Insights on DRGs, guideline compliance and economic sustainability. The case of mastectomy with immediate breast reconstruction.

Background: Immediate breast reconstruction is recommended for eligible patients undergoing mastectomy, raising the issue of economic sustainability of both mastectomy and breast reconstruction performed within the same hospitalization, as opposed to two surgical procedures in two different hospitalizations. Study design: A retrospective analysis was conducted to compare economic sustainability of mastectomies with or without immediate breast reconstruction. Methods: Economic data on hospitalizations for mastectomy in a Teaching Hospital between 1 January 2019 and 31 March 2021 were analyzed to assess their sustainability. Results: 338 admissions were selected (63.9% with immediate breast reconstruction (CI 99%: 57.2% to 70.6%). Compared to mastectomy alone, mastectomy with immediate breast reconstruction had higher cost of € 2,245 (p < 0.001), with operating rooms and devices as main cost drivers. Current reimbursements rates (which are the same for mastectomy alone and for mastectomy with immediate breast reconstruction) led to an average loss of € 1,719 for each mastectomy with immediate breast reconstruction. Conclusion: Current DRGs reimbursement rates for hospital admissions for breast cancer surgery do not guarantee immediate breast reconstruction's economic sustainability. DRGs system should be revised, or other solutions as bundled payment should be implemented in the light of the costs of innovation in healthcare, considering mastectomy and breast reconstruction steps in a path of linked actions aimed at improving patients' health.

Italian consensus on diagnosis and treatment of differentiated thyroid cancer: joint statements of six Italian societies.

BACKGROUND: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. METHODS: Six scientific Italian societies entitled to cure thyroid cancer patients (the Italian Thyroid Association, the Medical Endocrinology Association, the Italian Society of Endocrinology, the Italian Association of Nuclear Medicine and Molecular Imaging, the Italian Society of Unified Endocrine Surgery and the Italian Society of Anatomic Pathology and Diagnostic Cytology) felt the need to develop a consensus report based on significant scientific advances occurred in the field. OBJECTIVE: The document includes recommendations regarding initial evaluation of thyroid nodules, clinical and ultrasound criteria for fine-needle aspiration biopsy, initial management of thyroid cancer including staging and risk assessment, surgical management, radioiodine remnant ablation, and levothyroxine therapy, short-term and long-term follow-up strategies, and management of recurrent and metastatic disease. The objective of this consensus is to inform clinicians, patients, researchers, and health policy makers about the best strategies (and their limitations) relating to the diagnosis and treatment of differentiated thyroid cancer.

Replacement therapy with levothyroxine modulates platelet activation in recent-onset post-thyroidectomy subclinical hypothyroidism.

BACKGROUND AND AIM: Subclinical hypothyroidism has been linked to increased risk of atherosclerotic disease. Soluble CD40 ligand (sCD40L), mainly derived from activated platelets, and the lipid peroxidation product 8-iso-prostaglandin F2α (8-iso-PGF2α) are known to play a relevant pathophysiological role in atherogenesis. In this study, we analyzed the relationship between thyroid hormones and circulating levels of sCD40L and 8-iso-PGF2α in patient with recent-onset post-thyroidectomy subclinical hypothyroidism under replacement therapy. METHODS AND RESULTS: Circulating levels of thyroid hormones, sCD40L, and 8-iso-PGF2α were assessed in 40 recently thyroidectomized patients (33 females, mean age 52.0 ± 11.7 years) at baseline (5-7 day after surgery) and after 2 months under replacement therapy with levothyroxine (LT-4). At baseline, circulating levels of thyroid hormones were indicative of a subclinical hypothyroidism (TSH 7.7 ± 3.9 µU/mL, FT3 1.8 ± 0.6 pg/mL, and FT3 8.9 ± 3.0 pg/mL). Circulating levels of sCD40L and 8-iso-PGF2α were directly correlated with each other (r = 0.360, p = 0.023) and with TSH levels (r = 0.322, p = 0.043 and r = 0.329 p = 0.038, respectively). After 2 months under the replacement therapy with LT-4 circulating levels of TSH (from 7.7 ± 3.9 to 2.7 ± 2.8 µU/mL, p < 0.0001), sCD40L (from 6.11 ± 2.41 to 2.43 ± 2.00 ng/mL, p < 0.0001) and 8-iso-PGF2α (from 45.33 ± 6.94 to 40.36 ± 6.20, p < 0.0001) significantly decreased. Changes in circulating levels of sCD40L and 8-iso-PGF2α were directly correlated with each other (r = 0.349 p = 0.028) and with changes in TSH levels (r = 0.367 p = 0.020 and r = 0.339 p = 0.032, respectively). CONCLUSION: Our study suggests an influential role of TSH on proatherogenic activation of platelets, probably through enhanced lipid peroxidation. These findings could partially explain the increased susceptibility of patients with subclinical hypothyroidism to develop atherosclerotic disease.

