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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Content</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">To the Editor&#58;</span>&#160;</p><p class="elsevierStylePara">The incidence of bladder urothelial carcinoma in renal transplant patients on immunosuppressive therapy ranges from 0&#46;08&#37; to 0&#46;37&#37;&#44; although it frequently occurs in advanced stages compared with the general population&#46;<span class="elsevierStyleSup">1</span></p><p class="elsevierStylePara">Patients with high grade transitional cell carcinoma and&#47;or carcinoma in situ may be able to benefit from intravesical instillations with bacillus Calmette-Gu&#233;rin &#40;BCG&#41;&#46; The BCG is a live attenuated mycobacterium bovis that maintains immunostimulatory action&#44; but with decreased infective activity&#46;<span class="elsevierStyleSup">2</span></p><p class="elsevierStylePara">The management of bladder cancer in immunocompromised patients has been briefly described in case reports and retrospective series&#46; We report the management of a renal transplant patient with carcinoma in situ&#44; with immunosuppressive therapy at our institution&#46;</p><p class="elsevierStylePara">Our patient is a 71-year-old male with chronic kidney disease due to IgA glomerulonephritis&#44; who started haemodialysis in January 2004&#46; In December of the same year&#44; he received a deceased-donor kidney transplant and began receiving immunosuppressive therapy with mycophenolate mofetil and tacrolimus&#46;</p><p class="elsevierStylePara">Five years later&#44; he presented with haematuria with clots&#44; and no other associated symptoms&#46; Urine cytology was inconclusive and cystoscopy revealed a mass lesion of 1cm in the fundus of the bladder&#46; Transurethral resection of the bladder was performed in August 2009&#46; Anatomopathology&#58; high-grade papillary transitional cell carcinoma &#40;pTa G2&#41;&#46; Carcinoma in situ&#46; Intravesical mitomycin C &#40;MMC&#41; &#40;6 weeks&#41; was indicated&#46; In December 2009&#44; multiple bladder biopsy was performed randomly after MMC&#46; Anatomopathology&#58; bladder&#58; carcinoma in situ &#40;CIS&#41; in the fundus of the bladder&#46;</p><p class="elsevierStylePara">The case was presented to the Urology-Nephrology-Oncology Committee of our hospital and three weeks after surgery&#44; the patient received 6 weekly intravesical BCG instillations&#46; Anti-tuberculosis prophylaxis was added with 150mg&#47;24h isoniazid and 300mg&#47;24h rifampicin &#40;starting the day before instillation&#44; and ending the day after instillation&#41;&#46; The tacrolimus dose was increased from 4 to 8mg&#47;day&#46; He completed BCG on 25 March 2010&#44; without complications&#46;</p><p class="elsevierStylePara">Tacrolimus plasma levels were maintained between 5 and 12ng&#47;ml&#46; Renal function remained stable with plasma creatinine levels of 1&#46;2mg&#47;dl&#46; The patient experienced no adverse effects and was free of disease after 28 months of follow-up &#40;Table 1&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">The risk of bladder cancer increases about 2-3 times in the transplant population&#46;<span class="elsevierStyleSup">3</span> Compared with the general population&#44; transplant patients with a neoplasm de novo after transplantation are mostly diagnosed in advanced stages and have a lower survival rate&#46;<span class="elsevierStyleSup">1</span> The use of immunosuppressive agents prevents graft rejection&#44; but also means that transplant patients are predisposed to an increased risk of malignancy&#46;<span class="elsevierStyleSup">4</span></p><p class="elsevierStylePara">Superficial transitional cell carcinoma &#40;TCC&#41; of the bladder with associated CIS or primary CIS may progress to invasive disease in 40&#37; to 80&#37; of the patients&#46; A decrease in the recurrence and progression was obtained with the use of intravesical BCG that avoids&#44; in many cases&#44; the need for radical surgery&#46;<span class="elsevierStyleSup">5</span></p><p class="elsevierStylePara">Intravesical BCG stimulates the type 1 T helper lymphocytes &#40;Th1&#41; of the urothelial cells in the mass production of