What Is the Definition of a Satisfactory Erectile Function After Bilateral Nerve Sparing Radical Prostatectomy?

IntroductionDifferent cut‐offs of the erectile function (EF) domain of the International Index of Erectile Function (IIEF) have been used as definition of postoperative EF recovery.AimTo test the correlation between patient satisfaction and IIEF‐EF domain score cut‐offs.Main Outcome MeasureThe IIEF was used to evaluate EF and satisfaction before and after bilateral nerve sparing radical prostatectomy (BNSRP).MethodsThe study included 165 consecutive patients treated with retropubic BNSRP at a single institution. All patients had normal preoperative EF (IIEF‐EF ≥ 26) and reached an IIEF‐EF ≥ 17 following surgery. Complete data included EF, intercourse (IS), and overall satisfaction (OS) assessed by the corresponding domains of the IIEF administered prior and after surgery. Patients were divided into three groups according to the highest IIEF‐EF score reached postoperatively, namely 17–21 (group 1), 22–25 (group 2), and ≥26 (group 3). One‐way analysis of variance was used to compare IIEF‐OS and IIEF‐IS domain scores at the time the EF end point was reached. The same analyses were repeated separately in those patients with a complete EF recovery after surgery (group 3).ResultsMean preoperative IIEF‐OS and IIEF‐IS domain score was 8.4, 8.8, 8.7 and 11.6, 11.8, 11.9 in group 1, 2, 3, respectively (all P ≥ 0.3). After a mean follow‐up of 26.7 months, mean postoperative IIEF‐OS and IIEF‐IS domain scores assessed at the time of EF recovery were comparable for patients reaching an IIEF‐EF of 22–25 and for patients scoring postoperatively ≥26 (8.1, 8.1, and 10.6, 11.4; all P ≥ 0.3). However, mean IIEF‐OS and IIEF‐IS domain scores of these patients were significantly higher as compared to patients reaching an IIEF‐EF domain score < 22 (6.3 and 8.4, respectively; all P ≤ 0.006). Similar results were achieved considering only those patients (group 3) who had complete EF recovery after surgery.ConclusionsWe demonstrated that in preoperatively fully potent patients treated with BNSRP a lower satisfaction is expected when an IIEF‐EF cut‐off of 17 is used. Conversely, no difference was found using a cut‐off of 22 or 26. Therefore, our results support that a cut‐off of IIEF‐EF ≥ 22 might represent a reliable score for defining EF recovery after BNSRP. Briganti A, Gallina A, Suardi N, Capitanio U, Tutolo M, Bianchi M, Salonia A, Colombo R, Di Girolamo V, Martinez‐Salamanca JI, Guazzoni G, Rigatti P, and Montorsi F. What is the definition of a satisfactory erectile function after bilateral nerve sparing radical prostatectomy?.     

Patients' desire to preserve sexual activity and final decision for a nerve-sparing approach: results from the MIRROR (Multicenter Italian Report on Radical Prostatectomy Outcomes and Research) Study

IntroductionPreservation of sexual function after surgery represents a major issue for patients undergoing radical prostatectomy (RP).AimTo investigate determinants of patients’ desire to preserve sexual activity before RP and surgeons’ final decision to perform a nerve-sparing RP (NSRP).MethodsOverall, 2,408 prostate cancer patients, candidates to RP, from 136 urologic departments across the Italian territory were evaluated in a multicenter prospective observational study. All patients underwent RP, according to single-center indications and procedures.Main Outcome MeasuresAge, body mass index, previous benign prostatic hyperplasia history, preoperative tumor characteristics, quality of life through the Short Form Health Survey (SF-12), and the University of California Los Angeles Prostate Cancer Index (UCLA-PCI), erectile function through the International Index of Erectile Function (IIEF-5), desire to preserve sexual activity, NS operative outcomes, and surgical margins status were recorded.ResultsOverall, 1,667 were interested to preserve sexual activity. Age, physical component summary of SF12 (PCS-12), sexual function score of UCLA-PCI, and IIEF-5 score were the main determinants of such interest. Only 1,246 patients were suitable for a NSRP according to guidelines. Surgeons performed a non-NSRP (NNSRP) in 1,234 patients, a unilateral NSRP in 318 and a bilateral NSRP in 856. Age, bioptical Gleason score, percentage of positive cores, PCS-12, and patient's desire to preserve sexual activity were the main determinants of final decision for a NSRP. Surgeons performed a NSRP in 424 not suitable and in 121 not interested patients. Positive surgical margins in not suitable patients submitted to NSRP were not higher if compared to that obtained after NNSRP in the same subgroup. Limits include lack of oncological and functional follow-up.ConclusionsMost patients are interested to preserve sexual activity. Discrepancies exist among patients’ preferences, guidelines’ indications, and surgeon's final decision. Imbimbo C, Creta M, Gacci M, Simonato A, Gontero P, de Cobelli O, Briganti A, Fulcoli V, Martorana G, Nicita G, Mirone V, and Carmignani G. Patients’ desire to preserve sexual activity and final decision for a nerve-sparing approach: results from the M.I.R.R.O.R. (Multicenter Italian Report on Radical prostatectomy Outcomes and Research) study.     

