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Liver cancer is the sixth common cancer and the second leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC) accounts for ~90% of cases of liver cancer and is the fourth most common cause of cancer-related death in the world. Up to now, 4 oral multityrosine kinase inhibitors (sorafenib, lenvatinib, regorafenib and cabozantinib), 1 anti-angiogenic antibody (ramucirumab) and 5 immune checkpoint inhibitors, alone or in combination (atezolizumab in combination with bevacizumab, ipilimumab in combination with nivolumab, tremelimumab in combination with durvalumab, nivolumab and pembrolizumab in monotherapy) have been commercialized for advanced HCC patients’ treatment. The aim of this editorial is to provide an insight in current hepatocellular carcinoma systemic pharmacological treatment options.

Objective: The objective of this pilot study is to evaluate the ability of lung ultrasound to provide signs of suspicion of lung cancer in patients with respiratory symptoms related to a real-world setting. Patients and methods: This is a monocentric pilot study. All patients belonging to the Internal Medicine ward with respiratory symptoms including cough, chest pain or dyspnea were recruited. Patients with previous diagnoses of respiratory diseases were excluded. An ultrasound and chest radiography (CR) were performed by expert operator. Computed tomography was carried out in case of discrepant imaging or suspect of cancer. The gold standard was the discharge diagnosis. Results: The final diagnosis included 51 cases of lung cancer, and 386 other diagnoses, which included pneumonia, heart failure, chronic obstructive pulmonary disease (COPD), tuberculosis, pneumothorax or fibrosis/restrictive syndrome. Consolidation areas were found in 75.4% of patients diagnosed with lung cancer, in 51% of all other diseases. Single sides pleural effusion was found in 52.9% of lung cancer (4.2% in the absence of pathology vs. 25.1% other diagnoses. A significantly higher prevalence of pleural pain and lactate were observed in cancer patients (23.5% and 34.7%, respectively). A receiver operating characteristics curve (ROC) showed a high LUS accuracy for both operators (LUS-I AUROC: 0.855 [95% CI: 0.793-0.917]; p

This is an editorial on the efficacy of COVID-19 vaccines in immune system disorders and cancer.

e1299-Hepatocellular carcinoma and non-alcoholic fatty liver disease-a dangerous liaisonLiver cancer is one of the most frequent malignancies in the world, and its incidence rates are on the rise. Due to the global epidemic of metabolic syndrome, the incidence of hepatocellular carcinoma (HCC) secondary to non-alcoholic fatty liver disease (NAFLD) is increasing, contrary to viral forms. Characteristically NAFLD-related HCCs tend to occur at the earlier stages of liver disease, while often the diagnosis of neoplasia occurs later. They also affect an averagely older population, generally with a significantly higher number of co-morbidities. For these reasons, curative treatments are seldom applicable. Therefore, this work aims to illustrate the current state of knowledge on the NAFLD-related HCC and to underline the known pathogenetic mechanisms.

This work is part of Progetto Vela, a project that aims at "the promotion of health" in communities struck by natural and humanitarian emergencies. It is an initiative organized by a research group from University of Padova (FISSPA Department - Philosophy, Sociology, Pedagogy and Psychology), born in October 2011 with the goal to investigate the outcome on the interactive structure of the community of L’Aquila, meaning how it is shaping its own social reality, after the earthquake of April 6, 2009. The opening words of the article are dedicated to a theoretical reflection on how elements such as "catastrophe", "health" and "emergency" are known, which led to assume the relevance of investigating them as they are configured by the members of the community, instead of considering them as static entities. In line with these assumptions, through specific survey protocols, we researched the discourse modes that shape the "health" of L’Aquila before the earthquake, during the hours of post-earthquake emergency, today and in the future. The protocols were administered to different roles (citizens, merchants, teachers, law enforcement officers, Civil Protection operators, doctors and psychologists), in order to collect the words of all the voices of the community. The findings showed that the people of L’Aquila still see their community as "living a catastrophe" and linked to the earthquake, which pervaded, and still pervades, the community’s biography (in past, present and future perspective) with a high rate of potential social disintegration.

Background: Human exposures to bisphenol A (BPA) are widespread. The current study addresses uncertainties regarding human pharmacokinetics of BPA following dermal exposure. Objective: To examine the absorption, distribution, metabolism and excretion of BPA in humans following dermal administration. Methods: We dermally administered deuterated BPA (d6-BPA) to 10 subjects (6 men and 4 women) at a dose of 100 µg/kg over a 12-hour period and conducted blood and urine analysis from the beginning of dosing through a three- or six-day period. We present time-course serum and urine concentrations of total and unconjugated (“free”) d6-BPA and used this information to calculate terminal half-life and area under the curve. Results and Conclusions: Detectable serum levels of total d6-BPA were observed at 1.4 h after the start of dosing, and a maximum serum concentration (Cmax) of 3.26 nM was observed. Free d6-BPA was detectable in serum 2.8 h after start of dermal administration, with Cmax of 0.272 nM. Beginning at approximately seven hours and continuing to 12 h (which corresponds to cessation of exposure), the concentration of free and total serum d6-BPA plateaued. The terminal half-lives of total d6-BPA and free d6-BPA in the body were 21.4 ± 9.81 h and 17.6 ± 7.69 h, respectively. Elimination from the body was rate-limited by kinetics in the dermal compartment. Free d6-BPA was a greater percentage of the area under the curve of total serum BPA (8.81%) compared to the 0.56% observed in our previously published oral study. Recovery of total d6-BPA in urine was

A lipid-based physiologically based toxicokinetic (PBTK) model has been developed for a mixture of six polychlorinated biphenyls (PCBs) in rats. The aim of this study was to apply population Bayesian analysis to a lipid PBTK model, while incorporating an internal exposure-response model linking enzyme induction and metabolic rate. Lipid-based physiologically based toxicokinetic models are a subset of PBTK models that can simulate concentrations of highly lipophilic compounds in tissue lipids, without the need for partition coefficients. A hierarchical treatment of population metabolic parameters and a CYP450 induction model were incorporated into the lipid-based PBTK framework, and Markov-Chain Monte Carlo was applied to in vivo data. A mass balance of CYP1A and CYP2B in the liver was necessary to model PCB metabolism at high doses. The linked PBTK/induction model remained on a lipid basis and was capable of modeling PCB concentrations in multiple tissues for all dose levels and dose profiles.

