Gemcitabine based trimodality treatment in patients with muscle invasive bladder cancer: May neutrophil lymphocyte and platelet lymphocyte ratios predict outcomes?

PurposeCisplatin based chemoradiation has been commonly used as a definitive treatment for muscle-invasive bladder cancer (MIBC). The aim of the current study is to evaluate oncologic results and toxicity profile of bladder-sparing treatment with external beam radiotherapy (EBRT) and gemcitabine chemotherapy (ChT) in patients with MIBC.Materials and MethodsBetween April 2005 and November 2018 44 patients with nonmetastatic and N0 MIBC were treated with transurethral resection of bladder (TURB), EBRT and concurrent gemcitabine. All patients were staged using thorax-abdomen-pelvic CT and pelvic MRI. EBRT was delivered using 3D conformal technique or intensity modulated radiotherapy. Patients received 50 Gy in 25 to 28 fractions to full bladder followed by a boost dose of 10 Gy in 5 fractions to empty bladder with weekly concurrent gemcitabine of 50 mg/m². All patients were evaluated for age, gender, smoking status, neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) at diagnosis, presence of hydroureteronephrosis (HUN), preoperative tumor size, tumor multifocality, presence of CIS, clinical tumor stage. Acute/late genitourinary (GUS) and gastrointestinal (GIS) toxicity, recurrence status, cancer specific survival (CSS) and overall survival (OS) were evaluated. Statistical analysis was performed using SPSS v21.0. Kaplan-Meier survival estimates were calculated to describe CSS and OS. The effect of different parameters on survival was investigated using the log rank test.ResultsMedian age of the patients was 72 years (interquartile [IQR]; 66–80). The median tumor size was 30 mm (IQR, 15–59 mm). Thirty-two (77%) patients had T2, 6 (14%) patients had T3, and 4 (9%) patients had T4a disease. Median NLR was 2.6 (IQR, 1.7–3.8) and median PLR was 126.47 (IQR, 77.4–184.8). Median follow-up time was 21 months (range, 6–153 months). At the first TURB performed 6 weeks after CRT, complete response, partial response, stable disease, and progression was detected in 37 (84%), 3 (7%), 1 (2%), and 3 (7%) patients, respectively. One- and 2-year OS, CSS, LRFS, and DMFS rates were 86% and 64%; 88% and 66%; 65% and 44%; 68% and 48%, respectively. In univariate analysis; prognostic factors were age and presence of HUN for OS and DMFS; age, HUN, presence of CIS, NLR, and PLR for DSS; HUN, NLR, and PLR for LRFS, respectively. In multivariate analysis, the independent predictor was the presence of HUN for OS, LRFS, and DMFS; NLR for DSS; PLR for LRFS and age for DMSF. For a subgroup of 17 patients with complete TURB and no CIS and HUN symptoms, 2-year OS, DSS, LRFS, and DMFS rates were 88%, 88%, 72%, and 79%, respectively. The treatment was well-tolerated and all patients completed the planned EBRT and ChT. No acute or late ≥ grade 3 toxicity was observed. Grade II acute GIS toxicity was detected in 3 (7%) patients and grade II acute GUS toxicity was detected in 9 (21%) patients, respectively. Grade II late GUS toxicity was observed in 2 (5%) patients.ConclusionGemcitabine based trimodality treatment is well-tolerated with similar oncologic outcomes reported in the literature. Older age, presence of CIS and high NLR and PLR values seem to deteriorate DSS.     

Imatinib mesylate for the treatment of pulmonary arterial hypertension

INTRODUCTION: Despite recent advances, pulmonary arterial hypertension (PAH) remains a devastating disease which harbors a poor prognosis. Novel therapeutic approaches directly targeting pulmonary vascular remodeling are warranted. AREAS COVERED: This review delineates the current limitations in the management of PAH and focuses on a novel, anti-proliferative therapeutic concept. It will help readers understand the mechanisms of receptor tyrosine kinase signaling, with a special focus on platelet-derived growth factor (PDGF) receptors and their role in the pathobiology of PAH. Furthermore, it provides a comprehensive summary regarding the rationale, efficacy and safety of the tyrosine kinase inhibitor imatinib mesylate , which potently inhibits the PDGF receptor, as an additional treatment option in PAH. EXPERT OPINION: PDGF is a potent mitogen for pulmonary vascular smooth muscle cells and represents an important mediator of pulmonary vascular remodeling. Imatinib mesylate, a compound that inhibits the Bcr-Abl kinase and was developed for the treatment of chronic myeloid leukemia, also targets PDGF receptors. Both experimental and clinical data indicate that it reverses the vascular remodeling process even when it is fully established. Results from Phase II and III clinical trials suggest potent and prolonged efficacy in patients with severe PAH (i.e., pulmonary vascular resistance > 800 dynes*s*cm(-5)). Future studies should evaluate the long-term clinical efficacy and safety of imatinib, including patients with less impaired hemodynamics. Based on the current knowledge, this compound is likely to become an additional treatment option for patients with PAH and has the potential to at least partially correct the pathology of the disease.     

