Papillary Thyroid Carcinoma (PTC) in Children and Adults: Comparison of Initial Presentation and Long-Term Postoperative Outcome in 4432 Patients Consecutively Treated at the Mayo Clinic During Eight Decades (1936-2015).

BACKGROUND: Contemporary guidelines for managing PTC advise an approach wherein primary tumor and regional metastases (RM) are completely resected at first surgery and radioiodine remnant ablation (RRA) is restricted to high-risk patients, policies our group has long endorsed. To assess our therapeutic efficacy, we studied 190 children and 4242 adults consecutively treated during 1936-2015. SUBJECTS AND METHODS: Mean follow-up durations for children and adults were 26.9 and 15.2 years, respectively. Bilateral lobar resection was performed in 86% of children and 88% of adults, followed by RRA in 30% of children and 29% of adults; neck nodes were excised in 86% of children and 66% of adults. Tumor recurrence (TR) and cause-specific mortality (CSM) details were taken from a computerized database. RESULTS: Children, when compared to adults, had larger primary tumors which more often were grossly invasive and incompletely resected. At presentation, children, as compared to adults, had more RM and distant metastases (DM). Thirty-year TR rates were no different in children than adults at any site. Thirty-year CSM rates were lower in children than adults (1.1 vs. 4.9%; p = 0.01). Comparing 1936-1975 (THEN) with 1976-2015 (NOW), 30-year CSM rates were similar in MACIS <6 children (p = 0.67) and adults (p = 0.08). However, MACIS <6 children and adults in 1976-2015 had significantly higher recurrence at local and regional, but not at distant, sites. MACIS 6+ adults, NOW, compared to THEN, had lower 30-year CSM rates (30 vs. 47%; p < 0.001), unassociated with decreased TR at any site. CONCLUSIONS: Children, despite presenting with more extensive PTC when compared to adults, have postoperative recurrences at similar frequency, typically coexist with DM and die of PTC less often. Since 1976, both children and adults with MACIS <6 PTC have a <1% chance at 30 years of CSM; adults with higher MACIS scores (6 or more) have a 30-year CSM rate of 30%.

Survival in Response to Multimodal Therapy in Anaplastic Thyroid Cancer.

Context: Historical outcomes in anaplastic thyroid cancer (ATC) have been dismal. Objective: To determine whether an initial intensive multimodal therapy (MMT) is associated with improved ATC survival. Design: MMT was offered to all patients with newly diagnosed ATC treated at the Mayo Clinic from 2003 through 2015; MMT vs care with palliative intent (PI) was individualized considering clinical status and patient preferences. Outcomes were retrospectively analyzed by American Joint Committee on Cancer stage and treatments compared with patient cohort data from 1949 through 1999. Patients: Forty-eight patients (60% male; median age, 62 years); 18 treated with PI, 30 with MMT. Main Outcome Measure: Overall survival (OS) and progression-free survival determined by Kaplan-Meier method. Results: Median OS and 1-year survival for the later cohort were 9 months [95% confidence interval (CI), 4 to 22 months] and 42% (95% CI, 28% to 56%) vs 3 months and 10% for the earlier cohort. Median OS was 21 months compared with 3.9 months in the pooled MMT vs PI groups for the later cohort [hazard ratio (HR), 0.32; P = 0.0006]. Among only patients in the later cohort who had stage IVB disease, median OS was 22.4 vs 4 months (HR, 0.12; 95% CI, 0.03 to 0.44; P = 0.0001), with 68% vs 0% alive at 1 year (MMT vs PI). Among patients with stage IVC cancer, OS did not differ by therapy. Conclusion: MMT appears to convey longer survival in ATC among patients with stage IVA/B disease.

Selective Arterial Calcium Stimulation With Hepatic Venous Sampling Differentiates Insulinoma From Nesidioblastosis.

