Molecular subtypes and differentiation programmes of glioma stem cells as determinants of extracellular vesicle profiles and endothelial cell-stimulating activities.

We have previously uncovered the impact of oncogenic and differentiation processes on extracellular vesicles (EVs) in cancer. This is of interested in the context of glioma stem cells (GSC) that are responsible for recurrent nature of glioblastoma multiforme (GBM), while retaining the potential to undergo differentiation and self renewal.  GSCs reside in vascular niches where they interact with endothelial cells through a number of mediators including bioactive cargo of EVs. GSCs can be classified as proneural (PN) or mesenchymal (MES) subtypes on the basis of their gene expression profiles and distinct biological characteristics. In the present study we investigated how GSC diversity and differentiation programmes influence their EV-mediated communication potentials. Indeed, molecular subtypes of GBMs and GSCs differ with respect to their expression of EV-related genes (vesiculome) and GSCs with PN or MES phenotypes produce EVs with markedly different characteristics, marker profiles, proteomes and endothelial stimulating activities. For example, while EVs of PN GSC are largely devoid of exosomal markers their counterparts from MES GSCs express ample CD9, CD63 and CD81 tetraspanins. In both GSC subtypes serum-induced differentiation results in profound, but distinct changes of cellular phenotypes including the enhanced EV production, reconfiguration of their proteomes and the related functional pathways. Notably, the EV uptake was a function of both subtype and differentiation state of donor cells. Thus, while, EVs produced by differentiated MES GSCs were internalized less efficiently than those from undifferentiated cells they exhibited an increased stimulatory potential for human brain endothelial cells. Such stimulating activity was also observed for EVs derived from differentiated PN GSCs, despite their even weaker uptake by endothelial cells. These findings suggest that the role of EVs as biological mediators and biomarkers in GBM may depend on the molecular subtype and functional state of donor cancer cells, including cancer stem cells. Abbreviations: CryoTEM: cryo-transmission electron microscopy; DIFF: differentiated GSCs; EGF: epidermal growth factor; DUC: differential ultracentrifugation; EV: extracellular vesicle; FGF: fibroblast growth factor; GBM: glioblastoma multiforme; GFAP: glial fibrillary acidic protein; GO: gene ontology; GSC: glioma stem cells; HBEC-5i: human brain endothelial cells; MES: mesenchymal cells; MTS - [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt; PMT1: proneural-to-mesenchyman transition cell line 1; PN: proneural cells; TEM: transmission electron microscopy; WB: western blotting.

Cervical Lymph Node Metastases of Papillary Thyroid Carcinoma, in the Central and Lateral Compartments, in Children and Adolescents: Predictive Factors.

PROBLEM STATEMENT: The aim of our study was to identify predictive factors for lymph node metastases (LNM) in children and adolescents with papillary thyroid carcinoma (PTC) and their impact on survival. METHODS: The authors conducted an Italian multicentric retrospective analysis on 132 pediatric patients (0-18 years old) affected by PTC between 2000 and 2014. The investigated variables were demographic characteristics of the patients, clinicopathological features of PTCs, and persistence/recurrence of disease. The female/male ratio was 3.1:1. The median age was 14.3 ± 3.5 years (range 4-18 years). Total thyroidectomy was performed in all the patients, followed by lymph node dissection in 87 patients (65.9%). Metastatic lymph node involvement was confirmed in 73 patients (55.3%): lateral compartment (LC) in 25 patients (34.2%), central compartment (CC) in 17 patients (23.3%), and both compartments in 31 patients (42.5%). RESULTS: Multifocality (P < .00), vascular invasion (P = .04), infiltration of the thyroid capsule (P < .00), minimal extrathyroidal extension (P < .00), diffuse sclerosing variant of PTC (P = .02), and presence of LNM in the LC (P < .00) were significantly associated with LNM in CC. Infiltration of the thyroid capsule (P < .00), massive extrathyroidal extension (P = .03), distant metastases (P = .02), PTC, not otherwise specified (P < .00), and presence of LNM in the CC (P < .00) were significantly associated with LNM in LC. Age, sex and size of PTC were not correlated with the presence of cervical LNM. Moreover, presence of LNM in CC increases the risk of persistence (P < .01) and recurrence (P < .02) of PTC in children and adolescents. CONCLUSIONS: Most predictors, unfortunately, are only identified post-operatively by histopathologic examination: Just a small part of them can be pre-operatively detected with a low-sensitivity neck ultrasonography. In PTC patients with pre-operative predictors, we suggest an accurate pre- and intra-operative evaluation of CC and/or LC to find suspicious lymph nodes. The presence of LNM in CC has an impact on disease/progression/relapse-free survival. We suggest performing RAI therapy and an accurate follow-up for pediatric patients with only post-operative predictors.

