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1.
Anticancer Drugs ; 34(4): 605-608, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36729850

RESUMO

Lenvatinib is a multitargeted kinase inhibitor and maintaining its dose intensity has been shown to be beneficial in patients with thyroid and hepatocellular carcinomas. However, most patients require lenvatinib interruption and dose reduction due to the high incidence of adverse events (AEs). Lenvatinib was recently approved in Japan for patients with unresectable thymic carcinoma; however, real-world evidence of its clinical benefit is limited. Here, we report the case of chemotherapy-refractory thymic carcinoma in a patient who was administered a starting dose of lenvatinib using a 5-day on/2-day off (weekend-off) protocol, followed by alternate-day administration after fatigue onset derived from overt or subclinical hypothyroidism. Consequently, the patient exhibited a durable response to lenvatinib, with a 17-month progression-free survival without any severe or intolerable AEs. The present case suggests that maintaining lenvatinib dose intensity using such alternative administration regimens contributes to favorable clinical outcomes in thymic carcinoma.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Quinolinas , Timoma , Neoplasias do Timo , Humanos , Timoma/tratamento farmacológico , Timoma/induzido quimicamente , Antineoplásicos/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Carcinoma Hepatocelular/patologia , Quinolinas/uso terapêutico , Neoplasias Hepáticas/patologia , Neoplasias do Timo/tratamento farmacológico , Neoplasias do Timo/induzido quimicamente
2.
Mol Carcinog ; 61(10): 924-932, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35848137

RESUMO

The genetic concordance and heterogeneity of the two components of pulmonary carcinosarcoma (PCS), carcinoma, and sarcoma, have not been fully elucidated because of its rare occurrence. We performed targeted sequencing of the carcinoma and sarcoma components of four PCSs to identify genetic similarities and differences. Formalin-fixed paraffin-embedded tissue samples were macroscopically or microscopically dissected. DNA was extracted from each component, and genetic alterations were analyzed separately. Moreover, we performed RNA-seq analysis on both components of one PCS to compare differences in gene expression profiles. The carcinoma part consisted of adenocarcinoma in two cases, squamous cell carcinoma in one, and adenosquamous carcinoma in the last. TP53 mutation was observed in three samples from the trunk, although it was detected only in the sarcoma part in one case. No specific driver gene mutation was observed; however, KRAS mutations were observed in one case in the trunk. RNA-seq analysis revealed that the rhabdomyosarcoma component expressed various genes related to muscle development, whereas the carcinoma component did not; and that gene expression overall was completely different between the two components. Our study revealed that the two different components of PCS shared common gene mutations in most cases. Although gene expression was different among components, if driver genes such as KRAS were detected in PCS, molecular targeted therapy could be beneficial even when the tumor contains a sarcoma component.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Carcinossarcoma , Neoplasias Pulmonares , Sarcoma , Carcinoma de Células Escamosas/genética , Carcinossarcoma/genética , Carcinossarcoma/metabolismo , Carcinossarcoma/patologia , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo
3.
Ann Surg Oncol ; 29(11): 7149-7162, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35644860

