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1.
Front Oncol ; 14: 1307315, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38352893

RESUMO

Introduction: Despite the current effective treatments for acute promyelocytic leukemia (APL), early mortality (EM), defined as death within 30 days of presentation, is a major hurdle to long-term survival. Methods: We performed a multicenter retrospective study to evaluate the incidence and clinical characteristics of EM in patients with newly diagnosed APL and to develop a risk stratification model to predict EM. Results: We identified 313 eligible patients diagnosed between 2000 and 2021 from five academic hospitals. The median age was 50 years (range 19-94), and 250 (79.9%) patients were <65 years. Most patients (n=274, 87.5%) received their first dose of all-trans retinoic acid (ATRA) within 24 hours of presentation. EM occurred in 41 patients, with a cumulative incidence of 13.1%. The most common cause of EM was intracranial hemorrhage (n=22, 53.6%), and most EMs (31/41, 75.6%) occurred within the first seven days of APL presentation. In a multivariable analysis, we identified three independent factors predicting EM: age ≥65 years (HR, 2.56), white blood cell count ≥8.0 x 109/L (HR, 3.30), and ATRA administration >24 hours of presentation (HR, 2.95). Based on these factors, patients were stratified into three categories with a significantly increasing risk of EM: 4.1% for low risk (54.3%; no risk factors; HR 1), 18.5% for intermediate risk (34.5%; 1 factor; HR 4.81), and 40.5% for high risk (11.2%; 2-3 factors; HR 13.16). Discussion: The risk of EM is still not negligible in this era of ATRA-based therapies. Our risk model serves as a clinically useful tool to identify high-risk patients for EM who may be candidates for novel treatments and aggressive supportive strategies.

2.
Anticancer Res ; 44(1): 347-359, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38160001

RESUMO

BACKGROUND/AIM: This study investigated the treatment patterns and prognosis of patients with metastatic or unresectable colorectal cancer (mCRC) treated with chemotherapy with targeting agents. PATIENTS AND METHODS: This longitudinal multicenter study included 963 patients with mCRC who were treated in Korea between 2016 and 2020. Treatment patterns and efficacy were compared according to the mutation status and clinical factors. RESULTS: As first-line therapy, most of the patients (83.5%) received FOLFOX plus bevacizumab (35.4%), followed by FOLFIRI plus bevacizumab (18.8%), FOLFIRI plus cetuximab (17.0%), and FOLFOX plus cetuximab (12.3%). Bevacizumab was the most frequent agent (78.8%) combined with chemotherapy in RAS-mutated CRC, while cetuximab (57.2%) in RAS wild-type CRC. Cetuximab was frequently combined with a doublet regimen in patients with left-sided CRC than in those with right-sided CRC (34.4% vs. 16%). As second-line therapy, most patients (63.4%) also received doublet regimens with bevacizumab, and FOLFIRI plus aflibercept was administered in 15.1%. The objective response rate with FOLFIRI plus cetuximab was significantly higher in patients with left-sided CRC than in those with right-sided CRC (59.2% vs. 30.8%, p=0.008) and marginally higher in patients with RAS wild-type CRC than in those with RAS-mutated CRC (55.6% vs. 0.0%, p=0.092). Progression-free survival (PFS) with FOLFOX plus bevacizumab was significantly shorter than that with FOLFIRI plus bevacizumab (p=0.030) in RAS-mutated CRC, whereas there were no significant differences between regimens in RAS wild-type CRC. CONCLUSION: In patients with unresectable metastatic colorectal cancer, doublet chemotherapy with targeting agents is the most common therapy and efficacy depends on the mutation status as well as clinical factors.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Cetuximab , Neoplasias do Colo/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Prognóstico , Neoplasias Retais/tratamento farmacológico
3.
ACS Appl Mater Interfaces ; 15(39): 45539-45548, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37713436

