Surgical removal is recommended for recurrent thyroid carcinomas (RTCs) unable to uptake radioiodine and/or not responsive to chemotherapy. However, repeated neck dissection is difficult for surgeons. Thus, radiofrequency ablation (RFA) was proposed for RTCs. The aim of this prospective study is to assess RTC treatment response after RFA, according to well-established criteria.

Introduction: In 1997 a Minimally Invasive Video Assisted Technique for Parathyroidectomy (MIVAP) was developed in the University of Pisa. In this review we examine the last three years of MIVAP (240 cases) in order to identify the advantages and the limits of the procedure after the firstperiod development of the technique. Results: In our experience, 65% of patients affected by pri mary hyperparathyroidism (PHPT) turned out to be eligible for MIVAP. During the first years several selection criteria were strictly followed; more recently, some initially absolute contraindications to the operation have been interpreted more flexibly. Mean operative time is 35 minutes. 18 conversions (7.5%) to traditional open cervicotomy were needed and in 4 cases (1.6%) no affected parathyroid tissue was removed. Conclusions: At present, we consider absolutely necessary for MIVAP: preoperative localization of an adenoma with at least one imaging study (US or MIBI scintiscan) and the availability of QPTH intraoperative assay. No absolute con traindications other than the size of the lesions and the suspect of parathyroid carcinoma are identified for patients with PHPT. Moreover, MIVAP has proved to have further advantages when compared to other mini invasive procedures such as the demonstrated possibility to perform a traditional bilateral exploration, when indicated. Nevertheless, a great degree of experience is requested for this procedure. In conclusion, MIVAP permits to significantly reduce posto perative pain, size of the incision, days of hospitalisation and, finally, the cost of the entire procedure without affecting in any way the success rate of the traditional operation and without an increase of the complications.

Ultrasonography is supposed to provide a reliable preoperative estimate of thyroid volume. This prospective study compares the estimated thyroid volume (EV) to real volume (MV), obtained by measuring the excised gland after surgery. One hundred one patients undergoing total thyroidectomy were selected for the study. Indications for surgery were: multinodular goiter, diffuse toxic goiter (DTG), uninodular disease. In all cases, ultrasound was repeated 1 month after surgery to verify complete thyroid removal. EV was underestimated in 89 cases; it perfectly matched the MV in 5 and was overestimated in 7. Mean EV was 28.3 mL (range, 7-50) and mean MV 36.2 mL (range, 7-76); this difference was statistically significant (p < 0.0001). Patients were then divided in groups according to EV (< or > than 25 mL) and thyroid morphology. Highly significant differences were found between all groups (p < 0.0001) except the DTG population, where the difference was less significant (p < 0.042). The study demonstrates that a correct preoperative measurement of the thyroid gland is not achievable because the volume estimated by ultrasound is largely underestimated in comparison to the real volume of the excised gland. Nevertheless ultrasound is more reliable in DTG than in other thyroid diseases. Increasing the number of cases may help to verify a new mathematical model.

BACKGROUND:The diagnosis of incidental thyroid carcinoma (ITC) in patients operated on for a benign disease is frequent. This study aims to determine both its clinical effect and the possibility of identifying this class of patients preoperatively.METHODS:A total of 998 consecutive patients (697 women and 301 men; mean age, 49.5 years) undergoing surgery for benign thyroid pathology in a single institution were studied. The mean time between first diagnosis of thyroid disease and operation was 9.0 years (range, 0-50 years). All patients underwent at least one ultrasonography before surgery, and 678 patients underwent fine-needle aspiration cytology. Patients with undetermined cytology or follicular nodules were excluded from the study.RESULTS:Histology revealed an ITC in 104 patients (10.4%): 99 had a papillary carcinoma. Mean and median diameters of ITC were 1.4 and 0.7 cm, respectively (range, 0.1-7.5 cm). In 43 patients, the tumour size was greater than 1 cm, whereas it exceeded 2 cm in 25 patients. Tumours were multicentric in 19.8% of the patients and occurred in 8.2% of patients with nodular toxic goiter, 8.7% of patients with toxic diffuse goiter and 13.8% of patients with multinodular goiter.DISCUSSION:The results confirm the high frequency of ITC. ITC was more frequent in euthyroid patients than in thyrotoxic patients (P < 0.03). Sex, age, thyroid volume and interval between diagnosis and surgery did not significantly influence its incidence. The majority of ITC was represented by microcarcinomas, but in approximately 25% of patients, the tumour size was greater than 2 cm. The role played by FNAC in excluding malignancies proved to be fairly inconclusive.

