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Menopause is a natural phase in a woman’s aging process defined as the absence of menstrual periods for 12 consecutive months with no further pathological or physiological causes. With “Genitourinary syndrome of menopause (GSM)” we usually describe the collection of symptoms resulting from changes to the internal and external genitalia and lower urinary tract. The most common symptoms are vaginal dryness, itching, irritation, and dyspareunia. GSM may have a significant impact on quality of life and sexual function of women affected. The aim of this review is to make a brief reflection about the use of ultralow-concentration estriol vaginal gel in the treatment of GSM symptoms and its impact on sexuality and quality of life of the patients.

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.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.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.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).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.

Restorative proctocolectomy with ileal pouch-anal anastomosis has been accepted as the surgical treatment of choice for most patients with ulcerative colitis. The occurrence of adenocarcinoma arising near or into the ileal pouch is rare. Only 19 such cases have been reported so far. The authors report a case of a 67-year old male who developed an adenocarcinoma in the small rectal stump 12 years after a restorative proctocolectomy with double stapled ileal pouch-low rectal anastomosis for ulcerative colitis unresponsive to medical treatment. They, after a literature review, examine same steps of the procedure and emphasize the importance of regular and prolonged follow-up for all patients having restorative proctocolectomy for ulcerative colitis.

Intraoperative parathyroid hormone (iPTH) assay (QPTH) in combination with preoperative localization, permits a less invasive operative approach in the treatment of hyperparathyroidism. A 50% reduction of the intraoperative PTH level, mesured within 15 minutes with an immunochemestry system of III generation (ICMA), shows the completeness of the hypersecretive tissues surgical removal.From June 2003 to December 2005 a series of 39 patients underwent target parathyroidectomy with intraoperative parathyroid hormone assay for parathyroid disease. Intraoperative PTH was measured before, 5-10 and 20 minutes after parathyroidectomy. 79.5% of patients had secondary hyperparathyroidism, 29.5% had primary disease. In 38 patients (97,4%) the intraoperative PTH levels declined more than 70% and in only one patient (2,6%) intraoperative PTH levels declined less than 50%.QPTH has deeply modified the surgical approach to the treatment of hyperparathyroidism. Intraoperative measurement of iPTH is useful in prediction the complete removal of all parathyroid tissue after surgery for parathyroid disease, thus avoiding persistence or recurrence of disease and surgical failures. In well-studied cases QPTH can be considered a valid alternative to the intraoperative hystological examination.

Primary adenocarcinoma of the appendix is a rare malignancy that constitutes less than 0.5% of all gastrointestinal neoplasms. Usually the diagnosis is made only after histological examination of surgically removed inflamed appendix. Alternatively represent an unexpected finding, confirmed by frozen section, during surgery performed for acute appendicitis or other non appendiceal pathologies. Natural history is strongly influenced by anatomic peculiarities of the appendix that predispose to early spread and perforation. Frequently is associated with synchronous and metachronous colorectal or extraintestinal cancers. The correct management is the right hemicolectomy as a primary procedure in the case of preoperatively or intraoperatively diagnosis or as secondary procedure, after two-three weeks from appendectomy, when the microscopic examination of specimen reveals the presence of adenocarcinoma. Right hemicolectomy is the best treatment for all histologic types (colonic, mucinous, adenocarcinoid), in presence of perforation and even in Dukes A tumors. A careful intraoperative search for synchronous lesions and a life-long program of surveillance for the detection of early stage metachronous carcinomas are recommended. The Authors report a case of primary adenocarcinoma of the appendix occurred in a 78 year-old female patient, diagnosed incidentally during surgery performed for ileus from suspected cecal neoplasm.

The Authors report a case of strangulated paraesophageal hiatal hernia occurred in a elderly woman and treated with laparoscopic approach. After review of the literature regard on this uncommon pathology that present about 5% of the hiatal hernias, they emphasize that the laparoscopic approach is appropriated even in emergency and comprises complete reduction of the stomach in abdomen, control of suitable position of the distal esophagus and cardias and making of effective hiatus-plasty.

