Medullary Thyroid Carcinoma in a Patient with MEN 1 Syndrome. Case Report and Literature Review.

Medullary thyroid cancer (MTC) is typically associated with multiple endocrine neoplasia type 2 syndrome (MEN 2), but not with multiple endocrine neoplasia type 1 (MEN 1). We report a very rare case of MTC in a patient with MEN 1 syndrome. A 60-year-old Caucasian woman with sporadic MEN 1 syndrome was admitted in October 2018 for recurrent hyperparathyroidism unresponsive to medical therapy. Her medical history included the diagnosis of a non-functioning pancreatic neuroendocrine tumor (NF-pNET) of the head of the pancreas 1.5 cm in size in 2001, and subtotal parathyroidectomy for uncontrolled hyperparathyroidism due to bilateral parathyroid hyperplasia in the same year. This history prompted genetic studies, and MEN 1 syndrome was confirmed. Family screening was performed in first-degree relatives, with negative results. Other typical clinical manifestations of MEN 1 syndrome were ruled out. In November 2018, the patient underwent excision of the residual left inferior parathyroid, extended to include the left thyroid lobe, for recurrent uncontrolled hyperparathyroidism. The pathologist identified MTC and adenoma of the parathyroid gland. Genetic tests were performed to identify any RET mutation, with negative results. The patient underwent total thyroidectomy about 6 months later, and the subsequent histological report showed only focal reactive C-cell hyperplasia of the thyroid. A literature review identified only three previously published cases of MTC coexisting with MEN 1 syndrome. This association may have two etiological hypotheses: either a sporadic MTC arising in a patient with MEN 1 syndrome, or a rare case of medullary cancer linked to a MEN 1 gene mutation.

Parathyroidectomy Resolves Tooth Discoloration: A New Presenting Sign of Hyperparathyroidism?

INTRODUCTION: We report the resolution of tooth discoloration following parathyroidectomy in an otherwise asymptomatic woman with primary hyperparathyroidism-associated hypercalcemia. Case Report. A 59-year-old Caucasian woman, diagnosed with primary hyperparathyroidism in 2011, nonsmoker with excellent overall oral health. She complained of tooth discoloration starting in 2013. Pigmentation was particularly evident in the necks of the lower central and lateral incisors (Vita Classical score C2). No bleaching was undertaken. Parathyroidectomy was performed five years after primary hyperparathyroidism diagnosis. Six months later, a reduction in pigmentation was strikingly evident, with incisors scoring A1 and A2. The improvement persisted over time. Tooth value also increased compared to baseline. CONCLUSIONS: This is, to our knowledge, the first report that parathyroidectomy might resolve dental discoloration. This outcome deserves investigation in a meaningful sample size and may eventually prompt the inclusion of dental issues among the consequences of primary hyperparathyroidism.

The Impact of the "Slim-Mesh" Technique on Operation Time and Short/Midterm Outcomes in 67 Overweight, Obese and Superobese Patients from a 10-year Follow-up Study.

Purpose: We performed the sutureless "Slim-Mesh" laparoscopic procedure to repair ventral hernias in overweight/obese patients in order to decrease operative time and complications. Materials and Methods: Between 2009 and November 2018, 67 consecutive overweight/obese patients affected by ventral hernia were operated on at our center with the "Slim-Mesh" technique. This was a prospective (65%)-retrospective study. Results: Our study included 36 males and 31 females; the patients' mean age was 59 years old and mean BMI 31. There were 28 overweight patients, 28 Class I obese patients, and 11 Class II-III obese and superobese patients. Ventral hernia operative size was 3-10 cm (small/medium ventral hernia), 10-20 cm (large/giant) and ≥20 cm (massive) in 45, 17 and 5 cases respectively. Mean surgical time for overweight patients, Class I obese patients, and Class II-III obese and superobese patients was 95 minutes, 103 minutes, and 103 minutes respectively. In 28.3% of cases, ventral hernia operative size was larger than preoperative size, and in 16.4% laparoscopy detected additional fascial defects. We employed a composite mesh in 91% of patients and absorbable straps for mesh fixation in 85%. Mean length of hospital stay was 2.6 days. Mean follow-up time was more than 3.5 years. There were 3 cases (4.4%) of hernia recurrence. Conclusion: The sutureless "Slim-Mesh" technique in overweight/obese patients has several advantages, including a reduction in operative time, recovery, and rate of recurrence. The use of this approach would be fast, safe and simple option for overweight/obese patients.

