Di Lorenzo G

Role of pegylated lyposomal doxorubicin (PLD) in systemic Kaposi's sarcoma: a systematic review.

Kaposis sarcoma (KS) is a form of skin cancer that can involve internal organs. It is often found in patients with acquired immunodeficiency syndrome (AIDS) and can be fatal. Kaposis sarcoma produces pink, purple or brown tumors on the skin, mucous membranes or internal organs. Treatment goals for KS are simple: to reduce the severity of the symptoms, shrink tumors and prevent disease progression. Unfortunately, there is no single best treatment-plan that can achieve all these goals. With widespread KS lesions over the body surface or evidence of spreading to other parts of the body, the physicians need to treat the patients with systemic chemotherapy. A new class of drugs, called liposomal anthracyclines, appears to produce good results with fewer toxic side effects than more conventional cytotoxic drugs. One of these drugs, pegylated liposomal doxorubicin (PLD) has become the treatment of choice. This article summarizes all the studies with PLD in systemic Kaposis sarcoma.

Role of TLR4 receptor polymorphisms in Boutonneuse fever.

The genetics of the interaction between host and microbes plays an essential role in the survival of the individual and attainment of longevity. The activation of toll-like receptor (TLR)4 plays a key role in natural and clonotypic immune responses. We evaluated whether TLR4 genotype is a component of genetic background protective versus rickettsiosis and whether this background influences longevity. We genotyped for +896A/G TLR4 polymorphism 78 patients affected by Boutonneuse fever, 78 age-matched controls and 78 advanced age individuals from Sicily. The +869G allele, that attenuates receptor signalling, was significantly overrepresented in patients in comparison with age-matched controls. By analyzing data according to gender, this allele was significantly higher in female patients when compared to advanced age women. Pro-inflammatory responses are programmed to resist fatal infections. So, it is not surprising that the genetic background of people that survive to an advanced age may be protective against infections. However, this seems to occur in women but not in men. In a previous study, the +896G TLR4 allele was overrepresented in advanced age men and underrepresented in men affected by myocardial infarction. Thus, previous and present results tend to agree with the suggestion that men and women may follow different trajectories to reach longevity. For men it might be more important to control atherogenesis, whereas for women it might be more important to control infectious diseases.

Peg-filgrastim and cabazitaxel in prostate cancer patients.

To determine the impact of prophylaxis with granulocyte-colony stimulating growth factor (G-CSF) on the risk of febrile neutropenia in a cohort of patients enrolled at the University Federico II of Naples and treated with cabazitaxel for metastatic castration-resistant prostate cancer (mCRPC). We carried out a retrospective review of prospectively collected data of patients enrolled at our institution in a compassionate-use programme with cabazitaxel, aimed at providing early access to the drug before its commercial availability in mCRPC patients. Besides baseline clinical and demographic characteristics, data on treatment efficacy and toxicity, as well as those on the use of G-CSF per patient per cycle were extracted. Progression-free survival and overall survival were calculated using the Kaplan–Meier method. Fisher’s exact test was used to explore a relationship between a single event of grade 3 or more neutropenia or febrile neutropenia and previous use of G-CSF. Univariate analysis was carried out to evaluate predictors of grade 3 or more neutropenia and/or febrile neutropenia. Of 34 patients enrolled at our institution from December 2010 to December 2011, 32 had received at least one dose of cabazitaxel and were included in the analysis. Patients received a median of 10 cabazitaxel cycles. Grade 3 or more neutropenia was common, occurring in 64.5% of patients. Three patients (9.3%) developed febrile neutropenia. Twenty-seven patients received prophylaxis with G-CSF during at least one cycle using peg-filgrastim. The risk of grade 3 or more neutropenia and/or febrile neutropenia per patient and per cycle was seven times lower when G-CSF was used. Baseline neutrophil count of less than 4570/mm3 was the strongest predictor of grade 3 or more neutropenia and/or febrile neutropenia. No toxic death was reported. Only one patient discontinued cabazitaxel because of an adverse event. Our analysis suggests that prophylaxis with peg-filgrastim may considerably reduce the incidence of grade 3 or more neutropenia and, possibly, of febrile neutropenia in mCRPC patients treated with cabazitaxel. Further analyses involving a larger population are warranted to confirm our results.

Neuroendocrine immunophenotype as predictor of clinical recurrence in 110 patients with prostate cancer.

