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1.
Mayo Clin Proc ; 97(1): 124-133, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34996545

RESUMEN

Given previous biologic evidence of immunomodulatory effects of coffee, we hypothesized that the association between coffee intake of colorectal cancer patients and survival differs by immune responses. Using a molecular pathologic epidemiology database of 4465 incident colorectal cancer cases, including 1262 cases with molecular data, in the Nurses' Health Study and the Health Professionals Follow-up Study, we examined the association between coffee intake of colorectal cancer patients and survival in strata of levels of histopathologic lymphocytic reaction and T-cell infiltrates in tumor tissue. We did not observe a significant association of coffee intake with colorectal cancer-specific mortality (multivariable-adjusted hazard ratio [HR] for 1-cup increase of coffee intake per day, 0.93; 95% CI, 0.84 to 1.03). Although statistical significance was not reached at the stringent level (α=.005), the association of coffee intake with colorectal cancer-specific mortality differed by Crohn disease-like lymphoid reaction (Pinteraction=.007). Coffee intake was associated with lower colorectal cancer-specific mortality in patients with high Crohn disease-like reaction (multivariable HR for 1-cup increase of coffee intake per day, 0.55; 95% CI, 0.37 to 0.81; Ptrend=.002) but not in patients with intermediate Crohn disease-like reaction (the corresponding HR, 1.02; 95% CI, 0.72 to 1.44) or negative/low Crohn disease-like reaction (the corresponding HR, 0.95; 95% CI, 0.83 to 1.07). The associations of coffee intake with colorectal cancer-specific mortality did not significantly differ by levels of other lymphocytic reaction or any T-cell subset (Pinteraction>.18). There is suggestive evidence for differential prognostic effects of coffee intake by Crohn disease-like lymphoid reaction in colorectal cancer.


Asunto(s)
Café , Neoplasias Colorrectales/mortalidad , Anciano , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Linfocitos T/metabolismo
2.
Comput Math Methods Med ; 2021: 1619809, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34950221

RESUMEN

OBJECTIVE: To explore the effects of Xiaoyutang combined with intraperitoneal heat perfusion chemotherapy on immune function, circulating Mir, and prognosis and survival of postoperative patients with colorectal cancer. METHODS: A total of 96 patients with colorectal cancer who were treated in our hospital from May 2018 to August 2019 and followed up to August 2021 were selected as the study subjects. The patients were randomly divided into a control group and study group by a 1 : 1 random number table method, 48 cases in each group. Patients in the control group were given intraperitoneal thermal perfusion chemotherapy after surgery, and patients in the research group were treated with Xiaoyutang on this basis. The treatment cycle was 21 days, and all patients were treated for 3 consecutive cycles. The therapeutic efficacy, immune function (CD3+, CD4+, and CD4+/CD8+), circulating mir (mir-29a, mir-145, and mir-92a), prognosis, and survival of the two groups were compared. RESULTS: After 3 cycles of treatment, ORR and DCR in the study group were higher than those in the control group (60.42% vs. 37.50%) and 85.42% vs. 66.67%, respectively, with statistical significance (P < 0.05). There were statistically significant differences in CD3+, CD4+, CD4+/CD8+, mir-29a, mir-145, and mir-92a time points and intergroup and intergroup interactions between the two groups (P < 0.05); the levels of CD3+, CD4+, and CD4+/CD8+ in the study group were higher than those in the control group after 1, 2, and 3 cycles of treatment (P < 0.05); the expressions of mir-29a, mir-145, and mir-92a were significantly lower than those in the control group (P < 0.05). By the end of follow-up, 3 cases were lost to follow-up in the study group and 5 cases in the control group. The recurrence rate and mortality of the study group were lower than those of the control group at 1- and 2-year follow-up (P > 0.05), and the mean survival time of patients in the study group was higher than that in the control group; the differences were statistically significant (χ 2 = 5.151, P = 0.023). CONCLUSION: Xiaoyutang combined with peritoneal heat perfusion chemotherapy has a good postoperative effect on patients with colorectal cancer, which can effectively improve the immune function and circulating Mir of patients with colorectal cancer, reduce tumor recurrence, and improve the prognosis of patients.


Asunto(s)
Neoplasias Colorrectales/terapia , Medicamentos Herbarios Chinos/administración & dosificación , Quimioterapia Intraperitoneal Hipertérmica , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , China/epidemiología , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/mortalidad , Terapia Combinada , Biología Computacional , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , MicroARNs/sangre , MicroARNs/genética , Persona de Mediana Edad , Periodo Posoperatorio , Pronóstico
3.
Anticancer Res ; 41(12): 5903-5912, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34848444

RESUMEN

BACKGROUND/AIM: Colorectal cancer (CRC) is a disease of poor prognosis. An advantageous connection between vitamin D supplementation and prognostic improvement was depicted in CRC patients. However, the effects of circulating vitamin D on cancer outcomes are unclear for advanced CRC patients, especially for those receiving chemotherapy. MATERIALS AND METHODS: The review was registered on PROSPERO (register number: CRD42021243547). PUBMED, EMBASE, Cochrane Library, and Web of Science were searched for English-language publications using relevant keywords. Two reviewers independently selected articles, assessed quality, and extracted data. We applied RevMan5.4 and Stata14 for meta-analysis. RESULTS: We included an RCT and three prospective cohort studies, which were of high overall quality. Higher circulating 25(OH)D level was related with better disease outcomes in advanced CRC patients undergoing chemotherapy: progression-free survival (HR=0.85, 95% CI=0.71-0.99; I2=34.4%), overall survival (OR=0.56, 95% CI=0.38-0.82; I2=0%). CONCLUSION: High circulating 25(OH)D content is beneficial for improving prognosis of advanced CRC receiving chemotherapy.


