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1.
J Cancer Res Ther ; 19(5): 1350-1355, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37787307

RESUMEN

Introduction: Survival information for stereotactic body radiotherapy (SBRT) and surgery for stage I non-small cell lung cancer (NSCLC) was examined. Methods: Stage I NSCLC patients who underwent surgery or SBRT between 2012 and 2016 were retrospectively enrolled in this single-institution study. Using the Kaplan--Meier method and Cox regression model, overall survival (OS) was estimated and compared. Results: Among 538 enrolled patients, compared to the surgery group (443), the SBRT group (95) had more complications (P = 0.01), worse performance status (P = 0.001), and were older (P < 0.001). Three-year OS was 70.5% post SBRT and 90.1% postsurgery. The 3-year cancer-specific survival (CSS) and disease-free survival (DFS) post SBRT and postsurgery were 92.7% vs. 92.3% and 61.1% vs 79.3%, respectively. Three-year locoregional and distant control rates post SBRT and postsurgery were 85.6% vs. 90.1% and 82.5% vs. 86.4%, respectively. Multivariate analysis using the Cox model, including age, T-stage, CCI, and C/T ratio and treatment, showed the surgery group's OS to be significantly superior to that of the SBRT group (HR of SBRT per surgery: 1.90, 95%CI: 1.12-3.21, P = 0.017). No significant differences were observed in rates of adverse events. Conclusion: Although OS was better in the surgery group, no differences in CSS existed. This analysis suggests the need for future studies that compare specific radical surgeries and SBRT in a prospective and randomized setting.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Radiocirugia , Carcinoma Pulmonar de Células Pequeñas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirugía , Estudios Retrospectivos , Radiocirugia/efectos adversos , Radiocirugia/métodos , Estudios Prospectivos , Resultado del Tratamiento , Estadificación de Neoplasias
2.
Artículo en Inglés | MEDLINE | ID: mdl-37307071

RESUMEN

OBJECTIVES: This case series aimed to determine the feasibility of simultaneous modified Ravitch and David procedures for Marfan syndrome patients with pectus excavatum and annuloaortic ectasia. METHODS: Between March 2014 and December 2019, 7 consecutive patients underwent simultaneous surgery of modified Ravitch and David procedures for pectus excavatum and annuloaortic ectasia. The completion of cardiac surgery and sternal closure were followed by the modified Ravitch procedure. The bilateral fourth to seventh costal cartilages were resected, the sternal body partially wedge resected and the sternum raised anteriorly with re-suture. An oblique incision was performed on bilateral third costal cartilages, and they were fixed on top of each other, with the medial end superior and the lateral end inferior. The sternum was raised anteriorly, bypassing the fourth to seventh rib ends through the back of the sternum with threads. The feasibility and safety of the procedure were assessed through a retrospective review of the patients' clinical charts. RESULTS: The total sample had a median age of 28 years and comprised 5 males and 2 females. There was a significant difference in the preoperative and postoperative median Haller index, which were 6.8 and 3.9, respectively. All patients were discharged without serious complications, and there was no significant recurrence of pectus excavatum at 35-92 months postoperatively. CONCLUSIONS: The results of our case series suggest the feasibility of one-stage surgery for pectus excavatum combined with cardiac surgery using the modified Ravitch procedure. Future efforts should be tailored for more uneventful postoperative clinical courses.

3.
Respir Med Case Rep ; 44: 101879, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37313497

RESUMEN

A 16-year-old girl with a genetic diagnosis of cystic fibrosis was referred to us for consideration of lung transplantation. She had been hospitalized repeatedly for pneumonia and pneumothoraxes and her respiratory function had worsened progressively. Although she also had liver cirrhosis, she was considered a candidate for lung transplantation because her liver disease was compensated and only slowly progressive. After bilateral lung transplantation from a brain-dead donor, she developed ascites that was well controlled with diuretics. Otherwise, her post-operative course was uneventful and she was transferred to another hospital for rehabilitation 39 days after lung transplantation.

