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1.
JAMA Surg ; 158(11): 1159-1166, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37585215

RESUMEN

Importance: The COVID-19 pandemic led to the use of lung transplant as a lifesaving therapy for patients with irreversible lung injury. Limited information is currently available regarding the outcomes associated with this treatment modality. Objective: To describe the outcomes following lung transplant for COVID-19-related acute respiratory distress syndrome or pulmonary fibrosis. Design, Setting, and Participants: In this cohort study, lung transplant recipient and donor characteristics and outcomes following lung transplant for COVID-19-related acute respiratory distress syndrome or pulmonary fibrosis were extracted from the US United Network for Organ Sharing database from March 2020 to August 2022 with a median (IQR) follow-up period of 186 (64-359) days in the acute respiratory distress syndrome group and 181 (40-350) days in the pulmonary fibrosis group. Overall survival was calculated using the Kaplan-Meier method. Cox proportional regression models were used to examine the association of certain variables with overall survival. Exposures: Lung transplant following COVID-19-related acute respiratory distress syndrome or pulmonary fibrosis. Main Outcomes and Measures: Overall survival and graft failure rates. Results: Among 385 included patients undergoing lung transplant, 195 had COVID-19-related acute respiratory distress syndrome (142 male [72.8%]; median [IQR] age, 46 [38-54] years; median [IQR] allocation score, 88.3 [80.5-91.1]) and 190 had COVID-19-related pulmonary fibrosis (150 male [78.9%]; median [IQR] age, 54 [45-62]; median [IQR] allocation score, 78.5 [47.7-88.3]). There were 16 instances of acute rejection (8.7%) in the acute respiratory distress syndrome group and 15 (8.6%) in the pulmonary fibrosis group. The 1-, 6-, and 12- month overall survival rates were 0.99 (95% CI, 0.96-0.99), 0.95 (95% CI, 0.91-0.98), and 0.88 (95% CI, 0.80-0.94) for the acute respiratory distress syndrome cohort and 0.96 (95% CI, 0.92-0.98), 0.92 (95% CI, 0.86-0.96), and 0.84 (95% CI, 0.74-0.90) for the pulmonary fibrosis cohort. Freedom from graft failure rates were 0.98 (95% CI, 0.96-0.99), 0.95 (95% CI, 0.90-0.97), and 0.88 (95% CI, 0.79-0.93) in the 1-, 6-, and 12-month follow-up periods in the acute respiratory distress cohort and 0.96 (95% CI, 0.92-0.98), 0.93 (95% CI, 0.87-0.96), and 0.85 (95% CI, 0.74-0.91) in the pulmonary fibrosis cohort, respectively. Receiving a graft from a donor with a heavy and prolonged history of smoking was associated with worse overall survival in the acute respiratory distress syndrome cohort, whereas the characteristics associated with worse overall survival in the pulmonary fibrosis cohort included female recipient, male donor, and high recipient body mass index. Conclusions and Relevance: In this study, outcomes following lung transplant were similar in patients with irreversible respiratory failure due to COVID-19 and those with other pretransplant etiologies.


Asunto(s)
COVID-19 , Trasplante de Pulmón , Fibrosis Pulmonar , Síndrome de Dificultad Respiratoria , Humanos , Masculino , Femenino , Persona de Mediana Edad , Fibrosis Pulmonar/cirugía , Fibrosis Pulmonar/complicaciones , Fibrosis Pulmonar/mortalidad , Estudios de Cohortes , Pandemias , COVID-19/complicaciones , Trasplante de Pulmón/mortalidad , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/cirugía
2.
Surg Endosc ; 37(6): 4123-4130, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36754871

