Innovative surgical guidance for label-free real-time parathyroid identification.

BACKGROUND: Difficulty in identifying the parathyroid gland during neck operations can lead to accidental parathyroid gland excisions and postsurgical hypocalcemia. A clinical prototype called as PTeye was developed to guide parathyroid gland identification using a fiber-optic probe that detects near-infrared autofluorescence from parathyroid glands as operating room lights remain on. An Overlay Tissue Imaging System was designed concurrently to detect near-infrared autofluorescence and project visible light precisely onto parathyroid gland location. METHODS: The PTeye and the Overlay Tissue Imaging System were tested in 20 and 15 patients, respectively, and a modified near-infrared imaging system was investigated in 6 patients. All 41 patients underwent thyroidectomy or parathyroidectomy. System accuracy was ascertained with surgeon's visual confirmation for in situ parathyroid glands and histology for excised parathyroid glands. RESULTS: There was no observable difference between near-infrared autofluorescence of healthy and diseased parathyroid glands. The PTeye identified 98% of the parathyroid gland, whereas the near-infrared imaging system and the Overlay Tissue Imaging System identified 100% and 97% of the parathyroid glands, respectively. CONCLUSION: The PTeye can guide in real-time parathyroid gland identification even with ambient operating room lights. The near-infrared imaging system performs parathyroid gland imaging with high sensitivity, whereas the Overlay Tissue Imaging System enhances parathyroid gland visualization directly within the surgical field without requiring display monitors. These label-free technologies can be valuable adjuncts for identifying parathyroid glands intraoperatively.

Developing a Clinical Prototype to Guide Surgeons for Intraoperative Label-Free Identification of Parathyroid Glands in Real Time.

BACKGROUND: Patients undergoing thyroidectomy may have inadvertent damage or removal of the parathyroid gland(s) due to difficulty in real-time parathyroid identification. Near-infrared autofluorescence (NIRAF) has been demonstrated as a label-free modality for intraoperative parathyroid identification with high accuracy. This study presents the translation of that approach into a user-friendly clinical prototype for rapid intraoperative guidance in parathyroid identification. METHODS: A laboratory (lab)-built spectroscopy system that measures NIRAF in tissue was evaluated for identifying parathyroid glands in vivo across 162 patients undergoing thyroidectomy and/or parathyroidectomy. Based on these results, a clinical prototype called PTeye was designed with a user-friendly interface and subsequently investigated in 35 patients. The performance of the lab-built system and the clinical prototype were concurrently compared side by side by a single user with 20 patients in each group. The influence of (i) intrapatient and interpatient variability of NIRAF in thyroid and parathyroid glands and (ii) thyroid and parathyroid pathology on intraoperative parathyroid identification were investigated. The effect of blood on NIRAF intensity of parathyroid and thyroid was tested ex vivo with the PTeye system to assess if a hemorrhagic surgical field would affect parathyroid identification. Accuracy of both systems were determined by correlating the acquired data with either visual confirmation by a surgeon for unexcised parathyroid glands or histology reports for excised parathyroid glands. RESULTS: The overall accuracy of the lab-built system in guiding parathyroid identification was 92.5%, while the PTeye system achieved an accuracy of 96.1%. Unlike the lab-built system, the PTeye could guide parathyroid identification even as the operating room lights remained on and required only 25% of the laser power used by the lab-built setup. Parathyroid glands had elevated NIRAF intensity compared to thyroid and other neck tissues, regardless of thyroid or parathyroid pathology. Blood did not seem to affect tissue NIRAF measurements obtained with both systems. CONCLUSION: In this study, the clinical prototype PTeye demonstrated high accuracy for label-free intraoperative parathyroid identification. The intuitive interface of the PTeye that can guide in identifying parathyroid tissue in the presence of ambient room lights suggests that it is a reliable and easy-to-use tool for surgical personnel.

