Accuracy of FDG-PET/CT for Response Evaluation of Muscle-Invasive Bladder Cancer following Neoadjuvant or Induction Chemotherapy.

INTRODUCTION: The aim of the study was to confirm the diagnostic accuracy of a second FDG-PET/CT following neoadjuvant or induction chemotherapy (NAIC) prior to radical cystectomy for patients with localized muscle-invasive bladder cancer (MIBC). METHODS: Retrospective review of 62 consecutive patients with MIBC, that had a first FDG-PET/CT between April 2016 and September 2021. Patients then underwent NAIC, followed by a second FDG-PET/CT and radical cystectomy. Patients with no hypermetabolism in the bladder and lymph nodes on the second FDG-PET/CT were considered metabolic complete responders, while patients with no evidence of residual disease on histopathology were considered pathologic complete responders. The accuracy of the second FDG-PET/CT to distinguish complete responders from patients with residual disease was calculated, with histopathology as gold standard. RESULTS: Of 62 patients, 1 was lost to follow-up, 5 died before radical cystectomy, 5 had delay >2 months between the second FDG-PET/CT and radical cystectomy, and 6 did not undergo radical cystectomy and instead underwent alternative treatment. The study cohort comprised 45 patients, 39 males and 6 females, with an age of 66 ± 6 years. In comparison to histopathology, FDG-PET/CT provided (i) sensitivity of 95% and specificity of 42%, for the overall disease; (ii) sensitivity of 100% and specificity of 36%, for the primary tumor only; and (iii) sensitivity of 97% and specificity of 30%, for the lymph nodes only. CONCLUSION: FDG-PET/CT has over 95% sensitivity for distinguishing complete responders from patients with residual disease. Thus, FDG-PET/CT can be used for early response evaluation following NAIC to identify patients that did not completely respond to chemotherapy and may require alternative treatment pathways.

Efficacy and tolerance of one-third full dose bacillus Calmette-Guérin maintenance therapy every 3 months or 6 months: two-year results of URO-BCG-4 multicenter study.

OBJECTIVES: To assess bacillus Calmette-Guérin maintenance treatment schedule for non-muscle invasive bladder cancer at 2 years, using one-third of the full dose and fewer instillations every 3 months or 6 months. METHODS: This was a prospective, randomized, multicenter study. All patients had an intermediate- or high-risk non-muscle invasive bladder cancer. They received three weekly instillations of one-third dose bacillus Calmette-Guérin every 6 months (group I) and two weekly instillations every 3 months (group II) during 3 years. In the two schedules we assessed efficacy, tolerance, leukocyturia and prostate-specific antigen. RESULTS: No significant difference was observed between the two groups for recurrence at 6, 12 or 18 months. At 2 years, tumor recurrence was observed in 10.9% and muscle invasion in 2.9% of cases. Bacillus Calmette-Guérin tolerance was comparable - the adverse events score was 0.8 in group I and 1 in group II (P = 0.242). No statistical correlation was observed between the adverse events score over 2 years, either for leukocyturia (P = 0.8891) or prostate-specific antigen level (P = 0.7155). Leukocyturia level was not significantly associated with tumor recurrence or progression. CONCLUSION: One-third dose maintenance bacillus Calmette-Guérin is effective with no impact on tumor recurrence or muscle invasion. Furthermore, there seems to be no difference in tumor response or side-effects between patients receiving two or three maintenance instillations every 3 months or 6 months. In clinical practice, the use of leukocyturia or total prostate-specific antigen levels do not appear to be useful in predicting bacillus Calmette-Guérin toxicity.

Testicular-sparing surgery for bilateral or monorchide testicular tumours: a multicenter study of long-term oncological and functional results.

OBJECTIVE: To review long-term oncological and functional outcomes of testicular-sparing surgery (TSS) in men presenting with bilateral or monorchide testicular tumours at one of five reference centres for testicular neoplasm and infertility. PATIENTS AND METHODS: We review 25 cases of bilateral synchrone and metachrone testicular tumours treated in five academic centres between 1984 and 2013. Clinical, biological, ultrasonography and pathological tumour findings, overall survival (OS) times, local or metastatic recurrence, pre- and postoperative hormonal profile, paternity and the need for androgen substitution were assessed. RESULTS: Eleven patients with a bilateral synchrone tumour and 14 patients with a testicular tumour on a solitary testicle underwent a tumorectomy. The mean (sem) patient age was 31.9 (1.04) years, total testosterone level was 4.5 (0.57) ng.mL and tumour size was 11.66 (1.49) mm. Tumour types were as follows: 11 seminoma, nine non-seminomatous or mixed germ cell tumours, four Leydig tumours, and one hamartoma. Frozen-section examination was performed in 14 patients, and matched the final pathological analysis in 11 patients. There was an OS rate of 100% and three patients (12%) presented with a local recurrence after a mean follow-up of 42.7 months. Radical orchiectomy was performed for six patients. No patient with a preserved testicle required androgen therapy; the mean postoperative total testosterone level was 4.0 ng/mL. No patient remained fertile after radiation therapy. CONCLUSIONS: TSS for bilateral testicular tumour is safe and effective in selected patients, and should be considered to avoid definitive androgen therapy. Adjuvant radiotherapy remains poorly described in the literature, leading to adjuvant treatment heterogeneity for testicular tumours.

