Richards, Melanie L.

AbstractBackgroundPheochromocytoma with synchronous ipsilateral adrenal cortical adenoma (PSCA) may present with mixed clinical, biochemical, and radiological features characteristic to each neoplasm subtype. MethodsAll patients with a pathological diagnosis of pheochromocytoma were evaluated for an ipsilateral cortical adenoma from 1994 through 2015. Retrospectively extracted data included indications for adrenalectomy, diagnostic workup (biochemical and radiographic), operative characteristics, pathological findings, and postoperative complications. ResultsSixteen of 413 patients (4%) undergoing adrenalectomy for pheochromocytoma had a PSCA. Median patient age was 57.7 years (IQR 50.1, 63.1); 50% were male. On imaging, 75% of the adrenal neoplasms were found incidentally and only 50% were reported to have a synchronous ipsilateral neoplasm based on imaging findings. Clinically important cortical hormone secretion was diagnosed in 38% of these patients; 25% had glucocorticoid secretory autonomy; and 13% had primary aldosteronism. ConclusionPhysicians should be aware that adrenal neoplasms with mixed diagnostic findings may represent PSCA. Evaluation should be performed on this co‐occurrence to prevent perioperative complications from resection of an unexpected secretory cortical neoplasm.

AbstractBackgroundIn patients with persistent (P‐PHPT) or recurrent (R‐PHPT) primary hyperparathyroidism, preoperative localization is important. Selective parathyroid hormone venous sampling (sPVS) is an invasive technique that can be used to regionalize and/or lateralize the source of PHPT when noninvasive imaging studies are nonlocalizing. The aim of the present study was to assess the role of sPVS in the preoperative evaluation of patients with P‐PHPT or R‐PHPT and negative, equivocal, or discordant noninvasive imaging localization.MethodsAfter IRB‐approval a retrospective review of all patients with P‐PHPT or R‐PHPT and nonlocalizing noninvasive imaging that underwent sPVS from 2000 to 2014 was performed. The location of the source of PHPT at sPVS was predicted by a parathyroid hormone (PTH) gradient and compared to the surgical, pathology, and biochemical follow‐up data as the gold standard. Sensitivity and positive predictive value (PPV) were calculated.ResultsOf 30 patients who underwent sPVS, 12 patients did not undergo surgical exploration due to negative or non‐localizing PTH gradient (n = 8) or opted for medical management (n = 4). Of the 18 patients who underwent surgical exploration, 17 (94 %) had a positive PTH gradient and pathologic parathyroid tissue identified at surgery. Sensitivity and PPV of sPVS were 93 and 77 %, respectively, for all surgical cases, 86 and 60.0 % for cervical cases (n = 11), and 100 and 100 % for mediastinal cases (n = 7). Sixteen patients (89 %) were surgically cured.ConclusionsIn patients with P‐PHPT or R‐PHPT and nonlocalizing imaging studies, sPVS is a sensitive test for localizing the source of PHPT when a positive PTH gradient is present.

AbstractBackgroundParathyroidectomy is a definitive treatment for primary hyperparathyroidism. Patients contemplating this intervention will benefit from knowledge regarding the expected outcomes and potential risks of the currently available surgical options.PurposeTo appraise and summarize the available evidence regarding benefits and harms of minimally invasive parathyroidectomy (MIP) and bilateral neck exploration (BNE).Data sourcesA comprehensive search of multiple databases (MEDLINE, EMBASE, and Scopus) from each database’s inception to September 2014 was performed.Study selectionEligible studies evaluated patients with primary hyperparathyroidism undergoing MIP or BNE.Data extractionReviewers working independently and in duplicate extracted data and assessed the risk of bias.Data synthesisWe identified 82 observational studies and 6 randomized trials at moderate risk of bias. Most of them reported outcomes after MIP (n = 71). Using random‐effects models to pool results across studies, the cure rate was 98 % (95 % CI 97–98 %, I2 = 10 %) with BNE and 97 % (95 % CI 96–98 %, I2 = 86 %) with MIP. Hypocalcemia occurred in 14 % (95 % CI 10–17 % I2 = 93 %) of the BNE cases and in 2.3 % (95 % CI 1.6–3.1 %, I2 = 87 %) with MIP (P < 0.001). There was a statistically significant lower risk of laryngeal nerve injury with MIP (0.3 %) than with BNE (0.9 %), but similar risk of infection (0.5 vs. 0.5 %) and mortality (0.1 vs. 0.5 %).LimitationsThe available evidence, mostly observational, is at moderate risk of bias, and limited by indirect comparisons and inconsistency for some outcomes (cure rate, hypocalcemia).ConclusionMIP and BNE are both effective surgical techniques for the treatment of primary hyperparathyroidism. The safety profile of MIP appears superior to BNE (lower rate of hypocalcemia and recurrent laryngeal nerve injury).