CONTEXT: In adult patients with endogenous hyperinsulinemic hypoglycemia and negative or inconclusive noninvasive imaging, insulinoma and non-insulinoma pancreatogenous hypoglycemic syndrome (NIPHS) resulting from diffuse nesidioblastosis must be considered in the differential diagnosis. It is not known whether the biochemical results of selective arterial calcium stimulation (SACST) with hepatic venous sampling can differentiate insulinoma from diffuse nesidioblastosis. OBJECTIVE: To determine the specificity of SACST with hepatic venous sampling in differentiating insulinoma from diffuse nesidioblastosis. DESIGN: Retrospective review (January 1996 to March 2014). SETTING: Tertiary referral center. PATIENTS OR OTHER PARTICIPANTS: A total of 116 patients with biochemical evidence of endogenous hyperinsulinemic hypoglycemia and negative or inconclusive noninvasive imaging who were subsequently shown at surgery to have insulinoma (n = 42) or nesidioblastosis (n = 74) after undergoing SACST with hepatic venous sampling. INTERVENTION(S): SACST with hepatic venous sampling before pancreatic exploration. MAIN OUTCOME MEASURE(S): Receiver operating characteristic curves were generated from the biochemical results of SACST to determine the specificity of the maximum hepatic venous insulin concentration (mHVI) and the relative-fold increase in hepatic venous insulin concentration (rHVI) over baseline after calcium injection from the dominant artery in differentiating insulinoma from nesidioblastosis. RESULTS: The mHVI (21.5-fold; P < .001) and rHVI (3.9-fold; P < .001) were significantly higher in the insulinoma group compared to the nesidioblastosis group. The areas under the receiver operating characteristic curve for mHVI and rHVI were excellent (0.94; P < .0001) and good (0.83; P < .0001), respectively, for differentiating insulinoma from nesidioblastosis. mHVI cutoffs of > 91.5 and > 263.5 µIU/mL were 95 and 100% specific for insulinoma, respectively. A 19-fold increase in rHVI over baseline was 99% specific for insulinoma. CONCLUSIONS: These data suggest that the mHVI and rHVI at SACST may be useful in differentiating insulinoma from nesidioblastosis with high specificity in patients with hyperinsulinemic hypoglycemia and negative or inconclusive noninvasive imaging.

AACE/ACE disease state clinical review: pancreatic neuroendocrine incidentalomas.

Incidental detection of pancreatic neuroendocrine tumors (PNETs) has substantially increased over the last decade due to widespread use of advanced imaging studies. Reliable initial imaging-based characterization is crucial for the differential diagnosis from other exocrine neoplasms and to determine the appropriate management plan. Measurements of chromogranin A, pancreatic polypeptide, and calcitonin are recommended for the biochemical evaluation. A thorough medical history needs to be performed to rule out multiple endocrine neoplasia (MEN) type 1. The European Neuroendocrine Tumor Society (ENETS)/Tumor Node Metastasis (TNM) staging system together with a grading based on the Ki-67 proliferation index and mitotic counts has proven to give more appropriate prognostic information than the World Health Organization (WHO)/American Joint Committee on Cancer (AJCC) TNM staging but may still fail to safely differentiate benign from malignant lesions. Poorly differentiated PNETs generally present with metastases and are rarely amenable for resection. Well- or intermediately differentiated tumors ≥2 cm with imaging evidence of malignancy or with a Ki-67 >2% should be resected. It has been suggested that non-MEN related, nonfunctioning, and asymptomatic PNETs <2 cm with a Ki-67 index ≤2% carry a low risk of metastasis and may be observed in the absence of clinical or radiologic criteria of malignancy or progression, especially in older patients. However, because metastases may occur with long delay with smaller PNETS, physicians should consider patient age, lesion location, and the risks of operation, and patients not undergoing surgery need to be closely followed closely.

Impact of variant pancreatic arterial anatomy and overlap in regional perfusion on the interpretation of selective arterial calcium stimulation with hepatic venous sampling for preoperative localization of occult insulinoma.

