Which Ultrasound Characteristics Predict Lymphatic Spread of Papillary Thyroid Cancer?

INTRODUCTION: The 2015 American Thyroid Association guidelines recommend lymph node mapping US in patients with definitive cytological evidence of thyroid cancer. Suspicious lymph node features on imaging including enlarged size (>1 cm in any dimension), architectural distortion, loss of fatty hilum, and microcalcifications often prompt evaluation with fine needle aspiration. There is no universally agreed upon model for determining which ultrasound characteristics most strongly correlate with metastatic disease. METHODS: A retrospective review of patients with confirmed papillary thyroid cancer (PTC) undergoing lymph node mapping ultrasound from 2013 to 2019 was performed. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated for each individual ultrasound characteristic as well as for characteristic combinations. RESULTS: Data from 119 lymph nodes were included. Malignant lymph nodes were more likely to be enlarged (71% versus 61%, P < 0.001) and to have each individual suspicious feature. Loss of fatty hilum had the highest sensitivity (89%) but was not specific (19%) for metastatic disease. Architectural distortion was found to have the highest specificity (87%). A combination of the four features was found to have higher specificity (97%) and PPV (88%) than any individual feature or combination of two/three features. CONCLUSIONS: A combination of four sonographic features correlates with metastatic PTC to lymph nodes and has the highest specificity and PPV for malignancy. A risk stratification model based on these features may lead to better classification of ultrasound findings in PTC patients with concern for nodal metastases.

Integrated metabolic and genetic analysis reveals distinct features of human differentiated thyroid cancer.

BACKGROUND: Differentiated thyroid cancer (DTC) affects thousands of lives worldwide each year. Typically, DTC is a treatable disease with a good prognosis. Yet, some patients are subjected to partial or total thyroidectomy and radioiodine therapy to prevent local disease recurrence and metastasis. Unfortunately, thyroidectomy and/or radioiodine therapy often worsen(s) quality of life and might be unnecessary in indolent DTC cases. On the other hand, the lack of biomarkers indicating a potential metastatic thyroid cancer imposes an additional challenge to managing and treating patients with this disease. AIM: The presented clinical setting highlights the unmet need for a precise molecular diagnosis of DTC and potential metastatic disease, which should dictate appropriate therapy. MATERIALS AND METHODS: In this article, we present a differential multi-omics model approach, including metabolomics, genomics, and bioinformatic models, to distinguish normal glands from thyroid tumours. Additionally, we are proposing biomarkers that could indicate potential metastatic diseases in papillary thyroid cancer (PTC), a sub-class of DTC. RESULTS: Normal and tumour thyroid tissue from DTC patients had a distinct yet well-defined metabolic profile with high levels of anabolic metabolites and/or other metabolites associated with the energy maintenance of tumour cells. The consistency of the DTC metabolic profile allowed us to build a bioinformatic classification model capable of clearly distinguishing normal from tumor thyroid tissues, which might help diagnose thyroid cancer. Moreover, based on PTC patient samples, our data suggest that elevated nuclear and mitochondrial DNA mutational burden, intra-tumour heterogeneity, shortened telomere length, and altered metabolic profile reflect the potential for metastatic disease. DISCUSSION: Altogether, this work indicates that a differential and integrated multi-omics approach might improve DTC management, perhaps preventing unnecessary thyroid gland removal and/or radioiodine therapy. CONCLUSIONS: Well-designed, prospective translational clinical trials will ultimately show the value of this integrated multi-omics approach and early diagnosis of DTC and potential metastatic PTC.

Integrated metabolic and genetic analysis reveals distinct features of primary differentiated thyroid cancer and its metastatic potential in humans.

