RESUMO
OBJECTIVE: To evaluate the effect of intravenous administration of human multilineage-differentiating stress-enduring (Muse) cells on rat postoperative erectile dysfunction (ED) with cavernous nerve (CN) injury without an immunosuppressant. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomised into three groups after CN crush injury. Either human-Muse cells, non-Muse mesenchymal stem cells (MSCs) (both 1.0 × 105 cells), or vehicle was infused intravenously at 3 h after CN injury without immunosuppressant. Erectile function was assessed by measuring intracavernous pressure (ICP) and arterial pressure (AP) during pelvic nerve electrostimulation 28 days after surgery. At 48 h and 28 days after intravenous infusion of Muse cells, the homing of Muse cells and non-Muse MSCs was evaluated in the major pelvic ganglion (MPG) after CN injury. In addition, expressions of C-X-C motif chemokine ligand (Cxcl12) and glial cell line-derived neurotrophic factor (Gdnf) in the MPG were examined by real-time polymerase chain reaction. Statistical analyses and comparisons among groups were performed using one-way analysis of variance followed by the Tukey test for parametric data and Kruskal-Wallis test followed by the Dunn-Bonferroni test for non-parametric data. RESULTS: The mean (SEM) ICP/AP values at 28 days were 0.51 (0.02) in the Muse cell group, 0.37 (0.03) in the non-Muse MSC group, and 0.36 (0.04) in the vehicle group, showing a significant positive response in the Muse cell group compared with the non-Muse and vehicle groups (P = 0.013 and P = 0.010, respectively). In the MPG, Muse cells were observed to be engrafted at 48 h and expressed Schwann cell markers S100 (~46%) and glial fibrillary acidic protein (~24%) at 28 days, while non-Muse MSCs were basically not engrafted at 48 h. Higher gene expression of Cxcl12 (P = 0.048) and Gdnf (P = 0.040) was found in the MPG of the Muse group than in the vehicle group 48 h after infusion. CONCLUSION: Intravenously engrafted human Muse cells recovered rat erectile function after CN injury in a rat model possibly by upregulating Cxcl12 and Gdnf.
Assuntos
Disfunção Erétil , Ratos , Humanos , Masculino , Animais , Disfunção Erétil/etiologia , Disfunção Erétil/terapia , Ratos Sprague-Dawley , Fator Neurotrófico Derivado de Linhagem de Célula Glial/farmacologia , Alprostadil/farmacologia , Modelos Animais de Doenças , Ereção Peniana/fisiologia , Imunossupressores , PênisRESUMO
A group of temperate grassland plant species termed the "Mansen elements" occurs in Japan and is widely distributed in the grasslands of continental East Asia. It has been hypothesized that these species are continental grassland relicts in Japan that stretch back to a colder age, but their migration history has not been elucidated. To assess the migration history of the Mansen elements, we performed phylogeographic analyses of Tephroseris kirilowii, a member of this group, using single-nucleotide polymorphisms (SNPs) obtained from multiplexed inter-simple sequence repeat genotyping by sequencing (MIG-seq). It was estimated that the Japanese populations of T. kirilowii were divided from those of continental East Asia at 25.2 thousand years ago (ka) with 95% highest probability density interval (HPD) of 15.3-40.0 ka and that Japanese clades first diverged at 20.2 ka with 95% HPD of 10.4-30.1 ka. As the climatically suitable range during the last glacial maximum (LGM) estimated using ecological niche modeling (ENM) was limited in Japan and there was a slight genetic differentiation among Japanese populations, a post-glacial expansion of T. kirilowii in the Japanese Archipelago was indicated.