RESUMO

Fluorescent dyes have garnered significant attention as theranostic platforms owing to their inherent characteristics. In this study, we present the discovery of Medical Fluorophore 33 (MF33), a novel and potent theranostic agent with a phenaleno-isoquinolinium salt structure that can serve as a cancer therapeutic strategy. The synthesis of MF33 is readily achievable through a simple Rh(III)-catalyzed reaction. Moreover, MF33 displayed strong fluorescence signals, excellent microsomal stability, and high biocompatibility in vivo. It induces significant apoptosis in cancer cells via the p53/p21/caspase-3 signaling pathway, leading to selective cytotoxicity in various cancer cells. In vivo fluorescence imaging with MF33 enabled the visualization of sentinel lymph nodes in living mice. Notably, repeated intraperitoneal administration of MF33 resulted in antitumor activity in mice with colorectal cancer. Collectively, our findings suggest that phenaleno-isoquinolinium salt-based MF33 is a viable theranostic agent for biomedical imaging and cancer treatment.


Assuntos
Corantes Fluorescentes , Neoplasias , Animais , Camundongos , Corantes Fluorescentes/química , Medicina de Precisão , Estudos de Viabilidade , Neoplasias/terapia , Nanomedicina Teranóstica/métodos
4.
World J Clin Cases ; 11(21): 5129-5135, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37583856

RESUMO

BACKGROUND: Simultaneous bilineage hematologic malignancies are rare; however, several cases of acute myeloid leukemia (AML) and T-lymphoblastic lymphoma (T-LBL) co-occurrence have been reported. A standard treatment for simultaneous AML and T-LBL has not yet been established, and its prognosis is very poor. Further studies to develop standard treatments are required to increase patient survival rates. CASE SUMMARY: A 69-year-old man complaining of pleuritic chest pain visited the emergency room. Computed tomography revealed multiple enlarged lymph nodes (LNs) in the neck and groin and pulmonary thromboembolism with pulmonary infarction. Furthermore, a peripheral blood smear performed due to leukocytosis revealed circulating blasts. Acute myelomonocytic leukemia (AMML) was diagnosed after bone marrow examination, and T-LBL positivity for terminal deoxynucleotidyl transferase, cluster of differentiation (CD)34, and CD4 was confirmed by cervical LN biopsy. Decitabine and dexamethasone were administered because he could not receive intensive chemotherapy due to poor performance status. Complete remission of AMML and T-LBL was achieved after 4 cycles of decitabine plus dexamethasone. CONCLUSION: We report the therapeutic effect of decitabine, a hypomethylating agent (HMA), in patients with concurrent bilineage hematologic malignancies and suggest that further studies are required to evaluate the therapeutic effect of HMAs on both lymphoid and bilineage hematologic malignancies.

5.
Mol Pharmacol ; 104(5): 214-229, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37595967

RESUMO

Nonalcoholic steatohepatitis (NASH) is a severe liver metabolic disorder, however, there are still no effective and safe drugs for its treatment. Previous clinical trials used various therapeutic approaches to target individual pathologic mechanisms, but these approaches were unsuccessful because of the complex pathologic causes of NASH. Combinatory therapy in which two or more drugs are administered simultaneously to patients with NASH, however, carries the risk of side effects associated with each individual drug. To solve this problem, we identified gossypetin as an effective dual-targeting agent that activates AMP-activated protein kinase (AMPK) and decreases oxidative stress. Administration of gossypetin decreased hepatic steatosis, lobular inflammation and liver fibrosis in the liver tissue of mice with choline-deficient high-fat diet and methionine-choline deficient diet (MCD) diet-induced NASH. Gossypetin functioned directly as an antioxidant agent, decreasing hydrogen peroxide and palmitate-induced oxidative stress in the AML12 cells and liver tissue of MCD diet-fed mice without regulating the antioxidant response factors. In addition, gossypetin acted as a novel AMPK activator by binding to the allosteric drug and metabolite site, which stabilizes the activated structure of AMPK. Our findings demonstrate that gossypetin has the potential to serve as a novel therapeutic agent for nonalcoholic fatty liver disease /NASH. SIGNIFICANCE STATEMENT: This study demonstrates that gossypetin has preventive effect to progression of nonalcoholic steatohepatitis (NASH) as a novel AMP-activated protein kinase (AMPK) activator and antioxidants. Our findings indicate that simultaneous activation of AMPK and oxidative stress using gossypetin has the potential to serve as a novel therapeutic approach for nonalcoholic fatty liver disease /NASH patients.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/metabolismo , Antioxidantes/metabolismo , Fígado/metabolismo , Estresse Oxidativo , Colina/metabolismo , Colina/farmacologia , Colina/uso terapêutico , Metionina/metabolismo , Metionina/farmacologia , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
6.
J Cancer Res Clin Oncol ; 149(3): 1131-1143, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35344080

