Endoscopic stapedotomy: safety and audiological results in 150 patients.

OBJECTIVE: The most widely accepted treatment for otosclerosis is currently microscopic stapes surgery under either local or general anesthesia. The aim of the study is to describe the surgical steps in endoscopic stapes surgery and to evaluate the audiologic and surgical outcomes. MATERIALS AND METHODS: All patients who underwent exclusive endoscopic stapes surgery or revision surgery for previous stapedotomy between November 2014 and September 2018 were enrolled in this study. Demographic data, surgical information, preoperative and postoperative pure tone averages and air bone gaps, intraoperative and postoperative complications and follow-up data were summarized and gathered in a database for further consideration and analysis. RESULTS: In the period examined, 181 stapes surgical procedures were performed and out of these 150 met the inclusion criteria. There were no cases of major intraoperative complications. Sensorineural hearing loss was observed in one case. In one patient a gusher effect occurred during surgery. The postoperative air-bone gap improved significantly compared to the preoperative gap (8 vs 29 dB HL, respectively), and the mean air-bone gap closure was 20 dB HL. In 78.7% of cases, the observed postoperative air-bone gap was less than 10 dB HL and in 14% it was between 11 dB HL and 20 dB HL. An ABG closure lower than 20 dB HL was achieved in a total of 92.7% of patients. CONCLUSIONS: Endoscopic stapes surgery is a safe procedure with a low risk of peri- or postoperative complications and is a possible alternative to the traditional microscopic surgical procedure in the treatment of otosclerosis.

Update on histopathological evaluation of lymphadenectomy specimens from prostate cancer patients.

BACKGROUND: Metastases to lymph nodes (LNs) represent an unfavorable prognostic factor in patients with prostate cancer (PCa). Histological examination represents the gold standard in the evaluation of the lymphadenectomy (LND) specimens for the presence of secondary deposits. METHODS AND RESULTS: The metastatic detection rate can vary according to the approach adopted in the microscopic analysis of the LNs, which includes frozen-section examination, total inclusion of the tissue with and without whole-mount sections, serial sectioning, and the application of immunohistochemistry. The assessment of the sentinel LN, the search for micrometastases, and the evaluation of atypical LN metastatic sites further contribute to the detection of the metastatic spread. CONCLUSION: In this review, an update on the histopathological evaluation of LND specimens in patients with PCa is given, and focus is made on their clinical and prognostic significance.

Safety and efficacy of percutaneous nephrolithotomy in the Galdakao - Modified Supine Valdivia position: A prospective analysis.

OBJECTIVE: Aim of the present study was to evaluate the safety and efficacy of Percutaneous Nephrolithotomy (PCNL) in the Galdakao- Modified Supine Valdivia (GMSV) position in order to predict operative time, stone-free rate and onset of complications taking into account comorbidity, stone-related parameters and anatomic upper urinary tract abnormalities. MATERIAL AND METHODS: A prospective evaluation of patients who underwent to PCNL in GMSV position for renal stones > 2 cm, from January 2009 to February 2015 was performed. According to the technique, upper urinary tract abnormalities, stone chemical and morphological characteristics, and patients' history were matched with operative outcome, in terms of stone-free, intervention time and incidence of perioperative complications. RESULTS: Seventy-two cases were collected; mean operative time was 105 minutes (DS 41): staghorn stones and the presence of comorbidity resulted statistically significant variables. The complication-rate resulted in line with data showed in literature: hyperpyrexia and hemorrhage were the more frequently complications found. The overall stone-free was reached in 48 patients (67%), and it was influenced by patients' anatomic abnormalities. CONCLUSIONS: In the treatment of renal stones, PCNL may be a safe and effective choice; nevertheless, patients' anatomic abnormalities or staghorn-stones may influence the outcomes. Thus, a prospective study with a larger population is needed to verify our outcomes.

Emerging strategies to overcome the resistance to current mTOR inhibitors in renal cell carcinoma.

The mammalian target of rapamycin (mTOR) has emerged as an attractive cancer therapeutic target. Treatment of metastatic renal cell carcinoma (mRCC) has improved significantly with the advent of agents targeting the mTOR pathway, such as temsirolimus and everolimus. Unfortunately, a number of potential mechanisms that may lead to resistance to mTOR inhibitors have been proposed. In this paper, we discuss the mechanisms underlying resistance to mTOR inhibitors, which include the downstream effectors of the phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway, the activation of hypoxia-inducible factor (HIF), the PIM kinase family, PTEN expression, elevated superoxide levels, stimulation of autophagy, immune cell response and ERK/MAPK, Notch and Aurora signaling pathways. Moreover, we present an updated analysis of clinical trials available on PubMed Central and www.clinicaltrials.gov, which were pertinent to the resistance to rapalogs. The new frontier of inhibiting the mTOR pathway is to identify agents targeting the feedback loops and cross talks with other pathways involved in the acquired resistance to mTOR inhibitors. The true goal will be to identify biomarkers predictive of sensitivity or resistance to efficiently develop novel agents with the aim to avoid toxicities and to better choose the active drug for the right patient.