4.
Respir Med Case Rep ; 42: 101809, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36655007

RESUMEN

A 45-year-old woman with recurrent dyspnea for 40 years was previously diagnosed with bronchial asthma and spasmodic dysphonia. On admission, the patient was diagnosed with expiratory central airway collapse (ECAC) due to expiratory dynamic airway collapse based on radiographic examination, chest computed tomography, and bronchoscopy. After continuous positive airway pressure and temporal airway stenting, surgical tracheobronchoplasty and tracheal membranous portion reinforcement using polypropylene mesh successfully relieved the respiratory symptoms. In patients with airway obstructive disease refractory to conventional therapies, ECAC should be considered.

5.
Gen Thorac Cardiovasc Surg ; 71(5): 313-320, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36495469

RESUMEN

OBJECTIVES: Virtual-assisted lung mapping is a preoperative bronchoscopic multi-spot dye-marking technique used in sublobar lung resection for hardly palpable lung nodules. However, the number of marks required per nodule remains unknown. Therefore, we examined the correlation between the number of intraoperative visible marks and the successful resection rate. METHODS: We retrospectively examined 210 consecutive patients with 256 lesions who underwent virtual-assisted lung mapping during January 2014-December 2020 at our hospital. When a nodule was not resected at the initial attempt, or when a nodule was very close to the cut margin in the resected specimen and required additional resection, we categorized it as unsuccessful resection. We divided 256 lesions into successful and unsuccessful groups and compared the numbers of intraoperative visible marks between the two groups. RESULTS: Of 797 attempted marks, 738 (92.4%) were visible during the surgery. Fourteen (5.4%) of 256 lesions were determined to be unsuccessful according to the study criteria. There was a remarkable difference in the average numbers of intraoperative visible marks between both groups (3 [interquartile range: 2-4] vs. 2 [interquartile range: 1-2.8]; p < 0.01). Multivariable logistic analysis revealed a significant difference in the number of intraoperative visible marks (odds ratio: 0.28, 95% confidence interval: 0.14-0.57; p < 0.001) between both groups. CONCLUSIONS: Successful sublobar lung resection requires three or more intraoperative visible marks established using virtual-assisted lung mapping per lung nodule.


Asunto(s)
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Neumonectomía/métodos , Cirugía Torácica Asistida por Video/métodos , Broncoscopía/métodos , Pulmón/diagnóstico por imagen , Pulmón/cirugía , Pulmón/patología
6.
Sci Rep ; 12(1): 9100, 2022 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-35650221

RESUMEN

Rapid identification of lung-cancer micro-lesions is becoming increasingly important to improve the outcome of surgery by accurately defining the tumor/normal tissue margins and detecting tiny tumors, especially for patients with low lung function and early-stage cancer. The purpose of this study is to select and validate the best red fluorescent probe for rapid diagnosis of lung cancer by screening a library of 400 red fluorescent probes based on 2-methyl silicon rhodamine (2MeSiR) as the fluorescent scaffold, as well as to identify the target enzymes that activate the selected probe, and to confirm their expression in cancer cells. The selected probe, glutamine-alanine-2-methyl silicon rhodamine (QA-2MeSiR), showed 96.3% sensitivity and 85.2% specificity for visualization of lung cancer in surgically resected specimens within 10 min. In order to further reduce the background fluorescence while retaining the same side-chain structure, we modified QA-2MeSiR to obtain glutamine-alanine-2-methoxy silicon rhodamine (QA-2OMeSiR). This probe rapidly visualized even borderline lesions. Dipeptidyl peptidase 4 and puromycin-sensitive aminopeptidase were identified as enzymes mediating the cleavage and consequent fluorescence activation of QA-2OMeSiR, and it was confirmed that both enzymes are expressed in lung cancer. QA-2OMeSiR is a promising candidate for clinical application.