Establishing the clinical utility of autofluorescence spectroscopy for parathyroid detection.

BACKGROUND: The inability of surgeons to identify parathyroid glands accurately during cervical endocrine surgery hinders patients from achieving postoperative normocalcemia. An intrinsic, near-infrared fluorescence method was developed for real-time parathyroid identification with high accuracy. This study assesses the clinical utility of this approach. METHODS: Autofluorescence measurements were obtained from 137 patients (264 parathyroid glands) undergoing parathyroidectomy and/or thyroidectomy. Measurements were correlated to disease state, calcium levels, parathyroid hormone, vitamin D levels, age, sex, ethnicity, and body mass index. Statistical analysis identified which factors affect parathyroid detection. RESULTS: High parathyroid fluorescence was detected consistently and showed wide variability across patients. Near-infrared fluorescence was used to identify 256 of 264 (97%) of glands correctly. The technique showed high accuracy over a wide variety of disease states, although patients with secondary hyperparathyroidism demonstrated confounding results. Analysis revealed body mass index (P < .01), disease state (P < .01), vitamin D (P < .05), and calcium levels (P < .05) account greatly for variability in signal intensity. Age, sex, parathyroid hormone, and ethnicity had no effect. CONCLUSION: This intrinsic fluorescence-based intraoperative technique can detect nearly all parathyroid glands accurately in real time. Its discrimination capacity is largely unlimited by patient variables, but several factors affect signal intensity. These results demonstrate potential clinical utility of optical guidance for parathyroid detection.

Influence of adrenal pathology on perioperative outcomes: a multi-institutional analysis.

BACKGROUND: Endoscopic or open adrenalectomies are performed for variable pathologies. We investigated if adrenal pathology affects perioperative outcomes independent of operative approach. METHODS: A multi-institutional retrospective review of 345 adrenalectomies was performed. A multivariate analysis was utilized. RESULTS: Pathology groups included benign non-pheochromocytoma tumors (50.4%), pheochromocytomas (41%), adrenocortical carcinomas (5.2%), and metastatic tumors (3.4%). Controlling for age, body mass index, tumor size, procedure type, and pathology, pheochromocytomas exhibited greater blood loss (92 mL more, P = .007) and operative times (33 min more, P < .001) than benign non-pheochromocytoma tumors. Metastatic tumors demonstrated longer operative times (53 min more, P = .013). Open adrenalectomy was associated with greater blood loss (396 mL more, P = .001), transfusion requirement (P = .021), operative times (79 min more, P < .001), hospital stay (6.6 days more, P < .001) and complications (P < .001) when compared with endoscopic adrenalectomy. CONCLUSIONS: The type of adrenal pathology appears to influence blood loss and operative time but not complications in patients undergoing adrenalectomy. Open adrenalectomy remains a major driver of adverse perioperative outcomes.

Label-free intraoperative parathyroid localization with near-infrared autofluorescence imaging.

CONTEXT: The inability to accurately localize the parathyroid glands during parathyroidectomy and thyroidectomy procedures can prevent patients from achieving postoperative normocalcemia. There is a critical need for an improved intraoperative method for real-time parathyroid identification. OBJECTIVE: The objective of the study was to test the accuracy of a real-time, label-free technique that uses near-infrared (NIR) autofluorescence imaging to localize the parathyroid. SETTING: The study was conducted at the Vanderbilt University endocrine surgery center. SUBJECTS AND METHODS: Patients undergoing parathyroidectomy and/or thyroidectomy were included in this study. To validate the intrinsic fluorescence signal in parathyroid, point measurements from 110 patients were collected using NIR fluorescence spectroscopy. Fluorescence imaging was performed on 6 patients. Imaging contrast is based on a previously unreported intrinsic NIR fluorophore in the parathyroid gland. The accuracy of fluorescence imaging was analyzed in comparison with visual assessment and histological findings. MAIN OUTCOME MEASURE: The detection rate of parathyroid glands was measured. RESULTS: The parathyroid glands in 100% of patients measured with fluorescence imaging were successfully detected in real time. Fluorescence images consistently showed 2.4 to 8.5 times higher emission intensity from the parathyroid than surrounding tissue. Histological validation confirmed that the high intrinsic fluorescence signal in the parathyroid gland can be used to localize the parathyroid gland regardless of disease state. CONCLUSION: NIR fluorescence imaging represents a highly sensitive, real-time, label-free tool for parathyroid localization during surgery. The elegance and effectiveness of NIR autofluorescence imaging of the parathyroid gland makes it highly attractive for clinical application in endocrine surgery.