RESUMO

PURPOSE: To evaluate the safety and effectiveness of aflibercept in combination with fluorouracil, leucovorin, and irinotecan (FOLFIRI) in Korean patients with metastatic colorectal cancer (mCRC) who progressed with oxaliplatin-containing regimen. METHODS: This was a prospective observational study conducted at 22 sites across Korea between February 2018 and September 2019. Patients aged > 19 years with a diagnosis of mCRC who were prescribed aflibercept plus FOLFIRI, after progression with an oxaliplatin-containing regimen were included. Disease assessment was performed every 6 weeks. RESULTS: A total of 185 patients were included (males, 58.9%; right-sided tumors, 23.8%; and ECOG performance factor ≥ 1, 68.6%). A total of 514 adverse events (AEs) occurred in 134 patients, of which 206 (49.2%; 95% CI 42.0%, 56.4%) events were considered as adverse drug reactions (ADRs), 172 unexpected AEs (49.7%; 95% CI 42.5%, 56.9%), and 53 serious AEs (22.2%; 95% CI16.2%, 28.2%). The most common serious ADR was pneumonia (n = 2, 1.6%). The most common all grade hematological AE and non-hematological AE were neutropenia (21.6%) and nausea (16.2%), respectively. Over a median follow-up of 5.6 months, a total of five grade 5 (1.0%) AEs were reported. Median OS was 9.4 months, and median progression-free survival (PFS) was 7.3 months. The overall response rate was 14.6%. Right-sided tumor location and prior bevacizumab treatment were independent factors of poor PFS in multivariate analysis. CONCLUSION: Aflibercept in combination with FOLFIRI was effective and showed an acceptable safety profile in Korean patients with mCRC in daily clinical practice.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Masculino , Humanos , Oxaliplatina/uso terapêutico , Neoplasias Colorretais/patologia , Camptotecina/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Bevacizumab/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Fluoruracila/uso terapêutico , Leucovorina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , República da Coreia
7.
Arch Iran Med ; 26(9): 542-546, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38310409

RESUMO

An intramural gastric abscess is a rare condition often mistaken for other medical diseases such as gastric cancer and neoplasms. We present a case of a patient initially believed to have pancreatic cancer based on his computed tomography scan. The clinical diagnosis of locally advanced gastric cancer was made on subsequent magnetic resonance cholangiography and endoscopic ultrasound (EUS). However, several EUS-guided biopsies did not reveal malignant cells. A partial gastrectomy was performed for diagnostic and therapeutic purposes. The specimen showed only inflammatory cells, without any malignant cells. The final diagnosis was gastric wall abscess (GWA) that infiltrated and adhered to the adjacent tissues. This case reminds that physicians should include GWA as a differential diagnosis in the suspicion of gastric cancer. Although GWA is rare, it is often forgotten when focusing on the possibility of fatal cancer.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Abscesso/diagnóstico , Endossonografia/métodos , Erros de Diagnóstico
8.
Blood Res ; 57(3): 207-215, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-35880496