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Asteraceae , Pradaria , Filogeografia , Asteraceae/genética , Genótipo , Variação Genética , Repetições de Microssatélites/genética , FilogeniaRESUMO
Understanding adaptation mechanisms is important in evolutionary biology. Parallel adaptation provides good opportunities to investigate adaptive evolution. To confirm parallel adaptation, it is effective to examine whether the phenotypic similarity has one or multiple origins and to use demographic modeling to consider the gene flow between ecotypes. Solidago yokusaiana is a rheophyte endemic to the Japanese Archipelago that diverged from Solidago virgaurea. This study examined the parallel origins of S. yokusaiana by distinguishing between multiple and single origins and subsequent gene flow. The haplotypes of noncoding chloroplast DNA and genotypes at 14 nuclear simple sequence repeat (nSSR) loci and single-nucleotide polymorphisms (SNPs) revealed by double-digest restriction-associated DNA sequencing (ddRADseq) were used for phylogeographic analysis; the SNPs were also used to model population demographics. Some chloroplast haplotypes were common to S. yokusaiana and its ancestor S. virgaurea. Also, the population genetic structures revealed by nSSR and SNPs did not correspond to the taxonomic species. The demographic modeling supported the multiple origins of S. yokusaiana in at least four districts and rejected a single origin with ongoing gene flow between the two species, implying that S. yokusaiana independently and repeatedly adapted to frequently flooding riversides.
Assuntos
Solidago , DNA de Cloroplastos/genética , Repetições de Microssatélites , Filogeografia , Solidago/genéticaRESUMO
OBJECTIVE: To evaluate the impact of cancer therapy on post-treatment ejaculation in patients with testicular cancer. METHODS: A total of 74 testicular cancer survivors provided completed International Index of Erectile Function-15 questionnaires before and after treatment between 2010 and 2017. Sexual function, particularly ejaculatory function, was evaluated before and after treatment. In this study, patients who answered "1 = almost never/never" or "2 = a few times" for questionnaire number 9 (ejaculation frequency) were defined as having "ejaculation disorder." RESULTS: Of 74 testicular cancer survivors, 50 (68%) had no ejaculation disorders before treatment. Four (44%) of nine survivors, who received chemotherapy and retroperitoneal lymph node dissection, developed ejaculation disorders after treatment. On multivariate analysis, retroperitoneal lymph node dissection was a significant predictor of post-treatment ejaculation disorder (P = 0.042). Of 60 survivors with evaluable ejaculation function after treatment, 24 (40%) did not attempt sexual intercourse, and multivariate analysis showed ejaculation disorder had a significant negative impact on having sexual intercourse (P = 0.035). Furthermore, the mean International Index of Erectile Function-15 scores in the groups with and without ejaculation disorders after treatment were 24.0 and 51.9, respectively (P < 0.001). CONCLUSION: Ejaculation disorders occur at high rate after retroperitoneal lymph node dissection. Many testicular cancer survivors reporting no sexual intercourse have ejaculation disorders, suggesting an adverse impact on sexual life. Urologists should provide proper counselling regarding the risk of ejaculation disorder and its possible impact on sexual life.
Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Ejaculação , Humanos , Excisão de Linfonodo , Masculino , Espaço Retroperitoneal , Sobreviventes , Neoplasias Testiculares/cirurgiaRESUMO
Among advanced non-small cell lung cancer (NSCLC) patients in whom grade 2/3 immune-related adverse events (irAEs) that had developed during the initial immune checkpoint inhibitor (ICI) therapy had been successfully controlled, we experienced three patients in whom ICI therapy was resumed at the diagnosis of progressive disease (PD group, n = 3) and four patients in whom it was resumed immediately after successful control of irAEs (non-PD group, n = 4). The tumor response rate, disease control rate to the resumed ICI and progression-free survival from the resumption of ICI therapy were 0%, 0% and 2 months in the PD group and 25%, 75% and 4.8 months in the non-PD group. In advanced NSCLC patients in whom resumption of discontinued ICI therapy was planned, the ICI therapy should be resumed immediately after successful control of irAEs, rather than at the diagnosis of PD.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Retratamento , Tempo para o Tratamento , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
After the failure of first-line epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy, some non-small cell lung cancer patients desire to receive switching with another EGFR-TKI (TKI-switching), although cytotoxic chemotherapy has been recommended as second-line therapy. It is unclear who should not receive TKI-switching in these patients. We retrospectively evaluated overall survival (OS) from the initiation of first EGFR-TKI (first-TKI) therapy in advanced lung adenocarcinoma patients with active EGFR mutations (deletion of exon 19 or L858R in exon 21) who received TKI-switching according to the best response of the first-TKI. There was no difference in the OS between patients receiving TKI-switching (n = 35) and patients receiving additional chemotherapy between the first-TKI and second-TKI therapy (n =10) (P = 0.614). Among patients receiving TKI-switching, the OS in cases with progressive disease to the first-TKI (n = 9) was shorter than that in cases with disease control to the first-TKI (n = 26) (12.7 months vs. 49.4 months, P < 0.001). Five of the nine progressive disease cases who received TKI-switching missed an opportunity to receive chemotherapy. Their OS tended to be shorter than that in patients who received chemotherapy during the whole period of anticancer therapy (12.2 months vs. 20.3 months, P = 0.060). The multivariate analysis showed that disease control to the first-TKI therapy (P = 0.005) or the presence of chemotherapy (P = 0.087) decreased the risk of mortality. Chemotherapy should be performed in patients with progressive disease to the first-TKI.
Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Adenocarcinoma de Pulmão/enzimologia , Adenocarcinoma de Pulmão/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Receptores ErbB/administração & dosagem , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Testicular cancer occurs in the testes of the male reproductive system and is the most common cancer in adolescent and young adult (AYA) men. However, recently, there have been more cases of testicular cancer in men older than 40 years. Therefore, trends of testicular cancer during the past 40 years were retrospectively examined, focusing on age and histology. Patients who were diagnosed with testicular cancer at our institution between 1980 and 2019 were enrolled in this study. The patients were divided into groups by the year of diagnosis (1980s, 1990s, 2000s, and 2010s), age at diagnosis (14, 15 to 39, and older than 40 years), and histological type (seminoma and non-seminoma). A total of 563 patients were diagnosed with testicular cancer over the 40-year period. The median age at diagnosis increased continuously, from 28 years to 31 years, 34 years, and 38 years in each period, respectively (p < 0.001). Moreover, most testicular cancer patients were of the AYA generation, whereas the ratio of patients older than 40 years increased significantly since 2000 (p < 0.001). The relative proportion of seminoma also increased more than 50% since 2000. In the seminoma group, median age increased from 31 years to 41 years during the 40-year period (p < 0.001). In conclusion, the age at diagnosis is rising for testicular cancer patients. Clinicians should recognize that testicular cancer affects not only the AYA generation, but there has been a shift to older than 40 years, especially in seminoma.
Assuntos
Oncologia/tendências , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Seminoma/epidemiologia , Neoplasias Testiculares/epidemiologia , Adolescente , Adulto , Fatores Etários , Seguimentos , Humanos , Incidência , Japão , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Estudos Retrospectivos , Fatores de Risco , Seminoma/diagnóstico , Neoplasias Testiculares/diagnóstico , Adulto JovemRESUMO
BACKGROUND: Many elderly men suffer from benign prostatic hyperplasia (BPH). Recently, chronic ischemia in the prostate has been suggested to be related to BPH. Thus, the impact of chronic ischemia on the development of prostatic hyperplasia and the efficacy of phosphodiesterase type 5 (PDE5) inhibitor for hyperplasia were evaluated in a rat model with chronic ischemia induced by local atherosclerosis. METHODS: Eighteen male Sprague-Dawley rats were divided into three groups: sham operation, regular diet, placebo (SRP); arterial endothelial injury, high cholesterol diet, placebo (AHP); or arterial endothelial injury, high cholesterol diet, and tadalafil as a PDE5 inhibitor (AHT). The endothelial injury in the common iliac arteries was performed using a 2-Fr Fogarty arterial embolectomy catheter through an incision in the femoral artery into the common iliac artery. Diet and oral drugs were administrated for 8 weeks after surgery. At 8 weeks, blood flow to the ventral prostate (VP) was measured using laser speckle blood flow analysis, and the VP was histologically evaluated. RESULTS: In the AHP group, prostatic blood flow was reduced, and mean VP weight and the interstitial area were significantly enlarged compared with the SRP group. In the AHT group, tadalafil administration obviously ameliorated the reduction of prostatic blood flow relative to the AHP group. Importantly, mean VP weight and the morphological changes in the AHT group were significantly smaller than those in the AHP group. CONCLUSIONS: Enlargement of the VP resulted from chronic ischemia induced by local arteriosclerosis. Also, administration of tadalafil attenuated VP enlargement. Chronic ischemia in the prostate might thus contribute to the development of BPH, and PDE5 inhibitors might provide an innovative approach to preventing BPH.
