Angelo Filippini

Contractile response of peritubular myoid cells to prostaglandin F2alpha.

Prostaglandin (PG) F2alpha, a well known agonist of smooth muscle, is produced in the male gonad. We have investigated whether PG F2alpha stimulates seminiferous tubule contractility through direct action on peritubular myoid cells. Myoid cells from prepubertal rats were highly purified through Percoll density gradient and cultured in vitro. Stimulation with PG F2alpha was observed to induce: (i) rapid and dose-dependent production of inositol phosphates; (ii) mobilization of Ca2+ from intracellular stores and (iii) cell contraction. Moreover, at a concentration of 10 microM the agonist was found to induce immediate contractile response of peritubular tissue in freshly explanted tubular fragments from both young and adult rats; the explants were examined in whole-mount preparations and the peritubular myoid cell layer was identified by selective staining for alkaline phosphatase activity. Our observations demonstrate that myoid cells are a direct target for PG F2alpha and suggest a role of the eicosanoid in the intragonadal control of seminiferous tubule contractility.

Thyroid Imaging Reporting and Data System Score Combined with the New Italian Classification for Thyroid Cytology Improves the Clinical Management of Indeterminate Nodules

The new Italian cytological classification (2014) of thyroid nodules replaced the TIR3 category of the old classification (2007) with two subclasses, TIR3A and TIR3B, with the aim of reducing the rate of surgery for benign diseases. Moreover, thyroid imaging reporting and data system (TI-RADS) score appears to ameliorate the stratification of the malignancy risk. We evaluated whether the new Italian classification has improved diagnostic accuracy and whether its association with TI-RADS score could improve malignancy prediction. We retrospectively analyzed 70 nodules from 70 patients classified as TIR3 according to the old Italian classification who underwent surgery for histological diagnosis. Of these, 51 were available for cytological revision according to the new Italian cytological classification. Risk of malignancy was determined for TIR3A and TIR3B, TI-RADS score, and their combination. A different rate of malignancy (p = 0.0286) between TIR3A (13.04%) and TIR3B (44.44%) was observed. Also TI-RADS score is significantly (p = 0.003) associated with malignancy. By combining cytology and TI-RADS score, patients could be divided into three groups with low (8.3%), intermediate (21.4%), and high (80%) risk of malignancy. In conclusion, the new Italian cytological classification has an improved diagnostic accuracy. Interestingly, the combination of cytology and TI-RADS score offers a better stratification of the malignancy risk.

Prevention of complications during reoperative thyroid surgery.

BACKGROUND Thyroidectomy performed by an experienced surgeon is associated with a low incidence of recurrent laryngeal nerve injury and permanent hypoparathyroidism. During reoperative thyroid surgery there is a higher technical risk because detection and preservation of the recurrent laryngeal nerves and parathyroid glands are more difficult than in the primary surgery. AIM Our retrospective cohort study was to assess short- and long-term complications associated with reoperative thyroid surgery in order to suggest a technical approach to lower the morbidity rate. MATERIALS AND METHODS From January 2005 to September 2013, 745 patients underwent surgery for thyroid disease. Before surgery all patients underwent clinical examination, laboratory blood tests, hormonal assays, neck ultrasound, chest radiography and indirect laryngoscopy. Patients were followed up at 1, 3, 6 months and then annually after operation with hormonal assays, blood tests and neck ultrasound. RESULTS Eighty (10.7%) out of 745 patients (mean-age= 52.5 years; age-range 18-80) underwent reoperative surgery for recurrent thyroid disease. The primary treatments were enucleoresection (11.2%), thyroid lobectomy(56,3%), thyroid lobectomy with isthmectomy(10%) and subtotal thyroidectomy (22,5%). In the reoperative surgery group (Group Re) the transient RLN complications were 1.3% compared to 0.2% in the primary surgery group (Group P) (p= 0.51). The incidence of temporary hypocalcemia was 45% in the reoperative surgery group vs. 42.7% in the primary surgery group (p=0.72). CONCLUSIONS Reoperative surgery should be reserved to experienced surgeons. However, even in this case, when surgical maneuvers reserved for primary surgery are applied, then this surgery is associated with a low complications rate.

