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1.
Neurol Med Chir (Tokyo) ; 64(5): 192-196, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38432945

RESUMO

This study aimed to assess the prevalence, severity, and natural history of positional posterior plagiocephaly (PPP) and positional posterior brachycephaly in Japan. We conducted a cross-sectional study of pediatric patients, ranging from 0 to 15 years old, evaluated for head trauma with negative computed tomography (CT) findings. The cranial vault asymmetry index (CVAI) was calculated using CT images at the superior orbital rim. Asymmetry according to CVAI values was subcategorized as follows: mild (3.5%-7%), moderate (7%-12%), and severe (>12%). The results were analyzed according to different age groups: group 1, 2-23 months (54 patients); group 2, 2-6 years (123 patients); and group 3, 7-15 years (123 patients). Overall, 300 patients were included (109 [36.3%] girls and 191 [63.7%] boys). The overall prevalence of PPP in the 300 patients was 46.7% (140 patients). PPP prevalence decreased consistently with age group: group 1, 57.4%; group 2, 47.2%; and group 3, 41.5%. Severe asymmetry was seen in all age groups. The overall mean cephalic index (CI) was 85.2. Cephalic index scores decreased consistently with age: group 1, 87.4; group 2, 85.1; and group 3, 84.3. The prevalence of PPP in Japan was higher than that reported in other countries. Although there was an overall decrease in the prevalence and severity of PPP with increasing patient age, PPP does not necessarily resolve spontaneously in all children. Furthermore, severe asymmetry was seen across all age groups.


Assuntos
Plagiocefalia não Sinostótica , Humanos , Feminino , Masculino , Japão/epidemiologia , Adolescente , Criança , Lactente , Prevalência , Estudos Transversais , Pré-Escolar , Plagiocefalia não Sinostótica/epidemiologia , Plagiocefalia não Sinostótica/diagnóstico por imagem , Craniossinostoses/epidemiologia , Craniossinostoses/diagnóstico por imagem , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Recém-Nascido
2.
Acta Neurochir (Wien) ; 166(1): 70, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326658

RESUMO

PURPOSE: In posterior fossa decompression for pediatric Chiari malformation type 1 (CM-1), duraplasty methods using various dural substitutes have been reported to improve surgical outcomes and minimize postoperative complications. To obtain sufficient posterior fossa decompression without cerebrospinal fluid-related complications, we developed a novel duraplasty technique using a combination of a pedicled dural flap and collagen matrix. The objective of this study was to describe the operative nuances of duraplasty using a combination of a pedicled dural flap and collagen matrix in posterior fossa decompression for pediatric CM-1. METHODS: We reviewed the clinical and radiographic records of 11 consecutive pediatric patients who underwent posterior fossa decompression with duraplasty using a combination of a pedicled dural flap and collagen matrix followed by expansile cranioplasty for CM-1. The largest area of the syrinx and the size of the posterior fossa were calculated. RESULTS: The maximum syrinx area was reduced by a mean of 68.5% ± 27.3% from preoperatively to postoperatively. Four patients (36.4%) had near-complete syrinx resolution (> 90%, grade III reduction), five (45.5%) had 50% to 90% reduction (grade II), and two (18.2%) had < 50% reduction (grade I). The posterior fossa area in the midsagittal section increased by 8.9% from preoperatively to postoperatively. There were no postoperative complications, including cerebrospinal fluid leakage, pseudomeningocele formation, or infection. CONCLUSION: Duraplasty using a combination of a pedicled dural flap and collagen matrix in posterior fossa decompression is a promising safe and effective surgical technique for pediatric CM-1 with syrinx.


Assuntos
Malformação de Arnold-Chiari , Siringomielia , Criança , Humanos , Malformação de Arnold-Chiari/diagnóstico por imagem , Malformação de Arnold-Chiari/cirurgia , Malformação de Arnold-Chiari/complicações , Colágeno/uso terapêutico , Descompressão Cirúrgica/métodos , Dura-Máter/diagnóstico por imagem , Dura-Máter/cirurgia , Estudos Retrospectivos , Siringomielia/diagnóstico por imagem , Siringomielia/cirurgia , Siringomielia/complicações , Resultado do Tratamento
3.
Dig Endosc ; 36(4): 463-472, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37448120

