Nicholas M. Orme

Incidental Findings in Imaging Research Evaluating Incidence, Benefit, and Burden

BACKGROUND Little information exists concerning the frequency and medical significance of incidental findings (IFs) in imaging research. METHODS Medical records of research participants undergoing a research imaging examination interpreted by a radiologist during January through March 2004 were reviewed, with 3-year clinical follow-up. An expert panel reviewed all IFs generating clinical action to determine medical benefit/burden on the basis of predefined criteria. The frequency of IFs that generated further clinical action was estimated by modality, body part, age, and sex, along with net medical benefit or burden. RESULTS Of 1426 research imaging examinations, 567 (39.8%) had at least 1 IF (1055 total). Risk of an IF increased significantly by age (odds ratio [OR], 1.5; 95% confidence interval, 1.4-1.7 per decade increase). Abdominopelvic computed tomography generated more IFs than other examinations (OR, 18.9 vs ultrasonography; 9.2% with subsequent clinical action), with computed tomography of the thorax and magnetic resonance imaging of the head next (OR, 11.9 and 5.9; 2.8% and 2.2% with action, respectively). Of the 567 examinations with an IF, 35 (6.2%) generated clinical action, resulting in clear medical benefit in 1.1% (6 of 567) and clear medical burden in 0.5% (3 of 567). Medical benefit/burden was usually unclear (26 of 567 [4.6%]). CONCLUSIONS Frequency of IFs in imaging research examinations varies significantly by imaging modality, body region, and age. Research imaging studies at high risk for generating IFs can be identified. Routine evaluation of research images by radiologists may result in identification of IFs in a high number of cases and subsequent clinical action to address them in a small but significant minority. Such clinical action can result in medical benefit to a small number of patients.

Incidental Findings in CT Colonography: Literature Review and Survey of Current Research Practice

Incidental findings (IFs) of potential medical significance are seen in approximately 5-8 percent of asymptomatic subjects and 16 percent of symptomatic subjects participating in large computed tomography (CT) colonography (CTC) studies, with the incidence varying further by CT acquisition technique. While most CTC research programs have a well-defined plan to detect and disclose IFs, such plans are largely communicated only verbally. Written consent documents should also inform subjects of how IFs of potential medical significance will be detected and reported in CTC research studies.

Three-dimensional volumetric computed tomographic scoring as an objective outcome measure for chronic rhinosinusitis: clinical correlations and comparison to Lund-Mackay scoring.

We aimed to test the hypothesis that three‐dimensional (3D) volume‐based scoring of computed tomography (CT) images of the paranasal sinuses was superior to Lund‐Mackay CT scoring of disease severity in chronic rhinosinusitis (CRS). We determined correlation between changes in CT scores (using each scoring system) with changes in other measures of disease severity (symptoms, endoscopic scoring, and quality of life) in patients with CRS treated with triamcinolone.

Comparison of Surgical Septal Myectomy to Medical Therapy Alone in Patients With Hypertrophic Cardiomyopathy and Syncope

The presence of syncope despite medical therapy in patients with hypertrophic cardiomyopathy (HC) is considered an indication for surgical myectomy; however, no study has examined the long-term effects on recurrent syncope and survival after surgery in these patients. We examined 239 patients with HC and a history of syncope who had undergone surgical myectomy (mean age 48 ± 17 years; 56% men). The patients were age- and gender-matched to patients with HC and syncope who were treated medically without myectomy (mean age 51 ± 16 years; 59% men). The median follow-up period was 4.7 years (0.8, 11.3). The recurrence rate of syncope was 11% in the myectomy patients and 40% in the medical group (p <0.0001). Multiple episodes of syncope, left ventricular outflow tract obstruction, and recent syncope were identified as baseline predictors of recurrent syncope. Survival free of all-cause mortality was greater for patients who had undergone surgical myectomy than for the medically treated patients (10-year estimate 82 ± 4% vs 69 ± 4%; p = 0.01). In conclusion, surgical myectomy in patients with HC and a history of syncope was associated with a reduction in recurrent syncope and increased survival.

