Tina W.F. Yen

Reoperative parathyroidectomy: An algorithm for imaging and monitoring of intraoperative parathyroid hormone levels that results in a successful focused approach

BACKGROUND Advances in preoperative imaging and use of intraoperative parathyroid hormone (IOPTH) levels are changing the approach to reoperative parathyroidectomy (ReopPTX). We sought to develop a protocol for imaging and IOPTH monitoring that allows for a focused, successful operative approach. METHODS We reviewed our prospective database of consecutive patients with primary hyperparathyroidism who underwent ReopPTX with IOPTH monitoring between December 1999 and June 2007. RESULTS Thirty-nine patients underwent 43 ReopPTXs for persistent (79%)/recurrent (21%) disease. All underwent ultrasonography and sestamibi imaging; 24 cases (56%) underwent additional imaging studies. Sensitivity of ultrasonography was 56%, sestamibi 53%, both studies 67%, computed tomography (CT) 48%, magnetic resonance imaging (MRI) 67%, and selective venous sampling (SVS) 50%. IOPTH monitoring predicted accurately cure in 100% and failure in 78%. A focused/unilateral approach was performed in 60%; median operative time was 45 minutes (range, 12-127). At last follow-up, 36 (92%) patients were normocalcemic. CONCLUSIONS We propose that ultrasonography and sestamibi studies should be done before all ReopPTXs; failure to localize should prompt sequential CT, MRI, and SVS until localization is achieved. IOPTH monitoring defines cure and is recommended for all ReopPTXs. This algorithm allows for a focused operative approach in >50% of ReopPTXs with operative times comparable with first-time, minimally invasive parathyroidectomy.

Medullary thyroid carcinoma: results of a standardized surgical approach in a contemporary series of 80 consecutive patients

BACKGROUND The surgical management and follow-up strategy in patients with medullary thyroid carcinoma (MTC) remain controversial because of the lack of data on the natural history of these tumors and their patterns of progression. METHODS We reviewed the records of all patients who underwent a cervical operation for MTC between 1991 and 2002. Compartment-oriented surgery (COS) was performed to minimize the risk of cervical recurrence. RESULTS We identified 92 consecutive patients who underwent a cervical operation for MTC: 80 had invasive MTC, and 12 had C-cell hyperplasia after prophylactic thyroidectomy for familial MTC. Ten (13%) of the 80 patients with invasive MTC presented with distant metastases and underwent COS to achieve local-regional control; cervical recurrence developed in none, but three have died of MTC. The remaining 70 patients underwent COS for primary (n=23) or recurrent (n=47) MTC. Disease recurred in 18 (26%) of these 70 patients at a median follow-up of 35 months, with 10 (14%) of the recurrences being cervical. Recurrent disease was associated with a basal calcitonin level of >250 pg/mL in all but four patients, two of whom showed tumor dedifferentiation. In contrast, only 5 (11%) patients without evidence of recurrence had basal calcitonin levels of >250 pg/mL at last follow-up. CONCLUSIONS Complete COS minimizes cervical recurrence. Radiographic evidence of recurrent disease is unlikely when the calcitonin level is < or =250 pg/mL. These data could be used to develop a logical, cost-effective treatment and follow-up strategy for patients with MTC.

Operative failures after parathyroidectomy for hyperparathyroidism: the influence of surgical volume.

