Long-Term Outcomes of Parathyroidectomy in Hyperparathyroidism-Jaw Tumor Syndrome: Analysis of Five Families with CDC73 Mutations.

BACKGROUND: Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare disease caused by CDC73 germline mutations, with familial primary hyperparathyroidism (pHPT), ossifying jaw tumors, genito-urinary neoplasms. The present study was aimed at determining the long-term postoperative outcome of parathyroidectomy in HPT-JT. METHODS: A retrospective analysis of a single-center series of 20 patients from five unrelated HPT-JT families undergoing parathyroid surgery was performed. RESULTS: Pathology confirmed a single-gland involvement in 95% of cases at onset. Parathyroid carcinoma occurred in three patients undergoing en-bloc parathyroidectomy and thyroid lobectomy: parathyroid benign lesions in 17 patients undergoing subtotal parathyroidectomy for evident multiglandular involvement (n = 1) or selective parathyroidectomy for single-gland involvement (n = 16), during bilateral (n = 13) or targeted unilateral neck exploration (n = 7). At a median overall follow-up of 16 years (range 2.5-42), patients with parathyroid carcinoma had a persistent/recurrent disease in 66.6%; patients with benign lesions had recurrent pHPT in 23.5% after a prolonged disease-free period; recurrent benign pHPT occurred slightly more often in cases of discordant preoperative localization (60% vs 9%; p = 0.06). CONCLUSION: pHPT in HPT-JT is generally characterized by a benign and single-gland involvement, with a relatively increased risk of malignancy (15%). Parathyroid carcinoma needs extensive surgery because of high risk of permanent/recurrent disease (66.6%). In benign involvement, targeted unilateral exploration with selective parathyroidectomy may be effective in cases of concordant single-gland localization at preoperative localization imaging techniques. Bilateral neck exploration with subtotal parathyroidectomy might be preferred in cases of negative or discordant preoperative localization, because of the increased risk of multiglandular involvement and long-term recurrences (23.5%).

Mini-invasive videoassisted thyroid lobectomy for neonatal hyperfunctioning adenoma related to a somatic TSHr gene mutation.

We report here a case of a paediatric hyperthyroidism due to a micro-macro-follicular thyroid adenoma in the presence of heterozygous point mutation of TSH receptor (TSHr). We describe the case from the initial diagnosis, through laboratoristic examinations and imaging techniques, until the radical surgical treatment made by a mini-cervicotomic videoassisted technique. We also explained the genetic work-up from peripheral blood and thyroid adenoma tissue.

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.

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.

[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.

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.

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.

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.

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.

Incisional hernia treatment with progressive pneumoperitoneum and retromuscular prosthetic hernioplasty.

BACKGROUND AND AIM: Major incisional hernias of the abdominal wall often pose a serious surgical problem. The choice between simple suture repair and mesh repair remains uncertain. METHODS: Seventy-seven patients underwent surgery to repair large abdominal incisional hernias, i.e., with parietal defects of 10 cm or more, by retromuscular prosthetic hernioplasty between 1996 and 1999. All patients were treated preoperatively by progressive pneumoperitoneum and were followed up for 2-5 years (mean 38.3 months). RESULTS: Almost all patients tolerated the pneumoperitoneum; no postoperative death occurred. Six patients developed a subcutaneous infection but none of them required removal of the mesh. Two patients (2.6%) had recurrent incisional hernia. CONCLUSIONS: This study shows that pneumoperitoneum is useful in preparing patients for incisional hernioplasty. Retromuscular mesh repair represents an appropriate surgical procedure, particularly in view of its low rate of recurrence.

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.

(99m)Tc-MIBI radio-guided surgery for recurrent thyroid carcinoma: technical feasibility and procedure, and preliminary clinical results.

The preliminary results of technetium-99m methoxyisobutylisonitrile (MIBI) radio-guided surgery (RGS) in patients with differentiated thyroid carcinoma (DTC) and iodine-131-negative (non-functioning) recurrent disease are reported. Eight consecutive DTC patients were selected for RGS on the basis of pre-operative imaging findings: a (99m)Tc-MIBI scan consistent with local recurrence was taken as the principal inclusion criterion. The RGS procedure that we developed consisted in the injection of a low dose of (99m)Tc-MIBI (37 MBq) in the operating theatre a few minutes before the beginning of the intervention, with use of a hand-held gamma probe for the intra-operative detection of (99m)Tc-MIBI-avid tumoural foci. Radioactivity was measured in tumoural foci both in vivo and ex vivo, in the background and in the tumoural bed after lesion extirpation. After follow-up for 2-10 months, stable normalisation of serum thyroglobulin (Tg) levels was observed in six out of the seven patients in whom, during the intervention, the gamma probe-detected radioactivity in the neck fell to background values after tumour extirpation. In another patient the persistence of high radioactivity levels in the tumoural bed after lesion removal correctly suggested disease persistence (deep tracheal infiltration). These preliminary data suggest the feasibility of RGS in DTC patients with locoregional non-functioning but (99m)Tc-MIBI-avid recurrence by injection of a low, 37 MBq dose of (99m)Tc-MIBI just before the beginning of the intervention.