Assuntos
Isquemia/complicações , Inibidores da Fosfodiesterase 5/farmacologia , Próstata/irrigação sanguínea , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/etiologia , Animais , Modelos Animais de Doenças , Isquemia/tratamento farmacológico , Isquemia/patologia , Masculino , Próstata/patologia , Hiperplasia Prostática/patologia , Ratos , Ratos Sprague-Dawley , Tadalafila/farmacologiaRESUMO
It is not clear whether sequential chemotherapy can be performed immediately in patients with p-stage I non-small cell lung cancer recurring during a 2-year period of daily oral administration with tegafur-uracil (UFT) as postoperative adjuvant chemotherapy. Patients receiving chemotherapy within 1 month after the discontinuation of UFT (n = 10) (five cases with aggressive recurrent tumors) had the increased risk of grade 4 neutropenia, but the overall survival was not inferior to that in patients who received chemotherapy beginning more than 1 month (n = 11). We could perform sequential chemotherapy immediately while paying attention to grade 4 neutropenia.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neutropenia , Período Pós-Operatório , Estudos Retrospectivos , Análise de Sobrevida , Tegafur/administração & dosagem , Tegafur/efeitos adversos , Resultado do Tratamento , Uracila/administração & dosagem , Uracila/efeitos adversosRESUMO
Determinants of interindividual variability in erlotinib pharmacokinetics (PK) and adverse events remain to be elucidated. This study with 50 Japanese non-small-cell lung cancer patients treated with oral erlotinib at a standard dose of 150 mg aimed to investigate whether genetic polymorphisms affect erlotinib PK and adverse events. Single nucleotide polymorphisms (SNPs) in genes encoding metabolizing enzymes (CYP1A1, CYP1A2, CYP2D6, CYP3A4, CYP3A5, UGT1A1, UGT2B7, GSTM1, and GSTT1) or efflux transporters (ABCB1, and ABCG2) were analyzed as covariates in a population PK model. The ABCB1 1236C>T (rs1128503) polymorphism, not ABCB1*2 haplotype (1236TT-2677TT-3455TT, rs1128503 TT-rs2032582 TT-rs1045642 TT), was a significant covariate for the apparent clearance (CL/F), with the TT genotype showing a 29.4% decrease in CL/F as compared with the CC and the CT genotypes. A marginally higher incidence of adverse events (mainly skin rash) was observed in the TT genotype group; however, patients with high plasma erlotinib exposure did not always experience skin rash. None of the other SNPs affected PK or adverse events. The ABCB1 genotype is a potential predictor for erlotinib adverse events. Erlotinib might be used with careful monitoring of adverse events in patients with ABCB1 polymorphic variants.