Background: Basal cell carcinoma (BCC) is the most common cancer in the Caucasian population. It has a multifactorial pathogenesis, in which constitutive activation of the Sonic Hedgehog signalling (SHH) pathway (via mutations in PTCH1 or SMO genes) represents by far the most common genetic aberration. The introduction of vismodegib and sonidegib, two SHH pathway inhibitors, changed the therapeutic approach of locally advanced and metastatic BCCs. EADO's (European Association of Dermato-Oncology) new staging system refers to these as 'difficult-to-treat' BCCs., Objective: The aim was to evaluate sonidegib's effectiveness in patients affected by difficult-to-treat BCCs by using non-invasive diagnostic techniques., Methods: We retrospectively evaluated 14 patients (4 females, 10 males; mean age 77 ± 11 years) affected by difficult-to-treat BCCs treated with oral sonidegib 200 mg/day that were followed with total body videodermoscopy (V-Track, Vidix 4.0) and dynamic optical coherence tomography (D-OCT, VivoSight Dx) since May 2022. Considering the risk of rhabdomyolysis routine blood tests, especially for creatine kinase concentrations, were performed. All treated patients were inserted in the BasoCare database, which aims to offer support to patients taking sonidegib. Complete and partial responses were evaluated by the overall reduction of the number of lesions and their individual sizes. Safety was evaluated by assessing the occurrence and severity of adverse reactions., Results: Eighty per cent achieved complete clearance and 75% reduction of diameter. D-OCT scans performed at every follow-up showed concordance with clinical appearance and demonstrated reduction of hyporeflective structures, that is, islets of tumour cells and overall improvement of morphology., Conclusion: Sonidegib can be considered an effective treatment option in cases where surgery or radiotherapy would be unfeasible or has previously failed, although pigmented lesions did not show complete clearance, suggesting that there are factors other than the SHH pathway involved in tumour growth. Videodermoscopy and D-OCT were useful in the quick and seamless follow-up of lesions and added valuable information in assessing efficacy., (© 2024 European Academy of Dermatology and Venereology.)

In this review I propose to discuss the contribution that Smorti's book makes to the study of autobiographical memory, since it examines the benefits that narratives provide to understanding human experience and the ability they offer in discovering and representing uncertainty. Andrea Smorti has long been engaged in the study of memory, autobiography, storytelling and psychology, as evidenced by his numerous studies mentioned in the book. Furthermore, in exploring the more purely psychological aspects of narratives, Smorti investigates the benefits that narratives offer to individual psychological well-being. Firstly published in Italian in 2018, Andrea Smorti's (2021) "Telling to Understand" is now available for the first time to the English-speaking public., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Converging evidence indicates that the Fragile X Messenger Ribonucleoprotein (FMRP), which absent or mutated in Fragile X Syndrome (FXS), plays a role in many types of cancers. However, while FMRP roles in brain development and function have been extensively studied, its involvement in the biology of brain tumors remains largely unexplored. Here we show, in human glioblastoma (GBM) biopsies, that increased expression of FMRP directly correlates with a worse patient outcome. In contrast, reductions in FMRP correlate with a diminished tumor growth and proliferation of human GBM stem-like cells (GSCs) in vitro in a cell culture model and in vivo in mouse brain GSC xenografts. Consistently, increased FMRP levels promote GSC proliferation. To characterize the mechanism(s) by which FMRP regulates GSC proliferation, we performed GSC transcriptome analyses in GSCs expressing high levels of FMRP, and in these GSCs after knockdown of FMRP. We show that the WNT signalling is the most significantly enriched among the published FMRP target genes and genes involved in ASD. Consistently, we find that reductions in FMRP downregulate both the canonical WNT/β-Catenin and the non-canonical WNT-ERK1/2 signalling pathways, reducing the stability of several key transcription factors (i.e. β-Catenin, CREB and ETS1) previously implicated in the modulation of malignant features of glioma cells. Our findings support a key role for FMRP in GBM cancer progression, acting via regulation of WNT signalling., (© 2022. The Author(s).)

Many patients with inflammatory bowel disease (IBD) restrict dairy products to control their symptoms. The aim of the study was to investigate the prevalence of lactose intolerance assessed with hydrogen breath test (H-BT) in IBD patients in clinical remission compared to a sex, age and BMI matched control population. We further detected the prevalence of three single nucleotide polymorphisms of the lactase (LCT) gene: the lactase non persistence LCT-13910 CC (wildtype) and the intermediate phenotype LCT-22018 CT and LCT-13910 AG; finally, we assess the correlation between genotype and H-BT. A total of 54 IBD patients and 69 control who underwent clinical evaluation, H-BT and genetic test were enrolled. H-BT was positive in 64.8% IBD patients and 62.3% control ( p = 0.3). The wild-type genotype was found in 85.2% IBD patients while CT-22018, AG-13910 and CT-22018/AG-13910 polymorphisms were found in 9.3%, 1.8% and 3.7%. In the control group, the wild-type genotype, CT-22018, AG-13910 and CT-22018/AG-13910 polymorphisms were found in 87%, 5.8%, 5.8% and 1.4% of cases, respectively. Therefore, the wild-type and polymorphisms' prevalence did not differ between IBD population and control group (85.2% vs. 87%, p = 0.1) (14.8% vs. 13%, p = 0.7). The correlation between positive H-BT and genetic analysis showed that the wild-type genotype was associated with higher rate of lactose intolerance in the total population (OR 5.31, 95%CI 1.73-16.29, p = 0.003) and in the IBD (OR 7.61, 95%CI 1.36-42.7, p = 0.02). The prevalence of lactose intolerance in IBD patients did not differ from that of control. Despite suggestive symptoms, about 1/3 of IBD patients are not lactose intolerant, thus not needing "a priori" elimination diet. This may encourage a rationale and balanced dietary management in IBD.

Background: An initial epidemiological study carried out 18 years ago in Marseilles indicated that the air quality in schools was poor and that there was an association between the level of fine particulates and the occurrence of asthma in children. The aim of the present study was to evaluate the change in the prevalence of childhood asthma and allergic diseases and their link with the levels of air pollutants and other factors of potential risk., Methods: In 2016, using a questionnaire identical to the one used for the 1st survey in 1998-1999, we collected information regarding the symptoms, the diagnosis, and the potential confounding factors. We measured the main indoor and outdoor pollutants at the schools., Results: Overall, the prevalence of asthma and of allergic diseases exhibited an increasing trend in the time interval between the two studies, significant only for dry cough and pollen allergy. The level of air pollutants decreased significantly indoors. In spite of this, we found a correlation and a dose-effect relationship between the level of PM 2.5 and the prevalence of asthma. A family history of asthma and allergies, the insalubrity of the place of residence, and a non-Mediterranean diet were also associated with the risk of these diseases., Conclusion: In the time interval between the two studies, which were 18 years apart, despite a reduction in the level of air pollutants in classrooms, asthma was still related to PM 2.5 . Other potentially causative or contributing environmental factors were also related to asthma and allergies., (Copyright © 2019. Published by Elsevier Ltd.)