Asunto(s)
Biomarcadores/sangre , Neoplasias Colorrectales/sangre , Vitamina D/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Humanos , Metástasis de la Neoplasia , Estadificación de Neoplasias , Oportunidad Relativa , Pronóstico , Sesgo de Publicación , Resultado del Tratamiento , Vitamina D/sangre
4.
J Clin Oncol ; 39(36): 4009-4019, 2021 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-34752136

RESUMEN

PURPOSE: Early-onset (EO) colorectal cancer (CRC, age < 50 years) incidence is increasing. Decisions on optimal adjuvant therapy should consider treatment adherence, adverse events, and expected outcomes in a population with life expectancy longer than later-onset (LO) CRC (age ≥ 50 years). MATERIALS AND METHODS: Individual patient data from six trials in the International Duration Evaluation of Adjuvant Chemotherapy database were analyzed. Characteristics, treatment adherence, and adverse events in stage II or III EO-CRC and LO-CRC were compared. To reduce confounders of non-cancer-related deaths because of age or comorbidities, time to recurrence (3-year relapse-free rate) and cancer-specific survival (5-year cancer-specific mortality rate) were considered. RESULTS: Out of 16,349 patients, 1,564 (9.6%) had EO-CRC. Compared with LO-CRC, EO-CRC had better performance status (86% v 80%, P < .01), similar T stage (% T1-3/T4: 76/24 v 77/23, P = .97), higher N2 disease rate (24% v 22%, P < .01), more likely to complete the planned treatment duration (83.2% v 78.2%, P < .01), and received a higher treatment dose intensity, especially with 6-month regimens. Gastrointestinal toxicity was more common in EO-CRC; hematologic toxicity was more frequent in LO-CRC. Compared with LO-CRC, significantly worse cancer-specific outcomes were demonstrated especially in high-risk stage III EO-CRC: lower 3-year relapse-free rate (54% v 65%; hazard ratio [HR] 1.33; 95% CI, 1.14 to 1.55; P value < .001) and higher 5-year cancer-specific mortality rate (24% v 20%; HR 1.21; 95% CI, 1.00 to 1.47; P value < .06). In this subgroup, no difference was observed with 3 or 6 months of therapy, with equally poor disease-free survival rates (57% v 56%; HR 0.97; 95% CI, 0.73 to 1.29; P value = .85). CONCLUSION: Young age is negatively prognostic in high-risk stage III CRC and associated with significantly higher relapse rate; this is despite better treatment adherence and higher administered treatment intensity, suggesting more aggressive disease biology.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante/métodos , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Oxaliplatino/efectos adversos , Oxaliplatino/uso terapéutico , Adenocarcinoma/complicaciones , Adenocarcinoma/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Neoplasias Colorrectales/mortalidad , Femenino , Fluorouracilo/farmacología , Humanos , Masculino , Persona de Mediana Edad , Oxaliplatino/farmacología , Pronóstico , Tasa de Supervivencia , Factores de Tiempo
5.
Sci Rep ; 11(1): 14609, 2021 07 16.
Artículo en Inglés | MEDLINE | ID: mdl-34272423

RESUMEN

Several studies have reported that the prognostic effect of KRAS mutations on colorectal cancers (CRCs) varies depending on the type of mutation. Considering the effect of KRAS mutations on tumor microenvironment, we analyzed the prognostic significance of KRAS mutation types after adjusting for the tumor-infiltrating lymphocytes (TIL) and tumor-stromal percentage (TSP) statuses. In two independent cohorts, KRAS mutations were analyzed by Sanger sequencing and/or next-generation sequencing. TIL density and the TSP were quantified from whole-slide immunohistochemical images. KRAS-mutant CRCs were divided into three subgroups (G12D/V, other codon 12 mutations and codon 13 mutations) to examine their differential effect on TIL density, the TSP and recurrence-free survival (RFS). Among the KRAS mutations, only the G12D/V subgroups showed significantly less TIL infiltration than the wild-type CRCs. According to survival analysis, G12D/V mutations were associated with short RFS; codon 13 mutations showed discordant trends in the two cohorts, and other codon 12 mutations showed no significant association. Multivariate analysis further supported the prognostic value of G12D/V mutations. This result is not only consistent with a recent study suggesting the immunosuppressive effect of mutant KRAS but also provides insight into the type-specific prognostic effect of KRAS mutations.


Asunto(s)
Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Linfocitos Infiltrantes de Tumor/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/genética , Microambiente Tumoral , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/mortalidad , Femenino , Fluorouracilo/uso terapéutico , Humanos , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Mutación , Estadificación de Neoplasias , Compuestos Organoplatinos/uso terapéutico , Pronóstico , Análisis de Supervivencia
6.
Int J Biol Sci ; 17(4): 942-956, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33867820

