Massive expansion of regulatory T-cells following interleukin 2 treatment during a phase I-II dendritic cell-based immunotherapy of metastatic renal cancer.

Cytotoxic chemotherapy is ineffective in metastatic renal cancer. However, systemic administration of interleukin 2 (IL-2) or infusion of dendritic cells (DCs) loaded with tumor extracts can lead to some response rates with concomitant survival improvements. We report the results of a phase I-II pilot study combining DCs and IL-2 where six patients were included. DCs were derived from bone marrow CD34+ cells and loaded with autologous tumor extracts. CD34-DC vaccines were infused subcutaneously at day 45, 52, 59, 90 and 120 following surgery in combination with IL-2, that was subsequently administrated after the 3rd and 4th DC vaccinations. Preparation of tumor extracts and CD34-DCs were satisfactory in all patients but one. Due to rapid tumor progression, one patient was excluded before vaccination. In the 4 remaining patients, two received 3 vaccinations, while the 2 others received 5 vaccinations and the full IL-2 treatment. No adverse effect due to the vaccinations was observed. A specific immune response against autologous tumor cells was observed in the 2 patients who completed the treatment. Interestingly, these 2 patients had a more prolonged survival than the patients receiving 3 vaccinations. Importantly, a transient and massive increase of circulating natural regulatory T-cells (nTregs) was evidenced in 3 patients following IL-2 administration. Overall, the use of CD34-DC vaccines is feasible, safe and non-toxic. A specific anti-tumor immune response can be detected. However, our data highlights that IL-2 is a potent inducer of nTregs in vivo and as such may have a negative impact on cancer immunotherapy.

Successful heart transplantation following melphalan plus dexamethasone therapy in systemic AL amyloidosis.

Recurrence in the allograft and progression in other organs increase mortality after cardiac transplantation in AL amyloidosis. Survival may be improved after suppression of monoclonal light chain (LC) production following high dose melphalan and autologous stem cell transplantation (HDM/ASCT). However, because of high treatment related mortality, this tandem approach is restricted to few patients without significant extra-cardiac involvement. A diagnosis of systemic AL amyloidosis was established in a 45-year old patient with congestive heart failure related to restrictive cardiomyopathy, nephrotic syndrome, peripheral neuropathy, postural hypotension, macroglossia, and lambda LC monoclonal gammopathy. After melphalan and dexamethasone (M-Dex) therapy, which resulted in 80% reduction of serum free lambda LC, he underwent orthotopic cardiac transplantation. Two years later, he remains in a sustained hematologic remission, with no evidence of allograft or extra-cardiac amyloid accumulation. M-Dex should be considered as an alternative therapy in AL amyloid heart transplant recipients ineligible for HDM/ASCT.

Cardiomyopathy related to antimalarial therapy with illustrative case report.

The antimalarial agents, chloroquine (CQ) and hydroxychloroquine (HCQ) are used in long-term treatment of connective tissue diseases and dermatological disorders and are generally regarded as safe. We present one case of cardiotoxicity in a 59-year-old woman treated with antimalarials during 13 years for a discoid lupus erythematosus. She progressively developed conduction disturbances and congestive heart failure (CHF). When the diagnosis of antimalarials toxicity was suspected, CQ was withdrawn. However, heart transplantation had to be performed in the following 4 months for severe CHF. Indeed, rare but severe cardiotoxicity may develop following prolonged use of antimalarials with both conduction disturbances (45 patients) and CHF (25 patients). These cardiac toxic effects have been reported with CQ and less frequently with HCQ use alone. Diagnoses are often delayed since the toxicity of the drug might be misattributed to other factors in these patients. The endomyocardial biopsy, or in some cases the muscle biopsy, are essential to confirm the antimalarials toxicity. Antimalarials have been stopped in 12 cases of CHF, leading to improvement in 8 cases (within 3 months to 5 years) and to deaths or to heart transplantation in 4 cases (within 1 week to 3 months). In the latter cases, as in our patient, the lack of improvement may have been explained by the severity of the cardiomyopathy at diagnosis and the short delay since withdrawal. As a consequence, the potential for reversibility and the severity in undiagnosed cases of these toxic cardiomyopathies emphasize the importance of recognizing early signs of toxicity in order to withdraw antimalarials before the occurrence of life-threatening CHF.