Asunto(s)
Colorantes Fluorescentes , Neoplasias Pulmonares , Alanina , Aminopeptidasas , Dipeptidil Peptidasa 4/metabolismo , Colorantes Fluorescentes/química , Glutamina , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Rodaminas/química , Silicio
7.
J Thorac Dis ; 14(4): 1061-1069, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35572865

RESUMEN

Background: Virtual-assisted lung mapping (VAL-MAP) is a preoperative bronchoscopic multispot dye-marking procedure to facilitate sublobar lung resection for unidentifiable lung nodules. To increase detectable markings, we performed VAL-MAP using dual staining (VAL-MAP DS) with indocyanine green (ICG) and indigo carmine. This study was designed to evaluate the efficacy and safety of the modified technique. Methods: We retrospectively reviewed the records of patients who underwent VAL-MAP DS. Twenty patients with 27 lesions underwent 72 VAL-MAP DS markings. We investigated the overall detectable marking rate, visible marking rate, successful resection rate, and complications. Results: The overall detectable marking rate, thanks to both ICG and indigo carmine, tended to be higher than the indigo carmine visible marking rate (95.7% vs. 85.5%, P=0.08). The successful resection rate with sufficient margins was 92.0%. There were no adverse events related to the use of ICG. ICG markings of the lungs of patients with a history of smoking more than 50 pack-years tended to be visible, but the staining was too extensive compared with the staining in patients who smoked less or not at all (58.8% vs. 0.0%, P<0.001). Conclusions: VAL-MAP DS is likely be efficacious and safe in enhancing the detectability of markings. This bronchoscopic technique should be considered as one of the optimal preoperative marking methods in thoracic surgery.

8.
Surg Today ; 52(10): 1497-1503, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35237884

RESUMEN

PURPOSE: It is unknown whether intraoperative needle biopsy (INB) predisposes to the postoperative recurrence of lung cancer and compromises the prognosis of these patients. We conducted this study to identify the effect of INB before lobectomy on the postoperative recurrence rate and prognosis of patients with nonsmall cell lung cancer (NSCLC). METHODS: The subjects of this retrospective study were 953 patients with pathological stage I-III NSCLC who underwent lobectomy between 2001 and 2016. The patients were divided into two groups: the INB group (n = 94) and the non-INB group (n = 859). After propensity score matching (PSM), we compared the postoperative cumulative recurrence rate, recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) between the two groups. RESULTS: After PSM, 94 patient pairs were matched. The cumulative recurrence rate was significantly higher in the INB group than in the non-INB group (P = 0.01). The 5-year RFS rate was significantly lower in the INB group than in non-INB group (48% vs 68%), as were the 5-year DSS (76% vs 92%) and 5-year OS rates (67% vs 84%) (all P < 0.05). CONCLUSIONS: The findings of this analysis suggest that INB before lobectomy may increase the cumulative recurrence rate and worsen the prognosis of patients with resectable NSCLC. Thus, we believe that INB should be avoided unless a lung lesion cannot be diagnosed by another type of biopsy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Biopsia con Aguja , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Neoplasias Pulmonares/patología , Estadificación de Neoplasias , Neumonectomía , Puntaje de Propensión , Estudios Retrospectivos
9.
Ann Surg Oncol ; 29(3): 1816-1824, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34997412

