RESUMEN
BACKGROUND: Immune checkpoint inhibitors improve the efficacy of first-line chemotherapy for patients with programmed death-ligand 1 (PD-L1)-positive unresectable locally advanced/metastatic triple-negative breast cancer (aTNBC), but randomised data in rapidly relapsing aTNBC are scarce. PATIENTS AND METHODS: IMpassion132 (NCT03371017) enrolled patients with aTNBC relapsing <12 months after last chemotherapy dose (anthracycline and taxane required) or surgery for early TNBC. PD-L1 status was centrally assessed using SP142 before randomisation. Initially patients were enrolled irrespective of PD-L1 status. From August 2019, enrolment was restricted to PD-L1-positive (tumour immune cell ≥1%) aTNBC. Patients were randomised 1:1 to placebo or atezolizumab 1200 mg every 21 days with investigator-selected chemotherapy until disease progression or unacceptable toxicity. Stratification factors were chemotherapy regimen (carboplatin plus gemcitabine or capecitabine monotherapy), visceral (lung and/or liver) metastases and (initially) PD-L1 status. The primary endpoint was overall survival (OS), tested hierarchically in patients with PD-L1-positive tumours and then, if positive, in the modified intent-to-treat (mITT) population (all-comer patients randomised pre-August 2019). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety. RESULTS: Among 354 patients with rapidly relapsing PD-L1-positive aTNBC, 68% had a disease-free interval of <6 months and 73% received carboplatin/gemcitabine. The OS hazard ratio was 0.93 (95% confidence interval 0.73-1.20, P = 0.59; median 11.2 months with placebo versus 12.1 months with atezolizumab). mITT and subgroup results were consistent. Median PFS was 4 months across treatment arms and populations. ORRs were 28% with placebo versus 40% with atezolizumab. Adverse events (predominantly haematological) were similar between arms and as expected with atezolizumab plus carboplatin/gemcitabine or capecitabine following recent chemotherapy exposure. CONCLUSIONS: OS, which is dismal in patients with TNBC relapsing within <12 months, was not improved by adding atezolizumab to chemotherapy. A biology-based definition of intrinsic resistance to immunotherapy in aTNBC is urgently needed to develop novel therapies for these patients in next-generation clinical trials.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Gemcitabina , Recurrencia Local de Neoplasia , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Método Doble Ciego , Anciano , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Adulto , Carboplatino/administración & dosificación , Capecitabina/administración & dosificación , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/metabolismo , Supervivencia sin Progresión , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/efectos adversosRESUMEN
OBJECTIVES: To evaluate the prognostic utility of inflammation-based prognostic scores in patients with ALK-positive metastatic or non-resectable non-small-cell lung cancer (NSCLC) treated with crizotinib. PATIENTS AND METHODS: A total of 82 patients with ALK-positive metastatic or non-resectable NSCLC who received ALK TKI crizotinib were included. Pre-treatment modified Glasgow prognostic score (mGPS), prognostic nutritional index (PNI), and systemic immune-inflammation index (SII) were calculated. Multivariable logistic regression and Cox proportional hazards models were used to assess the impact of pretreatment mGPS, PNI, and SII on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). RESULTS: The ORR was 77.2%, while 1-year OS and PFS rates were 95.0% and 93.5%, respectively. The univariate analysis revealed significantly higher 1-year PFS (89.4 vs. 64.4%, p=0.043) and OS (92.0 vs. 83.3%, p=0.01) rates in patients with low (<934.7) vs. high (≥934.7) SII scores. Multivariate analysis revealed that PNI ≥0.09 was a significant determinant of poorer 1-year OS rates (hazard ratio [HR]: 2.46, 95% confidence interval [CI] 0.88-4.85, p=0.035). No significant difference was observed in survival rates according to gender, age, smoking status, prior lines of therapy, or mGPS scores, while higher mGPS scores (odds ratio [OR]: 0.1, 95%CI 0.16-1.04; p=0.009) and higher PNI scores (OR: 0.16, 95% CI 0.02-0.55; p=0.035) were associated with poorer ORR. CONCLUSION: Our findings indicate the prognostic significance of PNI and SII in terms of survival outcome and the impact of mGPS and PNI on treatment response in patients with ALK-positive NSCLC treated with crizotinib.
Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Crizotinib/uso terapéutico , Neoplasias Pulmonares/patología , Antineoplásicos/uso terapéutico , Inflamación , Proteínas Tirosina Quinasas Receptoras/uso terapéuticoRESUMEN
PURPOSE: In this study, we aimed to describe the real-life practice outcomes of pertuzumab-trastuzumab-taxane (PTT) combination in visceral organ metastatic, trastuzumab-naive breast cancer (BC) patients. METHODS: This study was conducted by Turkish Oncology Group and included 317 patients' data from 36 centers. RESULTS: Median age was 51 (22-82). Median PFS was 28.5 months, while median OS was 40.3 months. Patients with brain metastases (n: 13, 4.1%) had worse PFS (16.8 m vs. 28.5 m; p = 0.002) and OS (26.7 m vs. 40.3 m; p = 0.009). Patients older than 65 years of age (n: 42, 13.2%) had significantly lower OS results (19.8 m vs. 40.3 m; p = 0.01). Two hundred sixty-eight patients (86.7%) received docetaxel while 37 patients (11.7%) received paclitaxel. PFS and OS were similar between taxane groups. In eight patients (2.5%), 5-40% ejection fraction decrement from baseline was detected without any clinical sign of heart failure. CONCLUSIONS: Our RLP trial included only visceral metastatic, trastuzumab-naïve BC patients including cases with brain involvement who received PTT combination in the first-line treatment. Regardless of negative prognostic characteristics, our results are in parallel with pivotal trial. Further strategies for brain metastasis should be developed to improve outcomes despite encouraging results with PTT treatment. Taxane selection can be personalized and endocrine maintenance may further improve outcomes after taxanes were discontinued. To our knowledge, this is the largest scale real-life clinical practice study of pertuzumab-trastuzumab-taxane therapy to date.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/mortalidad , Carcinoma Ductal de Mama/mortalidad , Carcinoma Lobular/mortalidad , Pautas de la Práctica en Medicina , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/secundario , Carcinoma Lobular/tratamiento farmacológico , Carcinoma Lobular/secundario , Docetaxel/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Paclitaxel/administración & dosificación , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Trastuzumab/administración & dosificación , Adulto JovenRESUMEN
Bevacizumab is a monoclonal antibody which is a vascular endothelial growth factor inhibitor. It obscures vascularization of tumor tissue and damages intratumoral microcirculation. The damaged intratumoral microcirculation leads to tissue hypoxia and results in increase of uric acid level. The main aim of our study was to investigate the relationship between uric acid change and response to bevacizumab therapy. This study included a total of 158 patients with metastatic colorectal cancer who had received bevacizumab therapy. The number of male patients was 100 (63.3 %) while female patients number was 58 (37.7 %). The median age was 61 (29-83). There was relationship between increase of uric acid level of third month uric acid level and stable disease (p < 0.001). There was a significant overall survival increased in the group with increased uric acid level (p < 0.001). The decline of CEA level was related to uric acid level (p < 0.022). In conclusion, this study is the first showing significant increases of serum uric acid in patients with metastatic colorectal cancer who favorably responded to chemotherapy with bevacizumab. But further studies are justified to test whether monitoring uric acid levels might predict clinical outcomes of patients with metastatic colorectal cancer (AU)
No disponible
Asunto(s)
Humanos , Masculino , Femenino , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/inmunología , Bevacizumab/uso terapéutico , Metástasis de la Neoplasia/diagnóstico , Metástasis de la Neoplasia/tratamiento farmacológico , Metástasis de la Neoplasia/patología , Ácido Úrico/análisis , Ácido Úrico/sangre , Anticuerpos Monoclonales/análisis , Estudios de Cohortes , 28599RESUMEN
