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.

[Reoperations in hyperparathyroidism]. / I reinterventi nell'iperparatiroidismo.

Reoperative parathyroidectomy (PTx) is challenging for the surgeon. Before reintervention it is essential to evaluate the operative notes and pathology reports from the previous operation, the localization exams (sestaMIBI scintigraphy and ultrasound) and IOPTH assay are also essential. The surgeon is supposed to perfectly know the anatomy and embryology of parathyroid glands and experience with parathyroid surgery is still the most important predictor of success in reoperative PTx. Reinterventions in HPT have good results with a resolution of hyperparathyroidism in 85-90% for primary HPT and in 70% for secondary and tertiary HPT. Authors present their experience of 76 reinterventions after HPT I and 85 reinterventions after HPT II and III over a total of 2072 parathyroidectomies, carried out between January 1975 and October 2009.

The diagnostic accuracy of the immunocytochemical markers in the pre-operative evaluation of follicular thyroid lesions.

UNLABELLED: Aim of the study was to consider the diagnostic accuracy of galectine-3 (GAL3) in the pre-operative cytological evaluation of follicular lesions. MATERIALS AND METHODS: We retrospectively evaluated 100 patients suffering from thyroid nodular disease submitted to thyroidectomy from 2006 to 2007 in our Institution. Before surgery all patients underwent fine needle aspiration biopsy. The immunocytochemical analysis was performed on fine needle aspiration specimens using species-specific monoclonal antibodies and a biotin-free detection system. Based on preoperative cytological reports, 40 patients had pre-operative malignant results, and 60 patients (46 females and 14 males) showed follicular lesions. The sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of GAL3 was evaluated. STATISTICAL ANALYSIS: Chi-square test was used to compare frequencies of GAL3 expression between the different hystopathological groups. RESULTS: GAL3 proved to have 55% sensitivity, 100% specificity, 70% negative predictive value, and 78% diagnostic accuracy. The GAL3 expression in neoplastic and benign lesions was significantly different (GAL3+ in 16 out of 29 neoplastic lesions, GAL3+ 0 out of 31 benign lesions, p<0.01). Even comparing the GAL3 positivity between the follicular adenomas (0 GAL3+ out of 20) and the group of follicular carcinomas (5 GAL3+ out of 6), we found a statistically significant difference (p<0.01). CONCLUSIONS: Based on the data from our experience, the patients with a cytological diagnosis of GAL3 positive follicular neoformation should be referred for surgery without any further immunocytological testing.

[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.

[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.

Giant fibrovascular polyp of the esophagus.

Giant fibrovascular polyps are uncommon benign esophageal tumors almost always originating from the cervical esophagus, frequently from the upper esophageal sphincter. The case of a 74-year-old man with a long history of dysphagia and a weight loss of 9 kg is presented. Neither barium esophagogram, computed tomogram or magnetic resonance imaging correctly evidenced the lesion. Only fiberoptic endoscopy suggested the correct diagnosis because the mass fluctuated endoluminally with the spasm of vomiting. A left cervical exploratory incision with esophagotomy was performed following the experience of two previous similar cases. A giant fibrovascular polyp was observed and excised. If a malignant or benign extensive intramural tumor had been identified, a total esophagectomy would have been performed. In our opinion the possibility of the presence of a fibrovascular polyp should always be considered in the presence of an undetermined esophageal mass, and in these cases a left cervical incision is the preferred surgical access. Once the correct diagnosis is established, a major esophageal resection should always be avoided.

[The choice of surgical therapy in adenocarcinoma of the cardia]. / La scelta della terapia chirurgica nell'adenocarcinoma del cardias.

AIM: From 1996 the adenocarcinoma of the esophago-gastric junction (AEG) is divided into 3 types according to Siewert's classification. For AEG type I and III the surgical treatment is codified, while for type II is still controversial. The aim of our study is to understand what is the better surgical treatment for AEG type II. METHODS: From 1990 to 2002 we have performed 111 resections for adenocarcinoma of the cardia: 25 for AEG type I (all esophago-gastric resection), 39 for type II (22 esophago-gastric resection, 17 extended total gastrectomy with esophageal resection) and 47 for type III (8 esophago-gastric resection, 39 extended total gastrectomy with esophageal resection). RESULTS: The morbidity and mortality rates are 17 and 5.4%, without significant difference between the different surgical treatment (p>0.01). The 5 year survival rate is 35%. Significant prognostic factors are the staging TNM (p=0.002) and principally the presence of metastatic lymph nodes (p=0.001). For AEG type II any significant difference in survival is associated with surgical strategy, also in early stage (p>0.01). CONCLUSIONS: According to the results of our study and those of the other authors, who have showed that a 10 cm distance of the neoplasm by the gastric side and the esophageal one could assure oncologic radicality and also that metastatic lymph nodes below pylorus and near greater curvature are uncommon, we can consider esophago-gastric resection for AEG II a speedy, safe and oncologically correct surgical treatment.

