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1.
Respir Med Case Rep ; 46: 101949, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38046459

RESUMEN

We report the case of a 55-year-old man presented with a nodule in the right middle lung on computed tomography. The size of the nodule had increased at 12 years after the first visit. Consequently, the patient was diagnosed with a Mixed squamous cell and glandular papilloma (MSGP) by surgical resection. To our knowledge, there are no previous studies that MSGP in the lung which had been observed for 12 years before surgery. This study reports the case of a patient who underwent surgical resection of a MSGP.

2.
PLoS One ; 17(3): e0265603, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35312731

RESUMEN

INTRODUCTION: The prognosis of non-small cell lung cancer greatly depends on the presence of lymph node metastasis, which limits the need for surgery and adjuvant therapy for advanced cancer. One-step nucleic acid amplification of cytokeratin19 (CK19) mRNA was used to detect lymph node metastasis. Automated Gene Amplification Detector RD-200 and the LYNOAMP CK19 gene amplification reagent as components of the new one-step nucleic acid amplification system, which has increased gene amplification efficiency by improving the reagent composition, have shorter preprocessing and measurement times than conventional systems. We aimed to compare the clinical performance of the new system with that of histopathology and the conventional system. MATERIALS AND METHODS: 199 lymph nodes from 58 non-small cell lung cancer patients who underwent lymph node dissection were examined intraoperatively using the new system, conventional system, and histopathology. RESULTS: Lymph node metastasis was diagnosed in 32, 42, and 44 patients using histopathological analysis, the new system, and the conventional system, respectively. Compared with histopathological analysis, the concordance rate, sensitivity, specificity, positive predictive value, and negative predictive value of the new system were 92.0%, 90.6%, 92.2%, 69.0%, and 98.1%, respectively, and compared with the conventional system, the values were 95.0%, 86.4%, 97.4%, 90.5%, and 96.2%, respectively. CONCLUSION: The clinical performance of the new one-step nucleic acid amplification system in detecting lymph node metastasis of lung cancer is comparable to that of histopathology and the conventional system; its performance was sufficient for determining the appropriate clinical treatment. The new rapid system can be effectively utilized during lung cancer treatment intraoperatively and postoperatively.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Metástasis Linfática , Técnicas de Amplificación de Ácido Nucleico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Queratina-19/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Ganglios Linfáticos/patología , Metástasis Linfática/diagnóstico , Metástasis Linfática/patología , Técnicas de Amplificación de Ácido Nucleico/métodos , Valor Predictivo de las Pruebas , ARN Mensajero/genética , Sensibilidad y Especificidad , Biopsia del Ganglio Linfático Centinela
5.
Gen Thorac Cardiovasc Surg ; 69(10): 1407-1413, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34002337

RESUMEN

OBJECTIVE: Various surgical procedures have been performed to decrease the recurrence of primary spontaneous pneumothorax after video-assisted thoracic surgery. This study aimed to examine the efficiency of pleural coverage for the prevention of postoperative recurrence in relatively young patients. METHODS: Between January 2008 and December 2012, a total of 357 cases of 345 patients (age 15-29 years) with primary spontaneous pneumothorax who underwent bullectomy at 13 institutions were enrolled in this multi-institutional retrospective cohort study. A concurrent bilateral operation was counted as two cases. Polyglycolic acid sheets were used in 238 cases, and oxidized regenerated cellulose sheets were used in 37 cases to cover the visceral pleura, with no pleural coverage in 82 cases. The average observation period was 4.2 ± 2.0 years. RESULTS: Postoperative recurrence was observed in 50 cases (14.0%) after video-assisted thoracic surgery. Twenty-six cases (10.9%) in the polyglycolic acid group, eight (21.6%) in the oxidized regenerated cellulose group, and sixteen (19.5%) in the non-coverage group experienced postoperative recurrence. Kaplan-Meier analysis revealed that the rate of freedom from postoperative recurrence in the polyglycolic acid group was significantly higher than that in the non-coverage group. Multivariate analysis showed that age ≥ 20 years and coverage with polyglycolic acid sheets were associated with reduced risk factors for postoperative recurrence. CONCLUSION: Pleural coverage with a polyglycolic acid sheet is suggested to be effective in preventing postoperative recurrence of pneumothorax compared with non-coverage in relatively young patients.