Imaging Pandora's Box: Incidental Findings in Elderly Patients Evaluated for Transcatheter Aortic Valve Replacement

OBJECTIVE To determine the frequency and clinical impact of noncardiovascular incidental findings (IFs) detected on preoperative computed tomographic angiography (CTA) of the chest/abdomen/pelvis performed in elderly patients with severe aortic stenosis being considered for transcatheter aortic valve replacement (TAVR). PATIENTS AND METHODS The CTA studies for 424 consecutive patients being evaluated for TAVR between January 1, 2009, through January 24, 2012, were reviewed for noncardiovascular IFs (62.0% male; median ± SD age, 82 ± 8.3 years). The electronic medical record was reviewed to assess for subsequent clinical management and survival. RESULTS Potentially pathologic IFs (PPIFs) were present in 285 patients (67.2%). The mean ± SD number of PPIFs per patient was 1.1 ± 1.0 (range, 0-4). Factors associated with higher numbers of PPIFs were reduced ejection fraction (P=.02) and history of smoking (P=.06). Potentially pathologic incidental findings prompted clinical work-up in 39 patients (9.2%) and delayed or canceled treatment plans for aortic stenosis in 7 patients (1.7%). The number needed to image to diagnose a new malignancy or medical condition was 19. The number of PPIFs was predictive of poor overall survival before (hazard ratio, 1.58; 95% CI, 1.31-1.88) and after (hazard ratio, 1.45; 95% CI, 1.19-1.76) adjustment for baseline clinical variables (P<.001 for both). CONCLUSION This investigation found that PPIFs are common in elderly patients undergoing TAVR-CTA scans and, once discovered, commonly generate further clinical evaluation. Higher numbers of PPIFs may be predictive of poorer survival, but further study is required to guide the appropriateness of pursuing diagnostic evaluations for asymptomatic PPIFs in this elderly population.

Histologically proven, low-grade brainstem gliomas in children: 30-year experience with long-term follow-up at Mayo Clinic.

Introduction:To evaluate long-term overall survival (OS), progression-free survival (PFS), and outcomes in pathologically proven brainstem low-grade gliomas (BS-LGG) in children. Methods:The Mayo Clinic tumor registry identified 48 consecutive children (⩽20 y, 52% female) with biopsy-proven BS-LGG treated at Mayo Clinic between January 1971 and December 2004. Medical records were retrospectively reviewed. For analysis, patients were censored at the time of recurrence, death, or last follow-up. Results:The median age at diagnosis was 12 years with a median follow-up of 6.0 years. The majority of tumors were grade I (69%) and pathology was consistent with an astrocytoma in the majority of patients (98%). Gross total resection was obtained in 4, subtotal in 17, and 27 patients were biopsied only. Postoperative radiotherapy (RT) was used in 29 patients. Median OS for the entire group was 14.8 years with a 1-, 5-, and 10-year OS of 85%, 67% and 59%, respectively. Median PFS for the entire group was 7.3 years. Improved survival was associated with undergoing resection versus biopsy-only with 5-year OS rates of 85% and 50% (P=0.002), respectively. A high proportion of patients (42%) had diffuse tumors and 13 patients (27%) had diffuse pontine gliomas (DPGs). DPGs had an OS of 1.8 years with a worse median PFS than non-DPGs (1.8 vs. 11.1 y; P=0.009). RT was used preferentially in patients with poor prognosis such as those who had a biopsy-only procedure (19/27) and DPGs (9/13). Conclusions:OS in this single institution retrospective study in pathologically proven BS-LGG with extensive follow-up displayed favorable long-term outcomes. Improved outcomes were associated with nondiffuse classification.

Age-related changes among 25 patients with congenital cardiac left-to-right shunts and irreversible plexogenic pulmonary arteriopathy

BACKGROUND Some patients with congenital heart disease and irreversible plexogenic pulmonary arteriopathy survive into adulthood. The purpose of this study was to compare histopathological and antigen expression patterns in adults and children with congenital heart disease and plexogenic pulmonary arteriopathy. METHODS Autopsy/explant lung tissues from 25 patients with congenital heart disease and plexogenic pulmonary arteriopathy were reviewed for 24 histopathological parameters associated with plexogenic pulmonary arteriopathy, including the prevalence and character of plexiform lesions. Immunohistochemistry using antibodies against CD31, C-kit, smooth muscle actin, CD68, and Fli-1 was performed to evaluate plexiform lesions. RESULTS Group 1 consisted of 14 patients aged <20 years, and Group 2 included 11 patients aged >or=20 years (range, 20-69 years). Cellular plexiform lesions trended toward greater prevalence in Group 1 than in Group 2 (P=.081), whereas involuted plexiform lesions more frequently affected Group 2 than Group 1 (P=.0037). In addition, recent platelet-fibrin thrombi within plexiform lesions occurred more often in Group 1 than in Group 2 (P=.0419). Intimal proliferation/fibrosis of elastic arteries and pulmonary vein dilation were more common in Group 2 (P=.0172 and P=.0048, respectively). CD31 and C-kit staining in non-lumen-lining cells of plexiform lesions was more frequent in Group 2 than in Group 1 (P=.0858 and P=.0173, respectively). No statistically significant differences in expression patterns between cellular and involuted plexiform lesions existed. CONCLUSIONS Among patients with congenital heart disease and plexogenic pulmonary arteriopathy, histopathological differences were observed between those surviving into adulthood and those dying in childhood/adolescence. Plexiform lesions in adults undergo remodeling from a cellular morphology to an involuted morphology. It is unclear whether this simply represents the natural progression of plexiform lesions or also confers a survival advantage.