RESUMEN

Colorectal cancer (CRC) is one of the most deadly malignant tumors, which seriously threatens human health. Ferroptosis, a new type of iron-dependent cell regulatory necrosis. Inducing ferroptosis of tumor cells is regarded as a potential treatment strategy. However, the prognostic value of ferroptosis-related genes in CRC remains to be further elucidated. Gallic acid, widely used in the chemical, pharmaceutical, and food fields, is a dietary supplement with potential prescription significance. In this study, the mRNA expression profiles and corresponding clinical data of CRC patients were downloaded from public databases. Gene Expression Profiling Interactive Analysis (GEPIA) was used to evaluate the expression levels of ferroptosis-related genes. In addition, bioinformatics analysis showed the prognostic value of ferroptosis-related genes in CRC. Molecular docking predicts the binding status of gallic acid and ferroptosis-related genes. The experiment confirmed the correctness of the predicted results. Our results show that in the TCGA cohort, 30 ferroptosis-related genes are differentially expressed between CRC and adjacent normal tissues. Among them, eight differentially expressed genes are related to overall survival. Gallic acid can bind to ferroptosis-related targets and regulate the expression of corresponding proteins, and ferroptosis inhibitors reversed the experimental results. In summary, eight new ferroptosis-related genes can be used to predict the prognosis of CRC. Gallic acid can improve CRC by regulating ferroptosis.


Asunto(s)
Colitis Ulcerosa/tratamiento farmacológico , Neoplasias Colorrectales/genética , Ferroptosis/efectos de los fármacos , Ácido Gálico/uso terapéutico , Animales , Estudios de Casos y Controles , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/prevención & control , Modelos Animales de Enfermedad , Ensayos de Selección de Medicamentos Antitumorales , Ferroptosis/genética , Ácido Gálico/farmacología , Perfilación de la Expresión Génica , Células HCT116 , Humanos , Simulación del Acoplamiento Molecular , Mapas de Interacción de Proteínas , Ratas
7.
Surg Oncol ; 38: 101572, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33915487

RESUMEN

INTRODUCTION: Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is offered in specialist centres as a treatment for peritoneal surface tumours. Despite its demonstrated efficacy, intra-abdominal recurrence occurs in 31-57% of patients. The aim of this study is to review the early and long-term outcomes in patients who undergo repeat CRS/HIPEC. MATERIALS AND METHODS: A retrospective review of a prospectively maintained database of patients who had undergone repeat CRS/HIPEC for appendiceal neoplasms and colorectal peritoneal metastases (CRPM) from 2003 to 2019 was performed at a single specialist centre. Data pertaining to both short term outcomes and survival were evaluated. RESULTS: Of 1259 patients who had undergone CRS/HIPEC, 84(6.7%) underwent repeat surgery: 45(53.6%) had pseudomyxoma peritonei (PMP) secondary to low grade appendiceal mucinous neoplasms (LAMN), 21(25.0%) had appendix carcinoma and 18(21.4%) had CRPM. Demographics, intra-operative findings and short-term outcomes were comparable across tumour types and between procedures. Median (95% CI) interval between procedures was 22.7(18.9-26.6) months and was comparable between tumour types. Median (95%CI) overall survival was not reached for the cohort overall or for those with PMP, but was 61.0(32.6-89.4) months for those with appendix cancer and 76.9(47.4-106.4) months for CRPM (p=<0.001). Survival was favourable in the PMP group (HR [95%CI] 0.044 [0.008-0.262]; p = 0.000) and unfavourable in the CC2-3 at index CRS procedure group (HR [95%CI] 25.612 [2.703-242.703]; p = 0.005). CONCLUSION: Our findings demonstrate that repeat cytoredutive surgery with HIPEC can result in favourable survival, especially for patients with PMP when complete cytoreduction is achieved at index operation. We recommend that detailed patient assessment is performed through an expert multidisciplinary team meeting (MDT).


Asunto(s)
Adenocarcinoma Mucinoso/mortalidad , Neoplasias del Apéndice/mortalidad , Neoplasias Colorrectales/mortalidad , Procedimientos Quirúrgicos de Citorreducción/mortalidad , Hipertermia Inducida/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Neoplasias Peritoneales/mortalidad , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Apéndice/patología , Neoplasias del Apéndice/terapia , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/terapia , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Tasa de Supervivencia
8.
Am J Clin Nutr ; 113(6): 1458-1467, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-33740035

RESUMEN

BACKGROUND: Vitamin D plays a role in detoxifying free radicals, which might explain the previously reported lower mortality in colorectal cancer (CRC) patients with higher vitamin D concentrations. OBJECTIVES: We aimed to assess whether the associations of 25-hydroxyvitamin D [25(OH)D] with prognosis in CRC patients differ by total thiol concentration (TTC), a biomarker of antioxidant capacity. METHODS: CRC patients who were diagnosed from 2003 to 2010 and recruited into a population-based study in southern Germany (n = 2,592) were followed over a period of 6 y. 25(OH)D and TTC were evaluated from blood samples collected shortly after CRC diagnosis. Associations of 25(OH)D with all-cause and CRC mortality according to TTC were estimated using multivariable Cox proportional hazards regression. RESULTS: There was a weak positive correlation between 25(OH)D and TTC (r = 0.26, P < 0.001). 25(OH)D was inversely associated with mortality among patients in the lowest and middle TTC tertiles, but no associations were found among patients in the highest TTC tertile (P-interaction = 0.01). Among patients in the lowest/middle TTC tertiles, those in the middle and highest (compared with lowest) 25(OH)D tertiles had 31% and 44% lower all-cause mortality (P < 0.001) and 25% and 45% lower CRC mortality (P < 0.001), respectively. However, in the highest TTC tertile, 25(OH)D was not associated with all-cause (P = 0.638) or CRC mortality (P = 0.395). CONCLUSIONS: The survival advantages in CRC patients with adequate vitamin D strongly depend on antioxidant capacity and are most pronounced in cases of low antioxidant capacity. These findings suggest that TTC and other biomarkers of antioxidant status may be useful as the basis for enhanced selection criteria of patients for vitamin D supplementation, in addition to the conventional judgment based on blood 25(OH)D concentrations, and also for refining selection of patients for clinical trials aiming to estimate the effect of vitamin D supplementation.


