Jessica E. Gosnell

Vandetanib for the Treatment of Patients With Locally Advanced or Metastatic Hereditary Medullary Thyroid Cancer

PURPOSE There is no effective therapy for patients with distant metastasis of medullary thyroid carcinoma (MTC). Activating mutations in the RET proto-oncogene cause hereditary MTC, which provides a strong therapeutic rationale for targeting RET kinase activity. This open-label, phase II study assessed the efficacy of vandetanib, a selective oral inhibitor of RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, in patients with advanced hereditary MTC. METHODS Patients with unresectable locally advanced or metastatic hereditary MTC received initial treatment with once-daily oral vandetanib 300 mg. The dose was adjusted additionally in some patients on the basis of observed toxicity until disease progression or any other withdrawal criterion was met. The primary assessment was objective tumor response (by RECIST [Response Evaluation Criteria in Solid Tumors]). Results Thirty patients received initial treatment with vandetanib 300 mg/d. On the basis of investigator assessments, 20% of patients (ie, six of 30 patients) experienced a confirmed partial response (median duration of response at data cutoff, 10.2 months). An additional 53% of patients (ie, 16 of 30 patients) experienced stable disease at >/= 24 weeks, which yielded a disease control rate of 73% (ie, 22 of 30 patients). In 24 patients, serum calcitonin levels showed a 50% or greater decrease from baseline that was maintained for at least 4 weeks; 16 patients showed a similar reduction in serum carcinoembryonic antigen levels. The most common adverse events were diarrhea (70%), rash (67%), fatigue (63%), and nausea (63%). CONCLUSION In this study, vandetanib demonstrated durable objective partial responses and disease control with a manageable adverse event profile. These results demonstrate that vandetanib may provide an effective therapeutic option in patients with advanced hereditary MTC, a rare disease for which there has been no effective therapy.

Parathyroid Carcinoma: A 43-Year Outcome and Survival Analysis

CONTEXT Parathyroid carcinoma is a rare but ominous cause of primary hyperparathyroidism. OBJECTIVES AND MAIN OUTCOME MEASURES: The objective of the study was to review the outcomes of parathyroid cancer patients and to evaluate the factors associated with mortality. DESIGN, SETTING, AND PATIENTS This was a retrospective review performed on 37 patients with parathyroid cancer treated at a single university tertiary care center between 1966 and 2009. RESULTS The average age at cancer diagnosis was 53 yr (range 23-75 yr), and 23 patients (62%) were men. Eighteen patients (49%) recurred after their initial cancer operation. The average number of neck dissections done for cancer was three (range 1-11). After initial diagnosis, 22 patients (60%) eventually developed complications, including unilateral (n = 11) or bilateral (n = 3) vocal cord paralysis (38%). Eight patients (22%) had, at some point, an associated benign parathyroid adenoma. Median overall survival was 14.3 yr (range 10.5-25.7 yr) from the date of diagnosis. Factors associated with increased mortality included lymph node or distant metastases, number of recurrences, higher calcium level at recurrence, and a high number of calcium-lowering medications. Factors not associated with mortality included age, race, tumor size, time to first recurrence, and extent of initial operation. Initial operations done at our center had improved survival (P = 0.037) and decreased complication rates (P < 0.001) vs. those done elsewhere. CONCLUSION Parathyroid cancer patients typically have a long survival, which often includes multiple reoperations for recurrence and thus a high rate of surgical complications. Patients in whom there is a high index of suspicion for parathyroid cancer should be referred to a dedicated endocrine surgery center for their initial operation.

