Clinical and pathologic characteristics of BRCA-positive and BRCA-negative male breast cancer patients: results from a collaborative multicenter study in Italy

Recently, the number of studies on male breast cancer (MBC) has been increasing. However, as MBC is a rare disease there are difficulties to undertake studies to identify specific MBC subgroups. At present, it is still largely unknown whether BRCA-related breast cancer (BC) in men may display specific characteristics as it is for BRCA-related BC in women. To investigate the clinical-pathologic features of MBC in association with BRCA mutations we established a collaborative Italian Multicenter Study on MBC with the aim to recruit a large series of MBCs. A total of 382 MBCs, including 50 BRCA carriers, were collected from ten Italian Investigation Centres covering the whole country. In MBC patients, BRCA2 mutations were associated with family history of breast/ovarian cancer (p<0.0001), personal history of other cancers (p=0.044) and contralateral BC (p=0.001). BRCA2-associated MBCs presented with high tumor grade (p=0.001), PR-(p=0.026) and HER2+ (p=0.001) status. In a multivariate logistic model BRCA2 mutations showed positive association with personal history of other cancers (OR 11.42, 95% CI 1.79-73.08) and high tumor grade (OR 4.93, 95% CI 1.02-23.88) and inverse association with PR+ status (OR 0.19, 95% CI 0.04-0.92). Based on immunohistochemical (IHC) profile, four molecular subtypes of MBC were identified. Luminal A was the most common subtype (67.7%), luminal B was observed in 26.5% of the cases and HER2 positive and triple negative were represented by 2.1% and 3.7% of tumors, respectively. Intriguingly, we found that both luminal B and HER2 positive subtypes were associated with high tumor grade (p=0.003 and 0.006, respectively) and with BRCA2 mutations (p=0.016 and 0.001, respectively). In conclusion, our findings indicate that BRCA2-related MBCs represent a subgroup of tumors with a peculiar phenotype characterized by aggressive behavior. The identification of a BRCA2-associated phenotype might define a subset of MBC patients eligible for personalized clinical management.     

Dengue fever in internal medicine: a case report

Authors describe a case of dengue fever, accidentally seen for appearance of purple at the lower limbs, fever and fatigue. They want to signal this case not for the difficulty of the diagnosis, because the patient was just arrived from Venezuela and he went, during his travel, in endemic zones for dengue, but because this illness is very uncommon in our Country. Diagnosis was confirmed with the presence of antibody in the serum of the patient and treatment was limited to a careful monitoring of laboratory examination and at an hydratation. Recovery with return to normal value of renal and hepatic function was obtained after 15 days.     

Fas expression correlates with human germ cell degeneration in meiotic and post-meiotic arrest of spermatogenesis

Degeneration of human male germ cells was analysed by means of light (LM) and transmission electron (TEM) microscopy. The frequency of degenerating cells was correlated with that of Fas-expressing germ cells in human testes with normal spermatogenesis (n = 10), complete early maturation arrest (EMA) (n = 10) or incomplete late maturation arrest (LMA; n = 10) of spermatogenesis. LM analysis of testis sections with normal spermatogenesis indicated that degenerating germ cells were localized in the adluminal compartment of the seminiferous epithelium. TEM showed that apoptotic cells were mostly primary spermatocytes and, to a lesser extent, round or early elongating spermatids. Apoptotic germ cells appeared to be eliminated either in the seminiferous lumen or by Sertoli cell phagocytosis. An increased number of degenerating cells was observed in testes with LMA as compared with normal testes and testes with EMA of spermatogenesis (P < 0.001, Wilcoxon's rank sum test). Comparison of these results with those obtained from immunohistochemistry experiments demonstrated a tight correlation between the number of apoptotic cells and the number of Fas-expressing germ cells (P = 0.001, Spearman's rank = 0.69). These findings suggest that altered meiotic and post-meiotic germ cell maturation might be associated with an up-regulation of Fas gene expression capable of triggering apoptotic elimination of defective germ cells.     

111Indium labelled leukocyte scintigraphy in the detection of acute prostatitis

Although prostatitis is a common problem the diagnosis is still controversial despite the availability of a wide variety of diagnostic tools. In fact, there is still no accurate method of localizing the infected tissue. The aims of the present study were to assess whether 111In labelled leukocytes (ILLs) accumulated in the infected tissue of acute prostatitis and if such uptake responded to treatment. We prospectively studied 10 adult male patients who had community acquired prostatitis and compared them with six male patients who had urinary tract infections but without prostatitis. An initial urinary culture and two blood cultures were carried out for each patient. All patients were followed up for 8 weeks after therapy was completed. Pre- and post-treatment scintigraphies were performed. Before treatment, all patients with prostatitis showed uptake of ILLs in the prostate area. After the patients had completed treatment with antibiotics, the scintigraphy results showed no uptake in the prostate area in 9/10 patients. The remaining patient showed a marked decrease in the uptake of ILLs. None of the six patients with urinary tract infection showed ILL uptake in the prostate region. It is suggested that ILLs could be useful for detecting acute prostatitis, especially in clinically ambiguous patients with urological infections. Furthermore, scintigraphy with 111In labelled leukocytes could help to determine the most appropriate course of therapy.     

