Wen T. Shen

Double parathyroid adenomas. Clinical and biochemical characteristics before and after parathyroidectomy.

OBJECTIVE There is considerable debate about whether double parathyroid adenomas are a discrete entity or represent hyperplasia with parathyroid glands of varying sizes. This distinction is important because it impacts on the extent of parathyroid resection and the success of the parathyroid operation. SUMMARY BACKGROUND DATA Double parathyroid adenomas have been reported to occur in 1.7% to 9% of patients with primary hyperparathyroidism (HPT). It is important for surgeons to differentiate between double adenoma and hyperplasia with glands of varying sizes using gross examination during the initial procedure because microscopic findings of a small biopsy specimen at frozen-section examination may not be diagnostic. METHODS From 1982 to 1992, 416 unselected patients (309 women and 107 men) with primary HPT without familial HPT or multiple endocrine neoplasia (MEN) were treated by one surgeon at the University of California at San Francisco. Double adenoma occurred in 49 patients, solitary adenoma in 309 patients, and hyperplasia in 58 patients. The authors analyzed the clinical manifestations, the preoperative and postoperative serum levels of calcium, phosphate, and parathyroid hormone (PTH), and the success rate and outcome after parathyroidectomy and compared their results in 49 patients with double adenomas to the results for patients with solitary adenomas or hyperplasia. RESULTS Ten of the patients with double adenomas (20.4%) were referred for persistent HPT after removal of one abnormal parathyroid gland. The ages of the patients with double adenoma, single adenoma, and hyperplasia were 61 +/- 14, 56 +/- 15, and 58 +/- 7 years, respectively. Fatigue, muscle weakness, and bone pain were common in patients with double adenomas, whereas nephrolithiasis occurred more frequently in patients with solitary adenoma (p = 0.0001). Serum calcium and PTH levels (per cent of upper limit of normal) fell from 11.5 +/- 1.2 mg/dL and 487% to 9.5 +/- 0.8 mg/dL and 61% for patients with double adenomas; from 11.9 +/- 0.9 mg/dL and 378% to 9.3 +/- 1.4 mg/dL and 101% for patients with single adenoma; and from 10.9 +/- 0.5 mg/dL and 418% to 9.1 +/- 0.7 mg/dL and 94% for patients with hyperplasia, respectively. There was no recurrence in the patients with double adenomas with a mean follow-up time of 5.8 years. CONCLUSIONS Double adenomas are a discrete entity and occur more often in older patients. Patients with double adenomas can be successfully treated by removal of the two abnormal glands.

MicroRNA expression profiling is a potential diagnostic tool for thyroid cancer

Approximately 30% of fine‐needle aspiration (FNA) biopsies of thyroid nodules are indeterminate or nondiagnostic. Recent studies suggest microRNA (miRNA, miR) is differentially expressed in malignant tumors and may have a role in carcinogenesis, including thyroid cancer. The authors therefore tested the hypothesis that miRNA expression analysis would identify putative markers that could distinguish benign from malignant thyroid neoplasms that are often indeterminate on FNA biopsy.

Central Neck Lymph Node Dissection for Papillary Thyroid Cancer Comparison of Complication and Recurrence Rates in 295 Initial Dissections and Reoperations

