Does ocular treatment of uveal melanoma influence survival?

Treatment of uveal (intraocular) melanoma is aimed at prolonging life, if possible conserving the eye and useful vision. About 50% of patients develop fatal metastatic disease despite successful eradication of the primary intraocular tumour. The effect of ocular treatment on survival is unknown, because the same survival data from case series can be interpreted in different ways. Treatment is therefore based on intuition and varies greatly between centres. Randomised trials of treatment vs non-treatment of asymptomatic tumours are desirable but would be controversial, difficult, expensive and possibly inconclusive. Strategies for coping with uncertainty are needed to avoid unethical care

Distinguishing choroidal nevi from melanomas using the MOLES algorithm: Evaluation in an ocular nevus clinic

OBJECTIVE: The aim of this study was to determine the sensitivity and specificity of the MOLES scoring system in differentiating choroidal melanomas from nevi according to Mushroom shape, Orange pigment, Large tumor size, Enlarging tumor, and Subretinal fluid (SRF). METHODS: Color photographs, fundus-autofluorescence images, and optical coherence tomography of 222 melanocytic choroidal tumors were reviewed. Each MOLES feature was retrospectively scored between 0 and 2 and tumors categorized as "common nevus,""low-risk nevus,""high-risk nevus,"and "probable melanoma"according to the total score. MOLES scores were compared with the experts' diagnosis of melanoma. RESULTS: The MOLES scoring system indicated melanoma in all 81 tumors diagnosed as such by ocular oncologists (100% sensitivity) and nevus in 135 of 141 tumors given this diagnosis by these experts (95.7% specificity). Of the 6 tumors with discordant diagnoses, 4 had basal diameters exceeding 6 mm, all with SRF and/or orange pigment, and 2 small tumors showed either significant SRF with traces of orange pigment, or vice versa. CONCLUSIONS: The MOLES system for diagnosing melanocytic choroidal tumors compares well with expert diagnosis but needs to be evaluated when deployed by ophthalmologists and community optometrists in a wide variety of working environments

“Multidimensional child sex rings”: a systematic review of the literature

Background: In 1983 Kennet Lanning began his studies dealing with sexual rituals, and in 1985 there calls “Multidimensional Child Sex Rings” identifying features and modes (Lanning, 1992). In his studies Lanning (1992), describes the types of offences related to the dimension of ritual abuse by claiming that there is no clear evidence about some of these crimes. On the basis of those statements Weir and Wheatcroft (1995) list as possible by declaring a false ritual abuse and then of false memories, the suggestion of special interest about the growing psychotherapists induced ritual abuse and who believe in the existence of these crimes.This systematic review of the literature, in the light of subsequent events and subsequent updates of methodology aims to analyze the relationship between “Ritual Abuse” and the false memory that can appear during psychotherapy. Materials and Methods: This study was carried out using the PRISMA guidelines, by conducting a systematic search of the literature on PubMed, Scopus, ISI Web of Science, EBSCO, Google Scholar, and ScienceDirect. The following keywords used were “ritual abuse” “AND” (i.e., Boolean operator) “psychotherapy” combined with “AND” Boolean operator and “false memory”.Results: The initial search identified n = 167 citations. Only one research report met the predefined inclusion criteria and was analysed.Conclusion: In case of false memories in ritual abuse, it is necessary to implement the research activities to avoid that results obtained can be rejected by health professionals or by theories not scientifically validated.Background: Nel 1983 Kennet Lanning inizia i suoi studi occupandosi di abusi sessuali rituali, e nel 1985 lì definisce “Multidimensional Child Sex Rings” identificandone caratteristiche e modalità (Lanning, 1992). Nei suoi studi Lanning (1992), descrive le tipologie di reato connesse alla dimensione dell’abuso rituale sostenendo che non esistono prove certe in merito ad alcuni di questi reati. Sulla base di tali affermazioni Weir and Wheatcroft (1995) elencano come possibili ipotesi di generazione di falsi abusi rituali e quindi di falsi ricordi, la suggestione indotta di psicoterapeuti che coltivano speciali interessi circa gli abusi rituali e che credono nell’esistenza di questi crimini. La presente analisi sistematica della letteratura, alla luce dei successivi accadimenti e di successivi aggiornamenti metodologici ha lo scopo di analizzare la relazione tra “Abuso Rituale” ed il falso ricordo che può manifestarsi durante la psicoterapia. Materiali e Metodi: Tale studio è stato effettuato utilizzando le linee guida per l’utilizzo della metodología PRISMA, effettuando una ricerca sistematica su PubMed, Scopus, ISI Web of Science, EBSCO, Google Scholar e ScienceDirect. Le parole chiave utilizzate per la ricerca sono state “ritual abuse” “AND” (i.e. operatore Boleano) “psychotherapy” “AND” “false memory”.Risultati: Sono stati inizialmente trovati n = 167 records. Un solo articolo ha poi soddisfatto i criteri di inclusione ed è stato analizzati.Conclusioni: Nel caso delle false memorie negli abusi rituali, sembra necessario implementare l’attività di ricerca per evitare che qualsiasi risultato ottenuto possa essere contrastato dai professionisti della salute o da teorie non validate scientificamente

