Journal Information
Vol. 33. Issue. 3.May 2013
Pages 0-735
Share
Share
More article options
Vol. 33. Issue. 3.May 2013
Pages 0-735
DOI: 10.3265/Nefrologia.pre2012.Oct.11759
Full text access
Intravesical Bacillus Calmette-Guérin in immunosuppressed patients with carcinoma in situ
Bacilo Calmette-Guérin intravesical en paciente inmunodeprimido con carcinoma in situ
Visits
4818
Carlo R. Bonarribaa, Marta De la Cruz-Ruiza, Gonzalo Gómez-Marquésb
a Servicio de Urolog??a, Hospital Universitario Son Espases, Palma de Mallorca,
b Servicio de Nefrolog??a, Hospital Universitario Son Espases, Palma de Mallorca,
This item has received
4818
Visits
Article information
Full Text
Bibliography
Statistics
Figures (1)
Full Text

Content

To the Editor: 

The incidence of bladder urothelial carcinoma in renal transplant patients on immunosuppressive therapy ranges from 0.08% to 0.37%, although it frequently occurs in advanced stages compared with the general population.1

Patients with high grade transitional cell carcinoma and/or carcinoma in situ may be able to benefit from intravesical instillations with bacillus Calmette-Guérin (BCG). The BCG is a live attenuated mycobacterium bovis that maintains immunostimulatory action, but with decreased infective activity.2

The management of bladder cancer in immunocompromised patients has been briefly described in case reports and retrospective series. We report the management of a renal transplant patient with carcinoma in situ, with immunosuppressive therapy at our institution.

Our patient is a 71-year-old male with chronic kidney disease due to IgA glomerulonephritis, who started haemodialysis in January 2004. In December of the same year, he received a deceased-donor kidney transplant and began receiving immunosuppressive therapy with mycophenolate mofetil and tacrolimus.

Five years later, he presented with haematuria with clots, and no other associated symptoms. Urine cytology was inconclusive and cystoscopy revealed a mass lesion of 1cm in the fundus of the bladder. Transurethral resection of the bladder was performed in August 2009. Anatomopathology: high-grade papillary transitional cell carcinoma (pTa G2). Carcinoma in situ. Intravesical mitomycin C (MMC) (6 weeks) was indicated. In December 2009, multiple bladder biopsy was performed randomly after MMC. Anatomopathology: bladder: carcinoma in situ (CIS) in the fundus of the bladder.

The case was presented to the Urology-Nephrology-Oncology Committee of our hospital and three weeks after surgery, the patient received 6 weekly intravesical BCG instillations. Anti-tuberculosis prophylaxis was added with 150mg/24h isoniazid and 300mg/24h rifampicin (starting the day before instillation, and ending the day after instillation). The tacrolimus dose was increased from 4 to 8mg/day. He completed BCG on 25 March 2010, without complications.

Tacrolimus plasma levels were maintained between 5 and 12ng/ml. Renal function remained stable with plasma creatinine levels of 1.2mg/dl. The patient experienced no adverse effects and was free of disease after 28 months of follow-up (Table 1).

 

DISCUSSION

The risk of bladder cancer increases about 2-3 times in the transplant population.3 Compared with the general population, transplant patients with a neoplasm de novo after transplantation are mostly diagnosed in advanced stages and have a lower survival rate.1 The use of immunosuppressive agents prevents graft rejection, but also means that transplant patients are predisposed to an increased risk of malignancy.4

Superficial transitional cell carcinoma (TCC) of the bladder with associated CIS or primary CIS may progress to invasive disease in 40% to 80% of the patients. A decrease in the recurrence and progression was obtained with the use of intravesical BCG that avoids, in many cases, the need for radical surgery.5

Intravesical BCG stimulates the type 1 T helper lymphocytes (Th1) of the urothelial cells in the mass production of proinflammatory cytokines such as interleukin (IL)-1, IL-2, IL-6, IL-8, interferon gamma and tumour necrosis factor (TNF)-alpha. TNF-alpha has direct cytotoxic action on tumour cells.6

The main problem regarding BCG use is the associated morbidity. Lamm et al.7 state that 95% of patients tolerate BCG sufficiently, while less than 5% have serious complications. Theoretically, this morbidity would be expected to be greater in patients who receive immunosuppressive therapy after the transplant. Buzzeo et al.8 do not recommend the use of intravesical BCG in immunosuppressed patients.

Prophylaxis with isoniazid is administered with the aim of minimising toxicity induced by BCG, although, according to some authors, the frequency of cystitis, fever and feeling unwell do not differ between patients who receive intravesical BCG with or without isoniazid.9 This suggests that some complications occur due to inflammatory response and not due to the direct effects of bacteria per se.

