Luigi Filippo Da Pozzo

Università Vita-Salute San Raffaele, Milano, Lombardy, Italy

Are you Luigi Filippo Da Pozzo?

Claim your profile

Publications (14)90.15 Total impact

  • Source
    Article: Impact of venous tumour thrombus consistency (solid vs friable) on cancer-specific survival in patients with renal cell carcinoma.
    [show abstract] [hide abstract]
    ABSTRACT: To our knowledge, the impact of venous tumour thrombus (VTT) consistency in patients affected by renal cell carcinoma (RCC) has never been addressed. To analyse the effect of VTT consistency on cancer-specific survival (CSS). We retrospectively analysed 174 consecutive patients with RCC and renal vein or inferior vena cava (IVC) VTT who underwent surgical treatment between 1989 and 2007 at our institute. All patients underwent radical nephrectomy and thrombectomy. Pathologic specimens were reviewed by a single uropathologist. In addition to traditional pathologic features, the morphologic aspect of the tumour thrombus was evaluated to distinguish solid from friable patterns. The prognostic role of thrombus consistency (solid vs friable) on CSS was assessed by means of Cox regression models. The VTT was solid in 107 patients (61.5%) and friable in 67 patients (38.5%). The presence of a friable VTT increased the risk of having synchronous nodal or distant metastases, higher tumour grade, higher pathologic stage, and simultaneous perinephric fat invasion (all p < 0.05). The median follow-up was 24 mo. The median CSS was 33 mo; the median CSS was 8 mo in patients with a friable VTT and 55 mo in patients with a solid VTT (p < 0.001). On multivariable analyses, the presence of a friable VTT was an independent predictor of CSS (p = 0.02). The power of our conclusion may be somewhat limited by the relatively small study population and the retrospective nature of the study. In patients with RCC and VTT, the presence of a friable thrombus is an independent predictor of CSS. If our finding is confirmed by further studies, the consistency of the tumour thrombus should be introduced into routine pathologic reports to provide better patient risk stratification.
    European urology 08/2011; 60(2):358-65. · 7.67 Impact Factor
  • Article: Lymphatic spread of nodal metastases in high-risk prostate cancer: The ascending pathway from the pelvis to the retroperitoneum.
    [show abstract] [hide abstract]
    ABSTRACT: The aim of this study was to map the nodal metastases distribution in patients with high-risk prostate cancer (PCa) treated with extended pelvic lymph node dissection (ePLND) and retroperitoneal lymph node dissection (rLND) at the time of radical prostatectomy (RP). This prospective mapping study included 19 patients with high-risk PCa (sharing at least two out of the three following parameters: PSA >20 ng/ml, cT3, biopsy Gleason score ≥8). All patients were treated with RP, ePLND (removal of the obturator, hypogastric, external iliac, presacral, and common iliac lymph nodes) and rLND (removal of para-aortal/para-caval and inter-aorto-caval lymph nodes) by a single surgeon. All patients signed an informed consent highlighting the absence of clinical data supporting the benefit of this surgical approach. Overall, 18 out of 19 patients (94.7%) had pelvic lymph node invasion. The most commonly affected pelvic nodal landing site was obturator (88.8%), followed by external iliac (83.3%), common iliac (77%), hypogastric (44.4%), and presacral (33.3%). Moreover, 14 (77.8%) patients also had involvement of retroperitoneal lymph nodes. Only patients with positive common iliac lymph nodes having at least five positive lower pelvic lymph nodes (n = 14), also had invariably positive retroperitoneal lymph nodes. No patients with negative common iliac lymph nodes had positive retroperitoneal lymph nodes. PCa lymphatic spread ascends from the pelvis up to the retroperitoneum invariably through common iliac lymph nodes. PCa lymphatic spread can be divided in two main levels: pelvic and common iliac plus retroperitoneal lymph nodes.
    The Prostate 05/2011; 72(2):186-92. · 3.48 Impact Factor
  • Article: Combination of adjuvant hormonal and radiation therapy significantly prolongs survival of patients with pT2-4 pN+ prostate cancer: results of a matched analysis.
