mRECIST criteria to assess recurrent thyroid carcinoma treatment response after radiofrequency ablation: a prospective study.

PURPOSE: 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. METHODS: Sixteen lesions in 13 patients were treated by RFA. All patients refused/were excluded from repeated surgery or other conventional therapy. CT and US examinations were performed before RFA to evaluate lesion volume and vascularization. All RFA procedures were performed under US-guidance by an 18-gauge, electrode. Treatment response was evaluated by CT, according to RECIST 1.1 and to mRECIST guidelines; CT examinations were performed during follow-up (6-18 months); the volume of residual vital tumour tissue and the percentage of necrotic tissue were estimated by contrast enhanced CT. RESULTS: RFA was well tolerated by all patients; in two cases laryngeal nerve paralysis was observed. Mean pre-treatment volume was 4.18 ± 3.53 ml. Vital tumour tissue and percentage of necrosis at 6, 12 and 18 months were 0.18 ± 0.25, 0.11 ± 0.13, 0.29 ± 0.40 ml and 91.9 ± 11.1, 90.4 ± 13.3, 80.8 ± 23.1%. According to RECIST 1.1, target lesion response was classified as complete response (CR) in one case, partial response (PR) in 11/16, stable disease in 4/16 cases. According to mRECIST, 11/16 cases were classified as CR and the remaining 5 as PR. CONCLUSION: RFA is a safe procedure to treat the viable tumour tissue and to reduce the RTC volume; as to the criteria to assess treatment response, mRECIST appears to be more accurate.

Type I interferons modulate the expression of thyroid peroxidase, sodium/iodide symporter, and thyroglobulin genes in primary human thyrocyte cultures.

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 IFN alpha 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 IFN alpha 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 IFN alpha 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.

Video-assisted thyroidectomy for Graves' disease: report of a preliminary experience.

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.

[Minimally invasive video-assisted thyroidectomy--techniques and results over 4 years of experience (1999-2002)]. / Tiroidectomia video-assistita minimamente invasiva (Mivat)--cenni di tecnica an e risultati di 4 anni di esperienza (Analisi della casistica 1999-2002).

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.

[Early postoperative hyperamylasemia after parathyroidectomy for primary hyperparathyroidism]. / Early postoperative hyperamylasemia after parathyroidectomy for primary hyperparathyroidism.

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.

[Video-assisted minimally invasive parathyroidectomy with median access. Technical changes: case load 1999-2002]. / Paratiroidectomia miniinvasiva videoassistita con accesso mediano. Evoluzione tecnica: casistica 1999-2002.

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.

Evaluation of telomerase in the development and progression of colon cancer.

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.

Evaluation of telomerase mRNA (hTERT) in colon cancer.

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.

Impact of harmonic scalpel on operative time during video-assisted thyroidectomy.

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.

Neoangiogenesis in colon cancer: correlation between vascular density, vascular endothelial growth factor (VEGF) and p53 protein expression.

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.

[Video-assisted parathyroidectomy: learning curve]. / Parathyroïdectomie vidéoassistée: courbe d'apprentissage.

STUDY AIM: Minimally 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 METHODS: Between 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. RESULTS: The 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. CONCLUSIONS: This 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.

Minimally invasive video-assisted thyroidectomy.

BACKGROUND: In this paper we describe the results of our personal technique for minimally invasive video-assisted thyroidectomy (MIVAT). METHODS: Sixty-seven patients were selected for MIVAT. Selection criteria were nodule size less than 30 mm, thyroid volume less than 20 mL, no thyroiditis, no previous neck surgery or irradiation. The procedure, totally gasless, is carried out through a 15-mm central incision above the sternal notch. Dissection is performed under endoscopic vision, using conventional and endoscopic instruments. RESULTS: We performed 51 lobectomies and 15 total thyroidectomies. Mean operative time was 73.6 minutes for lobectomy and 109.6 minutes for total thyroidectomy. Conversion to open procedure was required twice (3%). We observed 2 cases of transient postoperative hypocalcemia and 1 case of transient recurrent laryngeal nerve palsy. The cosmetic result was considered excellent by most patients. CONCLUSIONS: MIVAT is safe and feasible. The indications are limited at present, but the results are encouraging, and we are optimistic about the future expansion of its applicability.

[Medullary carcinoma of thyroid gland]. / Il carcinoma midollare della tiroide.

The authors present the characteristic features of medullary carcinoma of thyroid (CMT) and underline the necessity to identify RET proto-oncogene that is the cause of hereditary transmission of CMT. Physiology of C cells and clinical syndromes are reported and the importance of a genetic screening in population at risk is emphasized; this test has shown to be reliable and easy to apply. They report their experience on techniques of amplification and restriction for RET proto-oncogene identification in relatives of patients with MEN or familial CMT syndromes. This study has allowed to recognize a population bearing the oncogene responsible of the disease and to achieve a correct prophylactic therapeutic management.