William A. Bulman

Posterior spinal fusion for scoliosis in patients with cerebral palsy: a comparison of Luque rod and Unit Rod instrumentation.

The development of the U-shaped Unit Rod for posterior spinal arthrodesis is a recent advance in the treatment of spinal deformity in patients with cerebral palsy. The results of 15 patients who underwent arthrodesis with dual Luque rod instrumentation (group I) are compared with the results of 15 patients in whom Unit Rod instrumentation was used (group II). The two treatment groups were similar with respect to age, gender, major spinal curve, and degree of pelvic obliquity. The Unit Rod instrumentation allowed significantly greater correction of both the major curve and pelvic obliquity, as assessed on postoperative radiographs. The mean postoperative major curve in group I was 44.1 degrees, compared with 31.7 degrees in group II (mean corrections of 48.6 and 61.7%, respectively). The mean angle of postoperative pelvic obliquity in group I was 12.6 degrees, compared with 5.2 degrees in group II, corrections of 49.5 and 79.3%, respectively. Sagittal-plane alignment was improved to a similar degree in both groups in those patients with preoperative imbalance and maintained in the remainder of patients.

Acquisition and Processing of Endobronchial Ultrasound-guided Transbronchial Needle Aspiration Specimens in the Era of Targeted Lung Cancer Chemotherapy

Recent advances in therapy for non-small cell lung carcinoma have shown that a personalized approach to treatment has the potential to significantly reduce lung cancer mortality. Concurrently, endoscopic ultrasound transbronchial needle aspiration has emerged as an accurate and sensitive tool for the diagnosis and staging of this disease. As knowledge of the molecular mechanisms that drive lung cancer progression increases, the amount of information that must be derived from a tumor specimen will also increase. Recent clinical studies have demonstrated that small specimens acquired by endoscopic ultrasound transbronchial needle aspiration are sufficient for molecular testing if specimen acquisition and processing are done with these needs in mind. Optimum use of this procedure requires a coordinated effort between the bronchoscopist and the cytopathologist to collect and triage specimens for diagnostic testing. When feasible, rapid onsite evaluation should be performed to assess the specimen for both diagnostic quality and quantity and to allocate the specimen for cell-block and possible immunohistochemistry and molecular studies. It is necessary for pulmonologists and bronchoscopists to understand the rationale for histologic and molecular testing of lung cancer diagnostic specimens and to ensure that specimens are acquired and processed in a fashion that provides information from small cytologic specimens that is sufficient to guide treatment in this era of targeted therapy.

Efficacy of spinal cord monitoring in scoliosis surgery in patients with cerebral palsy.

Although spinal cord monitoring is recommended during scoliosis surgery, a review from Rancho Los Amigos Medical Center stated that they were only able to obtain reproducible tracings in 53% of cerebral palsy patients. To ascertain that monitoring is both feasible and reliable in these patients, we reviewed the records of 34 consecutive patients with cerebral palsy who had scoliosis surgery at our institution. Spinal cord function was monitored by recording peripheral nerve, cervical/brainstem, and cortical somatosensory evoked potentials to posterior tibial nerve stimulation. Reproducible tracings were achieved in 31 of the 34 patients. Significant intraoperative changes were recorded in 12 of the 31 monitored patients, usually related to and requiring some modifications of the instrumentation. We conclude that with careful technique, spinal cord monitoring using cervical/brainstem somatosensory evoked potentials can be reliably achieved in most patients with cerebral palsy undergoing scoliosis surgery.

Periumbilical parasitic thumbprint purpura: Strongyloides hyperinfection syndrome acquired from a cadaveric renal transplant

J.A. Weiser, B.E. Scully, W.A. Bulman, S. Husain, M.E. Grossman. Periumbilical parasitic thumbprint purpura: Strongyloides hyperinfection syndrome acquired from a cadaveric renal transplant.
Transpl Infect Dis 2011: 13: 58–62. All rights reserved