Palou et al.10 reported safety in the administration of intravesical BCG with the use of prophylaxis with isoniazid and rifampicin in renal transplant patients with high grade superficial CCT of the bladder. Wang et al.11 also report safety, but without the use of tuberculosis prophylaxis in similar patients.

Medication with tuberculostatic drugs may cause adverse effects and increase the metabolism of some calcineurin inhibitors. Rifampicin induces cytochrome P450 3A4 and increases tacrolimus metabolism, with a dose adjustment being required to maintain the levels of immunosuppressants stable and avoid graft rejection.10

In literature we found 9 cases of kidney transplant patients with high-grade superficial CCT of the bladder and/or CIS, who received intravesical BCG, presenting a recurrence rate higher than the rate of the general population (44.4% compared with 26%). Rejection of the graft related to BCG use was not observed, probably because of the small number of cases recorded. One case of BCG treatment failure was reported.10-13

From an immunological point of view, there is a conflicting situation: immunosuppression is necessary to avoid graft rejection and immunological action is necessary to produce a cytotoxic effect on tumour cells.10 Systemic immunosuppression in transplant patients does probably not result in complete local immunosuppression; therefore, the inflammatory response with endovesical BCG could be effective. In deciding whether to use BCG in transplant patients, we should take into account the benefit of tumour control against the potential risk of graft loss or ineffective treatment.13

 

CONCLUSIONS 

— Treatment with intravesical BCG in our patient with high grade superficial transitional cell carcinoma of the bladder was effective and did not experience adverse effects.

— It is possible that intravesical BCG in immunosuppressed patients with carcinoma in situ is a good treatment option.

 

Conflicts of interest

The authors declare that they have no conflicts of interest related to the contents of this article.

Table 1. Characteristics of the patient, treatment and follow-up

Bibliography
[1]
Ehdaie B, Stukenborg G, Theodorescu D. Renal transplant recipients and patients with end stage renal disease present with more advanced bladder cancer. J Urol?? 2009;182(4):1482-7. [Pubmed]
[2]
Lamm DL, Blumenstein BA, Crawford ED. A randomized trial of?? intravesical doxorubicin and immunotherapy with Bacille Calmette-Gu??rin for transitional cell carcinoma of the bladder. N Engl J Med 1991;325:1205. [Pubmed]
[3]
MiaoY, Everly J, GrossTG. De novo cancers arising in organ transplant recipients are associated with adverse outcomes compared with the general population. Transplantation 2009;87(9):1347-59. [Pubmed]
[4]
Grulich AE, Van Leeuwen MT, Falster MO, Vajdic CM. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet 2007; 370(9581): 59-67. [Pubmed]
[5]
5.?? Huguet J, Palou J, Mill??n F. Cistectom??a radical en tumores superficiales en la era de la BCG. Arch Esp Urol 2002;55:50-6. [Pubmed]
[6]
B??hle A, for the EBIN group. BCG??s mechanism of action: increasing our understanding. Eur Urol 2000;37(suppl 1):1-8. [Pubmed]
[7]
Lamm D. Eficacy and safety of bacille Calmette-Guerin immunotherapy in superficial bladder cancer. Clin Infect Dis 2000;31(Suppl 3):S86-S90. [Pubmed]
[8]
??Buzzeo B,?? Heisey D. Bladder cancer in renal transplant recipients. Urology 1997;50(4):525-8. [Pubmed]
[9]
Viallard JF, Denis D, Texier-Maugein J. Disseminated infection after bacille Calmette-Guerin instillation for treatment of bladder carcinoma. Clin Infect Dis 1999;29(2):451-2. [Pubmed]
[10]
Palou J, Angerri O, Segarra J. Intravesical bacillus Calmette-Guerin for the treatment of superficial bladder cancer in renal transplant patients. Transplantation 2003;76(10):1514-6. [Pubmed]
[11]
Wang HB, Hsieh HH, Chen YT, Chiang CY. The outcome of post-transplant transitional cell carcinoma in 10 renal transplant recipients. Clin Transplant 2002;16(6):410-3. [Pubmed]
[12]
Tillou X, Raynal G, Limani K, Saint F, Petit J. [Carcinoma in situ in bladder and urethra among renal transplanted patient: failure of BCG therapy]. Prog Urol 2008;18(13):1097-9. [Pubmed]
[13]
Sun H, Singh N. Should intravesical Bacillus Calmette-Gu??rin be employed in transplant recipients with bladder carcinoma? Transpl Infect Dis 2010;12:358-62. [Pubmed]
Idiomas
Nefrología (English Edition)

Subscribe to our newsletter

Article options
Tools
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

es en
Política de cookies Cookies policy
Utilizamos cookies propias y de terceros para mejorar nuestros servicios y mostrarle publicidad relacionada con sus preferencias mediante el análisis de sus hábitos de navegación. Si continua navegando, consideramos que acepta su uso. Puede cambiar la configuración u obtener más información aquí. To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here.