Context:
The recent discovery of inducible brown adipose tissue (BAT) in adult humans, in which it is involved in controlling adiposity, is pivotal in the development of treatment strategies for ...obesity. However, the origin of these adipocytes in white adipose tissue (WAT) is still unclear, and no human brown adipose cell models are currently available.
Objective:
The objective of the study was to define the origin of inducible BAT (iBAT) by isolating brown adipose stem cells (B-ASCs) from periadrenal fat in adult patients with catecholamine-secreting pheochromocytoma.
Design:
This was a 1-year study to enroll adrenal tumor patients undergoing surgery.
Setting:
The study was conducted at a university hospital.
Patients and Intervention:
Eight patients operated for pheochromocytoma and three for adrenocortical adenoma participated in the study.
Main Outcome Measures:
Isolation of inducible B-ASCs from fat surrounding the pheochromocytoma was measured.
Results:
We demonstrated the presence of iBAT islets dispersed in periadrenal WAT in patients operated for pheochromocytoma. From this fat depot, which expresses brite/classical BAT markers and high levels of uncoupling protein-1, we isolated B-ASCs and compared their properties with precursors from sc WAT (S-ASC) of the same patients. B-ASCs showed mesenchymal, stem, and multipotency features and expression of brite/classical BAT markers. When differentiated toward white phenotype, B-ASCs accumulated lipid droplets smaller than S-ASCs and expressed adiponectin. Upon induction of brown differentiation, brown commitment was found only in B-ASCs and not in S-ASCs, with no mature brown adipocytes.
Conclusions:
Our findings demonstrate that iBAT developed in periadrenal WAT derives from adult stem cells, unlike WAT precursors, confirming an independent origin of the two fat depots. These stem cells represent a unique in vitro stem cell model to study brown adipogenesis and develop novel antiobesity therapies targeting WAT-BAT conversion.
Abstract
Conclusion: GelitaSpon gelatin sponge (GS) showed faster reabsorption than gelfoam (GF) in vitro, and GS-packed middle ears resulted in a faster hearing recovery and less inflammation than ...the ears packed with GF soaked in saline. Soaking GF sponges with boric acid (BA) appeared to offset the inflammatory response of saline-soaked GF, making this inflammatory response comparable to that of GS-packed ears. Objective: To describe the reabsorption and inflammatory effects of absorbable gelatin sponge in the middle ear. Methods: For in vitro evaluation, GF and GS were used as disks immersed in saline solution or 3% BA and placed in gel. Images were captured with a microscope and processed using image processing Toolbox. For in vivo tests, 16 female albino Sprague Dawley rats were divided into four groups: bulla opening; GF + 0.9% saline; GF + BA; and GS + 0.9% saline. An anterior approach to the right bulla was used for surgery. Preoperative and postoperative auditory brainstem response thresholds were measured. Results: In vitro, there was marked degradation of GF by day 14, while GS showed complete degradation by the third day. In vivo, hearing recovery occurred by day 21. GF produced a more severe inflammatory response, which could be reduced by treating the GF with BA.
To describe genetic analysis, treatment results, and complications of patients affected by retinal capillary hemangioblastoma (RCH) in von Hippel Lindau (VHL) syndrome.
We collected 17 patients with ...VHL syndrome, who underwent a molecular test and an ophthalmic evaluation at the Eye Clinic of the University Hospital of Florence from January 2005 to February 2020. We focused on eyes showing RCHs examined using color fundus photographs, fluorescein angiography, and optical coherence tomography.
Eight eyes of six patients (6/17; 35%) showed RCHs at the fundoscopic examination. All RCHs were treated with laser therapy. Three eyes underwent episcleral surgery, one eye showing vitreous hemorrhage received three intravitreal (IV) anti-VEGF injections and three cryotherapy procedures, and one eye underwent vitrectomy. In patients with RCHs, five were characterized by a truncating mutation of the VHL protein, and one patient showed a missense mutation. We have reported two VHL mutations not reported in literature.
Patients with multiple RCHs, who developed RCH secondary effects, showed truncating mutations of the VHL protein. We recommend early screening and close monitoring, especially if RCHs are detected at presentation, for every patient with VHL syndrome independently of the results of the molecular test for a missense or a truncating mutation in
.
The purpose of this study was to evaluate the impact of 3-dimensional (3D) digital reconstructions of renal models on the arterial clamping approach during partial nephrectomy (PN).
Fifty-seven ...patients with T1 renal mass, referred for PN, were prospectively enrolled in 2 groups: Group 1 (n = 32) with revision of both 2-dimensional (2D) computed tomography (CT) imaging and 3D virtual model before surgery; Group 2 (n = 25) with revision of 2D CT imaging. Segmentation of the 3D models from preoperative high-quality CT scan was achieved using D2P software. In a sub-analysis of patients treated with PN with the on-clamp approach (n = 36), the effective intraoperative level of arterial clamping was compared with the preoperative planning.
In the sub-group of patients referred to PN with the on-clamp approach, the intraoperative selective clamping was performed in 12 (57.1%) patients of Group 1 and in 2 (13.3%) cases of Group 2 (P = .01). The intraoperative management of the renal pedicle was done as preoperatively planned in 61.9% of patients in Group 1 and in 86.6% of cases in Group 2 (P = .1).