Only 5-10% of colorectal cancer patients (pts) with liver metastases are eligible for surgical resection. Regional and systemic chemotherapy represents the best therapeutic options for unresectable metastases.In a randomized phase II trial 123 pts were enrolled with a minimum follow-up of 3 years. In Arm A 58 pts were submitted to intraarterial continuous infusion of cisplatin (CDDP), 24 mg/m2/day, while the other 65 were included in Arm B (bolus of CDDP, 24 mg/m2/day). All the pts were also given i.v. escalating doses of fluorouracil. Response was evaluated after a minimum of 3 cycles.Toxicityor = G3 was lower in Arm B. The objective response rate was 52% in all the series, the complete responses being 17.3% (17.6% vs. 17% in Arms A and B, respectively). The overall median survival was 18 months rising to 28 months in the responders.CDDP HAI provided similar results as FUdR in terms of response to treatment. Moreover, long-term survivors were unexpectedly observed.

Myotonic dystrophy (MD) is an autosomal dominant inherit disease, slowly progressive, involving multiple organ systems. Disorders at any level of the gastrointestinal tract are relatively common and manifest as disturbances in motility, such as impaired esophageal transport, delayed gastric emptying, and megacolon. A 51 years-old man was admitted to our surgical department with obstructive symptoms. Diagnostic evaluation showed megacolon and the typical clinical features of the MD, such as weakness, myotonia, frontal baldness and testicular atrophy. Risk of perforation and dehydration led to emergency total colectomy with ileorectal stapled anastomosis. The patient didn't suffer for compliance related to surgical treatment but, after 1 month in intensive care, died of pneumonia and myocardial infarct. The overall frequency of perioperative complications in patients with MD ranges from 8.2 to 42.9%. The risk of perioperative pulmonary complications is particularly high. Thus, we believe that the conservative treatment of motility disorders of the bowel in patients with MD is to be justified and that surgical treatment should be reserved, as last resort, performing a early diagnosis and careful monitoring during perioperative period.

The Authors report an alternative technique for ileo-anal anastomosis in total proctocolectomy with ileal pouch. Their experience and results are discussed.

The goal of this study was to evaluate the complication rate of reoperative thyroid surgery and to find out the way to minimize the morbidity associated with it. We reviewed our experience in 622 patients, who underwent thyroid operation from January 2000 to September 2007. Among these ones, 76 were the patients who underwent reoperative thyroid surgery. Prior surgery in the 76 reoperations was: nucleo-resection in 9 pts (12.9%), lobectomy in 43 pts (55.5%), lobectomy+isthmectomy in 7 pts (9.3%), subtotal thyroidectomy in 17 pts (22.2%). Histologic examination revealed: benign lesions in 67 pts (88.15%), papillary cancer in 4 pts (5.26%), follicular cancer in 2 pts (2.63%), follicular adenoma in 1 pt (1.32%) and Hashimoto thyroiditis in 2 pts (2.63%). Complications included: section of recurrent laryngeal nerve, that was reconstructed in the same operation, and bilateral palsy of the recurrent laryngeal nerve so that was necessary to make a tracheotomy. One of the patient at the first thyroid surgery had monolateral palsy of the recurrent laryngeal nerve with dyspnoea and dysphonia. Temporary hypoparathyroidism (Ca8 mg/dl) occurred in 47.3% of the patients, who underwent reoperative thyroid surgery and in 45.2% of the patients, who underwent prior thyroid surgery. Conclusions. This study documents that reoperative thyroid surgery can be performed with little morbidity to the patient if precise operative rules are respected.