Predictors of hemodynamic instability during surgery for pheochromocytoma.

BACKGROUND: Resection of pheochromocytoma is often associated with hemodynamic instability (HDI). We examined patient and tumor factors that may influence HDI. The effect of pretreatment with nonselective α blockade phenoxybenzamine (PXB) versus selective α blockade on HDI and outcomes was also evaluated. METHODS: The records of 91 patients who underwent adrenalectomy between 2002 and 2013 were retrospectively reviewed. HDI was determined by number of intraoperative episodes of systolic blood pressure (SBP) > 200 mmHg, those greater than or less than 30 % of baseline, heart rate > 110 bpm, and the need for postoperative vasopressors. Fishers exact, t test and regressions were performed. RESULTS: Among 91 patients, 78 % received PXB, 18 % selective α blockade and 4 % no adrenergic blockade. Patient demographics, tumor factors and surgical approach were similar among the blockade groups. On multivariate analysis, increasing tumor size was associated with a significant rise in the number of episodes of SBP > 30 % [rate ratio (RR) 1.40] and an increased postoperative vasopressor requirement [odds ratio (OR) 1.23]. Open adrenalectomy and use of selective blockade were associated with an increased number of episodes of SBP > 200 mmHg (RR 27.8 and RR 20.9, respectively). Open adrenalectomy was also associated with increased readmissions (OR 12.3), complications (OR 5.6), use of postoperative vasopressors (OR 4.4) and hospital stay (4.6 days longer). There were no differences in other HDI measurements or postoperative outcomes among the blockade groups. CONCLUSIONS: Tumor size, open adrenalectomy, and type of α blockade were associated with intraoperative HDI during pheochromocytoma resection. Selective blockade was associated with significantly more episodes of intraoperative hypertension but no perioperative adverse outcomes.

A novel optical approach to intraoperative detection of parathyroid glands.

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.

Total thyroidectomy for Graves' disease: compliance with American Thyroid Association guidelines may not always be necessary.

BACKGROUND: Total thyroidectomy (TT) is the preferred operative approach to Graves' disease. Current guidelines of the American Thyroid Association call for the administration of potassium iodide (KI) and achievement of euthyroid state before operation. Small numbers and a mixture of operative approaches spanning several decades hinder previous operative series. We present the outcomes for TT at a single high-volume center. METHODS: A retrospective cohort study was conducted on 165 patients undergoing TT for Graves' disease from July 2007 to May 2012. RESULTS: Mean age was 43 years (range, 17-78), and 128 patients (78%) were female. A total of 95% of patients were on methimazole or propylthiouracil, and 42% remained hyperthyroid at time of TT. Only 3 (2%) patients received KI. Mean operative time was 132 minutes (range, 59-271). Mean gland size and blood loss were 41 g (range, 8-180) and 55 mL (range, 10-1050), respectively. No patient developed thyroid storm. Median follow-up was 7.5 months. Temporary and permanent hypocalcemia developed in 51 (31%) and 2 patients (1.2%), respectively. Temporary and permanent recurrent laryngeal nerve paresis occurred in 12 (7%) and one (0.6%) patient, respectively. Sixty-one (37%) patients experienced at least one complication. On multivariate analysis, patient age younger than 45 years (odds ratio 2.93, 95% confidence interval 1.39-6.19) and obesity (odds ratio 2.11, 95% confidence interval 1.00-4.43) were associated with the occurrence of complications. CONCLUSION: This high-volume surgeon experience demonstrates no appreciable detriment to patient outcomes when recommendations of the American Thyroid Association for routine use of KI and euthyroid state before thyroidectomy are not met. Transient hypocalcemia and hoarseness are frequent complications of TT for Graves' disease, resolving within 6 months in most patients. Age younger than 45 years and obesity are risk factors for postoperative complications.

