Negative Fine-Needle Aspiration in Patients with Goiter: Should We Doubt It?

BACKGROUND: Epidemiologic studies demonstrated higher incidence of thyroid cancer in patients with multinodular goiters compared to the general population. The aim of this study was to evaluate the risk of finding significant thyroid cancer in patients undergoing thyroidectomy for presumed benign disease. METHODS: The records of 273 patients operated for indications other than cancer or indeterminate cytology were reviewed and analyzed. RESULTS: 202 (74%) patients had a preoperative fine-needle aspiration (FNA) performed. FNA was benign in 96% of patients and non-diagnostic in 4%. Malignancy was unexpectedly found in 50 (19%) patients. Papillary carcinoma constituted 94% of cancers and 86% of cancers were incidental microcarcinomas. Only 7 (2.6%) patients of the entire cohort had tumors greater than 1 cm, of those only 3 had a previous benign FNA (false-negative rate 1.5%). CONCLUSIONS: The rate of significant thyroid cancer found unexpectedly in resected goiters is extremely low. A negative FNA excludes significant cancer with near certainty.

Concurrent Medullary, Papillary, and Follicular Thyroid Carcinomas and Simultaneous Cushing's Syndrome.

BACKGROUND: Papillary thyroid carcinoma is the most common thyroid cancer (85%). Follicular thyroid carcinoma is the second most common type of thyroid cancer, accounting for up to 10% of all thyroid cancers. Medullary thyroid carcinoma accounts for only 5-8% of thyroid cancers. Concurrent medullary, follicular, and papillary carcinomas of the thyroid gland are extremely rare and reported scarcely. CASE REPORT: A 72-year-old male presented with nonspecific neck pain. The workup revealed a nodular thyroid gland with a follicular lesion on fine-needle aspiration. Total thyroidectomy was performed and pathological examination identified a 25-mm follicular carcinoma, two papillary microcarcinomas, and two medullary microcarcinomas. The genetic workup was negative and no other family members were diagnosed with any endocrinopathy. Two months after surgery, the patient was diagnosed with Cushing's syndrome that was treated with laparoscopic left adrenalectomy. On 3-year follow-up, the patient is asymptomatic with no evidence of recurrent disease. CONCLUSION: We present a rare case of a patient with follicular, papillary, and medullary thyroid carcinoma, and Cushing's syndrome. To date, no known genetic mutation or syndrome can account for this combination of neoplastic thyroid and adrenal pathologies, although future research may prove differently.

Prospective validation of a surgical complications grading system in a cohort of 2114 patients.

BACKGROUND: We recently reported a grading system for surgical complications. This system proved to have a high sensitivity for recording minor but meaningful complications prolonging hospital stay in patients after colorectal surgery. We aimed to prospectively validate the complication grading system in a general surgery department over 1 year. METHODS: All surgical procedures and related complications were prospectively recorded between January 1st and December 31st, 2009. Surgical complications were graded on a severity scale of 1-5. The system classifies short-term outcome by grade emphasizing intensity of therapy required for treatment of the defined complication. RESULTS: During the study period, 2114 patients underwent surgery. Elective and oncological surgeries were performed in 1606 (76%) and 465 (22%) patients, respectively. There were 422 surgical complications in 304 (14%) patients (Grade 1/2: 203 [67%]; Grade 3/4: 90 [29%]; Grade 5: 11 [4%]). Median length of stay correlated significantly with complication severity: 2.3 d for no complication, 6.2 and 11.8 d for Grades 1/2 and 3/4, respectively (P < 0.001). Older age (OR 2.75, P < 0.001), comorbidities (OR 1.44, P = 0.02), American Society of Anesthesiology score >2 (OR 2.07, P < 0.001), contamination Grade (OR 1.85, P = 0.001), oncological (OR 2.82, P < 0.001), open (OR 1.22, P = 0.03), prolonged >120 min (OR 2.08, P < 0.001), and emergency surgery (OR 1.42, P = 0.02) independently predicted postoperative complications. CONCLUSIONS: This system of grading surgical complications permits standardized reporting of surgical morbidity according to the severity of impact. Prospective validation of this system supports its use in a general surgery setting as a tool for surgical outcome assessment and quality assurance.