Asunto(s)
Neumotórax , Adolescente , Adulto , Estudios de Cohortes , Humanos , Pleura/cirugía , Neumotórax/etiología , Neumotórax/prevención & control , Neumotórax/cirugía , Ácido Poliglicólico , Recurrencia , Estudios Retrospectivos , Cirugía Torácica Asistida por Video , Resultado del Tratamiento , Adulto Joven
6.
J Thorac Dis ; 13(2): 977-985, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33717570

RESUMEN

BACKGROUND: Solitary pulmonary nodules caused by nontuberculous mycobacteriosis are included as a category of pulmonary nontuberculous mycobacterium disease. Clinical characteristics, treatments and prognosis are not fully known because there are a few related reports. METHODS: This was a multi-center retrospective study of 101 cases diagnosed as solitary nodular type of nontuberculous mycobacteriosis from January 2000 to March 2017 that underwent resection at 9 related facilities belonging to the Thoracic Surgery Study Group of Osaka. RESULTS: The most common pathogen was Mycobacterium avium complex (n=77, 87.5%), followed by Mycobacterium kansasii (n=8, 9.1%). Chest computed tomography results showed subpleural locations that were difficult to distinguish from lung cancer. Fluorodeoxyglucose positron emission tomography/computed tomography was performed in 58 cases and positive results were obtained in 35 (60.3%), with an average maximum standardized uptake value of 3.87. The purpose of resection in most cases was for diagnosis. The surgical procedure was wedge resection in 87, segmentectomy in 3, and lobectomy in 11, while 77 underwent thoracoscopic surgery. Postoperative complications occurred in 7 cases, though no infections caused by nontuberculous mycobacteriosis were noted. The median observation period was 27 months. A worsened condition occurred in 10 (9.9%) with Mycobacterium avium complex, though none had local recurrence. CONCLUSIONS: Solitary pulmonary nodules due to nontuberculous mycobacteriosis is difficult to diagnose based on preoperative examination results or distinguish from lung cancer. Among the present cases, none had local complications or recurrence, even in those that underwent a wedge resection, thus postoperative chemotherapy was not considered necessary if a complete resection was performed. On the other hand, some cases showed reinfection after a long period following resection, thus patients should be informed of that future possibility.

7.
Respir Res ; 21(1): 153, 2020 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-32546152

RESUMEN

BACKGROUND: Lung resection in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) has been reported to be associated with favorable outcomes. However, little is known regarding the risk and prognostic factors for refractory and recurrent cases. We aimed to evaluate the overall impact and benefit of adjuvant lung surgery by comparing NTM-PD patients who underwent adjuvant lung resection with those treated exclusively with antibiotics. We also investigated the efficacy of serum IgA antibody against glycopeptidolipid (GPL) core antigen (GPL core antibody) to monitor disease activity and predict the recurrence of disease after adjuvant lung resection. METHODS: We retrospectively evaluated the clinical characteristics and surgical outcomes of 35 patients surgically treated for NTM-PD. Furthermore, we compared surgically treated patients and control patients treated exclusively with antibiotics who were matched statistically 1:1 using a propensity score calculated from age, sex, body mass index, and radiologic features of disease. RESULTS: In the surgically treated patients, the median age was 58 (interquartile range, 47-65) years and 65.7% were female. Twenty-eight patients had Mycobacterium avium complex. Operations comprised four pneumonectomies, two bilobectomies, one bilobectomy plus segmentectomy, 17 lobectomies, two segmentectomies, and nine lobectomies plus segmentectomies. Postoperative complications occurred in seven patients (20%), there were no operative deaths, and 33 (94.3%) patients achieved negative sputum culture conversion. Refractory and recurrent cases were associated with remnant bronchiectasis, contralateral shadows, and positive acid-fast bacilli staining or culture. Of 28 statistically matched pairs, long-term sustained negative culture conversion was observed in 23 (82.2%) surgical group patients and in 14 (50.0%) non-surgical group patients (0.0438). The mortality rate was lower in the surgical group, but did not reach statistical significance (one in the surgical group and four in the non-surgical group, p = 0.3516). GPL core antibody was correlated with disease activity and recurrence. CONCLUSIONS: NTM-PD patients who underwent adjuvant lung resection experienced overall favorable outcomes and achieved sputum culture conversion more frequently. Long-term mortality may have been reduced by this procedure, and the level of GPL core antibody was shown to be a good clinical indicator of disease activity after surgery.


