Liquid-based anal cytology as a screening tool for prevention of anal cancer in at-risk populations: a single-center retrospective analysis on 111 patients

Objective: Squamous cell carcinoma of the anus (SCCA) is associated with human papillomavirus (HPV) infection in almost 90% of the cases. Its incidence is alarmingly high among men who have sex with men (MSM) and continues to increase at an average rate of 2% per year. The objective of the present study is to evaluate the usefulness and performance of liquid-based anal cytology as a screening tool for prevention and early detection of SCCA in a cohort of at-risk men. Method: We conducted a retrospective study including 111 MSM, aged between 22 and 62 years old, who underwent anal cytological screening with a liquid-based Pap test at our sexually transmitted diseases (STDs) clinic from January 2015 to March 2017. Results: Out of 111 anal smears, 57 (51,4%) resulted negative, 42 (37,8%) abnormal, and 12 (10,8%) unsatisfactory for the cytological evaluation. Only patients with an abnormal cytology underwent anoscopy and subsequent biopsy. The histological results were as follows: negative for squamous intraepithelial lesion (SIL) in 5 cases, low-grade SIL (L-SIL) in 21, high-grade SIL (H-SIL) in 5, SCCA in 1. Five patients had a normal anoscopy and biopsy was not taken. Conclusion: Liquid-based cytology, reducing the "darkening factors" typical for the conventional smears, has a higher positive predictive value than the traditional technique. Moreover, a cytological diagnosis of atypical squamous cells of undetermined significance (ASC-US) or L-SILmay hide a severe dysplasia or even a carcinoma. Thus, all patients with an abnormal anal cytology at any grade should be considered for anoscopy. (AU)

Nutraceutical Value of Pantelleria Capers (Capparis spinosa L.).

Unopened flower buds of Capparis spinosa L. (capers), generally used in the Mediterranean area as food flavoring, are known to be a good source of bioactive compounds. The aim of this work was to evaluate the nutraceutical value of salt-fermented capers collected from different areas of Pantelleria Island (Italy), testing their methylglyoxal and glyoxal trapping capacity and antioxidant activity by 2,2-diphenyl-1-picryl hydrazyl (DPPH), [2,2-azinobis(3-ethylben- zothiazoline-6-sulfonic acid)] diammonium salt (ABTS), and oxygen radical absorbance capacity (ORAC) assays. Hydrophilic extracts were also characterized by high-performance liquid chromatography-electrospray ionization/mass spectrometry. Among 24 detected compounds, several flavonol derivatives and glucosinolates were identified. The levels of kaempferol and quercetin derivatives varied considerably among the five accessions considered (6.46 to 267.93 and 22.39 to 367.14 mg kaempferol and quercetin equivalent /g fresh weight, respectively), with kaempferol derivatives more representative than quercetin ones. Person's coefficient indicated a high correlation between total phenolic content and anti-DPPH radical capacity (R2 = 0.665), as well as between total flavonoid content and antioxidant capacity (by ORAC assay; R2 = 0.888) and between total flavonoid content and glyoxal and methylglyoxal trapping capacity (R2 = 0.918). Results indicate that capers from Pantelleria Island represent a rich source of bioactive compounds with potential nutraceutical relevance. PRACTICAL APPLICATION: The findings of this study highlight the health benefits of Pantelleria capers consumption due to their composition in antioxidants and their biological properties (antiradical and alpha-dicarbonyls trapping) correlated with the development of a high number of chronic-degenerative diseases. These results are also important for the agricultural and commercial sectors involved in the production of capers from Pantelleria, which received the Protected Geographical Indications recognition.

Vitamin D in malaria: more hypotheses than clues.

Vitamin D is a secosteroid hormone regulating calcium and phosphate metabolism, immune response and brain development. Low blood 25(OH)D levels have been reported in patients affected by infectious diseases caused by parasites, including malaria. Despite the high effectiveness of antimalarials, malaria is burdened with high morbidity and mortality, and the search for additional therapies is rapidly growing. Furthermore, available preventive measures have proved to be barely effective so far. Finding new prevention and therapy tools is a matter of urgency. Studies on animal models and humans have hypothesized some mechanisms by which the hormone can influence malaria pathogenesis, and the role of Vitamin D supplementation in preventing and treating this disease has been suggested. Few studies on the association between Vitamin D and malaria are available and disagreeing results have been reported. Studies in humans reporting an association between low 25(OH)D circulating levels and Malaria have a small sample size and observational study-set. Randomized controlled trials are needed in order to understand if Vitamin D administration might play a role in preventing and treating malaria.