Detection of spirochaetal DNA simultaneously in skin biopsies, peripheral blood and urine from patients with erythema migrans

Lyme borreliosis is an emerging zoonosis transmitted by infected hard-bodied ticks. The disease is multisystemic. In the initial stage its typical manifestation is the erythema migrans, a cutaneous lesion that occurs in up to 90% of patients. In order to investigate the presence of the specific agent, Borrelia burgdorferi, in the early stages of the disease, DNA from skin biopsies, urine and peripheral blood of 30 patients with clinically documented erythema migrans and without apparent systemic involvement was analysed by polymerase chain reaction. Borrelia DNA in both blood and skin biopsies was detected in 23 patients, while in 9 patients it was discovered in urine and skin biopsies. These results demonstrate that Borrelia DNA is detectable systemically also in patients with early Lyme borreliosis and strongly suggest a possible dissemination of the causative agents even when only a local infection is assumed.     

An allele-specific rt-PCR assay to detect type A mutation of the nucleophosmin-1 gene in acute myeloid leukemia

Nucleophosmin-1 (NPM1) mutations represent the most frequent gene alteration in acute myeloid leukemia (AML). The most common NPM1 mutation type, accounting for 75 to 80% of cases, is referred to as mutation A (NPM1-mutA). These NPM1 alterations have been shown to possess prognostic significance because they appear to identify patients who will benefit from chemotherapy. Given the high prevalence and stability of these mutations over the course of disease, NPM1 mutations may serve as ideal targets for minimal residual disease (MRD) assessment in AML. Current detection methods are costly, require sophisticated equipment, and are often not sufficiently sensitive. We report here an allele-specific (ASO)-RT-PCR assay that enables rapid and sensitive detection of NPM1-mutA. A semi-nested ASO-PCR method was also designed to increase the sensitivity of our assay for the monitoring of MRD. We analyzed bone marrow cells collected from 52 patients with AML at presentation. NPM1-mutA was detected in leukemic cells from 21 patients. Assay specificity was confirmed by capillary electrophoresis and DNA sequencing. ASO-RT-PCR and semi-nested ASO-PCR assays could detect NPM1-mutA with sensitivities of 10(-2) and 10(-5), respectively. Results obtained here verify that our ASO-RT-PCR assay is a specific and sensitive method for the routine screening of NPM1-mutA, as well as for MRD monitoring of AML patients with this alteration. This method is convenient and easily applicable in countries with limited resources and no access to real-time quantitative PCR-based technologies.     

Chemotherapeutic drugs may be used to enhance the killing efficacy of human tumor antigen peptide-specific CTLs

The effects of anticancer chemotherapy on antigen-specific cytotoxic T lymphocytes (CTLs) are mostly unknown. We tested the effects of cytotoxic drugs such as 5-fluorouracil, gemcitabine, and oxaliplatin on the functional activity of antigen-specific CTL cultures derived from the peripheral blood mononuclear cells of human donors. We found that a biweekly drug-exposure of human HLA-A(*)02.01+ CTLs derived from bulk cultures led to completely different effects if occurring early (day second) or late (day thirteenth) after the in vitro stimulations with the cognate peptides. In the first case, there was a significant CTL inhibition, whereas in the second, there was a marked enhancement of the antigen-specific cytolytic activity. Results of immunocytofluorimetric studies and CTL/natural killer inhibition assays suggested that the latter effect could be related to a more selective drug-mediated inhibition of cohabitant T regulatory (reg) cells. These results were translated in an in vivo therapeutic mouse model where humanized HLA-A(*)02.01 transgenic mice inoculated with EL-4/humanized HLA-A(*)02.01 transgenic mice showed a prolonged survival and the greatest rate of cure when receiving a combined treatment with a thymidylate synthase-specific peptide vaccine and a multidrug chemotherapy regimen administered late after immunization. Tumor samples derived from this group of mice showed a reduced expression of the target thymidylate synthase antigen, a marked reduction of T(reg)s, and a noteworthy infiltration of C8+ T cells. These results may have clinical implications for the design of new translational anticancer regimens aimed at combining chemotherapy and immunotherapy.     

Reversine, a novel Aurora kinases inhibitor, inhibits colony formation of human acute myeloid leukemia cells

The demonstration that the small synthetic molecule reversine [2-(4-morpholinoanilino)-N6-cyclohexyladenine] promotes the dedifferentiation of committed cells into multipotent progenitor-type cells has raised hopes on the exploitation of this small chemical tool for the generation of stem cells. Here, we show that reversine causes a failure in cytokinesis and induces polyploidization. These effects of reversine are due to the inhibition of Aurora A and B, two related kinases that are implicated in several aspects of mitosis and that are frequently amplified and overexpressed in human tumors. Reversine inhibits the phosphorylation of histone H3, a direct downstream target of Aurora kinases. Similarly to the Aurora kinase inhibitor VX-680, which has recently entered phase II clinical trials for cancer treatment, reversine inhibited colony formation of leukemic cells from patients with acute myeloid leukemia but was significantly less toxic than VX-680 on cells from healthy donors. The crystal structure of the reversine-Aurora B kinase complex shows that reversine is a novel class of ATP-competitive Aurora kinase inhibitors. Thus, although our studies raise serious doubts on the application of reversine in regenerative medicine, they support the paradigm that reversine might be a useful agent in cancer chemotherapy.