Differentiated thyroid cancer (DTC) affects thousands of lives worldwide every year. Typically, DTC is a treatable disease with a good prognosis. Yet, some patients are subjected to partial or total thyroidectomy and radioiodine therapy to prevent local disease recurrence and metastasis. Unfortunately, thyroidectomy and/or radioiodine therapy often worsen(s) the quality of life and might be unnecessary in indolent DTC cases. This clinical setting highlights the unmet need for a precise molecular diagnosis of DTC, which should dictate appropriate therapy. Here we propose a differential multi-omics model approach to distinguish normal gland from thyroid tumor and to indicate potential metastatic diseases in papillary thyroid cancer (PTC), a sub-class of DTC. Based on PTC patient samples, our data suggest that elevated nuclear and mitochondrial DNA mutational burden, intratumor heterogeneity, shortened telomere length, and altered metabolic profile reflect the potential for metastatic disease. Specifically, normal and tumor thyroid tissues from these patients had a distinct yet well-defined metabolic profile with high levels of anabolic metabolites and/or other metabolites associated with the energy maintenance of tumor cells. Altogether, this work indicates that a differential and integrated multi-omics approach might improve DTC management, perhaps preventing unnecessary thyroid gland removal and/or radioiodine therapy. Well-designed, prospective translational clinical trials will ultimately show the value of this targeted molecular approach. TRANSLATIONAL RELEVANCE: In this article, we propose a new integrated metabolic, genomic, and cytopathologic methods to diagnose Differentiated Thyroid Cancer when the conventional methods failed. Moreover, we suggest metabolic and genomic markers to help predict high-risk Papillary Thyroid Cancer. Both might be important tools to avoid unnecessary surgery and/or radioiodine therapy that can worsen the quality of life of the patients more than living with an indolent Thyroid nodule.

Association of Implementation of Operating Room-Based Parathyroid Hormone Testing with Operative Time and Cost.

BACKGROUND: Intraoperative parathyroid hormone (IOPTH) testing facilitates focused parathyroidectomy to establish biochemical cure but may be time-consuming. A dedicated immunoassay machine was relocated to the operating room for IOPTH. These data seek to determine association of operating room-based IOPTH with operative time, laboratory turnaround time (TAT), and cost. METHODS: Patients who underwent parathyroidectomy from June 2017 to February 2020 were reviewed. Clinical and demographic data, operative time, and TAT were collected. Patients were compared by operation dates pre- or post-machine acquisition. A cost model was created to evaluate cost of care before and after operating room-based testing. RESULTS: A total of 285 patients were included. Post-machine, median operative time decreased from 69 minutes (interquartile range [IQR] 60 to 84) to 57 minutes (IQR 50 to 84.5), p 0.03. Additionally, median TAT for IOPTH values (preoperative, 0, 5, 10, and 15 minutes) decreased post-machine: time preoperative, 29 minutes (IQR 23 to 40) vs 18 minutes (IQR 17 to 23.5), p < 0.001; time 0, 33 minutes (IQR 27 to 39) vs 18.5 minutes (17.5 to 21), p < 0.001; time 5 minutes, 31 minutes (IQR 26 to 36) vs 20 minutes (IQR 18.5 to 21), p < 0.001; time 10 minutes, 32 minutes (IQR 27 to 39) vs 20 minutes (IQR 18.5 to 22.5), p < 0.001; and time 15 minutes, 30 minutes (IQR 26 to 36) vs 19 minutes (IQR 17 to 21), p < 0.001. Total costs pre- and post-machine were $4,442 and $4,111, respectively. With $331 cost reduction per operation and 127 operations per year, the IOPTH machine pays for itself in 3 years, or 378 surgeries, and saves $168,589 in the machine's remaining 4-year life span. CONCLUSIONS: Operating room-based parathyroid hormone testing results in improved operating productivity by decreasing result TAT and operative time and reduces cost.

Serum Klotho levels in primary hyperparathyroidism patients before and after parathyroidectomy.