[Continuity of care in oncology. Quantitative analysis of data from patients treated in two different settings in Emilia--Romagna.] / La continuità delle cure in oncologia. Un'analisi quantitativa dell'esperienza dei pazienti in due realtà emiliano-romagnole.

INTRODUCTION: In order to ensure high-quality treatment for patients with cancer it is vital to implement organisational models (pathways and networks) and that guarantee continuity of care. Appropriate assessment tools that promote the evaluation and analysis of care pathways from the patients' perspective are available. Hence the aim of this study was to verify whether or not the coordination between the various stages and care providers in a cancer treatment pathway is perceived by our patients. METHODS: Patients being treated for cancer of the lung, breast or colorectal tract by the Ferrara University Hospital (FUH) and the wider Romagna regional health service (RRHS), Italy, were administered the OPTION evaluation questionnaire. Univariate descriptive statistics of patients' sociodemographic features and care pathways were generated, and means and standard deviations were calculated for patient responses to OPTION items 1-19 on continuity of care throughout their treatment pathway. RESULTS: Responses from 341 patients (37.2 % treated by the FUH and 62.8% by the RRHS) were obtained. All mean scores provided for items 1-19 were above 4 on a Likert scale of 1-5, showing that the patients' perception of the continuity of their care was very positive on the whole. The highest mean scores were given for items regarding their emotional experience, while the lowest were given for those regarding information and integration with the GPs. DISCUSSION AND CONCLUSIONS: Organisational efforts to promote patient-centred continuity of oncological care improved the experience of patients in our sample. Our data suggest that integration with the GPs still remains a problem, both from an organisational standpoint and in the perception of the patient being treated for cancer at one of the facilities under investigation. Although our findings are non-controlled and not generalisable to other geographical areas, they do show how such tools can be used to monitor and analyse patient's experience with continuity of care with a view to continual improvement in care provision.

Pap smear in the prevention of HPV-related anal cancer: preliminary results of the study in a male population at risk.

BACKGROUND: The aim of this work was to evaluate the role of human papillomavirus (HPV) testing and anal cytology, considering a population of HIV-positive and negative men who have sex with men (MSM), at high risk of sexually transmitted diseases (STD), in order to ascertain which of the methods examined is the best screening strategy for the prevention of anal cancer. METHODS: In the period 06/2013-07/2014 at the "MTS Centre" of the University of Florence, 87 male patients, homo/bi-sexual, of which 46 HIV-negative and 41 HIV-positive, were recruited for anal Pap smear and HPV testing. All patients with an "abnormal" cytological result underwent anoscopy with possible biopsy. RESULTS: HPV testing was positive in 73 patients (83.6%). Cytology was negative in 50 patients (57.5%), inconclusive in 14 patients (16.1%), abnormal in 23 patients (26.4%): 14 ASC-US (19.2%), 4 ASC-H (5.5%), 5 L-SIL (6.8%), 0 H-SIL. Anoscopy with biopsy led to diagnosis of AIN I in 10 cases, of which 6 ASC-US+ and 4L-SIL+, AIN II in only 1 case, LS-IL+. CONCLUSIONS: Anal HPV testing, when used in primary screening, lead to a high number of "false positives", given the too high prevalence of HPV infection in MSM, the highest risk population targeted for screening. So we propose a screening program with anal cytology which has a high sensitivity for detection of AIN while is a poor predictor of the severity of these lesions; therefore, all patients with abnormal anal Pap smear should undergo anoscopy with biopsy.

Role of p16(INK4a) cytology testing as an adjunct to enhance the diagnostic specificity and accuracy in human papillomavirus-positive women within an organized cervical cancer screening program.