RESUMEN

BACKGROUND: Nissen fundoplication is considered the cornerstone surgical treatment for hiatal hernia repair. Belsey Mark IV (BMIV) transthoracic fundoplication is an alternative approach that is rarely utilized in today's minimally invasive era. This study aims to summarize the safety and efficacy of BMIV and to compare it with Nissen fundoplication. METHODS: We searched MEDLINE, Scopus, and Cochrane Library databases for single arm and comparative studies published by March 31st, 2022, according to PRISMA statement. Inverse-variance weights were used to estimate the proportion of patients experiencing the studied outcome and random-effects meta-analyses were performed. RESULTS: 17 studies were identified, incorporating 2136 and 638 patients that underwent Belsey Mark IV or Nissen fundoplication, respectively. A total of 13.8% (95% CI: 9.6-18.6) of the patients that underwent fundoplication with the BMIV technique had non-resolution of their symptoms and 3.5% (95% CI: 2.0-5.4) required a reoperation. Overall, 14.8% (95% CI: 9.5-20.1) of the BMIV arm patients experienced post-operative complications, 5.0% (95% CI: 2.0-9.0) experienced chronic postoperative pain and 6.9% (95% CI: 3.1-11.9) had a hernia recurrence. No statistically significant difference was observed between Belsey Mark IV and Nissen fundoplication in terms of post-interventional non-resolution of symptoms (odds ratio [OR]: 1.49 [95% Confidence Interval (95%CI):0.6-4.0]; p = 0.42), post-operative complications (OR:0.83, 95%CI: 0.5-1.5, p = 0.54) and in-hospital mortality (OR:0.69, 95%CI: 0.13-3.80, p = 0.67). Belsey Mark IV arm had significantly lower reoperation rates compared to Nissen arm (OR:0.28, 95%CI: 0.1-0.7, p = 0.01). CONCLUSIONS: BMIV fundoplication is a safe and effective but technically challenging. The BMIV technique may offer benefits to patients compared to the laparoscopic Nissen fundoplication. These benefits, however, are challenged by the increased morbidity of a thoracotomy.


Asunto(s)
Hernia Hiatal , Laparoscopía , Humanos , Fundoplicación/métodos , Resultado del Tratamiento , Estómago , Esófago , Hernia Hiatal/complicaciones , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Laparoscopía/métodos
3.
Ann Thorac Surg ; 114(5): e319-e320, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35085520

RESUMEN

Our case is a 73-year-old male patient with persistent ventricular tachycardia leading to recent syncopal episodes despite ventricular tachycardia ablation and multiple stellate ganglion blocks, frequent hospital admissions, and acute on chronic congestive heart failure requiring an intraaortic balloon pump. The decision was made to proceed with left ventricular assist device placement and bilateral sympathectomies simultaneously. After performing the sternotomy and widely opening bilateral pleural spaces, the lower third of the stellate ganglia to the level of T4 was removed using a combination of the thoracoscope with the sternotomy incision. The use of thoracoscopy greatly assisted with visualization during the sympathectomy.


Asunto(s)
Corazón Auxiliar , Taquicardia Ventricular , Masculino , Humanos , Anciano , Esternotomía , Simpatectomía , Taquicardia Ventricular/cirugía , Toracoscopía
4.
Ann Thorac Surg ; 111(2): e133-e134, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32949610

RESUMEN

We have modified the HeartMate 3 (Abbott, Abbott Park, IL) implantation technique to better suit our patient population. This modification optimizes the placement of the HeartMate 3 sewing cuff and allows passage of the suture transmurally from endocardium to epicardium in a "cut then sew" technique. We believe this affords a superior seal and protection from tearing friable myocardium.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos/métodos , Insuficiencia Cardíaca/cirugía , Ventrículos Cardíacos/cirugía , Corazón Auxiliar , Implantación de Prótesis/métodos , Humanos
5.
J Thorac Dis ; 13(11): 6323-6330, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34992812

RESUMEN

BACKGROUND: Esophagectomies and repair of esophageal perforations are operations used for a variety of clinical indications. Anastomotic leaks are a major post-operative complication after these procedures. At our institution, we routinely use grape juice to detect esophageal leaks in the post-operative setting in addition to other standard imaging modalities. We hypothesize that grape juice can provide similar diagnostic sensitivity and specificity to other modalities for leak detection. METHODS: A retrospective review of all patients who underwent an esophagectomy or repair of esophageal perforations from 2013-2019 by the thoracic surgery service at our institution was performed. All patients underwent a barium swallow study, CT imaging or upper endoscopy, as well as ingesting purple grape juice on post-operative day 5 or greater. Purple grape juice observed in the tube thoracostomy drainage system was identified as a positive esophageal leak. RESULTS: Sixty-four patients were included in the study period (25% female, 88% white, median age 62 years old). Sixty-three patients had both a barium swallow study and grape juice test, while one patient underwent CT imaging and grape juice study. Grape juice test sensitivity and specificity were found to be 80% and 98.3%, respectively. CONCLUSIONS: This pilot study demonstrates the effectiveness of using grape juice in detecting esophageal leaks after esophageal operations in patients with tube thoracostomies. Grape juice may be cheaper and potentially less morbid than other studies performed to detect esophageal leaks. Further research is needed to justify the increased use of grape juice in patients who undergo esophageal operations.