    [show abstract] [hide abstract]
    ABSTRACT: Previous prospective randomised trials have shown a positive impact of adjuvant radiation therapy (RT) in patients with locally advanced prostate cancer. However, none of these trials included patients with lymph node invasion (LNI). The aim of this study was to assess the impact of combination adjuvant hormonal therapy (HT) and RT on the survival of patients with prostate cancer and histologically documented lymph node metastases (pN+). Data on 703 consecutive patients with LNI treated with radical prostatectomy, pelvic lymph node dissection, and adjuvant treatments between September 1986 and November 2002 at two large academic institutions were reviewed. For study purposes, patients treated with adjuvant HT plus RT and patients treated with adjuvant HT alone were matched for age at surgery, pathologic T stage and Gleason score, number of nodes removed, surgical margin status, and length of follow-up. Differences in cancer-specific survival (CSS) and overall survival (OS) were compared using the Kaplan-Meier method and life table analyses. Following the matching process, 117 pT2-4 pN1 patients of 171 (68.4%) treated with adjuvant HT plus RT (group 1) were compared with 247 pT2-4 pN1 patients of 532 (46.4%) receiving adjuvant HT alone (group 2). After matching, the two groups of patients were comparable in terms of pre- and postoperative characteristics (all p ≥ 0.07). Mean follow-up was 100.8 mo (median: 95.1 mo; range: 3.5-229.3 mo). Overall, prostate CSS and OS rates at 5, 8, and 10 yr were 90%, 82%, and 75%, and 85%, 70%, and 60%, respectively. Patients treated with adjuvant RT plus HT had significantly higher CSS and OS rates compared with patients treated with HT alone at 5, 8, and 10 yr after surgery (95%, 91%, and 86% vs 88%, 78%, and 70%, and 90%, 84%, and 74% vs 82%, 65%, and 55%, respectively; p = 0.004 and p<0.001, respectively). Similarly, higher survival rates associated with the combination of HT plus RT were found when patients were stratified according to the extent of nodal invasion (namely, two or fewer vs more than two positive nodes; all p ≤ 0.006). Lack of standardised HT and RT protocols represents the main limitations of our retrospective study. Adjuvant RT plus HT significantly improved CSS and OS of pT2-4 pN1 patients, regardless of the extent of nodal invasion. These results reinforce the need for a multimodal approach in the treatment of node-positive prostate cancer.
    European urology 02/2011; 59(5):832-40. · 7.67 Impact Factor
  • Article: Diagnosis of high-grade prostatic intraepithelial neoplasia: the impact of the number of biopsy cores at initial sampling on cancer detection after a saturation re-biopsy.
    [show abstract] [hide abstract]
    ABSTRACT: To evaluate factors that may predict prostate cancer (PCa) detection after initial diagnosis of high-grade prostatic intraepithelial neoplasia (HGPIN) on 6-24 cores prostatic biopsies (PBx). We retrospectively evaluated 193 patients submitted from 1998 to 2007 to prostate re-biopsy after initial HGPIN diagnosis in three urologic departments. HGPIN diagnosis was obtained on initial systematic PBx with 6 to 24 random cores. All patients were re-biopsied with a "saturation" PBx with 18-26 cores with a median time to re-biopsy of 12 months. All slides were reviewed by expert uro-pathologists. Plurifocal HGPIN (pHGPIN) was found in 103 patients and monofocal HGPIN (mHGPIN) in 90. Seventy-two and 121 patients were submitted to > 12-core initial biopsy and < or = 12-core, respectively. Overall PCa detection at re-biopsy was 28.4%. PSA (6.7 vs 8.5 ng/ml; p = 0.029) and age (64 vs 68 years; p = 0.005) were significantly higher in patients with PCa at re-biopsy. PCa detection was significantly higher in patients who underwent a < or = 12-core initial PBx than in those with > 12-core (35.5% vs 16.8%; p = 0.03), and in patients with pHGPIN than in those with mHGPIN (34.9% vs 21%; p = 0.035). At multivariable analysis, PSA value (p = 0.007; HR:1.18), prostate volume (p = 0.01; HR:0.966), age (p < 0.001; HR:1.15), pHGPIN (p = 0.003; HR:2.97) and < or = 12-core initial biopsy (p = 0.012; HR:3.62) were independent predictors of PC detection. We further analysed the 2 groups of patients submitted to < or = 12-core and > 12-core initial PBx. Plurifocal HGPIN and older age at biopsy were independent predictors in patients with < or = 12-core initial PBx. On the contrary, in patients with > 12-core initial biopsy, higher PSA values and lower prostate volume were independent predictors of PC detection. PCa detection on saturation re-biopsy after initial diagnosis of HGPIN is significantly higher in patients submitted to < or = 12-core than those submitted to > 12-core initial PBx. In patients with < or = 12-core initial biopsy pHGPIN and older age were predictors of PCa detection at re-biopsy. In patients with > 12-core initial biopsy, higher PSA values and lower prostate volume was associated to an increased risk of PCa detection at re-biopsy.
