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Successful Endovascular Treatment of Abdominal Aortic Rupture Secondary to Bacillus Calmette-Guerin Vaccine

Open AccessPublished:November 21, 2021DOI:https://doi.org/10.1016/j.jvscit.2021.11.002

      Abstract:

      Bacillus Calmette-Guerin (BCG) vaccine has been successfully used to treat bladder cancer, but sporadic cases of mycotic arterial aneurysms have appeared in the literature. These patients typically develop a mycobacterium bovis (M. bovis) infection of an existing aneurysm or graft. This report describes a patient who ruptured his non-aneurysmal abdominal aorta years after intravesicular BCG therapy. Emergent aortic endograft repair was successful, and after subsequent evaluation confirmed M. bovis infection, the patient was treated with a prolonged course of antimycobacterial therapy. Vascular surgeons should maintain suspicion for atypical aortic ruptures in patients with exposure to intravesicular BCG.

      Introduction

      Bladder cancer is the sixth most common neoplasm in the United States. Tobacco abuse is the biggest risk factor.
      • Saginala K.
      • Barsouk A.
      • Aluru J.S.
      • Rawla P.
      • Padala S.A.
      • Barsouk A.
      Epidemiology of Bladder Cancer.
      Bacillus Calmette-Guerin vaccine is the standard of care to treat non-muscle-invasive bladder cancer after resection.
      • Redelman-Sidi G.
      • Glickman M.S.
      • Bochner B.H.
      The mechanism of action of BCG therapy for bladder cancer-A current perspective.
      ,
      • Morales A.
      • Eidinger D.
      • Bruce A.W.
      Intracavitary Bacillus Calmette Guerin in the treatment of superficial bladder tumors.
      It is a live, attenuated strain of mycobacterium bovis (M. bovis).
      • Biot C.
      • Rentsch C.A.
      • Gsponer J.R.
      • Birkhauser F.D.
      • Jusforgues-Saklani H.
      • Lemaitre F.
      • et al.
      Preexisting BCG-specific T cells improve intravesical immunotherapy for bladder cancer.
      BCG vaccine may activate specific immunologic cells, as well as stimulate direct cytotoxicity of the mycobacterium culminating in the death of tumor cells while sparing benign bladder urothelium.
      • Redelman-Sidi G.
      • Glickman M.S.
      • Bochner B.H.
      The mechanism of action of BCG therapy for bladder cancer-A current perspective.
      Biot et al, showed that after instillation of the BCG vaccine into the bladders of mice, the bacteria travel to the paraaortic lymph nodes in order to become primed and exert maximum effect.
      • Biot C.
      • Rentsch C.A.
      • Gsponer J.R.
      • Birkhauser F.D.
      • Jusforgues-Saklani H.
      • Lemaitre F.
      • et al.
      Preexisting BCG-specific T cells improve intravesical immunotherapy for bladder cancer.
      Although rare, case reports of mycotic aneurysms becoming infected with mycobacterium following BCG vaccine have been reported.

      Leo E, Molinari ALC, Rossi G, Ferrari SA, Terzi A, Lorenzi G. Mycotic Abdominal Aortic Aneurysm after Adjuvant Therapy with Bacillus erin in Patients with Urothelial Bladder Cancer : A Rare but Misinterpreted Complication. doi:10.1016/j.avsg.2015.01.036

      Harding GEJ, Lawlor DK. Ruptured mycotic abdominal aortic aneurysm secondary to Mycobacterium bovis after intravesical treatment with bacillus Calmette-Guérin. 2007;(Fig 3):131-134. doi:10.1016/j.jvs.2007.01.054

      Higashi Y, Nakamura S, Kidani K, Matumoto K. Mycobacterium bovis -induced Aneurysm after Intravesical Bacillus Calmette-Guérin Therapy : A Case Study and Literature Review. 2017. doi:10.2169/internalmedicine.9102-17

