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1.
Oncol Rep ; 47(2)2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34859258

RESUMO

Malignant mesothelioma is a highly aggressive tumor, and an effective strategy for its treatment is not yet available. Long non­coding RNAs (lncRNAs) have been reported to be associated with various biological processes, including the regulation of gene expression of cancer­related pathways. Among various lncRNAs, plasmacytoma variant translocation 1 (PVT1) acts as a tumor promoter in several human cancers, but its mechanism of action has not yet been elucidated. Increased PVT1 expression was identified in ACC­MESO­1, ACC­MESO­4, CRL­5915, and CRL­5946 mesothelioma cell lines. PVT1 expression was investigated in mesothelioma cell lines by reverse transcription­quantitative polymerase chain reaction and its functional analysis by cell proliferation, cell cycle, cell migration, and cell invasion assays, as well as western blot analysis of downstream target genes. Knockdown of PVT1 expression in these cell lines by small interfering RNA transfection resulted in decreased cell proliferation and migration and increased the proportion of cells in the G2/M phase. The results of reverse transcription­quantitative polymerase chain reaction analysis revealed that PVT1 knockdown in mesothelioma cell lines caused the downregulation of Forkhead box M1 (FOXM1) expression, while the results of western blot analysis revealed that this knockdown reduced FOXM1 expression at the protein level. In addition, combined knockdown of PVT1 and FOXM1 decreased the proliferation of mesothelioma cell lines. In conclusion, PVT1 and FOXM1 were involved in the proliferation of cancer cells. Therefore, PVT1­FOXM1 pathways may be considered as candidate targets for the treatment of malignant mesothelioma.


Assuntos
Movimento Celular/genética , Proliferação de Células/genética , Proteína Forkhead Box M1/genética , Regulação Neoplásica da Expressão Gênica , Mesotelioma Maligno/genética , RNA Longo não Codificante/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Regulação para Baixo , Humanos , Mesotelioma Maligno/patologia
2.
Thorac Cancer ; 12(23): 3141-3149, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34643053

RESUMO

INTRODUCTION: Tumor size is an absolute recurrence risk in lung cancer. Although morphological features also reflect recurrence risk, its significance among lower-risk cases characterized by small size is unknown. We aimed to evaluate the relationship between pathological invasive tumor size and morphological features, and their prognostic impact by considering them simultaneously in lung adenocarcinoma. PATIENTS AND METHODS: We retrospectively reviewed 563 pN0M0 patients with pathological invasive size of ≤40 mm. The patients were classified by pathological invasive size and pathological malignant grading using the proportion of subhistological components. The prognostic impact was evaluated using recurrence-free survival (RFS) and overall survival (OS). The impact on prognosis was evaluated using uni- and multivariate analyses. RESULTS: The proportion of histological grade changed according to invasive tumor size. Patients with high malignant grade (G3) showed worse RFS than those with low and intermediate malignant grade (G1+2) with invasive size ≤20 mm. The 5-year RFS (G1+2 vs. G3) in 5-10 mm was 96.0% vs. 83.3% (HR = 5.505, 95% CI = 7.156-1850, p < 0.001) and in 10-20 mm was 87.8% vs. 67.1% (HR = 2.829, 95% CI = 4.160-43.14, p < 0.001). G3 patients were significantly bigger in invasive size and included more pleural/lymphatic/vascular invasion and recurrence. Multivariate analysis indicated pathological G3 status was significantly associated with worse RFS (HR = 2.097, 95% CI = 1.320-3.333, p = 0.002). CONCLUSIONS: Invasive tumor size and pathological malignant grade overlap in invasive adenocarcinoma. G3 patients are more likely to have pleural/lymphatic/vascular invasion and significantly worse RFS compared to G1/G2 cases, even with a small invasive size of ≤20 mm.