    Archivio italiano di urologia, andrologia: organo ufficiale [di] Società italiana di ecografia urologica e nefrologica / Associazione ricerche in urologia 12/2010; 82(4):242-7.
  • Article: Clinical factors predicting late severe urinary toxicity after postoperative radiotherapy for prostate carcinoma: a single-institute analysis of 742 patients.
    [show abstract] [hide abstract]
    ABSTRACT: To investigate the clinical factors independently predictive of long-term severe urinary sequelae after postprostatectomy radiotherapy. Between 1993 and 2005, 742 consecutive patients underwent postoperative radiotherapy with either adjuvant (n = 556; median radiation dose, 70.2 Gy) or salvage (n = 186; median radiation dose, 72 Gy) intent. After a median follow-up of 99 months, the 8-year risk of Grade 2 or greater and Grade 3 late urinary toxicity was almost identical (23.9% vs. 23.7% and 12% vs. 10%) in the adjuvant and salvage cohorts, respectively. On univariate analysis, acute toxicity was significantly predictive of late Grade 2 or greater sequelae in both subgroups (p <.0001 in both cases), and hypertension (p = .02) and whole-pelvis radiotherapy (p = .02) correlated significantly in the adjuvant cohort only. The variables predictive of late Grade 3 sequelae were acute Grade 2 or greater toxicity in both groups and whole-pelvis radiotherapy (8-year risk of Grade 3 events, 21% vs. 11%, p = .007), hypertension (8-year risk, 18% vs. 10%, p = .005), age ≤ 62 years at RT (8-year risk, 16% vs. 11%, p = .04) in the adjuvant subset, and radiation dose >72 Gy (8-year risk, 19% vs. 6%, p = .007) and age >71 years (8-year risk, 16% vs. 6%, p = .006) in the salvage subgroup. Multivariate analysis confirmed the independent predictive role of all the covariates indicated as statistically significant on univariate analysis. The risk of late Grade 2 or greater and Grade 3 urinary toxicity was almost identical, regardless of the RT intent. In the salvage cohort, older age and greater radiation doses resulted in a worse toxicity profile, and younger, hypertensive patients experienced a greater rate of severe late sequelae in the adjuvant setting. The causes of this latter correlation and apparently different etiopathogenesis of chronic damage in the two subgroups were unclear and deserve additional investigation.
    International journal of radiation oncology, biology, physics 11/2010; 82(1):191-9. · 4.59 Impact Factor
  • Source
    Article: When to perform bone scan in patients with newly diagnosed prostate cancer: external validation of the currently available guidelines and proposal of a novel risk stratification tool.