The peritoneal mesothelioma (PM) is a rare, benign or malignant, primary tumour, arising from the peritoneal membrane. The most frequent histological form is the malignant one with an incidence of 2-2.6 new cases per million per year. The symptomatology is insidious and poses difficult problems in the diagnosis and the treatment. Instrumental diagnostic investigations are useful only in the diagnostic orientation. Only the pathologic examination allows to distinguish a peritoneal carcinomatosis from PM. The prognosis of MPM is pour. An intense multimodal therapy, combining surgery with CT and RT, increases the survival rates in the patients with MPM. It has been proposed that hernia of abdominal wall play a role in the pathogenesis of this tumor. We believe that hypothesis seems unlikely considering the enormous discrepancy between the incidence of hernial pathology and PM.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Surgery remains the elective treatment. We retrospectively compared two group of patients, who underwent surgery for GIST before and after Imatinib advent in order to analyze the recurrence and survival rate.Two patient groups who underwent surgery for GIST, from January 1997 to December 2002 (Pre-Imatinib group) and from January 2003 to December 2008 (Post-Imatinib group) were compared. Patients were evaluated on the base of gender, age, clinical manifestations, primary location and metastasis positivity, tumor size, mitotic index, immunoreactivity for CD117 and the outcome, including date of death.In the Pre-IM group only one patient died for prostate cancer, 12 months after operation, the other died because of GIST with a 24.6 months of median survival rate (range 15-51). In the remaining 12 patients the median follow up period was 55 months (range 6-152 months). In the Post-IM group the mean follow up was 50.7 months (range 26-74) and they are still being assessed for oncological as well as surgical treatment.Early diagnosis and radical resection remain the standard of cure for GISTs. To date, the use of Imatinib lead to its utilization as adjuvant and neo-adjuvant therapy in adults. Our experience suggests that there is a correlation between the mutational status of KIT and clinical outcome. These aspects should be explored for targeted therapy that can effectively combine biological therapy to surgery.

Hepatic metastases represent one of major clinical problems in patients affected by solid tumours because liver is the first site of metastatic disease after lymph nodes, (1, 2). The most common origins among adults are from colon and rectum cancer followed by pancreas (adenocarcinoma or neuroendocrine), lung and breast (3-7). It is estimated that in 15-20% of patients affected by adenocarcinoma of colon-rectum liver metastases are present at the time of diagnosis (8-11), while in 40% of cases they will develop during the follow-up (10, 11). Liver metastases are the first determinant for survival (1, 3, 12-17), and both hepatic and extrahepatic involvement have a statistical significant impact on it (3, 14, 18-21). Prognosis of patients affected by untreated disease is very poor, being 5 to 14 months with rare 2-year survivors and a 5-year survival rate of 0% (10, 21-24). In half of all patients affected by colorectal cancer and undergoing to a radical surgery, disease will fail in the liver (8, 25-28); among patients dying for colorectal cancer, 60-70% have a liver involvement (9, 29), and in 20-25% liver is the only site of recurrence and death results from liver failure (3, 29-31). In Autoptic studies those rates increased up to 83% and 38% respectively (1, 10, 17, 32).

The Authors, on the basis of their experience with neoplastic colorectal pathology and after a review of the Literature, report a reappraisal of the problems related to colorectal multiple carcinomas. They emphasize the importance of routine preoperative pancolonoscopy for the identification of possible synchronous tumors (both benign and malignant) and periodic endoscopic follow-up (ideally a life-long one) for the detection and removal of all adenomatous polyps as well as early stage metachronous carcinomas, especially for patients with HNPCC. Besides, they stress the importance of sensibilization of the population about the heritability of colorectal carcinomas.

CD28 is an important co-stimulatory receptor for T lymphocytes that, in humans, delivers TCR-independent signal leading to the up-regulation of pro-inflammatory cytokines. We have recently reported that CD28 autonomous signaling induces the expression of IL-17A in peripheral CD4+ T lymphocytes from healthy donors, multiple sclerosis, and type 1 diabetes patients. Due to the relevance of IL-17A in the pathophysiology of several inflammatory and autoimmune diseases, we characterized the mechanisms and signaling mediators responsible for CD28-induced IL-17A expression. Here we show that CD28-mediated up-regulation of IL-17A gene expression depends on RelA/NF-κB and IL-6-associated STAT3 transcriptions factors. In particular, we found that CD28-activated RelA/NF-κB induces the expression of IL-6 that, in a positive feedback loop, mediates the activation and nuclear translocation of tyrosine phosphorylated STAT3 (pSTAT3). pSTAT3 in turn cooperates with RelA/NF-κB by binding specific sequences within the proximal promoter of human IL-17A gene, thus inducing its expression. Finally, by using specific inhibitory drugs, we also identified class 1A phosphatidylinositol 3-kinase (PI3K) as a critical upstream regulator of CD28-mediated RelA/NF-κB and STAT3 recruitments and trans-activation of IL-17A promoter. Our findings reveal a novel mechanism by which human CD28 may amplify IL-17A expression in human T lymphocytes and provide biological bases for immunotherapeutic approaches targeting CD28-associated class 1A PI3K to dampen IL-17A-mediated inflammatory response in autoimmune/inflammatory disorders.