proinflammatory cytokines such as interleukin &#40;IL&#41;-1&#44; IL-2&#44; IL-6&#44; IL-8&#44; interferon gamma and tumour necrosis factor &#40;TNF&#41;-alpha&#46; TNF-alpha has direct cytotoxic action on tumour cells&#46;<span class="elsevierStyleSup">6</span></p><p class="elsevierStylePara">The main problem regarding BCG use is the associated morbidity&#46; Lamm et al&#46;<span class="elsevierStyleSup">7</span> state that 95&#37; of patients tolerate BCG sufficiently&#44; while less than 5&#37; have serious complications&#46; Theoretically&#44; this morbidity would be expected to be greater in patients who receive immunosuppressive therapy after the transplant&#46; Buzzeo et al&#46;<span class="elsevierStyleSup">8</span> do not recommend the use of intravesical BCG in immunosuppressed patients&#46;</p><p class="elsevierStylePara">Prophylaxis with isoniazid is administered with the aim of minimising toxicity induced by BCG&#44; although&#44; according to some authors&#44; the frequency of cystitis&#44; fever and feeling unwell do not differ between patients who receive intravesical BCG with or without isoniazid&#46;<span class="elsevierStyleSup">9</span> This suggests that some complications occur due to inflammatory response and not due to the direct effects of bacteria per se&#46;</p><p class="elsevierStylePara">Palou et al&#46;<span class="elsevierStyleSup">10</span> 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&#46; Wang et al&#46;<span class="elsevierStyleSup">11</span> also report safety&#44; but without the use of tuberculosis prophylaxis in similar patients&#46;</p><p class="elsevierStylePara">Medication with tuberculostatic drugs may cause adverse effects and increase the metabolism of some calcineurin inhibitors&#46; Rifampicin induces cytochrome P450 3A4 and increases tacrolimus metabolism&#44; with a dose adjustment being required to maintain the levels of immunosuppressants stable and avoid graft rejection&#46;<span class="elsevierStyleSup">10</span></p><p class="elsevierStylePara">In literature we found 9 cases of kidney transplant patients with high-grade superficial CCT of the bladder and&#47;or CIS&#44; who received intravesical BCG&#44; presenting a recurrence rate higher than the rate of the general population &#40;44&#46;4&#37; compared with 26&#37;&#41;&#46; Rejection of the graft related to BCG use was not observed&#44; probably because of the small number of cases recorded&#46; One case of BCG treatment failure was reported&#46;<span class="elsevierStyleSup">10-13</span></p><p class="elsevierStylePara">From an immunological point of view&#44; there is a conflicting situation&#58; immunosuppression is necessary to avoid graft rejection and immunological action is necessary to produce a cytotoxic effect on tumour cells&#46;<span class="elsevierStyleSup">10</span> Systemic immunosuppression in transplant patients does probably not result in complete local immunosuppression&#59; therefore&#44; the inflammatory response with endovesical BCG could be effective&#46; In deciding whether to use BCG in transplant patients&#44; we should take into account the benefit of tumour control against the potential risk of graft loss or ineffective treatment&#46;<span class="elsevierStyleSup">13</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">CONCLUSIONS</span>&#160;</p><p class="elsevierStylePara">&#8212; 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&#46;</p><p class="elsevierStylePara">&#8212; It is possible that intravesical BCG in immunosuppressed patients with carcinoma in <span class="elsevierStyleItalic">situ</span> is a good treatment option&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflicts of interest</span></p><p class="elsevierStylePara">The authors declare that they have no conflicts of interest related to the contents of this article&#46;</p><p class="elsevierStylePara"><a href="grande&#47;11759&#95;16025&#95;46872&#95;en&#95;11759&#95;t1&#46;jpg" class="elsevierStyleCrossRefs"><img src="11759_16025_46872_en_11759_t1.jpg" alt="Characteristics of the patient&#44; treatment and follow-up"></img></a></p><p class="elsevierStylePara">Table 1&#46; Characteristics of the patient&#44; treatment and follow-up</p>"
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