A comprehensive analysis of GATA3 expression in carcinomas of various origins with emphasis on lung carcinomas.

GATA3 is a transcription factor involved in embryogenesis of multiple human tissues and in maintaining cell differentiation and tissue homeostasis in the adult organism. GATA3 is also involved in carcinogenesis and regarded as a sensitive marker for urothelial and breast carcinomas, albeit expression in carcinomas of non-breast/urothelial origin has been frequently reported. We sought to examine the extent and intensity of GATA3 expression in various carcinomas, mainly lung, urothelial, and breast and various other primary sites. Patients with breast carcinoma (N=40), carcinoma of the urinary bladder/renal pelvis (N=40), lung carcinoma (N=110) and various other origins (N=45) were included in the study. One hundred and sixty-five patients had a primary tumor diagnosis, and 70 cases had a metastatic tumor diagnosis. Our results showed that GATA3 expression was significantly more common in carcinomas of the breast, urinary bladder and renal pelvis compared to all other origins. All primary and 93% of metastatic urinary bladder carcinomas and 94% of the primary and 80% of metastatic breast carcinomas expressed GATA3. Expression was lower in non-urothelial histology of urinary primaries and in triple negative breast carcinomas. Focal staining, mostly faint, was seen in 5.6% of the primary lung adenocarcinomas and 35% of the primary lung squamous cell carcinomas. More extensive and intense staining was seen in 3.7% of the primary lung adenocarcinomas and 12% of the primary lung squamous cell carcinomas. Expression, mostly focal was also seen in 30% of the metastatic lung carcinomas. Finally, high expression was seen in 12.5% of the other tumors (one metastatic pancreatic carcinoma, one metastatic salivary gland adenocarcinoma NOS, one metastatic squamous cell carcinoma of the skin, one primary uterine cervix serous carcinoma, and one squamous cell carcinoma of the head and neck) and focal expression was present in another 22% of them. No ideal cut-off for positivity for GATA3 staining could be identified. In conclusion our study shows that GATA3 staining has two caveats in its use: the first is that non classical histologies of urothelial carcinomas and TNBC may be negative for the marker and secondly carcinomas of various origins may show (although rarely) intense positivity.

Effects of instrument-assisted soft-tissue mobilization at three different application angles on hamstring surface thermal responses.

[Purpose] This study aimed to examine the thermal skin responses (thermal buildup and retention rate) to instrument-assisted soft tissue mobilization (IASTM) procedures applied on hamstrings at different angles. [Participants and Methods] Thirty university students (age: 20 ± 4 years, weight: 70.61 ± 9.11 kg, height: 168.5 ± 7.5 cm) received three sessions of 10-min Ergon® IASTM treatment on their dominant limbs' hamstrings at 20°, 60°, and 90° application angles, respectively. The skin temperature was measured with a thermometer immediately before and after treatment, and every minute thereafter until it returned to the baseline value. [Results] IASTM resulted in a significant increase in skin temperature irrespective of the application angle. The thermal retention rate produced by the treatment at a 90° angle was significantly higher than that produced by the 20° application angle (78.9 vs. 64.53 min). No significant differences were observed between the 60° and 90° angle applications (72.5 vs. 78.9 min). [Conclusion] IASTM application at 60° and 90° angles can increase and retain the hamstring's skin temperature for more than an hour, creating the conditions for potential positive adaptations to local metabolism and muscle tone.

Posterior thigh thermal skin adaptations to radiofrequency treatment at 448 kHz applied with or without Indiba® fascia treatment tools.

[Purpose] This study aimed to evaluate the posterior thigh's skin thermal responses to 448-kHz radiofrequency-based therapy applied either in the form of standard application (Indiba®Activ) or combined soft tissue treatment (Indiba®Fascia treatment). [Participants and Methods] Ten healthy males (22 ± 3 years of age, weight 75.2 ± 4.9 kg, height 178.5 ± 4.7) received four different treatments which included a) Indiba®Activ (IA) radiofrequency treatment, b) Indiba®Fascia (IF), c) Indiba®Activ placebo (IAP) and d) Indiba®Fascia Placebo (IFP) in the posterior thigh of their dominant lower limb, while the non-dominant served as the control. Skin temperature was recorded pre- and post-treatment and every minute until the surface temperature reached pre-treatment levels using a wireless infrared thermometer. [Results] Both radiofrequency-based therapy groups IA and IF led to a significant increase in skin temperature compared to placebo applications. The IF intervention led to an average retention of elevated temperature for 164.2 minutes compared to 54.8 minutes of IA, 23.17 of IFP and 17.6 minutes of IAP. [Conclusion] These findings indicate that radiofrequency treatment at 448 kHz can induce and sustain significant thermal skin adaptations reflecting an increased blood circulation and metabolism of underlying tissues.