RESUMO

OBJECTIVES: In this study we aimed to develop an artificial intelligence-based model for predicting postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). METHODS: We retrospectively reviewed ERCP patients at Nagoya University Hospital (NUH) and Toyota Memorial Hospital (TMH). We constructed two prediction models, a random forest (RF), one of the machine-learning algorithms, and a logistic regression (LR) model. First, we selected features of each model from 40 possible features. Then the models were trained and validated using three fold cross-validation in the NUH cohort and tested in the TMH cohort. The area under the receiver operating characteristic curve (AUROC) was used to assess model performance. Finally, using the output parameters of the RF model, we classified the patients into low-, medium-, and high-risk groups. RESULTS: A total of 615 patients at NUH and 544 patients at TMH were enrolled. Ten features were selected for the RF model, including albumin, creatinine, biliary tract cancer, pancreatic cancer, bile duct stone, total procedure time, pancreatic duct injection, pancreatic guidewire-assisted technique without a pancreatic stent, intraductal ultrasonography, and bile duct biopsy. In the three fold cross-validation, the RF model showed better predictive ability than the LR model (AUROC 0.821 vs. 0.660). In the test, the RF model also showed better performance (AUROC 0.770 vs. 0.663, P = 0.002). Based on the RF model, we classified the patients according to the incidence of PEP (2.9%, 10.0%, and 23.9%). CONCLUSION: We developed an RF model. Machine-learning algorithms could be powerful tools to develop accurate prediction models.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Pancreatite , Humanos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Inteligência Artificial , Estudos Retrospectivos , Pancreatite/diagnóstico , Pancreatite/epidemiologia , Pancreatite/etiologia , Ductos Pancreáticos , Fatores de Risco
4.
EClinicalMedicine ; 66: 102303, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38034077

RESUMO

Background: Immune checkpoint inhibitors (ICI) plus platinum-based chemotherapy has been recognized as a standard first-line therapy in non-small cell lung cancer (NSCLC); however, no prospective clinical trials of docetaxel (DTX) plus ramucirumab (RAM) following first-line ICI plus platinum-based chemotherapy has been reported. Methods: In this multicentre, open-label, single-arm, phase 2 trial, we enrolled patients with NSCLC from eight centres in Japan. Patients with metastatic NSCLC with disease progression after platinum-based chemotherapy plus ICI were eligible for the study. Patients were intravenously treated with 60 mg/m2 of DTX and 10 mg/kg of RAM on day 1 with a strong recommendation of pegfilgrastim administration on day 2 every 3 weeks. The primary end point was objective response rate (ORR) in efficacy analysis population. Safety was assessed in all patients treated at least one dose. The ORR of the null and alternative hypotheses were 10% and 30%, with α error of 0.1 and ß error of 0.1. This trial is registered with the Japan Registry for Clinical Trials, jCRTs041190077. Findings: Between 16 January, 2020, and 24 August, 2021, 33 patients (median age 66 [range 42-79] years) were enrolled. Thirteen patients (41%) had Eastern Cooperative Oncology Group performance status of 1. Twenty-five patients (78%) had an interval of <60 days after the last administration of ICI. In the efficacy analysis population (n = 32), the primary endpoint was met as 11 patients achieved partial response (PR), with ORR of 34.4% (80% CI, 23.1-47.2). Grade ≥3 anaemia and febrile neutropenia were observed in 2 (6%) and 3 (9%) patients, respectively. No treatment-related deaths and no new safety signals were observed. Interpretation: DTX plus RAM demonstrated encouraging antitumor activity with a manageable safety profile in patients who have progressed on front-line ICIs plus platinum-based chemotherapy. The results of this trial can be a helpful reference in conducting further phase III trials of new second-line treatment options. Funding: Eli Lilly Japan K.K.