AbstractIntroductionFocused parathyroidectomy in primary hyperparathyroidism (1°HPT) is possible with accurate preoperative localization and intraoperative PTH monitoring (IOPTH). The added benefit of multimodal imaging techniques for operative success is unknown.MethodPatients with 1°HPT, who underwent parathyroidectomy in 2012–2014 at a single institution, were retrospectively reviewed. Only the patients who underwent the standardized multimodal imaging workup consisting of 123I/99Tc‐sestamibi subtraction scintigraphy, SPECT, and SPECT/CT were assessed.ResultsOf 360 patients who were identified, a curative operation was performed in 96 %, using pre‐operative imaging and IOPTH. Imaging analysis showed that 123I/99Tc‐sestamibi had a sensitivity of 86 % (95 % CI 82–90 %), positive predictive value (PPV) 93 %, and accuracy 81 %, based on correct lateralization. SPECT had a sensitivity of 77 % (95 % CI 72–82 %), PPV 92 % and accuracy 72 %. SPECT/CT had a sensitivity of 75 % (95 % CI 70–80 %), PPV of 94 %, and accuracy 71 %. There were 3 of 45 (7 %) patients with negative sestamibi imaging that had an accurate SPECT and SPECT/CT. Of 312 patients (87 %) with positive uptake on sestamibi (93 % true positive, 7 % false positive), concordant findings were present in 86 % SPECT and 84 % SPECT/CT. In cases where imaging modalities were discordant, but at least one method was true‐positive, 123I/99Tc‐sestamibi was significantly better than both SPECT and SPECT/CT (p < 0.001). The inclusion of SPECT and SPECT/CT in 1°HPT imaging protocol increases patient cost up to 2.4‐fold.Conclusion123I/99Tc‐sestamibi subtraction imaging is highly sensitive for preoperative localization in 1°HPT. SPECT and SPECT/CT are commonly concordant with 123I/99Tc‐sestamibi and rarely increase the sensitivity. Routine inclusion of multimodality imaging technique adds minimal clinical benefit but increases cost to patient in high‐volume setting.

AbstractBackgroundIntense postoperative monitoring has resulted in increasing detection of patients with recurrent papillary thyroid cancer (PTC). Our goals included quantifying successful reoperation, and analyzing surgical complications and reasons for relapse.MethodsFrom 1999 to 2008, a total of 410 patients underwent reoperation for PTC relapse. We analyzed post‐reoperative disease outcomes, reasons for relapse, and complications.ResultsBilateral reoperative thyroidectomy was performed in 13 (3 %) patients; lobectomy, 34 (8 %); central neck (VI) soft tissue local recurrence excision, 47 (11.5 %); bilateral VI node dissection, 107 (26 %); unilateral VI dissection, 112 (27 %); levels II–V dissection, 93 (23 %); levels III–V, 86 (21 %); lateral single‐ or two‐compartment dissection, 51 (12 %); and node picking, 20 (5 %) of level VI and 53 (13 %) lateral neck. Complications occurred in 6 %; including hypoparathyroidism, 3 %; unintentional recurrent laryngeal nerve (RLN) paralysis, 3 %; phrenic nerve injury, 0.5 %; spinal accessory nerve injury, 0.5 %; and chyle leak in 1.6 %. Of 380 (93 %) patients with follow‐up (mean 5.2 years); 274 (72 %) patients are alive with no structural evidence of disease, 38 % developed disease relapse (mean 2.1 years), 42 (11 %) died from PTC, and 55 (14 %) are alive with disease. The reason for relapse was a false negative pre‐reoperative ultrasound (US) in 18 (5 %), nodal recurrence in the operative field in 37 (10 %), a combination of these two reasons in 10 (3 %), and disease virulence (local or systemic recurrence) in 81 (21 %).ConclusionsAlthough 72 % of patients were rendered structurally disease free after reoperation, nearly 40 % suffered additional relapse. Improved surgical technique or preoperative localization might positively affect 15–20 %; at least 20 % reflect the biologic aggressiveness of the disease.