Purpose: The aim of this study is to present an algorithm for the evaluation of both symptomatic and asymptomatic patients., Methods: From November 2004 to May 2010, there were performed 296 operations: 245 total hip arthroplasty and 51 resurfacing arthroplasty with the ASR DePuy system. In April 2010, there was the first Medical Device Alert regarding all MoM hip replacements in the UK and in August 2010, DePuy recall started worldwide. In March 2012, we started our recall. All patients were invited to undergo clinical investigation, X-ray evaluations, and blood chrome and cobalt level determination. For a short period of time, there were performed second level exams and subsequently, we carried out MARS MRI hip study to all symptomatic patients and there was evidence of ALVAL lesions., Results: To the patients with ALVAL lesions were proposed surgical hip revision while the others frequent follow-up controls. One hundred patients underwent hip surgical revision., Conclusions: We recommend constant MoM THA patients monitoring and early revision if necessary.

Background: The choice of surgical approach for thoracic disc herniation should consider the location on the axial plane and the consistency of the herniated disc. Calcified midline disc herniations are difficult to remove with a transpedicular approach because of limitations due to blind spots; so they are usually treated via a transthoracic approach, although this entails a high risk of thoracopulmonary injuries., Methods: In this work we present two cases of calcified midline thoracic disc herniations treated with a transpedicular approach, improved by using a three-dimensional (3D) neuronavigation system to verify the extent of removal on the blind side., Results: Postoperative computed tomography (CT) scans demonstrated that this original technical innovation, in the two present cases, allowed us to reach the side opposite the disc herniation and to assess the extent of resection at the end of the procedure., Conclusions: The employment of a neuronavigation system in the transpedicular approach allowed safe and effective removal of calcified midline thoracic disc herniations. We did not observe any postoperative neurological worsening, onset of spinal instability, or other adverse events.

Our aim was to review the literature and discuss about penile curvature in order to have an update for management after 20 years experience in the field.Penile curvature may be congenital or acquired. Congenital penile curvature is a relatively uncommon condition that may present in late adolescent or early adult life. The incidence is estimated to be 0.6 %. On the other side, acquired penile curvature has an overall prevalence of 0.5-13%. Three main factors seem to increase the risk of developing an acquired penile curvature, often related to Peyronie's disease: penile traumatism, genetic and familiar conditions and a history of diseases of the genital tract. In treating Peyronie's disease, no medical therapy is fully effective, and surgery remains the gold standard in cases of severe deformity and/or erectile disfunction. Peyronie's disease is associated with significant psychological stress for patients and their partners. Appropriate treatment should be individualized and tailored to the patient's goals and expectations. There is not the 'best' surgical technique and outcomes are satisfactory when proper treatment decisions are made.

Lipases resistant to inhibition and denaturation by methanol are valuable tools for biotechnological applications, in particular for biofuel production. Microbial lipases have attracted a great deal of interest because of their stability at high concentrations of organic solvents. Burkholderia cepacia lipase (BCL) is tested here for robustness towards methanol in terms of conformational stability and catalytic activity in transesterification assays. This lipase turns out to be even more tolerant than the homologous and better characterized enzyme from Burkholderia glumae. BCL unfolding transition, as monitored by far-UV circular dichroism (CD) and intrinsic fluorescence, displays a Tm above 60°C in the presence of 50% methanol. The protein unfolds at low pH, and the organic solvent affects the nature of the denatured state under acidic conditions. The protein performs well in transesterification assays upon prolonged incubations at high methanol concentrations. BCL is highly tolerant to methanol and displays particularly high conformational stability under conditions employed for transesterification reactions. These features depict BCL as a promising enzyme for biofuel industry., (Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Kinetic modelling, molecular modelling, and experimental determination of the initial reaction velocity of lipase-catalyzed alcoholysis were combined to study the effect of the alcohol substrate to catalytic activity. The model system consisted of methanol or ethanol at varying concentrations, vinyl acetate as ester substrate 15.2% (v/v), toluene as organic solvent, water at a controlled thermodynamic activity of 0.09, and C. antarctica lipase B as enzyme. For both alcohol substrates, the initial reaction velocity increased sharply at low concentrations and reached a maximum at 0.7% (v/v) for methanol and 2% (v/v) for ethanol. For higher concentrations, the reaction rate decreased to a level of 74% and 60% of the peak value, respectively, due to substrate inhibition. The concentration dependency was described by a kinetic model, including a ping-pong bi-bi mechanism and competitive inhibition by the alcohol, and confirmed previous observations that methanol is more efficiently inhibiting the enzyme than ethanol. However, if the initial reaction velocity was expressed in terms of thermodynamic activity of the two alcohol substrates, the maximum of initial reaction velocity was similar for methanol (a MeOH(max)=0.19) and ethanol (a EtOH(max)=0.21). This was confirmed by molecular modelling which resulted in similar KM (0.22 and 0.19) and Ki values (0.44 and 0.49) for methanol and ethanol, respectively, if expressed in thermodynamic activities. Thus, the experimentally observed difference between methanol and ethanol is not due to differences in interaction with the enzyme but is a consequence of the thermodynamics of the substrate-solvent mixture. For low concentrations in toluene, the activity coefficient of methanol is 40% higher than the activity coefficient of ethanol (γ MeOH=8.5, γ EtOH=6.1)., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The catalytic activity of Candida antarctica lipase B upon alcoholysis of a constant concentration of 15.2% vinyl acetate (vol/vol) and varying concentrations of methanol (0.7-60%) in toluene was determined experimentally by measuring the initial reaction velocity. The molecular mechanism of the deactivation of the enzyme by methanol was investigated by fitting the experimental data to a kinetic model and by molecular dynamics simulations of C. antarctica lipase B in toluene-methanol-water mixtures. The highest catalytic activity (280 U/mg) was observed at methanol concentrations as low as 0.7% methanol (vol/vol), followed by a sharp decrease at higher methanol concentrations. For methanol concentrations above 10% (vol/vol), catalytic activity was at 30% of the maximum activity. A variation of water activity in the range 0.02-0.09 had only minor effects. These experimental observations are described by a simple kinetic model using three assumptions: (1) a ping-pong bi-bi mechanism of the enzyme, (2) competitive inhibition by the substrate methanol, and (3) by describing enzyme kinetics by the thermodynamic activities of the substrates rather than by their concentrations. Two equilibrium constants of methanol (KM,MeOH=0.05 and Ki,MeOH=0.23) were derived by modeling methanol binding to the substrate binding site of the lipase in molecular dynamics simulations of protein-solvent systems at atomic resolution. Thus, the sharp maximum of catalytic activity of C. antarctica lipase B at 0.7% methanol is a direct consequence of the fact that methanol-toluene mixtures are far from ideal. Understanding the thermodynamics of solvent mixtures is prerequisite to a quantitative model of enzymatic activity in organic solvents., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Methanol is often employed in biocatalysis with the purpose of increasing substrates solubility or as the acyl acceptor in transesterification reactions, but inhibitory effects are observed in several cases. We have studied the influence of methanol on the catalytic activity and on the conformation of the lipase from Burkholderia glumae, which is reported to be highly methanol tolerant if compared with other lipases. We detected highest activity in the presence of 50-70 % methanol. Under these conditions, however, the enzyme stability is perturbed, leading to gradual protein unfolding and finally to aggregation. These results surmise that, for this lipase, methanol-induced deactivation does not depend on inhibition of catalytic activity but rather on negative effects on the conformational stability of the catalyst.