RESUMO

Background: Gaucher disease (GD) is an autosomal recessive disorder characterized by excessive accumulation of glucosylceramide in multiple organs. This study was performed to determine the detection rate of GD in a selected patient population with unexplained splenomegaly in Korea. Methods: This was a multicenter, observational study conducted at 18 sites in Korea between December 2016 and February 2020. Adult patients with unexplained splenomegaly were enrolled and tested for ß-glucosidase enzyme activity on dried blood spots (DBS) and in peripheral blood leukocytes. Mutation analysis was performed if the test was positive or indeterminate for the enzyme assay. The primary endpoint was the percentage of patients with GD in patients with unexplained splenomegaly. Results: A total of 352 patients were enrolled in this study (male patients, 199; mean age, 48.42 yr). Amongst them, 14.77% of patients had concomitant hepatomegaly. The most common sign related to GD was splenomegaly (100%), followed by thrombocytopenia (44.32%) and, anemia (40.91%). The ß-glucosidase activity assay on DBS and peripheral leukocytes showed abnormal results in sixteen and six patients, respectively. Eight patients were tested for the mutation, seven of whom were negative and one patient showed a positive mutation analysis result. One female patient who presented with splenomegaly and thrombocytopenia was diagnosed with type 1 GD. The detection rate of GD was 0.2841% (exact 95% CI, 0.0072‒1.5726). Conclusion: The detection rate of GD in probable high-risk patients in Korea was lower than expected. However, the role of hemato-oncologists is still important in the diagnosis of GD.

9.
Poult Sci ; 101(6): 101852, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35405531

RESUMO

This research was conducted to determine the effects Achyranthes japonica extract (AJE) supplementation to corn-soybean meal-wheat-based diet on the growth performance, nutrient digestibility, cecal microflora, excreta noxious gas emission, and meat quality of broiler chickens. A total of 432 one-day-old male Ross 308 broiler chickens, having initial body weight (IBW) of 41.11 ± 1.65 g were randomly allotted to 4 dietary treatments. Each treatment had 6 replicates cages with 18 broilers per cage. Dietary treatments composed of corn-wheat-soybean meal-based diets along with the addition of 0, 0.025, 0.05, and 0.1% of AJE. Bodyweight gain (BWG) and average daily feed intake (ADFI) were linearly influenced by the supplementation of AJE duringphase1 and 2 and the overall trial period. Inclusion of increasing levels of AJE linearly improved the digestibility of dry matter (DM) on d 35. Dietary supplementation of increasing levels of AJE failed to show significant effects on cecal Lactobacillus, coliform, and Salmonella counts, excreta noxious gas ammonia, hydrogen sulfide, total mercaptans, carbon dioxide, acetic acid and propionic acid emission, meat quality, and relative organ weight. Therefore, we concluded that supplementation of 0.1% of AJE in diets could improve BWG and ADFI, dry matter digestibility in broilers.


Assuntos
Achyranthes , Microbioma Gastrointestinal , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Galinhas , Dieta/veterinária , Suplementos Nutricionais/análise , Digestão , Masculino , Carne/análise , Nutrientes , Extratos Vegetais , Glycine max , Triticum , Zea mays
10.
Ann Palliat Med ; 11(6): 2162-2169, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34328007

RESUMO

Lynch syndrome (LS) is an inherited syndrome associated with an increased risk of cancer caused by abnormalities in DNA mismatch repair (MMR) genes. Immune checkpoint inhibitors (ICIs) have been reported to lead to a good response in cancers accompanied by LS. However, ICI therapy can cause immune-related adverse events (irAEs). In addition, post ICI treatment, some patients can show a falsely aggravated response, called pseudoprogression, causing difficulties in initial drug response evaluation. A 61-year-old man presented with back and pelvic bone pain. He had a history of surgery for stomach and colon cancer, and his daughter was treated for endometrial cancer. The patient was diagnosed with primary urothelial carcinoma (UC) in the left ureter with adrenal gland and multiple bone metastases. Through next-generation sequencing (NGS), mutations in MLH1 and MSH2 were identified, and diagnosis of LS was confirmed. On the 11th day from the start of atezolizumab, left pleural effusion occurred with exacerbation of the rib metastasis; the amount of effusion increased, and percutaneous catheter drainage (PCD) was performed. On the 27th day, right pleural effusion developed, and drainage was initiated. After the third cycle of atezolizumab, the bilateral pleural fluid decreased, and the drainage tube was removed. Positron emission tomography/computed tomography (PET-CT) revealed improvement in the cancer lesions, including metastatic bone lesions. This is a rare case of bilateral pleural effusion due to pseudoprogression of rib lesions after atezolizumab treatment in a patient with ureter cancer accompanied by LS. UC associated with LS is expected to show a good response to ICI therapy. For proper identification of pseudoprogression, appropriate response evaluation and close monitoring of the side effects are necessary.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma de Células de Transição , Neoplasias Colorretais Hereditárias sem Polipose , Derrame Pleural , Neoplasias da Bexiga Urinária , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma de Células de Transição/complicações , Carcinoma de Células de Transição/tratamento farmacológico , Neoplasias Colorretais Hereditárias sem Polipose/complicações , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pleural/induzido quimicamente , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Bexiga Urinária/tratamento farmacológico
11.
World J Clin Cases ; 9(28): 8557-8562, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34754868

