RESUMEN
Objective: To investigate the detection of bone marrow tumor cells in small cell lung cancer (SCLC) patients and their relationship with clinical features, treatment response and prognosis. Methods: A total of 113patients with newly diagnosed SCLC from January 2018 to October 2022 at Beijing Chest Hospital were prospectively enrolled. Before treatment, bone marrow was aspirated and separately submitted for tumor cells detection by liquid-based cytology and disseminated tumor cells (DTCs) detection by the substrction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) platform. The correlation between the detection results of the two methods with patients' clinical features and treatment response was evaluated by Chi-square. Kaplan-Meier method was applied to create survival curves and the Cox regression model was used for multivariate analysis. Results: The positive rate of bone marrow liquid-based cytology in SCLC was 15.93% (18/113). The liver and bone metastases rates were significantly higher (55.56% vs 11.58% for liver metastasis, Pï¼0.001; 77.78% vs 16.84% for bone metastasis, Pï¼0.001) and thrombocytopenia was more common (16.67% vs 2.11%, P=0.033) in patients with tumor cells detected in liquid-based cytology than those without detected tumor cells. As for SE-iFISH, DTCs were detected in 92.92% of patients (105/113), the liver and bone metastasis rates were significantly higher (37.93% vs 11.90% for liver metastasis, P=0.002; 44.83% vs 20.23 % for bone metastasis, P=0.010), and the incidence of thrombocytopenia was significantly increased (13.79% vs 1.19%, P=0.020) in patients with DTCs≥111 per 3 ml than those with DTCsï¼111 per 3 ml. The positive rates of bone marrow liquid-based cytology in the disease control group and the disease progression group were 12.00% (12/100) and 46.15% (6/13), respectively, and the difference was statistically significant (P=0.002). However, the result of SE-iFISH revealed the DTCs quantities of the above two groups were 29 (8,110) and 64 (15,257) per 3 ml, and there was no statistical difference between the two groups (P=0.329). Univariate analysis depicted that the median progression-free survival (PFS) and median overall survival (OS) of liquid-based cytology positive patients were significantly shorter than those of tumor cell negative patients (6.33 months vs 9.27 months for PFS, P=0.019; 8.03 months vs 19.50 months for OS, P=0.019, P=0.033). The median PFS and median OS in patients with DTCs≥111 per 3 ml decreased significantly than those with DTCsï¼111 per 3 ml (6.83 months vs 9.50 months for PFS, P=0.004; 11.2 months vs 20.60 months for OS, P=0.019). Multivariate analysis showed that disease stage (HR=2.806, 95%CI:1.499-5.251, P=0.001) and DTCs quantity detected by SE-iFISH (HR=1.841, 95%CI:1.095-3.095, P=0.021) were independent factors of PFS, while disease stage was the independent factor of OS (HR=2.538, 95%CI:1.169-5.512, P=0.019). Conclusions: Both bone marrow liquid-based cytology and SE-iFISH are clinically feasible. The positive detection of liquid-based cytology or DTCs≥111 per 3 ml was correlated with distant metastasis, and DTCs≥111 per 3 ml was an independent prognostic factor of decreased PFS in SCLC.
