Emily Reiff

Selective Modified Radical Neck Dissection for Papillary Thyroid Cancer—Is Level I, II and V Dissection Always Necessary?

BackgroundThere is ongoing controversy as to the indications for and extent of lateral cervical lymphadenectomy for patients with papillary thyroid cancer (PTC). While most now agree that prophylactic lymph node dissections (LND) play no role, at the University of California, San Francisco (UCSF) we limit LND selectively on a level by level basis, and resect only the levels thought to harbor disease or to be at increased risk of metastases. This initial ‚selective LND’ usually includes levels III and IV (due to the well-documented increased likelihood of metastases to these levels) and levels I, II, and V are included when there is clinical or radiological evidence of disease or increased risk of it.MethodsA retrospective review of the clinical charts and hospital records of 106 consecutive patients who had metastatic PTC and who underwent at least one lateral cervical LND at UCSF between January 1995 and December 2003 was carried out. Data were collected to assess which patients had levels I, II, and/or V included in their initial ipsilateral and/or contralateral LND and to determine the recurrence rates at these levels if they had previously been excised compared with if they had not. Chi-squared and Fisher exact tests were utilized for statistical comparison, where appropriate.ResultsA total of 140 initial lateral LND were performed: 104 ipsilateral and 36 contralateral. In these initial LND, 3.9%, 72.5%, and 18.6% of patients had levels I, II, and V resected on the ipsilateral side, and 2.9%, 60.0%, and 37.1% of patients had levels I, II, and V resected on the contralateral side. Recurrence at levels I and V was uncommon in all patient populations. Recurrence at level II was 19% ipsilaterally and 10% contralaterally when the level was previously resected and 21% ipsilaterally and 14% contralaterally when the level was not previously resected. There was no statistically significant difference in recurrence at level II when the level had previously been resected compared with when it had not.ConclusionsIf utilized in the appropriate patient population, a selective approach to lateral cervical LND for PTC can be a successful alternative to the routine modified radical LND. Levels I and V do not require resection unless there is clinical or radiological evidence of disease. Guidelines for which patients may be considered for this less aggressive approach to level II nodal metastases are suggested.

ECM1 and TMPRSS4 Are Diagnostic Markers of Malignant Thyroid Neoplasms and Improve the Accuracy of Fine Needle Aspiration Biopsy

Objective:The objective of this study was to determine whether genes that regulate cellular invasion and metastasis are differentially expressed and could serve as diagnostic markers of malignant thyroid nodules. Summary and Background Data:Patients whose thyroid nodules have indeterminate or suspicious cytologic features on fine needle aspiration (FNA) biopsy require thyroidectomy because of a 20% to 30% risk of thyroid cancer. Cell invasion and metastasis is a hallmark of malignant phenotype; therefore, genes that regulate these processes might be differentially expressed and could serve as diagnostic markers of malignancy. Methods:Differentially expressed genes (2-fold higher or lower) in malignant versus benign thyroid neoplasms were identified by extracellular matrix and adhesion molecule cDNA array analysis and confirmed by real-time quantitative polymerase chain reaction (PCR). The area under the receiver operating characteristic (AUC) curve was calculated to determine diagnostic accuracy of gene expression level cutoffs established by logistic regression analysis. Results:By cDNA array analysis, ADAMTS8, ECM1, MMP8, PLAU, SELP, and TMPRSS4 were upregulated, and by quantitative PCR, ECM1, SELP, and TMPRSS4 mRNA expression was higher in malignant (n = 57) than in benign (n = 38) thyroid neoplasms (P< 0.002). ECM1 and TMPRSS4 mRNA expression levels were independent predictors of a malignant thyroid neoplasm (P < 0.003). The AUC was 0.956 for ECM1 and 0.926 for TMPRSS4. Combining both markers improved their diagnostic use (AUC 0.985; sensitivity, 91.7%; specificity, 89.8%; positive predictive value, 85.7%; negative predictive value, 82.8%). ECM1 and TMPRSS4 expression analysis improved the diagnostic accuracy of FNA biopsy in 35 of 38 indeterminate or suspicious results. The level of ECM1 mRNA expression was higher in TNM stage I differentiated thyroid cancers than in stage II and III tumors (P ≤ 0.031). Conclusions:ECM1 and TMPRSS4 are excellent diagnostic markers of malignant thyroid nodules and may be used to improve the diagnostic accuracy of FNA biopsy. ECM1 is also a marker of the extent of disease in differentiated thyroid cancers.

Diagnostic and prognostic value of cell-cycle regulatory genes in malignant thyroid neoplasms.

