Antonio Toniato

Surgical Versus Conservative Management for Subclinical Cushing Syndrome in Adrenal Incidentalomas: A Prospective Randomized Study

Objective:To compare the clinical outcome of patients with subclinical Cushing syndrome (SCS) due to an adrenal incidentaloma (the autonomous hypersecretion of a small amount of cortisol, which is not enough to cause clinically-evident disease) who underwent surgery or were managed conservatively. Summary Background Data:The most appropriate management of SCS patients is controversial, either adrenalectomy or close follow-up being recommended for their treatment. Methods:Over a 15-year period, 45 SCS patients were randomly selected to undergo surgery (n = 23) or conservative management (n = 22). All surgical procedures were laparoscopic adrenalectomies performed by the same surgeon. All patients were followed up (mean, 7.7 years; range, 2–17 years) clinically by 2 experienced endocrinologists 6 and 12 months after surgery and then yearly, or yearly after joining the trial, particularly monitoring diabetes mellitus (DM), arterial hypertension, hyperlipidemia, obesity, and osteoporosis. The study end point was the clinical outcome of SCS patients who underwent adrenalectomy versus those managed conservatively. Results:All 23 patients in the surgical arm had elective surgery. Another 3 patients randomly assigned to conservative management crossed over to the surgical group due to an increasing adrenal mass >3.5 cm. In the surgical group, DM normalized or improved in 62.5% of patients (5 of 8), hypertension in 67% (12 of 18), hyperlipidemia in 37.5% (3 of 8), and obesity in 50% (3 of 6). No changes in bone parameters were seen after surgery in SCS patients with osteoporosis. On the other hand, some worsening of DM, hypertension, and hyperlipidemia was noted in conservatively-managed patients. Conclusions:Based on the results of this study, laparoscopic adrenalectomy performed by skilled surgeons appears more beneficial than conservative management for SCS patients complying with our selection criteria. This trial is registered with Australian Clinical Trials Registry number, ANZCTR12608000567325.

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.

Zuckerkandl’s tuberculum: an arrow pointing to the recurrent laryngeal nerve (constant anatomical landmark)

A better knowledge of thyroid gland anatomy and embryology has made surgical management of thyroid disorders safer, particularly by decreasing the occurrence of injury to the recurrent laryngeal nerves. Although the best method for protecting these nerves during thyroidectomy is controversial, the most experienced surgeons agree about the need for their routine exposure. Recently, we have been considering Zuckerkandl’s tuberculum as an anatomic landmark for tracing the nerve during thyroidectomy, because of the constant relationship (demonstrated in specific contributions of embryology) between the tuberculum and the termination of the recurrent nerve before it enters the larynx. Our technique of thyroidectomy approaches the recurrent laryngeal nerve from Zuckerkandl’s tubercle if present; we report our criteria for determining whether Zuckerkandl’s tuberculum was there or not, and its relative size in a series of 104 consecutive thyroid lobectomies.

Carotid endarterectomy with patch closure versus carotid eversion endarterectomy and reimplantation: A prospective randomized study

BACKGROUND Although carotid eversion endarterectomy (CEE) has obtained consensus providing excellent early and late results, conventional carotid endarterectomy (CEA) with or without patching continues to be considered the gold standard surgical procedure. The few studies published to date comparing CEE with CEA in a small series of patients have failed to show substantial advantages of one technique over the other, and further randomized comparative studies are still required. The purpose of this study was to compare the outcome of CEA with routine patch closure (CEAP) with that of CEE and reimplantation (CEER) of the internal carotid artery in the common carotid artery. METHODS Three hundred thirty-six primary CEAs performed in 310 patients were randomized into 2 groups, 167 CEAPs and 169 CEERs. Surviving patients underwent duplex ultrasound scan control at 30 days, 6 months, 12 months, and every postoperative year thereafter. The mean follow-up was 34 months (range, 1 to 69 months). Demographic characteristics, risk factors, associated diseases, and indications for surgery were comparable in the 2 groups. RESULTS Although the rate of intraoperative electroencephalogram changes was comparable in the 2 groups, the incidence of shunting was statistically higher in the CEAP group (28.1% vs 1.2%, P < .00001). The carotid cross-clamping time was significantly lower in the CEER group (P = .01). Although all deaths were in the CEAP group, the overall perioperative death and stroke-related death rates were comparable in the 2 groups. The perioperative stroke rate was statistically higher in the CEAP group (2.9% vs 0%, P = .03). Although the recurrent stenosis rate was comparable in the 2 groups (1.2% vs 0%), the CEAP group had a statistically higher rate of combined recurrent stenoses and occlusions (4.9% vs 0%, P = .003). The late mortality rate was similar in both groups. CONCLUSIONS Although the outcome of CEAP in this series is consistent with that of the main reported trials, the CEER procedure is less likely than CEAP to cause perioperative stroke and death and seems superior in reducing the incidence of recurrent stenosis and late occlusive events.

Laparoscopic versus open approach for solitary insulinoma

BackgroundIn recent years, advances in laparoscopic techniques have allowed surgeons to treat pancreatic lesions laparoscopically. Insulinoma, the most prevalent pancreatic endocrine tumor, is mostly benign and curable with surgical resection. This study aimed to assess the results from laparoscopic resection (LG) of insulinomas and to compare them with the results from open surgery (OG).MethodsFrom September 1999 to December 2005, 56 laparoscopic pancreatic resections were performed for selected patients, including 12 laparoscopic resections of insulinomas. The results were compared with those of patients who underwent open resection of insulinomas selected from the authors’ pancreatic database.ResultsThree conversions to the open approach were required because of inability to identify the tumor. There were no deaths in either group, and the morbidity rates were 25% (3/12) for LG and 55% (5/9) for OG (nonsignificant difference). The pancreatic fistula rate after laparoscopic enucleation was statistically lower than after open enucleation (14% vs 100%; p = 0.015). The mean postoperative hospital stay was 13 ± 5.9 days for LG and 17.6 ± 7.5 days for OG (nonsignificant difference). After exclusion of the patients who underwent conversion to laparotomy, the mean postoperative hospital stay was 11.5 ± 5.8 days for LG and 17.6 ± 7.5 days for OG (p = 0.04).ConclusionThis study demonstrates the feasibility and safety of laparoscopic resection of insulinomas. The laparoscopic approach was associated with a decrease in hospital stay and pancreatic fistula after enucleation. Preoperative localization tests and laparoscopic ultrasonography seem necessary to prevent conversion.

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.

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

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

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.

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

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

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

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