Asunto(s)
Antibacterianos/administración & dosificación , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/cirugía , Anciano , Terapia Combinada/métodos , Terapia Combinada/tendencias , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento
8.
Cancer Med ; 9(7): 2343-2351, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32022477

RESUMEN

BACKGROUND: To report the follow up data and clinical outcomes of the JME study (UMIN 000008177), a prospective, multicenter, molecular epidemiology examination of 876 surgically resected non-small-cell lung cancer (NSCLC) cases, and the impact of somatic mutations (72 cancer-associated genes) on recurrence-free survival (RFS) and overall survival (OS). METHODS: Patients were enrolled between July 2012 and December 2013, with follow up to 30th November 2017. A Cox proportional hazards model was used to assess the impact of gene mutations on RFS and OS, considering sex, smoking history, age, stage, histology, EGFR, KRAS, TP53, and number of coexisting mutations. RESULTS: Of 876 patients, 172 had ≥2 somatic mutations. Median follow-up was 48.4 months. On multivariate analysis, number of coexisting mutations (≥2 vs 0 or 1, HR = 2.012, 95% CI: 1.488-2.695), age (≥70 vs <70 years, HR = 1.583, 95% CI: 1.229-2.049), gender (male vs female, HR = 1.503, 95% CI: 1.045-2.170) and pathological stage (II vs I, HR = 3.386, 95% CI: 2.447-4.646; ≥III vs I, HR = 6.307, 95% CI: 4.680-8.476) were significantly associated with RFS, while EGFR mutation (yes vs no, HR = 0.482, 95% CI: 0.309-0.736), number of coexisting mutations (≥2 vs 0 or 1, HR = 1.695, 95% CI: 1.143-2.467), age (≥70 vs <70 years, HR = 1.932, 95% CI: 1.385-2.726), and pathological stage (II vs I, HR = 2.209, 95% CI: 1.431-3.347; ≥III vs I, HR = 5.286, 95% CI: 3.682-7.566) were also significant for OS. CONCLUSION: A smaller number of coexisting mutations, earlier stage, and younger age were associated with longer RFS and OS, while EGFR mutations were significantly associated with improved OS.


Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Epidemiología Molecular/métodos , Mutación , Neumonectomía/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Femenino , Estudios de Seguimiento , Humanos , Japón/epidemiología , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Adulto Joven
9.
J Chemother ; 31(6): 343-348, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31409216