RESUMO

BACKGROUND: Fibroblast growth factor receptor (FGFR)-signaling in lung squamous cell carcinoma (LSCC) is associated with cancer aggressiveness and poor prognosis. Small GTPase RAB11A regulates the recycling of membrane proteins such as FGFR. This study evaluated the potential of RAB11A as a new therapeutic target for LSCC through its regulation of FGFR-signaling. METHODS: Immunohistochemical analysis of 84 LSCC samples was performed to determine the correlation between RAB11A expression, clinicopathologic features, and prognosis. Alterations in FGFR-signaling were assessed in RAB11A-suppressed and RAB11A-overexpressed LSCC cells both in vitro and in vivo. RESULTS: The study identified RAB11A as a strong predictor of poor prognosis in the LSCC cohort. Cell proliferation and invasion were promoted and inhibited respectively in RAB11A-overexpressed and RAB11A -suppressed LSCC cells. In RAB11A-overexpressed and RAB11A-suppressed LSCC cells, FGFR-signaling was respectively up- and downregulated. The viability of the cells treated with nintedanib and lenvatinib was greater in RAB11A-overexpressing cells than in control cells. The in vivo tumor growth and micro-vessel density of RAB11A-overexpressing tumors were significantly higher than in the control cells. CONCLUSION: As a potentially valuable prognostic marker, RAB11A is a promising therapeutic target for LSCC. Evaluation of RAB11A may be useful for identification of LSCC in patients whose cancer is refractory to FGFR inhibitors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Laríngeas , Neoplasias Pulmonares , Proteínas Monoméricas de Ligação ao GTP , Proteínas rab de Ligação ao GTP , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Laríngeas/patologia , Pulmão/metabolismo , Neoplasias Pulmonares/genética , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Proteínas Monoméricas de Ligação ao GTP/uso terapêutico , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/uso terapêutico
4.
Int J Clin Oncol ; 25(4): 641-650, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31773354

RESUMO

BACKGROUND: RAS/BRAF mutations of colorectal cancer (CRC) play a crucial role in carcinogenesis and cancer progression and need to be considered for the therapeutic strategy choice. We used next-generation-sequencing (NGS) technology to assess RAS/BRAF mutation differences between primary CRC and corresponding pulmonary metastases (PMs). METHODS: We examined the mutation statuses of the KRAS 12/13/61/146, NRAS 12/13/61/146, and BRAF 600 codons in genomic DNA from fresh-frozen or formalin-fixed paraffin-embedded tissues derived from 34 primary lesions and 52 corresponding PMs from 36 patients with CRC. RESULTS: We found RAS mutations in 76% (26/34) of primary CRC lesions and in 86% (31/36) of PMs. While 27% (7/26) of the primary CRC RAS mutations were heterogeneous, all the RAS mutations in PMs were homogeneous. Of the mutations in PMs, 71% (22/31) were KRAS G>A transitions, of which 82% (18/22) were KRAS G12D or G13D. The RAS mutation discordance between primary tumors and PMs was 12.1% (4/33). RAS mutations with the same genotyping were detected in all synchronous and metachronous PMs from 9 patients. We found no BRAF mutations in either primary or pulmonary tissues. CONCLUSION: Our NGS analysis suggests that RAS mutations of PM of patients with CRC are more common than initially thought. The presence of KRAS mutations in CRC specimens, especially G12D or G13D mutations, seems to promote PM formation.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Pulmonares/secundário , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/genética , Feminino , GTP Fosfo-Hidrolases/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/genética , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas B-raf/genética
5.
Ann Surg Oncol ; 26(6): 1744-1750, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30924018

RESUMO

BACKGROUND: Lung combined neuroendocrine carcinomas (NECs) comprise NEC and non-NEC components, such as adenocarcinoma and squamous cell carcinoma. Mutation of epidermal growth factor receptor (EGFR) often is observed in non-NEC but is very rare in sporadic NEC, which almost always has p53 mutation. Therefore, we hypothesized the following research concept: mutation analysis of EGFR and p53 in each component of combined NEC tissues can provide important information on whether such components originate from the same tumor cells or incidentally arise as collision cancers. METHODS: We compared the mutations of EGFR and p53 in laser-microdissected NEC and non-NEC from lungs of eight cases affected by combined NEC. We examined the expression of EGFR and NEC markers in the combined NECs by immunohistochemistry. RESULTS: Five of eight cases of combined NEC had the same mutations of EGFR and/or p53 in both non-NEC and NEC. One case had EGFR mutation in only the non-NEC component, and two cases did not have these mutations. Replacement transformation was observed in borderline areas between non-NEC and NEC. The signal of activated EGFR in non-NEC with the same EGFR mutation was more intense than that in NEC components. CONCLUSIONS: Our study suggests the mechanism behind the carcinogenesis of lung combined NEC, which is partially caused by the transformation from epithelial carcinoma of non-NEC to NEC.