BACKGROUND: To determine the impact of variant pancreatic arterial anatomy and overlap in regional perfusion on the interpretation of selective arterial calcium stimulation (SACST) with hepatic venous sampling for preoperative localization of occult insulinoma. METHODS: An institutional review board-approved retrospective review was undertaken of 42 patients with surgically confirmed, occult insulinoma who underwent SACST from January 1996 to March 2014. Location of the insulinoma was predicted initially based on the biochemical results of SACST alone according to Doppman's criteria. Pancreatic arteriograms were reviewed blinded to the biochemical results and the regional perfusion of each artery assessed. The anatomic and perfusion data were combined with the biochemical results to make a second prediction and compared with the surgical findings. RESULTS: The biochemical results were positive in 1, 2, and 3 arterial distributions in 73.8%, 21.4%, and 4.8% of patients, respectively. The celiac trunk and superior mesenteric artery (SMA) anatomy were aberrant in 38.1% and 35.7% of patients, respectively. Clinically significant variations included dorsal pancreatic artery replaced to SMA (21.4%) and celiac stenosis (4.8%). Significant variation and overlap in regional pancreatic perfusion was observed, particularly for the SMA. Sensitivity for insulinoma localization was 54.8% (diagnostic arteriography), 73.8% (biochemical data), 88.1% (biochemical, anatomic, perfusion data), and 92.8% (arteriographic, biochemical, anatomic, perfusion data). CONCLUSION: Careful review of the pancreatic arterial anatomy and regional perfusion is critical for correct interpretation of the biochemical results of SACST and improves the sensitivity of localization for occult insulinoma, particularly in the presence of pancreatic arterial variants or overlap in regional perfusion.

Challenges in the management of giant intraductal breast papilloma.

The differential diagnosis of a large breast mass in a post-menopausal woman can include both benign and malignant etiologies. Although rare, diagnosis of giant intraductal papilloma must be considered in the differential. Furthermore, although benign, papillomas presenting as a large breast mass affecting the skin require extensive breast surgical treatment.

Recurrence of papillary thyroid cancer after optimized surgery.

Recurrence of papillary thyroid cancer (PTC) after optimized surgery requires a full understanding of the disease, especially as it has changed in the last 15 years, what comprises optimized surgery, and the different types and implications of disease relapse that can be encountered. PTC has evolved to tumors that are much smaller than previously seen, largely due to various high quality imaging studies obtained for different reasons, but serendipitously identifying thyroid nodules that prove to be papillary thyroid microcarcinomas (PTMC). With rare exception, these cancers are cured by conservative surgery without additional therapy, and seldom result in recurrent disease. PTC is highly curable in 85% of cases because of its rather innocent biologic behavior. Therefore, the shift in emphasis from disease survival to recurrence is appropriate. As a result of three technologic advances-high-resolution ultrasound (US), recombinant TSH, and highly sensitive thyroglobulin (Tg)-disease relapse can be discovered when it is subclinical. Endocrinologists who largely control administration of radioactive iodine have used it to ablate barely detectable or even biochemically apparent disease, hoping to reduce recurrence and perhaps improve survival. Surgeons, in response to this new intense postoperative surveillance that has uncovered very small volume disease, have responded by utilizing US preoperatively to image this disease, and incorporated varying degrees of lymphadenectomy into their initial treatment algorithm. Bilateral thyroid resection-either total or near-total thyroidectomy-remains the standard for PTC >1 cm, although recent data has re-emphasized the value of unilateral lobectomy in treating even some PTC measuring 1-4 cm. Therapeutic lymphadenectomy has universal approval, but when lymph nodes in the central neck are not worrisome to the surgeon's intraoperative assessment, although that judgment in incorrect up to 50%, whether they should be excised has reached a central point of controversy. Disease relapse can occur individually or in combination of three different forms: lymph node metastasis (LNM), true soft tissue local recurrence, and distant disease. The latter two are worrisome for potentially life-threatening consequences whereas nodal metastases are often persistent from the initial operation, and mostly comprise a biologic nuisance rather than virulent disease. A moderate surgical approach of bilateral thyroid resection, with usual central neck nodal clearance, and lateral internal jugular lymphadenectomy for node-positive disease can be performed safely, and with about a 5% recurrence rate.

Introducing the SKIN score: a validated scoring system to assess severity of mastectomy skin flap necrosis.

