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1.
Leuk Res ; 143: 107542, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38924942

RESUMEN

Dasatinib is a potent second-generation tyrosine kinase inhibitor (TKI) used as a first-line treatment option for patients with chronic myeloid leukemia (CML). Currently, dose modification due to adverse events (AEs) is common in patients treated with dasatinib. This study compared the outcomes of two sequential prospective trials that enrolled patients with newly diagnosed chronic phase of CML (CP-CML) and initiated dasatinib at a starting dose of 100 mg daily. In the PCR-DEPTH study, CP-CML patients who started dasatinib 100 mg daily were enrolled and followed up, while in the DAS-CHANGE study, when patients achieved early molecular response with any grade of AEs were enrolled and treated with dasatinib 80 mg once daily. A total of 102 patients (PCR-DEPTH) and 90 patients (DAS-CHANGE) were compared. Although the median value of the relative dose intensity (RDI) of dasatinib was significantly higher in PCR-DEPTH than in DAS-CHANGE (99.6 % vs. 80.1 %, p <0.001), the MMR rate at 12months showed a trend toward superiority in DAS-CHANGE compared to PCR-DEPTH (77.1 % vs 65.2 %, p = 0.084). The frequencies of MR4.0 at 24 and 36 months were higher in DAS-CHANGE than in PCR-DEPTH (44.4 % vs 28.8 %, p = 0.052 and 63.6 % vs 40.3 %, p= 0.013, respectively). RDIs were not different according to the MMR, MR4.0 or MR4.5 in analyses using a pooled population. Our results suggest that early dose reduction of dasatinib does not compromise efficacy in patients achieving EMR at 3 months and could be an interventional strategy for improving long term outcomes.


Asunto(s)
Dasatinib , Leucemia Mielógena Crónica BCR-ABL Positiva , Inhibidores de Proteínas Quinasas , Humanos , Dasatinib/administración & dosificación , Dasatinib/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Adulto , Anciano , Estudios Prospectivos , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Resultado del Tratamiento , Adulto Joven , Anciano de 80 o más Años , Estudios de Seguimiento , Reducción Gradual de Medicamentos/métodos
2.
Curr Med Chem ; 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38639279

RESUMEN

INTRODUCTION: The CLDN18 gene, encoding claudin 18.1 and claudin 18.2, is a key component of tight junction strands in epithelial cells that form a paracellular barrier that is critical in Stomach Adenocarcinoma (STAD). METHODS: Our study included 1,095 patients with proven STAD, 415 from The Cancer Genome Atlas (TCGA) cohort and 680 from the Gene Expression Omnibus database. We applied various analyses, including gene set enrichment analysis, pathway analysis, and in vitro drug screening to evaluate survival, immune cells, and genes and gene sets associated with cancer progression, based on CLDN18 expression levels. Gradient boosting machine learning (70% for training, 15% for validation, and 15% for testing) was used to evaluate the impact of CLDN18 on survival and develop a survival prediction model. RESULTS: High CLDN18 expression correlated with worse survival in lymphocyte-poor STAD, accompanied by decreased helper T cells, altered metabolic genes, low necrosis-related gene expression, and increased tumor proliferation. CLDN18 expression showed associations with gene sets associated with various stomach, breast, ovarian, and esophageal cancers, while pathway analysis linked CLDN18 to immunity. Incorporating CLDN18 expression improved survival prediction in a machine learning model. Notably, nutlin-3a and niraparib effectively inhibited high CLDN18-expressing gastric cancer cells in drug screening. CONCLUSION: Our study provides a comprehensive understanding of the biological role of CLDN18-based bioinformatics and machine learning analysis in STAD, shedding light on its prognostic significance and potential therapeutic implications. To fully elucidate the molecular intricacies of CLDN18, further investigation is warranted, particularly through in vitro and in vivo studies.