Malacoplakia of the skin: overview of a rare clinical entity.

BACKGROUND: Malacoplakia is a rare acquired, infection-related granulomatous disorder, that may affect many systems, but typically occurs in the urinary tract. Cutaneous involvement is less prevalent, and most commonly presents with a perianal or genital region localization. Cutaneous malacoplakia is believed to be caused by an acquired bactericidal defect of macrophages in the setting of chronic infections and immunocompromised states. A diagnosis of cutaneous malacoplakia should be considered when encountering non-specific granulomatous lesions that are refractory to treatment. Histologic findings are marked by the presence of foamy macrophages containing the pathognomonic Michaelis-Gutman bodies. OBJECTIVES: The aim of this review is to discuss the current perspectives on the pathophysiology, clinical features, diagnosis, and treatment of this disease. We would also like to emphasize that the integration of clinical information, microscopic findings, and exclusion of other cutaneous granulomatous processes is necessary to accurately diagnose this exceedingly rare disease and provide opportunity for therapeutic intervention. PATIENTS/METHODS: Data for this work were collected from the published literature and textbooks. RESULTS: Combined surgical excision and protracted antibiotic courses appear to have the highest success rate. Antibiotics should be culture specific, but drugs that easily permeate the macrophages appear to be the best choice.

Can the application of the Ergon® IASTM treatment on remote parts of the superficial back myofascial line be equally effective with the local application for the improvement of the hamstrings' flexibility? A randomized control study.

[Purpose] This study was aimed to investigate the effects of Ergon® IASTM applications on the upper or lower part of the Superficial Back Line (SBL) on the hamstring's flexibility. [Participants and Methods] Sixty University students (age=24.4 ± 4.39; height=176.78 ± 8.31 cm; weight=75.16 ± 11.21 kg) were randomly divided into three sub-groups and received a single 15-minute treatment with Ergon® Technique in a) the upper and b) the lower part of SBL or c) served as control. The participants received one treatment per week for four weeks with a simultaneous pre-and post-therapy assessment of their hamstrings flexibility using the passive Straight Leg Raising (SLR). [Results] Both experimental groups improved SLR performance from pre to post during the four weeks from 4.4% to 9.2% in the trunk group and from 4.9% to 8.0% in the lower body group. These differences were significantly greater from the CTRL group. No differences were observed between the two experimental groups. [Conclusion] In conclusion, application of Ergon Technique of either the upper or lower part of the SBL may lead to a significant increase in the hamstring flexibility irrespective of the site of application.

Successful treatment of multifocal pigmented basal cell carcinomas with the application of topical 5% imiquimod cream.

Basal cell carcinoma (BCC) is one of the most frequent skin malignancies, with increasing incidence over the past years. Although the surgical excision is the gold-standard treatment, several other noninvasive therapies have also been developed for the management of these skin tumors, especially in the cases where a surgical intervention does not seem feasible. Imiquimod is an immunomodulatory agent, which has received approval in the topical treatment of superficial BCCs. With this short report, we present the case of a patient with multifocal pigmented BCCs, successfully treated with topical 5% imiquimod cream.

Assessing the use of haemostatic sealants in tubeless percutaneous renal access and their effect on renal drainage and histology: an experimental porcine study.

OBJECTIVE: To evaluate the mid-term effects of haemostatic sealant application during tubeless percutaneous nephrolithotomy (PCNL) on renal drainage and histology in an in vivo porcine study. MATERIALS AND METHODS: Bilateral percutaneous access was established in 28 porcine renal units. At the end of the procedure, a type 1 absorbable fish origin collagen powder, a human fibrinogen- and thrombin-coated sponge or a cross-linked gelatin granule/topical thrombin matrix were randomly placed on the nephrostomy tracts. Four nephrostomy accesses were left intact and served as controls. No percutaneous tube, ureteric stent or bladder catheter was left in place postoperatively. Computed tomography urography on postoperative days 1, 15, 30 and 40 was used to access renal drainage. On postoperative day 40, all animals were killed and both kidneys from each animal were harvested for histological evaluation. RESULTS: Evidence of risk for drainage occlusion after sealant application was found. The use of haemostatic sealants was associated with significant histological lesions in the renal parenchyma, regardless of which sealant was used. No sealant was identified as superior to the others. Nephrostomy tracts that were left without sealant application (control group) were associated with no morbidity and fewer histopathological changes. CONCLUSIONS: Based on these experimental results, the safety of the application of haemostatic sealants in tubeless PCNL should be reassessed, focusing not only on the potential of such materials to occlude urinary drainage but also on their effect on renal histology. Further investigation is considered necessary.

