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Piero Berti

Publications and source records attributed to Piero Berti.

At least 19 recordsLinked to original sources
PubMed2006

New trends in the treatment of undifferentiated carcinomas of the thyroid.

INTRODUCTION: Malignant tumours of the thyroid are generally classified as either well-differentiated thyroid carcinoma, which is composed of papillary and follicular carcinoma, or undifferentiated/anaplastic thyroid carcinoma (ATC). ATC is not only the most lethal disease in the field of endocrine surgery but also one of the most aggressive tumours characterized by an almost invariable fatal outcome, which only very rarely exceeds a 1-year course. DISCUSSION: The impact of surgical resection in association with external beam radiation on ATC outcome has been extensively investigated also in studies based on multicentric database, and there is a general agreement on the significance of a complete resection of the tumour. It has been difficult up to now to collect data regarding chemotherapy adjuvant treatment. In spite of the lack of an extensive review about the results of this kind of treatment by itself or as part of a multimodal approach, it seems that among the several chemotherapy agents experienced, none proved to influence significantly ATC prognosis. Neither doxorubicin (the most commonly used) nor other drugs, such as cisplatin, bleomycin, fluorouracil or cyclophosphamide, showed any real efficacy in controlling the disease. CONCLUSION: The most recent development in this field seems to be represented by the possibility offered by PPARg agonists; even more promising might be the use of adenovirus-mediated p53 tumour suppressor gene therapy or BMP-7. All these new therapies need further confirmation coming from ongoing clinical trials such as those involving the use of vascular and growth factor-targeted agents.

Antibiotics, Antineoplastic↗
PubMed2006

Intensive post-operative follow-up of breast cancer patients with tumour markers: CEA, TPA or CA15.3 vs MCA and MCA-CA15.3 vs CEA-TPA-CA15.3 panel in the early detection of distant metastases.

BACKGROUND: In breast cancer current guidelines do not recommend the routine use of serum tumour markers. Differently, we observed that CEA-TPA-CA15.3 (carcinoembryonic (CEA) tissue polypeptide (TPA) and cancer associated 115D8/DF3 (CA15.3) antigens) panel permits early detection and treatment for most relapsing patients. As high sensitivity and specificity and different cut-off values have been reported for mucin-like carcinoma associated antigen (MCA), we compared MCA with the above mentioned tumour markers and MCA-CA15.3 with the CEA-TPA-CA15.3 panel. METHODS: In 289 breast cancer patients submitted to an intensive post-operative follow-up with tumour markers, we compared MCA (cut-off values, > or = 11 and > or = 15 U/mL) with CEA or CA15.3 or TPA for detection of relapse. In addition, we compared the MCA-CA15.3 and CEA-TPA-CA15.3 tumour marker panels. RESULTS: Distant metastases occurred 19 times in 18 (6.7%) of the 268 patients who were disease-free at the beginning of the study. MCA sensitivity with both cut-off values was higher than that of CEA or TPA or CA15.3 (68% vs 10%, 26%, 32% and 53% vs 16%, 42%, 32% respectively). With cut-off > or = 11 U/mL, MCA showed the lowest specificity (42%); with cut-off > or = 15 U/mL, MCA specificity was similar to TPA (73% vs 72%) and lower than that of CEA and CA15.3 (96% and 97% respectively). With > or = 15 U/mL MCA cut-off, MCA sensitivity increased from 53% to 58% after its association with CA15.3. Sensitivity of CEA-TPA-CA15.3 panel was 74% (14 of 19 recurrences). Eight of the 14 recurrences early detected with CEA-TPA-CA15.3 presented as a single lesion (oligometastatic disease) (5) or were confined to bony skeleton (3) (26% and 16% respectively of the 19 relapses). With > or = 11 U/mL MCA cut-off, MCA-CA15.3 association showed higher sensitivity but lower specificity, accuracy and positive predictive value than the CEA-TPA-CA15.3 panel. CONCLUSION: At both the evaluated cut-off values serum MCA sensitivity is higher than that of CEA, TPA or CA15.3 but its specificity is similar to or lower than that of TPA. Overall, CEA-TPA-CA15.3 panel is more accurate than MCA-CA15.3 association and can "early" detect a few relapsed patients with limited metastatic disease and more favourable prognosis. These findings further support the need for prospective randomised clinical trial to assess whether an intensive post-operative follow-up with an appropriate use of serum tumour markers can significantly improve clinical outcome of early detected relapsing patients.

