Concomitant Pheochromocytoma and Primary Aldosteronism: A Case Series and Literature Review.

CONTEXT: The detection and management of concomitant pheochromocytoma (PHEO) and primary aldosteronism (PA) is not well understood. OBJECTIVE: To investigate varying presentations and outcomes of cases with coexisting PHEO and PA to provide an approach to its diagnosis and management. METHODS: We conducted a retrospective case series of adult patients with concomitant PHEO and PA at Mayo Clinic from 2000-2020 and an additional review of cases before 2000 and from the medical literature. Clinical, biochemical, radiologic, and histologic parameters were measured. RESULTS: Fifteen patients (53% men, median age 53 years) were diagnosed with concomitant PHEO and PA. The majority presented with hypertension (13, 87%) and hypokalemia (13, 87%), and 6 (40%) presented with symptoms suggestive of catecholamine excess. All patients who underwent preoperative workup for catecholamine excess (14, 93%) were found to have biochemical levels above the upper limits of normal. Adrenal vein sampling (AVS) was performed in 9 patients (60%), where 5 (56%) were diagnosed with bilateral PA, and 4 (44%) with unilateral PA. Patients underwent either unilateral (12, 80%) or bilateral (3, 20%) adrenalectomy. Biochemical improvement or resolution of catecholamine excess was confirmed in all cases with documented measurements. Recurrence of PHEO was not observed. Six patients (40%) displayed persistent PA postoperatively. CONCLUSION: Concomitant PHEO and PA is a rare but likely underreported condition. Hypertension with or without hypokalemia should prompt evaluation for PA, while any indeterminate adrenal mass should be assessed for PHEO. Coexisting disease warrants consideration of AVS to determine the laterality of PA to ensure appropriate management.

Surveillance imaging during first remission in follicular lymphoma does not impact overall survival.

BACKGROUND: Although many patients with follicular lymphoma (FL) undergo routine radiographic surveillance during their first remission, no consensus exists on the modality, duration, frequency, or need for routine imaging studies. The authors retrospectively examined the effect of surveillance imaging on relapse detection and overall survival (OS) in patients with FL. METHODS: Patients with newly diagnosed FL who had a response to induction therapy were identified from the Lymphoid Malignancies Enterprise Architecture Database (LEAD) at Emory University and from the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic. Patients were evaluated for both relapse and method of relapse detection (ie, clinical concerns vs radiologic detection through surveillance imaging in an asymptomatic patient). RESULTS: Of 148 patients in the LEAD cohort, 55 (37%) relapsed, and the majority (n = 35; 64%) of relapses were detected clinically. In the MER cohort, 63 of 177 relapses (54%) were detected clinically. There was no significant difference in OS from the date of diagnosis between the 2 methods of relapse detection in the LEAD (hazard ratio [HR], 0.61; 95% CI, 0.13-2.94; P = .54) and MER (HR, 1.02; 95% CI, 0.47-2.21; P = .96) cohorts. Similarly, there was no significant difference in OS from the date of relapse between the 2 methods of relapse detection in the LEAD (HR, 0.47; 95% CI, 0.10-2.27; P = .35) and MER (HR, 1.02; 95% CI, 0.47-2.21; P = .96) cohorts. CONCLUSIONS: These findings suggest a limited role for routine surveillance imaging in patients with FL who complete front-line therapy. Future studies should evaluate which patients may benefit from a more aggressive surveillance approach and should explore novel methods of relapse detection.

Presentation, disease progression and outcomes of adrenal gland metastases.

OBJECTIVE: Data on the presentations and outcomes of patients with adrenal gland metastases are limited. Our objectives were to characterize the prevalence of adrenal metastases subtypes and investigate how varying clinical presentations affect disease progression, development of primary adrenal insufficiency (PAI) and mortality. DESIGN: Single institution tertiary centre, retrospective cohort study from 1997 to 2020. PATIENTS AND MEASUREMENTS: Adult patients with adrenal metastases. Clinical, radiologic and biochemical presentations and outcomes were reviewed. RESULTS: Of 579 patients (62.3% men, median age 67 years [range 25-92]) with adrenal metastases (median tumour size of 30 mm [range 5-200]), 339 (58.5%) were discovered during cancer staging, 210 (36.3%) were found incidentally, and 29 (5.0%) based on symptoms. Tumours originated from the lung (226, 39.0%), genitourinary (GU) (160, 27.6%), gastrointestinal (GI) (79, 13.6%) and other (114, 19.7%) organ systems. Bilateral metastases were found in 140 (24.2%) patients at the time of initial diagnosis, and 249 (43.0%) had bilateral disease throughout the study course. PAI developed in 12.4% of patients with bilateral disease and was associated with larger tumour size. Median follow-up time was 14 months (range 0-232), and 442 (76.3%) patients died. Higher mortality was independently associated with older age, adrenal metastases originating from the lung, bilateral disease, and the absence of adrenalectomy. CONCLUSIONS: Adrenal gland metastases originated most commonly from lung, GU and GI malignancies. Bilateral adrenal metastases occurred in 43% of patients, and PAI occurred in 12.4% of those with bilateral disease, warranting further case detection strategies.

Next-generation sequencing applied to rare diseases genomics.