BACKGROUND The American Thyroid Association recently changed its management guidelines for papillary thyroid cancer (PTC) to include routine central neck lymph node dissection (CLND) during thyroidectomy. We currently perform CLND during thyroidectomy only if enlarged central nodes are detected by palpation or ultrasonography; we perform CLND in the reoperative setting for recurrence in previously normal-appearing or incompletely resected nodes. Critics of this approach argue that reoperative CLND has higher complication and recurrence rates than initial CLND. We sought to test this argument, using it as our hypothesis. DESIGN Retrospective review. SETTING University hospital. PATIENTS All patients undergoing CLND for PTC between January 1, 1998, and December 31, 2007. INTERVENTIONS Thyroidectomy and CLND. MAIN OUTCOME MEASURES Complications (neck hematoma, recurrent laryngeal nerve injury, and hypoparathyroidism) and recurrence of PTC. RESULTS Altogether, 295 CLNDs were performed: 189 were initial operations and 106 were reoperations. The rate of transient hypocalcemia (41.8% vs 23.6%) was significantly higher in patients undergoing initial CLND compared with those undergoing reoperative CLND. Rates of neck hematoma (1.1% vs 0.9%), transient hoarseness (4.8% vs 4.7%), permanent hoarseness (2.6% vs 1.9%), and permanent hypoparathyroidism (0.5% vs 0.9%) were not different between initial and reoperative CLND. In addition, recurrence rates in the central (11.6% vs 14.1%) and lateral (21.7% vs 17.0%) compartments were not different between the 2 groups. CONCLUSIONS Reoperative CLND for PTC has a lower rate of temporary hypocalcemia, the same rate of other complications, and the same rate of recurrence compared with initial CLND. Choosing to observe nonenlarged central neck lymph nodes for PTC does not result in increased complications or recurrence if reoperation is required.

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.

Central neck lymph node dissection for papillary thyroid cancer: The reliability of surgeon judgment in predicting which patients will benefit

Background. The role of routine prophylactic central-neck lymph node dissection (CLND) for papillary thyroid cancer (PTC) remains controversial. We perform CLND for PTC only in patients with enlarged nodes as determined by preoperative ultrasound and intraoperative inspection and palpation. Methods. We identified all patients with PTC who underwent CLND during thyroidectomy (group 1) at our institution, and then we identified an equivalent number of demographically matched patients who underwent thyroidectomy without CLND (group 2) and compared the outcomes of the 2 groups. Results. In all, 191 patients were identified for each group; 49/191 (26%) patients in group 1 developed locoregional nodal recurrence (12% central neck and 21% lateral neck), compared with 11/191 (6%) patients in group 2 (3% central neck and 3% lateral neck; P < .05). Overall, 161/191 (84%) patients in group 1 were disease free at last survey, compared with 180/191 (94%) patients in group 2 (P < .05). Transient hypocalcemia was significantly greater in group 1. No difference was found in disease-specific mortality. Conclusion. Surgeon assessment of the central neck compartment is an accurate predictor of which patients with PTC will benefit from CLND. Patients with nonenlarged central neck nodes who undergo total thyroidectomy without CLND have a low risk of developing recurrence. (Surgery 2010;148:398-403.)

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.

Reasons for conversion from laparoscopic to open or hand-assisted adrenalectomy: review of 261 laparoscopic adrenalectomies from 1993 to 2003.

Over the past decade, laparoscopic adrenalectomy has become the operation of choice for resecting adrenal tumors. However, few reported data exist regarding the reasons for conversion from laparoscopic to open or hand-assisted adrenalectomy. We retrospectively reviewed the records of 261 consecutive laparoscopic adrenalectomies performed by one surgeon between 1993 and 2003. Laparoscopic adrenalectomy could not be completed in 8 of the 261 patients (3%); four of the operations were converted to hand-assisted laparoscopic adrenalectomy and four to open adrenalectomy. The reasons for the conversion were as follows: In three patients the tumor was too adherent to surrounding structures to be resected laparoscopically; in three patients the tumor was found to have malignant features during laparoscopy, and the operation was converted to achieve proper resection margins; in two patients the tumors were too large (15 and 16 cm, respectively) to be safely removed laparoscopically. The eight resected tumors included three pheochromocytomas, one myelolipoma, one angiomyolipoma, one solitary fibrous tumor, one liposarcoma, and one metastatic hepatocellular carcinoma. There were no cases in which conversion was required emergently for bleeding or other intraoperative catastrophes. All eight of the tumors removed were at least 5 cm in size (range 5–16 cm). The mean length of hospitalization was 4.4 days (range 3–8 days).

Use of the electrothermal vessel sealing system versus standard vessel ligation in thyroidectomy.