3.
JTO Clin Res Rep ; 2(2): 100126, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34589986

RESUMO

Introduction: The International Association for the Study of Lung Cancer proposed a new grading criteria for invasive adenocarcinoma. However, its utility has not been validated. Methods: Patients who underwent complete resection of lung adenocarcinoma were included in this study. Then, they were divided into the following three groups on the basis of the criteria recently proposed by the International Association for the Study of Lung Cancer: grade 1, lepidic predominant tumor, with less than 20% of high-grade patterns; grade 2, acinar or papillary predominant tumor, with less than 20% of high-grade patterns; and grade 3, any tumor with greater than or equal to 20% of high-grade patterns. Results: Recurrence-free survival (RFS) was significantly different among the proposed grades (p < 0.001). The RFS of patients upgrading from current grade 2 (papillary or acinar predominant tumor) to proposed grade 3 (5-y RFS, 65.2%) was significantly worse than that of patients with proposed grade 2 (77.1%, hazard ratio = 1.882, 95% confidence interval: 1.236-2.866) but not significantly different from that of patients with grade 3 in both the current (micropapillary or solid predominant tumor) and proposed criteria (53.2%, hazard ratio = 0.761, 95% confidence interval: 0.456-1.269). Among patients with pathologic stage 0 or I, RFS was well stratified by the new grading system (p < 0.001) but not among patients with stage II or III (p = 0.334). In the multivariable analysis, the new grading was not a predictive factor of RFS. Conclusions: Although the proposed grading system well stratified RFS in patients with pathologic stage 0 or I lung adenocarcinoma, there is room for improvement.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34218331

RESUMO

PURPOSE: Liquid biopsy for early-stage lung cancer diagnosis is challenging, and optimal candidates' clinicopathological features are unknown. We investigated utility and clinicopathological features of optimal candidates in somatic mutation-targeted liquid biopsy using droplet digital polymerase chain reaction (ddPCR) in pN0M0 EGFR mutation-positive lung adenocarcinoma patients. METHODS: We performed EGFR mutation-targeted ddPCR liquid biopsy in 100 patients with resected pN0M0 invasive lung adenocarcinoma, whose tumor diameter in high-resolution computed tomography (HRCT) was ≤ 5 cm. Peripheral blood-derived serum was collected preoperatively. Two representative EGFR somatic variants (exon 19 [E746-A750 del (2235_2249 del)]; exon 21 (L858R)) were utilized as liquid biopsy targets. Clinicopathological features including radiological appearance, subhistology, and invasive status were compared between ddPCR-positive and ddPCR-negative patients. RESULTS: Among the 100 patients, 98 showed part-solid or pure-solid appearance in HRCT and 2 showed non-solid appearance; 98 were pathological stage IA1-IB. Of the 66 patients with EGFR mutation detection in ddPCR, 12 were significantly positive and 10 (83.3%, 10/12) exhibited pure-solid appearance in HRCT. Clinical invasive tumor ratio was significantly higher in ddPCR-positive than in ddPCR-negative patients (median: 100% vs. 85.4%, P = 0.0212), whereas other clinicopathological features were not significantly different. CONCLUSION: Mutation-targeted liquid biopsy using ddPCR detected lung cancer in 12.0% (12/100) of pN0M0 EGFR-mutant lung adenocarcinoma patients. In 83.3% of the ddPCR-positive patients, tumors showed pure-solid appearance in HRCT. The detection ratio increased to 21.3% (10/47) among patients with pure-solid appearance tumors. Tumor appearance might be useful for better selection of liquid biopsy candidates.

5.
BMC Pulm Med ; 21(1): 186, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078355

RESUMO

BACKGROUND: Acute exacerbation (AE) of interstitial pneumonia (IP) is the most fatal complication after lung resection for lung cancer. To improve the prognosis of lung cancer with IP, the risk factors of AE of IP after lung resection should be assessed. S100 calcium-binding protein A4 (S100A4) is a member of the S100 family of proteins and is a known marker of tissue fibrosis. We examined the usefulness of S100A4 in predicting AE of IP after lung resection for lung cancer. METHODS: This study included 162 patients with IP findings on preoperative high-resolution computed tomography scan who underwent curative-intent lung resection for primary lung cancer between April 2007 and March 2019. Serum samples were collected preoperatively. Resected lung tissue from 76 patients exhibited usual IP (UIP) pattern in resected lung were performed immunohistochemistry (IHC). Relationship between S100A4 and the incidence of AE of IP and short-term mortality was analyzed. RESULTS: The receiver operating characteristic area under the curve for serum S100A4 to predict postoperative AE of IP was 0.871 (95% confidence interval [CI], 0.799-0.943; P < 0.001), with a sensitivity of 93.8% and a specificity of 75.3% at the cutoff value of 17.13 ng/mL. Multivariable analysis revealed that a high serum S100A4 level (> 17.13 ng/mL) was a significant risk factor for AE of IP (odds ratio, 42.28; 95% CI, 3.98-449.29; P = 0.002). A 1-year overall survival (OS) was significantly shorter in patients with high serum levels of S100A4 (75.3%) than in those with low serum levels (92.3%; P = 0.003). IHC staining revealed that fibroblasts, lymphocytes, and macrophages expressed S100A4 in the UIP area, and the stroma and fibrosis in the primary tumor expressed S100A4, whereas tumor cells did not. CONCLUSIONS: Serum S100A4 had a high predictive value for postoperative AE of IP and short-term mortality after lung resection.


