Improving compliance with guidelines may lead to favorable clinical outcomes for patients with non-muscle-invasive bladder cancer: A retrospective multicenter study.

OBJECTIVES: Clinical guidelines recommend that patients with non-muscle-invasive bladder cancer (NMIBC) should be treated with appropriate adjuvant therapy. However, compliance with guideline recommendations is insufficient, and this may lead to unfavorable outcomes. We aimed to investigate the level of adherence to guideline recommendations in patients with NMIBC and evaluate the outcomes of those who did and did not receive guideline-recommended therapies. METHODS: We performed a retrospective analysis of patients with histologically diagnosed NMIBC. The percentage of patients with intermediate- and high-risk tumors who received adjuvant intravesical therapy or second transurethral resection (TUR) was calculated. Recurrence-free survival was assessed in patients who did and did not receive the therapies. We conducted a propensity score-matched analysis to compare outcomes between patients with intermediate-risk and T1 NMIBC who did and did not undergo guideline-recommended therapies. RESULTS: Overall, 1204 patients from the Tohoku Urological Evidence-Based Medicine Study Group and Kyoto University Hospital were included. Of patients with intermediate- and high-risk tumors, 91.0% and 74.0% did not receive maintenance bacillus Calmette-Guérin (BCG), respectively. In both groups, significantly better recurrence-free survival was found for patients treated with maintenance BCG. Among patients with T1 NMIBC, only 16.7% underwent guideline-recommended therapies, that is, a second TUR and maintenance BCG. Significantly greater recurrence-free survival was observed in patients who received guideline-recommended therapies compared with propensity-matched patients who did not. CONCLUSIONS: Guideline-recommended therapies may contribute to improvements in outcomes for patients with NMIBC, suggesting that improvements in adherence to clinical guidelines may lead to favorable outcomes.

Guillain-Barré Syndrome following intravesical Bacillus Calmette-Guérin therapy for bladder cancer: a rare and intriguing case report.

Intravesical Bacillus Calmette-Guérin (BCG) therapy is a standard treatment for non-muscle invasive bladder cancer, but some patients experience side effects that lead to treatment discontinuation. Local side effects are typically mild, while systemic side effects can be severe and life-threatening. BCG therapy has immunotherapy effects on bladder cancer, but the mechanism is not fully understood. Due to its effect on the immune system, patients may also develop rare autoimmune complications, such as neuropathy. This case report suggests a potential association between BCG therapy and Guillain-Barré Syndrome (GBS), as a patient developed GBS after receiving intravesical BCG therapy for invasive bladder cancer.

Effects of acupuncture to decrease adverse events in patients with high-risk non-muscle invasive bladder cancer receiving induction intravesical BCG therapy: Study protocol for a randomized, controlled pilot and feasibility study.

Background: Treatment-related serious adverse events (SAEs) are common in patients receiving intravesical Bacillus Calmette-Guerin (BCG) for the treatment of high-risk nonmuscle-invasive bladder cancer (NMIBC). Here we describe the protocol of a randomized, attention/waitlist-controlled feasibility pilot study testing the use of acupuncture to decrease SAEs and treatment interruptions in this population. The primary objectives are to evaluate the feasibility and efficacy of conducting pre-procedure acupuncture in a Urology Clinic. Methods: A total of 45 patients will be recruited and randomized in a 2:1 ratio (treatment arm: attention/waitlist control). Eligibility criteria include 1) age 18 years or older, 2) English-speaking, 3) high-risk NMIBC, 4) no acupuncture in the previous 3 months, and 5) willing and able to participate in trial activities. Patients in the treatment arm will receive acupuncture prior to weekly BCG for a total of six weeks. Methods were developed to train and monitor research acupuncturists and included online and in-person training, study manuals, and monthly meetings throughout the study period. Feasibility assessments include evaluation of the recruitment, retention and protocol adherence to acupuncture treatment, and measurement of CTCAE v5.0 adverse events specific to acupuncture, and clinic staff surveys regarding the intervention impact on clinic workflow. Efficacy measures will be compared between treatment and control groups including: EORTC-QLQ-NMIBC-24, EORTC-QLQ-C30, CTCAE v5.0, medication journal, healthcare utilization, current use of complementary, alternative, and integrative therapies, and acupuncture expectancy and treatment preference. Trial results will inform the design of a multi-center trial to expand testing of the protocol to a larger patient cohort.

How to reduce bacillus Calmette-Guérin discontinuation in patients with severe functional impairment.