Background: Both thiopurines and anti-tumor necrosis factor (TNF) α agents are effective for treating Crohn's disease (CD) as they can induce clinical remission (CR) and mucosal healing (MH) in most patients. Nevertheless, data on transmural healing (TH) induced by thiopurines and anti-TNF-α agents are still lacking. This study aimed to explore the rate of TH evaluated by bowel sonography in patients with CD treated with biologics and immunosuppressors and its correlation with CR and MH., Methods: We performed an observational longitudinal study evaluating TH, CR, and MH in all patients with CD attending our clinic who would complete 2 years of maintenance treatment with biologics or thiopurines. CR and MH were assessed in accordance with current literature, whereas TH was recorded using bowel sonography. All patients underwent endoscopy and bowel sonography before starting treatment and 2 years later., Results: The study included 66 patients with CD treated with biologics and 67 patients receiving thiopurines. Finally, TH was present in 17 patients on biologics and only 3 patients treated with thiopurines (25% versus 4%; P < 0.01; odds ratio = 6.2). CR was achieved in 37 patients on biologics and in 34 patients on thiopurines (59.7% versus 53%; P = not significant), whereas MH was more frequent in patients treated with anti-TNF-α agents even though without statistical significance (38% versus 25%; P = not significant)., Conclusions: TH can be achieved in approximately 25% of patients with CD treated with anti-TNF-α agents and significantly correlates with MH. Further studies are needed to define the potential role of TH as long-term prognostic factor.

Introduction: Radical surgery is the "gold standard" for treatment of invasive penile carcinoma but very poor aesthetic, functional and psychological outcomes have been reported. Our purpose was to assess the impact of organ potency-sparing surgery in locally confined carcinoma of the penis., Materials and Methods: We evaluated retrospectively 42 patients with early penile cancer (Ta,T1,T2), treated with glandulectomy and glanduloplasty with urethral mucosa and sparing of cavernosal apexes, or glandulectomy and limited apical resection in cases of Stage T2. Sexual function, ejaculation and libido were evaluated with an IIEF-15 questionnaire before the appearance of neoplasia (about three months before the surgery) and six months after surgery. Quality of life was evaluated by the Bigelow-Young questionnaire. The scores relating to two weeks prior to the surgery have been compared to those obtained six months after surgery. The statistical analysis was conducted using t-Student for repeated measures and analysis of variance., Results: Six months after surgery 73% of patients reported spontaneous rigid erections, 60% coital activity while 76% of the group treated with urethral glanduloplasty reported normal ejaculation and orgasm, regained an average of 35 days after surgery. The average IIEF-15 scores reported in the entire series in the domains of erection, libido and coital activity of the pre-cancer period were not statistically different than those recorded six months after surgery. In the group treated with glandular reconstruction, pre-and postoperative IIEF-15 mean scores related to ejaculation and orgasm domains were not significantly different. Mean scores of Bigelow-Young questionnaires related to sexual pleasure, familial, social and professional relationships showed significant improvement after surgery., Conclusions: Potency sparing-sparing surgical treatments have a positive impact on a wide spectrum of the patient's life including family relationships, and social and working conditions.

Transesterification of triglycerides with short chain alcohols is the key reaction in biodiesel production, in addition to other applications in chemical synthesis. However, it is crucial to optimize reaction conditions to make enzymatic transesterification a cost-effective and competitive process. In this work, a new, easy Fourier transform infrared (FTIR) spectroscopic approach for monitoring the transesterification reaction is reported and compared with a gas-chromatographic method. The concentration of the total methyl esters in the reaction mixture is determined from the peak intensity at ∼1435 cm(-1) in the second derivatives of the FTIR absorption spectra using a linear regression calibration. Interestingly, we found that the use of second derivatives allows an accurate determination of the methyl esters without the interference of free fatty acids. Moreover, information on substrate hydrolysis can be obtained within the same measurement by the infrared absorption at ∼1709 cm(-1) . We applied this approach to monitor methanolysis and hydrolysis reactions catalyzed by different commercial lipases, which displayed different sensitivities to methanol inhibition. Therefore, the FTIR approach reported in this work represents a rapid, inexpensive, and accurate method to monitor enzymatic transesterification, requiring very limited sample preparation and a simple statistical analysis of the spectroscopic data., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: To analyze data from the cultural examinations of different biological fluids, obtained from urologic patients from January 2007 to April 2010, in order to describe the incidence of infections in our setting., Methods: In the period of reference a urine culture was carried out for every patient admitted, in case of suspected urinary tract infection, a blood culture in case of suspected sepsis, and a wound culture in case of wound infection., Results: In the period of investigation 321 patients developed some kind of infection: 589 positive isolations obtained from cultural examinations have been diagnosed in urine (63%), blood (6%), surgical wound (6%), venous central catheter (7%) and other sites (18%) (tip of ureteral and bladder catheters). The most commonly isolated pathogenic agent for all the sites of infection has been Escherichia coli (22.5%). In urine, the most frequently isolated species have been Escherichia coli (27.8%), Enterococcus (12.5%), and Candida spp (9.3%). Escherichia coli (22.9%), Pseudomonas (5.7%), and Staphylococcus aureus (3.5%) were the most frequently found pathogenic agents responsible for sepsis, compared to others. In the period of investigation we have recorded 35 episodes of sepsis., Conclusions: Empiric antibiotic therapy is frequent in cases of clinical evidence of infection, before the identification of the causative microorganism is available; therefore, it is important to know which are the bacterial species mainly responsible for these specific infections. We need continuous surveillance of infections and the improvement in the use of antibiotic therapy in order to limit the antimicrobial resistance.

Aim of this paper is to report a systematic review of the literature about the incidence and putative mechanisms of genital tract injuries following open and laparoscopic herniorraphy and their effects on sexual function and fertility and to point out the measures of prevention and of treatment. The most frequently described events have been intraoperative complications as bladder or spermatic cord structure damage, immediate postoperative complications as ischaemic orchitis, urinary retention, urinary tract infection, hydrocele or scrotal haematoma and bacterial orchitis, or long-term complications as chronic orchialgia, testis atrophy, sexual dysfunction and infertility. The evidence of literature shows that urological complication after hernioplasty are under-reported. Only a small number of studies to date have essentially dealt with sexual quality of life after inguinal hernia surgical repair. The sexual needs of patients with groin hernias are rarely discussed. Extensive laparoscopic procedures, due to the need of learning curve, have increased the risk of vas damage and infertility in young patients candidate to hernioplasty. Early diagnosis prevents urological complication as well as possible legal claims after hernia repair: it should be include careful history, objective and subjective symptoms and signs of uro-genital pathologies, lab data when necessary, immediate eco-color-Doppler imaging and urgent urological consultation. Despite the lack of prospective randomized trials, there is a growing evidence in literature about positive impact of hernioplasty on sexual function, encouraging future studies on this issue.