BACKGROUND: With increasing use of immediate breast reconstruction (IBR), mastectomy skin flap necrosis (MSFN) is a clinical problem that deserves further study. We propose a validated scoring system to discriminate MSFN severity and standardize its assessment. METHODS: Women who underwent skin-sparing (SSM) or nipple-sparing mastectomy (NSM) and IBR from November 2009 to October 2010 were studied retrospectively. A workgroup of breast and plastic surgeons scored postoperative photographs using the skin ischemia necrosis (SKIN) score to assess depth and surface area of MSFN. We evaluated correlation of the SKIN score with reoperation for MSFN and its reproducibility in an external sample of surgeons. RESULTS: We identified 106 subjects (175 operated breasts: 103 SSM, 72 NSM) who had ≥1 postoperative photograph within 60 days. SKIN scores correlated strongly with need for reoperation for MSFN, with an AUC of 0.96 for SSM and 0.89 for NSM. External scores agreed well with the gold standard scores for the breast mound photographs with weighted kappa values of 0.82 (depth), 0.56 (surface area), and 0.79 (composite score). The agreement was similar for the nipple-areolar complex photographs: 0.75 (depth), 0.63 (surface area), and 0.79 (composite score). CONCLUSIONS: A simple scoring system to assess the severity of MSFN is proposed, incorporating both depth and surface area of MSFN. The SKIN score correlates strongly with the need for reoperation to manage MSFN and is reproducible among breast and plastic surgeons.

Surgical resection of synchronously metastatic adrenocortical cancer.

INTRODUCTION: Metastatic adrenocortical carcinoma (ACC) is rapidly fatal, with few options for treatment. Patients with metachronous recurrence may benefit from surgical resection. The survival benefit in patients with hematogenous metastasis at initial presentation is unknown. METHODS: A review of all patients undergoing surgery (European Network for the Study of Adrenal Tumors) stage IV ACC between January 2000 and December 2012 from two referral centers was performed. Kaplan-Meier estimates were analyzed for disease-free and overall survival (OS). RESULTS: We identified 27 patients undergoing surgery for stage IV ACC. Metastases were present in the lung (19), liver (11), and brain (1). A complete resection (R0) was achieved in 11 patients. The median OS was improved in patients undergoing R0 versus R2 resection (860 vs. 390 days; p = 0.02). The 1- and 2-year OS was also improved in patients undergoing R0 versus R2 resection (69.9 %, 46.9 % vs. 53.0 %, 22.1 %; p = 0.02). Patients undergoing neoadjuvant therapy (eight patients) had a trend towards improved survival at 1, 2, and 5 years versus no neoadjuvant therapy (18 patients) [83.3 %, 62.5 %, 41.7 % vs. 56.8 %, 26.6 %, 8.9 %; p = 0.1]. Adjuvant therapy was associated with improved recurrence-free survival at 6 months and 1 year (67 %, 33 % vs. 40 %, 20 %; p = 0.04) but not improved OS (p = 0.63). Sex (p = 0.13), age (p = 0.95), and location of metastasis (lung, p = 0.51; liver, p = 0.67) did not correlate with OS after operative intervention. Symptoms of hormonal excess improved in 86 % of patients. CONCLUSION: Operative intervention, especially when an R0 resection can be achieved, following systemic therapy may improve outcomes, including OS, in select patients with stage IV ACC. Response to neoadjuvant chemotherapy may be of use in defining which patients may benefit from surgical intervention. Adjuvant therapy was associated with decreased recurrence but did not improve OS.

Clinical and molecular features of Hürthle cell carcinoma of the thyroid.

CONTEXT: Hürthle cell cancer (HCC) of the thyroid remains the subject of controversy with respect to natural course, treatment, and follow-up. OBJECTIVE: The objective of the study was to evaluate the clinical and molecular features associated with outcome in HCC. DESIGN: The study was a review of 173 HCC cases treated at Mayo Clinic over 11 years with a median 5.8-year follow-up. RESULTS: None of the patients with minimally invasive histology had persistent disease, clinical recurrence, or disease-related death. Male gender and TNM stage were independently associated with increased risk of clinical recurrence or death in widely invasive patients. The 5-year cumulative probability of clinical recurrence or death was higher in patients with TNM stage III-IV (females, 74%; males, 91%) compared with patients with TNM stage I-II (females, 0%; males, 17%). Pulmonary metastases were best identified by computed tomography, whereas radioactive iodine scans were positive in only two of 27 cases. Thyroglobulin was detectable in patients with clinical disease, with the notable exception of five patients with distant metastases. The common TERT C228T promoter mutation was detected in both widely invasive and minimally invasive tumors. TERT mRNA was below the limit of detection in all samples. CONCLUSION: Widely invasive HCC with TNM stage III-IV is aggressive, with low probability of recurrence-free survival. Males have worse outcomes than females. Minimally invasive HCC appears to be considerably less aggressive. Radioactive iodine scan performs poorly in detecting distant disease. Although the TERT gene is mutated in HCC, the role of this mutation remains to be demonstrated.

