M.R. Pelizzo

Dual PET/CT with 18F-DOPA and 18F-FDG in metastatic medullary thyroid carcinoma and rapidly increasing calcitonin levels: Comparison with conventional imaging

BACKGROUND To evaluate the role of a multi-imaging PET with (18)F-DOPA and (18)F-FDG in comparison with conventional imaging (CI) in recurrent medullary thyroid carcinoma (MTC). METHODS 18 MTC patients who had thyroidectomy were included; they presented with elevated and rapidly increasing calcitonin levels during follow up. CI had revealed metastatic deposits in 9 patients. Patients were referred to us for a PET/CT with (18)F-DOPA and (18)F-FDG. Histologic/cytologic confirmation of recurrent MTC was obtained in at least one PET-positive lesion in all patients. RESULTS Foci of abnormal uptake were observed in 15 patients at (18)F-DOPA and in 11 at (18)F-FDG; 8 patients showed the same number of positive lesions with both tracers, 2 showed more lesions on (18)F-FDG, 1 was positive at (18)F-FDG alone and 5 at (18)F-DOPA alone. In 3 patients with a DOPA-positive loco-regional relapse a re-operation with curative intent was offered. SUV(max) values were higher for (18)F-FDG compared to (18)F-DOPA (mean 12.7+/-4.1 vs. 5.5+/-2.1, p<0.05). Calcitonin was higher in PET-positive patients compared to PET negative ones, while no significant differences were observed between (18)F-DOPA and (18)F-FDG positive patients. CONCLUSIONS In MTC patients with rapidly increasing calcitonin levels during follow up, (18)F-DOPA has a good sensitivity and a complementary role with (18)F-FDG PET/CT in detecting metastatic deposits. In our experience, the sensitivity of a multi-imaging (18)F-DOPA &(18)F-FDG PET/CT approach is greater than that obtained with CI. The higher SUV(max) values found with (18)F-FDG in some patients may reflect more aggressive tumors.

Laparoscopic treatment of benign insulinomas localized in the body and tail of the pancreas: a single-center experience

BackgroundThe increasingly widespread use of minimally invasive surgery has allowed surgeons to exploit this approach for complex procedures, such as pancreatic resections, though its actual role outside simple operations remains debated.MethodsThis is a study of 12 consecutive patients, 5 men and 7 women, with pancreatic insulinoma who were treated at our institution from 2000 to September 2005. All patients presented with typical symptoms and laboratory findings of hyperinsulinism and were good candidates for laparoscopic surgery. Preoperative diagnostic work-up, operating time, postoperative complication rate, length of hospital stayd and clinical outcome were assessed.ResultsSuccessful laparoscopic resection was performed in 11 out of 12 patients: 4 had tumor enucleation, and 7 had distal pancreatectomy; among these latter 5 had spleen-preserving distal pancreatectomy. In 1 case conversion to open surgery was necessary. Mean operative time was 170 minutes. The median tumor size was 18 mm, and all the insulinomas were benign. Four complications were observed in this group, and the median hospital stay was 8 days.ConclusionsThe laparoscopic approach proved to be feasible and safe, although the average operative time was longer and demanded good surgical skills as well as precise localization of the tumor and definition of its nature. Tumors located in the body or tail of the pancreas that are benign in nature can better benefit of laparoscopic approach.

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.

Ectopic parathyroid adenomas located at the carotid bifurcation: the role of preoperative Tc-99m MIBI scintigraphy and the intraoperative gamma probe procedure in surgical treatment planning.

Purpose The prevalence of ectopic parathyroid adenoma (PA) is relatively low, despite some studies in which it has been reported to be as high as 20%. Ectopic PA is a frequent cause of surgical failure, and therefore some authors recommend preoperative imaging to localize the condition in patients with primary hyperparathyroid (HPT) disease before initial surgery. Methods Two unusual cases of primary HPT caused by an ectopic PA located at the carotid bifurcation are reported. The patients were examined before operation using Tc-99m MIBI scintigraphy and then underwent radioguided surgery using the intraoperative gamma probe technique with injection of a low dose (37 MBq; 1 mCi) of Tc-99m MIBI. Results The first patient had a history of primary HPT and coexisting multinodular goiter. She had undergone total thyroidectomy in another center, but no enlarged parathyroid gland was found at bilateral neck exploration and serum calcium and parathyroid hormone levels remained elevated after intervention. The patient was referred to our center. A Tc-99m MIBI scan showed a focus of abnormal tracer uptake in the superior left laterocervical region that was thought to be a PA. The next day she underwent radioguided surgery and an 18-mm PA located at the left carotid bifurcation was easily removed through a 2.5-cm skin incision. The second patient was examined in our center before surgery. A neck ultrasound showed a multinodular goiter but no enlarged parathyroid glands. A pertechnectate–MIBI subtraction scan revealed a focus of abnormal Tc-99m MIBI uptake in the right superior laterocervical region that was thought to be a PA. One week later, at radioguided surgery, a 25-mm PA was identified at the right carotid bifurcation and removed successfully. Conclusions These data strongly support the utility of preoperative imaging with Tc-99m MIBI in patients with primary HPT before initial neck exploration with the aim of avoiding surgical failure. Furthermore, the intraoperative gamma probe technique seems to be useful to reduce surgical trauma and, possibly, complications in patients with ectopic PA.