Objective:To determine whether surgical volume influences the cause of operative failures after parathyroidectomy for hyperparathyroidism. Summary and Background Data:The surgical success rate for hyperparathyroidism from high-volume centers exceeds 95%, but some patients have unsuccessful parathyroidectomies. Although operative failure can be due to hyperfunctioning parathyroid glands in ectopic locations, less experienced surgeons may be more likely to miss an abnormal parathyroid in normal anatomic locations, which we describe as “preventable operative failure.” Methods:We used 2 prospective databases containing over 2000 consecutive patients who underwent parathyroidectomy. We identified 159 patients with persistent/recurrent hyperparathyroidism subsequently cured with additional surgery. The initially failed operations were classified as being performed at high- (>50 cases/yr) or low-volume (<50 cases/yr) hospitals. Hospital volume was obtained from a Wisconsin state database of 89 hospitals, which reported 6336 parathyroid operations during the same decade. Results:Patients who initially failed their operation performed at the high- or low-volume centers were similar with regard to age, laboratory values, gender, and parathyroid weights. Despite a higher incidence of multigland disease (which increases the likelihood of operative failure) in the high-volume group, patients in the low-volume group were more likely to have a missed parathyroid gland in a normal anatomic location (89% vs. 13%, P < 0.0001), and thus a higher proportion of preventable operative failures. Conclusions:Surgical volume influences the failure pattern after parathyroidectomy for hyperparathyroidism. Preventable operative failures are more common in low-volume centers.

Predicting the need for calcium and calcitriol supplementation after total thyroidectomy: Results of a prospective, randomized study

BACKGROUND The optimal protocol for the detection and treatment of postthyroidectomy hypoparathyroidism is unknown. We sought to identify and treat patients at risk for symptomatic hypocalcemia on the basis of a single parathyroid hormone (PTH) obtained the morning after surgery (POD1). METHODS We performed a prospective, randomized study of total thyroidectomy patients who had POD1 calcium and PTH (pg/mL) levels. Randomization was determined by POD1 PTH: if ≥ 10, patients received no supplementation unless symptomatic; if <10, patients were randomized to calcium, calcium and calcitriol, or no supplementation. RESULTS Of 143 patients, 112 (78%) had a POD1 PTH ≥ 10. Hypocalcemic symptoms were transiently reported in 11 (10%) and managed with outpatient calcium. Of 31 patients with PTH <10, 15 (48%) developed symptoms, including 5 who required intravenous calcium. On multivariate logistic regression analysis, when we adjusted for postoperative calcium level and performance of central neck dissection, we found that predictors of hypocalcemic symptoms were younger age (odds ratio 1.59, 95% confidence interval 1.07-2.32) and a PTH <10 (odds ratio 1.08, 95% confidence interval 1.04-1.12). There were no patient or treatment-related factors that predicted a POD1 PTH <10. CONCLUSION A single POD1 PTH level <10 can accurately identify those patients at risk for clinically significant hypocalcemia. All total thyroidectomy patients with a postoperative PTH ≥ 10 can be safely discharged without supplementation. Given the small number of patients with PTH <10, it is unclear whether both calcium and calcitriol are needed for these higher-risk patients.

Impact of Randomized Clinical Trial Results in the National Comprehensive Cancer Network on the Use of Tamoxifen After Breast Surgery for Ductal Carcinoma in Situ

PURPOSE The National Surgical Adjuvant Breast and Bowel Project B-24 trial, published in June 1999, demonstrated that tamoxifen after breast-conserving surgery (BCS) and radiotherapy for ductal carcinoma in situ (DCIS) reduced the absolute occurrence of ipsilateral and contralateral breast cancer. We assessed the impact of B-24 on practice patterns at selected National Comprehensive Cancer Network (NCCN) centers. PATIENTS AND METHODS Tamoxifen use after surgery was examined among 1,622 patients presenting for treatment of unilateral DCIS between July 1997 and December 2003 at eight NCCN centers. Associations of clinicopathologic and treatment factors with tamoxifen use were assessed in univariate and multivariable logistic regression analyses. RESULTS Overall, 41% of patients (665 of 1,622) received tamoxifen. The proportion increased from 24% before July 1, 1999, to 46% on or after July 1, 1999. Factors significantly associated with receipt of tamoxifen included diagnosis on or after July 1, 1999 (odds ratio [OR], 3.85; P < .0001), BCS in patients younger than 70 years (OR, 3.21; P = .0073), no history of cerebrovascular or peripheral vascular disease (OR, 3.13; P = .0071), receipt of radiotherapy (OR, 1.82; P = .0009), and previous hysterectomy (OR, 1.34; P = .0459). Tamoxifen use varied significantly by center, from 34% to 74% after BCS and 17% to 53% after mastectomy (P < .0001). CONCLUSION Tamoxifen use after surgery for DCIS at NCCN centers increased after presentation of the B-24 results. Rates varied substantially by institution, suggesting that physicians differ in how they weigh the modest reduction in breast cancer risk with tamoxifen against its potential adverse effects in this population.