3.
Thromb Res ; 236: 209-219, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38461615

RESUMEN

INTRODUCTION: There are few large-scale, population-based studies detailing the risks of thrombosis, hemorrhage, leukemic transformation in patients with myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF). METHODS: We performed a nationwide longitudinal cohort study using the Korean National Health Insurance System (NHIS) database. MPN patients (n = 11,991) and their 1:4 age- and sex-matched controls (n = 47,964) were enrolled. The risk of thrombosis, hemorrhage, leukemic transformation was estimated using a Cox proportional hazards regression, and stratified analyses were performed for related factors. RESULTS: During a median of 7.8 years of follow-up, 30.1 % of MPN patients (3614/11,991) and 19.0 % of the matched controls (9141/47,964) developed arterial thrombosis, 11.6 % of MPN patients (1397/11,991) and 6.4 % of the matched controls (3099/47,964) developed venous thrombosis and 18.7 % of MPN patients (2251/11,991) and 12.1 % of the matched controls (5836/47,964) developed hemorrhage. 4.9 % of MPN patients (597/11,991) and 0.1 % of matched controls (50/47,964) developed leukemia. The overall risk of developing thrombosis, hemorrhage, leukemic transformation was higher in MPN patients (adjusted hazard ratio [aHR] 1.695, 95 % confidence interval [CI]: 1.629-1.765 for arterial thrombosis, aHR 1.963, 95 % CI: 1.838-2.096 for venous thrombosis, and aHR 1.714, 95 % CI: 1.630-1.802 for hemorrhage) than in the controls. Patients with MPNs had a 10-year cumulative incidence of leukemic transformation of 6.2 %. CONCLUSION: The patients with MPNs have a higher risk of thrombosis, hemorrhage, and leukemic transformation than matched controls. Strategies are warranted to reduce the risk of thrombosis, hemorrhage, and leukemic transformation in MPN patients.


Asunto(s)
Trastornos Mieloproliferativos , Policitemia Vera , Trombosis , Trombosis de la Vena , Humanos , Estudios Longitudinales , Trastornos Mieloproliferativos/complicaciones , Trombosis/etiología , Policitemia Vera/epidemiología , Hemorragia/etiología , Hemorragia/epidemiología , Estudios de Cohortes
4.
Cancer Res Treat ; 55(4): 1096-1103, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37054719

RESUMEN

PURPOSE: Several previous studies and case reports have reported ethanol-induced symptoms in patients receiving anticancer drugs containing ethanol. Most docetaxel formulations contain ethanol as a solvent. However, there are insufficient data on ethanol-induced symptoms when docetaxel-containing ethanol is administered. The primary purpose of this study was to investigate the frequency and pattern of ethanol-induced symptoms during and after docetaxel administration. The secondary purpose was to explore the risk factors for ethanol-induced symptoms. MATERIALS AND METHODS: This was a prospective, multicenter, observational study. The participants filled out ethanol-induced symptom questionnaire on the day of chemotherapy and the following day. RESULTS: Data from 451 patients were analyzed. The overall occurrence rate of ethanol-induced symptoms was 44.3% (200/451 patients). The occurrence rate of facial flushing was highest at 19.7% (89/451 patients), followed by nausea in 18.2% (82/451 patients), and dizziness in 17.5% (79/451 patients). Although infrequent, unsteady walking and impaired balance occurred in 4.2% and 3.3% of patients, respectively. Female sex, presence of underlying disease, younger age, docetaxel dose, and docetaxel-containing ethanol amount were significantly associated with the occurrence of ethanol-induced symptoms. CONCLUSION: The occurrence of ethanol-induced symptoms was not low in patients receiving docetaxel-containing ethanol. Physicians need to pay more attention to the occurrence of ethanol-induced symptoms and prescribe ethanol-free or low-ethanol-containing formulations to high-risk patients.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Humanos , Femenino , Docetaxel/efectos adversos , Etanol/efectos adversos , Estudios Prospectivos , Antineoplásicos/efectos adversos , Pacientes , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico
5.
Cancer Res Treat ; 55(2): 684-692, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36596727