Acute hyperparathyroidism: our experience with 36 cases.

OBJECTIVES: Acute hypercalcemia is a serious condition and represents a physician-surgical emergency: the difficulty in setting a precise diagnosis is due to several possibilities that can cause the condition. It is our purpose to critically evaluate the most actual schemes of treatment and the conditions that could favour the appearance of a hypercalcemic acute crisis. MATERIALS AND METHODS: A retrospective study was performed considering 1321 patients (638 primary HPT, 683 secondary or tertiary HPT) operated from 1975 to December 2002 for Primary, Secondary and Tertiary HPT. RESULTS: It should be noticed that out of 638 cases of Primary HPT this syndrome was present in 35 patients (Ca higher than 15 mg/dl): if you compare these cases with the hyperparathyroid population with calcium less than 15 mg/dl it is possible to observe that a double adenoma or a carcinoma were more frequently found in acute HPT, as the cystic appearance of the lesion. The weight of the adenoma and the PTH assay are strictly correlated with the appearance of this syndrome. The mortality rate is also higher (2.8% to 0.1%) than in the hyperparathyroid patient who underwent parathyroidectomy without hypercalcemic crisis. CONCLUSION: These characteristics suggest that an early operation is mandatory in the patients in whom such a possibility could be expected, before serious involvement of the cardiovascular, renal or neuromuscular system. We can point out the rarity of this syndrome in Secondary and Tertiary HPT: just one case in Secondary out of 683 patients operated on from 1975 until December 2002.

[Adenocarcinoma of the cardia: surgical strategies compared]. / Adenocarcinoma del cardias: strategie chirurgiche a confronto.

BACKGROUND: The incidence of adenocarcinoma of the cardia is increasing. The choice of surgical strategy for AEG type II of Siewert classification is the subjects of controversial discussion. The aim of our retrospective study is to analyse the surgical results in 12 years. MATERIAL AND METHODS: Since 1990 to 2002, 111 patients underwent resection for adenocarcinoma of the cardia at III Division of General Surgery, University of Turin. Twenty-five patients had AEG type I, 39 had type II and 47 type III. Transthoracic or transhiatal oesophagectomy with resection of the proximal stomach were performed in 55 cases and extended total gastrectomy with transthoracic or transhiatal oesophagectomy in 56. RESULTS: The morbidity and mortality rates are 17% and 5.4%. The 5 years survival rate is poor (35%) for all Siewert type. Survival is significantly associated with stage and the presence of lymph node metastasis, but not correlated with Siewert classification and surgical approach. Also in the AEG II the survival is not modified by the surgical approach. CONCLUSION: In patient with AEG I the therapy of choice is a radical transthoracic or transhiatal oesophagectomy with resection of the proximal stomach. For type III extended total gastrectomy with transthoracic or transhiatal oesophagectomy is the procedure of choice. The superiority of the thoracoabdominal approach is therefore evident in terms of oncologic radicality. Survival is similar in AEG type II patients for both operations. A oesophagectomy with proximal gastric resection should be adopted for these tumors as the standard procedure in the majority of cases.

[Surgical treatment of secondary and tertiary hyperparathyroidism]. / Il trattamento chirurgico dell'iperparatiroidismo secondario e terziario.

AIMS: To determine whether, in secondary and tertiary hyperparathyroidism (HPT), quick parathyroid hormone (PTH) assay can be used to prevent persistent or recurrent HPT. Another point was to determine, considering the PTH decrease, the cut-off point at which the operation could be considered well performed. METHODS: A retrospective study was performed evaluating all cases operated on since 1975 until 2002, 679 patients, and particularly the analysis of two groups of patients that underwent surgical treatment for secondary and tertiary HPT in the period 1995-2002. In the first group, (January 1995-October 1999) 207 (167 HPT II and 40 HPT III) neck explorations were performed without the aid of quick PTH assay; in the second group (November 1999-December 2002), 192 (153 HPT II and 39 HPT III) patients were operated on with blood samples for quick PTH. RESULTS: In the first group the percentage of success for secondary HPT was 93.8 versus 96.2 of the second group and 91.7 versus 94.2 for tertiary HPT. In reoperations the percentage of success was 72.7 in the first group and 87.5 in the second one. CONCLUSIONS: There are no substantial differences in persistences or recurrences between subtotal or total parathyroidectomy (PTx) with autotransplantation (AT). The choice of the gland to be left in the neck or transplanted in the forearm and the modalities of doing so are very important, considering the macroscopical and histological aspects. Intraoperative PTH monitoring is a useful aid during the first cervical exploration for secondary and tertiary HPT to prevent the development of persistent or recurrent HPT. The cut-off point for secondary HPT is 70% (in difficult cases with more than 2 assays, 75%) and for tertiary HPT 50% and 70% respectively.