Impact of analysis of frozen-section margin on reoperation rates in women undergoing lumpectomy for breast cancer: evaluation of the National Surgical Quality Improvement Program data.

BACKGROUND: Reoperation for positive margins after lumpectomy for breast cancer is common. Intraoperative analysis of frozen-section (FS) margins permits immediate re-excision, avoiding reoperation. The aim of this study was to compare reoperation rates between an institution using routine FS analysis of all margins and the National Surgical Quality Improvement Program (NSQIP) data. METHODS: We designed a retrospective cohort analysis comparing the NSQIP data from a FS single institution with the national NSQIP data from 2006 to 2010. Women undergoing lumpectomy for cancer were identified (N = 24,217), and reoperation rates were compared by the use of χ(2) analyses and multivariable logistic regression. During this time period, NSQIP did not differentiate between reoperations for complications or oncologic reasons. Reoperation rates for mastectomy patients (N = 21,734) and lumpectomy patients without cancer (N = 2,777) over the same time period were analyzed as controls, because reoperations after these procedures likely would be for reasons other than positive margins. RESULTS: The 30-day reoperation rate after lumpectomy for cancer was greater nationally than at the FS institution (13.2% vs 3.6%, P < .001). Multivariable analysis showed that patients in the national NSQIP data set were over four times as likely to undergo reoperation as those at the FS institution's (odds ratio 4.19). The reoperation rates were similar between the two, both for patients undergoing mastectomy (4.7% vs 4.5%, P = .84) and those undergoing lumpectomy for benign diagnosis (2.9% vs 5.9%, P = .39). CONCLUSION: Intraoperative FS margin analysis decreases the number of reoperations for patients undergoing breast conservation for breast cancer. This technique has important implications for patient satisfaction and cost of care.

Papillary thyroid cancer: strategies for optimal individualized surgical management.

OBJECTIVE: The goal of this article was to describe the optimal individualized surgical management of patients with papillary thyroid cancer (PTC). METHODS: This summary reviews the relevant literature that takes into account description of the context of disease incidence, current practice guidelines, controversies in the management of thyroid resection and management of central neck lymph nodes, alternative methods of treatment, and evidence from the author's institution to support the final recommendations. RESULTS: Combining the rationale for treatment decisions from the Mayo Clinic's surgical management of PTC, plus recently published large institutional series and a meta-analysis of patient outcomes, the recommendations for PTC >1 cm include the following: (1) preoperative ultrasound to identify and map the location of lateral jugular lymph node metastasis; (2) bilateral total or near-total thyroidectomy; (3) routine central neck (compartment VI) lymph node dissection; and (4) inclusion of lateral neck lymph node dissection when indicated. Alterations are advised depending on either the level of expertise or anatomic findings at the time of performing the thyroidectomy and lymph node dissection. CONCLUSIONS: Because all of the data presented from the Mayo Clinic and the literature fall short of Level 1 evidence, these recommendations should not be considered dogmatic nor should they exclude reasonable alternatives that are also presented.

Reoperative experience with papillary thyroid cancer.