    [show abstract] [hide abstract]
    ABSTRACT: Several guidelines have indicated that in patients with well-differentiated or moderately well-differentiated prostate cancer (PCa), a staging bone scan may be omitted. However, the guidelines recommendations have not yet been externally validated. The aim of the study was to externally validate the available guidelines regarding the need for a staging bone scan in patients with newly diagnosed PCa. Moreover, we developed a novel risk stratification tool aimed at improving the accuracy of these guidelines. The study included 853 consecutive patients diagnosed with PCa between January 2003 and June 2008 at a single centre. All patients underwent bone scan using technetium Tc 99m methylene diphosphonate at diagnosis. The area under the curve (AUC) of the criteria suggested by the guidelines (European Association of Urology, American Urological Association, National Comprehensive Cancer Network, and American Joint Committee on Cancer) to perform a baseline bone scan was assessed and compared with the accuracy of a classification and regression tree (CART) including prostate-specific antigen (PSA), clinical stage, and biopsy Gleason sum as covariates. The AUC of the guidelines ranged between 79.7% and 82.6%. However, the novel CART model, which stratified patients into low risk (biopsy Gleason ≤7, cT1-T3, and PSA <10 ng/ml), intermediate risk (biopsy Gleason ≤7, cT2/T3, and PSA >10 ng/ml), and high risk (biopsy Gleason >7) was significantly more accurate (AUC: 88.0%) than all the guidelines (all p≤0.002). The limitation of this study resides in its retrospective design. Moreover, the proposed risk stratification tool can be considered only for patients who are candidates for radical prostatectomy until validated in other clinical settings. This is the first study aimed at externally validating the available guidelines addressing the need for staging baseline bone scans in PCa patients. All guidelines showed high accuracy. However, their accuracy was significantly lower compared with the accuracy of the novel risk stratification tool. According to this tool, staging bone scans might be considered only for patients with a biopsy Gleason score >7 or with a PSA >10 ng/ml and palpable disease (cT2/T3) prior to treatment. However, before recommending its use in clinical practice, our model needs to be externally validated.
    European urology 04/2010; 57(4):551-8. · 7.67 Impact Factor
  • Article: Need for high radiation dose (>or=70 gy) in early postoperative irradiation after radical prostatectomy: a single-institution analysis of 334 high-risk, node-negative patients.
    [show abstract] [hide abstract]
    ABSTRACT: To determine the clinical benefit of high-dose early adjuvant radiotherapy (EART) in high-risk prostate cancer (hrCaP) patients submitted to radical retropubic prostatectomy plus pelvic lymphadenectomy. The clinical outcome of 334 hrCaP (pT3-4 and/or positive resection margins) node-negative patients submitted to radical retropubic prostatectomy plus pelvic lymphadenectomy before 2004 was analyzed according to the EART dose delivered to the prostatic bed, <70.2 Gy (lower dose, median 66.6 Gy, n = 153) or >or=70.2 Gy (median 70.2 Gy, n = 181). The two groups were comparable except for a significant difference in terms of median follow-up (10 vs. 7 years, respectively) owing to the gradual increase of EART doses over time. Nevertheless, median time to prostate-specific antigen (PSA) failure was almost identical, 38 and 36 months, respectively. At univariate analysis, both 5-year biochemical relapse-free survival (bRFS) and disease-free survival (DFS) were significantly higher (83% vs. 71% [p = 0.001] and 94% vs. 88% [p = 0.005], respectively) in the HD group. Multivariate analysis confirmed EART dose >or=70 Gy to be independently related to both bRFS (hazard ratio 2.5, p = 0.04) and DFS (hazard ratio 3.6, p = 0.004). Similar results were obtained after the exclusion of patients receiving any androgen deprivation. After grouping the hormone-naïve patients by postoperative PSA level the statistically significant impact of high-dose EART on both 5-year bRFS and DFS was maintained only for those with undetectable values, possibly owing to micrometastatic disease outside the irradiated area in case of detectable postoperative PSA values. This series provides strong support for the use of EART doses >or=70 Gy after radical retropubic prostatectomy in hrCaP patients with undetectable postoperative PSA levels.
    International journal of radiation oncology, biology, physics 08/2009; 75(4):966-74. · 4.59 Impact Factor
  • Source
    Article: Two positive nodes represent a significant cut-off value for cancer specific survival in patients with node positive prostate cancer. A new proposal based on a two-institution experience on 703 consecutive N+ patients treated with radical prostatectomy, extended pelvic lymph node dissection and adjuvant therapy.
