Andrea Piotto

Identification of the Nonrecurrent Laryngeal Nerve during Thyroid Surgery: 20-Year Experience

The nonrecurrent laryngeal nerve, which is rarely observed during thyroidectomy, is at high risk for damage. During a 20-year period 6000 thyroidectomies were performed at our institution, and during these operations inferior laryngeal nerves were routinely identified in all the patients with a standard procedure based on the usual anatomic landmarks. A nonrecurrent laryngeal nerve was observed on the right side in 31 cases (0.51%), with no anatomic anomalies found on the left side. The nerve anomaly was diagnosed preoperatively in five patients. A vocal cord deficit, caused by a nerve lesion, was observed in four cases (12.9%). Our results suggest that the best way to avoid morbidity is routine identification of the nerve. This can be done by carefully identifying all the thyroid structures and being suspicious of the presence of the abnormality when the inferior laryngeal nerve is not found in a classic position.

High prevalence of occult papillary thyroid carcinoma in a surgical series for benign thyroid disease.

In a surgical series of 277 consecutive patients operated on the thyroid for benign diseases, a high prevalence rate (10.5%) of occult papillary carcinoma was found by means of an accurate histologic examination. Indications for surgery were euthyroid multinodular goiter in 25 patients, autonomously hyperfunctioning adenoma in 2 and Graves’ disease in 2 patients. Neoplastic foci were unilaterally found in 25 cases but multifocally in 6 and bilaterally in 4 cases: the diameters ranged from 2-10 mm. After operation (14 subtotal and 15 total thyroidectomies), all patients received TSH-suppressive doses of T4. At a mean follow-up of 5.6 years, neither local recurrences nor lymph node or distant metastases had occurred; no patient died of the tumor. In keeping with other surgical and autopsy series, the prevalence of occult thyroid carcinoma in a normal population is calculated to be about 5-10%, whereas it is known that the prevalence of clinically evident thyroid cancer is only 0.05%. This means that only 1-2% of occult carcinomas may evolve in an overt tumor during life. In view of such an epidemiologic difference and the favorable course of our patients, although the mean follow-up is rather short, we suggest that lobectomy plus T4 treatment may be considered an adequate therapeutic approach in patients with occult papillary thyroid carcinoma.

Pregnancy after high therapeutic doses of iodine-131 in differentiated thyroid cancer: potential risks and recommendations

Seventy female patients who had been treated with high doses of iodine-131 for differentiated thyroid cancer (DTC) and who had a subsequent pregnancy were evaluated. The total 131I dose ranged from 1.85 to 16.55 GBq (mean±SD=4.39±25.20 GBq). Age at first therapy ranged from 15 to 36 years (mean±SD = 24.3±5.0 years) and the interval from 131I therapy topregnancy varied from 2to 10 years (mean±SD = 5.3±2.8 years). The estimated radiation doseto the gonads ranged from 10 to 63 cGy (mean±SD = 24.0±13.5 eGy). All patients were treated with l-thyroxine at doses capable of suppressing thyroid-stimulating hormone. Seventy-three children were followed-up and seven pregnancies are still in progress. One child was affected by Fallots trilogy and three had a low birth weight though with subsequent normal growth; the others were healthy with subsequent normal growth. No newborn with clinical or biochemical thyroid dysfunctions was found. Two spontaneous abortions during the second month of pregnancy were recorded. One of two patients in question subsequently had two healthy children. On the basis of these data, previous administration of high 131I doses does not appear to be a valid reason for dissuading young female DTC patients from considering pregnancy. However, patients should be advised to avoid pregnancy after 131I administration for a period sufficient to ensure complete elimination of the radionuclide and to permit confirmation of complete disease remission, i.e. at least 1 year in our opinion.