Asunto(s)
Antioxidantes/farmacología , Neoplasias Colorrectales/mortalidad , Compuestos de Sulfhidrilo/sangre , Vitamina D/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Estudios de Cohortes , Neoplasias Colorrectales/epidemiología , Suplementos Dietéticos , Femenino , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Vitamina D/sangre
9.
Oncol Rep ; 45(3): 899-910, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33650652

RESUMEN

Colorectal cancer (CRC) is the third most frequently diagnosed type of cancer worldwide. Stage II CRC accounts for ~25% all CRC cases and their management after surgical resection remains a clinical dilemma due to the lack of reliable criteria for identifying patients who may benefit from adjuvant chemotherapy. Homeodomain­interacting protein kinase 2 (HIPK2), a multifunctional kinase involved in numerous signaling pathways, serves several key roles in cell response to different types of stresses, including chemotherapy­induced genotoxic damage. In the present study, immunohistochemistry was performed for HIPK2 on a tissue microarray of primary human tumor samples from 84 patients with stage II CRC, treated (30 patients) or not treated (54 patients) with adjuvant chemotherapy, and sequenced for the TP53 gene, a key HIPK2 target in genotoxic damage response. It was observed that, regardless of the TP53 gene status, a high percentage of HIPK2+ cells was associated with therapeutic vulnerability in stage II CRC, suggesting a contribution of HIPK2 to drug­response in vivo. For the in vitro characterization, HIPK2 was depleted in human CRC cells by CRISPR/Cas9 or RNA interference. HIPK2­proficient and HIPK2­defective cells were evaluated for their response to 5­fluorouracil (5­FU) and oxaliplatin (OXA). The results revealed that HIPK2 depletion induced resistance to 5­FU and OXA, and that this resistance was not overcome by brusatol, an inhibitor of the antioxidant response regulator nuclear factor erythroid 2­related factor 2 (NRF2), which is frequently overexpressed in CRC. By contrast, cell sensitivity to 5­FU and OXA was further induced by brusatol supplementation in HIPK2­proficient cells, further supporting the contribution of HIPK2 in chemotherapy response. Overall, the present results suggested that HIPK2 may be a potential predictive marker for adjuvant­treated stage II CRC and for prospective therapy with NRF2 modulators.


Asunto(s)
Proteínas Portadoras/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Antineoplásicos/farmacología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Proteínas Portadoras/genética , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Quimioterapia Adyuvante , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Fluorouracilo/farmacología , Humanos , Factor 2 Relacionado con NF-E2/antagonistas & inhibidores , Factor 2 Relacionado con NF-E2/metabolismo , Estadificación de Neoplasias , Oxaliplatino/farmacología , Proteínas Serina-Treonina Quinasas/genética , Cuassinas/farmacología , Cuassinas/uso terapéutico , Análisis de Supervivencia , Proteína p53 Supresora de Tumor/genética
10.
BMC Cancer ; 21(1): 41, 2021 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-33413223

RESUMEN

BACKGROUND: This study aimed to evaluate the impact of postoperative complications on long-term survival in patients with peritoneal metastasis (PM) arising from colorectal cancer (CRC) treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: Patients with PM arising from CRC treated with CRS and HIPEC were systematically reviewed at the China National Cancer Center and Huanxing Cancer Hospital from June 2017 to June 2019. High-grade complications that occurred within 30 days were defined as grade 3 to 4 events according to the Common Terminology Criteria for Adverse Events (CTCAE) classification. Univariate and multivariable Cox regression models for overall survival were created. Predictors of high-grade postoperative complications were evaluated with univariate and multivariate logistic regression analyses. RESULTS: In all, 86 consecutive cases were included in this study. Forty-one patients (47.7%) developed postoperative complications, while 22 patients (25.6%) experienced high-grade complications. No mortality occurred during the postoperative period. The median survival of all patients was 25 months, and the estimated 3-year overall survival (OS) rate was 35.0%. In the multivariable Cox regression analysis, a high peritoneal carcinomatosis index (PCI) score (HR, 1.07, 95% CI, 1.01-1.14; P=0.015) and grade 3-4 postoperative complications (HR, 1.86, 95% CI, 1.22-3.51; P=0.044) correlated with worse overall survival. High estimated blood loss (OR, 1.01, 95% CI, 1.01-1.02; P< 0.001) was identified as an independent risk factor for developing high-grade complications. CONCLUSION: Careful patient selection, high levels of technical skill and improved perioperative management are crucial to ensure patient survival benefits after CRS+HIPEC.


