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1.
Surg Today ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32052182

RESUMO

PURPOSE: Exosomes and their cargo microRNAs play a significant role in various biological processes in cancer. We hypothesized that microRNAs in exosomes secreted by gefitinib-resistant lung cancer cells might induce resistant phenotypes in otherwise gefitinib-sensitive lung cancer cells. METHODS: We isolated exosomes generated by the gefitinib-resistant human lung adenocarcinoma cell line PS-9/ZD. PC-9, which is a gefitinib-sensitive cell line, was treated with the PC-9/ZD exosomes, and these PC-9 cells were analyzed for cell proliferation after treatment with gefitinib. miRNA arrays were analyzed in PC-9 and PC-9/ZD cells, and we isolated microRNAs that were expressed at elevated levels in PC-9/ZD cells. Furthermore, we transfected these microRNAs into PC-9 cells and analyzed the effects on the cells' sensitivity to gefitinib. RESULTS: Exosomes isolated from PC-9/ZD cells significantly increased the proliferation of PC-9 cells during gefitinib treatment. A microRNA array analysis showed that miR-564, miR-658, miR-3652, miR-3126-5p, miR-3682-3p and miR-6810-5p were significantly upregulated in PC-9/ZD cells. PC-9 cells transfected with miR-564 or miR-658 showed chemo-resistant phenotypes. CONCLUSION: Exosomal miR-564 and miR-658 derived from gefitinib-resistant lung cancer cells induce drug resistance in sensitive cells. Cell-to-cell interaction via exosomal microRNAs may be a novel mechanism and therapeutic target of resistance against gefitinib.

2.
Medicine (Baltimore) ; 99(7): e19059, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049805

RESUMO

Nivolumab, a monoclonal antibody targeting programmed cell death-1, significantly prolongs survival for patients with advanced non-small-cell lung cancer (NSCLC). However, little is known about the value of predictive biomarkers. Hence, we investigated the impact of skeletal muscle (SM) mass loss on clinical outcomes in NSCLC patients undergoing nivolumab treatment. Thirty patients with histologically confirmed NSCLC treated with nivolumab were included in this study. Computed tomography was used to determine SM loss based on the SM index (SMI). The SMI is the cross-sectional area of the bilateral psoas muscles at the third lumbar vertebra, divided by height squared. The cut-off values were defined as 6.36 cm/m for men and 3.92 cm/m for women. Among the 30 patients, 13 (43%) had SM loss. There was no significant association between SM loss and immune-related adverse events. The SM loss group had undergone significantly more prior chemotherapy cycles (P = .04). SM loss was significantly associated with fewer nivolumab cycles (P = .01). No patients in the SM loss group achieved a partial response. Patients with SM loss had a significantly shorter progression-free survival period (P = .008) and median overall survival than those with normal SM mass (10 vs 25 months, respectively, P = .03). SM loss was an independent prognostic factor of poor survival. In conclusion, SM loss may be a predictive factor of poor outcomes in NSCLS patients undergoing nivolumab therapy.

3.
Anticancer Res ; 40(1): 261-269, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892575

RESUMO

BACKGROUND: Pulmonary pleomorphic carcinoma (PPC) is a rare aggressive neoplasm, with dismal prognosis. Whether tumor immunity is associated with the progressive biological behavior of PPC remains unclear. The purpose of this study was to examine the prognostic significance of tumor immunity-related markers such as programmed death-1 ligand (PD-L1) and CD4+ or CD8+ tumor-infiltrating lymphocytes (TILs) in patients with surgically resected PPC. PATIENTS AND METHODS: Ninety-nine patients with surgically resected PPC were assessed by immunohistochemistry. The expression of PD-L1, CD4, and CD8 was examined in specimens of the resected tumors. RESULTS: PD-L1 was highly expressed in 61% (60/99) of lesions and high expression of CD4 and CD8 was identified in 42% (42/99) and 51% (51/99) of lesions, respectively. There was no relationship between the expression PD-L1 and the numbers of CD4+ or CD8+ TILs. The expression of PD-L1 was not identified as a significant prognostic marker; however, a low number of CD4+ TILs was identified as an independent marker for predicting a worse outcome after surgical resection of PPC, especially in patients with an epithelial component of adenocarcinoma or early stage of disease. By univariate analysis, a low number of CD8+ TILs was found to be a significant prognostic marker linked to poor overall survival in patients with non-adenocarcinoma components. CONCLUSION: A low number of CD4+ TILs is an independent marker for predicting a favorable prognosis after surgical resection in patients with PPC, especially in patients with adenocarcinoma components or early stage of disease.


