A Series of Transbronchial Removal of Intracavitary Pulmonary Aspergilloma.

BACKGROUND: Intracavitary pulmonary aspergilloma is a chronic, debilitating fungal infection. Without definitive therapy, death can occur from massive hemoptysis, cachexia, or secondary infection. Although surgical resection is the standard therapy, it is not possible for many patients owing to poor pulmonary function or medical comorbidities. Aspergilloma removal through bronchoscopy is an important alternative therapy that may be available in select cases. METHODS: We retrospectively reviewed all cases referred to the University of Calgary Interventional Pulmonary Service for transbronchial removal of intracavitary aspergilloma from January 1, 2009, to January 1, 2014. RESULTS: Ten patients with intracavitary pulmonary aspergilloma were identified. In 3 patients, the aspergilloma cavity was not accessible by bronchoscopy. Successful removal of the aspergilloma with symptom improvement or resolution was achieved in 6 of 7 cases. One of the patients was lost to follow-up. Minor hypoxia lasting 12 to 72 hours was observed in 5 cases. Severe sepsis requiring an extended critical care unit stay occurred in 1 case. Follow-up ranged from 9 months to 5 years. CONCLUSIONS: Although not without risk of minor hypoxia and possible sepsis, for carefully selected patients, bronchoscopic removal of symptomatic intracavitary pulmonary aspergilloma may be an alternative therapy to surgical resection for this life-threatening disease.

Low Prevalence of High-Grade Lesions Detected With Autofluorescence Bronchoscopy in the Setting of Lung Cancer Screening in the Pan-Canadian Lung Cancer Screening Study.

BACKGROUND: Lung cancer screening with low-dose CT (LDCT) scan has been demonstrated to reduce lung cancer mortality. Preliminary reports suggested that up to 20% of lung cancers may be CT scan occult but detectable by autofluorescence bronchoscopy (AFB). We evaluated the prevalence of CT scan occult, invasive, and high-grade preinvasive lesions in high-risk participants undergoing screening for lung cancer. METHODS: The first 1,300 participants from seven centers in the Pan-Canadian Early Detection of Lung Cancer Study who had ≥ 2% lung cancer risk over 5 years were invited to have an AFB in addition to a LDCT scan. We determined the prevalence of CT scan and AFB abnormalities and analyzed the association between selected predictor variables and preinvasive lesions plus invasive cancer. RESULTS: A total of 776 endobronchial biopsies were performed in 333 of 1,300 (25.6%) participants. Dysplastic or higher-grade lesions were detected in 5.3% of the participants (n = 68; mild dysplasia: n = 36, moderate dysplasia: n = 25, severe dysplasia: n = 3, carcinoma in situ [CIS]: n = 1, and carcinoma: n = 4). Only one typical carcinoid tumor and one CIS lesion were detected by AFB alone, for a rate of CT scan occult cancer of 0.15% (95% CI, 0.0%-0.6%). Fifty-six prevalence lung cancers were detected by LDCT scan (4.3%). The only independent risk factors for finding of dysplasia or CIS on AFB were smoking duration (OR, 1.05; 95% CI, 1.02-1.07) and FEV1 percent predicted (OR, 0.99; 95% CI, 0.98-0.99). CONCLUSIONS: The addition of AFB to LDCT scan in a high lung cancer risk cohort detected too few CT occult cancers (0.15%) to justify its incorporation into a lung cancer screening program. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00751660; URL: www.clinicaltrials.gov.

The Feasibility of EBUS-Guided TBNA Through the Pulmonary Artery in Highly Selected Patients.