Oncologic outcomes and survival in pT0 tumors after radical cystectomy in patients without neoadjuvant chemotherapy: results from a large multicentre collaborative study.

PURPOSE: To assess the postsurgical survival of patients with urothelial carcinoma of the bladder with pT0 tumor at pathologic examination of cystectomy specimens. METHODS: A multi-institutional, retrospective database was analyzed with data from 4758 radical cystectomy (RC) patients who underwent RC without neoadjuvant chemotherapy and who were diagnosed with pT0 on the basis of the pathologic specimen. Survival curves were estimated. A multivariate Cox model was used to evaluate the association between prognosis factors and disease recurrence or survival. RESULTS: Overall, 258 patients (5.4%) were included in the study. The median age was 64 years. At last resection, 171 tumors were invasive (at least pT2), and 87 were not. Median follow-up was 51 months. At multivariate analysis, initial location of the tumor and absence of lymphadenectomy were associated with tumor recurrence (P = 0.03 and P = 0.005, respectively) and specific mortality (P = 0.005 and 0.001, respectively). The main limitation of the study is its retrospective design, which is due to the rarity of this situation. Cancer-specific and recurrence-free survival rates were 89 and 85%, respectively, at 5 years and 82 and 80%, respectively, at 10 years. CONCLUSIONS: Despite acceptable oncological outcomes, patients with a pT0 tumor at the time of RC are still at risk of recurrence and progression and should not be considered to be entirely cured. In this population, stringent follow-up according to current recommendations should be effective.

Renal cell carcinoma (RCC) in patients with end-stage renal disease exhibits many favourable clinical, pathologic, and outcome features compared with RCC in the general population.

BACKGROUND: Patients with end-stage renal disease (ESRD) are at risk of developing renal tumours. OBJECTIVE: Compare clinical, pathologic, and outcome features of renal cell carcinomas (RCCs) in ESRD patients and in patients from the general population. DESIGN, SETTING, AND PARTICIPANTS: Twenty-four French university departments of urology participated in this retrospective study. INTERVENTION: All patients were treated according to current European Association of Urology guidelines. MEASUREMENTS: Age, sex, symptoms, tumour staging and grading, histologic subtype, and outcome were recorded in a unique database. Categoric and continuous variables were compared by using chi-square and student statistical analyses. Cancer-specific survival (CSS) was assessed by Kaplan-Meier and Cox methods. RESULTS AND LIMITATIONS: The study included 1250 RCC patients: 303 with ESRD and 947 from the general population. In the ESRD patients, age at diagnosis was younger (55 ± 12 yr vs 62 ± 12 yr); mean tumour size was smaller (3.7 ± 2.6 cm vs 7.3 ± 3.8 cm); asymptomatic (87% vs 44%), low-grade (68% vs 42%), and papillary tumours were more frequent (37% vs 7%); and poor performance status (PS; 24% vs 37%) and advanced T categories (≥ 3) were more rare (10% vs 42%). Consistently, nodal invasion (3% vs 12%) and distant metastases (2% vs 15%) occurred less frequently in ESRD patients. After a median follow-up of 33 mo (range: 1-299 mo), 13 ESRD patients (4.3%), and 261 general population patients (27.6%) had died from cancer. In univariate analysis, histologic subtype, symptoms at diagnosis, poor PS, advanced TNM stage, high Fuhrman grade, large tumour size, and non-ESRD diagnosis context were adverse predictors for survival. However, only PS, TNM stage, and Fuhrman grade remained independent CSS predictors in multivariate analysis. The limitation of this study is related to the retrospective design. CONCLUSIONS: RCC arising in native kidneys of ESRD patients seems to exhibit many favourable clinical, pathologic, and outcome features compared with those diagnosed in patients from the general population.