Clinical Spectrum of Pheochromocytoma

BACKGROUND Pheochromocytomas vary in presentation, tumor size, and in catecholamine production. Whether pheochromocytoma size correlates with hormone levels, clinical presentation, and perioperative complications is not known. The goal of this study was to determine if tumor size and hormone level correlate according to the clinical presentation at diagnosis. STUDY DESIGN We retrospectively analyzed all patients who underwent an adrenalectomy with a diagnosis of a pheochromocytoma from February 1996 to October 2008. We grouped patients according to their clinical presentation at diagnosis (routine biochemical screening, incidentaloma, classic symptoms, pheochromocytoma crisis) and obtained preoperative radiographic tumor size and catecholamine hormone levels. ANOVA was used for the group effects and the Kruskal-Wallis rank test was used for pairwise comparison between groups with the Sidak/Bonferroni method for multiplicity adjustment according to age, tumor size, and hormone level. The Pearson correlation coefficient was then calculated to determine if hormone level correlated with tumor size. RESULTS Eighty-one of 107 patients had data available for complete analysis. The average age at diagnosis for all patients was 47.1 years, and the average tumor size was 4.9 cm. The average highest hormone ratio among all patients was 27.4. Tumor size and hormone ratio levels differed among all groups (p < or = 0.03). A direct correlation (p = 0.014) was apparent between tumor size and hormone level. Complication rates also differed among the four groups of patients (p < or = 0.02). CONCLUSIONS Our study showed that tumor size directly correlates with hormone level. Smaller tumors tend to secrete lower levels of catecholamines, but larger tumors have a wider variation in secretory potential. Larger tumors, however, produced the highest hormone ratios.

Experience of prophylactic thyroidectomy in multiple endocrine neoplasia type 2A kindreds with RET codon 804 mutations

Objective and design  Genetic screening in multiple endocrine neoplasia type 2 (MEN 2) has led to specific management guidelines based on genotype–phenotype analysis. However, there is controversy regarding the appropriate age for prophylactic thyroidectomy in families with mutations in codon 804 in exon 14 of the RET proto‐oncogene, where medullary thyroid cancer (MTC) may not develop until adulthood. We prospectively studied two MEN 2A families, one with the V804L and the other with the V804M RET mutation, to report our experience of genetic and biochemical screening and prophylactic thyroidectomy. Family 1 is one of the largest MEN 2A families in the literature, where 22 prophylactic thyroidectomies have been performed.

Minimal access thyroid surgery: technique and report of the first 25 cases

Background:  Minimal access thyroid surgery, using various techniques, is increasingly being reported. The present study reviews our experience with thyroid surgery using a lateral focused mini‐incision approach, and assesses its safety and feasibility.

A Population-Based Prospective Cohort Study of Complications after Thyroidectomy in the Elderly

CONTEXT Data on the risk of postthyroidectomy complications in elderly patients are sparse, unclear, and conflicting. OBJECTIVE We sought to use a population-based cohort to determine whether thyroid operations in the elderly are as safe as those done in younger patients. DESIGN This was a prospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program database from 2005 to 2008, with 30-d postoperative follow-up. SETTING The American College of Surgeons National Surgical Quality Improvement Program data set contains operative cases from a nationwide sampling of academic and community-based as well as high-volume and low-volume hospitals. PATIENTS All thyroidectomy and parathyroidectomy patients reported to the database during the study period were included in the analysis resulting in an experimental cohort of 7915 thyroidectomy cases and a control cohort of 3575 parathyroidectomy cases. MAIN OUTCOME MEASURES We aggregated 83 complications into the following outcome measures: urinary tract infection, wound infection, systemic infection, cardiac complications, pulmonary complications, 30-d mortality, and total hospital length of stay. RESULTS Increased age is a risk factor for significant pulmonary, cardiac, and infectious complications after thyroidectomy. Elderly patients are twice as likely (odds ratio 2.1, 95% confidence interval 1.4-3.3), and the superelderly are 5 times as likely (odds ratio 4.9, 95% confidence interval 2.5-9.6) to have a complication compared with their young counterparts. Preexisting comorbidities are effect modifiers and increase the risk of complications even further. CONCLUSIONS Elderly thyroidectomy patients are at increased risk for major systemic complications. A systematic approach to the care of elderly thyroidectomy patients is necessary to minimize their risk of serious postoperative complications.