Adult↗
PubMed2006

Combination of minimally invasive thyroid surgery and local anesthesia associated to iopanoic acid for patients with amiodarone-induced thyrotoxicosis and severe cardiac disorders: a pilot study.

BACKGROUND AND AIMS: Amiodarone-induced thyrotoxicosis is a life-threatening condition. A prompt control of thyrotoxicosis is obtained by thyroidectomy. Preparation with iopanoic acid proved to be very effective in reducing cardiovascular complications. Nevertheless, general anesthesia and extensive surgery may affect negatively patients also after adequate preparation. Safety and efficacy of minimally invasive video-assisted thyroidectomy performed under regional anesthesia (bilateral modified deep cervical block) in patients with amiodarone-induced thyrotoxicosis was evaluated. PATIENTS AND METHODS: Eight patients with amiodarone-induced thyrotoxicosis (three with type I and five with type II), mean age 66.2 years, were prepared with iopanoic acid. There were five men and three women. Three patients had dilatative cardiomyopathy, three had heart failure secondary to severe myocardial infarction, and two had refractory unstable rhythm disorders. RESULTS: Minimally invasive video-assisted thyroidectomy was performed under regional anesthesia. Mean operative time was 55.5 min. During surgery, lung and heart function remained well and no surgical complications occurred. After surgery, all patients remained on amiodarone therapy and two patients were subsequently removed from the checklist for heart transplantation. CONCLUSION: Minimally invasive video-assisted thyroidectomy under regional anesthesia can be proposed as resolution of amiodarone-induced thyrotoxicosis in high risk patients with severe cardiac disorders, after preparation with iopanoic acid.

Aged↗
PubMed2006

Video-assisted thyroidectomy: indications and results.

BACKGROUND AND AIMS: Minimally invasive video-assisted thyroidectomy (MIVAT) was set up and introduced in our department in 1998. Its results, after an acceptable relapse, can now be evaluated, also speculating on new possible indications. PATIENTS AND METHODS: The procedure is based on a unique incision in the central neck, 2 cm above the sternal notch, using small conventional retractors and needlescopic (2 mm) reusable instruments. Haemostasis is achieved by a harmonic scalpel. Patients, 833, underwent MIVAT since June 1998. There were 715 females and 118 males (ratio 4:1). Lobectomy was carried out in 323 (38.7%) patients, total thyroidectomy in 510 (61.2%) patients. RESULTS: Mean operative time of lobectomy was 36.2 min (range: 20-120); for total thyroidectomy, 46.1 min (30-130). Conversion to standard cervicotomy was required in 16 cases (1.9%); Operative complications were represented by transient monolateral recurrent nerve palsy in eight cases (0.9%), definitive monolateral recurrent nerve palsy in seven cases (0.8%). Twenty patients exhibited a hypoparathyroidism, which corresponds to 3.9% of total thyroidectomies performed, but only two showed permanent hypoparathyroidism (0.3%). CONCLUSION: MIVAT can be considered a safe operation offering significant cosmetic advantages with possible new promising indications such as prophylactic thyroidectomy in rearranged during transfection (RET) gene mutation carriers. It is still limited to a minority of patients, in particular, in endemic goitre countries.

Female↗
PubMed2006

Randomized controlled trial of harmonic scalpel use during thyroidectomy.

OBJECTIVE: To compare operative factors, postoperative outcomes, and surgical complications of thyroidectomy when using the harmonic scalpel (HS) vs conventional hemostasis (CH). DESIGN: Single-blind, randomized controlled trial. SETTING: Department of Surgery, S. Chiara Hospital, University of Pisa, Pisa, Italy. PATIENTS: One hundred patients undergoing thyroidectomy. MAIN OUTCOME MEASURES: Postoperative pain, drainage volume, hypocalcemia, nerve injury, and operative time. INTERVENTION: Patients underwent total thyroidectomy in which either the HS or CH was used. RESULTS: We found no significant differences between the HS and CH groups at baseline. Postoperative pain was reduced in the HS group at 24 hours (mean visual analog scale score, 3.90 vs 5.30; P<.001) and 36 hours (2.27 vs 3.95; P<.001). Drainage volume was significantly lower in the HS group (40.1 mL vs 75.4 mL; P<.001). Transient hypocalcemia was significantly lower in the HS group (5 patients [10%] vs 16 [32%]; P=.01). No patients experienced nerve injury or permanent hypocalcemia. Mean operative times were shorter in the HS group (40.0 vs 46.7 minutes, P<.001). CONCLUSIONS: Use of the HS may reduce postoperative pain, drainage volume, and transient hypocalcemia in patients undergoing thyroidectomy. Shorter operative times and improved outcomes might justify the cost of the HS compared with that of CH.