Plausible Emergence of Autocatalytic Cycles under Prebiotic Conditions.

The emergence of life in a prebiotic world is an enormous scientific question of paramount philosophical importance. Even when life (in any sense we can define it) can be observed and replicated in the laboratory, it is only an indication of one possible pathway for life emergence, and is by no means be a demonstration of how life really emerged. The best we can hope for is to indicate plausible chemical-physical conditions and mechanisms that might lead to self-organizing and autopoietic systems. Here we present a stochastic simulation, based on chemical reactions already observed in prebiotic environments, that might help in the design of new experiments. We will show how the definition of simple rules for the synthesis of random peptides may lead to the appearance of networks of autocatalytic cycles and the emergence of memory.

18F-DOPA and 18F-FDG PET/CT, scintigraphic localization and radioguided surgery of recurrent medullary thyroid cancer: two case reports.

Medullary thyroid cancer (MTC) is considered as a rare thyroid cancer. Surgical approaches such as, total thyroidectomy and bilateral lymph node dissection, represent the first-line treatment. Persistent or increasing serum levels of tumor markers, such as CEA and calcitonin, imply residual or recurrent disease. An early and precise detection of recurrence is very important for guiding appropriate treatment. Recent developments in positron emission tomography (PET) imaging with different radiopharmaceuticals targeting specific hallmark of MTC, such as 18F-DOPA and 18F-FDG, have offered increased sensitivity for identifying recurrences. Moreover, the ability of conventional scintigraphic imaging to guide the surgical approach can be useful for the treatment of MTC recurrent patients. In the present work, we reported two cases of patients with recurrent MTC sending to surgical treatment guided by "nuclear medicine approaches".

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.

Features of papillary thyroid carcinoma in patients older than 75 years.

The aim of this study was to evaluate the prognosis in elderly patients affected by papillary thyroid carcinoma. A retrospective review was conducted on 1,407 patients operated on for papillary thyroid carcinoma at our Department from 1990 to 2007. We analyzed the frequency, the stage, the treatment, the recurrence and the survival in a group of patients aged 75 years or more when compared with a group of patients younger. Among 1,407 patients affected by papillary thyroid carcinoma, 117 (8.3%) were older than 75 years while 1,290 (91.7%) patients were younger. There was no statistical difference between the two groups in frequency of papillary histotype and type of surgery. In the older group, the incidence of anaplastic cancer was higher, p < 0.001. The rate of IV stage was 3.8% in younger versus 15.4% in older patients, p < 0.001. The incidence of recurrence was 6.1% versus 17.9%, p < 0.001, in young and elderly patients, respectively. At a mean follow-up of 8.7 years (range 2-19 years) the overall 10 and 15-year survival in younger patients was 91.3 and 88.7%, while in the older group was 71.8 and 63.9%, respectively. The Kaplan-Meier curve showed a statistically significant difference of survival rate in the two groups (p < 0.0001). Although papillary thyroid cancer is widely considered a lymph-tropic tumor, it seems to have a stronger attitude to distant metastases in elderly patients with a worse prognosis due to a more advanced stage.

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.

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.

Galectin-3 cytotest in thyroid follicular neoplasia: a prospective, monoinstitutional study.