Background: Severe functional impairment is often considered a contraindication to intravesical therapy for nonmuscle-invasive bladder cancer (NMIBC). A tailored intravesical bacillus Calmette-Guérin (BCG) procedure was evaluated in high-risk (HR)-NMIBC patients with severe functional impairment. Materials and methods: Patients with a Katz Index score of 2 or less and an initial diagnosis of HR-NMIBC with atraumatic insertion of a Foley-type indwelling catheter, bladder emptying, and BCG instillation were prospectively treated; after 2 hours, the bladder was emptied and the catheter was removed (group A).After propensity score matching, 52 patients in group A were compared with that of 52 consecutive patients in group B using a retrospective database, with similar baseline/oncological characteristics and treated with standard intermittent catheterization. Moreover, groups A and B were compared with that of 130 consecutive patients (group C) retrospectively evaluated, with similar oncological characteristics but with a Katz Index score of 3 or greater and treated with standard intermittent catheterization. Results: The discontinuation rates were 11.5%, 35%, and 9% in groups A, B, and C, respectively (A vs. B, log-rank score 42.52 [p < 0.05]; B vs. C, 107.6 [p < 0.05]; A vs. C, 3.45 [p > 0.05]). The overall adverse event rates were 38.5%, 57.7%, and 39.2%, respectively (A vs. B, p = 0.04; B vs. C, 0.03; A vs. C, 0.92). The rates of severe adverse events were 1.9%, 1.9%, and 1.5%, respectively, without statistically significant differences. The cumulative HR disease-free survival rates were 63.4%, 48%, and 69.2%, respectively (A vs. B, log-rank score 154.9 [p < 0.05]; B vs. C, 415 [p < 0.05]; A vs. C, 244 [p < 0.05]). Conclusions: A tailored intravesical instillation procedure may reduce BCG discontinuation and adverse effects.

Two-stage posterior decompression and fusion for tuberculous spondylitis after intravesical bacillus Calmette-Guerin instillation.

Intravesical bacillus Calmette-Guerin (BCG) instillation is an effective treatment for nonmuscle invasive superficial bladder cancer. BCG induces a massive influx of inflammatory cells and production of cytokines in the bladder mucosa and lumen that leads to an immune response against tumor cells, acting as an immunotherapy. Cystitis, bladder ulceration, and bladder contracture are known local genitourinary complications, whereas systemic complications such as miliary pulmonary tuberculosis, mycotic aneurysms, tuberculous spondylodiscitis, and granulomatous hepatitis are very rare. A case of tuberculous spondylodiscitis at the T8 and T9 levels following intravesical BCG instillation for bladder carcinoma is reported. The patient initially underwent decompressive laminectomy for spastic paraparesis. After reporting improvement for few weeks, the patient again presented with similar complaints and was found to have an increased kyphotic deformity, for which he underwent fixation surgery.

A rare case of synchronous bilateral epididymal and testicular metastases of urothelial carcinoma of the bladder after intravesical bacillus Calmette-Guérin.

A 68-year-old man was diagnosed with non-muscle-invasive bladder cancer and underwent transurethral resection of the bladder tumor (TURBT) in June 2014. The pathological diagnosis was urothelial carcinoma (UC), Grade 2, pT1. He was treated with intravesical bacillus Calmette-Guérin (BCG) instillation after TURBT. In February 2016, he received anti-tuberculosis treatment for systemic BCG infection, and tuberculosis treatment was continued. In September 2018, he presented with bilateral scrotum swelling and underwent bilateral orchiectomy following a diagnosis of antituberculotics-resistant epididymitis. The pathological findings were metastatic UC of the bilateral epididymis and testis. One months later, fluorodeoxyglucose-positron emission tomography/computed tomography showed para-aortic lymph node and peritoneal metastases. He was treated with chemotherapy of gemcitabine and cisplatin. We herein report a very rare case of synchronous metastatic UC of the bilateral epididymis and testis after intravesical BCG treatment.

Intestinal ulcers induced by intravesical bacillus Calmette-Guérin therapy.

Intravesical bacillus Calmette-Guérin (iBCG) therapy, one of the established treatments for bladder carcinoma, is known for its association with adverse events, including rheumatic manifestations. We describe the case of a 72-year-old man with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome who developed inflammatory bowel disease unclassified after iBCG therapy for bladder carcinoma. The critical role of the IL-23/IL-17 axis in the pathogenesis IBD and all the domains of SAPHO syndrome has been reported previously. In the present case, the activation of the IL-23/IL-17 axis, probably due to the disease, could have been exacerbated by iBCG therapy, as observed in mice that received BCG immunotherapy. We suggest that patients with rheumatic diseases on iBCG therapy should be observed carefully since iBCG could be a contributing factor for autoimmune pathology including IBD.