Parathyroid surgery in the elderly: should minimally invasive surgery be abandoned?

BACKGROUND: Single adenoma is the cause of 80 % of primary hyperparathyroidism (PHPT) resulting in wide acceptance of minimally invasive parathyroidectomy (MIP). The incidence of PHPT increases with age. Little information is available regarding the prevalence of multiglandular disease (MGD) in older patients. METHODS: The records of 537 patients that underwent parathyroid surgery between January 2005 and October 2012 at two endocrine surgery referral centers were retrospectively reviewed. Comparison was performed between patients younger than 65 and older than 65 years of age. Clinical variables included preoperative laboratories and imaging, extent of neck exploration, number of glands excised, and intraoperative parathyroid hormone levels during surgery. RESULTS: There were 374 (70 %) patients in the younger age group (YG) and 163 (30 %) patients in the older age group (OG). The mean age was 50 ± 0.5 and 71 ± 0.4 years, respectively. There was no difference between the groups in terms of gender or laboratory results. MGD was significantly more common in the OG (24 % vs. 12 %; p = 0.001) and similarly MIP was less commonly completed in the OG (49 % vs. 68 %; p < 0.001). Cure rates were comparable between the OG and YG (93 % vs. 95 %; p = 0.27). In the OG, patients with MGD had significantly smaller glands as compared to patients with single adenomas in this group (331 ± 67 vs. 920 ± 97 mg; p = 0.006, respectively). CONCLUSIONS: MGD in PHPT was found to be more prevalent in older patients. Planning a bilateral neck exploration should be considered in older patients, especially when a relatively small gland is suggested by imaging or encountered during surgery.

Differentiating benign from malignant thyroid nodules using micro ribonucleic acid amplification in residual cells obtained by fine needle aspiration biopsy.

BACKGROUND: Fine needle aspiration biopsy (FNAB) is the most commonly used diagnostic tool to differentiate benign from malignant thyroid nodules. Nevertheless, some FNAB cytology results are not definite. In such cases diagnostic thyroid lobectomy is performed with malignancy rate on final histopathology ranging at 15%-75%. The aim of this study was to improve on the accuracy of FNAB-based cytology by amplification of microRNAs (micro ribonucleic acids [miRs]) from the residual cells left in the FNAB needle after submission for cytology. METHODS: Residual cells were collected from the needle cup after FNAB cytology of 77 consecutive patients with thyroid nodules. miR-enriched RNA was extracted for all patients with cytology showing either follicular lesion or suspicion for malignancy (n=11). The expression of miR-21, -31, -146b, -187, -221, and -222 was determined using real-time polymerase chain reaction. Results were compared with final surgical histopathology. RESULTS: RNA was successfully extracted from all FNAB specimens. Five patients had FNAB cytology suspicious for malignancy. The miR panel was positive in all five (100%). Six patients had follicular lesions on FNAB. The miR panel was positive in three of four patients (75%) with confirmed malignancy and was negative in two of two (0%) patients with benign pathology results. This corresponded to a specificity of 100%, sensitivity of 88%, and accuracy of 90%. CONCLUSIONS: RNA extraction from FNAB residual cells is feasible, and a miR panel amplified from the extracted RNA seems like a promising diagnostic tool in this limited number of patients.

Association between patient age, volume of breast tissue excised, and local recurrence.

