Sunitinib in the therapy of malignant paragangliomas: report on the efficacy in a SDHB mutation carrier and review of the literature

SUMMARY Metastatic pheochromocytomas (PHEOs) and paragangliomas (sPGLs) are rare neural crest-derived tumors with a poor prognosis. About 50% of them are due to germ-line mutations of the SDHB gene. At present, there is no cure for these tumors. Their therapy is palliative and represented by different options among which antiangiogenic drugs, like sunitinib, have been hypothesized to be effective especially in malignant SDHB mutated tumors. We report the effects of sunitinib therapy in a SDHB mutation carrier affected by a malignant sPGL. During 101 weeks of therapy at different doses, sunitinib was able to cause a partial response and then a stable disease for a total of 78 weeks. This favorable response is the longest, out of the 35 so far reported in the literature, registered in a patient treated exclusively with sunitinib but, similarly to the other responses, the effect was limited in time. From our analysis of the scanty data present in the literature, the effect of sunitinib does not seem to be different among wild-type patients and those carrying a cluster 1 germ-line mutation. Sunitinib seems able to slow the disease progression in some patients with malignant PHEO/PGL and therefore may represent a therapeutic option, although randomized controlled studies are needed to assess its efficacy definitively in the treatment of these aggressive tumors

Rosiglitazone Inhibits Adrenocortical Cancer Cell Proliferation by Interfering with the IGF-IR Intracellular Signaling

Rosiglitazone (RGZ), a thiazolidinedione ligand of the peroxisome proliferator-activated receptor (PPAR)-γ, has been recently described as possessing antitumoral properties. We investigated RGZ effect on cell proliferation in two cell line models (SW13 and H295R) of human adrenocortical carcinoma (ACC) and its interaction with the signaling pathways of the activated IGF-I receptor (IGF-IR). We demonstrate a high expression of IGF-IR in the two cell lines and in ACC. Cell proliferation is stimulated by IGF-I in a dose- and time-dependent manner and is inhibited by RGZ. The analysis of the main intracellular signaling pathways downstream of the activated IGF-IR, phosphatidyl inositol 3-kinase (PI3K)-Akt, and extracellular signal-regulated kinase (ERK1/2) cascades reveals that RGZ rapidly interferes with the Akt and ERK1/2 phosphorylation/activation which mediates IGF-I stimulated proliferation. In conclusion, our results suggest that RGZ exerts an inhibitory effect on human ACC cell proliferation by interfering with the PI3K/Akt and ERK1/2 signaling pathways downstream of the activated IGF-IR

Augmented Reality to Guide Selective Clamping and Tumor Dissection During Robot-assisted Partial Nephrectomy: A Preliminary Experience.

ABSTRACT Introduction to explore the feasibility of augmented reality (AR) to guide arterial clamping during robot-assisted partial nephrectomy (RAPN). Patients and Methods 15 consecutive patients with T1 renal mass underwent RAPN guided by AR. The 3D virtual model derived by computed tomography was superimposed on the actual view provided by the Da Vinci video stream thought AR technology. Preoperative plan of arterial clamping based on 2D conventional imaging, on 3D model and the effective intraoperative surgical approach guided by AR were compared using the McNeamar test. Results The plan of arterial clamping based on 2D preoperative imaging was recorded as follows: no clamping in 3 (20%), clamping of the main artery in 10 (66.7%) and selective clamping in 1 (6.7%) and super-selective clamping in 1 (6.7%) cases. After revision of the 3D model, the plan of clamping was modified as follows: no clamping in 1 (6.7%), clamping of the main artery in 2 (13.3%), selective clamping in 8 (53.3%) and super-selective clamping in 4 (26.7%) cases (p=0.03). The effective intraoperative clamping approach guided by AR-guidance was performed as planned in 13 (86.7%) patients. Conclusion AR for 3D guided renal surgery is useful to increase the adoption of selective clamping during RAPN

Protocol of the Italian Radical Cystectomy Registry (RIC): a non-randomized, 24-month, multicenter study comparing robotic-assisted, laparoscopic, and open surgery for radical cystectomy in bladder cancer