Assuntos
Adenoma Pleomorfo/imunologia , Imunidade , Neoplasias Pulmonares/imunologia , Adenoma Pleomorfo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Antígenos CD4/metabolismo , Antígenos CD8/metabolismo , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico
4.
Mol Imaging Biol ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31792836

RESUMO

PURPOSE: 3-[18F]Fluoro-α-methyl-L-tyrosine ([18F]FAMT) is an amino acid positron emission tomography (PET) tracer specific for cancer detection by assessment of tumor amino acid metabolism. Little is known on whether or not the uptake of [18F]FAMT within cancer cells is associated with the expression of programmed death ligand-1 (PD-L1), a predictor of anti-PD-1 antibody efficacy. We conducted a clinicopathological study to assess the expression of PD-L1 and the presence of tumor-infiltrating lymphocytes (TILs) in patients with non-small cell lung cancer (NSCLC) diagnosed by PET. PROCEDURES: A total of 75 patients with NSCLC who underwent [18F]FAMT and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET were enrolled in the study. Tumor specimens were stained by immunohistochemistry for glucose transporter 1 (Glut1), PD-L1 (using different antibody clones including E1L3N and 28-8), CD3, CD4, and CD8. The uptake of [18F]FAMT was correlated with clinicopathological variables. RESULTS: High uptake of [18F]FAMT was significantly associated with disease staging, initial treatment (surgical resection or chemotherapy), and the expression of PD-L1 (E1L3N). The value of the maximum standardized uptake value (SUVmax) for [18F]FAMT was significantly correlated with PD-L1 (E1L3N) expression, Glut1, and the SUVmax for [18F]FDG in patients with histological results of adenocarcinoma (AC) and advanced disease. A validation cohort for anti-PD-L1 using clone 28-8 showed a statistically significant correlation between SUVmax for [18F]FAMT and the expression of PD-L1 (28-8) and between the expression of PD-L1 (E1L3N) and PD-L1 (28-8). CONCLUSIONS: The uptake of [18F]FAMT on PET imaging was significantly correlated with PD-L1 expression in NSCLC, especially in patients with AC and advanced disease.

5.
Int J Clin Oncol ; 2019 Nov 26.
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.

6.
Cancers (Basel) ; 11(11)2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31653009

RESUMO

Various drug-sensitivity markers are potentially responsible for tumor progression and chemotherapy resistance in cancer patients with both epithelial and sarcomatous components; however, the clinicopathological significance of drug-sensitivity markers in patients with pulmonary pleomorphic carcinoma (PPC) remains unknown. Here, we clarified the prognostic impact of these drug-sensitivity markers in PPC by performing immunohistochemical and clinicopathologic analyses of samples from 105 patients with surgically resected PPC in order to evaluate levels of vascular endothelial growth factor 2 (VEGFR2), stathmin 1 (STMN1), tubulin ß3 class III (TUBB3), thymidylate synthetase (TS), topoisomerase II (Topo-II), glucose-regulated protein, and 78 kDa (GRP78)/binding immunoglobulin protein (BiP). We observed the rates of high expression for VEGFR2, STMN1, TUBB3, TS, Topo-II, and GRP78/BiP were 33% (39/105), 35% (37/105), 61% (64/105), 51% (53/105), 31% (33/105), and 51% (53/105) of the samples, respectively. Moreover, multivariate analysis identified VEGFR2 and GRP78/BiP as significant independent markers for predicting worse prognosis. These findings suggested elevated VEGFR2 and decreased GRP78/BiP levels as independent factors for predicting poor outcomes following surgical resection in patients with PPC.