Background: Medullary thyroid cancer, although most commonly sporadic, may be part of the multiple endocrine neoplasia type 2 (MEN2) syndromes, generally due to mutations in the RET proto-oncogene. The majority of these mutations are located in exons 10, 11, and 13–16. More rarely, mutations in other exons have been described. We report for the first time a family from the United States with a rare mutation involving exon 8 of the RET proto-oncogene, corresponding to a p.Gly533Cys substitution (G533C) leading to the development of MEN2A syndrome in several affected family members. This mutation had only been previously described in a large family in Brazil and in 7.75% of patients with apparently sporadic medullary thyroid cancer (MTC) in Greece. Methods: Given a strong index of suspicion, a genetic analysis to evaluate for uncommon mutations in the RET proto-oncogene identified the presence of the G533C missense mutation, despite initial negative screening for common mutations. We describe a family with a total of 47 individuals from five generations with multiple members affected with this mutation. Results: Our data suggest that in patients with this mutation, pheochromocytoma is more common than previously reported, and that in some cases this mutation may be associated with a more aggressive phenotype than initially described. Conclusions: MEN2A due to the G533C mutation in exon 8 may be more common and more aggressive than previously recognized. In patients with medullary thyroid cancer with negative screening for common mutations in the RET oncogene but a strong index of suspicion, DNA sequence analysis of less commonly involved exons should be considered.

The development of subspecialty tumor groups for uncommon malignancies represents an effective approach to building experience, increasing patient volumes and referrals, and fostering development of increased therapeutic options and clinical trials for patients afflicted with otherwise historically neglected cancers.

AbstractBackgroundIndications and survival benefit for adrenalectomy (ADX) in the setting of metastasis are not clearly defined. We aimed to determine which patients with primary malignancies may benefit from ADX performed for metastasis. Mayo Clinic institutional outcomes in patients with metastatic disease to the adrenal(s) treated by adrenalectomy were compared to stage‐matched historical controls from the Surveillance Epidemiology and End Results (SEER) database.MethodsA retrospective review (1992–2010) was conducted to identify patients treated with ADX for metastatic cancer at Mayo Clinic, Rochester. Associations of clinical, surgical, and pathologic features with overall survival (OS) were evaluated using Cox proportional regression models. OS for those treated with ADX was compared with that for SEER database stage‐matched patients who underwent primary resection without resection of distant disease using log‐rank tests.ResultsA total of 166 patients underwent ADX for metastatic primaries involving the kidney 60, lung 24, sarcoma 19, colon 15, pancreas 13, and other‐35. Patients with sarcoma and kidney, lung, and pancreatic tumors who underwent ADX had better OS at 1, 2, and 3 years than did the SEER‐matched controls. Respectively, the rates were for sarcoma (100, 93, 86% vs. 57, 36, 30%), kidney (86, 80, 72% vs. 55, 37, 27%), lung (91, 69, 52% vs. 52, 34, 25%), and pancreas (79, 56, 45% vs. 33, 20, 12%). Univariate analysis identified primary diagnosis <2 years before ADX, other distant site, pancreatic primary, palliative operation, and persistent disease as risk factors for death.ConclusionsAn aggressive surgical approach results in improved OS in patients with metastatic disease arising from soft tissues, kidney, lung, and pancreas. Other tumors may benefit, but larger study cohorts are needed for a meaningful comparison.