PURPOSE: To investigate Klotho level and its association with biochemical indices of primary hyperparathyroidism (PHPT). METHODS: Fifty PHPT patients and fifty-two age- and body mass index-(BMI) matched healthy control subjects were recruited. In addition, twenty-five PHPT patients underwent parathyroidectomy (PTX) and had 4-month follow-up visits. Intact parathyroid hormone (iPTH), 25-hydroxyvitamin D [25(OH)D], calcium, albumin, corrected calcium, and Klotho levels were determined. RESULTS: There was no significant difference in age and BMI between PHPT subjects and controls (p > 0.05). PHPT patients had Klotho levels (15.4 ± 1.2 ng/mL) about 23% higher compared with those of the controls (11.9 ± 0.8 ng/mL), but this difference was not significant (p = 0.063). However, postmenopausal PHPT patients had 45% higher Klotho levels (17.6 ± 1.5 ng/ml) compared with postmenopausal controls (12.1 ± 0.9 ng/mL, p = 0.008). For postmenopausal subjects, Klotho levels had positive correlation with levels of iPTH (r = 0.25, p = 0.026) and corrected calcium (r = 0.34, p = 0.003), but negative correlation with 25(OH)D (r = -0.23, p = 0.042). After PTX, levels of iPTH and corrected calcium decreased and 25(OH)D levels increased to normal range (p < 0.001). However, there was no significant change in Klotho levels after a 4-month follow-up. CONCLUSIONS: Serum Klotho levels are higher in postmenopausal PHPT patients than in healthy postmenopausal control subjects. The etiology of elevated Klotho level and its clinical significance requires further investigation.

Parathyroid gland weight is associated with high density lipoprotein levels in patients with primary hyperparathyroidism.

OBJECTIVE: To investigate the relationship between parathyroid gland weight and high-density lipoprotein (HDL) levels in patients with primary hyperparathyroidism (PHPT). METHODS: In this retrospective case control study, we reviewed 329 PHPT patients aged from 20 to 85 years who had a parathyroidectomy at Robert Wood Johnson University Hospital. The patients were divided into 5 quintiles according to their parathyroid gland weight: 68 patients had a parathyroid gland weight <0.3 g, 66 patients had a gland weight 0.3-0.45 g, 67 patients had a gland weight 0.45-0.7 g, 63 patients had a gland weight 0.7-1.25 g, and 65 patients had a gland weight ≥1.25 g. RESULTS: Body Mass Index (BMI) trended to be higher across the quintiles of parathyroid gland weight (P = 0.003). Serum calcium and PTH levels were significantly increased across parathyroid gland quintiles (p < 0.0001). HDL levels tended to be lower across the increasing quintiles of parathyroid gland weight (P = 0.01). There was a negative relationship between log parathyroid gland weight and HDL in patients with PHPT in a simple linear regression (r = -0.160, P = 0.003). The negative association remained significant after adjustment for age and BMI (r = -0.114, P = 0.039). Furthermore, parathyroid gland weight was significantly associated with levels of triglyceride (r = 0.126, P = 0.02), but this relationship lost its significance after adjustment for age and BMI (r = 0.082, P Ëƒ 0.05). CONCLUSIONS: PHPT patients with heavier parathyroid glands tended to have higher BMI and lower HDL levels.

Risk Factors for Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Hospital Workers: Results From a Screening Study in New Jersey, United States in Spring 2020.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a critical concern among healthcare workers (HCWs). Other studies have assessed SARS-CoV-2 virus and antibodies in HCWs, with disparate findings regarding risk based on role and demographics. METHODS: We screened 3904 employees and clinicians for SARS-CoV-2 virus positivity and serum immunoglobulin (Ig)G at a major New Jersey hospital from April 28 to June 30, 2020. We assessed positive tests in relation to demographic and occupational characteristics and prior coronavirus disease 2019 symptoms using multivariable logistic regression models. RESULTS: Thirteen participants (0.3%) tested positive for virus and 374 (9.6%) tested positive for IgG (total positive: 381 [9.8%]). Compared with participants with no patient care duties, the odds of positive testing (virus or antibodies) were higher for those with direct patient contact: below-median patient contact, adjusted odds ratio (aOR) = 1.71 and 95% confidence interval [CI] = 1.18-2.48; above-median patient contact, aOR = 1.98 and 95% CI = 1.35-2.91. The proportion of participants testing positive was highest for phlebotomists (23.9%), maintenance/housekeeping (17.3%), dining/food services (16.9%), and interpersonal/support roles (13.7%) despite lower levels of direct patient care duties. Positivity rates were lower among doctors (7.2%) and nurses (9.1%), roles with fewer underrepresented minorities. After adjusting for job role and patient care responsibilities and other factors, Black and Latinx workers had 2-fold increased odds of a positive test compared with white workers. Loss of smell, taste, and fever were associated with positive testing. CONCLUSIONS: The HCW categories at highest risk for SARS-CoV-2 infection include support staff and underrepresented minorities with and without patient care responsibilities. Future work is needed to examine potential sources of community and nosocomial exposure among these understudied HCWs.