Assuntos
Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Neuroendócrino/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Pulmonares/patologia , Mutação , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Idoso , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Análise Mutacional de DNA , Receptores ErbB/genética , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Proteína Supressora de Tumor p53/genética
6.
World J Surg ; 42(4): 1161-1170, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28983707

RESUMO

OBJECTIVES: The lung is one of the most common organs of metastasis from colorectal cancer (CRC), and we have encountered lung cancer patients with a history of CRC. There have been few studies regarding methods used to discriminate between primary lung cancer (PLC) and pulmonary metastasis from CRC (PM-CRC) based only on preoperative findings. We retrospectively investigated predictive factors discriminating between these lesions in patients with a history of CRC. METHODS: Between 2006 and 2015, 117 patients with a history of CRC (44 patients with 47 PLC and 73 patients with 102 PM-CRC) underwent subsequent or concurrent resection of pulmonary lesions. We compared the clinical and radiological characteristics of 100 patients with solitary lesions (43 PLC and 57 PM-CRC). Using univariate and multivariate analyses, we examined predictive factors for discrimination of these two lesions. RESULTS: All tumors with findings of ground-glass opacity (GGO) were PLC (n = 19). In a multivariate analysis of 81 radiologically solid tumors, two factors were found to be significant independent predictors of PLC: a history of stage I CRC and presence of pleural indentation. All tumors in 26 patients with either GGO or both a stage I CRC history and pleural indentation were PLC, while most tumors in patients without all three factors were PM-CRC (43/44; 97.7%). CONCLUSIONS: The presence or absence of GGO, pathological CRC stage, and pleural indentation could be useful factors to distinguish between PLC and PM-CRC.


Assuntos
Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pulmão , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Estadiamento de Neoplasias , Pleura/patologia , Prognóstico , Radiografia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
7.
Ann Surg Oncol ; 24(13): 4017-4024, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28933054

RESUMO

BACKGROUND: Known as a microtubule-destabilizing protein, STMN1 (gene symbol: STMN1) regulates the dynamics of microtubules, cell cycle progress, and chemo-resistance against taxane agents. It is highly expressed in various human cancers and involved in cancer progression as well as poor prognosis. METHODS: Expression of STMN1 was examined by immunohistochemistry using FFPE tissue sections from 186 patients with lung squamous cell carcinoma (LSCC). Analysis of STMN1 suppression was performed for STMN1 small interfering RNA (siRNA)-transfected LSCC cell lines to determine the change in proliferation, invasive and apoptosis abilities, and paclitaxel sensitivity. RESULTS: The cytoplasmic STMN1 expression in LSCC was higher than in normal tissues. The high expression was significantly associated with vascular invasion (P = 0.0477) and poor prognosis. In addition, the proliferating and invasive abilities were decreased, and the apoptosis ability and paclitaxel sensitivity were increased in STMN1-suppressed LSCC cells compared with control cells. CONCLUSION: The results suggest that STMN1 is a prognostic factor that also is associated with caner progression and chemo-resistance. Therefore, STMN1 could be a predictor for poor prognosis and a potential therapeutic target in LSCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/secundário , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/patologia , Estatmina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Paclitaxel/farmacologia , Prognóstico , RNA Interferente Pequeno , Estatmina/antagonistas & inibidores , Estatmina/genética , Taxa de Sobrevida
8.
World J Surg ; 41(3): 771-779, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27896403