5.
Front Oncol ; 13: 1249237, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37675220

RESUMO

Currently, immune checkpoint inhibitors (ICIs) are widely considered the standard initial treatment for advanced non-small cell lung cancer (NSCLC) when there are no targetable driver oncogenic alternations. NSCLC tumors that have two alterations in tumor suppressor genes, such as liver kinase B1 (LKB1) and/or Kelch-like ECH-associated protein 1 (KEAP1), have been found to exhibit reduced responsiveness to these therapeutic strategies, as revealed by multiomics analyses identifying immunosuppressed phenotypes. Recent advancements in various biological approaches have gradually unveiled the molecular mechanisms underlying intrinsic reprogrammed metabolism in tumor cells, which contribute to the evasion of immune responses by the tumor. Notably, metabolic alterations in glycolysis and glutaminolysis have a significant impact on tumor aggressiveness and the remodeling of the tumor microenvironment. Since glucose and glutamine are essential for the proliferation and activation of effector T cells, heightened consumption of these nutrients by tumor cells results in immunosuppression and resistance to ICI therapies. This review provides a comprehensive summary of the clinical efficacies of current therapeutic strategies against NSCLC harboring LKB1 and/or KEAP1 mutations, along with the metabolic alterations in glycolysis and glutaminolysis observed in these cancer cells. Furthermore, ongoing trials targeting these metabolic alterations are discussed as potential approaches to overcome the extremely poor prognosis associated with this type of cancer.

6.
Cancer Immunol Immunother ; 72(11): 3765-3772, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37638979

RESUMO

BACKGROUND: Evidence for use of second-line immunosuppressants for immune-related adverse events (irAEs) is inadequate. Therefore, a multicenter analysis should assess the efficacy of second-line immunosuppressants for severe irAEs associated with different malignant diseases. METHODS: This descriptive study aims to investigate the effects of second-line immunosuppressants on corticosteroid-refractory irAEs in patients with lung cancer. We analyzed the effects of second-line immunosuppressants on underlying lung cancer and associated adverse effects. RESULTS: Our study included 4589 patients who had received immune checkpoint inhibitor treatment, with 73 patients (1.6%) developing irAEs requiring second-line immunosuppressants. The most commonly observed irAE was pneumonitis (26 patients), followed by hepatobiliary disorders (15 patients) and enteritis (14 patients). We found a confirmed response rate of 42.3% for pneumonitis, which was lower than the response rates of 86.7% for hepatobiliary disorders and 92.9% for enteritis. The time from the start of corticosteroid therapy to the addition of a second-line immunosuppressant correlated significantly with the resolution of irAE to Grade 1 (correlation coefficients of r = 0.701, p < 0.005). The median progression-free survival and duration of response of underlying lung cancer from second-line immunosuppressant administration were 2.1 and 3.0 months, respectively. Of the patients with irAE, 27.4% developed infections and 5.5% might die due to infection. CONCLUSION: Second-line immunosuppressant response was confirmed in 72.2% of irAEs in patients with lung cancer, with lower response rates observed in irAE pneumonitis compared to other irAEs.


Assuntos
Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Doenças do Sistema Digestório , Enterite , Neoplasias Pulmonares , Pneumonia , Humanos , Corticosteroides/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Doenças do Sistema Digestório/induzido quimicamente , Enterite/induzido quimicamente , Imunossupressores/uso terapêutico , Neoplasias Pulmonares/patologia , Nivolumabe/uso terapêutico , Pneumonia/etiologia , Pneumonia/induzido quimicamente , Estudos Retrospectivos , Esteroides
8.
Childs Nerv Syst ; 39(11): 3307-3310, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37271777

RESUMO

BACKGROUND: Cerebral ventricular shunt infections caused by methicillin-resistant Staphylococcus aureus (MRSA), especially strains with elevated minimum inhibitory concentration (MIC) values, have a poor prognosis. Monitoring serum vancomycin (VCM) levels with therapeutic drug monitoring and maintaining high VCM concentrations in the cerebrospinal fluid (CSF) are critical to treatment success. However, there have been a few reports about the CSF penetration and the pharmacokinetics of VCM in children. CASE PRESENTATION: Here, we report the case of a pediatric patient with cysto-peritoneal shunt-related meningitis caused by MRSA with an MIC of 2 µg/mL. The adequate VCM concentration was maintained by monitoring the VCM concentration in the CSF via the external ventricular drain, and frequent blood taking was avoided. VCM showed a good CSF penetration in our patient, and she was discharged without complications. DISCUSSION: Therapeutic drug monitoring of VCM concentration in the CSF may result in successful treatment even if MRSA shows a higher MIC. Therapeutic drug monitoring of VCM concentration in the CSF may also reduce the side effects.