OBJECTIVE: We evaluated the performance of cytologic p16(INK4a) (p16) immunostaining within a cervical cancer screening program for the categories of atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LS after triage with high-risk human papillomavirus (HR-HPV) testing and atypical squamous cells, cannot exclude high-grade intraepithelial squamous lesion (ASC-H) and high-grade squamous intraepithelial lesion (HSIL). We also verified whether the routine introduction of p16 staining might enhance the specificity and positive predictive value (PPV) for cervical intraepithelial neoplasia grade 2 or higher (CIN2+) lesions predicted by a cytological screening test. STUDY DESIGN: Performance of the p16 cytology test was estimated in 578 cytological samples, of which 213 were HR-HPV+ ASC-US, 186 were HR-HPV+ LSIL, 74 were ASC-H, 56 were HSIL-CIN2 and 49 were HSIL-CIN3. All samples had histological follow-up. RESULTS: In the ASC-US category, p16 sensitivity was 91% for CIN2+ and 100% for CIN3, while specificity was 64 and 58%, respectively, negative predictive value (NPV) was 96 and 100%, respectively, and PPV was 39%. In the LSIL category, sensitivity was 77 and 75%, respectively, for CIN2+ and CIN3, while specificity was 64 and 57%, NPV was 93 and 98% and PPV was 30%. Sensitivity for ASC-H and HSIL-CIN3 was 100% for CIN2+ and CIN3, while for HSIL-CIN2 it was 91 and 95%, respectively; NPV for ASC-H was 100%, and for HSIL-CIN2 it was 43 and 86%, respectively. Follow-up examinations of 8 cases diagnosed as p16+ ASC-H and HSIL-CIN3, but histologically negative or CIN1 on the first biopsy, showed 4 CIN2 and 4 CIN3 lesions. CONCLUSIONS: Sensitivity, specificity, PPV and NPV confirm the importance of the utilization of p16 in the categories ASC-US and LSIL after triage with an HR-HPV test. In the ASC-H and HSIL-CIN3 lesions, p16 was shown to be an excellent marker for picking up CIN2+ lesions, especially in cases with cytohistological discordance.

Metastatic breast carcinoma to parathyroid adenoma on fine needle cytology sample: report of a case.

Metastases to the thyroid gland diagnosed by means of fine needle cytology or by excision have been reported in the literature. To our knowledge, metastatic neoplasms to the parathyroid gland have never been described up to now. In this article, we introduce a rare case of metastatic breast carcinoma to a parathyroid adenoma in a 56-year-old woman, which clinically simulated a left thyroid nodule. The patient had a history of left breast carcinoma; the recent discovery of a palpable mass in the left thyroid area had elicited fine needle cytology sampling for its diagnostic evaluation. The obtained cytopathological sample was cellular but limited to a single Diff-Quik-stained smear; hence, no ancillary studies could be entertained. A cytopathological diagnosis of positive for malignant cells of query metastatic breast origin was performed. The permanent histopathological examination of the surgical sample disclosed multiple small foci of metastatic high-grade carcinoma of ductal type within a somewhat atypical adenoma of the parathyroid gland. The cytopathological findings and some differential diagnostic considerations are briefly commented, as well as the deranging imaging data concerning this interesting case.

Antioxidant activity of Sicilian pistachio (Pistacia vera L. var. Bronte) nut extract and its bioactive components.

Pistacia vera L. is the only species of Pistacia genus producing edible nuts. This paper investigates the antioxidant potential of a Sicilian variety of pistachio nut by chemical as well as biological assays and measured antioxidant vitamins and a number of antioxidant polyphenols in either the hydrophilic and/or the lipophilic nut extract. In accordance with the majority of foods, the total antioxidant activity, measured as a TAA test, was much higher (50-fold) in the hydrophilic than in the lipophilic extract. Substantial amounts of total phenols were measured. The hydrophilic extract inhibited dose-dependently both the metal-dependent and -independent lipid oxidation of bovine liver microsomes, and the Cu+2-induced oxidation of human low-density lipoprotein (LDL). Peroxyl radical-scavenging as well as chelating activity of nut components may be suggested to explain the observed inhibition patterns. Among tocopherols, gamma-tocopherol was the only vitamin E isomer found in the lipophilic extract that did not contain any carotenoid. Vitamin C was found only in a modest amount. The hydrophilic extract was a source of polyphenol compounds among which trans-resveratrol, proanthocyanidins, and a remarkable amount of the isoflavones daidzein and genistein, 3.68 and 3.40 mg per 100 g of edible nut, respectively, were evaluated. With the exception of isoflavones that appeared unmodified, the amounts of other bioactive molecules were remarkably reduced in the pistachio nut after roasting, and the total antioxidant activity decreased by about 60%. Collectively, our findings provide evidence that the Sicilian pistachio nut may be considered for its bioactive components and can effectively contribute to a healthy status.

Distribution of betalain pigments in red blood cells after consumption of cactus pear fruits and increased resistance of the cells to ex vivo induced oxidative hemolysis in humans.