Nosocomial transmission of hepatitis B virus associated with endomyocardial biopsy.

OBJECTIVES: A high prevalence of chronic hepatitis B has been previously reported in heart transplant recipients in our center. Nosocomial transmission of hepatitis B has been therefore suggested. The aim of the present study was to investigate an outbreak of hepatitis B infection in heart transplant recipients and to to look for nosocomial acquisition of hepatitis B in these patients. METHODS: In a retrospective case-control study, review of transvenous endomyocardial biopsy (TEB) procedure, line probe assay and DNA sequencing for characterization of the outbreak isolate genotypes were performed in order to assess the possible risk of nosocomial transmission of hepatitis B in the setting of heart transplantation. Case was defined as a patient negative for HBsAg before heart transplantation and positive after. Controls were matched with cases by date of transplantation and time-interval of HBV infection occurrence in the cases patients. RESULTS: Transmission of HBV was associated with the number of HBsAg positive patients undergoing TEB the same day and in the same ward (OR=1.17, per additional encounter; 95%CI=1.01-1.37, P=0.02) and with the total number of TEB undergone after a HBsAg positive patient (OR=1.43 for additional encounter, 95%CI=0.97-2.1, P=0.056) but not with the number of biopsies. The virological study identified eight different strains. No common devices nor gloves, drapes, or medical solution were shared among patients during TEB. One staff member, but no surgeon, was HBsAg positive. No further case occurred after implementation of control measures. CONCLUSIONS: Patient-to-patient transmission during TEB sessions was demonstrated by the virological and the case-control studies. This transmission occurred without evidence of blood contact through vials or devices. There is strong evidence that this transmission may be due to the spread of infective blood droplets on the environmental surfaces and the material during the TEB procedure.

[Left paravesical cystic urothelial tumour: an exceptional case?]. / Tumeur urothéliale kystique para-vésicale gauche: une observation exceptionnelle?

Pelvic cystic masses are frequent in women of childbearing potential and usually arise from the adnexae. The authors report a rare case of paravesical malformative cyst (Gartner cyst) with left silent kidney. In view of the unusual histology, comprising carcinoma in situ and a transitional cell papillary tumour with metastatic lymph node extension, the authors reviewed the literature on this subject and identified only one similar case (5).

Histologic features in the urinary bladder wall affected from neurogenic overactivity--a comparison of inflammation, oedema and fibrosis with and without injection of botulinum toxin type A.

OBJECTIVES: To study histological features and morphological differences in bladder wall specimen from patients with and without botulinum toxin A injections and to compare those issues in responders and non-responders to the toxin therapy. MATERIAL AND METHODS: Bladder wall specimen obtained from cystectomy in 45 patients with neurogenic overactive bladders with and without injection of botulinum toxin A into the detrusor muscle for treatment of neurogenic incontinence were evaluated concerning the histological criteria inflammation, oedema and fibrosis of the bladder wall. RESULTS: Bladder wall specimen obtained from patients suffering from neurogenic detrusor overactivity showed important histological alterations. Generally, inflammatory infiltration, oedema and fibrosis of the bladder wall were frequently observed. When comparing specimen from patients who had received botulinum toxin injection to those from patients who had not, there was no difference concerning inflammation and oedema. However, patients who had received botulinum toxin injection showed significantly less fibrosis of the bladder wall than those who had not received the toxin injection (p<0.00073). When comparing specimen from responders and non-responders to the botulinum toxin therapy, there was no difference in inflammation. Although not significant, a trend was observed that responder to the toxin therapy had less fibrosis and oedema of the bladder wall than non-responder. CONCLUSION: In our study injection of botulinum toxin into the detrusor muscle did not lead to increased fibrotic activity within the bladder wall, on the contrary patients with previous botulinum toxin injection revealed significant less fibrosis than patients without toxin injection.