RESUMEN

Feasibility is one of the major concerns during adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. A phase II clinical trial of adjuvant chemotherapy with four courses of carboplatin (AUC 5 at day 1) and S-1 (80 mg/m2/day for 2 weeks followed by a 2-week rest) was performed to evaluate the feasibility (UMIN 9101). The primary endpoint was the completion rate and the secondary endpoints were adverse events, 2-year overall survival and disease-free rates. Thirty-five non-small cell lung cancer patients were enrolled. The adjuvant chemotherapy completion rate was 85.3% (29/34); 17/34 (50%) patients completed 4 courses without dose reduction. There were no treatment-related deaths, and Grade 3/4 adverse events included neutropenia (38.2%), leukocytopenia (14.7%), anemia (20.6%), thrombocytopenia (20.6%), anorexia (5.9%), fatigue (5.9%), and oral mucositis (2.9%). Two-year overall and disease-free survival rates were 96.3% and 53.3%, respectively. Adjuvant chemotherapy with carboplatin plus S-1 is safe and feasible.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Quimioterapia Adyuvante/métodos , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Quimioterapia Adyuvante/efectos adversos , Supervivencia sin Enfermedad , Combinación de Medicamentos , Estudios de Factibilidad , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Ácido Oxónico/administración & dosificación , Ácido Oxónico/efectos adversos , Tegafur/administración & dosificación , Tegafur/efectos adversos
10.
Arch Biochem Biophys ; 664: 167-173, 2019 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-30677406

RESUMEN

Human airway trypsin-like protease (HAT) localizes at human bronchial epithelial cells (HBECs). HAT enhanced release of interleukin-8 (IL-8) from HBECs at 10-100 mU/mL and the enhanced release was almost completely abolished by 50 µM leupeptin, a serine protease inhibitor. Previous reports suggested that HAT displays its physiological functions via protease-activated receptor 2 (PAR2). In the present study, we examined the mechanism whereby HAT upregulates IL-8 synthesis in HBECs with a focus on PAR2. Northern blot analysis revealed that HAT enhanced IL-8 mRNA expression at concentrations of 10-100 mU/mL. PAR2 activating peptide (PAR2 AP) also enhanced IL-8 release and IL-8 mRNA expression in HBECs at 50-1,000 µM at similar levels as HAT. Knockdown of PAR2 mRNA by siRNA methods showed that PAR2 mRNA expression was significantly depressed in primary HBECs, and both HAT- and PAR2 AP-induced IL-8 mRNA elevation was significantly depressed in PAR2 siRNA-transfected HBECs. Additionally, HAT cleaved the PAR2 activating site (R36-S37 bond) of synthetic PAR2 N-terminal peptide. These results indicate that HAT stimulates IL-8 synthesis in airway epithelial cells via PAR2 and could help to amplify inflammation in chronic respiratory tract disease.


Asunto(s)
Bronquios/enzimología , Interleucina-8/biosíntesis , Receptor PAR-2/metabolismo , Serina Endopeptidasas/metabolismo , Secuencia de Aminoácidos , Bronquios/citología , Células Cultivadas , Células Epiteliales/metabolismo , Humanos , Interleucina-8/genética , ARN Mensajero/genética , ARN Interferente Pequeño/genética
11.
Surg Case Rep ; 4(1): 51, 2018 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-29882097

RESUMEN

BACKGROUND: Surgical resection is the first choice for intralobar sequestration (ILS). A lobectomy is often performed, though we consider that a segmentectomy may be sufficient for benign cases if the sequestration is completely included within a segment. CASE PRESENTATION: We treated a 36-year-old female diagnosed with ILS. Chest computed tomography (CT) revealed several cystic lesions with niveau formation and consolidation in left segment (S)10 without communication of the bronchus and abnormal artery branching from the descending aorta. We performed a sublobar resection of left S10 including sequestration through a thoracoscopic minimally sized incision. The sequestration had dark red appearance and was completely included in the S10. The boundary line of S10 was clear with inflation of the lung after cutting bronchus 10. The postoperative course was uneventful. Chest CT findings at 2 years after surgery showed good expansion of the residual left lower lobe with no consolidation and respiratory function were nearly the same as the preoperative condition. CONCLUSIONS: A thoracoscopic segmentectomy for ILS is a feasible and useful procedure for qualified cases, even in adult patients who had repeated inflammation.