Betalain pigments are bioavailable phytochemicals recently acknowledged as natural radical scavengers. This work, which extends previous research on the postabsorbitive fate of dietary betalains, investigated the distribution of betanin and indicaxanthin in red blood cells (RBCs) isolated from healthy volunteers (n = 8), before and during the 1-8 h interval after a cactus pear fruit meal, and the potential antioxidative activity of the pigments in these cells. A peak concentration of indicaxanthin (1.03 +/- 0.2 microM) was observed in RBCs isolated at 3 h after fruit feeding, whereas the concentration at 5 h was about half, and even smaller amounts were measured at 8 h. Indicaxanthin was not detected at 1 h. Betanin (30.0 +/- 5.2 nM) was found only in RBCs isolated at 3 h from fruit feeding. In comparison with homologous RBCs before fruit ingestion, a significant delay (P < 0.05) of the onset of an ex vivo cumene hydroperoxide (cumOOH)-induced hemolysis was evident in the RBCs isolated at 3 h (33.0 +/- 4.5 min) and at 5 h (16.0 +/- 2.0 min). Neither vitamins C and E nor GSH was modified in the RBCs at any time point. Blood collected from the same volunteers after a 12-h fasting was incubated with the purified betalains in the range of 5-25 microM, to enrich the erythrocytes with either betanin or indicaxanthin, and then the cells were exposed to cumOOH. When compared to the relevant nonenriched cells, the betalain-enriched erythrocytes exhibited an enhanced resistance to the cumOOH-induced hemolysis, which was positively correlated (r (2) = 0.99) to the amount of the incorporated compound. On a micromolar basis, betanin and indicaxanthin showed a comparable effectiveness. Taken together, these findings provide evidence that human RBCs incorporate dietary betalains and support the concept that these phytochemicals may offer antioxidative protection to the cells.

Absorption, excretion, and distribution of dietary antioxidant betalains in LDLs: potential health effects of betalains in humans.

BACKGROUND: Betalains were recently identified as natural antioxidants. However, little is known about their bioavailability from dietary sources. OBJECTIVE: The objective was to evaluate the bioavailability of betalains from dietary sources. DESIGN: The plasma kinetics and urinary excretion of betalains were studied in healthy volunteers (n = 8) after a single ingestion of 500 g cactus pear fruit pulp, which provided 28 and 16 mg indicaxanthin and betanin, respectively. The incorporation of betalains in LDL and the resistance of the particles to ex vivo-induced oxidation was also researched. RESULTS: Betanin and indicaxanthin reached their maximum plasma concentrations 3 h after the fruit meal and declined according to first-order kinetics. The half-life of betanin (0.94 +/- 0.07 h) was shorter than that of indicaxanthin (2.36 +/- 0.17 h). Both compounds had disappeared from plasma by 12 h after intake. The urinary excretion of indicaxanthin and betanin over 12 h represented 76 +/- 3.0% and 3.7 +/- 0.2%, respectively, of the ingested compounds. LDL isolated 3 and 5 h after the fruit meal incorporated betalains at concentrations of 100.5 +/- 11 and 50 +/- 7.2 pmol/mg LDL protein, respectively. In addition, the particles appeared more resistant to ex vivo-induced oxidative injury than did the samples isolated before fruit ingestion (P < 0.05)-the higher the amount of betalains incorporated, the higher the resistance. The concentrations of vitamin E and beta-carotene in LDL did not change significantly after fruit ingestion. CONCLUSION: Our results show that cactus pear fruit is a source of bioavailable betalains and suggest that indicaxanthin and betanin may be involved in the observed protection of LDL against ex vivo-induced oxidative modifications.

Supplementation with cactus pear (Opuntia ficus-indica) fruit decreases oxidative stress in healthy humans: a comparative study with vitamin C.