7.
Ann Surg Oncol ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31571056

RESUMO

BACKGROUND: We investigated whether the expression of transforming growth factor-beta-induced protein (TGFBI) and intratumoral immune cells including CD8- and Forkhead box protein P3 (Foxp3)-positive T cells in clinical lung cancer patients could predict the therapeutic response to nivolumab. METHODS: Thirty-three patients who were treated with nivolumab were enrolled in this study. Immunohistochemical analyses of TGFBI, PD-L1, CD8, Foxp3, and vimentin expression were conducted. Serum concentrations of TGFBI and transforming growth factor-beta1 (TGF-ß1) were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Cancer TGFBI was not associated with prognosis and therapeutic response to nivolumab, but cancer stromal TGFBI and intratumoral CD8-positive T cells were associated with them. Therefore, we evaluated cancer stromal TGFBI and intratumoral CD8-positive T cells. The high-TGFBI-expression group had poorer clinical responses than did the low-TGFBI-expression group (p < 0.0001). The number of times nivolumab was administered in the high-CD8-expression group was significantly higher than that in the low-CD8-expression group (p = 0.0046). The high-CD8-expression group had better clinical responses than did the low-CD8-expression group (p = 0.0013). Interestingly, all patients in the high-TGFBI/low-CD8-expression group had progressive disease (PD). In contrast, all patients in the low-TGFBI/high-CD8-expression group had PR + SD (partial response + stable disease) by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CONCLUSIONS: The dual evaluation of stromal TGFBI and intratumoral CD8-positive T cells could be a useful predictive marker for nivolumab.

8.
Mol Clin Oncol ; 11(3): 309-312, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31396389

RESUMO

Anaplastic lymphoma kinase (ALK) gene rearrangements are identified in approximately 5% of patients with non-small cell lung cancer (NSCLC). Despite initial dramatic responses to ALK inhibitors, the majority of patients relapse within 1 year, owing to the development of resistance. Herein we present a case of variant type 2 ALK-rearranged lung adenocarcinoma recurrence with multiple lung metastasis that maintained complete response over 5 years with crizotinib, which is the first approved ALK inhibitor. The efficacy of crizotinib may vary among ALK fusion variants and thus, variant type may represent an important factor in guiding the treatment strategy for ALK-rearranged lung adenocarcinoma.

9.
Lung Cancer ; 134: 180-186, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31319979

RESUMO

OBJECTIVES: Positron emission tomography (PET) using 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) is a clinically useful modality for cancer evaluation. The mechanism of 18F-FDG uptake within cancer cells involves the glucose transporter 1 (GLUT1) and hypoxia-inducible factor-1 α (HIF-1α). Although recent research has shown its clinical efficacy in small-cell lung cancer (SCLC), no suitable biomarker has been identified. We conducted a clinicopathological study to examine the relationship between tumor immunity and 18F-FDG uptake in patients with SCLC. MATERIALS AND METHODS: Tumor sections were stained by immunohistochemistry for GLUT1, HIF-1α, PD-L1, CD4, CD8, and Foxp3. The relationship between clinicopathological features and 18F-FDG uptake was analyzed. Student's t-test, χ2 test, non-parametric Spearman's rank test, and Kaplan-Meier method were used to evaluate associations between the variables. RESULTS: A total of 98 patients 78 men and 20 women who underwent 18F-FDG PET, were enrolled in this study. PD-L1 was expressed in 36.7% (36/98) of all patients; this was significantly associated with GLUT1 expression (p = 0.04). The accumulation of 18F-FDG was significantly higher in patients with low CD8 and CD4 TILs than in those with high TILs (p = 0.03 and p = 0.01, respectively). The uptake of 18F-FDG was not significantly associated with the expression of either Foxp3 or PD-L1. Multivariate analysis demonstrated that advanced stage, poor ECOG-PS, and high SUVmax were independent predictors of poor OS. Among patients with limited-stage disease, multivariate analysis confirmed high PD-L1 expression and a high SUVmax to be independent predictors of poor OS. However, only ECOG-PS was found to be an independent predictor of poor OS among patients with extensive-stage tumors. CONCLUSION: High SUVmax on 18F-FDG-PET is correlated with low expression of CD8(+) and CD4(+) TILs, but is an independent prognostic factor for OS, particularly in those with limited disease. Further studies are warranted to validate our findings.