Assuntos
Meningite , Staphylococcus aureus Resistente à Meticilina , Feminino , Criança , Humanos , Vancomicina/uso terapêutico , Antibacterianos/uso terapêutico
9.
Childs Nerv Syst ; 39(12): 3595-3600, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37369950

RESUMO

INTRODUCTION: Intraparenchymal meningiomas in the basal ganglia are extremely rare, and to the best of our knowledge, only three case reports have been published to date. Owing to concerns regarding major vessels, gross total resection (GTR) is difficult to achieve; therefore, subtotal resection and radiation therapy are often chosen as treatment options. We present a pediatric case with an intraparenchymal meningioma in the left basal ganglia that was successfully treated with GTR. We also reviewed the relevant literature to discuss the pathogenesis, radiological findings, and treatment methods of this rare disease. CASE REPORT: A 4-year-old girl presented with progressive right facial paralysis, aphasia, and right incomplete hemiplegia. Imaging revealed a mass lesion in the left basal ganglia and unilateral obstructive hydrocephalus. Neuroendoscopic septostomy, tumor biopsy, and cerebrospinal fluid reservoir placement were performed, and the initial pathological diagnosis was suspected glioma. Thus, craniotomy was performed to remove the tumor, which was white, elastic, and well-defined. Intraoperative rapid pathology revealed a meningioma. Postoperatively, the patient experienced transient worsening of the right incomplete hemiplegia, which subsequently improved. The final pathological diagnosis was a fibrous meningioma. CONCLUSION: Surgery for intraparenchymal meningiomas in the basal ganglia is challenging owing to the proximity of major blood vessels; however, GTR may be preferable to subtotal resection, considering the possibility of recurrence. Even in cases of intraparenchymal tumors, it is important to consider meningioma as a differential diagnosis and to carefully plan the appropriate treatment.


Assuntos
Neoplasias Meníngeas , Meningioma , Pré-Escolar , Feminino , Humanos , Gânglios da Base/diagnóstico por imagem , Gânglios da Base/cirurgia , Hemiplegia , Imageamento por Ressonância Magnética , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/cirurgia , Neoplasias Meníngeas/patologia , Meningioma/diagnóstico por imagem , Meningioma/cirurgia
11.
Intern Med ; 62(3): 453-457, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35793962

RESUMO

We herein report a rare case of spinal cord compression due to epidural involvement of acute myeloid leukemia (AML). A 14-year-old boy presented with a 7-day history of back pain, paraplegia and hypoesthesia. Contrast-enhanced computed tomography revealed an epidural mass. Emergency laminectomy and resection of the mass were performed. Histopathologically, the resected mass was comparable to an extramedullary mass of AML. Chemotherapy was initiated, and complete remission was achieved. Neurological sequelae remained after the treatment. Based on the present and previous reports, spinal cord compression from epidural AML involvement may progress rapidly.


Assuntos
Leucemia Mieloide Aguda , Compressão da Medula Espinal , Masculino , Humanos , Adolescente , Compressão da Medula Espinal/diagnóstico por imagem , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/cirurgia , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/diagnóstico , Progressão da Doença , Tomografia Computadorizada por Raios X/efeitos adversos , Medula Espinal , Imageamento por Ressonância Magnética/efeitos adversos
12.
Thorac Cancer ; 14(2): 168-176, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36408699

RESUMO

BACKGROUND: The therapeutic efficacy of cytotoxic anticancer drugs has been reported to be enhanced after immune checkpoint inhibitors (ICI) in non-small cell lung cancer; however, it is unclear whether the same is applicable for small cell lung cancer (SCLC). We evaluated the efficacy of second-line amrubicin (AMR) following first-line platinum-based chemotherapy and ICI combination therapy (chemo-ICI) in SCLC. PATIENTS AND METHODS: We retrospectively enrolled consecutive patients with SCLC treated with AMR as a second-line following chemo-ICI as first-line between July 2019 and April 2021 from 16 institutions throughout Japan. We investigated the therapeutic effectiveness, safety, and efficacy-enhancing variables of AMR. RESULTS: Overall, 89 patients treated with AMR after first-line chemo-ICI were analyzed. The overall response rate (ORR) was 29.2% (95% confidence intervals [CI], 20.1-39.8) and median PFS (m PFS) was 2.99 months (95% CI, 2.27-3.65). Patients who relapsed more than 90 days after receiving first-line platinum combination therapy (sensitive relapse) exhibited greater ORR (58.3% vs. 24.7%, p = 0.035) and m PFS (5.03 vs. 2.56 months, p = 0.019) than patients who relapsed in <90 days (refractory relapse). Grade 3 or higher adverse events were mainly hematological toxicity. CONCLUSIONS: Our study suggested that the therapeutic effect of AMR was not enhanced after ICI on SCLC. However, AMR may be effective in cases of sensitive relapse after chemo-ICI. There was no increase in severe toxicity associated with AMR after ICI.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/induzido quimicamente , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Estudos Retrospectivos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Antineoplásicos/uso terapêutico , Resultado do Tratamento , Recidiva
13.
J Cancer Res Clin Oncol ; 149(7): 3885-3893, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36006483