RESUMO

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, and patients with DLBCL typically present rapidly growing masses. Lymphoma involving muscle is rare and accounts for only 5%; furthermore, multiple muscles and soft tissue involvement of DLBCL is unusual. Due to unusual clinical manifestation, accurate diagnosis could be delayed. CASE SUMMARY: A 61-year-old man complained of swelling, pain and erythematous changes in the lower abdomen. Initially, soft tissue infection was suspected, however, skin lesion did not respond to antibiotics. 18Fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography-computed tomography demonstrated FDG uptake not only in the skin and subcutaneous tissue of the abdomen but also in the abdominal wall muscles, peritoneum, perineum, penis and testis. DLBCL was confirmed by biopsy of the abdominal wall muscle and subcutaneous tissue. After intensive treatment including chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone, central nervous system prophylaxis (intrathecal injection of methotrexate, cytarabine and hydrocortisone) and orchiectomy, he underwent peripheral blood stem cell mobilization for an autologous hematopoietic stem cell transplantation. Despite intensive treatment, the disease progressed rapidly and the patient showed poor outcome (overall survival, 9 mo; disease free survival, 3 mo). CONCLUSION: The first clinical manifestation of soft tissue DLBCL involving multiple muscles was similar to the infection of the soft tissue.

12.
J Alzheimers Dis ; 84(3): 995-1003, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34602480

RESUMO

BACKGROUND: Being a spousal caregiver (SCG) for a patient with cognitive impairment is well known to be associated with increased risk for dementia and cognitive decline. OBJECTIVE: This study examined the impact of the care-recipient's cognitive status on lifestyle factors influencing cognitive decline in SCGs, focusing on nutritional status and blood biomarkers. METHODS: Fifty-one SCGs participated (mean age 73.5±7.0 years) in this study. All participants underwent clinical assessment including the Mini Nutritional Assessment (MNA), Geriatric Depression Scale, Pittsburgh Sleep Quality Index, and International Physical Activity Questionnaire to evaluate lifestyle factors, and the Mini-Mental State Examination to assess global cognition. Also, nutritional blood biomarkers were measured. RESULTS: SCGs caring for a demented spouse showed significantly higher depression scores (t = -3.608, p = 0.001) and malnutrition risk (t = 2.894, p = 0.006) compared to those caring for a non-demented spouse. Decreased care recipients' cognition was significantly correlated with higher GDS (ß= -0.593, t = -4.471, p < 0.001) and higher MNA scores (ß= 0.315, t = 2.225, p = 0.031) and lower level of high-density lipoprotein (HDL) cholesterol (ß= 0.383, t = 2.613, p = 0.012) in their SCGs. Gender had moderating effects on association of care-recipients' cognition with sleep quality (B[SE] = 0.400[0.189], p = 0.041) and HDL cholesterol (B[SE] = -1.137[0.500], p = 0.028) among SCGs. Poorer care-recipient's cognition was associated with worse sleep quality and low HDL cholesterol among wives but not husband caregivers. CONCLUSION: This study provides substantial evidence that SCGs are at risk for depression and malnutrition, which can further affect cognitive decline. As such, these factors should be well assessed and monitored among SCGs for patient with cognitive impairment.