RESUMEN

BACKGROUND: Few studies have assessed the comprehensive skeletal muscle depletion associated with loss of muscle quantity (sarcopenia) and reduced muscle quality in cancer patients. This study aimed to clarify the impact of skeletal muscle depletion on outcomes after non-small cell lung cancer surgery. METHODS: Data for 341 patients with pathologic stages 1 to 3A non-small cell lung cancer who underwent lobectomy and mediastinal lymph node dissection from 2009 to 2013 were retrospectively reviewed. The integrative pectoralis muscle index (IPMI) was assessed by multiplying the normalized pectoralis muscle area (area/body mass index) and mean radiodensity on chest images. Postoperative outcomes were compared among sex-specific quartiles of IPMI. The trend of continuous and categorical variables was analyzed using the Jonckheere-Terpstra test and the Cochrane-Armitage test, respectively. RESULTS: Respiratory strength declined with decreasing quartiles of IPMI (P < 0.001). The risk of major complications escalated with the decrease of IPMI among four quartiles (7.1 %, 16.7 %, 18.4 %, and 22.4 %; P = 0.008). The hospital stay was prolonged for patients with reduced IPMI (P = 0.001). Patients in the lowest and highest quartiles had the worst and best 5-year overall survival, respectively, compared with those in the two intermediate quartiles of IPMI (67.0 %, 87.9 %, and 81.2 %, respectively; P=0.001). Multivariate analysis identified the lowest quartile of IPMI as an independent poor prognostic factor (hazard ratio, 1.88; 95 % confidence interval, 1.11-3.19; P = 0.020). CONCLUSION: Comprehensive skeletal muscle profiling, including morphometric mass and componential density on chest imaging, has the potential to refine risk stratification and prognostication in non-small cell lung cancer.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Sarcopenia , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Masculino , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/patología , Complicaciones Posoperatorias/patología , Pronóstico , Estudios Retrospectivos , Sarcopenia/diagnóstico por imagen , Sarcopenia/etiología , Sarcopenia/patología , Tomografía Computarizada por Rayos X
10.
J Thorac Cardiovasc Surg ; 163(3): 779-787.e2, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33317785

RESUMEN

OBJECTIVES: Physical biomarkers to stratify patients with lung cancer into subtypes predictive of outcome beyond tumor-related characteristics are underexplored. This study was designed to investigate the clinical utility of preoperative sarcopenia based on respiratory strength and pectoralis muscle mass to predict the risk of death. METHODS: This retrospective study included 346 consecutive patients undergoing curative-intent resection of non-small cell lung cancer from 2009 to 2013. Respiratory strength and muscle mass were assessed by peak expiratory flow rate and pectoralis muscle index (pectoralis muscle area/body mass index) using preoperative spirometry and chest axial images, respectively. Sarcopenia cutoff points were defined by gender-specific medians of peak expiratory flow rates and pectoralis muscle indices. Survival was compared between patients with sarcopenia and patients without. RESULTS: Sarcopenia was present in 98 patients (28.3%) and was significantly associated with advancing age (P < .001). Patients with sarcopenia exhibited worse 5-year overall survival compared with patients without sarcopenia (69.9% vs 87.2%, P < .001). Multivariate analysis revealed that sarcopenia was an independent adverse prognostic factor (hazard ratio, 1.88; 95% confidence interval, 1.09-3.24; P = .023) after adjustment for gender, age, smoking status, coronary heart disease, diffusing capacity for carbon monoxide, neutrophil-to-lymphocyte ratio, albumin, histologic type, and pathologic stage. CONCLUSIONS: Preoperative sarcopenia as identified by the criteria of low respiratory strength and reduced pectoralis muscle mass is significantly associated with poor overall survival. This may help to develop more individualized management strategies and optimize longitudinal care for patients.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Fuerza Muscular , Músculos Pectorales/diagnóstico por imagen , Neumonectomía , Respiración , Sarcopenia/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/fisiopatología , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/fisiopatología , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Ápice del Flujo Espiratorio , Músculos Pectorales/fisiopatología , Neumonectomía/efectos adversos , Neumonectomía/mortalidad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Sarcopenia/mortalidad , Sarcopenia/fisiopatología , Factores de Tiempo , Resultado del Tratamiento
11.
Ann Thorac Cardiovasc Surg ; 28(4): 298-301, 2022 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-33148928

RESUMEN

A 40-year-old woman with idiopathic pleuroparenchymal fibroelastosis (IPPFE) and flat chest underwent left single lung transplantation (SLT). Although she had developed over-systemic pulmonary arterial pressure (PAP) at transplantation, it was alleviated. However, her PAP gradually increased again. Her transplanted lung was well-inflated, but progression of fibrosis in her right native lung appeared to have caused a mediastinal shift, and her flat chest caused obstruction of the outflow tract of the pulmonary vein. She died of heart failure and associated infection 1.5 years after transplantation. An autopsy confirmed irreversible pulmonary arterial and venous changes in the transplanted lung, suggestive of chronic pressure overload. The flat chest associated with IPPFE can affect pulmonary circulation after SLT.


