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Background: Parathyroid carcinoma is a rare malignancy with high recurrence rates. Liquid biopsy is a stratifying tool in disease recurrence/progression in other malignant processes. This study sought to assess the feasibility and application of liquid biopsy in parathyroid carcinoma and its impact on surveillance., Methods: Retrospective review of a prospectively maintained database of adults treated for parathyroid carcinoma at a tertiary care center (2017-2023). Demographics, clinical characteristics, and laboratory variables were collected. Circulating cell-free deoxyribonucleic acid enrichment and circulating tumor cell enumeration were obtained from serial blood samples., Results: A total of 25 patients were identified-64% were male patients, with a median age of 56 years (interquartile range 45-63). Fifty blood samples were collected postoperatively. At first, circulating tumor cell enumeration, 56% (14/25) of patients had no evidence of disease, and 32% (8/25) had distant metastasis. Median follow-up was 53 months (interquartile range 23-107). At the last follow-up, 40% (10/25) of patients were found to have distant metastasis. Serial circulating tumor cell enumeration was performed in 52% of patients, median highest circulating tumor cell was (interquartile range 1-22). Circulating cell-free deoxyribonucleic acid was assessed in 64% of patients (16/25). There was no difference in circulating tumor cells or circulating cell-free deoxyribonucleic acid between those with distant metastasis and those without distant metastasis. The most common mutation identified was TP53, present in 88% of circulating cell-free deoxyribonucleic acid samples with a mutation. Circulating cell-free deoxyribonucleic acid and parathyroid hormone levels were not found to have any association (r = -0.27, P = .39), but parathyroid hormone and circulating tumor cell had a linear relationship (r = 0.76, P < .001)., Conclusion: Liquid biopsy appears to be a feasible tool in parathyroid carcinoma surveillance. The relationship between circulating cell-free deoxyribonucleic acid and parathyroid hormone levels remains unclear, and the association between circulating tumor cell enumeration and parathyroid hormone levels may be impactful. The finding that TP53 mutation is more prevalent in patients with distant metastasis may impact further management., (Copyright © 2023. Published by Elsevier Inc.)

Background: Posterior retroperitoneoscopic adrenalectomy is an appealing approach for patients with hereditary pheochromocytoma and lends well to cortex preservation. We sought to examine pheochromocytoma recurrence in patients with hereditary pheochromocytoma in the era of posterior retroperitoneoscopic adrenalectomy and evaluate the predictors of recurrence., Methods: Patients with hereditary pheochromocytoma who underwent adrenalectomy for pheochromocytoma between 1995 and 2020 with biochemical cure and follow-up >1 year were identified. Recurrence was defined as plasma metanephrines above the upper limit of normal with radiographic evidence of disease in the ipsilateral adrenal bed., Results: Seventy-eight hereditary pheochromocytoma patients (median age = 32.4 years; 60.3% women) underwent 114 adrenalectomies for pheochromocytoma. Of these patients, 40 had multiple endocrine neoplasia type 2A (51.3%), 10 had multiple endocrine neoplasia type B (12.8%), 17 had von Hippel-Lindau disease (21.8%), and 11 had neurofibromatosis type 1 (14.1%). Thirty-eight adrenalectomies (33.3%) were performed before the introduction of posterior retroperitoneoscopic adrenalectomy and 76 (66.7%) after. Cortical-sparing technique was performed in 62 (54.4%) adrenalectomies, with no difference in its use before and after posterior retroperitoneoscopic adrenalectomy introduction (P > .05). During a median follow-up of 80.7 months (interquartile range 43.4-151.2), 12 ipsilateral recurrences (10.5%) were identified. There was no difference in recurrence before and after the introduction of posterior retroperitoneoscopic adrenalectomy or by surgical technique or approach of the entire cohort (P > .05). Recurrence was more common in those with RET M918T mutation (23.5% vs 8.2%; P = .05). Patients with RET M918T mutations had a shorter recurrence-free survival (P = .013). On multivariate analysis, only RET M918T mutation was independently associated with an increased recurrence risk (hazard ratio = 4.30; 95% confidence interval, 1.26-14.66; P = .019)., Conclusion: The introduction of posterior retroperitoneoscopic adrenalectomy did not influence the recurrence rate after adrenalectomy for hereditary pheochromocytoma patients. Patients with a RET M918T germline mutation are at increased risk for pheochromocytoma recurrence and may benefit from initial total adrenalectomy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Postoperative hypoparathyroidism from inadequate parathyroid hormone is of concern after multigland resections in multiple endocrine neoplasia type 1-related primary hyperparathyroidism. We evaluated risk factors, long-term outcomes, and roles of autotransplantation and cryopreservation in postoperative hypoparathyroidism in multiple endocrine neoplasia type 1., Methods: Retrospective cohort study of patients with multiple endocrine neoplasia type 1 and parathyroidectomy who were evaluated