Is potassium iodide solution necessary before total thyroidectomy for Graves disease?

BACKGROUND: Potassium iodide (KI) has traditionally been used to reduce gland vascularity and diminish blood loss in patients undergoing thyroidectomy for Graves disease (GD). Current American Thyroid Association (ATA) guidelines (Recommendation 22) call for its routine administration in GD but avoidance in toxic multinodular goiter (TMNG). METHODS: A retrospective review (July 2008-May 2012) of perioperative data was performed on 162 patients undergoing total thyroidectomy without preoperative KI and compared to 102 patients with TMNG. Statistical analysis included Student's t test, χ2 test, and multivariate linear regression. RESULTS: Compared to TMNG patients, GD patients had a lower mean age (42.7 vs. 49.6 years, p<0.001) and were less likely to be obese (37 vs. 54%, p=0.047). No patients were provided KI in preparation. GD patients did not differ significantly from TMNG patients with respect to mean estimated blood loss (55.4 vs. 51.5 mL, p=0.773) or mean operative time (131.5 vs. 122.6 min, p=0.084). GD patients had a lower rate of transient hypocalcemia (31 vs. 49%, p=0.004), but the two groups did not statistically differ in rates of prolonged hypocalcemia, temporary recurrent laryngeal nerve (RLN) palsy, prolonged RLN paralysis, or hematoma formation. CONCLUSIONS: Although current ATA recommendations for the management of GD call for routine use of KI before thyroidectomy, this large series demonstrates no appreciable detriment to patient outcomes when this goal is not met.

Differentiating familial hypocalciuric hypercalcemia from primary hyperparathyroidism.

OBJECTIVE: Because the clinical features of familial hypocalciuric hypercalcemia (FHH) overlap significantly with those of primary hyperparathyroidism (PHPT), various means of differentiating between the two diseases have been suggested. Here we present a review of the clinical delineation of these two diseases. METHODS: Review of the English language literature on FHH and PHPT. RESULTS: FHH is a rare genetic disorder generally resulting in asymptomatic hypercalcemia of minimal clinical consequence. It is easily misdiagnosed as PHPT because both entities can manifest as hypercalcemia with an inappropriately normal or elevated level of parathyroid hormone. The 2 disorders differ in renal processing of calcium, and a number of indices of renal calcium excretion have been proposed to differentiate the 2 entities. However, the two disorders have considerable overlaps in their ranges on these indices making differentiation a challenge. There are many mutations in the calcium-sensing receptor (CaSR) gene associated with FHH and it is becoming increasingly recognized that the CaSR has broad functional variability. CONCLUSION: The calcium:creatinine clearance ratio (CCCR) is the consensus biochemical test to differentiate between PHPT and FHH. However, this test is still limited by a considerable indeterminate range, and definitive diagnosis of FHH requires genetic testing. A combination of clinical suspicion, biochemical testing, and genetic analysis is required to differentiate PHPT from FHH and thus spare patients with FHH from nontherapeutic operative treatment.

Cancer after thyroidectomy: a multi-institutional experience with 1,523 patients.