RESUMO

PURPOSE: We determined the clinical relevance of early C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR) change in blood as surrogate markers of pro-tumor inflammation (PTI) for predicting clinical outcome of programmed cell death (PD)-1/programmed cell death ligand (PD-L) 1 inhibitor treatment in non-small-cell lung carcinoma (NSCLC). METHODS: We retrospectively reviewed NSCLC patients treated with anti-PD-1 or PD-L1 inhibitors. Early CRP change was defined as the ratio of 6 weeks CRP to baseline CRP, and early NLR change was defined as that of the 6 weeks NLR to baseline NLR. PTI index was determined by combinatorial evaluation of early CRP change and early NLR change, PTI index low: both of these were low, intermediate: either of these was low, high; both of these were high. RESULTS: The study included 217 patients. Early CRP change and early NLR change were both associated with PFS and OS. The combinatorial evaluation using these two markers enabled the clear stratification of PFS and OS. The median PFS in patient with PTI index low was 13.9 months, while the median PFS in those with PTI index high was 2.5 months (p < 0.01, log-rank test). The median OS in patients with PTI index low was not reached; the median OS in those with PTI index high was only 15.4 months (p < 0.01, log-rank test). CONCLUSIONS: The combinatorial early CRP change and early NLR change as PTI biomarkers have clinical potential in identifying NSCLC patients who can achieve a durable response and long-term survival using PD-1/PD-L1 inhibitors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Proteína C-Reativa/análise , Neoplasias Pulmonares/patologia , Neutrófilos , Estudos Retrospectivos , Prognóstico , Linfócitos , Biomarcadores Tumorais , Inflamação/patologia
14.
Vasc Endovascular Surg ; 57(2): 137-148, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36189731

RESUMO

BACKGROUND: Among tandem occlusions, atherosclerotic cervical internal carotid artery occlusion (ACICAO) can be technically challenging and associated with its unique complications. We evaluated our experience with endovascular treatment (EVT) of ACICAO in the setting of acute ischemic stroke. METHODS: In total, 154 consecutive patients who underwent EVT for acute anterior circulation stroke at our institute were retrospectively reviewed. Patients with tandem ACICAO were analyzed in this study. Procedures, recanalization rates, complications, and prognoses were evaluated. RESULTS: Ten patients (6%) of all 154 patients had ACICAO. In nine (90%) of the 10 patients, cervical lesions were successfully crossed and intervened upon. Four patients underwent stenting and five underwent angioplasty alone, followed by intracranial procedure. Eight patients (80%) achieved successful recanalization following mechanical thrombectomy for intracranial occlusion. However, one patient had massive subarachnoid hemorrhage during the procedure and another patient developed massive intracranial hemorrhage after EVT, both after stenting. Four of the five patients who initially underwent angioplasty alone subsequently underwent staged endarterectomy or stenting for residual stenosis on or after the next day. The single patient in whom the cervical lesion could not be crossed and another with reocclusion after EVT underwent a rescue bypass procedure due to persistent ischemic symptoms. After 90 days, four patients (40%) were functionally independent (modified Rankin scale score 0-2). CONCLUSIONS: Our experience suggests that EVT for ACICAO is technically feasible; however, it involves the potential risk of several significant complications. To avoid serious hemorrhagic complications, cervical lesions may be better treated with angioplasty alone first.