at MD Anderson from 1990 to 2020., Results: We included 206 patients. Median follow-up after the last operation (index 65%, reoperation 35%) was 8 years. Index parathyroidectomy was subtotal in 47%, less than subtotal in 42%, and total in 12%; hypoparathyroidism was more frequent after total parathyroidectomy. Forty-seven patients (23%) had hypoparathyroidism ≥6 months; odds were significantly higher when cumulative ≥4 glands were resected (odds ratio 6 [2.96-12.24]) or when immediate postoperative parathyroid hormone was <15 pg/mL (odds ratio 13.10 [3.61-47.47]). After median 26 months postoperatively, 30% recovered parathyroid function spontaneously; this was less likely when ≥4 glands were resected (odds ratio 0.19 [0.05-0.72]). None of the 4 patients who were aparathyroid (parathyroid hormone undetectable or ≤3 pg/mL) at 6 months postoperatively recovered parathyroid function. Immediate autotransplantation success rate was 72%. Cryopreservation was performed in 96 operations with delayed autotransplantation in 10 patients (10% utilization), of whom 5 recovered parathyroid function (time to recovery 12-93 months)., Conclusion: Odds of prolonged hypoparathyroidism are higher when cumulative ≥4 glands are resected or postoperative parathyroid hormone is <15 pg/mL. Spontaneous recovery occurred but was less likely when ≥4 glands were resected or patients were aparathyroid at 6 months postoperatively. Cryopreservation should be sparingly used, but there is value in select high-risk patients such as reoperative parathyroidectomy/cervical surgery., (Copyright © 2021. Published by Elsevier Inc.)

Background: Preventing cervical reoperations is important-especially after parathyroidectomy. We sought to examine early predictors of recurrence of primary hyperparathyroidism after surgical cure., Methods: Adult patients with sporadic primary hyperparathyroidism treated with parathyroidectomy between September 1, 1997, and September 1, 2019, with confirmed eucalcemia at 6 months postoperatively were identified. Recurrence was defined as hypercalcemia (>10.2 mg/dL) with an elevated or nonsuppressed parathyroid hormone level on subsequent follow-up., Results: Parathyroidectomy was performed in 522 patients (median age, 62.1 years, 77% female) with the majority undergoing planned minimally invasive parathyroidectomy (85.4%, n = 446). After a median follow-up of 30.9 months, 13 patients (2.5%) recurred (median time to recurrence 50.2 months, interquartile range 27.9-66.5), all of whom underwent planned minimally invasive parathyroidectomy (n = 13/446, 2.9%). Recurrence was more common in those with higher (but still normal) 6-month calcium (10.1 vs 9.3 mg/dL, P < .001) or parathyroid hormone values (64 vs 46 pg/mL, P < .01). Multivariate analysis revealed that age >66.5 years, calcium ≥9.8mg/dL and parathyroid hormone ≥80 pg/mL at 6 months were associated with increased risk of recurrence. In addition, the presence of at least 1 preoperative imaging study that conflicted with intraoperative findings among minimally invasive parathyroidectomy patients (n = 446) was associated with increased risk of recurrence (hazard ratio 4.93, 95% confidence interval 1.25-16.53, P = .016)., Conclusion: Recurrence of sporadic primary hyperparathyroidism after initial surgical cure in the era of minimally invasive parathyroidectomy is 2.5%. Identification of those at risk for recurrence using 6-month serum calcium ≥9.8 mg/dL, parathyroid hormone ≥80 pg/mL, and/or potentially conflicting localization studies may inform surveillance strategies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: It is unclear whether genotype-negative clinical multiple endocrine neoplasia type 1 patients derive equal benefit from prospective surveillance as genotype-positive patients., Methods: In this retrospective cohort study, we compared genotype-negative patients with clinical multiple endocrine neoplasia type 1 with genotype-positive index cases. Primary outcome was age-related penetrance of manifestations; secondary outcomes were disease-specific survival and clinical course of endocrine tumors., Results: We included 39 genotype-negative patients with clinical multiple endocrine neoplasia type 1 (Male: 33%) and 63 genotype-positive multiple endocrine neoplasia type 1 index cases (Male: 59%). Genotype-negative patients with clinical multiple endocrine neoplasia type 1 were 65 years old at last follow-up; genotype-positive multiple endocrine neoplasia type 1 index cases were 50 (P < .001). Genotype-negative patients with clinical multiple endocrine neoplasia type 1 were significantly older at their first and second primary manifestation. Only 1 developed a third primary manifestation. No genotype-negative patients with clinical multiple endocrine neoplasia type 1 with primary hyperparathyroidism and a pituitary adenoma developed a duodenopancreatic neuroendocrine tumor. Disease-specific survival was significantly better in genotype-negative patients with clinical multiple endocrine neoplasia type 1. In genotype-negative patients with clinical multiple endocrine neoplasia type 1, primary hyperparathyroidism was single-gland disease in 47% of parathyroidectomies versus 0% in genotype-positive multiple endocrine neoplasia type 1 index cases. In genotype-negative patients with clinical multiple endocrine neoplasia type 1, 17% of duodenopancreatic