Adult↗
PubMed2006

Ultrasonography estimated thyroid volume: a prospective study about its reliability.

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.

Adolescent↗
PubMed2006

Genetic analyses in familial isolated hyperparathyroidism: implication for clinical assessment and surgical management.

OBJECTIVE: Familial isolated primary hyperparathyroidism (FIPH) can result from either incomplete expression of a syndromic form of familial primary hyperparathyroidism [multiple endocrine neoplasia type 1 (MEN 1), hyperparathyroidism-jaw tumour syndrome (HPT-JT) or familial hypocalciuric hypercalcaemia (FHH)] or still unrecognized causes. Design Genetic analyses of MEN1, HRPT2 and CASR genes in FIHP. PATIENTS: Seven well-characterized Italian kindreds with FIHP, with negative clinical features for MEN 1, HPT-JT and FHH. The mean age (+/- SD) at diagnosis was 45 +/- 17 years (range 18-70 years) in the probands and 42 +/- 18 years (range 15-69 years) in the other affected subjects. MEASUREMENTS: Direct sequencing of germline DNA of the MEN1, HRPT2 and CASR genes from probands. The region of interest was amplified in some family members. RESULTS: Germline MEN1 mutations were detected in three kindreds. Multiglandular involvement was found in all but one affected subject belonging to the three kindreds with MEN1 mutations. In these patients persistence/relapse of the disease was observed unless an extensive parathyroidectomy (excision of 3(1)/(2) glands) had been performed, with the exception of one patient, who is currently normocalcaemic 168 months after excision of two glands. No mutations of MEN1, HRPT2 and CASR genes were identified in the remaining four families. CONCLUSIONS: MEN1 genotyping appears worthwhile in FIHP families, as the finding of mutation(s) may predict multiglandular involvement and therefore have practical surgical implications, and prompt further investigation in the family, with the possibility of identifying new cases and beginning a programme of periodic surveillance for emergence of tumours in all carriers.

Adenoma↗
PubMed2006

Incidental thyroid carcinoma in a large series of consecutive patients operated on for benign thyroid disease.

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.

Adolescent↗
PubMed2005

Metachronous adrenal masses in resected non-small cell lung cancer patients: therapeutic implications of laparoscopic adrenalectomy.

OBJECTIVE: In literature only few reports focused on the resection of solitary adrenal gland metastasis in patients operated on for non-small cell lung cancer (NSCLC). We report our experience on laparoscopic adrenalectomy for suspected or confirmed metachronous solitary adrenal metastasis from NSCLC and discuss its therapeutic role. METHODS: From June 1993 to March 2003, 14 patients (pts), who had been undergone lung resection for NSCLC, with suspected or confirmed solitary adrenal gland metastasis at the follow-up, underwent 15 laparoscopic adrenalectomy (in 1 patient it was bilateral). All the patients had enlarged adrenal glands at the abdominal ultrasound or CT. All but 2 pts underwent at least 1 adrenal fine needle aspiration. All the patients underwent a careful staging to exclude other sites of metastasis. The adrenal gland was in 6 cases the right, in 9 cases the left. RESULTS: In 7 cases we had a preoperative cytological diagnosis of metastasis. In 1 case adrenalectomy was not performed because of infiltration of vena cava and in 1 case it was necessary to perform a small laparotomy because of bleeding. The pathologic examination confirmed in 11 cases a NSCLC metastasis while in 4 cases it was a cortical adenoma. Regarding the 10 patients with NSCLC metastases, 3 are still alive and well at 37-80 months from the lung resection. One patient (who underwent bilateral adrenalectomy) is still alive at 44 months with local relapse. Two patients died 5 and 6 months after the adrenalectomy for other causes, 1 died at 14 months for local and systemic relapse and the remaining 3 patients died at 12 to 38 months for systemic relapse. CONCLUSIONS: Laparoscopic adrenalectomy in patients resected for NSCLC is a safe mini-invasive procedure. Even though this series is still too small, laparoscopic adrenalectomy should be considered an effective therapeutic tool in case of progressive adrenal gland enlargement, also with negative cytological examinations. A bigger series and other institution experiences will clarify its oncological value.