RESUMEN

PURPOSE: We conducted a nationwide, multicenter, prospective registry study for newly diagnosed patients with peripheral T-cell lymphoma (PTCL) to better define the clinical characteristics, treatment patterns, survival outcomes, and the role of upfront autologous stem cell transplantation (ASCT) in these patients. Materials and Methods: Patients with PTCL receiving chemotherapy with curative intent were registered and prospectively monitored. All patients were pathologically diagnosed with PTCL. RESULTS: A total of 191 patients with PTCL were enrolled in this prospective registry study. PTCL, not otherwise specified (PTCL-NOS) was the most common pathologic subtype (n=80, 41.9%), followed by angioimmunoblastic T-cell lymphoma (AITL) (n=60, 31.4%). With a median follow-up duration of 3.9 years, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 39.5% and 60.4%, respectively. The role of upfront ASCT was evaluated in patients who were considered transplant-eligible (n=59). ASCT was performed as an upfront consolidative treatment in 32 (54.2%) of these patients. There were no significant differences in PFS and OS between the ASCT and non-ASCT groups for all patients (n=59) and for patients with PTCL-NOS (n=26). However, in patients with AITL, the ASCT group was associated with significantly better PFS than the non-ASCT group, although there was no significant difference in OS. CONCLUSION: The current study demonstrated that the survival outcomes with the current treatment options remain poor for patients with PTCL-NOS. Upfront ASCT may provide a survival benefit for patients with AITL, but not PTCL-NOS.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/tratamiento farmacológico , Linfoma de Células T Periférico/patología , Trasplante Autólogo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , República de Corea/epidemiología
7.
Cancer Res Treat ; 54(3): 644-650, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35436813

RESUMEN

Although palliative sedation (PS) is a common practice in the palliative care of cancer patients in Western countries, there is little related research on the practice in Korea. PS can be classified into several categories according to sedation level and continuity. PS is clearly distinct from euthanasia. While euthanasia is illegal and regarded as unethical in Korea, there is little ethical and legal controversy about PS in terms of the doctrine of double effect. Most studies have asserted that PS does not shorten the survival of terminal cancer patients. Since preference for PS heavily depends on stakeholder value, it should be preceded by shared decision-making through full communication among the patient, family members, and medical team. This is a narrative review article analyzing previous studies, especially from the three Eastern Asian countries, Korea, Japan and Taiwan, which share similar cultures compared with Western countries. Practical issues concerning PS-for example, prevalence, type and dosage of medications, salvage medication, timing of its initiation, and assessment-are described in detail.


Asunto(s)
Sedación Profunda , Neoplasias , Cuidado Terminal , Muerte , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/epidemiología , Cuidados Paliativos , República de Corea
8.
Cancer Res Treat ; 53(4): 908-916, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34082495

RESUMEN

PURPOSE: In Korea, the "Act on Hospice and Palliative Care and Decisions on Life-sustaining Treatment for Patients at the End of Life" was enacted on February 4, 2018. This study was conducted to analyze the current state of life-sustaining treatment decisions based on National Health Insurance Service (NHIS) data after the law came into force. MATERIALS AND METHODS: The data of 173,028 cancer deaths were extracted from NHIS qualification data between November 2015 and January 2019. RESULTS: The number of cancer deaths complied with the law process was 14,438 of 54,635 cases (26.4%). The rate of patient self-determination was 49.0%. The patients complying with the law process have used a hospice center more frequently (28% vs. 14%). However, the rate of intensive care unit (ICU) admission was similar between the patients who complied with and without the law process (ICU admission, 23% vs. 21%). There was no difference in the proportion of patients who had undergone mechanical ventilation and hemodialysis in the comparative analysis before and after the enforcement of the law and the analysis according to the compliance with the law. The patients who complied with the law process received cardiopulmonary resuscitation at a lower rate. CONCLUSION: The law has positive effects on the rate of life-sustaining treatment decision by patient's determination. However, there was no sufficient effect on the withholding or withdrawing of life-sustaining treatment, which could protect the patient from unnecessary or harmful interventions.


Asunto(s)
Toma de Decisiones , Cuidados para Prolongación de la Vida/psicología , Neoplasias/terapia , Cuidados Paliativos/psicología , Cuidado Terminal/psicología , Privación de Tratamiento/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Muerte , Demografía , Femenino , Estudios de Seguimiento , Humanos , Cuidados para Prolongación de la Vida/legislación & jurisprudencia , Masculino , Persona de Mediana Edad , Neoplasias/mortalidad , Neoplasias/psicología , Pronóstico , República de Corea , Factores Socioeconómicos , Tasa de Supervivencia , Cuidado Terminal/legislación & jurisprudencia , Privación de Tratamiento/ética , Privación de Tratamiento/legislación & jurisprudencia , Adulto Joven
9.
Cancer Res Treat ; 53(4): 926-934, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34082493