Diagnostic, therapeutic and health-care management protocol in thyroid surgery: a position statement of the Italian Association of Endocrine Surgery Units (U.E.C. CLUB).

PURPOSE: The diagnostic, therapeutic and health-care management protocol (Protocollo Gestionale Diagnostico-Terapeutico-Assistenziale, PDTA) by the Association of the Italian Endocrine Surgery Units (U.E.C. CLUB) aims to help treat the patient in a topical, rational way that can be shared by health-care professionals. METHODS: This fourth consensus conference involved: a selected group of experts in the preliminary phase; all members, via e-mail, in the elaboration phase; all the participants of the XI National Congress of the U.E.C. CLUB held in Naples in the final phase. The following were examined: diagnostic pathway and clinical evaluation; mode of admission and waiting time; therapeutic pathway (patient preparation for surgery, surgical treatment, postoperative management, management of major complications); hospital discharge and patient information; outpatient care and follow-up. RESULTS: A clear and concise style was adopted to illustrate the reasons and scientific rationales behind behaviors and to provide health-care professionals with a guide as complete as possible on who, when, how and why to act. The protocol is meant to help the surgeon to treat the patient in a topical, rational way that can be shared by health-care professionals, but without influencing in any way the physician-patient relationship, which is based on trust and clinical judgment in each individual case. CONCLUSIONS: The PDTA in thyroid surgery approved by the fourth consensus conference (June 2015) is the official PDTA of U.E.C. CLUB.

Effects of biliopancreatic diversion on diurnal leptin, insulin and free fatty acid levels.

BACKGROUND: Free fatty acid (FFA) levels are raised in obesity as a consequence of increased production and reduced clearance. They may link obesity with insulin resistance. Bariatric surgery can result in considerable weight loss and reduced insulin resistance, but the mechanism of action is not well understood. Although drugs such as metformin that lower insulin resistance can contribute to weight loss, a better understanding of the links between obesity, weight loss and changes in insulin resistance might lead to new approaches to patient management. METHODS: Variations in circulating levels of leptin, insulin and FFAs over 24 h were studied in severely obese (body mass index over 40 kg/m(2) ) women before and 6 months after biliopancreatic diversion (BPD). Body composition was measured by dual-energy X-ray absorptiometry. A euglycaemic-hyperinsulinaemic clamp was used to assess insulin sensitivity. Levels of insulin, leptin and FFAs were measured every 20 min for 24 h. Pulsatile hormone and FFA analyses were performed. RESULTS: Among eight patients studied, insulin sensitivity more than doubled after BPD, from mean(s.d.) 39·78(7·74) to 96·66(27·01) mmol per kg fat-free mass per min, under plasma insulin concentrations of 102·29(9·60) and 93·61(9·95) µunits/ml respectively. The secretory patterns of leptin were significantly different from random but not statistically different before and after BPD, with the exception of the pulse height which was reduced after surgery. Both plasma insulin and FFA levels were significantly higher throughout the study day before BPD. Based on Granger statistical modelling, lowering of daily FFA levels was linked to decreased circulating leptin concentrations, which in turn were related to the lowering of daily insulin excursions. Multiple regression analysis indicated that FFA level was the only predictor of leptin level. CONCLUSION: Lowering of circulating levels of FFAs after BPD may be responsible for the reduction in leptin secretion, which in turn can decrease circulating insulin levels. Surgical relevance Insulin resistance is a common feature of obesity and type II diabetes. These patients are also relatively insensitive to the biological effects of leptin, a satiety hormone produced mainly in subcutaneous fat. Biliopancreatic diversion, a malabsorptive bariatric operation that drastically reduces circulating lipid levels, improves insulin resistance independently of weight loss. The mechanism of action, however, has still to be elucidated. This study demonstrated that normalization of insulin sensitivity after bariatric surgery was associated with a reduction in 24-h free fatty acid concentrations and changes in the pattern of leptin peaks in plasma. Bariatric surgery improves the metabolic dysfunction of obesity, and this may be through a reduction in circulating free fatty acids and modification of leptin metabolism.