Targeted therapies in non-muscle-invasive bladder cancer according to the signaling pathways.

With 300,000 annually new cases worldwide, urothelial-cell carcinoma of the bladder (UCCB) is the second most common urologic neoplasm after prostate carcinoma. Non-muscle-invasive bladder cancer (NMIBC), which is not immediately life-threatening, represents 70% to 80% of these initial cases. Despite optimal treatment (transurethral resection with intravesical chemo- or immunotherapy), 70% of these NMIBC will recur, and 10% to 20% will progress, highlighting the need for a new therapeutic approach. Indeed, the identification of patients at high risk of disease recurrence and progression would be beneficial in predicting which patients with NMIBC would benefit from strict follow-up and which would benefit from a more aggressive therapy. To date, conventional treatment remains disappointing in terms of oncologic results and morbidity. The growing understanding in tumor biology has enabled the signaling pathways involved in bladder tumorigenesis and progression to be identified, but few molecular targets have been available until now. The encouraging results seen in various human carcinomas suggests that these new agents should become part of the arsenal of drugs available in the treatment of NMIBC, alone or in combination with already known agents. In this article, we have tried to highlight the main molecular signaling pathways involved in NMIBC tumorigenesis and progression, and the potential targets useful for improving the treatment of NMIBC.

Interpretation of positive flow cytometric crossmatch in the era of the single-antigen bead assay.

BACKGROUND: Prognosis of renal transplants with positive flow cytometric crossmatch (FCXM) remains controversial. METHODS: We analyzed the outcome of these kidney transplant recipients by human leukocyte antigen (HLA) donor-specific antibodies (HLA-DSA) using single-antigen bead (SAB) assays in major histocompatibility complex classes I and II. We compared them with controls with a negative FCXM. RESULTS: Forty-five patients consecutively transplanted with a positive FCXM had significantly more acute rejection episodes than the control patients (33.3% vs. 8.9%, P=0.002). Risk of acute rejection was increased with day 0 (D0) positive T-cell FCXM (odds ratio [OR]=9.04, P=0.002), D0 positive B-cell FCXM (OR=7.43, P=0.02), and D0 HLA-DSA identified by SAB assay (OR=6.5, P=0.03). The 21 patients with D0 positive FCXM and D0 HLA-DSA had more acute rejection (62%, P=0.0001) and a lower estimated glomerular filtration rate 1-year posttransplantation (P=0.0001), when compared with controls. Mainly anti-Cw and anti-DP HLA-DSA were found in patients displaying acute rejection. The remaining FCXM-positive patients displayed short-term outcomes similar to controls. The presence of HLA-DSA detected only by the SAB assay in the context of a negative FCXM crossmatch was not associated with increased risk of acute rejection. CONCLUSION: Identification of HLA-DSA in D0 sera by the two sensitive techniques FCXM and SAB assay indicates which patients are at highest risk of subsequent acute allograft rejection and chronic allograft dysfunction.

Tyrosine-kinase inhibitors in the treatment of muscle invasive bladder cancer and hormone refractory prostate cancer.

OBJECTIVES: Various protein kinases are known to be activated in cancer cells and drive tumor growth and progression. In metastatic renal cell carcinoma tyrosine-kinase inhibitors (TKIs) have achieved significant progression-free and overall survival improvements. For bladder and prostate cancers TKIs may also be considered as a promising treatment option. Our aim was to report the most relevant published articles to support the interest of the use of TKIs in the treatment of bladder and prostate cancer. METHOD: PubMed database and bibliographies of retrieved articles were reviewed. The key words used were tyrosine-kinase inhibitor, protein-kinase inhibitor, hormone refractory prostate cancer, muscle invasive bladder cancer. The most relevant publications from basic science and clinical randomized controlled studies were summarized and analyzed. RESULTS: Regarding bladder cancer, TKI treatment is one of the most studied therapeutic strategies in the field of targeted therapy. Indeed, it has been suggested that targeting TK alone and/or in association with cytotoxic chemotherapy may represent a promising option for treating locally advanced and/or metastatic bladder cancer. Concerning hormone refractory prostate cancer (HRPC), collected data are still confusing. Basic science studies found an interesting expression of EGF and VEGF receptors on cancer cells supporting the idea that TKIs could be efficient in HRPC. Nonetheless most of published clinical phase II studies found a weak effect on symptoms and quality of life without any decrease in PSA levels or overall survival. CONCLUSION: TKIs have not yet achieved in bladder and prostate cancers similar efficacy to what has been obtained in metastatic renal cell carcinoma. Further studies are needed to establish the place of such an approach in non renal tumors.