Reply: Musculoskeletal Pain and Cancer Risk of Staff Working With Fluoroscopically Guided Procedures.

We greatly appreciate the interest of Dr. Fan and colleagues in our recent study published in the Journal [(1)][1]. We reported that hours per week involved in radiation-utilizing procedures and time per week wearing the lead apron were associated with increased musculoskeletal pain. It was

33-Year-Old Man With Syncope

A 33-year-old man presented for evaluation of syncope. A few weeks earlier, he had become light-headed and developed mild chest discomfort and visual changes while running from home plate to first base during a softball game. A few days before evaluation, he had been running on his treadmill when he became light-headed, lost consciousness, fell, injured his nose, and broke his glasses. Bystanders observed no seizure-like activity. He experienced no bowel or bladder incontinence, tongue biting, or postevent confusion. He denied antecedent palpitations, chest pain, sneezing, coughing, Valsalva maneuver, or change in emotion. His medical history was remarkable for mild depression and gastroesophageal reflux disease. He was taking 20 mg/d of citalopram and 20 mg/d of pantoprazole. He denied use of illicit drugs or excessive alcohol. His family history was notable for the unexplained death of 3 siblings (at ages 3 days, 1 week, and 3 years) and the unexpected death of his father at age 44 years. No autopsies were performed. The patients cardiac examination demonstrated a regular rhythm with a normal S1/S2 and a soft S4. At rest, no significant murmur was appreciated, but with the Valsalva maneuver a systolic ejection murmur appeared and reached a 3/6 intensity. Otherwise, findings on physical examination were unremarkable. Results of laboratory tests, including a complete blood cell count and an electrolyte panel, were within normal limits. Electrocardiography (ECG) showed normal sinus rhythm and biatrial enlargement. A 24-hour ambulatory ECG showed no significant atrial or ventricular dysrhythmia despite patient-reported episodes of light-headedness. Which one of the following is the most appropriate next diagnostic test? Tilt-table testing Electroencephalography Transthoracic echocardiography (TTE) Exercise ECG stress test Carotid ultrasonography Although neurocardiogenic syncope can often be detected using tilt-table testing, exertional syncope is not usually due to a vasovagal event. Electroencephalography is a reasonable choice when a generalized seizure is suspected as the cause of syncope, but in this case no convulsive activity or postictal state was reported by event observers. In a patient with exertional syncope, TTE is an appropriate diagnostic test, especially if there is auscultatory evidence of dynamic outflow tract obstruction.1 Exercise ECG stress testing can evaluate for cardiac ischemia but would not be the best next step given the patients age and lack of risk factors. Carotid ultrasonography is not the best choice because the patients lack of neurologic deficit and young age make a cerebrovascular event an unlikely cause of his syncope. Evidence of increased ventricular septal thickness (18 mm) with systolic anterior motion of the mitral valve apparatus was noted on TTE. Left ventricular outflow tract (LVOT) obstruction was noted at rest (36 mm Hg) and became severe with the Valsalva maneuver (88 mm Hg). These findings were consistent with a diagnosis of obstructive hypertrophic cardiomyopathy (HCM). Which one of the following is the best initial treatment option for this patient? β-Blocker Digoxin Angiotensin-converting enzyme inhibitor Long-acting nitrate Spironolactone A negative inotropic medication such as a β-blocker or non-dihydropyridine calcium channel blocker would be the most appropriate initial therapeutic intervention. Both β-blockers and calcium channel blockers can decrease the obstructive gradient in HCM by decreasing catecholamine-mediated contractility.2 These agents also increase diastolic filling by decreasing the heart rate. Digoxin is not appropriate in most patients with HCM because it has the opposite effect of a β-blocker, acting as an inotropic agent and increasing LVOT obstruction by increasing contractility. Angiotensin-converting enzyme inhibitors decrease preload and afterload and thus exacerbate the obstructive gradient in HCM. Likewise, diuretics and long-acting nitrates decrease cardiac preload, which also can exacerbate symptoms secondary to outflow tract obstruction. In contrast, patients with HCM should be instructed to avoid dehydration. The patient was prescribed metoprolol, titrated to 100 mg twice daily. He continued to experience presyncope and syncope and developed new symptoms of exertional dyspnea and chest pain. Despite dose titration and combination therapy with verapamil and later disopyramide, he did not improve. Follow-up TTE confirmed persistent LVOT obstruction, and 24-hour ambulatory ECG showed no evidence of arrhythmia. Which one of the following therapies would be most appropriate given the patients continued symptoms despite maximal medical therapy? Heart transplant Percutaneous alcohol septal ablation Initiation of amiodarone therapy Surgical septal myectomy Dual-chamber pacemaker Heart transplant would not be indicated at this stage but should be considered in patients with end-stage HCM refractory to medical and surgical therapy.3 Percutaneous alcohol septal ablation involves administration of ethanol into a septal perforator branch of the left anterior descending coronary artery supplying the involved hypertrophic segment. This causes a controlled myocardial infarction and subsequent atrophy of the obstructing myocardium. Complications from the procedure include infarction of an uninvolved segment or of an undesirable size (due to variations in coronary anatomy and distribution) and a relatively high incidence of complete heart block. Because of these potential complications and the lack of long-term follow-up, alcohol ablation is not considered the primary therapy for medically refractory HCM.3 Amiodarone would not be indicated in the absence of atrial fibrillation or ventricular arrhythmia.2 Surgical septal myectomy is the primary treatment option for symptomatic HCM refractory to medical therapy.2-4 Dual-chamber pacemakers have been used for drug-refractory, symptomatic HCM. However, they are not the primary treatment option, and their efficacy has been disputed in clinical trials.5 Which one of the following is an established major risk factor for sudden death (SD) in patients with HCM? Male sex First-degree family member with a history of SD Atrial fibrillation (AF) Presence of established HCM-associated gene mutation European ancestry In patients with HCM, sex is not associated with SD.6 A first-degree family member with SD is a significant risk factor and should prompt consideration of an implantable cardioverter-defibrillator (ICD).3,5,6 Atrial fibrillation has been associated with inappropriate ICD shocks, but no clear evidence suggests that it is a predictor of SD.3,6 It was hoped that the identification of certain genetic mutations would assist in the risk stratification of HCM. Unfortunately, considerable phenotypic variation among patients with genetic mutations has, to date, precluded widespread clinical use for risk stratification in HCM. No clear association has been established between race and SD risk.6 Given the patients recurrent syncopal episodes, significant LVOT obstruction, and family history of SD, an ICD was implanted for primary prophylaxis. Which one of the following would be an additional recommendation for this patient? Infective endocarditis prophylaxis with dental procedures Vigorous exercise regimen Anticoagulation Clinic follow-up in 3 years Echocardiographic screening for HCM in first-degree family members Infective endocarditis prophylaxis is no longer routinely recommended for patients with HCM.7 Patients with HCM are generally advised to abstain from high-intensity exercises.3 Anticoagulation is not indicated for HCM in the absence of another indication. Although follow-up intervals should be based on clinical symptoms and risk factors, patients should be seen at least annually for symptom assessment and ongoing screening for SD. Screening for HCM is strongly recommended in first-degree family members.3 The patient underwent a surgical septal myectomy without perioperative complications. He had a marked reduction in exertional dyspnea and chest pain and no recurrent syncope. He continued receiving β-blocker therapy and experienced no ICD discharges during 4 years of follow-up.