Diagnostic, therapeutic and healthcare management protocols in parathyroid surgery: II Consensus Conference of the Italian Association of Endocrine Surgery Units (U.E.C. CLUB).

AIM: To update the Diagnostic-Therapeutic-Healthcare Protocol (Protocollo Diagnostico-Terapeutico-Assistenziale, PDTA) created by the U.E.C. CLUB (Association of the Italian Endocrine Surgery Units) during the I Consensus Conference in 2008. METHODS: In the preliminary phase, the II Consensus involved a selected group of experts; the elaboration phase was conducted via e-mail among all members; the conclusion phase took place during the X National Congress of the U.E.C. CLUB. The following were examined: diagnostic pathway and clinical evaluation; mode of admission and waiting time; therapeutic pathway (patient preparation for surgery, surgical treatment, postoperative management, management of major complications); hospital discharge and patient information; outpatient care and follow-up. CONCLUSIONS: The PDTA for parathyroid surgery approved by the II Consensus Conference (June 2013) is the official PDTA of the U.E.C. CLUB.

Ethical and medico-legal issues of TOETVA procedure and simulation on cadavers: a scoping review.

Conventional open thyroidectomy is still considered the gold standard for thyroid surgery. Transoral endoscopic thyroidectomy vestibular approach (also known as TOETVA) is often considered to be more advantageous than the other approaches, such as minimally invasive video assisted thyroidectomy, thyroidectomy via breast/axillary/retroauricular access, bilateral axillo-breast approach and axillo-bilateral breast approach. In this scoping review, we discuss the risks and the benefits of this surgical approach and its medico-legal and ethical implications, particularly focusing on the importance of practice on cadavers. Currently, there is little scientific evidence supporting TOETVA, since there are few papers on the comparison with the traditional open thyroidectomy that have been published and thus little data on the long-term outcomes of TOETVA are available. Since the better cosmetic outcome currently represents the main indication for this surgical technique, substantial medico-legal and ethical issues arise. Moreover, practice on cadavers can help surgeons to develop the technical and non-technical skills required to perform efficiently and safely this new surgical procedure.

Suspect carbon dioxide embolism during retroperitoneoscopic adrenalectomy.