      We discuss a case of presumed BCG-induced psoas abscess with subsequent erosion into non-aneurysmal abdominal aorta treated with emergent endovascular stent graft repair. Our patient has given permission for this case to be shared.
      Case:
      The patient is an 82-year-old male with a past medical history of hyperlipidemia, tobacco abuse, and bladder cancer (GaT1). Treatment for bladder cancer included multiple transurethral resections as well as intravesicular mitomycin C and BCG vaccine roughly five years prior. He presented to a referring Emergency Department with low back pain and was discharged. One month later, he returned with increasing lower abdominal and low back pain with the CT findings in Figure 1, and this was thought to be a retroperitoneal/intramuscular hematoma. No aortic pathology was noted, and he was referred for outpatient follow up.
      Figure thumbnail gr1
      Figure 1CT from second emergency department visit showing a loculated, heterogeneous hypodense structure measuring 9.2 x 7 x 12.5 cm in the left psoas concerning for hematoma.
      Three days later he had a syncopal episode and was admitted. CT scan showed lytic lesions of L2 and L3 vertebra (Figure 2). Empiric antibiotic therapy was started and biopsy showed necrotic muscle with a minor granulomatous component and negative gram stain. The patient was discharged 9 days after admission on ceftriaxone with cultures negative for bacterial growth.
      Figure thumbnail gr2
      Figure 2CT from 3 days later showing a reduction in size of left psoas suspected hematoma (now 3.6 x 7.1 x 8.4) but with development of new 5 cm suspected hematoma lateral and inferior to other mass. As well, lytic lesions were now noted in the vertebral bodies.
      Two days later, the patient presented to the referring ED with increasing leg pain, difficulty walking, and abdominal pain with guarding and tenderness. He was afebrile but tachycardic and hypotensive. CBC was notable for a Hg of 5.3 g/dl (11.1 four days prior), WBC 14.9 103/uL. CT showed active extravasation from the aorta (Figure 3). Large bore IV access was obtained, red blood cell transfusion was initiated, and the patient was transferred and underwent emergent endovascular aortic repair with a Gore bifurcated stent graft.
      Figure thumbnail gr3
      Figure 3Transverse and coronal CT images 14 days from initial CT showing rupture of posterior wall of abdominal aorta with a posterior saccular aneurysm approximately 1.4 cm with active extravasation into the left psoas muscle. Not pictured above was a 6.4 x 7.5 x 17.8 cm new retroperitoneal hematoma in the left iliac fossa.
      The unusual progression of the patient’s aortic rupture without a pre-existing aneurysm prompted an infectious disease (ID) consult. On initial evaluation, there was suspicion of a possible BCG-related infection, and a biopsy of the vertebral lesions was obtained. Prior cultures had been discarded without PCR testing. Broad spectrum antibiotic therapy was initiated. The patient was discharged in stable condition on post-operative day three. Empiric anti-tuberculous therapy was started based on his history of BCG therapy and absence of conventional bacterial growth. Ethambutol, isoniazid, and rifampin (RIE) therapy with moxifloxacin was chosen. After twenty-two days his cultures grew acid fast bacilli with speciation showing M. bovis.

      Discussion:

      Existing literature contains at least 31 cases of BCG-related infection involving an existing aortic aneurysm or pseudoaneurysm. The majority of these cases involved the infrarenal aorta, and most commonly the repair was with aortic resection and an in-situ prosthesis.

      Higashi Y, Nakamura S, Kidani K, Matumoto K. Mycobacterium bovis -induced Aneurysm after Intravesical Bacillus Calmette-Guérin Therapy : A Case Study and Literature Review. 2017. doi:10.2169/internalmedicine.9102-17

      In the few instances where endovascular repair was involved, stent grafts were placed to treat pre-existing aortic aneurysms before any signs of M. bovis infection. It is hypothesized that these grafts may have ultimately acted as a nidus of infection.

      Leo E, Molinari ALC, Rossi G, Ferrari SA, Terzi A, Lorenzi G. Mycotic Abdominal Aortic Aneurysm after Adjuvant Therapy with Bacillus erin in Patients with Urothelial Bladder Cancer : A Rare but Misinterpreted Complication. doi:10.1016/j.avsg.2015.01.036

      ,

      Laberge JM, Kerlan RK, Reilly LM, Chuter TA. Case 9 : Mycotic Pseudoaneurysm of the Abdominal Aorta in Association with Mycobacterial Psoas Abscess — A Complication of BCG Therapy 1. 1999.

      • Rozenblit A.
      • Wasserman E.
      • Mann L.
      • Veith F.J.
      Infected Aortic Aneurysm and Vertebral Osteomyelitis After Bacillus Calmette-Guerin.

      Mizoguchi H, Iida O, Dohi T, Kaname T, Hayato K, Inoue K, et al. Abdominal Aortic Aneurysmal and Endovascular Device Infection With Iliopsoas Abscess Caused by Mycobacterium Bovis as a Complication of Intravesical Bacillus Calmette e Gu erin Therapy. Ann Vasc Surg. 2013;27(8):1186.e1-1181186.e5. doi:10.1016/j.avsg.2012.12.004

      There are only a few identified instances of non-aneurysmal abdominal aortic infections with M. bovis.