The role of BRAF(V600E) mutation as poor prognostic factor for the outcome of patients with intrathyroid papillary thyroid carcinoma.

BACKGROUND BRAF(V600E) mutation, which represents the most frequent genetic mutation in papillary thyroid carcinoma (PTC), is widely considered to have an adverse outcome on PTC outcome, however its real predictive value is not still well stated. The aim of the present study was to evaluate if BRAF(V600E) mutation could be useful to identify within patients with intrathyroid ultrasound-N0 PTC those who require more aggressive treatment, by central neck node dissection (CLND) or subsequent postoperative (131)I treatment. METHODS Among the whole series of 931 consecutive PTC patients operated on at 2nd Clinical Surgery of University of Padova and at General Surgery Department of University of Trieste during a period from January 2007 to December 2012, we selected 226 patients with an intrathyroid tumor and no metastases (preoperative staging T1-T2, N0, M0). BRAF(V600E) mutation was evaluated by PCR-single-strand conformation polymorphism analysis and direct genomic sequencing. We analyzed the correlation between the presence/absence of the BRAF(V600E) mutation in the fine-needle aspiration (FNA) and the clinical-pathological features: age, gender, extension of surgery, node dissection, rate of cervical lymph node involvement, tumor size, TNM stage, variant of histotype, mono/plurifocality, association with lymphocitary chronic thyroiditis, radioactive iodine ablation doses, and outcome. RESULTS The BRAF(V600E) mutation was present in 104 of 226 PTC patients (47.8%). BRAF(V600E) mutation correlated with multifocality, more aggressive variants, infiltration of the tumoral capsule, and greater tumors diameter. BRAF(V600E) mutation was the only poor prognostic factor in these patients. DISCUSSION In our series, BRAF(V600E) mutation demonstrated to be an adverse prognostic factor indicating aggressiveness of disease and it could be useful in the management of low-risk PTC patients, as supplementary prognostic factor to assess the preoperative risk stratification with the aim to avoid unnecessary central neck node dissection (BRAF pos.) or to perform complementary (131)I-therapy (BFAF neg.).

PDCD4 expression in thyroid neoplasia

Both the morphogenesis and the molecular pathways of thyroid cancers are controversial. Programmed cell death 4 (PDCD4) is a tumor suppressor gene whose expression is controlled by miR-21. By applying immunohistochemistry for PDCD4 and both quantitative real-time PCR (qRT-PCR) and in situ hybridization for miR-21, this study explored PDCD4 expression in human follicular-cell-derived thyroid neoplastic lesions. PDCD4 protein expression was semiquantitatively assessed in 100 consecutive thyroid tumors (25 follicular adenomas (FA), 25 follicular carcinomas (FC), 25 papillary carcinomas (PC), and 25 poorly-differentiated/anaplastic cancers (PD-AC)). Twenty-five additional nonneoplastic thyroid tissue samples were included as controls. To further support the data, miR-21 expression was tested (by qRT-PCR and in situ hybridization) in a different series of 75 cases (15 FAs, 15 FCs, 15 PCs, 15 PD-ACs, and 15 controls). Nonneoplastic thyrocytes consistently featured a strong nuclear PDCD4 expression, while the protein’s expression was significantly downregulated in neoplastic epithelia. PDCD4 downregulation was significantly associated with less well-differentiated cancer phenotypes (p < 0.001) and more advanced tumor stages (p < 0.001). Consistently with PDCD4 downregulation, miR-21 was upregulated in neoplastic by comparison with nonneoplastic tissue samples. The present results provide evidence of PDCD4 having a role in thyroid carcinogenesis; further studies should investigate the diagnostic value and the prognostic impact of PDCD4 in thyroid neoplasia.

Hypoglycemic Syndrome in a Patient with Proinsulin-Only Secreting Pancreatic Adenoma (Proinsulinoma)

We describe an unusual case of hypoglycemic syndrome in a 69-year old woman with a proinsulin-only secreting pancreatic endocrine adenoma. The clinical history was highly suggestive of an organic hypoglycemia, with normal or relatively low insulin concentrations and elevated proinsulin levels. Magnetic resonance and computed tomography of the abdomen showed a 1 cm pancreatic nodule and multiple accessory spleens. The diagnosis was confirmed by selective angiography, showing location and vascularization of the nodule, despite no response to intra-arterial calcium. After resection, the hypoglycemic syndrome resolved. The surgical specimen was comprised of a neuroendocrine adenomatous tissue with high proinsulin immunoreactivity. Study of this unusual case of proinsulinoma underlines (i) the need to assay proinsulin in patients with hypoglycemia and normal immunoreactive insulin, (ii) the differential diagnosis in the presence of accessory spleens, (iii) the unresponsiveness to intra-arterial calcium stimulation, and (iv) the extensive evaluation needed to reach a final diagnosis.