Background: Although Ras-association domain family of gene 2 (RASSF2) has been shown to undergo promoter methylation at high frequency in some cancer types and in brain metastases, its clinical utility as a useful prognostic molecular marker remains unclear in gastric cancer. Methods: Prognostic significance of RASSF2 expression was retrospectively analysed by immunohistochemically in 105 patients with gastric cancer who underwent curative gastrectomy. Results: Low RASSF2 expression was detected in 58 (55 %) patients, whereas 47 patients (45 %) had high RASSF2 expression. Lymph node involvement, pT stage, TNM stage, vascular invasion, perineural invasion and the presence of recurrence were found to be significantly related to RASSF2 expression levels. Low PRL-3 expression was closely correlated with lymph node metastasis (p = 0.001), advanced pT stage (p = 0.021), advanced TNM stage (p < 0.001), the presence of vascular invasion (p < 0.001), perineural invasion (p = 0.018) and high prevalence of recurrence (p = 0.003) compared with high RASSF2 expression. The median disease-free survival (DFS) time for patients with low RASSF2 expression was significantly worse than that of patients with high RASSF2 expression (10.2 vs. 50.6 months, p < 0.001). In addition, patients with high RASSF2 expression had the higher overall survival (OS) interval compared to patients with low RASSF2 expression (NR vs. 14.9 months, p < 0.001). In the multivariate analysis, the rate of RASSF2 expression levels was an independent prognostic factor, for DFS [p < 0.001, HR 0.12 (0.10-0.88)] and OS [p < 0.001, HR 0.10 (0.04-0.46)], as were pT stage and TNM stage, respectively. Conclusions: RASSF2 may be an important molecular marker for carcinogenesis, prognosis and progression in gastric cancer, but the potential value of RASSF2 expression as a useful molecular marker in gastric cancer progression should be evaluated, comprehensively. It would be possible to develop treatments targeting RASSF2 and advance new treatment strategies for gastric cancer
No disponible
Asunto(s)
Humanos , Masculino , Femenino , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patología , Pronóstico , Gastrectomía/métodos , Genes ras , Proteínas ras/análisis , Quimioterapia Adyuvante , Estudios Retrospectivos , Carcinoma/diagnóstico , Carcinoma/tratamiento farmacológico , Quimioradioterapia/métodos , Quimioradioterapia , Leucovorina/uso terapéutico , Fluorouracilo/uso terapéuticoRESUMEN
Bevacizumab is a monoclonal antibody which is a vascular endothelial growth factor inhibitor. It obscures vascularization of tumor tissue and damages intratumoral microcirculation. The damaged intratumoral microcirculation leads to tissue hypoxia and results in increase of uric acid level. The main aim of our study was to investigate the relationship between uric acid change and response to bevacizumab therapy. This study included a total of 158 patients with metastatic colorectal cancer who had received bevacizumab therapy. The number of male patients was 100 (63.3 %) while female patients number was 58 (37.7 %). The median age was 61 (29-83). There was relationship between increase of uric acid level of third month uric acid level and stable disease (p < 0.001). There was a significant overall survival increased in the group with increased uric acid level (p < 0.001). The decline of CEA level was related to uric acid level (p < 0.022). In conclusion, this study is the first showing significant increases of serum uric acid in patients with metastatic colorectal cancer who favorably responded to chemotherapy with bevacizumab. But further studies are justified to test whether monitoring uric acid levels might predict clinical outcomes of patients with metastatic colorectal cancer.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Biomarcadores de Tumor/sangre , Neoplasias del Colon/patología , Ácido Úrico/sangre , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Neoplasias del Colon/sangre , Neoplasias del Colon/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la NeoplasiaRESUMEN
INTRODUCTION: Our aim in this study was to analyze the findings of brain magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) of children with vitamin B12 deficiency. METHODS: This study included 14 cases. The findings of brain MRI and MRS in all cases were investigated. Four patients had been followed up and mean follow-up time 71.8 (59-85) day. RESULTS: Eight patients of the cases (57 %) had at least one abnormal MRI finding. The most commonly found MRI findings were thinning of the corpus callosum and brain atrophy, respectively. The mean ratio of NAA/Cr and Cho/Cr were measured in MRS, with values of 1.31 ± 0.17 and 1.04 ± 0.27, respectively. In two of three patients with abnormal MRI studies at presentation, subsequent MRI showed improvement while one patient remained unchanged. An increase in the ratios of metabolites were found in one case with control MRS. There was no lactate peak. CONCLUSION: Brain MRI was abnormal in more than half of the cases of children with vitamin B12 deficiency. Our radiologic findings similar with literature. There was no identifiable lactate peak. B12 deficiency could be the cause of the thinning of the corpus callosum and brain atrophy in the children that were given a brain MRI.