OBJECTIVE: To analyze the utility of galectin-3 (Gal3) immunohistochemistry (IHC) on preoperatively obtained fine needle aspiration biopsy (FNAB) in identifying the subgroup of follicular neoplasia (FN) patients who were candidates for thyroidectomy. STUDY DESIGN: This prospective, monoinstitutional study applied a standardized Gal3 immunostaining protocol (cell block specimens; Gal3 scores: G0 [no Gal3+ve IHC reaction], G1 [Gal3+ve thyrocytes < or = 10%], G2 [Gal3+ve thyrocytes > 10%) in 100 consecutive cytologically assessed FN. All patients underwent thyroidectomy, and the FNs were always histologically categorized (World Health Organization criteria). RESULTS: The overall malignancy rate was 15%. Gal3 expression in presurgical samples significantly correlated with the postoperative diagnosis (p < 0.0001). When all positive Gal3 cases were pooled together (G1+G2), the IHC test performed as follows: sensitivity = 80%; specificity = 86%; positive predictive value = 50%; negative predictive value = 96%. All the Gal3-G2 cases (presurgical cell block) showed postoperative evidence of malignancy. All 9 cases of papillary tumor expressed Gal3 in both cell block and postoperative histology. Among the 6 follicular cancers, the prevalence of Gal3 overexpression in the cell block was 50%. CONCLUSION: The cell block procedure applied to thyroid FNAB samples enables the Gal3 cytotest to be implemented usefully in the preoperative identification of those cases of FN postoperatively found to be malignant (also significantly reducing the number of inappropriate thyroidectomies). Strong Gal3 expression should prompt immediate surgical treatment.

Can we avoid inadvertent parathyroidectomy during thyroid surgery?

OBJECTIVES: To identify risk factors of inadvertent parathyroidectomy (IP) during thyroid surgery with the aim of decreasing the incidence of this unpleasant complication and to evaluate the impact on temporary and permanent hypocalcaemia following bilateral thyroidectomy. PATIENTS AND METHODS: All consecutive thyroid surgical procedures performed at the Special Surgical Pathology Department of Padova General Hospital and Padova University during one year (January-December 2005) were retrospectively reviewed. Demographic data as well as data on diagnosis, operative reports, pathology findings, and postoperative serum calcium values were collected. A total of 882 patients (F=685 M=197) were included in the study. The patients were divided into 2 groups: those with IP and those without IP, and their data were compared to find factors affecting the occurrence of IP. The impact of IP on residual early and late postoperative parathyroid function was assessed. Hypercalcaemic (calcium level below 2.10 mMol/L) patients were followed from 1 week to 3 years. RESULTS: Seventy of 882 patients (7.9%) were found to have IP. In 11 cases (16% of IP cases and 1.2 % of entire series) the parathyroid glands were completely intrathyroidal. The results of bivariate analysis showed young age (p=0.037), malignant disease (p<0.0001), total thyroidectomy with lymph node dissection (p<0.0001), low weight of thyroid specimen (p<0.0001), and non-visualisation of any parathyroid gland at operation (p<0.0001) as predictive factors for IP. Multivariate analysis revealed significant correlation between IP and malignant disease (p=0.004), and between lymph node dissection and permanent postoperative hypocalcaemia (p=0.018). The incidence rate of transient and permanent hypocalcaemia was higher in IP than in those without. The mean diameter of excised parathyroid glands was 3.2 mm, suggesting more extended or difficult surgical procedures. CONCLUSION: IP is not uncommon during thyroidectomy and is associated with a higher, though not statistically significant, incidence of transient and permanent postoperative hypocalcaemia. Malignant disease, lymph node dissection, non-visualization of any parathyroid gland at operation and younger age seem to be risk factors and should be considered by the surgeon. Further efforts must be taken to reduce the incidence beginning by avoiding parathyroid fragmentation.

99Tc Nanocolloid sentinel node procedure in thyroid carcinoma.