Genomics has revolutionized the study of rare diseases. In this review, we overview the latest technological development, rare disease discoveries, implementation obstacles and bioethical challenges. First, we discuss the technology of genome and exome sequencing, including the different next-generation platforms and exome enrichment technologies. Second, we survey the pioneering centers and discoveries for rare diseases, including few of the research institutions that have contributed to the field, as well as an overview survey of different types of rare diseases that have had new discoveries due to next-generation sequencing. Third, we discuss the obstacles and challenges that allow for clinical implementation, including returning of results, informed consent and privacy. Last, we discuss possible outlook as clinical genomics receives wider adoption, as third-generation sequencing is coming onto the horizon, and some needs in informatics and software to further advance the field.

A prospective pilot clinical trial evaluating the utility of a dynamic near-infrared imaging device for characterizing suspicious breast lesions.

INTRODUCTION: Characterizing and differentiating between malignant tumors, benign tumors, and normal breast tissue is increasingly important in the patient presenting with breast problems. Near-infrared diffuse optical imaging and spectroscopy is capable of measuring multiple physiologic parameters of biological tissue systems and may have clinical applications for assessing the development and progression of neoplastic processes, including breast cancer. The currently available application of near-infrared imaging technology for the breast, however, is compromised by low spatial resolution, tissue heterogeneity, and interpatient variation. MATERIALS AND METHODS: We tested a dynamic near-infrared imaging schema for the characterization of suspicious breast lesions identified on diagnostic clinical ultrasound. A portable handheld near-infrared tissue imaging device (P-Scan; ViOptix Inc., Fremont, CA, USA) was utilized. An external mechanical compression force was applied to breast tissue. The tissue oxygen saturation and hemoglobin concentration were recorded simultaneously by the handheld near-infrared imaging device. Twelve categories of dynamic tissue parameters were derived based on real-time measurements of the tissue hemoglobin concentration and the oxygen saturation. RESULTS: Fifty suspicious breast lesions were evaluated in 48 patients. Statistical analyses were carried out on 36 out of 50 datasets that satisfied our inclusion criteria. Suspicious breast lesions identified on diagnostic clinical ultrasound had lower oxygenation and higher hemoglobin concentration than the surrounding normal breast tissue. Furthermore, histopathologic-proven malignant breast tumors had a lower differential hemoglobin contrast (that is, the difference of hemoglobin concentration variability between the suspicious breast lesion and the normal breast parenchyma located remotely elsewhere within the ipsilateral breast) as compared with histopathologic-proven benign breast lesions. CONCLUSION: The proposed dynamic near-infrared imaging schema has the potential to differentiate benign processes from those of malignant breast tumors. Further development and refinement of the dynamic imaging device and additional subsequent clinical testing are necessary for optimizing the accuracy of detection.

Development of a handheld near-infrared imager for dynamic characterization of in vivo biological tissue systems.

A handheld near-infrared imager was developed for real-time monitoring of tissue physiologic changes in response to dynamic compression stimuli. Both 2D and 3D imaging schemas were developed for reconstruction of tissue heterogeneities based on optical measurements. The handheld imager and the dynamic imaging schema were validated on both benchtop phantoms and in vivo human tissues. The benchtop tests demonstrated that the imager was able to reconstruct absorption properties of the embedded heterogeneity with accuracy and repeatability. The tests on in vivo human tissues demonstrated that the imager was able to generate various dynamic loading profiles with reproducibility and to detect tissue optical, mechanical, and physiologic changes under the dynamic loading condition.

Localization and functional parameter reconstruction of suspicious breast lesions by near infrared/ultrasound dual modal imaging.

A novel imaging scheme integrating a continuous wave (CW) hand held near infrared tissue imager and a portable ultrasound probe was proposed for evaluation of suspicious breast lesions. A new methodology was developed to reconstruct functional properties of the lesion and the surrounding tissue based on the optical measurement of the diffusive light and the ultrasound measurement of the tumor morphology. The first order Born approximation was used to solve the absorption coefficients for both the tumor tissue and the background tissue assuming that optical properties within each tissue type are uniform. A compression force was applied by the handheld near infrared imager to the breast tissue in order to enhance the optical contrast. The force was monitored by a built-in load cell. 2D projection algorithm was used to find the center of the tumor and to co-register the near infrared image with the ultrasound image. The proposed imaging scheme was tested by a clinical trial where both near infrared and ultrasound data were collected on subjects' breast tissues with embedded suspicious lesions. 3D image algorithm on single patient successfully reconstructed the oxygen saturation and the hemoglobin concentration in both the tumor area and the surrounding tissue. More data collection and analysis are required to confirm this imaging scheme.

Near infrared imaging of tissue heterogeneity: probe design and sensitivity analysis.

A CW type handheld near infrared tissue oximeter called P-Scan tissue imager was developed for real time imaging of tissue oxygen saturation ([StO2]) and hemoglobin concentration ([Hbt]). The probe consists of eight dual-wavelength light sources (690nm and 830nm) and eight photon detectors forming a 2.5cm X 2.5cm matrix. The local tissue oxygen saturation and hemoglobin concentration was calculated based on optical measurement of absorption coefficients for oxy and deoxy hemoglobin. A superimposition algorithm was developed for direct imaging of local tissue [StO2]/[Hbt] without complex inverse reconstruction. The measurement sensitivity of such a P-Scan device with respect to tumor size, tumor depth, tumor lateral location and tumor optical contrast was studied. First order Born approximation was used to simulate the photon migration in a 2D turbid model with an embedded absorber. The simulation results implied that the P-Scan imager is able to detect the tissue heterogeneity up to 1.5 cm deep with reasonably high sensitivity. Simulation also indicated that among multiple factors that may influence the P-Scan sensitivity, tumor size and tumor depth are dominant factors.*