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Médula Ósea , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Carcinoma Pulmonar de Células Pequeñas/patología , Neoplasias Pulmonares/patología , Pronóstico , Médula Ósea/patología , Estudios Prospectivos , Femenino , Masculino , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Neoplasias Óseas/secundario , Persona de Mediana Edad , Neoplasias de la Médula Ósea/secundario , Tasa de Supervivencia , Células de la Médula Ósea , Anciano , Trombocitopenia , Modelos de Riesgos Proporcionales , Estimación de Kaplan-Meier , Relevancia ClínicaRESUMEN
Objective: To analyze the survival benefits and treatment related toxic effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB-RT) for non-operative esophageal squamous cell carcinoma patients. Methods: The data of 2 132 ESCC patients who were not suitable for surgery or rejected operation, and underwent radical radiotherapy from 2002 to 2016 in 10 hospitals of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) were analyzed. Among them, 518 (24.3%) cases underwent SIB (SIB group) and 1 614 (75.7%) cases did not receive SIB (No-SIB group). The two groups were matched with 1â¶2 according to propensity score matching (PSM) method (caliper value=0.02). After PSM, 515 patients in SIB group and 977 patients in No-SIB group were enrolled. Prognosis and treatment related adverse effects of these two groups were compared and the independent prognostic factor were analyzed. Results: The median follow-up time was 61.7 months. Prior to PSM, the 1-, 3-, and 5-years overall survival (OS) rates of SIB group were 72.2%, 42.8%, 35.5%, while of No-SIB group were 74.3%, 41.4%, 31.9%, respectively (P=0.549). After PSM, the 1-, 3-, and 5-years OS rates of the two groups were 72.5%, 43.4%, 36.4% and 75.3%, 41.7%, 31.6%, respectively (P=0.690). The univariate survival analysis of samples after PSM showed that the lesion location, length, T stage, N stage, TNM stage, simultaneous chemoradiotherapy, gross tumor volume (GTV) and underwent SIB-RT or not were significantly associated with the prognosis of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Cox model multivariate regression analysis showed lesion location, TNM stage, GTV and simultaneous chemoradiotherapy were independent prognostic factors of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Stratified analysis showed that, in the patients whose GTV volume≤50 cm(3), the median survival time of SIB and No-SIB group was 34.7 and 30.3 months (P=0.155), respectively. In the patients whose GTV volume>50 cm(3), the median survival time of SIB and No-SIB group was 16.1 and 20.1 months (P=0.218). The incidence of radiation esophagitis and radiation pneumonitis above Grade 3 in SIB group were 4.3% and 2.5%, significantly lower than 13.1% and 11% of No-SIB group (P<0.001). Conclusions: The survival benefit of SIB-RT in patients with locally advanced esophageal carcinoma is not inferior to non-SIB-RT, but without more adverse reactions, and shortens the treatment time. SIB-RT can be used as one option of the radical radiotherapy for locally advanced esophageal cancer.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Neoplasias de Cabeza y Cuello , Radioterapia de Intensidad Modulada , Neoplasias Gástricas , Quimioradioterapia , Análisis de Datos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Humanos , Estudios RetrospectivosRESUMEN
KEY MESSAGE: WSL8 encoding a deoxyribonucleoside kinase (dNK) that catalyzes the first step in the salvage pathway of nucleotide synthesis plays an important role in early chloroplast development in rice. The chloroplast is an organelle that converts light energy into chemical energy; therefore, the normal differentiation and development of chloroplast are pivotal for plant survival. Deoxyribonucleoside kinases (dNKs) play an important role in the salvage pathway of nucleotides. However, the relationship between dNKs and chloroplast development remains elusive. Here, we identified a white stripe leaf 8 (wsl8) mutant that exhibited a white stripe leaf phenotype at seedling stage (before the four-leaf stage). The mutant showed a significantly lower chlorophyll content and defective chloroplast morphology, whereas higher reactive oxygen species than the wild type. As the leaf developed, the chlorotic mutant plants gradually turned green, accompanied by the restoration in chlorophyll accumulation and chloroplast ultrastructure. Map-based cloning revealed that WSL8 encodes a dNK on chromosome 5. Compared with the wild type, a C-to-G single base substitution occurred in the wsl8 mutant, which caused a missense mutation (Leu 349 Val) and significantly reduced dNK enzyme activity. A subcellular localization experiment showed the WSL8 protein was targeted in the chloroplast and its transcripts were expressed in various tissues, with more abundance in young leaves and nodes. Ribosome and RNA-sequencing analysis indicated that some components and genes related to ribosome biosynthesis were down-regulated in the mutant. An exogenous feeding experiment suggested that the WSL8 performed the enzymic activity of thymidine kinase, especially functioning in the salvage synthesis of thymidine monophosphate. Our results highlight that the salvage pathway mediated by the dNK is essential for early chloroplast development in rice.
