[Recurrent invasive bladder urothelial carcinoma treated by cystectomy with substitutive ileal enterocystoplasty: case report]. / Carcinome urothélial invasif vésical récidivant traité par cystectomie avec enterocystoplastie iléale de substitution: à propos d'un cas.

We here report a case of bladder urothelial carcinoma, a rare tumor in subjects less than 40 years, as well as our therapeutic experience. The study involved a 37-year old patient with a history of urinary tract infection and of staying at a riparian area (bilharzia) presenting with hypogastralgia and total macroscopic hematuria. Clinical and paraclinical assessment showed voluminous bladder mass suggesting infiltrative tumor without local or distant lymph node or organic involvement. Surgical management was based on resection of bladder tumor and biopsy followed by total cystectomy with substitutive ileal enterocystoplasty. The postoperative course was uneventful. The patient also underwent adjuvant chemotherapy and vitamin B-12 therapy. Clinical and paraclinical assessment, performed after 6 and 12 months, showed no recurrence.

Recent advances in upper tract urothelial carcinomas: From bench to clinics.

Urothelial carcinoma in the upper tract is rare and often discussed separately. Many established risk factors were identified for the disease, including genetic and external risk factors. Radiographic survey, endoscopic examination and urine cytology remained the most important diagnostic modalities. In localized upper tract urothelial carcinomas, radical nephroureterectomy with bladder cuff excision are the gold standard for large, high-grade and suspected invasive tumors of the renal pelvis and proximal ureter, whereas kidney-sparing surgeries should be considered in patients with low-risk disease. Advances in technology have given endoscopic surgery an important role, not only in diagnosis, but also in treatment. Although platinum-based combination chemotherapy is efficacious in advanced or metastatic disease, current established chemotherapy regimens are toxic and lack a sustained response. Immune checkpoint inhibitors have led to a new era of treatment for advanced or metastatic urothelial carcinomas. The remarkable results achieved thus far show that immunotherapy will likely be the future treatment paradigm. The combination of immune checkpoint inhibitors and other agents is another inspiring avenue to explore that could benefit even more patients. With respect to the high incidence rate and different clinical appearance of upper tract urothelial carcinomas in Taiwan, a possible correlation exists between exposure to certain external risk factors, such as arsenic in drinking water and aristolochic acid in Chinese herbal medicine. As more gene sequencing differences between upper tract urothelial carcinomas and various disease causes are detailed, this has warranted the era of individualized screening and treatment for the disease.

Risk stratification for locoregional recurrence after radical cystectomy for urothelial carcinoma of the bladder.

PURPOSE: To externally validate the Christodouleas risk model incorporating pathological tumor stage, lymph node (LN) count and soft tissue surgical margin (STSM) and stratifying patients who develop locoregional recurrence (LR) after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). In addition, we aimed to generate a new model including established clinicopathological features that were absent in the Christodouleas risk model. METHODS: Prospectively assessed multicenter data from 565 patients undergoing RC for UCB in 2011 qualified for final analysis. For the purpose of external validation, risk group stratification according to Christodouleas was performed. Competing-risk models were calculated to compare the cumulative incidences of LR after RC. RESULTS: After a median follow-up of 25 months (interquartile range 19-29), the LR-rate was 11.5 %. The Christodouleas model showed a predictive accuracy of 83.2 % in our cohort. In multivariable competing-risk analysis, tumor stage ≥pT3 (HR 4.32, p < 0.001), positive STSM (HR 2.93, p = 0.005), lymphovascular invasion (HR 3.41, p < 0.001), the number of removed LNs <10 (HR 2.62, p < 0.001) and the administration of adjuvant chemotherapy (HR 0.40, p = 0.008) independently predicted the LR-rate. The resulting risk groups revealed significant differences in LR-rates after 24 months with 4.8 % for low-risk patients, 14.7 % for intermediate-risk patients and 38.9 % for high-risk patients (p < 0.001 for all), with a predictive accuracy of 85.6 %, respectively. CONCLUSIONS: The Christodouleas risk model has been successfully externally validated in the present prospective series. However, this analysis finds that overall model performance may be improved by incorporating lymphovascular invasion. After external validation of the newly proposed risk model, it may be used to identify patients who benefit from an adjuvant therapy and suit for inclusion in clinical trials.

Age at diagnosis in bladder cancer: does opium addiction play a role?