Asunto(s)
Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Imagen por Resonancia Magnética , Espectroscopía de Protones por Resonancia Magnética , Deficiencia de Vitamina B 12/diagnóstico por imagen , Deficiencia de Vitamina B 12/metabolismo , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Biomarcadores/metabolismo , Encéfalo/patología , Preescolar , Colina/metabolismo , Creatina/metabolismo , Femenino , Humanos , Lactante , Masculino , Imagen Molecular/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Deficiencia de Vitamina B 12/patologíaRESUMEN
BACKGROUND: Although Ras-association domain family of gene 2 (RASSF2) has been shown to undergo promoter methylation at high frequency in some cancer types and in brain metastases, its clinical utility as a useful prognostic molecular marker remains unclear in gastric cancer. METHODS: Prognostic significance of RASSF2 expression was retrospectively analysed by immunohistochemically in 105 patients with gastric cancer who underwent curative gastrectomy. RESULTS: Low RASSF2 expression was detected in 58 (55 %) patients, whereas 47 patients (45 %) had high RASSF2 expression. Lymph node involvement, pT stage, TNM stage, vascular invasion, perineural invasion and the presence of recurrence were found to be significantly related to RASSF2 expression levels. Low PRL-3 expression was closely correlated with lymph node metastasis (p = 0.001), advanced pT stage (p = 0.021), advanced TNM stage (p < 0.001), the presence of vascular invasion (p < 0.001), perineural invasion (p = 0.018) and high prevalence of recurrence (p = 0.003) compared with high RASSF2 expression. The median disease-free survival (DFS) time for patients with low RASSF2 expression was significantly worse than that of patients with high RASSF2 expression (10.2 vs. 50.6 months, p < 0.001). In addition, patients with high RASSF2 expression had the higher overall survival (OS) interval compared to patients with low RASSF2 expression (NR vs. 14.9 months, p < 0.001). In the multivariate analysis, the rate of RASSF2 expression levels was an independent prognostic factor, for DFS [p < 0.001, HR 0.12 (0.10-0.88)] and OS [p < 0.001, HR 0.10 (0.04-0.46)], as were pT stage and TNM stage, respectively. CONCLUSIONS: RASSF2 may be an important molecular marker for carcinogenesis, prognosis and progression in gastric cancer, but the potential value of RASSF2 expression as a useful molecular marker in gastric cancer progression should be evaluated, comprehensively. It would be possible to develop treatments targeting RASSF2 and advance new treatment strategies for gastric cancer.
Asunto(s)
Adenocarcinoma/patología , Biomarcadores de Tumor/análisis , Neoplasias Gástricas/patología , Proteínas Supresoras de Tumor/biosíntesis , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Gastrectomía , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/cirugía , Proteínas Supresoras de Tumor/análisisRESUMEN
Purpose. In the literature, small number of study has addressed time of recurrence in breast cancer. We analyzed clinicopathological factors predicting early or late recurrence in breast cancer patients and also prognostic factors related with recurrence-free survival (RFS) in recurrent patients. Patients/methods. We evaluated retrospectively 1980 breast cancer patients. Relapsed was defined as early if it was occured first 5 year of follow-up (Group 1) and late if it was occured after 5 years (Group 2). The clinicopathological factors were compared in respect of time of recurrence. The prognostic factors were evaluated using univariate and multivariate analyses. Results. Recurrence wase detected in 141 patient during follow-up. Tumors recurred after 5 years more likely to have lower stage (p = 0.05), tumors without lymphovascular invasion (LVI) (p < 0.001) and perineural invasion (PNI) (p = 0.01), and also HER2 negative (p < 0.001). The median RFS time and 5 years RFS rates were 42.9 months and 31.9 %, respectively. LVI (p = 0.01), PNI (p = 0.03), HER2 (p = 0.003), progesterone receptor (PR) (p = 0.04), the presence of neoadjuvant chemotherapy (p = 0.003), adjuvant hormonotherapy (p = 0.05) were found to be related with RFS. Axillary lymph node metastasis (p = 0.05) and the presence of PNI (p = 0.009) were poor prognostic factors for early recurrent group. PR-positive tumors (p = 0.001) and luminal subtypes (p = 0.03) had instances of late recurrences significantly. Conclusions. Clinicopathological factors predicting the recurrence time in breast cancer were important to modify adjuvant therapy (AU)
No disponible
Asunto(s)
Femenino , Humanos , Persona de Mediana Edad , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/diagnóstico , Recurrencia Local de Neoplasia/complicaciones , Recurrencia Local de Neoplasia/diagnóstico , Progesterona/uso terapéutico , Terapia Neoadyuvante , Mastectomía/métodos , Estudios de Seguimiento , Pronóstico , Estudios Retrospectivos , Análisis Multivariante , Menopausia , Menopausia/fisiologíaRESUMEN