RESUMO

OBJECTIVES: There are only a few detailed reports concerning the prognosticators following surgical resection of pulmonary metastases (PMs) from renal cell carcinoma (RCC). We investigated the prognosis of patients with RCC PMs undergoing pulmonary metastasectomy and identified prognostic factors in a multi-institutional retrospective study. METHODS: We retrospectively evaluated 84 patients who underwent resection of PMs from RCC between 1993 and 2014. We assessed the clinicopathological characteristics, focusing on the histological findings of PMs. We classified the histology into three types: pure clear cell carcinoma (N = 68), clear cell carcinoma combined with other histology type (N = 8), and non-clear cell carcinoma (N = 8). We examined the relationship between these histological types and the prognosis of patients with PMs from RCC. RESULTS: Complete resection was achieved in 78 patients (93%). The 5-year overall survival rate after metastasectomy was 59.7%. In multivariate analysis, three factors were found to be independent favorable prognostic factors of overall survival after lung metastasectomy [tumor size <2 cm, hazard ratio (HR) = 0.31, 95% confidence interval (CI) 0.13-0.78, P = 0.012; clear cell type, HR = 0.37, 95% CI 0.16-0.83, P = 0.025; and complete resection, HR = 0.27, 95% CI 0.10-0.78, P = 0.015]. CONCLUSIONS: This study indicates that a histological finding of the clear cell type is a significant favorable prognostic factor in addition to complete resection and a tumor size <2 cm. Histological evaluation of PM lesions is important for predicting survival after metastasectomy.


Assuntos
Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Neoplasias Pulmonares/cirurgia , Metastasectomia , Pneumonectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
9.
Surg Today ; 46(10): 1196-208, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26782692

RESUMO

PURPOSE: The aim of this study was to identify risk factors for recurrence in non-small cell lung cancer (NSCLC) patients with lymph node metastases after surgical resection. METHODS: We reviewed 66 consecutive patients with surgically resected NSCLC who had pathologically proven positive lymph nodes (pN1 or pN2). All patients underwent a preoperative 2-[(18)F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) evaluation. We analyzed the recurrence-free survival (RFS) and recurrence-free proportion (RFP) according to the clinicopathological factors. RESULTS: A total of 27 patients were pathologically N1 and 39 were N2. The 5-year overall survival rate and the RFS rate were 47.2 and 27.7 %, respectively. The cut-off values for the SUVmax of the tumor and the lymph node ratio (LNR) were determined to be 6.5 and 0.12, respectively, using a receiver operating characteristics curve analysis. Both univariate and multivariate analyses revealed three significant independent factors for RFS: namely, the SUVmax of the tumor, the LNR, and the use of adjuvant chemotherapy. Only the SUVmax was an independent significant predictor of the RFP. CONCLUSIONS: Both the SUVmax and the LNR can serve as prognostic factors for patients with pN + NSCLC. Our study suggests that the LNR could be a stronger prognostic factor than the N classification of the TNM system and the SUVmax may predict recurrence in node-positive NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/etiologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimioterapia Adjuvante , Feminino , Radioisótopos de Flúor , Fluordesoxiglucose F18 , Seguimentos , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Excisão de Linfonodo , Metástase Linfática , Masculino , Recidiva Local de Neoplasia/diagnóstico por imagem , Seleção de Pacientes , Pneumonectomia , Tomografia por Emissão de Pósitrons , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
10.
Pathol Res Pract ; 262: 155557, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39191195

RESUMO

Emerin and lamins not only influence nuclear morphology but are also involved in differentiation. We herein examined 82 resected cases of invasive lung adenocarcinoma using computer-assisted image analysis of nuclear morphology on Feulgen-stained and immunohistochemical sections of lamin A, B1, B2, and emerin (four proteins) to calculate the rank sum of the cell positivity rates for these four proteins. The rank sum of four proteins showed weak negative correlations with the nuclear area and perimeter and a weak positive correlation with the nuclear shape factor. Interestingly, the top three cases with the highest rank sum were papillary adenocarcinoma, and the bottom three cases were acinar adenocarcinomas containing cribriform patterns. We compared the rank sum for grading (differentiation: G1, G2, and G3) and predominant histological subtypes and found that the rank sum of G3 was lower than that of G1 and G2. Furthermore, the rank sum was lower for acinar adenocarcinoma with >20 % cribriform pattern (acinar+cribri) and solid adenocarcinoma than for lepidic and papillary adenocarcinoma. Individual examination of the four proteins revealed that emerin expression was lower in G3 than in G1, and lamin B2 expression was lower in G3 than in G1 and G2. Compared with lepidic adenocarcinoma, acinar+cribri showed significantly lower expression of all four proteins among histological subtypes. These data indicated that the expression of lamin A, B1, B2, and emerin was markedly decreased in poorly differentiated adenocarcinoma (i.e., G3), especially in acinar+cribri. Our data suggested that changes in these four proteins can not only affect nuclear morphology but also histological structure in lung adenocarcinoma.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Proteínas de Membrana , Proteínas Nucleares , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Proteínas de Membrana/análise , Feminino , Pessoa de Meia-Idade , Idoso , Proteínas Nucleares/metabolismo , Proteínas Nucleares/análise , Adenocarcinoma/patologia , Adenocarcinoma/metabolismo , Núcleo Celular/patologia , Núcleo Celular/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Laminas/metabolismo , Adulto , Idoso de 80 Anos ou mais
11.
Thorac Cancer ; 15(2): 131-141, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38014454