BACKGROUND: The use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for diagnosis and staging of benign and malignant thoracic disease has rapidly evolved into the standard of care. The lymph node stations that can be reached by EBUS and EUS are substantially more than those that can be accessed by mediastinoscopy. In rare cases, the clinician is faced with extraordinary circumstances in which a minimally invasive approach to the lymph nodes in station 5 is required. We present our findings in 10 cases, at 7 different institutions, where EBUS was instrumental in reaching a diagnosis. METHODS: We retrospectively collected 10 cases where EBUS-TBNA was performed through the pulmonary artery in an attempt to reach the territory of lymph node station 5. All cases were performed by experienced interventional pulmonologists at 7 tertiary care centers in the United States and Canada. We describe the patients' demographics, comorbidities, complications, and cytopathology. RESULTS: A definitive diagnosis was reached in 9 of the 10 patients. One case showed atypical cells and required a confirmatory Chamberlain procedure. No complications occurred as a result of careful transpulmonary artery needle aspiration. CONCLUSIONS: This multicenter case series suggests that transpulmonary artery needle aspiration guided by EBUS is possible and safe in the hands of experienced interventional pulmonologists. It is important to recognize that this is not an alternative to left VATS or Chamberlain procedure, but a last resort procedure.

Endobronchial ultrasound learning curve in interventional pulmonary fellows.

BACKGROUND AND OBJECTIVE: Little published data exist regarding the learning curve for endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA). We sought to assess the improvement in skill as trainees learned EBUS-TBNA in a clinical setting. METHODS: This is a multicentre cohort study of EBUS-TBNA technical skill of interventional pulmonology (IP) fellows as assessed with EBUS-TBNA computer simulator testing every 25 clinical cases throughout IP fellowship training. RESULTS: Nine fellows from three academic centres in the United States and Canada were enrolled in the study. Ongoing improvements were seen for EBUS-TBNA efficiency score and percentage of lymph nodes correctly identified on ultrasound exam, even after 200 clinical cases. Expert-level technical skill was obtained for EBUS efficiency score and for percentage of lymph nodes correctly identified on ultrasound exam at a median of 212 and 164 procedures, respectively; however, 33% of fellows did not achieve expert-level technical skill for either metric during their fellowship training. Significant variation in learning curves of the fellows was observed. CONCLUSIONS: Significant variation is seen in the EBUS-TBNA learning curves of individual IP fellows and for individual procedure components, with ongoing improvement in EBUS-TBNA skill even after 200 clinical cases. These results highlight the need for validated, objective measures of individual competence, and can assist training programmes in ensuring adequate procedure volumes required for a majority of trainees to successfully complete these assessments.

Evaluation of a novel method of teaching endobronchial ultrasound: physician- versus respiratory therapist-proctored simulation training.

BACKGROUND: Computer endobronchial ultrasound (EBUS) simulators have been demonstrated to improve trainee procedural skills before attempting to perform EBUS procedures on patients. OBJECTIVE: To compare EBUS performance following training with computer simulation proctored by EBUS-trained respiratory therapists versus the same simulation training proctored by an interventional respirologist. METHODS: The present analysis was a prospective study of respiratory medicine trainees learning EBUS. Two cohorts of trainees were evaluated using a previously validated method using simulated cases with performance metrics measured by the simulator. Group 1 underwent EBUS training by performing 15 procedures on an EBUS simulator (n=4) proctored by an interventional respirologist. Group 2 received identical training proctored by a respiratory therapist with special training in EBUS (n=10). RESULTS: No significant differences between group 1 and group 2 were apparent for the primary outcome measures of total procedure time (15.15±1.34 min versus 14.78±2.88 min; P=0.816), the percentage of lymph nodes successfully identified (88.8±5.4 versus 80.91±8.9; P=0.092) or the percentage of successful biopsies (100.0±0.0 versus 98.75±3.95; P=0.549). The learning curves were similar between groups, and did not show an obvious plateau after 19 simulated procedures in either group. DISCUSSION: Acquisition of basic EBUS technical skills can be achieved using computer EBUS simulation proctored by specially trained respiratory therapists or by an interventional respirologist. There appeared to be no significant advantage to having an interventional respirologist proctor the computer EBUS simulation.

Trainee impact on procedural complications: an analysis of 967 consecutive flexible bronchoscopy procedures in an interventional pulmonology practice.

