Long-Term Experience with Hyperthermic Chemotherapy (HIVEC) Using Mitomycin-C in Patients with Non-Muscle Invasive Bladder Cancer in Spain.

(1) Background: Intravesical mitomycin-C (MMC) combined with hyperthermia is increasingly used in non-muscle invasive bladder cancer (NMIBC), especially in the context of a relative BCG shortage. We aim to determine real-world data on the long-term treatment outcomes of adjunct hyperthermic intravesical chemotherapy (HIVEC) with MMC and a COMBAT® bladder recirculation system (BRS); (2) Methods: A prospective observational trial was performed on patients with NMIBC treated with HIVEC using BRS in nine academic institutions in Spain between 2012-2020 (HIVEC-E). Treatment effectiveness (recurrence, progression and overall mortality) was evaluated in patients treated with HIVEC MMC 40mg in the adjuvant setting, with baseline data and a clinical follow-up, that comprise the Full Analysis Set (FAS). Safety, according to the number and severity of adverse effects (AEs), was evaluated in the safety (SAF) population, composed by patients with at least one adjunct HIVEC MMC instillation; (3) Results: The FAS population (n = 502) received a median number of 8.78 ± 3.28 (range 1-20) HIVEC MMC instillations. The median follow-up duration was 24.5 ± 16.5 (range 1-81) months. Its distribution, based on EAU risk stratification, was 297 (59.2%) for intermediate and 205 (40.8%) for high-risk. The figures for five-year recurrence-free and progression-free survival were 50.37% (53.3% for intermediate and 47.14% for high-risk) and 89.83% (94.02% for intermediate and 84.23% for high-risk), respectively. A multivariate analysis identified recurrent tumors (HR 1.83), the duration of adjuvant HIVEC therapy <4 months (HR 1.72) and that high-risk group (HR 1.47) were at an increased risk of recurrence. Independent factors of progression were high-risk (HR 3.89), recurrent tumors (HR 3.32) and the induction of HIVEC therapy without maintenance (HR 2.37). The overall survival was determined by patient age at diagnosis (HR 3.36) and the treatment duration (HR 1.82). The SAF population (n = 592) revealed 406 (68.58%) patients without AEs and 186 (31.42%) with at least one AE: 170 (28.72%) of grade 1-2 and 16 (2.7%) of grade 3-4. The most frequent AEs were dysuria (10%), pain (7.1%), urgency (5.7%), skin rash (4.9%), spasms (3.7%) and hematuria (3.6%); (4) Conclusions: HIVEC using BRS is efficacious and well tolerated. A longer treatment duration, its use in naïve patients and the intermediate-risk disease are independent determinants of success. Furthermore, a monthly maintenance of adjunct MMC HIVEC diminishes the progression rate of NMIBC.

Neoadjuvant chemohyperthermia: Our experience after 10 years. / Quimiohipertermia neoadyuvante: nuestra experiencia después de 10 años.

Neoadjuvant chemohyperthermia (QHT) with MMC has demonstrated its efficacy in NMIBC both in the level of complete response at the time of TURBT and reduction of recurrences after several years of follow up. We present our experience with this treatment. METHODS: We performed a case control study in a group of 104 patients with middle-high risk NMIBC. 43 of them received neoadjuvant recirculated intravesical QHT and 61 passively administered standard adjuvant MMC. Patient follow up was 43 months (3 - 108) evaluating their clinical efficacy and adverse effects in both groups. RESULTS: After neoadjuvant QHT, 27 patients showed CR (63%), 13 PR (30.2%) and 3 NR (6.9%). 5 year recurrence rate after QHT passive MMC were 16.2% and 26.2% respectively. No patient in the QHT group presented tumor progression compared to 5% progressions in the group treated with MMC at room temperature and 1.6% deaths due to metastatic disease. 94% QHT programmed doses were administered in comparison to 97%in the group of standard MMC. In the QHT group there were 60.5% grade 1-2 AEs in comparison with 49% in the standard MMC group (p<0.4). Likewise, 9.3% cases in the QHT group presented Grade 3 AEs versus 6.5% in the standard MMC (p<0,06). CONCLUSIONS: Recirculating neoadjuvant QHT achieves a reduction in tumor recurrence after 4 years with a similar AE rate in comparison with passive instillation of MMC.