Variation by stage in the effects of prediagnosis weight loss on mortality in a prospective cohort of esophageal cancer patients.

Cancer cachexia is increasingly recognized as a poor prognostic marker for various tumor types. Weight loss in esophageal cancer is multifactorial, as patients with bulky tumors also have reduced ability to eat. We aimed to investigate the relationship between prediagnosis weight loss and mortality in esophageal cancer and to determine whether these associations vary with tumor stage. We conducted a prospective cohort study of esophageal cancer patients at two tertiary centers. We recorded baseline patient characteristics including medications, smoking, body mass index, and weight loss in the year prior to diagnosis, and collected data on treatment and outcomes. We used Cox regression modeling to determine the associations between percent weight loss and outcomes. The main outcome of interest was all-cause mortality; secondary endpoints were esophageal cancer-specific mortality and development of metastases. We enrolled 134 subjects, the majority of whom had adenocarcinoma (82.1%); median percent weight loss was 4.7% (IQR: 0%-10.9%). Increasing percent weight loss was not associated with all-cause mortality (ptrend = 0.36). However, there was evidence of significant interaction by tumor stage (p = 0.02). There was a strong and significant association between prediagnosis weight loss and mortality in patients with T stages 1 or 2 (adjusted HR 8.26 for highest versus lowest tertile, 95%CI 1.11-61.5, ptrend = 0.03) but not for T stages 3 or 4 (ptrend = 0.32). Body mass index one year prior to diagnosis was not associated with mortality. Prediagnosis weight loss was associated with increased all-cause mortality only in patients with early stage esophageal cancer. This suggests that tumor-related cachexia can occur early in esophageal cancer and represents a poor prognostic marker.

Motor phenotype is not associated with vascular dysfunction in symptomatic Huntington's disease transgenic R6/2 (160 CAG) mice.

Whereas Huntington's disease (HD) is unequivocally a neurological disorder, a critical mass of emerging studies highlights the occurrence of peripheral pathology like cardiovascular defects in both animal models and humans. The overt impairment in cardiac function is normally expected to be associated with peripheral vascular dysfunction, however whether this assumption is reasonable or not in HD is still unknown. In this study we functionally characterized the vascular system in R6/2 mouse model (line 160 CAG), which recapitulates several features of human pathology including cardiac disease. Vascular reactivity in different arterial districts was determined by wire myography in symptomatic R6/2 mice and age-matched wild type (WT) littermates. Disease stage was assessed by using well-validated behavioural tests like rotarod and horizontal ladder task. Surprisingly, no signs of vascular dysfunction were detectable in symptomatic mice and no link with motor phenotype was found.

Surgical management of papillary thyroid carcinoma in childhood and adolescence: an Italian multicenter study on 250 patients.

