasias del Recto/patología , Adenocarcinoma/diagnóstico , Adenocarcinoma/terapia , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Orbitales/patología , Neoplasias Orbitales/terapia , Neoplasias del Recto/diagnóstico , Neoplasias del Recto/terapiaRESUMEN
: Human embryonic carcinoma (EC; NCCIT) cells have self-renewal ability and pluripotency. Cancer stem cell markers are highly expressed in NCCIT cells, imparting them with the pluripotent nature to differentiate into other cancer types, including breast cancer. As one of the main cancer stem cell pathways, Wnt/ß-catenin is also overexpressed in NCCIT cells. Thus, inhibition of these pathways defines the ability of a drug to target cancer stem cells. Tannic acid (TA) is a natural polyphenol present in foods, fruits, and vegetables that has anti-cancer activity. Through Western blotting and PCR, we demonstrate that TA inhibits cancer stem cell markers and the Wnt/ß-catenin signaling pathway in NCCIT cells and through a fluorescence-activated cell sorting analysis we demonstrated that TA induces sub-G1 cell cycle arrest and apoptosis. The mechanism underlying this is the induction of mitochondrial reactive oxygen species (ROS) (mROS), which then induce the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated extrinsic apoptosis pathway instead of intrinsic mitochondrial apoptosis pathway. Moreover, ribonucleic acid sequencing data with TA in NCCIT cells show an elevation in TRAIL-induced extrinsic apoptosis, which we confirm by Western blotting and real-time PCR. The induction of human TRAIL also proves that TA can induce extrinsic apoptosis in NCCIT cells by regulating mROS.
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Apoptosis/efectos de los fármacos , Carcinoma/metabolismo , Carcinoma/patología , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Taninos/farmacología , Adenosina Trifosfato/metabolismo , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Humanos , Mitocondrias/efectos de los fármacos , Modelos Biológicos , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Vía de Señalización Wnt/efectos de los fármacosRESUMEN
OBJECTIVE: To determine the feasibility of stereotactic body radiotherapy (SBRT) using 3 fractions for isolated colorectal lung metastases. METHODS: From June 2003 to December 2006, 13 cases of isolated pulmonary metastasis from colorectal cancer were treated by SBRT due to an inoperable state (7 patients), or the patient's refusal to undergo surgical excision (6 patients). All patients underwent chemotherapy for salvage treatment. SBRT doses ranged from 39 to 51 Gy in 3 fractions. Nine patients had a solitary lesion, 3 patients had 2 lesions, and 1 patient had 3 lesions. Median tumor volume for the 18 lesions was 5.9 ml (range 1.6-45 ml). RESULTS: Follow-up duration was 15-57 months. Three-year overall survival, local control and progression-free survival rates were 64.7, 52.7 and 11.5%, respectively.Univariate analysis showed that total internal target volume was a significant prognostic factor for local control. During the follow-up, 11 of the 13 patients experienced local recurrence, distant metastasis or both. The most frequent site of failure was in a nontargeted lung region. No severe complication was attributed to SBRT. CONCLUSION: Our study suggests the potential feasibility of SBRT for selected patients with 1-3 small metastatic nodules. A further larger-scale study is required to define the indications for SBRT in cases with isolated pulmonary metastasis from colorectal cancer.
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Neoplasias Colorrectales/patología , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Radiocirugia/métodos , Anciano , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Radiocirugia/efectos adversos , Insuficiencia del TratamientoRESUMEN
AIMS: To determine the feasibility and efficacy of 3-fraction stereotactic body radiation therapy for isolated colorectal cancer liver metastases. MATERIALS AND METHODS: Ten patients with isolated inoperable liver metastasis from colorectal cancer with progression after salvage chemotherapy underwent stereotactic body radiation therapy. Follow-up was 7-49 months (median, 12). Six patients had a solitary lesion and 4 patients had 2 lesions. Internal target volumes of metastatic liver tumors ranged from 3.4 to 271 ml. Stereotactic body radiation therapy doses ranged from 36 to 51 Gy and were administered in three fractions. All patients demonstrated disease progression despite chemotherapy prior to stereotactic body radiation therapy. RESULTS: Three-year overall survival and local control rates were 40% and 60%, respectively. Tumors with an internal target volume < 100 ml showed better local control rate than larger tumors. No severe complication was attributed to the therapy. CONCLUSION: Our study suggests the potential feasibility of stereotactic body radiation therapy for selected patients with colorectal cancer liver metastasis and no treatment option. The study showed that excellent local control was achieved in patients with a total tumor volume of < 100 ml but failed to clarify the role of stereotactic body radiation therapy for larger tumors. Further large scale studies are needed to define the indications of such therapy.