Objective: To evaluate Sorafenib's efficacy (60 mg/kg/d per os) in preventing the transformation of high grade prostate intraepithelial neoplasia (HGPIN) into adenocarcinoma (ADC) and in inhibiting the onset and progression of poorly differentiated carcinoma (PDC) in transgenic adenocarcinoma mouse prostate (TRAMP) mice., Study Design: Forty-four TRAMP mice were randomly divided into 2 groups of 22 and assigned to daily treatment by gavage with vehicle only or Sorafenib from the 10th to the 26th week of age. At 26 weeks of age the mice were killed, and their genitourinary apparatus was removed and examined by histology, immunohistochemistry and confocal microscopy., Results: Sorafenib reduced HGPIN growth and progression to ADC and was probably also effective in PDC inhibition. The major effect of Sorafenib was on tumor angiogenesis. Interestingly a dissociation between endothelial cells and pericytes was noted in treated PDC since inhibition of pericyte recruitment was less complete than that of endothelial cells., Conclusion: Sorafenib's potent antiangiogenic action may be supposed to be exerted primarily by inhibiting endothelial proliferation and sprouting, whereas its inhibition of pericyte recruitment and maturation is less complete. These observations suggest that Sorafenib's effects could be improved by the joint employment of substances capable of interfering with the recruitment and organization of pericytes.

In the last decades a growing interest has been dedicated to prevention, diagnosis and therapy of male genital pathologies, such as varicocele, infertility and erectile dysfunction in the population involved in sport activities. High incidence (up to 30%) of varicocele has been reported in a population of athletes and up to 60-80% in the subgroup of body-builders. The incidence of varicocele specifically increases with hours of training, in a linear model. Controversial data come from literature about the effects of physical activity on fertility, with prevalence of trials demonstrating worsening of seminal parameters. Furthermore, it has been demonstrated that physical stress in healthy male athletes can interfere with LH levels. Bicycling is one of the major risk factors for erectile dysfunction, with incidence of 13-24%. This is due to the prolonged compression of perineal arteries leading to reduced chronic penile perfusion. Bioengineering studies have been the basis for industry to produce specifically shaped saddles that significantly reduce and minimize compressive effects. Finally, high frequency of lower urinary tract symptoms (LUTS) in cyclists has been related to increased incidence of erectile dysfunction in comparison with normal population.

Introduction: Paraneoplastic syndromes (PNS) may represent the main clinical problem in cancer patients; however, the knowledge of their clinical aspect remains quite poor among urologists., Objective: To provide urologists with an overview on main clinical aspects of PNS that have been reported to be associated to urological cancers., Methods: Literature search of peer-reviewed papers published by July 2008., Results: All genitourinary tumors can cause a PNS, and renal cell carcinoma is the most frequent urological malignancy involved. Prostate cancer is the second urological tumor associated with PNS which, conversely, are uncommon in bladder cancer and rare in testicular cancer. Tumor neuroendocrine differentiation is involved in most endocrine PNS. Neurologic PNS are very uncommon but may dominate the clinical picture and need a high suspicion index to be recognized. Important advances have been made on radionuclide scan methods in order to detect the primary tumor. The most effective treatment strategy is always represented by the radical therapy of the underlying cancer, but specific therapeutic options are sometimes available., Conclusions: Endocrine PNS are frequently associated with urological cancers, especially renal and prostate carcinoma. PNS have been rarely reported in association with cancers of bladder, urethra and testicle., (Copyright 2009 S. Karger AG, Basel.)

Androgen ablation is thought to exert selective pressure for the development of androgen-independent forms of prostate cancer. This study was set up to investigate the effects of surgical castration on the development of prostate adenocarcinoma (ADC) from its precursor (high-grade prostate intraepithelial neoplasia (HGPIN)) and on the occurrence of androgen-independent, poorly differentiated carcinoma (PDC) in (C57Bl/6 transgenic adenocarcinoma of mouse prostate) TRAMP mice. It was found that castration cures HGPIN and ADC and prevents their further occurrence and growth, but has no effect on PDC. This indicates that in this model, PDC is not the progression of ADC favoured by androgen ablation and that its initiating cells are different from those of HGPIN and ADC.

Since its introduction in 1980, extracorporeal shockwave lithotripsy (SWL) has become the first therapeutic option in most cases of upper-tract urolithiasis, and the technique has been used for pediatric renal stones since the first report of success in 1986. Lithotripter effectiveness depends on the power expressed at the focal point. Closely correlated with the power is the pain produced by the shockwaves. By reducing the dimensions of the focus, it becomes possible to treat the patient without anesthesia or analgesia but at the cost of a higher re-treatment rate. Older children often tolerate SWL under intravenous sedation, and minimal anesthesia is applicable for most patients treated with second- and third-generation lithotripters. Ureteral stenting before SWL has been controversial. Current data suggest that preoperative stent placement should be reserved for a few specific cases. Stone-free rates in pediatric SWL exceed 70% at 3 months, with the rate reaching 100% in many series. Even the low-birth-weight infant can be treated with a stone-free as high as 100%. How can one explain the good results? Possible explanations include the lesser length of the child's ureter, which partially compensates for the narrower lumen. Moreover, the pediatric ureter is more elastic and distensible, which facilitates passage of stone fragments and prevents impaction. Another factor is shockwave reproduction in the body: there is a 10% to 20% damping of shockwave energy as it travels through 6 cm of body tissue, so the small body volume of the child allows the shockwaves to be transmitted with little loss of energy. There are several concerns regarding the possible detrimental effect of shockwaves on growing kidneys. Various renal injures have been documented with all type of lithotripters. On the other hand, several studies have not shown adverse effects. In general, SWL is considered to be the method of choice for managing the majority of urinary stones in children of all ages. Re-treatments improve the stone-free rate, often raising it to 100%. Among the predictors of success, stone size seems to be the most important. In the absence of guidelines, selecting the appropriate treatment modality for each child requires planning and depends on instrument availability and local expertise.

Purpose: No satisfactory techniques are available to replace the anatomy and function of the penile glans after radical surgery for penile carcinoma. We report a new technique of glans reconstruction using distal urethra. We evaluated anatomical, physiological and esthetic features as well as short-term and long-term clinical outcomes., Materials and Methods: A total of 14 patients with a mean age of 54 who had squamous penile carcinoma underwent glans reconstruction after simple glansectomy in 8 and after amputation of the distal third of the shaft in 6. Glans sensibility, erectile function, ejaculation, orgasm, penile length, local recurrence, patient and partner satisfaction, and quality of life were evaluated before and after the operation. Mean followup was 13 months., Results: All patients noticed subjective and objective thermal and tactile epicritic sensibility in the area of the neoglans. Ten of 14 patients (71%) noticed spontaneous and/or induced rigid erections. Interestingly International Index of Erectile Function scores in the ejaculation and orgasm domains did not significantly change in the period before and after surgery. No local disease recurrence or penile retraction were reported at long-term followup., Conclusions: Reconstructive glanuloplasty with distal urethra in penile tumor surgery is an innovative, easy and rapid surgical technique with appreciable functional and esthetic results.