We evaluated the relationship between NE expression and well-known prognostic factors and assessed whether tumor relapse after radical surgery correlates with the extent of NE differentiation. Radical prostatectomy specimens from 110 patients with clinically localized prostate cancer were assessed. Patients were followed up every three months for the first two years after surgery and six monthly for 5 additional years until failure, or for a mean of 48 months from the time of surgery for those who did not experience failure. The percentage of cells showing CgA immunoreactivity was evaluated using a visual quantitative method. Tumor staining was categorized as positive if >10% and negative if <10% of tumor cells were stained, to ensure that only cases with significant positivity were included in the positive group. The median follow-up was 5.4 years (range 1.8 to 7.2). The median time to clinical recurrence was 7.5 years and the median time to biochemical recurrence was 2.8 years. Of 31 patients (28%) who experienced a PSA recurrence, 15 developed a clinical recurrence. The mean preoperative PSA level was 9 ng/ml (range 2.7 to 25). Most cases were well differentiated (Gleason score <7), intraprostatic (≤pT2) tumors. Immunoreactivity in ≥10% of the cells was seen in 17.2% (n=19) of the tumor specimens. The preoperative PSA level, Gleason score, use of neoadjuvant or adjuvant therapy, lymphnode positivity were not statistically associated with NE expression. Only the primary pathologic stage appeared to be associated with CgA staining in the primary tumor (p=0.001). On the univariate analysis NE expression did not predict biochemical recurrence free survival, whereas it was associated with clinical recurrence. NE differentiation in clinically localized prostate cancer can be associated with failure after definitive surgical treatment, even if no conclusions can be drawn regarding its value as an independent prognostic factor.

Determinants of bronchial hyperresponsiveness in subjects with rhinitis.

Subjects with rhinitis but without asthma may have coexisting bronchial hyperresponsiveness, although the reasons for this are uncertain. To evaluate the factors that determine BHR in rhinitis we examined 410 patients with symptomatic rhinitis with forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) ≥ 80% of the predicted value. In all subjects a skin prick test (SPT) was performed, a determination of total serum IgE and an eosinophils count in the blood. Of the 410 subjects we found that 161 (39.3%) exhibited a methacholine PD20 of 800 mg or less (Group A), whereas 249 (60.7%) had a methacholine PD20 more of 800 mg (Group B). Despite the matched mean values for FEV1 and FVC, compared with Group B, Group A had a lower predicted forced expiratory flow between 25% and 75% (FEF25%-75%) (86.7 ± 12.0 vs. 93.7±7.3, P < 0.0001). A great portion of the subjects of the Group A in respect to subjects of the Group B were exposed to passive smoke (37.8% vs. 22.0%, P = 0.0008), reported having mothers with asthma (34.1% vs. 6.0%, P < 0.0001), presented a positive skin prick test (93.7% vs. 67.0%, P < 0.0001), had higher levels of total serum IgE (geometric mean of Log10 2.46 ± 0.27 kU/L vs. 2.06 ± 0.38 kU/L, P < 0.0001) and higher blood eosinophil counts (geometric mean of Log10 2.67 ± 0.07 × 10−3 mL vs. 2.57 ± 0.09 × 10−3 mL, P < 0.0001), and reported increased nasal obstruction (2.0 (95%CI 1.8 to 2.2) vs. 0.6 (95%CI 0.5 to 0.7), P < 0.0001). Logistic regression demonstrates that nasal obstruction (OR 2.19,95%CI 1.72 to 2.80) and the presence of positive SPT (OR 6.15,95%CI 2.42 to 15.61) were the most available predictors to discriminate between subjects with BHR and subjects without BHR. In addition, BHR was positively related to blood eosinophil counts (OR= 2.80, 95%CI 1.54 to 5.07), FEF25%-75% values (OR= 2.72, 95%CI 1.23 to 5.99) and familiarity (mother) for asthma (OR = 2.45, 95%CI 1.10 to 5.46). Whereas passive smoke and total serum IgE were not positively related to BHR. Increased nasal obstruction and the presence of positive SPT were the most available predictors to discriminate between subjects with and without BHR. Finally, BHR was positively related to blood eosinophil counts, FEF25%-75% values and to familiarity (mother) for asthma.

Relationship between specific serum IgE to Ascaris lumbricoides and onset of respiratory symptoms in Bangladesh immigrants.

