Meningeal carcinomatosis underdiagnosis and overestimation: incidence in a large consecutive and unselected population of breast cancer patients.

BACKGROUND: The incidence of meningeal carcinomatosis appears to be higher than in the past due to advances in neuro-imaging diagnostic techniques and improvements in cancer survival. Among solid tumors, breast cancer is the cancer most commonly associated with meningeal carcinomatosis, with an incidence rate of between 0.8 and 16%. Aim of this study has been i) to evaluate the incidence of meningeal carcinomatosis in a continuous breast cancer unselected series treated in a dedicated Breast Unit and ii) to define the clinico-pathological and molecular parameters associated with meningeal carcinomatosis development. METHODS: A retrospective series of 1915 consecutive patients surgically treated for breast cancer between 1998 and 2010 was collected. Clinico-pathological data were recorded from medical charts and pathological reports, including the date of development of symptomatic meningeal carcinomatosis. Meningeal carcinomatosis incidence was determined at both 5- and 10-year follow-ups. RESULTS: Three patients in the first 5 years of follow-up and six patients in 10 years of follow-up developed meningeal carcinomatosis. An incidence rate of 5.44 per 10,000 patients (95% CI: 1.75-16.9) was observed, with a 5-year risk of 0.3%. At 10-year follow up, the rate increased to 7.55 per 10,000 patients (95% CI: 3.39-16.8). In a univariate analysis, young age, tumor size larger than 15 mm, histological grade 3, more than three metastatic lymph nodes, negative estrogen receptor, positive HER2 and high proliferative index were significantly associated with meningeal carcinomatosis development. CONCLUSIONS: In an unselected breast cancer population, meningeal carcinomatosis is a rare event that is associated with adverse prognostic factors. Meningeal carcinomatosis incidence is overestimated when recorded in biased/high-risk selected breast cancer patients and should not be considered to accurately reflect the overall breast cancer population.

Biopsy and radical prostatectomy pathological patterns influence Prostate cancer gene 3 (PCA3) score.

AIM: To evaluate the relationship between Prostate cancer gene 3 (PCA3) score and prostate cancer as assessed by Gleason Score (GS) and pathological stage in a series of Italian patients, with elevated Prostate specific antigen (PSA) undergoing radical prostatectomy (RP). PATIENTS AND METHODS: A total of 222 patients underwent RP for clinically localized prostate cancer; total PSA, free-PSA (%fPSA) and PCA3 score were collected and the possible associations among PCA3 and histological grade/pathological stage at biopsy and RP were investigated. RESULTS: Median PCA3 scores by GS at radical prostatectomy were 51 vs. 67 (GS <7 vs. GS ≥ 7, p=0.007), while scores at the biopsy were 56 vs. 67 (GS <7 vs. GS ≥ 7, p=0.007), and in pT2 vs. pT3 patients they were 54 vs. 80 (p=0.001). Positive digital rectal examination (DRE) (odds ratio (OR)=5.47, p=0.026), pT3 pathological stage (OR=3.68, p=0.006) and PCA3 ≥ 35 (OR=2.04, p=0.030) were the main risk factors for the presence of an aggressive disease (GS ≥ 7 at RP). CONCLUSION: PCA3 score could play an interesting role in predicting significant disease: positive DRE (OR=5.47, p=0.026), pT3 pathological stage (OR=3.68, p=0.006) and PCA3 ≥ 35 (OR=2.04, p=0.030) were the main independent risk factors for GS ≥ 7 at RP.

Histological chronic prostatitis and high-grade prostate intra-epithelial neoplasia do not influence urinary prostate cancer gene 3 score.

UNLABELLED: What's known on the subject? and What does the study add? While the relationship between PCA3 score and clinical or histological prostatitis was quite proven even in small patient groups, conversely the relationship between PCA3 score and HG-PIN is still under debate. We demonstrated in a large series (432 patients) that histologically documented chronic prostatitis and HG-PIN have similar PCA3 scores to patients with BPH and/or normal parenchyma at biopsy. OBJECTIVE: To determine whether histological chronic prostatitis and high-grade prostate intra-epithelial neoplasia (HG-PIN) influence the prostate cancer gene 3 (PCA3) score in Italian patients with an elevated prostate-specific antigen (PSA) level and a negative digital rectal examination (DRE) who were undergoing a first or repeat prostate biopsy. PATIENTS AND METHODS: A urinary PCA3 test was prospectively performed in 432 consecutive patients who were admitted to Gradenigo Hospital (Turin, Italy) between January and December 2011 and scheduled for first or repeat prostate biopsy as a result of an elevated PSA level and negative DRE. A comparison of the PCA3 score and patients with a negative biopsy (normal parenchyma, benign prostatic hyperplasia, chronic prostatitis, HG-PIN) or positive biopsy was performed. RESULTS: PCA3 median (range) scores varied significantly (P < 0.001) in men with a negative vs positive biopsy: 33 (2-212) and 66 (5-324), respectively. By contrast, men with chronic prostatitis and HG-PIN showed no significant difference with respect to PCA3 score compared to other negative biopsy patients. No correlation was found between the number of positive cores for chronic prostatitis, HG-PIN and PCA3 score. Of all patients with a positive biopsy, 23 (20%) of 114 men had a PCA3 score ≤ 35. In total, 79 (40%) of 197 men with a negative biopsy (normal parenchyma and benign prostatic hyperplasia), 24 (37.5%) of 64 men with chronic prostatitis and 19 (39.6%) of 48 men with HG-PIN had a PCA3 score >35. CONCLUSION: At this early stage of clinical evaluation, cancer specificity of the urinary PCA3 test appears to be maintained in the face of chronic prostatitis and HG-PIN.