Backgrounds. A disintegrin and metalloproteinase (ADAM) 17 has been indicated to be an indispensable regulator of cellular events from proliferation to migration. Although prognostic importance of ADAM17 expression has been investigated in several tumours, its clinical utility as a useful prognostic molecular marker remains unclear in gastric cancer. In the current study, we evaluated the expression of ADAM17 and its prognostic significance in gastric cancer patients after curative gastrectomy. Methods. The prognostic significance of ADAM17 expression was analysed immunohistochemically in 156 patients with gastric cancer who had undergone curative gastrectomy, and the relationship between its expression and clinicopathological factors was also evaluated. Results. High ADAM17 expression was detected in 79 patients (51 %), whereas low expression was found in 77 cases (49 %). There was significant correlation between gender, histology, lymph node metastasis, vascular invasion, the presence of recurrence and high ADAM17 expression. Recurrence in patients with high ADAM17 expression was significantly higher than that for patients with low ADAM17 expression (p = 0.032). The median disease-free survival (DFS) time for patients with tumours with high ADAM17 expression was worse than that of patients with tumours with low ADAM17 expression (16.6 vs. 44.2 months, p = 0.004). In addition, patients with low ADAM17 expression had a higher median overall survival (OS) (49.6 vs. 26.9 months, p = 0.019) compared to those with high ADAM17 expression. Multivariate analysis indicated that the rate of ADAM17 expression was an independent prognostic factor for DFS, in addition to the already known important clinicopathological prognostic indicator. But the prognostic importance of ADAM17 expression could not be proved by multivariate analysis for OS. Conclusions. The potential value of ADAM17 expression as a useful molecular marker in gastric cancer progression should be evaluated comprehensively; it may predict recurrence and poor prognosis in patients with gastric cancer after curative resection (AU)
No disponible
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/diagnóstico , Gastrectomía/métodos , Metaloproteinasa 17 de la Matriz , Metaloproteinasa 17 de la Matriz/análisis , Neoplasias de la Mama/complicaciones , Adenocarcinoma/diagnóstico , Adyuvantes Farmacéuticos/administración & dosificación , Pronóstico , Inmunohistoquímica/métodos , Análisis MultivarianteRESUMEN
PURPOSE: In the literature, small number of study has addressed time of recurrence in breast cancer. We analyzed clinicopathological factors predicting early or late recurrence in breast cancer patients and also prognostic factors related with recurrence-free survival (RFS) in recurrent patients. PATIENTS/METHODS: We evaluated retrospectively 1980 breast cancer patients. Relapsed was defined as early if it was occured first 5 year of follow-up (Group 1) and late if it was occured after 5 years (Group 2). The clinicopathological factors were compared in respect of time of recurrence. The prognostic factors were evaluated using univariate and multivariate analyses. RESULTS: Recurrence wase detected in 141 patient during follow-up. Tumors recurred after 5 years more likely to have lower stage (p = 0.05), tumors without lymphovascular invasion (LVI) (p < 0.001) and perineural invasion (PNI) (p = 0.01), and also HER2 negative (p < 0.001). The median RFS time and 5 years RFS rates were 42.9 months and 31.9 %, respectively. LVI (p = 0.01), PNI (p = 0.03), HER2 (p = 0.003), progesterone receptor (PR) (p = 0.04), the presence of neoadjuvant chemotherapy (p = 0.003), adjuvant hormonotherapy (p = 0.05) were found to be related with RFS. Axillary lymph node metastasis (p = 0.05) and the presence of PNI (p = 0.009) were poor prognostic factors for early recurrent group. PR-positive tumors (p = 0.001) and luminal subtypes (p = 0.03) had instances of late recurrences significantly. CONCLUSIONS: Clinicopathological factors predicting the recurrence time in breast cancer were important to modify adjuvant therapy.
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Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Recurrencia Local de Neoplasia/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/genética , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Receptor ErbB-2/biosíntesis , Receptores de Estrógenos/biosíntesis , Receptores de Progesterona/biosíntesis , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUNDS: A disintegrin and metalloproteinase (ADAM) 17 has been indicated to be an indispensable regulator of cellular events from proliferation to migration. Although prognostic importance of ADAM17 expression has been investigated in several tumours, its clinical utility as a useful prognostic molecular marker remains unclear in gastric cancer. In the current study, we evaluated the expression of ADAM17 and its prognostic significance in gastric cancer patients after curative gastrectomy. METHODS: The prognostic significance of ADAM17 expression was analysed immunohistochemically in 156 patients with gastric cancer who had undergone curative gastrectomy, and the relationship between its expression and clinicopathological factors was also evaluated. RESULTS: High ADAM17 expression was detected in 79 patients (51 %), whereas low expression was found in 77 cases (49 %). There was significant correlation between gender, histology, lymph node metastasis, vascular invasion, the presence of recurrence and high ADAM17 expression. Recurrence in patients with high ADAM17 expression was significantly higher than that for patients with low ADAM17 expression (p = 0.032). The median disease-free survival (DFS) time for patients with tumours with high ADAM17 expression was worse than that of patients with tumours with low ADAM17 expression (16.6 vs. 44.2 months, p = 0.004). In addition, patients with low ADAM17 expression had a higher median overall survival (OS) (49.6 vs. 26.9 months, p = 0.019) compared to those with high ADAM17 expression. Multivariate analysis indicated that the rate of ADAM17 expression was an independent prognostic factor for DFS, in addition to the already known important clinicopathological prognostic indicator. But the prognostic importance of ADAM17 expression could not be proved by multivariate analysis for OS. CONCLUSIONS: The potential value of ADAM17 expression as a useful molecular marker in gastric cancer progression should be evaluated comprehensively; it may predict recurrence and poor prognosis in patients with gastric cancer after curative resection.