We evaluated in primary human thyrocyte cultures the effect of interferon (IFN)-alpha and -beta on the expression of thyroid peroxidase (TPO), sodium/iodide symporter (NIS), and thyroglobulin (Tg) as well as T-4 release. Human thyrocyte cultures were carried out with fresh normal thyroid tissue. Gene and protein expression of Tg, TPO, and NIS were assessed by RT-PCR and Western blot analysis after 24, 48, and 72 h of treatment with TSH alone (10 mIU/ml) and in combination with IFNalpha or -beta (10(4) U/ml). IFN inhibited the TSH-stimulated gene expression of Tg, TPO, and NIS in a time-dependent manner without significant differences between IFNalpha and -beta. Moreover, the addition of both type I IFNs clearly reduced the TSH-stimulated protein expression of Tg, TPO, and NIS after 72 h of exposure. Finally, this down-regulation was associated with a reduction of T-4 release by almost 50%. In conclusion, our study shows that both IFNalpha and -beta down-regulate the TSH-stimulated expression of Tg, TPO, and NIS as well as T-4 release. Indeed, the development of hypothyroidism during type I IFN therapy may be related, at least in part, to an abnormal expression and function of key proteins involved in iodine uptake and organification.

AIM:The postoperative pancreatitis was a classical complication in the historical series of primary hyperparathyroidism (HPT), but the causal association was never demonstrated and even recent studies denied it. The aim of this study was to determine the augmentation of postoperative amylasemia, and its possible clinical traduction in patients operated for primary HPT.MATERIAL AND METHODS:Fifty consecutive patients operated for cure of a primary HPT were included in this study. Total amylase, as well as isoenzyme fractions P (pancreatic) and S (salivary), calcium, phosphorus and intact PTH serum concentrations were determined on the days prior and after parathyroidectomy. Fifteen normocalcemic patients operated for secondary HPT constituted the control group.RESULTS:The study deals with 42 female and eight male patients, their mean age was 58.5 years (range 19-89 years). All patients underwent parathyroidectomy for adenoma or hyperplasia. No patient had pancreatitis before parathyroidectomy. Postoperative amylasemia developed in four patients (8%), one with increased total amylase and P fraction, one with only increased total amylase, and two with increased total amylase and S fraction. No patients exhibited abdominal symptoms suggesting acute pancreatitis in the postoperative period. There was no correlation between pre- and post-operative calcium serum levels and pre- and post-operative amylasemia. In the secondary HPT group no significant diminution of the total amylasemia or of P and S fractions were observed.CONCLUSIONS:These results indicate that acute pancreatitis is an exceptional postoperative complication of primary HPT nowadays. The 8% incidence reported in the present study matches the incidence of hyperamylasemia reported postoperatively in non-abdominal or non-parathyroid surgery.

INTRODUCTION:This study reviews four years of Minimally Invasive Video Assisted Thyroidectomy (MIVAT) technique and compares the results to those of traditional thyroid surgery.MATERIALS AND METHODS:Between 1999 and 2002, a series of 427 patients were submitted to MIVAT at our Department. Selection criteria were: thyroid nodule maximum diameter of 3.5 cm, total thyroid volume under 25 cc, no signs associated thyroiditis, diagnosis of benign thyroid disease or "low risk" thyroid tumor, no evidence of nodal disease of the neck.RESULTS:We operated on 362 females and 65 males and the mean age of the population was 39.6 years (range 10-77). A total thyroidectomy was performed in 208 cases, and 219 patients underwent a single-side procedure. Mean operative time was 30.4 minutes for lobectomy (range 20-140 minutes) and 50.2 for total thyroidectomy (range 35-140). Complications were represented by definitive recurrent nerve palsy in 3 patients (0.7%) and one case of definitive hypoparathyroidism (0.4%). A wound infection is reported in 3 cases and we had no major bleeding that required surgical revision. A conversion to open procedure was performed in 5 cases (1.2%); mean hospitalisation was 1.28 days (range: 1-4).CONCLUSIONS:This series demonstrates that MIVAT is not different to conventional open surgery in terms of complications, radicality of the procedure and operative time. Moreover, even if not statistically proved, MIVAT appears to offer some advantages in terms of cosmetic results and postoperative pain. In conclusion, we believe that MIVAT is a perfectly reproducible and safe technique for both benign and low-risk malignant thyroid disease, when correct indications are strictly followed.