Assuntos
Doenças Pulmonares Intersticiais/sangue , Neoplasias Pulmonares/cirurgia , Pulmão/metabolismo , Proteína A4 de Ligação a Cálcio da Família S100/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Modelos Logísticos , Pulmão/cirurgia , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/mortalidade , Neoplasias Pulmonares/complicações , Masculino , Complicações Pós-Operatórias , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Proteína A4 de Ligação a Cálcio da Família S100/metabolismo , Taxa de Sobrevida
6.
Case Rep Oncol ; 14(1): 538-544, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33976631

RESUMO

Sarcomatoid carcinoma (SC) is a rare malignant tumor with properties of both epithelial and mesenchymal carcinomas. SC has been reported in various organs, but the number of reports for each type is small. Small intestinal tumors make up about 3-6% of gastrointestinal malignancies. Discovering them in the early stage is rare and difficult, with anemia and/or abdominal pain as the major symptoms of small intestinal tumors. Primary small intestinal SC (SISC) is rare among small intestinal tumors, and currently very few cases have been reported in the literature. Previous studies have reported that neither chemotherapy nor radiotherapy improves the overall survival rate of patients with SISC, and the prognosis is extremely poor. Currently, surgical resection remains the only optimal therapeutic approach for SISC. Here, we present the case of a 90-year-old woman who had acute peritonitis due to perforation of a small intestinal tumor. She underwent emergency exploratory laparotomy and partial resection of the small intestine, including the tumor. The tumor was pathologically identified as a primary SISC with mesenteric lymph node metastasis. Subsequently, she had recurrence in the intra-abdominal area and lymph node metastasis anterior to the inferior vena cava and died 15 months after surgery without any additional treatment.

7.
Gan To Kagaku Ryoho ; 48(4): 523-525, 2021 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-33976038

RESUMO

We present the case of a 72‒year‒old male patient with anorexia who was diagnosed with advanced gastric cancer with multiple liver metastasis. He had marked hypoglycemia and lightheadedness from the time of admission. The serum insulin level was very low and other endocrinology test results were normal. He was finally diagnosed with non‒islet cell tumor hypoglycemia(NICTH)based on IHC findings that tumor cells expressed insulin‒like growth factor (IGF)Ⅱ. After the patient received intravenous glucocorticoid therapy along with S‒1 plus CDDP combination chemotherapy, the hypoglycemia was quickly resolved. However, he developed septic shock in reaction to the chemotherapy and died on the 35th day of hospitalization. The autopsy showed the presence of IGF‒Ⅱ in the liver metastasis, as well as in the primary tumor.


Assuntos
Hipoglicemia , Neoplasias Hepáticas , Neoplasias Gástricas , Idoso , Autopsia , Humanos , Hipoglicemia/etiologia , Fator de Crescimento Insulin-Like II , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Neoplasias Gástricas/complicações , Neoplasias Gástricas/tratamento farmacológico
8.
J Cancer Res Clin Oncol ; 147(12): 3709-3718, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33796913