Peyronie's disease (PD) is characterized by the onset of a fibrous plaque within the tunica albuginea of the penile corpora cavernosa, resulting in pain and bending during the erection, which can make the intercourse difficult or impossible. Evidence from literature supports the autoimmune etiology of PD, and suggests genetic and familiar conditions, penile traumatisms and history of genital tract diseases as risk factors, even though no definitive conclusions arise about the pathogenesis of the disease. Few randomized trials demonstrated that medical therapies, such as Vitamin E, Colchicine, Potassium amminobenzoate, Tamoxifen and injection therapy with Verapamil are effective in stabilizing the acute phase of the disease. Extracorporeal shock wave therapy (ESWT) and ionophoresis cannot be considered as first line or gold standard therapies. Satisfactory results have been published about Nesbit operation in large number of cases with low-stage disease, whereas plication procedures have shown significant rates of relapse. High incidence of long-term penile retraction have been reported in high-stage disease treated with plaque incision and simple graft insertion. Malleable, soft or inflatable prostheses combined with graft implant have given the best results in terms of penile straightening and lengthening and patients' satisfaction. In conclusion, the PD etiopathogenesis hasn't been clearly understood-yet, no medical therapy is fully effective; surgery remains therefore the gold standard in case of severe deformity and/or erectile dysfunction.

Peyronie's disease (PD) is characterized by the onset of fibrous plaque inside the tunica albuginea of the penile corpora cavernosa that can cause pain and bending during the erection, making intercourse difficult or impossible. Evidence of the literature supports the autoimmune etiology of PD and suggests genetic and familiar conditions, penile traumatisms, and a history of genital tract diseases as risk factors, but no definitive conclusions arise about the pathogenesis of the disease. Few randomized trials demonstrated that medical therapies, such as vitamin E, colchicine, potassium aminobenzoate, tamoxifen, and injection therapy with verapamil, can stabilize the acute phase of the disease. Extracorporeal shock wave therapy and iontophoresis cannot be considered first-line or gold standard therapies. Satisfactory results have been published with the Nesbit operation in large series with low-stage disease, whereas plication procedures have shown significant relapse rates. A high incidence of long-term penile retractions has been reported in high-stage disease treated with plaque incision and simple graft insertion. Malleable, soft, or inflatable prostheses combined with graft implantation have given the best results in terms of penile straightening and lengthening and patient satisfaction. In conclusion, the etiopathogenesis of PD is not yet clearly understood, no medical therapy is fully effective, and surgery remains the gold standard in patients with severe deformity and/or erectile dysfunction.

Sentinel lymph node and clinically negative axillary node status was compared with well-known clinicopathological characteristics such as tumor size, histologic and nuclear grade, lymphovascular invasion, steroid receptor, and HER-2 status in patients with breast cancer (pT1 and pT2). Positive sentinel lymph nodes were found in 29 of 100 patients: 19 with metastases detected by hematoxylin and eosin staining and 10 with micrometastases confirmed by immunohistochemistry with cytokeratin. Positive sentinel lymph nodes were present in larger carcinomas (P < 0.03), more frequently in tumors with negative PR status (P < 0.037) and evident lymphovascular invasion (P < 0.002). Lymphovascular invasion was also associated with breast cancer of higher histologic (P = 0.011) and nuclear grade (P = 0.039). Tumor size and the presence of lymphovascular invasion were found to be significant predictors of pathologically positive sentinel lymph node in T1 and T2.

Background: The choice of graft for anterior cruciate ligament reconstruction is a matter of debate, with patellar and hamstring tendons being the two most popular autologous graft options. The objective of this study was to determine in a prospective, randomized clinical trial whether two grafts (bone-patellar tendon-bone or doubled hamstring tendons) fixed with modern devices affect the two-year minimum clinical and radiographic outcomes of anterior cruciate ligament reconstruction., Methods: One hundred and twenty patients with a chronic unilateral rupture of the anterior cruciate ligament underwent arthroscopically assisted reconstruction with use of either autologous bone-patellar tendon-bone or doubled hamstring tendon grafts, in a strictly alternating manner. Both groups were comparable with regard to demographic data, preoperative activity level, mechanism of injury, interval between the injury and the operation, and the amount of knee laxity present preoperatively. The same well-proven surgical technique and aggressive controlled rehabilitation was used. An independent observer, who was blinded with regard to the involved leg and the type of graft, performed the outcome assessment with use of a visual analog scale, the new International Knee Documentation Committee form, the Knee Injury and Osteoarthritis Outcome Score, the Functional Knee Score for Anterior Knee Pain, and an arthrometric and an isokinetic dynamometric evaluation. Radiographs were also made., Results: At the two-year follow-up evaluation, no differences were found in terms of the visual analog score, the Knee Injury and Osteoarthritis Outcome Score, the new International Knee Documentation Committee subjective and objective evaluation scores, the KT-1000 side-to-side laxity measurements, the Functional Knee Score for Anterior Knee Pain, muscle strength recovery, or return to sports activities. In the bone-patellar tendon-bone group, we found a higher prevalence of postoperative kneeling discomfort (p < 0.01) and an increased area of decreased skin sensitivity (p < 0.001). In the hamstring tendon group, we recorded a higher prevalence of femoral tunnel widening (p < 0.01). In this group, a correlation was also found between medial meniscectomy and an increased prevalence of pivot-shift glide (p = 0.035)., Conclusions: We believe that, with use of accurate and proven surgical and rehabilitation techniques, both grafts are an equivalent option for anterior cruciate ligament reconstruction.

Besides generating renal damage, hypertension plays an important role in the progression of diabetic nephropathy. The fructose-fed rat is a well-established model both of high blood pressure and renal impairment, which is similar to diabetic nephropathy. To clarify the relationship between hypertension, glucose metabolism, and kidney remodeling, we investigated the renal level of Glut 1 and Glut 5, their relation to fibrosis and the effects of an antihypertensive drug on renal damage. Twenty-four male WK rats were divided into three groups: 8 animals received a fructose-enriched diet, 8 a control diet, and 8 animals a high-fructose diet plus amlodipine (5 mg/Kg). After six weeks of treatment, we observed a significant increase in Glut 5, fibronectin, and sorbitol in fructose-fed rats compared with control and amlodipine-treated animals; there was a positive correlation between Glut 5 and fibronectin levels (r = 0.63). Glut 1 levels were similar in all three groups, whereas collagen IV was higher in fructose-fed rats; amlodipine prevented the increase of collagen IV and sorbitol. Collagen I was statistically higher in the fructose group than in the other two groups. Therefore, prolonged fructose feeding results in renal fibrosis via polyol pathway overactivity that can be prevented by means of an antihypertensive drug.

