[A Randomized Controlled Study of Intravesical Instillation Therapy of Bacillus Calmette-Guérin vs. Epirubicinin Treating Non-muscular Invasive Bladder Cancer].

Objective: To explore the best treatment plan of intravesical instillation for patients with non-muscular invasive bladder cancer (NMIBC), to explore recurrence-related clinicopathological factors after intravesical instillation, and to evaluate the value of the prognosis and prediction models currently used for NMIBC patients. Methods: Starting from 2016, patients who underwent transurethral resection of bladder tumor (TURBT) in our hospital and who received post-surgery diagnosis of having intermediate or high risks for NMIBC were enrolled in the study. They were randomly assigned to different group sat a ratio of 2∶2∶1 for receiving intravesical instillation therapy of Bacillus Calmette-Guérin (BCG) for 19 times, BCG for 15 times, and epirubicin (EPI) for 18 times. The clinicopathological data of the patients were recorded before, during and after instillation therapy, and survival curves were drawn to evaluate the effects of the three regimens, using recurrence-free survival as the endpoint. Clinicopathological data were analyzed to study the associations between various factors and post-instillation recurrence. The consistency index (c-index) was used to evaluate the predictive accuracy of the scoring model of the Spanish Urological Club for Oncological Treatment (CUETO) and the risk tables of European Organization for Research and Treatment of Cancer (EORTC). Results: A total of 93 NMIBC patients (35 in the 19-time BCG group, 37 in the 15-time BCG group, and 21 in the EPI group) were included, with a median follow-up time of 33.46 months. Twenty-two patients experienced tumor recurrence and eight, tumor progression. The survival curve showed that the BCG group had better recurrence-free survival than the EPI group ( P=0.002), while the difference in recurrence-free survival between 19-time BCG and 15-time BCG groups was not statistically significant. Higher general complication rate was seen in the BCG groups compared with the EPI group (84.7% vs. 61.9%, P=0.022), but there was no grade 3-5 adverse events in any group. The c-index of CUETO scoring model and EORTC risk tables was higher than that of the prediction based solely on T stage, nuclear grade, or EAU risk stratification. In addition, the c-index in the BCG group was higher than that in the whole cohort. Conclusion: Among the subjects of this study, the recurrence rate of bladder cancer in the intravesical BCG instillation groups was lower than that of the epirubicin group. EORTC risk tables and CUETO scoring model exhibited higher predictive accuracies in BCG-treated patients than its performance for the whole NMIBC cohort.

Aortic aneurysm and aortic graft infection related to Mycobacterium bovis after intravesical Bacille Calmette-Guérin therapy-a case series.

BACKGROUND: So called "mycotic" aortic aneurysms account for only 0.7 to 1.3% of all aortic aneurysms and are commonly caused by Staphylococcus aureus and Salmonella species. Bacillus Calmette-Guérin (BCG), a live attenuated strain of Mycobacterium bovis, is part of the therapy of non-muscle-invasive bladder cancer (NMIBC). CASE PRESENTATION: We report a case series of three patients with a mycobacterial graft infection related to BCG after surgical treatment of a presumed mycotic aortic aneurysm as an extremely rare complication after NMIBC treatment. All three patients developed aortic aneurysm after BCG instillation and subsequent mycobacterial graft infection. CONCLUSION: Diagnosis requires a high degree of suspicion because of its nonspecific symptoms and imaging. The pathogen is not detected by standard microbiological testing. Treatment includes triple antimycobacterial therapy and radical surgical interventions. Graft preservation may be considered if no anastomosis is involved.

Oncology and complications.