Assuntos
Antineoplásicos/farmacocinética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Cloridrato de Erlotinib/farmacocinética , Neoplasias Pulmonares/metabolismo , Modelos Biológicos , Polimorfismo de Nucleotídeo Único , Transportadores de Cassetes de Ligação de ATP/genética , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Sistema Enzimático do Citocromo P-450/genética , Relação Dose-Resposta a Droga , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Cloridrato de Erlotinib/efeitos adversos , Cloridrato de Erlotinib/uso terapêutico , Feminino , Glucuronosiltransferase/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Masculino , Estudos ProspectivosRESUMO
In the setting of partial nephrectomy (PN) for renal cell carcinoma, postoperative renal dysfunction might be caused by surgical procedure. The aim of this study was to clarify the technical safety and renal damage after off-clamp laparoscopic PN (LPN) with a piezo actuator-driven pulsed water jet (ADPJ) system. Eight swine underwent off-clamp LPN with this surgical device, while off-clamp open PN was also performed with radio knife or soft coagulation. The length of the removed kidney was 40 mm, and the renal parenchyma was dissected until the renal calyx became clearly visible. The degree of renal degeneration from the resection surface was compared by Hematoxylin-Eosin staining and immunostaining for 1-methyladenosine, a sensitive marker for the ischemic tissue damage. The mRNA levels of neutrophil gelatinase-associated lipocalin (Ngal), a biomarker for acute kidney injury, were measured by quantitative real-time PCR. Off-clamp LPN with ADPJ system was successfully performed while preserving fine blood vessels and the renal calix with little bleeding. In contrast to other devices, the resection surface obtained with the ADPJ system showed only marginal degree of ischemic changes. Indeed, the expression level of Ngal mRNA was lower in the resection surface obtained with the ADPJ system than that with soft coagulation (p = 0.02). Furthermore, using the excised specimens of renal cell carcinoma, we measured the breaking strength at each site of the human kidney, suggesting the applicability of this ADPJ to clinical trials. In conclusion, off-clamp LPN with the ADPJ system could be safely performed with attenuated renal damage.
Assuntos
Rim/cirurgia , Laparoscopia/instrumentação , Nefrectomia/instrumentação , Água , Adenosina/análogos & derivados , Adenosina/metabolismo , Animais , Fenômenos Biomecânicos , Humanos , Imuno-Histoquímica , Rim/patologia , Rim/fisiopatologia , Lipocalina-2/genética , Lipocalina-2/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sus scrofaRESUMO
We retrospectively evaluated whether preoperative percutaneous transthoracic needle biopsy (PTNB) affected the incidence of pleural recurrence in pathological stage I lung cancer patients. Pleural recurrence occurred in pure solid nodule (PSN) cases but not in ground-glass nodule cases, as evaluated using thin-section computed tomographic imaging. When the cases were restricted to sub-pleural PSN, the incidence of recurrence tended to be higher in a PTNB group (63 patients diagnosed by PTNB) than in a non-PTNB group (86 patients diagnosed by transbronchial biopsy or intraoperative diagnosis) (25% vs. 4%, p =.050). PTNB should not be performed in patients with a sub-pleural PSN.
Assuntos
Biópsia por Agulha/efeitos adversos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pleurais/diagnóstico , Nódulo Pulmonar Solitário/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha/métodos , Terapia Combinada , Feminino , Humanos , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Cuidados Pré-Operatórios , Estudos Retrospectivos , Risco , Nódulo Pulmonar Solitário/cirurgia , Nódulo Pulmonar Solitário/terapia , Tomografia Computadorizada por Raios X , Carga TumoralRESUMO
INTRODUCTION: The tissue sealing sheet has recently been used to prevent intraoperative bleeding from the neurovascular bundles in radical prostatectomy. Surgical stress or inflammatory changes likely play a role in erectile dysfunction after cavernous nerve injury. However, the efficacy of a tissue sealing sheet for preventing erectile function after nerve-sparing radical prostatectomy remains unclear. AIM: To evaluate the effect of a tissue sealing sheet on erectile dysfunction after cavernous nerve dissection. METHODS: Male Sprague-Dawley rats were randomly divided into three groups and subjected to sham operation or bilateral cavernous nerve dissection with (sheet group) or without (non-sheet group) a tissue sealing sheet. In the sheet group, cavernous nerves were sealed with a tissue sealing sheet immediately after cavernous nerve dissection. MAIN OUTCOME MEASURES: Erectile function was assessed by measuring intracavernous pressure and arterial pressure during pelvic nerve electrostimulation at 4 weeks after surgery. Expressions of interleukin-6, tumor growth factor-ß1, and heme-oxygenase-1 in the major pelvic ganglion were examined by real-time polymerase chain reaction. RESULTS: Mean intracavernous pressure along with mean arterial pressure in the sheet group were similar to those in the sham group and showed a significant positive response compared with the non-sheet group (P < .05). Furthermore, expressions of interleukin-6, tumor growth factor-ß1, and heme-oxygenase-1 were significantly lower in the sheet group than in the non-sheet group (P < .05). CONCLUSION: Use of a tissue sealing sheet attenuated postoperative inflammatory changes and oxidative stress and improved erectile function after cavernous nerve injury in rats. The tissue sealing sheet might become a useful therapeutic approach to preserve erectile function after nerve-sparing radical prostatectomy.