25-Hydroxyvitamin D and Vitamin D Binding Protein Levels in Patients With Primary Hyperparathyroidism Before and After Parathyroidectomy.

Objective: To evaluate vitamin D binding protein and free 25-hydroxyvitamin D [25(OH)D] levels in healthy controls compared to primary hyperparathyroidism (PHPT) patients, and to examine PHPT before and after surgery. Methods: Seventy-five PHPT patients and 75 healthy age, gender, and body mass index (BMI) -matched control subjects were examined. In addition, 25 PHPT patients underwent parathyroidectomy and had a 3-month follow up visit. Levels of total and free 25(OH)D, DBP, and intact parathyroid hormone (iPTH) were determined before and 3 months after surgery. Results: There was no significant difference in age and BMI between PHPT patients and controls. Levels of 25(OH)D and DBP were lower in PHPT patients compared to controls (p < 0.01). There was no significant difference in calculated free and bioavailable 25(OH)D levels between PHPT patients and controls. Calcium and iPTH levels decreased to normal but DBP and DBP-bound-25(OH)D increased (P < 0.001) after parathyroidectomy. Levels of DBP were inversely correlated with iPTH (r = -0.406, P < 0.001) and calcium levels (r = -0.423, P < 0.001). Conclusion: Serum DBP levels were lower in patients with PHPT and parathyroidectomy restored DBP levels. We suggest that lower DBP levels is one of contributing mechanisms of low total 25(OH)D in PTHP patients and the total 25(OH)D levels might not reflect true vitamin D status in PHPT patients.

Operative bed recurrence of thyroid cancer: utility of a preoperative needle localization technique.

BACKGROUND: Surgical management of recurrent disease after total thyroidectomy and/or neck dissection for thyroid carcinoma remains a challenging clinical problem. Reoperation is associated with a significant increase in morbidity. Preoperative needle localization technique for non-palpable breast tumors has recently been extrapolated to head and neck surgery. We report on the use of preoperative ultrasound-guided needle localization for non-palpable recurrent operative bed disease as an intraoperative aid in resection. METHODS: Patients with thyroid carcinoma were identified from a retrospective database at a tertiary care center from 2011-2014. Inclusion criteria were history of thyroidectomy and/or neck dissection, non-palpable recurrent disease in the resection bed on surveillance, and ultrasound-guided needle localization of recurrent disease before resection. Perioperative data and outcomes were analyzed. RESULTS: Seventeen patients were identified using the inclusion criteria listed above. Median patient age was 46 years (53% male, 47% female). A total of 23 masses in the previous operative bed were needle-localized successfully with no major long-term sequelae from this technique. The recurrent laryngeal nerve was involved with tumor in six patients. Two patients, in whom the tumor surrounded the nerve circumferentially, experienced recurrent laryngeal nerve injuries. No patients experienced postoperative hypocalcemia. With a routine surveillance and a median follow-up of 558 days, sixteen of the patients remain with no evidence of disease. CONCLUSIONS: Preoperative ultrasound-guided needle localization of non-palpable recurrent operative bed disease after thyroidectomy and/or neck dissection is a potentially safe method to aid in resection and cure.

An Evaluation of Postoperative Complications and Cost After Short-Stay Thyroid Operations.