Asunto(s)
Hipertensión Pulmonar , Trasplante de Pulmón , Enfermedades Torácicas , Adulto , Femenino , Humanos , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/cirugía , Pulmón , Trasplante de Pulmón/efectos adversos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
12.
Semin Thorac Cardiovasc Surg ; 34(2): 752-759, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-33713829

RESUMEN

Lung transplantation is the only treatment for end-stage lung disease; however, donor organ shortage and intense immunosuppression limit its broad clinical impact. Bioengineering of lungs with patient-derived cells could overcome these problems. We created bioartificial lungs by seeding human-derived cells onto porcine lung matrices and performed orthotopic transplantation to assess feasibility and in vivo function. Porcine decellularized lung scaffolds were seeded with human airway epithelial cells and human umbilical vein endothelial cells. Following in vitro culture, the bioartificial lungs were orthotopically transplanted into porcine recipients with planned 1-day survival (n = 3). Lungs were assessed with histology and in vivo function. Orthotopic transplantation of cadaveric lungs was performed as control. Engraftment of endothelial and epithelial cells in the grafts were histologically demonstrated. Technically successful orthotopic anastomoses of the vasculatures and airway were achieved in all animals. Perfusion and ventilation of the lung grafts were confirmed intraoperatively. The gas exchange function was evident immediately after transplantation; PO2 gradient between pulmonary artery and vein were 178 ± 153 mm Hg in the bioartificial lung group and 183 ± 117 mm Hg in the control group. At time of evaluation 24 hours after reperfusion, the pulmonary arteries were found to be occluded with thrombus in all bioartificial lungs. Engineering and orthotopic transplantation of bioartificial lungs with human cells were technically feasible in a porcine model. Early gas exchange function was evident. Further progress in optimizing recellularization and maturation of the grafts will be necessary for sustained perfusability and function.


Asunto(s)
Trasplante de Pulmón , Andamios del Tejido , Animales , Células Endoteliales , Estudios de Factibilidad , Humanos , Pulmón/cirugía , Porcinos , Resultado del Tratamiento
14.
Surg Case Rep ; 7(1): 116, 2021 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-33970364

RESUMEN

BACKGROUND: A bronchial fistula is a relatively rare and potentially fatal complication after lung transplantation. Thoracic surgeons and pulmonologists often face challenges when selecting treatment options. We herein report an exceptional case of intrabronchial migration of a nonabsorbable hemostatic agent, which had been placed around the pulmonary artery at the time of lung transplantation, through a bronchial fistula. CASE PRESENTATION: A 61-year-old man developed respiratory distress 1 year after left single-lung transplantation for idiopathic interstitial pneumonia. Bronchoscopic examination revealed an apparent foreign body protruding from the mediastinum into the distal site of the bronchial anastomosis. The foreign body was easily removed bronchoscopically and appeared to be a hemostatic agent that had been placed during the previous lung transplantation. The patient developed a similar clinical episode and finally developed hemoptysis. Computed tomography revealed a foreign body located between the bronchus and pulmonary artery, partially protruding into the bronchial lumen. Given the possibility of a bronchopulmonary arterial fistula, surgical treatment was performed. The foreign body was located between the bronchus and left pulmonary artery and was easily removed. Multiple bronchial fistulas were found, and all were closed with direct sutures. Bypass grafting of the left pulmonary artery was then performed, initially with a homograft but eventually with an extended polytetrafluoroethylene graft. The patient was finally discharged 5 months after the surgery. CONCLUSION: We experienced an extremely rare case of intrabronchial migration of hemostatic agents used during the previous lung transplantation through a bronchial fistula, which were successfully managed by direct bronchial closure and bypass grafting of the left pulmonary artery.

