Urothelial carcinoma in COVID-19: lessons from a pandemic and their impact on clinical practice

The COVID-19 pandemic has modified the management of urothelial carcinoma (UC). Eighteen months after the onset of the pandemic, a scoping narrative review was able to state that radical cystectomy for UC should not be delayed beyond 10 weeks when neoadjuvant chemotherapy (NAC) was administered and 12 weeks when it was not. NAC should be considered when imminent chemotherapy cannot be performed. Early cystectomy should not be delayed when indicated for patients with high-risk non-MIBC. Patients with non-MIBC should still receive their induction doses of intravesical instillations. Diagnostic cystoscopy should not be deferred in symptomatic patients. Surgical management of upper tract urothelial carcinoma (UTUC) allows for a wider deferral interval.

Beware of Drug Interactions Treating Iatrogenic Mycobacterium bovis Endocarditis from Intravesical BCG Instillation

We report a case of mechanical mitral valve endocarditis associated with miliary disseminated bacillus Calmette-Guerin (BCG) infection following intravesical instillations for minimally invasive bladder cancer in a 65-year-old man. The diagnosis was established by echocardiographic evidence of vegetation on the prosthetic mitral valve, miliary lesions in the lungs and evidence of bloodstream infection sustained by Mycobacterium. We successfully treated the patient with the classical regimen of quadruple antituberculous therapy.

THE EFFECTIVENESS OF UROTHELIAL APPROACH IN TREATMENT RESISTANT OVERACTIVE BLADDER AND CHRONIC BACTERIAL CYSTITIS, THE HYDROGEL IS ALGINATE SODIUM, BUT ("KOLETEKS-GEL-DNA»)

Гиперактивный мочевой пузырь и хронический бактериальный цистит являются сложным симптомокомплексом, требующим разновекторные подходы в лечении. Факторы риска развития ГАМП приводят к тому, что уротелий путем метаплазии трансформируется из переходного типа эпителия в однослойный кубический. Таким образом, чтобы прервать цикличность симптомокомплекса ГАМП необходимо восстановить нормальный тип уротелия (снова вернув его из кубического в переходный). В исследовании изучали клиническую эффективность терапии указанных нозологий внутрипузырными инстилляциями гидрогелем альгината натрия с деринатом («Колетекс-гель-ДНК») в сочетании с традиционной терапией. Обследование пациентов проводилось врачами-урологами, клинико-лабораторное наблюдение включало в себя определением ОАМ, уровня ИЛ-8 и β-NGF в моче. После завершения лечения выявлены снижение на 45% значений ИЛ-8 и повышение на 35,4% показателей β-NGF в моче у пациентов в исследовании. Такой эффект обусловлен применением традиционной терапии в сочетании с внутрипузырными инстилляциями и свидетельствует о ведущей роли воспалительного компонента не только при ХБЦ, но и при РГАМП, а статистически значимые изменения у ряда пациентов связаны с проведением курса терапии гидрогелем альгината натрия с деринатом («Колетекс-гель-ДНК»), который способствовал регенерации поврежденного слоя уротелия и нормализации его иммунно-защитных свойств. Полученные результаты имеют довольно стойкий эффект и сохраняются в течении последующего 6-ти месячного наблюдения в периоде ремиссии более чем у 90% пациентов, как у пациентов с бактериальным циститом, так и у больных, страдающих гиперактивным мочевым пузырем. Положительный клинический эффект определяется снижением дистрофических и воспалительных реакций в уротелии и усилением локального иммунного ответа мочевого пузыря Overactive bladder and chronic bacterial cystitis are complex symptoms that require different treatment approaches. Risk factors for the development of GAMP lead to the fact that the urothelium is transformed by metaplasia from a transitional type of epithelium to a single-layer cubic one. Thus, to break the cycle of the GAMP symptom complex, it is necessary to restore the normal type of urothelium (again returning it from the cubic to the transitional one). The study studied the clinical effectiveness of treatment of these nosologies with intravesical instillations of sodium alginate hydrogel with derinate ("Coletex-gel-DNA") in combination with traditional therapy. Examination of patients was performed by urologists, clinical and laboratory observation included the determination of OAM, IL-8 and β-NGF levels in the urine. After completion of treatment, a 45% decrease in IL-8 values and a 35.4% increase in β-NGF in the urine of patients in the study were detected. This effect is due to the use of traditional therapy in combination with intravesical instillations and indicates the leading role of the inflammatory component not only in CBC, but also in RGAMP, and statistically significant changes in a number of patients are associated with a course of therapy with sodium alginate hydrogel with derinate ("Coletex-gel-DNA"), which contributed to the regeneration of the damaged urothelium layer and normalization of its immune-protective properties. The results obtained have a fairly stable effect and persist during the subsequent 6-month follow-up in remission in more than 90% of patients, both in patients with bacterial cystitis and in patients suffering from overactive bladder. The positive clinical effect is determined by a decrease in dystrophic and inflammatory reactions in the urothelium and an increase in the local immune response of the bladder