Inhibidores de la Tirosin-Quinasa en el tratamiento del cáncer de vejiga músculo-infiltrante y el cáncer de próstata hormono-refractario / Tirosin kinase inhibitor in the treatment of muscle-invasive bladder cancer and hormone refractory prostate cancer

OBJETIVO: Se sabe que varias proteín-quinasas son activadas en las células tumorales e impulsan el crecimiento y progresión tumoral. En el carcinoma de células renales metastásico, los inhibidores de la tirosin-quinasa (TKIs) han logrado importantes beneficios en progresión libre de enfermedad y supervivencia global. Los TKIs pueden ser también considerados como una prometedora opción de tratamiento en tumores vesicales y prostáticos. Nuestro objetivo fue dar a conocer los artículos más relevantes publicados para confirmar el interés de la utilización de los TKI en el tratamiento de estos tumores.MÉTODOS: Se realizó una busqueda sistemática en PubMed y se revisaron los artículos recuperados. Las palabras clave utilizadas fueron: inhibidor de la tirosin-quinasa, inhibidor de la protein-quinasa, cáncer de próstata hormono-refractario, cáncer de vejiga músculo-infiltrante. Las publicaciones más relevantes de ciencia básica y ensayos clínicos controlados y aleatorizados fueron resumidas y analizadas.RESULTADOS: En cuanto al cáncer de vejiga, el tratamiento TKI es una de las estrategias terapéuticas más estudiadas en el campo de la terapia dirigida. De hecho, se ha sugerido que dirigiendo solamente TK y/o asociándola con quimioterapia citotóxica puede representar una opción prometedora para tratar el cáncer de vejiga localmente avanzado y/o metastásico. En cuanto al cáncer de próstata hormono-refractario (CPHR), los datos recogidos son aún confusos. Los estudios de ciencia básica encontraron una interesante expresión de receptores EGF y VEGF en las células tumorales confirmando la idea de que los TKI podrían resultar eficientes en el CPHR. Sin embargo la mayoría de estudios publicados de fase II encontraron un débil efecto sobre los síntomas y la calidad de vida sin ninguna disminución en los niveles de PSA o en la supervivencia general. CONCLUSIÓN: Los TKIs todavía no han alcanzado en tumores vesicales o prostátivos una eficacia similar a lo que se ha obtenido en el carcinoma renal metastásico. Se necesitan más estudios para establecer el papel de ese enfoque en tumores no renales (AU)

OBJECTIVES: Various protein kinases are known to be activated in cancer cells and drive tumor growth and progression. In metastatic renal cell carcino-ma tyrosine-kinase inhibitors (TKIs) have achieved signifi-cant progression-free and overall survival improvements. For bladder and prostate cancers TKIs may also be con-sidered as a promising treatment option. Our aim was to report the most relevant published articles to support the interest of the use of TKIs in the treatment of bladder and prostate cancer.METHOD: PubMed database and bibliographies of retrieved articles were reviewed. The key words used were tyrosine-kinase inhibitor, protein-kinase inhibitor, hormone refractory prostate cancer, muscle invasive bladder cancer. The most relevant publications from ba-sic science and clinical randomized controlled studies were summarized and analyzed.RESULTS: Regarding bladder cancer, TKI treatment is one of the most studied therapeutic strategies in the field of targeted therapy. Indeed, it has been suggested that targeting TK alone and/or in association with cytotoxic chemotherapy may represent a promising option for treating locally advanced and/or metastatic bladder cancer. Concerning hormone refractory prostate cancer (HRPC), collected data are still confusing. Basic scien-ce studies found an interesting expression of EGF and VEGF receptors on cancer cells supporting the idea that TKIs could be efficient in HRPC. Nonetheless most of published clinical phase II studies found a weak effect on symptoms and quality of life without any decrease in PSA levels or overall survival.CONCLUSION: TKIs have not yet achieved in bladder and prostate cancers similar efficacy to what has been obtained in metastatic renal cell carcinoma. Further stu-dies are needed to establish the place of such an appro-ach in non renal tumors(AU)

Salvage radiotherapy after high-intensity focussed ultrasound for recurrent localised prostate cancer.