Adrenal Gland Neoplasms↗
PubMed2004

Results of video-assisted parathyroidectomy: single institution's six-year experience.

Endoscopic surgery for primary hyperparathyroidism (PHPT) started in 1996 with a parathyroidectomy performed by Michel Gagner. The technique we propose and have been using for 6 years is based on a unique central access and external retraction. From February 1997 to October 2003, 370 of 520 patients affected with PHPT (71%) underwent minimally invasive video-assisted parathyroidectomy (MIVAP). There were 72 men and 298 women, with a mean age of 55.8 years. Twenty-four patients (6.5%) of the 370 in this series underwent MIVAP under loco-regional anesthesia, and the others had general anesthesia. Eleven patients were lost to follow-up. Surgical cure of PHPT was achieved in 353 patients (98,3%), as confirmed by a median follow-up of 35.1 months (range: 2-82 months). Video-assisted exploration was successfully performed in 350 patients (94%). The mean operative time was 36.2 minutes. In 21 cases (5.6%) a concomitant procedure was performed: a thyroid lobectomy in 14 cases and a total thyroidectomy in 7 cases. Patients were generally discharged the day after surgery. Most of the patients (91%) were satisfied with the cosmetic result 6 or more months after the procedure. Complications developed in 14 cases: 10 cases (2.7%) of transient hypoparathyroidism 3 cases (0.8%) of definitive palsies of the recurrent nerve, and 1 case of postoperative bleeding (0.27%). After 6 years of experience, MIVAP appears to be as safe and curative as traditional surgery, with better cosmetic results and better postoperative outcome.

Adenoma↗
PubMed2004

Minimally invasive video-assisted thyroidectomy: five years of experience.

BACKGROUND: In the last decade, development of videolaparoscopic surgery allowed several operations to be performed with minimally invasive techniques, making them less invasive and painful. Neck surgery was also involved in this effort, in spite of the skepticism shown by some authors. STUDY DESIGN: Minimally invasive video-assisted thyroidectomy was developed in 1998, and since then, about 600 operations have been performed. Access was the same as was previously described for parathyroidectomy; it was based on a small central incision (1.5 cm) and on external retraction without neck insufflation. RESULTS: From July 1998 to October 2003, 579 patients were selected from 5,450 for minimally invasive video-assisted thyroidectomy. The operation consisted of a total thyroidectomy in 312 patients and lobectomy in 267 patients. Mean operative time was 41 +/- 19.5 minutes (range 15 to 120 minutes) for lobectomy and 51.6 +/- 18.8 minutes (range 30 to 140 minutes) for total thyroidectomy. Postoperative hospital stay was 24 hours (overnight discharge) for all patients. Complications were postoperative bleeding (0.1%), recurrent nerve palsy (1.3%), and definitive hypoparathyroidism (0.2%). CONCLUSIONS: After 5 years of experience using this approach for various indications, we achieved a good esthetic result with an operative time comparable to that of conventional open surgery. Minimally invasive video-assisted thyroidectomy was found to be a safe operation, with advantages over traditional procedures represented by better cosmetic outcomes and postoperative course, as demonstrated by visual analogue scales and statistically analyzed numeric scales.

Adolescent↗
PubMed2004

Extent of surgery in thyroglossal duct carcinoma: reflections on a series of eighteen cases.

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.

Adenoma↗
PubMed2004

A reappraisal of the indications for laparoscopic treatment of adrenal metastases.