neuroendocrine tumors were multifocal versus 68% in genotype-positive multiple endocrine neoplasia type 1 index cases. Genotype-negative patients with clinical multiple endocrine neoplasia type 1 had more pituitary macroadenomas, fewer prolactinomas, and more somatotroph adenomas., Conclusion: Genotype-negative patients with clinical multiple endocrine neoplasia type 1 have a different clinical course than genotype-positive multiple endocrine neoplasia type 1 index cases. This may support a separate classification and a tailored surveillance regimen. Of the genotype-negative patients with clinical multiple endocrine neoplasia type 1 who had parathyroidectomy, almost half had no evidence of multigland disease and may be potential candidates for a more targeted single-gland approach., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The cyclin-dependent-kinase inhibitor/retinoblastoma pathway has been implicated in sporadic medullary thyroid carcinoma tumorigenesis. Somatic CDKN2C loss has been associated with decreased overall survival in medullary thyroid carcinoma patients. We evaluated CDKN2C loss in a prospective clinical environment using a novel Clinical Laboratory Improvement Amendments-certified assay to confirm its association with aggressive disease and to interrogate response to targeted therapy., Methods: Patients with advanced sporadic medullary thyroid carcinoma underwent tumor genotyping for the purpose of management of targeted therapy and prognostication., Results: Of patients with informative CDKN2C assay results, 30 (51.8%) were haploinsufficient/1N and 28 (48.3%) were 2N. Forty patients (69.0%) had a somatic RET mutation, and 36.9% had alterations of both genes. Thirty patients (51.7%) were treated with systemic therapy. Presence of genetic alterations in CDKN2C or RET did not predict treatment response. Patients with 1N CDKN2C loss had significantly shorter time-to-distant-metastasis than patients with normal copy number (P = .03)., Conclusion: This is the first evaluation in the clinical setting of CDKN2C haploinsufficiency in sporadic medullary thyroid carcinoma. Although a larger cohort and longer follow-up will be required, loss seems to be associated with more aggressive disease and may indicate patients that might receive benefit from treatment with a CDK inhibitor., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: We sought to determine whether obesity is correlated with complications after posterior retroperitoneoscopic adrenalectomy for benign diseases and to develop surrogate markers of abdominal fat in preoperative computed tomography., Methods: We conducted a retrospective chart review of all patients who had undergone posterior retroperitoneoscopic adrenalectomy and preoperative computed tomography between January 1, 2008 and December 31, 2015. The cross-sectional components of fat assessed by computed tomography included total fat area, subcutaneous fat area, retroperitoneal fat area, and peritoneal fat area. The patients were grouped into 2 categories according to the absence or presence of a postoperative complication (the no-complications group and the complications group, respectively)., Results: Of 116 study patients, 20 patients (17%) had a postoperative complication. Operations of greater duration and smaller adrenal gland size were significantly correlated with complications both in univariate and multivariate analyses. Body mass index, total fat area, subcutaneous fat area, retroperitoneal fat area, peritoneal fat area, and distance of skin to muscle (in axial and sagittal images) correlated with complications in univariate analysis but not in multivariate analysis. In the no-complications group, the removed adrenal gland was larger than that removed in the complications group (6 vs 4 cm, respectively, P = .001), whereas the complications group had a greater operative duration (139 vs 104 min, respectively, P = .001) and a greater duration of hospital stay (3 days vs 1 day, respectively, P = .001)., Conclusion: In this study, operations of greater duration and smaller adrenal gland size were better predictors of complications after posterior retroperitoneoscopic adrenalectomy for benign disease than measures of obesity, including body mass index., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Radiation-associated fusion oncogenes play a direct role in papillary thyroid cancer development and pathogenic fusions have recently been reported in medullary thyroid cancer. To date, no studies have evaluated oncogenic events in medullary thyroid cancer in a radiation-exposed population., Methods: Somatic and germline alterations, including RET fusions, were evaluated in paired medullary thyroid cancer tumor and normal samples from the Chernobyl Tissue Bank, a heavily screened population affected by the Chernobyl disaster., Results: Tissue was available for 49 individuals. The median age of diagnosis was 26 years (range 9 to 43 years); 16 were radiation-exposed at a median age of 6 (range 2 days to 17 years). A total of 21 patients harbored germline RET mutations (codons 634[13], 918[5], 790[1], 609[1], and 620[1]); 4 had family history. Sporadic medullary thyroid cancer was identified in 27 patients (RET[18], KRAS[1], RET+KRAS[1], TP53[1], wild type [6]), with 1 RET fusion (1/49;2%). The age at operation for patients with hereditary medullary thyroid