BACKGROUND: The incidence of thyroid cancer in patients treated operatively for thyroid disease has been historically low (<5%). Previous series have not specifically addressed cancer rates in both euthyroid and hyperthyroid patients. This study examined cancer frequency in patients referred for removal of benign thyroid disease in a multi-institutional series. STUDY DESIGN: A total of 2,551 patients underwent thyroidectomy at 3 high-volume institutions. Indeterminate/malignant fine-needle aspiration diagnosis was excluded (n = 1,028). Cancer cases were compared among 1,523 patients with Graves' disease (n = 264), nodular goiter (n = 1,095), and toxic nodular goiter (n = 164). Fisher's exact test, chi-square test, Wilcoxon rank sum, Kruskal-Wallis nonparametric t-tests, and multivariable logistic regression were used. RESULTS: Overall, 238 (15.6%) cancers were recorded: Graves' disease (6.1%), nodular goiter (17.5%), and toxic nodular goiter (18.3%). Cancer rates were significantly different among these groups (p < 0.01) and significantly higher in nodular goiter and toxic nodular goiter vs Graves' disease (p < 0.01); no significant differences in cancer rates were noted among institutions. Overall, 275 patients had thyroiditis (18%). There was a significant association with younger age, male sex, nodular thyroids, and cancer (p < 0.05). Presence of thyroiditis or performance of preoperative fine-needle aspiration was not associated with cancer. Mean cancer size was 1.1 cm (46% >0.5 cm; 39% >1 cm). Most patients underwent total thyroidectomy (80%). CONCLUSIONS: These data confirm higher than expected incidental thyroid cancer rates (15.6%) in the largest multi-institutional surgical series to date. Nodular thyroids, males, and young patients were more likely to harbor incidental carcinoma. These data support consideration of initial total thyroidectomy as the preferred approach for patients referred to the surgeon with bilateral nodular disease.

Impact of surgical mentorship on retroperitoneoscopic adrenalectomy with comparison to transperitoneal laparoscopic adrenalectomy.

Retroperitoneoscopic adrenalectomy (RA) provides a direct approach to the adrenal gland. RA represents a complex approach with unique orientation that is less intuitive. The authors objectively evaluated the impact of mentorship on the performance of RA and also compared it with laparoscopic adrenalectomy (LA). After implementing the use of RA, a retrospective review of the operative experience of two high-volume endocrine surgeons was performed. Both surgeons participated in a hands-on RA mentorship. Clinical presentation and perioperative outcomes were compared. Subgroup analysis was used to compare RA pre- and postmentorship and with LA. Sixty-one LAs and 31 RAs were included in the analysis. The mean operative time was 115 for LA versus 90 minutes for RA (P = 0.002). Blood loss was greater for LA versus RA (56 vs 22 mL; P = 0.001). Length of stay (LOS) for LA was 2.2 versus 1.5 days for RA (P = 0.029). Ten patients were treated by RA in the prementorship era versus 21 in the postmentorship era. The mean operative time for the prementorship group was 118 minutes, which decreased to 77 minutes postmentorship (P < 0.0001). LOS also decreased from 2.0 to 1.2 days (P = 0.04) in the postmentorship era. RA demonstrates a shorter operative time, less blood loss, and decrease length of hospital stay as compared with standard LA. After proper mentorship and patient selection, RA may represent a superior option for removal of small, benign adrenal tumors.

Toxic nodular goiter and cancer: a compelling case for thyroidectomy.