During a retroperitoneoscopic adrenalectomy in the prone position, a sudden increase in end-Tidal CO2 (EtCO2) (from 42 to 68 mmHg) followed by an abrupt decrease (from 68 to 35 mmHg) was observed, concomitantly with a right adrenal vein laceration. Heart rate decreased to 30 bpm, and the systolic blood pressure decreased to 40 mmHg. The patient was slightly turned in the left lateral and Trendelenburg position and vasoactive drugs were administered. The systemic blood pressure, EtCO2, CO2 elimination (VCO2) and pulse oximetry (SpO2) progressively improved within 10 minutes and, at the end of the surgery, the blood pressure recovered from hypotension. ECG returned to normal, with sinusal rhythm and heart rate approximately 70 bpm. The patient was extubated and moved to the Intensive Care Unit (ICU). This case suggests that gas embolisms may occur during retroperitoneoscopic adrenalectomy, and acute changes in EtCO2 should alert the clinicians to these rare but potentially lethal complication. EtCO2 monitoring is essential during laparoscopy, as it may help an early detection of CO2 embolism, characterized by a transient and rapid increase in EtCO2, followed by an abrupt decrease.

Modulating the extension of thyroidectomy in patients with papillary thyroid carcinoma pre-operatively eligible for lobectomy: reliability of ipsilateral central neck dissection.

PURPOSE: Pre-operative work-up and macroscopic intraoperative inspection could overlook occult central neck nodal metastases in patients with papillary thyroid carcinoma (PTC). An occult N1a status is able to change the initial risk stratification in small, clinically unifocal PTC potentially scheduled for thyroid lobectomy (TL) making total thyroidectomy (TT) the preferable option. We aimed to verified the reliability of an intraoperative management protocol based on frozen section examination (FSE) of ipsilateral central neck nodes (IpsiCND) to identify, among patients scheduled for TL, those who could benefit of a more extensive surgical resection (TT plus bilateral central neck dissection -CND-). METHODS: Thirty PTC patients preoperatively classified as T1N0 underwent TL plus IpsiCND-FSE (TL-group). In case of positive FSE, TT plus bilateral CND was accomplished during the same surgical procedure. A comparative analysis was performed between TL-group and a control group (C-group), who underwent TT plus IpsiCND-FSE, matched by a propensity score analysis. RESULTS: Nodal metastases (>2 mm) were found at final histology in 5/30 patients in the TL-group and in 6/30 in the C-group (p = 1.00). Micrometastases (≤2 mm) were retrieved in 5/30 TL-group patients and in 4/30 C-group patients (p = 1.00). Final histology staged as pN1a 10 (33.3%) patients for each group. FSE correctly identified five patients with occult nodal metastases >2 mm (16.6%) in TL-group, who underwent TT plus bilateral CND during the same surgical procedure. No permanent complications occurred. At a mean follow-up of 22.2 months, no local and/or nodal recurrence were observed. CONCLUSIONS: Intraoperative assessment of N status obtained with IpsiCND plus FSE allows for an accurate risk stratification. IpsiCND plus FSE real time modulated thyroidectomy seems a safe and effective surgical strategy reducing the need of a subsequent completion surgery and, theoretically, the risk of local recurrence.

Combined molecular and mathematical analysis of long noncoding RNAs expression in fine needle aspiration biopsies as novel tool for early diagnosis of thyroid cancer.

PURPOSE: In presence of indeterminate lesions by fine needle aspiration (FNA), thyroid cancer cannot always be easily diagnosed by conventional cytology. As a consequence, unnecessary removal of thyroid gland is performed in patients without cancer based on the lack of optimized diagnostic criteria. Aim of this study is identifying a molecular profile based on long noncoding RNAs (lncRNAs) expression capable to discriminate between benign and malignant nodules. METHODS: Patients were subjected to surgery (n = 19) for cytologic suspicious thyroid nodules or to FNA biopsy (n = 135) for thyroid nodules suspicious at ultrasound. Three thyroid-specific genes (TG, TPO, and NIS), six cancer-associated lncRNAs (MALAT1, NEAT1, HOTAIR, H19, PVT1, MEG3), and two housekeeping genes (GAPDH and P0) were analyzed using Droplet Digital PCR (ddPCR). RESULTS: Based on higher co-expression in malignant (n = 11) but not in benign (n = 8) nodules after surgery, MALAT1, PVT1 and HOTAIR were selected as putative cancer biomarkers to analyze 135 FNA samples. Cytological and histopathological data from a subset of FNA patients (n = 34) were used to define a predictive algorithm based on a Naïve Bayes classifier using co-expression of MALAT1, PVT1, HOTAIR, and cytological class. This classifier exhibited a significant separation capability between malignant and benign nodules (P < 0.0001) as well as both rule in and rule out test potential with an accuracy of 94.12% and a negative predictive value (NPV) of 100% and a positive predictive value (PPV) of 91.67%. CONCLUSIONS: ddPCR analysis of selected lncRNAs in FNA biopsies appears a suitable molecular tool with the potential of improving diagnostic accuracy.