Asunto(s)
Proteínas ADAM/metabolismo , Adenocarcinoma Mucinoso/secundario , Adenocarcinoma/secundario , Carcinoma de Células en Anillo de Sello/secundario , Gastrectomía/mortalidad , Recurrencia Local de Neoplasia/patología , Neoplasias Gástricas/patología , Proteína ADAM17 , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/mortalidad , Adenocarcinoma Mucinoso/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Carcinoma de Células en Anillo de Sello/metabolismo , Carcinoma de Células en Anillo de Sello/mortalidad , Carcinoma de Células en Anillo de Sello/cirugía , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Pronóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/cirugía , Tasa de SupervivenciaRESUMEN
AIM: To evaluate the blood flow in arteries of the orbit in patients with psoriasis. METHODS: In total, 30 patients with psoriasis and 30 healthy control subjects were recruited to the study. Standard ophthalmic evaluation, fundus examination and retrobulbar colour Doppler ultrasonography assessment were performed. The ophthalmic, posterior ciliary and central arteries were evaluated, and peak systolic blood flow velocity, end diastolic velocity, resistance index and pulsatility index were measured. Results of the measurements were compared between the two study groups. RESULTS: There were significant differences in blood flow parameters of the orbital arteries between the psoriasis group and the control group. CONCLUSIONS: The haemodynamics of the orbit might be affected in patients with psoriasis.
Asunto(s)
Ojo/irrigación sanguínea , Psoriasis/fisiopatología , Adolescente , Adulto , Estudios de Casos y Controles , Arterias Ciliares/diagnóstico por imagen , Arterias Ciliares/fisiopatología , Ojo/diagnóstico por imagen , Femenino , Hemodinámica/fisiología , Humanos , Masculino , Arteria Oftálmica/diagnóstico por imagen , Arteria Oftálmica/fisiopatología , Psoriasis/diagnóstico por imagen , Flujo Sanguíneo Regional/fisiología , Arteria Retiniana/diagnóstico por imagen , Arteria Retiniana/fisiopatología , Ultrasonografía Doppler en Color , Adulto JovenRESUMEN
OBJECTIVES: The aim of the present study was to evaluate variations in celiac trunk and hepatic artery with multi-detector computed tomography (MDCT). PATIENTS AND METHODS: Totally 820 patients who underwent angiography of the abdominal aorta were evaluated. Anatomical findings were grouped according to the Michels classification. RESULTS: Several variations and/or anomalies were noted in 33.2% of the patients (n=272). The most common abnormality was Michels type III (10.1%), followed by type V (7.3%), type II (4.7%) and others. Type X was not observed in our series. We have noted additional, previously unclassified variations in 12 cases (1.5%). CONCLUSIONS: Preoperative knowledge of variant anatomy may assist in the selection of treatment options and surgical planning, which in turn facilitates surgical dissection and helps avoiding iatrogenic injury. MDCT angiography allows detailed visualization of the vascular anatomy.
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Arteria Celíaca/diagnóstico por imagen , Arteria Hepática/diagnóstico por imagen , Angiografía/métodos , Humanos , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND: Several biomarkers have been previously studied for breast cancer to define risk of recurrence and metastasis. Phosphatase of regenerating liver-3 (PRL-3) is one of them. High PRL-3 expression has been found to be correlated with axillary lymph node metastasis and survival in breast cancer. Herein, we evaluated the prognostic significance of PRL-3 expression and the relationship between PRL-3 and other clinicopathological factors. METHODS: PRL-3 expression was analyzed immunohistochemically in 122 invasive breast cancer tissues. We evaluated the correlation between PRL-3 and other clinicopathological factors by χ² test. Kaplan-Meier test and log rank method were used to define prognostic importance of PRL-3 expression. RESULTS: Of 122 breast cancer tumor samples, 46 (37.7 %) were negative while 76 (62.3 %) were positive in respect to PRL-3 expression. There was significant correlation between PRL-3 expression and other clinicopathological factors, such as histology, lymphovascular invasion (LVI), necrosis, progesterone receptor (PR) status, and the presence of triple negative disease. Tumors with LVI and necrosis had more positive PRL-3 expression compared to tumors without LVI or necrosis (P = 0.05 and 