PURPOSE: The purposes of this study were to investigate the efficacy of radiocolloid lymphoscintigraphy and of handheld gamma probe procedure for sentinel lymph node biopsy (SLNB) in papillary thyroid carcinoma (PTC) and to evaluate its results in clinical staging. MATERIALS AND METHODS: Sixty-five PTC consecutive patients entered the study. Patients underwent radiocolloid lymphoscintigraphy before surgery. Intraoperative sentinel lymph node (SLN) localization was performed using a handheld gamma probe. They were followed up at 2, 6 months, and yearly. RESULTS: SLN metastases were diagnosed in 52%. Fifty-one patients underwent ablative 131-I therapy. The mean Tireoglobulin level in N0 vs N1 cases was 2.2 ng/ml vs 4.73 (p = 0.03) and 0.68 vs 2.1 ng/ml (p = 0.005) before and after 131-I therapy, respectively. CONCLUSIONS: In patients classified N0 by SLNB, ablative 131-I therapy could be avoided.

[The surgical treatment of the nodular goiter]. / Il trattamento chirurgico del gozzo nodulare.

BACKGROUND: The simple nodular goiter, the etiology of which is multifactorial, encompasses the spectrum from the incidental asymptomatic small solitary nodule to the large intrathoracic goiter, causing pressure symptoms as well as cosmetic complaints. The mainstay in the diagnostic evaluation is related to functional and morphological characterization with serum TSH and (some kind of) imaging. Because malignancy is just as common in patients with a multinodular goiter as patients with a solitary nodule, the increasing use of fineneedle aspiration biopsy (cytology) is supported Its management is still the cause of considerable controversy. Prevalence of nodular goiter and results of surgical treatment in a large series of patients operated on at our center are reported. METHODS: From January to December 2004, 1009 out of 1580 patients admitted to our Center underwent surgical treatment for thyroid disease. RESULTS: Nodular goiter accounted for 80% of the whole series. More in detail, toxic multinodular goiter was found in 13.5% of the patients, euthyroid multinodular goiter in 46.6%, single hyperplastic nodule in 2.3%, follicular lesion in 14%, Plummer's adenoma in 4.4%, relapsing goiter in 2.6% and thyroid cyst in 0.12%. Thyroid lobectomy was carried out in 20.8% of patients, while the remaining 79.2% underwent to total thyroidectomy. A carcinoma was incidentally found in 7.6% of the multinodular goiters. CONCLUSIONS: Surgery should be advocated for the treatment of thyroid nodules whenever a patient presents with either pressure symptoms, hyperthyroidism or follicular cytology. Serum TSH measurement, ultrasounds and fine needle aspiration cytology are the main diagnostic tools. Bilateral surgical exploration of the gland should be always carried out to assess the extension of the disease. Total or near total thyroidectomy in order to minimize the risk of recurrent nerve palsy and hypoparathyroidism represents the treatment of choice for bilateral goiter. Thyroid lobectomy with frozen section should be limited to unilateral nodular goiter.

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.

Complications in thyroid surgery for carcinoma: one institution's surgical experience.

BACKGROUND: The purpose of this study was to evaluate the factors influencing morbidity after total thyroidectomy for carcinoma, such as the histotype, the extension of surgery, the primary surgery versus reoperation, and the surgeon's experience. METHODS: We performed a retrospective analysis on inferior laryngeal nerve (ILN) injury and permanent hypoparathyroidism (HPT) rates in 504 consecutive patients with thyroid carcinoma who were operated on by the same surgeon from 1999 to 2006. The following parameters were assessed at univariate analysis: histotype, total thyroidectomy with or without central node dissection (level VI), primary surgery versus reoperation, and early (group 1: 1999-2002, 143 patients) and late (group 2: 2003-2006, 361 patients) experience. RESULTS: The global incidence rates of ILN palsy and permanent HPT were 2.18% and 6.3%, respectively. The incidence of ILN damage after total thyroidectomy plus node dissection versus total thyroidectomy without node excision was 2.87% vs. 0.36% (p = 0.029). The incidence of permanent HPT in group 1 was 13.2% vs. 3.6% in group 2 (p = 0.0001). Moreover, the incidence rate of ILN palsy resulted higher in group 1 (2.8%) and in reoperation (3.4%), while the permanent HPT resulted higher in thyroidectomy with node dissection (6.8%) and reoperation (6.9%), although the difference was not significant. CONCLUSIONS: The complications after total thyroidectomy were progressively reduced as a result of a more accurate technique. Nevertheless, our study showed that the incidence of complications is mostly related to the dissection of central lymph node (level VI) and the surgeon's experience.