BACKGROUND: Bladder cancer is a major health problem, especially among men. Opium addiction can be an important risk factor. One important question is whether it can affect the age of onset of bladder cancer .We performed this study to evaluate this question. MATERIALS AND METHODS: In a cross-section study, records of patients diagnosed with bladder carcinoma in Shahid Labbafinejad Medical Center, within 1999-2008 were included. Data were extracted from records regarding age at onset, gender, smoking status, and opioid addiction and analyzed with SPSS 13. RESULTS: Within 10 years, 920 cases were diagnosed with bladder cancer of which 97 percent were transitional cell carcinoma. In 698 cases, opium addiction status was recorded in 21.3% (n=149). Age at diagnosis was 59.7±11.51 (median: 60) among opioid addicts which was significantly lower than non- addicts (63.1±13.65, Median: 65) (P<0.001). CONCLUSIONS: Opium addiction can decrease the age of onset of bladder cancer.

[Non-muscle invasive transitional cell carcinoma of the bladder. New developments in diagnostics and therapy]. / Das nicht muskelinvasive Urothelkarzinom der Harnblase. Neuigkeiten in der Diagnostik und Therapie.

Due to the high incidence and recurrence rate non-muscle invasive bladder cancer (NMIBC) has a relevant impact. Raman spectroscopy and optical coherence tomography represent innovative diagnostic tools. Urine markers still play a minor role in the diagnostics of NMIBC. New therapeutic options are thermochemotherapy and mitomycin-C electromotive drug administration (MMC-EMDA) as well as gemcitabine and apaziquone for intravesical administration.

Dietary patterns and risk of bladder cancer: a factor analysis in Uruguay.

OBJECTIVE: To determine the major dietary patterns associated with bladder cancer risk, we conducted a principal components analysis (PCA) in a case-control study from Uruguay. METHODS: A total of 255 newly diagnosed and microscopically confirmed cases of transitional cell carcinoma of the bladder and 501 hospitalized controls were included in the study. Both series were drawn from the four major public hospitals in Montevideo, Uruguay. Cases and controls were frequency matched on age and sex. Controls were submitted to factor (principal components) analysis. RESULTS: We retained three factors that explained 25.1% of the total variance (including error variance). The first factor was labeled as the sweet beverages pattern. This factor was characterized by high loadings of coffee, tea, and added sugar and was strongly associated with risk of bladder cancer (OR 3.27, 95% CI 1.96-5.45). The second factor was labeled as the Western pattern and displayed high loadings of red meat, fried eggs, potatoes, and red wine. This pattern was directly associated with risk of bladder cancer (OR 2.35, 95% CI 1.42-3.89). Finally, the third factor was labeled as the prudent pattern and showed high loadings of fresh vegetables, cooked vegetables, and fruits. This pattern was not associated with risk of bladder cancer. CONCLUSIONS: According to our study, non-alcoholic beverages were the strongest risk factor for bladder cancer, whereas the Western pattern was also associated with a significant increase in risk of bladder cancer.

Visualization of the basement membrane zone of the bladder by optical coherence tomography: feasibility of noninvasive evaluation of tumor invasion.

OBJECTIVES: Imaging techniques with high resolution are evolving rapidly for medical applications and may substitute invasive diagnostic techniques. The use of ultrahigh resolution optical coherence tomography (UHR-OCT) to image healthy and morphologically altered bladder tissue with virtual histology is evaluated ex vivo to define parameters necessary for future, diagnostically relevant in vivo systems. Here, special focus is on the visualization of the basement membrane zone. METHODS: Optical coherence tomography examinations were performed by using a modified commercial OCT system comprising a Ti:sapphire femtosecond laser to support an enhanced resolution of 3 microm axial x 10 microm lateral. Tomograms of 142 fresh human bladder tissue samples from cystectomies, radical prostatectomies, and transurethral tumor resections were recorded and referenced to histologic sections using standard hematoxylin and eosin staining. RESULTS: OCT of normal bladder mucosa allows for a clear differentiation of urothelium and lamina propria. The basement membrane zone is identified as a narrow, low-scattering band between these layers. This allows for reliable exclusion of invasion. Healthy urothelial tissue, carcinoma in situ, and transitional cell carcinoma can be differentiated using this imaging technique. Sensitivity of UHR-OCT for malignant bladder tissue could be determined to be 83.8%, and specificity to be 78.1%. CONCLUSIONS: UHR-OCT is considered promising in the attempt to strive for fluorescence cystoscopy-guided virtual histology as a means of supporting therapeutic decisions for bladder neoplasia.

Transitional cell carcinoma in renal transplant recipients: a single center experience.