PURPOSE: The extent of surgery for pediatric papillary thyroid carcinoma is debatable. The aim of this study was to evaluate the feasibility of offering pediatric patients a tailored surgical approach based on certain clinical features. METHODS: A national multicenter retrospective review of 250 pediatric patients treated for papillary thyroid carcinoma in a 14-year period was performed. Outcomes of interest included tumor-related features, type of surgery, surgical morbidity, disease-free and overall survival rates. Recurrence was thoroughly analyzed with particular focus on how it correlated with certain patient- and tumor-related features. RESULTS: The majority of patients (58.8 %) had tumors >2 cm in size. Nodal involvement occurred in 115/250 (46 %) patients and distant metastasis in 4 % (10/250). Total thyroidectomy and lobectomy were performed in 90.4 % (226/250) and 9.6 % (24/250) of patients, respectively. The overall rate of surgical complications was 20.8 % (52/250). These included transient and permanent hypoparathyroidism (13.6 and 4.4 %, respectively), and vocal fold palsy (2.8 %). All surgical complications occurred exclusively in the total thyroidectomy group. The rate of recurrent disease was 12 % (30/250) with the vast majority of recurrences (96.6 %) occurring in the total thyroidectomy group. The risk of recurrence correlated significantly with certain tumor-related features (size > 2 cm, multifocality, extrathyroidal invasion, nodal positivity, and distant metastasis). However, it did not correlate with the patient's age or sex. Overall survival was 100 %. CONCLUSION: Pediatric patients are likely to benefit from a tailored surgical strategy. Uniformly offering patients total thyroidectomy seems to be an overly radical approach.

Branchial cleft and pouch anomalies in childhood: a report of 50 surgical cases.

BACKGROUND AND AIMS: Branchial abnormalities occur when there is disturbance in the maturation of the branchial apparatus during fetal development. Branchial anomalies are congenital lesions usually present in childhood, even if they can be diagnosed later for enlargement or infection. A correct diagnosis will lead to proper management: complete surgical excision is the treatment of choice. The purpose of this article is to present clinical features, diagnostic methods and surgical treatment of branchial anomalies in childhood, based on a series of 50 patients. METHODS: We conducted a retrospective analysis of a total of 50 pediatric patients operated from June 2005 to June 2014 for the presence of branchial cleft anomalies. RESULTS: 27 cases (54 %) presented a second branchial cleft fistula and 11 cases (22 %) a second branchial cleft cyst and one case (2 %) presented both cyst and sinus of the second branchial cleft; four cases (8 %) presented first branchial cleft cyst whereas four cases (8 %) a first branchial cleft sinus and two cases (4 %) a first branchial cleft fistula; one case (2 %) presented a piriform sinus fistula (third branchial cleft). None of our patients presented anomalies of the fourth branchial cleft. All patients underwent surgical treatment and lesions have been removed by excision or fistulectomy. No post-surgical complication occurred. The rate of recurrence was 4 %. CONCLUSIONS: Pre-operative diagnosis supplies important information to the surgeon for a proper therapy: a complete excision of the lesion without inflammatory signs is essential to avoid re-intervention and to achieve a good outcome.

Incidental ganglioneuromas: a presentation of 14 surgical cases and literature review.

BACKGROUND AND AIMS: Ganglioneuromas are benign tumors which originate from the neural crest. This tumor affects mainly young patients rather than adult ones, and its most frequent localizations are mediastinum, retroperitoneum, adrenal glands and cervical region. Usually, ganglioneuromas are discovered as incidentalomas since they are often asymptomatic, even if they could present sympathetic or mass-related symptoms. To obtain a definitive diagnosis, histological exam is necessary since CT scan and MRI are not capable of distinguishing ganglioneuromas from other tumors, such as neuroblastomas or pheocromocytomas. The surgical excision is the chosen treatment and it offers an excellent prognosis. METHODS: We conducted a retrospective analysis of our cases of ganglioneuroma from 2004 to 2014; this study aims to compare our experience with literature review (2000-2014). Data about patients' features, tumor localization, symptoms, treatment and follow-up were analyzed and reported in detailed tables. RESULTS: Between 2004 and 2014 we treated 14 patients affected by ganglioneuroma. For all of them the diagnosis was incidental; 9 out of 12 (64.3 %) patients presented an adrenal mass; in 2 patients (14.3 %) the tumor was localized in cervical region; in other 2 patients (14.3 %) the tumor was in the retroperitoneum and one patient (7.1 %) presented a ganglioneuroma in the costo-vertebral space. All our patients underwent surgical removal and none of them present surgery-related complications or recurrences to date. CONCLUSIONS: Our data widen the knowledge about ganglioneuroma and confirm that the surgical approach has an excellent prognosis with very low incidence of surgery-related complications and recurrences.