12.
J Thorac Dis ; 10(12): 6828-6837, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30746228

RESUMEN

BACKGROUND: Direct lymphatic drainage from a primary tumor to the right paratracheal or aortic window lymph nodes is often noted in pN2 disease. This multi-institutional retrospective study investigated the outcomes of upfront surgery in patients with clinical skip N2 disease (N2 disease without N1 disease) and a tumor in the right upper lobe or left upper segment based on results of modern radiological examinations, including positron emission tomography (PET). METHODS: We identified 143 patients with cN2 disease who underwent upfront surgery in 12 institutions under the Thoracic Surgery Study Group of Osaka University between January 2006 and December 2013. Among 143 patients, 94 who underwent PET were analyzed. We classified these patients into Group A (n=39; clinical skip N2 disease and a tumor in the right upper lobe or left upper segment) and Group B (n=55; other). RESULTS: The median follow-up was 56.5 months. Among the 94 patients, 50 (53.2%) had skip N2 disease and 65 (69.1%) had a tumor in the right upper lobe or left upper segment. The 5-year overall survival (OS) rates of the 94 patients with cN2 disease was 47.9%. The 5-year OS rates for the cN2pN0/1 (n=22) and cN2pN2 (n=70) groups were 74.9% and 41.2%, respectively (P=0.034). The univariate analysis of OS revealed no significant differences in age, sex, histology, carcinoembryonic antigen (CEA) level, tumor size, PET findings, and number of metastatic lymph nodes when these parameters were dichotomized. A significantly better 5-year OS rate was observed in Group A than in Group B (64.0% vs. 37.0%; P=0.039). The multivariate analysis of OS revealed that Group A was a significantly prognostic factor (P=0.030). CONCLUSIONS: Patients with cN2 disease in Group A had a more favorable prognosis. Upfront surgery may be a treatment option for such selected patients with non-small lung cancer in the specific group.

13.
Interact Cardiovasc Thorac Surg ; 26(1): 18-24, 2018 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-29049806

RESUMEN

OBJECTIVES: A thymic neuroendocrine tumour (TNET) is rare, and few comprehensive reports of treatment results have been presented. To clarify the clinicopathological characteristics of TNET in affected patients, outcomes were retrospectively examined using cases accumulated in a multicentre survey. METHODS: Thirty patients (25 men and 5 women) who underwent surgical resection or biopsy procedures at 10 institutions of the Thoracic Surgery Study Group of Osaka University (TSSGO) between January 1986 and June 2015 and pathologically diagnosed with TNET were enrolled. RESULTS: The examined tumours were classified as typical carcinoid in 7 patients, atypical carcinoid in 11 patients, large-cell neuroendocrine carcinoma in 3 patients and small-cell carcinoma in 9 patients, of which 2 underwent surgical biopsy procedures and 28 surgical resection, with a macroscopic complete resection procedure performed in 27 patients. Induction therapy was performed in 2 patients and adjuvant therapy in 10 patients. Thirteen patients had recurrence, with distant metastasis, especially in bone and lung tissues, more frequent than local recurrence. Overall survival was 77% after 5 years and 35% after 10 years, whereas relapse-free survival was 48% and 29%, and cancer-specific survival was 90% and 48%, respectively. Overall survival was significantly better in patients who underwent macroscopic complete resection (P = 0.010). As for relapse-free survival patients, TNM Stage I or II (P = 0.011) and received adjuvant therapy patients (P = 0.042) showed good survival rates. CONCLUSIONS: The prognosis of patients with TNET was favourable in those treated with macroscopic complete resection. Survival is promising even in patients with postoperative recurrence, following treatment utilized for pulmonary neuroendocrine tumour or gastroenteropancreatic neuroendocrine tumour.


