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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Minimally invasive radio-guided parathyroidectomy.

We reported here the data on minimally invasive radio-guided parathyroidectomy (MIRP) in a large group of 253 patients enrolled from the whole series of 355 consecutive patients affected by primary hyperparathyroidism (P-HPT) referred to our center. On the basis of preoperative imaging including Sestamibi scintigraphy and neck ultrasound (US), 263 patients (74% of the whole series) with evidence of a solitary parathyroid adenoma (PA) and a normal thyroid gland were addressed to MIRP and in 253 (96%) of them this minimally invasive neck exploration was successfully performed. The MIRP protocol developed in our center consisted of a very low 1 mCi Sestamibi injection in the operating room a few minutes before the start of intervention, thus minimizing the radiation exposure dose to the patient and personnel. No major intraoperative complication was recorded in patients treated by MIRP and only a transient hypocalcemia in 8.5% of cases. The mean duration time for MIRP was 35 min and the mean hospital stay 1.2 days. Local anesthesia was also performed in 62 patients, 54 of whom were elderly patients with concomitant invalidating diseases contraindicating general anesthesia. No HPT relapse was observed during subsequent follow-up. The gamma probe was used also during bilateral neck exploration in the group of 92 patients excluded from MIRP. The most frequent cause of exclusion from MIRP in our series was the presence of concomitant Sestamibi avid thyroid nodules (68.5% of cases) that can give false positive results at radio-guided surgery. In conclusion, MIRP is an effective treatment in patients with a high likelihood of a solitary PA and a normal thyroid gland at scintigraphy and US so that an accurate preoperative localizing imaging is required for MIRP. A low 1 mCi Sestamibi dose appears sufficient to perform MIRP. Patients with concomitant Sestamibi avid thyroid nodules should be excluded from MIRP.

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.

Radioguided surgery of primary hyperparathyroidism using the low-dose 99mTc-sestamibi protocol: multiinstitutional experience from the Italian Study Group on Radioguided Surgery and Immunoscintigraphy (GISCRIS).

UNLABELLED: This study evaluated the accuracy of (99m)Tc-sestamibi scintigraphy and neck ultrasonography in patients with primary hyperparathyroidism (PHPT) and the role of intraoperative hand-held gamma-probes in minimally invasive radioguided surgery (MIRS) of patients with a high likelihood of a solitary parathyroid adenoma (PA). The study was undertaken under the aegis of the Italian Study Group on Radioguided Surgery and Immunoscintigraphy (GISCRIS). METHODS: Clinical records were reviewed for 384 consecutive PHPT patients undergoing radioguided surgery using a low dose of (99m)Tc-sestamibi. Selection of patients for MIRS instead of traditional bilateral neck exploration was based on preoperative imaging indicating a solitary PA. (99m)Tc-Sestamibi (37-110 MBq, or 1-3 mCi) was injected in the operating theater 10-30 min before the start of the intervention. Either 11-mm collimated (309 patients) or 14-mm collimated (75 patients) gamma-probes were used. Intraoperative quick parathyroid hormone (IQPTH) assay was used on 308 patients (80.2%). RESULTS: MIRS was successfully performed on 268 (96.8%) of 277 patients. Conversion to bilateral neck exploration was necessary in 9 patients (3.3%) because of either persistently high IQPTH levels after removal of the preoperatively visualized PA (4 patients), intraoperative frozen-section diagnosis of parathyroid carcinoma (2 patients), or hard-to-remove PA (3 patients). MIRS, which was performed under locoregional anesthesia in 72 patients, required a mean operating time of 37 min and a mean hospital stay of 1.2 d. MIRS was successfully performed also on 32 (78.0%) of 41 patients who had previously undergone thyroid or parathyroid surgery. No major surgical complications were observed in the MIRS group, and there were only 24 cases (11%) of transient postoperative hypocalcemia. The probe was of little help in patients with concomitant (99m)Tc-sestamibi-avid thyroid nodules and not helpful at all in patients with negative scan findings preoperatively. IQPTH measurement helped to disclose some cases of multigland parathyroid disease. CONCLUSION: (99m)Tc-Sestamibi scintigraphy, especially if combined with neck ultrasonography, is highly accurate in selecting PHPT candidates for MIRS. The low-dose (99m)Tc-sestamibi protocol (which entails a low-to-negligible radiation exposure to the surgical team) is safe and effective for MIRS. MIRS plays a limited role in patients with concomitant (99m)Tc-sestamibi-avid thyroid nodules and should be discouraged in patients with negative (99m)Tc-sestamibi finding preoperatively. IQPTH can be recommended during MIRS to facilitate intraoperative identification of previously undiagnosed multigland parathyroid disease.