OBJECTIVE The electrothermal vessel sealing system (LigaSure) facilitates operative haemostasis by fusing blood vessel walls to form a collagen seal. The LigaSure is currently used in a variety of gastrointestinal, gynaecological and urological operations. We report our experience with LigaSure for thyroidectomy to test the hypothesis that it reduces operating time without increasing complications compared with standard vessel ligation. METHODS This non-randomized, retrospective review included 234 consecutive patients who underwent thyroidectomy by one surgeon. Standard vessel ligation was used in 99 patients between 1997 and 2000, and the LigaSure was used in 135 patients between 2001 and 2003. The following data were collected: patient demographics, thyroid pathology, type of operation (total thyroidectomy vs lobectomy), operating time, complications (transient or permanent hypocalcaemia, <or=8 mg/dL), recurrent or superior laryngeal nerve injury, neck haematoma, wound complications, prolonged intubation), incision length and hospital stay. RESULTS The two groups had similar demographics, thyroid pathology, types of operations and complication rates. The LigaSure group had lower operating times and incision lengths. CONCLUSION We found that the LigaSure was as safe as standard vessel ligation for thyroidectomy, with the benefit of reduced operating time. A future prospective study has been designed.

Distinct loci on chromosome 1q21 and 6q22 predispose to familial nonmedullary thyroid cancer: A SNP array-based linkage analysis of 38 families

BACKGROUND Familial nonmedullary thyroid cancer (FNMTC) is associated with earlier onset and more aggressive behavior than its sporadic counterpart. Although candidate chromosomal loci have been proposed for isolated families with variants of FNMTC, the etiology of most cases is unknown. We aimed to identify loci linked to FNMTC susceptibility using single-nucleotide polymorphism (SNP) array-based linkage analysis in a broad sampling of affected families. METHODS We enrolled and pedigreed 38 FNMTC families. Genomic DNA was extracted from the peripheral blood of 110 relatives, and hybridized to Affymetrix SNP arrays. We performed genotyping and linkage analysis, calculating exponential logarithm-of-the-odds (LOD) scores to identify chromosomal loci with a significant likelihood of linkage. RESULTS Forty-nine affected and 61 unaffected members of FNMTC families were genotyped. In pooled linkage analysis of all families, 2 distinct loci with significant linkage were detected at 6q22 and 1q21 (LOD=3.3 and 3.04, respectively). CONCLUSION We have identified 2 loci on chromosomes 1 and 6 that demonstrate linkage in a broad sampling of FNMTC families. Our findings suggest the presence of germline mutations in heretofore-undiscovered genes at these loci, which may potentially lead to accurate genetic tests. Future studies will consist of technical validation and subset analyses of higher-risk pedigrees.

An International Multi-Institutional Validation of Age 55 Years as a Cutoff for Risk Stratification in the AJCC/UICC Staging System for Well-Differentiated Thyroid Cancer

BACKGROUND Age is a critical factor in outcome for patients with well-differentiated thyroid cancer. Currently, age 45 years is used as a cutoff in staging, although there is increasing evidence to suggest this may be too low. The aim of this study was to assess the potential for changing the cut point for the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system from 45 years to 55 years based on a combined international patient cohort supplied by individual institutions. METHODS A total of 9484 patients were included from 10 institutions. Tumor (T), nodes (N), and metastasis (M) data and age were provided for each patient. The group was stratified by AJCC/UICC stage using age 45 years and age 55 years as cutoffs. The Kaplan-Meier method was used to calculate outcomes for disease-specific survival (DSS). Concordance probability estimates (CPE) were calculated to compare the degree of concordance for each model. RESULTS Using age 45 years as a cutoff, 10-year DSS rates for stage I-IV were 99.7%, 97.3%, 96.6%, and 76.3%, respectively. Using age 55 years as a cutoff, 10-year DSS rates for stage I-IV were 99.5%, 94.7%, 94.1%, and 67.6%, respectively. The change resulted in 12% of patients being downstaged, and the downstaged group had a 10-year DSS of 97.6%. The change resulted in an increase in CPE from 0.90 to 0.92. CONCLUSIONS A change in the cutoff age in the current AJCC/UICC staging system from 45 years to 55 years would lead to a downstaging of 12% of patients, and would improve the statistical validity of the model. Such a change would be clinically relevant for thousands of patients worldwide by preventing overstaging of patients with low-risk disease while providing a more realistic estimate of prognosis for those who remain high risk.