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.

Contribution of SLN investigation with 99mTc-nanocolloid in clinical staging of thyroid cancer: technical feasibility.

PURPOSE: It is a matter of controversy whether prophylactic lymph node dissection improves prognosis and survival in papillary thyroid carcinoma (PTC) patients without suspicion of lymph node metastases either clinically or on ultrasonography. It is possible that in such patients the use of lymphatic mapping and sentinel lymph node (SLN) biopsy, as are employed for other tumours, will be of assistance. The aim of this study was to evaluate the feasibility of preoperative 99mTc-nanocolloid lymphoscintigraphy and an intra-operative SLN procedure in the management of PTC patients. METHODS: Twenty-five consecutive patients were entered in the study between April 2005 and October 2005. All had a preoperative diagnosis of malignancy obtained by fine-needle aspiration cytology (FNAC), without clinical or ultrasonographic evidence of loco-regional lymph node involvement. Patients underwent preoperative lymphoscintigraphy after the injection of 99mTc-nanocolloid [median 6 MBq (range 4-9 MBq) in 0.1-0.2 ml saline injected intratumorally under ultrasound guidance] and an intra-operative SLN procedure using a hand-held gamma probe. Surgery was performed by the same surgeon in all patients. RESULTS: Preoperative lymphoscintigraphy identified at least one SLN in all patients. During surgery, using the gamma probe, the surgeon was able to find at least one SLN in all cases. A good correlation was found between preoperative imaging and probe results. Metastasis was found in at least one SLN in 12 (48%) patients. In seven (28%) patients the involved SLN was the most radioactive SLN, while in five (20%) patients a less radioactive SLN was involved by malignancy. Ten of these 12 patients had only micrometastases (<2 mm). Micrometastases were found in the most radioactive SLN in six cases and in less radioactive SLNs in four cases, while in two patients more lymph nodes visualised at lymphoscintigraphy ipsilateral to the primary tumour were sites of metastasis. CONCLUSION: The rate of nodal involvement was very high in our series: in 48% of patients at least one metastatic lymph node was found. From a technical point of view the intra-operative SLN procedure in PTC patients was easy to perform, without major intra-operative complications. Our promising preliminary experience needs to be confirmed in larger series of patients series with longer follow-up.

Radio-guided surgery for non-131I-avid thyroid cancer.

OBJECTIVE: In this paper we report in a larger series the use of radio-probe-guided surgery (RGS) in nonradioiodine avid, well-differentiated thyroid cancer (DTC). DESIGN: Thirty-seven patients with locoregional recurrent, nonradioiodine avid DTC were studied with (99m)Tc-sestamibi directed RGS using a handheld gamma probe as an intraoperative detector. OUTCOME: Twenty-three women and 14 men were followed after RGS for 35.4 +/- 12.5 months (range 9-57). There were 33 papillary (one "tall" cell variant), 2 follicular, and 2 Hürthle cell cancers. In 7 patients, thyroid cancer recurred in the neck while cervical lymph node metastases were found in 31 patients (one patient had papillary cancer in both the thyroid bed and cervical lymph nodes). Sixty-six discrete nodules ranging from 6 to 45mm (mean tumor diameter, 18.4 +/- 8.5mm) were identified by both high-resolution ultrasound and (99m)Tc-sestamibi probe-guided RGS. After RGS, Tg (thyroglobulin) fell in 33 of 37 patients and mean target=nontarget sestamibi uptake ratios decreased in all 37 patients ( p < 0.0001). CONCLUSION: These data confirm our earlier observations that a (99m)Tc-sestamibi intraoperative gamma probe can be used to identify and guide resection of recurrent tumor and involved lymph nodes in locoregional metastases of nonradioiodine-avid thyroid cancer.