46-Year-Old Man With Treatment-Resistant Hypertension

A 46-year-old man presented for evaluation of treatment-resistant hypertension (HTN). He recalled being told that his systolic blood pressure was high when he was in high school; however, he did not begin taking antihypertensive medications until age 42 years. Despite multiple antihypertensive regimens, his HTN has been difficult to control and is consistently above his blood pressure target (<140/90 mm Hg) in multiple settings, including the physicians office and at home. His current regimen consists of 320 mg of valsartan, 200 mg/d of extended-release metoprolol, and 10 mg/d of amlodipine, which were his only medications. He had previously taken 25 mg/d of hydrochlorothiazide (in combination with valsartan and metoprolol); however, this was discontinued because of the inability to reach his blood pressure target and the development of hypokalemia (potassium level, 2.8 mmol/L). The patient reported that he adhered strictly to a low-sodium diet, rarely drank alcohol, never smoked, and rode a stationary bicycle for 60 minutes every day. He had intentionally lost about 11.4 kg (25 lbs) in the past 4 years. His medical history included obesity, hyperlipidemia, impaired fasting glucose levels, hypothyroidism treated with thyroid hormone replacement therapy, gout, and obstructive sleep apnea treated with continuous positive airway pressure (CPAP). He was recently evaluated in the sleep clinic, and his obstructive sleep apnea was being adequately treated with his current CPAP settings. The patient reported adherence to his antihypertensive medication regimen and CPAP use. He denied using nonsteroidal anti-inflammatory drugs or stimulant medications. He also denied headaches, palpitations, and diaphoresis.