Hypotheses  Decitabine recovers expression of silenced genes on chromosome 11q13 and has antineoplastic effects in adrenocortical carcinoma (ACC) cells.

Design  NCI-H295R cells were treated with decitabine (0.1-1.0µM) over 5 days. Cells were evaluated at 24-hour intervals for the effects of decitabine on ACC cell proliferation, cortisol secretion, and cell invasion. Expression was quantified for 6 genes on 11q13 (DDB1, MRPL48, NDUFS8, PRDX5, SERPING1, and TM7SF2) that were previously shown to be underexpressed in ACC.

Setting  Academic research.

Study Specimen  Human ACC cell line.

Main Outcome Measures  Adrenocortical carcinoma cell proliferation, cortisol secretion, and cell invasion were measured using immunometric assays. Quantitative reverse transcription–polymerase chain reaction was used to measure gene expression relative to GAPDH.

Results  Decitabine inhibited ACC cell proliferation by 39% to 47% at 5 days after treatment compared with control specimens (P < .001). The inhibitory effect was cytostatic, time dependent, and dose dependent. Decitabine decreased cortisol secretion by 56% to 58% at 5 days after treatment (P = .02) and inhibited cell invasion by 64% at 24 hours after treatment (P = .03). Of 6 downregulated genes on 11q13, decitabine recovered expression of NDUFS8 (OMIM 602141) (P < .001) and PRDX5 (OMIM 606583) (P = .006).

Conclusions  Decitabine exhibits antitumoral properties in ACC cells at clinically achievable doses and may be an effective adjuvant therapy in patients with advanced disease. Decitabine recovers expression of silenced genes on 11q13, which suggests a possible role of epigenetic gene silencing in adrenocortical carcinogenesis.

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.