The role of helminths in asthma and/or rhinitis and in allergic sensitization is still unclear. We assessed the relationship between Ascaris-specific IgE, respiratory symptoms and allergic sensitization in Bangladesh immigrants. 246 individuals were examined from 1996 to 2001. Serum total IgE, Ascaris IgE, specific IgE to inhalant allergens, skin prick tests (SPT) and parasitological evaluation of the stool were performed. Total serum IgE were significantly higher in Ascaris-IgE positive (> 0.35 kU/L) individuals (806.5 [409.0–1436.0] kU/L vs. 207.0 [127.0–332.5] kU/L; P < 0.0001) and in subjects with respiratory symptoms (413.0 [239.0–1096.0] kU/L vs. 259.5 [147.0–387.0] kU/L), (P < 0.0001), but not in SPT positive subjects (413.0 [179.0–894.0] kU/L vs. 404.6 [305.0–1201.0] kU/L (P= 0.5). Ascaris-specific IgE were detected in 48 subjects with respiratory symptoms (40.0%) and in 46 subjects without respiratory symptoms (36.5%) (P = 0.5). The SPT positivity was similar between Ascaris-IgE seropositive (38.2%) and Ascaris-IgE seronegative (38.1%) subjects (P = 0.9). Total IgE and length of stay in Italy correlated with SPT positivity (OR 5.6 [CI 95% 1.5–19.8], P = 0.007, and OR 1.5 [CI 95% 1.3–1.7], P < 0.0001), and with respiratory symptoms (OR 13.7 [CI 95% 3.0–62.4], P = 0.0007, and OR 2.4 [CI 95% 1.9–3.0], P < 0.0001). Ascaris-IgE were negatively associated with SPT positivity (OR 0.3 [CI 95% 0.1–0.8], P = 0.02) and with respiratory symptoms (OR 0.1 [CI 95% 0.04–0.7], P = 0.01). Our findings favour the role of environmental factors in the development of respiratory symptoms in immigrants, irrespective of Ascaris-IgE.

A complete response with rituximab in metastatic diffuse large B-cell lymphoma of the testis: case report.

Primary testicular lymphoma is an uncommon testicular tumour. We present a case of a primary non-Hodgkin lymphoma of the testis, describing its clinical and pathological features and discussing our treatment strategy. A 68-year-old man showed a firm erythematous testicular mass within the right emiscrotum. Subsequent ultrasonography demonstrated a right inferior pole testicular mass with disomogenously hypoecogenic. The patient was submitted to inguinal orchidectomy. Light microscopy demonstrated the classic appearance of a diffuse large B-cell lymphoma. The immunohistochemical study showed tumour cells intensively positive for CD45, Ki67 and CD20. No evidence of extra-testicular involvement by lymphoma was found. At 6 months, a TC-PET showed a clinical relapse in lung and abdominal lymphonodes, while clinical examination demonstrated a single, indolent and erythematous nodule in the left foot. The histologic analysis confirmed diagnosis of CD-20 positive B-cell lymphoma. The patient was treated with an anti-CD 20 monoclonal antibody (rituximab) alone every 3 weeks. After 3 months a complete response was observed in all sites of disease. The patient was free from disease at 12 months follow-up.

Expression of HECA-452 in parapsoriasis and mycosis fungoides.

We have investigated the HECA-452 expression in large plaque parapsoriasis (PP) and mycosis fungoides (MF) patients, evaluating the potential role of this biomarker in both cutaneous disorders. Skin specimens from 72 PP and 61 MF patients were selected in this study. We compared their actual histological diagnosis with their previous diagnosis and we found that all 72 PP patients had the same diagnosis as before (stable PP), while 26 out of 61 MF had a previous PP histological diagnosis (evolving PP). Our results show an increased expression of HECA-452 in MF compared to PP (p<0.01). Furthermore, evolving PP showed a significantly higher level of HECA-452 than stable PP (p<0.05). We conclude that HECA-452 expression increases during the natural history of Mycosis Fungoides. HECA-452 could be used as a biomarker for MF and predict which PP evolves to MF.

Rapidly progressive disease in a castration-resistant prostate cancer patient after cabazitaxel discontinuation.

We report the case of a 51-year-old patient with metastatic prostate cancer at diagnosis and primary refractoriness to both androgen ablation therapy and docetaxel. At the time of cabazitaxel initiation, the patient had only osseous metastases and was constrained to a wheelchair because of bone pain. Ten cycles of cabazitaxel were administered, and a remarkable response was achieved, with improvement in biochemical markers, performance status, and bone scan findings. Two months after suspension of treatment by choice, the patient developed jaundice because of massive hepatic metastases and died after a few days because of hepatic failure.