Analysis of tolerance and security of chemo hyperthermia with Mitomycin C for the treatment of non-muscle invasive bladder cancer. / Aálisis de tolerancia y seguridad de la quimiohipertermia con Mitomicina C en el tratamiento del cúncer de vejiga no músculo invasivo.

OBJECTIVES: The treatment of non muscle invasive bladder cancer (NMIBC) continues to be a challenge. Hyperthermia (HT) combined with intravesical chemotherapy is used to enhance the effects of chemotherapy. METHODS: A review of the publications was carried out to synthesize the adverse effects (AE) reported by the use of chemohyperthermia (QHT) with Mitomycin-C (MMC). The most relevant data are exposed for each of the devices currently used in the QHT. RESULTS: SYNERGO®: The dropout rate varied between 3-40%, and the AE rate is up to 88%. The most common AEs were pain (2-40%), thermal reaction of the posterior wall (13-100%), bladder spasms (2-32%), dysuria (3-60%) and hematuria (2-62%). COMBAT BRS®: The dropout rate is 3-11%. The AEs reported were CTCAE Grade 1-2: Pain 13-27%, bladder spasms 6-27%and hematuria 3-20% are the most relevant. In general, CTCAE grade 3-4 toxicity is not reported. UNITHERMIA®: The dropout rate is 7-12%. The AEs described are: Pain 6-23%, bladder spasms 6-23%, hematuria 9-11, frequency 15-25% and allergy 6-11%. The majority of toxicities are CTCAE grade 1-2 (17-53%), with grade 3-4 in 9-15% and Grade 5 in 0-2%. QHT adds little to the AEs of the treatment with MMC. It neither adds severe effects, nor increases dropouts significantly, and does not increase the incidence of allergic reactions. The comparative study between BCG and QHT-MMC, is less likely to present urinary frequency, nocturia, incontinence, hematuria, fever, fatigue and arthralgia in patients in the QHT group. CONCLUSIONS: QHT has proven to be a safe alternative for the treatment of intermediate and high risk NMIBC, with AE mainly grade 1-2. The AEs reported have little variation with respect to the dose of MMC used, presenting different "profiles" related to the device used for its administration. The treatments with QHTMMC are well tolerated, without adding significantly more AE than the instillations of MMC alone and presenting a better toxicity profile than those reflected in the literature with respect to the treatment with BCG.

Thermal dosimetry for bladder hyperthermia treatment. An overview.

The urinary bladder is a fluid-filled organ. This makes, on the one hand, the internal surface of the bladder wall relatively easy to heat and ensures in most cases a relatively homogeneous temperature distribution; on the other hand the variable volume, organ motion, and moving fluid cause artefacts for most non-invasive thermometry methods, and require additional efforts in planning accurate thermal treatment of bladder cancer. We give an overview of the thermometry methods currently used and investigated for hyperthermia treatments of bladder cancer, and discuss their advantages and disadvantages within the context of the specific disease (muscle-invasive or non-muscle-invasive bladder cancer) and the heating technique used. The role of treatment simulation to determine the thermal dose delivered is also discussed. Generally speaking, invasive measurement methods are more accurate than non-invasive methods, but provide more limited spatial information; therefore, a combination of both is desirable, preferably supplemented by simulations. Current efforts at research and clinical centres continue to improve non-invasive thermometry methods and the reliability of treatment planning and control software. Due to the challenges in measuring temperature across the non-stationary bladder wall and surrounding tissues, more research is needed to increase our knowledge about the penetration depth and typical heating pattern of the various hyperthermia devices, in order to further improve treatments. The ability to better determine the delivered thermal dose will enable clinicians to investigate the optimal treatment parameters, and consequentially, to give better controlled, thus even more reliable and effective, thermal treatments.

Adjustable suburethral sling (male remeex system) in the treatment of male stress urinary incontinence: a multicentric European study.