Réintervention pour carcinome médullaire de la thyroïde : résultats à long terme

Study aim: The impact of iterative surgery in medullary thyroid carcinoma is still debated. The study aim was to evaluate long-term results following reoperation for residual or recurrent medullary thyroid carcinoma. Patients and method: Among the 136 patients operated on in our centre for medullary thyroid carcinoma (MTC) between 1970 and 2000, 25 patients (10 men and 15 women) were reoperated on for locoregional residual or recurrent lesions. Their mean age was 46 years (range: 19–73 years). The MTC was sporadic in 21 patients and familial in 4: NEM 2A (n=3), NEM 2B (n=1). In 11 patients (44%) operated in another centre, the first procedure was a total thyroidectomy; in 2 patients (8%) a total thyroidectomy with central lymphadenectomy was performed, and in 12 patients (48%) a total thyroidectomy with central and jugulo-carotid lymphadenectomy. After the first operation, 6 patients (24%) were classified stage II, 15 (60%) stage III and 4 (16%) stage IV. Basal and post-stimulation calcitonin dosages were performed for all the patients before and after reoperation. Results: Thirty three reoperations were performed. In 24 cases, the recurrence was located in the laterocervical site; in 5 cases, the lymph node involvement was both central and laterocervical, in 2 cases, there was a mediastinal involvement and in 2 cases a spinal involvement. After reoperation, the calcitonin rate became normal in 4 patients (16%) ; in the other 21 (84%), the calcitonin rate was still high. With a mean 110 month- follow-up (range: 320–12 months), 4 patients (16%) were alive without disease, 2 (8%) died of their disease, 19 (76%) were alive with their disease, five of them with hypercalcitonemia without detectable metastasis. In addition to patients having metastasis at the time of reoperation, seven developed metastases secondarily (liver, bone, lung). Conclusion: Biological cure of medullary thyroid carcinoma is rarely obtained with reoperation. Reoperations may reduce progression of the disease in selected patients. Complete removal of the lesions at the time of the first procedure must be the ideal treatment for medullary thyroid carcinoma.

Does the ultrasound dissector improve parathyroid gland preservation during surgery

BACKGROUND The most common complication of thyroid surgery is hypoparathyroidism, usually temporary. Ischemic injury or parathyroid avulsion are the causes of surgical hypoparathyroidism. We assessed the value of an ultrasound scalpel, the Harmonic Focus(®) (HF), could prevent surgical-related hypoparathyroidism. METHODS Patients consecutively undergoing total thyroidectomy using the HF from November 2009 to February 2011 were recruited and their clinical characteristics, type of operation, histology, and postoperative calcium levels (normal range: 2.10-2.55 mMol/l) were recorded. The prevalence of transient and permanent hypocalcemia was calculated for benign vs. malignant diseases and compared with a control group of 147 patients treated surgically in 2005 using manual technique. RESULTS 139 patients treated by the same surgeon with a total thyroidectomy (41.7% for a malignant disease) were considered. Prevalence of transient hypoparathyroidism (THP) was 45.2% and of definitive hypoparathyroidism (DHP) 1.4%. None of the patients with malignancies were hypocalcemic at 1-year follow-up. In the control group THP was found in 51.7% of cases and DHP in 5.4% (p < 0.001). CONCLUSIONS Use of the ultrasound scalpel improved the likelihood of the parathyroid glands preservation during thyroid surgery. Paradoxically, the HF appears to be more effective in treating malignant disease, i.e. when central node dissection is required.

Role of Pituitary Tumour Transforming Gene 1 in Medullary Thyroid Carcinoma

Background: Pituitary tumour transforming gene 1 (PTTG1) is over-expressed in a variety of endocrine-related tumours. We aimed at evaluating PTTG1 expression and function in human neoplastic parafollicular C-cells, represented by medullary thyroid carcinoma (MTC) and C-cell hyperplasia (CCH) samples and by the TT cell line. Methods: TT cells and tissues derived from human CCH (8 samples) and MTC (12 samples) were analyzed by northern blot, furthermore TT cells were subjected to PTTG gene silencing and cells were analyzed for DNA synthesis. Results: PTTG1 expression was significantly higher (p < 0.01) in CCH (3-fold), in papillary thyroid cancer and in MTC (5-fold) than in normal thyroid, and in MTC lymph-node metastases as compared to primary lesions (~2-fold; p < 0.05). PTTG1 mRNA and protein correlated with tumour diameter and TNM status (p < 0.05). In TT cells, PTTG1 silencing did not completely block DNA synthesis, but significantly reduced [3H]Thymidine incorporation (~50%; p < 0.01) for up to 3 days. Conclusion: PTTG1 levels correlate with tumour aggressiveness. PTTG1 silencing causes reduced MTC cell proliferation, supporting the hypothesis that PTTG1 might have an important role in C-cell neoplastic proliferation.