Radioguided surgery of parathyroid adenomas and recurrent thyroid cancer using the "low sestamibi dose" protocol.

PURPOSE: The aim of this study was to establish the clinical efficacy of the "low sestamibi dose" (LSD) protocol to perform thyroid and parathyroid radioguided surgery in a large series of patients homogeneously studied and operated on by the same surgeon. The LSD protocol was initially developed in our center to cure primary hyperparathyroid (PHPT) patients with a high likelihood of a solitary parathyroid adenoma (PA) by minimally invasive radioguided surgery (MIRS). Since then, the same protocol has been applied to differentiated thyroid cancer (DTC) patients with 131I-negative, but sestamibi-positive, locoregional recurrent disease in order to obtain radical radioguided extirpation of tumoral lesions at reoperation. STUDY DESIGN: We reviewed the clinical charts of 453 consecutive patients referred at the surgical department at Padova University (Padova, Italy) to investigate a PHPT or a DTC recurrence: 336 patients (74.2%) met the inclusion criteria for radioguided surgery, and these patients were analyzed for the aim of this study. There were 298 patients affected by PHPT with a high likelihood of a solitary sestamibipositive PA and 38 DTC patients affected by 131I-negative, but sestamibi-positive, locoregional recurrence. All patients underwent a preoperative imaging work-up, including sestamibi scintigraphy (doubletracer subtraction scan in PHPT patients and single-tracer, wash-out scan in DTC patients) and high-resolution neck ultrasonography (US). The LSD protocol we developed consists of the intravenous injection of a very low (1 mCi) sestamibi dose in the operating theater just 10 minutes before commencing intervention for the purpose of radioguided surgery only. At variance with the traditional "high (20-25 mCi) sestamibi dose (HSD)" protocol in which imaging and radioguided surgery are obtained in the same day, in the LSD protocol, imaging and radioguided surgery are performed in different days. The LSD protocol allows some advantages over the HSD protocol: (1) more time for acquiring and interpreting preoperative imaging (planar scintigraphy, single-photon emission computed tomography [SPECT], US); (2) an accurate selection of patients to whom MIRS is offered, especially in countries where the prevalence of nodular goiter with sestamibi-avid thyroid nodules (exclusion criteria for MIRS) is relatively high, as in mid-south-European countries; (3) it facilitates the work planning in the operating theater (bilateral neck exploration requires an operating time of at least double to that of MIRS); and (4) the radiation exposure dose to operating theater personnel is very low-substantially negligible, using the LSD protocol: This aspect assumes great importance in countries where radioproteximetric rules are stringent, as in Europe. RESULTS: PHPT patients. MIRS was successfully performed by a 1.5-2-cm skin incision in 287 of 298 PHPT patients (96.3%) in whom such an approach was scheduled on the basis of preoperative imaging, including 41 of 57 patients (71.9%) who had previously received thyroid or unsuccessful parathyroid surgery in another center. No case of major intraoperative complication was recorded. No case of persistent or recurrent PHPT was observed during postsurgical follow-up. DTC patients. A total of 79 metastatic lesions were intraoperatively detected by the gamma probe and successfully removed (68 of them had been correctly visualized at preoperative sestamibi scintigraphy). During subsequent follow-up, 18 patients (72%) were considered disease-free, whereas 7 had persistent disease (increased serum thyroglobulin levels). The radiation exposure dose to the surgeon using the LSD protocol was 1.2 uSi/hour, that is, 20-30-fold lower than that delivered with the HSD protocol used for PHPT patients and with the 131I protocol used for DTC patients with recurrence. CONCLUSIONS: On the basis of our data, it can be concluded that the LSD protocol is a safe and effective protocol to perform in both MIRS in PHPT patients and radioguided reoperation in DTC patients with 131I-negative recurrence. Furthermore, from a radioproteximetric point of view, in comparison with other radioguided protocols used for the same purposes, the LSD protocol minimizes the radiation-exposure dose to the surgeon and operating theater personnel.