cancer was not different than sporadic medullary thyroid cancer (23.5 vs 28 years, P = .063). In sporadic medullary thyroid cancer, radiation was not associated with a difference in age at operation, tumor size, or tumor stage (P > .05)., Conclusion: In a heavily screened cohort, genetic analysis revealed germline RET mutations in previously unrecognized probands and a remarkable number of sporadic medullary thyroid cancer cases with a young age at presentation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The aim of this study was to investigate the genotype-phenotype relationship of pancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1 treated at our institution., Methods: We conducted a retrospective chart review of all patients with multiple endocrine neoplasia type 1 treated at our center from January 1993 to December 2015. Presence of a pancreatic neuroendocrine tumor was determined based on imaging performed at any time from presentation to conclusion of follow-up., Results: We reviewed 188 patients. The most common site of multiple endocrine neoplasia type 1 mutation was in exon 2 (34/188; 18%). Of 188 patients, 125 had a pancreatic neuroendocrine tumor (61%). Among all patients, 30 of 34 (88%) with an exon 2 mutation had a pancreatic neuroendocrine tumor compared with 95 of 154 (62%) with a mutation in exons 3-10 (P = .002). In the age group of 20 to 40 years, 8 of 9 patients with an exon 2 mutation had a pancreatic neuroendocrine tumor, compared with 24 of 52 patients (46%) with a mutation in exons 3-10 (P = .028). Patients with an exon 2 mutation had a greater frequency of pancreatic neuroendocrine tumor distant metastasis (53% vs 23%, P = .049)., Conclusion: Young patients with multiple endocrine neoplasia type 1 and an exon 2 mutation appear to have a 2-fold greater risk for developing a pancreatic neuroendocrine tumor, and patients with an exon 2 mutation may be at greater risk for developing distant metastasis. Consideration should be given to more intensive screening and more liberal application of primary operative intervention in this potentially high-risk group., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Duty-hour regulations have increased the frequency of trainee-trainee patient handoffs. Each handoff creates a potential source for communication errors that can lead to near-miss and patient-harm events. We investigated the utility, efficacy, and trainee experience associated with implementation of a novel, standardized, electronic handoff system., Methods: We conducted a prospective intervention study of trainee-trainee handoffs of inpatients undergoing complex general surgical oncology procedures at a large tertiary institution. Preimplementation data were measured using trainee surveys and direct observation and by tracking delinquencies in charting. A standardized electronic handoff tool was created in a research electronic data capture (REDCap) database using the previously validated I-PASS methodology (illness severity, patient summary, action list, situational awareness and contingency planning, and synthesis). Electronic handoff was augmented by direct communication via phone or face-to-face interaction for inpatients deemed "watcher" or "unstable." Postimplementation handoff compliance, communication errors, and trainee work flow were measured and compared to preimplementation values using standard statistical analysis., Results: A total of 474 handoffs (203 preintervention and 271 postintervention) were observed over the study period; 86 handoffs involved patients admitted to the surgical intensive care unit, 344 patients admitted to the surgical stepdown unit, and 44 patients on the surgery ward. Implementation of the structured electronic tool resulted in an increase in trainee handoff compliance from 73% to 96% (P < .001) and decreased errors in communication by 50% (P = .044) while improving trainee efficiency and workflow., Conclusion: A standardized electronic tool augmented by direct communication for higher acuity patients can improve compliance, accuracy, and efficiency of handoff communication between surgery trainees., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Airway compromise from postoperative neck hematoma remains the most feared complication after cervical endocrine operative procedures. Events are rare and potentially lethal, and clear multidisciplinary guidelines for management of these patients are lacking. The aim of our study was to review the experience of a tertiary cancer center in this scenario., Methods: Data prospectively collected over a 10-year period, between 2005 and 2014, were retrospectively analyzed. We included all adult patients who had had a neck operation and needed reoperation for postoperative neck hematoma after an endocrine procedure. We excluded pediatric patients and cases with incomplete records., Results: The inclusion criteria were met for 21 patients (21/2,930; 0.7%). The median age at operation was 56.2 years (SD: 16.7). The M:F ratio was 1:2. All 21 patients presented with a neck swelling at the time of reoperation. Eight of 21 patients (38%) underwent emergency bedside clot evacuation. Presentation was within 6 hours for two thirds (14/21) of the patients; the remaining one third of the patients had the hematoma develop during the evening/night (from 1700-0500). The mean estimated hematoma size