Mammary Paget's disease and radiotherapy: a systematic literature review.

OBJECTIVE: Paget disease of the breast (PDB) is a rare form of cutaneous breast cancer. Up to date, no randomized studies evaluated the different management strategies. This systematic review investigates the role of radiotherapy and its best technical profile in the treatment of this disease, with great attention to doses and fractionation regimens. MATERIALS AND METHODS: A systematic search was performed on PubMed, Embase and Scopus in order to detect case reports, case series and prospective as well as retrospective clinical studies describing histologically proven PDB and providing information about pertinent radiation treatments. Searching strategy followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. RESULTS: Inclusion criteria were met by six papers, dealing with radiation treatments performed postoperatively and in exclusive settings. No evaluations were performed on preoperative radiotherapy. CONCLUSIONS: Actually, the standard treatment of PDB reflects oncological principles of breast carcinoma therapy, including the role of breast-preserving surgery. The traditional radiotherapic dose is 50 Gy, with daily fractionation of 2 Gy. Adjuvant radiotherapy following breast preserving surgery represents the current standard of care; prospective studies could be of help in defining the role of exclusive radiotherapy, hypofractionated schemes and smaller target volumes.

Tailored-BODIPY/Amphiphilic Cyclodextrin Nanoassemblies with PDT Effectiveness.

Amphiphilic cyclodextrins (aCDs) are an intriguing class of carrier systems which, recently, have been proposed to deliver porphyrinoids and anticancer drugs or combined dose of both for dual therapeutic applications. The design of nanoassemblies based on aCD and photosensitizers (PSs) aims to preserve the photodynamic therapy (PDT) efficacy of PS, reducing the tendency of PS to self-aggregate, without affecting the quantum yield of singlet oxygen (1O2) production, and, not less importantly, minimizing dark toxicity and reducing photosensitization effects. With this idea in mind, in this paper, we focus on nanoassemblies between a non-ionic aCD (SC6OH) and halo-alkyl tailored iodinated boron-dipyrromethenes (BODIPY) dye, a class of molecules which recently have been successfully proposed as a stimulating alternative to porphyrinoids for their high photodynamic efficacy. Nanoassemblies of BODIPY/aCD (BL01I@SC6OH) were prepared in different aqueous media by evaporation of mixed organic film of aCD and BODIPY, hydration, and sonication. The nanostructures were characterized, measuring their hydrodynamic diameter and ξ-potential and also evaluating their time-stability in biological relevant media. Taking advantage of emissive properties of the not-iodinated BODIPY analogue (BL01), nanoassemblies based on aCD and BL01 were investigated as model system to get insight on entanglement of BODIPY in the amphiphile in aqueous dispersion, pointing out that BODIPY is well-entrapped in monomeric form (τ ≅ 6.5 ns) within the colloidal carriers. Also morphology and fluorescence emission properties were elucidated after casting the solution on glass. BL01@SC6OH is easily detectable in cytoplasm of HCT116 cell lines, evidencing the remarkable intracellular penetration of this nanoassembly similar to free BODIPY. On the same cell lines, the photodynamically active assembly BL01I/aCD shows toxicity upon irradiation. Despite the fact that free BL01I is more PDT active than its assembly, aCD can modulate the cell uptake of BODIPY, pointing out the potential of this system for in vivo PDT application.

Is retrograde intrarenal surgery a viable treatment option for renal stones in patients with solitary kidney?

PURPOSE: To evaluate the effectiveness and safety of retrograde intrarenal surgery (RIRS) for stones up to 2 cm in diameter in patients with solitary kidney. METHODS: From January 2008 to January 2013, we prospectively enrolled all consecutive patients with solitary kidney and renal stones. Plain abdominal computed tomography scan was performed preoperatively and 1 month after the procedure to assess the stone-free rates (SFR). Serum creatinine levels were detected preoperatively, at day 1 postoperatively, at 1 month postoperatively, and then every 6 months postoperatively. RESULTS: During the study period, we prospectively enrolled a total of 29 patients. The mean age was 55.7 ± 12.3 years; the mean stone size was 1.3 ± 0.4 cm. The primary SFR was 72.4 %; the secondary SFR was 93.1 %. The mean number of procedures per patient was 1.24. The mean serum creatinine levels were 1.5 ± 0.6, 1.6 ± 0.7, 1.6 ± 0.6, and 1.7 ± 0.7 mg/dl preoperatively, at 1 day after RIRS, at 1 month after RIRS, and at 1 year after RIRS, respectively, without detection of any statistical difference (p = 0.76). Median follow-up time was 35.7 ± 19.3 (12-72) months, but that was available for only 18 patients. The mean serum creatinine level at the last follow-up was 1.7 ± 0.9 mg/dl. No major complications were recorded. Grade I complications occurred in eight patients (27.4 %). CONCLUSIONS: RIRS is safe and effective in the treatment of renal stones in patients with solitary kidney, without worsening renal function.

