Metallic nanoparticle contamination from environmental atmospheric particulate matter in the last slab of the trophic chain: Nanocrystallography, subcellular localization and toxicity effects.

Atmospheric particulate material (PM) from mining and steel industries comprises several metallic contaminants. PM10 samples collected in a Brazilian region with a recognized influence of the steel and iron pelletizing industries were used to investigate metallic nanoparticle incorporation into human fibroblast cells (MRC-5). MRC-5 cells were exposed to 0 (control, ultrapure water), 2.5, 5, 10, 20 and 40 µg PM10 mL-1, for 24 h. Cytotoxic and genotoxic dose-response effects were observed on lysosome and DNA structure, and concentrations high as 20 and 40 µg PM10 mL-1 induced elevated cell death. Ultrastructure analyses showed aluminosilicate, iron, and the emerging metallic contaminants titanium, bismuth, and cerium nanoparticles were incorporated into lung cells, in which the nanocrystallography analysis indicated the bismuth as Bi2O3. All internalized metallic nanoparticles were free and unbound in the cytoplasm and nucleus thereby indicating bioavailability and potential interaction to biological processes and cellular structures. Pearson's correlation analysis showed Fe, Ni, Al, Cr, Pb and Hg as the main cytotoxic elements which are associated with the stainless steel production. The presence of internalized nanoparticles in human lung cells exposed to environmental atmospheric matter highlights the need for a greater effort by regulatory agencies to understand their potential damage and hence the need for future regulation, especially of emerging metallic contaminants.

Classification of gastritis in first-degree relatives of patients with gastric cancer in a high cancer-risk area in Italy.

BACKGROUND: Screening gastroscopic examinations were performed in a cohort of individuals at high risk for developing gastric carcinoma (GC). PATIENTS AND METHODS: Five gastric biopsies were obtained following the Houston schema. Five histological parameters of gastritis were investigated: acute gastritis, chronic gastritis, and its sequelae; mucosal atrophy, intestinal metaplasia and pseudopyloric metaplasia. RESULTS: Out of 134 patients, 50% (n=67) had Helicobacter pylori (HP) infection. The sum of scores for the first four parameters was significantly higher in HP-positive cases than in HP-negative ones (p<0.0001). The frequency of these histological parameters was similar to other series from Northern and Central Italy. Hence, none of the histological parameters of gastritis explain the high GC risk in this borough of Florence, considering that the incidence rate of GC is higher in Central than in Northern Italy. CONCLUSION: Similarities in the frequency of chronic gastritis and sequelae in Northern and Central Italy substantiate the conviction that the difference in GC risk in these regions might be the result of local environmental or lifestyle factors, rather than HP infection. This knowledge is crucial, considering that environmentally related diseases are theoretically preventable.

Clinical importance of lymph node density in predicting outcome of prostate cancer patients.

BACKGROUND: To evaluate the prognostic role of lymph node density (LND) in patients affected by prostate cancer (PCa) and treated with radical prostatectomy (RP), pelvic lymph node dissection (PLND), and adjuvant hormonal blockade. METHODS: A total of 124 consecutive patients with lymph node positive PCa formed the basis of this report. Clinical and pathological parameters were collected. All patients were stratified in two groups according to LND: Group A (LND ≤ 32%) and Group B (LND ≥ 33%). Time to the first biochemical recurrence (BCR) was the main measure of outcome. RESULTS: Mean number of lymph nodes removed was 5.2 (range 1-17). The mean number of positive lymph nodes was 1.6 (range 1-5). At a mean follow-up of 84.3 mo, 22 patients in Group A (43.1%) and 40 in Group B (54.7%) had BCR. The mean overall BCR-free survival was 46.2 mo (range 8-90). No significant correlation was found between the number of positive lymph nodes and BCR-free survival (P = 0.68). In addition, the patients with LND ≥ 33% had a poor prognosis with significantly decreased disease-specific and BCR-free survival rates (hazard ratio: 0.48; 95% CI, 0.28-0.78; P = 0.0039). At multivariate and artificial neural network (ANN) analyses, LND, Gleason score, and stage were identified as independent prognostic factors of BCR-free survival (P = 0.002; P = 0.003; P = 0.003). CONCLUSIONS: The current study highlights the role of LND in predicting BCR-free survival in patients with lymph node positive PCa after prostatectomy. It also reinforces the need for a stratification of patients with nodal metastasis.

Non-sentinel lymph node involvement in a patient with an atypical Spitz tumor and a positive sentinel node. Report of a case and review of the literature.