Assuntos
Modelos Animais de Doenças , Disfunção Erétil/etiologia , Separação Imunomagnética , Prostatectomia/efeitos adversos , Animais , Disfunção Erétil/tratamento farmacológico , Humanos , Plexo Hipogástrico , Masculino , Pênis/inervação , Prostatectomia/métodos , Ratos , Ratos Sprague-Dawley , Traumatismos do Sistema Nervoso/patologiaRESUMO
We retrospectively evaluated whether the ratio KL-6 to SLX in serum (K/S ratio) before chemotherapy was a predictor for the occurrence of drug-induced interstitial lung disease (D-ILD) in lung cancer patients with idiopathic interstitial pneumonias (IIPs). D-ILD occurred in 8 of 20 IIPs-positive cases and in 14 of 100 IIPs-negative cases (40 vs. 14%, p = .015). In IIPs-positive cases, the high K/S ratio (>20) before first-line chemotherapy had a tendency to increase the risk of D-ILD (p = .085). Serum K/S ratio may be a useful predictor for the occurrence of D-ILD in lung cancer patients with IIPs.
Assuntos
Endonucleases/metabolismo , Pneumonias Intersticiais Idiopáticas/tratamento farmacológico , Doenças Pulmonares Intersticiais/induzido quimicamente , Mucina-1/metabolismo , Idoso , Endodesoxirribonucleases , Endonucleases/sangue , Feminino , Humanos , Masculino , Mucina-1/sangue , Estudos RetrospectivosRESUMO
OBJECTIVES: This study was designed to determine the recommended dose of carboplatin and pemetrexed for elderly (≥70-year-old) chemotherapy-naïve patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) and to investigate the pharmacokinetics of pemetrexed. METHODS: The patients were treated with 4-6 cycles of carboplatin plus a fixed dose of pemetrexed (500 mg/m(2)) every 3 weeks; the dose of carboplatin was escalated [from area under the curve (AUC) 4 to AUC 6]. To examine the pharmacokinetics of pemetrexed, blood samples were collected before and after pemetrexed infusion, and the blood levels of pemetrexed were measured by liquid chromatography-mass spectrometry. RESULTS: Grade 3 infection as a dose-limiting toxicity was observed at a carboplatin dose of AUC 6. We therefore determined a carboplatin dose of AUC 5 and a pemetrexed dose of 500 mg/m(2) as the recommended doses from this study. The pharmacokinetic study showed a significant inverse correlation between the AUC of pemetrexed and the creatinine clearance. CONCLUSIONS: For elderly chemotherapy-naïve patients with advanced nonsquamous NSCLC, the combination of carboplatin AUC 5 plus pemetrexed 500 mg/m(2) is recommended as a promising regimen; however, a reduction of the pemetrexed dose may be required for patients with renal dysfunction because of the high risk of hematotoxicities.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Glutamatos/administração & dosagem , Guanina/administração & dosagem , Guanina/análogos & derivados , Humanos , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias , Pemetrexede , Prognóstico , Distribuição TecidualRESUMO
A 44-year-old man discovered a swollen right testis more than 4 years earlier. He was brought to our hospital because of abdominal pain and vomiting. Enhanced computed tomography (CT) showed a swollen right testis, lung nodules, and swollen retroperitoneal and mediastinal lymph nodes. The swollen lymph nodes compressed the duodenum, causing ileus. HCG, HCG-ß, and AFP levels were normal, but the LDH level was high (2,933 IU/L). A diagnosis of testicular cancer with lung and lymph node metastases was made, and a right orchidectomy was performed. However, the pathological diagnosis was unclear, and it was necessary to consult another pathologist, but this took .6 weeks. While awaiting the pathological diagnosis, the patient was given chemotherapy with two 3-week courses of BEP. On pathological examination, the tumor consisted of small round cells with a rosette-like arrangement. Cartilage and keratinized tissues were also present. Immunohistochemical staining was positive for CD56, synaptophysin, vimentin, GFAP, and CD99 (MIC2), but negative for AE1/AE3, OCT-4, chromogranin, INI-1, and desmin. The patient was then diagnosed as having a primitive neuroectodermal tumor and teratoma. The metastatic lymph nodes decreased in size after chemotherapy; therefore, two further courses of BEP were added. However, CT showed disease progression. The patient refused further therapy and returned home. Eight months later, he was hospitalized because of swollen retroperitoneal and mediastinal lymph nodes and ileus. Despite treatment with radiation therapy, which resulted in decreased lymph nodes, the patient died. This was a very rare case, the first such case in Japan.
