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Background Recent guidelines suggested a wider use of long-acting injectable antipsychotics (LAI) than previously, but naturalistic data on the consequences of LAI use in terms of discontinuation rates and associated factors are still sparse, making it hard for clinicians to be informed on plausible treatment courses. Objective Our objective was to assess, under real-world clinical circumstances, LAI discontinuation rates over a period of 12 months after a first prescription, reasons for discontinuation, and associated factors. Methods The STAR Network ‘Depot Study’ was a naturalistic, multicentre, observational prospective study that enrolled subjects initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centres were assessed at baseline and at 6 and 12 months of follow-up. Psychopathology, drug attitude and treatment adherence were measured using the Brief Psychiatric Rating Scale, the Drug Attitude Inventory and the Kemp scale, respectively. Results The study followed 394 participants for 12 months. The overall discontinuation rate at 12 months was 39.3% (95% confidence interval [CI] 34.4–44.3), with paliperidone LAI being the least discontinued LAI (33.9%; 95% CI 25.3–43.5) and olanzapine LAI the most discontinued (62.5%; 95% CI 35.4–84.8). The most frequent reason for discontinuation was onset of adverse events (32.9%; 95% CI 25.6–40.9) followed by participant refusal of the medication (20.6%; 95% CI 14.6–27.9). Medication adherence at baseline was negatively associated with discontinuation risk (hazard ratio [HR] 0.853; 95% CI 0.742–0.981; p = 0.026), whereas being prescribed olanzapine LAI was associated with increased discontinuation risk compared with being prescribed paliperidone LAI (HR 2.156; 95% CI 1.003–4.634; p = 0.049). Conclusions Clinicians should be aware that LAI discontinuation is a frequent occurrence. LAI choice should be carefully discussed with the patient, taking into account individual characteristics and possible obstacles related to the practicalities of each formulation. Supplementary Information The online version contains supplementary material available at 10.1007/s40263-021-00809-w.

This study, based on the 'Servizi Territoriali Associati per la Ricerca' (STAR) Network Depot Study nationwide baseline data, explored whether individual symptoms severity and clusters might influence the prescription of paliperidone palmitate 1-month (PP1M) vs. aripiprazole monohydrate. The Brief Psychiatric Rating Scale (BPRS) was used to assess psychopathology and relevant symptoms clusters. Drug Attitude Inventory, 10 items, was used to test attitude towards medications. Adherence to treatments was rated according to the Kemp seven-point scale. We assessed for eligibility 451 individuals and, among them, we included 195 subjects (n = 117 who started PPM1 and n = 78 aripiprazole monohydrate). Individuals were comparable in terms of age, gender, treatment years, recent hospitalizations, previous long-acting injectable antipsychotic treatments, additional oral treatments, attitude toward drugs, medication adherence, and alcohol/substance-related comorbidities. Subjects starting PP1M presented higher BPRS overall (P = 0.009), positive (P = 0.015), and negative (P = 0.010) symptom scores compared to subjects starting aripiprazole monohydrate. Results were confirmed by appropriate regression models and propensity score matching analysis. No differences were found comparing the other BPRS subscale scores: affect, resistance, and activation. Clinicians may be more prone to prescribe PPM1, rather than aripiprazole monohydrate, to subjects showing higher overall symptom severity, including positive and negative symptoms. No additional clinical factors influenced prescribing attitudes in our sample.

Minifascicular neuropathy (MN) is a rare, autosomal recessive disease with prominent structural changes of peripheral nerves. So far, it has been observed in females with a 46,XY karyotype and mutations of the Desert Hedgehog (DHH) gene, thus linking MN to gonadal dysgenesis (GD) and disorders of sex development (DSD). However, a 46,XX proband with normal female sex and gender development underwent clinical evaluations, nerve conduction studies and genetic screening for a severe motor-sensory neuropathy with a pathological phenotype that hinted at MN. Indeed, sural nerve biopsy revealed a profound disturbance of perineurium development with a thin and loose structure. High-resolution ultrasound (HRUS) also disclosed diffuse changes of nerve echotexture that visibly correlated with the pathological features. After extensive genetic testing, a novel homozygous DHH null mutation (p.Ser185*) was identified in the proband and in her sister, who was affected by a similar motor-sensory neuropathy, but was eventually found to be a 46,XY patient according to a late diagnosis of DSD with complete GD. DHH should therefore be considered as a possible cause of rare non-syndromic hereditary motor-sensory neuropathies, regardless of DSD. Furthermore, HRUS could effectively smooth the complex diagnostic workup as it demonstrated a high predictive power to detect MN, providing the same detailed correlations to the pathologic features of the nerve biopsy and Dhh-/- mice in both sisters. Hence, HRUS may assume a pivotal role in guiding molecular analysis in individuals with or without DSD.

Purpose Chronic topical treatment for glaucoma may lead to Ocular Surface Disease (OSD). This study aimed to evaluate: (1) the prevalence of OSD in glaucoma patients under topical treatment, quantifying symptoms and objective ocular surface parameters and (2) the impact of ocular surface treatment on OSD and IOP control. Methods Patients with primary open angle or primary angle closure glaucoma under topical treatment for at least 6 months were enrolled in the study. Patients underwent symptom screening with the ocular surface disease index (OSDI) questionnaire, assessment of objective ocular surface parameters, ocular surface staining and Schirmer test. A treatment for OSD with eyelid hygiene, fluorometholone acetate 0.1%, preservative-free lubricants, free-acid supplementation and oral tetracyclin derivate was started, and the same evaluation was performed. Results In our sample (n=19), 73.68% of the patients reported severe symptoms of dry eye disease, with OSDI scores higher than 33 at baseline. Tear film instability was found in 50% of patients, while 23.53% had severe meibomian gland abnormalities. Fluorescein and lissamine green stainings were abnormal in 88.24% and 82.35% of patients, respectively. After ocular surface treatment, statistically significant improvement was found in best-corrected visual acuity (p=0.0003), OSDI score (p

The diagnostic criteria published by the PNS (Paraneoplastic Neurological Syndromes) Euronetwork in 2004 provided a useful classification of PNS, including paraneoplastic neuropathies. Subacute sensory neuronopathy (SSN) was the most frequently observed peripheral PNS, whereas other forms of neuropathy, as sensory polyneuropathy, sensorimotor polyneuropathy, demyelinating neuropathies, autonomic neuropathies, and focal nerve or plexus lesions, were less frequent. At the time of publication, the main focus was on onconeural antibodies, but knowledge regarding the mechanisms has since expanded. The antibodies associated with PNS are commonly classified as onconeural (intracellular) and neuronal surface antibodies (NSAbs). Since 2004, the number of antibodies and the associated tumors has increased. Knowledge has grown on the mechanisms underlying the neuropathies observed in lymphoma, paraproteinemia, and multiple myeloma. Moreover, other unrevealed mechanisms underpin sensorimotor neuropathies and late-stage neuropathies, where patients in advanced stages of cancer—often associated with weight loss—experience some mild sensorimotor neuropathy, without concomitant use of neurotoxic drugs. The spectrum of paraneoplastic neuropathies has increased to encompass motor neuropathies, small fiber neuropathies, and autonomic and nerve hyperexcitability syndromes. In addition, also focal neuropathies, as cranial nerves, plexopathies, and mononeuropathies, are considered in some cases to be of paraneoplastic origin. A key differential diagnosis for paraneoplastic neuropathy, during the course of cancer disease (the rare occurrence of a PNS), is chemotherapy-induced peripheral neuropathy (CIPN). Today, novel complications that also involve the peripheral nervous system are emerging from novel anti-cancer therapies, as targeted and immune checkpoint inhibitor (ICH) treatment. Therapeutic options are categorized into causal and symptomatic. Causal treatments anecdotally mention tumor removal. Immunomodulation is sometimes performed for immune-mediated conditions but is still far from constituting evidence. Symptomatic treatment must always be considered, consisting of both drug therapy (e.g., pain) and attempts to treat disability and neuropathic pain.

Guillain Barré syndrome (GBS) is an acute polyradiculoneuropathy associated with dysimmune processes, often related to a previous infectious exposure. During Italian Severe Acute Respiratory Syndrome Coronavirus-2 outbreak, a woman presented with a rapidly progressive flaccid paralysis with unilateral facial neuropathy after a few days of mild respiratory symptoms. Coronavirus was detected by nasopharyngeal swab, but there was no evidence of its presence in her cerebrospinal fluid, which confirmed the typical albumin-cytological dissociation of GBS, along with consistent neurophysiological data. Despite immunoglobulin infusions and intensive supportive care, her clinical picture worsened simultaneously both from respiratory and neurological point of view, as if reflecting different aspects of the same systemic inflammatory response. Similar early complications have already been observed in patients with para-infectious GBS related to Zika virus, but pathological mechanisms have yet to be established.