Immunohistochemical expression of p63, p53 and MIB-1 in urinary bladder carcinoma. A tissue microarray study of 158 cases.

P63 is a member of the p53 family, which plays a role in the differentiation of urothelium and is supposed to play a role in urothelial carcinogenesis. P53 and MIB-1 are recognised in many studies as predictive markers of progression, but few studies in the literature have examined p63. The aims of our study were to explore the expression of p63 in bladder carcinomas and to compare this expression to p53 and MIB-1, as well as to stage and grade. Tissue microarrays were performed on 158 urothelial carcinomas (56 pTa, 45 pT1 and 57>or=pT2). Immunohistochemical studies were performed with p63, p53 and MIB-1 antibodies. In our study we observed that p63 immunostaining is present in all cell layers in papillary urothelial neoplasm of low malignant potential (PUNLMP), but partially lost in non-invasive papillary urothelial carcinoma low grade (NILGC) and in pT1/>or=pT2 bladder cancers. P53 and MIB-1 displayed lower expression in PUNLMP/NILGC vs non-invasive papillary urothelial carcinoma high grade (NIHGC)/pT1, but there was no correlation between the expression of p63, p53 and MIB-1. Our study demonstrates that p63 expression distinguishes between PUNLMP/NILGC and NIHGC/pT1 (p=4.10(5)). A statistical difference disserving pTa and pT1/>or=pT2 with a statistical significance (p<10(-6)) could also be observed. P63 should be considered as an additional biomarker that might help pathologists to classify their patients.

[Cavernosal metastases from bladder tumour after cystoprostatectomy]. / Métastases caverneuses de tumeurs de vessie après cystoprostatectomie.

OBJECTIVE: To evaluate the predictive factors for cavernosal metastases after cystoprostatectomy for transitional cell bladder cancer. MATERIAL AND METHOD: Between February 1998 and January 2002, 61 men were treated by cystectomy for transitional cell bladder cancer (56 total cystoprostatectomies and 5 partial cystectomies). Five patients (8%) subsequently developed cavernosal metastases. The assessment criteria were classified into three categories: clinical history, histological findings on the operative specimen and follow-up data. RESULTS: The metastasis was observed an average of 8.4 months (range: 3-17) after cystoprostatectomy. Three of the 5 patients had a history of transurethral procedure at the same time as resection of a high-grade invasive bladder tumour: a urethral recurrence concomitant with the penile metastasis was observed in these cases. In 4 out of 5 cases, the bladder tumour was multifocal, involving the bladder neck, extensive and high-grade (> or = pT3 G3). Vascular tumour emboli were detected on the cystoprostatectomy specimen in 4 cases. All urethral sections performed during cystectomy were negative. All 5 patients died with a mean survival of 7 months (range: 1 to 21 months). CONCLUSION: The development of penile metastases after cystectomy appears to be frequently associated with the presence of extensive tumour (> or = pT3) on the operative specimen, involving the bladder neck, with a high histoprognostic grade and with the presence of tumour embolus. No transurethral procedures should be performed at the same time as resection of an obviously invasive bladder tumour. Health urethral sections do not exclude the risk of penile metastases.

CT diagnosis of ureteral fibroepithelial polyps.

We report a case of fibroepithelial polyp of the ureter with serial CT examinations. Progressive growth of the fibroepithelial polyp was documented by CT within a period of 62 months. Excretory phase contrast-enhanced CT images accurately contributed to the diagnosis of ureteral fibroepithelial polyp and allowed limited surgical resection. Accurate imaging assessment of ureteral fibroepithelial polyps is essential for a conservative surgical approach and/or observation alone.