Notes

Kid Head ache Attributed to Infection.
Batrachochytrium salamandrivorans (Bsal), a pathogenic fungus causing the fatal disease chytridiomycosis in amphibians, was likely introduced to Europe through the trade in pet salamanders from Asia and then escaped into wild populations. Among European countries, Spain has a large number of private breeders and keepers of pet salamanders, and cases of Bsal in wild and captive populations already have been confirmed there. However, surveillance for the pathogen in Spanish collections of amphibians is sparse. Therefore, assisted by private owners and breeders, we surveyed 10 amphibian collections and analysed a total of 317 samples for presence of Bsal. All of our analyses yielded negative results. However, this apparent lack of Bsal cases in captivity should not encourage relaxation of vigilance, quarantine efforts or good practices. Because amphibian collections represent highly dynamic environments (animals are coming in and out), the pathogen could easily be introduced into a collection by new individuals. Any case of Bsal infection in captive animals could lead to its further spread to wild populations of susceptible species, potentially decimating them, and thus should be prevented.In the last decades, only few improvements have been made in the comprehension of bladder cancer tumor leading to few improvements in the development of new diagnostic and therapeutic approaches.However, in the last years several step forwards in the field of precision medicine have been made. In this review we focused on some of these elements such as the available biomarkers, the role of enhanced transurethral resection of the bladder and the role of the molecular classification in defining prognosis and therapeutic approaches in bladder cancer patients. Although several progresses have been made, at the time none of the existing biomarkers appear to be able to safely avoid the need of cystoscopy during the follow up of bladder cancer patients. However, these biomarkers representan important tool to follow up patients with a less invasive methods and in the near future might be able to substitute the need of cystoscopy. Enhanced transurethral resection technique can in some cases reduce the risk of recurrence during follow up, although its impact on survival outcomes is still under debate. Transurethral resection of the bladder represents a fundamental diagnostic and therapeutic step in the management of bladder cancer and these techniques can successfully improve its outcomes. Finally, the molecular classification of the bladder cancer represents one of the most exciting novelty in this field, improving consistently the knowledge of bladder cancer. Improvements regarding prognoses and therapeutics can be achieved although data stil need validation.Until 2016, the treatment options for patients with urothelial carcinoma who had progressed to first line treatment were limited. Vinflunine has been the only approved treatment in Europe for this indication. The only alternatives in these patients were clinical trials or other chemotherapies with low efficacy and high toxicity. The last couple of years, three immune-checkpoint inhibitors have been approved in Europe (pembrolizumab, atezolizumab and nivolumab) and five in USA (pembrolizumab, atezolizumab, nivolumab, durvalumaband avelumab), showing improved overall survival (OS), response rate (ORR) and tolerance. Recently, the FDA has approved two new treatments based on the results from the phase II trials. Erdafitinib, the first anti-FGFR treatment in patients with mutations/fusions in FGFR2/3 showed an ORR of 40% and an OS of 13,8 months. Likewise, enfortumab-vedotin, an antibody conjugates, was approved by the FDA based on the phase II trial results. Enfortumab-vedotin presented an ORR of 44%(12% of complete response) and an OS of 11,7 months. Other antiFGFR, antibody conjugates and immunotherapy combinations are in development, with promising results that need to be further confirmed in order to be approved. As a result, the landscape of urothelial canceris rapidly evolving. However, the challenge of individualizing and sequencing treatments remains.
Over the last 30 years researchon metastatic bladder cancer has been slow and limited to chemotherapy. Chemotherapy has provided high initial response rates but very few complete responses that remain overtime. Recently, European medical agency has granted approval to immunotherapy inmetastatic disease. We will review the clinical trials that drove to EMA approval as well as new promising therapies for metastatic bladder cancer.

A search on PubMed and clinicaltrials.gov through the combination of the following words in English and Spanish was performed "carcinoma urotelial","cáncer de vejiga", "localmente avanzado","metastásico", "inmunoterapia", "CTLA-4", "PD1","PDL-1", "atezolizumab", "nivolumab", "ipilimubab", "pembrolizumab", "avelumab", "durvalumab", "tremelimumab", "terapia antiangiogénica", "terapia molecular dirigida" e "inhibidores VEGF".

Cisplatin chemotherapy-based regimens remain standard treatment for metastatic bladder cancer as per phase III trials. click here Immunotherapy is available for cisplatin-ineligible patients with high PD-L1 expression,including atezolizumab or pembrolizumab. Trials comparing immunotherapy, chemotherapy or antiangiogenic drugs o targeted drugs are recruiting.