Background: Worldwide, efforts to control SARS-CoV-2 transmission have included lockdowns and restrictions on contact with others, including sexual partners. Our research (Natsal-COVID) indicates that in the UK, 10% of people aged 18–59 had physical or sexual contact with a romantic or sexual partner outside their household (PCOH) during a period in which contact was limited. We explored motivations and decision-making among people reporting PCOH in the four months following the initial national lockdown on 23rd March 2020. Method: Semi-structured interviews were conducted with 18 individuals reporting PCOH during a period in which physical distancing measures were in place. Participants were recruited through a large, quasi-representative survey investigating sexual behaviour in the UK during the COVID-19 pandemic (Natsal-COVID). Interviews were analysed thematically. Results: Participants were single (n=8) or in long-term, non-cohabiting, relationships (n=10). While participants in the two groups differed in their reported motivations for PCOH, all demonstrated complex and individualised decision-making, weighing up risks such as SARS-CoV-2 transmission, judgement of peers, and benefits, including feelings of security and improved mental health. For those in relationships, the primary motivation was continuity: participants expected to continue seeing their romantic partner. Participants rationalised this contact as ‘low risk’ in relation to other ‘risks’ of COVID-19 exposure, and reduced other activities (such as shopping, seeing friends) to maintain this contact. For single participants, loneliness and boredom were reported as the primary motivators for PCOH, with dating apps often used to facilitate contact. For both groups, evidence of considered decision-making was clear, with participants referencing government guidance, personal situations, and risk when describing their deliberations. Conclusion: Individuals did not make decisions about PCOH lightly. However, physical contact with partners was considered important and thus rationalised. Public health policy-makers must therefore consider sexual behaviour and needs for physical contact in designing effective future public health messaging.

Background: COVID-19 restrictions led to widespread disruption of SRH services in Britain following the first national lockdown (23/3/2020). One-in-ten people who tried to access SRH services during reported being unable to do so (Natsal-COVID). We used mixed-methods research to quantify unmet need and explore its context and impact. Methods: 6,657 participants aged 18–59 years completed a web-panel survey (29/07–10/08/20). Quota-based sampling and weighting enabled a quasi-representative population sample to be achieved. Quantitative analysis focused on participants’ challenges accessing contraception and STI-related services since lockdown. We conducted 23 in-depth interviews with participants, 15 who reported not receiving an SRH service and eight who discussed this in a different topic interview. Results: Reasons for not receiving STI-related (n=103) or contraception services (n=144) despite need included that appointments were unavailable (STI-related services: 28.6% (95%CI:19.5–39.8)/Contraception services 36.3% (28.1% – 45.4%)), were cancelled (22.8% (14.9%- 33.3%)/23.9% (16.8%-32.8%) or services were closed (21.2% (13.7%-31.4)/26.1% (19.1%-34.5%). Discomfort with using online/telephone services was more common amongst those not receiving STI-related services 26.0% (17.4%-36.9%) than for contraception services 6.7% (3.4%-12.8%). Interviewees described how some services were unavailable, while others were disrupted. Many were offered and received alternatives to in-person service (e.g. telephone/online) and some had to use different contraceptive methods. Most understood attempts to limit SARS-CoV-2 transmission and found alternatives convenient, though others saw them as inferior due to interaction limitations. Tenacity was required to access some services. Several participants described how they had avoided or deprioritised their own needs. Fears of contracting COVID-19 and of judgement for having sex against restrictions deterred help-seeking. Conclusion: While some people were unable to access an anticipated service, many were offered alternatives with varied consequences. Services may need to adapt further to improve access by offering efficient face-to-face and remote provision while emphasising lack of judgement and validating help seeking.

Background Physical distancing as a non-pharmaceutical intervention (NPI) to prevent SARS-CoV-2 transmission aims to reduce interactions between people, including between different households. We explored whether sexual intimacy needs impacted on compliance with physical distancing at a population level in Britain following the initial national lockdown on 23 March 2020. Methods We undertook the Natsal-COVID web-panel survey between 29 July-10 August 2020. Quota-based sampling and weighting were used to obtain a quasi-representative sample of the British population. We estimated reporting of physical contact outside of the household (PCOH) with a romantic/sexual partner in the four weeks prior to interview, described the type of contact, identified demographic and behavioural factors associated with PCOH and present age-adjusted odds ratios (aORs). Results Of the 6,654 participants aged 18–59 years, 9.9% (95%CI:9.9–10.6%) reported PCOH. Of these, 86.1% reported oral/anal/vaginal sex or genital contact, while the remaining reported kissing (10.4%) or only holding hands/hugging/cuddling (3.4%). PCOH varied by age and gender and was highest in those aged 18–24 (20.6% of women and 15.6% of men). PCOH was more likely in participants identifying as gay/lesbian (aOR 2.5; 1.82–3.45) or bisexual (aOR 1.52; 1.12–2.05) and those reporting >1 partner (aOR 1.71; 3.77–5.88) or condomless sex with a new partner (OR 5.03; 1.07–6.21) in the past year. PCOH was less likely in those reporting a steady or cohabiting relationship (aOR 0.66; 0.55–0.79 and aOR 0.11; 0.08–0.14 respectively), and in those reporting bad/very bad health (aOR 0.54; 0.32–0.93). Conclusion The intimate nature of sexual contact is high-risk for SARS-CoV-2 transmission and PCOH may expand transmission networks by connecting households. Mathematical models of NPIs might consider age- and gender-specific PCOH in the context of other mixing patterns. Public health messaging needs to recognise the importance of sexual and romantic contact in people’s decision-making and adherence to control measures.

The pathological gambling results from the interaction of multiple risk factors. Among these, the second-generation antipsychotic (SGA) aripiprazole has been described as a new potential risk factor. In this work we present the case of a young man, affected by schizoaffective disorder and pathological gambling, who showed significant improvements of both conditions after aripiprazole long acting administration. We discuss the importance of a complete assessment, that could evidence all psychopathological factors implicated in the onset or worsening of a pathological gambling, included, in this case, the schizoaffective disorder. The aripiprazole long acting was well tolerated and, compared with the oral aripiprazole, produced less sedative effects, favoring, at the same time, a good compliance to the therapy. Between the side effects we remark the weight gain -often find in all the SGA-, that was managed with a psycho-educational and nutritional approach. An important reflection regards the health service chosen by the patient, i.e. the Dependence Service, considered as less stigmatizing and suitable for his debt condition. We think that the Dependence Service plays a crucial role in these complex pathological conditions, managing the gambling disorder and coordinating, at the same time, the network of territorial services, that is necessary to favor an optimal outcome.

Background: Early detection and intervention of children living with Autism Spectrum Disorders have shown a great improvement of the child's behaviour, predominantly in language and motor skills development. We are proposing to conduct a systematic scoping review that will map all evidence available on children living with Autism Spectrum Disorders in Africa.Methods and analysis: This study will be guided by Arksey and O’Malley’s framework of scoping reviews. A comprehensive literature search will be done in the following electronic databases. Cumulative Index to Nursing and Allied Health Literature (CINAHL), Science Direct, EBSCOhost, MEDLINE, Health Sources, and Google Scholar. Primary studies, published in peer-reviewed journals and grey literature such as unpublished studies, studies in press and Theses that address our research question will be included. To reduce research bias two independent reviewers will perform title, abstract, and full article screening in parallel. Data extraction from the selected studies will be conducted by two independent reviewers. NVivo version 12 software will be used to assist with the extraction of relevant answers to the study questions from selected studies using content thematic analysis. The results for this planned study will be presented following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Review (PRISMA-ScR). Mixed Methods Assessment Tool version 2018 will be used for quality appraisal of included studies.Discussion: We anticipate that the proposed mapped evidence on Children living with Autism Spectrum Disorders in Africa will reveal indicators for early detection that would facilitate strategies for intervention. We are also anticipating that this systematic scoping review will reveal gaps that can be addressed to ensure context-sensitive interventions and identify caregiver burdens of children living with Autism. This will contribute to the reduction of a scarcity of literature on children living with Autism in Africa.

The standard treatment for advanced ovarian cancer (AOC) is cytoreduction surgery and adjuvant chemotherapy. Tumor volume after surgery is a major prognostic factor for these patients. The ability to perform complete cytoreduction depends on the extent of disease and the skills of the surgical team. Several predictive models have been proposed to evaluate the possibility of performing complete cytoreductive surgery (CCS). External validation of the prognostic value of three predictive models (Fagotti index and the R3 and R4 models) for predicting suboptimal cytoreductive surgery (SCS) in AOC was performed in this study. The scores of the 3 models were evaluated in one hundred and three consecutive patients diagnosed with AOC treated in a tertiary hospital were evaluated. Clinicopathological features were collected prospectively and analyzed retrospectively. The performance of the three models was evaluated, and calibration and discrimination were analyzed. The calibration of the Fagotti, R3 and R4 models showed odds ratios of obtaining SCSs of 1.5, 2.4 and 2.4, respectively, indicating good calibration. The discrimination of the Fagotti, R3 and R4 models showed an area under the ROC curve of 83%, 70% and 81%, respectively. The negative predictive values of the three models were higher than the positive predictive values for SCS. The three models were able to predict suboptimal cytoreductive surgery for advanced ovarian cancer, but they were more reliable for predicting CCS. The R4 model discriminated better because it includes the laparotomic evaluation of the peritoneal carcinomatosis index.