Reactive Arthritis - A Rare Complication of Intravesical BCG Instillation.

Reactive arthritis (ReA) with the classic triad of arthritis, conjunctivitis and urethritis, previously termed Reiter's syndrome, is a systemic illness, usually induced by genitourinary or gastrointestinal infections. However, it can be a rare complication of intravesical Bacillus Calmette-Guérin instillation (iBCG), a therapy prepared from attenuated strains of Mycobacterium bovis, a common and effective treatment for carcinoma in situ of the bladder (CisB). We report a case of a patient with CisB who developed ReA after iBCG. The symptoms resolved completely with corticosteroids. iBCG was stopped with no recurrence of carcinoma within 2 years. LEARNING POINTS: ReA is an aseptic arthritis, usually triggered by genitourinary or gastrointestinal infections, generally in individuals positive for HLA-B27.Septic arthritis and microcrystalline arthritis can mimic ReA and they must be ruled out with arthrocentesis.ReA may be considered as a complication in patients under iBCG.

Intravesical Bacillus Calmette-Guérin (BCG) treatment's severe complications: A single institution review of incidence, presentation and treatment outcome.

OBJECTIVES: Intravesical Bacillus Calmette-Guérin (BCG) treatment for superficial bladder cancer is interrupted in approximatively 8% of cases as a result of complications. The objective is to report the severe related complications of Bacillus Calmette-Guérin (BCG) following an intravesical instillation for bladder tumor encountered at our institution for the past 5 years. METHODS: Medical records of a tertiary teaching hospital, located in Beirut, Lebanon, were retrospectively analyzed from June 2014 to June 2019 searching for severe related complications of BCG. A comprehensive review of articles on this subject was conducted. RESULTS: The incidence of severe systemic adverse events related to BCG instillation was 1.5% (5 out of 332 patients). A total of five patients were found to have a severe BCG related complication, with fever, chills, and irritative urinary signs being the most frequent symptoms. All patients received antituberculosis therapy (Isoniazid, Rifampin and Ethambutol). Two were put on add-on corticosteroids. Three patients had a computed tomography scan image in favor of an infection. Two patients had a favorable outcome, three patients died. CONCLUSION: BCG severe adverse events were mostly seen in patients with a traumatic instillation. Treatment used at our institution was similar to most cases reported in the literature. A standardized diagnostic and treatment approach should be implemented to help physicians tackle these life-threatening complications.

Emerging concepts and spectrum of renal injury following Intravesical BCG for non-muscle invasive bladder cancer.

BACKGROUND: Intravesical Bacilli Calmette-Guerin (IVBCG) therapy for non-muscle invasive bladder cancer (NMIBC) has long been in use successfully. Albeit rarely, we still face with its safety concerns more than 25 years on since its approval by US Food and Drug Agency in 1990. Local and systemic infection following intravesical BCG is widely reported as compared to immune mediated local or systemic hypersensitivity reactions involving kidneys; acute kidney injury (AKI) and other renal manifestations are well reported but not of chronic kidney disease (CKD). CASE: An interesting case of a female was referred to nephrologists in advanced stages of CKD at an eGFR of 10 ml/min/1.732 following IVBCG for NMIBC. Our patient's renal function plateaued when IVBCG was held; and worsened again when reinstilled. It introduces the concept of 'repetitive' immune mediated renal injury presenting as progressive CKD rather than AKI, as is generally reported. Although response was poor, corticosteroids stopped CKD progression to end stage renal disease. CONCLUSIONS: We highlight the need for increased awareness and early recognition of IVBCG renal complications by both urologists and nephrologists in order to prevent progressive and irreversible renal damage. Low incidence of IVBCG renal complications may also be due to under recognition in the era prior to CKD Staging and AKI Network (and AKI e-alerts) that defined AKI as a rise in serum creatinine of ≥26umol/L; hence an unmet need for urgent prospective studies. Major literature review focuses on emerging spectrum of histopathological IVBCG related renal complications and their outcomes.

Disfunción orgánica múltiple como complicación de la instilación intravesical de bacilo de Calmette-Guérin: comunicación de un caso y revisión de la literatura / Multiple organ dysfunction as a complication of Bacille Calmette-Guérin intravesical instillation (BCG): report of a case an literature review

La instilación intravesical de bacilo de Calmette-Guérin (BCG) es el tratamiento de primera línea para el carcinoma superficial de células transicionales de la vejiga. Aunque su uso es relativamente seguro, complicaciones graves como hepatitis granulomatosa, osteomielitis, neumonía, sepsis y disfunción orgánica múltiple se producen en algunos pacientes. Presentamos el caso de un paciente con diagnóstico de carcinoma de células de transición superficial de la vejiga (T1), que fallece como consecuencia de una complicación sistémica grave con severo compromiso del sistema nervioso central, secundaria a la instilación intravesical de BCG.