11.
Artigo em Inglês | MEDLINE | ID: mdl-30937818

RESUMO

The technique of medial-basal segment (S7)-sparing basal segmentectomy has not previously been reported. Herein we report the technical details of thoracoscopic anatomical basal segmentectomy preserving S7 in patients with B7ab branching pattern.

12.
Ann Thorac Surg ; 108(2): e141-e143, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30951697

RESUMO

Intravenous indocyanine green injection is useful for the identification of the intersegmental border by infrared thoracoscopy during anatomic segmentectomy. However, surgeons encounter cases in which visualization of the intersegmental border is difficult. In particular, intravenous indocyanine green fluorescence in the upper lobe is occasionally obscured by to the relatively lesser blood flow in the upper lobe pulmonary arteries. This report describes an interlobar pulmonary artery compression method that is a simple and effective technique for clearly visualizing the intersegmental border through infrared thoracoscopy with intravenous indocyanine green during upper lobe segmentectomy.


Assuntos
Verde de Indocianina/farmacologia , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Artéria Pulmonar/cirurgia , Toracoscopia/métodos , Idoso , Corantes/farmacologia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino
13.
Ann Thorac Surg ; 108(1): 235-243, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30910656

RESUMO

BACKGROUND: Stathmin-1 regulates microtubule dynamics and is associated with malignant phenotypes in non-small cell lung cancer (NSCLC). This study evaluated its diagnostic value for differentiating between NSCLC and high-grade lung neuroendocrine tumor (HGNET). METHODS: Stathmin-1 protein expression was assessed by immunohistochemistry in 414 NSCLC (305 adenocarcinoma [AD], 102 squamous cell carcinoma [SCC], 7 large-cell carcinoma), 5 typical carcinoid (low-grade lung neuroendocrine tumor), and 34 HGNET (17 small-cell carcinoma [SCLC] and 17 large-cell neuroendocrine carcinoma [LCNEC]) surgical specimens and 57 NSCLC (29 AD and 28 SCC) and 42 HGNET (17 LCNEC and 25 SCLC) biopsy specimens. We also analyzed stathmin-1 mRNA levels in 81 NSCLCs and 26 HGNETs with the use of reverse transcription-polymerase chain reaction. RESULTS: Among NSCLC samples, we saw high stathmin-1 protein expression in only three ADs, one SCC, and one large-cell carcinoma surgical samples, all five of which showed neuroendocrine characteristics in pathologic re-review; and low or intermediate expression in all five typical carcinoid surgical samples and all 57 NSCLC biopsy samples. In contrast, all HGNET surgical (n = 34) and biopsy (n = 42) samples showed high stathmin-1 expression. In reverse transcription-polymerase chain reaction, stathmin-1 expression was significantly higher in HGNET tissues than in NSCLC tissues (p < 0.001). CONCLUSIONS: Stathmin-1 expression can help in differentiating NSCLC from HGNET.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Tumores Neuroendócrinos/diagnóstico , Estatmina/metabolismo , Biópsia , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Diagnóstico Diferencial , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/patologia , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estatmina/genética
14.
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
15.
Oncotarget ; 10(13): 1306-1319, 2019 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-30863491