Efficacy and timing of adjunctive therapy in the anti-VEGF treatment regimen for macular oedema in retinal vein occlusion:12-month real-world result

PurposeVarious combination treatment regimens have been tried to improve the short-term efficacy of intravitreal monotherapy for the treatment of macular oedema (MO) secondary to retinal vein occlusion (RVO). Our study introduces the RandOL protocol (Ranibizumab and Ozurdex with Laser photocoagulation) of initial anti-VEGF therapy, controlling recurrent non-ischaemic MO with an intravitreal steroid and applying laser therapy to non-perfused retina. We describe our 12-month follow-up experience on timing for adjunctive therapy and real-world effectiveness and safety data.MethodsA retrospective analysis was carried out on 66 consecutive treatment-naive RVO patients with MO who received our RandOL treatment regimen. Baseline visual acuity (VA) and central retinal thickness (CRT) were compared with 12-month result.ResultsAt 12 months, 77% had significant VA improvement, 52% had ≥3-line improvement, and 15% were worse. Significant improvements in CRT were observed in 97% (baseline median CRT=531 μm (IQR 435-622) reduced to 245 μm (IQR 221-351, P<0.001) at 12 months); 76% achieved a dry fovea at 1 year. Mean number of total injections required was 5.5 (range 2-11) and 6% required ≥9 injections in 1 year. Although 70% received additional Ozurdex, 82% received ≥1 sessions of laser therapy. The BRVO subgroup achieved better VA and CRT improvement at 1 year, but small numbers limit definitive statistical conclusions.ConclusionsOur real-world results using a combination treatment protocol for RVO-related MO achieved similar desirable anatomical and visual outcomes as with a single-agent therapy with less intravitreal re-treatment rates at first year. Randomised controlled studies are needed to evaluate the role of laser and the ideal timing of combination therapy

Temozolomide chronotherapy in patients with glioblastoma: A retrospective single-institute study

BACKGROUND: Chronotherapy is an innovative approach to improving survival through timed delivery of anti-cancer treatments according to patient daily rhythms. Temozolomide (TMZ) is a standard-of-care chemotherapeutic agent for glioblastoma (GBM). Whether timing of TMZ administration affects GBM patient outcome has not previously been studied. We sought to evaluate maintenance TMZ chronotherapy on GBM patient survival. METHODS: This retrospective study reviewed patients with newly diagnosed GBM from January 1, 2010 to December 31, 2018 at Washington University School of Medicine who had surgery, chemoradiation, and were prescribed TMZ to be taken in the morning or evening. The Kaplan-Meier method and Cox regression model were used for overall survival (OS) analyses. The propensity score method accounted for potential observational study biases. The restricted mean survival time (RMST) method was performed where the proportional hazard assumption was violated. RESULTS: We analyzed 166 eligible GBM patients with a median follow-up of 5.07 years. Patients taking morning TMZ exhibited longer OS compared to evening (median OS, 95% confidence interval [CI] = 1.43, 1.12-1.92 vs 1.13, 0.84-1.58 years) with a significant year 1 RMST difference (-0.09, 95% CI: -0.16 to -0.018). Among MGMT-methylated patients, median OS was 6 months longer for AM patients with significant RMST differences at years 1 (-0.13, 95% CI = -0.24 to -0.019) to 2.5 (-0.43, 95% CI = -0.84 to -0.028). Superiority of morning TMZ at years 1, 2, and 5 (all CONCLUSIONS: Our study presents preliminary evidence for the benefit of TMZ chronotherapy to GBM patient survival. This impact is more pronounced in MGMT-methylated patients