RESUMO

BACKGROUND: Molecular abnormalities in the Wnt/ß-catenin pathway confer malignant phenotypes in lung cancer. Previously, we identified the association of leucine-rich repeat-containing G protein-coupled receptor 6 (LGR6) with oncogenic Wnt signaling, and its downregulation upon ß-catenin knockdown in non-small cell lung cancer (NSCLC) cells carrying CTNNB1 mutations. The aim of this study was to explore the mechanisms underlying this association and the accompanying phenotypes. METHODS: LGR6 expression in lung cancer cell lines and surgical specimens was analyzed using quantitative RT-PCR and immunohistochemistry. Cell growth was assessed using colony formation assay. Additionally, mRNA sequencing was performed to compare the expression profiles of cells subjected to different treatments. RESULTS: LGR6 was overexpressed in small cell lung cancer (SCLC) and NSCLC cell lines, including the CTNNB1-mutated NSCLC cell lines HCC15 and A427. In both cell lines, LGR6 knockdown inhibited cell growth. LGR6 expression was upregulated in spheroids compared to adherent cultures of A427 cells, suggesting that LGR6 participates in the acquisition of cancer stem cell properties. Immunohistochemical analysis of lung cancer specimens revealed that the LGR6 protein was predominantly overexpressed in SCLCs, large cell neuroendocrine carcinomas, and lung adenocarcinomas, wherein LGR6 overexpression was associated with vascular invasion, the wild-type EGFR genotype, and an unfavorable prognosis. Integrated mRNA sequencing analysis of HCC15 and A427 cells with or without LGR6 knockdown revealed LGR6-related pathways and genes associated with cancer development and stemness properties. CONCLUSIONS: Our findings highlight the oncogenic roles of LGR6 overexpression induced by aberrant Wnt/ß-catenin signaling in lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Via de Sinalização Wnt/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , beta Catenina/genética , beta Catenina/metabolismo , RNA Mensageiro , Linhagem Celular Tumoral , Proliferação de Células , Receptores Acoplados a Proteínas G/genética
12.
Thorac Cancer ; 15(11): 859-866, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38414316

RESUMO

BACKGROUND: Regional lymph node recurrence after radical surgery for non-small cell lung cancer (NSCLC) is an oligo-recurrent disease; however, no treatment strategy has been established. In the present study we aimed to determine the clinical outcomes of postoperative regional lymph node recurrence and identify prognostic predictors in the era of molecular-targeted therapy. METHODS: We retrospectively analyzed data on clinical characteristics and outcomes of patients with regional lymph node recurrence after surgery who underwent treatment for NSCLC between 2002 and 2022. RESULTS: A total of 53 patients were included in this study. The median time between surgery and detection of recurrence was 1.21 years. Radiotherapy (RT) alone and chemoradiotherapy (CRT) were performed in 38 and six patients, respectively. Driver gene alterations were detected in eight patients (EGFR: 6, ROS1:1, and BRAF: 1) and programmed death-ligand 1 (PD-L1) expression was examined in 22 patients after 2016. Median progression-free survival (PFS) and overall survival (OS) after lymph node recurrences were 1.32 and 4.34 years, respectively. Multiple lymph node recurrence was an independent prognostic factor for PFS, whereas driver gene alteration was the only prognostic factor for OS. There was no significant difference in the OS between patients stratified according to the initial treatment modality for lymph node recurrence. CONCLUSION: Our results suggest that the number of tumor recurrences may correlate with PFS, while detection of driver gene alterations could guide decision-making for the appropriate molecular-targeted therapy to achieve longer OS.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Proteínas Tirosina Quinases , Recidiva Local de Neoplasia/patologia , Proteínas Proto-Oncogênicas , Prognóstico , Linfonodos/patologia
13.
Kyobu Geka ; 66(4): 291-7, 2013 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-23575180