Cystoman® and calculi: a good alternative to standard therapies in preventing stone recurrence.

To assess the efficacy and tolerability of D-mannose-containing product (Cystoman(®)) in preventing recurrence in patients who underwent surgical treatment for infection related urinary stones. From January 2011 to February 2013 we have enrolled all consecutive patients affected by staghorn calculi and recurrent urinary tract infections (UTIs). All patients recommended for surgery were scheduled for percutaneous nephrolithotomy. The study agent was administered daily for 5 months after surgical procedure. At baseline and 5-month follow-up all patients underwent abdominal Computed Tomography (CT) scan and they also completed Medical Outcomes Study short-form, 36-item questionnaire (SF-36). They performed urine and urine culture monthly. The primary endpoints were the assessment of the efficacy with regard to infection-related urinary stone recurrence and the tolerability of Cystoman(®). The secondary endpoint was the evaluation of quality-of-life symptoms. During the study period, a total of 27 patients were included in the study. The data from 25 patients were analyzable. Seventeen patients (68%) did not report UTIs during follow-up. Eight patients (32%) remained infected and the average number of UTIs was 2.6 ± 1.6 in 5 months. At 5-month follow-up 17 (68%) patients were free from stones recurrence; in 8 (32%) cases CT scan revealed stone recurrence with an average stone diameter of 1.1 ± 0.4 cm. In nonrecurring patients, 2 (11.7%) reported an average of 1.5 ± 0.7 UTIs episodes; in recurring patients, 6 (75%) showed 3 ± 1.67 of UTIs episodes. Statistically significant differences were seen in the occurrence of UTIs episodes were detected between nonrecurring stone patients and recurring patients (p < 0.05). Moreover, statistically significant changes were detected in SF-36 scores from baseline to month 5 in the categories of physical functioning and energy/fatigue (p < 0.05). Cystoman(®) is effective in preventing infection-related urinary stones.

Epidural analgesia with ropivacaine and sufentanil is associated with transient fetal heart rate changes.

AIM: Fetal heart rate (FHR) changes have been reported after regional labor analgesia. In this prospective single-blinded study, we aimed to assess whether epidural analgesia with ropivacaine and sufentanil is associated with significant changes in fetal heart rate. METHODS: Fetal heart rate traces from 120 women in active labor requesting epidural analgesia were recorded and analyzed by two reviewers 90 minutes before and after epidural analgesia for baseline fetal heart rate, accelerations, decelerations and long-term variability. RESULTS: A significantly decreased number of fetal heart rate accelerations (ANOVA P=0.0001) and a higher percentage of segments with decelerations (P<0.05) were observed in the three segments after analgesia as compared to the three preceding segments. The minimum number of accelerations occurred during the 30 minutes immediately after analgesia was initiated. The reviewers were concordant in finding a significant change from the 60 minutes before to the 60 minutes after analgesia, a period in which there CONCLUSION: Epidural analgesia with ropivacaine and sufentanil is associated with fetal heart rate changes. These modifications are transient and should be considered when evaluating fetal heart rate monitoring during labor to prevent inappropriate obstetric management decisions to proceed with operative labor.

Identification of a new allele in a Sicilian individual: HLA-DPB1*0302.

We report here the identification and characterization of a novel human leucocyte antigen (HLA)-DPB1 allele that was subsequently named HLA-DPB1*0302 by the WHO Nomenclature Committee. HLA-DPB1*0302 was identified in a single Sicilian individual by a combination of sequence-specific primers, reverse line sequence-specific oligonucleotide probing and DNA sequencing-based typing. The DPB1*0302 allele is most similar to the DPB1*3101 allele, differing by a single mismatch at nucleotide position 301 (T to G).

Elevated vascular endothelial growth factor (VEGF) serum levels in idiopathic myelofibrosis.