[Diagnostic, therapeutic and healthcare management protocols in thyroid surgery. 2nd Consensus Conference (U.E.C. CLUB)]. / Protocolli Gestionali Diagnostico-Terapeutico-Assistenziali in Chirurgia Tiroidea. 2 feminine Consensus Conference.

AIM: To review and to update the management protocols in thyroid surgery proposed two years ago by 1st Consensus Conference called on the topic by the Italian Association of Endocrine Surgery Units (UEC Club). METHOD: The 2nd Consensus Conference took place November 30, 2008 in Pisa within the framework of the 7th National Congress of the UEC Club. A selected board of endocrinologists and endocrine surgeons (chairmans: Paolo Miccoli and Aldo Pinchera; speaker: Lodovico Rosato) examined the individual chapters and submitted the consensus text for the approval of several experts. This plain and concise text provides the rationale of the thyroid patient management and wants to be the most complete possible tool for the physicians and other professionals in the field. CONCLUSIONS: The diagnostic, therapeutic and healthcare management protocols in thyroid surgery approved by the 2nd Consensus Conference are officially those proposed by the Italian Association of Endocrine Surgery Units (UEC Club) and are subject to review by two years.

Synchronous bilateral adrenalectomy in ACTH-dependent hypercortisolism: predictors, biomarkers and outcomes.

INTRODUCTION: Hypercortisolism requires a prompt therapeutic management to reduce the risk of development of a potential fatal emergency. A synchronous bilateral adrenalectomy (SBA) is effective in recovering hypercortisolism. However, specific indications for an SBA are not available. We aimed to evaluate the outcome of patients who underwent an SBA and to identify biomarkers able to predict the requirements of an SBA. PATIENTS AND METHODS: A mono-centric and longitudinal study was conducted on 19 consecutive patients who underwent SBA for ACTH-dependent hypercortisolism between December 2003 and December 2017. This study population was compared to two control groups composed of patients cured after the resection of the ACTH secreting pituitary adenoma (Group A: 44 patients) and of the ACTH-secreting neuroendocrine tumours (Group B: 8 patients). RESULTS: Short- or long-term SBA complications or the recurrence of hypercortisolism did not occur. A single patient experienced Nelson syndrome. Clinical features after SBA showed improvement in the glico-metabolic assessment, hypertension, bone metabolism and the occurrence of hypokalaemia and infections. The younger the age at the time of Cushing's disease diagnosis, the longer the duration of active hypercortisolism, higher values of plasmatic ACTH and Cortisol (1 month after pituitary neurosurgery) and higher values of Ki67 in pituitary adenomas were detected in this study population as compared to Group A. CONCLUSIONS: SBA is an effective and safe treatment for patients with unmanageable ACTH-dependent hypercortisolism. A multidisciplinary team in a referral centre with a high volume of patients is strongly recommended for the management of these patients and the identification of patients, for better surgical timing.

[Diagnostic, therapeutic and healthcare management protocols in parathyroid surgery. 1st Consensus Conference]. / Protocolli Gestionali Diagnostico-Terapeutico-Assistenziali in Chirurgia Paratiroidea. 1 feminine Consensus Conference.