Assuntos
Cuidadores/psicologia , Cognição/fisiologia , Disfunção Cognitiva/enfermagem , Estilo de Vida , Estado Nutricional , Cônjuges/psicologia , Idoso , Escalas de Graduação Psiquiátrica Breve , Depressão/psicologia , Feminino , Humanos , Masculino , Desnutrição/psicologia , Testes de Estado Mental e Demência/estatística & dados numéricos , Avaliação Nutricional , Qualidade do Sono
13.
Medicine (Baltimore) ; 100(43): e27620, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34713848

RESUMO

RATIONALE: Pulmonary foreign body aspiration is a serious medical problem. The risk of foreign body aspiration into the airways increases considerably in patients with end stage cancer with reduced consciousness and impaired airway reflexes. However, few studies have reported on foreign body aspiration in the airways in patients with terminal cancer or receiving end-of-life care. Herein, we report the use of flexible bronchoscopy in patients with end-of-life cancer with pulmonary aspiration. PATIENT CONCERNS: A 71-year-old man with neuroendocrine carcinoma was admitted to a palliative care unit for end-of-life care. He accidentally aspirated implant teeth into the airway with decreased consciousness and death rattle. DIAGNOSIS: On chest x-ray, the foreign material was observed in the left main bronchus. INTERVENTIONS: Despite concerns regarding the use of bronchoscopy given the deterioration of the overall organ function, flexible bronchoscopy was performed. OUTCOMES: Eventually, the foreign body was removed using a basket in the nasal cavity without major complications. The patient died comfortably after 7 days. LESSONS: The possibility of patients in the palliative care unit with reduced consciousness and death rattle to aspirate foreign bodies into the airways must be carefully considered. Flexible bronchoscopy should be considered to carefully remove aspirated foreign bodies in the airway without any side effects, even in patients with terminal cancer or receiving end-of-life care.


Assuntos
Broncoscopia/métodos , Corpos Estranhos , Aspiração Respiratória/cirurgia , Idoso , Carcinoma Neuroendócrino/patologia , Humanos , Masculino , Testes de Estado Mental e Demência , Cuidados Paliativos/métodos , Neoplasias Gástricas/patologia , Assistência Terminal/métodos
14.
Eur J Cancer ; 157: 21-30, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34464782

RESUMO

BACKGROUND: The efficacy of modified FOLFIRINOX (mFOLFIRINOX) as a second-line chemotherapy treatment for metastatic pancreatic adenocarcinoma (mPAC), remains unclear. This multi-center randomised phase III trial aimed to elucidate the efficacy of mFOLFIRINOX as a second-line chemotherapy treatment for mPAC patients with good performance status. PATIENTS AND METHODS: Eighty mPAC patients (age, 19-75 years) refractory to first-line gemcitabine-based chemotherapy were randomly selected to receive mFOLFIRINOX or S-1. mFOLFIRINOX comprised oxaliplatin (65 mg/m2), irinotecan (135 mg/m2), and leucovorin (400 mg/m2) on day 1 and continuous 5-FU infusion (1000 mg/m2) over 24 h on days 1-2 every 2 weeks. S-1 comprised body surface area-dependent oral S-1, divided into two doses per day on days 1-28 every 6 weeks. RESULTS: Overall survival was the primary endpoint. The objective response and disease control rates were higher in the mFOLFIRINOX than in the S-1 group (15% versus 2%; p = .04 and 67% versus 37%; p = .007). The median progression-free survival rates were 5.2 and 2.2 months in the mFOLFIRINOX and S-1 groups, respectively (adjusted hazard ratio [HR]: .4; 95% confidence interval [CI]: .2-.6; p < .001). The median overall survival rates were 9.2 and 4.9 months in the mFOLFIRINOX and S-1 groups, respectively (adjusted HR: .4; 95% CI: .2-.7; p = .002). Grade 3-4 adverse events occurred in 56% and 17% of the patients in the mFOLFIRINOX and S-1 groups, respectively (p < .001). CONCLUSION: Administration of mFOLFIRINOX as a second-line chemotherapy treatment for mPAC patients refractory to gemcitabine-based chemotherapy resulted in increased survival rates than S-1 treatment alone.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Ácido Oxônico/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Tegafur/uso terapêutico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/uso terapêutico , Combinação de Medicamentos , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Irinotecano/efeitos adversos , Irinotecano/uso terapêutico , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Oxaliplatina/efeitos adversos , Oxaliplatina/uso terapêutico , Ácido Oxônico/efeitos adversos , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Qualidade de Vida , Tegafur/efeitos adversos , Gencitabina
15.
Blood Res ; 56(2): 102-108, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34187943