BACKGROUND: Recent American Thyroid Association guidelines call for thyroidectomy or (131)I (Recommendation 31) in managing hyperthyroidism due to toxic nodular goiter (TNG). Concern for concomitant malignancy favors surgery. A 3 % thyroid cancer incidence in TNG patients has been reported, yet recent studies suggest this rate is underestimated. This multi-institutional study examined cancer incidence in TNG patients referred to surgery. METHODS: Patients referred for thyroidectomy at three tertiary-care institutions were included (2002-2011). Patients with concurrent indeterminate or malignant diagnosis by fine-needle aspiration (FNA) were excluded. Cancer incidence in TNG patients was determined. Fisher's exact and chi-square tests and nonparametric t tests were used. RESULTS: Among 2,551 surgically treated patients, 164 had TNG (6.4 %). Median age at presentation was 49.7 years, and 86 % were female. Overall cancer incidence was 18.3 % (30 of 164), and rates were not significantly different between institutions. A significantly greater cancer rate was noted in toxic multinodular goiter versus single toxic nodule patients (21 vs. 4.5 %, P < 0.05). Mean tumor size was 0.71 cm (range 0.1-1.5 cm; 23 % ≥1 cm). Most patients underwent total or near-total thyroidectomy. There were no significant differences in tumor sizes among institutions (P > 0.05). No significant cancer association was noted with age, preoperative dominant nodule size, lymphocytic thyroiditis or preoperative FNA (P > 0.05). CONCLUSIONS: These data demonstrate a higher than expected incidental cancer rate in TNG patients compared to historical reports (18.3 vs. 3 %). This higher cancer incidence may alter the risk/benefit analysis regarding TNG treatment. This information should be provided to TNG patients before decision making regarding treatment.

Expense of robotic thyroidectomy: a cost analysis at a single institution.

HYPOTHESIS The cost of robotic thyroidectomy (RT) is significantly higher than that of standard open thyroidectomy (ST). DESIGN A retrospective cost analysis of ST was compared with a projected cost analysis of RT using institution-specific data. SETTING Endocrine surgery division at an academic center. PARTICIPANTS Standard open thyroidectomy data from 2 high-volume endocrine surgeons vs published variables from high-volume RT surgeons. MAIN OUTCOME MEASURES A cost analysis was performed for ST (Current Procedural Technology code 60240). The cost of RT was estimated as operative time plus anesthesia fees plus consumables plus the robotic system (da Vinci Surgical System; Intuitive Surgical, Inc). Institution-specific data were collected for ST, and only those costs that varied between ST and RT were included in the analysis. The mean operative time for ST was based on data from 2 high-volume endocrine surgeons at our institution. The RT operative data were extracted from published series of high-volume RT surgeons. RESULTS The relative costs calculated were $2668 for ST vs $5795 for RT. This represents a 217% increased cost of RT compared with ST. The mean operative times were 113 minutes for ST vs 137 minutes for RT. CONCLUSIONS Technologic advances are paramount in providing the best medical care for patients. This progress must be tempered by a rational, open discussion about the costs of these advancements. Only then can the proposed benefits of a new technology be weighed accurately against the overall societal cost. Surgeons need to be aware of the cost of their technologic choices and the burdens that those place on limited resources.

The impact of atypia/follicular lesion of undetermined significance on the rate of malignancy in thyroid fine-needle aspiration: evaluation of the Bethesda System for Reporting Thyroid Cytopathology.

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) was developed to refine definitions and improve clinical communication and management. This study evaluates the impact of the BSRTC in a large cohort of patients undergoing thyroidectomy before and after its adoption at a single institution. METHODS: The records from 469 patients in the pre-BSRTC (n = 187) and post-BSRTC (n = 282) periods were reviewed. Cytologic categories in group 1 included nondiagnostic, benign, follicular/Hürthle neoplasm, suspicious for malignancy, and malignant. Atypia/follicular lesion of undetermined significance (AUS/FLUS) was included in group 2. The percentage of each fine-needle aspiration (FNA) category, malignancy rate per category, and rate of AUS/FLUS utilization were calculated. RESULTS: Group 1 FNA results included 3% (n = 6) nondiagnostic, 48% (n = 89) benign, 17% (n = 32) follicular/Hürthle, 13% (n = 25) suspicious for malignancy, and 19% (n = 35) malignant. Group 2 results included 4% (n = 11) nondiagnostic, 34% (n = 96) benign, 29% (n = 82) AUS/FLUS, 12% (n = 33) follicular/Hürthle, 10% (n = 29) suspicious for malignancy, and 11% (n = 31) malignant. The rate of cancer changed from 25% to 36% for follicular/Hürthle lesions. AUS/FLUS was utilized in 154 of 1095(14%) FNAs reviewed with a malignancy rate of 20%. CONCLUSION: The new AUS/FLUS category was used more often than recommended (14%) with a higher than expected rate of malignancy (20%). Rigorous cytopathology to histopathology correlation is needed to accurately reflect the malignancy rates of the different BSRTC categories at each individual institution. Clinical management should be tailored based on such institutional findings.