RESUMEN

PURPOSE: Six forms relating to decisions on life-sustaining treatment (LST) for patients at the end-of-life (EOL) in hospital are required by the "Act on Decision of LST for Patients at the EOL." We investigated the preparation and creation status of these documents from the database of the National Agency for Management of LST. MATERIALS AND METHODS: We analyzed the contents and details of each document necessary for decisions on LST, and the creation status of forms. We defined patients completing form 1 as "self-determined" of LST, and those whose family members had completed form 11/12 as "family decision" of LST. According to the determination subject, we compared the four items of LST on form 13 (the paper of implementation of LST) and the documentation time interval between forms. RESULTS: The six forms require information about the patient, doctor, specialized doctor, family members, institution, decision for LST, and intention to use hospice services. Of 44,381 who had completed at least one document, 36,693 patients had form 13. Among them, 11,531, 10,976, and 12,551 people completed forms 1, 11, and 12, respectively. The documentation time interval from forms 1, 11, or 12 to form 13 was 8.6±13.6 days, 1.0±9.5 days, and 1.5±9.7 days, respectively. CONCLUSION: The self-determination rate of LST was 31% and the mean time interval from self-determination to implementation of LST was 8.6 days. The creation of these forms still takes place when the patients are close to death.


Asunto(s)
Enfermedad/psicología , Familia/psicología , Formularios como Asunto , Hospitales/tendencias , Médicos/psicología , Pautas de la Práctica en Medicina/estadística & datos numéricos , Cuidado Terminal/psicología , Privación de Tratamiento/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Toma de Decisiones , Enfermedad/etiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , República de Corea , Tasa de Supervivencia , Cuidado Terminal/legislación & jurisprudencia , Privación de Tratamiento/ética , Privación de Tratamiento/legislación & jurisprudencia
10.
Cancer Res Treat ; 53(4): 917-925, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34082494

RESUMEN

PURPOSE: The main purpose of the Life-Sustaining Treatment Decisions Act recently enacted in Korea is to respect the patient's self-determination. We aimed to investigate the current status and features of patient self-determination after implementation of the law. MATERIALS AND METHODS: Between February 2018 and January 2019, 54,635 cancer deaths were identified from the National Health Insurance Service (NHIS) database. We analyzed the characteristics of decedents who complied with the law process by self-determination compared with decedents with family determination and with decedents who did not comply with the law process. RESULTS: In multivariable analysis, patients with self-determination were younger, were less likely to live in rural areas, were less likely to belong to the highest income quintile, were less likely to be treated in general hospitals, and were more likely to show a longer time from cancer diagnosis compared with patients with family determination. Compared with patients who did not comply with the law process, patients with self-determination were younger, lived in Seoul or capital area, were less likely to belong to the highest income quintile, were treated in general hospitals, were less likely to have genitourinary or hematologic malignancies, scored higher on the Charlson comorbidity index, and showed a longer time from cancer diagnosis. Patients with self-determination were more likely to use hospice and less likely to use intensive care units (ICUs) at the end-of-life (EOL). CONCLUSION: Decedents with self-determination were more likely to be younger, reside in the Seoul or capital area, show a longer time from cancer diagnosis, and were less likely to belong to the highest income quintile. They utilized hospice more frequently, and received less ICU care at the EOL.


Asunto(s)
Toma de Decisiones , Neoplasias/terapia , Cuidados Paliativos/psicología , Autonomía Personal , Autocontrol/psicología , Cuidado Terminal/psicología , Privación de Tratamiento/estadística & datos numéricos , Anciano , Muerte , Femenino , Estudios de Seguimiento , Humanos , Masculino , Neoplasias/mortalidad , Neoplasias/psicología , Pronóstico , República de Corea , Tasa de Supervivencia , Cuidado Terminal/legislación & jurisprudencia , Privación de Tratamiento/ética , Privación de Tratamiento/legislación & jurisprudencia
11.
Cancer Res Treat ; 53(4): 897-907, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34082496