    [show abstract] [hide abstract]
    ABSTRACT: Currently, the 2002 American Joint Committee on Cancer (AJCC) staging system of prostate cancer does not include any stratification of patients according to the number of positive nodes. However, node positive (N+) patients share heterogeneous outcomes according to the extent of lymph node invasion (LNI). To test whether the accuracy of cancer specific survival (CSS) predictions may be improved if node positive patients are stratified according to the number of positive nodes. The study cohort included 703 N+ M0 patients treated with radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND) between September 1988 and January 2003 at two large Academic Institutions. Number of positive nodes was dichotomized according to the most informative cut-off predicting CSS. Kaplan-Meier curves assessed cancer specific survival rates. Predictive accuracy of the current N stage and of the new N classification in predicting CSS was quantified with Harrell's concordance index after adjusting for pathological (T) stage and internally validated with 200 boostraps resamples. Differences in predictive accuracy were compared with the Mantel-Haentzel test. Mean follow-up was 113.7 months (median: 112.5, range 3.5-243). The mean number of nodes removed was 13.9 (range: 2-52). The mean number of positive nodes was 2.3 (range: 1-31). The most informative cut-off of positive nodes in predicting CSS was 2. Of all, 532 (75.7%) patients had 2 or less positive nodes, while 171 (24.3%) had more than 2 positive nodes. Patients with 2 or less positive nodes had significantly better CSS outcome at 15 year follow-up compared to patients with more than 2 positive nodes (84% vs 62%; p<0.001). After adjusting for pathological stage, multivariable predictive accuracy of the new N staging (<or=2 or >2 positive nodes) was 65.0% vs 60.1% when the number of positive nodes was not considered (4.9% gain; p<0.001). We demonstrated that patients with up to 2 positive nodes experienced excellent CSS, which was significantly higher compared to patients with more than 2 positive nodes. Moreover, a significant improvement in CSS prediction was reached when the number of positive nodes was considered. Thus, our results reinforce the need for a stratification of node positive patients according to the number of positive nodes and may warrant consideration in the next revision of the pathologic TNM classification.
    European urology 10/2008; 55(2):261-70. · 7.67 Impact Factor
  • Article: Prognostic value of lymph node dissection in patients with muscle-invasive transitional cell carcinoma of the upper urinary tract.
    [show abstract] [hide abstract]
    ABSTRACT: To analyze the prognostic role of lymphadenectomy (LND) in patients with muscle-invasive transitional cell carcinoma (TCC) of the upper urinary tract (UUT) managed with radical surgery. From 1986 to 2003, 132 consecutive patients with muscle-invasive TCC of the UUT underwent radical surgery. LND was performed in 95 cases. Patients were stratified according to the presence of LND and lymph node (LN) status. Univariable and multivariable Cox regression models determined the effect of age, pT, grade, nodal status (pN), number of LNs removed, year of surgery, and postoperative chemotherapy on disease-free survival (DFS) and cancer-specific survival (CSS) in the overall population and in patients who underwent LND. The actuarial 5-yr CSS in pNx patients was significantly worse than in pN0 patients (48% vs. 73%, p=0.001) and comparable to pN+ outcome (48% vs. 39%, p=0.476). In the entire population, multivariable Cox regression analyses indicated that pT and pN status were independent predictors of DFS (p=0.04, hazard ratio [HR]=1.82 and p<0.01, HR=1.34, respectively) and CSS (p<0.01, HR=2.42 and p=0.04, HR=1.32, respectively). In patients who underwent LND, the number of LNs removed was an independent predictor of DFS (p=0.03, HR=0.928) and of CSS (p=0.007, HR=0.903). The extent of LND again resulted in an independent predictor either of DFS or CSS (p=0.04, HR=0.904 and p=0.01, HR=0.867, respectively) in the subgroup of pN0 patients. LND emerged as a strong independent predictor of DFS and CSS in patients surgically managed for a muscle-invasive TCC of the UUT.
    European Urology 05/2008; 53(4):794-802. · 8.49 Impact Factor
  • Article: A nomogram for staging of exclusive nonobturator lymph node metastases in men with localized prostate cancer.