Clearance of Metal Particles After Percutaneous Nephrolithotomy with Trilogy Lithotripter.

Purpose: To evaluate the clearance of metal particles produced and released in the pelvicaliceal system (PCS) during percutaneous nephrolithotomy (PCNL) with the use of the Swiss Lithoclast® Trilogy dual-energy (EMS Urology, Nyon, Switzerland) lithotripter. Methods: An experimental in vivo study and a clinical investigation of case series were conducted. An in vivo porcine model with two pigs for lithotripsy (after inserting artificial stones into the collecting system) and two pigs for submucosal injection of metal particles (provided by the manufacturer of Trilogy) was conducted. Porcine kidney histology analysis for metal leftovers was conducted immediately or 2 weeks after the surgery. A prospective observational study design included 10 consecutive patients treated with conventional 30F PCNL or with 22F mini-PCNL technique. Only the patients with the confirmed metal particles in the PCS during the initial PCNL and the need for additional retrograde intrarenal surgery over a period of 2-4 weeks were selected. The presence of metal particles was evaluated during the second endoscopic surgery. Results: The generated metal particles during PCNL and the submucosally injected particles were not found macroscopically 2 weeks postoperatively in porcine models. No pathologic changes such as foreign body granuloma or inflammation were found. Similarly, no metal particles were observed during the second look endoscopy (n = 10). Conclusion: Metal particles observed endoscopically using the Trilogy lithotripter are cleared with no pathologic evidence of tissue damage from the metal particles 2 weeks after the procedure. Thus, the intraoperative release of any particle by the Trilogy lithotripter should not raise any safety concerns.

Microtubule Dynamics Deregulation Induces Apoptosis in Human Urothelial Bladder Cancer Cells via a p53-Independent Pathway.

Bladder cancer (BLCA) is the sixth most common type of cancer and has a dismal prognosis if diagnosed late. To identify treatment options for BLCA, we systematically evaluated data from the Broad Institute DepMap project. We found that urothelial BLCA cell lines are among the most sensitive to microtubule assembly inhibition by paclitaxel treatment. Strikingly, we revealed that the top dependencies in BLCA cell lines include genes encoding proteins involved in microtubule assembly. This highlights the importance of microtubule network dynamics as a major vulnerability in human BLCA. In cancers such as ovarian and breast, where paclitaxel is the gold standard of care, resistance to paclitaxel treatment has been linked to p53-inactivating mutations. To study the response of BLCA to microtubule assembly inhibition and its mechanistic link with the mutational status of the p53 protein, we treated a collection of BLCA cell lines with a dose range of paclitaxel and performed a detailed characterization of the response. We discovered that BLCA cell lines are significantly sensitive to low concentrations of paclitaxel, independently of their p53 status. Paclitaxel induced a G2/M cell cycle arrest and growth inhibition, followed by robust activation of apoptosis. Most importantly, we revealed that paclitaxel triggered a robust DNA-damage response and apoptosis program without activating the p53 pathway. Integration of transcriptomics, epigenetic, and dependency data demonstrated that the response of BLCA to paclitaxel is independent of p53 mutational signatures but strongly depends on the expression of DNA repair genes. Our work highlights urothelial BLCA as an exceptional candidate for paclitaxel treatment. It paves the way for the rational use of a combination of paclitaxel and DNA repair inhibitors as an effective, novel therapeutic strategy.

How Safe Are the Laparoscopic and Robotic Graspers? Evaluation of the Novel Avatera Robotic Surgical System: An Acute In Vivo Study on a Porcine Model.