was 98 cc (SD: 58). A source of bleeding was identified in 12 of 21 cases (57%). A total of 15.8% of patients had an airway classified as difficult/awkward under the American Society of Anesthesiologists classification for their wound re-exploration., Conclusion: Postoperation, increased vigilance is needed for the first 6 hours to detect patients with neck swelling. Emergency drainage by the bedside was performed in 38% of patients. A difficult airway was uncommon in our series., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Whole-exome sequencing studies have not established definitive somatic mutation patterns among patients with sporadic hyperparathyroidism (HPT). No sequencing has evaluated multiple endocrine neoplasia type 1 (MEN1)-related HPT. We sought to perform whole-exome sequencing in HPT patients to identify somatic mutations and associated biological pathways and tumorigenic networks., Methods: Whole-exome sequencing was performed on blood and tissue from HPT patients (MEN1 and sporadic) and somatic single nucleotide variants (SNVs) were identified. Stop-gain and stop-loss SNVs were analyzed with Ingenuity Pathways Analysis (IPA). Loss of heterozygosity (LOH) was also assessed., Results: Sequencing was performed on 4 MEN1 and 10 sporadic cases. Eighteen stop-gain/stop-loss SNV mutations were identified in 3 MEN1 patients. One complex network was identified on IPA: Cellular function and maintenance, tumor morphology, and cardiovascular disease (IPA score = 49). A nonsynonymous SNV of TP53 (lysine-to-glutamic acid change at codon 81) identified in a MEN1 patient was suggested to be a driver mutation (Cancer-specific High-throughput Annotation of Somatic Mutations; P = .002). All MEN1 and 3/10 sporadic specimens demonstrated LOH of chromosome 11., Conclusion: Whole-exome sequencing revealed somatic mutations in MEN1 associated with a single tumorigenic network, whereas sporadic pathogenesis seemed to be more diverse. A somatic TP53 mutation was also identified. LOH of chromosome 11 was seen in all MEN1 and 3 of 10 sporadic patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: We assessed the efficiency, consistency, and appropriateness of perioperative processes for standard (total) thyroidectomy and devised a valuable strategy to decrease variability and waste., Methods: Our multidisciplinary team evaluated <23-hour stay standard thyroidectomy performed by 3 surgical endocrinologists. We used the nominal group technique, process flowcharts, and root cause analysis to evaluate 6 perioperative processes. Anticipated decreases in costs, charges, and resources from improvements were calculated., Results: Median total charge for standard thyroidectomy was $27,363 (n = 80; $48,727 variation). Perioperative coordination between surgery and anesthesia clinics could eliminate unnecessary testing (potential decrease in charges of $1,505). Nonoperating room time was less in the outpatient operating room (43 vs 52 minutes; P < .001). Consistent scheduling could decrease charges by $585.49 per case. By decreasing 20% of nondisposable instruments on the surgical tray, we could decrease sterile processing costs by $13.30 per case. Modification of postoperative orders could decrease charges by $643 per patient. Overall, this comprehensive analysis identified an anticipated decrease in cost/charge of >$200,000 annually., Conclusion: Perioperative process analyses revealed wide variability for a single, presumed uniform procedure. Systematic assessment helped to identify opportunities to improve efficiency, decrease unnecessary waste and procedures/instrument usage, and focus on patient-centered, quality care. This multidisciplinary strategy could substantially decrease costs/charges for common operative procedures., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: In patients with refractory adrenocorticotropic hormone-dependent Cushing’s syndrome,we evaluated steroidogenesis inhibition (SI) and bilateral adrenalectomy (BA) to predict which patients might benefit most from each treatment modality., Methods: Clinical data from patients treated 1970-2012 were reviewed retrospectively by treatment group (SI or SI+BA). Validated severity scales were used to calculate metabolic (M) score (hypokalemia, hyperglycemia, hypertension, proximal muscle weakness) and adverse events (AE) score (thrombosis, fracture, infection)., Results: A total of 65 patients (16 pituitary, 49 ectopic) were treated with SI+BA (n = 21,32%) or SI alone (n = 44,68%). Presenting M scores and source of adrenocorticotropic hormone excess (ectopic versus pituitary) were similar. Both groups improved metabolically after treatment. Over one-third of AEs in the SI+BA group occurred within 12 months of presentation. Half (n = 24, 55%) of the patients treated with SI died (median survival, 24.0 months). Steroid excess contributed to 71% of complications. Six SI+BA patients died (29%), including all 3 patients with recurrent Cushing’s syndrome after BA. Minor perioperative complications occurred in 7 patients (33%)., Conclusion: Posttreatment M and AE scores improved for all patients and 70% of AEs occurred in SI+BA patients within 12 months of presentation, emphasizing the importance of early operative intervention. These data argue for the safety and efficacy of early BA in selected patients with uncontrollable Cushing’s syndrome.