A congenital anterior urethrocutaneous fistula in a boy whose mother was exposed to ionizing radiations: case report and literature review.

Anterior congenital urethrocutaneous fistula is a rare anomaly that may present in an isolated fashion or in association with other anomalies of the genital urinary tract or anorectal malformations. A case of congenital anterior urethrocutaneous fistula nonassociated with other congenital anomalies in a 3-year-old male whose mother has been exposed to Chernobyl's nuclear fallout is described. The patient was successfully operated with no recurrence. We report a review of the literature about etiology and surgical strategy including the role of ionizing radiations. The congenital anterior urethrocutaneous fistula represents a rare malformation. The etiopathogenesis is unknown.

Primary retroperitoneal müllerian adenocarcinoma: a case report and literature review.

Primary retroperitoneal müllerian adenocarcinoma (PRMA) is an extremely rare clinical entity. We report the case of a 54-year-old woman who presented with a mass in the right lower retroperitoneum, identified during an ultrasound exam. Computed tomography confirmed a retroperitoneal mass measuring 11 cm. The patient underwent laparotomy and the mass was completely excised. The histopathological exam revealed PRMA.

Minimally-invasive surgery in paediatric oncology: proposal of recommendations.

The Authors report a proposal of recommendations concerning Minimally Invasive Surgery (MIS) in Paediatric Oncology. Since the exact role of MIS in Paediatric Oncology is still not completely defined, a restrict panel of Italian Paediatric Surgeons, some interested in Oncologic Surgery, others in MIS, prepared a schematic document, mainly founded on literature data, to provide Paediatric Surgeons with recommendations useful to approach paediatric tumours with MIS. The final draft was approved by the Italian Group of Paediatric Oncologic Surgeons. The Authors summarize the feasibility of MIS, when performed with different purposes (biopsy / resection) and timing (initial / delayed surgery) for the most common solid tumours in children. The oncologic criteria must be always followed with MIS as well as with "open" surgery.

Hemorrhagic corpus luteum cysts: an unusual problem for pediatric surgeons.

STUDY OBJECTIVE: Hemorrhagic corpus luteum cysts (HCLC) constitute a common disorder in pediatric subjects undergoing surgical intervention. HCLCs especially develop in the early period after menarche, and they are commonly associated with dysfunctional ovulation. DESIGN: Retrospective analysis of surgery outcome of HCLC patients. SETTING: Pediatric Surgery Unit, S. Chiara University Hospital. PARTICIPANT: 13 girls with HCLC diagnosis. INTERVENTIONS: Surgical treatment of HCLCs. MAIN OUTCOME MEASURES: We reviewed the clinical presentation and outcome of 13 post-menarcheal girls surgically treated for HCLCs in the Pediatric Surgical Unit from 2002 to 2006. RESULTS: Primary presentation was persistent abdominal pain in 84.6% and acute abdominal pain in 15.4% of patients, respectively. Ultrasound examination showed complex ovarian masses in 77.23% cases and simple ovarian masses in 33.7% cases, respectively. Although laparoscopic excision of HCLC was performed in more than 45% cases, laparotomic approach was commonly required. After conservative surgery, ovarian size and viability were normal, as assessed by 6-month ultrasound scan. No recurrences of disease and regular menses were reported at 2 years follow-up. CONCLUSIONS: In pediatric subjects with HCLC that required surgical intervention, no complications or disorder recurrence were reported. In order to preserve ovarian function, conservative surgery has to be performed whenever feasible.

Functional ovarian lesions in children and adolescents: when to remove them.

