Prevalence and risk factors of diabetic retinopathy in adult and elderly subjects: The Casteldaccia Eye Study

Purpose To investigate the prevalence and risk factors of diabetic retinopathy in subjects aged 40 years or older living in Casteldaccia, Sicily.Methods A population-based survey was performed on 1,588 subjects randomly enrolled among people aged 40 years or older. A total of 1,068 persons could be examined and in 1,019 the fundus of the eye was adequately observed (64.2% of the enrolled population). Diabetic retinopathy was diagnosed by ophthalmoscopy and fundus photographs; fluorescein angiography was performed in 91% of retinopathic subjects. In addition, a case–control study was carried out in order to demonstrate the association of diabetic retinopathy with a number of variables.Results Diabetic retinopathy was found in 4.4% of the whole population studied and in 34.1% of the diabetics. Nonproliferative diabetic retinopathy was found in 29.6% and proliferative diabetic retinopathy in 4.5% of the diabetics. Diabetic retinopathy was significantly associated with the following univariate variables: duration of diabetes, duration and type of antidiabetic treatment, and duration of alcohol intake. After multivariate logistic regression the only variable independently associated with diabetic retinopathy was duration of antidiabetic treatment.Conclusion Diabetic retinopathy affects more than one third of diabetics and represents a leading cause of retinal disease. The antidiabetic treatment is the most important risk factor for diabetic retinopathy, even stronger than the duration of diabetes.     

Effects of riboflavin/UVA corneal cross‐linking on keratocytes and collagen fibres in human cornea

Purpose: To evaluate the effects of corneal cross‐linking on keratocytes and collagen fibres in human corneas. Methods: Fifteen corneal buttons were examined. Ten were from patients with keratoconus submitted to penetrating keratoplasty and five of them were treated with cross‐linking 6 months before penetrating keratoplasty. Five normal corneal buttons from healthy donors were used as controls. All samples were prepared for TUNEL assay and Western blot analysis for the detection of keratocyte apoptosis and immunohistochemical analysis for the morphological evaluation of keratocytes and collagen fibre diameter. Results: Normal corneas exhibited no TUNEL‐positive keratocytes and keratoconic and cross‐linked corneas showed moderate apoptotic cells mainly in the anterior part of the stroma. This apoptotic trend was confirmed by the cleavage of poly (ADP‐ribose) polymerase assessed using Western blot. The Ki‐67 staining showed a significant increase in the keratocyte proliferation in cross‐linked corneas compared with normal and keratoconus. In cross‐linked corneas CD34‐positive keratocytes were regularly distributed throughout the whole corneal stroma as in the control, and keratoconus was associated with patchy loss of immunoreactivity. The immunohistochemical analysis of collagen type I showed a significant increase in fibre diameter of cross‐linked corneas compared with control and keratoconus. Conclusion: Corneal cross‐linking leads to keratocyte damage; after 6 months a repopulation by proliferating cells, a distribution of CD34‐positive keratocytes as in control and an increase in collagen fibre diameter were observed. These modifications are the morphological correlate of the process leading to an increase in biomechanical stability.     

Gender identity disorder and eating disorders

We report three cases of transsexual patients who are suffering from an eating disorder: a biological male patient diagnosed with anorexia nervosa (AN), a biological male patient with bulimia nervosa (BN), and a biological female patient with AN as well as a severe alcohol dependence. The relationship between eating behavior, gender identity, sexual orientation, and body dissatisfaction is discussed.     