We report a 20-year-old male patient with an atypical Spitz tumor, located in the dorsal aspect of his left hand, and a positive sentinel axillary lymph node. After lymphadenectomy, 1 of 23 non-sentinel lymph nodes excised was found to contain small multiple deposits of large spindle atypical melanocytes. Reviewing the pertinent literature, 5 of 29 patients with atypical Spitz tumors and positive sentinel nodes who had undergone lymphadenectomy have shown non-sentinel node involvement (17.2%), a proportion similar to that reported in melanoma patients. The exact nature of atypical Spitz tumors and the interpretation of cell deposits detected in sentinel nodes are still debated; data regarding the non-sentinel lymph node involvement in patients with atypical Spitz tumors may contribute to better understand the real biological potential of such tumors.

Transperineal microwave thermoablation in patients with obstructive benign prostatic hyperplasia: a phase I clinical study with a new mini-choked microwave applicator.

PURPOSE: To evaluate the tolerability and safety of a newly designed probe for trans-perineal microwave thermoablation (TPMT) of the prostate in patients with benign prostatic hyperplasia (BPH), and the in vivo microwave effects on prostatic tissue. PATIENTS AND METHODS: Nine patients with obstructive BPH who were candidates for open prostatectomy were selected for this study. Under local anesthesia and transrectal ultrasound monitoring, all patients underwent a single standardized application of TPMT. The visual analog scale (VAS) and Short Form-36 health survey (SF-36) questionnaire were administered to each patient prior to, during, and 1 month after TPMT in order to evaluate pain and quality of life. Then the International Index of Erectile Function (IIEF-5) and International Prostate Symptom Score (IPSS) questionnaires were administered to each patient at baseline and 1 month after prostatectomy in order to evaluate sexual and urinary function, respectively. Then all patients were divided into three groups and underwent open prostatectomy 7, 15, and 30 days after TPMT, respectively. The prostatic adenomas were then evaluated by a pathologist. RESULTS: No adverse events from TPMT treatment were noted. In particular, no patients reported local, pelvic, or abdominal pain during the procedure or subsequent alterations of defecation rhythm, ano-rectal/intestinal problems, or hematuria. No differences in quality of life or in sexual function were reported. The diameters of the lesions obtained with TPMT treatment ranged from 16 to 18.1 mm in all patients. Quasi-spheroid lesions with a well-defined area of complete coagulative necrosis were documented in all removed adenomas 7, 15, and 30 days after TMPT. CONCLUSIONS: The AMICA-PROBE is a safe, well-tolerated, and repeatable method to treat BPH with microwave thermotherapy. The spheroid lesions obtained demonstrated the maximal control over the radial and longitudinal coagulative effects of the therapy. Phase II studies are needed to further evaluate the efficacy of this new probe.

Sensitivity and specificity of histological criteria in the diagnosis of conventional cutaneous melanoma.

The efficacy of the histological criteria currently used in the diagnosis of melanoma is still to be defined. We performed a quantitative analysis of 72 conventional (non-Spitzoid, nondesmoplastic) melanomas and 73 conventional melanocytic naevi, used as controls, for 13 histological diagnostic parameters (dimension >6 mm, asymmetry, poor circumscription, irregular and confluent nests, single melanocytes predominating, absence of maturation, suprabasal melanocytes, asymmetrical melanin, melanin in deep cells, cytological atypia, mitoses, necrosis and dermal lymphocytic infiltrate). Differences in the distribution of selected parameters between the two groups were investigated by Fisher's exact test; for each parameter sensitivity and specificity were calculated. Results showed that all parameters, except poor circumscription, seemed to be significantly associated with melanoma (P<0.05). Cytological atypia, dermal lymphocytic infiltrate, asymmetry, dimension >6 mm and absence of maturation showed a high sensitivity (>90%); absence of maturation, mitoses, necrosis, asymmetrical melanin, suprabasal melanocytes and melanin in deep cells showed a high specificity (>90%); irregular-confluent nests and single melanocytes predominating were poorly sensitive and poorly specific. In melanomas < or =2 mm, two additional parameters were sensitive (> or =90%): suprabasal melanocytes and single melanocytes predominating. We conclude that not all parameters showed to have the same diagnostic value. Absence of maturation and, limited to melanomas < or =2 mm, suprabasal melanocytes were the most discriminating (sensitive and specific) histological features. Cytological atypia, dimension >6 mm, suprabasal melanocytes and mitoses were additional reliable diagnostic features, showing a relatively high sensitivity and a relatively high specificity. Other useful features were dermal lymphocytic infiltrate and asymmetry (sensitive) and necrosis, asymmetrical melanin and melanin in deep cells (specific).

Can early single dose instillation of epirubicin improve bacillus Calmette-Guerin efficacy in patients with nonmuscle invasive high risk bladder cancer? Results from a prospective, randomized, double-blind controlled study.