Neuroendocrine differentiation in prostate cancer: novel morphological insights and future therapeutic perspectives.

Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer that commonly arises in later stages of castration resistant prostate cancer (CRPC) The detection of NEPC has clinical implications as these patients are often treated with platinum chemotherapy rather than with androgen receptor targeted therapies. The poor molecular characterization of NEPC accounts in part for the lack of disease specific therapeutics. Several mechanisms are involved in NE differentiation, including inflammation and autophagy, and may actually represent future therapeutic targets for advanced NEPC patients. Furthermore, a growing body of evidence suggests a potential role of circulating tumor cells in the early diagnosis and treatment of NEPC. Here we summarize the recent findings on NEPC pathogenesis and we discuss the ongoing clinical trials and future perspectives for the treatment of NEPC patients.

Treatment-related fatigue with sorafenib, sunitinib and pazopanib in patients with advanced solid tumors: an up-to-date review and meta-analysis of clinical trials.

Fatigue is the most common symptom associated with cancer and cancer treatment. We performed an up-to-date meta-analysis to determine the incidence and relative risk (RR) of fatigue in patients (pts) with cancer treated with sorafenib (SO), sunitinib (SU) and pazopanib (PZ). PubMed databases were searched for articles published till August 2013. Eligible studies were selected according to PRISMA statement. Summary incidence, RR and 95% confidence intervals were calculated using random-effects or fixed-effects models based on the heterogeneity of selected studies. Fifteen studies were included in our analysis. A total of 6,996 pts was enrolled: 2,260 had renal cell carcinomas (RCC), 1,691 non-small cell lung cancers, 1,290 breast cancers, 823 hepatocellular carcinomas, 362 soft tissue sarcomas, 304 gastrointestinal solid tumors, 165 neuroendocrine tumors and 101 melanomas. When stratified by drug, SO registered lower incidence and RR of all and high-grade fatigue when compared to SU, whereas the difference between SO and PZ was significant only for all-grade fatigue (p < 0.001). The difference between SU and PZ was significant for high-grade (p < 0.001) but not for all-grade fatigue (p = 0.52). In RCC pts, PZ showed the lower incidence and RR of all and high-grade fatigue. The differences were significant for SU vs. SO (p < 0.001), SU vs. PZ (p < 0.001) and SO vs. PZ (p < 0.001). Treatment with SO, SU and PZ is associated with an increased incidence of fatigue in pts with cancer. Early and appropriate management is required to avoid unnecessary dose reductions and transitory or definitive treatment discontinuations.

Heterogeneous drug target expression as possible basis for different clinical and radiological response to the treatment of primary and metastatic renal cell carcinoma: suggestions from bench to bedside.

Metastatic disease occurs in a significant percentage of patients with renal cell carcinoma (RCC) and is usually associated with an overall poor prognosis. However, not all of the sites of metastases seem to have the same prognostic significance in patients receiving targeted agents. Indeed, patients with lung-only metastases seem to present a better survival than patients with other sites, whereas liver and bone metastases are associated with a worst prognosis. Some clinical studies suggest that metastatic sites are more responsive than primary tumors. This event may be due to intratumor heterogeneity in terms of somatic mutations, chromosome aberrations, and tumor gene expression, primarily centered around Von Hippel-Lindau (VHL) pathway, such as VHL mutations, HIF levels, vascular endothelial growth factor (VEGF) isoforms, and VEGF receptor levels. Nevertheless, these data do not completely explain the discordant biological behavior between primary tumor and metastatic sites. Understanding the causes of this discordance will have profound consequences on translational research and clinical trials in RCC. In this review, we overview current data on the differences between primary RCC and metastases in terms of drug target expression and clinical/radiological response to targeted agents, thus describing the prognostic role of different metastatic sites in RCC patients.

Sunitinib, pazopanib or sorafenib for the treatment of patients with late relapsing metastatic renal cell carcinoma.