RESUMO

PURPOSE: The clinicopathological or genetic features related to the prognosis of mucinous adenocarcinoma are unknown because of its rarity. The clinicopathological or targetable features were investigated for better management of patients with mucinous adenocarcinoma of the lung. METHODS: We comprehensively evaluated the clinicopathological and genetic features of 60 completely resected mucinous lung adenocarcinomas. Targetable genetic variants were explored using nCounter and polymerase chain reaction, PD-L1 and TTF-1 expression were evaluated using immunohistochemistry. We analyzed the prognostic impact using the Kaplan-Meier method and log-rank test. RESULTS: Of the 60 enrolled patients, 13 (21.7%) had adenocarcinoma in situ/minimally invasive adenocarcinoma, and 47 (78.3%) had invasive mucinous adenocarcinoma (IMA). Fifteen patients (25%) showed a pneumonic appearance on computed tomography (CT). CD74-NRG1 fusion, EGFR mutations, and BRAF mutation were detected in three (5%), four (6.7%), and one (1.7%) patient(s), respectively. KRAS mutations were detected in 31 patients (51.7%). Two patients (3.5%) showed immunoreactivity for PD-L1. No in situ or minimally invasive cases recurred. IMA patients with pneumonic appearance had significantly worse recurrence-free survival (RFS) and overall survival (OS) (p < 0.001). Furthermore, IMA patients harboring KRAS mutations had worse RFS (p = 0.211). Multivariate analysis revealed that radiological pneumonic appearance was significantly associated with lower RFS (p < 0.003) and OS (p = 0.012). KRAS mutations served as an unfavorable status for RFS (p = 0.043). CONCLUSION: Mucinous adenocarcinoma had a low frequency of targetable genetic variants and PD-L1 immunoreactivity; however, KRAS mutations were frequent. Pneumonic appearance on CT imaging and KRAS mutations were clinicopathological features associated with a worse prognosis.


Assuntos
Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Prognóstico , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas p21(ras)/genética , Estudos Retrospectivos
9.
Transl Lung Cancer Res ; 10(2): 766-775, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33718020

RESUMO

Background: The histological classification of non-small cell lung cancer (NSCLC) is essential in determining new cancer-specific targeted therapies. However, the accurate typing of poorly differentiated is difficult, particularly for poorly differentiated squamous cell carcinoma and adenocarcinoma of the lung with limited immunohistochemical markers. Thus, novel immunohistochemical markers are required. We assumed the possibility of the immunohistochemical expression of glypican-1 in lung squamous cell carcinoma. Methods: The microarray dataset GSE43580 from Gene Expression Omnibus database were analyzed for confirming the gene expression of glypican-1 in lung squamous cell carcinoma. We immunohistochemically investigated the use of glypican-1 as a novel positive diagnostic marker for lung squamous cell carcinoma. Glypican-1 expression in 63 cases of poorly differentiated lung squamous cell carcinoma and 60 cases of solid predominant lung adenocarcinoma was investigated by immunohistochemistry. Additionally, we compared glypican-1 expression with the expressions of p40, cytokeratin 5/6, thyroid transcription factor-1 (TTF-1), and napsin A. Results: All 63 cases of lung squamous cell carcinoma showed glypican-1 expression. In contrast, only 2 cases of lung adenocarcinoma showed glypican-1 expression. The sensitivity, specificity, and diagnostic accuracy of glypican-1 expression for differentiating lung squamous cell carcinoma from lung adenocarcinoma were 100%, 96.7%, and 98.4%, respectively. These were similar to those of p40 and significantly better than those of CK 5/6. Conclusions: We recommend the use of glypican-1 as an additional positive marker of lung squamous cell carcinoma.

10.
J Med Case Rep ; 15(1): 71, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33596992

RESUMO

BACKGROUND: Bronchial fistula is a severe complication of pneumonectomy with a high mortality rate. We previously reported a technique for bronchial closure to prevent bronchial fistula in a canine model. We described that mucosal ablation could result in primary wound healing and involve mucosal tight adhesions histologically. In this paper, the pathologic findings of one patient, who underwent autopsy 4 years after surgery, were reviewed. CASE PRESENTATION: A 70-year-old Japanese man was diagnosed with malignant pleural mesothelioma and underwent right extra-pleural pneumonectomy. The right main bronchus was cut using a scalpel. When closing the bronchial stump, the bronchial mucosa was ablated by electric cautery and sutured manually using 3-0 absorbable sutures. The bronchial fistula was not found after pneumonectomy. Four years after surgery, the patient died of recurrent malignant pleural mesothelioma and underwent autopsy. Macroscopic evaluation showed tight adhesions and white scars on the bronchial stump. Microscopic findings showed few inflammatory cells and α-smooth muscle actin (α-SMA)-positive cells. CONCLUSIONS: The results from this case suggested that bronchial mucosal ablation leads to robust agglutination of bronchial stump over years. This technique is not only simple but also reliable to prevent bronchial fistula.