In this contribution, we present a non-conventional core-shell nanoparticle, named supersphere, for implementing optical devices whose performances cannot be easily achieved with conventional nanoparticles. Superspheres are solids with intermediate shape between a sphere and a cube, whose external boundaries are described by Lamè surface equation. Thanks to its particular shape, a core-shell supersphere resonates at a lower resonant frequency with respect to a conventional core-shell spherical nanoparticle with same electrical dimensions. Such a characteristic allows relaxing the fabrication constrains, i.e. extremely thin shells, typically required for making the conventional spherical core-shell nanoparticles to operate in the lowest region of the visible spectrum. Here, after having discussed the geometry and electrical response of a core-shell supersphere, we report some preliminary results on their successful employment in the implementation of three optical devices: a trasparent screen, a biosensor and a mantle cloak.

Functional and morphological studies in children affected by Attention Deficit Hyperactivity Disorder (ADHD) suggest a prefrontal cortex (PFc) dysfunction. This cortical region is regulated by subcortical systems including noradrenergic (NEergic), dopaminergic (DAergic), cholinergic, serotonergic, and histaminergic pathways. A wealth of data in humans and in animal models demonstrates altered dopamine (DA) regulation. Drugs that modulate norepinephrine (NE) transmission are also effective in ADHD patients, thus leading to the hypothesis of a NEergic disorder. This review covers the regulation of PFc functions by NE and the interaction between the NE and DA systems, as suggested by pharmacological, electrophysiological, morphological, and gene knock out (KO) studies. A negative feedback between NE and DA neurons emerges from KO studies because KO mice showing increased (NE transporter (NET) KO) or decreased (DBH and VMAT2 KO) NE levels are respectively associated with lower and higher DA levels. Locomotor activity can be generally predicted by the DA level, whereas sensitivity to amphetamines is by NE/DA balance. Some animal models of ADHD, such as spontaneously hypertensive rats (SHR), show alterations in the PFc and in the DA system. Evidence about a correlation between the NE system and hyper-locomotion activity in such animals has not yet been clarified. Therefore, this review also includes recent evidence on the behavioral effects of two NET blockers, reboxetine and atomoxetine, in two animal models of ADHD: SHR and Naples High Excitability rats. As these drugs modulate the DA level in the PFc, certain effects are likely to be due to a rebalanced DA system. We discuss the significance of the results for theories of ADHD and make suggestions for future experimentation.

Despite anticonvulsant efficacy in animal models of generalized epilepsy, levetiracetam was not effective in the maximal subcutaneous PTZ model in mice and rats. Aim of this study was to assess the efficacy of levetiracetam (LEV) against submaximal, s.c. MET test (PTZ at the dose of 70 mg/kg) acute seizures in Wistar rats, in comparison to valproic acid (VPA). Thirty male Wistar rats (P42) were divided in three drug-treatment groups (10 rats in each group) as follows: valproic acid, levetiracetam, and controls. All animals were tested for seizure threshold at age P50. VPA (110 mg/kg) and LEV (108 mg/kg) were freshly dissolved in saline and injected i.p. in 2-3 ml/kg, 15 and 30 min, respectively, before pentylenetetrazol (PTZ) injection at the dose of 70 mg/kg. The average latency of the seizure type 3 (generalized clonic seizure with loss of righting reflexes) significantly differed between controls and the drug-treated animal groups (p < or = 0.02). The average duration of the seizure type 2 (threshold seizure) was significantly longer in both groups compared to controls (