Lithium use and primary hyperparathyroidism.

OBJECTIVE: To review suspected causes of lithium-induced hyperparathyroidism, disease presentation, underlying pathology, and current recommendations and trends in medical and surgical treatment. METHODS: Relevant literature was reviewed. RESULTS: Lithium carbonate therapy has continued to be a mainstay of treatment for bipolar disease and schizoaffective disorder since its introduction into clinical use. Several metabolic consequences are associated with its long-term use, including hypercalcemia and hyperparathyroidism. CONCLUSIONS: Until further data become available, the surgeon should remain vigilant for the presence of pathologically active glands that may manifest their function at different times during the disease course.

Parathyroid carcinoma arising from four-gland hyperplasia.

OBJECTIVE: To report the use of immunohistochemical staining for parafibromin, APC, and galectin-3 to evaluate the malignant potential of a resected parathyroid specimen in a patient initially presenting with primary hyperparathyroidism attributable to 4-gland hyperplasia, who subsequently developed metastatic parathyroid carcinoma. METHODS: We describe a patient with primary hyperparathyroidism who underwent a 3-gland resection of hypercellular parathyroid glands, with postoperative normalization of her serum calcium and parathyroid hormone levels. She returned 4 years later with recurrent hypercalcemia and underwent partial resection of her remaining hypercellular parathyroid gland, without improvement of her hypercalcemia. Selective venous sampling localized the source as draining into her azygos vein, and metastatic parathyroid carcinoma was ultimately diagnosed. RESULTS: Immunohistochemical staining for parafibromin, APC, and galectin-3 suggested the malignant potential of the atypical adenoma removed during the patient's original operation, which is believed to be the source of her metastatic disease. Access to this information by the treating surgeon may have prompted a more extensive en bloc resection or more vigilant follow-up that could have altered the patient's clinical course. CONCLUSION: Immunohistochemical staining for parafibromin, APC, and galectin-3 can be used to help distinguish the source of metastatic disease in patients with parathyroid carcinoma. Selective venous sampling may help localize metastatic parathyroid carcinoma when the source is otherwise not apparent.

Changing intraoperative parathyroid hormone collection sites from peripheral to central does not affect predictive accuracy during minimally invasive parathyroidectomy.

BACKGROUND: Intraoperative parathyroid hormone (ioPTH) monitoring (IPM) is vital to minimally invasive parathyroidectomy. Techniques vary in assay sampling, potentially affecting predictive accuracy of operative success. Initial guidelines were established using peripheral sites, but central sites may be preferred or necessary when peripheral access is not feasible. We hypothesize that changing collection sites from preexcision peripheral sites to postexcision central sites would not affect IPM accuracy. METHODS: Analysis of 64 consecutive patients who underwent parathyroidectomy for primary hyperparathyroidism was undertaken. PTH assays were collected simultaneously from a peripheral vein (PV) and central vein (CV) preexcision and at a 10-min interval after initial parathyroid excision. IPM success was defined as PTH decrease ≥50% 10 min after initial excision. Predictive accuracy was determined by the need to resect another abnormal gland and biochemical normalization in the postoperative clinic. Receiver operating characteristic (ROC) method with area under the curve (AUC) compared diagnostic accuracy of different assay approaches. RESULTS: Centrally, a statistically higher mean pre- and postexcision ioPTH of 391 pg/ml and 58 pg/ml was found compared with peripheral means of 156 pg/ml and 49 pg/ml, respectively (p < 0.001). The AUC when changing from a PV preexcision to a CV postexcision ioPTH was 0.89, comparable to AUC for peripheral or central assay collections alone (AUC = 0.83 and 0.85, respectively). CONCLUSIONS: This study suggests that altering collection sites does not alter assay validity. In cases where peripheral sampling is compromised, changing from a peripheral to central sites will not likely alter the predictive accuracy of IPM significantly.