BackgroundApproximately 30% of patients with thyroid nodules have indeterminate or suspicious fine-needle aspiration (FNA) biopsy results. Because their risk of cancer is approximately 20%, these patients undergo thyroidectomy. We hypothesized that genes that regulate cell-cycle progression would be differentially expressed in malignant versus benign thyroid nodules and could serve as diagnostic markers and markers of disease aggressiveness.MethodsWe used a cDNA array with 96 cell-cycle regulatory genes to identify differentially expressed genes in pooled benign versus malignant thyroid neoplasms. Genes up- or down-regulated by more than 2-fold in malignant thyroid neoplasms were further evaluated by real-time quantitative polymerase chain reaction (PCR) in 95 patients with hyperplastic nodules (n = 19), follicular adenoma (n = 19), follicular thyroid cancer (n = 19), the follicular variant of papillary thyroid cancer (n = 19), and papillary thyroid cancer (n = 19).ResultscDNA array analysis showed that cyclin B1, MCM5, MCM7, RAD9, ubiquitin C, CDK6, SKP2, and APAF1 were up-regulated in malignant thyroid neoplasms. Real-time quantitative PCR showed that MCM5, MCM7, and RAD9 mRNA expression were significantly higher in malignant than in benign thyroid neoplasms (≤0.0012). The combined use of MCM5, MCM7, and RAD9 mRNA expression had a sensitivity of 98.2% and a specificity of 65.7%. The level of MCM7 mRNA expression was higher in T4 than in T1, T2, and T3 differentiated thyroid cancers (P < 0.0127).ConclusionsMCM5, MCM7, and RAD9 are overexpressed in malignant thyroid neoplasms of follicular cell origin. These genes may be useful markers of malignant thyroid neoplasms as an adjunct to FNA biopsy. MCM7 mRNA expression is higher in locally invasive differentiated thyroid cancer.

Single bone intramedullary fixation of the ulna in pediatric both bone forearm fractures: analysis of short-term clinical and radiographic results.

Background Although single bone intramedullary (IM) fixation has been advocated in the treatment of unstable diaphyseal forearm fractures, some reports have questioned the ability of single bone fixation to maintain adequate reduction. The purpose of this investigation is to report the radiographic and early clinical results of single bone IM fixation for diaphyseal forearm fractures and to identify factors leading to loss of reduction of the radius after ulnar fixation. Methods A retrospective analysis of 38 children who underwent single bone IM fixation of the ulna for both bone forearm fractures was performed. Mean age was 9 years (range: 4-14 y). Preoperative, postoperative, and final follow-up radiographs were examined for radiographic alignment. Patient data (including age, fracture type, delay to fixation, open vs. percutaneous reduction and fixation, and time to implant removal) was collected to identify predictors for loss of reduction of the radius. Loss of reduction of the radius was defined as 10 degrees or greater change of angulation in either the frontal or lateral plane from initial postoperative radiographs to final follow-up. Multivariate analysis was used to determine associations between patient factors and loss of reduction. Results All patients went on to bony union with restoration of forearm rotation. Twenty-five patients (66%) healed with <10 degrees of angulation of the radius, whereas 11 patients (29%) had between 10 and 20 degrees of angulation at final follow-up. Two patients demonstrated greater than 20 degrees of radial angulation requiring additional surgical care. There was no statistically significant association between any patient factors and loss of radial reduction, though there was a trend for increased radial angulation in patients who had sustained open fractures. Conclusions Single-bone IM fixation of the ulna is a safe and efficacious option for the treatment of unstable diaphyseal forearm fractures in children. Owing to the increased risk of loss of radial reduction, however, consideration should be made for IM fixation of both bones in older children and cases of open fractures. Level of Evidence IV, therapeutic.

Patient Choice and Clinical Outcomes Following Positive Noninvasive Prenatal Screening for Aneuploidy with Cell‐free DNA (cfDNA).

Evaluate patient choices and outcomes following positive cfDNA.

What is the role of the 11‐ to 14‐week ultrasound in women with negative cell‐free DNA screening for aneuploidy?

This study aimed to examine the role of the 11‐ to 14‐week ultrasound in women with negative cell‐free DNA screening.

Patients with differentiated thyroid cancer have a venous gradient in thyroglobulin levels.

Although serum thyroglobulin (Tg) is an excellent marker for detecting recurrent or persistent differentiated thyroid cancer (DTC), it is unreliable in patients who have positive anti‐Tg antibodies. Furthermore, a growing number of patients with DTC have elevated Tg levels but no detectable disease on radioiodine scanning or other imaging studies. The objective of this study was to determine whether a gradient in Tg protein level exists in patients with DTC.

The Influence of Noninvasive Prenatal Testing on Gestational Age at Time of Abortion for Aneuploidy

The objective of this study is to compare the gestational age at termination for trisomy 13, 18, or 21 (aneuploidy) before and after the introduction of noninvasive prenatal testing (NIPT).