6.
J Thorac Dis ; 13(11): 6536-6549, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34992833

RESUMEN

Transplantation of any organ into a recipient requires a donor. Lung transplant has a long history of an inadequate number of suitable donors to meet demand, leading to deaths on the waiting list annually since national data was collected, and strict listing criteria. Before the Uniform Determination of Death Act (UDDA), passed in 1980, legally defined brain death in the U.S., all donors for lung transplant came from sudden death victims [uncontrolled Donation after Circulatory Death donors (uDCDs)] in the recipient's hospital emergency department. After passage of the UDDA, uDCDs were abandoned to Donation after Brain Death donors (DBDs)-perhaps prematurely. Compared to livers and kidneys, many DBDs have lungs that are unsuitable for transplant, due to aspiration pneumonia, neurogenic pulmonary edema, trauma, and the effects of brain death on lung function. Another group of donors has become available-patients with a devastating irrecoverable brain injury that do not meet criteria for brain death. If a decision is made by next-of-kin (NOK) to withdraw life support and allow death to occur by asphyxiation, with NOK consent, these individuals can have organs recovered if death occurs relatively quickly after cessation of mechanical ventilation and maintenance of their airway. These are known as controlled Donation after Circulatory Death donors (cDCDs). For a variety of reasons, in the U.S., lungs are recovered from cDCDs at a much lower rate than kidneys and livers. Ex-vivo lung perfusion (EVLP) in the last decade has had a modest impact on increasing the number of lungs for transplant from DBDs, but may have had a larger impact on lungs from cDCDs, and may be indispensable for safe transplantation of lungs from uDCDs. In the next decade, DCDs may have a substantial impact on the number of lung transplants performed in the U.S. and around the world.

7.
Semin Thorac Cardiovasc Surg ; 33(2): 547-555, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32979480

RESUMEN

Few studies examine outcomes by surgical approach in non-small-cell lung cancer (NSCLC) with N2 disease. We examined time trends in surgical approach and outcomes among patients undergoing minimally invasive (MIS, robotic and video-assisted thoracoscopic surgery [VATS]) vs open lobectomy in this patient population. We performed a retrospective analysis of patients from the National Cancer Database diagnosed with clinical Stage IIIA-N2 NSCLC from 2010 to 2016. We examined the yearly proportion of MIS vs open resections. Multivariable regression was used to assess the association of surgical approach with length of stay, unplanned readmissions, 30-day and 90-day mortality. Multivariable Cox proportional hazards modeling was used to assess the association of surgical approach with 5-year overall mortality. We identified 5741 patients who underwent lobectomy for Stage IIIA-N2 NSCLC (459 robotic, 1403 VATS, 3879 open). From 2010 to 2016, the proportion of minimally invasive procedures increased from 20% to 45%. MIS patients, on average, stayed 1 day less in the hospital (95% confidence interval [CI] 0.7, 1.5) and had lower odds of 90-day (odds ratio [OR] 0.74; 95% CI 0.54, 0.99) and 5-year mortality (OR 0.82; 95% CI 0.75, 0.91), compared to open resections. There was no difference in odds of readmission by surgical approach (OR 0.97; 95% CI 0.71, 1.33). Among MIS procedures, robotic resections had lower odds of 90-day mortality (OR 0.42; 95% CI 0.18, 0.97) than VATS. Among patients undergoing lobectomy for locally advanced N2 NSCLC robotic and VATS techniques appear safe and effective compared to open surgery and may offer short- and long-term advantages.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Procedimientos Quirúrgicos Robotizados , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Humanos , Neoplasias Pulmonares/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos , Neumonectomía/efectos adversos , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Cirugía Torácica Asistida por Video/efectos adversos
8.
Ann Thorac Surg ; 111(3): 1036-1043, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-32805268