Background For many years, long-acting intramuscular (LAI) antipsychotics have been prescribed predominantly to chronic and severe patients, as a last resort when other treatments failed. Recently, a broader and earlier use of LAIs, particularly second-generation LAIs, has been emphasized. To date, few studies attempted to frame how this change in prescribing took place in real-world practice. Therefore, this study aimed to describe the clinical features of patients prescribed with LAIs, and to explore possible prescribing differences between first- and second-generations LAIs under ordinary clinical practice in Italy. Methods The STAR Network "Depot" Study is an observational, longitudinal, multicenter study involving 35 centers in Italy. In the cross-sectional phase, patients prescribed with LAIs were consecutively recruited and assessed over a period of 12 months. Descriptive statistics and multivariable logistic regression analyses were employed. Results Of the 451 recruited patients, 61% were males. The level of social and working functioning was heterogeneous, as was the severity of disease. Seventy-two per cent of the patients had a diagnosis of the schizophrenia spectrum. Seventy per cent were prescribed with second-generation antipsychotic (SGA) LAIs (mostly paliperidone, aripiprazole and risperidone). Compared to first-generation antipsychotic (FGA) LAIs, patients prescribed with SGA LAIs were more often younger; employed; with a diagnosis of the schizophrenia spectrum or bipolar disorder; with higher levels of affective symptoms; with fewer LAI prescriptions in the past. Discussion LAIs' prescribing practices appear to be more flexible as compared to the past, although this change is mostly restricted to SGA LAIs.

Background and purpose: Capecitabine-based radiochemotherapy (cbRCT) is standard for preoperative long-course radiochemotherapy of locally advanced rectal cancer. This prospective, parallel-group, randomised controlled trial investigated two intensification regimens. cT4 lesions were excluded. Primary objective: pathological outcome (TRG 1-2) among arms.Materials and methods: Low-located cT2N0-2M0, cT3N0-2M0 (up to 12 cm from anal verge) presentations were treated with cbRCT randomly intensified by either radiotherapy boost (Xelac arm) or multidrug concomitant chemotherapy (Xelox arm). Xelac: concomitant boost to bulky site (45 Gy/1.8 Gy/die, 5 sessions/week to the pelvis, + 10 Gy at 1 Gy twice/week to the bulky) plus concurrent capecitabine (1650 mg/mq/die). Xelox: 45 Gy to the pelvis + 5.4 Gy/1.8 Gy/die, 5 sessions/week to the bulky site + concurrent capecitabine (1300 mg/mq/die) and oxaliplatin (130 mg/mq on days 1,19,38). Surgery was planned 7-9 weeks after radiochemotherapy.Results: From June 2005 to September 2013, 534 patients were analysed: 280 in Xelac, 254 in Xelox arm. Xelox arm presented higher G >= 3 haematologic (p = 0.01) and neurologic toxicity (p < 0.001). Overall, 98.5% patients received curative surgery. The tumour regression grade distribution did not differ between arms (p = 0.102). TRG 1+2 rate significantly differed: Xelac arm 61.7% vs. Xelox 52.3% (p = 0.039). Pathological complete response (ypT0N0) rates were 24.4 and 23.8%, respectively (p non-significant). Median follow-up: 5.62 years. Five-year disease-free survival rate were 74.7% (Xelac) and 73.8% (Xelox), respectively (p = 0.444). Five-year overall survival rate were 80.4% (Xelac) and 85.5% (Xelox), respectively (p = 0.155).Conclusion: Xelac arm significantly obtained higher TRG1-2 rates. No differences were found about clinical outcome. Because of efficacy on TRG, inferior toxicity and good compliance, Xelac schedules or similar radiotherapy dose intensification schemes could be considered as reference treatments for cT3 lesions. (C) 2018 Published by Elsevier B.V.

Purpose To report early safety and efficacy of Descemet stripping only (DSO) supplemented with ripasudil. Methods A pre-post clinical trial with a historical control group for time to heal and cell count parameters. The study received ethics approval and was conducted with oversight of a data safety monitoring board. All enrolled patients had a superior endothelial cell count of >1000 cells/mm2 and were symptomatic from the presence of central guttata degrading vision and/or producing glare. DSO was carried out with a peeling technique and not combined with any other intervention. Ripasudil 0.4% was applied topically from day 1 postoperatively at a dose of 6 times/d until corneal clearance. Cases with relapse of edema were permitted to restart on ripasudil at a reduced dose of 2 drops/d for a further 2 weeks. Stopping rules with progression to a corneal graft were established. Baseline ocular and systemic investigations were carried out and repeated at varying intervals to monitor for local and systemic adverse events. Results Twenty-three eyes of 23 patients met the inclusion criteria and underwent DSO. Twenty-two of 23 eyes achieved corneal clearance at a mean time of 4.1 weeks. In all patients achieving clearance, improvement in vision was recorded. Improvement in mean uncorrected visual acuity was 0.20 Logarithm of the minimum angle of resolution (LogMar), and improvement in mean best spectacle corrected visual acuity was 0.156 LogMar. One patient failed to clear and underwent Descemet membrane endothelial keratoplasty at week 12. Twenty-one of 22 patients achieving corneal clearance expressed satisfaction with the procedure. The commonest systemic side effect of topical ripasudil was gastrointestinal upset (24%), and the commonest local side effect was ocular irritation (43%). No patient experienced a serious adverse event in the course of the trial. Thirty-nine percent of patients experienced a relapse of edema on ceasing ripasudil, with clearance again on recommencing. Conclusions This trial of DSO supplemented with ripasudil included local and systemic safety analysis. We judge that this treatment option is emerging as a reliable intervention for select patients with Fuchs' Endothelial Corneal Dystrophy (FECD) with an acceptable safety profile. The observation of relapse edema is strong evidence of a drug effect. The longevity of these results remains unknown.

Background: Long acting injectable (LAI) antipsychotics have been claimed to ensure treatment adherence and possibly reduce the daily burden of oral formulations. So far, only surveys investigating the theoretical prescribing attitudes of clinicians have been employed. On this basis, we aimed to investigate reasons for prescribing LAIs in a real-world, unselected sample of patients. Methods: The STAR Network Depot Study is an observational, multicentre study consecutively enrolling adults initiating a LAI over a 12-months period. Clinical severity was assessed with the Brief Psychiatric Rating Scale, and patient’s attitude toward medications with the Drug Attitude Inventory 10 items. Psychiatrists recorded reasons for LAI prescribing for each study participant. Responses were grouped into six non-mutually exclusive categories: aggressiveness, patient engagement, ease of drug taking, side-effects, stigma, adherence. Results: Of the 451 patients included, two-thirds suffered from chronic psychoses. Improving patient engagement with the outpatient psychiatric service was the most common reason for prescribing LAIs (almost 80% of participants), followed by increasing treatment adherence (57%), decreasing aggressiveness (54%), and improving ease of drug taking (52%). After adjusting for confounders, logistic regression analyses showed that reasons for LAI use were associated with LAI choice (e.g. first-generation LAIs for reducing aggressiveness). Conclusion: Despite the wide availability of novel LAI formulation and the emphasis on their wider use, our data suggest that the main reasons for LAI use have remained substantially unchanged over the years, focusing mostly on improving patient’s engagement. Further, clinicians follow implicit prescribing patterns when choosing LAIs, and this may generate hypotheses for future experimental studies.

// Salvatore Pucciarelli 1 , Manuel Zorzi 2 , Nicola Gennaro 3 , Francesco Marchegiani 1 , Andrea Barina 1 , Massimo Rugge 2, 4 , Matteo Zuin 1 , Alessandro Perin 1 , Isacco Maretto 1 , Francesca Bergamo 5 , Caterina Boso 6 , Emanuele Damiano Luca Urso 1 , Patrick Frambach 1 and Maria Chiara Corti 3 1 Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy 2 Regional Health Service, Veneto Tumor Registry, Veneto Region, Padua, Italy 3 Regional Health Service, Epidemiology Unit, Veneto Region, Padua, Italy 4 Department of Medicine DIMED, Pathology and Cytopathology Unit, University of Padua, Padua, Italy 5 Medical Oncology 1, Veneto Institute of Oncology IOV – IRCCS, Padua, Italy 6 Radiation Oncology, Veneto Institute of Oncology IOV – IRCCS, Padua, Italy Correspondence to: Salvatore Pucciarelli, email: puc@unipd.it Keywords: rectal cancer; hospital volume; volume-outcome relationship; short-term outcomes; population study Abbreviations: APR: abdominoperineal resection; CI: confidence interval; HV: hospital volume; LOS: length of stay; OR: odds ratio Received: July 12, 2017 Accepted: February 28, 2018 Published: March 30, 2018 ABSTRACT There is growing interest on the potential relationship between hospital volume (HV) and outcomes as it might justify the centralization of care for rectal cancer surgery. From the National Italian Hospital Discharge Dataset, data on 75,280 rectal cancer patients who underwent elective major surgery between 2002 and 2014 were retrieved and analyzed. HV was grouped into tertiles: low-volume performed 1-12, while high-volume hospitals performed 33+ procedures/year. The impact of HV on in-hospital mortality, abdominoperineal resection (APR), 30-day readmission, and length of stay (LOS) was assessed. Risk factors were calculated using multivariate logistic regression. The proportion of procedures performed in low-volume hospitals decreased by 6.7 percent (p

Background Large sample sizes are often required to detect statistically significant associations between pharmacogenetic markers and treatment response. Meta-analysis may be performed to synthesize data from several studies, increasing sample size and, consequently, power to detect significant genetic effects. However, performing robust synthesis of data from pharmacogenetic studies is often challenging because of poor reporting of key data in study reports. There is currently no guideline for the reporting of pharmacogenetic studies that has been developed using a widely accepted robust methodology. The objective of this project was to develop the STrengthening the Reporting Of Pharmacogenetic Studies (STROPS) guideline. Methods and findings We established a preliminary checklist of reporting items to be considered for inclusion in the guideline. We invited representatives of key stakeholder groups to participate in a 2-round Delphi survey. A total of 52 individuals participated in both rounds of the survey, scoring items with regards to their importance for inclusion in the STROPS guideline. We then held a consensus meeting, at which 8 individuals considered the results of the Delphi survey and voted on whether each item ought to be included in the final guideline. The STROPS guideline consists of 54 items and is accompanied by an explanation and elaboration document. The guideline contains items that are particularly important in the field of pharmacogenetics, such as the drug regimen of interest and whether adherence to treatment was accounted for in the conducted analyses. The guideline also requires that outcomes be clearly defined and justified, because in pharmacogenetic studies, there may be a greater number of possible outcomes than in other types of study (for example, disease–gene association studies). A limitation of this project is that our consensus meeting involved a small number of individuals, the majority of whom are based in the United Kingdom. Conclusions Our aim is for the STROPS guideline to improve the transparency of reporting of pharmacogenetic studies and also to facilitate the conduct of high-quality systematic reviews and meta-analyses. We encourage authors to adhere to the STROPS guideline when publishing pharmacogenetic studies., Marty Chaplin and co-authors recount the development of a guideline for reporting pharmacogenetic studies.