INTRODUCTION: Young breast cancer patients undergoing breast-conserving surgery have a significantly higher rate of local recurrence compared with older women. The aim of this study was to assess whether the volume of tissue excised may be associated with the higher local recurrence rate seen in young patients. METHODS: Medical records of patients who underwent breast-conserving surgery at a single institution between 1987 and 2001 were reviewed retrospectively. Tumor and specimen volumes were extracted from pathology reports, and specimen-to-tumor-volume ratio (STVR) was calculated. STVR and local recurrence rates were compared for women under 40 and over 50 y of age. RESULTS: Data were available for 97 patients under age 40 and 150 women over age 50. Patients under 40 had significantly more high-grade tumors (57% versus 25%, P < 0.0005). There was no significant difference in average tumor size; however, both specimen volume and STVR (log scale) were lower in younger women: 4.63 versus 5.20, P < 0.001 and 3.81 versus 4.55, P < 0.001, respectively. Younger women also had a significantly higher rate of local recurrence: 17% versus 7%, P = 0.03. On multivariate analysis, lower STVR was significantly associated with a higher recurrence rate for the entire group (P < 0.005) and, to a lesser degree, in younger women (P = 0.05). CONCLUSIONS: The volume of tissue removed in women younger than 40 undergoing breast-conserving therapy tends to be smaller than in older women. This may contribute to the higher local recurrence rates observed in young breast cancer patients.

Role of antibiotic therapy in mild acute calculus cholecystitis: a prospective randomized controlled trial.

BACKGROUND: Current recommendations for treating acute calculus cholecystitis include the use of intravenous antibiotics, although these recommendations were never tested scientifically. The aim of this study was to evaluate the role of intravenous antibiotic therapy in patients with mild acute calculus cholecystitis. METHODS: In this prospective, randomized controlled trial, 84 patients with a diagnosis of mild acute calculus cholecystitis were randomly assigned to supportive treatment only or supportive treatment with intravenous antibiotic treatment (42 patients in each arm). Patients were followed through their index admission and until delayed laparoscopic cholecystectomy was performed. RESULTS: The two study groups did not differ in their demographic data or in the clinical presentation and disease severity. Analysis was conducted on the intent-to-treat basis. Patients in the intravenous antibiotics arm resumed a liquid diet earlier (1.7 vs. 2.2 days, p = 0.02) but did not significantly differ in resumption of regular diet (2.8 vs. 3.2 days, p = 0.16) or hospital length of stay (LOS) (3.9 vs. 3.8 days, p = 0.89). Patients in the intravenous antibiotics arm had rates of percutaneous cholecystostomy tube placement (12 vs. 5 %, p = 0.43), readmissions (19 vs. 13 %, p = 0.73), and perioperative course similar to those not receiving antibiotics. The overall hospital LOS, including initial hospitalization and subsequent cholecystectomy, was similar for both groups (5.6 vs. 5.1 days, p = 0.29). Eight (19 %) patients in the supportive arm were crossed over to the intravenous antibiotic arm during the index admission. CONCLUSIONS: Intravenous antibiotic treatment does not improve the hospital course or early outcome in most of the patients with mild acute calculus cholecystitis.

Fragmentation of general surgery: burning to death or rising from the ashes.

General Surgery is losing its appeal and is facing a critical shortage of surgeons. It therefore has to change and adapt to this new reality and we surgeons are responsible for meeting this challenge. If we want students and residents to embrace surgery we need to show them the rewards and satisfaction that we derive from the profession. A 5 year curriculum is needed to train the "abdominal surgery" or "general surgery specialist," who will maintain and teach comprehensive care of the surgical patient and practice a more limited scope of surgical procedures. In addition, we should train a limited number of disease-oriented specialists by means of 1-2 year fellowships.

Mature Results of a Prospective Randomized Trial Comparing 5-Flourouracil with Leucovorin to 5-Flourouracil with Levamisole as Adjuvant Therapy of Stage II and III Colorectal Cancer- The Israel Cooperative Oncology Group (ICOG) Study.