RESUMEN

PURPOSE: The "Act on Hospice and Palliative Care and Decisions on Life-Sustaining Treatment for Patients at the End-of-Life" was enacted on February 3, 2016 and went into effect on February 4, 2018 in Korea. This study reviewed the first year of determination to life-sustaining treatment (LST) through data analysis of the National Agency for Management of Life-Sustaining Treatment. MATERIALS AND METHODS: The National Agency for Management of LST provided data between February 4, 2018 and January 31, 2019 anonymously from 33,549 patients. According to the forms patients were defined as either elf-determinants or family-determinants. RESULTS: The median age of the patient was 73 and the majority was male (59.9%). Cancer patients were 59% and self-determinants were 32.1%. Cancer patients had a higher rate of self-determinants than non-cancer (47.3% vs. 10.1%). Plan for hospice service was high in cancer patients among self-determinants (81.0% vs. 37.5%, p < 0.001). In comparison to family-determinants, self-determinants were younger (median age, 67 years vs. 75 years; p < 0.001) and had more cancer diagnosis (87.1% vs. 45.9%, p < 0.001). Decision of withholding or withdrawing of LSTs in cancer patients was higher than non-cancer patients in four items. CONCLUSION: Cancer patients had a higher rate in self-determination and withholding or withdrawing of LSTs than non-cancer patients. Continued revision of the law and education of the public will be able to promote withdrawing or withholding the futile LSTs in patients at end-of-life. Further study following the revision of the law should be evaluated to change of end-of-life care.


Asunto(s)
Toma de Decisiones , Cuidados para Prolongación de la Vida/psicología , Neoplasias/terapia , Cuidados Paliativos/psicología , Cuidado Terminal/psicología , Privación de Tratamiento/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Muerte , Femenino , Estudios de Seguimiento , Humanos , Cuidados para Prolongación de la Vida/legislación & jurisprudencia , Masculino , Persona de Mediana Edad , Neoplasias/mortalidad , Neoplasias/psicología , Pronóstico , República de Corea , Tasa de Supervivencia , Cuidado Terminal/legislación & jurisprudencia , Privación de Tratamiento/ética , Privación de Tratamiento/legislación & jurisprudencia , Adulto Joven
13.
Ann Hematol ; 99(2): 255-264, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31897676

RESUMEN

We assessed the efficacy and toxicity of etoposide, methylprednisolone, high-dose cytarabine, and oxaliplatin (ESHAOx) combination chemotherapy in patients with refractory or relapsed Hodgkin's lymphoma (HL). This was an open-label, non-randomized, multi-center phase II study. The ESHAOx regimen consisted of intravenous (i.v.) etoposide 40 mg/m2 on days 1 to 4, i.v. methylprednisolone 500 mg on days 1 to 5, i.v. cytarabine 2 g/m2 on day 5, and i.v. oxaliplatin 130 mg/m2 on day 1. Cycles (up to six) were repeated every 3 weeks. In an effort to identify prognostic markers, the serum levels of cytokines including tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and vascular endothelial growth factor (VEGF) were measured at the time of study entry. A total of 37 patients were enrolled, and 36 were available for evaluation of tumor response. The overall response rate was 72.2% (26/36) (complete response, 33.3% [12/36]; partial response, 38.9% [14/36]). The median time to progression was 34.9 months (95% confidence interval, 23.1-46.7 months). The most common grade 3 or 4 hematological adverse events were neutropenia (16/37, 43.2%), followed by thrombocytopenia (10/37, 27.0%). Grade 3 or 4 non-hematological adverse events were nausea (3/37, 8.1%), anorexia (2/37, 5.4%), mucositis (1/37, 2.7%), and skin rash (1/37, 2.7%). There were no treatment-related deaths. High levels of TNF-α and CRP were significantly associated with poorer overall survival (p = 0.00005 for TNF-α, p = 0.0004 for CRP, respectively). The ESHAOx regimen exhibited antitumor activity and an acceptable safety profile in patients with refractory or relapsed HL. Trial Registration: ClinicalTrials.gov. Registered February 21, 2011, https://clinicaltrials.gov/ct2/show/NCT01300156.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Enfermedad de Hodgkin , Proteínas de Neoplasias/sangre , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Proteína C-Reactiva/metabolismo , Citarabina/administración & dosificación , Citarabina/efectos adversos , Supervivencia sin Enfermedad , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Enfermedad de Hodgkin/sangre , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/mortalidad , Humanos , Masculino , Metilprednisolona/administración & dosificación , Metilprednisolona/efectos adversos , Persona de Mediana Edad , Oxaliplatino/administración & dosificación , Oxaliplatino/efectos adversos , Recurrencia , Tasa de Supervivencia , Factores de Tiempo , Factor de Necrosis Tumoral alfa/sangre , Factor A de Crecimiento Endotelial Vascular/sangre
14.
Ann Hematol ; 99(1): 213, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31844930