Assuntos
Doenças das Artérias Carótidas , Estenose das Carótidas , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/etiologia , AVC Isquêmico/terapia , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/terapia , Artéria Carótida Interna/diagnóstico por imagem , Artéria Carótida Interna/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/complicações , Doenças das Artérias Carótidas/complicações , Trombectomia/efeitos adversos , Trombectomia/métodos , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Stents/efeitos adversos
15.
BMC Cancer ; 22(1): 654, 2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35698083

RESUMO

BACKGROUND: Osimertinib-the third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)-has been widely used as a first-line treatment for patients with metastatic EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib demonstrated central nervous system activity in patients with brain metastasis; however, its efficacy against other distant metastatic organs, including bone and liver, remains unclear. Therefore, we retrospectively analyzed the clinical efficacy of osimertinib in these patients in comparison to other EGFR-TKIs. METHODS: Clinical data of patients with advanced NSCLC receiving gefitinib/erlotinib (n = 183), afatinib (n = 55), or osimertinib (n = 150) at five medical institutions were retrospectively assessed for progression-free survival (PFS), overall survival (OS), and best overall response rate (ORR). RESULTS: In univariate and multivariate analyses, most distant metastases, including the brain and bone, were unrelated to the therapeutic efficacy of osimertinib, although liver metastasis and L858R mutation were independently associated with shorter PFS. PFS and OS in patients with liver metastases were significantly shorter than those in patients without liver metastases (PFS: 7.4 vs. 19.7 months, OS: 12.1 months vs. not reached, respectively). Osimertinib provided significantly longer PFS in patients with brain or bone metastasis and exon 19 deletion than the other EGFR-TKIs. The PFS of patients with liver metastases was not significantly different among the three EGFR-TKI groups. Furthermore, the ORR of osimertinib in patients with liver metastases was significantly attenuated, and the effectiveness was similar to 1st- or 2nd -generation EGFR-TKIs. CONCLUSION: Osimertinib provided better clinical benefits than 1st- and 2nd-generation EGFR-TKIs for patients with EGFR-mutant NSCLC, particularly those with brain or bone metastases and exon 19 deletion; however, its efficacy against liver metastasis was remarkably attenuated. New therapeutic developments for patients with EGFR-mutant NSCLC with liver metastases are needed.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Hepáticas , Neoplasias Pulmonares , Acrilamidas , Compostos de Anilina/farmacologia , Compostos de Anilina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB , Humanos , Indóis , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Metástase Neoplásica , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas , Estudos Retrospectivos , Resultado do Tratamento
16.
Childs Nerv Syst ; 38(6): 1185-1188, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35536350

RESUMO

INTRODUCTION: Cerebrospinal fluid (CSF) leak and pseudomeningocele are common complications after surgery for spinal dysraphism. CASE REPORT AND TECHNIQUE: We report a 6-month-old girl with a lumbosacral lipomyelomeningocele and accessory lower limb who developed a refractory cerebrospinal fluid leak and pseudomeningocele after lipomyelomeningocele repair and removal of the accessory limb. The pseudomeningocele was successfully repaired using a reversed dermis flap made from excess skin that covered the meningocele. CONCLUSION: This technique can be performed without using synthetic material or an additional surgical incision.


Assuntos
Rinorreia de Líquido Cefalorraquidiano , Complicações Pós-Operatórias , Vazamento de Líquido Cefalorraquidiano/complicações , Vazamento de Líquido Cefalorraquidiano/cirurgia , Rinorreia de Líquido Cefalorraquidiano/etiologia , Criança , Derme , Feminino , Humanos , Lactente , Meningomielocele , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
17.
Intern Med ; 61(5): 703-708, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34433708

RESUMO

Amelanotic melanoma is a rare type of melanoma that shows little or no melanin pigmentation. When tumor lesions are not detected in cutaneous sites, the presence of melanin is the hallmark sign of malignant melanoma. We herein report a case of amelanotic melanoma with a BRAF V600E mutation mimicking primary lung cancer that was finally diagnosed on an autopsy. The current case suggests important caveats for the differential diagnosis of patients with BRAF V600E mutation-positive poorly differentiated lung tumors. In terms of the pathological diagnosis, routine immunohistochemical staining may be useful, especially in patients with a poorly differentiated lung tumor without TTF-1 expression.