RESUMO

Introduction: Thymic epithelial tumors (TETs) comprise several histologies of thymoma and thymic carcinomas (TCs), and TC frequently metastasizes and causes death. We therefore aimed here to identify key molecules closely related to prognosis and their biological roles in high-risk TETs, particularly TCs. Results: RNA sequence analysis demonstrated that hypoxia-related genes were highly expressed in TETs. The expression of the hypoxia-related gene CA9 was noteworthy, particularly in TCs. Immunohistochemical analysis revealed that CA9 was expressed in 81.0% of TCs and 20.7% of all TET samples. CA9 expression was significantly associated with Masaoka stage, WHO classification, and recurrence-free survival after tumor resection (P = 0.005). The down-regulation of CA9 transcription in TC cell lines by small interfering RNAs significantly inhibited CA9 expression, which inhibited proliferation and increased sensitivity to irradiation. Conclusions: CA9 expression may serve as a significant prognostic marker of TETs and therefore represents a potential target for the development of novel drugs and radiation-sensitizing therapy designed to improve the outcomes of patients with TCs. Materials and Methods: We performed comprehensive transcriptome sequencing of 23 TETs and physiologic thymic specimens to identify genes highly and specifically expressed in high-risk TETs, particulary TCs. We performed immunohistochemical analysis of 179 consecutive surgically resected TETs to evaluate the significance of the association of protein expression with clinicopathological features and prognosis. The biological significance of the most promising prognostic marker was further studied using the TC cell lines, Ty-82 and MP57.

16.
J Thorac Cardiovasc Surg ; 157(5): 2049-2057.e1, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30745042

RESUMO

OBJECTIVES: Outcomes and prognostic factors remain obscure in patients with colorectal cancer after pulmonary metastasectomy who had previously received a curative hepatic metastasectomy. METHODS: We collected data of 757 patients with pulmonary metastasis from colorectal cancer who underwent curative metastasectomy between 2004 and 2008 from 46 Japanese institutions, from which we extracted data on patients who previously received curative hepatic metastasectomy. Disease-free survival, overall survival, and prognostic factors were analyzed. RESULTS: The subjects of this study were 160 patients, of whom 44% had primary rectal tumor, 73% had a single pulmonary metastasis, 11% had a bilateral pulmonary metastasis, and 39% had high (>5 ng/mL) serum carcinoembryonic antigen. Patients' median age was 66 years, and 58% were male. The median follow-up was 64 months. Five-year overall survival and disease-free survival were 65.2% (95% confidence interval, 56.8-72.5) and 33.5% (95% confidence interval, 26.1-41.0), respectively. In multivariable analyses, high prethoracotomy carcinoembryonic antigen level was an independent prognostic factor for overall survival (hazard ratio, 2.01; 95% confidence interval, 1.16-3.47) and disease-free survival (hazard ratio, 2.10; 95% confidence interval, 1.41-3.12). Five-year overall survival and disease-free survival of patients with normal prethoracotomy carcinoembryonic antigen level were 76.4% (95% confidence interval, 66.1-83.9) and 40.7% (95% confidence interval, 30.5-50.5), respectively. CONCLUSIONS: After pulmonary metastasectomy, approximately two thirds of patients with colorectal cancer with a history of curative hepatic metastasectomy survived for 5 years-half of them disease-free. Our results indicate that patients with colorectal cancer with pulmonary metastasis and a history of curative hepatic metastasectomy may benefit from sequential pulmonary metastasectomy, especially if prethoracotomy serum carcinoembryonic antigen levels are within normal range.