Il minore vittima di abusi sessuali e le garanzie del giusto processo penale

Criminal proceedings concerning the assessment of sexual abusive behaviour affecting minors includes, among its most delicate stages, the collection of the young victim’s statements, especially if the victims are in their earliest years.The collection of a minor’s testimony must follow rules and procedures whose main goal is to safeguard the minor.Up to now, Italian Criminal Justice System does not provide an organic system for the Young victim’s protection; on the part of the legislator, there is a lack of specific rules and regolations for the minor’s testimony.According to Article 196, paragraph 1 and 2 of the Italian Code of Criminal Procedures, “every person is competent to testify,” but “in order to evaluate the witness’ statement, the judge can order appropriate verifications using all lawful means, even ex officio.”More effectively, Article 10 of the Carta of Noto recommend, for children under 12 and apart from exceptional cases, “that a valuation must always occur in order to verify the victim’s fitness to testify about the matters,” unless the judge can evaluate the reliability of the testimony.Therefore, is it possible for the judge to establish the truthfulness of the minor’s testimony apart from a technical advice of an expert, that is without making a psychological evaluation of the child first?” The prevailing jurisprudential orientation in recent years confirms the prevalence of the so-called principle of the all-encompassing evaluation, whereby “on the subject of sexual offenses against young children, it is illegal, for violation of the principle of the formation of evidence in contradictory, the refusal of judge to arrange a psychological examination, in order to ascertain the adherence to the reality or not of the narration of the facts, depending on possible fanciful elaborations of the age or of the personological structure of the minor2”.Nei procedimenti penali aventi ad oggetto l’accertamento della condotta di abuso sessuale a danno di minore, fra le fasi più delicate, vi è quella inerente l’acquisizione delle dichiarazioni della giovane vittima specie se in tenera età.E’ pacifico che l’assunzione della testimonianza di un minore, perché tale, deve avvenire con criteri e modalità che abbiano quale obiettivo principale, quello della tutela del minore stesso. Il sistema penale italiano a tutt’oggi rileva l’assenza di un organico sistema di protezione del minore vittima di abusi; manca una specifica disciplina da parte del legislatore, della testimonianza del soggetto minore di età.Secondo quanto disposto dall’art. 196, comma 1 e 2 c.p.p.“Ogni persona ha la capacità di testimoniare” tuttavia “qualora, al fine di valutare le dichiarazioni del testimone, sia necessario verificarne l’idoneità física o mentale a rendere testimonianza, il giudice anche di ufficio può ordinare gli accertamenti opportuni con i mezzi consentiti dalla legge”.Più efficacemente la Carta di Noto all’art. 10 raccomanda per i minori di anni dodici e salvo casi eccezionali “che sia sempre disposta perizia al fine di verificarne la idoneità a testimoniare sui fatti oggetto d’indagine”, salvo al giudice valutare l’attendibilità della testimonianza resa.E’ possibile allora per il decidente, accertare la veridicità della condotta abusante dal racconto del minore, prescindendo dall’ausilio del parere tecnico di un perito, ovvero senza aver prima disposto una perizia psicologica sul bambino?L’orientamento giurisprudenziale prevalente negli ultimi anni, conferma il prevalere del principio cosiddetto della valutazione onnicomprensiva, per cui “in tema di reati sessuali su minori in tenera età, è illegittimo, per violazione del principio della formazione della prova in contraddittorio, il rifiu to dei giudice di disporre una perizia psicologica, al fine di accertare l’aderenza alla realtà o meno della narrazione dei fatti, in dipendenza di eventuali elaborazioni fantasiose proprie dell’età o della struttura personologica del minore”1