BACKGROUND: Radiotherapy is a treatment option in the case of local failure following treatment for localised prostate cancer with high-intensity focussed ultrasound (HIFU). OBJECTIVE: Our aim was to evaluate tolerance and oncologic control with salvage radiotherapy (SRT) after HIFU failure and to identify predictive factors of success. DESIGN, SETTING, AND PARTICIPANTS: From March 1995 to March 2008, all patients who presented with histologically proven persistent local disease following HIFU and were treated with curative intent SRT (with or without hormonal treatment) were included in this single-centre retrospective study. INTERVENTION: Patients underwent conformal radiotherapy. The median dose of conformal treatment was 72 Gy (65-78 Gy). MEASUREMENTS: The primary outcome measure was progression-free survival (PFS) defined as no biochemical relapse (three consecutive rises in prostate-specific antigen [PSA] with a velocity >0.4 ng/ml per year or PSA >1.5 ng/ml) and no additional treatment. Predictive factors of failure were examined in univariate and multivariate analyses. Adverse events in terms of urinary and digestive toxicity, urine incontinence, and erectile dysfunction (ED) were reported. RESULTS AND LIMITATIONS: The median (range) and mean (standard deviation) follow-up of the 100 patients analysed was 33 mo (5-164 mo) and 37.2 mo (23.6 mo), respectively. Eighty-three patients received SRT alone, and 17 received SRT and androgen-deprivation therapy. For the 83 patients treated with exclusive radiation therapy, PFS was 72.5% at 5 yr and 93%, 67%, and 55% for the low-, intermediate-, and high-risk groups, respectively. In the univariate analysis, PSA level prior to SRT, risk status, PSA nadir after SRT, PSA nadir after SRT >0.2 ng/ml, and time to achieve this nadir were all predictive of failure. In the multivariate analysis, PSA nadir post-SRT with a threshold at 0.2 ng/ml and time to achieve this nadir were the significant predictive factors of failure. Gastrointestinal toxicity was low; urinary toxicity grade < or =2 was 34.5%. Four were grade 3 (4.7%), one was grade 4 (1.2%), and one was grade 5 (1.2%). The incidence of severe ED (International Index of Erectile Dysfunction-5 score 5-10) was 14% pre-HIFU, and 51.9% and 82.3% pre- and post-SRT, respectively. Because our study was retrospective, results have to be interpreted cautiously. CONCLUSIONS: SRT provides satisfactory oncologic control after HIFU failure with little (or mild) additional toxicity. These results warrant further investigation.

Bladder cancer in patients after organ transplantation.

PURPOSE OF REVIEW: Bladder cancer development in organ transplant recipients remains a complex problem to manage as it has been demonstrated that the clinical course seems worse than in the general population. Most of the reports on bladder cancer after organ transplantation were done for kidney transplantation. Both virally and nonvirally are involved in bladder tumor development. The immunosuppressed status of the transplant recipients renders the screening, the therapeutic management, and the post-treatment surveillance very difficult. RECENT FINDINGS: With the increase of organ transplantation, especially renal transplantation, graft survival, and age of donor and recipient, urological cancer, including bladder cancer, become a critical problem affecting the survival. The advent of the new immunosuppressed drugs, mTOR inhibitors, leads to the hope of improving both survivals of the graft and of the recipients. SUMMARY: The molecular pathway P13K/Akt/mTOR is frequently activated during human solid tumor development and progression. However, mTOR inhibitors are also used in order to avoid renal allograft rejection. The combination of both actions could significantly improve graft and organ recipient survival and could provide progresses in targeted therapy management of bladder cancer.

Predictive factors for ipsilateral recurrence after nephron-sparing surgery in renal cell carcinoma.

BACKGROUND: Ipsilateral recurrence after nephron-sparing surgery (NSS) is rare, and little is known about its specific determinants. OBJECTIVE: To determine clinical or pathologic features associated with ipsilateral recurrence after NSS performed for renal cell carcinoma (RCC). DESIGN, SETTING, AND PARTICIPANTS: We analysed 809 NSS procedures performed at eight academic institutions for sporadic RCCs retrospectively. MEASUREMENTS: Age, gender, indication, tumour bilaterality, tumour size, tumour location, TNM stage, Fuhrman grade, histologic subtype, and presence of positive surgical margins (PSMs) were assessed as predictors for recurrence in univariate and multivariate analysis by using a Cox proportional hazards regression model. RESULTS AND LIMITATIONS: Among 809 NSS procedures with a median follow-up of 27 (1-252) mo, 26 ipsilateral recurrences (3.2%) occurred at a median time of 27 (14.5-38.2) mo. In univariate analysis, the following variables were significantly associated with recurrence: pT3a stage (p=0.0489), imperative indication (p<0.01), tumour bilaterality (p<0.01), tumour size >4cm (p<0.01), Fuhrman grade III or IV (p=0.0185), and PSM (p<0.01). In multivariate analysis, tumour bilaterality, tumour size >4cm, and presence of PSM remained independent predictive factors for RCC ipsilateral recurrence. Hazard ratios (HR) were 6.31, 4.57, and 11.5 for tumour bilaterality, tumour size >4cm, and PSM status, respectively. The main limitations of this study included its retrospective nature and a short follow-up. CONCLUSIONS: RCC ipsilateral recurrence risk after NSS is significantly associated with tumour size >4cm, tumour bilaterality (synchronous or asynchronous), and PSM. Careful follow-up should be advised in patients presenting with such characteristics.