RESUMEN

An additional affiliation for the first author was not indicated. Hyewon Lee is also affiliated with: Department of Internal Medicine, Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul, South Korea.

15.
Cancer Res Treat ; 52(1): 277-283, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31319640

RESUMEN

PURPOSE: The purpose of this study was to evaluate clinical characteristics and treatment pattern of ovarian clear cell carcinoma (OCCC) in Korea and the role of adjuvant chemotherapy in early stage. MATERIALS AND METHODS: Medical records of 308 cases of from 21 institutions were reviewed and data including age, performance status, endometriosis, thromboembolism, stage, cancer antigen 125, treatment, recurrence, and death were collected. RESULTS: Regarding stage of OCCC, it was stage I in 194 (63.6%), stage II in 34 (11.1%), stage III in 66 (21.6%), and stage IV in 11 (3.6%) patients. All patients underwent surgery. Optimal surgery (residual disease ≤ 1 cm) was achieved in 89.3%. Majority of patients (80.5%) received postoperative chemotherapy. The most common regimen was taxane-platinum combination (96%). Median relapse-free survival (RFS) was 138.5 months for stage I, 33.4 for stage II, 19.3 for stage III, and 9.7 for stage IV. Median overall survival (OS) were not reached, 112.4, 48.7, and 18.3 months for stage I, II, III, and IV, respectively. Early-stage (stage I), endometriosis, and optimal debulking were identified as favorable prognostic factors for RFS. Early-stage and optimal debulking were also favorable prognostic factors for OS. Majority of patients with early-stage received adjuvant chemotherapy. However, additional survival benefit was not found in terms of recurrence. CONCLUSION: Majority of patients had early-stage and received postoperative chemotherapy regardless of stage. Early-stage and optimal debulking were identified as favorable prognostic factors. In stage IA or IB, adding adjuvant chemotherapy did not show difference in survival. Further study focusing on OCCC is required.


Asunto(s)
Adenocarcinoma de Células Claras/diagnóstico , Neoplasias Ováricas/diagnóstico , Adenocarcinoma de Células Claras/etiología , Adenocarcinoma de Células Claras/mortalidad , Adenocarcinoma de Células Claras/terapia , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neoplasias Ováricas/etiología , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/terapia , Pronóstico , República de Corea , Estudios Retrospectivos , Resultado del Tratamiento
16.
Orphanet J Rare Dis ; 14(1): 114, 2019 05 23.
Artículo en Inglés | MEDLINE | ID: mdl-31122244

RESUMEN

BACKGROUND: Current diagnostic tests for hereditary spherocytosis (HS) focus on the detection of hemolysis or indirectly assessing defects of membrane protein, whereas direct methods to detect protein defects are complicated and difficult to implement. In the present study, we investigated the patterns of genetic variation associated with HS among patients clinically diagnosed with HS. METHODS: Multi-gene targeted sequencing of 43 genes (17 RBC membrane protein-encoding genes, 20 RBC enzyme-encoding genes, and six additional genes for the differential diagnosis) was performed using the Illumina HiSeq platform. RESULTS: Among 59 patients with HS, 50 (84.7%) had one or more significant variants in a RBC membrane protein-encoding genes. A total of 54 significant variants including 46 novel mutations were detected in six RBC membrane protein-encoding genes, with the highest number of variants found in SPTB (n = 28), and followed by ANK1 (n = 19), SLC4A1 (n = 3), SPTA1 (n = 2), EPB41 (n = 1), and EPB42 (n = 1). Concurrent mutations of genes encoding RBC enzymes (ALDOB, GAPDH, and GSR) were detected in three patients. UGT1A1 mutations were present in 24 patients (40.7%). Positive rate of osmotic fragility test was 86.8% among patients harboring HS-related gene mutations. CONCLUSIONS: This constitutes the first large-scaled genetic study of Korean patients with HS. We demonstrated that multi-gene target sequencing is sensitive and feasible that can be used as a powerful tool for diagnosing HS. Considering the discrepancies of clinical and molecular diagnoses of HS, our findings suggest that molecular genetic analysis is required for accurate diagnosis of HS.


