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BACKGROUND - Misidentifying parathyroid glands (PGs) during thyroidectomies or parathyroidectomies could significantly increase postoperative morbidity. Imaging systems based on near infrared autofluorescence (NIRAF) detection can localize PGs with high accuracy. These devices, however, depict NIRAF images on remote display monitors, where images lack spatial context and comparability with actual surgical field of view. In this study, we designed an overlay tissue imaging system (OTIS) that detects tissue NIRAF and back-projects the collected signal as a visible image directly onto the surgical field of view instead of a display monitor, and tested its ability for enhancing parathyroid visualization.
STUDY DESIGN - The OTIS was first calibrated with a fluorescent ink grid and initially tested with parathyroid, thyroid, and lymph node tissues ex vivo. For in vivo measurements, the surgeon's opinion on tissue of interest was first ascertained. After the surgeon looked away, the OTIS back-projected visible green light directly onto the tissue of interest, only if the device detected relatively high NIRAF as observed in PGs. System accuracy was determined by correlating NIRAF projection with surgeon's visual confirmation for in situ PGs or histopathology report for excised PGs.
RESULTS - The OTIS yielded 100% accuracy when tested ex vivo with parathyroid, thyroid, and lymph node specimens. Subsequently, the device was evaluated in 30 patients who underwent thyroidectomy and/or parathyroidectomy. Ninety-seven percent of exposed tissue of interest was visualized correctly as PGs by the OTIS, without requiring display monitors or contrast agents.
CONCLUSIONS - Although OTIS holds novel potential for enhancing label-free parathyroid visualization directly within the surgical field of view, additional device optimization is required for eventual clinical use.
Copyright © 2019 American College of Surgeons. Published by Elsevier Inc. All rights reserved.
BACKGROUND - Inadvertent removal of parathyroid glands is a challenge in endocrine operations. There is a critical need for a diagnostic tool that provides sensitive, real-time parathyroid detection during procedures. We have developed an intraoperative technique using near-infrared (NIR) fluorescence for in vivo, real-time detection of the parathyroid regardless of its pathologic state.
METHODS - NIR fluorescence was measured intraoperatively from 45 patients undergoing parathyroidectomy and thyroidectomy. Spectra were measured from the parathyroid and surrounding neck tissues during the operation with the use of a portable, probe-based fluorescence system at 785-nm excitation. Accuracy was evaluated by comparison with histology or visual recognition by the surgeon.
RESULTS - NIR fluorescence detected the parathyroid in 100% of patients. Parathyroid fluorescence was stronger (1.2-18 times) than that of the thyroid with peak fluorescence at 822 nm. Surrounding tissues showed no auto-fluorescence. Disease state did not affect the ability to discriminate parathyroid glands but may account for signal variability.
CONCLUSION - NIR fluorescence spectroscopy can detect intraoperatively the parathyroid regardless of tissue pathology. The signal may be caused by calcium-sensing receptors present in the parathyroid. The signal strength and consistency indicates the simplicity and effectiveness of this method. Its implementation may limit operative time, decrease costs, and improve operative success rates.
Copyright © 2013 Mosby, Inc. All rights reserved.
Observational studies in primary hyperaldosteronism suggest a positive relationship between aldosterone and parathyroid hormone (PTH); however, interventions to better characterize the physiological relationship between the renin-angiotensin-aldosterone system (RAAS) and PTH are needed. We evaluated the effect of individual RAAS components on PTH using 4 interventions in humans without primary hyperaldosteronism. PTH was measured before and after study (1) low-dose angiotensin II (Ang II) infusion (1 ng/kg per minute) and captopril administration (25 mg×1); study (2) high-dose Ang II infusion (3 ng/kg per minute); study (3) blinded crossover randomization to aldosterone infusion (0.7 µg/kg per hour) and vehicle; and study (4) blinded randomization to spironolactone (50 mg/daily) or placebo for 6 weeks. Infusion of Ang II at 1 ng/kg per minute acutely increased aldosterone (+148%) and PTH (+10.3%), whereas Ang II at 3 ng/kg per minute induced larger incremental changes in aldosterone (+241%) and PTH (+36%; P<0.01). Captopril acutely decreased aldosterone (-12%) and PTH (-9.7%; P<0.01). In contrast, aldosterone infusion robustly raised serum aldosterone (+892%) without modifying PTH. However, spironolactone therapy during 6 weeks modestly lowered PTH when compared with placebo (P<0.05). In vitro studies revealed the presence of Ang II type I and mineralocorticoid receptor mRNA and protein expression in normal and adenomatous human parathyroid tissues. We observed novel pleiotropic relationships between RAAS components and the regulation of PTH in individuals without primary hyperaldosteronism: the acute modulation of PTH by the RAAS seems to be mediated by Ang II, whereas the long-term influence of the RAAS on PTH may involve aldosterone. Future studies to evaluate the impact of RAAS inhibitors in treating PTH-mediated disorders are warranted.