Asunto(s)
Carcinoma de Células Pequeñas/patología , Carcinoma de Células Pequeñas/terapia , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/terapia , Neoplasias del Timo/patología , Neoplasias del Timo/terapia , Adulto , Anciano , Carcinoma de Células Pequeñas/mortalidad , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/mortalidad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias del Timo/mortalidad , Resultado del Tratamiento
14.
Surg Today ; 48(4): 380-387, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28993901

RESUMEN

PURPOSE: We conducted a prospective clinical study to individualize adjuvant chemotherapy after complete resection of non-small-cell lung cancer (NSCLC), based on the drug sensitivity test. METHODS: Patients with resectable c-stage IB-IIIA NSCLC were registered between 2005 and 2010. We performed the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) on a fresh surgical specimen to assess in vitro chemosensitivity and evaluated the prognostic outcome after adjuvant chemotherapy with carboplatin/paclitaxel based on the CD-DST. RESULTS: Among 92 registered patients, 87 were eligible for inclusion in the analysis. The success rate of CD-DST was 86% and chemosensitivity to carboplatin and/or paclitaxel was evident in 57 (76%) of the 75 patients. Adjuvant chemotherapy was completed in 22 (73%) of 30 patients. The 5-year overall survival rates were 71, 73, and 75% for all, CD-DST success, and chemosensitive patients, respectively. The 5-year disease-free survival and overall survival rates of the chemosensitive patients who completed adjuvant chemotherapy using carboplatin/paclitaxel were 68 and 82%, respectively. The 5-year disease-free survival and overall survival rates of the patients with stage II-IIIA chemosensitive NSCLC were 58 and 75%, respectively. Comparative analyses of the chemosensitive and non-chemosensitive/CD-DST failure groups showed no significant survival difference. CONCLUSIONS: CD-DST can be used to evaluate chemosensitivity after lung cancer surgery; however, its clinical efficacy for assessing individualized treatment remains uncertain.


Asunto(s)
Carboplatino/farmacología , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Quimioterapia Adyuvante , Colágeno , Medios de Cultivo , Técnicas de Cultivo/métodos , Ensayos de Selección de Medicamentos Antitumorales/métodos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Paclitaxel/farmacología , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Quimioterapia Combinada , Femenino , Geles , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neumonectomía , Medicina de Precisión , Estudios Prospectivos , Tasa de Supervivencia , Resultado del Tratamiento
15.
EBioMedicine ; 21: 86-93, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28625519

RESUMEN

Epidermal growth factor receptor (EGFR) mutations have been used as the strongest predictor of effectiveness of treatment with EGFR tyrosine kinase inhibitors (TKIs). Three most common EGFR mutations (L858R, exon 19 deletion, and T790M) are known to be major selection markers for EGFR-TKIs therapy. Here, we developed a multiplex picodroplet digital PCR (ddPCR) assay to detect 3 common EGFR mutations in 1 reaction. Serial-dilution experiments with genomic DNA harboring EGFR mutations revealed linear performance, with analytical sensitivity ~0.01% for each mutation. All 33 EGFR-activating mutations detected in formalin-fixed paraffin-embedded (FFPE) tissue samples by the conventional method were also detected by this multiplex assay. Owing to the higher sensitivity, an additional mutation (T790M; including an ultra-low-level mutation, <0.1%) was detected in the same reaction. Regression analysis of the duplex assay and multiplex assay showed a correlation coefficient (R2) of 0.9986 for L858R, 0.9844 for an exon 19 deletion, and 0.9959 for T790M. Using ddPCR, we designed a multiplex ultrasensitive genotyping platform for 3 common EGFR mutations. Results of this proof-of-principle study on clinical samples indicate clinical utility of multiplex ddPCR for screening for multiple EGFR mutations concurrently with an ultra-rare pretreatment mutation (T790M).