Negative pressure wound therapy using gauze and foam: histological, immunohistochemical and ultrasonography morphological analysis of the granulation tissue and scar tissue. Preliminary report of a clinical study.

Negative pressure wound therapy (NPWT) is becoming routine for the preparation of wounds prior to grafting for wound closure. We have been using both foam- and gauze-based NPWT to prepare wounds for closure prior to skin grafting and have obtained similar proportions of closed wounds; 7/7 for wounds treated with gauze-based NPWT and 11/11 for wounds treated with foam-based NPWT. In our follow-up consultations we observed that skin grafts on the foam-treated patients were less pliable than those on the gauze-treated patients. To assess what the mechanism of this effect might be, we compared the specific details of the treatments of both 11 foam and 7 gauze patients, including depth, location, patients' age and co-morbidity; biopsies of granulation and scar tissue were taken and stained with haematoxylin-eosin and by Masson's trichrome staining and conducted ultrasound analysis of the closed wounds, to see if there were features which explained those effects. All foam patients were treated at -125 mm Hg for an average of 25·9 days before skin grafts were applied. All gauze patients were treated at -80 mm Hg for an average of 24·7 days before skin grafts were applied. Biopsies of granulation tissue prior to skin grafting from five foam and four gauze-based NPWT patients did not reveal any obvious histological differences between the treatments. Ultrasound analysis of the skin-grafted wounds showed an average depth of scar tissue of 18 mm in the wound beds of the foam-treated wounds and 7 mm in the gauze-treated ones. Biopsies taken on the scar tissue after treatment with the gauze showed a minor tissue thickness and disorganisation and less sclerotic components. The findings of this preliminary analysis suggest that foam-based NPWT may induce a thicker layer of scar tissue beneath skin grafts than gauze-based NPWT which might explain a reduced pliability of the reconstructed bed. At present it is unclear which mechanism might be responsible for the difference in pressure (-125 versus -80 mm Hg), either the length of the time taken to reconstruct the wound bed or the intrinsic nature of the foam or gauze on the tissue surface. Prospective studies are necessary to investigate whether these preliminary observations are confirmed and to investigate what the mechanism might be.

Determinants of 4-aminobiphenyl-DNA adducts in bladder cancer biopsies.

Exposure to 4-aminobiphenyl (4-ABP) is an important determinant of urinary bladder cancer in humans. We have analyzed by gas chromatography-mass spectrometry the DNA adducts of 4-ABP in 75 bladder cancer biopsies. The purpose was to understand whether smoking, N-acetyltransferase 2 (NAT2) polymorphism, diet or tumor grade were determinants of 4-ABP-DNA levels. 4-ABP-DNA adducts were above the detection limit of 0.1 fmol/microg DNA for 37/75 patients. Overall the level of adducts was 2.7 +/- 0.7 (mean +/- SE) fmol/microg DNA (86 +/- 22 adducts/10(8) normal nucleotides, mean +/- SE). A strong association with grade was observed. In the group of patients with detectable 4-ABP-DNA adducts the odds ratio for having a tumor grade of 2 or 3 was respectively 4.3 (95% CI 0.8-21.9) and 6 (1.3-27.5), compared with grade 1. A non-statistically significant association was found between adduct levels and the deduced slow acetylator phenotype in grades 2 and 3. The intake of fruit and vegetables produced a lower frequency of detectable adducts, though the association was not statistically significant. Detectable 4-ABP-DNA adducts were clearly associated with current smoking in higher tumor grades (grade 3 versus grades 1 + 2, odds ratios 10.4; 95% CI 1.7-63.1). Overall, our findings indicate that higher levels of DNA adducts characterize more invasive tumors (higher tumor grades). This seems to be facilitated by smoking and contrasted by the intake of fruit and vegetables.