Locally advanced differentiated thyroid carcinoma: a 35-year mono-institutional experience in 280 patients.

AIM: Debate exists in the literature about the optimal treatment to be adopted in patients with locally advanced differentiated thyroid carcinoma. We aimed to better define the most appropriate diagnostic and therapeutic protocol for this type of tumour. METHODS: The clinical and histopathological records of 280 consecutive patients with locally advanced differentiated thyroid carcinoma, studied and operated on by the same surgical team in the period between 1967 and 2002, were reviewed. RESULTS: With regard to overall survival, at univariate statistical analysis, the patient's age at diagnosis (threshold, 45 years), primary tumour size, local cancer extension at diagnosis (subtypes of T4), extent of thyroidectomy, performance of lymph node dissection and performance of post-surgical external radiotherapy were found to be significant prognostic variables. With regard to the appearance of recurrent disease during follow-up, at univariate statistical analysis, the patient's age at initial diagnosis (threshold, 45 years), primary tumour size, local cancer extension at diagnosis (subtypes of T4), extent of thyroidectomy, performance of lymph node dissection, presence of metastatic lymph nodes, performance of post-surgical 131I therapy and performance of post-surgical external radiotherapy were found to be significant prognostic variables. At multivariate statistical analysis, the patient's age at initial diagnosis, extent of tumour, extent of thyroidectomy and performance of lymph node dissection were the only independent prognostic variables. CONCLUSIONS: In our experience, an aggressive surgical approach at first diagnosis appears to offer a better prognosis in terms of both overall survival and disease-free time interval in patients with locally advanced differentiated thyroid carcinoma, especially those over 45 years of age.

Role of gamma probes in performing minimally invasive parathyroidectomy in patients with primary hyperparathyroidism: optimization of preoperative and intraoperative procedures.

OBJECTIVE: In the last decade, surgery of primary hyperparathyroidism (HPT) due to a solitary adenoma has moved on from the traditional wide bilateral neck exploration (BNE) to more limited approaches such as unilateral neck exploration and minimally invasive parathyroidectomy. DESIGN: To define the role of intraoperative gamma probe and injection of a low (99m)Tc-MIBI dose in performing minimally invasive radio-guided surgery (MIRS) in HPT patients with a solitary parathyroid adenoma. METHODS: From September 1999 to July 2002, 214 patients with primary HPT entered the study. All patients were preoperatively investigated by a (99m)Tc-pertechnetate/MIBI subtraction scan and high-resolution neck ultrasound. The intraoperative technique we developed differs from other previously described techniques being based on the injection of a low (37 MBq) MIBI dose in the operating theatre a few minutes before the beginning of intervention. RESULTS: On the basis of scan/ultrasound findings 147 patients were selected for a MIRS and 144 of them (98%) were successfully treated by this approach: a solitary parathyroid adenoma was removed through a small 2-2.5 cm skin incision with a mean operative time of 35 min, and a mean hospital stay of 1.2 days. In the other 67 patients with scan/ultrasound evidence of concomitant nodular goiter (n=45) or multi-gland disease (n=13) or with a negative scan (n=9), the gamma probe was utilized during a traditional BNE. A low 37 MBq MIBI dose proved to be sufficient to perform a MIRS; moreover it delivered to the patient and surgeon a low, negligible, radiation exposure dose. CONCLUSIONS: The combination of a (99m)Tc-pertechnetate/MIBI subtraction scan and neck ultrasound appears to be an accurate imaging protocol in selecting primary HPT patients as candidates for a MIRS. A MIBI dose as low as 37 MBq injected in the operating theatre just before the start of surgery appears to be adequate to perform radio-guided surgery.

Natural history, diagnosis, treatment and outcome of papillary thyroid microcarcinoma (PTMC): a mono-institutional 12-year experience.

The clinical and histopathological records of 149 consecutive patients with papillary thyroid microcarcinoma (PTMC), homogeneously studied and operated on by the same surgeon in the period 1990 to 2001, were reviewed. After a mean 6.5-year follow-up, three cases of loco-regional recurrence (2%) were observed. These three patients had all undergone partial thyroidectomy only and tumour relapse occurred in the residual thyroid tissue. No recurrence was observed in patients treated by total thyroidectomy and I. At variance with other reported series, no lymph node recurrence was observed in our series, in particular in the group of 23 patients with evidence of nodal metastases at initial diagnosis (three of whom were revealed by I scan after surgery). Therefore, a preventive effect of I treatment in our patient population can be hypothesized. However, prolonged follow-up will be necessary to clarify this. Due to the inability of current imaging modalities to select pre-operatively PTMC patients at risk for recurrence (presence of thyroid capsular invasion, multifocality and microscopic lymph node metastases), it appears reasonable to offer the patient total thyroidectomy when a pre-operative diagnosis of PTMC is reached. Moreover, the policy of our thyroid cancer centre is that, in these patients, post-surgical I scan should be obtained in order to detect unknown metastatic deposits, and I treatment should also be considered in patients with poor clinical and histopathological prognostic factors. In contrast, in patients operated on for benign thyroid disease and with delayed diagnosis of PTMC at definitive histopathological examination, re-operation might be avoided in the presence of unifocal disease without thyroid capsular invasion and with ultrasound-'normal' residual thyroid tissue. Close clinical and ultrasound follow-up is recommended, especially in patients who have undergone conservative surgery only.