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Técnicas de Genotipaje , Neoplasias Pulmonares/genética , Reacción en Cadena de la Polimerasa Multiplex , Mutación , Alelos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Análisis Mutacional de ADN , Exones , Técnicas de Genotipaje/métodos , Técnicas de Genotipaje/normas , Humanos , Neoplasias Pulmonares/diagnóstico , Reacción en Cadena de la Polimerasa Multiplex/métodos , Reacción en Cadena de la Polimerasa Multiplex/normas , Sensibilidad y Especificidad
16.
Ann Surg Oncol ; 24(4): 1135-1142, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27785660

RESUMEN

BACKGROUND: Postoperative complications are associated with poor cancer-specific survival in various types of cancer surgery. Recent studies suggest that systemic inflammation induced by surgical trauma can accelerate the adhesion of circulating tumor cells to the vascular endothelium of distant organs, resulting in early cancer recurrence. We investigated the impact of postoperative cardiopulmonary complications on cancer recurrence following lung cancer surgery. METHODS: From a prospective database of 675 consecutive patients who underwent curative surgery for lung cancer between 2007 and 2012, the incidence of postoperative cardiopulmonary complications, white blood cell counts, and C-reactive protein levels were evaluated in the acute phase after surgery. Four patients had both cardiovascular and respiratory complications. The remaining 671 patients were divided into 3 groups: patients without cardiopulmonary complications; those with cardiovascular complications; and those with respiratory complications. The incidence of cancer recurrence was compared among the three groups. RESULTS: Postoperative cardiovascular or respiratory complications were identified in 94 (14%) or 25 (4%) patients, respectively. Postoperative white blood cell counts and C-reactive protein levels were significantly higher in those with postoperative respiratory complications than in those without. There was a significantly higher incidence of cancer recurrence in those with postoperative respiratory complications than in those without (48.0 vs. 16.8%; p < 0.0001). Multiple regression analysis adjusted for age, sex, and pathological staging showed that the incidence of postoperative respiratory complications was a significant predictor of cancer recurrence. CONCLUSIONS: The presence of respiratory complications following lung cancer surgery was a significant predictor of cancer recurrence.


Asunto(s)
Reacción de Fase Aguda/etiología , Enfermedades Cardiovasculares/etiología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Recurrencia Local de Neoplasia/epidemiología , Complicaciones Posoperatorias/etiología , Reacción de Fase Aguda/sangre , Anciano , Proteína C-Reactiva/metabolismo , Enfermedades Cardiovasculares/sangre , Supervivencia sin Enfermedad , Femenino , Humanos , Incidencia , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Complicaciones Posoperatorias/sangre , Periodo Posoperatorio , Enfermedades Respiratorias/sangre , Enfermedades Respiratorias/etiología , Factores de Tiempo
17.
Respirol Case Rep ; 4(6): e00200, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28031835

RESUMEN

A pulmonary lymphoepithelioma-like carcinoma (PLELC) is similar to a lymphoepithelioma, a subtype of nasopharyngeal carcinoma and commonly associated with Epstein-Barr virus infection which is a rare tumour and classified in the group of "other and unclassified carcinoma" in the latest 2015 World Health Organization (WHO) classification. Some reports of lymphoepithelioma-like carcinoma (LELC) have noted an epidermal growth factor receptor (EGFR) mutation, whereas none have noted a mutation of the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene. This is the first reported case of PLELC with ALK rearrangement. A 76-year-old woman underwent a right lower lobectomy and complicated partial resection of the upper lobe with lymph node dissection under complete thoracoscopic approach. A histopathological diagnosis of PLELC was made and the stage was classified as T1aN1(#12l) M0, pl0, G2, Ly1, V1. The results of both ALK immunohistochemistry and EML4-ALK fusion gene on fluorescence in situ hybridization (FISH) examinations were positive; however, EGFR mutational analysis results showed wild-type mutation.