RESUMO

OBJECTIVES: Our objective was to evaluate the validity of pulmonary metastasectomy for postoperative colorectal cancer with hepatic metastasis and to investigate the role of clinicopathological factors as predictors of outcome. METHODS: Consecutive patients undergoing pulmonary metastasectomy for colorectal cancer with (group PH, n=27) or without (group P, n=46) a history of hepatic metastasis were included in the study. Clinicopathological variables, including sex, age, site, serum carcinoembryonic antigen level of the primary tumor, disease-free interval, prior hepatic resection, timing of pulmonary metastases, preoperative chemotherapy, type of pulmonary resection, and number, size, and location of pulmonary metastases were retrospectively collected and investigated for prognostic significance. RESULTS: The 5-year survivals were 59.5% (PH) and 70.0% (P) with no significant difference. Among all investigated prognostic variables, sex (female vs male) and the number of pulmonary metastases( 1 vs >1) were the most important factors affecting outcome after colorectal resection and pulmonary resection. CONCLUSIONS: Pulmonary resection is not contraindicated in clinical practice. The presence of female gender and a single pulmonary metastasis were favorable predictors of survival after complete pulmonary resection for metastatic colorectal cancer.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Pulmão/cirurgia , Metastasectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonectomia
14.
Intern Med ; 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37839880

RESUMO

A 75-year-old man underwent chemoradiotherapy for advanced esophageal cancer. After nine years, he was hospitalized for left pyothorax. Consequently, the patient underwent drainage and window opening surgery. He experienced cardiopulmonary arrest but was resuscitated. Based on cardiac catheterization data, the patient was diagnosed with constrictive pericarditis. Unfortunately, extracorporeal circulation did not improve his condition, and he ultimately died. An autopsy revealed adhesion between the pericardium and pleura, especially the pericardium in contact with the left thoracic cavity, which was markedly thickened. This suggests that constrictive pericarditis, a latent complication of chemoradiotherapy, is aggravated by pyothorax.

15.
J Thorac Dis ; 15(3): 1009-1017, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37065586

RESUMO

Background: Late-onset pulmonary fistula (LOPF) is a well-described complication after segmentectomy, but the precise incidence and risk factors are still unclear. We aimed to determine the incidence of, and risk factors for, LOPF development after segmentectomy. Methods: A single-institution retrospective study was performed. A total of 396 patients who underwent segmentectomy were enrolled. Perioperative data were analyzed to identify the risk factors for LOPF requiring readmission according to univariate and multivariate analyses. Results: The overall morbidity rate was 19.4%. The incidence rates of prolonged air leak (PAL) in the early phase and LOPF in the late phase were 6.3% (25/396) and 4.5% (18/396), respectively. The most common surgical procedures with LOPF development were segmentectomy of the upper-division (n=6) and S6 (n=5). With a univariate analysis, presence of smoking-related diseases did not affect LOPF development (P=0.139). Conversely, segmentectomy with cranial side free space (CSFS) in the intersegmental plane and use of electrocautery to divide the intersegmental plane were associated with a high risk of LOPF development (P=0.006 and 0.009, respectively). A multivariate logistic regression analysis showed that segmentectomy with CSFS in the intersegmental plane and use of electrocautery were independent risk factors for LOPF development. Approximately 80% of patients who developed LOPF recovered by prompt drainage and pleurodesis without reoperation, whereas the remaining patients developed empyema due to delayed drainage. Conclusions: Segmentectomy with CSFS is an independent risk factor for LOPF development. Careful postoperative follow up and rapid treatment are necessary to avoid empyema.