BACKGROUND: Concern for postoperative complications causing airway compromise has limited widespread acceptance of ambulatory thyroid surgery. We evaluated differences in outcomes and hospital costs in those monitored for a short stay of 6 h (SS), inpatient observation of 6-23 h (IO), or inpatient admission of >23 h (IA). METHODS: We retrospectively reviewed all patients undergoing thyroidectomy from 2006 to 2012. The incidence of postoperative hemorrhage, nerve dysfunction, and hypocalcemia were evaluated, as well as cost data comparing the SS and IO groups. RESULTS: Of 1447 thyroidectomies, 880 (60.8 %) were performed as SS, 401 (27.7 %) as IO, and 166 (11.5 %) as IA. Fewer patients in the SS group (59 %) underwent total thyroidectomy than IO (73 %) and IA (71 %; p < 0.01), and SS patients had smaller thyroid weights (27.9 g) compared with IO and IA (47.2 and 98.9 g, respectively; p < 0.01). Ten (0.69 %) patients developed hematomas requiring reoperation, five of the ten patients received antiplatelet or anticoagulant therapy perioperatively. Only one patient in the IA group bled within the 6- to 23-h period, and no patients with bleeding who were discharged at 6 h would have benefitted from 23-h observation. Twenty-four (1.66 %) recurrent laryngeal nerve injuries were identified, 16 with temporary neuropraxias. In addition, 24 (1.66 %) patients had symptomatic hypocalcemia, which was transient in 17 individuals. Financial data showed higher payments and lower costs associated with SS compared with IO. CONCLUSIONS: Selective SS thyroidectomy can be safe and cost effective, with few overall complications in patients undergoing more complex operations involving larger thyroids who were admitted to hospital.

IMPACT OF ETHNIC BACKGROUND ON CLINICAL CHARACTERISTICS AND CARDIOVASCULAR RISK FACTORS AMONG PATIENTS WITH PRIMARY HYPERPARATHYROIDISM.

OBJECTIVE: To compare initial laboratory values and cardiovascular risk factors (CRF) among patients with primary hyperparathyroidism (PHPT) of different ethnic backgrounds. METHODS: In this retrospective study, we reviewed 500 charts of PHPT patients who presented at Robert Wood Johnson University Hospital from January 2000 to December 2013. Among these patients were 46 African Americans (AA), 31 Asians (A), 19 Hispanics (H), and 404 Caucasians (C). The following characteristics were compared between the groups: age; body mass index (BMI); levels of serum calcium, intact parathyroid hormone (iPTH), 25-OH vitamin D, and 24-hour urine calcium; and parathyroid adenoma weight. Presence of CRF including BMI, diabetes mellitus, hypertension, and hyperlipidemia were also recorded for comparison. Associations of adenoma weight and several other parameters were also assessed. RESULTS: Among different ethnic groups, AA patients with PHPT had higher iPTH levels compared to the A and C groups (P<.05), while 25-OHD levels were lower in the AA compared to the A and C groups (P<.05). Adenoma weight was significantly greater in AA than in C and A PHPT patients (P<.01). Adenoma weight was positively correlated with iPTH levels (r = 0.493, P <.001) and serum calcium levels (r = 0.255, P<.01). The group BMIs were C: 29.5 ± 6.9, AA: 33.8 ± 10, A: 24.7 ± 3.3, and H: 30.2 ± 6.6. AA patients had a lower rate of renal stones (9%) compared to other groups (21-29%, P<.05). CONCLUSION: The results of our study indicate that AA patients with PHPT presented with a more severe PHPT profile but had lower 24-hour urine calcium and fewer renal stones. AA patients with PHPT also had higher prevalence of CRF when compared to A and C.

A risk model to determine surgical treatment in patients with thyroid nodules with indeterminate cytology.