BACKGROUND: Laparoscopic adrenalectomy (LA) is unanimously recognized as the gold standard for the surgical treatment of adrenal lesions, but when to remove malignant lesions by this approach still remains controversial. STUDY DESIGN: We reviewed all cases of LA for suspected adrenal metastases carried out in our hospital, trying to focus on what should be the ideal preoperative workup, so as to avoid unnecessary operations. The possible role of fine needle aspiration biopsy (FNAB) in selecting patients was evaluated. RESULTS: Twenty-two patients underwent LA for suspected adrenal metastases from May 1994 to March 2003. Primary tumors were from lung in 14 cases, colon in 2 cases, kidney in 3 cases, thyroid in 2 cases, and breast in 1 case. LA was successfully performed in all but three cases. In 13 patients, 14 FNAB were performed: 8 cases proved to be true positive, 4 true negative, and 2 false negative. Final histology showed 6 cortical adenomas. Local relapse was present only in one patient, who died after 14 months. Of the metastatic patients, 8 are alive and free of disease after a mean followup of 39 months. CONCLUSIONS: The most accurate workup is of the greatest importance in order to avoid unnecessary surgery for suspected adrenal metastases. The absence of false positives (FP) and the fairly high number of true positives (TP) does not justify the effort of performing FNAB routinely. Indeed, laparoscopic exploration, being simple and quick, allows optimal diagnosis at a low cost, even when histological definition cannot be obtained.

Adrenal Gland Neoplasms↗
PubMed2004

A reappraisal of the Rb1 gene abnormalities in the diagnosis of parathyroid cancer.

OBJECTIVES: Some histological features may suggest the malignant nature of a parathyroid tumour. However, the diagnosis of parathyroid cancer can only be definitively established in the presence of local invasion or metastases. DESIGN: We further investigated the role of the retinoblastoma gene (Rb1) and the breast cancer susceptibility gene (BRCA2) in the differential diagnosis between benign and malignant parathyroid tumours by evaluating loss of heterozygosity (LOH) at these loci and Rb protein (pRb) immunohistochemistry. PATIENTS AND MEASUREMENTS: Fifty-three parathyroid adenomas from patients with sporadic primary hyperparathyroidism (PHPT) and 10 parathyroid cancer specimens were studied. Microsatellite polymorphisms at the Rb1 and BRCA2 loci were polymerase chain reaction (PCR) amplified from each patient's paired tumour and leucocyte DNA samples, using oligonucleotide primers flanking the repeat sequence. Immunohistochemical staining of pRb was carried out using a monoclonal antibody. RESULTS: All but one of the 53 tumour-leucocyte pairs was informative for at least one of the three polymorphic markers of the Rb1 gene. Fifteen adenomas (28.8%) showed LOH. Regarding the BRCA2 gene, 46 tumour-leucocyte pairs were informative and LOH was present in eight (17.4%). All six carcinomas had LOH for at least one marker at the Rb1 locus. LOH for the BRCA2 microsatellite was found in three of the five informative primary tumour samples. Immunohistochemical analysis revealed that all adenomas were positive and the number of pRb-positive cells varied significantly among different samples. The mean percentage of stained cells was 15.7%. Eleven of the 30 (36.7%) adenomas showed sparse positive staining, 13 (43.3%) intermediate staining and six (20%) extensive staining. All parathyroid cancers were entirely negative for pRb immunostaining. CONCLUSIONS: Inactivation of the Rb1 gene is a common event in parathyroid tumorigenesis. Retention of heterozygosity seems to exclude parathyroid malignancy, which is suggested by the combined finding of LOH and lack of protein expression.

Adenoma↗
PubMed2004

Genetic analyses of the HRPT2 gene in primary hyperparathyroidism: germline and somatic mutations in familial and sporadic parathyroid tumors.

We investigated the involvement of the HRPT2 gene by loss of heterozygosity analysis and direct sequencing in a kindred with hyperparathyroidism-jaw tumor syndrome (HPT-JT) and three kindreds with familial isolated primary hyperparathyroidism (FIHP). Seven patients with sporadic parathyroid cancers and 35 with parathyroid adenomas with no family history of primary hyperparathyroidism or HPT-JT were also studied. A germline heterozygous substitution G to A was found in the donor splice site of intron 1 in one of the three FIHP families. No mutations were identified in the HPT-JT kindred. A somatic HRPT2 mutation was found in four of seven patients with parathyroid cancers, two of which were unreported frameshift mutations (195insT and 195insA) in exon 2. Consistent with recent findings, two of seven patients with sporadic parathyroid cancer had germline mutations. Four adenomas showed loss of heterozygosity at HRPT2, whereas a somatic HRPT2 mutation was found in one. In conclusion, we provide additional evidence for a strong association between HRPT2 gene mutations and sporadic parathyroid cancer. The finding that two of the seven patients with sporadic parathyroid cancer carried an HRPT2 germline mutation suggests that they might have occult HPT-JT. Our results also confirm the need for testing HRPT2 gene in FIHP families.