0.03, respectively). Triple negative and cerb-B overexpressed breast cancers were found to be more positive PRL-3 expression than hormone receptor positive with cerb-B negative groups (luminal A) (P = 0.02).We could not find any relationship between PRL-3 expression and overall survival (OS) or disease-free survival (DFS) (P > 0.05). CONCLUSION: Although PRL-3 expression was related to LVI or necrosis which is important for tumor invasiveness, we could not find that PRL-3 as an important prognostic factor in breast cancer patients. In addition, triple negative and cerb-B overexpressed tumors, which had worse prognosis compared to hormone receptor positive without cerb-B expressed group, associated with also PRL-3 positivity more than PRL-3 negative group (AU)
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Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Neoplasias de la Mama/enzimología , Proteínas Tirosina Fosfatasas/metabolismo , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Ganglios Linfáticos/patología , Metástasis Linfática , PronósticoRESUMEN
PURPOSE: It is well known that an association exists between the pathogenesis of lymphomas and autoimmune diseases. Autoantibodies are detected at higher frequency in lymphoproliferative diseases, but neither the precise role of the immune system nor the cause of this is comprehensively understood. In this study we evaluated the presence and significance of some autoantibodies for patients with non- Hodgkin's lymphoma (NHL). METHODS: 150 patients with NHL who had either newly diagnosed disease, or active disease being under chemotherapy or were disease-free during follow-up, were analyzed. The frequency of autoantibodies and the relationship between autoantibodies and several clinicopathological factors were evaluated. RESULTS: The majority of the patients (50%) had diffuse large B-cell lymphoma (DLBCL). Thirty-two patients (21.4%) were newly diagnosed, 81 (54%) had active disease and were receiving chemotherapy and 37 (24.6%) were disease-free and followed-up. Fifty-one patients (34%) had stage IV disease. Antinuclear antibodies (ANA) were found in 7 (4.7%) patients, perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) in 10 (6.7%), anti dsDNA in 1 (0.7%), anti ssDNA in 16 (10.7%), anti Jo-1 in 3 (2%), anti-scleroderma antibody (anti Scl-70) in 4 (2.7%), and rheumatoid factor (RF) in 85 (56.7%) patients. No c7horbar;ANCA positivity was found. The mean levels of anti Jo-1 (p=0.028), anti ssDNA (p=0.014), c-ANCA (p=0.015), ANA (p=0.026) and RF (p=0.046) were significantly higher in cases with DLBCL compared to patients with non-DLBCL. In addition, in patients with newly diagnosed NHL the mean levels of anti Scl- 70 (p=0.023), anti Jo-1 (p7equals;0.017), and RF (p=0.046) were significantly higher than the other patient groups. No significant correlation was detected between the presence of autoantibodies and other clinicopathological factors. CONCLUSION: Our results show that the frequency of autoantibodies is high in NHL patients, especially in DLBCL and newly diagnosed cases. Autoantibodies may be helpful for the diagnosis of autoimmune diseases, but regular and long follow-up is needed in NHL patients with high levels of autoantibodies.
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Autoanticuerpos/sangre , Linfoma no Hodgkin/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/análisis , Femenino , Humanos , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/patología , Masculino , Persona de Mediana EdadRESUMEN
Triple-negative breast cancer (TNBC) has a greater risk of recurrence despite more aggressive therapy even in lowrisk category. TNBC is high grade, hormone receptor and HER-2 negative, it exhibits a high level of Ki-67 staining and expresses the epithelial growth factor receptor (EGFR). Because of its expression profile, treatment options are limited to cytotoxic chemotherapy. Molecular defects that give rise to BRCA1-associated breast cancer also occur in TNBC. Thus, the combination of poly-(ADP-ribose)-polymerase (PARP) inhibitors with drugs that cause DNA breakages, such as alkylating agents and topoisomerase I inhibitors, could theoretically potentiate the efficacy of each drug in patients with TNBC. Clinical trials with various targeted approaches alone or in combination with different chemotherapeutic agents are currently underway. In this review, current and future treatment approaches in TNBC with novel targeted agents are discussed.