OBJECTIVE: Survival benefit with adjuvant therapy was shown in patients with Stage III colorectal cancer (CRC). This study evaluates long-term (10-year) outcome in patients with CRC randomly assigned to adjuvant 5-Fluorouracil/Leucovorin (5FU+LV) or 5-FU/Levamisole (5FU+LEV). METHODS: Between 1990 and 1995, 398 patients with curatively resected Stage II-III CRC were randomly assigned to adjuvant 5FU+LV or 5FU+LEV for 12 months. RESULTS: No difference was evident in 10-year relapse-free or overall survival between study groups. Grade III toxicity was similar between groups; however, neurotoxicity was significantly greater with 5FU+LEV (p=0.02) and gastrointestinal toxicity with 5FU+LV (p=0.03). Female patients treated with 5FU+LEV had improved overall survival. CONCLUSIONS: Adjuvant treatment of CRC is still based on leucovorin modulated fluorouracil. The long-term follow-up results of this trial indicate that the adjuvant treatment of Stage II-III CRC with 5FU+LV or 5FU+LEV is equally effective. The finding of improved survival in female subjects treated with 5FU+LEV warrants further study to determine if Levamisole is a better modulator of 5-FU than Leucovorin in this patient subset.

Development of a microRNA-based molecular assay for the detection of papillary thyroid carcinoma in aspiration biopsy samples.

BACKGROUND: Although thyroid nodules are common and diagnosed in over 5% of the adult population, only 5% harbor malignancy. Patients with clinically suspicious thyroid nodules need to undergo fine-needle aspiration biopsy (FNAB). The main limitation of FNAB remains indeterminate cytopathology. Only 20%-30% of the indeterminate nodules harbor malignancy, and therefore up to 80% of patients undergo unnecessary thyroidectomy. The aim of this study was to identify and validate a panel of microRNAs (miRNAs) that could serve as a platform for an FNAB-based diagnostic for thyroid neoplasms. METHODS: The study population included 27 consecutive patients undergoing total thyroidectomy for FNAB-based papillary thyroid cancer (n = 20) and benign disorders (n = 7). Aspiration biopsy was performed from the index lesion and from the opposite lobe normal tissue in all study patients at the time of operation. RNA was extracted from all aspiration biopsy samples. Quantitative polymerase chain reaction on a panel of previously selected miRNAs was performed. Polymerase chain reaction results were compared with final histopathology. miRNA from tumor tissues was amplified using the highest value of each miRNA expression in normal tissue as a threshold for malignancy detection. RESULTS: Diagnostic characteristics were most favorable for mir-221 in differentiating benign from malignant thyroid pathology. mir-221 was overexpressed in 19 patients (p < 0.0001) with a sensitive yield of 95%. Specificity, negative and positive predictive value, and accuracy of the miRNA panel were 100%, 96%, 100%, and 98%, respectively. CONCLUSIONS: miRNA quantification for differential diagnosis of thyroid neoplasms within aspiration biopsy samples is feasible and may improve the accuracy of FNAB cytology.

Asymptomatic pancreatic perivascular epithelial cell tumor (PEComa) in a male patient: report and literature review.

CONTEXT: Perivascular epithelial cell tumors (PEComas) are a family of rare mesenchymal neoplasms which share cellular, immunohistochemical and ultrastructural characteristics but are found in different visceral and soft tissue sites. PEComas of the pancreas are extremely rare neoplasms. CASE REPORT: We describe a 49-year-old male who was incidentally diagnosed with a pancreatic mass. Endoscopic ultrasound-guided biopsy suggested a PEComa. An uneventful pylorus-preserving pancreaticoduodenectomy was thus performed. The tumor was a solid well-circumscribed mass in the pancreatic head with dilatation of the main pancreatic duct. Histopathology revealed a well-circumscribed and vascularized neoplasm, measuring 32x27x30 mm, composed of epithelioid smooth muscle cells with clear cytoplasm rich in glycogen. The tumor exhibited immunoreactivity to alpha-smooth muscle actin and to melanoma-associated antigen HMB-45. CONCLUSIONS: Although rare, pancreatic PEComas should be included in the differential diagnosis of a pancreatic mass. Currently, the paucity of cases published makes it impossible to predict the behavior and prognosis of these tumors or to advocate an optimal therapy.