Background: Bladder cancer is the ninth most common type of cancer worldwide. In the past, radical cystectomy via open surgery has been considered the gold-standard treatment for muscle invasive bladder cancer. However, in recent years there has been a progressive increase in the use of robot-assisted laparoscopic radical cystectomy. The aim of the current project is to investigate the surgical, oncological, and functional outcomes of patients with bladder cancer who undergo radical cystectomy comparing three different surgical techniques (robotic-assisted, laparoscopic, and open surgery). Pre-, peri- and post-operative factors will be examined, and participants will be followed for a period of up to 24 months to identify risks of mortality, oncological outcomes, hospital readmission, sexual performance, and continence. Methods: We describe a protocol for an observational, prospective, multicenter, cohort study to assess patients affected by bladder neoplasms undergoing radical cystectomy and urinary diversion. The Italian Radical Cystectomy Registry is an electronic registry to prospectively collect the data of patients undergoing radical cystectomy conducted with any technique (open, laparoscopic, robotic-assisted). Twenty-eight urology departments across Italy will provide data for the study, with the recruitment phase between 1st January 2017-31st October 2020. Information is collected from the patients at the moment of surgical intervention and during follow-up (3, 6, 12, and 24 months after radical cystectomy). Peri-operative variables include surgery time, type of urinary diversion, conversion to open surgery, bleeding, nerve sparing and lymphadenectomy. Follow-up data collection includes histological information (e.g., post-op staging, grading, and tumor histology), short- and long-term outcomes (e.g., mortality, post-op complications, hospital readmission, sexual potency, continence etc). Discussion: The current protocol aims to contribute additional data to the field concerning the short- and long-term outcomes of three different radical cystectomy surgical techniques for patients with bladder cancer, including open, laparoscopic, and robot-assisted. This is a comparative-effectiveness trial that takes into account a complex range of factors and decision making by both physicians and patients that affect their choice of surgical technique. Trial registration: ClinicalTrials.gov , NCT04228198 . Registered 14th January 2020- Retrospectively registered

Protocol of the Italian Radical Cystectomy Registry (RIC): a non-randomized, 24-month, multicenter study comparing robotic-assisted, laparoscopic, and open surgery for radical cystectomy in bladder cancer

Bladder cancer is the ninth most common type of cancer worldwide. In the past, radical cystectomy via open surgery has been considered the gold-standard treatment for muscle invasive bladder cancer. However, in recent years there has been a progressive increase in the use of robot-assisted laparoscopic radical cystectomy. The aim of the current project is to investigate the surgical, oncological, and functional outcomes of patients with bladder cancer who undergo radical cystectomy comparing three different surgical techniques (robotic-assisted, laparoscopic, and open surgery). Pre-, peri- and post-operative factors will be examined, and participants will be followed for a period of up to 24\u2009months to identify risks of mortality, oncological outcomes, hospital readmission, sexual performance, and continence

An ultrahot Neptune in the Neptune desert

About 1 out of 200 Sun-like stars has a planet with an orbital period shorter than one day: an ultrashort-period planet. All of the previously known ultrashort-period planets are either hot Jupiters, with sizes above 10 Earth radii (R⊕), or apparently rocky planets smaller than 2 R⊕. Such lack of planets of intermediate size (the ‘hot Neptune desert’) has been interpreted as the inability of low-mass planets to retain any hydrogen/helium (H/He) envelope in the face of strong stellar irradiation. Here we report the discovery of an ultrashort-period planet with a radius of 4.6 R⊕ and a mass of 29 M⊕, firmly in the hot Neptune desert. Data from the Transiting Exoplanet Survey Satellite revealed transits of the bright Sun-like star LTT 9779 every 0.79 days. The planet’s mean density is similar to that of Neptune, and according to thermal evolution models, it has a H/He-rich envelope constituting 9.0^(+2.7)_(−2.9)% of the total mass. With an equilibrium temperature around 2,000 K, it is unclear how this ‘ultrahot Neptune’ managed to retain such an envelope. Follow-up observations of the planet’s atmosphere to better understand its origin and physical nature will be facilitated by the star’s brightness (V_(mag) = 9.8)

Best buy: what does it mean in corporate travel?

Corporate travel departments manage travel costs prescribing best buy decisions. With reference to flights, the crucial choice concerns the fare. As the difference in price can be great, it might seem convenient to always purchase the cheapest ticket, neglecting that the more expensive a fare, the lower the cost of change or cancellation. We define \u201cbest buy\u201d minimizing the expected global cost of flights, whence estimating the probability distribution of travellers\u2019 behaviour is necessary. Variables useful to this aim are detected. This statistical approach can improve the efficiency of corporate policies, leading to diversified purchasing strategies

Rating hotel quality for corporate business travel departments

Purpose: The present study aims to suggest a new approach to hotel quality rating, specifically designed for the business travel segment, where the evaluation of surveyed consumers (business travelers) does not necessarily reflect the priority of customers (corporate travel departments [CTDs]). Design/methodology/approach: Preliminarily, the authors defined key areas (domains), exploring what was done by quality certifiers recognized worldwide. Then, each domain quality was considered as a latent variable measured by a set of observable attributes (sub-domains) surveyed by a professional assessor. A continuous, fine-grained, composite indicator (CI) for quality was finally obtained by a weighted average of the domain (latent) quality measures. Weights were endogenously determined by data envelopment analysis. Findings: The suggested CI shows both the existence of large quality disparities within the same star rating and a relevant bias in the internet reviews. A “soundproofed” room, a front desk open 24 h with sufficient staff and an adequate urban context are necessary features of any business hotel. Research limitations/implications: Data came from a professional assessor’s database; therefore, the authors could only consider a three-domains measurement model. The database is mainly composed of three- and four-star hotels in Italy; nonetheless, these accommodations are the most widespread in the Italian corporation hotel programs, preserving the practical utility of the results. Originality/value: This study provides a transparent (replicable) evaluation protocol that is of potential use in the most popular models for quality measurement; any assessor can use it to underline its impartiality to CTD and assessed hotels