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Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Neoplasias de la Mama/metabolismo , Femenino , Humanos , PronósticoRESUMEN
BACKGROUND: M30 and M65 are derivatives of cytokeratin 18 and released from the epithelial cell during cell death. These markers can be used to evaluate prognosis and chemotherapy response in several tumours. We evaluated serum M30 and M65 values in patients with advanced nonsmall- cell lung cancer (NSCLC) compared with those in a healthy group. MATERIAL AND METHODS: Thirty-two patients with advanced NSCLC and thirty-two healthy people were included in the study. Serum M30 and M65 values were measured by quantitative ELISA method. The best cut-off value for serum M65 was calculated by ROC analysis and then univariate analysis was performed to determine the importance of M65 value in predicting progression-free survival (PFS). RESULTS: There were no differences between mean serum M30 values between patients and controls (445.44±536.17 vs. 340.56±345.07, p=1). The mean serum M65 values were found to be significantly higher in patients than in healthy controls (1421.30±1662.59 vs. 648.85±341.17, p<0.001). The best cut-off value for serum M65 predicting PFS was 1311.64 U/l (AUC 0.58, sensitivity and specificity were 45.5% and 85.7% respectively). The patients with serum M65 values ≥1311.64 U/l had worse PFS than patients with serum M65 values <1311.64 U/l, p=0.01). There was no correlation between serum M30 value and PFS in the patient group (p=0.4). CONCLUSIONS: Our results indicated that serum M65 values elevated in advanced NSCLC compared to a healthy control group and elevated serum M65 level can predict PFS in patients (AU)
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Humanos , Masculino , Femenino , Carcinoma de Pulmón de Células no Pequeñas/química , Carcinoma de Pulmón de Células no Pequeñas/inducido químicamente , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/irrigación sanguínea , Carcinoma de Pulmón de Células no Pequeñas/metabolismoRESUMEN
This study was aimed to establish clinical efficacy and tolerability of gemcitabine and cisplatin combination in patients with metastatic triple negative breast cancer progressing after anthracycline and taxane based chemotherapies.Thirty-three patients who were given cisplatin and gemcitabine for triple negative and metastatic breast cancer were evaluated retrospectively. A total of 141 cycles were administered with a median 4 cycles per patient. Median follow-up time was 14 months (range, 2-36 months). Objective response rate was 27.3%. Total clinical benefit of the combination was 48.4%. The estimated median progression free survival and median overall survival were 5 months and 14 months, respectively. The most common Grade 3 and 4 toxicity were neutropenia and thrombocytopenia observed in 10 (27.7%) and 9 (24.9%) patients, respectively. The combination of the gemcitabine and cisplatin after taxane/anthracycline is well tolerated and seems to be effective with acceptable toxicity profile.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/secundario , Terapia Recuperativa , Adulto , Anciano , Antraciclinas/administración & dosificación , Neoplasias de la Mama/química , Carcinoma Ductal de Mama/química , Carcinoma Ductal de Mama/tratamiento farmacológico , Cisplatino/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Evaluación de Medicamentos , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Neutropenia/inducido químicamente , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Taxoides/administración & dosificación , Trombocitopenia/inducido químicamente , GemcitabinaRESUMEN
PURPOSE: Adiponectin is secreted from adipose tissue and is characterized by hyperinsulinemia which is related with obesity. Although serum adiponectin levels in patients with breast cancer have been studied previously, adiponectin levels in the serum, tumor and normal tissue of the same patients have not been simultaneously investigated. The aim of this study was thus to evaluate the relationship among serum, tumor and normal tissue adiponectin levels in patients with breast cancer. METHODS: Fifty-three patients with breast cancer who were operated at the Dr. Lutfi Kirdar Kartal Education and Research Hospital, Department of Surgery, between February 2008 and June 2008, were analyzed. Their serum adiponectin levels, tumor tissue and normal breast tissue adiponectin levels were compared. The correlation between postoperative histopathological parameters, insulin resistance parameters and adiponectin levels was also examined. RESULTS: The mean adiponectin levels in tumor tissue, normal breast tissue and serum were 56 ± 9.6 ng/ml, 56 ± 10 ng/ml and 43.5 ± 3.1 ng/ml, respectively. The serum adiponectin levels were inversely correlated with tumor tissue adiponectin levels (p=0.001, r=-0.43). When tumor tissue adiponectin levels were increased, serum adiponectin levels were decreased. O n the other hand, there was a positive correlation between normal breast tissue adiponectin levels and tumor tissue adiponectin levels (p=0.0001, r= 0.850). The tumor tissue adiponectin level was inversely correlated with tumor stage (p=0.037 , r= -0.29). Moreover, in early-stage and low grade tumors, both tumor tissue and normal tissue adiponectin levels were high compared with those of advanced stage or high grade tumors (p=0.027, r= -0.32 and p=0.004, r= -0.408, respectively). In the subgroup analyses, no significant relationship was found between insulin resistance parameters and adiponectin levels (p>0.05). CONCLUSION: Our results indicate that serum adiponectin levels were inversely correlated with tumor tissue adiponectin levels, but no relationship between normal breast tissue and tumor tissue adiponectin levels was demonstrated. Adiponectin levels in breast tumor tissue increase while serum adiponectin levels decrease. Adiponectin might play an important role in the prevention of tumor progression by decreasing tissue neovascularization.