    [show abstract] [hide abstract]
    ABSTRACT: Some patients with localized prostate cancer are at risk of nonobturator lymph node invasion (NOLNI) and may require an extended pelvic lymph node dissection (ePLND). We explored the rate of exclusive NOLNI and developed a nomogram to predict it. We mapped all ePLND specimens according to their anatomic location (obturator, external iliac, internal iliac lymph nodes) and assessed the location-specific rate of LNI in 565 patients. A multivariate logistic regression-based nomogram predicting NOLNI was then internally validated with 200 bootstrap resamples. Overall, 11.1% (63 of 565) had LNI and 21 (3.7%) had exclusive NOLNI. The nomogram predicting exclusive NOLNI was 80.2% accurate. The nomogram's negative predictive value was 99%, when it predicted 0-10% probability of NOLNI. This approach could allow the omission of an ePLND in 350 of 565 (61.9%) patients and still correctly stage 85.8% of NOLNI cases. Our nomogram-based approach offers the possibility of identifying men who are at virtually zero risk of exclusive NOLNI. In these men, an ePLND may be safely avoided.
    European Urology 02/2007; 51(1):112-9; discussion 119-20. · 8.49 Impact Factor
  • Article: Complications and other surgical outcomes associated with extended pelvic lymphadenectomy in men with localized prostate cancer.
    [show abstract] [hide abstract]
    ABSTRACT: More-extensive pelvic lymph node dissection (PLND) may be associated with a higher rate of complications and a longer hospital stay than more limited PLND. Before radical retropubic prostatectomy, PLNDs were performed in 963 patients. Of these, 767 (79.6%) had >or=10 lymph nodes removed and examined (extended PLND [ePLND]), while 1-9 nodes (limited PLND [lPLND]) were removed in the remaining 196 (20.4%). Limits included external iliac, obturator, internal iliac, and iliac bifurcation. PLND-related complications and the length of hospital stay were recorded prospectively and analyzed according to the extent of PLND. In patients subjected to ePLND, the overall rate of complications was 19.8% versus 8.2% in those treated with lPLND (p<0.001). In individual analyses of specific complications, only the lymphocele rate was significantly higher after ePLND (10.3% vs 4.6%; p=0.01). Similarly, ePLND translated into a longer hospital stay (9.9 vs 8.2 d; p<0.001). These differences persisted when adjustment was made for prostate-specific antigen and either clinical or pathologic tumor characteristics. Our data indicate that, even in the hands of experienced urologic surgeons, ePLNDs are associated with higher complication rates and longer hospital stay. These detriments need to be taken into account when the staging benefit associated with ePLND is considered.
    European Urology 12/2006; 50(5):1006-13. · 8.49 Impact Factor
  • Article: Multicentric study comparing intravesical chemotherapy alone and with local microwave hyperthermia for prophylaxis of recurrence of superficial transitional cell carcinoma.
    [show abstract] [hide abstract]
    ABSTRACT: To compare the efficacy and local toxicity of the intravesical instillation of a cytostatic drug versus the same cytostatic agent in combination with local hyperthermia as an adjuvant treatment, after complete transurethral resection (TURB) of superficial transitional cell carcinoma (TCC) of the bladder. The study was designed as a prospective, multicentric, randomized trial. Eighty-three patients suffering from primary or recurrent superficial (Ta-T1) TCC of the bladder, after a complete TURB, were randomly assigned to receive intravesical instillations of mitomycin C (MMC) alone, for 41 patients, and MMC in combination with local microwave-induced hyperthermia, for 42 patients. For the combined approach, a new system, Synergo101-1 (Medical Enterprises, Amsterdam, the Netherlands) was used. The effectiveness evaluation end points of the study were evaluation of recurrence-free survival and the estimated probability of recurrence. The safety evaluation end points included subjective and objective side effects and clinical complications. For the efficacy end point, Kaplan-Meier analysis was employed, with the log-rank test for significance. Minimum follow-up time was 24 months. Of the 83 randomly assigned patients, 75 completed the study according to the protocol and had valid cystoscopy results. Survival analysis of the 75 assessable patients demonstrated a highly significant difference in the survival curves in favor of thermochemotherapy. Subjective intolerance and clinical complications were significantly higher but transient and moderate in the combined treatment group. In our series, endovesical thermochemotherapy appears to be more effective than standard endovesical chemotherapy as an adjuvant treatment for superficial bladder tumors at 24-month follow-up, despite an increased but acceptable local toxicity.