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Adenocarcinoma/cirugía , Neoplasias Colorrectales/cirugía , Neoplasias Hepáticas/cirugía , Radiocirugia/métodos , Adenocarcinoma/secundario , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Terapia Combinada , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Terapia Recuperativa/métodosRESUMEN
The association between red meat intake and colorectal cancer (CRC) may be modulated by genetic polymorphisms of cytochrome P450 2E1 (CYP2E1), a key enzyme in the metabolism of nitrosamines, and peroxisome proliferator-activated receptor gamma (PPARγ), a transcription factor involved in adipogenesis and lipid and glucose metabolism. We conducted a case-control study of 971 patients with CRC and 658 controls who were admitted to two university hospitals between 1995 and 2004 in Seoul, Korea. Participants were asked about red meat intake by using a validated food frequency questionnaire. Polymorphisms of CYP2E1 (rs3813867) and PPARγ (rs1801282 or rs3856806) were identified using the TaqMan assay. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression models. We found that the association between red meat and CRC varied by CYP2E1 polymorphisms; ORs (95% CIs) for at least five or more vs. less than one time/week of red meat intake were 2.77 (1.23-6.25) among individuals with C alleles of CYP2E1 and 0.89 (0.51-1.54) among individuals with the GG allele (Pinteraction=0.05). Compared with those individuals with the CC allele, increasing risk of CRC with increasing red meat intake was more pronounced among individuals with T alleles of PPARγC161T (rs3856806), but the association was not significant. Our data provide evidence that East Asians with the variant type of CYP2E1 may have high susceptibility to development of CRC risk.
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Neoplasias Colorrectales/epidemiología , Citocromo P-450 CYP2E1/genética , Predisposición Genética a la Enfermedad , PPAR gamma/genética , Carne Roja/efectos adversos , Adulto , Anciano , Estudios de Casos y Controles , Neoplasias Colorrectales/etiología , Encuestas sobre Dietas/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , República de Corea/epidemiología , Factores de RiesgoRESUMEN
PURPOSE: The detection rate of brain metastasis (BM) from colorectal cancer (CRC) is increasing. This study was designed to analyze the clinical features of BM and prognosis according to the therapeutic modalities. METHODS: A total of 19 cases were collected in this study between November 2008 and December 2015. We reviewed the patients' demographic data and the clinical features of BM retrospectively and investigated their prognostic significance. RESULTS: Nineteen patients included 8 male and 11 female patients. The median age at diagnosis of BM was 62.4 years (range, 32-83 years). The median interval between diagnosis of CRC and BM was 39 months (range, 0-98 months). Eighteen patients (94.7%) had extracranial metastasis at the diagnosis of BM. Lung was the most common site of extracranial metastasis in 14 patients (73.7%). Synchronous BMs were found at the diagnosis of primary CRC in 2 patients (10.5%). The location of primary CRC was the colon in 6 patients (31.6%) and the rectum in 13 patients (68.4%). At the diagnosis of BM, 10 patients (52.6%) had a solitary BM. The common neurologic symptoms were headache in 8 cases (42.1%) and ataxia in 6 cases (31.6%). The median survival after the diagnosis of BM was 3 months (range, 1-10 months). The patients who underwent surgery plus stereotactic radiosurgery (SRS) had an improved survival (range, 3-10 months) than the other patients (range, 1-6 months) (P = 0.016). CONCLUSION: In patients with BM from CRC, surgical resection plus SRS might improve survival.