RESUMEN

BACKGROUND: Enhanced recovery after surgery (ERAS) is an evidence-based, multidisciplinary perioperative care model shown to reduce complications and hospital length of stay (LOS). While some thoracic ERAS studies were inconclusive, others demonstrated that ERAS improves patient outcomes after lung resections and provides more cost-effective care. We aimed to investigate the effects of preliminary implementation of an ERAS protocol, in comparison with conventional care, on lung resection outcomes at a single academic institution. METHODS: In this observational study, adult patients undergoing lung resections during the pre-ERAS (April 2014 to September 2015) and post-ERAS (January 2016 to May 2017) periods were identified. Relevant demographic, preoperative, anesthesia, and surgical variables were collected. Pre-ERAS and post-ERAS cohorts were compared in terms of hospital LOS, postoperative complications, and 30-day outcomes. RESULTS: We identified 264 patients, half in each cohort. Pre-ERAS and post-ERAS groups were similar with respect to age, race, and comorbidities. There were no significant differences in LOS, complications, 30-day readmission and mortality rates, or patient-reported outcomes. Of the patients with prolonged LOS, 31% had pulmonary complications, almost half of which were prolonged air leaks. ERAS adherence rate was approximately 60%. CONCLUSIONS: In the first year of implementation, median LOS, complications, and 30-day outcomes did not differ significantly between the pre-ERAS and post-ERAS groups. Prolonged air leaks commonly led to prolonged LOS; therefore, thoracic ERAS protocols could include interventions to reduce air leak and consideration for discharging patients with chest tubes placed to Heimlich valves. Buy-in and adherence to a new protocol are necessary for implementation to be effective.


Asunto(s)
Recuperación Mejorada Después de la Cirugía , Enfermedades Pulmonares/cirugía , Atención Perioperativa/métodos , Neumonectomía , Anciano , Femenino , Estudios de Seguimiento , Humanos , Tiempo de Internación/tendencias , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
9.
J Thorac Dis ; 12(10): 5281-5288, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33209362

RESUMEN

BACKGROUND: Flail chest and severely displaced rib fractures due to blunt trauma can be associated with intrathoracic injuries. At our institution, two thoracic surgeons perform all surgical stabilization of rib fractures (SSRF): one performs routine uniportal thoracoscopy (R-VATS) at the time of SSRF and the other for only select cases (S-VATS). In this pilot study, we hypothesized that R-VATS at the time of SSRF identifies and addresses intrathoracic injuries not seen on imaging and may impact patient outcomes. METHODS: A retrospective review of all patients who underwent SSRF from 2013-2019 at our institution was performed for severely displaced rib fractures or flail chest. Data collected included demographics, imaging results, treatment strategy, and operative findings. RESULTS: Ninety-nine patients underwent SSRF. Uniportal thoracoscopy was performed on 69% of these patients. When thoracoscopy was performed, 31 additional injuries were identified. R-VATS identified 23 additional intrathoracic findings at time of thoracoscopy not seen on CT scan compared to 8 findings in the S-VATS group (P=0.367). At 3 months follow-up, one empyema and one diaphragmatic hernia required reoperation-neither of which underwent thoracoscopy at time of SSRF. There were no differences in LOS, operative times, and overall mortality between the SSRF/thoracoscopy and SSRF only groups. CONCLUSIONS: R-VATS at the time of SSRF did not identify a statistically significant greater number of occult intrathoracic injuries compared to S-VATS. R-VATS was not associated with increased operative time, LOS, and mortality. Further study is needed to determine if there is benefit to R-VATS in patients meeting requirements for rib fracture repair.