Assuntos
Fístula Brônquica , Neoplasias Pulmonares , Doenças Pleurais , Idoso , Animais , Brônquios/cirurgia , Fístula Brônquica/etiologia , Fístula Brônquica/cirurgia , Cães , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Membrana Mucosa , Recidiva Local de Neoplasia , Pneumonectomia , Complicações Pós-Operatórias
11.
Ann Thorac Surg ; 112(3): 935-943, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33144104

RESUMO

BACKGROUND: This study aimed to investigate the prognosis after segmentectomy as compared with lobectomy for small-sized lung adenocarcinoma with spread through air spaces (STAS). METHODS: This retrospective study included 609 patients who underwent lobectomy or segmentectomy with lymph node dissection for clinical stage IA lung adenocarcinoma between April 2011 and March 2020 at Hiroshima University Hospital. Patient characteristics and prognosis after segmentectomy and lobectomy were investigated. RESULTS: STAS was detected in 293 patients (48.1%). The recurrence-free survival (RFS) rate was significantly worse with STAS-positive adenocarcinoma than with STAS-negative adenocarcinoma both in patients who underwent lobectomy (5-year RFS, 68.2% vs 90.2%; P < .001) and in patients who underwent segmentectomy (5-year RFS, 81.3% vs 93.0%; P = .003). Among the patients with STAS, there was no significant difference in RFS between patients who underwent lobectomy (5-year RFS, 68.2%) and those who underwent segmentectomy (5-year RFS, 81.3%; P = .225). In a multivariable analysis using propensity score to adjust clinical patient characteristics, segmentectomy was not found to be an independent prognostic factor of RFS (hazard ratio 0.732, P = .326) among patients with STAS. Among the patients with STAS, only 1 patient (1%) with insufficient resection margin (0.5 mm) had local recurrence and 1 patient (1%) with invasive mucinous adenocarcinoma had recurrence in preserved lobe after segmentectomy. CONCLUSIONS: Spread through air spaces was a poor prognostic factor in patients with clinical stage IA lung adenocarcinoma. Prognosis after segmentectomy was comparable with that of lobectomy in lung adenocarcinoma with STAS without increasing locoregional recurrence.


Assuntos
Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
12.
Am J Surg Pathol ; 44(9): 1259-1265, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32496433

RESUMO

The differential diagnosis of epithelioid mesothelioma from lung adenocarcinoma using immunohistochemistry is improving. However, immunohistochemical markers with high sensitivity and specificity have yet to be identified. In this study, we investigated the utility of sex-determining region Y box 6 (SOX6) as a novel immunohistochemical marker, identified by analyzing previous gene expression data. Immunohistochemically, SOX6 expression was present in 53 of 54 (98%) cases of epithelioid mesothelioma, compared with its expression in only 5 of 69 (7%) cases of lung adenocarcinoma. The sensitivity and specificity of SOX6 expression for differentiating epithelioid mesothelioma and lung adenocarcinoma were 98% and 93%, respectively. SOX6 expression showed similar sensitivity and far better specificity than those of calretinin or podoplanin (D2-40). In addition, SOX6 expression was more sensitive than Wilms' tumor 1 expression. The combination of SOX6 with other markers showed comparable or better sensitivity and specificity relative to other combinations. In particular, the sensitivity of positivity for both SOX6 and calretinin (96%) and the specificity of positivity for both SOX6 and Wilms' tumor 1 (93%) were higher than those of the other combinations. In conclusion, SOX6 is a novel candidate immunohistochemical marker for differentiating epithelioid mesothelioma from lung adenocarcinoma.