Parathyroid imaging with pertechnetate plus perchlorate/MIBI subtraction scintigraphy: A fast and effective technique

We set up a modified technetium-99m (Tc-99m) pertechnetate/Tc-99m MIBI (Tc-MIBI) subtraction scintigraphy for parathyroid imaging by introducing the use of potassium perchlorate (KCLO4). Initially, the effect of KCLO4 on technetium thyroid wash-out was evaluated in five healthy volunteers: 40-minute dynamic studies of the thyroid were obtained 20 minutes after the injection of technetium 150 MBq (4 mCi), both in baseline conditions and after the oral administration of 400 mg KCLO4. After an average latency time of 10.5 minutes, KCLO4 administration resulted in fast and relevant technetium thyroid wash-out with a mean half-time of 16.2 minutes (the half-time was 142.8 minutes in baseline conditions), and a 40-minute reduction of thyroid activity of 78% (it was 14% in baseline conditions). Based on these findings, a new Tc-MIBI subtraction procedure was established as follows: 1) 150 MBq technetium (4 mCi) injection; 2) 400 mg KCLO4 administered orally; 3) patient neck immobilization; 4) acquisition of a 5-minute technetium thyroid scan; 5) 500 MBq MIBI (13.5 mCi) injection; 6) acquisition of a sequence of seven MIBI images, each lasting 5 minutes; and 7) processing (image realignment when necessary, background subtraction, normalization of MIBI images to the maximum pixel count of the technetium image, and subtraction of the technetium image from the MIBI images). In addition, high-resolution neck ultrasound (US) was performed in all cases on the same day as the scintigraphic evaluation. Eighteen consecutive patients with primary hyperparathyroidism were enrolled in the study. Tc-MIBI scintigraphy revealed a single adenoma in all cases and US showed this finding in 15 of 18 cases (83.3%). Furthermore, in three patients, a thyroid nodule associated with hyperparathyroidism was detected by technetium thyroid scans and neck US. In all patients, the parathyroid adenoma was easily identified on both the 20- to 40-minute MIBI and subtracted (MIBI-Tc) images. Regarding the scintigraphic parameters, no difference was found between parathyroid adenomas located in the region of the thyroid bed or in ectopic sites and in parathyroid adenomas with a retrothyroid location. Surgical findings confirmed the presence of a single parathyroid adenoma in all cases. In the three patients with a concomitant thyroid nodule, thyroid lobectomy was performed. These preliminary data suggest that 1) double-tracer subtraction scintigraphy, combined with neck US, appears to be the preferable preoperative imaging procedure in hyperparathyroidism patients with concomitant thyroid nodular disease, 2) in the Tc-MIBI parathyroid scan, the use of KCLO4 results in a rapid and relevant technetium thyroid clearance, improving the quality of MIBI images and making the visualization of parathyroid adenomas, particularly those located behind the thyroid gland, easier.

The Sentinel Node Procedure with Patent Blue V Dye in the Surgical Treatment of Papillary Thyroid Carcinoma

How far to extend the surgical treatment of papillary thyroid carcinoma (PTC) is still an open question. A contribution may come from intra-operative lymphatic mapping because, in other malignancies, the procedure has become an important aid in defining lymph node status. To assess the feasibility of using the sentinel lymph node (SLN) technique with the intratumoral injection of Patent Blue V dye to guide nodal dissection in PTC, 29 patients with a preoperative diagnosis of PTC and no clinical or ultrasonographic evidence of nodal involvement underwent cervicotomy and exposure of the thyroid gland, followed by Patent Blue V dye injection into the thyroid nodule. Total thyroidectomy was subsequently performed, resecting the lymph nodes at levels III, IV, VI and VII. The thyroid, SLN and the other lymph nodes were snap-frozen and submitted for both intra-operative and subsequent definitive pathological evaluation. Intra-operative lymphatic mapping located the SLN in 22/29 patients (75.9%) and the SLN revealed neoplastic involvement in 4/22 (18.2%); other lymph nodes were also positive in 2 cases. In the 18 patients whose SLNs were not metastatic, the other nodes were also disease-free. The SLN technique thus seems helpful in avoiding unnecessary lymph node dissection in PTC without spread to the SLN.How far to extend the surgical treatment of papillary thyroid carcinoma (PTC) is still an open question. A contribution may come from intra-operative lymphatic mapping because, in other malignancies, the procedure has become an important aid in defining lymph node status. To assess the feasibility of using the sentinel lymph node (SLN) technique with the intratumoral injection of Patent Blue V dye to guide nodal dissection in PTC, 29 patients with a preoperative diagnosis of PTC and no clinical or ultrasonographic evidence of nodal involvement underwent cervicotomy and exposure of the thyroid gland, followed by Patent Blue V dye injection into the thyroid nodule. Total thyroidectomy was subsequently performed, resecting the lymph nodes at levels III, IV, VI and VII. The thyroid, SLN and the other lymph nodes were snap-frozen and submitted for both intra-operative and subsequent definitive pathological evaluation. Intra-operative lymphatic mapping located the SLN in 22/29 patients (75.9%) and the SLN revealed neoplastic involvement in 4/22 (18.2%); other lymph nodes were also positive in 2 cases. In the 18 patients whose SLNs were not metastatic, the other nodes were also disease-free. The SLN technique thus seems helpful in avoiding unnecessary lymph node dissection in PTC without spread to the SLN.