An increase of angiogenesis has been shown in idiopathic myelofibrosis with myeloid metaplasia (MMM) by microvessel density count method but evaluation of circulating angiogenic factors is still incomplete. In 31 patients affected by MMM and in 12 healthy subjects we evaluated the serum levels of VEGF (vascular endothelial growth factor) and correlated VEGF with clinical and laboratory features of disease. We found that MMM patients had circulating VEGF concentrations much higher than controls (Median 1208 ng/ml vs 138 ng/ml, P < 0.0001). No correlation was found between VEGF and Hb, WBC, PLT, LDH, creatinine, bone marrow cellularity, fibrosis, splenomegaly, hepatomegaly, and therapy. However, in the subgroup of patients with a normal or low VEGF concentration, a direct correlation between VEGF and platelet count (r = 0.90, P = 0.002) was detected. Moreover, patients with a platelet count < 300 x 10(9)/l had VEGF serum levels lower than patients with a higher PLT count (median VEGF 864 vs 1557 pg/ml, P = 0.001). In six patients and in eight controls we also had the opportunity to measure VEGF in the plasma and we calculated that VEGF concentration was much higher in platelet-rich than in platelet-poor plasma and that platetets of MMM patients contained four times more VEGF than those of healthy controls. These results indicate that VEGF is overproduced in MMM, thus confirming an increased angiogenic activity. Platelets are probably a major source of VEGF in MMM but not the only one.

Recurrent pelvic pain in women.

We conducted a prospective survey from January to September 1999 on a random population from the city of Turin, Italy, to highlight pain pathologies at various ages and possible differences between sexes. By means of a questionnaire, women were asked about age, profession, marital status, menstrual pain, type of delivery, number of children, onset and presence of pain of any type. Pain-related questions included its characteristics, familial tendencies, treatment, type, duration, daily and monthly quantity of medication taken, habits, previous pathologies, or surgical operations. A control group of men was investigated.

Angiogenic factors in multiple myeloma: higher levels in bone marrow than in peripheral blood.

BACKGROUND AND OBJECTIVES: To study the role of some soluble factors in the process of angiogenesis that accompanies multiple myeloma (MM). DESIGN AND METHODS: The concentrations of three well-known angiogenic peptides, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and hepatocyte growth factor (HGF) were evaluated by an ELISA method. All of these factors were measured in the plasma obtained from peripheral blood (PB) and bone marrow (BM) aspirates of 34 patients affected by plasma cell disorders. This series included one patient with a solitary extramedullary plasmacytoma, 17 patients with MM at diagnosis, and 16 with previously treated MM. RESULTS: In all the patients, the concentration of each angiogenic factor was higher in bone marrow than in peripheral blood. Mean values of the three angiogenic factors in BM or in PB were lower in stage I than stage II-III. One patient with extramedullary solitary myeloma had high levels of VEGF and bFGF but this increase was not found in the other 6 patients with extramedullary disease when compared with patients without extramedullary disease. VEGF and bFGF did not correlate with each other while HGF showed a weak correlation with VEGF and a stronger one with bFGF. Moreover, VEGF correlated with features of disease activity, such as C-reactive protein, and 2-microglobulin, while both bFGF and HGF showed an inverse correlation with albumin level. No correlation was found between VEGF, bFGF and HGF levels and age, M protein level, osteolytic lesions, or percentage of BM plasma cells. Since angiogenic factors may be released by normal cells in response to hypoxia, we also evaluated erythropoietin (EPO) levels (which correlate with the hypoxic stimulus) both in PB and BM plasma of these patients but none of the measured angiogenic factors correlated with EPO levels. Interpretation and Conclusions. Several soluble factors may play a role in the angiogenic activity described in MM but their contribution to the progression of disease may be different. The finding of higher levels of these factors in BM than in PB might indicate that the bone marrow environment is their major source. Concentrations of angiogenic factors parallel the activity of disease and are independent of the hypoxic stimulus.

[Oral surgery and histologic reports: the incidence of various diseases in eastern Sicily]. / Chirurgia orale e referti istologici: considerazioni sull'incidenza delle varie pathologie in Sicilia orientale.

According to the histological exams executed from January 1975 to June 1988, the authors assessed the frequency in the years, in the sex and in the decades and of the pathology surgery executed. For simplicity of graphic representation, the authors subdivided the pathologies in nine groups: phlogistic trial, cysts, epulis, leukoplakia and precancerous lesion, epithelial tumor, connectival tumor, vascular tumor and osseous tumor. With the voice "other" we consider some neoplasies which are not numerous and which are not differently classificable. According to the present statistics numerous operations are excluded like dysodontiasis, dental embedding, fractures, supernumerary teeth and so on. The authors ascertained on elevated frequency of cysts and of osteitis of maxillary bone caused by an inadequate and late treatment of the cavity. During the passing of the years the incidence of phlogistic trial is particularly reduced while the cysts presented a notable increase. Comparison of leukoplakia was exceptional while among the tumors predominate the epithelial tumors one. According to the presented information the Authors come to an end hoping a more preventive sensibility of people and dentistries.

