Molecular diagnostic tools for the detection of nodal micrometastases in prostate cancer patients undergoing radical prostatectomy with extended pelvic lymph node dissection: a prospective study

Background: Routine pathological examination can miss micro-metastatic tumor foci in the lymph nodes (LN) of patients with prostate cancer (PCa) that undergo radical prostatectomy and pelvic lymph node dissection (PLND). The aim of the present prospective study was to evaluate the impact of micrometastases assessed by serial section (SS), immunohistochemistry (IHC), and Real-time Polymerase Chain Reaction (RT-PCR) in patients undergoing radical prostatectomy with extended PLND. Materials and methods: 32 consecutive patients who underwent radical prostatectomy with extended PLND (obturator, internal/external and distal 2cm common iliac lymph-nodes (LN)) for intermediate (clinical T1c-T2 and PSA:10-20 ng/mL and clinical Gleason Score = 7) or high (clinical stage T3 or PSA>20 or clinical Gleason Score = 8-10) PCa were enrolled. The nodes were processed by the one uropathologist, both according to the routine pathological examination (analysis of the central section for 4 mm nodes or every 2 mm for LN>4 mm), which served as comparative method, both according to SS, IHC with antibodies against PSA and broad-spectrum Cytokeratins (BSCK), and quantitative RT-PCR targeting PSA, PSMA (PS Membrane Antigen), and Glucuronidase-S-Beta (GUSB) mRNA, that are over-expressed in prostatic cancer cells. Results: A total of 628 LN were analyzed, with a mean number of LN removed of 19.6 (SD = 7.2). Applying the routine pathological examination, 10 (31.2%) patients and 23 (3.9%) LN resulted positive for nodal involvement, with mean positive LN of 2.2 (SD = 1.4). After applying the SS and the molecular method of analysis (IHC and RT-PCR), micrometastases were found in 7 LN (SS showed micrometastases in 3 of them, IHC in 6 of them and RT-PCR in 7 of them); a total of 3 (9.3%) node-negative patients showed micrometastases at routine pathological examination (in 2 patients with RT-PCR and in 1 with IHC). Conclusions: The significance of micrometastases in PCa and the potential therapeutic role of PLND is not yet clarified, but the molecular analysis of the LN can detect a significant percentage of patients who harbor micro-metastatic PCa missed at routine pathological examination, and can enhance the accuracy of lymphadenectomy as a staging method.     

Hepatitis E Virus Genotype 4 Outbreak,Italy, 2011

During 2011, 5 persons in the area of Lazio, Italy were infected with a monophyletic strain of hepatitis E virus that showed high sequence homology with isolates from swine in China. Detection of this genotype in Italy parallels findings in other countries in Europe, signaling the possible spread of strains new to Western countries.     

Combined therapy with bevacizumab and photodynamic therapy for myopic choroidal neovascularization:A one-year follow-up controlled study

AIM: To evaluate the efficacy and safety of a combined treatment for myopic choroidal neovascularization (CNV) using photodynamic therapy (PDT) and intravitreal bevacizumab and to compare it with intravitreal bevacizumab monotherapy.METHODS: Thirty-four eyes with angiographic evidence of myopic CNV were randomly divided into two groups:17 were treated with one intravitreal bevacizumab injection (1.25 mg) and low-fluence-rate PDT within seven days of the injection (Group A). The other 17 received monotherapy with bevacizumab injections (Group B). Clinical evidence of complications, best corrected visual acuity (BCVA) and fluorescein leakage were evaluated. BCVA and optical coherence tomography (OCT) were evaluated monthly. The timepoints follow-up was established at 6 and 12mo. All patients were retreated following a PRN protocol.RESULTS:A total of 34 eyes of 34 patients (26 women and 8 men) with a mean age of 62.35 years were included. In Group A (17 eyes) the mean BCVA increased from 0.55±0.13 logMAR before the treatment to 0.40±0.09 logMAR at the 12mo follow-up (P<0.01). In Group B (17 eyes) the mean BCVA increased from 0.60±0.11 logMAR before the treatment to 0.55±0.12 logMAR at the 12mo follow-up (P<0.01). There was no statistically significant difference between the two groups in terms of LogMar visual acuity. In Group A the mean number of combined treatments was 1.8±0.11 per patient; in Group B the mean number of intravitreal bevacizumab injections was 3.1±0.08 per patient. The number of treatments was significantly fewer in Group A (P<0.01). No local or systemic side effects occurred among any of the patients treated in this study.CONCLUSION:The combination of anti-angiogenic injections and PDT appears to be a safe and effective option for myopic CNV treatment and allows for a significant reduction of intravitreal injections.     

Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab

Background Post hoc analyses assessed the prognostic and predictive value of baseline alpha-fetoprotein (AFP), as well as clinical outcomes by AFP response or progression, during treatment in two placebo-controlled trials (REACH, REACH-2).Methods Serum AFP was measured at baseline and every three cycles. The prognostic and predictive value of baseline AFP was assessed by Cox regression models and Subpopulation Treatment Effect Pattern Plot method. Associations between AFP (≥ 20% increase) and radiographic progression and efficacy were assessed.Results Baseline AFP was confirmed as a continuous (REACH, REACH-2; p < 0.0001) and dichotomous (≥400 vs. <400 ng/ml; REACH, p < 0.01) prognostic factor, and was predictive for ramucirumab survival benefit in REACH (p = 0.0042 continuous; p < 0.0001 dichotomous). Time to AFP (hazard ratio [HR] 0.513; p < 0.0001) and radiographic (HR 0.549; p < 0.0001) progression favoured ramucirumab. Association between AFP and radiographic progression was shown for up to 6 (odds ratio [OR] 5.1; p < 0.0001) and 6–12 weeks (OR 1.8; p = 0.0065). AFP response was higher with ramucirumab vs. placebo (p < 0.0001). Survival was longer in patients with an AFP response than patients without (13.6 vs. 5.6 months, HR 0.451; 95% confidence interval, 0.354–0.574; p < 0.0001).Conclusions AFP is an important prognostic factor and a predictive biomarker for ramucirumab survival benefit. AFP ≥ 400 ng/ml is an appropriate selection criterion for ramucirumab.Clinical Trial Registration ClinicalTrials.gov, REACH ({"type":"clinical-trial","attrs":{"text":"NCT01140347","term_id":"NCT01140347"}}NCT01140347) and REACH-2 ({"type":"clinical-trial","attrs":{"text":"NCT02435433","term_id":"NCT02435433"}}NCT02435433).Subject terms: Oncology, Biomarkers     

Validity and reliability of the Unified Classification System applied to periprosthetic femur fractures: a comparison with the Vancouver system

Abstract

Objective: The Unified Classification System (UCS) presents itself as an evolution of the Vancouver Classification (VCS) for the evaluation of periprosthetic fractures of the proximal femur (PPF). The aim of our study was to highlight any loss of reproducibility or validity of the new classification system, compared to the previous one.

Material and methods: We tested the interobserver and intraobserver agreement using 40 PPF clinical cases. Each classifying subtype of the UCS and VCS was present in at least two cases. Six experienced hip surgeons (Senior Surgeon, SS) and 5 surgeons in training (Junior Surgeon, JS) classified the clinical cases, using VCS and UCS. The validity of both classifications was then tested with intraoperative surveys.

Results: The mean κ value for interobserver agreement for the VCS in the JS group was 0.65 and 0.81 for the SS group. The mean κ value for interobserver agreement for the UCS in the JS group was 0.63 and 0.65 for the SS group. The mean κ value for intraobserver agreement for the VCS in the JS group was 0.71 and 0.73 for the SS group. The mean κ value for intraobserver agreement for the UCS in the JS group was 0.72 and 0.7 for the SS group. Validity analysis showed a moderate agreement for the VCS and a good agreement for the UCS.

Conclusion: The UCS completes the Vancouver classification, expanding it. It is reliable, despite the increase in classification categories and number of parameters to evaluate, with a slightly higher validity.     

Caveolin-1 expression in lung carcinoma varies according to tumour histotype and is acquired de novo in brain metastases

Aims:  To study caveolin-1 (Cav-1) expression in metastatic lung carcinomas.
Methods and results:  Cav-1 expression was investigated in a series of 121 lung carcinomas and it was shown that 18/121 tumours (14.9%) were Cav-1+. None of the pure bronchioloalveolar carcinomas proved to be positive, vs. 42.8% of the large cell carcinomas (neuroendocrine subtype excluded). Adenocarcinomas (8.5%), large cell neuroendocrine carcinomas (20%) and squamous cell carcinomas (29.6%) displayed an intermediate percentage of positive cases, suggesting a gradient of Cav-1 expression according to tumour histotype-related aggressiveness. Moreover, the percentage of Cav-1+ tumours with distant metastases was almost double that of non-metastatic tumours (17.8% vs. 8.1%), irrespective of the histotype. In 34 tumours metastatic to the brain, primary and secondary lesions were compared and 53% of brain metastases were Cav-1+ vs. 20.6% of primaries, indicating a de novo acquisition of Cav-1 expression. This pattern was exclusive to the brain, as it was not acquired in adrenal metastases. In our series, the presence of epidermal growth factor receptor amplification, determined by fluorescence in situ hybridization, was not related to Cav-1 reactivity.
Conclusions:  Cav-1 immunoreactivity in lung carcinoma is histotype-dependent and acquired de novo in brain metastases, suggesting a site-specific phenotypic shift in secondary lesions.     

Liposomal daunorubicin versus standard daunorubicin: long term follow-up of the GIMEMA GSI 103 AMLE randomized trial in patients older than 60 years with acute myelogenous leukaemia

This randomized phase III clinical trial explored the efficacy of DaunoXome (DNX) versus Daunorubicin (DNR) in acute myeloid leukaemia (AML) patients aged >60 years. Three hundred and one AML patients were randomized to receive DNR (45 mg/m(2) days 1-3) or DNX (80 mg/m(2) days 1-3) plus cytarabine (AraC; 100 mg/m(2) days 1-7). Patients in complete remission (CR) received a course of the same drugs as consolidation and then were randomized for maintenance with AraC+ all trans retinoic acid or no further treatment. Among 153 patients in the DNR arm, 78 (51.0%) achieved CR, 55 (35.9%) were resistant and 20 (13.1%) died during induction. Among 148 patients in the DNX arm, 73 (49.3%) achieved CR, 47 (31.8%) were resistant and 28 (18.9%) died during induction. Univariate analysis showed no difference as to induction results. After CR, DNX showed a higher incidence of early deaths (12.5% vs. 2.6% at 6 months, P = 0.053) but a lower incidence of relapse beyond 6 months (59% vs. 78% at 24 months, P = 0.064), with a cross in overall survival (OS) and disease-free survival (DFS) curves and a later advantage for DNX arm after 12 months from diagnosis. DNX seems to improve OS and DFS in the long-term follow-up, because of a reduction in late relapses.