Papillary thyroid carcinoma: 35-year outcome and prognostic factors in 1858 patients.

Background and Aim: Papillary thyroid carcinoma (PTC) is universally regarded as a curable malignancy with a favorable prognosis. However, a minority of patients may present, or subsequently develop, locoregional and distant metastases that may adversely affect survival. The value of the various staging methods is complicated by different approaches to diagnostic, therapeutic and follow-up strategies. We aimed at assessing the prognostic factors and survival rate in a large cohort of patients treated and followed up in the same center. Materials and Methods: A total of 1858 patients with PTC operated on by the same surgeon, and followed in the same center over a period of 35 years, were included. Total thyroidectomy was performed in the majority of patients after I-131 diagnostic scans and thyroglobulin assays. When the latter 2 were positive, therapy with I-131 was given. Follow-up was performed periodically and further therapy doses were administered when necessary. All patients were maintained on life-long thyroxine. Results: Ninety-three patients (5%) developed evidence of locoregional or distant metastases after an average follow-up period of 7.9 years (range 1.53–30.5 years). Univariate analysis showed all variables (except for gender) to be significantly correlated with disease recurrence and survival. Multivariate analysis showed 4 variables to be significant and independent prognostic factors: patient age at first treatment, extent of disease, extent of surgery, and the presence of I-131 positive metastases. Discussion and Conclusion: Our data agree with other scoring systems in that patient age at first treatment and the extent of disease are significant and independent prognostic factors. However, and at variance with other methods, we found that the extent of primary surgery and the presence of I-131 positive or negative metastases have similar prognostic significance. In high risk patients, total thyroidectomy and lymphadenectomy followed by I-131 treatment and TSH-suppressive hormonal therapy are recommended.

Thyroidectomy and parathyroid hormone: tracing hypocalcemia-prone patients

BACKGROUND The aim of this prospective study was to identify patients at high risk of developing hypocalcemia after thyroidectomy on the basis of the parathyroid hormone (PTH) level on the first postoperative day. METHODS We included 160 patients undergoing total thyroidectomy in a period of 6 months by the same surgical team in this study. In all patients the PTH level was measured before surgery on the day of surgery (PTH1), and on the first postoperative day (PTH2), whereas serum calcium level was measured daily until discharge. Patients were classified as hypocalcemic if they had a serum calcium level less than the normal range on the first postoperative day, independently of symptoms of hypocalcemia. RESULTS At an average follow-up period of 5.9 months (range, 4-9 mo), 66 patients were considered hypocalcemic, 57 patients (35.6%) had a transient hypocalcemia, and 9 patients (5.6%) required calcium-vitamin D supplementation for persistent hypocalcemia. The mean PTH1 value was 54.4 +/- 17.2 pg/mL (median, 53.85 pg/mL), the mean PTH2 value was 22.8 +/- 13.3 pg/mL (median, 21 pg/mL). The mean PTH decrease in value was 51.54% +/- 27.4% (median, 51.83%; range, 4%-94%) and 43.7% of patients presented a PTH decrease of more than 50%. The presence of a postoperative hypocalcemia was statistical correlated both with the PTH2 level and with the PTH drop percent value (P < .001 and P = .002, respectively). With the use of the receiver operating characteristic curve, the maximum sum of the sensitivity and specificity for the correlation of PTH2 levels and hypocalcemia occurred at a PTH2 level of 9.6 pg/mL. CONCLUSIONS The PTH measurement on the first postoperative day may be considered a useful method to predict postthyroidectomy hypocalcemia, thus avoiding prolonged hospitalization. Moreover, PTH dosage at first postoperative day is more reliable and less expensive than intraoperative quick PTH assay.

