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In the last decade, the emergence of effective systemic therapies (ESTs) in the form of both targeted and immuno-based therapies has revolutionized the treatment of patients with advanced stage III and stage IV melanoma. Even though lungs represent the most frequent site of melanoma metastases, only limited data are available on the role of surgery in isolated pulmonary metastases from malignant melanoma (PmMM) in the era of ESTs. The aim of this study is to describe the outcomes of patients who underwent metastasectomy of PmMM in the era of ESTs, in order to identify prognostic factors affecting survival and to provide a framework for more informed patient selection of treatmeant with lung surgery in the future. Clinical data of 183 patients who underwent metastasectomy of PmMM between June 2008 and June 2021 were collected among four Italian Thoracic Centers. The main clinical, surgical and oncological variables reviewed were: sex, comorbidities, previous oncological history, melanoma histotypes and primary site, date of primary cancer surgical treatment, melanoma growth phase, Breslow thickness, mutation pattern disease, stage at diagnosis, metastatic sites, DFI (Disease Free Interval), characteristics of lung metastases (number, side, dimension, type of resection), adjuvant therapy after lung metastasectomy, site of recurrence, disease-free survival (DFS) and cancer-specific survival (CSS; defined as the time interval between the first melanoma resection or lung metastasectomy and death from cancer). All patients underwent surgical resection of the primary melanoma before lung metastasectomy. Twenty-six (14.2%) patients already had a synchronous lung metastasis at the time of primary melanoma diagnosis. A wedge resection was performed in 95.6% of cases to radically remove the pulmonary localizations, while an anatomical resection was necessary in the remaining cases. The incidence of major post-operative complications was null, while only 21 patients (11.5%) developed minor complications (mainly air leakage followed by atrial fibrillation). The mean in-hospital stay was 4.46 ± 2.8 days. Thirty- and sixty-day mortality were null. After lung surgery, 89.6% of the population underwent adjuvant treatments (47.0% immunotherapy, 42.6% targeted therapy). During a mean FUP of 107.2 ± 82.3 months, 69 (37.7%) patients died from melanoma disease, 11 (6.0%) from other causes. Seventy-three patients (39.9%) developed a recurrence of disease. Twenty-four (13.1%) patients developed extrapulmonary metastases after pulmonary metastasectomy. The CSS from melanoma resection was: 85% at 5 years, 71% at 10 years, 54% at 15 years, 42% at 20 years and 2% at 25 years. The 5- and 10-year CSS from lung metastasectomy were 71% and 26%, respectively. Prognostic factors negatively affecting CSS from lung metastasectomy at multivariable analysis were: melanoma vertical growth ( p = 0.018), previous metastatic sites other than lung ( p < 0.001) and DFI < 24 months ( p = 0.007). Our results support the evidence that surgical indication confirms its important role in stage IV melanoma with resectable pulmonary metastases, and selected patients can still benefit from pulmonary metastasectomy in terms of overall cancer specific survival. Furthermore, the novel systemic therapies may contribute to prolonged survival after systemic recurrence following pulmonary metastasectomy. Patients with long DFI, radial growth melanoma phase and no site of metastatization other than lung seem to be the best candidate cases for lung metastasectomy; however, to drive stronger conclusions, further studies evaluating the role of metastasectomy in patients with iPmMM are needed.

Background: Age-related macular degeneration (AMD) is a multifactorial disease for which an involvement of alterations in the retinal ABC transporter gene (ABCA4) is still debated. Oxidative stress in retinal pigment epithelial cells has been postulated to contribute to the pathogenesis of the disease. Mitochondrial ferritin (FtMt), an iron-sequestering protein, is expressed in cell types characterized by high metabolic activity and oxygen consumption, including human retina, suggesting a role in protecting mitochondria from iron-dependent oxidative damage. Based on these findings we wanted to investigate whether mutations in this gene could be found in AMD patients., Methods: Mutational scanning of the FTMTgene was performed in a cohort of 50 patients affected by age-related macular degeneration. The ABCA4 gene was also scanned in one patient carrying an FtMt mutation. In silico analyses were carried out on the identified variants. The recombinant form of FtMt variant was expressed in Escherichia coli and biochemically characterized., Results: One patient was found to be heterozygous for two previously unreported genetic changes: a complex FtMt mutation (c.437&#95;450delinsCT: delAGGACATCAAGAAGinsCT) and a missense p.Leu973Phe (c.2919G>T) mutation in exon 20 of ABCA4. Computational analyses predicted a severe structural impairment for FtMt variant and a mild destabilizing effect for ABCA4. E. coli expression of recombinant FtMt variant yielded a highly insoluble protein that could not be renatured under in vitro conditions suitable for wild-type ferritins., Conclusions: Our findings suggest that the FtMt mutation may determine a condition similar to haploinsufficiency resulting in a reduced protection from iron-dependent oxidative stress in mitochondria.