BACKGROUND: Intense postoperative monitoring has resulted in increasing detection of patients with recurrent papillary thyroid cancer (PTC). Our goals included quantifying successful reoperation, and analyzing surgical complications and reasons for relapse. METHODS: From 1999 to 2008, a total of 410 patients underwent reoperation for PTC relapse. We analyzed post-reoperative disease outcomes, reasons for relapse, and complications. RESULTS: Bilateral reoperative thyroidectomy was performed in 13 (3 %) patients; lobectomy, 34 (8 %); central neck (VI) soft tissue local recurrence excision, 47 (11.5 %); bilateral VI node dissection, 107 (26 %); unilateral VI dissection, 112 (27 %); levels II-V dissection, 93 (23 %); levels III-V, 86 (21 %); lateral single- or two-compartment dissection, 51 (12 %); and node picking, 20 (5 %) of level VI and 53 (13 %) lateral neck. Complications occurred in 6 %; including hypoparathyroidism, 3 %; unintentional recurrent laryngeal nerve (RLN) paralysis, 3 %; phrenic nerve injury, 0.5 %; spinal accessory nerve injury, 0.5 %; and chyle leak in 1.6 %. Of 380 (93 %) patients with follow-up (mean 5.2 years); 274 (72 %) patients are alive with no structural evidence of disease, 38 % developed disease relapse (mean 2.1 years), 42 (11 %) died from PTC, and 55 (14 %) are alive with disease. The reason for relapse was a false negative pre-reoperative ultrasound (US) in 18 (5 %), nodal recurrence in the operative field in 37 (10 %), a combination of these two reasons in 10 (3 %), and disease virulence (local or systemic recurrence) in 81 (21 %). CONCLUSIONS: Although 72 % of patients were rendered structurally disease free after reoperation, nearly 40 % suffered additional relapse. Improved surgical technique or preoperative localization might positively affect 15-20 %; at least 20 % reflect the biologic aggressiveness of the disease.

Operative intervention for recurrent adrenocortical cancer.

INTRODUCTION: Adrenocortical cancer (ACC) recurs despite apparent complete resection. We examined the survival and palliative benefit of resection for recurrent ACC. METHODS: A review of all patients undergoing operation for ACC between 1980 and 2010 at our institution was performed in which we compared resection with nonoperative therapy. RESULTS: Overall, 164 patients underwent operation for ACC, 125 of whom underwent a complete resection (R0). Recurrence occurred in 93 R0 patients (median, 15 months; range, 1.5-150 months). Symptoms at recurrence were present in 71% (66/93), including pain (34%) and hormone excess (43%). There were 67 patients who underwent reoperation for recurrence. Forty-eight of 67 patients underwent R0 resection for recurrence. Operative patients had a greater overall operative versus nonoperative management or no therapy (65 months vs 6 months, P < .01). Median survival for nonoperatively managed patients (226 days) and those undergoing no therapy (179 days) was less than for debulking (1,272 days, P = .002). R0 for recurrence (P = .005) and a disease-free interval >6 months (P < .001) were associated with survival after operation, whereas original tumor size (P = .47), grade (P = .8), and stage (P = .23) were not. Pain and hormonal symptoms improved in 84% of operative patients versus 29% of nonoperatively managed patients (P = .005). Debulking had similar symptomatic improvement to R0 resection (P = .52). CONCLUSION: Patients with recurrent ACC can benefit from operative intervention with improvement in survival and symptoms. Patients with a disease-free interval >6 months and complete resection are likely to benefit from resection of the recurrence, but the near universal improvement in symptoms may expand the criteria for operation in recurrent ACC.

PTTG1 overexpression in adrenocortical cancer is associated with poor survival and represents a potential therapeutic target.

BACKGROUND: Adrenocortical carcinoma (ACC) is associated with poor survival rates. The objective of the study was to analyze ACC gene expression profiling data for prognostic biomarkers and therapeutic targets. METHODS: We profiled 44 ACC and 4 normal adrenals on Affymetrix U133 Plus 2 expression microarrays. Pathway and transcriptional enrichment analysis was performed. Protein levels were determined by Western blot. Drug efficacy was assessed against ACC cell lines. Previously published expression datasets were analyzed for validation. RESULTS: Pathway enrichment analysis identified marked dysregulation of cyclin-dependent kinases and mitosis. Overexpression of PTTG1, which encodes securin, a negative regulator of p53, was identified as a marker of poor survival. Median survival for patients with tumors expressing high PTTG1 levels (log2 ratio of PTTG1 to average ß-actin <-3.04) was 1.8 years compared with 9.0 years if tumors expressed lower levels of PTTG1 (P < .0001). Analysis of a previously published dataset confirmed the association of high PTTG1 expression with a poor prognosis. Treatment of 2 ACC cell lines with vorinostat decreased securin levels and inhibited cell growth (median inhibition concentrations of 1.69 µmol/L and 0.891 µmol/L, for SW-13 and H295R, respectively). CONCLUSION: Overexpression of PTTG1 is correlated with poor survival in ACC. PTTG1/securin is a prognostic biomarker and warrants investigation as a therapeutic target.