AIM: The aim of the study was to draw up a management protocol in parathyroid surgery promoted by the Italian Association of Endocrine Surgery Units (UEC Club), based on the guidelines of the main international scientific societies and shared by the experts and applied by the operators in the sector. METHODS AND CONSENSUS: The management protocols, already presented in 2003, on the occasion of the current review were examined by the 1st Consensus Conference called on the topic by the Italian Association of Endocrine Surgery Units (UEC). The Conference comprised two distinct sessions, the first in November 2006 within the framework of the 5th National Congress of the UEC Club in Verona, and the second in September 2007 within the framework of the 10th Multidisciplinary Scanno Prize Meeting. A selected board of endocrinologists and endocrine surgeons examined the individual chapters and submitted the consensus text for the approval of several experts. CONCLUSIONS: The diagnostic, therapeutic and healthcare management protocols in parathyroid surgery approved by the 1st Consensus Conference are officially those proposed by the Italian Association of Endocrine Surgery Units (UEC Club) and are subject to review by October, 2009.

Intensive lifestyle modifications with or without liraglutide 3mg vs. sleeve gastrectomy: A three-arm non-randomised, controlled, pilot study.

BACKGROUND/OBJECTIVES: As only 1% of clinically eligible subjects choose to undergo surgical treatment for obesity, other options should be investigated. This study aimed to assess the effects of intensive lifestyle modification (ILM) with or without 3-mg liraglutide daily vs. sleeve gastrectomy (SG) on BMI after 1 year. SUBJECTS/METHODS: In this study performed at an Italian university hospital, non-diabetic patients eligible for bariatric surgery were recruited from a weight-loss clinic and had the option to choose from three possible weight-loss programmes up to an allocation of 25 subjects in each arm matched by BMI and age. ILM consisted in 813kcal of a very low-calorie diet (VLCD) for 1 month, followed by a diet of 12kcal/kg body weight of high protein and high fat for 11 months plus 30min of brisk walking daily and at least 3h of aerobic exercise weekly. SG patients followed a VLCD for 1 month and a free diet thereafter. Patients were evaluated at baseline and at 1, 3, 6, 9 and 12 months. RESULTS: A total of 75 patients were enrolled; retention was 100% in the SG and 85% in the two medical arms. SG reduced BMI by 32% (P<0.001 vs. medical arm), while ILM+liraglutide and ILM led to BMI reductions of 24% and 14%, respectively (P<0.001). More women allocated themselves to the ILM+liraglutide group. Weight loss was 43kg with SG, 26kg with ILM+liraglutide and 15kg with ILM alone. Lean body mass reductions were -11.6kg with SG, -6.3kg with ILM and -8.3kg with ILM+liraglutide. Prevalence of prediabetes was significantly lower with ILM+liraglutide, and insulin resistance was reduced by about 70% by both ILM+liraglutide and SG vs. 39% by ILM alone. Cardiometabolic risk factors were greatly reduced in all three groups. DISCUSSION: At least in the short-term, liraglutide 3.0mg once daily associated with drastic calorie-intake restriction and intensive physical activity promoted a 24% weight loss, which was almost two times greater than ILM alone and only about 25% less than with SG, while preserving lean body mass. Although this study was non-randomised, it was designed to explore the efficacy of medical treatments for obesity in everyday clinical practice.

Evaluation of the surgical completeness after total thyroidectomy for differentiated thyroid carcinoma.