Objective: Apolipoprotein E (apoE) is an important regulator of cholesterol and lipid transport during compensatory synaptogenesis. Our purpose was to investigate the role of apoE gene polymorphisms in Italian patients with age-related macular degeneration (AMD)., Methods: We used the polymerase chain reaction technique to analyze apoE genotypes in 87 patients with AMD, in 47 age-matched controls and in 1,287 individuals from a general reference population., Results: The frequency of allele epsilon4 carriers was significantly higher (p = 0.002) in the general population than in AMD patients, while the frequency of allele epsilon2 was higher in the patients (p = 0.069) with an increased risk for AMD in the patients versus the population-based controls (odds ratio = 1.7; 95% confidence interval: 1.0-2.9). Allele epsilon4 was associated with a decreased risk for AMD in the patients versus the population-based controls (odds ratio = 0.3; 95% confidence interval: 0.1-0.8)., Clinical Relevance: These data suggest that apoE testing may represent a tool for the evaluation of the relative risk of AMD. Consequently, a preventive strategy can be initiated at an early stage of the disorder., Conclusion: The apoE gene polymorphism showed a significant association with the risk of AMD. The lower frequency of the epsilon4 allele in AMD patients suggests that the apoE gene could play a protective role in the pathogenesis of the disease. In contrast, the epsilon2 allele was found associated with a slightly increased risk of AMD, although we did not find a statistically significant effect., (Copyright 2001 S. Karger AG, Basel)

Mutations in the retina-specific ABC transporter (ABCR) gene are responsible for autosomal recessive Stargardt disease (arSTGD). Mutation detection efficiency in ABCR in arSTGD patients ranges between 30% and 66% in previously published studies, because of high allelic heterogeneity and technical limitations of the employed methods. Conditions were developed to screen the ABCR gene by double-gradient denaturing-gradient gel electrophoresis. The efficacy of this method was evaluated by analysis of DNA samples with previously characterized ABCR mutations. This approach was applied to mutation detection in 44 Italian arSTGD patients corresponding to 36 independent genomes, in order to assess the nature and frequency of the ABCR mutations in this ethnic group. In 34 of 36 (94.4%) STGD patients, 37 sequence changes were identified, including 26 missense, six frameshift, three splicing, and two nonsense variations. Among these, 20 had not been previously described. Several polymorphisms were detected in affected individuals and in matched controls. Our findings extend the spectrum of mutations identified in STGD patients and suggest the existence of a subset of molecular defects specific to the Italian population. The identification of at least two disease-associated mutations in four healthy control individuals indicates a higher than expected carrier frequency of variant ABCR alleles in the general population. Genotype-phenotype analysis in our series showed a possible correlation between the nature and location of some mutations and specific ophthalmoscopic features of STGD disease.

We describe a case of a four year-old boy, with congenital ectopia lentis et pupillae, who developed patchy unilateral depigmentation of the skin, hair and lashes. The association between ectopia lentis et pupillae and transillumination of the iris is well documented in the literature, but it has never been reported with skin hypopigmentation.

Pigmented paravenous retino-choroidal atrophy (P P R C A) is a rare retinal disease characterized by bilateral patches of pigment and areas of chorioretinal atrophy distributed along the veins. The authors present a 21-year-old male with pigmented paravenous retinochoroidal atrophy and unilateral macular dysplasia. To their knowledge, this is the second reported case of macular involvement. They believe that such association is not occasional, but may be suggestive of a variable expressivity of the disease.

The authors report a child with a phenotype typical of a first branchial arch defect. The patient has a balanced translocation involving chromosome 2. They propose a defect that has occurred during the translocation in a gene mapped to chromosome 2 and belonging to the HOXD family. HOX gene defects can perturb the expression of other genes important for head development.

Neuron-specific enolase (NSE) is a unique form of the glycolytic enzyme enolase found exclusively in neurons and neuroendocrine tissues. Immunohistochemical techniques in which antineuron-specific enolase antibodies are used have made it possible to map out derivatives of the neural crest in humans. By using affinity-purified antibodies against NSE, we investigated whether the contribution of the neural crest cells to the development of the anterior ocular structures in the rat is similar to that in man. We found that filtration structures in rats show morphologically striking similarities with the analogous region of the human eye. Hence, the rat eye, with certain reservations, is a suitable model for experimental studies on ocular diseases that are characterized by chamber angle anomalies or congenital glaucoma.

Ocular pharmacokinetics of rufloxacin (MF 934), a new monofluorinated quinolone derivative, has been investigated in rabbits. A long half-life, good g.i. absorption and a higher tissue/plasma concentration than that of other quinolones, are its interesting pharmacokinetic properties. However, there is reason to believe that drug accumulation may occur in deep body compartments. We determined plasma, aqueous, and vitreous concentrations of the drug at 1, 4, 8, and 24h after a single 50 mg/kg i.v. administration of rufloxacin. Our data show that rufloxacin, administered by the i.v. route, rapidly reaches chemotherapeutically useful levels in aqueous and vitreous fluids. Although still present in plasma 8 hours after administration, it proved to be undetectable in ocular fluids, signifying that the depletion of the deep compartments occurs well in advance of the next invasion. Due to its antibacterial effectiveness and pharmacokinetic properties rufloxacin may take a relevant place among the quinolone derivatives in the treatment of ocular infections.