Bacille Calmette-Guérin intravesical instillation (BCG) is the main treatment for superficial transitional cell carcinoma of the bladder. In spite of it being a safe procedure, severe complications as granulomatous hepatitis, osteomyelitis, pneumonia, sepsis and multiple organ dysfunction syndrome occur in a few patients. The study presents the case of a patient with a diagnosis of superficial transitional cell carcinoma of the bladder (T1), who died as a consequence of a severe systemic compromise of the central nervous system, secondary to instravesical instillation of BCG.

A instilação intravesical de bacilo de Calmette-Guérin (BCG) é o tratamento de primeira linha para o carcinoma superficial de células transicionais de bexiga. Embora seu seja relativamente seguro, as complicações graves como hepatite granulomatosa, osteomielite, pneumonia, sepse e disfunção orgânica múltipla possam ocorrem em alguns pacientes. Apresentamos o caso de um paciente com diagnóstico de carcinoma de células de transição superficial de bexiga (T1), que falece como consequência de uma complicação sistêmica grave com severo compromisso do Sistema Nervoso Central, secundária à instilação intravesical de BCG.

Determining optimal maintenance schedules for adjuvant intravesical bacillus Calmette-Guerin immunotherapy in non-muscle-invasive bladder cancer: a systematic review and network meta-analysis.

OBJECTIVES: To figure out optimal bacillus Calmette-Guerin (BCG) maintenance schedules for non-muscle-invasive bladder cancer (NMIBC) patients by comparing different schedules in a systematic review using conventional and network meta-analysis. MATERIALS AND METHODS: Literature was searched in the databases of Medline, Embase, Cochrane library, Clinicaltrials.gov, Wanfang, CNKI and SinoMed in April 2016 and 9 randomized clinical trials comparing intravesical BCG maintenance therapy with BCG induction-only therapy or comparing different BCG maintenance schedules (induction-only, 1 year, 1.5 year, 2 year, 3 year maintenance) in NMIBC patients were included. Conventional and network meta-analyses within a Bayesian framework were performed to calculate odds ratios of tumor recurrence, progression and side effects (cystitis, hematuria, general malaise and fever). The surface under the cumulative ranking curve (SUCRA) mean ranking was used to obtain schedule hierarchy. RESULTS: Data from 1951 patients showed that longer-term maintenance BCG therapy does not significantly decrease tumor recurrence and progression rate of NMIBC compared to shorter-term maintenance BCG therapy. However, longer-maintenance therapy does not increase side effect incidence compared to induction-only therapy. According to SUCRA results, induction-only therapy has the highest probability of recurrence and progression but least probability of side effects. CONCLUSIONS: Longer BCG maintenance therapy (such as 3 years) is not superior to shorter maintenance therapy (such as 1 year). But maintenance therapy overall is better than induction-only BCG therapy while not increasing side effects. Though further evidence and clinical practice with balanced confounding factors (risk stratification and BCG strain) are wished for, the current study suggests the common use of 1 year intravesical BCG instillation for NMIBC patients.

Asymptomatic renal BCG granulomatosis: An unusual complication of intravesical BCG therapy for carcinoma urinary bladder.

Bacillus Calmette-Guerin (BCG) is considered the most effective adjunctive treatment available to treat superficial bladder carcinoma. Although BCG is well tolerated by most patients, it may be associated with adverse effects. One of these is BCG granulomas in the kidney. We herein report a case of a 52-year-old patient who, during a surveillance contrast-enhanced computed tomography (CT) scan, was found to have multiple hypodense lesions in the left kidney. Ultrasound-guided biopsy proved it to be BCG granulomas. After 3 months of anti-tubercular treatment, a repeat CT showed complete resolution of the lesions.

