Steven E. Rodgers

Long-term outcome of patients with elevated parathyroid hormone levels after successful parathyroidectomy for sporadic primary hyperparathyroidism.

HYPOTHESIS Untreated long-term elevated parathyroid hormone (PTH) levels after successful parathyroidectomy may predict recurrent hyperparathyroidism (HPT). Although elevated PTH levels have been reported in eucalcemic patients after parathyroidectomy for sporadic primary HPT, the long-term clinical significance of this finding remains unclear. DESIGN Retrospective case series. SETTING Tertiary referral center. PATIENTS Five hundred seventy-six consecutive patients with HPT. INTERVENTION Parathyroidectomy guided by intraoperative monitoring of PTH levels. MAIN OUTCOME MEASURES Overall incidence of elevated PTH levels (measurements of >or= 70 pg/mL at any time during follow-up) and recurrent HPT (hypercalcemia and elevated PTH levels more than 6 months after parathyroidectomy). RESULTS Of the 505 patients who underwent successful parathyroidectomy in this series and were followed up for more than 6 months, 337 (66.7%) consistently had PTH levels within the reference range, and 168 (33.3%) had elevated PTH levels. Of the 168 patients with elevated PTH levels, only 8 (4.8%) developed recurrent disease. The earliest recurrence occurred 2 years postoperatively. Factors associated with elevated PTH levels included advanced age, higher preoperative PTH levels, and mild postoperative renal insufficiency. CONCLUSION Although one-third of the patients had elevated PTH levels after successful parathyroidectomy, most of these patients with elevated PTH levels (95%) will achieve long-term eucalcemia.

Intra-operative parathyroid hormone monitoring in patients with parathyroid cancer

BackgroundIntra-operative parathyroid hormone (PTH) monitoring (IPM) is 97% accurate in predicting postoperative eucalcemia in sporadic primary hyperparathyroidism (SPHPT). However, its usefulness in parathyroid cancer has not been demonstrated. This study reports IPM accuracy during surgical resections for parathyroid cancer.MethodsEight of 556 consecutive patients with SPHPT underwent parathyroidectomy using IPM and had parathyroid cancer. Operative success was defined as eucalcemia > six months and operative failure/persistent cancer as hypercalcemia within six months of parathyroidectomy. The IPM criterion for operative success was defined as a >50% decrease of peripheral PTH levels from the highest either pre-incision or pre-excision values, 10 minutes after resection.ResultsIn eight patients, 11 operations were performed. Ten operations (91%) resulted in >50% intra-operative PTH decrease. However, in only seven (70%) of these resections, eucalcemia was achieved for >6 months with five of these seven (71%) procedures being initial en bloc resections. The remaining 3/10 (30%) operations with >50% intra-operative PTH decrease resulted in operative failures. In the last operation, intraoperative parathormone monitoring (IPM) correctly predicted operative failure. IPM sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy in predicting outcome were 100, 40, 70, 100, and 75%, respectively.ConclusionsIPM with the criterion of >50% PTH drop from the highest level is less accurate in predicting operative success in parathyroid cancer when compared to SPHPT. A >50% intra-operative PTH level decrease in patients with parathyroid cancer, particularly in reoperative cases, is less predictive of complete resection. The initial recognition of this disease followed by proper resection remains essential in the treatment of parathyroid cancer.

Developments in the use of ultrasound for thyroid cancer

Purpose of review This article reviews the recent developments in neck ultrasound for thyroid cancer published in the last 18 months, with emphasis on the emerging role of surgeon-performed ultrasound in clinical endocrine practice. Recent findings Ultrasound has evolved beyond the simple differentiation of solid and cystic thyroid nodules and their measurement. Although no single ultrasound feature has the highest accuracy in distinguishing between benign and malignant thyroid lesions, the combination of several ultrasound characteristics (e.g. hypoechogenicity, irregular borders and microcalcifications) within such thyroid nodules may have a stronger correlation for thyroid cancer. Based on these ultrasound features and risk for thyroid malignancy, the need for ultrasound-guided fine needle aspiration, preoperative staging, lymph node mapping and extent of surgery can subsequently be determined and performed. Furthermore, ultrasound has an additional value intraoperatively and in the postoperative surveillance of patients treated for thyroid cancer. Surgeon-performed ultrasound has recently become indispensible in clinical practice where endocrine surgeons have integrated this versatile imaging modality in the evaluation and treatment of patients with thyroid cancer. Summary Ultrasound is an essential modality in the evaluation of thyroid malignancy. Surgeon-performed ultrasound has proved invaluable in the preoperative, intraoperative and postoperative setting. Future developments in ultrasound may lead to further improvement in the diagnostic accuracy of this modality.

