We report a case of Mycobacterium bovis BCG vertebral osteomyelitis 1.8 years after intravesical BCG therapy for bladder cancer. We differentiated BCG from other Mycobacterium tuberculosis complex members by PCR analysis of deletion regions and started an appropriate chemotherapy regimen resulting in the remission of symptoms within 1 month. CASE REPORTAn 86-year-old man was referred to our institution for unrelenting back pain. He first noticed the pain without any particular cause in December 2004. He had no fever, chills, cough, or motor or sensory deficits, but his ability to perform daily activities progressively decreased due to his back pain. The patient had a history of hypertension but denied any history of active tuberculous infection or ever having received Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine. He also had a history of left ureteral transitional cell carcinoma and bladder cancer diagnosed in 2002. As he elected bladder preservation, these tumors were surgically resected by total left nephroureterectomy and transurethral resection followed by cisplatin-based chemotherapy in September 2002. As the follow-up cystoscopy and biopsy in December 2002 demonstrated a carcinoma in situ, treatment with intravesical BCG (Tokyo strain) immunotherapy was started in January 2003. Eight weekly instillations were administered with no significant side effects, and no prophylaxis was given during the BCG treatment. However, follow-up cystoscopy and urine cytology examination again demonstrated the presence of a carcinoma. Subsequently, pelvic radiation therapy (total, 40 Gy) was added in April 2003 with cisplatin-based chemotherapy on the first day of radiation therapy. Thereafter, the results of follow-up examinations revealed no recurrent carcinoma.Physical examination elicited focal knock pain, but motor function was intact. Laboratory studies showed a white blood count of 6,600/mm 3 , a C-reactive protein level of 1.6 mg/dl, and an erythrocyte sedimentation rate of 35 mm. Thoracolumbar X-ray and computed tomography showed destructive changes involving the anterior end plate of the T12 and L1 vertebral bodies. A magnetic resonance imaging study confirmed the presence of a destructive lesion involving the T12 and L1 vertebral bodies and intervertebral disc and also showed an abscessed lesion in the left paraspinal soft tissue of the L1 vertebral body (Fig. 1). A needle biopsy of the involved disc space pathologically revealed necrosis and acute inflammation in this region. Ziehl-Neelsen stains were positive for acid-fast bacilli and 4 weeks later yielded a positive culture for mycobacteria. At the Department of Clinical Laboratory of our hospital, the initial examinations for the differentiation of the acid-fast bacilli used PCR (Amplicor PCR; Roche Diagnostic, Basel, Switzerland) and immunochromatography testing (CapiliaTB; Becton Dickinson, NJ). On the basis of those examinations, the acid-fast bacilli from the biopsy samples were reported to belong to the Mycobacterium tuberculosis complex (MT...
Electrochemotherapy is a novel cancer treatment in which electric pulses (EP) are used as a means of delivering anticancer agents to the cytoplasm of cancer cells (electroporation). The present study evaluates whether electrochemotherapy has in vitro and in vivo anticancer effects in murine bladder cancer. Using mouse bladder tumor cells (MBT-2 cells), in vitro electrochemotherapy was performed by applying EP to the cell suspension immediately after the addition of anticancer agents. The cytotoxicity of adriamycin (ADM), bleomycin (BLM) and cis-diamminedichloroplatinum(II) (CDDP) was determined by measuring succinate dehydrogenase (SD) activity in both electroporated and non-electroporated cells. In addition, intracellular concentrations of these anticancer agents were also measured. In the in vivo study, tumor-bearing C3H/He mice were treated with an intraperitoneal injection of anticancer agents followed by a local delivery of EP at the tumor site. Then, tumor growth rate (TGR) was determined and compared to that in the sham-treated control group, the EP-only group and the drug-only group. The in vitro study showed that, with electroporation, the cytotoxicity of BLM in electroporated cells was increased by as much as 95.7-fold compared to that of non-electroporated MBT-2 cells; CDDP showed only an increase of 1.8-fold and ADM showed no increase. After electroporation, the intracellular concentration of BLM, CDDP and ADM showed an increase of 120-, 1.7- and 0.8-fold, respectively. In electrochemotherapy for in vivo growing tumors, the potentiation of the antitumor effect was most prominent when combined with BLM, only slightly with CDDP, and totally absent with ADM. It is clear from in vitro and in vivo studies that, in a murine bladder tumor, the anticancer effect of BLM can be considerably potentiated by applying EP. Thus, BLM seems to be the most suitable anticancer agent for electrochemotherapy of bladder cancer.
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