A Pseudoaneurysm of the Left Internal Iliac Artery after Intravesical Bacillus Calmette-Guerin Therapy / 日本心臓血管外科学会雑誌

We report a case of pseudoaneurysm of the left internal iliac artery after intravesical Bacillus Calmette-Guerin (BCG) therapy for bladder cancer. A 75-year-old man was referred to us with lumbar pain and recurring fever. One year previously he was treated for bladder cancer with transurethral resection, followed by adjuvant intravesical BCG therapy lasting 11 months. Computed tomography scanning demonstrated a pseudoaneurysm and perianeurysmal inflammatory changes in the region of the left internal iliac artery. An emergency operation was performed under a diagnosis of impending rupture of the tuberculous left internal iliac arterial aneurysm. Because of the urinary tract stenosis, which was caused by the aneurysm, we inserted a ureteral stent preoperatively. We performed aneurysmectomy and femorofemoral cross over bypass. After 10 months of antituberculous chemotherapy, CT showed no recurrence of infectious aneurysm. Although intravesical BCG therapy is generally considered safe, serious complications including vascular complication have been reported. A mycotic origin should be considered when an aneurysm is discovered after BCG therapy. The prophylactic use of a ureteral stent in mycotic iliac arterial surgery may lead to minor complications.

Bacillary prostatitis after intravesical immunotherapy: a rare adverse effect.

Nowadays, the most efficient form of intravesical immunotherapy for superficial transitional cell carcinoma of the urinary bladder is the instillation of bacillus Calmette-Guérin (BCG), proceeding from an attenuated strain of Mycobacterium bovis. In up to 40% of cases, its instillation is associated with significantly elevated prostate-specific antigen (PSA) levels. In these cases, prostate biopsy should be withheld for 3 months and PSA should be monitored. Bacillary prostatitis is a rare occurrence in patients treated with intravesical BCG immunotherapy. Although symptomatic bacillary prostatitis is even rarer, it is the worst type of this condition. The aims of this study are to report a case of bacillary prostatitis as a rare adverse effect of intravesical BCG immunotherapy and to make a theoretical review about how to manage this complication. A 58-year-old man, former smoker, underwent a transurethral resection of the bladder in February 2004 because of a papillary transitional cell carcinoma of the bladder (pT1G2N0M0). After surgery, BCG instillation therapy was given in a total of 15 instillations, the last one in March 2007. In the last 3 months of therapy, until May 2007, a progressive increase in his PSA level was registered, and he underwent a prostate biopsy revealing granulomatous prostatitis of bacillary etiology. The semen culture was positive for M. bovis. After 3 months of a two-drug (isoniazid and rifampin) antituberculous regimen, the semen culture became negative and the PSA level decreased. The early identification of intravesical BCG immunotherapy complications allows their effective treatment. However, when a histological diagnosis of asymptomatic granulomatous prostatitis is made, the execution and type of treatment are controversial.

"BCGitis": A rare case of tuberculous epididymo-orchitis following intravesical Bacillus Calmette-Guérin therapy.

Tuberculous epididymo-orchitis is a rare complication of intravesical Bacillus Calmette-Guérin (BCG) therapy for urothelial cancer of the bladder. We present such a case, describe its sonographic appearance and review the literature. The difficulties in diagnosing this condition based on imaging alone, given the extensive overlap with the appearance of bacterial epididymo-orchitis, malignant testicular disease and testicular torsion, are discussed. Adequate knowledge of tuberculous epididymo-orchitis is of capital importance in order to ensure a proper diagnosis and treatment.

Assessment of angiogenic factor, vascular endothelial growth factor, serum and urine level changes in superficial bladder tumor immunotherapy by intravesical Bacillus Calmette-Guerin.

BACKGROUND AND AIM: Bladder tumor is one of the most common genitourinary tumors. Management of non-muscle invasive (NMI) bladder tumors is primarily by transurethral resection (TURBT) followed by intravesical immunotherapy or chemotherapy. Bacillus Calmette-Guerin (BCG) is the most effective adjuvant therapy in NMI bladder tumor. Since angiogenesis is an essential factor in solid tumor progression and vascular endothelial growth factor (VEGF) is an important factor in angiogenesis, the aim of this study is the assessment of angiogenic factor, VEGF, serum and urine level changes in superficial bladder tumor immunotherapy by intravesical BCG. MATERIALS AND METHODS: A total of 23 patients with bladder transitional cell carcinoma (TCC) in stage Ta/T1 or carcinoma insitu (CIS), low or high grade, which passed a 2-4 week period from TURBT participated in this study. Blood and urine samples were obtained at first and sixth sessions before instillation of BCG. Enzyme-linked immunosorbent assay (ELISA) method was used to obtain VEGF level in samples. RESULTS: Urine and serum VEGF levels did not change significantly before and after BCG therapy. Changes in VEGF level were significantly different neither in low grade against high grade tumors nor in stage T1 against stage Ta tumors. A significant difference in VEGF level was seen between low grade and high grade tumors in serum after BCG therapy (P=0.007); but not in urine samples. CONCLUSION: Although intravesical BCG possesses anti-angiogenic activity, it seems that it exerts its effect through pathways other than VEGF, especially in low grade tumors.