BACKGROUND: Increased complications have been demonstrated in patients undergoing some medical procedures performed by trainees. Flexible bronchoscopy is generally considered a safe procedure; however, complications can include pneumothorax, bleeding and even death. OBJECTIVES: This study aimed to determine the impact of trainees during interventional pulmonology procedures on procedure time, sedation use and complications. METHODS: A retrospective review of a quality improvement database from all consecutive medical procedures performed by an interventional pulmonologist (D.R.S.) at the University of Calgary, from July 1, 2007, to April 1, 2011. RESULTS: Of 1,100 consecutive procedures during the study period, 967 were flexible bronchoscopies. A trainee participated in 82.2% of the procedures. Complications occurred in 38 patients (3.9%). No death occurred. Significant differences were seen when a trainee participated in the procedure versus when no trainee participated for procedure length [50.81 vs. 32.49 min, difference 18.32 min (95% CI 16.04-20.60), p = 0.001], dose of midazolam used [6.34 vs. 5.73 mg, difference 0.61 mg (95% CI 0.15-1.08), p = 0.01], dose of propofol used [153.08 vs. 111.60 mg, difference 41.48 mg (95% CI 21.81-61.15), p = 0.001], as well as the number of complications [4.5 vs. 1.2%, difference 3.3%, p = 0.048]. CONCLUSIONS: In an academic interventional pulmonology practice utilizing the apprenticeship model for procedural education, trainee participation in procedures can increase procedure time and the amount of sedation required, and result in increased complications. Medical procedural training methods that do not involve practicing on patients warrant further investigation in order to reduce the burden of procedural learning for patients.

Diagnostic utility of peripheral endobronchial ultrasound with electromagnetic navigation bronchoscopy in peripheral lung nodules.

BACKGROUND AND OBJECTIVE: This study aimed to investigate the diagnostic utility of peripheral endobronchial ultrasound (pEBUS) followed by as-needed electromagnetic navigation bronchoscopy (ENB) for sampling peripheral lung nodules. METHODS: The study was a single-arm, prospective cohort study of patients with peripheral lung nodules. Peripheral lung lesion localization was initially performed using a pEBUS probe with guide sheath. If localization failed with pEBUS alone, ENB was used to help identify the lesion. Transbronchial biopsy, bronchial brush, transbronchial needle aspiration and bronchial washings were performed. RESULTS: Sixty patients were enrolled with average lesion size of 27 mm and mean pleural distance of 20 mm. Lesions were found with pEBUS alone in 75% of cases. The addition of ENB improved lesion localization to 93%. However, diagnostic yield for pEBUS alone and pEBUS with ENB were 43% and 50%, respectively. Factors predicting need for ENB use included smaller lesion size and absence of an air bronchus sign on computed tomography. CONCLUSIONS: ENB improves localization of lung lesions after unsuccessful pEBUS but is often not sufficient to ensure confirmation of a specific diagnosis. Technical improvements in sampling methods could improve the diagnostic yield.

Characterization of small spheres derived from various solid tumor cell lines: are they suitable targets for T cells?

T cell based immunotherapy has been investigated in a variety of malignancies and analyses have been mostly founded on in vitro data with tumor cell monolayers. However, three-dimensional (3D) culture models might mimic more closely the 'in vivo' conditions than 2D monolayers. Therefore, we analyzed the expression of tumor-associated antigens (TAA) and of molecules involved in antigen processing and presentation (APM) in tumor spheres, which served as an in vitro model for micrometastasis which might be enriched in tumor propagating cancer stem cells. For enrichment of sphere cells 12 human solid tumor cell lines were cultured in serum-free medium. Expression of a variety of TAA and APM were analyzed by RT-PCR and/or flow cytometry and compared to expression in corresponding adherent bulk cells grown in regular growth medium. Compared to adherent cells, spheres showed equal or higher mRNA expression levels of LMP2, LMP7 and MECL-1, of TAP1 and TAP2 transporters and, surprisingly, also of TAA including differentiation antigens. However, downregulation or loss of HLA-I and HLA-II molecules in spheres was observed in 8 of 10 and 1 of 2 cell lines, respectively, and was unresponsive to stimulation with IFN-γ. Although tumor spheres express TAA and molecules of intracellular antigen processing, they are defective in antigen presentation due to downregulation of HLA surface expression which may lead to immune evasion.