Adenoma↗
PubMed2004

Identification of a novel point mutation in the RET gene (Ala883Thr), which is associated with medullary thyroid carcinoma phenotype only in homozygous condition.

The RET protooncogene mutations responsible for multiple endocrine neoplasia type 2 are inherited as autosomic dominant traits. We describe here a novel germline homozygous mutation in exon 15 of the RET gene that determines an amino acid substitution (Ala->Thr) at codon 883. The index case was a 51-yr-old patient with an apparently sporadic form of medullary thyroid cancer (MTC). RET gene mutations screening was performed in exons 10, 11, 13, 14, 15, and 16 by automatic sequence analysis. An unexpected homozygous GCT->ACT point mutation was found at codon 883 in exon 15 and confirmed by restriction analysis (Alu I). The presence of the two chromosomes 10 was confirmed by fluorescence in situ hybridization analysis on lymphocytes. As expected on the basis of the homozygosity of the index case, the parents were consanguineous (second-degree cousins). Eight relatives were further investigated: the mother, two sisters, and the son were positive for heterozygous RET mutation. The mother (82 yr old) showed a nodular goiter but was negative both for basal and pentagastrin stimulated calcitonin. The young son (15 yr old) and the two sisters (63 and 58 yr old) did not show any clinical and/or biochemical sign of MTC. One brother (59 yr old) was negative both for RET mutation and clinical/biochemical examination. The other brother, 56 yr of age, was positive for both homozygous RET mutation and serum calcitonin. When operated, the histological examination of the thyroid showed the presence of MTC and C cell hyperplasia. In conclusion, we identified a new germline RET gene mutation during a routine RET gene screening of an apparently sporadic MTC case. This mutation showed a very low transforming activity as demonstrated by the absence of MTC phenotype in heterozygous subjects. The possibility that the homozygous gene carriers were indeed carrying a germline loss of heterozygosity was excluded by fluorescence in situ hybridization analysis for RET gene performed on lymphocytes derived from one homozygous patient. The analysis of several RET polymorphisms also confirmed the presence of two mutated alleles in MTC affected patients and both mutated and wild-type allele in heterozygous subjects.

Carcinoma, Medullary↗
PubMed2004

Plasma chromogranin A in incidental non-functioning, benign, solid adrenocortical tumors.

OBJECTIVE: To evaluate whether adenomas arising from the adrenal cortex, a tissue of epithelial origin, are associated with high chromogranin A (CgA) levels and whether such tumors may express and release this protein. In addition, to investigate whether high CgA levels imply a neuroendocrine differentiation of the adrenocortical adenomas and, therefore, represent a humoral marker of malignant transformation of these tumors. DESIGN: Plasma CgA of 80 patients with non-functioning, benign adrenocortical adenomas was compared with that of 137 tumor-free subjects. In 15 patients, the masses were surgically removed and CgA was measured 2 months later. The other 65 patients with adrenocortical adenomas underwent clinical and radiological follow-up (range 24-36 months). METHODS: CgA was evaluated by immunoradiometric assay in peripheral blood and by immunohistochemistry in adrenal tissue specimens. RESULTS: An increase in plasma CgA (P<0.001) was observed in patients with adrenocortical adenomas (83.4+/-7.5 ng/ml) in comparison with tumor-free subjects (43.1+/-1.5 ng/ml). The prevalence of high CgA levels was 25% in the former and 0.7% in the latter. By multiple regression analysis, an increase (49%) in the expected median CgA value was estimated for adrenocortical adenomas (P<0.001). Receiver operating characteristic analysis showed a good diagnostic performance of CgA in identifying patients with adrenocortical adenomas (pure accuracy=0.78, 95% CI=0.71-0.84). In the operated patients, CgA levels did not change before (80.6+/-16.5 ng/ml) and after (74.3+/-16.3 ng/ml) surgery and in no case was CgA immunoreactivity found in adenoma tissues. The non-operated patients did not develop signs or symptoms of disease and showed no features of malignant transformation of the masses. CONCLUSIONS: Our data showed a strong association between adrenocortical adenomas and high CgA levels. CgA hypersecretion was not due to adenoma tissue, which did not show immunoreactivity for CgA. Finally, elevated CgA levels did not represent a humoral marker of malignant transformation of cortical adenomas.

Adenoma↗