OBJECTIVE: To evaluate the effectiveness of a readjustable sling for the treatment of male stress urinary incontinence (SUI). MATERIALS AND METHODS: Between October 2002 and August 2005, 51 male patients with mild to severe SUI were prospectively operated with the use of a readjustable sling (MRS) at seven different European hospitals: Spain (2), Italy (2), Greece (1), Germany (1), and Portugal (1). The origin of incontinence was radical prostatectomy in 43 cases, TUR in 4, and open prostatectomy in another 4. Duration of incontinence ranged from 1 to 10 yr with an average of 3.5 yr. RESULTS: All patients but 5 were regulated during the early postoperative period; 44 patients (including all 5 not regulated during the early period) required a second regulation under local anaesthesia between 1 to 4 mo after surgery, and 17 other patients required more than one delayed regulation. After that, 33 patients (64.7%) were considered cured (25 of them wore no pads at all, and 8 used small pads or sanitary napkins for security but normally remained dry); another 10 cases showed important improvement (19.6%); and only 8 patients remain unchanged (15.7%). The average follow-up time was 32 mo (range: 16-50). The mesh was removed in 1 case owing to urethral erosion and the varitensor in 2 cases owing to infection. There were five (9.8%) uneventful intraoperative bladder perforations at the postoperative period, and there were three mild perineal haematomas (5.9%). Most patients felt perineal discomfort or pain, which was easily treated with oral medications. CONCLUSIONS: The MRS((R)) allowed postoperative readjustment of the suburethral sling pressure at the immediate or midterm postoperative period, which allowed the achievement of good midterm results in almost 85% of patients without significant postoperative complications.

[Spanish registry of the TRT Reemex system in women with stress urinary incontinence (SUI)]. / Registro español del sistema TRT Remeex en mujeres con incontinencia urinaria de esfuerzo.

OBJECTIVES: Due to the absence of randomized studies, the Spanish Reemex Working Group started a registry to analyze and review the results of a large group of patients with mid-term and long-term follow-up to obtain conclusions based on clinical experience. METHODS: A registry of 715 patients who underwent surgical intervention for insertion of the SUI readjustable prosthesis Reemex TRT (tension free readjustable tape) in 15 Spanish hospitals (40% urology departments, 60% gynecology departments). The registry was established to evaluate the safety and efficacy of the sling adjustability concept in the surgical treatment of female SUI. The Spanish Working Group was able to evaluate results of the Reemex system in 683 patients of a total of 715. Mean age was 59.9 yr (range 21-87) with a mean follow-up of 23 months (6-93). The group includes: 30.2% patients with mixed incontinence, 73.1% patients with urodynamic intrinsic sphincteric deficit, 35.7% patients with previous history of failed surgical interventions for urinary incontinence, and 54.3% previous pelvic floor associated operations. All patients were evaluated preoperatively with history, physical examination and urinary incontinence questionnaire. Each follow-up visit included incontinence questionnaire, physical examination and stress test. RESULTS: Cure rate was 92.2%, with 6.9% improvement and 0.9% failures. Readjustment was performed in 416 patients (60.9%) as a second phase of surgery over the following 24-48 hours, before hospital discharge. 80 patients (11.7%) were readjusted in the mid- or long-term (between 6 and 8 months after surgery). The level of support of the sling was successfully reduced in three patients between 6 and 14 months after surgery. No other patient suffered voiding difficulties in the long-term. 1.7% of the patients needed extraction of the tensor due to persistent abdominal wall seroma. 0.8% presented vaginal extrusion of the sling. CONCLUSIONS: The Reemex system is a minimally invasive technique with consistent results and even improved in heterogeneous groups of patients including intrinsic sphincter defficiency, reoperations, mixed incontinence and associated pathologies.

Externally readjustable sling for treatment of male stress urinary incontinence: points of technique and preliminary results.

BACKGROUND AND PURPOSE: Slings have been successful in the treatment of male stress urinary incontinence (SUI). However, in many situations, the sling may have either an excess of or inadequate tension, producing voiding difficulties or urinary leakage, respectively. The effectiveness of a readjustable sling for the treatment of male SUI has been evaluated. PATIENTS AND METHODS: Between October 2001 and November 2002, six consecutive male patients with SUI, aged 69 to 81 years, received a readjustable sling (Remeex) at the Monforte Comarcal Hospital. RESULTS: Five patients (83%) achieved continence, while the remaining patient showed important improvement. All patients were satisfied or very satisfied with the results. The average follow-up time was 18 months (range 12-50 months). There were no postoperative complications. CONCLUSIONS: This original treatment allows readjustment of the sling tension in the immediate or mid-term postoperative period. Initial clinical results are encouraging.