Ocular trauma is an important cause of preventable visual impairment worldwide. An estimated 2.4 million cases occur every year in the USA, with serious vision-threatening injuries ranging from 20,000 to 68,000 of these. Most cases presented in a study by the National Eye Trauma System Registry were seen in young male patients and happened in a home or workplace setting (Parver et al. 1993); therefore, the economic and social burden of this topic cannot be overstated. According to the Birmingham Eye Trauma Terminology (BETT) system, intraocular foreign bodies (IOFBs) or retained foreign objects are a subset of penetrating injuries, when there is an entrance wound without an exit wound (Kuhn et al. 2004). They account for 14–43% of open-globe injuries (OGIs) (Patel et al. 2012; Zhang et al. 2011; Shock and Adams 1985) and pose challenging surgical cases in which the goal is to remove the foreign body (FB) while attempting to preserve vision and restore ocular architecture (Greven et al. 2000). The most common site of entry is the cornea (65%), followed by the sclera (25%) and the limbus (10%) (Rathod and Mieler 2011). Most IOFBs are seen in the posterior segment (Katz and Moisseiev 2009; Zhang et al. 2011) but can also be found in the anterior chamber or even in the lens (Fig. 9.1). The composition of IOFBs differ, ranging from organic material such as wood and insect parts to inert substances like plastic and glass, but most of them are metallic in nature (Greven et al. 2000; Woodcock et al. 2006).

Highlights • A large population based analysis to evaluate pathologic response according to time of surgery. • LARC patients were treated with modern techniques of radiotherapy and surgery. • The rate of pCR increased according to time interval from 12.6% to 31.1%. • The pCR increasing was 1.5% (about 0.2%/die) per each week of waiting. • Lengthening the interval (>13 weeks) significantly improved the pathological response., Background To retrospectively evaluate the difference in terms of pathologic complete response (pCR) according to time elapsed between chemoradiation (CRT) and total mesorectal excision (TME) on a large unselected real-life dataset of locally advanced rectal cancer (LARC) patients. Methods A multicentre retrospective cohort study of LARC patients from 21 Italian Radiotherapy Institutions was performed. Patients were stratified into 3 different time intervals from CRT. The 1st group included 300 patients who underwent TME within 6 weeks, the 2nd 1598 patients (TME within 7–12 weeks) and the 3rd 196 patients (TME within 13 or more weeks after CRT), respectively. Results Data on 2094 LARC patients treated between 1997 and 2016 were considered suitable for analysis. Overall, 578 patients had stage II while 1516 had stage III histological proven invasive rectal adenocarcinoma. A CRT schedule of one agent (N = 1585) or 2-drugs (N = 509) was administered. Overall, pCR was 22.3% (N = 468 patients). The proportion of patients achieving pCR with respect to time interval was, as follows: 12.6% (1st group), 23% (2nd group) and 31.1% (3rd group) (p 5040 cGy (p = 0.002) and longer interval (p 13 weeks) from CRT to surgery improves the pathological response (pCR and pathologic partial response; pPR) in comparison to historic data. Furthermore, radiotherapy dose >5040 cGy and two drugs chemotherapy correlated with pPR rate.

Background: The prediction of lymph node status using MRI has an impact on the management of rectal cancer, both before and after preoperative chemoradiotherapy. Objective: The purpose of this study was to maximize the negative predictive value and sensitivity of mesorectal lymph node imaging after chemoradiotherapy because postchemoradiation node-negative patients may be treated with rectum-sparing approaches. Design: This was a retrospective study. Settings: The study was conducted at a tertiary care hospital. Patients: Sixty-four patients with locally advanced rectal cancer who underwent preoperative chemoradiotherapy and MRI for staging and the assessment of response were evaluated. Main Outcome Measures: The sums of the sizes of all mesorectal lymph nodes in each patient on both prechemoradiotherapy and postchemoradiotherapy imaging data sets were calculated to determine the lymph node global size reduction rates, taking these to be the outcomes of the histopathologic findings. Other included measures were interobserver agreement regarding the prediction of node status based on morphologic criteria and the diagnostic performance of contrast-enhanced images. Results: Using a cutoff value of a 70% lymph node global size reduction rate with only 15 node-positive patients on histopathology, the sensitivity in the prediction of nodal status and negative predictive value were 93% (95% CI, 70.2%-98.8%) and 97% (95% CI, 82.9%-99.8%) for observer 1 and 100% (95% CI, 79.6%-100%) and 100% (95% CI, 62.9%-100%) for observer 2. The areas under the receiver operating characteristic curves for the 2 observers were 0.90 (95% CI, 0.82-0.98; p < 0.0001) for observer 1 and 0.65 (95% CI, 0.50-0.79; p = 0.08) for observer 2. The efficacy of the morphologic criteria and contrast-enhanced images in predicting node status was limited after chemoradiotherapy. Limitations: This study is limited by its small sample size and retrospective nature. Conclusions: Assessing the lymph node global size reduction rate value reduces the risk of undetected nodal metastases and may be helpful in better identifying suitable candidates for the local excision of early stage rectal cancer. © 2017 The ASCRS.

Aim: The Objective of our study was to evaluate the chromosomal analysis results that were obtained from amniocentesis, cordocentesis and chorionic villus sampling (CVS) inpatients whom had applied to the perinatology unit of Cukurova University Faculty of Medicine gynecology and obstetrics clinic with high risk in terms of chromosome anomaly according to Ultrasonography (USG).Material and Methods: Our study was conducted as a retrospective pattern. CVS, amniocentesis and cordosentesis were performed in 1298 pregnant women whom had applied to the Cukurova University Faculty of Medicine, Gynecology and Obstetrics Clinic, Perinatology Unit in the date interval between 1st December 2014-31st December 2016 with the indication of abnormal maternal serum screening tests, maternal request because of advanced maternal age, history of fetal anomaly with previous pregnancies, history of relatives with Trisomy 21, fetal abnormalities or signs of trisomy which were detected by ultrasonography and only depending on maternal request without any risk factors. Data obtained in the study were assessed using the SPSS (Statistical Package for Social Sciences) 22.0 package program. The relationships between categorical variables were determined by Chi-Square test. Relationship between normal distribution-matched, numerical data were assessed by ANOVA, Independent Sample t-test, and relationship between non-normal distributions of numerical data were assessed using Mann-Whitney U and Wilcoxon Test. Statistical significance level was determined as p 0.05.Results: Fetal anomalies were observed in 28.9% (n: 366) of the patients while 369 (28.4%) of the 1298 patients who had prenatal diagnosis had abnormalities in the maternal screening results. No chromosomal abnormalities were detected in 1120 (86.2%) of the 1298 patients who were taken into the study. 49 patients had Trisomy 21, 27 patients had Trisomy18 and 14 patients had Trisomy13. Turner syndrome was seen in 10 of thepatients. In our study, chromosomal abnormality rate of patients with more than one minor marker was found to be statistically significant (p: 0.01). Chromosomal anomaly was detected in 319 (8.4%) of 349 patients with combined test. Chromosomal anomaly was detected in 70 (19.1%) of the 366 patients who detected fetal anomaly. Chromosomal anomaly was detected in 27 (24.1%) of the 112 increased NT patients.Conclusion: In our study, 1298 invasive procedures are listed as follows; amniocentesis was performed in 841 (64.8%), cordocentesis in 57 patients (4.4%) and CVS in 400 patients (30.8%). As a result of karyotype analysis of the patients, nochromosomal anomaly was detected in 1120 patients (86.28%). In 178 patients, chromosomal anomaly (13.71%) was detected. This study aimed to determine the prevalence of fetal chromosomal anomaly in the Mediterranean region by determining the prevalence of invasive prenatal test indications and evaluating the results of invasive prenatal tests performed in our clinic in the 2-year period.