This collection of cases describes some unusual urological tumors and complications related to urological tumors and their treatment. Case 1: A case of uretero-arterial fistula in a patient with long-term ureteral stenting for ureteral oncological stricture and a second case associated to retroperitoneal fibrosis were described. Abdominal CT, pyelography, cystoscopy were useful to show the origin of the bleeding. Angiography is useful for confirming the diagnosis and for subsequent positioning of an endovascular prosthesis which represents a safe approach with reduced post-procedural complications. Case 2: A case of patient who suffered from interstitial pneumonitis during a cycle of intravesical BCG instillations for urothelial cancer. The patient was hospitalized for more than two weeks in a COVID ward for a suspected of COVID-19 pneumonia, but he did not show any evidence of SARS-CoV-2 infection during his hospital stay. Case 3: A case of a young man with a functional urinary bladder paraganglioma who was successfully managed with complete removal of the tumor, leaving the urinary bladder intact. Case 4: A case of a 61 year old male suffering from muscle invasive bladder cancer who was admitted for a radical cystectomy and on the eighth postoperative day developed microangiopathic hemolytic anemia and thrombocytopenia, which clinically defines thrombotic microangiopathy.

Protective role of intravesical BCG in COVID-19 severity.

OBJECTIVES: To establish the role of BCG instillations in the incidence and mortality of COVID-19. PATIENTS AND METHODS: NMIBC patients in instillations with BCG (induction or maintenance) during 2019/2020 were included, establishing a COVID-19 group (with a diagnosis according to the national registry) and a control group (NO-COVID). The cumulative incidence (cases/total patients) and the case fatality rate (deaths/cases) were established, and compared with the national statistics for the same age group. T-test was used for continuous variables and Fisher's exact test for categorical variables. RESULTS: 175 patients were included. Eleven patients presented CIS (11/175, 6.3%), 84/175 (48.0%) Ta and 68/175 (38.9%) T1. Average number of instillations = 13.25 ± 7.4. One hundred sixty-seven patients (95.4%) had complete induction. Forty-three patients (cumulative incidence 24.6%) were diagnosed with COVID-19. There is no difference between COVID-19 and NO-COVID group in age, gender or proportion of maintenance completed. COVID-19 group fatality rate = 1/43 (2.3%). Accumulated Chilean incidence 70-79 years = 6.3%. Chilean fatality rate 70-79 years = 14%. CONCLUSIONS: According to our results, patients with NMIBC submitted to instillations with BCG have a lower case-fatality rate than the national registry of patients between 70 and 79 years (2.3% vs. 14%, respectively). Intravesical BCG could decrease the mortality due to COVID-19, so instillation schemes should not be suspended in a pandemic.

[Complete Transurethral Resection of Large Non-Muscle-Invasive Bladder Cancer Preoperatively Suspected to Be Muscle-Invasive Disease : A Case Report and Literature Review].

A 69-year-old man presented with gross hematuria. Cystoscopy revealed a large papillary tumor occupying the bladder. Magnetic resonance imaging showed a large bladder tumor more than 8cm in maximum diameter,suspected to be muscle-invasive disease. We performed the 1st transurethral resection of bladder tumor (TURBT) for the main purpose of pathological confirmation. Histopathological findings of the resected specimens showed urothelial carcinoma,low grade pTa. We performed subsequent treatments with TURBT twice,resulting in complete resection. The histopathological findings showed the same results as those of the 1st TURBT conclusively,which was consistent with non-muscle-invasive bladder cancer. He received intravesical instillation of pirarubicin eight times in total and has remained free from recurrence for more than 26 months after the final TURBT.

Prosthetic hip joint infection by Bacillus Calmette-Guerin therapy following intravesical instillation for bladder cancer identified using whole-genome sequencing: a case report.

BACKGROUND: Joint replacement is an effective intervention and prosthetic joint infection (PJI) is one of the most serious complications of such surgery. Diagnosis of PJI is often complex and requires multiple modalities of investigation. We describe a rare cause of PJI which highlights these challenges and the role of whole-genome sequencing to achieve a rapid microbiological diagnosis to facilitate prompt and appropriate management. CASE PRESENTATION: A 79-year-old man developed chronic hip pain associated with a soft-tissue mass, fluid collection and sinus adjacent to his eight-year-old hip prosthesis. His symptoms started after intravesical Bacillus Calmette-Guerin (BCG) therapy for bladder cancer. Synovasure™ and 16S polymerase chain reaction (PCR) tests were negative, but culture of the periarticular mass and genome sequencing diagnosed BCG infection. He underwent a two-stage joint revision and a prolonged duration of antibiotic therapy which was curative. CONCLUSIONS: BCG PJI after therapeutic exposure can have serious consequences, and awareness of this potential complication, identified from patient history, is essential. In addition, requesting appropriate testing is required, together with recognition that traditional diagnostics may be negative in non-pyogenic PJI. Advanced molecular techniques have a role to enhance the timely management of these infections.