An international perspective on ultrasound training and use for thyroid and parathyroid disease.

BACKGROUND: Use of ultrasound (USN) by endocrine surgeons has dramatically increased. Presently, optimal training and certification requirements have not been standardized at any level (resident/fellow/attending). We sought to define the types of USN training endocrine surgeons receive and how USN is employed in practice. We hypothesized that in more recent years fellowship-trained endocrine surgeons were more likely to receive formal training in the use of USN during their endocrine surgery fellowship. METHODS: A survey link was sent via email to a large group of endocrine surgeons around the world asking about the settings in which they received USN training, the type of instruction received, current use of USN, and other various questions. chi(2) analysis was performed and P < 0.05 was considered significant. RESULTS: One hundred twenty-one surveys were collected from respondents in 27 countries. Median time from completion of residency to the present was 17 years (range = 2-49). Fifty-nine percent of both fellowship- and nonfellowship-trained endocrine surgeons currently use USN in their practice. Of those currently performing USN, 38% reported no USN training of any kind (47% international vs. 23% United States). USN experience among international and U.S. residents was not different (P = 0.27). Fifty-nine percent of respondents reported completing an endocrine surgery fellowship; of those, 85% reported no formal USN training. Forty-one percent reported not being comfortable performing USN at the completion of their endocrine surgery fellowships, requiring the presence of someone else to assist with the exam. CONCLUSIONS: USN training among endocrine surgeons varies widely around the world. Despite an increase in the number of formal endocrine surgery fellowships offered, it does not appear that the number with formal USN training and certification has increased. Formal USN certification is achieved in only a minority of cases among practicing endocrine surgeons. It is currently unknown whether there is a difference in competency between endocrine surgeons with formal versus informal USN training.

Completion pancreatectomy and duodenectomy for recurrent MEN-1 pancreaticoduodenal endocrine neoplasms.

BACKGROUND: The purpose of this study is to describe outcomes of MEN-1 patients with recurrence requiring completion pancreatectomy and duodenectomy after initial treatment of pancreatic endocrine neoplasms (PENs) and hypergastrinemia with distal pancreatectomy, enucleation of pancreatic head PENs, and duodenotomy. METHODS: After undergoing this initial operation, 8 of 49 patients (16%) have required completion pancreatectomy and duodenectomy for recurrent PENs and hypergastrinemia. Retrospective review was performed. RESULTS: Median age was 39 years (27-51) at completion pancreatectomy compared to 31 years (20-40) at initial operation. Pathology revealed multiple PENs in 100%, duodenal neoplasms in 63%, and metastatic lymph nodes in 75%. There was no operative mortality and 88% of patients are currently alive. Preoperative gastrin levels were 934 +/- 847 pg/mL while postoperative levels are 93 +/- 79 pg/mL (normal 25-111 pg/mL). Mean Hemoglobin A1C levels are 8.3 +/- 3.3% (normal 3.8%-6.4%). Mean follow-up is 44 +/- 25 months. CONCLUSION: This initial operation may provide tumor control and prevent metastases but recurrent PENs are multifocal and progressive. Completion pancreatectomy and duodenectomy is arduous but outcomes are acceptable. Considering the radical nature of this treatment, individual consideration should be given to MEN-1 patients amenable to initial alternative pancreatic resections that preserve pancreatic mass and allow future pancreas-preserving reoperations.