OBJECTIVE: To evaluate the tissue injury caused by the force applied by the roboticassisted graspers of avatera robotic surgical system on bowel tissue. METHODS: An experimental in vivo porcine model with 1 pig was conducted. After a standard transperitoneal setup of the avatera robotic surgical system, different laparoscopic and robotic graspers were used on the bowel with maximum force applied each time. Robotic atraumatic grasper, laparoscopic right angle grasper, laparoscopic curved grasper, and laparoscopic atraumatic grasper were used. After using all graspers, the pig was sacrificed. The bowel segments were resected and sent for histological analysis. RESULTS: The pathologist reported that all the graspers caused signs of acute inflammation without any irreversible damage or signs compatible with ischemia of the tissue. No significant difference in histology was observed between the graspers. CONCLUSION: No permanent damage was caused by graspers, except for acute, reversible inflammation. Concluding, the avatera grasper could be safe to use on bowel segments, independent of the applied pressure.

Cold-Water Immersion and Sports Massage Can Improve Pain Sensation but Not Functionality in Athletes with Delayed Onset Muscle Soreness.

This study aimed to investigate the effects of cold-water immersion (CWI) and sports massage on delayed-onset muscle soreness (DOMS) in amateur athletes. Sixty male amateur athletes were randomised into four equal groups (n = 15) receiving either CWI, sports massage, their combination, or served as controls after applying plyometric training to their lower extremities. The main outcomes measures were pain, exertion, rectus femoris perimeter, knee flexion range of motion, knee extensors isometric strength and serum creatine phosphokinase (CPK) levels examined before the plyometric training, immediately after the treatment, and 24, 48 and 72 h post exercise. We observed no significant differences between study groups in the most tested variables. CWI improved pain compared to the combined application of CWI and sports massage, and the control group both on the second and third day post exercise. Sports massage combined with CWI also led to a significant reduction in pain sensation compared to the control group. In conclusion the treatment interventions used were effective in reducing pain but were unable to affect other important adaptations of DOMS. Based on the above, sports scientists should reconsider the wide use of these interventions as a recovery strategy for athletes with DOMS.

A Unique Technique for Precise Targeting in Treatment of Rare Bifocal Intraosseous Ganglion Cysts of the Talus: A Case Report and Review of the Literature.

BACKGROUND This article presents a rare case of 2 separate intraosseous ganglion cysts of the talus in a 51-year-old man, treated with a unique technique of precise lesion targeting to avoid extensive bone loss and minimize articular chondral injury of the talus. CASE REPORT Two separate intraosseous ganglion cysts of the talus were diagnosed in a 51-year-old man with chronic ankle pain. A single straight-line incision with an entry point through the talonavicular joint was created to spare the precarious blood supply of the talus network. The 2 distinct subchondral lesions were approached under fluoroscopic control for curettage and autologous bone grafting using the anterior cruciate ligament tibial guide in a pair-of-compasses fashion. In almost 5 years of follow-up the patient has been asymptomatic. Magnetic resonance imaging has revealed no signs of degenerative changes in the ankle or the talonavicular joint, and the intraosseous edema has almost disappeared. CONCLUSIONS To the best of our knowledge, this case is the first report of 2 distinct intraosseous ganglion cysts of the talus. We recommend the precise targeting technique used in our case for treating intraosseous talar lesions with intact articular cartilage.

From Proteomic Mapping to Invasion-Metastasis-Cascade Systemic Biomarkering and Targeted Drugging of Mutant BRAF-Dependent Human Cutaneous Melanomagenesis.

Melanoma is classified among the most notoriously aggressive human cancers. Despite the recent progress, due to its propensity for metastasis and resistance to therapy, novel biomarkers and oncogenic molecular drivers need to be promptly identified for metastatic melanoma. Hence, by employing nano liquid chromatography-tandem mass spectrometry deep proteomics technology, advanced bioinformatics algorithms, immunofluorescence, western blotting, wound healing protocols, molecular modeling programs, and MTT assays, we comparatively examined the respective proteomic contents of WM115 primary (n = 3955 proteins) and WM266-4 metastatic (n = 6681 proteins) melanoma cells. It proved that WM115 and WM266-4 cells have engaged hybrid epithelial-to-mesenchymal transition/mesenchymal-to-epithelial transition states, with TGF-ß controlling their motility in vitro. They are characterized by different signatures of SOX-dependent neural crest-like stemness and distinct architectures of the cytoskeleton network. Multiple signaling pathways have already been activated from the primary melanoma stage, whereas HIF1α, the major hypoxia-inducible factor, can be exclusively observed in metastatic melanoma cells. Invasion-metastasis cascade-specific sub-routines of activated Caspase-3-triggered apoptosis and LC3B-II-dependent constitutive autophagy were also unveiled. Importantly, WM115 and WM266-4 cells exhibited diverse drug response profiles, with epirubicin holding considerable promise as a beneficial drug for metastatic melanoma clinical management. It is the proteome navigation that enables systemic biomarkering and targeted drugging to open new therapeutic windows for advanced disease.