Hybrid operation for infectious thoracic and abdominal aortic aneurysms complicated with Bacillus Calmette-Guérin therapy for bladder cancer: A case report.

RATIONAL: Bacillus Calmette-Guérin (BCG) intravesical instillation therapy is a widely used treatment for bladder cancer; however, an infectious aneurysm has been reported as a rare complication. PATIENT CONCERNS: A 76-year-old man who underwent BCG intravesical instillation therapy for bladder cancer presented with prolonged dull back pain for 3 months. DIAGNOSIS: Computed tomography (CT) revealed both thoracic and abdominal aortic aneurysms (AAAs). Follow-up CT at 4 weeks after the initial examination showed rapid enlargement of both aneurysms and typical findings of inflammation. Therefore, he was diagnosed with an impending rupture of infectious aneurysms. INTERVENTIONS: Although open surgical resection of both aneurysms and vascular reconstruction were ideal, these operations were considered highly invasive for the patient. Therefore, a hybrid operation consisting of simultaneous endovascular repair of the thoracic aneurysm and open surgery of the abdominal lesion was performed. OUTCOMES: BCG "Tokyo-172" strain was identified in the resected sample from the aneurysmal wall, and he continued to receive oral antituberculosis drugs for 6 months. No sign of recurrent infection was observed 1 year after the operation. LESSONS: A hybrid operation might be justified as an alternative to the conventional open surgical procedure, especially for patients with infectious aneurysms caused by weak pathogenic bacteria such as, the BCG mycobacteria.

The clinicopathological characteristics of muscle-invasive bladder recurrence in upper tract urothelial carcinoma.

This study aimed to clarify the clinical characteristics and oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) who developed muscle-invasive bladder cancer (MIBC) after radical nephroureterectomy (RNU). We identified 966 pTa-4N0-2M0 patients with UTUC who underwent RNU and clarified the risk factors for MIBC progression after initial intravesical recurrence (IVR). We also identified 318 patients with primary pT2-4N0-2M0 MIBC to compare the oncological outcomes with those of patients with UTUC who developed or progressed to MIBC. Furthermore, immunohistochemical examination of p53 and FGFR3 expression in tumor specimens was performed to compare UTUC of MIBC origin with primary MIBC. In total, 392 (40.6%) patients developed IVR after RNU and 46 (4.8%) developed MIBC at initial IVR or thereafter. As a result, pT1 stage on the initial IVR specimen, concomitant carcinoma in situ on the initial IVR specimen, and no intravesical adjuvant therapy after IVR were independent factors for MIBC progression. After propensity score matching adjustment, primary UTUC was a favorable indicator for cancer-specific death compared with primary MIBC. Subgroup molecular analysis revealed high FGFR3 expression in non-MIBC and MIBC specimens from primary UTUC, whereas low FGFR3 but high p53 expression was observed in specimens from primary MIBC tissue. In conclusion, our study demonstrated that patients with UTUC who develop MIBC recurrence after RNU exhibited the clinical characteristics of subsequent IVR more than those of primary UTUC. Of note, MIBC subsequent to UTUC may have favorable outcomes, probably due to the different molecular biological background compared with primary MIBC.

Colistina intravesical en el tratamiento de la infección urinaria complicada por Klebsiella pneumoniae BLEE OXA-48 / Intravesical colistin as treatment of complicated urinary infection due to Klebsiella pneumoniae BLEE OXA-48

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[Minimally invasive methods of treatment of interstitial cystitis/painful bladder syndrome].

