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1.
Clin J Gastroenterol ; 14(5): 1517-1524, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34291386

RESUMO

The overall survival of patients with advanced hepatocellular carcinoma with tumor thrombosis of the main trunk or bilobar branches of the portal vein is extremely poor. Moreover, there is no standard treatment established for the condition. Herein, we present the case of a 65-year-old man who were treated the patient with hepatic arterial infusion chemotherapy, radiation therapy for tumor thrombosis, portal vein stent placement, lenvatinib administration, and renal venous shunt embolization. A complete response was observed according to mRECIST and the patient has been alive for 14 months since treatment initiation with no tumor recurrence.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Trombose , Idoso , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/terapia , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/terapia , Masculino , Recidiva Local de Neoplasia , Veia Porta , Trombose/etiologia , Trombose/terapia
2.
J Exp Clin Cancer Res ; 40(1): 215, 2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34174931

RESUMO

BACKGROUND: There has been a recent surge in interest in predicting biological effects associated with genomic alterations in order to implement personalized cancer treatment strategies. However, no reports have yet evaluated the utility of profiling blood-based circulating tumor DNA (ctDNA) in hepatocellular carcinoma (HCC) patients treated with lenvatinib (LEN). METHOD: We retrospectively performed ctDNA next-generation sequencing (NGS) analysis in 24 patients with advanced HCC at baseline and 4 weeks after initiation of LEN. Association of the changes in variant allele frequencies (VAFs) during treatment and clinical outcome were evaluated. RESULTS: In total, 131 single nucleotide variants, 17 indels, and 23 copy number variations were detected as somatic alterations in 28, 6, and 12 genes, respectively in 23 of 24 patients. The most frequently altered genes were TP53 (54%), CTNNB1 (42%), TERT (42%), ATM (25%), and ARID1A (13%). The reduction in the mean frequency of variants (VAFmean) following 4 weeks of LEN treatment was associated with longer progression-free survival. The specificity and sensitivity of the reduction of VAFmean for predicting partial response were 0.67 and 1.0, respectively, which were higher than those of serum α-fetoprotein level (0.10 and 0.93, respectively). No association between the mutation status at baseline and the effectiveness of LEN was observed. CONCLUSION: Our study demonstrated that somatic alterations could be detected in the majority of advanced HCC patients by ctDNA profiling and that ctDNA-kinetics during LEN treatment was a useful marker of disease progression. These results suggest that ctDNA profiling is a promising method that provides valuable information in clinical practice.

3.
Intern Med ; 60(6): 829-837, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33087674

RESUMO

Objective Lusutrombopag is a thrombopoietin receptor agonist that improves thrombocytopenia in patients with chronic liver disease scheduled to undergo invasive procedures. However, information on the efficacy of repeated lusutrombopag treatment and factors associated with the treatment is scarce. We analyzed the efficacy of repeated lusutrombopag treatment and the factors associated with a response to lusutrombopag. Methods Thirty-nine patients with chronic liver disease who received lusutrombopag treatment before undergoing invasive procedures were enrolled in this retrospective study. Of the 39 patients, 10 received lusutrombopag treatment multiple times for a total of 53 regimens of lusutrombopag treatment. Changes in platelet counts, the effects of repeated lusutrombopag treatment, and factors associated with response to lusutrombopag were analyzed. Results The median platelet count increased significantly from 4.5×104/µL before lusutrombopag treatment to 7.2×104/µL before the invasive procedure (p<0.01), and patients undergoing 49 of the 53 (92%) treatment regimens succeeded in undergoing invasive procedures without needing platelet transfusions. In patients who received lusutrombopag treatment repeatedly, the median platelet count significantly increased following the second administration of lusutrombopag, and the effects of lusutrombopag were similar between the first and second administration. A multivariate analysis identified the absence of diabetes mellitus (odds ratio, 5.56 for presence; p=0.04) as a significant and independent predictor of a response to lusutrombopag. Conclusion Lusutrombopag treatment significantly increased platelet counts in patients with chronic liver disease, making it possible to receive invasive procedures. The treatment produced identical effects when it was repeated. The efficacy of lusutrombopag might be decreased in patients with diabetes mellitus.


Assuntos
Hepatopatias , Trombocitopenia , Doença Crônica , Cinamatos , Humanos , Hepatopatias/complicações , Hepatopatias/tratamento farmacológico , Receptores de Trombopoetina , Estudos Retrospectivos , Tiazóis , Trombocitopenia/tratamento farmacológico
4.
J Gastroenterol Hepatol ; 36(6): 1685-1693, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33326154

RESUMO

BACKGROUND AND AIM: The aim of this study was to identify the factors that contribute to the maintenance of relative dose intensity (RDI) of lenvatinib in hepatocellular carcinoma (HCC) patients. METHODS: Thirty-two patients with advanced HCC treated with lenvatinib were enrolled. We evaluated the relationship between maintenance of RDI and various clinical data, parameters obtained by body composition measurements with bioelectrical impedance analysis (BIA) and grip strength at the start of lenvatinib treatment. RESULTS: Multivariate analysis showed that only the extracellular water to total body water ratio (ECW/TBW) ≤ 0.400 at initiation of treatment was associated with RDI ≥ 50% (odds ratio, 6.94; 95% confidence interval [CI], 1.00-48.00; P = 0.049). When the RDI was compared between ECW/TBW ≤ 0.400 group and ECW/TBW > 0.400 group, the RDI was significantly higher in the ECW/TBW ≤ 0.400 group at each of 0-4W, 4-6W, and 6-8W points. The P value at each point was 0.003, 0.003, and 0.005, respectively. On the other hand, multivariate analysis showed that only the ECW/TBW ≤ 0.400 at initiation of treatment was associated with the extension of duration until reduction or withdrawal of lenvatinib (hazard ratio, 4.86; 95% CI, 1.52-15.50; P = 0.007). CONCLUSION: The extracellular water to total body water ratio, a parameter of body composition measurement by BIA, was significantly associated with the maintenance of RDI and the duration until reduction or withdrawal of lenvatinib in HCC patients. In addition to standard predictors such as Child-Pugh score and modified albumin-bilirubin grade that have been used to date, ECW/TBW might be a new predictor of RDI in HCC patients treated with lenvatinib.