Asunto(s)
Quimioterapia del Cáncer por Perfusión Regional/mortalidad , Neoplasias Colorrectales/mortalidad , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Hipertermia Inducida/mortalidad , Quimioterapia Intraperitoneal Hipertérmica/mortalidad , Neoplasias Peritoneales/mortalidad , Complicaciones Posoperatorias/mortalidad , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/terapia , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/patología , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia
11.
Clin Colorectal Cancer ; 20(1): 72-78, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33436306

RESUMEN

BACKGROUND: MAP2K1 mutations, otherwise known as MEK mutations, are rare oncogenic alterations that have been implicated in MAPK pathway activation. The impact of MAP2K1 mutations in colorectal cancer on EGFR antibody response has not been characterized. PATIENTS AND METHODS: Antitumor activity was assessed in mouse xenograft models with SW48 cell lines harboring MAP2K1 mutation, and protein expression of the RAS signaling pathway was studied by Western blot analysis. We retrospectively identified patients with MAP2K1-mutated metastatic colorectal cancer patients treated at City of Hope Comprehensive Cancer Center between 2015 and 2020 using next-generation sequencing. Patients' tumor characteristics, treatment response, and outcome are described. Additional patients with the MAP2K1 mutation were identified from The Cancer Genome Atlas and Memorial Sloan Kettering Cancer Center oncogenomic databases. RESULTS: Antitumor activity in mouse xenograft models demonstrated efficacy with combination therapy with EGFR and MEK inhibition with either BRAF or ERK inhibitors. Five patients treated at City of Hope between 2015 and 2020 harbored a MAP2K1 mutation at a frequency of 1%. APC and TP53 were common coalterations. All disease was RAS and BRAF wild type, except 1 case that harbored a concurrent KRAS mutation. Four RAS/BRAF wild-type MAP2K1-mutated patients was treated with anti-EGFR, anti-EGFR + MEK and BRAF inhibitors, and anti-EGFR + ERK inhibitors. All 4 patients experienced disease progression. CONCLUSION: MAP2K1 mutation in colorectal cancer is associated with poor response to EGFR inhibition. EGFR inhibition with or without MEK, BRAF, or ERK inhibitors did not result in any clinical benefit in our limited experience.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Resistencia a Antineoplásicos/genética , MAP Quinasa Quinasa 1/genética , Anciano , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Línea Celular Tumoral , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Receptores ErbB/antagonistas & inhibidores , Femenino , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones , Persona de Mediana Edad , Mutación , Supervivencia sin Progresión , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Estudios Retrospectivos , Ensayos Antitumor por Modelo de Xenoinjerto
12.
J Gastrointest Cancer ; 52(1): 169-176, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32086781

RESUMEN

PURPOSE: Resection of liver-only colorectal liver metastases (CRLM) with perioperative chemotherapy is potentially curative. Specific primary tumor and liver metastasis characteristics have been validated to estimate the risk of recurrence. We hypothesize that the time interval from diagnosis of CRLM to surgery, or time to surgery (TTS), is clinically prognostic. METHODS: Patients from a prospectively maintained institutional database at a Comprehensive Cancer Center from May 2003 to January 2018 were reviewed. Clinicopathologic, perioperative treatment, and TTS data were collected. TTS was categorized into short (< 3 months), intermediate (3-6 months), and long (> 6 months) intervals. RESULTS: Two hundred eighty-one patients were identified. While overall survival (OS) was similar across TTS, postoperative overall survival (postoperative OS) of long TTS was associated with worse survival, 44 months (95% CI, 34-52) compared to short TTS, 59 months (95% CI, 43-79), and intermediate TTS, 63 months (95% CI, 52-108), both p < 0.01. With regard to long-term OS, intermediate TTS had 5-year OS of 59% and 8-year OS of 43% compared to long TTS (5-year OS 53% and 8-year OS 18%) and short TTS (5-year OS 54% and 8-year OS 29%). Long TTS was negatively associated with postoperative OS on multivariate analysis (HR 1.6, p < 0.01) when adjusting for resection margin, CRLM size, age, and use of postoperative chemotherapy. CONCLUSION: Short and intermediate TTS had similar survival although patients with intermediate TTS may have better odds of long-term OS. While long TTS was associated with worse survival, likely due to higher disease burden, long-term survivors were still observed.


Asunto(s)
Neoplasias Colorrectales/terapia , Hepatectomía/estadística & datos numéricos , Neoplasias Hepáticas/terapia , Recurrencia Local de Neoplasia/epidemiología , Tiempo de Tratamiento/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia Adyuvante/métodos , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Recurrencia Local de Neoplasia/prevención & control , Pronóstico , Estudios Retrospectivos , Factores de Tiempo , Adulto Joven
13.
Oncol Res ; 28(7): 701-714, 2021 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-32859280

RESUMEN

This study evaluated the survival effects of metronomic maintenance therapy with oral fluoropyrimidine in patients with stage III colorectal cancer (CRC) according to epidermal growth factor receptor (EGFR) expression. We enrolled 197 patients with stage III CRC who had undergone radical resection and FOLFOX regimen adjuvant chemotherapy. The clinicopathological features and effects of metronomic maintenance therapy with oral capecitabine (daily dose of 850 mg/m², twice daily, on days 114 every 3 weeks for 6 months) on survival according to treatment group and EGFR expression were analyzed. By conducting an in vitro cell line study and in vivo study through knockout of the EGFR gene, we analyzed the capacities of cell proliferation and migration. Relapse and survival were significantly more common in the FOLFOX group. Metronomic maintenance therapy was a significantly independent associated factor of relapse and survival as well as a prognostic factor of disease-free survival and overall survival. Significant intergroup differences in survival were only observed in patients with positive EGFR expression. Thus, our findings suggest EGFR expression is a prognostic factor in patients with stage III CRC receiving metronomic maintenance therapy. Analysis of EGFR expression in these patients helps identify potential candidates who may receive the optimal survival benefit from metronomic maintenance therapy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Capecitabina/administración & dosificación , Neoplasias Colorrectales/genética , Oxaliplatino/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Células CACO-2 , Capecitabina/farmacología , Proliferación Celular/efectos de los fármacos , Quimioterapia Adyuvante/métodos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/cirugía , Supervivencia sin Enfermedad , Receptores ErbB/genética , Receptores ErbB/metabolismo , Femenino , Fluorouracilo/administración & dosificación , Expresión Génica , Genes erbB-1 , Humanos , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias/métodos , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino/farmacología , Pronóstico , Análisis de Supervivencia
14.
Asian J Surg ; 44(1): 221-228, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32605790