10.
Am Surg ; 86(11): 1553-1555, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32804549

RESUMEN

A term female infant with tracheoesophageal fistula (TEF) and esophageal atresia (EA) underwent primary operative repair that failed with 3 TEF recurrences, which all presented with feeding and respiratory issues. Recurrences were managed with reoperation and an interpositional flap of pleura and a flap of intercostal muscle on 2 separate occasions. The third recurrence was managed with complete dissection of the esophagus prior to the division of the fistula and the interposition of an omental flap between the esophageal and tracheal repair. We present the use of a viable omental flap and complete esophageal mobilization to prevent subsequent TEF recurrences and avoid the additional morbidity of reconstructive surgery.


Asunto(s)
Epiplón/cirugía , Colgajos Quirúrgicos/cirugía , Fístula Traqueoesofágica/cirugía , Atresia Esofágica/cirugía , Esófago/cirugía , Femenino , Humanos , Recién Nacido , Recurrencia , Reoperación , Tráquea/cirugía
12.
J Thorac Dis ; 11(8): 3650-3658, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31559073

RESUMEN

BACKGROUND: Approximately twenty percent of lymph node (LN) negative non-small cell lung cancer (NSCLC) patients who undergo curative intent surgery have pan-cytokeratin immunohistochemistry (IHC)-detectable occult micro-metastases (MMs) in resected LNs. The presence of the MMs in NSCLC is associated worsened outcomes. As a substantial proportion of NSCLC LN staging is conducted using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), we sought to determine the frequency of detection of occult MMs in EBUS-TBNA specimens and to evaluate the impact of MMs on progression-free and overall survival. METHODS: We performed retrospective IHC staining for pan-cytokeratin of EBUS-TBNA specimens previously deemed negative by a cytopathologist based on conventional hematoxylin and eosin staining. The results were correlated with clinical variables, including survival outcomes. RESULTS: Of 887 patients screened, 44 patients were identified meeting inclusion criteria with sufficient additional tissue for testing. With respect to the time of the EBUS-TBNA procedure, 52% of patients were clinical stage I, 34% clinical stage II, and clinical 14% stage IIIa NSCLC. Three patients (6.8%) were found to have cytokeratin positive MMs. All 3 MMs detected were at N2 LN stations. The presence of MMs was associated with significantly decreased progression-free (median 210 vs. 1,293 days, P=0.0093) and overall survival (median 239 vs. 1,120 days, P=0.0357). CONCLUSIONS: Occult LN MMs can be detected in EBUS-TBNA specimens obtained during staging examinations and are associated with poor clinical outcomes. If prospectively confirmed, these results have significant implications for EBUS-TBNA specimen analyses and possibly for the NSCLC staging paradigm.

14.
Lung Cancer ; 86(2): 255-61, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25224251

RESUMEN

BACKGROUND: Brain metastases are one of the most malignant complications of lung cancer and constitute a significant cause of cancer related morbidity and mortality worldwide. Recent years of investigation suggested a role of LKB1 in NSCLC development and progression, in synergy with KRAS alteration. In this study, we systematically analyzed how LKB1 and KRAS alteration, measured by mutation, gene expression (GE) and copy number (CN), are associated with brain metastasis in NSCLC. MATERIALS AND METHODS: Patients treated at University of North Carolina Hospital from 1990 to 2009 with NSCLC provided frozen, surgically extracted tumors for analysis. GE was measured using Agilent 44,000 custom-designed arrays, CN was assessed by Affymetrix GeneChip Human Mapping 250K Sty Array or the Genome-Wide Human SNP Array 6.0 and gene mutation was detected using ABI sequencing. Integrated analysis was conducted to assess the relationship between these genetic markers and brain metastasis. A model was proposed for brain metastasis prediction using these genetic measurements. RESULTS: 17 of the 174 patients developed brain metastasis. LKB1 wild type tumors had significantly higher LKB1 CN (p<0.001) and GE (p=0.002) than the LKB1 mutant group. KRAS wild type tumors had significantly lower KRAS GE (p<0.001) and lower CN, although the latter failed to be significant (p=0.295). Lower LKB1 CN (p=0.039) and KRAS mutation (p=0.007) were significantly associated with more brain metastasis. The predictive model based on nodal (N) stage, patient age, LKB1 CN and KRAS mutation had a good prediction accuracy, with area under the ROC curve of 0.832 (p<0.001). CONCLUSION: LKB1 CN in combination with KRAS mutation predicted brain metastasis in NSCLC.