To determine the reliability of the vestibolo-ocular reflex test measured via Vorteq, 16 subjects underwent head-autorotation test at the frequencies 1-5 Hz. All patients underwent the re-test. No linear correlation was observed between the measurements, i.e., no repeatability of the same measurements at the various frequencies. The Head Auto-Rotation Test by Vorteq has demonstrated advantages: patients are not disturbed by the active head movements; the full test protocol, lasts only a few minutes; the method enables the vestibolo-ocular reflex to be evaluated at high head-rotation frequencies. However, the test has disadvantages: poor test-retest inter-individual repeatability, wide standard deviations of results with heterogeneous inter-individual spread with regard to phase and asymmetry values especially at high rotation frequencies. In the light of the above findings, it can be seen that the test-retest of the Vorteq system is not sufficiently reliable and hence cannot be used in clinical practice.

Treatment satisfaction, subanalysed by demographic variables, was evaluated in patients switching from successful intracavernosal prostaglandin E(1) (PGE(1)) therapy to oral sildenafil citrate. The validated Erectile Dysfunction Inventory of Treatment Satisfaction questionnaire was administered at the end of PGE(1) therapy and after 12 weeks of sildenafil treatment in a multicentre, open-label study. Men with erectile dysfunction (n=176) who were switched from stable PGE(1) therapy to sildenafil (25-100 mg) were equally satisfied with onset of action, duration of action, and confidence in ability to engage in sexual activity, but expressed greater overall treatment satisfaction with sildenafil (P<0.01), better ease of use (P<0.001), naturalness of erectile process (P<0.001), and intention to continue treatment (P<0.001). Partners (n=32) were overall more satisfied with sildenafil (P<0.05), and their responses correlated with patient satisfaction (r=0.68). Compared with PGE(1) injection, these data suggest that patients may be less likely to discontinue taking sildenafil treatment for their erectile dysfunction.

The aim of this work was to characterize p53 and PCNA expression in primary tumours and lymph node metastases of oral/oropharynx carcinomas by flow cytometry and to evaluate the possibility of a relationship between these parameters in primary tumours and locoregional metastasis, clinical-histopathological parameters and survival time. A group of 28 patients was retrospectively selected: 13 with metastasis and 15 without metastasis. The following clinical and histopathological parameters were considered: degree of keratinization, Broders' grading of histological differentiation, invasive cell grading, thickness and tumour size. The nuclei of appropriately prepared cells were stained using anti-p53 and anti-PCNA FITC conjugated monoclonal antibodies. Analyses were performed by a Coulter Epics Elite flow cytometer. The following results were obtained: a close relationship between p53 and PCNA in primary tumours but no correlation between them and clinical-histopathological parameters; no correlation between p53 and PCNA expression in primary tumours and in lymph node metastasis; no correlation between p53 and PCNA values in primary tumours and survival. In conclusion, the difference in expression of these biological parameters in primary tumours and in lymph node metastases supports the theory that tumour cells in lymph nodes can display an independent behaviour. Since these biological parameters fail to correlate either with clinical-histopathological parameters or survival, their prognostic role is questionable.

Purpose: We evaluated corpora cavernosa metabolism in flaccidity and in erection, analyzing some blood gas analytical parameters and comparing them by histomorphometric examination to find a direct relation between biochemical-metabolic parameters and histological data., Materials and Methods: We selected 33 patients with erectile dysfunction and divided them into 2 groups, including 1-those with congenital penile deviation who were responders to prostaglandin E1, and 2-those with severe organic erectile dysfunction who were not responders to prostaglandin E1. We evaluated O(2) and CO(2) pressure, pH and O(2) saturation in blood samples. We then made a histomorphometric study of cavernous tissue. We obtained specimens by cavernous biopsies and calculated O(2) and CO(2) exchange, the Haldane effect and the respiratory quotient into the corpora cavernosa. All data were evaluated by statistical analysis., Results: Mean O(2) arterial pressure and saturation +/- SD were lower in group 2 than in group 1 (74.85 +/- 8.78 versus 96.43 +/- 14.87 and 94.98 +/- 1.4 versus 97.35 +/- 0.83, respectively). Mean CO(2) arterial pressure was 35.59 +/- 4.78 group 1 versus 38.8 +/- 2.71 in group 2 with borderline statistical significance. The Haldane effect was superior in flaccidity than in erection because of the influence of arterial-venous O(2) difference and the respiratory quotient, which was also an inverse ratio. Cavernous histomorphometry showed that in group 1 smooth muscle was a mean of 38.8 +/- 8.94% of cavernous tissue versus 24.9% in group 2., Conclusions: Our study shows that starting with blood gas analytical data we can completely study the metabolism of the corpora cavernosa and its relationships to erectile dysfunction. Cavernous histomorphometry can suggest the presence of smooth muscle into cavernous tissue, whereas our mathematical elaboration allowed us to evaluate all data in a more complete manner.

Depth of invasion and stage of the disease are well known prognostic indicators in cutaneous melanoma (CM). However, the role of other parameters, such as the variations in cytomorphology of melanocyte tumours, mitotic activity and angiogenesis is still open to question. The aim of this study was to analyse proliferation by mitotic activity index (MAI) and immunostaining of proliferating cell nuclear antigen (PCNA), and the intensity of neovascularization (microvessel density; MVD) in CM clinical stage I in relation to epithelioid, spindle and nevoid cell type, histological type (superficial spreading melanoma and nodular melanoma), Clark's level and Breslow thickness. Finally, the role of all parameters in the prognosis of CM was evaluated. Statistical analysis demonstrated that cytological characteristics of CM correlate only with Clark's level, while histological types correlate with MAI, PCNA and MVD. MAI and PCNA also showed correlation between groups according to Clark's level and Breslow thickness. Finally, tumour cell PCNA was found to correlate with MVD. Survival of patients with CM correlated significantly with MAI. These results suggest that cytological variation, histological type, PCNA and MVD alone are not independent prognostic parameters, whereas MAI is a potentially important prognostic marker in CM.

Background: To evaluate the efficacy of tamoxifen as primary treatment in women aged over 70 years with operable breast cancer versus surgery followed by adjuvant tamoxifen., Patients and Methods: Patients randomly received tamoxifen alone (160 mg day 1, then 20 mg/day) for 5 years or surgery followed by tamoxifen (20 mg/day) for 5 years. Overall survival was the main study end point; secondary objectives included breast cancer survival and local control of the disease., Results: Between 1987 and 1992, 239 patients were assigned to surgery plus tamoxifen and 235 to tamoxifen alone. Treatment arms were comparable for tumor size, clinical nodal status and performance status. At a median follow-up of 80 months 274 patients had died. No difference between groups had emerged in overall and breast cancer survival. There were 27 local progressions in the surgery plus tamoxifen group and 106 in the tamoxifen-alone group (P = 0.0001). In the surgery plus tamoxifen group, no difference in overall survival had emerged according to the extension of operation., Conclusions: The long-term results of the study confirm the 3-year interim analysis already reported. Surgery (radical or minimal) followed by adjuvant tamoxifen does not modify overall and breast cancer survival as compared with tamoxifen alone in early breast cancer of older women. Because of the high rate of local progressions with tamoxifen alone, minimal surgery followed by tamoxifen appears to be the appropriate treatment in such patients. More extensive surgery is not useful. Tamoxifen alone is an adequate alternative treatment in very old or frail patients.