15.
Surg Case Rep ; 7(1): 79, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33796902

RESUMEN

BACKGROUND: Bronchial necrosis is a rare but fatal complication after radiation therapy. Because of the anatomical complexity and rarity of this condition, determining the most appropriate management for individual patients is extremely challenging. Lung autotransplantation is a surgical technique that has been applied to hilar neoplastic lesions to preserve pulmonary function and avoid pneumonectomy. We herein report a case of bronchial necrosis secondary to radiotherapy that was treated with lung autotransplantation. CASE PRESENTATION: A 46-year-old man developed broad necrosis and infection of the right bronchus secondary to previous stereotactic body-radiation therapy. This treatment was supplied close to a right hilar metastatic pulmonary tumor derived from a mediastinal malignant germ cell tumor that had been surgically resected with the left phrenic nerve. The bronchial necrosis accompanied by infection with Aspergillus fumigatus was progressive despite antibiotics and repetitive bronchoscopic debridement. Because of the patient's critical condition and limited pulmonary function, right lung autotransplantation with preservation of the right basal segment was selected. An omental flap was placed around the bronchial anastomosis to prevent later complications. The postoperative course involved multiple complications including contralateral pneumonia and delayed wound healing at the bronchial anastomosis with resultant stenosis, the latter of which was overcome by placement of a silicone stent. The patient was discharged 5 months postoperatively. Three months after discharge, however, the patient developed hemoptysis and died of bronchopulmonary arterial fistula formation. CONCLUSIONS: We experienced an extremely challenging case of bronchial necrosis secondary to radiotherapy. The condition was managed with lung autotransplantation and omental wrapping; however, the treatment success was temporary and the patient eventually died of bronchopulmonary arterial fistula formation. This technique seems to be a feasible option for locally advanced refractory bronchial necrosis, although later complications can still be fatal.

16.
Semin Thorac Cardiovasc Surg ; 33(1): 263-271, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32348880

RESUMEN

The use of bioartificial lungs may represent a breakthrough for the treatment of end-stage lung disease. The present study aimed to evaluate the feasibility of transplanting bioengineered lungs created from autologous cells. Porcine decellularized lung scaffolds were seeded with porcine recipient-derived airway and vascular cells. The porcine recipient-derived cells were collected from lung tissue obtained by pulmonary wedge resection. Following culture of autologous cells in the scaffolds, the resulting grafts were unilaterally transplanted into porcine recipients (n = 3). Allograft left unilateral lung transplantation was performed in the control group (n = 3). Left unilateral transplantation of decellularized grafts was also performed in a separate control group (n = 2). In vivo functions were assessed for 2 hours after transplantation. Histologic evaluation and immunostaining showed the presence of airway and vascular cells in the bioengineered lungs. No animals survived in the decellularized transplant group, whereas all animals survived in the bioengineered transplant and allotransplant groups. However, bioengineered lung grafts showed marked bullous changes. The oxygen exchange was comparable between the bioengineered lung graft transplant and allograft transplant groups. However, the carbon dioxide gas exchange of the bioengineered lung graft transplant group was significantly lower than that of the allograft transplant group at 2 hours after transplantation (4.10 ± 0.87 mm Hg vs 24.7 ± 10.1 mm Hg, P = 0.02). Transplantation of bioartificial lung grafts created from autologous cells was feasible in the super-acute phase. However, bullous changes and poor carbon dioxide gas exchange remain limitations of this method.