Idiopathic subglottic stenosis: a familial predisposition.

Idiopathic subglottic stenosis is a narrowing of the trachea at the level of the cricoid cartilage of unknown etiology. It is a rare condition for which the real incidence has never been established owing to the difficulty of making the diagnosis. Although there is a female preponderance, no familial cases have been reported in the literature. We describe two pairs of sisters as well as a mother and daughter presenting with idiopathic subglottic stenosis. All known causes of tracheal stenosis were excluded, including prolonged intubation, surgery, autoimmune and inflammatory disorders, infection and gastroesophageal reflux disease. These are the first cases reported in the literature that suggest a genetic predisposition for idiopathic subglottic stenosis.

Bronchoscopic removal of a large intracavitary pulmonary aspergilloma.

Pulmonary aspergilloma is a chronic fungal infection that has a high mortality when hemoptysis occurs. Surgery is the treatment of choice, but patients often have severe physiologic impairment putting them at risk for significant surgical morbidity and mortality. We present the case of a 63-year-old woman with a large aspergilloma, unfit for surgery due to medical reasons. The aspergilloma was enlarging, with progression of the patient's symptoms of anorexia, cough, chest discomfort, and hemoptysis. Bronchoscopy revealed an airway leading into a cavity with a large fungal ball. Biopsy confirmed Aspergillus fumigatus. Using flexible and rigid bronchoscopy, the aspergilloma was mechanically removed. Eighteen months later the patient reported no hemoptysis, reduced pain and cough, significant weight gain, and improved appetite, with no recurrence of the aspergilloma on repeat imaging. To our knowledge, this is the first reported case of bronchoscopic removal of a large cavitary aspergilloma. This important new treatment modality provides a viable alternative therapy for this potentially life-threatening problem.

The impact of tunneled pleural catheters on the quality of life of patients with malignant pleural effusions.

BACKGROUND: Tunneled pleural catheters (TPC) are used in the management of malignant pleural effusions (MPE), but the impact of this palliative procedure on patient quality of life (QoL) has not been well described. OBJECTIVES: To ascertain the impact of TPCs on symptoms and QoL of patients with recurrent MPE. METHODS: Patients with recurrent MPE completed the EORTC QLQ-C30 and LC13 QoL questionnaires at baseline, 2 and 14 weeks; FACIT-TS-G© treatment satisfaction surveys were completed at 14 weeks. RESULTS: A total of 82 patients were recruited. Thirty-seven patients (37/82, 45%) died prior to their 14-week follow-up appointment. Significant improvements in dyspnea at 2 weeks were demonstrated with both dyspnea scores (LC13 baseline score 64.1, 2-week score 43.7, mean change -20.4, n = 56, p < 0.001; C30 baseline score 78.9, 2-week score 46.6, mean change -32.4, n = 68, p < 0.001), as well as with the MRC score (baseline median score 4, 2-week score 3, n = 70, p < 0.001). Global health status/QoL was also significantly improved at 2 weeks (baseline score 34.1, 2-week score 46.3, mean change 12.3, n = 68, p < 0.001). Improvements in cough, fatigue and all functional scales were noted at 2 weeks. The improvements in dyspnea and global health status/QoL were maintained to 14 weeks in surviving subjects and there was further improvement in the MRC score at 14 weeks. Patients who completed the FACIT-TS-G survey demonstrated overall satisfaction with TPC treatment. CONCLUSIONS: TPCs are associated with a significant improvement in global health status, QoL and dyspnea at the 2-week time point in patients with recurrent MPE.

Trainee impact on advanced diagnostic bronchoscopy: an analysis of 607 consecutive procedures in an interventional pulmonary practice.