PURPOSE: We evaluated the impact of epirubicin perioperative instillation in improving subsequent bacillus Calmette-Guerin instillation efficacy in high risk patients with nonmuscle invasive bladder cancer. MATERIALS AND METHODS: Between January 2005 and June 2007, 161 patients affected by high risk nonmuscle invasive bladder cancer were enrolled in this prospective, randomized, controlled, double-blind study. A total of 80 patients were assigned to group A (perioperative epirubicin 80 mg/50 ml normal saline) plus delayed bacillus Calmette-Guerin instillations (5 x 108 colony-forming units in 50 ml saline) and 81 to group B (delayed bacillus Calmette-Guerin alone). The main outcome measures were time to first recurrence and recurrence rate. All data obtained from a median followup of 15.3 months in group A and 14.8 months in group B, were analyzed. RESULTS: At the end of followup 46 of 80 patients in group A (57.5%) had no evidence of disease, just like 41 of 81 in group B (50.6%). No statistical difference was observed between the 2 groups in terms of recurrence rate (p = 0.82) or time to first recurrence (p = 0.095). Kaplan-Meier analysis of recurrence showed no significant differences between group A and group B (p = 0.0952). On multivariate analysis the early single dose instillation of epirubicin was not indicated as an independent prognostic factor (HR 0.50, 95% CI 0.32-1.18). CONCLUSIONS: The present study showed no statistically significant differences in terms of disease-free time and recurrence rate between high risk patients with nonmuscle invasive bladder cancer who had undergone perioperative epirubicin instillation plus delayed bacillus Calmette-Guerin and those who had undergone delayed bacillus Calmette-Guerin alone.

Interleukin-6/10 ratio as a prognostic marker of recurrence in patients with intermediate risk urothelial bladder carcinoma.

PURPOSE: Several potential markers have been investigated to improve the noninvasive diagnosis of recurrent superficial bladder carcinoma. We evaluated the role of the interleukin-6/10 ratio as a prognostic marker of recurrence in patients with intermediate risk superficial bladder carcinoma. MATERIALS AND METHODS: A total of 65 consecutive urological patients seen in the office, including 41 with intermediate risk superficial bladder carcinoma and 24 controls, were selected for this prospective study. Five urine samples for urinary cytology and interleukin analyses were collected from each subject at baseline, and 3, 6, 9 and 12 months after surgery, respectively. Interleukin-6 and 10 were determined in urine by the Quantikine solid phase interleukin-6 and 10 enzyme-linked immunosorbent assay, respectively. Sensitivity, specificity, and positive and negative predictive values of the method were calculated. RESULTS: At baseline sample collection the interleukin-6/10 ratio was not statistically different between patients and controls (p = 0.58). Interleukin-6/10 was statistically different between patients with vs without recurrence 3 (0.009 vs 0.408), 6 (0.011 vs 0.268), 9 (0.012 vs 0.288) and 12 months (0.009 vs 0.302) after pre-transurethral bladder tumor resection (each p <0.001). Multivariate analysis indicated that interleukin-6/10 was an independent prognostic factor of recurrence (HR 3.62, 95% CI 2.80-4.92, p <0.001). Test sensitivity and specificity were 0.83% (95% CI 0.57-0.95) and 0.76% (95% CI 0.45-0.93), respectively. CONCLUSIONS: The current study highlights the feasible role of the interleukin-6/10 ratio for predicting intermediate risk superficial bladder carcinoma recurrence. However, clinical trials with a greater number of patients are needed to consider its use in clinical urological practice.

Penile metastasis from a T1b prostate carcinoma.

BACKGROUND: Penile metastasis from incidental prostate carcinoma has not been described to date. CASE REPORT: The case of a 72-year-old man affected by penile metastasis from incidental prostate carcinoma is described. In March 1998, the patient underwent prostate surgery for lower urinary tract symptoms related to benign prostatic obstruction. Histological examination revealed an incidental adenocarcinoma of the prostate. The pre-operative prostate-specific antigen (PSA) value was 3.6 ng/ml. A prostate biopsy in the peripheral prostate lobes was negative. PSA progressively rose to 8 ng/ml. The prostate biopsy was repeated and was still negative. The patient was subjected to radiotherapy, as a result of which his PSA fell to 0.7 ng/ml. 4 years after prostatectomy, the PSA rose again and the patient underwent hormonal therapy. The PSA fell to < 0.001 ng/ml. In May 2004, the patient reported a painful, erythematous nodule on his penis glans. Surgical biopsy showed a metastasis from prostate adenocarcinoma and he underwent partial penectomy. Due to disease progression, the patient underwent medical therapy. PSA and testosterone were always at minimum levels. 20 months later the patient died. CONCLUSION: We underline the uncertainty of the biological behaviour and optimal management of incidentally identified prostate carcinoma. In addition, we highlight that biological and clinical progression could be the consequence of inadequate treatment recommendations.