17.
Kyobu Geka ; 72(1): 4-10, 2019 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-30765622

RESUMO

BACKGROUND: We present wedge resection as an alternative procedure for primary pulmonary carcinoma in poor-risk patients. PATIENTS AND METHODS: We examined the overall survival of 94 patients who underwent wedge resection for pN0M0 primary pulmonary carcinoma over the last 20 years because of their intolerance of lobectomy. RESULTS: In the wedge resection group, the postoperative 5-year survival in all causes of death was 59.6%, indicating significantly better prognoses in patients with adenocarcinoma aged less than 75 years old. The 5-year survival in the lobectomy group was 77.5%, while the 5-year survival in terms of primary causes of death in the wedge resection and lobectomy groups was 89.3% and 88.0%, respectively. There was a significant difference between wedge resection and lobectomy in all causes of death, but not between groups in primary causes of death. CONCLUSION: Because there were many non-primary deaths in the wedge resection group, care should be taken to follow comorbidities that cause limited lung resection. Survival in the wedge resection group was not inferior to that in the lobectomy group in analyses of the primary causes of death. We suggest that wedge resection should be a favorable procedure for primary pulmonary carcinoma in poor-risk patients to obtain a large enough sample volume of tumor cells.


Assuntos
Adenocarcinoma/cirurgia , Neoplasias Pulmonares/cirurgia , Adenocarcinoma/mortalidade , Fatores Etários , Idoso , Causas de Morte , Humanos , Neoplasias Pulmonares/mortalidade , Pneumonectomia/mortalidade , Prognóstico , Estudos Retrospectivos , Risco
18.
Interact Cardiovasc Thorac Surg ; 28(6): 953-956, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30649311

RESUMO

Carbon ion radiotherapy (CIRT) shows higher local control rates and minimal damage to normal lung parenchyma compared with conventional radiotherapy; however, some patients experience local recurrence. The efficacy and safety of salvage surgery after CIRT for non-small-cell lung cancer are unclear. We reviewed clinical, surgical, pathological and prognostic data of 6 patients who underwent salvage surgery after CIRT between 2010 and 2015. All patients were men with a smoking history, and their median age was 67 years. The time from CIRT to surgery was 18 (range 12-24) months. All patients underwent at least lobectomy with mediastinal node dissection. Viable tumour cells were confirmed pathologically in all cases. Five patients required combined resection or extra procedure because of strong adhesions and the possibility of tumour extension; however, none of the patients had a tumour invasion to the adjacent organ. None of the patients had severe complications, perioperative death and local recurrence, and 3 patients are alive without recurrence (range 28-84 months). Salvage surgery appears to be safe and effective. Even though the tumours did not invade the adjacent organs, combined resection was required because of severe adhesion.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Radioterapia com Íons Pesados/métodos , Neoplasias Pulmonares/cirurgia , Terapia de Salvação/métodos , Idoso , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Feminino , Humanos , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Resultado do Tratamento
19.
Hum Pathol ; 84: 142-149, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30300664

RESUMO

Amino acid transporters are necessary for tumor growth, metastasis, and survival of various neoplasms; however, the clinicopathological significance of L-type amino acid transporter 1 (LAT1) and 4F2 cell surface antigen (4F2hc) in patients with pulmonary pleomorphic carcinoma (PPC) remainsunknown. The aim of this study is to clarify the prognostic impact of these amino acid transporters in PPC. One hundred five patients with surgically resected PPC were assessed by immunohistochemistry. The expression of LAT1 and 4F2hc, and Ki-67 labeling index were investigated using specimens of the resected tumors. LAT1 and 4F2hc were highly expressed in 35% and 53% of all patients (n = 105, P < .01), 25% and 48% of patients with an adenocarcinoma component (n = 48, P = .02), and 44% and 58% of patients with a nonadenocarcinoma component (n = 57, P = .18), respectively. A high LAT1 expression was significantly related to advanced disease, lymphatic permeation, tumor cell proliferation, and 4F2hc expression. By multivariate analysis, LAT1 and 4F2hc were identified as significant independent markers for predicting a worse prognosis. LAT1 is highly expressed in PPC, and high LAT1 expression can serve as a significant predictor linked to a worse prognosis in patients with PPC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Cadeia Pesada da Proteína-1 Reguladora de Fusão/biossíntese , Transportador 1 de Aminoácidos Neutros Grandes/biossíntese , Neoplasias Pulmonares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico
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