Factors That Influence Parathyroid Hormone Half-life: Determining if New Intraoperative Criteria Are Needed

IMPORTANCE Minimally invasive parathyroidectomy using intraoperative parathyroid hormone monitoring remains the standard approach to the majority of patients with primary hyperparathyroidism. This study demonstrates that individual patient characteristics do not affect existing criteria for intraoperative parathyroid hormone monitoring. OBJECTIVE To identify patient characteristics, such as age, sex, race, body mass index (BMI), and renal function, that may affect existing criteria for intraoperative parathyroid hormone (IOPTH) levels during minimally invasive parathyroidectomy. DESIGN Retrospective review of a prospectively collected parathyroid database populated from August 2005 to April 2011. SETTING Academic medical center. PARTICIPANTS Three hundred six patients with sporadic primary hyperparathyroidism who underwent initial parathyroidectomy between August 2005 and April 2011. INTERVENTIONS All patients underwent minimally invasive parathyroidectomy with complete IOPTH information. MAIN OUTCOME AND MEASURES Individual IOPTH kinetic profiles were fitted with an exponential decay curve and individual IOPTH half-lives were determined. Univariate and multivariate analyses were performed to determine the association between patient demographics or laboratory data and IOPTH half-life. RESULTS Mean age of the cohort was 60 years, 78.4% were female, 90.2% were white, and median BMI was 28.3. Overall, median IOPTH half-life was 3 minutes, 9 seconds. On univariate analysis, there was no association between IOPTH half-life and patient age, renal function, or preoperative serum calcium or parathyroid hormone levels. Age, BMI, and an age × BMI interaction were included in the final multivariate median regression analysis; race, sex, and glomerular filtration rate were not predictors of IOPTH half-life. The IOPTH half-life increased with increasing BMI, an effect that diminished with increasing age and was negligible after age 55 years (P = .001). CONCLUSIONS AND RELEVANCE Body mass index, especially in younger patients, may have a role in the IOPTH half-life of patients undergoing parathyroidectomy. However, the differences in half-life are relatively small and the clinical implications are likely not significant. Current IOPTH criteria can continue to be applied to all patients undergoing parathyroidectomy for sporadic primary hyperparathyroidism.

A Single Parathyroid Hormone Level Obtained 4 Hours after Total Thyroidectomy Predicts the Need for Postoperative Calcium Supplementation

BACKGROUND Parathyroid hormone (PTH) levels after total thyroidectomy have been shown to predict the development of symptomatic hypocalcemia and the need for calcium supplementation. This study aimed to determine whether a PTH level drawn 4 hours postoperatively is as effective as a level drawn on postoperative day 1 (POD1) in predicting this need. STUDY DESIGN This is a single-institution retrospective review of 4-hour and POD1 PTH levels in patients who underwent total thyroidectomy from January 2012 to September 2012. If POD1 PTH was ≥10 pg/mL, patients did not routinely receive supplementation; if PTH was <10 pg/mL, patients received oral calcium with or without calcitriol. RESULTS Of 77 patients, 20 (26%) had a 4-hour PTH <10 pg/mL; 18 (90%) of these patients had a POD1 PTH <10 pg/mL. No patient with a 4-hour PTH ≥10 pg/mL had a POD1 PTH <10 pg/mL. All 18 patients with POD1 PTH <10 pg/mL received calcium supplementation. Three additional patients received supplementation due to reported symptoms or surgeon preference. A 4-hour PTH ≥10 pg/mL compared with a POD1 PTH had a similar ability to predict which patients would not need calcium supplementation; sensitivity was 98% vs 98%, specificity was 90% vs 86%, and and negative predictive value was 95% vs 95%. Of 21 patients who received supplementation, 13 (62%) also received calcitriol, including 9 patients (69%) with a 4-hour PTH <6 pg/mL. CONCLUSIONS A single PTH level obtained 4 hours after total thyroidectomy that is ≥10 pg/mL accurately identifies patients who do not need calcium supplementation or additional monitoring of serum calcium levels. Same-day discharge, if deemed safe, can be accomplished with or without calcium supplementation based on the 4-hour PTH level. Greater consideration should be given to calcitriol supplementation in patients with a 4-hour PTH <6 pg/mL.