STUDY OBJECTIVE: Functional ovarian lesions represent 45% of all pediatric adnexal abnormalities. Their surgical management, even if frequent, is not clear, especially in pediatric age. MATERIALS AND METHODS: We retrospectively reviewed 22 pediatric patients surgically treated for functional ovarian lesions from 2000 to 2006. The following characteristics were analysed: age, size of the lesion, ultrasound (US) aspect and clinical presentation. RESULTS: The average age was 16.1 years of age (range: 6 months-18 years). Of the 22 functional lesions, 12 (55%) were follicular cysts and 10 (45%) corpus luteum ones. The average size was 6.7 cm (range: 5.1-33 cm). US scan showed simple lesions in 10 cases (45%) and complex ones in 12 cases (55%). In 16 girls (72.8%) the presenting symptom was abdominal pain while 2 patients (9%) presented abdominal distention. In the other 4 patients (16.2%) the lesion was found accidentally during US examination. CONCLUSION: In pediatric subjects, functional ovarian cysts rarely required surgical intervention, though no complications or disorder recurrence were reported. To preserve ovarian function, conservative surgery has to be performed whenever feasible.

[Update of the Italian Society of Nephrology Project No. 1 of the 2004-2006 SIN programme]. / Update sul progetto SIN n. 1 del programma SIN 2004-2006: qualità e accreditamento delle strutture di nefrologia, dialisi e trapianto.

In the last few years the Italian Society of Nephrology has addressed many technical-scientific and management aspects to better patient satisfaction. Project No. 1 of the 2004-2006 programme on 'Quality and Accreditation of National Renal Units' focuses on four essential points. The first is the questionnaire mailed to all the Presidents and Regional Delegates on the relationship between Nephrology units, Local Government Health-System and the Regional Healthcare Agency. The results evidence that the 'political' decision-making power of nephrologists decreases in the absence of a national strategy. The second point, in collaboration with the National Census Group, includes the quality analysis and the standardization of resources (human and structural) and management of the Renal Units. The third point is based on 'Educational Courses for Quality and Accreditation' held in Rome (3-5 October 2005: L'Accreditamento all'Eccellenza dell'Unita' Operativa di Nefrologia, Dialisi e Trapianto; 17-19 October 2005: Il Manuale di Accreditamento della Specialità di Nefrologia). The courses aim at training members responsible for each region to hold courses in their specific region to create a network including each single Renal Unit to create an acceptable homogenous language on the models of analysis and on the correct use of 'The Guide for Excellence Accreditation'. The fourth point concerns both the on-line Guide for Excellence Accreditation and 'Peer Review Accreditation' and the NEQUASY (Nephrology Quality System) project. The manual must be 'user friendly' allowing each Centre to self-evaluate using national and regional standards.

Vascular endothelial growth factor (VEGF) and other common tissue prognostic indicators in breast cancer: a case-control study.

VEGF is a specific mitogen and survival factor for endothelial cells and a key promoter of angiogenesis in physiological and pathological conditions. Nevertheless, VEGF tissue evaluation in cancer patients as a prognostic factor compared to the conventional histological and biological parameters is still controversial. In this case-control study, tissue VEGF was retrospectively determined by immunohistochemistry and related to T, N, ER, PgR, c-erbB-2, p53, MIB-1 and cyclin D1 in 129 breast cancer patients. Seventy-four of these patients had developed distant metastases postoperatively. The remaining 55 patients had remained disease-free >10 years after surgery. In 17 (13%) of the 129 patients (six with distant metastases and eleven disease-free) tissue and plasma VEGF were concomitantly evaluated. In univariate analysis no significant differences in VEGF and tumor size were found between metastatic and disease-free patients, whereas there were significant differences in N, ER, PgR, c-erbB-2, p53, MIB-1 and cyclin D1 (p ranging from 0.001 to 0.0001). In multivariate analysis VEGF showed less significance than N, ER, c-erbB-2, MIB-1 and cyclin D1 (p = 0.012, p = 0.007, p = 0.005, p = 0.005, p = 0.002 and p = 0.001, respectively). VEGF was a significant unfavorable prognostic indicator only in the N+ subset (p = 0.015), while ER (p = 0.05 and p = 0.021) and MIB-1 (p = 0.031 and p = 0.022) were significant in both the N+ and N- subgroups. In multivariate analysis in the 74 metastatic cases VEGF did not show any significance in relation to disease-free interval and overall survival from the time of mastectomy and from the time of relapse, whereas N and PgR did (p ranging from 0.018 to 0.001). In conclusion, tissue VEGF does not seem a suitable candidate to replace conventional histological and other common biological prognostic factors in breast cancer.