Whole-genome microarray detects deletions and loss of heterozygosity of chromosome 3 occurring exclusively in metastasizing uveal melanoma

PURPOSE. To detect deletions and loss of heterozygosity of chromosome 3 in a rare subset of fatal, disomy 3 uveal melanoma (UM), undetectable by fluorescence in situ hybridization (FISH). METHODS. Multiplex ligation-dependent probe amplification (MLPA) with the P027 UM assay was performed on formalinfixed, paraffin-embedded (FFPE) whole tumor sections from 19 disomy 3 metastasizing UMs. Whole-genome microarray analyses using a single-nucleotide polymorphism microarray (aSNP) were performed on frozen tissue samples from four fatal disomy 3 metastasizing UMs and three disomy 3 tumors with Ͼ5 years&apos; metastasis-free survival. RESULTS. Two metastasizing UMs that had been classified as disomy 3 by FISH analysis of a small tumor sample were found on MLPA analysis to show monosomy 3. No ubiquitous gene deletions of chromosome 3 were seen in the remaining 17 metastasizing disomy 3 UMs by MLPA. aSNP analysis revealed 95 deleted genes and 16 genes with loss of heterozygosity (LOH) on chromosome 3 in the disomy 3 metastasizing UMs that were not deleted or showing LOH in the nonmetastatic tumors. CONCLUSIONS. MLPA can detect monosomy 3 cell populations in FFPE whole tumor sections previously missed by FISH performed on small tumor samples. Consistent deletion and LOH of genes on chromosome 3 occur in metastasizing disomy 3 UM and are detectable by aSNP analysis. Ninety-five genes were found to be deleted, and 16 genes showed LOH exclusively in disomy 3 metastasizing UM, suggesting a potential role for these genes in UM metastasis. (Invest Ophthalmol Vis Sci. 2010;51:4884 -4891) DOI:10.1167/iovs.09-5083 U veal melanoma (UM), the most common primary intraocular cancer in adults, is fatal in almost 50% of patients, because of metastatic spread often involving the liver. Chemotherapy of metastases has limited success 1,2 and disseminated disease is fatal in 92% of patients within 2 years of diagnosis. Clinical and histopathologic risk factors for UM metastasis include large basal tumor diameter (LBD), ciliary body involvement, epithelioid cytomorphology, extracellular matrix periodic acid-Schiff-positive (PAS ϩ ) loops, and high mitotic count. 3,4 Prescher et al. 3,6 -10 Consequently, fluorescence in situ hybridization (FISH) detection of chromosome 3 using a centromeric probe became routine practice for UM prognostication; however, 5% to 20% of disomy 3 UM patients unexpectedly develop metastases. We hypothesize that disomy 3 UMs that metastasize do so by the same mechanisms as metastasizing monosomy 3 UMs. However, instead of loss of a single copy of chromosome 3 facilitating this process, specific genes are deleted on chromosome 3 that are essential to an early progression to metastasis, not commonly seen in disomy 3 UM. The purpose of our study was to identify key MSGs that are deleted exclusively in a rare subset of UMs that metastasized despite apparent disomy 3 on FISH testing. We investigated whether deletions of chromosome 3 could be detected using either multiplex ligationdependent probe amplification (MLPA) or a single-nucleotide polymorphism microarray (aSNP; SNP 6.0; Affymetrix, Santa Clara, CA). Knowledge of such deletions on chromosome 3 may allow more accurate prognostication, increase understanding of the natural history of UM, and help identify aberrant cell signaling pathways that may be amenable to therapy. MATERIALS AND METHODS Tumor Samples Fresh primary UM samples were routinely obtained at the Royal Liverpool University Hospital between 2001 and 2007 and analyzed by FISH for chromosome 3 copy number. Of these UMs, formalin-fixed, paraffin-embedded (FFPE) tumor samples were available in our archive for 34 disomy 3 UMs that were known to have metastasized (Di3M-UM). Nineteen of these samples were selected for MLPA studies, as they provided sufficient extracted DNA (700 ng) for quality control PCR and analysis by MLPA in triplicate. Four snap-frozen Di3M-UM samples from patients with fatal metastasis within 5 years of diagnosis and samples from three disomy 3 surviving UM (Di3S-UM) patients with no detectable metastases after a minimum of 5 years since diagnosis were used for aSNP analysis. Personalized survival curves were generated for all three patients with disomy 3 nonmetastasizing UM using the Cox proportional hazards model. The model predicts survival up to 8 years after diagnosis and specifies 95% CI based on the following information: age at treatment, sex, ciliary body involvement, largest basal From th