Asunto(s)
Fragilidad Osmótica/fisiología , Esferocitos/metabolismo , Esferocitosis Hereditaria/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proteína 1 de Intercambio de Anión de Eritrocito/genética , Proteína 1 de Intercambio de Anión de Eritrocito/metabolismo , Ancirinas/genética , Ancirinas/metabolismo , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Niño , Preescolar , Proteínas del Citoesqueleto/genética , Proteínas del Citoesqueleto/metabolismo , Femenino , Glucuronosiltransferasa/genética , Glucuronosiltransferasa/metabolismo , Humanos , Lactante , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Persona de Mediana Edad , Mutación/genética , Fragilidad Osmótica/genética , Patología Molecular , República de Corea , Espectrina/genética , Espectrina/metabolismo , Esferocitosis Hereditaria/genética , Adulto Joven
17.
J Pain Symptom Manage ; 58(1): 65-71, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31026509

RESUMEN

CONTEXT: Limited information is available regarding the detailed clinical patterns of palliative sedation (PS), that is, the symptom control rate, salvage medication, and the effectiveness of intermittent PS (IPS) versus continuous PS (CPS). OBJECTIVES: The primary aim was to investigate clinical outcomes of PS in a real clinical setting. METHODS: Clinical information was prospectively collected for patients who were treated according to a prescribed protocol and assessment tools in a hospice unit affiliated with a tertiary cancer center between September 2015 and March 2017. Data were analyzed retrospectively. Midazolam was used as the first medication for PS, and propofol and phenobarbital were subsequently used as salvage medications. Indications of PS, the depth of sedation, the quality of sleep, and the level of consciousness were assessed. RESULTS: A total of 306 patients were enrolled, 89 of whom (29.1%) received PS. No difference in survival time was found between patients with and without PS (median survival, 34.0 vs 25.0 days, P = 0.109). Delirium was the most common indication of PS. The symptoms of 73 (82.0%) of 89 patients with PS were relieved with midazolam. Twelve (75.0%) of 16 midazolam-failure patients responded to propofol, five of whom (31%) exhibited respiratory depression. Of the 89 patients receiving PS, 61 (68.5%) received IPS and 28 patients (31.5%) received CPS. The median survival times from PS initiation to death were six days in the IPS group and one day in the CPS group (P < 0.001). Interestingly, consciousness levels were significantly improved after IPS in the delirium group compared with those in the other group (41.7% vs 16.7%, P = 0.002). CONCLUSION: The refractory symptoms of end-of-life patients with cancer can ultimately be relieved with various medications for PS. IPS may improve the consciousness level of patients with delirium.


Asunto(s)
Sedación Consciente/métodos , Sedación Profunda/métodos , Midazolam/uso terapéutico , Neoplasias , Cuidados Paliativos/métodos , Enfermo Terminal , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
18.
Cancer Res Treat ; 51(4): 1612-1619, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30999722