Assuntos
Adenocarcinoma de Pulmão/química , Biomarcadores Tumorais/análise , Células Epitelioides/química , Imuno-Histoquímica , Neoplasias Pulmonares/química , Mesotelioma/química , Fatores de Transcrição SOXD/análise , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/genética , Diagnóstico Diferencial , Células Epitelioides/patologia , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mesotelioma/genética , Mesotelioma/patologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fatores de Transcrição SOXD/genética
13.
Oncol Lett ; 19(6): 4161-4168, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32382354

RESUMO

Malignant pleural mesothelioma is a notorious human malignancy. Despite combination chemotherapy with cisplatin and pemetrexed, the majority of patients with advanced malignant pleural mesothelioma have a poor prognosis. MicroRNAs (miRNAs/miRs) are short non-coding RNAs that regulate various biological processes by binding to the 3'-untranslated region of target gene mRNAs and suppressing their expression. Since abnormal expression patterns of miRNAs are a common feature in human malignancies, a number of them have been researched as potential therapeutic targets. Our previous study demonstrated that microRNA-18a (miR-18a) is upregulated in mesothelioma cell lines compared with in non-neoplastic mesothelial tissues, but its function remains unclear. In the present study, miRNA inhibitor was transfected into mesothelioma cell lines and then analyzed various cellular functions. Mesothelioma cells transfected with the miR-18a inhibitor exhibited lower proliferation and migration rates compared with cells transfected with a negative control inhibitor in proliferation and wound scratch assays, respectively. Additionally, the present study revealed that downregulation of miR-18a increased mesothelioma cell apoptosis. In a chemosensitivity assay, transfection of the miR-18a inhibitor significantly increased the sensitivity of mesothelioma cells to cisplatin but not to pemetrexed. Therefore, miR-18a may be a potential therapeutic target for mesothelioma resistant to cisplatin.

14.
Gen Thorac Cardiovasc Surg ; 68(6): 609-614, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31858404

RESUMO

OBJECTIVE: Bronchial fistulae following lung surgery are associated with high mortality. We examined the histological effects of mucosal ablation as a technique for closing bronchial stumps to prevent bronchial fistulae in an animal model. METHODS: Left lower lobectomy was performed in beagles under general anesthesia. The bronchial stumps were closed using one of the following four methods: (A) manual suturing using 3-0 absorbable sutures, (B) ablation of bronchial mucosa with electric cautery and manual sutures, (C) stapling and reinforcement with manual sutures, or (D) ablation and stapling followed by reinforcement with manual sutures. Bronchial stumps were histologically evaluated on postoperative day 14. RESULTS: No bronchial fistulae were noted in the animals during the observation period. Histologically, there were no adhesions between the bronchial mucosae at the suture and staple lesions in groups A and C. The bronchial mucosae were adherent at the ablation sites in groups B and D. Inflammatory cells, myofibroblasts, and neovascular vessels were abundant around the ablated lesions. CONCLUSIONS: Bronchial mucosal ablation may play a key role in mucosal adhesion and tight union of the bronchial stump.


Assuntos
Brônquios/cirurgia , Fístula Brônquica/prevenção & controle , Pneumonectomia/métodos , Mucosa Respiratória/cirurgia , Animais , Fístula Brônquica/etiologia , Modelos Animais de Doenças , Cães , Feminino , Pneumonectomia/efeitos adversos , Mucosa Respiratória/patologia , Grampeamento Cirúrgico , Suturas , Aderências Teciduais/etiologia
15.
Ann Surg Oncol ; 27(3): 945-955, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31732945