Background: We investigated the incidence and impact of postoperative complications in children who underwent total thyroidectomy (TTx)., Methods: The records of all pediatric patients undergoing TTx (2001-2011) at our institution were retrospectively reviewed for the occurrence of biochemical hypothyroidism (thyroid-stimulating hormone >10 mIU/mL), laboratory assessments, and medication nonadherence., Results: The 74 patients (median age, 12.5 years) had thyroid cancer (differentiated, n = 39; medullary, n = 16) or benign pathology (n = 19; 16 with multiple endocrine neoplasia type 2A). The median postoperative follow-up was 3.2 years; 46 patients (62%) had ≥ 1 year follow-up. Forty-one percent had ≥ 1 period of medication nonadherence; this was not associated with age at TTx (P = .30). Non-treatment-related hypothyroidism occurred in 33% of patients during postoperative year (POY) 1. The number of POY1 laboratory assessments among the 30% of patients with parathyroid dysfunction was more than twice that among patients with normal parathyroid function (median assessments per year 8 vs 3; P < .0001). Forty-four percent of patients/families reported behavioral or physiologic changes; 40% were concomitant with abnormal thyroid function., Conclusion: More than 40% of pediatric patients were unable to fully adhere to postoperative medication regimens, and non-treatment-related hypothyroidism was common. Postoperative hypoparathyroidism doubled the number of laboratory assessments obtained. These data may help families better prepare for TTx sequelae., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: Controversy exists regarding the role and extent of operation for patients with multiple endocrine neoplasia type 1 (MEN1) and hypergastrinemia., Methods: An institutional MEN1 database was reviewed to identify patients with evidence of hypergastrinemia. The relationship of extent of resection to achievement of eugastrinemia was evaluated., Results: Operation was performed in 20 patients with MEN1 and hypergastrinemia with a median follow-up of 71 months. Duodenal gastrinomas were identified in 85% of patients who underwent duodenal evaluation. Nodal metastases were identified in 80%. Patients who underwent anatomic regional lymph node dissection (RLND) had a median of 16 nodes removed, vs 1 in patients who did not undergo a formal regional lymphadenectomy. Eugastrinemia was achieved in 12 patients (60%), and 8 (40%) had persistent hypergastrinemia. Compared with patients with persistent hypergastrinemia, patients rendered eugastrinemic more often underwent duodenal evaluation (11/12 vs 2/8; P = .01) and RLND (11/12 vs 3/8; P = .03); there was no relationship between pancreatic resection and achievement of eugastrinemia (P = .32)., Conclusion: For patients with MEN1-associated hypergastrinemia selected for operative treatment, a strategy including duodenal evaluation and anatomic regional lymphadenectomy is associated with long-term eugastrinemia. In contrast, the extent of pancreatic resection should be dictated by the extent and distribution of pancreatic neuroendocrine neoplasms, rather than by the presence of hypergastrinemia., (Copyright © 2011. Published by Mosby, Inc.)