Multifocality in well-differentiated thyroid carcinomas calls for total thyroidectomy.

BACKGROUND: Multifocality is an important factor when recommending surgery for papillary thyroid cancer (PTC). The aim of this study is to assess the incidence and characterize the spread pattern of multifocal PTC (mPTC) in patients undergoing total thyroidectomy. METHODS: All thyroidectomies performed between 2003 and 2008 were reviewed identifying 289 patients. Data were obtained for demographics, clinical data, and histopathological findings. RESULTS: Of the patients with papillary carcinoma, mPTC was identified in 150 patients (57%), of which 71% had lesions in the contralateral lobe. There were no significant differences in multifocality rate for gender, pathology type, and all tumor size subgroups including ≤1 cm. Pathology examination of representative sections versus the entire gland examination resulted in a significantly lower incidence of contralateral disease (P = .04). CONCLUSIONS: Multifocal and contralateral lesions are common in PTC and their incidence is not related to tumor size. Pathology entire gland examination is strongly recommended to properly assess the rate of mPTC.

Medical students and general surgery--Israel's National Survey: lifestyle is not the sole issue.

BACKGROUND: In recent years, a significant decline in the number of medical school graduates who choose general surgery as a career has been noted in Israel. The aim of this study is to characterize the factors that deter Israeli medical students from choosing general surgery. Previous studies in the United States identified lifestyle and financial issues as the most important factors. METHODS: A web-based survey was distributed to graduating medical students throughout Israel. The survey covered different factors and aspects affecting career choice, requiring participants to rate their choices with a 1-5 score. RESULTS: In all, 218 surveys were completed; 72 (33%) students considered general surgery before the surgical clerkship versus only 48 (22%) students after. Professional interest and satisfaction (4.7) were ranked as the most important factors for choosing a residency, followed by an amiable working atmosphere (4.3). The 2 strongest deterrents from general surgery were doctors' inter-relationships (3.5) and compromised lifestyle (3.3). The decision to avoid surgery can be reversed by improving both lifestyle (3.5) and inter-relationships (3.0), but it is less influenced by a substantial increase in residents' salary. CONCLUSIONS: More medical graduates would consider general surgery as a career option if the lifestyle and inter-relationships were perceived as better. An increase in monetary reward did not seem to have a paramount impact among Israeli medical graduates. The surgical clerkship is an important turning point in the students' attitude toward surgery as a career and efforts must be made to improve students' experience significantly during this clerkship.

Internal mammary artery injury during central venous catheter insertion for TPN: rare but fatal.

Vascular injuries caused by subclavian central venous catheter (CVC) insertion can be associated with major complications. Such injuries differ in clinical presentation as well as optimal management, which ranges from observation only to surgical or endovascular repair. We report an injury to a branch of the internal mammary artery following an attempt to introduce a subclavian CVC, resulting in a massive hemothorax. This very rare injury was diagnosed and treated by angiography and embolization; however, the patient later succumbed to multi-organ failure. Suspicion of such an injury in a similar clinical setting should result in immediate angiography that can be lifesaving. To the best of our knowledge, this is the only report of such an adverse event in an adult.

From Mount Sinai to Mount Scopus: differences in the role and value of fine needle aspiration for evaluating thyroid nodules.