PURPOSE OF REVIEW - Improved recognition of velocardiofacial syndrome (VCFS) has led to increasing awareness of VCFS by otolaryngologists. Understanding the developmental biologic processes affected in VCFS patients will help improve treatment and outcomes. Advanced application of molecular labeling techniques has better outlined the role of T-Box transcription factor 1 (TBX1) as the primary genetic anomaly leading to VCFS. TBX1 plays multiple roles during branchial, cardiac, and craniofacial development and increased understanding of how these systems are affected by TBX1 mutations will improve patient outcomes. Furthermore, additional modifiers of TBX1 expression have been identified that may explain the variability of VCFS phenotypes. The phenotypic spectrum of VCFS may include cardiac anomalies, velopharyngeal insufficiency, aberrant calcium metabolism, and immune dysfunction. Recent interest has focused on the cognitive and neuropsychiatric manifestations of VCFS. Improved understanding of the biology of VCFS associated mutations has the potential to improve therapeutic outcomes.
RECENT FINDINGS - This article will discuss recent developmental biologic understanding of the role of TBX1 and genetic modifiers generating the phenotypic variability seen in VCFS patients. Special attention is given to advances in the realms of immunodeficiency, hypocalcemia, cardiac and arterial patterning anomalies, velopharyngeal insufficiency, as well as cognitive and psychiatric problems.
SUMMARY - Enhanced understanding of the multiple systems affected by TBX1 mutations will result in improved patient outcomes and improved family education. Future research will lead to improved detection of potential targets for gene therapy and change the way physicians counsel families and treat patients.
A major challenge in endocrine surgery is the intraoperative detection of parathyroid glands during both thyroidectomies and parathyroidectomies. Current localization techniques such as ultrasound and sestamibi scan are mostly preoperative and rely on an abnormal parathyroid for its detection. In this paper, we present near-infrared (NIR) autofluorescence as a nonintrusive, real-time, automated in vivo method for the detection of the parathyroid gland. A pilot in vivo study was conducted to assess the ability of NIR fluorescence to identify parathyroid glands during thyroid and parathyroidectomies. Fluorescence measurements at 785 nm excitation were obtained intra-operatively from the different tissues exposed in the neck region in 21 patients undergoing endocrine surgery. The fluorescence intensity of the parathyroid gland was found to be consistently greater than that of the thyroid and all other tissues in the neck of all patients. In particular, parathyroid fluorescence was two to eleven times higher than that of the thyroid tissues with peak fluorescence occurring at 820 to 830 nm. These results indicate that NIR fluorescence has the potential to be an excellent optical tool to locate parathyroid tissue during surgery.
This article reviews the current state of the art regarding therapy for primary hyperparathyroidism. Clinical evaluation and indications for parathyroidectomy are described, followed by a review of surgical techniques currently being practiced and possible outcomes involved. Focused parathyroidectomy has become a successful alternative to conventional bilateral cervical exploration.
BACKGROUND - Ultrasound has been used successfully to localize parathyroid glands. This study evaluates surgeon-performed ultrasound (SUS) for pre-operative parathyroid localization prior to parathyroidectomy.
METHODS - In all, 442 patients with primary hyperparathyroidism (HPT) underwent SUS at a single institution. Patients were divided into 2 groups: group 1 (n = 338) had correct localization, and group 2 (n = 104) had incorrect localization. The true-positive (TP) rate and peri-operative findings were compared. TP was defined as localization of all abnormal parathyroids resulting in operative success. A P value >.05 was considered significant.