Asunto(s)
Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Genes ras , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , Proteínas Serina-Treonina Quinasas/genética , Quinasas de la Proteína-Quinasa Activada por el AMP , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Análisis Mutacional de ADN , Femenino , Dosificación de Gen , Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Oportunidad Relativa , Pronóstico , Curva ROC , Factores de Riesgo
15.
Ann Thorac Surg ; 96(2): 403-10, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23731611

RESUMEN

BACKGROUND: Endobronchial ultrasonography with transbronchial needle aspiration (EBUS-TBNA) has been shown to be equivalent to mediastinoscopy in lung cancer staging for mediastinal node involvement. Rapid on-site evaluation (ROSE) to determine the adequacy of nodal sampling has been claimed to be beneficial. METHODS: A retrospective evaluation was performed in 170 patients who underwent EBUS-TBNA from July 2008 to May 2011. The patients were classified as having either high or low pretest probability for mediastinal disease based on history and radiographic imaging. ROSE was compared with the final pathology reports based on slides and cell blocks. RESULTS: One hundred thirty-one (77%) patients were classified as being in the high pretest cohort based on clinical staging. Of these, 101 (77%) patients had adequate tissue sampling based on ROSE, with 70 (69%) patients having positive mediastinal disease. In the 30 (23%) patients who had inadequate tissue by ROSE, the final analysis of all the prepared slides and cell blocks allowed for a diagnosis in all but 8 patients. The sensitivity and specificity of ROSE in the high pretest probability cohort were 89.5% and 96.4%, respectively, whereas the overall sensitivity and specificity of EBUS-TBNA was 92.1% and 100%, respectively. Despite having inadequate tissue on ROSE in 30 of 131 patients, sufficient tissue was available on final analysis for diagnosis in 22 of 30 patients. CONCLUSIONS: ROSE does not impact clinical decision making if a thorough mediastinal staging using EBUS is performed. Despite inadequate tissue sampling assessment by ROSE, a final diagnosis was made in most patients, potentially avoiding an additional surgical procedure to prove mediastinal disease.


Asunto(s)
Broncoscopía , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias/métodos , Estudios Retrospectivos , Factores de Tiempo
16.
PLoS One ; 7(5): e36530, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22590557

RESUMEN

BACKGROUND: Lung adenocarcinoma (LAD) has extreme genetic variation among patients, which is currently not well understood, limiting progress in therapy development and research. LAD intrinsic molecular subtypes are a validated stratification of naturally-occurring gene expression patterns and encompass different functional pathways and patient outcomes. Patients may have incurred different mutations and alterations that led to the different subtypes. We hypothesized that the LAD molecular subtypes co-occur with distinct mutations and alterations in patient tumors. METHODOLOGY/PRINCIPAL FINDINGS: The LAD molecular subtypes (Bronchioid, Magnoid, and Squamoid) were tested for association with gene mutations and DNA copy number alterations using statistical methods and published cohorts (n = 504). A novel validation (n = 116) cohort was assayed and interrogated to confirm subtype-alteration associations. Gene mutation rates (EGFR, KRAS, STK11, TP53), chromosomal instability, regional copy number, and genomewide DNA methylation were significantly different among tumors of the molecular subtypes. Secondary analyses compared subtypes by integrated alterations and patient outcomes. Tumors having integrated alterations in the same gene associated with the subtypes, e.g. mutation, deletion and underexpression of STK11 with Magnoid, and mutation, amplification, and overexpression of EGFR with Bronchioid. The subtypes also associated with tumors having concurrent mutant genes, such as KRAS-STK11 with Magnoid. Patient overall survival, cisplatin plus vinorelbine therapy response and predicted gefitinib sensitivity were significantly different among the subtypes. CONCLUSIONS/ SIGNIFICANCE: The lung adenocarcinoma intrinsic molecular subtypes co-occur with grossly distinct genomic alterations and with patient therapy response. These results advance the understanding of lung adenocarcinoma etiology and nominate patient subgroups for future evaluation of treatment response.