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Cloroplastos/enzimología , Cloroplastos/metabolismo , Oryza/enzimología , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Clorofila/metabolismo , Cloroplastos/patología , Cloroplastos/ultraestructura , Clonación Molecular , Regulación de la Expresión Génica de las Plantas , Mutación Missense , Oryza/genética , Oryza/crecimiento & desarrollo , Oryza/ultraestructura , Fenotipo , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Proteínas de Plantas/genética , Plantas Modificadas Genéticamente , Especies Reactivas de Oxígeno/metabolismo , Ribosomas/metabolismo , Plantones/genética , Plantones/metabolismoRESUMEN
Objective: To evaluate the prognostic factors of T1-2N0M0 esophageal squamous cell carcinoma (ESCC) treated with definitive radiotherapy. Methods: The clinical data of 196 patients with T1-2N0M0 ESCC who were treated with definitive radiotherapy in 10 hospitals were retrospectively analyzed. All sites were members of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG). Radiochemotherapy were applied to 78 patients, while the other 118 patients received radiotherapy only. 96 patients were treated with three-dimensional conformal radiotherapy (3DCRT) and 100 treated with intensity-modulated radiotherapy (IMRT). The median dose of plan target volume(PTV) and gross target volume(GTV) were both 60 Gy. The median follow-up time was 59.2 months. Log rank test and Cox regression analysis were used for univariat and multivariate analysis, respectively. Results: The percentage of normal lung receiving at least 20 Gy (V(20)) was (18.65±7.20)%, with average dose of (10.81±42.05) Gy. The percentage of normal heart receiving at least 30 Gy (V(30)) was (14.21±12.28)%. The maximum dose of exposure in spinal cord was (39.65±8.13) Gy. The incidence of radiation pneumonia and radiation esophagitis were 14.80%(29/196) and 65.82%(129/196), respectively. The adverse events were mostly grade 1-2, without grade 4 toxicity. Median overall survival (OS) and progression-free survival (PFS) were 70.1 months and 62.3 months, respectively. The 1-, 3- and 5-year OS rates of all patients were 75.1%ã57.4% and 53.2%, respectively. The 1-, 3- and 5-year PFS rates were 75.1%ã57.4% and 53.2%, respectively. Multivariate analysis demonstrated that patients'age (HR=1.023, P=0.038) and tumor diameter (HR=1.243, P=0.028)were the independent prognostic factors for OS, while tumor volume were the independent prognostic factor for PFS. Conclusions: Definitive radiotherapy is a promising therapeutic method in patients with T1-2N0M0 ESCC. Patients' age, tumor diameter and tumor volume may impact patients' prognosis.
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Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas de Esófago/radioterapia , Antineoplásicos/uso terapéutico , Quimioradioterapia , Relación Dosis-Respuesta en la Radiación , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Humanos , Pronóstico , Dosificación Radioterapéutica , Radioterapia Conformacional , Radioterapia de Intensidad Modulada , Estudios RetrospectivosRESUMEN
Objective: To evaluate the survival and prognostic factors of radiotherapy in patient with â £ stage esophageal squamous carcinoma treated with radiation or chemoradiation. Methods: The medical records of 608 patients with stage â £ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed. Results: The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage â £A patients, and 58.8%, 29.0% and 23.5% in stage â £B patients. There was no statistical difference between the two groups (P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with â £ stage esophageal carcinomas after radiotherapy and chemotherapy (P<0.05). Multivariate analysis demonstrated that PGTV dose (OR=0.693, P=0.004), radiation esophagitis (OR=0.867, P=0.038), and radiation pneumonia (OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions: For patients with stage â £ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/métodos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/radioterapia , China/epidemiología , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Humanos , Estadificación de Neoplasias , Radioterapia de Intensidad Modulada/métodos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Angiogenesis is regulated by a balance of pro-angiogenic and anti-angiogenic factors. Vascular endothelial growth factor (VEGF) and endostatin respectively represents a frequent component of inducers and inhibitors in the process of angiogenesis. The ratio of VEGF/endostatin may reflect the balance of angiogenic switch. This study aimed to determine whether an imbalance between VEGF/endostatin exists in operable non-small cell lung cancer (NSCLC) patients and to assess the correlation, if any, between the imbalance and the prognosis. METHODS: Preoperative serum levels of VEGF and endostatin were simultaneously determined by quantitiative enzyme-linked immunosorbent assay (ELISA) and the ratio of them was calculated among 98 NSCLC patients and 51 healthy controls. The relationship between these factors and clinicopathological features, including prognosis, was examined. RESULTS: The ratio of VEGF/endostatin levels was significantly higher in operable NSCLC patients [median, 10.4; interquartile range (IQR), 5.9-19.8] than in normal controls [median, 5.1; IQR, 3.3-9.7] (P = 0.002). While the ratio in patients who were still alive for more than 60 months was 8.3 (IQR, 4.3-17.9), the ratio in those who died was 12.9 (IQR, 8.0-22.1) (p = 0.017). In subgroup analysis of patients with pathological stage N0, there was a statistically significant increase of the survival time in the group with a lower ratio than in the group with a higher ratio (p = 0.032). Multivariate analysis confirmed that the VEGF/endostatin ratio was an independent prognostic factor (p = 0.018). CONCLUSION: There was an imbalance between VEGF and endostatin in serum of operable NSCLC patients. The imbalance correlated with the prognosis of operable NSCLC.