[Collaborative study on peritoneal dialysis (PD) as first dialysis treatment in an Italian region: 1994-2000]. / Studio collaborativo sulla dialisi peritoneale (DP) come primo trattamento nel Lazio: 1994-2000.

BACKGROUND: In Lazio, only about 5% of uremic patients are on peritoneal dialysis (PD). The present study focuses on the parameters of PD selection, the treatment schedules, and the clinical outcomes of PD patients in the nine public facilities offering a PD program. A cohort of 249 first-time PD patients, from July 1, 1994 to December 31, 2000, was retrospectively considered. METHODS: For the enrollment of the patients, the Regional Dialysis Registry databank was consulted. On December 31, 2000, a systematic review of patient charts was performed to extract the reasons for the PD choice, details of PD schedule, peritonitis episodes, reasons for drop-out, and patient survival rates. In regard to technique success-defined as the probability of having a patient alive on PD-change of modality and death were considered as final events. In regard to patient survival, only death, even in the first 2 months after a shift to hemodialysis, was considered the end point. RESULT: The main PD selection reasons were patient and/or nephrologist preference in 90% of cases. One-hundred eighty-nine patients (76%) had been started on CAPD. During the follow-up, 38.2% dialysis schedules had been modified at least once. At the end of follow-up, 41.2% patients were on APD. The peritonitis rate was one episode per 30 patient-months (1 per 27 patient-months in CAPD; 1 per 37 patient-months in APD; p = 0.08). The technique success rate was 66.3% after 2 years and 49.8% after 3 years. The patient survival rate was 81.1% after 2 years and 68.7% after 3 years. CONCLUSIONS: Patients chose PD as a first dialysis treatment mainly because of reasons unrelated to their clinical status. The technique's success, patient mortality rates, and the peritonitis rate do not explain the low PD diffusion in the region. The peritonitis rate meets the target criteria for excellence recommended by the Italian Society of Nephrology. The observed outcomes may have been favored by the selection of motivated patients and by the increased use of APD.

Muscle thickness in infants hypertrophic pyloric stenosis.

Hypertrophic pyloric stenosis (IHPS) is the most common abdominal abnormality requiring surgery in infants. It occurs due to the hypertrophic and hyperplasia of the muscular layers of the pyloric. The usual age of clinical presentation is about three weeks of life. The most important symptom is non bilious emesis, intermittent or after each feeding. From march 1996 to June 2001, 21 infants, 20 males and 1 female, were subjected to ultrasonographic, radiographic exams and after diagnosis to the pyloromyotomy extramucosa. Ultrasonography was the study of choice used to identify hypertrophic pyloric stenosis; the markers to analyse were the length and the overall diameter of the pyloric canal and the muscle thickness of the wall. The results showed that a length of the pyloric canal 20 +/- 6 mm, a diameter 13.6 +/- 2.5 mm and a muscle thickness 4.1 +/- 1 mm are diagnostics for hypertrophic pyloric stenosis.

Graves-Basedow's disease in children and adolescents: total vs subtotal thyroidectomy.

"Graves' disease" is an autoimmune pathology and is the most important cause of hyperthyroidism in children and adolescents. The treatment for this disease is controversial; there are three different options: synthetic antithyroid drugs, ablation of the thyroid gland with I 131 or surgery. Our study reports the clinical and therapeutic aspects and long-term results of 27 patients (< = 18 years old) treated with total thyroidectomy or "near-total" thyroidectomy from 1975 to August 2001. Antithyroid drugs represent the preliminary treatment of choice. For a long time in the past therapy with radioactive iodine was not recommended; now it represents an efficiently therapy with low morbility. Surgical treatment is suitable when a young patient presents a considerable enlargement of the thyroid gland or when antithyroid medical treatment does not achieve a good control of the disease, or when rapid control of hyperthyroidism is necessary. The surgical treatment can be a total thyroidectomy or a "near-total" thyroidectomy. The first is the best choice for us, because it has a low risk of relapse and a major efficacy in the ophthalmopathy.