Therapeutic management of de novo urological malignancy in renal transplant recipients: the experience of the French Department of Urology and Kidney Transplantation from Bordeaux.

OBJECTIVES: To determine and analyze the incidence, prognosis, and therapeutic strategy of de novo urological malignancies in a series of renal transplant recipients (RTRs). METHODS: A retrospective study of 1350 recipients between January 1998 and January 2008 was carried out; we reviewed the data of 42 de novo urological malignancies in 39 recipients. RESULTS: There were 21 cases of prostate cancer, 13 cases of renal cell carcinoma in 10 patients, 3 cases of renal graft tumors, and 5 cases of transitional cell carcinoma of the bladder. The overall incidence of urological neoplasms was 3.1%. The mean age of cancer diagnosis was 60 +/- 8.3 years. The mean duration of dialysis before cancer diagnosis was 35 +/- 37.5 months. About 92% of patients underwent hemodialysis (34/39) and the remaining underwent peritoneal dialysis (5/39). All the 39 recipients received cadaveric kidneys. The mean follow-up period for this study was 33 +/- 34.4 months (range 2-160 months). There appears to be a greater risk of urological neoplasm in RTRs. Prostate cancer and renal carcinoma can be treated in a similar manner than in general population with encouraging oncological results and low morbidity. However, the transitional cell carcinoma of the bladder remains particularly aggressive requiring optimal treatment despite the morbidity concerning the intravesical therapy. CONCLUSIONS: We can apply the standard medical and surgical treatment in RTRs, with encouraging oncological results if a strict screening program is established and followed by the patients.

The epithelial-mesenchymal transition-inducing factor TWIST is an attractive target in advanced and/or metastatic bladder and prostate cancers.

PURPOSE: Metastasis remains the main cause of death in both bladder (BCa) and prostate (PCa) cancers. The results of chemotherapy did not show any significant improvement of the survival the past years. Cancer research has led to the identification of signaling pathways involved and molecular targets that could change the natural history. The epithelial-mesenchymal transition (EMT), critical during embryonic development, becomes potentially destructive in many epithelial tumors progression where it is inappropriately activated. The cell-cell and cell-extracellular matrix interactions are altered to release cancer cells, which are able to migrate toward metastatic sites. Hallmarks of EMT include the down-regulation of E-cadherin expression, which is the main component of the adherens junctions. The protein TWIST is a transcriptional repressor of E-cadherin, tumor progression, and metastasis, and could be used as a molecular target to restore the chemosensitivity in BCa and PCa. MATERIALS AND METHODS: We selected the last 5-year basic research literature on EMT and TWIST but also clinical studies on BCa and PCa in which TWIST is overexpressed and could be considered as an efficient prognostic marker and molecular target. RESULTS: TWIST is considered as a potential oncogene promoting the proliferation and inhibiting the apoptosis. TWIST promotes the synthesis of the pro-angiogenic factor, vascular endothelial growth factor (VEGF) involved in tumor progression and metastasis. Apoptosis and angiogenesis are two essential cancer progression steps in many epithelial tumors, including BCa and PCa. CONCLUSIONS: With the targeted therapy, oncology has entered into a new era, which is going to be critical in cancer treatment in combination with traditional anticancer drugs.

Phospho-Akt pathway activation and inhibition depends on N-cadherin or phospho-EGFR expression in invasive human bladder cancer cell lines.