Aim. - The postoperative pancreatitis was a classical complication in the historical series of primary hyperparathyroidism (HPT), but the causal association was never demonstrated and even recent studies denied it. The aim of this study was to determine the augmentation of postoperative amylasemia, and its possible clinical traduction in patients operated for primary HPT.Material and methods. - Fifty consecutive patients operated for cure of a primary HPT were included in this study. Total amylase, as well as isoenzyme fractions P (pancreatic) and S (salivary), calcium, phosphorus and intact PTH serum concentrations were determined on the days prior and after parathyroidectomy. Fifteen normocalcemic patients operated for secondary HPT constituted the control group.Results. - The study deals with 42 female and eight male patients, their mean age was 58.5 years (range 19-89 years). All patients underwent parathyroidectomy for adenoma or hyperplasia. No patient had pancreatitis before parathyroidectomy. Postoperative amylasemia developed in four patients (8%), one with increased total amylase and P fraction, one with only increased total amylase, and two with increased total amylase and S fraction. No patients exhibited abdominal symptoms suggesting acute pancreatitis in the postoperative period. There was wno correlation between pre- and post-operative calcium serum levels and pre- and post-operative amylasemia. In the secondary HPT group no significant diminution of the total amylasemia or of P and S fractions were observed.Conclusions. - These results indicate that acute pancreatitis is an exceptional postoperative complication of primary HPT nowadays. The 8% incidence reported in the present study matches the incidence of hyperamylasemia reported postoperatively in non-abdominal or non-parathyroid surgery. (C) 2003 Elsevier SAS. Tons droits reserves.

BACKGROUND:Ever since the introduction of video-assisted thyroidectomy (VAT), Graves' disease has represented a contraindication. This study aimed to demonstrate that VAT can be proposed also for Graves' disease.METHODS:From January 2002 to March 2003, 21 patients (20 women and 1 man) with Graves' disease underwent VAT. One patient showed positive test results for gene RET. The mean age of the patients was 36.4 years.RESULTS:No conversions of procedure were necessary. The mean operative time was 56.9 min. The RET-positive patient underwent total thyroidectomy and central compartment lymphadenectomy. Postoperative bleeding occurred in the patient with the largest gland. Histology showed goiter in 18 cases, medullary carcinoma in 1 case, and papillary carcinoma in 2 cases. No cases of vocal cord palsy but three cases of transient hypocalcemia were registered.CONCLUSIONS:Graves' disease can be treated safely using VAT only if selection criteria are carefully respected. The young age of the patients with this disease encourages us to propose VAT for its good cosmetic and postoperative outcome.

Telomeres are the distal ends of human chromosomes composed of tandem repeats of the sequence TTAGGG. In most human somatic cells, telomerase activity is undetectable, and the telomere length is progressively shortened during cell proliferation, leading to cellular senescence. In contrast, telomerase is activated in the vast majority of cancer cells, including colorectal cancer. The human telomerase complex is comprised of multiple components, but telomerase reverse transcriptase (hTERT) is the most important component for the control of telomerase activity. The p53 protein is a transcription factor with multiple biological activities, including cell cycle arrest and/or apoptosis upon DNA damage, hypoxia and oncogene activation; this requires transactivation or repression of specific target genes by wild-type p53. To better understand if a link between hTERT/telomerase regulation and p53 status exists in colorectal carcinogenesis, we analysed 43 cases of colorectal carcinoma for hTERT mRNA expression and telomerase activity. Moreover, a complete analysis of p53 status was performed. Alterations of p53 gene were found in 44.19% of cases and missense point mutations represented a high proportion of p53. Both telomerase activity (p=0.014) and hTERT expression (p=0.03) were significantly associated with p53 mutations, suggesting a role of p53 in the signaling pathway for telomerase control.

The occurrence of carcinoma of the thyroglossal duct remnant (TDRCa) is reported to be less than 1%. We retrospectively analyzed 18 cases (14 females, 4 males; mean age, 38.17 years) of TDRCa who underwent surgery in our department, to evaluate the correct workup for diagnosis and treatment. Nine patients underwent a total thyroidectomy and a Sistrunk procedure (SP) whereas 8 underwent a completion total thyroidectomy after a postoperative diagnosis of TDRCa. One patient was diagnosed with TDRCa several years after total thyroidectomy for goiter. Postoperatively all patients were given radioiodide and levothyroxine therapy. Mean follow-up was 85 months. No patient died of tumor-related disease. Thyroglossal duct neoplasms were represented by papillary carcinoma in 16 cases; thyroid histology demonstrated papillary carcinoma in 6 cases (33.3%). Three patients demonstrated single regional node metastasis and only one of them demonstrated the presence of malignant thyroid disease. When clinical diagnosis of thyroglossal duct cyst is made, the workup should be completed by ultrasound (US) scan and fine-needle aspiration cytology (FNAC) in order to plan the correct surgery for a possible TDRCa. Total thyroidectomy should always be considered with SP to permit the correct treatment and follow-up in those patients. Long-term survival of patients with cTDRCa is excellent.