Congenital diaphragmatic hernia (CDH) is a neonatal defect in which the diaphragm muscle does not develop properly, thereby raising abdominal organs into the thoracic cavity and impeding lung development and function. Large diaphragmatic defects require correction with prosthetic patches to close the malformation. This treatment leads to a consequent generation of unwelcomed mechanical stress in the repaired diaphragm and hernia recurrences, thereby resulting in high morbidity and significant mortality rates. We proposed a specific diaphragm-derived extracellular matrix (ECM) as a scaffold for the treatment of CDH. To address this strategy, we developed a new surgical CDH mouse model to test the ability of our tissue-specific patch to regenerate damaged diaphragms. Implantation of decellularized diaphragmatic ECM-derived patches demonstrated absence of rejection or hernia recurrence, in contrast to the performance of a commercially available synthetic material. Diaphragm-derived ECM was able to promote the generation of new blood vessels, boost long-term muscle regeneration, and recover host diaphragmatic function. In addition, using a GFP + Schwann cell mouse model, we identified re-innervation of implanted patches. These results demonstrated for the first time that implantation of a tissue-specific biologic scaffold is able to promote a regenerating diaphragm muscle and overcome issues commonly related to the standard use of prosthetic materials. STATEMENT OF SIGNIFICANCE: Large diaphragmatic hernia in paediatric patients require application of artificial patches to close the congenital defect. The use of a muscle-specific decellularized scaffold in substitution of currently used synthetic materials allows new blood vessel growth and nerve regeneration inside the patch, supporting new muscle tissue formation. Furthermore, the presence of a tissue-specific scaffold guaranteed long-term muscle regeneration, improving diaphragm performance to almost complete functional recovery. We believe that diaphragm-derived scaffold will be key player in future pre-clinical studies on large animal models. ispartof: Acta Biomaterialia vol:89 pages:115-125 ispartof: location:England status: published

With this study we wanted to analyse a cohort of 135 patients who in the period beginning of the year 2014/february 2018 have reached our observation at Ser.T. in Voghera and Ser.T. of Pavia. These subjects have arrived at our services with problems related to the various forms of dependence, with more or less urgent needs related to the use and the abuse of substances, alcohol and with behaviours, lifestyles and pathologies related to them. After a first and cognitive interview, associated with a first and scrupulous analysis, a first reception is carried out. It was noted that they complained about some clinical and behavioural disorders typical of an important inner suffering, such as to be recognized and defined by a real request for “help” as in need of suggestive analyses and further investigations. It was therefore thought of a possible hospital evaluation to better study the cases and any related pathologies. The project is therefore exposed to the corporate management Asst of Pavia, which takes it into account, and collected by the Department of Internal Medicine of the hospital of Stradella. A collaborative, ductile, elastic, itinerant network is therefore created. A network of observation, protection, safety and rescue around the patient itself: the so-called “Car (a) vain”. It was then made arrangements and it began to evaluate patients individually. After about 45 months and in the light of the 135 patients studied, a mosaic of pathologies related to drug dependence and alcohol dependence came out with a suggestive clinical picture of further deepening of the project.

Resumo Introducao: O pterigio e uma proliferacao de tecido fibrovascular centripeta, que avanca da conjuntiva bulbar em direcao ao centro da cornea. A excisao do pterigio pode causar melhora na acuidade visual. A excisao cirurgica tem como objetivo atingir uma superficie ocular topograficamente regular. A melhora da acuidade visual decorre da alteracao do poder refrativo corneano, que e aferido na topografia como alteracao do astigmatismo topografico. O objetivo do estudo foi avaliar a variacao do astigmatismo topografico final apos a cirurgia de exerese de pterigio. Metodos: Foi realizado um estudo prospectivo de acompanhamento de pacientes apos cirurgia de exerese de pterigio com a realizacao de topografias corneanas antes e 1 mes apos a cirurgia. A populacao foi do tipo nao-probabilistica de voluntarios, com n de 74 olhos. A amostragem foi por conveniencia, sendo oferecida a participacao aos pacientes do ambulatorio geral de oftalmologia que foram submetidos ao procedimento de exerese de pterigio entre julho e dezembro de 2015. Resultados: Foram realizadas 74 cirurgias no periodo e 44 foram incluidas na analise estatistica. Os valores medios do astigmatismo topografico (CYL) mostraram reducao estatisticamente significativa de 2,715D para 1,448D (p=0,0037). A alteracao do meridiano mais curvo (Ks) nao mostrou alteracao significativa com variacao de 45,60 D para 45,32 D (p=0,1050), enquanto o meridiano plano a 90o Ks (Kf) mostrou aumento significativo de 42,86 D para 43,87 D (p=0,0052). A analise isolada dos grupos mostrou que apenas o grupo com pterigios grau 3 sofreu alteracao significativa do CYL de 7,12 D para 1,82 D (p=0,0002). Conclusao: A cirurgia resultou em uma reducao significativa do astigmatismo topografico apenas em pacientes com pterigio grau 3, isso em decorrencia da reducao do aplanamento provocado pelo pterigio.

To compare the functional results from surgical treatment for anatomical reconstruction of the anterior cruciate ligament (ACL) with a single band, using two types of autologous grafts.Twenty-seven patients who underwent anatomical reconstruction of the ACL by means of the Chambat technique were evaluated prospectively. They were divided into two groups: A, with 14 patients, using grafts from flexor tendons; and B, with 13 patients, using grafts from the patellar tendon. In both groups, fixation was performed using an absorbable interference screw.Based on the Lysholm score, group A presented a mean score of 71.6 in the first month, while B presented 75. At the end of the sixth month, both groups presented 96.6. Evaluation of the total IKDC showed that in the first month, the majority of the patients, both in group A (85.7%) and in group B (76.9%), presented a knee assessment that was close to normal. In the sixth month, 92.9% of group A had normal presentations, and 100% of group B.According to the Lysholm functional evaluation and the IKDC subjective assessment, there was no statistically significant difference in the results between the groups, and the results were better in the sixth month.Comparar o resultado funcional do tratamento cirúrgico da reconstrução anatômica do ligamento cruzado anterior (LCA) com banda única com o uso de dois tipos de enxerto autólogos.Foram avaliados prospectivamente 27 pacientes, submetidos à reconstrução anatômica do LCA pela técnica de Chambat, divididos em dois grupos: A, com 14 e uso como enxerto dos tendões flexores; e B, com 13 e uso como enxerto do tendão patelar. Em ambos os grupos foi feita fixação com parafuso de interferência absorvível.Com base no escore de Lysholm, o grupo A apresentou pontuação média de 71,6 no primeiro mês, enquanto o B apresentou 75. Já no fim do sexto mês ambos apresentaram 96,6. A avaliação do IKDC total mostrou que no primeiro mês a maioria dos pacientes, tanto no grupo A (85,7%) no grupo B (76,9%), apresentava uma avaliação do joelho próximo do normal e no sexto mês o grupo A apresentou 92,9% como normal e o grupo B, 100%.Os resultados, segundo avaliação funcional de Lysholm e subjetiva do IKDC, não apresentaram diferenças estatisticamente significantes entre os grupos e foram melhores no sexto mês.

Background: Pathological complete response (pCR) to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) is still ascribed to a minority of patients. A pathway based-approach could highlight the predictive role of germline single nucleotide polymorphisms (SNPs). The primary aim of this study was to define new predictive biomarkers considering treatment specificities. Secondary aim was to determine new potential predictive biomarkers independent from radiotherapy (RT) dosage and cotreatment with oxaliplatin. Methods: Thirty germ-line SNPs in twenty-one genes were selected according to a pathway-based approach. Genetic analyses were performed on 280 LARC patients who underwent fluoropyrimidine-based CRT. The potential predictive role of these SNPs in determining pathological tumor response was tested in Group 1 (94 patients undergoing also oxaliplatin), Group 2 (73 patients treated with high RT dosage), Group 3 (113 patients treated with standard RT dosage), and in the pooled population (280 patients). Results: Nine new predictive biomarkers were identified in the three groups. The most promising one was rs3136228-MSH6 (p = 0.004) arising from Group 3. In the pooled population, rs1801133-MTHFR showed only a trend (p = 0.073). Conclusion: This exploratory study highlighted new potential predictive biomarkers of neoadjuvant CRT and underlined the importance to strictly define treatment peculiarities in pharmacogenetic analyses.

Background: Preoperative chemoradiotherapy (CRT) followed by surgery is the standard care for locally advanced rectal cancer, but tumour response to CRT and disease outcome are variable. The current study aimed to investigate the effectiveness of plasma telomerase reverse transcriptase (TERT) levels in predicting tumour response and clinical outcome. Methods: 176 rectal cancer patients were included. Plasma samples were collected at baseline (before CRT=T0), 2 weeks after CRT was initiated (T1), post-CRT and before surgery (T2), and 4–8 months after surgery (T3) time points. Plasma TERT mRNA levels and total cell-free RNA were determined using real-time PCR. Results: Plasma levels of TERT were significantly lower at T2 (P

The purpose of the study was to assess the relationship of the continuous mode contrast-enhanced harmonic ultrasound (CEUS) imaging with the histopathological and immunohistochemical (IHC) quantitative estimation of microvascular proliferation on synovial samples of patients affected by sustained psoriatic arthritis (PsA). A dedicated linear transducer was used in conjunction with a specific continuous mode contrast enhanced harmonic imaging technology with a second-generation sulfur hexafluoride-filled microbubbles C-agent. The examination was carried out within 1 week before arthroscopic biopsies in 32 active joints. Perfusional parameters were analyzed including regional blood flow (RBF); peak (PEAK) of the C-signal intensity, proportional to the regional blood volume (RBV); beta (β) perfusion frequency; slope (S), representing the inclination of the tangent in the origin; and the refilling time (RT), the reverse of beta. Arthroscopic synovial biopsies were targeted in the hypervascularity areas, as in the same knee recesses assessed by CEUS; the synovial cell infiltrate and vascularity (vessel density) was evaluated by IHC staining of CD45 (mononuclear cell) and CD31, CD105 (endothelial cell) markers, measured by computer-assisted morphometric analysis. In the CEUS area examined, the corresponding time-intensity curves demonstrated a slow rise time. Synovial histology showed slight increased layer lining thickness, perivascular lymphomonocyte cell infiltration, and microvascular remodeling, with marked vessel wall thickening with reduction of the vascular lumen. A significant correlation was found between RT and CD31+ as PEAK and CD105+ vessel density; RT was inversely correlated to RBF, PEAK, S, and β. The study demonstrated the association of the CEUS perfusion kinetics with the histopathological quantitative and morphologic estimation of synovial microvascular proliferation, suggesting that a CEUS imaging represents a reliable tool for the estimate of the synovial hypervascularity in PsA.