RESUMO

BACKGROUND: Lung adenocarcinoma with the micropapillary (MP) component poses a higher risk of recurrence even when the MP component is not predominant. This study explored genetic features associated with highly malignant behavior of lung adenocarcinoma with the MP component. METHODS: The MP and papillary (PaP) components were captured separately in three patients. Comprehensive mRNA expressions of somatic variants were compared between the MP and PaP components of each patient using next-generation sequencing (NGS). The protein expression of the NGS-detected variant was validated by immunohistochemistry. The prognostic impact of the detected variant was evaluated in 288 adenocarcinoma patients with resection of pN0M0. RESULTS: In two cases, NGS suggested higher RNA expression of EGFR L858R in the MP component than in the PaP component (allele frequency, 0.485 vs. 0.155 and 1.000 vs. 0.526, respectively; P < 0.001 for both). Immunohistochemistry validated intense expression of L858R in the MP component of 27 MP-positive (MP+) patients. Among 288 pN0M0 patients, L858R was more frequently harbored in the MP+ patients than in the MP-negative (MP-) patients. The MP+ patients harboring L858R showed significantly worse recurrence-free survival (RFS) than the MP+ patients without L858R (median RFS 38.7 and 55.0 months, respectively; hazard ratio [HR] 3.004; 95% confidence interval [CI] 1.306-9.132; P = 0.012). Multivariate analysis of the MP+ patients showed that positive L858R status was associated with poorer RFS (HR 2.976; 95% CI 1.190-7.442; P = 0.020). CONCLUSIONS: EGFR L858R was more frequently harbored in the MP+ adenocarcinoma patients than in the MP- adenocarcinoma patients. Intense expression of L858R in the MP component was suggested, and the MP+ patients harboring L858R were at comparatively higher risk of recurrence in the group with pN0M0 lung adenocarcinoma.


Assuntos
Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/genética , Carcinoma Papilar/patologia , Neoplasias Pulmonares/patologia , Mutação , Recidiva Local de Neoplasia/patologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar/genética , Carcinoma Papilar/cirurgia , Receptores ErbB/genética , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida
16.
Int J Surg Case Rep ; 62: 77-84, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31466012

RESUMO

INTRODUCTION: Liver metastasis of an anal squamous cell carcinoma (SCC) with a pseudocyst is uncommon. There are many diseases which form hepatic cystic lesions and sometimes it is difficult to arrive at an accurate diagnosis. PRESENTATION OF CASE: A 69-year-old woman visited our hospital with complaints of bloody stool and difficult defecation. A palpable mass in the anal canal was found on digital examination. The laboratory tests revealed anemia and raised levels of SCC antigen. On endoscopy a type 2 tumor was identified in the anal canal and biopsy revealed SCC. The patient was diagnosed with advanced anal SCC (cT2N1aM0, cStage IIIA) as a result of the examination and underwent chemoradiotherapy (CRT); unfortunately the tumor persisted after CRT. A salvage abdominoperineal resection with D2 and left lateral lymph node dissection was conducted. Histopathologically, the tumor was diagnosed as poorly differentiated SCC. She was readmitted for fever 3 weeks after surgery, and the abdominal CT showed multiple low density areas with enhancement at the edge of the liver, suggesting abscess or metastasis. The metastatic SCC was revealed by cytology of liver drainage and liver biopsy. DISCUSSION: Anal cancers are sometimes encountered however; a pseudo cystic presentation of a liver metastasis is very rare which makes it difficult to distinguish from other diseases. CONCLUSION: We present a case of SCC in the anal canal with liver metastasis presenting as a hepatic pseudocyst.

17.
J Cancer Res Clin Oncol ; 145(9): 2325-2333, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31317326

RESUMO

PURPOSE: Nodal positive lung adenocarcinoma includes wide range of survival. Several methods for the classification of nodal-positive lung cancer have been proposed. However, classification considering the impact of targetable genetic variants are lacking. The possibility of genetic variants for the better stratification of nodal positive lung adenocarcinoma was estimated. METHODS: Mutations of 36 genes between primary sites and metastatic lymph nodes (LNs) were compared using next-generation sequencing. Subsequently, mutations in EGFR and BRAF, rearrangements in ALK and ROS1 were evaluated in 69 resected pN1-2M0 adenocarcinoma cases. Recurrence-free survival (RFS), post-recurrence survival (PRS), and overall survival (OS) were evaluated with respect to targetable variants and tyrosine kinase inhibitor (TKI) therapy after recurrence. RESULTS: About 90% of variants were shared and allele frequencies were similar between primary and metastatic sites. In 69 pN1-2M0 cases, EGFR/ALK were positive in primary sites of 39 cases and same EGFR/ALK variants were confirmed in metastatic LNs of 96.7% tissue-available cases. Multivariate analyses indicated positive EGFR/ALK status was associated with worse RFS (HR 2.366; 95% CI 1.244-4.500; P = 0.009), and PRS was prolonged in cases receiving TKI therapy (no post-recurrence TKI therapies, HR 3.740; 95% CI 1.449-9.650; P = 0.006). OS did not differ with respect to targetable variants or TKI therapy. CONCLUSIONS: Cases harbouring targetable genetic variants had a higher risk of recurrence, but PRS was prolonged by TKI therapy. Classification according to the targetable genetic status provides a basis for predicting recurrence and determining treatment strategies after recurrence.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Neoplasias Pulmonares/diagnóstico , Pulmão/metabolismo , Linfonodos/metabolismo , Mutação , Transcriptoma/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA/métodos , Feminino , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Metástase Linfática , Masculino , Análise em Microsséries/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Prognóstico , Estudos Retrospectivos
19.
Histopathology ; 74(4): 545-554, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30329165