Asunto(s)
Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Inestabilidad Cromosómica , Metilación de ADN , ADN de Neoplasias , Dosificación de Gen , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Mutación , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/terapia , Anciano , Estudios de Cohortes , ADN de Neoplasias/genética , ADN de Neoplasias/metabolismo , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Tasa de Supervivencia
17.
Ann Thorac Surg ; 91(3): 860-3; discussion 863-4, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21353015

RESUMEN

BACKGROUND: The use of fibrinolytics has been described for the treatment of complex pleural processes. This has evolved from streptokinase to urokinase to alteplase. Intrapleural fibrinolysis has added an alternative to surgical intervention in patients with complex pleural processes. This study describes the use of alteplase as an alternative to surgical intervention for these processes. METHODS: From December 2004 to March 2009, 118 patients required alteplase for complex pleural processes. The type of tube thoracostomy, pleural process, antithrombotic type, international normalized ratio, prothrombin time, partial thromboplastin time, platelets, doses, and outcomes were reviewed for each patient. Complications and the need for additional interventions were evaluated. RESULTS: Patients received one to eight doses of intrapleural alteplase through a tube thoracostomy. Indications for intrapleural alteplase were empyema (n = 32; 27.1%), loculated pleural effusion (n = 44; 37.3%), hemothorax (n = 13; 11.0%), parapneumonic effusion (n = 25; 21.2%), and malignant effusion (n = 6; 5.1%). The success rate was 86.4% (102 of 118 patients). The incidence of bleeding was 8.5% (n = 10). Binary analysis did not demonstrate an increase in bleeding with abnormal coagulation variables. Of the patients with a bleeding complication, 7 required operative interventions. Twenty (16.9%) required a second tube thoracostomy for incomplete evacuation of the pleural process. Nine (7.6%) required an operative intervention for incomplete evacuation of the pleural process. CONCLUSIONS: Intrapleural alteplase appears to be effective in treating complex parapneumonic processes. Systemic anticoagulation, prothrombin time, partial thromboplastin time, international normalized ratio, and platelet count do not appear to be risk factors for bleeding complications. One or two doses of alteplase appear most successful.


Asunto(s)
Fibrinolíticos/administración & dosificación , Enfermedades Pleurales/terapia , Toracostomía/instrumentación , Activador de Tejido Plasminógeno/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Cavidad Pleural , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
18.
Ann Thorac Surg ; 90(6): 1967-73; discussion 1973-4, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21095347

RESUMEN

BACKGROUND: Applications to cardiothoracic training programs have declined dramatically. Increased effort in recruiting trainees is paramount. In this study, we test our hypothesis that mentored instruction on cardiothoracic simulators will enhance the interest of junior medical students in cardiothoracic surgery. METHODS: First- and second-year medical students were recruited from a "surgery interest group" to receive mentored instruction on high-fidelity cardiothoracic simulators. Before and after simulation assessment tools were used to assess attitudes toward simulation, general surgery, and cardiothoracic surgery. RESULTS: Forty-four medical students participated in the study. Although 80% of the students were interested in pursuing a career in surgery before the course, the majority (64%) indicated they were "neutral" about pursuing a career in cardiothoracic surgery. After participating in the course, 61% of the students agreed or strongly agreed that they were interested in pursuing a career in cardiothoracic surgery (p = 0.001). When asked to select a surgical subspecialty for their third-year clerkship rotation, 18% of the students selected thoracic surgery before participating in the simulator course versus 39% after completing the course. This increase was most evident among the female participants, of whom only 3 (12%) selected a thoracic rotation before the simulator course versus 9 (35%) after completion of the course (p < 0.05). CONCLUSIONS: High-fidelity surgical simulators are an effective way to introduce medical students to cardiothoracic surgery. Participation in moderated simulator sessions improves attitudes toward cardiothoracic surgery as a career choice and correlates with a greater interest in selecting thoracic surgery as a third-year clerkship rotation. The role of surgical simulation as a recruitment tool should be further delineated.