BACKGROUND AND OBJECTIVE: Complications during advanced diagnostic bronchoscopy are rare and include: pneumothorax, bleeding, mediastinitis and lymphadenitis. Increased complications have been demonstrated in patients undergoing routine bronchoscopy procedures performed by trainees. This study aimed to determine the impact of trainees during advanced diagnostic bronchoscopy on procedure time, sedation use and complications. METHODS: A retrospective review of a quality improvement database including consecutive pulmonary procedures performed by an interventional pulmonologist (D.R.S.) at the University of Calgary, from 1 July 2007 to 1 April 2011. RESULTS: Six hundred seven (55.2%) of the 1100 procedures involved an advanced diagnostic procedure defined as: endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), electromagnetic navigation bronchoscopy (ENB) and/or peripheral EBUS. A trainee participated in 512 (84.3%) procedures. A complication occurred in 25 patients (4.1%), with a trend towards increased complication rates in the trainee group (4.7% vs 1.1%, difference 3.6%, P = 0.076). Significant differences were seen when a trainee participated versus when no trainee participated for procedure length (58.32 min vs 37.69 min, difference 20.63 min (95% confidence interval: 19.07-22.19), P = 0.001) and for the dose of propofol (178.3 mg vs 137.1 mg, difference 41.2 mg (95% confidence interval: 19.81-63.38), P = 0.002). CONCLUSIONS: In an academic interventional pulmonology practice utilizing the apprenticeship model, trainee participation in advanced diagnostic bronchoscopy increased procedure time, increased the amount of sedation used and resulted in a trend to increased complications. Attempts to modify trainee procedural training to reduce the burden of procedural learning for patients are warranted.

Cytologic assessment of endobronchial ultrasound-guided transbronchial needle aspirates in sarcoidosis.

BACKGROUND: The purpose of this study was to determine interobserver variability, the relative importance of cytologic preparations, and factors influencing the diagnostic yield of mediastinal lymph node aspirates in suspected sarcoidosis. METHODS: Analysis of mediastinal lymph node aspirates obtained during a randomized study of endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) and conventional TBNA in patients with suspected sarcoidosis. All aspirates were processed by the monolayer ThinPrep method and cell blocks were prepared when feasible. The slides were reviewed by 2 cytopathologists, blinded to the study group. Lymph node location, size, number of aspirates, and diagnosis were recorded. A research cytopathologist recorded the presence of noncaseating granulomas in the monolayer and cell block preparations separately. RESULTS: Fifty patients were enrolled in the study, with 152 lymph nodes available for analysis (95 EBUS-TBNA, 57 conventional TBNA). The overall diagnostic yield was 64.5% on a per-lymph node basis. There was good agreement between cytopathologists (κ=0.677, P<0.001). Both liquid-based cytology and cell blocks were important in identifying granulomatous inflammation, with each being solely positive in 22% of cases. The diagnostic yield was not altered by lymph node location, size, or number of aspirates per node. CONCLUSIONS: Liquid-based cytology and cell block specimens are equally important in maximizing the diagnostic yield in EBUS-guided and conventional TBNA in suspected sarcoidosis. Good interobserver agreement between cytopathologists was noted, with improved diagnostic yield after review by a pulmonary cytopathologist. None of the clinical factors assessed impacted on the diagnostic yield of the procedure on a per-node basis.

Endobronchial schwannoma.

Schwannomas are benign nerve-sheath tumors that arise from Schwann cells. They can present as endobronchial lesions with symptoms of obstruction and hemoptysis. We describe the first case of multiple endobronchial schwannomas at 3 different sites in a single patient. The autofluorescence ratio was <0.5 for 2 of 3 lesions. The optimal follow-up and treatment plan for these lesions remain unknown, especially in asymptomatic patients.

Wet laboratory versus computer simulation for learning endobronchial ultrasound: a randomized trial.