RESUMO

BACKGROUND: To estimate real-world outcomes in East Asian populations, we conducted a nationwide retrospective analysis of the efficacy and safety of lenalidomide for del(5q) myelodysplastic syndrome (MDS) patients with transfusion-dependent anemia in Korea. METHODS: Patients aged ≥19 years who had received lenalidomide for the treatment of lower-risk, red blood cell (RBC) transfusion-dependent del(5q) MDS were selected. A filled case report form (CRF) with information from electronic medical records was requested from members of the acute myeloid leukemia (AML)/MDS Working Party of the Korean Society of Hematology. All the CRFs were gathered and analyzed. RESULTS: A total of 31 patients were included in this study. Of 28 evaluable patients, 19 (67.9%) achieved RBC transfusion independence (RBC-TI). Female sex and the development of thrombocytopenia during treatment were associated with achieving RBC-TI. The most common non-hematologic toxicities were pruritus, fatigue, and rashes. All non-hematologic toxicities of grades ≥3 were limited to rash (12.9%) and pruritus (6.5%). Dose reduction was required in 15 of the 19 responders (78.9%). The most common final stable dosing schedule for the responders was 5 mg once every other day (31.6%). CONCLUSION: Lenalidomide efficacy and tolerability were similar in the Asian del(5q) MDS patients and western patients. Dose reduction during treatment was common, but it was not associated with inferior outcomes.

17.
Neurology ; 95(7): e815-e826, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32690787

RESUMO

OBJECTIVES: To investigate the relationships of serum albumin with in vivo Alzheimer disease (AD) pathologies, including cerebral ß-amyloid (Aß) protein deposition, neurodegeneration of AD-signature regions, and cerebral white matter hyperintensities (WMH), in the human brain. METHODS: A total of 396 older adults without dementia underwent comprehensive clinical assessments, measurement of serum albumin level, and multimodal brain imaging, including [11C] Pittsburgh compound B-PET, 18F-fluorodeoxyglucose-PET, and MRI. Serum albumin was categorized as follows: <4.4 g/dL (low albumin), 4.4 to 4.5 g/dL (middle albumin), and >4.5 g/dL (high albumin; used as a reference category). Aß positivity, AD-signature region cerebral glucose metabolism (AD-CM), AD-signature region cortical thickness (AD-CT), and WMH volume were used as outcome measures. RESULTS: Serum albumin level (as a continuous variable) was inversely associated with Aß deposition and Aß positivity. The low albumin group showed a significantly higher Aß positivity rate compared to the high albumin group (odds ratio 3.40, 95% confidence interval 1.67-6.92, p = 0.001), while the middle albumin group showed no difference (odds ratio 1.74, 95% confidence interval 0.80-3.77, p = 0.162). Neither serum albumin level (as a continuous variable) nor albumin categories were related to AD-CM, AD-CT, or WMH volume. CONCLUSIONS: Low serum albumin may increase the risk of AD dementia by elevating amyloid accumulation. In terms of AD prevention, more attention needs to be paid to avoid a low serum albumin level, even within the clinical normal range, by clinicians.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/sangue , Encéfalo/metabolismo , Albumina Sérica/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Amiloide/metabolismo , Amiloidose/patologia , Encéfalo/patologia , Feminino , Fluordesoxiglucose F18/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos
18.
Medicine (Baltimore) ; 99(19): e19962, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384445