BACKGROUND: Cactus pear (Opuntia ficus-indica) fruit contains vitamin C and characteristic betalain pigments, the radical-scavenging properties and antioxidant activities of which have been shown in vitro. OBJECTIVE: We investigated the effects of short-term supplementation with cactus pear fruit compared with vitamin C alone on total-body oxidative status in healthy humans. DESIGN: In a randomized, crossover, double-treatment study, 18 healthy volunteers received either 250 g fresh fruit pulp or 75 mg vitamin C twice daily for 2 wk, with a 6-wk washout period between the treatments. Before (baseline) and after each treatment, 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)) and malondialdehyde in plasma, the ratio of reduced to oxidized glutathione (GSH:GSSG) in erythrocytes, and lipid hydroperoxides in LDL were measured as biomarkers of oxidative stress; plasma Trolox-equivalent antioxidant activity (TEAC) and vitamins A, E, and C were evaluated as indexes of antioxidant status. RESULTS: Both treatments caused comparable increases compared with baseline in plasma concentrations of vitamin E and vitamin C (P < 0.05); vitamin A and TEAC did not change significantly. After supplementation with cactus pear fruit, 8-epi-PGF(2)alpha and malondialdehyde decreased by approximately 30% and 75%, respectively; GSH:GSSG shifted toward a higher value (P < 0.05); and LDL hydroperoxides were reduced by almost one-half. Supplementation with vitamin C did not significantly affect any marker of oxidative stress. CONCLUSIONS: Consumption of cactus pear fruit positively affects the body's redox balance, decreases oxidative damage to lipids, and improves antioxidant status in healthy humans. Supplementation with vitamin C at a comparable dosage enhances overall antioxidant defense but does not significantly affect body oxidative stress. Components of cactus pear fruit other than antioxidant vitamins may play a role in the observed effects.

Antioxidant activities of sicilian prickly pear (Opuntia ficus indica) fruit extracts and reducing properties of its betalains: betanin and indicaxanthin.

Sicilian cultivars of prickly pear (Opuntia ficus indica) produce yellow, red, and white fruits, due to the combination of two betalain pigments, the purple-red betanin and the yellow-orange indicaxanthin. The betalain distribution in the three cultivars and the antioxidant activities of methanolic extracts from edible pulp were investigated. In addition, the reducing capacity of purified betanin and indicaxanthin was measured. According to a spectrophotometric analysis, the yellow cultivar exhibited the highest amount of betalains, followed by the red and white ones. Indicaxanthin accounted for about 99% of betalains in the white fruit, while the ratio of betanin to indicaxanthin varied from 1:8 (w:w) in the yellow fruit to 2:1 (w:w) in the red one. Polyphenol pigments were negligible components only in the red fruit. When measured as 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) equivalents per gram of pulp, the methanolic fruit extracts showed a marked antioxidant activity. Vitamin C did not account for more than 40% of the measured activity. In addition, the extracts dose-dependently inhibited the organic hydroperoxide-stimulated red cell membrane lipid oxidation, as well as the metal-dependent and -independent low-density lipoprotein oxidation. The extract from the white fruit showed the highest protection in all models of lipid oxidation. Purified betanin and indicaxanthin were more effective than Trolox at scavenging the [2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)] diammonium salt cation radical. Cyclic voltammetric measurements show two anodic waves for betanin and indicaxanthin, and differential pulse voltammetry shows three anodic waves for betanin, with calculated peak potentials of 404, 616, and 998 mV, and two anodic waves for indicaxanthin, with peak potentials of 611 and 895 mV. Betanin underwent complex formation through chelation with Cu(2+), whereas indicaxanthin was not modified. These findings suggest that the above betalains contribute to the antioxidant activity of prickly pear fruits.

Exposure to malondialdehyde induces an early redox unbalance preceding membrane toxicity in human erythrocytes.

This work investigated the oxidative injury to human red blood cells (RBCs) by the exposure to exogenous malondialdehyde (MDA), in a physiological environment. When a 10% RBC suspension was incubated in autologous plasma, in the presence of 50 microM MDA, 30% of MDA entered into the cells. A time-course study showed that MDA caused early (30-120 min) and delayed (3-18 h) effects. MDA caused a fast depletion of reduced glutathione, and loss of the glucose-6-phosphate dehydrogenase activity, followed by a decrease of HbO2. Accumulation of methemoglobin, and formation of small amounts of hemichrome were later evident. Also, an HbO2-derived fluorescent product was measured in the membrane. The redox unbalance was followed by structural and functional damage to the membrane, evident as the formation of conjugated diene lipid hydroperoxides, concurrent with a sharp accumulation of MDA, consumption of membrane vitamin E, and egress of K+ ions. SDS--PAGE of membrane proteins showed formation of high molecular weight aggregates. In spite of the marked oxidative alterations, the incubation plasma prevented a substantial hemolysis, even after a 18 h incubation. On the contrary, the exposure of RBCs to 50 microM MDA in glucose-containing phosphate saline buffer, resulted in a 16% hemolysis within 6 h. These results indicate that the exposure to MDA causes a rapid intracellular oxidative stress and potentiates oxidative cascades on RBCs, resulting in their dysfunction.