INTRODUCTION:In 1997 a Minimally Invasive Video Assisted Technique for Parathyroidectomy (MIVAP) was developed in the University of Pisa. In this review we examine the last three years of MIVAP (240 cases) in order to identify the advantages and the limits of the procedure after the first-period development of the technique.RESULTS:In our experience, 65% of patients affected by primary hyperparathyroidism (PHPT) turned out to be eligible for MIVAP. During the first years several selection criteria were strictly followed; more recently, some initially absolute contraindications to the operation have been interpreted more flexibly. Mean operative time is 35 minutes. 18 conversions (7.5%) to traditional open cervicotomy were needed and in 4 cases (1.6%) no affected parathyroid tissue was removed.CONCLUSIONS:At present, we consider absolutely necessary for MIVAP: preoperative localization of an adenoma with at least one imaging study (US or MIBI scintiscan) and the availability of QPTH intraoperative assay. No absolute contraindications other than the size of the lesions and the suspect of parthyroid carcinoma are identified for patients with PHPT. Moreover, MIVAP has proved to have further advantages when compared to other mini invasive procedures such as the demonstrated possibility to perform a traditional bilateral exploration, when indicated. Nevertheless, a great degree of experience is requested for this procedure. In conclusion, MIVAP permits to significantly reduce postoperative pain, size of the incision, days of hospitalisation and, finally, the cost of the entire procedure without affecting in any way the success rate of the traditional operation and without an increase of the complications.

The external branch of the superior laryngeal nerve (ESLN) innervates the cricothyroid muscle, which regulates the tension of the vocals cords. Damage to the ESLN causes changes of the voice like hoarseness, weakness, decreased range of pitch or volume, and fatigue after extensive use. This complication will diminish the preservation of the recurrent laryngeal nerve during the same operation and can be a disaster, especially for singers and professional speakers. Visualization of the ESLN, which always should be achieved, is not routinely obtained during thyroidectomy, because of the small diameter of this branch (0.2 mm), its very variable course, and the anatomic position (the space between the medial surface of the upper pole of the thyroid and the cricothyroid muscle, which is covered by the strap muscles). In about 10% to 15% of cases, the nerve runs within the cricothyroid muscle in its entire course, so it cannot be seen by direct inspection using any technique, but luckily, in this case it is not at risk. To preserve the ESLN, most surgeons tend to avoid rather than expose the nerve, suggesting selective ligation of the upper pedicle vessels. In fact, the ESLN usually crosses the superior thyroid artery more than 1 cm above the upper edge of the superior thyroid pole (type 1) and successively runs on the surface of the cricothyroid muscle. But this “blind” step will jeopardize the nerve variants type 2a and type 2b (20% to 35%) crossing the upper pedicle less than 1 cm, respectively, above and below the upper edge of the superior thyroid pole. In minimally invasive video-assisted thyroidectomy, a procedure introduced by Miccoli and colleagues in No competing interests declared.

BACKGROUND:Minimally invasive video-assisted thyroidectomy (MIVAT) has been practiced in our department since 1998. It has some advantages over conventional surgery in terms of postoperative pain and cosmetic result. The aim of this study was to evaluate the use of the Harmonic scalpel (HS) on the performance of this procedure.METHODS:Between October 1998 and January 2001, 116 patients underwent MIVAT. The HS was used for the last 26 operations. We compared this group of patients (HS-G) with a control group (C-G) of 26 patients who had undergone MIVAT before the introduction of the HS. The following parameters were considered: age, gender, preoperative diagnosis, size of the lesion, type of operation (lobectomy or total thyroidectomy), operative time, complication rate, and postoperative hospital stay.RESULTS:The two groups were well matched for age, gender, preoperative diagnosis, lesion size, and type of operation. The mean operative time was significantly reduced in the HS-G for both lobectomy (37.3 +/- 8.4 vs 49.4 +/- 18.0 min) and total thyroidectomy (53.8 +/- 16.3 vs 90.6 +/- 22.1 min). No differences were found for postoperative stay. One patient in the C-G experienced a transient recurrent nerve palsy. There were no other complications.CONCLUSIONS:This study showed that the utilization of the HS for MIVAT is safe and associated with a shorter operative time. A reduction of the rates for such complications such as hypoparathyroidism and recurrent nerve injuries was not possible to demonstrate in the present study. Much larger series are needed for further evaluation of this instrument.