Minimally invasive radioguided parathyroidectomy: an attractive therapeutic option for elderly patients with primary hyperparathyroidism.

BACKGROUND AND AIM: Surgery for primary hyperparathyroidism (PHPT) due to a solitary parathyroid adenoma (PA) is moving from traditional bilateral neck exploration (BNE) towards the use of limited neck exploration. The aim of the present study was to define the efficacy of minimally invasive radioguided surgery (MIRS) in PHPT patients with a high probability of a solitary PA with particular regard to benefits achievable in elderly patients. PATIENTS AND METHODS: The study population included a total of 266 consecutive PHPT patients who had undergone surgery at our centre between September 1999 and February 2003. Preoperative imaging consisted of [Tc]pertechnetate/Tc sestamibi (TcO4/sestamibi) scintigraphy and neck ultrasound obtained in the same session. One hundred and eighty-seven patients from the whole series (75 of whom were older than 65 years) with a high scan/ultrasound probability of a solitary PA, a high PA sestamibi uptake, and a normal thyroid gland were selected for MIRS. The other 79 patients were selected for traditional BNE. The intra-operative technique was based on the injection of a low dose (37 MBq) of sestamibi in the operating theatre a few minutes before the beginning of intervention and on the use of an 11 mm collimated gamma probe. RESULTS: MIRS was successfully performed in 97.8% of all PHPT patients selected for this type of surgery and, in particular, in 100% of the subgroup (n=75) of elderly patients. MIRS required a mean operating time of 35 min and a mean hospital stay of 1.2 days; that is, approximately half of that required for traditional BNE. Moreover, local anaesthesia was successfully performed in 27 patients, 19 of whom were >65 years with concomitant invalidating diseases contraindicating general anaesthesia. No major surgical complications were recorded. Transitory hypocalcaemia was observed in 9% of cases treated with MIRS compared with 27% of patients treated with BNE. CONCLUSION: MIRS can be accurately planned in elderly PHPT patients with a solitary PA on the basis of a TcO4/sestamibi scan and neck ultrasound. MIRS has been proven to be safe and effective in our experience, and allows a significant reduction of operating and recovery time, as well as the possibility of using local anaesthesia, especially in elderly patients with concomitant invalidating diseases.

Determinant role of Tc-99m MIBI SPECT in the localization of a retrotracheal parathyroid adenoma successfully treated by radioguided surgery.

PURPOSE: The authors' aim was to evaluate the role of MIBI SPECT acquired just after planar pertechnetate-MIBI (TcO(4)-MIBI) subtraction scintigraphy in planning radioguided surgery in a patient with persistent primary hyperparathyroidism after initial surgery performed to treat a retrotracheal parathyroid adenoma (PA). METHODS: A 73-year-old man with persistent primary hyperparathyroidism after a previous left parathyroidectomy and left thyroid lobectomy is described. The patient was examined in our center in a single-day preoperative imaging protocol based on findings of planar TcO(4)-MIBI subtraction scintigraphy, MIBI SPECT, high-resolution neck ultrasound, and computed tomography. RESULTS: Neck ultrasound did not reveal enlarged parathyroid glands. Findings of a neck-chest computed tomographic scan were also inconclusive. Instead, planar scintigraphy clearly depicted a single focus of MIBI uptake over the thyroid gland in a median position. The SPECT examination precisely localized a PA in the retrotracheal space. The day after imaging, the patient underwent unilateral left cervical surgical exploration. A 16 x 21 mm PA was easily detected using the gamma probe technique after injection of a low dose of 37 MBq (1 mCi) Tc-99m MIBI, and the PA was rapidly removed with limited surgical trauma. Rapid serum PTH and calcium levels normalized after intervention and remained in the normal range during subsequent follow-up. CONCLUSIONS: The current data indicate the importance of preoperative imaging with MIBI scintigraphy in patients with primary hyperparathyroidism and strongly support the utility of MIBI SPECT acquisition in PAs located deep in the neck and in ectopic sites. Furthermore, the gamma probe can help the surgeon to detect the PA during surgery and to minimize the surgical trauma in patients who have had previous thyroid or parathyroid surgery.