BACKGROUND: Fine needle aspiration is the main diagnostic tool used to assess thyroid nodules. OBJECTIVES: To correlate FNA cytology results with surgical pathological findings in two teaching medical centers across the Atlantic. METHODS: We retrospectively identified 484 patients at Hadassah Hebrew University Medical Center, Jerusalem and Mount Sinai Hospital, New York, by means of both preoperative FNA cytology and a final histopathological report. Results compared FNA diagnosis, histological findings and frozen section results (Mt. Sinai only). RESULTS: The sensitivity value of FNA at Hadassah was 83.0% compared with 79.1% at Mt. Sinai (NS). Specificity values were 86.6 vs. 98.5% (P < 0.05), negative predictive value 78.7 vs. 77.6% (NS) and positive predictive value 89.7 vs. 98.6% (P < 0.05), respectively. "Follicular lesion" was diagnosed on FNA in 33.1% of the patients at Hadassah and in 21.5% at Mt Sinai (P < 0.005) with a malignancy rate of 42.5 vs. 23.1% (P < 0.05), respectively. Frozen section was used in 190 patients at Mt. Sinai (78.5%) with sensitivity and specificity values of 72.3% and 100%. Frozen section results altered the planned operative course in only 6 patients (2.5%). Follicular carcinoma was diagnosed in 12 patients at Hadassah vs. 2 patients at Mt. Sinai (P < 0.05). CONCLUSION: The sensitivity of FNA at the two institutions was comparable. While malignancy on frozen section is highly specific, it should be used selectively for suspicious FNA results. Follicular lesions and the rate of malignancy in such lesions were more common at Hadassah, favoring a more aggressive surgical approach.

Application of a novel severity grading system for surgical complications after colorectal resection.

BACKGROUND: Uniform and accurate reporting of surgical complications is the basis for quality control. We developed a computerized system for reporting and grading surgical complications in colorectal surgery. This study was conducted to evaluate this computerized reporting system. STUDY DESIGN: A retrospective chart review was conducted of all surgical complications in patients who underwent resection of the colon or rectum at our institution between the years 1999 and 2004 (n = 408). All complications were recorded using the computerized reporting system and compared with complications reported in the literature. RESULTS: Elective operations were performed in 75.7% of patients, and 24.3% required emergency operations. Of the 408 patients in the study, 239 (58.6%) had an uneventful recovery without complications. At least 1 complication was recorded in 169 (41.4%) patients. Grades 1 and 2 complications were recorded in 83 (20.3%) and 105 (25.7%) patients, respectively, requiring observation or medical treatment only, and 59 patients (14.5%) had grades 3 to 5 complications. The three leading complications were surgical site infection, intraabdominal abscess, and hemorrhage requiring blood transfusion. The grades 3 to 5 complication rate was within the range described in the literature, and the rate of grades 1 and 2 complications was substantially higher. These grades 1 and 2 complications were associated with a substantially longer hospital stay. CONCLUSIONS: This novel complication reporting system was found feasible and proved to have a higher sensitivity for recording minor but meaningful complications that tend to prolong hospital stay.

Lithium-associated hyperparathyroidism: report of four cases and review of the literature.

CONTEXT: Lithium-associated hyperparathyroidism (LAH) was first described in 1973 but many issues remain in question regarding the pathophysiology as well as the appropriate management of this condition. OBJECTIVE: Report of four new cases and review of the literature. RESULTS: We describe two males and two females, treated for more than 10 years with lithium due to bipolar disorder, who developed LAH. All underwent parathyroidectomy. In three cases (75%), pathology revealed multiglandular disease, with hyperplasia or two parathyroid adenomas. We observed a cure status in three (75%) of the operated patients. The fourth patient had a residual disease, but had controlled hypercalcemia under the calcimimetic drug cinacalcet. We also observed the association of LAH with incidental papillary thyroid carcinoma in two patients. Review of the literature identified a higher prevalence of LAH in women than men (four out of one) and a controversy in regard to the prevalence of multiglandular disease. As a result, there is no consensus regarding the preferred surgical procedure. The use of cinacalcet as an effective treatment of LAH was previously described in only five cases. CONCLUSION: In our view, there are apparently two different mechanisms leading to LAH: exacerbation of a pre-existing state of hyperparathyroidism and multiglandular disease. For uncontrolled hypercalcemia, parathyroidectomy is recommended. The issue of routine four-gland exploration and subtotal parathyroidectomy versus intraoperative PTH-determination-guided excision of enlarged glands is still unresolved. The use of the recently developed calcimimetics may offer an alternative to patients who are not candidates for surgery.