RESUMO

AIMS: The process of differential diagnosis between epithelioid mesothelioma and lung adenocarcinoma has been progressing; however, there are no absolute immunohistochemical markers with which to definitively diagnose epithelioid mesothelioma. The aim of this study was to search for a novel negative marker of epithelioid mesothelioma. METHODS AND RESULTS: We immunohistochemically studied the applicability of mucin 21 (MUC21), which was identified in our previous study, as a novel, negative diagnostic marker for epithelioid mesothelioma. Seventy epithelioid mesotheliomas and 70 lung adenocarcinomas were investigated for the expression of MUC21, along with other previously reported markers, by the use of immunohistochemistry. MUC21 was expressed in only two of the 70 (3%) epithelioid mesotheliomas, as compared with 67 of the 70 (96%) lung adenocarcinomas. The sensitivity, specificity and accuracy of negative MUC21 expression for differentiating epithelioid mesothelioma from lung adenocarcinoma were 97%, 96%, and 96%, respectively; these are similar to those of carcinoembryonic antigen and claudin-4, and better than those of thyroid transcription factor-1, napsin-A, and mucin 4. CONCLUSION: MUC21 could be used as an additional, novel, negative immunohistochemical marker to differentiate mesothelioma from lung adenocarcinoma.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Neoplasias Pulmonares/diagnóstico , Glicoproteínas de Membrana/biossíntese , Mesotelioma/diagnóstico , Mucinas/biossíntese , Biomarcadores Tumorais/análise , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Glicoproteínas de Membrana/análise , Mesotelioma Maligno , Mucinas/análise
20.
Front Oncol ; 8: 446, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30406026

RESUMO

Dysregulation of miR-182 and miR-183 has been implicated in the progression of several human cancers. Our previous study showed that miR-182 and miR-183 are upregulated in malignant mesothelioma. However, their biological functions remain unclear. We performed in-situ hybridization to analyze the expression of miR-182 and miR-183 in human tissues. Functional analysis was performed by treatment of two mesothelioma cell lines (ACC-MESO1 and CRL-5915) with miR-182 and miR-183 inhibitors. RT-PCR and western blot analysis were conducted to analyze the expression of FOXO1, a known target of both miR-182 and miR-183. Mesothelioma cells treated with FOXO1 siRNA and miR-182/183 inhibitors were also analyzed by evaluating cell proliferation and invasion, as well as expression of FOXO1 and its downstream targets. We confirmed miR-182 expression in 25/29 cases and miR-183 expression in 29/29 cases of human mesothelioma tissue by in-situ hybridization. Notably, inhibition of miR-182 or miR-183 reduced cell proliferation, invasion, migration, and adhesion abilities of mesothelioma cells. Surprisingly, transfection with both miR-182 and miR-183 inhibitors showed even more effects on cell progression. Furthermore, FOXO1 was identified as a target of miR-182 and miR-183 in mesothelioma cells. Inhibition of miR-182 and miR-183 reduced cell proliferation ability via upregulation of FOXO1 and its downstream targets, namely, p27. Moreover, inhibition of miR-182 and miR-183 reduced the cell invasion properties of mesothelioma cells. Our findings indicated that miR-182 and miR-183 promote mesothelioma cell progression via downregulation of FOXO1 and p27. Targeting the miR-182/183-FOXO1 axis could serve as a novel treatment against malignant mesothelioma.

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