The 3D-guided plan of PN allows to perform selective clamping in higher proportion of patients compared with the standard 2D-guided approach without increasing intraoperative and postoperative complications.
The genetic approach of pheochromocytomas and paragangliomas has changed in the last two decades. Nowadays, we know that more than 40% of patients have a germline mutation in one of the ...susceptibility genes identified to date. Our aim is to underline how genetic diagnosis by next-generation sequencing (NGS) can improve the management of patients affected by pheochromocytomas and paragangliomas in our routine diagnostic screening. We reported a case presentation and next-generation sequencing analysis supported by in silico studies and evaluation of mitochondrial status in KIF1Bβ tissue. A 46-year-old male affected by a left secreting pheochromocytoma underwent surgery in 2017. After surgery, the normetanephrine levels decreased very slowly and a suspected abdominal lymph node was detected. We found a novel germline KIF1Bβ gene mutation, c.4052C > T, p. Pro1351Leu associated with tumor loss of heterozygosity, and resulted likely-pathogenetic by in silico studies. This mutation was also associated with an increased number of mitochondria through the electron microscopy compared with wild-type tissues as suggestive for mitochondria neoformation compensatory to the mitochondrial autophagic figures observed. Our results underline the usefulness of next-generation sequencing in the presence of multiple tumor predisposition genes and how, at the same time, its use may result challenging for the clinicians. To date, performing the genetic analysis according to the latest Consensus Statement is mandatory in patients affected by PHEO/PGL.
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.
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).
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.
ClinicalTrials.gov , NCT04228198 . Registered 14th January 2020- Retrospectively registered.
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.
The medicalisation of birth pathway may negatively impact on women's empowerment, enhancing distress even in cases of healthy pregnancies. We have built a program which is comprised of Mindfulness, ...Yoga, Nutrition, development & Counselling, Coaching, antenatal classes, and Osteopathic treatment (MYNd&CO).
This study is a randomized controlled trial involving low-risk pregnant women. They will be randomized to the experimental (MYNd&CO intervention plus standard care) or control group (standard care). The primary (general health and wellbeing, maternal distress) and secondary outcome measures (urinary incontinence, sexual problems, and physical wellbeing) will be assessed via questionnaires at baseline and 6 months after childbirth. The independent-samples t-test and Chi-square will be used to detect changes in the outcomes between intervention and control group.
The trial is expected to increase knowledge about the effectiveness of a holistic approach in low-risk pregnant women, in terms of obstetrical and psychophysiological outcomes.
BMP7 is a growth factor playing pro- or anti-oncogenic roles in cancer in a cell type-dependent manner. We previously reported that the BMP7 gene is overexpressed in pheochromocytomas (PCCs) ...developing in MENX-affected rats and human patients. Here, analyzing a large cohort of PCC patients, we found that 72% of cases showed elevated levels of the BMP7 protein. To elucidate the role of BMP7 in PCC, we modulated its levels in PCC cell lines (overexpression in PC12, knockdown in MPC and MTT cells) and conducted functional assays. Active BMP signaling promoted cell proliferation, migration, and invasion, and sustained survival of MENX rat primary PCC cells. In PCC, BMP7 signals through the PI3K/AKT/mTOR pathway and causes integrin β1 up-regulation. Silencing integrin β1 in PC12 cells suppressed BMP7-mediated oncogenic features. Treatment of MTT cells with DMH1, a novel BMP antagonist, suppressed proliferation and migration. To verify the clinical applicability of our findings, we evaluated a dual PI3K/mTOR inhibitor (NVP-BEZ235) in MENX-affected rats in vivo. PCCs treated with NVP-BEZ235 had decreased proliferation and integrin β1 levels, and higher apoptosis. Altogether, BMP7 activates pro-oncogenic pathways in PCC. Downstream effectors of BMP7-mediated signaling may represent novel targets for treating progressive/inoperable PCC, still orphan of effective therapy.
The Italian Radical Cystectomy Registry (RIC) is an observational prospective study aiming to understand clinical variables and patient characteristics associated with short- and long-term outcomes ...among bladder cancer (BC) patients undergoing radical cystectomy (RC). Moreover, it compares the effectiveness of three RC techniques - open, robotic, and laparoscopic.
From 2017 to 2020, 1400 patients were enrolled at one of the 28 centers across Italy. Patient characteristics, as well as preoperative, postoperative, and follow-up (3, 6, 12, and 24 months) clinical variables and outcomes were collected.
Preoperatively, it was found that patients undergoing robotic procedures were younger (p<.001) and more likely to have undergone preoperative neoadjuvant chemotherapy (p<.001) and BCG instillation (p<.001). Hypertension was the most common comorbidity among all patients (55%), and overall, patients undergoing open and laparoscopic RC had a higher Charlson Comorbidities Index (CCI) compared to robotic RC (p<.001). Finally, laparoscopic patients had a lower G-stage classification (p=.003) and open patients had a higher ASA score (p<.001).
The present study summarizes the characteristic of patients included in the RIC. Future results will provide invaluable information about outcomes among BC patients undergoing RC. This will inform physicians about the best techniques and course of care based on patient clinical factors and characteristics.
PDF