RESUMEN

INTRODUCTION: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly used to treat peritoneal metastases from appendiceal or colorectal origin. We evaluate our institution's experience and survival outcomes with this procedure, and its efficacy in symptom relief. METHODS: This is a single-centre retrospective observational study on patients with peritoneal metastases (PM) from appendiceal neoplasm or colorectal cancer who underwent CRS/HIPEC in Queen Mary Hospital. Our primary endpoints were overall survival (OS) and morbidity and mortality of this procedure; secondary endpoints included disease-free survival (DFS) and symptom-free survival. RESULTS: Between 2006 and 2018, thirty CRS/HIPEC procedures were performed for 28 patients - 17 (60.7%) had appendiceal PM while 11 (39.9%) had colorectal PM. The median peritoneal cancer index was 20; complete cytoreduction was achieved in 83.3% patients. High-grade morbidity occurred in 13.3% cases. There was no 30-day mortality. Two-year OS were 71.6% and 50% for low-grade appendiceal PM and colorectal PM patients (p = 0.20). Complete cytoreduction improved OS (2-year OS 75.4% vs 20%, p = 0.04). Median DFS was 11.8 months. Median symptom-free duration was 36.8 months; patients with complete cytoreduction were more likely to remain asymptomatic (82.9% at 1 year, vs 60% in incomplete cytoreduction group, p < 0.01). 91.7% low-grade appendiceal PM patients and 58.4% colorectal PM patients remained asymptomatic at post-operative one year (p = 0.31). CONCLUSION: CRS/HIPEC is beneficial to appendiceal PM and selected colorectal PM patients - improving survival and offering prolonged symptom relief, with reasonable morbidity and mortality. Complete cytoreduction is key to realising this benefit.


Asunto(s)
Antineoplásicos/administración & dosificación , Neoplasias del Apéndice/secundario , Neoplasias del Apéndice/terapia , Neoplasias Colorrectales/terapia , Procedimientos Quirúrgicos de Citorreducción/métodos , Quimioterapia/métodos , Hipertermia Inducida/métodos , Infusiones Parenterales/métodos , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/terapia , Adulto , Anciano , Neoplasias del Apéndice/mortalidad , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Femenino , Hong Kong/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Peritoneales/mortalidad , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento
15.
Clin Cancer Res ; 27(1): 288-300, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-33028592

RESUMEN

PURPOSE: The DNA damage immune response (DDIR) assay was developed in breast cancer based on biology associated with deficiencies in homologous recombination and Fanconi anemia pathways. A positive DDIR call identifies patients likely to respond to platinum-based chemotherapies in breast and esophageal cancers. In colorectal cancer, there is currently no biomarker to predict response to oxaliplatin. We tested the ability of the DDIR assay to predict response to oxaliplatin-based chemotherapy in colorectal cancer and characterized the biology in DDIR-positive colorectal cancer. EXPERIMENTAL DESIGN: Samples and clinical data were assessed according to DDIR status from patients who received either 5-fluorouracil (5-FU) or 5FUFA (bolus and infusion 5-FU with folinic acid) plus oxaliplatin (FOLFOX) within the FOCUS trial (n = 361, stage IV), or neoadjuvant FOLFOX in the FOxTROT trial (n = 97, stage II/III). Whole transcriptome, mutation, and IHC data of these samples were used to interrogate the biology of DDIR in colorectal cancer. RESULTS: Contrary to our hypothesis, DDIR-negative patients displayed a trend toward improved outcome for oxaliplatin-based chemotherapy compared with DDIR-positive patients. DDIR positivity was associated with microsatellite instability (MSI) and colorectal molecular subtype 1. Refinement of the DDIR signature, based on overlapping IFN-related chemokine signaling associated with DDIR positivity across colorectal cancer and breast cancer cohorts, further confirmed that the DDIR assay did not have predictive value for oxaliplatin-based chemotherapy in colorectal cancer. CONCLUSIONS: DDIR positivity does not predict improved response following oxaliplatin treatment in colorectal cancer. However, data presented here suggest the potential of the DDIR assay in identifying immune-rich tumors that may benefit from immune checkpoint blockade, beyond current use of MSI status.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Bioensayo/métodos , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/terapia , Daño del ADN/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante/métodos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/mortalidad , Daño del ADN/efectos de los fármacos , Análisis Mutacional de ADN , Femenino , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Perfilación de la Expresión Génica , Humanos , Leucovorina/farmacología , Leucovorina/uso terapéutico , Masculino , Inestabilidad de Microsatélites , Persona de Mediana Edad , Mutación , Terapia Neoadyuvante/métodos , Compuestos Organoplatinos/farmacología , Compuestos Organoplatinos/uso terapéutico , Supervivencia sin Progresión , Ensayos Clínicos Controlados Aleatorios como Asunto
16.
Int J Biol Macromol ; 167: 1349-1360, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33202274