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Adenocarcinoma/sangre , Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Células Escamosas/sangre , Endostatinas/sangre , Neoplasias Pulmonares/sangre , Factor A de Crecimiento Endotelial Vascular/sangre , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Células Escamosas/cirugía , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Neumonectomía , Pronóstico , Estudios ProspectivosRESUMEN
OBJECTIVE: To determine the efficacy and safety of early (<1 year post-disease onset) use of intrathecal baclofen (ITB). DESIGN: Consecutive case series of 14 individuals with spastic hypertonia due to trauma (5), anoxia (6) and stroke (3). MAIN OUTCOME MEASURES: Modified Ashworth (MAS) and Disability Rating (DRS) scales. INTERVENTIONS: ITB pump placement within 1 year of onset, after inadequate response to other previous treatment modalities. RESULTS: At follow-up after ITB pump implantation (mean = 13.9 months; mean daily dose = 591.5 microg per day), mean MAS scores improved from baseline by 1.0 and 2.1 points in the upper and lower limbs, respectively. DRS scores did not change significantly. Functional gains included decreased pain and improved gait speed and motor skills. The only complication was spinal leak in one subject. CONCLUSIONS: ITB therapy within 1 year of onset of acquired brain injury appears effective and safe in decreasing spastic hypertonia and does not appear to adversely affect recovery.
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Baclofeno/administración & dosificación , Lesiones Encefálicas/complicaciones , Relajantes Musculares Centrales/administración & dosificación , Espasticidad Muscular/tratamiento farmacológico , Adolescente , Adulto , Anciano , Lesiones Encefálicas/fisiopatología , Niño , Evaluación de la Discapacidad , Sistemas de Liberación de Medicamentos , Femenino , Humanos , Hipoxia/complicaciones , Hipoxia/fisiopatología , Infusiones Parenterales/métodos , Inyecciones Espinales/métodos , Masculino , Persona de Mediana Edad , Espasticidad Muscular/etiología , Espasticidad Muscular/fisiopatología , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/fisiopatología , Resultado del TratamientoRESUMEN
Twenty pediatric patients with primary hepatocellular carcinoma in Taiwan were tested for HBsAg, and all were found to be positive. The youngest case was 8 months of age, five cases occurred between 9 and 10 years of age, and 14 cases occurred between 11 and 16 years of age. The serum alpha-fetoprotein was elevated in all 20 primary hepatocellular carcinoma patients, and the average survival of these cases after diagnosis was 4.7 months. Seventy per cent of the mothers of the pediatric primary hepatocellular carcinoma cases and 52.9% of their siblings who were tested also were positive for HBsAg. In addition, two families had clustering of primary hepatocellular carcinoma cases. The occurrence of primary hepatoceullar carcinoma in the pediatric age group suggests the need for close follow-up of young HBsAg-positive carriers. Also, prevention of perinatal transmission of hepatitis B virus by immunoprophylaxis will significantly decrease both the hepatitis B virus carrier rate and the incidence of primary hepatocellular carcinoma in the asian population.
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Carcinoma Hepatocelular/inmunología , Portador Sano/inmunología , Antígenos de Superficie de la Hepatitis B/análisis , Neoplasias Hepáticas/inmunología , Adolescente , Carcinoma Hepatocelular/patología , Niño , Preescolar , Femenino , Hepatitis B/genética , Hepatitis B/microbiología , Hepatitis B/prevención & control , Humanos , Lactante , Neoplasias Hepáticas/patología , Masculino , alfa-Fetoproteínas/análisisRESUMEN
To have a better understanding of rubella seroepidemiology among female population in Taiwan, we report a serologic survey of 4030 examinations for 2030 school girls and 2000 pregnant women, using enzyme-linked immunosorbent assay for the detection of rubella specific IgG. RA 27/3 vaccines were given to susceptible volunteer students and postpartum women for the evaluation of vaccine efficiency and its side effects. The results showed that the rubella susceptible female among 8 to 22-year-old girl students was 44.97%, which was higher than expected, as most of them experienced the outbreak of rubella in 1977. The susceptibility rate among the pregnant women was 19.35%, which was also higher than expected for an age group having been through two outbreaks in the past. All the vaccinees showed good tolerance to the vaccine and the seroconversion rate was 100%. With such high susceptibility rate among women of child bearing age and girl students, plus the endemic property of rubella infection in Taiwan, we can expect a high risk of congenital rubella syndrome. Mass vaccination against rubella should be brought into effect immediately.