Secondary and tertiary hyperparathyroidism: causes of recurrent disease after 446 parathyroidectomies.

OBJECTIVE: To determine, in a series of patients with secondary and tertiary parathyroid hyperplasia, whether the type of parathyroidectomy (subtotal, total with autotransplantation, or total), the histologic pattern of the parathyroid tissue, or the proliferative index, as determined by Ki-67 analysis, could predispose patients to recurrent hyperparathyroidism. SUMMARY BACKGROUND DATA: Recurrent hyperparathyroidism appears in 10--70% of the patients undergoing surgery for secondary or tertiary hyperparathyroidism. The incidence could be related to the type of operation (Rothmund) but also depends on the histologic pattern of the glands removed (Niederle). METHODS: The retrospective investigation was performed on 446 patients undergoing parathyroid surgery. They were also studied in relation to the possibility of renal transplantation. In this population, two homogeneous groups were subsequently identified (23 patients with clear signs of recurrence and 27 patients apparently cured); they were studied from the histologic and immunohistochemical point of view using antibody to Ki-67 antigen. RESULTS: Subtotal parathyroidectomy, total parathyroidectomy with autotransplantation, and total parathyroidectomy produced similar results when considering the regression of osteodystrophy, pruritus, and ectopic calcification. As one could anticipate, total parathyroidectomy increased the incidence of hypoparathyroidism. The percentage of recurrence was 5% to 8% after subtotal parathyroidectomy, total parathyroidectomy with autotransplantation, and total parathyroidectomy, and only after incomplete parathyroidectomy did this percentage climb to 34.7%. In the recurrence group, the nodular form was more common and the proliferative fraction detected by Ki-67 was 1.9%; it was 0.81% in the control group. CONCLUSIONS: Because more radical procedures were not more effective, the authors favor a less radical procedure such as subtotal parathyroidectomy. Histologic patterns and proliferative fraction could be useful indices of a recurrence, and these patients should be watched closely after surgery.

AgNOR quantity as a prognostic tool in hyperplastic and neoplastic parathyroid glands.

Prediction of evolution of secondary hyperplasia and tumours of the parathyroid glands is still a problem in histopathology. To assess whether the quantity of silver-stained nucleolar organiser region (AgNOR) proteins might be used as a prognostic tool in parathyroid pathology, a standardised AgNOR analysis has been performed on 19 cases of parathyroid hyperplasia caused by secondary hyperparathyroidism (PH), 8 cases of adenoma (PA) and 10 cases of carcinoma (PC). Clinico-pathological data and follow-up information were available. On formalin-fixed and paraffin-embedded sections, the visualisation and quantification of AgNORs were achieved according to the 1995 guidelines of the Committee on AgNOR Quantification. Then, the mean area (square micrometres) of AgNORs per nucleus (NORA) was evaluated by means of an image analyser and specific softwares. After testing the normal distribution of NORA values, statistical parametric tests were utilised; Kaplan-Meier and Cox multivariate analyses were also performed. In parathyroid lesions, a progressive increase of mean NORA values was observed from PH (2.895 microm2; SE 0.171) through PA (3.638 microm2; SE 0.125) to PC (4.701 microm2; SE 0.179); these differences were highly significant (P<0.001), although some degree of overlap was found among single NORA values. A significantly higher mean NORA value was revealed in PC with distant metastases than was noted in cases with no current clinical evidence of disease progression. Furthermore, a significantly (P<0.001) higher mean NORA value was encountered in the group of PH with recurrences (3.600 microm2; SE 0.106) than in nonrecurrent PH (2.261 microm2; SE 0.087). Multivariate analyses indicated that the NORA value was an independent prognostic parameter determining the risk of recurrence in PH. We suggest that AgNOR quantity may be a promising additional tool for predicting the biological behaviour of parathyroid lesions.

Optimizing efficacy of quick parathyroid hormone determination in the operating theater.

The usefulness of intraoperative parathyroid hormone (PTH) monitoring has been extensively documented in primary hyperparathyroidism (HPT), whereas few data have been published on its use in reoperations or in secondary and tertiary HPT. We report our initial experience with a rapid (12 min response) PTH immunochemiluminometric assay performed in the operating room during surgery in 12 patients with primary HPT, 16 end-stage renal disease patients with secondary HPT and five kidney transplanted subjects with tertiary HPT. Blood samples were taken at baseline, within 10 min after resection and subsequently at various intervals whenever needed. The mean PTH levels before and after parathyroidectomy were 230.5 pg/mL (range 69-842) and 47.3 pg/mL (range 5-184), respectively, in primary HPT, 855.0 pg/mL (416-1655) and 202.2 pg/mL (53-440) in secondary HPT, and 205.6 pg/mL (116-301) and 45.4 pg/mL (18-97) in tertiary HPT. All patients but one had a significant percentage decline from pre-excision values (mean 76.9%, 76.0%, and 76.1% in primary, secondary and tertiary HPT, respectively). While a reduction of more than 50% was observed in 30 out of 33 patients after the first intraoperative sampling, additional measurements were performed in 10 cases. On-site PTH monitoring with this user-friendly and reliable system has proved helpful in targeting PTH tests to give the surgeon a rapid and accurate assessment of the intervention. The development of optimal PTH sequence strategies with decision-focused analytical and clinical limits will improve the efficacy of "point-of-care" PTH assay and resource utilization.