BACKGROUND: Linear endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) is a revolutionary bronchoscopic procedure that is challenging to learn. OBJECTIVES: To compare two methods used to teach EBUS-TBNA: wet laboratory (lab) versus computer EBUS-TBNA simulation. METHODS: A prospective, randomized study of respirologists, thoracic surgeons and trainees learning EBUS-TBNA at a two-day continuing medical education course. All subjects received education via a series of lectures and live cases, followed by randomization to learn EBUS-TBNA predominantly either by wet lab simulation (n=6) or computer simulation (n=6). All subjects then completed testing of their EBUS-TBNA skills via a previously validated method using simulated cases on EBUS-TBNA simulators and questionnaires evaluating learner preferences. RESULTS: There were no significant differences between the computer EBUS-TBNA simulator group and the wet lab group in procedure time (25.3±6.1 min versus 25.2±2.5 min; P=0.984) and percentage of successful biopsies (81.3±14.9% versus 74.0±17.3%; P=0.453). The computer simulator group performed significantly better than the wet lab group in the percentage of lymph nodes correctly identified (70.4±16.7% versus 42.9±19.9%; P=0.002). Wet lab simulation was associated with increased learner confidence with operating the real EBUS-TBNA bronchoscope. All subjects responded that wet lab and computer EBUS-TBNA simulation offered important complementary learning opportunities. CONCLUSION: Computer EBUS-TBNA simulation and wet lab simulation are effective methods of learning basic EBUS-TBNA skills and appeared to be complementary.

Safety of endobronchial ultrasound-guided transbronchial needle aspiration for patients taking clopidogrel: a report of 12 consecutive cases.

BACKGROUND: Clopidogrel is an oral agent commonly used for primary or secondary prevention of cardiovascular disease. It is associated with an increased risk of bleeding during some medical and surgical procedures. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a new bronchoscopic technique used to accurately biopsy intrathoracic structures during flexible bronchoscopy. It is currently unknown whether clopidogrel increases bleeding complications during EBUS-TBNA procedures. OBJECTIVES: To evaluate the safety of clopidogrel use in EBUS-TBNA by identifying consecutive cases of EBUS-TBNA procedures performed on patients taking clopidogrel. METHODS: A retrospective review of a prospectively collected quality improvement database from 1,100 consecutive pulmonary procedures performed by an interventional pulmonologist (D.R.S.) at the University of Calgary from July 1st, 2007 to April 1st, 2011 was performed. RESULTS: Twelve cases of EBUS-TBNA procedures performed on patients taking clopidogrel were identified. Mean age was 74 years (range 61-85). Seven patients (66.7%) were taking aspirin in addition to clopidogrel. There was no significant bleeding seen in any cases at the time of bronchoscopy and no additional complications were identified during follow-up (at least 4 weeks; median follow-up 3 months). CONCLUSIONS: This series of 12 cases suggests that EBUS-TBNA can be performed safely by experienced operators in patients taking clopidogrel. Nevertheless, until larger prospective studies confirm this hypothesis, proceeding to EBUS-TBNA without first withdrawing clopidogrel should only be performed in situations where the risk of short-term thrombosis is believed to outweigh the (theoretical) risk of bleeding.

Evaluation of clinical endobronchial ultrasound skills following clinical versus simulation training.

BACKGROUND AND OBJECTIVE: Endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) is a pulmonary procedure that can be challenging to learn. This study aims to compare trainee EBUS-TBNA performance during clinical procedures, following training with a computer EBUS-TBNA simulator versus conventional clinical EBUS-TBNA training. METHODS: A prospective study of pulmonary trainees performing EBUS-TBNA procedures on patients with suspected lung cancer and mediastinal adenopathy. Two cohorts of trainees were each evaluated while performing EBUS-TBNA on two patients. Group 1 received training by performing 15 cases on an EBUS-TBNA simulator (n = 4) and had never performed a clinical EBUS-TBNA procedure. Group 2 received training by doing 15-25 EBUS-TBNA procedures on patients (n = 4). RESULTS: There was no significant difference in the primary outcome measure of total EBUS-TBNA procedure time/number of successful aspirates between Groups 1 and 2 (3.95 (±0.93) vs 3.64 (±0.89), P = 0.51). Total learner EBUS-TBNA procedure time in minutes (23.67 (±5.58) vs 21.81 (±5.36), P = 0.17) and percentage of successful aspirates (93.3% (±5.8%) vs 86.3% (±6.7%), P = 0.12) were not significantly different between Group 1 and Group 2. The only significant difference found between Group 1 and Group 2 was time to intubation in minutes (0.99 (±0.46) vs 0.50 (±0.42), P = 0.04). CONCLUSIONS: EBUS-TBNA simulator use leads to rapid acquisition of clinical EBUS-TBNA skills comparable with that obtained with conventional training methods using practice on patients, suggesting that skills learned using an EBUS-TBNA simulator are transferable to clinical EBUS-TBNA performance. EBUS-TBNA simulators show promise for training, potentially minimizing the burden of procedural learning on patients.