BACKGROUND: Thyroid nodules are present in 19-67 % of the population and have a 5-10 % risk of malignancy. Fine needle aspiration biopsies are indeterminate in 20-30 % of patients, often necessitating thyroid surgery for diagnosis. We hypothesized that developing a risk model incorporating factors associated with malignancy could help predict the risk of malignancy in patients with indeterminate thyroid nodules. METHODS: We identified 151 patients with a cytologic diagnosis of follicular neoplasm (Bethesda IV) who progressed to surgery. We retrospectively analyzed demographic, clinical, sonographic, and cytological variables in relation to thyroid carcinoma. RESULTS: Of 151 patients, 51 (33.8 %) had a final diagnosis of thyroid carcinoma. Papillary carcinoma was diagnosed in 34 patients (66.7 %), follicular carcinoma in 15 (29.4 %), and Hürthle cell carcinoma in 2 (3.9 %). On univariate analysis, younger age, male gender, tobacco use, larger nodule size, and calcifications on ultrasound, nuclear atypia on cytology, and suspicious frozen section were associated with the presence of malignancy. When determining odds ratios, four factors were most predictive of malignancy: nodule calcification [odds ratio (OR) 6.37, 95 % confidence interval (CI) 1.62-25.1, p < 0.01] and nodule size (OR 1.75, 95 % CI 1.19-2.57, p < 0.01) on ultrasound, nuclear atypia on cytology (OR 4.91, 95 % CI 1.90-12.66, p < 0.01), and tobacco use (OR 4.59, 95 % CI 1.30-16.27, p < 0.02). A multivariable model based on these four factors resulted in a c-statistic of 0.82. CONCLUSIONS: A multivariable model based on calcification, nodule size, nuclear atypia, and tobacco use may predict the risk of thyroid cancer requiring a total thyroidectomy in patients with thyroid nodules of indeterminate cytology.

Does nodule size predict compressive symptoms in patients with thyroid nodules?

BACKGROUND: Thyromegaly and thyroid nodules are known to cause compressive symptoms, but the exact relationship between nodule size and development of compressive symptoms is unclear. We sought to determine whether compressive symptoms are directly related to nodule size. METHODS: A retrospective analysis of 99 patients who underwent thyroidectomy by a single surgeon was performed. Patients were placed into one of two cohorts: those who experienced preoperative compressive symptoms (N=51) and those who did not (N=48). Compressive symptoms were defined as experiencing neck fullness, dysphagia, choking, or dyspnea. Nodule size, thyroid lobe size, and the presence of visible thyromegaly were compared between the two groups. RESULTS: Average nodule size in patients with compressive symptoms was 3.8 versus 2.2 cm in asymptomatic patients (P<0.0001). Average lobe diameter was 6.2 cm in patients with compressive symptoms versus 4.9 cm in asymptomatic patients (P<0.001). Visible thyromegaly was present in 65.2% of patients with compressive symptoms and 15.4% of asymptomatic patients (P<0.0001). The most common symptom was dysphagia, occurring in 80% of patients, followed by neck fullness (69%), choking (49%), and dyspnea (32%). Of patients who underwent surgery for compressive symptoms, 92.7% had improvement in their symptoms postoperatively. Of patients with a thyroid nodule greater than 1.5 cm, 97% showed improvement in symptoms postoperatively. CONCLUSIONS: Thyroid nodule size and lobe size appear to directly correlate with compressive symptoms. Of patients with compressive symptoms and a thyroid nodule >1.5 cm, 97% experienced improvement in symptoms postoperatively.

The utility of lymph node mapping sonogram and thyroglobulin surveillance in post thyroidectomy papillary thyroid cancer patients.

BACKGROUND: The American Thyroid Association recommends lymph node mapping (LNM) ultrasonography 6-12 months after thyroidectomy for patients with papillary thyroid cancer (PTC). The yield of LNM over thyroglobulin (TG) screening is not well defined. We sought to investigate this relationship. METHODS: Post thyroidectomy LNM was performed on 163 patients with PTC. LNM was considered positive based on these criteria: Loss of fatty hilum (LOFH), microcalcifications, hypervascularity, architectural distortion, or short axis (>8 mm). Serum TG levels were compared to LNM and fine needle aspiration (FNA). RESULTS: Sixty-nine patients had suspicious LNM (42%) and 17 had PTC on FNA (25%). There were 135 suspicious lymph nodes described with malignant nodes found in 6 of 65 patients (9%) with LOFH, 13 of 18 patients (76%) with microcalcifications, 11 of 12 patients (92%) with hypervascularity, 16 of 28 patients (52%) with architectural distortion, and 4 of 7 patients (52%) with enlarged size on FNA. The positive predictive value of LNM was 0.34, increasing to 0.66 when LOFH was excluded. Among 152 patients with documented TG data, LNM identified cervical nodal metastasis in 4 patients with TG < 0.5 pg/mL (anti-TG antibody negative, thyroid-stimulating hormone suppressed). Of the 15 patients with positive anti-TG antibody, 3 with recurrence were found on LNM. CONCLUSION: LNM can detect recurrent PTC when TG level is undetectable, and LOFH is a low-yield sonographic characteristic.