18.
J Clin Oncol ; 34(19): 2247-57, 2016 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-27161973

RESUMEN

PURPOSE: Oncogenic driver mutations are critical for lung cancer development and serve as therapeutic targets. However, their associations with environmental factors are not fully understood. We aimed to elucidate the relationship between tumor developmental biology and exposure to environmental factors. PATIENTS AND METHODS: This was a prospective, multicenter, molecular epidemiology study. Eligible patients were those with newly diagnosed stages I to IIIB non-small-cell lung cancer (NSCLC) who underwent surgery. The tumors were examined for somatic mutations in 72 cancer-associated genes by targeted deep sequencing, estrogen receptor ß (ERß) expression using immunohistochemical staining, and infection with any of 37 types of human papillomavirus (HPV) using a polymerase chain reaction-based microarray system. Detailed information on patient demographics and environmental factors was obtained from a comprehensive questionnaire. RESULTS: From July 2012 to December 2013, 957 patients were enrolled, and molecular analyses were performed on 876 samples (from 441 ever- and 435 never-smokers). Oncogenic driver mutations in P53 and KRAS increased proportionally with smoking status, whereas mutations in EGFR and SMAD4 decreased. KRAS mutations in smokers and SMAD4 mutations were observed more frequently in proportion to body mass index. TP53 and NFE2L2 mutations were observed more frequently in advanced NSCLC stages. As for never-smokers, no environmental factors were significantly associated with mutational changes. EGFR mutations and TP53 mutations were observed more frequently in women and in men, respectively. Mutations in these two genes were also potentially associated with ERß expression. Only three patients (0.3%) were HPV positive. CONCLUSION: The mutational spectrum is associated with smoking, body mass index, and other environmental factors, as well as with ERß expression. Little association was observed between HPV and NSCLC.


Asunto(s)
Genes p53 , Neoplasias Pulmonares/genética , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genética , Fumar/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Receptores ErbB/genética , Receptor beta de Estrógeno/análisis , Femenino , Humanos , Neoplasias Pulmonares/virología , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Papillomaviridae/aislamiento & purificación , Estudios Prospectivos , Proteína Smad4/genética
19.
Surg Case Rep ; 2(1): 40, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27108124

RESUMEN

A colopleural fistula is a rare condition reported to be caused by Crohn's disease, a malignant tumor of the gastrointestinal tract, and other clinical conditions. Some studies have noted that a sub-diaphragmatic abscess, usually organized following abdominal surgery, may play some role in the formation of this type of fistula. Therefore, a colopleural fistula is a complication very rarely encountered by thoracic surgeons after lung resection.We experienced an extremely rare case of colopleural fistula following a left lower lobectomy for lung aspergillosis. Here, we report a 71-year-old man with a surgical history of proximal gastrectomy for gastric cancer. He underwent left lower lobectomy of the lung for aspergillosis, and a colopleural fistula occurred on the second operative day as a complication. Aspergillus might be responsible for forming a fistula between the colon and lung via the diaphragm, and lung surgery manifested this rare condition. Although some reports suggest that surgical treatment is mandatory to cure this fistula, an immediate colostomy in our case reduced the internal pressure of the colon, thus enabling spontaneous closure of the fistula with appropriate drainage and antibiotics. The patient was discharged in a good condition.

20.
Surg Case Rep ; 2(1): 10, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26943686

RESUMEN

Cavernous hemangioma is not a neoplasm, but rather a congenital venous malformation with the potential to develop in all parts of the body, though it is very rarely seen in the thymus. We report a case of cavernous hemangioma in the thymus partially resected. A 71-year-old woman presented with pericardial discomfort, and chest computed tomography (CT) showed a left lateral mediastinal mass which was 2.0 × 1.2 × 1.8 cm in size, with border regularity and without calcification. Its interior was partially enhanced. Three-dimensional chest computed tomography image showed a tortuous vessel connecting to the tumor. Surgical resection was performed for the purpose of providing a definitive diagnosis and treatment because a mediastinal tumor such as thymoma or teratoma was suspected. Partial resection of the thymus including the mass was done by utilizing a three-port, left-sided video-assisted thoracic surgery (VATS) approach with hoisting of the third rib with the patient in a spinal position. A wine-colored mass bulging from the surface of the left lobe of the thymus was identified along with the communicating vessel which could only be cut with an energy device. It is considered that thymic partial resection using VATS is a better option for small and non-infiltrative lesions.

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