Assuntos
Antineoplásicos/administração & dosagem , Água Corporal/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Cálculos da Dosagem de Medicamento , Impedância Elétrica , Espaço Extracelular/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/administração & dosagem , Quinolinas/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Composição Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias
5.
Oncology ; 98(10): 727-733, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32712613

RESUMO

OBJECTIVE: Functional hepatic reserve is important when considering sequential tyrosine kinase inhibitor (TKI) therapy for patients with advanced hepatocellular carcinoma (HCC). We assessed albumin-bilirubin (ALBI) score and Child-Pugh class as indices of liver function during sorafenib and lenvatinib treatment. METHODS: A total of 212 patients with advanced HCC and Child-Pugh class A status who initiated TKI treatment at our hospital were enrolled in this retrospective cohort study. A total of 74 of the 212 patients underwent blood testing before starting sorafenib treatment and every 2 months after treatment initiation. RESULTS: In 74 patients, the median ALBI score before TKI treatment was -2.53, and after 2, 4, and 6 months it was -2.45, -2.44, and -2.36, respectively. ALBI scores tended to increase during TKI therapy. Among patients who experienced a time to progression ≤3.8 months, ALBI scores had increased 2 months after treatment initiation, and at 4 and 6 months, significant differences were observed (p < 0.01). In all 212 patients, during first-line TKI treatment, the Child-Pugh class deteriorated to B or C in 72.2% of the patients, and the median time to deterioration was 3.9 months. The factors in hepatic reserve deterioration were serum albumin ≤3.8 g/dL and the presence of macroscopic vascular invasion. The hepatic reserve of 68.0% of the patients with deterioration of liver function recovered to Child-Pugh class A following dose reduction, drug withdrawal, or treatment intended for recovery of liver function. CONCLUSION: ALBI scores deteriorate in patients treated with TKIs, suggesting that tumor progression induces these changes.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/fisiopatologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/fisiopatologia , Fígado/fisiopatologia , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Estudos Retrospectivos , Sorafenibe/uso terapêutico , Adulto Jovem
6.
Intern Med ; 59(13): 1649-1654, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32269187

RESUMO

Immunoglobulin G4-related disease (IgG4-RD) is defined as an inflammatory lymphoproliferative disorder. The relationship between malignancies and IgG4-RD remains unclear. We herein present a case of IgG4-RD that occurred during chemotherapy for advanced breast cancer. In this case, it was challenging to determine which of these diseases was responsible for the patient's mediastinal lymphadenopathy. Lymphadenopathy with IgG4-RD was diagnosed by assessing the reactivity to corticosteroids, which were used as premedication in chemotherapy, over time. The administration of prednisolone, which was initiated to treat active IgG4-RD, led to stable systemic therapy for malignancy. It is imperative to assess the disease activity and consider each treatment.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Doença Relacionada a Imunoglobulina G4/etiologia , Linfadenopatia/etiologia , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Feminino , Humanos , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Prednisolona/uso terapêutico
7.
Int Cancer Conf J ; 9(1): 18-23, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31950012

RESUMO

Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate approved for use in the treatment of human epidermal growth factor receptor 2-positive metastatic breast cancer. Here, we present the cases of two patients with metastatic breast cancer who received T-DM1 monotherapy and developed noncirrhotic portal hypertension (NCPH). Patient 1 presented with ruptured gastric varices at 2 years and 5 months after T-DM1 treatment. Patient 2 presented with intrahepatic portal-hepatic venous shunt at 2 years and 6 months and portal-systemic shunt encephalopathy at 4 years and 11 months after T-DM1 treatment. In both the patients, liver biopsies revealed sinusoidal obstruction syndrome (SOS). T-DM1-induced hepatotoxicity can result from SOS. In long-term administration of T-DM1 the unfavorable events associated with chronic liver circulatory disorder due to SOS, such as NCPH, are concerning.

8.
Gastroenterol Res Pract ; 2017: 1515260, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28487727

RESUMO

Background. Several previous studies assessed the competence in endoscopic retrograde cholangiopancreatography (ERCP) using the bile duct cannulation success rate. However, the cannulation time is also important, because a long cannulation time was reported to be a risk factor for post-ERCP pancreatitis. Aim. To determine the number of ERCP procedures required for short cannulation time of the bile duct. Methods. We retrospectively analyzed 605 ERCP procedures performed for bile duct cannulation in patients with native papilla at our institution between March 2012 and December 2015. The successful procedures were divided into 2 groups: group L and group S (cannulation time > 15 minutes and ≤15 minutes, resp.). An analysis of the relationship among the biliary cannulation time, ERCP experience, and other factors was then conducted. Results. Multivariate analysis showed that the ERCP experience of ≤300 procedures (odds ratio, 2.080; 95% confidence interval, 1.337-3.142; P = 0.001) and malignant biliary stricture due to pancreatic cancer (odds ratio, 1.912; 95% confidence interval, 1.072-3.412; P = 0.028) were found to be significantly associated with a cannulation time of >15 minutes. Conclusions. Our findings suggested that an ERCP experience of ≤300 procedures and malignant biliary stricture due to pancreatic cancer were associated with prolonged biliary cannulation time.

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