Laparoscopic inguinal hernia repair on a general surgery ward: 5 years' experience.

BACKGROUND: Laparoscopic hernia repair has been gaining acceptance as an alternative to open repair. The aim of this study was to present the experience of a general surgery ward with laparoscopic inguinal hernia repair. MATERIALS AND METHODS: A retrospective search of all laparoscopic inguinal hernia repairs between January 1999 and December 2003 was obtained. Data, including perioperative course, postoperative complication, and long-term follow-up, was documented. RESULTS: A total of 423 hernias were repaired in 220 patients. Long-term follow-up was performed by questionnaire, clinic visit, or both in 182 of the 220 patients (82.7%). Median follow-up time was 27.5 (range, 4-61) months. Two hundred and three (92.3%) hernias were bilateral. Fifty-seven patients (25.9%) had recurrent hernias. There was no conversion to an open hernia repair. There were 10 recurrences (2.3%). Minor complications (e.g., abdominal wall hematoma, epigastric vessels injury, and urinary retention requiring catheterization) occurred in 17 (7.7%) patients. A bladder injury occurred in 1 patient (0.45%). There was no mortality. Mean postoperative stay was 1.1 days (range, 1-10). Satisfaction with the laparoscopic repair was expressed by using a scoring system of 1 to 5, with 85.2% being very satisfied (score of 4-5) and 8.2% being dissatisfied (score of 1-2). CONCLUSIONS: The laparoscopic herniorrhaphy offers a safe and effective repair with acceptable complication and recurrence rates. Good results with the total extraperitoneal technique can be achieved by general laparoscopists and not only in highly specialized hernia centers. It is especially suited for bilateral repair and for recurrent hernias.

Prospective trial evaluating electrical impedance scanning of thyroid nodules before thyroidectomy: final results.

BACKGROUND: Electrical impedance scanning (EIS) identifies tissue impedance changes associated with malignancy. Methods to distinguish benign from malignant thyroid nodules, particularly in patients with indeterminate cytology are lacking. PURPOSE: To determine the diagnostic accuracy of EIS in the preoperative evaluation of thyroid nodules. PATIENTS AND METHODS: From September 2002 to December 2006, 216 patients underwent thyroid fine needle aspiration (FNA) and EIS prethyroidectomy in this prospective cohort study. EIS, either positive or negative for malignancy, was correlated with final histopathology. A focal bright spot over a thyroid nodule correlating with increased conductivity and/or capacitance >25% baseline sternocleidomastoid muscle impedance defined positive EIS. Study endpoints were EIS accuracy, sensitivity (Sn), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV). This study has been registered in the National Institutes of Health's public trials registry at ClinicalTrials.gov. The registration number is NCT00571077. RESULTS: EIS correctly diagnosed 96 of 110 patients with malignant and 75 of 106 patients with benign dominant thyroid nodules: Sn = 87%, Sp = 71%, PPV = 76%, NPV = 84%: overall EIS accuracy = 79%. Pretest cancer probability of 51% (110 of 216) increased to 76% (96 of 127) post-EIS, and preoperative use of EIS would result in a significant reduction (71%, 75 of 106) in number of operations performed for benign nodules. EIS performance was similar for 109 patients with indeterminate FNA: Sn = 83%, Sp = 67%, PPV = 61%, NPV = 87%, accuracy = 73%. Pretest probability of cancer increased from 39% (42 of 109) to 61% (35 of 57) post-EIS. The use of EIS would result in a significant reduction (67%, 45 of 67) in the number of purely diagnostic thyroidectomy for indeterminate FNA. CONCLUSION: EIS shows promise in differentiating thyroid nodules. Further EIS hardware and software optimization is warranted to improve upon the already favorable negative predictive value in indeterminate thyroid nodules.