RESUMEN

PURPOSE: Malnutrition and a loss of muscle mass are frequent in cancer patients and have a negative effect on clinical outcome. Nutrition risk screening aims to increase awareness and allow early recognition and treatment of cancer cachexia. Therefore, screenings should be brief, inexpensive, highly sensitive, and have good specificity. Simplified Nutritional Appetite Questionnaire (SNAQ) is a simple screening tool including four questions, and validated to predict weight loss within 6 months in community-dwelling adults and nursing home residents. Our study aimed to translate the SNAQ into Korean, and to assess the validity and reliability of the translated screening tool in advanced cancer patients. MATERIALS AND METHODS: The SNAQ was translated into Korean according to linguistic validation. The internal consistency of the SNAQ was evaluated by Cronbach's alpha coefficient. Test-retest reliability was evaluated using the intraclass correlation coefficient. Concurrent validity was evaluated by measuring the Pearson's correlation coefficient between the SNAQ and Mini-Nutritional Assessment (MNA) and Patient-Generated Subjective Global Assessment (PG-SGA). RESULTS: In the 194 patients included in full analysis set, cancer stage was predominantly metastatic (98.5%), the mean age was 60 years (range, 23 to 81 years), and the mean body mass index was 24 kg/m2 (range, 15.6 to 39.6 kg/m2). According to MNA score ≤ 11, 57 patients (29.4%) were malnourished. The mean score (±standard deviation) of the Korean version of the SNAQ was 13.8±2.5 with a range of 6-19. Cronbach's alpha coefficient was 0.737, and intraclass correlation coefficient was 0.869. The SNAQ was moderately correlated with MNA (r=0.404, p < 0.001) and PG-SGA (r=-0.530, p < 0.001). A significant weight loss of > 5% of the original bodyweightwithin 6 months occurred in 46 of the 186 patients (24.7%). SNAQ score ≤ 14 predicted > 5% weight loss with a sensitivity of 56.5% and a specificity of 44.3%. CONCLUSION: The Korean version of the SNAQ had high validity and reliability. SNAQ is useful for the screening tool for advanced cancer patients. The SNAQ had a limitation to predict impending weight loss in advanced cancer patients.


Asunto(s)
Desnutrición/epidemiología , Neoplasias/complicaciones , Sarcopenia/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Estudios Longitudinales , Masculino , Desnutrición/diagnóstico , Persona de Mediana Edad , Neoplasias/patología , Evaluación Nutricional , Reproducibilidad de los Resultados , Sarcopenia/diagnóstico , Adulto Joven
19.
Oncotarget ; 9(5): 6607-6614, 2018 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-29464096

RESUMEN

Decitabine is widely accepted as the treatment options for elderly acute myeloid leukemia (AML) patients. However, the efficacy has yet been assessed in Asian population. We retrospectively analyzed the outcomes of 80 Korean elderly AML patients who were treated with decitabine. The median age was 74 years (range, 64 to 86 years) and 6 (7.5%), 48 (60.0%), and 25 (31.3%) patients were categorized to favorable, intermediate, and poor risk group, respectively. The median OS was 10.2 months (95% CI 5.0-15.4). Given that decitabine treatment demonstrated improved clinical outcomes, it could be considered as one of the first-line treatment for Korean elderly AML patients.

20.
Int J Oncol ; 51(6): 1739-1746, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29039521

RESUMEN

KML001 (sodium metaarsenite;NaAs2O3) is known to have antitumor activity against a variety of cancers. In this study, we examined its effect on multiple myeloma (MM). KML001 reduced the growth of all MM cell lines examined with an IC50 of 5x10­8 M. Exposure to KML001 (5x10­8 M) decreased levels of cyclins A/B1/D1/E1, CDK2/4/6 in U266 cells and increased the p21 and p27 levels. Furthermore, p21 became bound to CDK2/4/6, resulting in a reduction of CDK2/4/6 kinase activity. The cleaved forms of Bcl-2, and caspases­3, ­8 and ­9 were detected, and the anti-apoptotic molecule, Bax, also increased. Activation of STAT1/3, NF-κB (p65 and p50 subunits), pAKT and pERK decreased, and p­PTEN increased. There was also a significant reduction of hTERT at 12 h and upregulation of γ-H2AX and CHK1/2 molecules at 24 h. Thus, KML001 appears to have antitumor activity against MM by inhibiting various oncogenic signaling pathways. It may be useful for treating MM.


Asunto(s)
Arsenitos/farmacología , Mieloma Múltiple/tratamiento farmacológico , Compuestos de Sodio/farmacología , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Procesos de Crecimiento Celular/efectos de los fármacos , Línea Celular Tumoral , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Quinasas Ciclina-Dependientes/metabolismo , Daño del ADN , Relación Dosis-Respuesta a Droga , Humanos , Mieloma Múltiple/genética , Mieloma Múltiple/metabolismo , Mieloma Múltiple/patología , Transducción de Señal/efectos de los fármacos , Telomerasa/biosíntesis , Telomerasa/genética , Telómero/genética , Telómero/metabolismo
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