RESUMEN

Large intestine cancer is one of the most relevant chronic diseases taking place at present. Despite therapies have evolved very positively, this pathology is still under deep investigation. One of the recent approaches is the prevention by natural compounds such as pectin. In this paper, we have assessed the impact of citrus pectin and modified citrus pectin on colorectal cancer in rats (Rattus norvegicus F344) to which azoxymethane and DSS were supplied. The lowest intake of food and body weight were detected in animals fed with citrus pectin, together with an increase in the caecum weight, probably due to the viscosity, water retention capacity and bulking properties of pectin. The most striking feature was that, neither citrus pectin nor modified citrus pectin gave rise to a tumorigenesis prevention. Moreover, in both, more than 50% of rats with cancer died, probably ascribed to a severe dysbiosis state in the gut, as shown by the metabolism and metagenomics studies carried out. This was related to a decrease of pH in caecum lumen and increase in acetate and lactic acid levels together with the absence of propionic and butyric acids. A relevant increase in Proteobacteria (Enterobacteriaceae) were thought to be one of the reasons for enteric infection that could have provoked the death of rats and the lack of cancer prevention. However, a reduction of blood glucose and triacylglycerides level and an increase of Bifidobacterium and Lactobacillaceae were found in animals that intake pectin, as compared to universal and modified citrus pectin feeding.


Asunto(s)
Azoximetano/toxicidad , Carcinogénesis/efectos de los fármacos , Neoplasias Colorrectales/dietoterapia , Microbioma Gastrointestinal/efectos de los fármacos , Pectinas/uso terapéutico , Acetatos/metabolismo , Animales , Azoximetano/farmacología , Bifidobacterium/aislamiento & purificación , Glucemia/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Butiratos/metabolismo , Carcinogénesis/metabolismo , Carcinogénesis/patología , Cromatografía Líquida de Alta Presión , Citrus/química , Neoplasias Colorrectales/inducido químicamente , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/mortalidad , Sulfato de Dextran/farmacología , Modelos Animales de Enfermedad , Concentración de Iones de Hidrógeno , Ácido Láctico/metabolismo , Lactobacillaceae/aislamiento & purificación , Masculino , Metagenómica , Pectinas/análisis , Filogenia , Propionatos/metabolismo , Proteobacteria/aislamiento & purificación , Ratas , Ratas Endogámicas F344 , Triglicéridos/sangre
17.
Medicine (Baltimore) ; 99(51): e23216, 2020 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-33371062

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is a public health problem and the world's leading cancer killer. It is a disease with high incidence and mortality. Although chemotherapy has achieved some success in the treatment of CRC, drug resistance and tumor metastasis caused by chemotherapy are still the main causes of death in patients with CRC. Notably, many side effects associated with chemotherapy, such as nausea, vomiting, and peripheral neurotoxicity, are major challenges in the treatment of patients with CRC. Chinese herbal medicine (CHM) has been widely used as an adjunctive therapy for CRC, but its efficacy and safety are still uncertain. The aim of this systematic review is to assess the efficacy and safety of CHM for the treatment of CRC. METHODS: A comprehensive retrieval will be performed in the following electronic databases: PubMed, Cochrane Library, EMBASE, Web of Science, CNKI, SinoMed, VIP, and Wan Fang Data. The methodologic quality of randomized controlled trials will be assessed using the Cochrane risk assessment tool. Review Manager 5.3 software will be used for data synthesis and analysis. Funnel plot analysis and Egger test will be used to assess publication bias. The Grading of Recommendations Assessment, Development and Evaluation standard will be used to generate summary of finding table. RESULTS: The results of this systematic review will be used to summarize and evaluate the evidence from randomized controlled clinical trials of CHM as adjuvant therapy for CRC. CONCLUSION: This review will provide a detailed summary of the evidence to assess the efficacy and safety of CHM for CRC. OSF REGISTRATION: DOI 10.17605/OSF.IO/X2SKJ.


Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/mortalidad , Quimioterapia Combinada , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/efectos adversos , Humanos , Estado de Ejecución de Karnofsky , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Análisis de Supervivencia
18.
J Cell Mol Med ; 24(24): 14160-14170, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33118286

RESUMEN

Fatty acids are involved in the development and progression of colorectal cancer (CRC). However, genetic effects of fatty acid biosynthesis pathway on CRC outcome are unclear. Cox regression model was used to evaluate genetic effects on CRC overall survival (OS) and progression-free survival (PFS), accompanied by calculating hazard ratios (HRs) and confidence intervals (CIs). Differential expression analysis, expression quantitative trait loci analysis, dual-luciferase reporter assay and chromatin immunoprecipitation assay were performed to explore the genetically biological mechanism. The rs10838164 C>T in HSD17B12 was significantly associated with an increased risk of death and progression of CRC (OS, HR = 2.12, 95% CI = 1.40-3.22, P = 4.03 × 10-4 ; PFS, HR = 1.64, 95% CI = 1.11-2.44, P = 1.35 × 10-2 ), of which T allele could increase HSD17B12 expression (P = 1.78 × 10-11 ). Subsequently, the functional experiments indicated that rs10838164 T allele could not only enhance the binding affinity of transcription factor YY1 to HSD17B12 region harbouring rs10838164 but also promote the transcriptional activity of HSD17B12, which was significantly up-regulated in colorectal tumour tissues. Our findings suggest that genetic variants in fatty acid biosynthesis pathway play an important role in CRC outcome.