Does BRAF V600E mutation predict aggressive features in papillary thyroid cancer? Results from four endocrine surgery centers.

BACKGROUND: Existing evidence is controversial regarding the association between BRAF mutation status and aggressive features of papillary thyroid cancer (PTC). Specifically, no study has incorporated multiple surgical practices performing routine central lymph node dissection (CLND) and thus has patients who are truly evaluable for the presence or absence of central lymph node metastases (CLNMs). METHODS: Consecutive patients who underwent total thyroidectomy and routine CLND at 4 tertiary endocrine surgery centers were retrospectively reviewed. Descriptive and bivariable analyses examined demographic, patient, and tumor-related factors. Multivariable analyses examined the odds of CLNM associated with positive BRAF status. RESULTS: In patients with classical variant PTC, bivariate analysis found no significant associations between BRAF mutation and aggressive clinicopathologic features; multivariate analysis demonstrated that BRAF status was not an independent predictor of CLNM. When all patients with PTC were analyzed, including those with aggressive or follicular subtypes, bivariate analysis showed BRAF mutation to be associated with LNM, advanced American Joint Committee on Cancer (AJCC) stage, and histologic subtype. Multivariable analyses showed BRAF, age, size, and extrathyroidal extension to be associated with CLNM. CONCLUSION: Although BRAF mutation was found to be an independent predictor of central LNM in the overall cohort of patients with PTC, this relationship lost significance when only classical variant PTC was included in the analysis. The usefulness of BRAF in predicting the presence of LNM remains questionable. Prospective studies are needed before BRAF mutation can be considered a reliable factor to guide the treatment of patients with PTC, specifically whether to perform prophylactic CLND.

Preoperative axillary ultrasound in breast cancer: safely avoiding frozen section of sentinel lymph nodes in breast-conserving surgery.

BACKGROUND: The American College of Surgeons Oncology Group Z0011 trial results provided convincing evidence that completion axillary lymph node dissection (CALND) was unnecessary in selected patients with 1 to 2 positive sentinel lymph nodes (SLNs). We hypothesized that preoperative axillary ultrasound (AUS) with fine-needle aspiration is sufficiently sensitive to detect worrisome macrometastasis to preclude the need for frozen-section pathology of SLNs. STUDY DESIGN: We conducted a retrospective single-institution study at a tertiary academic referral center. A total of 1,140 T1 to 2 breast cancer patients who underwent SLN biopsy with or without CALND from January 1, 2007 to December 31, 2010 were reviewed. All patients had negative preoperative AUS with or without fine-needle aspiration. RESULTS: One hundred forty-four (13%) patients were node positive at surgery. Mean age, tumor size, histology, and estrogen receptor and progesterone receptor status were similar comparing 996 SLN-negative with 144 (13%) SLN-positive patients. Of the SLN-positive patients, 25% were premenopausal, 9% were estrogen receptor-negative, and 19% had additional lymph nodes at CALND. Only 19 (2%) patients had SLN metastasis ≥6 mm, 10 (1%) had metastasis >7 mm, and only 1 patient had ≥3 positive SLNs. CONCLUSIONS: The addition of preoperative AUS with or without fine-needle aspiration to management of patients who meet American College of Surgeons Oncology Group Z0011 trial eligibility criteria reduced the risk of macrometastasis measuring ≥6 mm to only 2%; very few of these patients would be premenopausal, have estrogen receptor-negative tumors, or ≥3 positive SLNs. With the addition of AUS with or without fine-needle aspiration, we endorse the conclusions of the American College of Surgeons Oncology Group Z0011 trial to avoid CALND, and see marginal gain in frozen-section analysis of SLNs.