16.
J Thorac Dis ; 15(3): 1075-1085, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37065588

RESUMO

Background: Segmentectomy is a standard procedure, and there is considerable data on routine segmentectomies. However, there are only few reports on lobectomy performed in combination with segmentectomy (lobectomy + segmentectomy). Thus, we aimed to clarify the clinicopathological features and surgical outcomes of lobectomy + segmentectomy. Methods: We reviewed patients who underwent lobectomy + segmentectomy between January 2010 and July 2021 at Gunma University Hospital, Japan. We comparatively analyzed clinicopathological data of patients who underwent lobectomy + segmentectomy and those who underwent lobectomy in combination with wedge resection (lobectomy + wedge resection). Results: We collected data from 22 patients who underwent lobectomy + segmentectomy and 72 who underwent lobectomy + wedge resection. Lobectomy + segmentectomy was mainly performed to treat lung cancer, and the median number of resected segments was 4.5 and the median number of lesions was 2. Lobectomy + segmentectomy was associated with a higher rate of thoracotomy and a longer operation time. Incidence of overall complications, including pulmonary fistula and pneumonia was higher in the lobectomy + segmentectomy group. However, there were no significant differences in the length of drainage, major complications, and mortality. For lobectomy + segmentectomy, the only left-sided procedure was a left lower lobectomy + lingulectomy, whereas procedures were diverse on the right side, mostly combining a right upper or middle lobectomy with atypical segmentectomies. Conclusions: Lobectomy + segmentectomy was performed for (I) multiple lung lesions, (II) lesions invading an adjacent lobe, or (III) lesions with a metastatic lymph node invading the bronchial bifurcation. Although lobectomy + segmentectomy is a lung-preserving procedure that can benefit patients with multiple or advanced diseases involving two lobes, this procedure should still be performed following a careful patient selection process.

17.
Surg Case Rep ; 9(1): 68, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37133711

RESUMO

BACKGROUND: Thymoma is associated with autoimmune diseases. Myasthenia gravis is frequently associated with thymoma, but cases of thymoma complicated by alopecia areata are very rare. In this report, we present a case of thymoma associated with alopecia areata, but without Myasthenia gravis. CASE PRESENTATION: A 60-year-old woman had a complaint of rapid progression of alopecia areata. A hair follicular biopsy was performed, which showed the infiltration of CD8-positive lymphocytes. She was prescribed topical steroids for 2 months prior to surgery, but her hair loss was not improved. Screening computed tomography showed a mass in the anterior mediastinum, which was suspected to be a thymoma. Myasthenia gravis was ruled out because she had no relevant symptoms or physical findings, and no anti-acetylcholine receptor antibodies were detected in serum. We performed a transsternal extended thymectomy based on a diagnosis of thymoma Masaoka stage I, without myasthenia gravis. Pathological examination showed Type AB thymoma, Masaoka stage II. The chest drainage tube was removed on postoperative day 1, and the patient was discharged on postoperative day 6. The patient has continued topical steroids and showed improvement 2 months postoperatively. CONCLUSIONS: Although alopecia areata is a rare complication in thymoma cases without myasthenia gravis, thoracic surgeons need to keep this condition in mind because alopecia reduces the patient's quality of life.