Asunto(s)
Trasplante de Pulmón , Pulmón , Animales , Modelos Animales de Enfermedad , Pulmón/cirugía , Trasplante de Pulmón/efectos adversos , Oxígeno , Porcinos
17.
J Immunother Cancer ; 8(2)2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32948652

RESUMEN

BACKGROUND: Not all non-small cell lung cancer (NSCLC) patients possess drug-targetable driver mutations, and response rates to immune checkpoint blockade therapies also remain unsatisfactory. Therefore, more effective treatments are still needed. Here, we report the results of a phase 2 clinical trial of adoptive cell therapy using zoledronate-expanded autologous Vγ9Vδ2 T-cells for treatment-refractory NSCLC. METHODS: NSCLC patients who had undergone at least two regimens of standard chemotherapy for unresectable disease or had had at least one treatment including chemotherapy or radiation for recurrent disease after surgery were enrolled in this open-label, single-arm, multicenter, phase 2 study. After preliminary testing of Vγ9Vδ2 T-cell proliferation, autologous peripheral blood mononuclear cells were cultured with zoledronate and IL-2 to expand the Vγ9Vδ2 T-cells. Cultured cells (>1×109) were intravenously administered every 2 weeks for six injections. The primary endpoint of this study was progression-free survival (PFS), and secondary endpoints included overall survival (OS), best objective response rate (ORR), disease control rate (DCR), safety and immunomonitoring. Clinical efficacy was defined as median PFS significantly >4 months. RESULTS: Twenty-five patients (20 adenocarcinoma, 4 squamous cell carcinoma and 1 large cell carcinoma) were enrolled. Autologous Vγ9Vδ2 T-cell therapy was administered to all 25 patients, of which 16 completed the foreseen course of 6 injections of cultured cells. Median PFS was 95.0 days (95% CI 73.0 to 132.0 days); median OS was 418.0 days (179.0-479.0 days), and best overall responses were 1 partial response, 16 stable disease (SD) and 8 progressive disease. ORR and DCR were 4.0% (0.1%-20.4%) and 68.0% (46.5%-85.1%), respectively. Severe adverse events developed in nine patients, mostly associated with disease progression. In one patient, pneumonitis and inflammatory responses resulted from Vγ9Vδ2 T-cell infusions, together with the disappearance of a massive tumor. CONCLUSIONS: Although autologous Vγ9Vδ2 T-cell therapy was well tolerated and may have an acceptable DCR, this trial did not meet its primary efficacy endpoint. TRIAL REGISTRATION NUMBER: UMIN000006128.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Ácido Zoledrónico/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ácido Zoledrónico/farmacología
18.
Lung Cancer ; 147: 71-76, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32673829

RESUMEN

OBJECTIVES: The impact of sarcopenia on the outcome in patients following resection of non-small cell lung cancer is yet to be fully determined. This study aimed to evaluate the clinical utility of a computed tomography-based pectoralis muscle assessment, which reflects sarcopenia, to predict the risk of postoperative outcomes. MATERIALS AND METHODS: This retrospective study included 347 consecutive patients undergoing curative-intent resection of non-small cell lung cancer from 2009 to 2013. The pectoralis muscle index (pectoralis muscle area/body mass index) was assessed at the level of the fourth thoracic vertebra on chest axial images. The primary outcomes were compared between the lowest gender-specific quintile (sarcopenia) and the other quintiles according to the index. The prognostic significance of low pectoralis muscle index was calculated by the Cox proportional hazards regression model. A propensity score matching analysis was performed to adjust the differences in clinical characteristics. RESULTS: Sixty-nine patients were identified with sarcopenia according to the lowest gender-specific quintile of pectoralis muscle index. Patients with sarcopenia exhibited worse 5-year overall survival rate compared with patients without sarcopenia (64.2 % vs. 86.7 %, P < 0.001). Even in stage I non-small cell lung cancer, the rate of 5-year overall survival in the sarcopenia group was lower than that in the non-sarcopenia group (74.2 % vs. 92.4 %, P = 0.001). Multivariate analysis revealed that low pectoralis muscle index was independently associated with adverse overall survival (hazard ratio: 2.09, 95 % confidence interval: 1.20-3.62, P = 0.009). After propensity score matching, the prognostic impact of sarcopenia based on low pectoralis muscle index was also robust for overall survival (hazard ratio: 3.23, 95 % confidence interval: 1.38-7.60, P = 0.007). CONCLUSIONS: Low pectoralis muscle index was significantly associated with poor long-term outcomes in patients with localized non-small cell lung cancer after curative surgery. This may help assist preoperative risk stratification and longitudinal management after surgery.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Sarcopenia , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Músculo Esquelético/patología , Músculos Pectorales/cirugía , Pronóstico , Estudios Retrospectivos , Sarcopenia/diagnóstico , Tomografía Computarizada por Rayos X
19.
Gen Thorac Cardiovasc Surg ; 68(12): 1418-1424, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32488832