OBJECTIVE: To present a single center experience in managing transitional cell carcinoma (TCC) in Chinese renal transplant (RTx) recipients. METHODS: In a cohort of 1429 patients who received RTx operation, 27 patients (six males and 21 females) were pathologically diagnosed with TCC in their native urologic system. The data were analyzed retrospectively. RESULTS: The incidence of TCC was 1.89% and accounted for 41.5% of the patients with post-transplant de novo malignancies among 1429 recipients. Among the 27 recipients with TCC, 77.8% were female, 59.3% had taken a Chinese herb that contains aristolochic acid for at least 2 months before RTx, 51.9% had painless gross hematuria, while 40.7% had microscopic hematuria and/or repeated urologic infection. Two patients were found to have asymptomatic hydronephrosis during a routine check-up. The patients with upper tract carcinoma underwent simultaneous bilateral nephroureterectomy or unilateral nephroureterectomy and bladder cuff resection. Transurethral resection of the bladder tumor was carried out in patients with concomitant or solitary superficial bladder lesions. Intravesical chemotherapy was started and immunosuppressants were adjusted in all patients immediately after the surgery. Tumor recurrence in the bladder was noted in five patients. In one patient, residual and/or recurrent carcinoma in the contralateral pelvis was detected. CONCLUSIONS: Transitional cell carcinoma is the predominant malignancy in Chinese RTx recipients. Female sex, the Chinese herb containing aristolochic acid and immunosuppression are markedly associated with the development of TCC. Risk-adapted screening, strict follow up, standard surgical intervention and dose reduction of immunosuppressants are very important for early diagnosis and treatment of TCC.

Urachal carcinoma: surgical and chemotherapeutic options.

The urachal ligament is an embryologic remnant connecting the dome of the bladder to the umbilicus via the ligamentum commune. Autopsy series suggest that in approximately a third of subjects, the urachal remnant may persist with tubular or cystic structures. However, tumors of this site are extremely rare. Patients usually present with hematuria and upon imaging, have evidence of a cystic or solid structure in the bladder dome or in the bladder midline. If a biopsy confirms adenocarcinoma, these tumors should be considered an urachal cancer until proven otherwise. Although there are no prospective clinical trials reported to date, large single-institution reports suggest surgical resection with a partial cystectomy and en bloc resection of the urachal ligament with umbilicus as the treatment of choice in the setting of localized disease. Although there is currently no definitive role for neoadjuvant or adjuvant chemotherapy in this tumor, risk factors predicting progression may allow for the selection of patients at higher relapse risk for prospective studies. Unfortunately, there are many patients who present with metastatic disease that currently is not likely to be curable. There is no standard chemotherapy regimen for these patients; however, there is new-found hope with a currently accruing clinical trial exploring a 5-fluorouracil-based chemotherapy combination in this patient population.

Treatment of urethral recurrence following radical cystectomy and ileal bladder substitution.

PURPOSE: With the introduction of orthotopic bladder substitution after radical cystectomy in patients with invasive bladder cancer urethral recurrences have become a therapeutic challenge. MATERIALS AND METHODS: We retrospectively evaluated our patients with urethral recurrences treated with a urethra sparing approach after orthotopic bladder substitution. Depending on the extension of recurrence and eventual concomitant metastases patients were treated with urethrectomy, no treatment, systemic chemotherapy or intraurethral bacillus Calmette-Guerin (BCG). Three times the common dose of BCG (ImmuCyst, Aventis, Paris, France or OncoTICE, Organon, West Orange, New Jersey) in 150 ml NaCl 0.9% was used for intraurethral BCG perfusion therapy according to an institutional protocol using a modified Foley catheter. This regimen was repeated weekly for 6 weeks and patients were followed prospectively. RESULTS: Between 1985 and 2001, 15 of 371 patients (4%) who received an orthotopic bladder substitute had urethral recurrence. Two patients were treated with systemic chemotherapy (methotrexate, vinblastine, doxorubicin and cisplatin) alone due to metastatic disease and 10 received intraurethral BCG therapy. Five of 6 patients (83%) with carcinoma in situ remained free of recurrence following treatment with BCG, while in 4 with papillary or invasive disease treatment failed. Three patients underwent urethrectomy, including 2 following failed BCG therapy for papillary disease. CONCLUSIONS: Carcinoma in situ urethral recurrence following orthotopic bladder substitution can be treated successfully with intraurethral BCG perfusion therapy in approximately 80% of patients. However, papillary and invasive transitional cell urethral recurrence should be treated with urethrectomy.

Management and prognosis of transitional cell carcinoma superficial recurrence in muscle-invasive bladder cancer after bladder preservation.