Problems in reconstructive surgery in the treatment of carcinoma of the hypopharyngoesophageal junction.

BACKGROUND AND OBJECTIVES: Thirty percent of carcinomas of the pyriform sinus manifest generally with infiltrations in the cervical esophagus. In recent years, progress in reconstructive surgery has broadened surgical indications to include tumors previously managed with palliative measures alone. In some cases, radical surgery has been extended to creating safer resection margins, with more and more indications for circular pharyngectomy. Lesions involving the hypopharyngoesophageal junction pose particular problems; furthermore, the high rate of synchronous or metachronous tumors warrants the indication for total esophagectomy, which requires complex reconstructive techniques. METHODS: We report on a series of 21 patients who underwent pharyngocoloplasties after receiving total pharyngolaryngoesophagectomy. RESULTS: With regard to the oncologic results, after a follow-up of 2-60 months, 9 patients had no evidence of disease, 5 patients died during the postoperative course, 2 patients survived with disease, 4 died with disease, 1 died from metachronous breast carcinoma, and 7 underwent reintervention. CONCLUSIONS: In cases in which reconstruction by gastric pull-up is considered risky, if not contraindicated, pharyngocoloplasty represents a particularly reliable treatment option. The limits and advantages of the technique are discussed. The procedure permitted us to reconstruct the digestive tract, without encountering problems any more serious than those a normal gastric pull-up procedure would pose.

Calcium blood level modulates endogenous nitric oxide action: effects of parathroidectomy in patients with hyperparathyroidism.

UNLABELLED: Platelet cyclic guanosine monophosphate (cGMP) is produced by soluble guanylate cyclase (sGC), the activity of which is modulated by the activity of nitric oxide (NO) constitutive synthase (cNOS) which, in turn, is activated by a calcium/calmodulin complex. In primary hyperparathyroidism (H-PTH) an increase in platelet free calcium levels is present. In this study we evaluate the platelet cGMP levels, as an expression of NO production, in the presence of 3-isobutyl-1-methylxanthine (IBMX) alone (IBMXcGMP) and after stimulation by ionomycine (IONO; IONOcGMP) and sodium nitroprusside (SNP; SNPcGMP), in eight subjects affected by H-PTH before and after removal of adenoma. Platelet cGMP levels were also measured in seven normal subjects. IBMXcGMP and IONOcGMP were elevated in H-PTH patients compared with normal subjects (1.9 +/- 0.3 vs 0.8 +/- 0.2 fmol/10(6) platelets and 2.7 +/- 0.4 vs 1.4 +/- 0.3; P < 0.02 and P < 0.05 respectively) but SNPcGMP was unaffected (3.9 +/- 0.6 vs 2.5 +/- 0.5). After parathyroidectomy, blood levels of intact parathyroid hormone (i-PTH), total calcium (t-Ca), IBMXcGMP and IONOcGMP all decreased (177.5 +/- 23.9 vs 45.0 +/- 8.8 pg/ml, P < 0.005; 6.5 +/- 0.5 vs 4.6 +/- 0.1 mEq/1, P < 0.005; 1.9 +/- 0.3 vs 0.8 +/- 0.2, P < 0.005; 2.7 +/- 0.4 vs 1.8 +/ 0.3, P < 0.05 respectively), while SNPcGMP was not modified (3.9 +/- 0.6 vs 4.3 +/- 0.9). t-Ca and i-PTH were directly correlated with IBMXcGMP (P < 0.02, rs = 0.613; P < 0.02, rs = 0.576 respectively) and i-PTH was also correlated with t-Ca (P < 0.001), rs = 0.840). IN CONCLUSION: (1) levels of IBMXcGMP and IONOcGMP are high in subjects with H-PTH; (2) after surgery both IBMXcGMP and IONOcGMP decrease to normal values. As IBMXcGMP expresses basal cGMP and IONOcGMP expresses the cGMP after cNOS stimulation, it can be speculated that the increase in NO production could be a mechanism to downregulate the vasoconstriction which may be caused by the high calcium levels in smooth muscle cells. After surgery, together with the normalization of calcium levels, NO production also returned to normal values.