Asunto(s)
Selección de Profesión , Simulación por Computador , Educación de Pregrado en Medicina/métodos , Aprendizaje Basado en Problemas/métodos , Estudiantes de Medicina/psicología , Procedimientos Quirúrgicos Torácicos/educación , Evaluación Educacional , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados
19.
Ann Thorac Surg ; 90(5): 1645-9; discussion 1649-50, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20971280

RESUMEN

BACKGROUND: Locoregional recurrence can occur despite complete anatomic resection of T1N0 non-small cell lung cancer. That may be the result of incomplete resection or inaccurate staging. We assessed the impact of extent of nodal staging on the rate of locoregional failure and patient survival. METHODS: The records of 742 patients undergoing lobectomy, bilobectomy, or pneumonectomy for non-small cell lung cancer from 1996 to 2006 were reviewed. Operative reports and pathology reports were reviewed for the number of lymph nodes and the anatomic nodal stations examined. The Kaplan-Meier method was applied to analyze recurrence-free survival. RESULTS: A total of 119 patients with pathologically staged Ia lung cancer were identified. Histology type included 61% (n = 73) adenocarcinoma, 27% (n = 32) squamous cell cancer, and 12% (n = 14) other. Median age was 65 years (range, 34 to 88). Mean follow-up duration was 40 months (median 47; range, 1 to 121). Locoregional recurrence occurred in 20% (n = 18). The N2 nodal stations were examined in 94% (n = 112). At least one defined N1 nodal station was examined in 70% (n = 83). Station undefined N1 nodes were examined in 27% (n = 32), and no N1 nodes were examined in 3% (n = 4). Median number of N1 lymph nodes analyzed was 5 (range, 0 to 18). The locoregional recurrence rate was 14% (12 of 83) for patients with a defined N1 station node versus 31% (11 of 36) for patients in whom there were undefined N1 nodes (p = 0.03). Similar differences were seen in disease-free survival, 78.2% versus 62.6%, respectively (p = 0.06). CONCLUSIONS: Despite anatomic resection of stage Ia lung cancer and uniform analysis of N2 nodal stations, a high rate of locoregional recurrence occurs. Imprecise staging of N1 lymph nodes may contribute to the understaging and undertreatment of patients with early stage lung cancer.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias
20.
Cancer ; 116(20): 4825-32, 2010 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-20597134

RESUMEN

BACKGROUND: Identifying strong markers of prognosis is critical to optimize treatment and survival outcomes in patients with nonsmall cell lung cancer (NSCLC). The authors investigated the prognostic significance of preoperative cardiorespiratory fitness (peak oxygen consumption [VO(2peak)]) among operable candidates with NSCLC. METHODS: By using a prospective design, 398 patients with potentially resectable NSCLC enrolled in Cancer and Leukemia Group B 9238 were recruited between 1993 and 1998. Participants performed a cardiopulmonary exercise test to assess VO(2peak) and were observed until death or June 2008. Cox proportional models were used to estimate the risk of all-cause mortality according to cardiorespiratory fitness category defined by VO(2peak) tertiles (<0.96 of 0.96-1.29/>1.29 L/min⁻¹) with adjustment for age, sex, and performance status. RESULTS: Median follow-up was 30.8 months; 294 deaths were reported during this period. Compared with patients achieving a VO(2peak) <0.96 L/min⁻¹, the adjusted hazard ratio (HR) for all-cause mortality was 0.64 (95% confidence interval [CI], 0.46-0.88) for a VO(2peak) of 0.96 to 1.29 L/min⁻¹, and 0.56 (95% CI, 0.39-0.80) for a VO(2peak) of >1.29 L/min⁻¹) (P(trend) = .0037). The corresponding HRs for resected patients were 0.66 (95% CI, 0.46-0.95) and 0.59 (95% CI, 0.40-0.89) relative to the lowest VO(2peak) category (P(trend) = .0247), respectively. For nonresected patients, the HRs were 0.78 (95% CI, 0.34-1.79) and 0.39 (95% CI, 0.16-0.94) relative to the lowest category (P(trend) = .0278). CONCLUSIONS: VO(2peak) is a strong independent predictor of survival in NSCLC that may complement traditional markers of prognosis to improve risk stratification and prognostication.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/fisiopatología , Prueba de Esfuerzo/métodos , Neoplasias Pulmonares/fisiopatología , Consumo de Oxígeno , Anciano , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Causas de Muerte , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Periodo Preoperatorio
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