Long-term monitoring of cell-mediated immunity in disease-free breast cancer patients: a preliminary retrospective study.

In 102 N- and 44 N+ disease-free breast cancer patients, lymphocytic populations and skin reaction of delayed hypersensitivity (SRDH) were monitored up to 266 months after mastectomy to find out whether they were similar or different from control values. In two selected groups of 34 N- and 11 N+ breast cancer patients, the whole 10 year follow-up was divided into three subintervals, each of them lasting 40 months and the time course of lymphocytic populations was evaluated. In the 102 N- patients, mean CD4+, CD8+, CD3+ values were lower (P < 0.01, P < 0.001, P < 0.01, respectively) while CD4+/CD8+ ratio was higher (P < 0.05) than in controls. Fifteen N- breast cancer patients (16%) were anergic compared to 30(32%) of controls (P < 0.05). In the 34 selected N- breast cancer patients soon after mastectomy the mean value of CD4+, CD8+, CD3+ T subpopulations was lower (P < 0.01, P < 0.001, P < 0.01, respectively) than in controls. Successively their mean value increased so that in the last subinterval they were not or were only slightly lower (P n.s., P < 0.05, P < 0.05, respectively) than in controls. In the 44 N+ patients, mean CD4+, CD8+, CD3+ values were lower (P < 0.001, v < 0.05, P < 0.01, respectively) and CD19+ lymphocytes higher (P < 0.001) than in controls. Five N+ breast cancer patients (13%) were anergic compared to 32% of controls (P < 0.05). In the 11 selected N+ breast cancer patients soon after mastectomy, the mean value of CD4+, CD8+ T subpopulations and CD16+56+ cells was significantly lower (P < 0.001, P < 0.001, P < 0.01, respectively) than in controls. Successively their mean value constantly increased so that in the last subinterval, no or slight (P n.s., P < 0.05, P n.s., respectively) significant difference compared to controls occurred. The mean CD4+/CD8+ ratio value of N- patients was significantly higher than in controls. However in the last subinterval, the significance was lower than in the first one (P < 0.05 and P < 0.01, respectively). In the N+ patients, the mean value of CD4+/CD8+ ratio was constant, although not significantly, lower than in controls; however it progressively increased from the first to the last subinterval. Therefore the significance of the difference of the mean CD4+/CD8+ ratio between N- and N+ patients strongly decreased from the first to the last subinterval (P < 0.001 and P < 0.05, respectively). These data indicate that in breast cancer patients, following mastectomy, a significant activation of memory and CD4+ T cells and long-term decrease of the circulating immunocompetent CD4+, CD8+ and CD16+56+ cells occurs. The prolonged disease-free interval observed in the 34 N- and 11 N+ breast cancer patients can be correlated with the restoration of the normal state of cell-mediated immunity.

[Video-assistive minimally invasive surgical procedures in the treatment of thyroid in children and adolescents]. / Chirurgia mini-invasiva video-assistita della tiroide nei bambini e negli adolescenti.

Minimally invasive video-assisted (MIVA) surgery of the thyroid is now widely accepted by endocrinel surgeons, especially in adult age. This report describes indications, limits, technical aspects and results of MIVA in 10 young patients (mean age 16 years, range 11-18) enrolled in a study of 213 patients (mean age 45 years, range 11-81) operated with this technique, from October 1998 to August 2001, in the Department of Surgery at the University of Pisa. Young patients were submitted to surgery: 8 lobectomies (6 for microfollicular lesions and 2 for adenomas functionally autonomous) and 2 total thyroidectomies for papillary carcinoma. No case has been converted in "open" surgery and no post-operatory complications have been observed. Elective indications of MIVA are the volume of the nodule and the istological type. This technique cannot be performed in voluminous goiters, in medullary carcinomas and in scarcely differentiated carcinomas. Minimally invasive video-assisted surgery of the thyroid, in our experience, represents a reliable technique also in pediatric age.