Assuntos
Tumores Neuroectodérmicos Primitivos/terapia , Neoplasias Testiculares/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Evolução Fatal , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Tumores Neuroectodérmicos Primitivos/secundário , Orquiectomia , Neoplasias Testiculares/patologiaRESUMO
BACKGROUND: In elderly patients with malignant central airway obstruction (MCAO), the treating physicians often hesitate to undertake transbronchial interventions (TBIs) as a palliative procedure in view of the advanced age of the patients. METHODS: We conducted this retrospective study to evaluate the differences in the feasibility, tolerability, and effectiveness of TBIs between elderly (aged 75 years old or above; elderly group; n=27) and nonelderly (aged below 75 years old; nonelderly group; n=50) patients with MCAO. The primary endpoint was the incidence of complications during (within 24 hours) and after (>24 hours) TBIs. RESULTS: The mean age of the patients was 81 years in the elderly group and 61 years in the nonelderly group. The complications encountered during/after TBI included endobronchial bleeding or hypoxemia requiring intubation occurring during the TBIs, and bacterial pneumonia, airway reocclusion, and stent migration occurring after the TBIs, although there was no difference in the frequency of complications during/after the TBIs between the elderly group and nonelderly group (26% vs. 30%, P =0.706). There was no difference in the percentage of patients in whom successful airway recanalization was achieved by TBI (93% vs. 80%, P =0.197), the percentage of patients who showed symptomatic improvement after the TBIs (67% vs. 76%, P =0.380) and the OS after the TBIs (6.1 vs. 7.3 months, P =0.704) between the 2 groups. CONCLUSION: TBIs can be undertaken without hesitation as a palliative procedure in elderly patients with MCAO.
Assuntos
Obstrução das Vias Respiratórias , Broncoscopia , Estudos de Viabilidade , Humanos , Estudos Retrospectivos , Idoso , Masculino , Feminino , Obstrução das Vias Respiratórias/etiologia , Obstrução das Vias Respiratórias/terapia , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Broncoscopia/métodos , Cuidados Paliativos/métodos , Resultado do Tratamento , Neoplasias Pulmonares/complicaçõesRESUMO
BACKGROUND/AIM: This study aimed to determine whether the prognosis of small-cell lung cancer (SCLC) patients with malignant central airway obstruction (MCAO) who receive chemotherapy without undergoing transbronchial intervention (TBI) is not inferior to that of SCLC patients without MCAO. PATIENTS AND METHODS: We compared overall survival (OS) from the time of SCLC diagnosis between stage III or IV SCLC patients with MCAO (MCAO group, n=22) and those without MCAO (non-MCAO group, n=88). MCAO is generally defined as >50% obstruction of the trachea or mainstem bronchi. RESULTS: The median interval from the time of SCLC diagnosis until the initiation of anticancer therapy and the median number of chemotherapy regimens were 6 days and 2 regimens, respectively, in the MCAO group and 15 days and 2 regimens in the non-MCAO group. During the median follow-up period of 11.7 months after SCLC diagnosis, 95% of the patients in the MCAO group and 85% of the patients in the non-MCAO group died. No difference in the median OS (11.9 months vs. 12.4 months, p=0.455) was seen between the MCAO group and the non-MCAO group. A multivariate analysis showed that the presence of MCAO was not associated with an increased risk of death in SCLC patients who received chemotherapy (p=0.664). CONCLUSION: The prognosis of SCLC patients with MCAO who receive chemotherapy without undergoing TBI is not inferior to that of SCLC patients without MCAO.