A Retrospective Case-Control Study Evaluating the Bowel Preparation Quality during Surveillance Colonoscopy after Colonic Resection

Purpose. Bowel preparation for surveillance endoscopy following surgery can be impaired by suboptimal bowel function. Our study compares two groups of patients in order to evaluate the influence of colorectal resection on bowel preparation. Methods. From April 2010 to December 2011, 351 patients were enrolled in our retrospective study and divided into two homogeneous arms: resection group (RG) and control group. Surgical methods were classified as left hemicolectomy, right hemicolectomy, anterior rectal resection, and double colonic resection. Bowel cleansing was evaluated by nine skilled endoscopists using the Aronchick scale. Results. Among the 161 patients of the RG, surgery was as follows: 60 left hemicolectomies (37%), 62 right hemicolectomies (38%), and 33 anterior rectal resections (20%). Unsatisfactory bowel preparation was significantly higher in resected population (44% versus 12%; P value = 0.000). No significant difference (38% versus 31%, P value = ns) was detected in the intermediate score, which represents a fair quality of bowel preparation. Conclusions. Our study highlights how patients with previous colonic resection are at high risk for a worse bowel preparation. Currently, the intestinal cleansing carried out by 4 L PEG based preparation does not seem to be sufficient to achieve the quality parameters required for the post-resection endoscopic monitoring.

New perspectives in the diagnosis of thyroid follicular lesions

Thyroid nodules are very common, affecting 19%-67% of the adult population. However, about 10% of them harbor a malignant lesion. Consequently, the first aim in their clinical evaluation is to exclude malignancy. Fine-needle aspiration cytology (FNAC) represents the main diagnostic tool for the evaluation of thyroid nodules. However, FNAC has a main diagnostic limit, namely cellular atypias of indeterminate significance, which require surgical excision and histological examination to differentiate benign from malignant lesions. Histology reports show that approximately 80% of these patients harbor a benign lesion. Therefore, in order to reduce unnecessary thyroidectomy, over the last years, the cytological classification of thyroid nodules has been revised and a number of new instrumental and molecular approaches have been proposed. In the present article, we will attempt to summarize the most recent cytological, molecular and echographic strategies to enhance the diagnostic accuracy of preoperative thyroid follicular lesions. In particular, we will discuss the new cytological classifications from the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), the British Thyroid Association-Royal College of Pathologists (PTA-RCPath) and the new Italian Society for Anatomic Pathology and Cytology (SIAPEC 2014. We will review molecular tests evaluated to ameliorate follicular lesion diagnosis as well as the clinical utility of the new echographic Thyroid Imaging Reporting and Data System (TI-RADS) score.

Bloodless surgery in geriatric surgery.

In bloodless surgery a series of measures has to be implemented to reduce the perioperative need for transfusion of whole blood or its components. Jehovahs Witness are the most representative group of patients opting for bloodless surgery as their faith follows strict believes that prohibits receiving blood. Geriatric patients requiring bloodless surgery are even more delicate and represent a challenge for surgeons. The physiological response of the over 65 year population to decreased hemoglobin level is slower and less effective than in young and adult patients. Herby we describe the perioperative protocol implemented in our surgical Department offered to geriatric Jehovahs Witness patients. Preoperative optimization of the patients is the key step in the preparation period. Intraoperative anesthetic and surgical measures are also required along with a strict postoperative follow-up. From our experience, bloodless surgery is feasible in the geriatric population as long as it is performed in specialized centers where a multidisciplinary team is prepared to specifically manage this scenario. Rigorous patients selection and preparation are mandatory.

Staples versus subcuticular closure in cervicotomy incisions

Collar transverse incision is the typical surgical access for operations on thyroid and parathyroids. The cosmetic outcome resulting from its closure is of paramount importance given its anatomical exposure. The traditional methods of closure include metal clips, subcuticular stitch and glue. In this study we evaluated the cosmetic results on 10 patients who had their cervicotomy wound closed with clips comparing it to a second group of 10 patients who had the same incision closed with subcuticular stitch. The cosmetic outcome was evaluated with a questionnaire answered by the patients, by the operating surgeon and by a surgical nurse who was blinded to the technique used. The results of the questionnaire were grossly similar with no differences in the two groups. Only two complications were recorded in the subcuticular group. Both the techniques associate to similar cosmetic outcome, and the choice between the two should be left to the surgeons personal preference.