BACKGROUND: To quantify the rate of patients without thyroid remnants, to identify predictive factors for the absence of residual thyroid tissue and to evaluate number, site, size and function of thyroid remnants after total thyroidectomy for differentiated thyroid carcinoma (DTC). METHODS: Thousand one hundred and seventy-eight patients who underwent total thyroidectomy for DTC were evaluated; 343 patients with lymph node or distant metastases and 115 patients with detectable thyroglobulin autoantibodies (TgAb) were excluded. (131)I ablative treatment (RAI) without preliminary diagnostic (131)I whole body scans (DxWBS), and 24-h (131)I quantitative neck uptake (RAIU test) and thyroglobulin (Tg) off L-T4 evaluation were performed in the remaining 720 pts. In 252 patients a 99mTc-pertechnetate pre-operative thyroid scan (99mTc-scan) was used for comparison with (131)I neck scans after RAI to evaluate site of thyroid remnants. Only patients with thyroid remnants were evaluated for successful ablation 6-10 months after RAI. RESULTS: Post-treatment whole body scan (TxWBS) demonstrated lack of thyroid remnants in 50/720 patients and the best predictive factors for the absence of residual thyroid tissue were RAIU <1% and undetectable Tg off L-T4. Thyroid remnants were present in 670/720 patients. In 252 patients with (99m)Tc-scan, 617 sites of functioning thyroid tissue were found: 381 within and 236 outside the thyroid bed. Complete successful ablation was achieved in 610/670 patients with thyroid remnants. CONCLUSIONS: This study confirms that most patients (93.1%) have thyroid remnant after total thyroidectomy for DTC. Most thyroid remnants were contralateral to tumour site and were even observed outside thyroid bed. However, a real total thyroidectomy, demonstrated by negative TxWBS, RAIU <1% and undetectable Tg off L-T4, was achieved in 6.9% of patients.

[Complications in thyroid surgery]. / Complicanze in chirurgia tiroidea.

Thyroidectomy is one of the most frequently performed surgical procedure worldwide, even if the risks of lethal postoperative complications prevented its evolution and diffusion until the beginning of the XX century. At that time, T. Kocher described his meticulous technique, reporting excellent results in terms of mortality and morbidity. At present, mortality for this procedure approaches 0% and overall complication rate is less than 3%. Nonetheless, major complications of thyroidectomy (i.e. compressive hematoma, recurrent laryngeal nerve palsy and hypoparathyroidism) are still fearful complications and account for a significant percentage of medico-legal claims. Patients volume and surgical skill play an important role in reducing the risk of complications. Accurate knowledge of anatomy and pathophysiology, complications incidence and pathogenesis and a careful surgical performance are essential. In this review, post-thyroidectomy complications basing on literature analysis and personal experience are described. The main anatomical, technical and pathophysiological factors that help preventing post-thyroidectomy complications are analyzed, taking into proper account new technologies and the minimally invasive surgical procedures that influenced thyroid surgery during the last decade.

Gene expression profiling of adrenal cortical tumors by cDNA macroarray analysis. Results of a preliminary study.

Adrenocortical carcinoma (ACC) are highly malignant tumors with poor prognosis. To verify if it is possible to assess their differential gene expression by a cDNA macroarray analysis using RNA extracted from paraffin sections, we analyzed two different cohorts of adrenal cortical adenoma (ACA) and ACC. Paraffin sections of seven ACC and seven ACA were analyzed. Transcriptional profiles were generated by commercially available c-DNA arrays testing 82 genes. Hybridization signals were quantified by densitometry and the intensity signal was compared for each gene between ACA and ACC cohorts. RNA was successfully extracted in only four out of 14 cases. Four genes displayed a significantly different expression (ACC/ACA ratio>1.5 or<0.6). Heat shock protein 60 (HSP-60) (ratio>2), Ciclin D1 and topoisomerase I (ratio>1.5) were overexpressed in the ACC cohort, while jun proto-oncogene was down-regulated. cDNA macroarray analysis from paraffin sections of adrenal tumors is feasible, despite with a low success rate. The different expression of HSP-60, Ciclin D1, jun proto-oncogene and topoisomerase I indicates that these genes may play a role in ACC pathogenesis and could represent potential diagnostic/prognostic/therapeutic target markers. Larger series of patients are necessary to confirm the biologic, diagnostic, prognostic and therapeutic implications of these findings.