A 63-year-old man was analyzed for platypnea-orthodeoxia syndrome (POS). A complete obstruction due to bronchial carcinoma was found in the left main bronchus with bronchoscopy. After left sided... Show moreA 63-year-old man was analyzed for platypnea-orthodeoxia syndrome (POS). A complete obstruction due to bronchial carcinoma was found in the left main bronchus with bronchoscopy. After left sided pneumonectomy POS resolved completely. Historical reports suggest increased shunting through the left lung could occur in the upright position caused by decreased compression of the left pulmonary artery due to the central bronchial carcinoma. Partially absent hypoxic vasoconstriction was confirmed in this case and suggests (without a relevant shunt through a patent foramen ovale) this 'historical' hypothesis could explain the POS due to increased shunting in the upright position in this patient. Show less
Introduction: Frequently, patients with locally advanced or metastatic NSCLC are screened for mutations and fusions. In most laboratories, molecular workup includes a multitude of tests:... Show moreIntroduction: Frequently, patients with locally advanced or metastatic NSCLC are screened for mutations and fusions. In most laboratories, molecular workup includes a multitude of tests: immunohistochemistry (ALK, ROS1, and programmed death-ligand 1 testing), DNA sequencing, in situ hybridization for fusion, and amplification detection. With the fast-emerging new drugs targeting specific fusions and exon-skipping events, this procedure harbors a growing risk of tissue exhaustion.Methods: In this study, we evaluated the benefit of anchored, multiplexed, polymerase chain reaction-based targeted RNA sequencing (RNA next-generation sequencing [NGS]) in the identification of gene fusions and exon-skipping events in patients, in which no pathogenic driver mutation was found by DNA-based targeted cancer hotspot NGS (DNA NGS). We analyzed a cohort of stage IV NSCLC cases from both in-house and referral hospitals, consisting 38.5% cytology samples and 61.5% microdissected histology samples, mostly core needle biopsies. We compared molecular findings in a parallel workup (DNA NGS and RNA NGS, cohort 1, n = 198) with a sequential workup (DNA NGS followed by RNA NGS in selected cases, cohort 2, n = 192). We hypothesized the sequential workup to be the more efficient procedure.Results: In both cohorts, a maximum of one oncogenic driver mutation was found per case. This is in concordance with large, whole-genome databases and suggests that it is safe to omit RNA NGS when a clear oncogenic driver is identified in DNA NGS. In addition, this reduced the number of necessary RNA NGS to only 53% of all cases. The tumors of never smokers, however, were enriched for fusions and exon-skipping events (32% versus 4% in former and current smokers, p = 0.00), and therefore benefited more often from the shorter median turnaround time of the parallel approach (15 d versus only 9 d in the parallel workup).Conclusions: We conclude that sequentially combining DNA NGS and RNA NGS is the most efficient strategy for mutation and fusion detection in smoking-associated NSCLC, whereas for never smokers we recommend a parallel approach. This approach was shown to be feasible on small tissue samples including for cytology tests, can drastically reduce the complexity and cost of molecular workup, and also provides flexibility in the constantly evolving landscape of actionable targets in NSCLC. (C) 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Show less
A 42-year old male was referred with a 6-week history of new onset dyspnea. The patient had normal vital signs, no relevant medical history and the only abnormality was a left sided inspiratory... Show moreA 42-year old male was referred with a 6-week history of new onset dyspnea. The patient had normal vital signs, no relevant medical history and the only abnormality was a left sided inspiratory wheeze. No abnormalities were seen on the chest X-ray. A bronchoscopy was performed which showed a well-circumscribed hypervasculated mass in the left main bronchus. A biopsy was taken, which was complicated after the procedure by dislocation of the mass and coughed up by the patient. Both samples were send for pathologic review. A contrast CT was performed which showed a localized remaining mass in the left main bronchus and no lymph node involvement. Pathological evaluation showed spindle-shaped cell proliferation with mitotic activity in the second larger tissue which could be consistent with an inflammatory myofibroblastic tumor (IMT), whereas the first biopsy sample only showed granulomatous inflammation. Following multidisciplinary review the diagnosis of IMT was made and a treatment plan was decided. Because of the localized position of the mass the patient was treated with laser coagulation via rigid bronchoscopy instead of surgery. Bronchoscopic review afterwards showed complete resolution of the mass and the dyspnea had resolved. This case highlights the difficulty of making the IMT-diagnosis and the option of treating it with laser coagulation via rigid bronchoscopy. Show less
Nieuwkoop, C. van; Hoppe, B.P.C.; Bonten, T.N.; van't Wout, J.W.; Aarts, N.J.M.; Mertens, B.J.; ... ; Dissel, J.T. van 2010
Background. Radiologic evaluation of adults with febrile urinary tract infection (UTI) is frequently performed to exclude urological disorders. This study aims to develop a clinical rule predicting... Show moreBackground. Radiologic evaluation of adults with febrile urinary tract infection (UTI) is frequently performed to exclude urological disorders. This study aims to develop a clinical rule predicting need for radiologic imaging. Methods. We conducted a prospective, observational study including consecutive adults with febrile UTI at 8 emergency departments (EDs) in the Netherlands. Outcomes of ultrasounds and computed tomographs of the urinary tract were classified as "urgent urological disorder" (pyonephrosis or abscess), "nonurgent urologic disorder," "normal," and "incidental nonurological findings." Urgent and nonurgent urologic disorders were classified as " clinically relevant radiologic findings." The data of 5 EDs were used as the derivation cohort, and 3 EDs served as the validation cohort. Results. Three hundred forty-six patients were included in the derivation cohort. Radiologic imaging was performed for 245 patients (71%). A prediction rule was derived, being the presence of a history of urolithiasis, a urine pH >= 7.0, and/or renal insufficiency (estimated glomerular filtration rate, <= 40 mL/min/1.73 m(3)). This rule predicts clinically relevant radiologic findings with a negative predictive value (NPV) of 93% and positive predictive value (PPV) of 24% and urgent urological disorders with an NPV of 99% and a PPV of 10%. In the validation cohort (n = 131), the NPV and PPV for clinically relevant radiologic findings were 89% and 20%, respectively; for urgent urological disorders, the values were 100% and 11%, respectively. Potential reduction of radiologic imaging by implementing the prediction rule was 40%. Conclusions. Radiologic imaging can selectively be applied in adults with febrile UTI without loss of clinically relevant information by using a simple clinical prediction rule. Show less