Prognostic significance of changes in CA 15-3 serum levels during chemotherapy in metastatic breast cancer patients

Summary Tumor response to first-line chemotherapy in advanced breast cancer offers prognostic information and may be used as a surrogate marker for evaluating treatment efficacy. With this study we wanted to determine whether changes in circulating serum CA 15-3 levels during chemotherapy provided additional information for prognostic prediction. Serum CA 15-3 was measured at baseline and after 3 and 6 months during anthracycline-based first-line chemotherapy in 526 patients with advanced breast cancer prospectively enrolled in five phase II-III trials. Changes in marker levels were correlated with disease response, time to progression and overall survival. In all, 336 patients attained a disease response. A significant relationship was found between disease response and CA 15-3 variations, although many individual discrepancies were also observed. At the 6-month time point, the median time to progression was 15.3 months in patients with normal marker levels throughout the study, 11.7 months in those with a CA15-3 reduction >25%, 9.6 months in those with elevated baseline CA 15-3 levels which did not change during therapy and 8.6 months in those with increased marker levels (p < 0.001). The median survival was 42.3, 29.7, 28.5, and 24.8 months, respectively (p < 0.002). The prognostic role of changes in CA 15-3 levels was maintained in the patient subset attaining disease response or stabilization to treatment (p < 0.001) and after adjusting for clinical response and major prognostic parameters in the multivariate analysis (p < 0.001). In conclusion, monitoring serum CA 15-3 levels during first-line chemotherapy in advanced breast cancer patients provides prognostic information independently from tumor response.     

Corneal Manifestations of Systemic Sclerosis

Purpose: Corneal involvement in systemic sclerosis (SSc) is rare, but due to rich collagen composition cornea is especially vulnerable to connective tissue diseases. Therefore, our aim was to evaluate corneal parameters of SSc patients.

Methods: The study included 32 SSc patients and 39 control subjects with no ocular symptoms or ocular surface disorders. All study participants underwent Pentacam evaluation and objective signs of dry eye disease (DED), and clinical parameters were evaluated.

Results: All pachymetric values, most of the corneal front surface, corneal volume, as well as anterior chamber depth measurements were significantly lower in the SSc group than in the control group (p < 0.05). Significant negative correlation was found between corneal parameters and age on the one hand, and disease duration on the other.

Conclusions: Early recognition of corneal impairment, a possible extraintestinal manifestation of SSc, should be included in the check-up of the disease in order to reduce sight-threatening complications.     

Plasma miRNA-based signatures in CRC screening programs

Colorectal cancer (CRC) screening programs help diagnose cancer precursors and early cancers and help reduce CRC mortality. However, currently recommended tests, the fecal immunochemical test (FIT) and colonoscopy, have low uptake. There is therefore a pressing need for screening strategies that are minimally invasive and consequently more acceptable to patients, most likely blood based, to increase early CRC identification. MicroRNAs (miRNAs) released from cancer cells are detectable in plasma in a remarkably stable form, making them ideal cancer biomarkers. Using plasma samples from FIT-positive (FIT+) subjects in an Italian CRC screening program, we aimed to identify plasma circulating miRNAs that detect early CRC. miRNAs were initially investigated by quantitative real-time PCR in plasma from 60 FIT+ subjects undergoing colonoscopy at Fondazione IRCCS Istituto Nazionale dei Tumori, then tested on an internal validation cohort (IVC, 201 cases) and finally in a large multicenter prospective series (external validation cohort [EVC], 1121 cases). For each endoscopic lesion (low-grade adenoma [LgA], high-grade adenoma [HgA], cancer lesion [CL]), specific signatures were identified in the IVC and confirmed on the EVC. A two-miRNA-based signature for CL and six-miRNA signatures for LgA and HgA were selected. In a multivariate analysis including sex and age at blood collection, the areas under the receiver operating characteristic curve (95% confidence interval) of the signatures were 0.644 (0.607–0.682), 0.670 (0.626–0.714) and 0.682 (0.580–0.785) for LgA, HgA and CL, respectively. A miRNA-based test could be introduced into the FIT+ workflow of CRC screening programs so as to schedule colonoscopies only for subjects likely to benefit most.     