PURPOSE: Late recurrence of renal cell carcinoma is not a rare event. In this retrospective study we investigate the clinicopathological features and the outcome of patients treated with sorafenib, sunitinib and pazopanib for late relapsing renal cell carcinoma. MATERIALS AND METHODS: Data were collected from 21 Italian centers involved in the treatment of metastatic renal cell carcinoma. Late relapse was defined as more than 5 years after initial radical nephrectomy. RESULTS: A total of 2,490 patients were screened and 269 (11%) were included in the study. First line therapy was sunitinib in 190 patients (71%), sorafenib in 58 (21%) and pazopanib in 21 (8%). Median progression-free survival was 20.0 months for sunitinib (95% CI 17.0-25.1), and 14.1 months for sorafenib (95% CI 11.0-29.0) and pazopanib (95% CI 11.2-not reported). On multivariate analysis MSKCC score and metastases to lymph nodes, liver and brain were associated with worst overall survival, while pancreatic metastases were associated with longer survival. Furthermore, age, MSKCC score and brain metastases were associated with worst progression-free survival. CONCLUSIONS: Patients with late relapsing renal cell carcinoma seem to present a characteristic pattern of metastatic spread without showing significant differences in terms of progression-free survival among sorafenib, sunitinib and pazopanib.

High neutrophil-to-lymphocyte ratio persistent during first-line chemotherapy predicts poor clinical outcome in patients with advanced urothelial cancer.

BACKGROUND: Increased neutrophil-to-lymphocyte ratio (NLR), an index of systemic inflammation, is associated with poor outcome for various types of cancers. We assessed the role on outcome prediction of NLR at baseline and persistent during first-line chemotherapy in patients with advanced urothelial cancer. METHODS: We retrospectively reviewed 292 patients with unresectable or metastatic urothelial cancer treated with first-line chemotherapy between January 2003 and December 2012. The cutoff values of NLR (>3 vs. <3) were evaluated before therapy and at day 1 of the second and third cycle (follow-up NLR). After univariate analysis, a multivariate analysis was carried out by Cox regression model and included the following variables: Eastern Cooperative Oncology Group (ECOG) performance status (≥ 2 vs. 0-1), visceral disease (present vs. absent), hemoglobin (<12 g/dL vs. >12 g/dL), pretherapy NLR (>3 vs. <3), and follow-up NLR (>3 vs. ≤ 3). RESULTS: Patients with pre- and follow-up NLR of >3 had a median progression-free survival of 3.2 months and a median overall survival of 5.7 months. In multivariate analysis, visceral metastases, pretherapy hemoglobin, and follow-up NLR were significant predictors of progression-free survival [hazard ratio (HR) 1.75, P = 0.0001; HR 1.57, P = 0.0015; HR 2.77, P < 0.0001, respectively], and of overall survival (HR 1.60, P = 0.0023; HR 1.59, P = 0.0024; HR 2.89, P < 0.0001, respectively); whereas pretherapy NLR remained as predictor of overall survival only (HR 1.53, P = 0.0101). CONCLUSIONS: An increased NLR persistent during first-line chemotherapy is an independent predictive factor for patients with advanced urothelial cancer.

Surgical resection does not improve survival in patients with renal metastases to the pancreas in the era of tyrosine kinase inhibitors.

BACKGROUND: The aim of this study was to compare survival of resected and unresected patients in a large cohort of patients with metastases to the pancreas from renal cell carcinoma (PM-RCC). METHODS: Data from 16 Italian centers involved in the treatment of metastatic RCC were retrospectively collected. The Kaplan-Meier and log-rank test methods were used to evaluate overall survival (OS). Clinical variables considered were sex, age, concomitant metastasis to other sites, surgical resection of PM-RCC, and time to PM-RCC occurrence. RESULTS: Overall, 103 consecutive patients with radically resected primary tumors were enrolled in the analysis. PM-RCCs were synchronous in only three patients (3 %). In 56 patients (54 %), the pancreas was the only metastatic site, whereas in the other 47 patients, lung (57 %), lymph nodes (28 %), and liver (21 %) were the most common concomitant metastatic sites. Median time for PM-RCC occurrence was 9.6 years (range 0-24 years) after nephrectomy. Surgical resection of PM-RCC was performed in 44 patients (median OS 103 months), while 59 patients were treated with tyrosine kinase inhibitors (TKIs; median OS 86 months) (p = 0.201). At multivariate analysis, Memorial Sloan Kettering Cancer Center risk group was the only independent prognostic factor. None of the other clinical variables, such as age, sex, pancreatic surgery, or the presence of concomitant metastases, were significantly associated with outcome in PM-RCC patients. CONCLUSIONS: The presence of PM-RCC is associated with a long survival, and surgical resection does not improve survival in comparison with TKI therapy. However, surgical resection leads to a percentage of disease-free PM-RCC patients.