The publication of the comparative studies on chemotherapy and immunotherapy as well as targeted therapy would provide a window of opportunity for an effective personalized treatment. Those treatment would decrease side-effects as well.
The publication of the comparative studies on chemotherapy and immunotherapy as well as targeted therapy would provide a window of opportunity for an effective personalized treatment. Those treatment would decrease side-effects as well.Radical cystectomy remains as gold standard for treatment of muscle-invasive bladder cancer. Radical cystectomy has a high morbidity and mortalityas sociated even with the new anesthetic and surgical techniques. Some patients are still not candidates for this major surgery. Besides, some patients reject radical cystectomy. Bladder preservation strategies were develop aiming to decrease morbidity and mortality related to major surgery. Bladder preservation allow for improved quality of life and similar oncologic control rates. Radical cystectomy remains as gold standard for treatment of muscle-invasive bladder cancer. Radical cystectomy has a high morbidity and mortality associated even with the new anesthetic and surgical techniques. Some patients are still not candidates for this major surgery. Besides, some patients reject radical cystectomy. Bladder preservation strategies were develop aiming to decrease morbidity and mortality related to major surgery. link2 Bladder preservation allow for improved quality of life and similar oncologic control rates.Bladder preservation has historically been used in 2clinical scenarios 1) Patients unable to under go a radicalcystectomy due to comorbidities o patients that rejectradical cystectomy, and 2) patients that are offeredbladder preservation strategies with and oncologicalsafety and curative intent.This is the real scenario for bladder preservation, thefirst scenario belongs to palliation, not cure.In the current manuscript, we will review the bladderpreservation strategies for muscle invasive bladdercancer, specially focusing on trimodal therapy (recommendedby international guidelines) and tetramodaltherapy.
Fifty percent of muscle-invasive bladder cancer (MIBC) patients succumb from metastatic disease despite radical cystectomy (RC). Neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (ACT) randomized clinical trials (RCT) investigated whether peri-operative chemotherapy improves survival. More recently, immune checkpoint inhibitors (ICI) are explored as peri-operative single agent, ICI-ICI or ICI-chemotherapy combinations. Our goal is to provide the status of neoadjuvant and adjuvant treatment in MIBC.

The literature on NAC and ACT trials in MIBC was reviewed.

Since the 1980s, NAC RCTs were performed in cisplatin-fit patients, mainly using cisplatin combination chemotherapy. Meta-analyses indicated a small, but significant 5% improvement in overall survival in T2-T4N0M0 MIBC patients. Mostly MVAC or gemcitabine-cisplatin (GC) regimens were used without clearbenefit of one regimen over the other. NAC value in N+MIBC is not established and predictive value of associated~25-40% complete downstaging (patecommended alternative for peri-operative treatment. Molecular tumour subtyping will support selecting novel agents for neoadjuvant or adjuvant strategies.
Neoadjuvant MVAC or GC in cT2-T4N0 MIBC patients fit for cisplatin is still recommended based on OS benefit shown in meta-analyses, butreal-world adherence to NAC is low as ~40-50% ofpatients are unfit for cisplatin. The value of neoadjuvant treatment in node-positive MIBC is not clearly demonstrated requiring more accurate clinical staging and prospective studies. Adjuvant cisplatin-based chemotherapy may be considered in selected, chemo-naïve pT3-T4N+patients. Results from prospective checkpoint inhibitor immunotherapy RCTs are needed before immunotherapy becomes a recommended alternative for peri-operative treatment. Molecular tumour subtyping will support selecting novel agents for neoadjuvant or adjuvant strategies.
With increasing survival from bladder cancer, quality of life, should be one of the main goals following radical cystectomy and bilateral pelvic lymph node dissection (PLND). link3 This techniqueis associated with significant morbidity, which may have a critical effect on quality of life. Concerns about functional outcomes, such as continence, potency, and sexual function in women, play a role in decision making for urologists and younger patients with muscle-invasive bladder cancer. Several modifications to the classic radical cystectomy technique, include preservation of genital or pelvic organs, developing in the improvement of postoperative continence, potency rates and sexual functionin female patients.OBJECTIVE This review summarizes the organ-sparing cystectomy techniques and its functional and oncological outcomes.

A PubMed-based literature search was conducted up to April 2020. We selected the most recent and relevant original articles, metanalysis and reviews that have provided relevant information tohout compromising oncological outcomes in well selected patients. But no one of these techniques can be recommended over the classical standard radical cystectomy. Large-scale of prospective and multi-institutional studies are needed to conclude which patients are suitable for these techniques.
Bladder cancer is a frequent, chemosensitive disease and has shown good outcomes on several chemotherapy regimens over last 60 years. However, very little improvement has been shown in terms of overall survival and side-effects decrease.

A review on manuscripts published in English and Spanish from 1949 including the terms chemotherapy and bladder cancer has been performed.

Locally advanced or metastatic bladder cancer chemotherapy was initially introduced for metastasis management. The utilization of cisplatin base regimens has shown superiority over single therapy. The most commonly used regimens are cisplatine-metotrexate-vinblastine, metotrexate-vinblatine-adriamicine-cisplatin y gemcitabine-cisplatin. Neoadjuvant chemotherapy has shown to provide a minimal overall survival advantage, based on level 1 evidence. Neoadjuvant chemotherapy utilizes the same cisplatin-based regimens. Neoadjuvant chemotherapy is underutilized due to the inability to identify non-responders. Adjuvant chemotherapy is more controversial due to the lack of strong evidence.
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