RESUMEN

OBJECTIVE: ɤ-glutamyltranspeptidase is an enzyme expressed in various malignancies including lung cancer. It rapidly activates non-fluorescent ɤ-glutamyl hydroxymethyl rhodamine green to highly fluorescent hydroxymethyl rhodamine green. The resultant tumor fluorescence is therefore an indicator of cellular ɤ-glutamyltranspeptidase activity. We have explored the use of ɤ-glutamyl hydroxymethyl rhodamine green as an intraoperative imaging tool for visualizing cancers. Herein, we evaluated the potential of the tumor fluorescence as a postoperative prognostic indicator. METHODS: We included patients with non-small cell lung cancer who had undergone radical resection from 2012 to 2014 in the study. We assessed the fluorescence intensity of the resected tumor and normal lung tissue by ex vivo imaging using ɤ-glutamyl hydroxymethyl rhodamine green. RESULTS: Sixty-seven patients were eligible for the study (adenocarcinomas, n = 44; squamous cell carcinoma, n = 14; other histologies, n = 8). The pathological stages were I, II, III, and IV in 39, 15, 12, and 1 patient, respectively. Based on the fluorescence of the tumor tissue, the patients were divided into high fluorescence (n = 33) and low fluorescence (n = 34) groups. The 5-year overall survival rate was significantly higher in the high fluorescence group (72.7%) compared to the low fluorescence group (47.1%, P = 0.025). Similarly, pathological stage I patients of the high fluorescence group had higher 5-year overall survival (85.7% vs. 44.4%, P = 0.009) and recurrence-free survival (76.2% vs. 44.4% P = 0.044) rates compared to those of the low fluorescence group. CONCLUSIONS: ɤ-glutamyl hydroxymethyl rhodamine green fluorescence is a good postoperative prognostic indicator in patients with non-small cell lung cancer.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Fluorescencia , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Pronóstico , Rodaminas
20.
Kyobu Geka ; 72(12): 997-1000, 2019 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-31701910

RESUMEN

We report a case of giant solitary fibrous tumor( SFT) of the pleura postoperatively complicated with probable reexpansion pulmonary edema and atrial fibrillation. An 85-year-old woman was diagnosed to have a 13 cm sized intrathoracic neoplasm. Upon thoracotomy, the tumor was found to pedunculate from the right lung with no direct invasion to the surrounding structures. Complete resection of the tumor and expansion of the right lung was obtained. Histopathology revealed the tumor was a benign SFT arising from the visceral pleura. An infiltrative shadow in the right lower lung field soon after the surgery suggested a reexpansion pulmonary edema, which eventually recovered within a week. The patient suffered from a refractory atrial fibrillation that led to a congestive heart failure requiring an intensive medical treatment. It is emphasized that thoracic surgeons should be aware of these postoperative complications in treating such a case like this.


Asunto(s)
Fibrilación Atrial , Neoplasias Pleurales , Edema Pulmonar , Tumor Fibroso Solitario Pleural , Anciano de 80 o más Años , Femenino , Humanos , Pleura , Tumor Fibroso Solitario Pleural/cirugía , Tomografía Computarizada por Rayos X
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