Decreased endothelin receptor B expression in large primary uveal melanomas is associated with early clinical metastasis and short survival

The most devastating aspect of cancer is the metastasis of tumour cells to organs distant from the original tumour site. The major problem facing oncologists treating uveal melanoma, the most common cancer of the eye, is metastatic disease. To lower mortality, it is necessary to increase our understanding of the molecular genetic alterations involved in this process. Using suppression subtractive hybridisation, we have analysed differential gene expression between four primary tumours from patients who have developed clinical metastasis and four primary tumours from patients with no evidence of metastasis to date. We have identified endothelin receptor type B as differentially expressed between these tumours and confirmed this observation using comparative multiplex RT–PCR. In a further 33 tumours, reduced endothelin receptor type B expression correlated with death from metastatic disease. Reduced expression also correlated with other known prognostic indicators, including the presence of epithelioid cells, chromosome 3 allelic imbalance and chromosome 8q allelic imbalance. Endothelin receptor type B expression was also reduced in four out of four primary small cell lung carcinomas compared to normal bronchial epithelium. We also show that the observed down-regulation of endothelin receptor type B in uveal melanoma was not due to gene deletion. Our findings suggest a role for endothelin receptor type B in the metastasis of uveal melanoma and, potentially, in the metastasis of other neural crest tumours

Is accurate routine cancer prognostication psychologically harmful? 5-year outcomes of life expectancy prognostication in uveal melanoma survivors

Abstract Purpose Prognostication in cancer is growing in importance as increasingly accurate tools are developed. Prognostic accuracy intensifies ethical concerns that a poor prognosis could be psychologically harmful to survivors. Uveal melanoma (UM) prognostication allows survivors to be reliably told that life expectancy is either normal (good prognosis) or severely curtailed because of metastatic disease (poor prognosis). Treatment cannot change life expectancy. To identify whether prognosis is associated with psychological harm, we compared harm in UM survivors with good and poor prognoses and those who declined testing and compared these outcomes to general population norms. Methods Non-randomized 5-year study of a consecutive series of 708 UM survivors (51.6% male, mean age 69.03, SD=12.12) with observations at 6, 12, 24, 36, 48 and 60 months. We operationalized psychological harm as anxiety and depression symptoms, worry about cancer recurrence (WREC) and poor quality of life (QoL). Results Compared to other groups, survivors with poor prognoses showed initially elevated anxiety and depression and consistently elevated worry about local or distant recurrence over 5 years. Good prognoses were not associated with outcomes. Generally, no prognostic groups reported anxiety, depression and WREC or QoL scores that exceeded general population norms. Conclusions Using a large sample, we found that harm accruing from a poor prognosis was statistically significant over 5 years, but did not exceed general non-cancer population norms. Implications for Cancer Survivors Survivors desire prognostic information. At a population level, we do not believe that our findings show sufficiently strong links between prognostication outcome and psychological harm to deny patients the option of knowing their prognosis. Nonetheless, it is important that patients are informed of potential adverse psychological consequences of a poor prognosis. </jats:sec