Asunto(s)
17-Hidroxiesteroide Deshidrogenasas/genética , Vías Biosintéticas , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Ácidos Grasos/biosíntesis , Variación Genética , Alelos , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Bases de Datos de Ácidos Nucleicos , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Genes Reporteros , Genotipo , Humanos , Estimación de Kaplan-Meier , Polimorfismo de Nucleótido Simple , Pronóstico , Sitios de Carácter Cuantitativo , Activación Transcripcional , Factor de Transcripción YY1/metabolismo
19.
Theranostics ; 10(24): 11063-11079, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33042270

RESUMEN

Metastasis is a major cause of death in patients with colorectal cancer (CRC). Cysteine-rich protein 2 (CSRP2) has been recently implicated in the progression and metastasis of a variety of cancers. However, the biological functions and underlying mechanisms of CSRP2 in the regulation of CRC progression are largely unknown. Methods: Immunohistochemistry, quantitative real-time polymerase chain reaction (qPCR) and Western blotting (WB) were used to detect the expression of CSRP2 in CRC tissues and paracancerous tissues. CSRP2 function in CRC was determined by a series of functional tests in vivo and in vitro. WB and immunofluorescence were used to determine the relation between CSRP2 and epithelial-mesenchymal transition (EMT). Co-immunoprecipitation and scanning electron microscopy were used to study the molecular mechanism of CSRP2 in CRC. Results: The CSRP2 expression level in CRC tissues was lower than in adjacent normal tissues and indicated poor prognosis in CRC patients. Functionally, CSRP2 could suppress the proliferation, migration, and invasion of CRC cells in vitro and inhibit CRC tumorigenesis and metastasis in vivo. Mechanistic investigations revealed a physical interaction between CSRP2 and p130Cas. CSRP2 could inhibit the activation of Rac1 by preventing the phosphorylation of p130Cas, thus activating the Hippo signaling pathway, and simultaneously inhibiting the ERK and PAK/LIMK/cortactin signaling pathways, thereby inhibiting the EMT and metastasis of CRC. Rescue experiments showed that blocking the p130Cas and Rac1 activation could inhibit EMT induced by CSRP2 silencing. Conclusion: Our results suggest that the CSRP2/p130Cas/Rac1 axis can inhibit CRC aggressiveness and metastasis through the Hippo, ERK, and PAK signaling pathways. Therefore, CSRP2 may be a potential therapeutic target for CRC.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/patología , Proteína Sustrato Asociada a CrK/metabolismo , Proteínas con Dominio LIM/metabolismo , Proteínas Musculares/metabolismo , Proteínas Nucleares/metabolismo , Proteína de Unión al GTP rac1/metabolismo , Aminoquinolinas/farmacología , Animales , Biomarcadores de Tumor/genética , Carcinogénesis/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Colon/patología , Colon/cirugía , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/cirugía , Progresión de la Enfermedad , Regulación hacia Abajo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Vía de Señalización Hippo , Humanos , Estimación de Kaplan-Meier , Proteínas con Dominio LIM/genética , Masculino , Ratones , Persona de Mediana Edad , Proteínas Musculares/genética , Invasividad Neoplásica/patología , Proteínas Nucleares/genética , Fosforilación , Pronóstico , Proteínas Serina-Treonina Quinasas/metabolismo , Pirimidinas/farmacología , Recto/patología , Recto/cirugía , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Quinasas p21 Activadas/metabolismo , Proteína de Unión al GTP rac1/antagonistas & inhibidores
20.
Medicine (Baltimore) ; 99(33): e21546, 2020 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-32872001

RESUMEN

INTRODUCTION: The efficacy of different timings of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in controlling malignant ascites caused by peritoneal carcinomatosis of colorectal cancer (CRC) is not well defined. The study aims to investigate the clinical efficacy and safety of different timings of CRS with HIPEC for malignant ascites caused by peritoneal carcinomatosis from CRC. MATERIALS AND METHODS: This was a preliminary randomized controlled study performed at the Intracelom Hyperthermic Perfusion Therapy Center of the Cancer Hospital of Guangzhou Medical University (China) from December 2008 to December 2016. The patients were randomized to: CRS, followed by HIPEC (CRS+HIPEC; n = 14), and ultrasound-guided HIPEC, followed by CRS 1 to 2 weeks later (HIPEC+ delayed cytoreductive surgery (dCRS) group, n = 14). The endpoints were complete remission rate of ascites, successful complete CRS rate, and overall survival. RESULTS: Malignant ascites in all patients showed complete remission; the total effective rate was 100%. Complete CRS was not feasible in any patient. The median follow-up of the 2 groups was 41.9 and 42.3 months in the CRS+HIPEC and HIPEC+dCRS groups, respectively. Overall survival was 14.5 (95%CI: 7-19 months) and 14.3 months (95%CI: 4-21 months) (P > .05). The adverse effects of HIPEC were manageable. CONCLUSIONS: CRS+HIPEC and HIPEC+dCRS have the same efficacy in controlling malignant ascites caused by CRC and peritoneal carcinomatosis. The timing of CRS and HIPEC does not prolong the survival of patients with peritoneal carcinomatosis from CRC, even when a complete CRS is not feasible.


Asunto(s)
Ascitis/etiología , Ascitis/terapia , Neoplasias Colorrectales/complicaciones , Procedimientos Quirúrgicos de Citorreducción , Hipertermia Inducida , Adulto , Anciano , Ascitis/mortalidad , China , Neoplasias Colorrectales/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Ultrasonografía Intervencional
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