BRAF analysis by fine needle aspiration biopsy of thyroid nodules improves preoperative identification of papillary thyroid carcinoma and represents a prognostic factor. A mono-institutional experience.

Abstract Background: The current preoperative diagnosis of a thyroid mass relies on microscopic evaluation of thyroid cells obtained by fine needle aspiration biopsy (FNAB). More recently, FNAB has been combined with molecular analysis to increase the accuracy of the cytological evaluation. In this mono-institutional prospective study, we evaluated whether the routine introduction of BRAF testing in thyroid FNAB could help ameliorate the preoperative recognition of papillary thyroid carcinoma (PTC) in “suspended” or malignant cytological categories. Moreover, we investigated the prognostic role of the BRAFV600E mutation in PTC. Methods: BRAFV600E analysis was performed in thyroid FNAB from 270 patients classified into one of five cytological categories THY1, THY2, THY3, THY4, THY5. All subsequently underwent thyroidectomy±node dissection, from October 2008 to September 2009 in our Department. For each cytological category, we considered the definitive histological diagnosis of PTC and the presence of the BRAFV600E mutation. In 141 patients with a final tissue diagnosis of PTC, we correlated the presence of BRAFV600E with gender, age, histotype, TNM, size of the lesion, extracapsular extension, node metastases and multifocality. Results: The prevalence of the BRAFV600E mutation, among PTCs at final tissue diagnosis, was 69%. It improved the FNAB diagnostic accuracy from 88% to 91%. The BRAFV600E mutation was correlated with older age, classical variant of PTC, advanced stages in patients >45 years. Conclusions: BRAFV600E testing could play a role in improving the diagnostic accuracy of FNAB for PTC, representing a useful adjuvant tool in presurgical characterization of thyroid nodes in particular cases. There is an association between the BRAFV600E mutation and some clinico-pathological characteristics of PTC.

FDG-PET/CT and parathyroid carcinoma: Review of literature and illustrative case series

Parathyroid cancer is an uncommon malignant cancer and is associated with a poor prognosis. The staging of parathyroid cancer represents an important issue both at initial diagnosis and after surgery and medical treatment. The role of positron emission tomography/computed tomography (PET/CT) with 18F-Fluorodeoxyglucose (18F-FDG) as an imaging tool in parathyroid cancer is not clearly reported in the literature, although its impact in other cancers is well-defined. The aim of the following illustrative clinical cases is to highlight the impact of PET/CT in the management of different phases of parathyroid cancer. We describe five patients with parathyroid malignant lesions, who underwent FDG PET/CT at initial staging, restaging and post-surgery evaluation. In each patient we report the value of PET/CT comparing its findings with other common imaging modalities (e.g., CT, planar scintigraphy with 99mTc-sestamibi, magnetic resonance imaging) thus determining the complementary benefit of FDG PET/CT in parathyroid carcinoma. We hope to provide an insight into the potential role of PET/CT in assessing the extent of disease and response to treatment which are the general principles used to correctly evaluate disease status.

Metastatic thyroid carcinoma of the adrenal gland

Follicular thyroid carcinoma may spread distant metastases in sites such as bone, lung and brain. In our series of 448 patients with follicular thyroid carcinoma, distant metastases were present in 25% of cases. We report here a case of follicular thyroid carcinoma with a single metastasis at the right adrenal gland, that was found 12 years after total thyroidectomy and radioiodine therapy. Chest X ray, neck and liver echography and total body scan (TBS), performed after radioiodine therapy, were negative. During hormone therapy, serum thyroglobulin (Tg) levels were less than 1 ng/ml until 1990, and then Tg progressively increased in eighteen months up to 149 ng/ml. A new TBS was negative. At computer tomography a node at the right adrenal gland was found. The patient underwent adrenalectomy and histology showed a metastatic follicular thyroid cancer with Hurthle cells. After 1 and 5 months from surgery Tg serum levels were 0.9 ng/ml. This case shows once again the importance of Tg serum levels during follow-up of differentiated thyroid cancer.