OBJECTIVES: A particular interest in epithelial-mesenchymal transition (EMT), which takes place during embryonic development, provided potential mechanisms involved in the progression of many epithelial tumors, including bladder cancer (BC). The phospho-Akt signaling pathway is supposed to be involved in invasion and progression of human tumors, including BC. Moreover, it has been demonstrated in bladder cancer cell lines that N-cadherin or phospho-epithelial growth factor receptor (EGFR) expression are correlated to tumor progression. Our objectives were to evaluate the potential phospho-Akt pathway involvement in N-cadherin and/or phospho-EGFR positive BC cell lines and to evaluate the prognostic value of E- and N-cadherin expression in patients undergoing cystectomy for invasive BC. MATERIALS AND METHODS: We screened a panel of invasive and noninvasive BC cell lines for E- and N-cadherin, phospho-EGFR, and phospho-Akt expression using the Western blot technique (WB). The potential role of N-cadherin in invasion was assessed by Matrigel assays with and without the N-cadherin blocking monoclonal antibody GC-4. Then we used the Affymetrix microarray technique to evaluate the prognostic value of E- and N-cadherin expression in 30 patients undergoing a cystectomy for invasive BC. RESULTS: N-cadherin and phospho-EGFR expression are associated with Akt activation and with invasive behavior modulation. Even if Akt activation is sufficient in promoting invasion, its inactivation by LY294002 (PI-3 kinase inhibitor) is less efficient on invasion than inhibition of N-cadherin and phospho-EGFR by GC-4 (monoclonal antibody) and gefitinib (anti-tyrosine kinase), respectively. N-cadherin and phospho-EGFR inhibition decreased phospho-Akt activation but also caused restoration and reinforcing of E-cadherin expression, respectively, while phospho-Akt inhibition did not have any impact on E-cadherin expression. In a group of high-risk bladder tumors (T(1)G(3)), N- and E-cadherin expression could be considered as a prognostic marker. In a group of patients with invasive BC (pT(2)-T(4)) undergoing cystectomy, we showed a shorter overall survival when BC expressed N-cadherin (P = 0.0064) and when E-cadherin expression was down-regulated (P = 0.00165). The N (positive) /E (negative) profile has the worst prognosis (P = 0.00153). CONCLUSIONS: We confirmed the partial responsibility of p-Akt activation in invasion of some BC cell lines expressing N-cadherin or p-EGFR and also the potential role of N-cadherin and p-EGFR as target in cancer therapy. N/E- cadherin expression profile has a significant prognostic value in invasive BC.

Predictive risk factors for pain during extracorporeal shockwave lithotripsy.

PURPOSE: Extracorporeal shockwave lithotripsy (SWL) is a noninvasive but painful procedure. The aim of this study was to identify predictive risk factors for pain during SWL. PATIENTS AND METHODS: Two hundred twenty-two SWL treatments with the Lithostar lithotripter (Siemens) were included in a monocentric study. Patient and stone characteristics were prospectively collected in a database, and a standardized pain control protocol was administered 1 hour before treatment: paracetamol, nefopam, ketoprofen, and alprazolam. Subjective pain level was assessed with visual analog scale (VAS, 0-10). If VAS was >or=3, tramadol was added. If VAS was still >or=3, shockwave intensity was decreased or treatment was interrupted. The efficacy on stone fragmentation was evaluated 1 month after treatment. The need for adjuvant analgesia was compared with patient and stone characteristics to find out predictive risk factors for pain. RESULTS: The average subjective pain was 3.1. The need for supplementary analgesia was more frequent in women (p = 0.035), younger patients (p < 0.001), anxious and depressed patients (p = 0.018), in patients with previous SWL (p = 0.0185), in patients with a rib projected stone (p < 0.001), in patients with renal stones (p = 0.0535), and finally in patients with homogeneous stones (p = 0.02). Multivariate analysis revealed two independent risk factors for pain: young age (odds ratio = 5; p < 0.001) and rib projected stone (odds ratio = 5.23; p < 0.001). Stone fragmentation was worse in patients with an adjuvant analgesia requirement (p = 0.0311). CONCLUSION: Predictive risk factors for pain during SWL treatments were found: young age, rib projected stones, anxious and depressed patients, previous SWL treatment, and homogeneous stones. A higher analgesic requirement is necessary for these preselected patients to perform SWL and optimize its efficacy.

Laparoscopic radical prostatectomy in renal transplant recipients.

OBJECTIVES: To report our experience with 9 consecutive laparoscopic radical prostatectomy (LRP) on renal transplant recipients (RTR) and to compare it with other LRPs performed during the same period by the same surgeons. Retropubic radical prostatectomy has widely been described in RTR, whereas LRP has rarely been studied. METHODS: Between January 2007 and December 2008, all clinical data from patients undergoing radical prostatectomy were prospectively collected in a database. The database was searched to find information of LRP on RTR. We compared RTR and other patients for all relevant clinical data and for surgical complications. RESULTS: A total of 9 LRP on RTR (5.8%) and other 164 LRP were performed. LRP on RTR were compared with other LRP. No statistically relevant difference was observed in patient characteristics, biopsy core pathologic analysis, prostate specimen pathologic analysis, and oncologic outcomes. Surgical procedure was also achieved under the same conditions in RTR than in other patients (surgical time, blood loss, transfusion rate, bladder injury). Rectal injury rate was significantly higher in RTR than in other patients (22.2% vs 1.8%, P = .022). CONCLUSIONS: LRP in RTR is feasible. The procedure can be managed the same way as LRP on other patients, but special care must be taken to avoid rectal injury. In our experience, the dissection of the posterior side of the prostate was more difficult on RTR than on other patients.