The role of Protopine associated with Nuciferine in controlling adverse events during hyperthermic intravesical chemotherapy instillations. A nutraceutical approach to control adverse event during intravesical instillations

Objectives: The aim of this study was to analyse the role of two alkaloid, Protopine and Nuciferine, in the prevention and the treatment of the low and mild grade adverse events related to the use of HIVEC® (Hyperthermic IntraVEsical Chemotherapy) instillations. Materials and methods: From September 2017 to September 2019, 100 patients were prospectively randomized into two groups: Group A = Protopine and Nuciferine syrup, 10 ml, once a day, for 8 weeks; Group B = placebo (flavoured coloured water), 10 ml, once a day, for 8 weeks. The primary endpoint was the evaluation of the efficacy of the therapy with Protopine and Nuciferine in controlling of the irritative symptoms. The secondary endpoint was the evaluation of the influences of the treatment on the uroflowmetric parameters. Results: The patients of Group A showed a better International Prostatic Symptoms Score (IPSS) score, a better control of urgency symptoms (PPIUS) and tolerate well the pain (VAS score). The treatment doesn’t modify Uroflow-Qmax and seems to improve the Uroflow-Voided Volume (ml) without influencing the Uroflow-Post Void Residual volume (PVR). Moreover, the treatment with Protopine and Nuciferine has been proven to be effective in the treatment of overactive bladder (OAB) symptoms. Patients’ evaluation of the two different treatments assessed with Patient Global Impression of Improvement questionnaire (PGI-I), demonstrated improvements in the Group A, while the Group B showed a lower satisfaction.Conclusions: Protopine and Nuciferine can be interesting nutraceutical compounds useful to control irritative and pain related symptoms of intravesical chemo/immunotherapy.

CyTOF analysis identifies unusual immune cells in urine of BCG-treated bladder cancer patients

High grade non-muscle-invasive bladder tumours are treated with transurethral resection followed by recurrent intravesical instillations of Bacillus Calmette Guérin (BCG). Although bladder cancer patients respond well to BCG, important questions remain unanswered, including how to identify at early stages non-responder patients and patients at risk to abandon the treatment. Here, we analysed the cells released into the urine of bladder cancer patients longitudinally 3-7 days after BCG instillations. Mass cytometry (CyTOF) analyses revealed that most cells were granulocytes and monocytes rather than effector lymphocytes, and most expressed activation markers. A novel population of CD15+CD66b+CD14+ CD16+ cells was very abundant in several samples and expression of these markers was confirmed using flow cytometry and qPCR. Samples of patients with a stronger inflammatory response contained more cells in urine; however, this was not due to haematuria, as the proportions of the cell populations observed were different from blood. We provide the proof-of-concept for a new approach to analyse samples that may help classify patients and identify those at risk of BCG infection and other unwanted BCG-related events.