Lung Volume Reduction Surgery Using the NETT Selection Criteria

BACKGROUND The National Emphysema Treatment Trial (NETT) proved that lung volume reduction surgery (LVRS) was safe and effective in patients with certain clinical characteristics and using defined inclusion-exclusion criteria. Based on the selection criteria developed in that trial, we performed bilateral LVRS on 49 patients during the period of February 2004 until May 2009. METHODS Forty-nine patients underwent lung volume reduction by either median sternotomy (10) or video-assisted thoracoscopic surgery (39) selected according to NETT described parameters. Preoperative characteristics were the following: mean (±SD) age 62.5±6.6 years, preoperative FEV1 (forced expiratory volume in the first second of expiration) 691 cc (±159), % of predicted FEV1 25.3 (±6.2), preoperative Dlco (diffusing capacity of lung for carbon monoxide) 7.6 (±2.7), and % of predicted DLCO 27% (±7.3). All patients had upper lobe predominant disease and either low exercise capacity (n=23) or high exercise capacity (n=26) as defined by the NETT. RESULTS There was no operative or 90-day mortality. Median length of stay was 8 days (interquartile range=6 to 10). Two patients required reintubation and tracheostomy but were decannulated prior to discharge. The BODE index (body mass index, airflow obstruction, dyspnea, and exercise capacity), a multidimensional predictor of survival in chronic obstructive pulmonary disease, improved -2.3 (±1.5, p<0.0001) (missing data: 5 of 42, 11.9%) and the FEV1 improved 286 cc (±221, p<0.0001), both 1 year after surgery. Probability of survival was 0.98 (95% CI [confidence interval]=0.94 to 1) at 1 year, and 0.95 (95% CI=0.88 to 1) at 3 years. CONCLUSIONS Surgical lung volume reduction for emphysema can be performed in patients using selection criteria developed by the NETT with very low surgical risk and excellent midterm results. Surgical LVRS is the standard against which other nonsurgical treatments for advanced emphysema should be judged.

Molecular testing guidelines for lung adenocarcinoma: Utility of cell blocks and concordance between fine-needle aspiration cytology and histology samples.

Background: Lung cancer is a leading cause of mortality, and patients often present at a late stage. More recently, advances in screening, diagnosing, and treating lung cancer have been made. For instance, greater numbers of minimally invasive procedures are being performed, and identification of lung adenocarcinoma driver mutations has led to the implementation of targeted therapies. Advances in molecular techniques enable use of scant tissue, including cytology specimens. In addition, per recently published consensus guidelines, cytology-derived cell blocks (CBs) are preferred over direct smears. Yet, limited comparison of molecular testing of fine-needle aspiration (FNA) CBs and corresponding histology specimens has been performed. This study aimed to establish concordance of epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma (KRAS) virus homolog testing between FNA CBs and histology samples from the same patients. Materials and Methods: Patients for whom molecular testing for EGFR or KRAS was performed on both FNA CBs and histology samples containing lung adenocarcinoma were identified retrospectively. Following microdissection, when necessary, concordance of EGFR and KRAS molecular testing results between FNA CBs and histology samples was evaluated. Results: EGFR and/or KRAS testing was performed on samples obtained from 26 patients. Concordant results were obtained for all EGFR (22/22) and KRAS (17/17) mutation analyses performed. Conclusions: Identification of mutations in lung adenocarcinomas affects clinical decision-making, and it is important that results from small samples be accurate. This study demonstrates that molecular testing on cytology CBs is as sensitive and specific as that on histology.

Cytomorphological features of ALK-positive lung adenocarcinomas: psammoma bodies and signet ring cells.

Correlation between histology and genotype has been described in lung adenocarcinomas. For example, studies have demonstrated that adenocarcinomas with an anaplastic lymphoma kinase (ALK) gene rearrangement may have mucinous features. The objective of the current study was to determine whether a similar association can be identified in cytological specimens.

Molecular testing on endobronchial ultrasound (EBUS) fine needle aspirates (FNA): Impact of triage

Endobronchial ultrasound (EBUS)‐guided fine needle aspiration (FNA) is performed to diagnose and stage lung cancer. Multiple studies have described the value of Rapid On‐Site Evaluation (ROSE), but often the emphasis is upon diagnosis than adequacy for molecular testing (MT). The aim was to identify variable(s), especially cytology‐related, that can improve MT.