Successful localization of recurrent thyroid cancer in reoperative neck surgery using ultrasound-guided methylene blue dye injection

BACKGROUND Reoperation in the neck can be challenging and is associated with increased complication rates and operative times. Here we analyze our methylene blue dye injection method to localize reoperative neck pathology in patients with thyroid cancer and lymph node metastases. STUDY DESIGN We retrospectively reviewed the records of all patients at a single university tertiary care center who had reoperative neck surgery for recurrent thyroid cancer between 2004 and 2009, and who also underwent intraoperative methylene blue dye injection. Outcomes measured were efficacy and safety of the injection technique as well as complication rates. RESULTS Fifty-three operations were performed in 44 patients (average age, 51.2 years [range 16 to 83 years]). Ninety-one percent (48 of 53) of the operations resulted in successful resection of recurrent disease. Of these, 96% (46 of 48) were guided successfully by blue dye injection. Thyroglobulin became undetectable in 42% (11 of 26) of patients. Neck pathology included the following thyroid cancers: papillary (48 of 53), follicular (2 of 53), medullary (2 of 53), and tall cell variant (1 of 53). Among these patients, there were a total of 26 central and 38 lateral neck dissections. The average number of previous neck dissections was 2 (range 1 to 5). The mean intraoperative ultrasound/injection time was 21.3 min (n = 13). Median operative time was 90 minutes (range 40 to 300 minutes). Complications included 2 permanent vocal cord paralyses, 1 instance of permanent hypocalcemia, and 3 instances of temporary hypocalcemia. There were no complications related to the dye injection. CONCLUSIONS Intraoperative, ultrasound-guided, methylene blue dye injection is a safe and effective technique. It facilitates tumor localization and removal especially in patients requiring reoperative neck surgery.

Prognostic significance of extranodal extension of regional lymph node metastasis in papillary thyroid cancer

The presence and location of regional lymph node metastasis affect the prognosis of patients with thyroid cancer. Lymph node classification of the current TNM system may be inadequate because it insufficiently characterizes the nature and severity of lymph node metastasis that may influence prognosis.

Adrenal incidentaloma: Does an adequate workup rule out surprises?

BACKGROUND Adrenal incidentaloma remains a diagnostic challenge. Despite well-established management guidelines, the long-term results of following these guidelines are unknown. We sought to determine how accurately these guidelines identify functioning incidentalomas and how often these guidelines result in adrenalectomy for benign tumors. METHODS We catalogued adrenal incidentalomas from a retrospective review of 500 consecutive adrenalectomies at a single institution. The outcome measures studied were patient demographics, preoperative biochemical analysis, imaging characteristics, tumor size, type of operation performed, and postoperative histologic diagnosis. RESULTS Eighty-one of the 500 adrenalectomies performed were for incidentalomas. Size was the only significant characteristic that distinguished cortical cancers from benign adenomas. Only 1 out of 26 functioning tumors was incorrectly identified on preoperative workup. We also found that 25% of cortisol-secreting incidentalomas were cystic, and that benign adenomas accounted for 42% of all tumors resected. CONCLUSION Current guidelines accurately predict the functional status of adrenal incidentalomas. Some cystic lesions may be functioning and should therefore be screened for hormonal hypersecretion. However, even with the most up-to-date diagnostic tools available, most adrenal incidentalomas resected are benign tumors.

Round ligament varices: sonographic appearance in pregnancy

Round ligament varices (RLV) are an important clinical entity as they may cause hernia‐like symptoms in the absence of a true hernia. When this condition is diagnosed correctly, unnecessary intervention may be prevented. We aimed to determine the significance and anatomy of RLV in pregnancy and to review and describe their clinical and sonographic appearance. We followed prospectively five patients who presented during pregnancy with clinical symptoms suspicious of an inguinal hernia. All patients were diagnosed with RLV on ultrasound examination. All patients were managed conservatively and in all five cases, RLV resolved spontaneously postpartum. The diagnosis of RLV should be considered in pregnant women presenting with a groin mass. Sonography is diagnostic and can save unnecessary surgical exploration and associated morbidity. Copyright