Assuntos
Neoplasias Pulmonares , Melanoma Amelanótico , Neoplasias Cutâneas , Biomarcadores Tumorais/genética , Análise Mutacional de DNA , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Melanoma Amelanótico/diagnóstico , Melanoma Amelanótico/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia
18.
Nagoya J Med Sci ; 83(4): 773-785, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34916721

RESUMO

Carboplatin (CBDCA)-induced emetic risk is currently classified on the basis of CBDCA-area under the curve (CBDCA-AUC). We investigated the utility of three CBDCA dosage parameters for predicting emesis by CBDCA. Patients with thoracic cancer treated with CBDCA were included. The endpoints were complete response (CR) and total control (TC). CR was defined as no vomiting and no use of rescue medication during the overall assessment period, whereas TC was defined as no vomiting, nausea, nor use of rescue medication during the overall assessment period. The parameters of CBDCA were defined as follows: (1) CBDCA-AUC; (2) CBDCA/body surface area (BSA): the administered dose of CBDCA per body surface area (mg/m2); and (3) total CBDCA/body: the total administered dose of CBDCA (mg). Eighty-five patients were evaluated. The median CBDCA/BSA but not CBDCA-AUC was higher in patients with non-CR compared to those with CR. Receiver operating characteristic curve analysis revealed that the AUC of CBDCA/BSA for predicting non-CR was higher than that of CBDCA-AUC. CBDCA/BSA shows greater potential for predicting CBDCA-induced emetic risk compared with CBDCA-AUC, which is the parameter in current antiemetic guidelines.


Assuntos
Carboplatina/efeitos adversos , Eméticos , Náusea/induzido quimicamente , Medição de Risco/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antieméticos , Carboplatina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/tratamento farmacológico , Estudos Retrospectivos
19.
Lung Cancer ; 162: 140-146, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34808485

RESUMO

OBJECTIVES: Several preclinical data proposed a potential efficacy of osimertinib, a third-generation EGFR tyrosine kinase inhibitor, for EGFR exon 20 insertion (EGFR ex20ins)-positive non-small cell lung cancer (NSCLC). However, reported case series and a retrospective study proposed controversial efficacy. The efficacy of osimertinib in EGFR ex20ins-positive NSCLC have not been well evaluated in prospective clinical trials. In this study, we performed a prospective, single-arm, multi-center, open-label, non-randomized phase I/II study to evaluate efficacy of osimertinib for EGFR ex20ins-positive NSCLC. MATERIALS AND METHODS: From August 2018 to January 2020, 14 NSCLC patients with EGFR ex20ins were enrolled, of whom 2 were excluded because they did not meet the inclusion criteria. Efficacy and safety of 80 mg osimertinib were evaluated. In addition, we performed a translational exploratory study to clarify the association of mutation type-specific drug sensitivity, osimertinib pharmacokinetic data, and clinical efficacy. RESULTS: Of the evaluated patients, none experienced objective response, 7 experienced stable disease (58.3%), and 5 experienced disease progression (41.7%). The median progression free survival (PFS) was 3.8 months, and the median overall survival was 15.8 months. Interestingly, the exploratory study demonstrated statistically significant positive correlation between plasma osimertinib concentration/in vitro IC50 ratio and PFS (R = 0.9912, P = 0.0001), highlighting the mutation type-specific concentration-dependent efficacy of osimertinib for EGFR ex20ins-positive NSCLC. CONCLUSIONS: Regular dose, 80 mg/day, of osimertinib has limited clinical activity in NSCLC patients with EGFR ex20ins. The translational study proposed the potential efficacy of higher dose osimertinib in a subgroup of EGFR ex20ins-positive NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Acrilamidas , Compostos de Anilina , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Éxons/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutagênese Insercional , Mutação , Estudos Prospectivos , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos
20.
Childs Nerv Syst ; 37(12): 3957-3961, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33619591

RESUMO

Takotsubo syndrome (TTS) can develop after intense physical or emotional stress and is uncommon in children. We report a 2-year-old girl who developed TTS caused by acute hydrocephalus after posterior fossa tumor resection and required mechanical ventilation and administration of vasopressor/inotropic agents. Her cardiac function gradually recovered over the course of 2 weeks. Hydrocephalus after posterior fossa surgery can cause compression of the medulla oblongata, resulting in solitary nucleus dysfunction and TTS, a potentially life-threatening complication.


Assuntos
Hidrocefalia , Neoplasias Infratentoriais , Cardiomiopatia de Takotsubo , Criança , Pré-Escolar , Feminino , Humanos , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Neoplasias Infratentoriais/complicações , Neoplasias Infratentoriais/diagnóstico por imagem , Neoplasias Infratentoriais/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Cardiomiopatia de Takotsubo/diagnóstico por imagem , Cardiomiopatia de Takotsubo/etiologia
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