Novel Clinical Trial Designs for Treatment of Ductal Carcinoma In Situ of the Breast with Trastuzumab (Herceptin)

Abstract:  Because ductal carcinoma in situ (DCIS) avidly expresses Her2/neu, the target of the monoclonal antibody trastuzumab, and because trastuzumab has been shown to be effective against invasive breast cancer, trastuzumab may be effective for reducing the tumor burden and abrogating or reversing the hypothesized transition from in situ to invasive disease in patients with DCIS. To test this hypothesis, a trial of neoadjuvant trastuzumab for DCIS has been opened at our institution. Because trastuzumab has been shown to act as a radiosensitizing agent for Her2/neu‐overexpressing cancer and because there are currently no systemic treatments for estrogen‐receptor‐negative DCIS, it makes sense to investigate whether use of trastuzumab concurrently with postoperative radiation therapy improves local control of DCIS. The National Surgical Adjuvant Breast and Bowel Project (NSABP) is planning a trial to test this hypothesis. The risk of cardiac toxicity associated with the doses of trastuzumab planned for these trials (cumulative doses of 8 mg/kg for our trial and 14 mg/kg in the NSABP trial) is believed to be minimal, but the safety profile of these approaches will need to be closely monitored.

The utility of routine preoperative cervical ultrasonography in patients undergoing thyroidectomy for differentiated thyroid cancer

BACKGROUND Preoperative ultrasonography (US) is recommended in all patients with differentiated thyroid cancer (DTC) to evaluate for clinically occult metastatic lymphadenopathy. The purpose of this study was to examine the influence of preoperative US findings on the initial operative management of patients with DTC. METHODS This is a retrospective review of 70 patients with biopsy-proven DTC who underwent total thyroidectomy between February 2010 and January 2012. All patients underwent preoperative cervical US (thyroid, central, and lateral neck lymph node compartments). RESULTS Palpable lateral neck adenopathy was thought to be present in 5 (7%) of the 70 patients, but confirmed by US in only 3; 2 patients avoided lateral compartment neck dissection (LCND). Of 65 patients with no palpable lymphadenopathy, 14 (22%) had abnormal lymphadenopathy on preoperative US. All 14 patients underwent total thyroidectomy with central compartment neck dissection (CCND); 12 patients with abnormal US findings in the lateral compartment(s) also underwent LCND. Metastatic disease was confirmed in 13 (93%) of the 14 patients: 13 of 14 who underwent CCND and 11 (92%) of 12 who underwent LCND. CONCLUSION This study confirms the importance of preoperative, high-quality cervical US in patients with DTC because it changed the operative management in 16 of 70 patients (23%); 13 had a more complete operation for pathologically confirmed, clinically occult, lymph node metastases, 2 avoided nontherapeutic LCND, and 1 had false-positive US results.

Socioeconomic factors associated with adjuvant hormone therapy use in older breast cancer survivors.

The authors sought to identify socioeconomic (SES) factors associated with adjuvant hormone therapy (HT) use among a contemporary population of older breast cancer survivors.