The paper concerns the experience of our Institute in the field of radical plaque removal in Peyronie's disease with special focus to the new biomaterials used as a graft on replace the fibrotic tunica albuginea. This is a retrospective study that evaluated clinical outcomes with a follow-up ranging from the early post-operative period to six years later. Ninety-eight patients aged from 32 to 64 with compliant of high stage Peyronie's disease have been treated. Which surgery meanly occurred 12 months after the first diagnosis. The different biomaterials implanted have been studied in terms of biophysical properties and clinical features at short and long term follow-up. These results suggest that surgical therapy appears as the main option in the treatment of Peyronie' disease, specially in the advanced state, plaque surgery being the most radical one; today we have a lot of different materials for substitution of albuginea but maybe noone represents the real gold standard. As concerns elasticity and biocompatibility, vein gave the best results, even if the operating time is longer. A new enthusiasm comes from SIS (porcine intestinal sub-mucose), whose early clinical and biological results are satisfactory in terms of elasticity and reduced operating time.

Angiogenic and anti-angiogenic factors, secreted by tumor, inflammatory, and stromal cells play an important role in regulation of neovascularization. Among the most important of these is vascular endothelial growth factor (VEGF), a specific mitogen for endothelium, which increases vascular permeability and induces proteolytic enzymes necessary for vascular remodeling. Tumor-associated macrophages (TAMs) can express complex functions related to tumor biology, including growth, proliferative rate, stroma formation and dissolution, and neovascularization. The aim of this study was to define, using immunohistochemical analysis, the microvessel density (MVD), VEGF expression, and TAMs level in 97 human invasive ductal breast carcinomas not otherwise specified (NOS), investigate a possible relationship between them and then correlate their values with tumor grade, mitotic activity index (MAI), tumor size and lymph-node status. Statistical analysis showed a strong positive relationship between MVD and VEGF expression ( P<0.001). Furthermore, both MVD and VEGF expression were significantly correlated with tumor grade and lymph-node status, and TAMs infiltration with MAI. TAM level showed a significant positive connection with VEGF expression and MVD. These in situ observations suggest that VEGF stimulates angiogenesis in human invasive ductal breast carcinoma NOS and attracts macrophages to the tumor locus, which then may be involved in angiogenesis promotion. The expression of this angiogenic molecule, and MVD and TAM level, can provide additional prognostic significance and help in the identification of patients who need postoperative adjuvant therapy.

Tumour cell proliferation is an important biological prognostic parameter to be considered alongside clinical and histopathological parameters. It has been evaluated by immunohistochemistry using proliferative markers (PCNA, Ki67, etc.) and by flow cytometry considering DNA content, growth fraction (S + G2M) and S-phase fraction. Our aim was to evaluate by flow cytometry both Ki67 and S-phase fraction, S + G2M, DNA content in patients surgically treated for oral cavity and/or oropharynx carcinomas. The study, performed on archival material, analysed the significance and prognostic reliability of these biological parameters to reveal locoregional metastasis and evaluated their possible correlation with clinical and histopathological parameters. In conclusion, tumour cell proliferation seems not to be useful in revealing the presence of locoregional metastasis in oral cavity and oropharynx carcinomas. Thus, new approaches are required.

Background: Although hepatic steatosis is seen with increasing frequency in clinical practice, its prevalence and risk factors are unknown., Objective: To investigate the prevalence of and risk factors for hepatic steatosis, such as alcohol consumption and obesity., Design: Cross-sectional, observational study., Setting: Participants in the Dionysos Study., Patients: 257 participants assigned to one of four categories (67 controls, 66 obese persons, 69 heavy drinkers, and 55 obese heavy drinkers)., Measurements: Ethanol intake, assessed by a validated questionnaire and expressed as daily (g/d) and lifetime (kg) consumption, and body mass, expressed as body mass index. Biochemical tests of liver and metabolic function and hepatic ultrasonography were done., Results: The prevalence of steatosis was increased in heavy drinkers (46.4% [95% CI, 34% to 59%]) and obese persons (75.8% [CI, 63% to 85%]) compared with controls (16.4% [CI, 8% to 25%]). Steatosis was found in 94.5% (CI, 85% to 99%) of obese heavy drinkers. Compared with controls, the risk for steatosis was higher by 2.8-fold (CI, 1.4-fold to 7.1-fold) in heavy drinkers, 4.6-fold (CI, 2.5-fold to 11.0-fold) in obese persons, and 5.8-fold (CI, 3.2-fold to 12.3-fold) in persons who were obese and drank heavily. In heavy drinkers, obesity increased the risk for steatosis by twofold (CI, 1.5-fold to 3.0-fold) (P < 0.001), but heavy drinking was associated with only a 1.3-fold (CI, 1.02-fold to 1.6-fold) increase in risk in obese persons (P = 0.0053). Elevated alanine aminotransferase and triglyceride levels are the most reliable markers of steatosis., Conclusions: Steatosis is frequently encountered in healthy persons and is almost always present in obese persons who drink more than 60 g of alcohol per day. Steatosis is more strongly associated with obesity than with heavy drinking, suggesting a greater role of overweight than alcohol consumption in accumulation of fat in the liver.

A rare case of bilateral pararenal abscess secondary to staghorn calculi is reported. It is characterized by a singular evolution in both side, with fistulization along iliopsoas muscle until the Scarpa triangle. Considering the seriousness of this illness, the importance of an early surgical therapy of complicated staghorn lithiasis is underlined.

Purpose: We evaluated short and long-term results of simple and complex venous surgery in patients with veno-occlusive dysfunction unresponsive to maximum recommended doses of intracavernous alprostadil, who were selected with newly developed diagnostic indicators., Materials and Methods: A total of 23 impotent men with a mean age of 41 years (range 20 to 50) underwent complex penile venous surgery. Only patients fulfilling at least 3 criteria were included in study. The criteria were mild cavernous leak assessed by cavernosometry (grades 1 and 2), more than 30% cavernous smooth muscle tissue (histomorphometric analysis), normal analogical corpus cavernosum electromyography recordings according to international standards, cavernosal oxygen tension greater than 65 mm. Hg at erection and age younger than 50 years., Results: Of 23 patients 17 (74%) had normal erections within a year after surgery, and 5 of them (29%) complained of recurrent erectile dysfunction. At long-term followup 6 of 12 patients had spontaneous erections., Conclusions: Careful selection with advanced diagnostic techniques should be mandatory before performing venous surgery in patients with high degree veno-occlusive dysfunction as the only alternatives are major therapeutical solutions.