Assuntos
Obstrução das Vias Respiratórias , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Obstrução das Vias Respiratórias/tratamento farmacológico , Obstrução das Vias Respiratórias/etiologia , Brônquios , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
INTRODUCTION: Some elderly stage I non-small cell lung cancer (NSCLC) patients may refuse both stereotactic body radiotherapy (SBRT) and surgery and may instead desire best supportive care (BSC) alone, despite having a medically operable condition. METHODS: We retrospectively evaluated the differences in the 3-year overall survival (3-year OS) rates among elderly stage I NSCLC patients aged ≥ 80 years who received surgery (OP group, n = 39), SBRT (RT group, n = 32) or BSC alone (BSC group, n = 28), stratifying the later groups according to those who were medically inoperable (MI subgroup) and those who were considered medically operable but refused surgery (MO subgroup). RESULTS: During a median 39.1-month follow-up period, 44 patients died. The 3-year OS rates were longer and higher in the MI-RT subgroup and the OP group than in the MI-BSC subgroup (67%, 89%, and 22%, respectively; p = 0.001). No differences in the 3-year OS rates were seen among the MO-RT subgroup, the MO-BSC subgroup, and the OP group (75%, 70%, and 89%, respectively; p = 0.164). However, a multivariate analysis identified a performance status (PS) score of 1-2 or a Charlson comorbidity index (CCI) score of ≥2, as well as stage IB disease and BSC, as independently increasing the risk of death. CONCLUSIONS: Elderly stage I NSCLC patients who were medically operable but who refused surgery and desire BSC alone should be encouraged to undergo SBRT unless they have a good PS and are otherwise in healthy condition.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Idoso , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Estadiamento de NeoplasiasRESUMO
BACKGROUND/AIM: Transbronchial microwave ablation (MWA) can be performed safely in patients with malignant central airway obstruction (MCAO), under moderate sedation and a high fraction of inspired oxygen. PATIENTS AND METHODS: We retrospectively evaluated the difference in the overall survival (OS) after transbronchial interventions (TBIs) between MCAO patients with endoluminal or mixed-type obstruction who were treated by MWA (MWA group, n=34) and those with extraluminal obstruction who were treated by stent placement (STP) (STP group, n=27). RESULTS: The OS was longer in the MWA group than in the STP group (10.2 months vs. 4.5 months, p=0.001). A significant difference in the OS between the two groups was observed in the patients who received post-TBI anticancer therapy (27.2 months vs. 6.0 months, p=0.002). The OS tended to be longer in the MWA group than in the STP group, among the patients who received best supportive care alone (3.8 months vs. 1.8 months, p=0.068). Nine patients (26%) of the MWA group underwent additional MWA when tumor regrowth into the airway lumen was noted (median of TBI sessions, 3). Multivariate analysis identified the adoption of MWA as the initial treatment procedure to be independently associated with a reduced risk of death in patients with MCAO (hazard ratio=0.473, p=0.031). CONCLUSION: Adoption of MWA as the initial treatment procedure is beneficial in MCAO patients with endoluminal or mixed-type obstruction, regardless of whether patients receive post-TBI anticancer therapy or not.