Continuous positive airway pressure for treatment of postoperative hypoxemia: a randomized controlled trial

Context  Hypoxemia complicates the recovery of 30% to 50% of patients after abdominal surgery; endotracheal intubation and mechanical ventilation may be required in 8% to 10% of cases, increasing morbidity and mortality and prolonging intensive care unit and hospital stay. Objective  To determine the effectiveness of continuous positive airway pressure compared with standard treatment in preventing the need for intubation and mechanical ventilation in patients who develop acute hypoxemia after elective major abdominal surgery. Design and Setting  Randomized, controlled, unblinded study with concealed allocation conducted between June 2002 and November 2003 at 15 intensive care units of the Piedmont Intensive Care Units Network in Italy. Patients  Consecutive patients who developed severe hypoxemia after major elective abdominal surgery. The trial was stopped for efficacy after 209 patients had been enrolled. Interventions  Patients were randomly assigned to receive oxygen (n = 104) or oxygen plus continuous positive airway pressure (n = 105). Main Outcome Measures  The primary end point was incidence of endotracheal intubation; secondary end points were intensive care unit and hospital lengths of stay, incidence of pneumonia, infection and sepsis, and hospital mortality. Results  Patients who received oxygen plus continuous positive airway pressure had a lower intubation rate (1% vs 10%; P = .005; relative risk [RR], 0.099; 95% confidence interval [CI], 0.01-0.76) and had a lower occurrence rate of pneumonia (2% vs 10%, RR, 0.19; 95% CI, 0.04-0.88; P = .02), infection (3% vs 10%, RR, 0.27; 95% CI, 0.07-0.94; P = .03), and sepsis (2% vs 9%; RR, 0.22; 95% CI, 0.04-0.99; P = .03) than did patients treated with oxygen alone. Patients who received oxygen plus continuous positive airway pressure also spent fewer mean (SD) days in the intensive care unit (1.4 [1.6] vs 2.6 [4.2], P = .09) than patients treated with oxygen alone. The treatments did not affect the mean (SD) days that patients spent in the hospital (15 [13] vs 17 [15], respectively; P = .10). None of those treated with oxygen plus continuous positive airway pressure died in the hospital while 3 deaths occurred among those treated with oxygen alone (P = .12). Conclusion  Continuous positive airway pressure may decrease the incidence of endotracheal intubation and other severe complications in patients who develop hypoxemia after elective major abdominal surgery.      

Prostate specific antigen levels in young adulthood predict prostate cancer risk: results from a cohort of Black and White Americans

PURPOSE: Prostate specific antigen (PSA) is a serine protease produced by normal and malignant prostate epithelial cells. Serum PSA increases with age, due largely to age related increases in the prevalence of benign prostatic disease. Little is known about PSA distribution in young adulthood, when benign and malignant prostatic diseases are rare, or about how PSA within the normal range in youth relates to subsequent prostate cancer risk. MATERIALS AND METHODS: We evaluated serum PSA and subsequent prostate cancer occurrence in a cohort of young black and white American men with a median age at blood draw of 34 years, who in 1959 to 1966 participated as the fathers of newborns enrolled in the Child Health and Development Study, and who were followed for several decades for prostate cancer. We examined associations between PSA in young adulthood and subsequent prostate cancer risk using a nested case-control design based on 119 black and 206 white cases with 2 control men matched to each case on race and year of birth. RESULTS: Prostate cancer risk increased with increasing PSA in black and white men. The OR comparing risk in the highest to lowest quartiles of PSA was 4.4 (95% CI 2.0 to 9.6) in black men and 3.5 (95% CI 2.0 to 6.1) in white men. ORs relating risk to PSA were higher when analysis was restricted to cases diagnosed before age 65 years. CONCLUSIONS: These findings suggest that PSA levels in young adulthood indicate increased risk of prostate cancer and, thus, they may be useful for targeting men for screening and early diagnosis.     

A novel cell line and xenograft model of ampulla of Vater adenocarcinoma

Ampulla of Vater cancers (AVC) are of clinical relevance, as they represent more than one-third of patients undergoing surgery for pancreaticoduodenal malignancies and have a better prognosis than periampullary cancers of pancreaticobiliary origin. The availability of cellular models is crucial to perform cell biology and pharmacological studies and clarify the relationship between AVC and pancreatic and biliary cancers. Numerous cell lines are available for pancreatic and biliary adenocarcinomas, while only two have been reported recently for AVC. These were derived from a poor and a well-differentiated AVC, and both had wild-type K-ras and mutated p53. We report the establishment of a novel AVC cell line (AVC1) derived from a moderately differentiated cancer, having a mutated K-ras, wild-type p53, and methylated p16. Thus, our cell line adds to the spectrum of available in vitro models representative of the different morphological and molecular presentations of primary AVC. We further characterized AVC1 for the expression of relevant cell surface molecules and sensitivity to chemotherapeutic agents of common clinical use. It expresses MHC-I and CD95/Fas, while HLA-DR, CD40, CD80, CD86, MUC-1, MUC-2, and ICAM-1/CD54 are absent. It has a low to moderate sensitivity to both 5-FU and gemcitabine, at variance with much higher sensitivity displayed by two pancreatic ductal carcinoma cell lines. Lastly, AVC1 can be readily xenografted in immunodeficient mice, making it a suitable model for pre-clinical studies.