[Nimesulide: multicenter clinical study for evaluation of its therapeutic effect in odontostomatology]. / Nimesulide: studio clinico multicentrico per la valutazione dell'attività terapeutica in odontostomatologia.

A Polycentric Study was carried out so as to assess the anti-inflammatory effectiveness and pain-killing activity of Nimesulide in Odontostomatological practice, in 78 patients suffering from alveolo-gingival and parodontal abscesses, consequences of tooth extraction, suppurated radicular cysts, dysodontiasis, osteitis, periodontitis, periostitis. The results obtained confirm the anti-inflammatory and analgesic effect as well as the good tolerability of this drug.

Beta S gene in Sicily is in linkage disequilibrium with the Benin haplotype: implications for gene flow.

Hemoglobin beta-like gene cluster haplotypes defined by restriction enzyme polymorphic sites are useful in determining the origin of the beta S gene found in several human populations. We present here evidence that the beta S gene found among Sicilians is associated with the same haplotype observed among sickle cell anemia patients from Central West Africa. In addition, this haplotype is either nonexistent or very rare among normal Sicilian individuals. We conclude that the beta S gene was introduced to Sicily from North Africa and that the gene flow originated in Central West Africa and traveled north through historically well-defined trans-Saharan commercial routes.

Heterogeneity of haplotypes among patients with severe Cooley disease in Eastern Sicily.

There is a large variation of clinical severity among thalassemic patients in Sicily. A heterogeneous molecular basis has already been demonstrated among the patients presenting with thalassemia intermedia. The same approach, based mostly on linked haplotypes of the beta gene cluster polymorphisms and in some cases on the demonstration of the molecular defect itself, was used to investigate 55 patients presenting with severe Cooley anemia, all maintained under permanent transfusion regimen. A large heterogeneity was demonstrated in the observed haplotypes, and only a limited overlap with those already found in thalassemia intermedia. It has been noted that many of the patients are compound heterozygotes, the various observed associations making the antenatal diagnosis at the DNA level difficult in the near future.

Haplotype VI associated beta + thalassaemia intermedia. First Italian case.

We report the study of a family originating from eastern Sicily with mild beta thalassaemia intermedia which is similar both at a molecular level and in clinical form to that called "beta + thalassaemia intermedia-Portuguese type". Our patients were homozygous beta + thalassaemics with high HbA2 and low HbF levels. The mild clinical course was as a result of their age and because regular blood transfusion was established only in adulthood. All of the heterozygote parents were asymptomatic with a blood picture and haemoglobin pattern typical of beta thalassaemia. Studies at a molecular level revealed no abnormalities in the beta-like globin gene cluster and excluded the presence of a deletional form of alpha thalassaemia. Restriction enzyme site polymorphisms around the beta gene cluster showed that all patients were homozygous for the haplotype described as VI. Comparison of these homozygous haplotypes with the Portuguese ones revealed a clear difference in the polymorphic Pvu II site. In all Sicilian homozygous cases, this site was present on one chromosome and absent on the other. Therefore our hypothesis is that Portuguese beta + thalassaemia intermedia is different from the Sicilian type.

T-subset abnormalities in thalassaemia intermedia: possible evidence for a thymus functional deficiency.

Peripheral blood T-lymphocyte subsets, evaluated by means of a series of monoclonal antibodies, were assessed in 14 patients affected by thalassaemia intermedia, 7 of them previously splenectomized. A significant reduction of T+4 cells ('helper' T cells) was found in almost all patients, whereas T+8 cells ('suppressor/cytotoxic') showed a marked increase only in splenectomized subjects. Together with these quantitative T-subset abnormalities, which seemed to be partly affected by either splenectomy or high serum iron levels, an unusual circulating T-cell subpopulation labelled by T6 monoclonal antibody was detected in all patients. Complete disappearance of T+6 cells ('thymocyte-like' T lymphocytes) and normalization of the T4/T8 ratio was observed after 'in vitro' incubation of patient's lymphocytes with a crude thymus extract (Thymostimulin). This would suggest the presence of a so far unreported thymus-dependent defect of T-lymphocyte phenotypic maturation occurring in thalassaemia intermedia.