Gastrointestinal endoscopy training in general surgery residency: what has changed since 2009?

BACKGROUND: The Residency Review Committee for Surgery increased the endoscopy requirement for general surgery residents graduating in 2009 and thereafter. These changes led to the release of a position paper from 4 major gastroenterology societies claiming that the brief exposure of general surgery residents to endoscopy is not sufficient to gain competency. The societies also stated that these increased requirements will place an undue burden on gastroenterologists to supervise surgical residents in endoscopy training. METHODS: We designed a retrospective study to see if general surgery residents at our university-based training program were able to meet the 2009 requirements, and if reliance on nonsurgical faculty has increased. The case logs of all general surgery residents graduating from our institution during seven consecutive years were reviewed. SETTING: All endoscopic procedures were carried out at our main university hospital and at our two affiliated university hospitals. Residents spend two thirds of the year at the main campus and the remaining time at the affiliates. RESULTS: We found that our surgical residents have met the new Accreditation Council for Graduate Medical Education requirements. In our program, surgeons continue to provide most of the resident supervision for endoscopic procedures. Although there was an initial increased utilization of nonsurgical faculty for upper endoscopy, reliance on nonsurgical faculty for endoscopy training has declined every year since the guidelines were revised. CONCLUSIONS: It is possible for general surgery residents to meet the new Accreditation Council for Graduate Medical Education requirements in endoscopy without placing an undue burden on gastroenterologists.

Serum monocyte chemokine protein-1 levels before and after parathyroidectomy in patients with primary hyperparathyroidism.

OBJECTIVE: To investigate the effects of parathyroidectomy on serum monocyte chemokine protein-1 (MCP-1) levels in patients with primary hyperparathyroidism (PHPT). METHODS: Forty-three PHPT patients, age 56 ± 12 years, underwent minimally invasive parathyroidectomy. Serum samples were collected at 0 and 15 to 20 minutes after parathyroid adenoma removal. Serum samples were stored at -70°C until time of assay. RESULTS: In 40 PHPT patients with a single adenoma, MCP-1 levels decreased from 342 ± 103 to 250 ± 77 pg/mL (P<.001) 15 to 20 minutes after parathyroid adenoma removal. MCP-1 levels were positively correlated with intact parathyroid hormone (PTH) levels (R = 0.47; P<.01). In 3 PHPT patients with double parathyroid adenoma, MCP-1 levels did not decrease after removal of the first adenoma but decreased 15 to 20 minutes after second adenoma removal. CONCLUSION: Our results provide evidence that the decrease in serum intact PTH due to minimally invasive parathyroidectomy results in an immediate decrease in serum MCP-1 levels.

Carbonic anhydrase 4 and crystallin α-B immunoreactivity may distinguish benign from malignant thyroid nodules in patients with indeterminate thyroid cytology.