18.
J Cardiothorac Surg ; 17(1): 265, 2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36217204

RESUMO

BACKGROUND: Resection of lung cancer with chest wall involvement is an invasive procedure. CASE PRESENTATION: We report a case of pulmonary adenocarcinoma with chest wall involvement that was resected through video-assisted thoracoscopic segmentectomy and combined en bloc resection of the chest wall (2nd to 4th ribs). Surgical stress was decreased by reducing the extent of lung parenchymal resection and applying a video-assisted technique with an additional posterior paravertebral incision. CONCLUSION: A thoracoscopic surgical approach involving incisions in areas requiring resection of the proximal, lateral, and posterior sides of the involved ribs can be applied to tumors invading the chest wall.


Assuntos
Neoplasias Pulmonares , Parede Torácica , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Costelas/cirurgia , Cirurgia Torácica Vídeoassistida/métodos , Parede Torácica/patologia , Parede Torácica/cirurgia
19.
Sci Rep ; 12(1): 10589, 2022 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-35732684

RESUMO

The lateral costal artery and vein are under recognized yet potentially important vessels for physicians, especially cardiothoracic surgeons. This study sought to determine the prevalence and clinical, anatomical, and radiological features of lateral costal vessels. We retrospectively analyzed lateral costal vessels based on intraoperative images in patients who underwent thoracic surgery at our institute between January 2016 and March 2020. Clinical data and surgical videos were analyzed for patient characteristics, prevalence, length, laterality, and additional anatomical and radiological features. The overall prevalence of lateral costal vessels was 19% and was significantly higher in males than females (22% vs. 14%, p = 0.003). The lateral costal vessels extended beyond the 2nd intercostal space in 74% of the cases, with differing length between the right and left sides in bilateral cases. Lateral costal vessels could be identified intraoperatively using indocyanine green or preoperatively through three-dimensional computed tomography. The prevalence of lateral costal vessels is relatively high and should be acknowledged by physicians prior to procedures involving the vessels.


Assuntos
Costelas , Veias , Artérias/diagnóstico por imagem , Feminino , Humanos , Masculino , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
20.
Immunol Res ; 70(3): 414-418, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35288824

RESUMO

Thymoma-associated multiorgan autoimmunity (TAMA) is a rare autoimmune disorder associated with thymoma that causes a pathology similar to graft-versus-host disease (GVHD) targeting the skin, digestive organs, and liver. Herein, we report the case of a 38-year-old male with myasthenia gravis (MG) preceded by TAMA. The patient developed intractable diarrhea 2 years before admission. Subsequently, dysphagia, dysarthria, and left blepharoptosis were observed. The patient was admitted to the hospital because of fever and dyspnea, was positive for anti-AChR antibody, and chest-computed tomography revealed thymoma, which led to the diagnosis of thymoma-related MG. Biopsied specimens from the sigmoid colon revealed apoptotic colonopathy with lymphocyte-rich lamina propria. Immunohistochemical staining revealed that the infiltrating cells were predominantly labeled with anti-CD3-antibody. The patient did not show skin lesions or liver dysfunction. Therefore, TAMA limited to the gastrointestinal tract was diagnosed. Although TAMA typically has a poor prognosis, immediate multimodal immunotherapy for MG was successful, resulting in a good outcome for TAMA of this case. TAMA is caused by the inability of the thymoma to suppress self-reactive T lymphocytes, which subsequently leads to a disease that is clinically indistinguishable from GVHD. Based on the characteristics of this case, limited gastrointestinal tract involvement in TAMA without lesions in other organs may lead to a favorable prognosis. TAMA cases lacking skin lesions may present with nonspecific gastrointestinal or liver disease. If a patient with thymoma-associated MG has gastrointestinal symptoms such as diarrhea, TAMA should be considered, and the diagnosis should be made early by pathological evaluation of gastrointestinal tissues.


Assuntos
Doença Enxerto-Hospedeiro , Miastenia Gravis , Timoma , Neoplasias do Timo , Adulto , Autoimunidade , Diarreia/complicações , Doença Enxerto-Hospedeiro/terapia , Humanos , Imunoterapia , Masculino , Miastenia Gravis/complicações , Miastenia Gravis/terapia , Timoma/complicações , Timoma/terapia , Neoplasias do Timo/complicações , Neoplasias do Timo/terapia
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