Number of lymph nodes removed during modified radical neck dissection for papillary thyroid cancer does not influence lateral neck recurrence

BACKGROUND This study examines the relationship between the number of lymph nodes removed during modified radical neck dissection and the incidence of disease recurrence. METHODS A retrospective review of 117 patients with papillary thyroid cancer and lateral neck involvement (levels 2-5) who underwent modified radical neck dissection was performed. Data were analyzed for patient demographics, operative procedure, lymph node involvement, complications, radioactive iodine therapy, and disease recurrence. RESULTS Of 117 patients who underwent modified radical neck dissection, the median follow-up of the entire study group was 25 months (range, 1-256 months). Recurrent disease was found in 8% of patients, with a median time to recurrence of 35 months. The median number of lymph nodes removed during modified radical neck dissection was similar in recurrent and nonrecurrent patients (P = .78). There was also no difference in the median number of positive lymph nodes removed (P = .14) between these 2 groups. On multivariate analysis, however, the number of positive lymph nodes (odds ratio, 1.16 [95% confidence interval, 1.01-1.34]) and tumor size (odds ratio, 1.60 [95% confidence interval, 1.03-2.49]) were independent predictors of recurrence of disease after modified radical neck dissection. CONCLUSION Recurrence of papillary thyroid cancer after modified radical neck dissection is unrelated to the number of lymph nodes removed. This study suggests that attempts to maximize the number of lymph nodes removed during modified radical neck dissection for papillary thyroid cancer may not be necessary.

Risk factors for locoregional failure in patients with inflammatory breast cancer treated with trimodality therapy

PURPOSE To compare patterns of local and regional failure between patients with inflammatory breast cancer (IBC) and non-IBC in patients treated with trimodality therapy. MATERIALS AND METHODS We reviewed records of 463 patients with stage II/III breast cancer, including IBC, who completed trimodality therapy from January 1999 to December 2009. RESULTS The median follow-up was 46.3 months (range, 4-152 months). Clinical stage was 29.4% (n = 136) II, 56.4% (n = 261) non-IBC III, 14.2% (n = 66) IBC, 30.5% (n = 141) cN0/Nx, and 69.5% (n = 322) N1-N3c. All the patients received neoadjuvant therapy and mastectomy (98%, n = 456 with axillary dissection), and all had postmastectomy radiation therapy to the chest wall with or without supraclavicular nodes (82.5%, n = 382) with or without axilla (6%, n = 28). The median chest wall dose was 60.4 Gy. Patients with IBC presented with larger tumors (P < .001) and exhibited a poorer response to neoadjuvant therapy: after surgery, fewer patients with IBC were ypN0 (P = .003) and more had ≥ 4 positive nodes (P < .001). Four-year cumulative incidence of locoregional recurrence was 5.9%, with 25 locoregional events, 9 of which had a regional component. On multivariate analysis, triple-negative disease (hazard ratio [HR] 7.75, P < .0001) and residual pathologic nodes (HR 7.10, P < .001) were associated with an increased risk of locoregional recurrence, but IBC was not. However, on multivariate analysis, the 4-year cumulative incidence of regional recurrence specifically was significantly higher in IBC (HR 9.87, P = .005). CONCLUSION In this cohort of patients who completed trimodality therapy, the patients with IBC were more likely to have residual disease in the axilla after neoadjuvant therapy and were at greater risk of regional recurrence. Future study should focus on optimizing regional nodal management in IBC.

Adjuvant therapy of gastrointestinal stromal tumors.

Purpose of review The treatment of gastrointestinal stromal tumors (GISTs) with tyrosine kinase inhibitors (TKIs), such as imatinib and sunitinib, has produced improved outcomes and survival. However, patients with high-risk tumors still have unacceptably high rates of recurrence and disease progression. In the current review, we examine the various strategies for optimizing the treatment of GISTs. Recent findings Extended duration of treatment (36 months) with adjuvant imatinib resulted in improved recurrence-free survival and overall survival, whereas discontinuation of the TKI led to relapse of disease in most high-risk patients. High-dose therapy of imatinib was beneficial for patients with KIT exon 9 mutations. Patients with KIT exon 11 mutations experienced the most improvement in outcomes from adjuvant imatinib. Summary The extended duration of TKI treatment, dose optimization, mutation status, and the effects of TKI discontinuation have recently been examined in more detail. As our understanding of TKI therapy grows, an individualized approach to each patient should lead to better outcomes.

Higher Chest Wall Dose Results in Improved Locoregional Outcome in Patients Receiving Postmastectomy Radiation