    Journal of Clinical Oncology 01/2004; 21(23):4270-6. · 18.37 Impact Factor
  • Article: Effect of local hyperthermia of the bladder on mitomycin C pharmacokinetics during intravesical chemotherapy for the treatment of superficial transitional cell carcinoma
    [show abstract] [hide abstract]
    ABSTRACT: Aims  To assess the effect of local hyperthermia on the systemic absorption of mitomycin C (MMC) during intravesical chemotherapy for the treatment of superficial transitional cell carcinoma of the bladder, and to establish the likely safety of this procedure.Methods  Group 1 (n = 12) received 20 mg intravesical MMC plus local hyperthermia, group 2 (n = 13) 20 mg MMC alone, group 3 (n = 16) 40 mg MMC plus local hyperthermia and group 4 (n = 10) 40 mg MMC alone. Patients in groups 1, 2, and 4 underwent post-tumour resection adjuvant treatment, whereas those in group 3 still had tumour present and were treated to eradicate it. Intravesical instillation lasted 60 min, with the solution (50 ml) being replaced after the first 30 min. Blood samples were taken before, and every 15 min during instillation. MMC concentrations in plasma and in urine were determined by h.p.l.c.Results  The highest MMC plasma concentration (67.9 ng ml−1) occurred in a patient in group 3. This value was well below the threshold concentration (400 ng ml−1) for myelosuppression. Local hyperthermia associated with the intravesical chemotherapy enhanced plasma MMC concentrations at 30, 45 and 60 min compared with chemotherapy alone (Group 1 vs 2, P ≤ 0.008). Systemic exposure to MMC was not significantly increased by doubling the intravesical dose when intravesical chemotherapy alone was administered. Patients in group 3 displayed the highest degree of MMC absorption and the greatest variability in pharmacokinetics between patients.Conclusions Local hyperthermia enhances the systemic absorption of MMC during intravesical chemotherapy for bladder cancer. In the doses used, plasma MMC concentrations were always more than six times lower than those shown to cause toxicity.
    British Journal of Clinical Pharmacology 08/2001; 52(3):273 - 278. · 2.96 Impact Factor
  • Article: LOCAL MICROWAVE HYPERTHERMIA AND INTRAVESICAL CHEMOTHERAPY AS BLADDER SPARING TREATMENT FOR SELECT MULTIFOCAL AND UNRESECTABLE SUPERFICIAL BLADDER TUMORS
    [show abstract] [hide abstract]
    ABSTRACT: PurposeThe role of a combined regimen of local hyperthermia and topical chemotherapy in patients with multifocal and recurrent superficial bladder tumors not curable by transurethral resection was evaluated in a neodjuvant organ sparing clinical study.Materials and MethodsA total of 19 patients with multifocal, superficial grades 1 to 3 bladder tumors that recurred after intravesical chemoprophylaxis or immunoprophylaxis underwent local combined administration of microwave induced hyperthermia and intravesical chemotherapy as a debulking approach. Due to extensive superficial involvement of the bladder walls complete transurethral resection of all tumors seemed technically unfeasible in all cases and radical cystectomy was considered the treatment of choice. Endovesical hyperthermia at 42.5 to 46C was delivered using the SB-TS 101 system,* based on a microwave transurethral applicator that irradiates the bladder filled with a circulating solution of mitomycin C. Patients underwent 8 weekly 1-hour sessions on an outpatient basis without anesthesia. When possible, after treatment patients underwent transurethral resection of residual tumors and all suspicious areas.*Boston Scientific Corp., Natick, Massachusetts.ResultsAfter treatment transurethral resection appeared to be feasible and curative in 16 patients (84%). Histological study revealed complete and partial responses in 9 (47%) and 7 (37%) cases, respectively. Due to extensive residual tumors radical cystectomy was performed in 3 patients (16%). At a median 33-month followup 8 superficial transitional tumor recurrences were documented and easily eradicated by transurethral resection or laser therapy in patients in whom the bladder had been saved.ConclusionsMicrowave induced hyperthermia combined with intravesical mitomycin C seems to be a feasible, safe and elective approach for conservative treatment of multifocal and recurrent superficial bladder tumors when other treatment strategies have failed.
    The Journal of Urology.