The safety, efficacy, and durability of lung-volume reduction surgery: A 10-year experience.

OBJECTIVES The National Emphysema Treatment Trial (NETT) validated the efficacy of lung-volume reduction surgery (LVRS) in selected patients with emphysema; however, concerns about the safety and durability of the operation have limited its clinical application. We evaluated our experience with LVRS, for the time period since approval was given by the Centers for Medicare and Medicaid Services, with respect to surgical morbidity and mortality, early and late functional outcomes, and long-term survival. METHODS Retrospective analysis was performed on 91 patients for whom consent was obtained for bilateral LVRS at our institution between January 2004 and June 2014. Primary outcomes analyzed were 6-month surgical mortality and overall survival at 1, 2, and 5 years. Secondary outcomes (forced expiratory volume in 1 second [FEV1], residual volume, carbon monoxide diffusing capacity, a 6-minute walk test, exercise capacity, and a shortness-of-breath questionnaire) were analyzed for mean change from baseline at 1, 2, and 5 years after LVRS. RESULTS The 6-month surgical mortality rate was 0%. At the 1- and 5-year follow-up, 69% and 36% of the patients had an improvement in FEV1. The 1-, 2-, and 5-year FEV1 change in % predicted of the FEV1, compared with baseline after LVRS, respectively, was 11.1% (95% CI: 8.6%, 13.6%); 8.7% (95% CI: 6.1%, 11.4%); and 11.1% (95% CI: 7.1%, 15.0%); and the maximal workload (in watts [W]) had an average increase of: 10.7 W (95% CI: 6.9, 14.6); 7.6 W (95% CI: 2.8, 12.4); and 10.24 W (95% CI: 4.4, 16.1). Overall survival (95% CI) for the group was: 0.99 (95% CI: 0.96, 1.00) at 1 year; 0.97 (95% CI: 0.93, 1.00) at 2 years; and 0.78 (95% CI: 0.67, 0.89) at 5 years. CONCLUSIONS Given proper patient selection, LVRS is a safe operation. Early functional measurements are consistent with significant clinical benefit. Long-term results demonstrate that improvements can be durable. Surgical LVRS continues to represent the standard for lung-volume reduction therapy.

Next-generation sequencing of non-small cell lung cancer using a customized, targeted sequencing panel: Emphasis on small biopsy and cytology

Background: Next-generation sequencing (NGS) with a multi-gene panel is now available for patients with lung adenocarcinoma, but the performance characteristics and clinical utility of this testing are not well-described. We present the results of an extended 467 gene panel in a series of advanced, highly selected nonsmall cell lung cancer (NSCLC) patients using a range of specimens, including predominantly small biopsy and cytology specimens. Materials and Methods: A retrospective review of 22 NSCLC biopsies sent for NGS using an extended gene panel from January 2014 to July 2015. The customized NGS panel sequences 467 cancer-associated genes with exonic and intronic sequences obtained from purified tumor DNA. Genomic alterations, patient characteristics, and success of testing were determined. Results: The majority of samples tested were metastatic lung adenocarcinoma on final pathology. Of the 22 specimens tested, 5 (22.7%) were surgical resections and 17 (77.3%) were small biopsy and cytology specimens. Twenty-one (95%) of the specimens were adequate for full sequencing and yielded a total of 204 genomic alterations (average 8.9 per tumor), of which 17 (average 0.81 per tumor) were actionable and/or clinically relevant. Genomic alterations were found most commonly in the TP53, EGFR, EPHB1, MLL3, APC, SETD2, KRAS, DNMT3A, RB1, CDKN2A, ARID1A, EP300, KDM6B, RAD50, STK11, and BRCA2 genes. Conclusions: NGS using a comprehensive gene panel was performed successfully in 95% of all NSCLC cases in this series, including 94% small biopsy and cytology specimens and 100% surgical resections. This custom assay was performed on a range of tumor specimens and demonstrates that small specimens are able to provide a similar depth of information as larger ones. As many patients present at an advanced stage and only small specimens are obtained, the information these provide has the potential for guiding treatment in highly selected patients with advanced lung adenocarcinoma.