Telomerase activation, a cardinal requirement for immortalization, is a crucial step in the development of malignancy and requires the induction of the catalytic component, human telomerase reverse transcriptase (hTERT), encoded by the hTERT gene. By reverse transcription-PCR, using primers within the reverse transcriptase domain of hTERT, we investigated telomerase messenger in 8 adenomatous and 9 dysplastic polyps, and in 32 paired cancer-normal mucosa specimens, one liver and one spleen metastasis from patients resected for sporadic colorectal cancer. Telomerase messenger was absent or very low in normal mucosa and in adenomatous polyps. Dysplastic polyps and adenocarcinoma samples showed hTERT mRNA, with higher levels in cancer tissues compared to dysplastic lesions. A high telomerase messenger level was shown to be associated with late-staged cancers and with metastasis; thus, detection of telomerase messenger may be useful in the early diagnosis of colon cancer, and telomerase may be a new target for therapeutic intervention.

Telomerase activity, a cardinal requirement for immortalization, is a crucial step in the development of cancer and has been studied in many kinds of malignant tumours for clinical diagnostic and/or prognostic utilities, Using a PCR-based TRAP assay, we investigated telomerase activity in 8 adenomatous polyps, 9 dysplastic polyps, and in 36 paired cancer-normal mucosa specimens, one liver and one spleen metastasis from patients resected for sporadic colorectal cancer. Telomerase was absent or very low in normal mucosa and in adenomatous polyps. Dysplastic polyps and adenocarcinoma samples showed telomerase activity, with higher levels in cancer tissues compared to dysplastic lesions. A high telomerase activity was shown to be associated with late-staged cancers and metastasis, providing arguments supporting the role of telomerase not only in the development but also in the progression of colorectal carcinoma. Moreover, telomerase evaluation may help to confirm the malignant transformation in polypoid colorectal lesions with different levels of dysplastic alterations.

Angiogenesis is an essential requirement for the development, progression and metastasis of malignant tumors. Vascular endothelial growth factor (VEGF) plays an essential role in the development of angiogenesis of numerous solid malignancies, including colon cancer. The tumor suppressor gene p53 is a potent transcriptional regulator of genes which are involved in many cellular activities, including cell-cycle arrest, apoptosis and angiogenesis. In order to better understand the relation among p53 status, VEGF expression and microvessels count (MVC) in colon cancer, we evaluated immunoreactivity for CD34 endothelium-associated antigen, VEGF and p53 proteins in 43 cases of colon adenocarcinoma. Our results demonstrated an association between VEGF expression, p53 status and angiogenesis, suggesting that mutant p53 plays a central role in promoting angiogenesis in colon cancer progression.

STUDY AIMMinimally invasive video-assisted parathyroidectomy (MIVAP) was introduced in 1997 for the treatment of sporadic primary hyperparathyroidism (sPHPT). The study aim was to review the entire series of patients operated on in order to analyse the learning curve of this procedure.PATIENTS AND METHODSBetween February 1997 to January 2001, 185 patients underwent MIVAP. All these patients were divided into three groups: group A (GA) included 63 patients operated on between February 1997 and September 1998; group B (GB) 64 patients operated on between October 1998 and January 2000; Group C (GC) 64 patients operated on between January 2000 and January 2001. Mean operative time, complications and conversions rates of the three groups were compared.RESULTSThe three groups were well matched for age and gender. Mean operative time was significantly shorter in patients of GC (28.3 +/- 13.6 min) when compared with GA (62.3 +/- 24.6 min) and GB (48.4 +/- 18.1 min). Conversion was required in 3 cases of GA (4.8%), in 8 cases of GB (12.8%) and in 4 cases of GC (6.5%). One transient postoperative recurrent nerve palsy and 4 cases of transient postoperative hypocalcemia were observed among patients of GA. No complications were registered in the other groups.CONCLUSIONSThis study shows that with increasing experience, the operative time of MIVAP was dramatically reduced, as well as postoperative complications rate. The higher percentage of conversion in groups B and C may be explained by the fact that, with increasing experience, more difficult and ambiguous cases were operated with this technique.