Wilms' tumor protein 1 (WT1) peptide vaccination in AML patients: predominant TCR CDR3ß sequence associated with remission in one patient is detectable in other vaccinated patients.

BACKGROUND: Clinically effective T-cell responses can be elicited by single peptide vaccination with Wilms' tumor 1 (WT1) epitope 126-134 in patients with acute myeloid leukemia (AML). We recently showed that a predominant T-cell receptor (TCR) ß chain was associated with vaccine-induced complete remission in an AML patient (patient 1). In this study, we address the question of whether this predominant clone or the accompanying Vß11 restriction could be found in other AML patients vaccinated with the same WT1 peptide. MATERIALS AND METHODS: For assessment of Vß usage, cytotoxic T lymphocytes (CTLs) from four vaccinated patients were divided into specific and non-specific by epitope-specific enrichment. Vß families were quantified in both fractions using reverse transcribed quantitative PCR. Vß11-positive 'complementary determining region 3' (CDR3) sequences were amplified from these samples, from bone marrow samples of 17 other vaccination patients, and from peripheral blood of six healthy controls, cloned and sequenced. RESULTS: We observed a clear bias towards Vß11 usage of the WT1-specific CTL populations in all four patients. The predominant CDR3ß amino acid (AA) sequence of patient 1 was detected in two other patients. CDR3ß loops with closely related AA sequences were only found in patient 1. There were no CDR3ß AA sequences with side chains of identical chemical properties detected in any patient. CONCLUSION: We provide the first data addressing TCR Vß chain usage in WT1-specific T-cell populations after HLA A*0201-restricted single peptide vaccination. We demonstrate both shared Vß restriction and the sharing of a TCR ß transcript with proven clinical impact in one patient.

Assessment and learning curve evaluation of endobronchial ultrasound skills following simulation and clinical training.

BACKGROUND AND OBJECTIVE: Endobronchial ultrasound is a revolutionary diagnostic pulmonary procedure. The use of a computer endobronchial ultrasound simulator could improve trainee procedural skills before attempting to perform procedures on patients. This study aims to compare endobronchial ultrasound performance following training with simulation versus conventional training using patients. METHODS: A prospective study of pulmonary medicine and thoracic surgery trainees. Two cohorts of trainees were evaluated using simulated cases with performance metrics measured by the simulator. Group 1 received endobronchial ultrasound training by performing 15 cases on an endobronchial ultrasound simulator (n=4). Group 2 received endobronchial ultrasound training by doing 15-25 cases on patients (n=9). RESULTS: Total procedure time was significantly shorter in group 1 than group 2 (15.15 (±1.34) vs 20.00 (±3.25) min, P<0.05). The percentage of lymph nodes successfully identified was significantly better in group 1 than group 2 (89.8 (±5.4) vs 68.1 (±5.2), P < 0.05). There was no difference between group 1 and group 2 in the percentage of successful biopsies (100.0 (±0.0) vs 90.4 (±11.5), P=0.13). The learning curves for simulation trained fellows did not show an obvious plateau after 19 simulated cases. CONCLUSIONS: Using an endobronchial ultrasound simulator leads to more rapid acquisition of skill in endobronchial ultrasound compared with conventional training methods, as assessed by an endobronchial ultrasound simulator. Endobronchial ultrasound simulators show promise for training with the advantage of minimizing the burden of procedural learning on patients.