Introduction: Laparoscopic adrenalectomy (LA) is a safe minimally invasive approach for treatment of pheochromocytoma (PHEO). Posterior retroperitoneoscopic adrenalectomy (PRA) is an alternative minimally invasive technique; however, there is a lack of data regarding the appropriateness of this approach in patients with PHEO., Methods: Our endocrine surgery database was queried to identify patients who underwent LA or PRA for PHEO. Patient and tumor characteristics, as well as operative details and postoperative course were compared between the 2 groups., Results: LA or PRA was attempted in 46 patients with PHEO (23 LA, 23 PRA). There were no differences in age, BMI, or tumor size between these groups. PRA was associated with significantly reduced operative times (99 min vs 145 min, P < .001), estimated blood loss (8.4 cc vs 123.8 cc, P = .02), and postoperative length of stay (1.9 nights vs 3.1 nights, P < .01). There was no significant difference in rates of conversion to an open procedure or perioperative complications between these groups., Conclusion: LA and PRA are both safe and effective approaches in patients with PHEO. In our experience, PRA results in decreased operative times, blood loss, and postoperative length of stay compared with LA. PRA has become our preferred approach for patients with PHEO., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Robotic assisted transaxillary surgery (RATS) is a minimally invasive approach for the removal of the thyroid and/or parathyroid glands through the axilla. This anatomically directed technique, popularized by Chung, eliminates a visible scar and affords excellent high definition optics of the cervical anatomy. We report an initial series of single access RATS in the U.S., Methods: The prospective endocrine surgery database at a tertiary care center was used to capture all patients who underwent RATS between October 2009 and March 2010. All procedures were performed using a single transaxillary incision., Results: Fourteen operations were performed on 13 patients. Indications for RATS were indeterminate thyroid nodules in 11 patients, the need for completion thyroidectomy in 1 patient, and primary hyperparathyroidism in 2 patients. For patients who underwent robotic assisted thyroid lobectomy, the median thyroid nodule size was 2.1 cm (range, 0.8-2.8 cm), and the median body mass index was 25.33 (range, 21.3-34.4). Mean and median total operative times for robotic assisted thyroid lobectomies were 142 minutes and 137 minutes respectively (range, 113-192 minutes). Operative time for the 2 patients who underwent robotic assisted parathyroidectomy was 115 and 102 minutes. Minor complications occurred in 4 patients (28.5%), with no significant perioperative morbidity or mortality., Conclusion: RATS is feasible. We believe that further study of the RATS technique for removing thyroid lobes and parathyroid glands is warranted. This initial series suggests that careful, continued investigation is necessary prior to routine implementation into clinical practice across the U.S., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: In 2009, the American Thyroid Association (ATA) published consensus guidelines for timing of prophylactic thyroidectomy (PrThy) for treatment of hereditary medullary thyroid cancer (MTC). The aim of this study was to assess whether the clinical guidelines outlined in the ATA recommendations added to the specific mutation risk level could predict the presence of MTC on final pathology., Methods: A retrospective study was performed of patients undergoing PrThy. We evaluated mutation-based risk levels in combination with 2009 ATA guidelines for resection., Results: Overall, 54 patients underwent PrThy between 1972 and 2009. The median age at PrThy was 11.5 years (range, 2-68). Only 4 patients (8%) underwent PrThy prior to age 5 years. Most patients with MTC (16/22, 73%) had a level C mutation, and the youngest age of MTC in a level C mutation carrier was 5 years. The youngest age of MTC in level A or B carriers was 15 years. The single factor that predicted an overall decreased risk of MTC at the time of PrThy was meeting all ATA mutation-based postponement guidelines for surgical intervention (P = .04)., Conclusion: ATA guidelines that includes risk assessment of RET mutation are important in predicting the presence of MTC in patients who are candidates for prophylactic thyroidectomy and in determining the timing of operative resection., (Published by Mosby, Inc.)

Background: Pre-operative ultrasonography (US) is now part of published treatment guidelines for papillary thyroid carcinoma (PTC), despite the lack of long-term data on its potential value in preventing neck recurrence. We report the follow-up of patients with PTC in whom pre-operative US was used to accurately stage the extent of neck disease., Methods: Patients with PTC who underwent pre-operative US and surgery were evaluated by indication for surgery (primary surgery, surgery for persistent PTC, and surgery for recurrent PTC). Patients who underwent their primary surgery at our institution were further evaluated by time period in which their pre-operative US was performed. Primary outcome studied was cervical recurrence., Results: A total of 275 patients underwent pre-operative US; median follow-up was 41 months. Neck recurrence occurred in 6% of primary surgery patients, 5% of persistent-disease patients, and 23% of recurrent-disease patients (P < .001). By multivariate analysis, the era in which US was performed appeared to be an independent predictor of disease-free survival, with less cervical recurrences in the recent eras during which there was more US specialization., Conclusion: Once a patient with PTC experiences neck recurrence, they are at an increased risk for subsequent neck recurrence. Pre-operative US followed by compartment-oriented surgery may decrease recurrence rates in patients if performed before their primary operation.