Prognostic significance of TGFbeta-1 and pSmad2/3 in breast cancer patients with T1-2,N0 tumours.

BACKGROUND: The transforming growth factor beta (TGFbeta) signaling pathway has been shown to exert divergent effects and to cross-talk with estrogen pathways in mammary gland tumorigenesis. TGF signaling in early stage breast cancer was investigated by examining the expression of TGFbeta-1 and the signaling mediators pSmad2/3 and Smad4. Their association with oestrogen and progesterone receptors, as well as with clinical and pathological features was also analyzed. PATIENTS AND METHODS: Sixty-one tumor specimens from surgically treated patients with primary T12,N0 breast cancer were examined. The expression of TGFbeta-1, pSmad2 and Smad4 was assessed implementing immunohistochemical assays. RESULTS: TGFbeta-I, pSmad2/3 and Smad4 were expressed in 50.9%, 74.0% and 61.0% of specimens, respectively. The degree of expression of the three molecules was significantly associated with each other. Loss of pSmad2/3 expression indicated a shorter disease-free survival in all patients, including those with oestrogen receptor-positive tumors. Patients not expressing TGFbeta-1 were 4.6 times more likely to experience distant recurrence. CONCLUSION: Our results demonstrate that pSmad2/3 and TGFP-1 may be promising novel prognostic markers for T1.2,N0 breast carcinomas.

A minimally invasive endovascular rabbit model for experimental induction of progressive myocardial hypertrophy.

The purpose of this paper is to describe a novel minimally invasive endovascular model of progressive myocardial hypertrophy in rabbits as an experimental protocol of hypertrophic cardiomyopathy. Nine New Zealand White rabbits underwent transauricular aortic catheterization. Under fluoroscopy a bare metal stent was partially deployed in the descending thoracic aorta (balloon length/stent length=1/2) so as to produce a funnel-shaped thoracic stent. Another nine animals underwent a sham procedure without stent placement (control). Follow-up computed tomography imaging was performed to exclude aortic occlusion. Subjects were killed after 3 months and their hearts were harvested and weighed. Cardiac hypertrophy was assessed with the heart weight-to-body weight (HW/BW) ratio and post-mortem histology was performed. We also used immunohistochemical staining for myogenin to compare the thickness of the wall between the two groups. The stents were polymer embedded for histomorphometry. Expressions of vascular endothelial growth factor (VEGF) and pleiotrophin (PTN) were analyzed by western blot analysis of total protein heart extracts. Computerized image analysis of CD34 and VEGF immunoreactivity was used to quantify myocardial angiogenesis. After 3 months, cross-sectional microscopic analysis of the harvested aortas showed total stent occlusion of the distal underdeployed area and some evidence of thrombus formation at the transitional zone toward the fully deployed stent in all cases. There was a nearly +10% increase of the adjusted HW/BW ratio compared with controls (absolute ratio difference was 0.02±0.01%; P=0.02). VEGF and CD34 expression was significantly suppressed, but expression of PTN was significantly increased in case of myocardial hypertrophy (stent group). Cardiac hypertrophy was evidenced using immunohistochemical staining for myogenin by significantly increased cardiomyocyte cross-sectional area (+38.4%; P<0.0001) compared with the control animals. In conclusion, this minimally invasive novel technique of transauricular funnel-shaped stent insertion in the descending thoracic aorta may achieve progressive myocardial hypertrophy in rabbits.

A "reverse" Maffucci's syndrome: case report and short review of the literature.

Maffucci's syndrome is a congenital, non-hereditary mesodermal dysplasia associated with multiple enchondromas and after some years accompanied by hemangiomas. We describe a rare case of "reverse" Maffucci's syndrome in a 42-year-old woman who has suffered from multiple hemangiomas for the last 24 years. The last two years she complained for heel pain. Bone scintigraphic examination showed abnormal findings in the left calcaneal bone. The scintigraphy, radiology and histology findings revealed multiple enchondromas, so the diagnosis was changed into Maffucci's syndrome. After one year, the left calcaneal bone showed sarcomatous transformation.