BACKGROUND: Thyroid nodules are present in 19%-67% of the population and carry a 5%-10% risk of malignancy. Unfortunately, fine-needle aspiration biopsies are indeterminate in 20%-30% of patients, often necessitating thyroid surgery for diagnosis. Numerous DNA microarray studies including a recently commercialized molecular classifier have helped to better distinguish benign from malignant thyroid nodules. Unfortunately, these assays often require probes for >100 genes, are expensive, and only available at a few laboratories. We sought to validate these DNA microarray assays at the protein level and determine whether simple and widely available immunohistochemical biomarkers alone could distinguish benign from malignant thyroid nodules. METHODS: A tissue microarray (TMA) composed of 26 follicular thyroid carcinomas (FTCs) and 53 follicular adenomas (FAs) from patients with indeterminate thyroid nodules was stained with 17 immunohistochemical biomarkers selected based on prior DNA microarray studies. Antibodies used included galectin 3, growth and differentiation factor 15, protein convertase 2, cluster of differentiation 44 (CD44), glutamic oxaloacetic transaminase 1 (GOT1), trefoil factor 3 (TFF3), Friedreich Ataxia gene (X123), fibroblast growth factor 13 (FGF13), carbonic anhydrase 4 (CA4), crystallin alpha-B (CRYAB), peptidylprolyl isomerase F (PPIF), asparagine synthase (ASNS), sodium channel, non-voltage gated, 1 alpha subunit (SCNN1A), frizzled homolog 1 (FZD1), tyrosine related protein 1 (TYRP1), E cadherin, type 1 (ECAD), and thyroid hormone receptor associated protein 220 (TRAP220). Of note, two of these biomarkers (GOT1 and CD44) are now used in the Afirma classifier assay. We chose to compare specifically FTC versus FA rather than include all histologic categories to create a more uniform immunohistochemical comparison. In addition, we have found that most papillary thyroid carcinoma could often be reasonably distinguished from benign disease by morphological cytology findings alone. RESULTS: Increased immunoreactivity of CRYAB was associated with thyroid malignancy (c-statistic, 0.644; negative predictive value [NPV], 0.90) and loss of immunoreactivity of CA4 was also associated with malignancy (c-statistic, 0.715; NPV, 0.90) in indeterminate thyroid specimens. The combination of CA4 and CRYAB for discriminating FTC from FA resulted in a better c-statistic of 0.75, sensitivity of 0.76, specificity of 0.59, positive predictive value (PPV) of 0.32, and NPV of 0.91. When comparing widely angioinvasive FTC from FA, the resultant c-statistic improved to 0.84, sensitivity of 0.75, specificity of 0.76, PPV of 0.11, and NPV of 0.99. CONCLUSIONS: Loss of CA4 and increase in CRYAB immunoreactivity distinguish FTC from FA in indeterminate thyroid nodules on a thyroid TMA with an NPV of 91%. Further studies in preoperative patient fine needle aspiration (FNAs) are needed to validate these results.

Diagnosing thyroid lymphoma: steroid administration may result in rapid improvement of dyspnea : a report of two cases.

INTRODUCTION: Thyroid nodules, whether benign or malignant, are slow growing masses. There are certain clinical situations where sudden rapid growth may occur and cause acute respiratory compromise secondary to tracheal compression. CASE PRESENTATION: Here we describe two patients with suddenly enlarging thyroid nodules, who developed acute respiratory compromise in the absence of tracheal compression. Their symptoms rapidly improved with administration of corticosteroids, and in subsequent workup, both were diagnosed as thyroid lymphoma. CONCLUSIONS: The potent effect of corticosteroids in the rapid improvement of respiratory compromise associated with thyroid lymphoma represents an important clinical finding. This opens the possibility for the favorable response to corticosteroid therapy to be regarded as a possible preliminary diagnostic tool for thyroid lymphoma in acute respiratory distress patients in the absence of tracheal compression. Subsequent retrospective studies are necessary to verify this hypothesis.

Is one benign fine needle aspiration enough?

BACKGROUND: Fine needle aspiration (FNA) is used to diagnose thyroid nodules, but the follow-up of benign FNA is unclear. We sought to determine whether routine repeat FNAs after initial benign FNA reduces false negatives. METHODS: We identified 265 patients who had at least one benign FNA that either progressed to surgery or had at least one repeat FNA. We reviewed their ultrasonography, FNA cytology, and surgical pathology. RESULTS: Of 127 patients with initial benign FNA that had surgery, 13 had a malignancy, yielding a 10.2% false-negative rate. Of 22 patients who had surgery after at least two benign FNAs, one had a malignancy, yielding a 4.5% false-negative rate. Initially benign cytology (Bethesda II) was upgraded to a cytology requiring surgical intervention (Bethesda IV-VI) in 7 of 129 (5.4%) patients after two FNAs. Suspicious features on ultrasound, including size >4 cm, calcifications, or increased vascularity were found in 90% of patients with a false-negative FNA. CONCLUSIONS: The overall false-negative rate of thyroid FNAs is 10.2%, which is reduced to 4.5% with a second benign FNA. Ninety percent of patients with a false-negative FNA had suspicious sonographic features. Reaspiration should be considered in patients with sonographically suspicious nodules.