Background: Disruptions in cognitive function have been described in the constellation of symptoms associated with "asymptomatic" primary hyperparathyroidism (PHPT). The aim of this study was to determine the impact of parathyroidectomy (PTX) on brain function and sleep in "asymptomatic" PHPT patients., Methods: We conducted a prospective, randomized trial comparing immediate PTX with observation in patients with asymptomatic PHPT. We performed functional magnetic resonance imaging (fMRI) of the brain, sleep assessment, and validated neuropsychological battery at baseline, 6 weeks, and 6 months. Wilcoxon rank-sum and Pearson and Spearman correlations were used., Results: A total of 18 patients were randomized. Subjective sleepiness correlated with worse performance on executive function tests during fMRI at 6 weeks (Pearson, -0.473; P = .047) and 6 months (Pearson, -0.673; P = .002). Total sleep time correlated with PTH levels at both 6 weeks (Pearson, 0.518; P = .048) and 6 months (Pearson, 0.567; P = .018). At 6 weeks, hypersomnolence as measured subjectively was decreased in the PTX group, but increased in those observed (-2.56 vs 2.22; P = .03), Conclusion: This prospective, randomized trial for asymptomatic PHPT patients demonstrated an association of sleep with brain function. Sleep seemed to be an indicator of brain activation in the anterior cingulate gyrus and precentral cortex. Subjective sleepiness was associated with executive function. The results of this pilot study suggest that decreased serum PTH levels correlate with improved sleep and that PTX decreases sleepiness in patients with asymptomatic PHPT.

Background: The significance of vitamin D deficiency with primary hyperparathyroidism (PHPT) remains unclear. The safety and value of preoperative vitamin D (Vit D) replacement is unknown., Methods: A prospective surgical database of PHPT patients was queried to identify those who were vitamin D sufficient, deficient, and deficient but repleted. Biochemical parameters were measured preoperatively, after vitamin D replacement, at 1-month follow-up, and at 6-months follow-up., Results: Of 301 patients, 118 (39%) had a vitamin D level of 30 ng/mL or more; 71 patients (24%) were deficient, and 112 patients (37%) were vitamin D deficient but underwent repletion. The median duration of replacement was 28 days, and the dose of ergocalciferol was 400,000 U. Among the 112 patients who underwent repletion, the mean serum calcium remained relatively unchanged or decreased in 91 patients (81%). The gland size was smallest in patients with a preoperative sufficiency and largest in those deficient and not repleted. Postoperative PTH values at 1 month and at 6 months in the baseline-normal group were significantly less than in the other 2 groups (P = .05 and = .009, respectively), with no differences observed between the deficient and the deficient-repleted groups., Conclusion: Preoperative Vit D replacement therapy was safe in PHPT patients and did not increase serum calcium levels. Vit D status affects gland size and postoperative PTH elevation. Repletion in this population is not durable.

Background: The presence of resistance to chemotherapy is associated with poor tumor response and patient survival in a variety of tumors. Attempts to modulate resistance in conjunction with systemic chemotherapy have been limited by the toxicity of combined therapy, particularly gastrointestinal or hematopoetic toxicity. This study explored systemic modulation of resistance in conjunction with intra-arterial regional therapy to determine if tumor responses to melphalan could be improved with acceptable toxicity., Methods: Using a nude rat human xenograft model of extremity melanoma,we analyzed tumors for glutathione (GSH), the main protein in the melphalan resistance pathway. Modulation of GSH was performed with intraperitoneal buthionine sulfoximine (BSO). In parallel, BSO-modulated and nonmodulated animals underwent survival studies after regional intra-arterial perfusion with melphalan or saline. Rats were monitored daily for tumor growth and toxicity., Results: BSO depleted tumor GSH levels by 71.8% with minimal toxicity. Survival studies using increasing melphalan concentrations demonstrated similar tumor growth. The combined use of modulator and chemotherapeutic agent showed a significant tumor growth delay as compared to control and drug-alone group without enhanced toxicity., Conclusions: Modulation of resistance in conjunction with regional chemotherapy allows for improved tumor responses with minimal toxicity. These results demonstrate that BSO can potentiate the cytotoxic effects of regional melphalan therapy in the setting of extremity melanoma., (Copyright 2004 Elsevier Inc.)