Introduction In the USA, breast cancer is the second most common cancer in women after skin cancer. Approximately 12.3 % of women will be diagnosed with breast cancer at some point during their lifetime, based on 2010–2012 data. The number of new cases of breast cancer expected for Brazil in the year 2014 is 57,120, with an estimated risk of 56.09 cases per 100,000 women.

Introduction: The evolution of techniques in abdominal surgery has lowered postoperative morbidity and complication rates and has continually encouraged surgeons to search for new innovations. This study describes an abdominoplasty technique that combines a wide undermining (2–3 cm lateral to the external border of the rectus muscles) with complete body liposuction, not preserving the Scarpa’s fascia. Methods: From January 2005 to May 2011, abdominoplasty associated with liposuction was performed on 203 patients with an average age of 45 years. Seventy-seven (37.93 %) patients were smokers. Results: The follow-up period ranged from 3 months to 5 years and 3 months (mean of 2 years). No patient showed suprapubic skin necrosis, infection, hematomas, or thromboembolism. Two patients showed seroma, eight hypertrophic scars and six dog ear scar revision. Conclusion: The technique presented in this study has a low complication rate and achieves a more extensive improvement of the body contouring.

Central nervous system involvement (CNS) is a serious and mostly fatal complication of aggressive lymphoma. The incidence of CNS disease in diffuse large B-cell lymphoma (DLBCL) is low (about 5%) and there are not randomised prospective trial which specifically address a decision-making process for CNS prophylaxis. Potentially two methods exist for identifying patients requiring CNS directed treatment. Surveillance lumbar puncture and brain magnetic resonance (MRI) at the time of diagnosis could identify the presence of lymphoma; another method is the identification of patients whose characteristics are indicative of a high risk of CNS disease. Several site-specific risks are described in literature such as testicular, breast, paranasal sinuses, epidural spaces, and intravascular involvement with an incidence of CNS relapse ranging from 15% to 50%. Recently a modified IPI score (CNS IPI) was described to predict risk of CNS relapse. The efficacy of different forms of CNS prophylaxis has never formally been demonstrated. In the RICOVER 60 trial, patients treated with R-CHOP-14 instead of CHOP-14 presented a lower incidence of CNS relapse while intrathecal methotrexate (MTX) has not showed a role in preventing CNS disease for patients treated with combined immunochemotherapy. Recently, combination of intrathecal MTX and high dose MTX infusion after R-CHOP treatment was considered an effective strategy of prevention of CNS relapse. In order to evaluate the efficacy and feasibility of intrathecal MTX administration and high dose MTX after first line chemotherapy, we retrospectively reviewed 27 patients (11 males and 16 females, mean age 61 yrs, range 27-79) with newly diagnosed DLBCL at high risk for CNS relapse, treated from January 2009 to April 2018 at Veneto Institute of Oncology IOV-IRCCS. In our cohort 21 (78%) patients were at advanced stage (III-IV Ann Arbor stage) and 15 (56%) belonged to intermediate-high or high risk IPI categories, two patients presented with orbital localization. Almost all patients received R-CHOP as first line treatments, two patients with paravertebral localization received HyperCVAD as front line approach. For 20 patients CNS-IPI was intermediate or high. In the other cases with low CNS-IPI, disease localization was considered at high risk of CNS relapse (breast, paravertebral, orbit, paranasal sinus). In all patients we performed brain MRI and diagnostic lumbar puncture at diagnosis (all negative at flow cytometry analysis). All 14 patients >65 yrs were evaluated with comprehensive geriatric assessment (CGA) and 8 (57%) were considered fit. Nineteen (19) patients (70%) received at least 3 lumbar punctures with MTX and 24 (89%) two courses of high dose intravenous MTX during first line therapy. At the end of planned first line treatment, 24 (89%) patients obtained a complete remission at PET scan evaluation and 3 patients (11%) presented progressive disease, 2 with CNS involvement and another with peritoneal disease; this last patient had a Double Hit lymphoma with BCL6 and c-MYC rearrangements. Another patient in complete remission after R-CHOP chemotherapy, experienced CNS relapse three year after obtaining complete remission. Among the two patients treated with Hyper CVAD regimen, one is still in complete remission 5 years after the end of treatment; another developed early CNS relapse. All the 3 patient who experienced CNS involvement after R-CHOP, didn't receive prophylaxis because were evaluated frail at CGA. So, at a median follow up of 26.2 months (3.5-100 months) all patients who received the planned treatment at full dose including CNS prophylaxis did not experience central nervous system relapse. In conclusion, CNS prophylaxis including intrathecal MTX administration and high dose MTX infusion after first line chemotherapy is feasible and effective. Larger prospective trials are needed to evaluate the most effective prophylactic therapy and the correct timing of intravenous MTX infusion. Disclosures No relevant conflicts of interest to declare.

Glucocorticoids are beneficial in many muscular dystrophies but they are ineffective in treating dysferlinopathy, a rare muscular dystrophy caused by loss of dysferlin. We sought to understand the molecular basis for this disparity by studying the effects of a glucocorticoid on differentiation of the myoblast cell line, C2C12, and dysferlin-deficient C2C12s. We found that pharmacologic doses of dexamethasone enhanced the myogenic fusion efficiency of C2C12s and increased the induction of dysferlin, along with specific myogenic transcription factors, sarcolemmal and structural proteins. In contrast, the dysferlin-deficient C2C12 cell line demonstrated a reduction in long myotubes and early induction of particular muscle differentiation proteins, most notably, myosin heavy chain. Dexamethasone partially reversed the defect in myogenic fusion in the dysferlin-deficient C2C12 cells. We hypothesize that a key therapeutic benefit of glucocorticoids may be the up-regulation of dysferlin as an important component of glucocorticoid-enhanced myogenic differentiation.

Purpose: The optimal therapy for primary mediastinal large B-cell lymphoma (PMLBCL) remains undefined. The superiority of intensive chemotherapy regimens (Methotrexate, Doxorubicin, Cyclophosphamide, Vincristine, Prednisone, Bleomycin [MACOP-B]/Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Prednisone, Bleomycin [VACOP-B]) over Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP)-like chemotherapy is upheld by some authors. The role of radiotherapy is still debated. In the absence of randomized trials, we report clinical findings and treatment response in 53 consecutive patients treated with intensive chemotherapy and mediastinal involved-field radiation therapy (IFRT). Methods and Material: Fifty-three consecutive patients with PMLBCL were retrospectively analyzed. Planned treatment consisted of induction chemotherapy (I-CT; Prednisone, Methotrexate, Doxorubicin, Cyclophosphamide, Etoposide-Mechloroethamine, Vincristine, Procarbazine, Prednisone [ProMACE-MOPP] in the first 2 patients, MACOP-B in the next 11, and VACOP-B in the last 40) followed by IFRT. Planned treatment was concluded in 43 of 53 patients; in 10 patients, I-CT was not immediately followed by IFRT. Among these 10 patients, 6 received high-dose chemotherapy (HD-CT) followed by IFRT, 2 received HD-CT, and 2 received no further treatment. Results: After a median follow-up of 93.9 months (range, 6–195 months), 45 of 53 patients (84.9%) were alive without disease. Eight patients died: 7 of PMLBCL and 1 of toxicity during HD-CT. The 5-year disease-free survival (DFS) and overall survival rates were 93.42% and 86.6%, respectively. The response rates after I-CT were complete response (CR) in 20 (37.73%) and partial response (PR) in 30 (56.60%); 3 patients (5.66%) were considered nonresponders. Among patients in PR after chemotherapy, 92% obtained a CR after IFRT. Conclusions: Our report confirms the efficacy of intensive chemotherapy plus mediastinal IFRT. IFRT plays a pivotal role in inducing CR in patients in PR after chemotherapy.