RESULTS - Of 442 patients, 338 (76.5%) had TP results. Group 1 patients were younger (57 vs 63 years; P < .0001) with larger gland size: 2.1 versus 1.8 cm (P = .08). In group 2, 45/104 (43%) patients had false-positive SUS, and 59/104 (57%) had negative studies or missed multiglandular disease (MGD). Group 1 patients had shorter operative times (60 vs 80 min, P = .002), fewer bilateral neck explorations (BNEs) (8% vs 39%; P < .0001), and lower MGD rates (2% vs 19%; P < .0001). Operative failure was 0.3% in group 1 and 9.6% in group 2 (P < .0001).
CONCLUSION - Younger patients have a greater rate of correct localization. When SUS correlates with operative findings, MGD is significantly lower and fewer BNEs are performed. Additionally, operations are shorter with a higher success rate.
BACKGROUND - Many patients with sporadic primary hyperparathyroidism (SPHPT) have discordant preoperative Tc-99m-sestamibi (MIBI) and ultrasonography studies prior to focused parathyroidectomy (PTX). This study examines the usefulness of intraoperative parathormone monitoring (IPM) during PTX in patients with discordant preoperative localization studies.
METHODS - A retrospective series of 225 consecutive SPHPT patients with MIBI scans and surgeon performed ultrasonography (SUS) prior to focused parathyroidectomy were studied. All patient operations were reviewed, and how IPM changed operative management was determined. Correct gland localization, presence of multigland disease (MGD), and operative outcome were also examined.
RESULTS - In 225 patients, overall operative success was 97%, and IPM changed operative management in 29% of patients. In 85 patients (38%) with discordant studies, operative success was 93%; IPM changed operative management in 74% of these patients. IPM allowed for 66% (56/85) of these operations to be performed as unilateral neck exploration and confirmed removal of abnormal glands in 7 patients with MGD. In 140 patients (62%) with concordant localization, in which operative success was 99%, IPM changed operative management in only 2% (3/140) of these patients with MGD.
CONCLUSION - Although of marginal benefit in patients with concordant imaging studies, IPM remains essential for performing successful PTX with discordant or incorrect concordant localization.
BACKGROUND - Parathyroid histopathology has been used to predict single or multiglandular disease (MGD). "Hyperplasia" implies MGD, whereas "adenoma" suggests single gland involvement. Intraoperative parathyroid hormone (PTH) monitoring (IPM) guides parathyroidectomy based on function. We sought to evaluate the accuracy of histopathology in the diagnosis of single or MGD and in predicting operative success.
METHODS - We reexamined the parathyroid glands from 402 patients with sporadic primary hyperparathyroidism (SPHPT) who underwent initial IPM-guided parathyroidectomies. Operative findings and outcome were correlated with histopathology of excised glands. Operative success was eucalcemia for >or=6 months and recurrence of hypercalcemia/high PTH after successful parathyroidectomy.
RESULTS - Of 402 patients, 384 had 1 gland excised resulting in operative success; hyperplasia was diagnosed in 244 of the 384 (64%), with only 2 developing recurrence. Of the 384 patients, 140 (37%) had adenomas with 1 late recurrence. There were 18 patients with MGD (14 hyperplasias, 4 adenomas). There were 5 failures with hyperplasia predicting MGD. Histopathology was incorrect in predicting the number of glands involved in 249 of 402 (62%) patients, and IPM was incorrect in only 13 (3%).
CONCLUSION - Histopathology of excised abnormal parathyroid glands does not predict the secretory function of the remaining parathyroid glands left in situ. IPM guided parathyroidectomy accurately based on function alone; however, histopathology was inaccurate in predicting MGD and should not be used to guide parathyroidectomy in patients with SPHPT.
PURPOSE OF REVIEW - This article reviews the diagnosis and treatment of primary hyperparathyroidism, including recent literature on the subject.
RECENT FINDINGS - Important recent advancements in the field of parathyroid disease include improvements in preoperative localization, the use of intraoperative parathyroid hormone monitoring, and the development of minimally invasive and videoscopic surgical techniques. Additionally, there has been significant interest in better understanding the clinical changes and presentation of sporadic primary hyperparathyroidism, including the assessment of neurocognitive symptoms before and after surgery. This has led to a change in the definition of the 'asymptomatic patient' and altered the criteria used to trigger surgical intervention.
SUMMARY - Although the cause of primary hyperparathyroidism is still poorly understood, surgical parathyroidectomy results in long-term cure in greater than 95% of cases. Improvements in our understanding of this disease continue to make diagnosis and treatment safer and more effective.