Systematische Übersichtsarbeit: aortale Komplikationen nach intravesikaler Bacillus Calmette-Guérin-Behandlung

Zusammenfassung Hintergrund Aortale Pathologien nach intravesikaler BCG-Applikation (BCG: Bacillus Calmette-Guérin) stellen eine seltene Komplikation nach der Behandlung von nicht muskelinvasiven Harnblasentumoren dar. Das Ziel dieser Studie war es, eine deskriptive Analyse der bisher publizierten Studien im Rahmen einer systematischen Übersichtsarbeit durchzuführen und die besonderen Herausforderungen der Diagnosestellung und Behandlung dieser seltenen Komplikation zu diskutieren. Material und Methode Es erfolgte eine Literaturrecherche in den Datenbanken PubMed (1949–2021) und Web of Science (1900–2021) mit den Suchtermini „mycobacterium“ OR „bovis“ OR „BCG“ AND „aorta“ OR „aneurysm“. In einem stufenweisen Bewertungsverfahren wurden Publikationen mit folgenden Einschlusskriterien in die finale Datenauswertung eingeschlossen: Originalarbeit, Volltextverfügbarkeit in englischer oder deutscher Sprache und aortale Komplikation nach intravesikaler BCG-Instillation. Ergebnisse In 55 publizierten Arbeiten wurden insgesamt 60 Einzelfälle beschrieben. BCG-induzierte, mykotische Aortenaneurysmen können in allen Segmenten der Aorta auftreten, wobei das infrarenale Aortensegment am häufigsten betroffen war (65% aller Fälle). Häufig handelte es sich um sakkuläre (65%) Aussackungen mit (28%) oder ohne Aortenruptur (63%). Begleitinfektionen in anderweitigen Geweben waren typisch (65%). Die Diagnose beruhte auf der Kombination aus pathologischen und mikrobiologischen Analysemethoden. Ein gängiger Therapiealgorithmus war die chirurgische Infektsanierung (85%) und die antimykobakterielle Therapie (83%). Gleichzeitig durchgeführt führten sie zu einem Langzeitüberleben von 81%. Eine Protheseninfektion nach initialem Aortenrepair mit alloplastischem Material (n = 40) entwickelte sich im Verlauf bei 10 Patienten (25%). Diskussion Die Diagnosestellung beruht auf der Probengewinnung jeglichen infizierten Gewebes und der Kombination aus passender Anamnese, Klinik und Laboranalysen. Die Kombination aus chirurgischer Infektsanierung und pharmakologischer Begleittherapie scheint die besten Ergebnisse zu erzielen. Bereits bei der Initialoperation sollte die Möglichkeit eines autologen oder allogenen Aortenersatzes evaluiert werden, da das Risiko eines Protheseninfektes nach Verwendung alloplastischer Materialien hoch ist.

Case Report: Acquired Disseminated BCG in the Context of a Delayed Immune Reconstitution After Hematological Malignancy

ContextDisseminated infections due to Mycobacterium bovis Bacillus Calmette-Guérin (BCG) are unusual and occur mostly in patients with inborn error of immunity (IEI) or acquired immunodeficiency. However, cases of secondary BCGosis due to intravesical BCG instillation have been described. Herein, we present a case of severe BCGosis occurring in an unusual situation.Case DescriptionWe report one case of severe disseminated BCG disease occurring after hematological malignancy in a 48-year-old man without BCG instillation and previously vaccinated in infancy with no complication. Laboratory investigations demonstrated that he was not affected by any known or candidate gene of IEI or intrinsic cellular defect involving IFNγ pathway. Whole genome sequencing of the BCG strain showed that it was most closely related to the M. bovis BCG Tice strain, suggesting an unexpected relationship between the secondary immunodeficiency of the patient and the acquired BCG infection.ConclusionThis case highlights the fact that, in addition to the IEI, physicians, as well as microbiologists and pharmacists should be aware of possible acquired disseminated BCG disease in secondary immunocompromised patients treated in centers that administrate BCG for bladder cancers.

Effectiveness of Steroid Pulse Therapy for Systemic Side Effects after Bacillus Calmette-Guérin Intravesical Instillation Therapy: A Series of Five Cases

Introduction. Bacillus Calmette-Guérin (BCG) instillation is an established therapy for the treatment of carcinoma in situ (CIS) of the bladder and prevention of recurrence after transurethral resection of bladder tumor noninvasive bladder cancer. However, serious systemic side effects may occur in less than 5% of patients with BCG intravesical instillation. Systemic side effects can sometimes be fatal and require early and accurate treatment. We describe five cases wherein steroid pulse therapy was effective for treating the systemic side effects after BCG intravesical instillation. Case Presentations. BCG intravesical instillation was used to prevent the recurrence of nonmuscle invasive bladder cancer and treat CIS of the bladder; the dose used was 40–80 mg each time, and the Tokyo strain was used. The patients developed fever, impaired consciousness, arthralgia, conjunctival hyperemia, and symptoms of cystitis. The median time from installation to side effect manifestation was 6 days (0–8). One to two courses of steroid pulse therapy were administered (1 course in 3 days), and the dose of methylprednisolone was 500–1000 mg/day. BCG sepsis was observed in one case; however, in the other four cases, one course of steroid pulse therapy showed a rapid improvement in symptoms. In the case of BCG sepsis, hemodialysis and mechanical ventilation were required because of septic shock and acute renal failure. Antituberculosis drugs (isoniazid, rifampicin, and ethambutol) were started promptly; however, no improvement was noticed. Two courses of steroid pulse therapy improved the patient’s general condition, and hemodialysis and mechanical ventilation were no longer required. All patients survived without relapse of symptoms. Conclusion. Our cases suggest that early steroid pulse therapy may be effective for rapid symptom improvement of the systemic side effects of BCG instillation therapy.

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.

Does the Urinary Mast Cell Mediators Predict the Immune Response to BCG in Patients with Primary High-Grade Non-Muscle Invasive Bladder Cancer?

Background: Mast cells play a critical role in tumor-associated immune pathways. We aimed to determine whether the urinary mast cell mediators predict the immune response in patients with non-muscle invasive bladder cancer (NMIBC) treated with Bacillus Calmette-Guérin (BCG) immunotherapy. Methods: Nineteen patients who have received immunotherapy due to NMIBC and 19 healthy participants were enrolled. Urine samples were collected to assay N-methylhistamine, histamine, and tryptase levels immediately before the first BCG instillation, immediately after the third and sixth instillations, and four weeks after the sixth instillation in patients with NMIBC and at a single visit in healthy participants. Cystoscopic examinations were performed on the patient with NMIBC at three-month intervals for two years. The changes in urinary markers due to BCC response, BCG instillation, and the presence of NMIBC were assessed. Results: The average age was 56.1 ± 10.5 years in patients with NMIBC. Fourteen patients had high-grade Ta tumors, and 5 had high-grade T1 tumors. While 12 patients responded, 6 presented with recurrence and 1 with progression. There was no correlation between the levels of mast cell mediators and BCG response. The N-methylhistamine and histamine levels were increased significantly with the onset of immunotherapy, and N-methylhistamine levels were significantly decreased when immunotherapy was terminated. Pre-BCG estimated marginal means of N-methylhistamine were significantly higher in patients with NMIBC than healthy participants. Conclusions: Our study is the first study to identify the changes in mast cell mediators with the onset of immunotherapy and with the presence of bladder cancer. However, these mediators were not found to predict the patients’ response to immunotherapy.