Purpose The role of photodynamic therapy (PDT) in the treatment of small cancers has been established in several clinical studies. Here, we report on the efficacy of PDT for early inoperable or recurrent non-small-cell lung cancer (NSCLC). Methods and Materials From June 1989 to November 2004, 40 patients with 50 NSCLC were treated with PDT. Twelve cases were inoperable for medical reasons and were staged as T1N0M0, and 28 had recurrent in situ carcinoma. Patients with residual disease after PDT received definitive radiotherapy and/or brachytherapy. Follow-up ranged from 6 to 167 months (median 43.59). Twenty of the 40 patients received i.v. injections of hematoporphyrin derivative (5 mg/kg), the other 20 had injections of porfimer sodium (Photofrin, 2 mg/kg). An argon dye laser (630 nm wavelength, 200–300 J/cm2) was used for light irradiation in 24 of the 40 patients, a diode laser (Diomed, 630 nm wavelength, 100–200 J/cm2) in the other 16. Results PDT obtained a 72% complete response (CR) rate (36/50 treated lesions), that is 27 CR among the 37 Tis carcinomas and 9 among the 13 T1 cases. Kaplan–Meier curves showed a mean overall survival (OS) of 75.59 months (median 91.4 months). Two- and 5-year OS rates were 72.78% and 59.55%. The mean and median survival rates for patients with Tis stage were 86.5 and 120.4 months, respectively (standard error 9.50) and for patients with T1 disease they were 45.78 and 35.71 months, respectively; the difference was statistically significant (P = 0.03). No severe early or late PDT-related adverse events were recorded. Conclusions PDT is effective in early primary or recurrent NSCLC, resulting in a CR rate of 72%. The incorporation of PDT in standard clinical practice, in combination with radiotherapy, warrants further investigation. Lasers Surg. Med. 39:394–402, 2007. © 2007 Wiley-Liss, Inc.

Since September 1996, 48 untreated patients with bulky or advanced-stage Hodgkin’s disease received the 12-week Stanford V chemotherapy regimen followed by consolidation radiotherapy at a dose of 36 Gy to bulky mediastinal disease and 30.6 Gy to the initial sites of disease ≧3 cm in transverse diameter. After the combined therapy, 46 of 48 (96%) achieved complete remissions. With a median follow-up of 48 months, the 5-year overall survival was 95% and freedom from progression 86%.There were no treatment-related deaths. All but one premenopausal female patient (who received pelvic and inguinal irradiation) recovered normal menses. Until now no case of secondary leukemia or myelodysplasia was observed. Our results confirm that the Stanford V regimen with consolidation radiotherapy is safe and effective in patients with bulky or advanced-stage Hodgkin’s disease, achieving very high remission and overall 5-year survival rates. Longer follow-up is necessary to evaluate the extent of all complications.

This multisite study was conducted to compare the efficacy and tolerability of combination treatment with clozapine plus aripiprazole versus combination treatment with clozapine plus haloperidol in patients with schizophrenia who do not have an optimal response to clozapine. Patients continued to take clozapine and were randomly assigned to receive daily augmentation with aripiprazole or haloperidol. Physicians prescribed the allocated treatments according to usual clinical care. Withdrawal from allocated treatment within 3 months was the primary outcome. Secondary outcomes included severity of symptoms on the Brief Psychiatric Rating Scale and antipsychotic subjective tolerability on the Liverpool University Neuroleptic Side Effect Rating Scale. A total of 106 patients with schizophrenia were randomly assigned to treatment. After 3 months, we found no difference in the proportion of patients who discontinued treatment between the aripiprazole and haloperidol groups (13.2% vs 15.1%, P = 0.780). The 3-month change of the Brief Psychiatric Rating Scale total score was similar in the aripiprazole and haloperidol groups (-5.9 vs -4.4 points, P = 0.523), whereas the 3-month decrease of the Liverpool University Neuroleptic Side Effect Rating Scale total score was significantly higher in the aripiprazole group than in the haloperidol group (-7.4 vs -2.0 points, P = 0.006). These results suggest that augmentation of clozapine with aripiprazole offers no benefit with regard to treatment withdrawal and overall symptoms in schizophrenia compared with augmentation with haloperidol. However, an advantage in the perception of adverse effects with aripiprazole treatment may be meaningful for patients.

Hyperoxia causes a transient decrease in CBF, followed by a later rise. The mediators of these effects are not known. We used mice lacking endothelial or neuronal nitric oxide synthase (NOS) isoforms (eNOS−/− and nNOS−/− mice) to study the roles of the NOS isoforms in mediating changes in cerebral vascular tone in response to hyperoxia. Resting regional cerebral blood flow (rCBF) did not differ between wild type (WT), eNOS−/− mice, and nNOS−/− mice. eNOS−/− mice showed decreased cerebrovascular reactivities to NG-nitro-L-arginine methyl ester (L-NAME), PAPA NONOate, acetylcholine (Ach), and SOD1. In response to hyperbaric oxygen (HBO2) at 5 ATA, WT and nNOS−/− mice showed decreases in rCBF over 30 minutes, but eNOS−/− mice did not. After 60 minutes HBO2, rCBF increased more in WT mice than in eNOS−/− or nNOS−/− mice. Brain NO-metabolites (NOx) decreased in WT and eNOS−/− mice within 30 minutes of HBO2, but after 45 minutes, NOx rose above control levels, whereas they did not change in nNOS−/− mice. Brain 3NT increased during HBO2 in WT and eNOS−/− but did not change in nNOS−/− mice. These results suggest that modulation of eNOS-derived NO by HBO2 is responsible for the early vasoconstriction responses, whereas late HBO2-induced vasodilation depends upon both eNOS and nNOS.

Physiological dead space (Vds), end-tidal CO2(Pet CO2 ), and arterial CO2(PaCO2 ) were measured at 1 and 2.8 ATA in a dry hyperbaric chamber in 10 older (58–74 yr) and 10 younger (19–39 yr) air-breathing subjects during rest and two levels of upright exercise on a cycle ergometer. At pressure, Vd(liters btps) increased from 0.34 ± 0.09 (mean ± SD of all subjects for normally distributed data, median ± interquartile range otherwise) to 0.40 ± 0.09 ( P= 0.0060) at rest, 0.35 ± 0.13 to 0.45 ± 0.11 ( P = 0.0003) during light exercise, and 0.38 ± 0.17 to 0.45 ± 0.13 ( P = 0.0497) during heavier exercise. During these conditions, PaCO2 (Torr) increased from 33.8 ± 4.2 to 35.7 ± 4.4 ( P = 0.0059), 35.3 ± 3.2 to 39.4 ± 3.1 ( P < 0.0001), and 29.6 ± 5.6 to 37.4 ± 6.5 ( P < 0.0001), respectively. During exercise, Pet CO2 overestimated PaCO2 , although the absolute difference was less at pressure. Capnography poorly estimated PaCO2 during exercise at 1 and 2.8 ATA because of wide variability. Older subjects had higher Vd at 1 ATA but similar changes in Vd, PaCO2 , and Pet CO2 at pressure. These results are consistent with an effect of increased gas density.

From 1985 to 1998, at the Regional Cancer Center of Padua, patients with Hodgkin's disease (HD) routinely underwent a clinical staging procedure including lymphangiography and laparoscopy with multiple liver and spleen biopsies. Patients with IA and IIA nonbulky HD were treated with radiotherapy alone. The aim of this study is to analyze the efficacy of radiotherapy as radical treatment in this group of patients, and the role of lymphangiography and laparoscopy in the selection of patients with abdominal disease located to the spleen, liver, or the pelvic lymphatic chains. From January 1985 to January 1998, 94 previously untreated patients with biopsy-proven HD underwent clinical staging procedures consisting of history, physical examination, routine laboratory tests, chest radiography, total-body computed tomography scan, and bone marrow biopsy and were considered in stage I-IIA nonbulky. In addition, all patients underwent bipedal lymphangiography, which was positive in 12 (12.8%). Of the 82 patients with negative lymphangiography, 9 (11%) showed disease below the diaphragm at laparoscopy with multiple random spleen and liver biopsies. Of the remaining 73 patients, 32 were male and 41 were female with a median age of 29 years (range: 14-72 years). The stage at diagnosis was IA in 34 patients and IIA in 39. Histology was nodular sclerosis (NS) in 44 patients, lymphocyte predominance (LP) in 16, and mixed cellularity (MC) in 13. Of the 39 IIA stage patients, 27 showed an involvement of 2 lymph-nodal regions, 1 1 of 3 regions, and 1 of 4 regions. All patients were treated with radiotherapy alone for a total dose of 39.6 Gy in 22 fractions. Of the 39 IIA stage patients, 36 were treated with subtotal lymphoid irradiation (STLI), mantle plus paraaortic and spleen field, and 3 with mantle field alone, while of the 34 IA stage patients, 20 were treated with STLI, 13 with mantle field, and 1 with involved field. After a medium follow-up of 104 months (minimum 27, maximum 195, median 101), 71 patients (97%) are still alive without evidence of disease. Seven patients (10.4%) relapsed 3, 11, 12, 15, 28, 29, and 48 months after the diagnosis. Initially the stage of these patients was IA in 3 and IIA in 4, whereas the histology was NS in 5, LP in 1, and MC in 1. One patient alone had a pelvic failure, 48 months after the first diagnosis. The other sites of relapse were: bone marrow in 2 patients, bone marrow plus liver in 2, axillary nodes in 1, and internal mammary chain nodes in another. All relapsed patients had previously undergone subtotal lymphoid irradiation (STLI). At relapse, 5 patients received chemotherapy, 1 chemotherapy plus radiotherapy, and 1 radiotherapy alone. Five of 7 patients obtained a second complete remission still lasting after 27, 68, 70, 98, 103 months, respectively, whereas 2 patients (2.9%) died of progressive disease, respectively, 3 and 35 months after relapse. Our data suggest that a well-defined group of patients with early stage HD, who undergo an accurate clinical staging procedure, can be effectively treated with radiotherapy alone.