Detection and serotyping of Mediterranean plum pox virus isolates by means of strain-specific monoclonal antibodies

Plum pox virus (PPV) is a major threat to the expanding Mediterranean stone fruit industry. In order to control the plum pox disease it is of utmost importance to detect early PPV foci and to identify the PPV isolates involved. A survey was therefore carried out in Albania, Cyprus, Egypt, Greece, Italy and Turkey by a double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) with the following monoclonal antibodies (MAbs): 5B (universal), 4DG5 (PPV-D-specific), AL (PPV-M-specific), TUV and AC (PPV-C-specific), and EA24 (PPV-El Amar-specific). A hundred and seventy Mediterranean PPV isolates were tested for strain type. PPV-M was detected in Albania, Cyprus, Greece, Italy, and Turkey; PPV-D was detected in Albania and Italy, whereas samples with natural mixtures of both strains were found in a couple of orchards in Albania. Seven PPV isolates from apricots in two Egyptian localities were recognized only by MAb EA24. In conclusion, DAS-ELISA with a combination of the universal MAb5B and the MAbs specific to the four PPV serotypes currently known (M, D, C and El Amar) is an efficient tool for a simple, sensitive and routine detection of PPV and discrimination of its serotypes.     

Role of radiotherapy in oligometastatic breast cancer: Review of the literature

Metastatic breast cancer has been historically considered as an incurable disease. Radiotherapy (RT) has been traditionally used for only palliation of the symptoms caused by metastatic lesions. However, in recent years the concept of oligometastatic disease has been introduced in Cancer Medicine as a clinical scenario with a limited number of metastases (≤ 5) and involved organs (≤ 2) with controlled primary tumor. The main hypothesis in oligometastatic disease is that locoregional treatment of primary tumor site and metastasis-directed therapies with surgery and/or RT may improve outcomes. Recent studies have shown that not all metastatic breast cancer patients have the same prognosis, and selected patients with good prognostic features as those younger than 55 years, hormone receptor-positive, limited bone or liver metastases, a low-grade tumor, good performance status, long disease-free interval (> 12 mo), and good response to systemic therapy may provide maximum benefit from definitive treatment procedures to all disease sites. While retrospective and prospective studies on locoregional treatment in oligometastatic breast cancer demonstrated conflicting results, there is an increasing trend in favor of locoregional treatment. Currently, available data also demonstrated the improvements in survival with metastasis-directed therapy in oligometastatic breast cancer. The current review will discuss the concept of oligometastases and provide up-to-date information about the role of RT in oligometastatic breast cancer.     

Idiopathic benign bilateral testicular enlargement in a pubertal boy: a case report and review of literature

We present a case of 12-year-old boy with idiopathic benign bilateral testicular enlargement. We eliminated precocious puberty, juvenile hypothyroidism, adrenal rest tumors, X-linked mental retardation, and bilateral testicular neoplasms. The clinical and laboratory features and differential diagnosis of benign bilateral testicular enlargement are discussed.     

An investigation of the factors that affect surgical hand disinfection with polyvidone iodine

This study investigated the factors influencing the effectiveness of 7.5% polyvidone iodine as a surgical antiseptic. The study involved 100 operating staff (75 doctors and 25 nurses) from hospital surgical teams. Fingertips of both hands of the subjects were pressed on to agar culture before and after washing and after completion of surgery. Handwashing lasting for more than 3 min led to a significant decrease in the number of colonies compared with handwashing lasting for less than 3 min. Moreover, the number of colonies was significantly higher when surgery lasted for longer than 95 min. However, the handwashing style (with or without brushing) was not found to have a significant effect on the outcome of the disinfection procedure in terms of bacterial colonization. Subjects who had colonization of their hands after surgery were found to have significantly higher colony counts before handwashing compared with those who did not have any colonization on their hands after surgery. The results of this study revealed that in order to attain effective disinfection with polyvidone iodine, the duration of handwashing should be at least 3 min. The risk of recolonization increases when the duration of surgery exceeds 95 min.