      Berchiolli R, Mocellin DM, Marconi M, Tomei F, Bargellini I, Zanca R, et al. Ruptured Mycotic Aneurysm After Intravesical Instillation for Bladder Tumor. Ann Vasc Surg. 2019;59(February):310.e7-310.e11. doi:10.1016/j.avsg.2018.12.100

      Long et al proposed three mechanisms of tuberculous spread to the aorta: Bacilli spreading to the vessel wall, spread via the vasa vasorum, and/or direct extension of a contiguous focus, such as an abscess.
      • Long R.
      • Guzman R.
      • Greenberg H.
      • Safneck J.
      • Hershfield E.
      Tuberculous mycotic aneurysm of the aorta: Review of published medical and surgical experience.
      Due to the lack of a pre-existing aneurysm, we believe the cause of rupture in our patient was due to direct extension into the wall of a previously normal aorta from adjacent infected lymphatic tissue.
      Traditional treatment of infected aortic tissue involves resection of the involved aorta and retroperitoneal tissues with either inline or extra-anatomic reconstruction. Given the lack of knowledge about his mycobacterial infection and with his clinical presentation of hemorrhagic shock, and endovascular repair was chosen for our patient. Since his repair his symptoms of back pain and leg weakness have resolved. He has not had fevers or other systemic signs of infection. His most recent postoperative CT scan was about 10 months after repair and shows no evidence of infection (Figure 4) . We plan follow up with CT scans every 6-12 months; however, the patient developed stage 3 CKD (GFR 45 mL/min/1.73m2 & Creatinine 1.4 mg/dL) after institution of anti-mycobacterial therapy. This may limit contrast enhanced imaging in the future. At his most recent follow up 14 months after repair he had a normal white blood cell count and was riding a stationary bike daily and living independently. Anti-tuberculous therapy is planned for a total of 18 months.
      Figure thumbnail gr4
      Figure 4Postoperative CT scan 10 months after endovascular stent graft repair showing complete resolution of left psoas mass.
      Berchiolli et al discussed that there are no well-defined guidelines for treatment of infected aortic endografts with M. bovis. The “gold standard” is surgical excision with either in line reconstruction or extra-anatomic bypass, but these operations carry a high risk of complications and perioperative morbidity and mortality.

      Berchiolli R, Mocellin DM, Marconi M, Tomei F, Bargellini I, Zanca R, et al. Ruptured Mycotic Aneurysm After Intravesical Instillation for Bladder Tumor. Ann Vasc Surg. 2019;59(February):310.e7-310.e11. doi:10.1016/j.avsg.2018.12.100

      M. bovis is typically treated with a 9 month course (2 months of RIE, 7 months of RI and consideration of a fluroquinolone if Isoniazid resistant).
      • LoBue P.A.
      • Moser K.S.
      Treatment of Mycobacterium bovis infected tuberculosis patients: San Diego County, California, United States, 1994-2003.
      ,
      • Nahid P.
      • Dorman S.E.
      • Alipanah N.
      • Barry P.
      • Brozek J.
      • Cattamanchi A.
      • et al.
      Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis.
      No clear data exists on M. bovis treatment in the setting of a newly placed aortic endograft. A retrospective chart review of prosthetic joints infected with M. Tuberculosis found that an extended course of antibiotics (18 months) was effective and did not require removal of the joint.
      • Uhel F.
      • Corvaisier G.
      • Poinsignon Y.
      • Chirouze C.
      • Beraud G.
      • Grossi O.
      • et al.
      Mycobacterium tuberculosis prosthetic joint infections: A case series and literature review.
      We believe that the best option for our patient is an extended course of anti-tuberculous therapy (18 months) which we hope will eliminate the M. bovis and forego the need for major open aortic surgery (graft explant and revascularization).

      Conclusion

      We present a case of an 82-year-old male with a ruptured, non-aneurysmal infrarenal abdominal aorta secondary to mycobacterium infection of the paraaortic tissues from prior intravesicular BCG vaccine. The progression of disease seen on CT was profound, and although aortic rupture is a very rare occurrence, this case report highlights the connection between intravesicular BCG treatment and atypical aortic pathology. We plan close surveillance of the aortic repair and are hopeful that after an extended course of anti-mycobacterial therapy he will not require future open aortic resection and revascularization.

      Acknowledgements

      The authors wish to thank Samuel Bloomsburg, MD, MS, for their contributions and insights on the development of this case report.
      Disclosures:
      The authors have no financial disclosures to make.

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