Background One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study. Methods/Design The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome. Discussion The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia. Trial Registration Clincaltrials.gov Identifier: NCT00395915

Background As lithium treatment might be effective in reducing the risk of deliberate self-harm (DSH) in adult patients with unipolar affective disorders, we designed a pragmatic randomised trial to assess its efficacy in more than 200 patients with treatment-resistant depression. However, we randomised 56 patients only. The aim of this report is therefore twofold: first, to disseminate the results of this underpowered study which may be incorporated into future meta-analytical reviews; second, to analyse some critical aspects of the study which might explain failure to reach the target sample size. Methods We carried out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode were allocated to add lithium to usual care (intervention arm) versus usual care alone (control arm). Suicide completion and acts of DSH during the 12 months of follow-up constituted the composite primary outcome. Results Of 58 patients screened for inclusion, 29 were allocated to lithium plus usual care and 27 were assigned to usual care without lithium. Six patients in the lithium plus usual care group and seven in the usual care group committed acts of DSH during the follow-up phase. The survival probability did not differ between the two treatment arms (Chi2 = 0.17, p =0.676). With regard to changes in the severity of depressive symptomatology from baseline to endpoint, no significant differences were detected. Conclusions The present study failed to achieve the minimum sample size needed to detect a clinically meaningful difference between the two treatment arms. Consequently, the finding that lithium, in addition to usual care, did not exert a positive effect in terms of reduction of DSH after 12 months of follow-up is likely due to the lack of sufficient statistical power to detect a difference, if a difference existed. The dissemination of the results of this underpowered study will inform future meta-analytical reviews on lithium and suicide-related outcomes. Trial registration ClinicalTrials.gov identifier: NCT00927550

Here we report the clinical and pathological findings in a 30-year-old drug addict in whom an intravenous injection of heroin led to reversible coma with respiratory depression and heart failure. On regaining consciousness, the patient was found to have rhabdomyolysis with renal failure requiring dialysis and peripheral neuropathy. Three weeks later his neurological condition suddenly deteriorated and delayed encephalopathy developed, leading to death 20 days later. The neuropathological study of the brain disclosed pale, spongy myelin with diffuse reactive astrogliosis and microglial proliferation, without hypoxic necrotic lesions. The cerebral and cerebellar cortices were unchanged. The absence of typical hypoxic lesions and the presence of spongiosis with massive astrocytosis distinguished this case from the previously reported cases of delayed leukoencephalopathy following severe hypoxia. An immunocytochemical study designed to exclude an underlying alteration of the metabolic oxidative pathway detected normal expression of the respiratory chain complexes IV, III and V. Despite the absence of an oxidative chain alteration in our patient, we cannot exclude the possibility that an individual predisposition played a pathogenetic role in this delayed leukoencephalopathy.

Recent years have witnessed an increasing interest in the concept of ‘recovery’ in the field of mental health and psychiatry. Anthony (1993) described personal recovery as occurring in the presence of ongoing symptoms but involving ‘a way of living a satisfying, hopeful and contributing life even with limitations caused by illness’ (Anthony, 1993). Recovery from mental illnesses has been conceptualized to involve not only remission of symptoms and achievement of psychosocial milestones but also subjective changes in how persons appraise their lives and the extent to which they experience themselves as meaningful agents in the world (Jacobson & Greenley, 2001). Diverse forms of recovery are possible. In people with optimal outcome, recovery may produce important remission and changes, including the exit from mental health services for a long time period or, sometimes, permanently (Emsley et al, 2011). For other patients, it may mean continuing to receive medical, personal or social support, enabling people to get on with their lives (Emsley et al, 2011). However, in all conditions, the role played by the service in promoting, maintaining and restoring an adequate level of recovery for each patients is pivotal.

Since 1982, our department has used photodynamic therapy (PDT) in the treatment of loco-regional recurrences of gynaecological cancers. We have treated 26 patients in this time. In the majority of cases the site of vaginal recurrences was the vaginal vault. The light sources were an Argon-dye laser (Meditec) and, in some cases, a CO2 laser. The light dose ranged between 60 and 500 J cm−2. The photosensitizing drug used was Hematoporphyrin (HP) (Monico Farmaceutici) at the dose of 5 mg kg−1 body weight. Patients were evaluated 45 days after the treatment with a gynaecological examination and after 75–90 days with a vaginal smear. The results were divided into 2 groups: objective and symptomatic. The symptomatic response concerned only the patients treated with a palliative aim and, in this case, a complete response (CR) was a complete absence of symptoms at least for 60 days. In this group the complete response rate was 66%. In the curative group, the complete response was a cytological and/or histological absence of lesions. In this group we had 12 CR (70.58%). The survival rate was also evaluated. A significant review of the photodynamic therapy in gynaecological neoplasms has also been done.

DLBCL is the most common type of non-Hodgkin lymphoma and it usually affects elderly patients, with a median age at diagnosis of 70 years and an incidence that rises with increasing age. Nevertheless patients > 70 years are rarely included in clinical trials and the management is often different according to local practice. A pre-treatment evaluation based on Performance Status (PS) or comorbidity index is not sufficient to identify patients suitable for treatment with curative intent. We retrospectively reviewed 93 patients with newly diagnosed DLBCL, ≥65 years old , treated from January 2009 to December 2015 at Veneto Institute of Oncology-IRCCS (median age 76 years, range 65-96). Twenty-eight patients (28) were older than 80 years. All but one received at least first line treatment. All patients were evaluated with CGA at diagnosis, based on Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL) and Cumulative Illness Rating Scale (CIRS). According to these variables they were classified into three categories named 'fit', 'vulnerable' and 'frail'. In addition, a cancer-specific modified multidimensional prognostic index (MPI), called Onco-MPI, was calculated for all patients. Onco-MPI score identify three risk score categories (low, moderate and high risk) that predict one-year mortality in older cancer patients. Onco-MPI was calculated according to a validate algorithm as a weighted linear combination of the following CGA domains: age, sex, ADL, IADL, PS, mini-mental state examination, body mass index, CIRS, number of drugs and the presence of caregiver. Cancer sites were also included in the model. Other features analyzed included clinical characteristics, treatment management and outcomes. In our cohort 48% of patients were at advanced Ann Arbor stage (III-IV) with intermediate-high or high risk IPI score in 31%. In 61% of patients we observed extranodal disease, mainly Waldeyer's ring and gastrointestinal tract. First line treatments received included R-CHOP (38%), R-COMP (R-CHOP with non-pegylated liposomial doxorubicin - 23%), R-CVP (14%), R-CEOP (3%), high dose methotrexate (4 patients with primary central nervous system lymphoma), R-VACOP-B (3%), R-Bendamustine in 2 patients and radiotherapy alone was used in 5 patients. Sixty-eight patients (84%) completed the planned cycles of immunochemotherapy. In this group 48,5% required dose reduction for subsequent cycles of treatment because of side effects, in particular hematological toxicities of grade 3-4 or neurological toxicities. In 23 chemotherapy-treated patients initial doses were reduced according to CGA . We observed, after first line therapy, complete response in 63% and partial response in 21%, 8% of patients experienced a disease progression at the end of treatment and 8% died during first line therapy because of lymphoma progression. At time of diagnosis 49% of patients were considered fit at CGA, 16% vulnerable and 35% frail. According to onco-MPI 24 patients (26%) were at low risk of one year mortality, 31 (33%) at medium risk and 38 (41%) at high risk. With a median follow up of 41,1 months the overall survival (OS) of our cohort is 55,9% (95% CI 25,3-56,9). OS correlates with CGA ( 84,4% in fit patients, 31,2 % in vulnerable and 28,1% in unfit, p< 0,001) and Onco-MPI score seems to discriminate our cohort for one-year mortality (95% in low risk, 77% in moderate and 63% in high, p Our retrospective, single Center experience demonstrates that elderly DLBCL need a multidimensional evaluation at diagnosis in order to identify patients candidate to treatment with curative intent. CGA confirm its role for choosing correct management. Also Onco-MPI can be a useful tool even if more data are needed in lymphoma patients. Disclosures No relevant conflicts of interest to declare.

The incidence of locoregional recurrences of gynecological tumors is still a major problem. Many authors suggest that it is the major cause of death in patients affected by cervical-endometrial cancers. The results achieved by retreating these patients with conventional therapies are still unsatisfactory. Since 1982, in our department, we have been using photodynamic therapy (PDT) for treatment of locoregional recurrences in gynecological cancers. We have treated 26 patients. In the majority of the cases, vaginal recurrences were on the vaginal vault. Out of 26 cancers, 17 were epidermoid cancers. Lasers used were the argon dye laser (Meditec) and, in some cases, the CO2 laser. Light dose ranged between 60 and 500 J/cm2. The photosensitizing drug used was hematoporphyrin (HP) (Monico Farmaceutici, Venezia, Italy) at a dose of 5 mg/kg body weight. Patients were evaluated 45 days after treatment with gynecological examination and again after 75-90 days with a vaginal smear. Results were divided into 2 groups: objective and symptomatic. The symptomatic response concerned only patients treated with a palliative aim and, in this case, a complete response (CR) was a complete absence of symptoms for at least 60 days. In this group the complete response rate was 66.6%. In the curative group, the complete response was a cytological and/or histological absence of lesion. In this group we had 12 CR (70.58%). The survival rate of patients treated only with PDT ranged between 3 and 92 months (mean 50.7 months). No major acute or side effects were recorded.