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PURPOSE: Virtual colonoscopy is the most recently developed tool for detecting colorectal cancers and polyps, but its effectiveness is limited. In our study, we compared the result of preoperative virtual colonoscopy to result of preoperative and postoperative colonoscopy. We evaluated also the accuracy of preoperative virtual colonoscopy in patients who had obstructive colorectal cancer that did not allow passage of a colonoscope. METHODS: A total of 164 patients who had undergone preoperative virtual colonoscopy and curative surgery after the diagnosis of a colorectal adenocarcinoma between November 2008 and August 2013 were pooled. We compared the result of conventional colonoscopy with that of virtual colonoscopy in the nonobstructive group and the results of preoperative virtual colonoscopy with that of postoperative colonoscopy performed at 6 months after surgery in the obstructive group. RESULTS: Of the 164 patients, 108 were male and 56 were female patients. The mean age was 62.7 years. The average sensitivity, specificity, and accuracy of virtual colonoscopy for all patients were 31.0%, 67.2%, and 43.8%, respectively. In the nonobstructive group, the average sensitivity, specificity, and accuracy were 36.6%, 66.2%, and 48.0%, respectively, whereas in the obstructive group, they were 2%, 72.4%, and 25.4%. Synchronous cancer was detected via virtual colonoscopy in 4 of the 164 patients. CONCLUSION: Virtual colonoscopy may not be an effective method for the detection of proximal colon polyps, but it can be helpful in determining the therapeutic plan when its results are correlated with the results of other studies.
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We hypothesised that the blood levels of immune cells would be related to the progression of colorectal cancer and regional lymph node metastasis. We investigated the association between the blood levels of immune cells and regional lymph node metastasis in colorectal cancer patients. Patients with American Joint Committee on Cancer (AJCC) stages 1 and 2 colorectal cancer were assigned to Early stage group and those with AJCC stages 3 and 4 were assigned to Late stage group. Blood levels of circulating immune cells, such as cluster of differentiation (CD)4+ including T helper 1 (Th1) and 17 (Th17) cells, regulatory T (Treg) cells, CD8+ T cells, and natural killer (NK) cells were assessed using fluorescence-activated cell sorting (FACS). The blood levels of CD4+ T, Treg, CD8+ T, and NK cells did not significantly differ between the two groups. However, the blood levels of Th1 and Th17 cells did significantly differ between the groups. Specifically, Late stage group had higher levels of Th1 and Th17 cells than Early stage group (Th1, 11.14±1.22% vs. 16.25±1.57%, p = 0.015; Th17, 3.32±0.05% vs. 1.11±0.15%, p < 0.01). In conclusion, the blood levels of Th1 and Th17 cells significantly increased as the N stage increased. The blood levels of Th1 and Th17 cells might be useful as predictive markers of lymph node invasion in colorectal cancer.
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BACKGROUND: Correlation between colorectal cancer (CRC) and abdominal obesity has been established, but there is a paucity of data on non-obese CRC patients. The aim of this study was to establish the characteristics of CRCs that occur in such patients. MATERIALS AND METHODS: Consecutive CRC patients without cachexia were included. Unintended body weight loss, T4- or M1-staged CRCs, extensive lymph node involvement, or synchronous malignancy were classified as cachectic conditions. Abdominal fat volumes were measured using a multidetector CT unit with software (Rapidia, INFINITT, Seoul, Korea). RESULTS: Of the newly-diagnosed CRC patients, 258 non-cachectic and 88 cachectic patients were analyzed. The cancer size (p<0.001) and T stage (p<0.001) were inversely correlated with body mass index (BMI), visceral fat and subcutaneous fat volumes. Cancer size was the only independent factor related to BMI (p=0.016), visceral fat volume (p=0.002), and subcutaneous fat volume (p=0.027). In non-cachectic patients, a significant inverse correlation was found only between the cancer size and visceral fat volume (p=0.017). CONCLUSIONS: Non-obese CRC patients tend to have larger CRC lesions than their obese counterparts even under non-cachectic conditions. Such an inverse correlation between cancer size and visceral fat volume suggests that considerable CRCs are not correlated with abdominal obesity.