PURPOSE Randomized trials demonstrating decreased locoregional recurrence (LRR) and improved overall survival (OS) in women receiving postmastectomy radiation therapy (PMRT) used up to 50 Gy to the chest wall (CW), but in practice, many centers boost the CW dose to ≥60 Gy, despite lack of data supporting this approach. We evaluated the relationship between CW dose and clinical outcome. METHODS AND MATERIALS We retrospectively reviewed medical records of 582 consecutively treated patients who received PMRT between January 1999 and December 2009. We collected data on patient, disease, treatment characteristics, and outcomes of LRR, progression-free survival (PFS) and OS. RESULTS Median follow-up from the date of diagnosis was 44.7 months. The cumulative 5-year incidence of LRR as first site of failure was 6.2%. CW dose for 7% (43 patients) was ≤50.4 Gy (range, 41.4-50.4 Gy) and 93% received >50.4 Gy (range, 52.4-74.4 Gy). A CW dose of >50.4 Gy vs. ≤50.4 Gy was associated with lower incidence of LRR, a 60-month rate of 5.7% (95% confidence interval [CI], 3.7-8.2) vs. 12.7% (95% CI, 4.5-25.3; p = 0.054). Multivariate hazard ratio (HR) for LRR controlling for race, receptor status, and stage was 2.62 (95% CI, 1.02-7.13; p = 0.042). All LRR in the low-dose group occurred in patients receiving 50 to 50.4 Gy. Lower CW dose was associated with worse PFS (multivariate HR, 2.73; 95% CI, 1.64-4.56; p < 0.001) and OS (multivariate HR, 3.88; 95% CI, 2.16-6.99; p < 0.001). CONCLUSIONS The addition of a CW boost above 50.4 Gy resulted in improved locoregional control and survival in this cohort patients treated with PMRT for stage II-III breast cancer. The addition of a CW boost to standard-dose PMRT is likely to benefit selected high-risk patients. The optimal technique, target volume, and patient selection criteria are unknown. The use of a CW boost should be studied prospectively, as has been done in the setting of breast conservation.

Predictors of locoregional outcome in HER2-Overexpressing breast cancer treated with neoadjuvant chemotherapy

Objectives:We identified prognostic factors for locoregional recurrence (LRR) in a cohort of patients with HER2-overexpressing breast cancer treated with neoadjuvant chemotherapy (NACT). Methods:We reviewed records of 157 patients with HER-overexpressing tumors who received NACT between May 1999 and December 2009 and collected demographics, disease/treatment characteristics, and clinical outcome. We estimated rate of LRR by the method of cumulative incidence. Results:Presentation was 33% stage II and 67% stage III; 29.9% were clinically node positive. All patients received NACT, 94% trastuzumab containing. 90.4% had mastectomy and 6.4% breast-conserving surgery; 3.2% had no surgery. Among surgical patients, 48% were pathologically N0, 28.8% had 1 to 3 positive nodes, and 23.7% had ≥4 positive nodes. 79.6% received radiation therapy (RT) to the breast/chest wall±supraclavicular field. Median follow-up was 43 months. Three-year cumulative incidence of LRR was 8.2%; 50% of LRR had a regional component. Predictors for LRR included use of RT (HR=4.70, P=0.006), lymph node positivity (≥4 vs. 0 HR=19.99, P=0.008; 1 to 3 vs. 0 HR=10.8, P=0.031), and ER status (negative vs. positive HR=6.02, P=0.006). The only risk factor for regional failure specifically was residual nodal disease (≥4 HR=6.5, 1 to 3 HR=5.1, P=0.031). Conclusions:In a cohort with stage II to III HER2-overexpressing breast cancer treated predominantly with trastuzumab-containing NACT followed by mastectomy±RT, we identified omission of RT, negative ER status, and residual positive lymph nodes as significant predictors of LRR, with 50% of LRR having a regional component.

The parathyroid hormone assay.

OBJECTIVE To review the history and application of laboratory assays for the measurement of parathyroid hormone. METHODS Perinent literature documenting the development of the parathyroid hormone assay was reviewed. RESULTS Following its introduction in 1963, the parathyroid hormone assay has evolved into a highly sensitive and specific test. It is now a rapid (less than 20 minutes), relatively inexpensive modality that can be performed without the use of radioactive isotopes. However, the assays commonly used today in clinical practice are still susceptible to certain types of interference and artifact. CONCLUSIONS In-house measurement of parathyroid hormone, as well as intraoperative parathyroid hormone monitoring, is now widely available to clinicians in most larger hospitals. This accessibility has greatly facilitated the study and understanding of primary hyperparathyroidism. Despite assay improvements, the measurement of parathyroid hormone in patients with renal disease remains problematic.

Impact of Surgery‐Radiation Interval on Locoregional Outcome in Patients Receiving Neo‐adjuvant Therapy and Mastectomy

Delays in the initiation of radiation are increasingly common for medically underserved patients. We evaluated the impact of delay in initiation of postmastectomy radiation (PMRT) in breast cancer patients treated with neo‐adjuvant therapy (NAT) in a cohort of medically underserved patients with multiple barriers to timely care. We retrospectively reviewed medical records of 248 consecutively treated patients. Clinical stage was 34.4% II, 65.6% III. The median interval from surgery to PMRT was 11.9 weeks; 22.2% started PMRT within 8 weeks of surgery, 52% within 12 weeks, and 67.3% within 16 weeks. The cumulative 5‐year incidence of locoregional recurrence (LRR) was 5.8% (95% CI: 3.2–9.7). There was no significant difference in locoregional outcome among patients starting PMRT within 8 weeks versus >8 weeks (p = 0.634), ≤12 versus >12 weeks (p = 0.332), or ≤16 versus >16 weeks (p = 0.549) after surgery. Although timely initiation of PMRT remains a priority, the locoregional control benefit of PMRT appears to be maintained up to at least 16 weeks, and in those without early locoregional recurrence, PMRT should be offered despite such a delay.