Expression and prognostic value of the cell polarity PAR complex members in thyroid cancer

Establishment and maintenance of the apical-basal cell polarity, required for proper replication, migration, specialized functions and tissue morphogenesis, relies on three evolutionary conserved complexes: PAR, CRUMBS and SCRIBBLE. Loss of cell polarity/cohesiveness (LOP/C) is implicated in cancer progression, and members of the polarity complex have been described as either oncogenes or oncosuppressors. However, no information on their role in thyroid cancer (TC) progression is available. In the present study, we evaluated the gene expression of the PAR complex members aPKCι, PARD3α/β and PARD6α/β/γ in 95 papillary TC (PTC), compared to their normal matched tissues and in 12 anaplastic TC (ATC). The mRNA and protein levels of investigated genes were altered in the majority of PTC and ATC tissues. In PTC, univariate analysis showed that reduced expression of aPKCι, PARD3β and PARD6γ mRNAs is associated with increased tumor size, and the reduced expression of PARD3β mRNA is associated also with recurrences. Multivariate analysis demonstrated that the presence of lymph node metastasis at diagnosis and the reduced expression of PARD3β are independent risk factors for recurrences, with hazard ratio, respectively, of 8.21 (p=0.006) and 3.04 (p=0.029). The latter result was confirmed by the Kaplan-Meier analysis, which evidenced the association between decreased PARD3β mRNA levels and shorter disease-free interval. In conclusion, we demonstrated that the expression of PAR complex components is deregulated in the majority of PTC and there is a general trend towards their reduction in ATC tissues. Moreover, a prognostic value for the PARD3β gene in PTCs is suggested.

Multiple, zonal and multi-zone adenoma detection rates according to quality of cleansing during colonoscopy

Background The safety and diagnostic accuracy of colonoscopy depend on the quality of colon cleansing. The adenoma detection rate is usually used as a quality measurement score. Objective We aimed to introduce and evaluate three new parameters to determine polyps and adenomas segmental localization and their distribution in association with different bowel preparation levels during colonoscopy. We introduce the multiple adenoma detection rate (the percentage of patients with >2 adenomas diagnosed during colonoscopy), the zonal adenoma detection rate (the percentage of patients with >2 adenomas diagnosed during colonoscopy in different colon areas (rectum, sigmoid, descending, transverse, ascending and cecum colon)), and multi-zone adenoma detection rate (the percentage of patients with >2 adenomas diagnosed during colonoscopy in different colon areas with at least a segment between them with or without lesions (i.e. rectum and descending colon with or without lesions in the sigmoid)). Methods We prospectively enrolled outpatients who underwent colonoscopy from January 2013 to October 2014. The bowel preparation quality, according to the Aronchick modified scale, number and location of lesions, Paris classification and histology, were recorded. The multiple adenoma/polyp detection rate, zonal adenoma/polyp detection rate, and multi-zone adenoma/polyp detection rate were determined. Results In total, 519 consecutive patients (266/253 M/F; mean age 55.3 ± 12.8 years) were enrolled. The adenoma and polyp detection rates were 21% and 35%, respectively. Multiple adenomas were detected in 28 patients. Adenoma and polyp detection rate and new parameters were statistically significantly higher in the optimal as compared with the adequate bowel preparation. Conclusions An optimal level of bowel preparation was strongly associated not only with a higher adenoma detection rate, but also with a higher chance of detecting multiple clinically relevant lesions in adjacent or discrete segments of the colon.

Emerging Therapeutic Approaches for the Most Aggressive Epithelial Thyroid Cancers

The majority of epithelial thyroid carcinomas (TC) have a differentiated (DTC) histotype and include the papillary (PTC) and the follicular (FTC) TC which, ensuing dediffer‐ entiation, generate the aggressive poorly differentiated (PDTC) and anaplastic (ATC) TC. Although derived from the same cell type, each TC shows specific histological features, biological behavior, and degree of differentiation because of different genetic alterations. Total thyroidectomy, followed by adjuvant therapy with 131I, is the treatment of choice for most patients affected by DTC. The prognosis of DTC patients is favora‐ ble, with 10‐year survival rate of nearly 90%. However, one third of them face the morbidity of disease recurrence and TC‐related deaths. The worst outcomes are encountered in patients with PDTC and ATC. The latter, in particular, has a mean survival time of few months from the diagnosis, which is not influenced by current anticancer treatments. Following the progress made in the comprehension of the underlying molecular mechanisms deregulated in TC progression, novel therapeutic approaches have come to light. Here, we will attempt to review new targeted thera‐ pies, which are currently being exploited in preclinical and clinical studies, with tyrosine kinase inhibitors as well as with emerging inhibitors of mitotic kinases, in PDTC and ATC.