Interstitial Cystitis (IC) or Painful Bladder Syndrome (PBS) is a heterogeneous disease which pathogenetic mode development is not fully studied. In the presented literature review IC/PBS is considered as urothelial dysfunction. The main issues discussed relate to IC/PBS diagnosis and minimally invasive methods of its treatment including intravesical instillations of therapeutic agents, botulinum toxin injections into bladder wall and hydrodistension. Efficacy of the above therapeutic methods is far from the desired what gives rise to search novel minimally invasive technologies and protocols to improve the outcomes of traditional treatment methods.

[A new approach to understanding the pathogenesis and treatment of infectious and inflammatory diseases of the urogenital tract].

The current trends in understanding the pathogenesis of infectious and inflammatory urogenital disorders are highlighted in the review. The etiological and pathogenetic significance of increased intestinal permeability for pathogens in the development of various diseases has been convincedly proved. There is no doubt about the pathogenetic role of increased permeability of the bladder mucosa, which can result in interstitial cystitis (IC). The association of intestinal diseases with IC has been established. In rats, the induction of intestinal inflammation may cause increased permeability of the bladder mucosa. In the postoperative period, bacteria are translocated from the gastrointestinal tract to the urinary tract, which is associated with stress. Particular attention is paid to the therapy based on new knowledge about the pathogenesis of infectious and inflammatory diseases of the urogenital tract. Possibilities of decreasing intestinal and bladder permeability using rebamipide are described. Various therapeutic mechanisms of action made it possible to use this drug in endoscopy, ophthalmology, chemotherapy and rheumatology. The antioxidant and anti-inflammatory properties of rebamipide has been shown in-vitro. Intravesical instillation of rebamipide accelerates the recovery of damaged urothelium and its barrier function, and also influences on bladder hyperactivity. Thus, the first results of using rebamipide in urology are encouraging; however, further researches are required.

[BCGitis following intravesical administration of bacillus Calmette-Guérin]. / « BCGite ¼ secondaire à l'instillation intravésicale de bacilli de Calmette-Guérin.

Intravesical bacillus Calmette-Guérin immunotherapy is currently the most effective treatment for non-infiltrating bladder tumors. Although rare, « BCGitis ¼, local or disseminated, is a serious complication of this therapy. The diagnosis is difficult and often delayed but the infection may progress to multi-systemic failure and can be fatal. The microbiological samples are often negative, and biopsies sometimes do not help. Treatment consists of antimycobacterial agents in combination with corticosteroids in case of severe presentation.

Instilación intravesical de ácido hialurónico y sulfato de condroitina para infecciones recurrentes del tracto urinario / Intravesical instillation of hyaluronic acid and chondroitin sulfate for recurrent urinary tract infections

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Disseminated Bacillus Calmette-Guérin (BCG) infection and acute exacerbation of interstitial pneumonitis: an autopsy case report and literature review.

BACKGROUND: Intravesical administration of Bacillus Calmette-Guérin (BCG) has proven useful for treatment and prevention of recurrence of superficial bladder cancer and in situ carcinoma. However, fatal side effects such as disseminated infections may occur. Early diagnosis and accurate therapy for interstitial pneumonitis (IP) are important because exacerbation of IP triggered by infections is the major cause of death. Although some fatality reports have suggested newly appeared IP after intravesical BCG treatment, to our knowledge, there are no reports which have demonstrated acute exacerbation of existing IP. Moreover, autopsy is lacking in previous reports. We report the case of a patient with fatal IP exacerbation after BCG instillation and the pathological findings of the autopsy. CASE PRESENTATION: A 77-year-old man with a medical history of IP was referred to our hospital because of fever and malaise. He had received an intravesical injection of BCG 1 day before the admission. His fever reduced after the use of antituberculosis drugs, so he was discharged home. He was referred to our hospital again because of a high fever 7 days after discharge. On hospitalisation, he showed high fever and systemic exanthema. Hepatosplenomegaly and myelosuppression were also observed. Biopsies revealed multiple epithelioid cell granulomas with Langhans giant cells of the liver and bone marrow. Biopsy DNA analyses of Mycobacterium bovis in the bone marrow, sputum, and blood were negative. His oxygen demand worsened drastically, and the ground-glass shadow expanded on the computed tomography scan. He was diagnosed with acute exacerbation of existing IP. We recommenced the antituberculosis drugs with steroid pulse therapy, but he died on day 35 because of respiratory failure. The autopsy revealed a diffuse appearance of multiple epithelioid cell granulomas with Langhans giant cells in multiple organs, although BCG was not evident. CONCLUSIONS: We report the first case of acute exacerbation of chronic IP by BCG infection. This is also the first case of autopsy of a patient with acute exacerbation of existing IP induced by intravesical BCG treatment. Whether the trigger of acute IP exacerbation is infection or hypersensitivity to BCG is still controversial, because pathological evidence confirming BCG infection is lacking. Physicians who administer BCG against bladder cancer should be vigilant for acute exacerbation of IP.