RESUMO

INTRODUCTION: After tyrosine kinase inhibitors (TKIs) targeting BCR-ABL1 were introduced for the treatment of chronic myeloid leukemia, clinical outcomes have improved dramatically. However, together with the increase in the survival rate, a more frequent occurrence of secondary malignancies has been observed as well. TKIs have been demonstrated to be a risk factor of malignancies such as non-Hodgkin lymphoma, prostate cancer, and skin cancer. However, lymphoplasmacytic lymphoma (LPL) has never been reported as a secondary malignancy after TKI treatment in chronic myeloid leukemia (CML). PATIENT CONCERNS: An 81-year-old male patient diagnosed with CML and treated with TKIs for a long period (15 years) was admitted due to a chief complaint of abdominal pain. A large abdominal mass was detected by imaging that included computed tomography. DIAGNOSIS: LPL was confirmed from biopsies after ultrasonography and sigmoidoscopy. Serum IgM level was increased and M protein and monoclonal gammopathy, IgM_kappa light chain type were detected. INTERVENTIONS: The patient received six cycles of R-CHOP chemotherapy. OUTCOMES: After chemotherapy, he showed response. The sizes of the abdominal mass and lymph nodes decreased; moreover, serum M protein and IgM levels decreased, as well. CONCLUSION: Herein, for the first time, we describe a patient who developed LPL as a secondary malignancy after administration of TKIs for the treatment of CML. Our observations indicate the importance of awareness of this secondary malignancy that can develop in CML patients treated with TKIs.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Segunda Neoplasia Primária , Macroglobulinemia de Waldenstrom , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Biópsia/métodos , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Humanos , Imunoglobulina M/sangue , Masculino , Segunda Neoplasia Primária/sangue , Segunda Neoplasia Primária/tratamento farmacológico , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/patologia , Prednisona/administração & dosagem , Radiografia Abdominal/métodos , Rituximab/administração & dosagem , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Vincristina/administração & dosagem , Macroglobulinemia de Waldenstrom/sangue , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/etiologia , Macroglobulinemia de Waldenstrom/patologia
20.
Ann Hematol ; 98(12): 2739-2748, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31712879

RESUMO

The aim of this study was to evaluate the prognostic relevance of early risk stratification in diffuse large B-cell lymphoma (DLBCL) using interim Deauville score on positron emission tomography-computed tomography (PET-CT) scan and baseline International Prognostic Index (IPI). This retrospective study included 220 patients (median age, 64 years; men, 60%) diagnosed with DLBCL between 2007 and 2016 at our institution, treated with rituximab-based chemotherapy. Interim PET-CT was performed after three cycles of immuno-chemotherapy. Interim Deauville score was assessed as 4 or 5 in 49 patients (22.3%), and 94 patients (42.7%) had high-intermediate or high-risk IPI scores. In multivariate analysis, interim Deauville score (1-3 and 4-5) and baseline IPI (low/low-intermediate and high-intermediate/high) were independently associated with progression-free survival (for Deauville score, hazard ratio [HR], 1.00 vs. 2.96 [95% confidence interval (CI), 1.83-4.78], P < 0.001; for IPI, HR, 1.00 vs. 4.84 [95% CI, 2.84-8.24], P < 0.001). We stratified patients into three groups: low-risk (interim Deauville scores 1-3 and low/low-intermediate IPI), intermediate-risk (Deauville scores 1-3 with high-intermediate/high IPI or Deauville scores 4-5 with low/low-intermediate IPI), and high-risk (Deauville scores 4-5 and high-intermediate/high IPI). This early risk stratification showed a strong association with progression-free survival (HR, 1.00 vs. 3.98 [95% CI 2.10-7.54] vs. 13.97 [95% CI 7.02-27.83], P < 0.001). Early risk stratification using interim Deauville score and baseline IPI predicts the risk of disease progression or death in patients with DLBCL. Our results provide guidance with interim PET-driven treatment intensification strategies.


Assuntos
Linfoma Difuso de Grandes Células B , Tomografia por Emissão de Pósitrons , Rituximab/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida
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