Case study of the month. Complete histologic remission after sunitinib neoadjuvant therapy in T3b renal cell carcinoma.

The authors present the first case report of complete histologic remission after neoadjuvant sunitinib treatment on primary renal tumour and vena cava thrombus. A 78-yr-old woman with an Eastern Cooperative Oncology Group (ECOG) score of 0 presented with a T3b renal tumour. She refused surgical treatment but agreed to percutaneous biopsy and medical treatment. A Fuhrman III renal cell carcinoma was histologically confirmed on percutaneous biopsy, and sunitinib treatment was administered over 6 mo. A significant objective response was observed for tumour size and thrombus. The patient finally accepted surgical treatment. Pathologic examination concluded with a complete response of primary tumour and thrombus.

Oncological risk of laparoscopic surgery in urothelial carcinomas.

OBJECTIVE: To assess the oncological safety of laparoscopic procedures for the management of urothelial carcinomas of the urinary tract. METHODS: Data on laparoscopic management of urothelial carcinomas in the literature were analysed using MEDLINE and by matching the following keywords: urological malignancies, upper tract tumours, bladder carcinomas, laparoscopic approach, recurrence, follow-up and metastasis site. RESULTS: Minimally invasive techniques are being used increasingly in the management of these tumours and successfully achieving the benefits of lower blood loss and more rapid patient recovery. To date, no evidence level 1 information is available and published series of these technically challenging cases are small and follow-up limited. Short to medium term follow-up appears encouraging in terms of recurrence and survival rates, but long-term data are immature compared to the established open techniques these procedures seek to duplicate. Specific concerns in terms of the oncologic safety of laparoscopy, especially with regard to the pneumoperitoneum, tumour manipulation and specimen extraction are addressed. Port-site metastases and tumour seeding are rare events and appear to be mainly related to the grade and stage of the tumour. Specific precautions are required to minimise these risks. CONCLUSION: Oncological results of the laparoscopic approach are difficult to compare with those of open surgery. However, recent series have not reported unusual tumour dissemination or a higher rate of recurrence with this approach. Laparoscopic techniques are not yet standard of care in invasive urothelial carcinomas. Long-term assessment is ongoing and awaited.

The expression of Twist has an impact on survival in human bladder cancer and is influenced by the smoking status.

OBJECTIVES: Twist is considered as transcription factor that regulates epithelial mesenchymal transition (EMT) by at least inhibition of E-cadherin expression. EMT is a key event in the tumor invasion process. The purpose of this study is to investigate the expression of Twist but also those of E- and N-cadherin in human primary bladder tumor and to evaluate its prognostic value. As smoking cigarettes is a strong bladder cancer risk factor, we tried to evaluate the impact of the tobacco status on these molecular abnormalities. MATERIALS AND METHODS: To delineate on the oncogenic role for Twist in human bladder cancer, we evaluated the E- and N-cadherin but also Twist expression (n = 70) by immunohistochemistry. We evaluated the prognostic value of these expressions. Moreover, we tried to correlate these protein expressions to the smoking status of the patients. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. RESULTS: Of the 70 bladder tumors, 28 (40%) cases were positive for Twist expression, 16 (23%) cases were negative for E-cadherin expression, and 12 (17%) were positive for N-cadherin expression. When categorized into negative vs. positive expression, Twist was associated with the stage (P = 0.001), the grade (P < 0.001), the progression (P = 0.02), and the E-cadherin expression (P = 0.01). Moreover, positive Twist expression clearly predicted poorer PFS (P = 0.02). In the multivariate analysis, both positive Twist expression and loss of E-cadherin expression were independent prognostic factors for PFS (P = 0.046 and P = 0.001, respectively) and only loss of E-cadherin expression for the OS (P < 0.001). We also demonstrated that almost 60% (16/28) of patients with Twist-positive expression were current smokers at the time of the diagnosis, corroborating the fact that smoking modulates the expression of EMT markers including Twist. CONCLUSION: Positive Twist expression may be a useful prognostic marker for patients with bladder cancer. Its expression seems to be correlated to the tobacco status of the patients.