Randomized Study of Postoperative Single Intravesical Instillation With Pirarubicin and Mitomycin C for Low-risk Bladder Cancer.

BACKGROUND: To assess the prophylactic efficacy of postoperative single intravesical instillation with pirarubicin (THP) and mitomycin C (MMC) for low-risk non-muscle-invasive bladder cancer (NMBC). PATIENTS AND METHODS: A total of 103 clinically low-risk NMBC patients were preoperatively randomized into either THP (n=49) or MMC (n=54) groups. The primary endpoint was recurrence-free survival. RESULTS: The median follow-up periods of the THP and MMC groups were 955 and 1008 days, respectively (p=0.76). Twelve patients (24.5%) in the THP group and 7 (13%) in the MMC group had bladder cancer recurrences. The two-year recurrence-free survival of the THP group and the MMC group was 77.8% and 86.4%, respectively (p=0.20). Neither groups had severe toxicity. CONCLUSION: In low-risk NMBC, the prophylactic effect against postoperative single intravesical instillation with THP was not superior to that with MMC.

[Rupture of Tuberculous Infective Abdominal Aortic Aneurysm after Intravesical Bacillus Calmette-Guérin Instillation Therapy].

The patient was a 74-year-old male who had undergone intravesical Bacillus Calmette-Guérin(BCG) instillation therapy for bladder cancer. He visited our hospital with chief complaints of fever and abdominal pain. Abdominal aortic aneurysmal rupture and iliopsoas muscle abscess were confirmed by computed tomography( CT). We performed semi-emergency surgery, including replacement of the abdominal aorta with a synthetic graft, iliopsoas abscess debridement, and omentopexy. A rifampicin-bonded synthetic graft was used because of the possibility of tuberculous involvement after BCG instillation therapy. Examination of the tissues collected during surgery were positive for tuberculosis deoxyribonucleic acid (DNA) in a polymerase chain reaction (PCR), and showed multiple giant cell granulomas with caseous necrosis, which both strongly suggested involvement of tuberculosis. Therefore, 4 types of antituberculous drugs were administered for 40 days. This case shows that an infective aneurysm should be suspected when fever and abdominal pain develop after intravesical BCG instillation therapy.

Efficacy and safety of Bacillus Calmette-Guerin for bladder cancer: A protocol of systematic review.

BACKGROUND: This study will systematically assess the efficacy and safety of Bacillus Calmette-Guerin (BCG) for patients with bladder cancer (BC). METHODS: Literature searches will be performed in multiple electronic databases from inception to present: MEDLINE, EMBASE, CINAHL, Science Direct, Cochrane Library, Web of Science, and China National Knowledge Infrastructure. We will also examine grey literature through identifying conference proceedings, thesis, dissertations, and website of clinical trials registry. Two investigators will independently scan all citation titles, abstracts, and full-text studies. The study quality will be assessed by Cochrane Risk of Bias Tool. If possible, we will perform meta-analysis. Additional analyses will be carried out to test the potential sources of heterogeneity among included trials. RESULTS: The present study will summarize high quality trials on investigating the efficacy and safety of BCG for patients with BC. CONCLUSION: The results of this study will supply helpful evidence to determine whether BCG is effective or not for BC. STUDY REGISTRATION NUMBER: INPLASY202070042.