Clinical presentation,diagnosis and management of therapy‐related hematological disorders in women with epithelial ovarian cancer treated with chemotherapy and poly‐ADP‐ribose polymerase inhibitors: A single‐center experience

We investigated the occurrence and management of therapy‐related hematological disorders (tr‐HDs) in women with epithelial ovarian cancer (EOC) exposed to poly‐ADP‐ribose polymerase inhibitors (PARPi), after previous chemotherapy. We analyzed 130 consecutive EOC patients treated with PARPi at the European Institute of Oncology, Milan. In line with the literature, overall survival of the entire population was 37% at 5.5 years (89% were advanced stages). Cell blood counts were collected prior to start PARPi, at each new cycle and at monthly intervals. Patients displaying persistent and/or marked hematological abnormalities underwent bone marrow evaluation, with cytogenetic and molecular analysis. Nine patients (6,9%) developed tr‐HDs, after a median 22.8 months of PARPi exposure. Two patients died early and could not be treated. Two patients have no indication for active treatment and are presently under close hematological monitoring. Five patients underwent chemotherapy followed, in three cases, by allogeneic hematopoietic transplantation: three patients are in complete remission of their hematological and gynecological malignancies at 13, 19, and 25 months; the remaining two patients died due to progression of their hematological disease. We show the potential risk of hematological disorders in EOC patients treated with chemotherapy and prolonged PARPi therapy. In our series, tr‐HDs incidence was higher compared to recent reports in large series. Our observations suggest careful monitoring in order to conclusively define, on large series and prolonged follow‐up, the actual risk of tr‐HDs in patients under PARPi. Notably, prompt diagnosis of hematological abnormalities and appropriate management allow achievement of remission from severe hematological complications, at least in most patients.     

Advanced head and neck cancer in older adults: Results of a short course accelerated radiotherapy trial

ObjectivesTo assess the feasibility and safety of a repeated SHort course Accelerated RadiatiON therapy (SHARON) regimen in the palliative setting of Head and Neck (H&N) cancer in older adults.Material and MethodsPatients with histological confirmed H&N cancers, age ≥ 80 years, expected survival >3 months, and Eastern Cooperative Oncology Group (ECOG) performance status of ≤3 were enrolled. Patients were treated in cohorts of six patients: a total dose of 20 Gy was delivered in 2 consecutive days with a twice-daily fractionation (5 Gy per fraction) and at least 8-h interval. If no Grade 3 toxicity was registered, a second enrollment started with another cohort of six patients to whom were administered two cycles (total dose of 40 Gy). The primary endpoint was to evaluate the feasibility of the two cycles of treatment. Secondary endpoints were evaluation of symptoms control rate, symptoms-free survival (SFS), and Quality of Life (QoL) scores.ResultsSeventeen consecutive patients (median age: 85 years) were treated. Nine patients were treated with one cycle and 8 patients with two cycles. No G3 toxicity was reported in either cohort. With a median follow-up time of 4 months, 3-month SFS in the first and second cohorts was 83.3%, and 87.5%, respectively. The overall palliative response rate was 88%. Among 13 patients reporting pain, 8 (61.5%) showed an improvement or resolution of their pain.ConclusionRepeated short course accelerated radiotherapy in a palliative setting of H&N cancers is safe and well-tolerated in older adults.     

Contact stimulation of fibroblasts for tenascin production by melanoma cells

Tenascin, an extracellular matrix glycoprotein, is widely expressed in the stroma of almost all types of solid tumours including malignant melanomas. On the basis of its antiadhesive character, it has been supposed that tenascin accumulation facilitates tumour cell invasion and consequent metastasis formation. We aimed to investigate the mechanism by which melanoma cells can modulate the production of tenascin by host stromal cells. The expression of tenascin in cocultures of fibroblasts and five melanoma cell lines, as well as in fibroblast monocultures treated with melanoma conditioned media, was analysed by immunofluorescent staining and image analysis. Tenascin production could not be observed in control fibroblasts or in melanoma cell monocultures. Faint labelling for tenascin could be detected in fibroblast monocultures treated with melanoma cell conditioned media while a very intense staining for tenascin could be seen in melanoma cell-fibroblast cocultures. The tenascin staining in the cocultures was associated with the fibroblasts that were in close contact with melanoma cells. The level of tenascin production around the fibroblasts in different areas of the cocultures correlated well with the density of melanoma cells. Our results indicate that tenascin production of fibroblasts in the tumour stroma is directly modulated by melanoma cells mainly through cell-to-cell contact signalling.