Malignant metastatic perirenal schwannoma.

Only seven cases of malignant renal or perirenal schwannomas have previously been reported in the literature. Herein we report the case of a 74-year-old female with a previous history of malignant subcutaneous schwannoma and breast ductal adenocarcinoma who presented with a renal mass that was preoperatively diagnosed as a metastatic schwannoma. This is the first case of malignant perirenal schwannoma of metastatic origin.

Externally readjustable device to regulate sling tension in stress urinary incontinence: preliminary results.

BACKGROUND AND PURPOSE: Slings, especially those called "tension free," have low complication rates and good long-term success rates. However, they still have problems with either an excess or a lack of tension, which produces voiding difficulties or urinary leakage persistence, respectively. The effectiveness of a new adjustable sling for the treatment of stress urinary incontinence (SUI) has been evaluated. PATIENTS AND METHODS: Between November 1999 and May 2002, 113 consecutive patients were operated for SUI by means of a new adjustable sling. The results were analyzed retrospectively. The average follow-up time was 22 months (range 6-36 months). RESULTS: Objective success was achieved in 108 of 113 patients (95.5%), but subjectively, only 90.3% of the patients were completely satisfied with the procedure because of persistent urge incontinence in 6 cases (5.3%). Morbidity was minimal. CONCLUSIONS: This new minimally invasive treatment allows readjustment of sling tension at the immediate or mid-term postoperative period. It is applicable to primary and recurrent SUI and has shown encouraging results.

Neo-adjuvant treatment of infiltrating transitional-cell carcinoma of the bladder with paclitaxel and cisplatin: a phase II trial.

BACKGROUND: A phase II multicentric trial of paclitaxel and cisplatin was conducted in previously untreated patients, with locally advanced transitional-cell carcinoma (TCC) of the bladder, to assess its toxicity and efficiency in preserving the bladder. METHODS: Forty-four patients with locally advanced TCC of the bladder (seven with T3a, 27 with T3b, and eight with T4a) were treated with paclitaxel 175 mg/m(2) over 3 h, and cisplatin 75 mg/m(2) over 30 min, on the first day of each 21-day treatment cycle. Therapy was continued for three cycles. Patients were re-evaluated and scheduled for radiotheraphy or radical surgery depending on tumoral response. Tumoral response was measured by citology, computed tomographical scans, and deep randomized biopsies of the bladder. RESULTS: Thirty-two out of 42 patients (76%; 95% confidence interval 45-93%) showed a major response (22 complete, and 10 partial). Response times ranged from 18 to 54 months. Three patients with T4 bladder primary tumors experienced a pathological CR. At a median follow-up of three years, 20 patients remain free of disease (47.6%), six patients are alive with disease (14.3%), 12 patients died of disease (28.5%), and four others died of unrelated causes (9.5%). Hematological toxicity included anemia, thrombocytopenia, and neutropenia. No grade four febrile neutropenia was observed. Non-hematological toxicity included alopecia (93.2%), diarrhea (11.4%), vomiting (18.5%) mucosytis (4.6%), and neuropathy (4.6%). Drug omissions or dose delay for adverse events were only necessary in one patient (2.2%), and three patients (6.8%), respectively. CONCLUSIONS: Paclitaxel and cisplatin is an active and well-tolerated neo-adjuvant regimen for previously untreated patients with pure TCC of the bladder, achieving a vesical preservation rate of 52%.

[Acute scrotum secondary to testicular tumor]. / Escroto agudo secundario a tumor testicular.

OBJECTIVE: To report a case of testicular tumor, classified as seminoma, with a very uncommon form of presentation since it presented as acute scrotum. METHODS: The clinical features, treatment and outcome of this uncommon condition are presented. RESULTS: A review of the literature showed that this form of presentation is rare although in the present case it is impossible to determine if testicular inflammation was due to tumor necrosis or infection from the associated hydrocele. CONCLUSIONS: Testicular tumor should be considered in all male patients aged 20 to 35 years with acute scrotum.