PURPOSE: To assess the bladder preservation rate and cancer-specific survival after conservative treatment of superficial relapses in invasive tumors after bladder preservation. MATERIAL AND METHODS: Fifty-one patients with invasive bladder tumor (T2) were treated using transurethral resection (TUR) followed by three cycles of systemic chemotherapy (carboplatin-vinblastine). After three weeks, an endoscopic reappraisal was made including deep TUR of the site of the original tumor and multiple cold cup biopsies. Forty-two patients retained their bladder (33 complete responses and 9 partial responses). RESULTS: With a median follow-up of 63 months, 18 patients recurred as superficial TCC tumor (43%). Fourteen patients with high grade superficial recurrence were treated with TUR and Bacillus Calmette-Guerin (BCG) instillations; two patients (G2-3 T1) with TUR as well as endovesical mytomicine, and two patients with low grade recurrence with only TUR. With a median follow-up of 44 months after TUR of first superficial relapse, there was only one case with progression of the disease without any evidence of bladder tumor. Two cystectomies were made due to carcinoma in situ (Cis) persistence and high grade superficial recurrence. Eighty-three percent of the patients who had superficial recurrence retained their bladders, with 94% cancer-specific survival. CONCLUSIONS: A very strict follow-up is mandatory due to the high rate of superficial relapses (43%). Cis is the most frequent type of superficial recurrence. Superficial recurrences in bladder preservation may be treated with TUR and BCG instillations when they are high grade and and/or associated with Cis. Superficial recurrences do not imply a worse prognosis for bladder preservation or cancer-specific survival.

Prediagnostic toenail selenium and risk of bladder cancer.

The association between several cancers and selenium status has been investigated in epidemiological studies. However, few results concerning bladder cancer have been reported thus far. The association between toenail selenium status and subsequent bladder cancer incidence was investigated in a prospective cohort study among 120,852 men and women aged 55-69 years at baseline (September 1986). The cohort members completed a questionnaire on risk factors for cancer and provided toenail clippings for determination of baseline selenium status. Follow-up for incident cancer was established by record linkage to cancer registries until December 1992. The multivariable case-cohort analysis was based on 431 bladder cancer cases and 2,459 subcohort members, for whom toenail selenium levels were available. The age-, sex- and smoking-adjusted rate ratios (95% confidence intervals) for increasing quintiles of toenail selenium were 1.00 (reference), 1.09 (0.80-1.48), 0.55 (0.38-0.79), 0.63 (0.43-0.91), and 0.67 (0.46-0.97), respectively (P-trend < 0.01). Analyses with selenium as a continuous variable supported these findings. An inverse association between toenail selenium and bladder cancer risk was most pronounced among ex-smokers (P-trend < 0.01); was similar for subjects with high versus low intakes of beta-carotene, vitamin C, and vitamin E; and was mainly confined to invasive transitional cell carcinomas of the urinary bladder, irrespective of tumor morphology. We conclude that the evidence is in favor of an inverse association between selenium and bladder cancer risk.

A phase I-II study of synchronous chemoradiotherapy for poor prognosis locally advanced bladder cancer.

BACKGROUND: The management of locally advanced bladder cancer remains controversial with poor local control with radiotherapy alone. Synchronous chemotherapy regimens have yielded encouraging results in other primary sites. PATIENTS AND METHODS: Patients with T2-T4a N0/NX M0 bladder cancer were entered into this single centre phase I-II study. Patients received radiotherapy to 55 Gy in 20 fractions over four weeks. Concurrent chemotherapy was given with Mitomycin C 12 mg/m2 day 1 and 5-fluorouracil 500 mg/m2/24 hours weeks one and four of radiotherapy for five or seven days on each occasion. RESULTS: Thirty-one patients entered the trial from March 1998 to December 1999 (22: 5-day; 9: 7-day schedule). Median age was 68 (range 58-79) years, 23 males and 8 females. T2: 9 (29%); T3a: 4 (12%); T3b: 9 (29%); T4: 9 (29%); TCC grade 2: 8 (26%) and grade 3: 23 (74%); 14 of 31 had hydronephrosis. Ten of thirty-one had a GFR < 50 ml/min. Toxicity was mild to moderate with the five-day schedule. More severe toxicity was seen with the seven-day schedule: five of nine patients failed to complete planned therapy. Pathological complete response rate at three months was 74% (5-day regimen) and 50% (7-day regimen). Overall 12-month survival was 65%. CONCLUSION: Chemoradiotherapy with the five-day schedule is feasible with acceptable toxicity in poor prognosis patients. A randomised trial is being launched.

A practical approach to bladder sampling and diagnostic reporting of pathological findings.

The most common bladder specimens are obtained from endoscopic biopsies and transurethral resections (TURB), both of which sample subepithelial tissue of varying depth. Other specimens can be obtained from cystectomy, cystoprostatectomy, pelvic exenteration ("en bloc" resection), and partial cystectomy including resection of diverticulae and surgical excision of a urachal carcinoma. The correct assessment of bladder specimens may provide clinically relevant diagnostic and prognostic data. This protocol is intended to assist pathologists in providing clinically useful information as a result of examination of surgical specimens.

Holmium laser resection v transurethral resection of the prostate: results of a randomized trial with 2 years of follow-up.

BACKGROUND AND PURPOSE: The holmium laser (2140 nm) can be used to ablate, resect, and enucleate the enlarged prostate. The 2-year results of a randomized trial comparing holmium laser resection of the prostate (HoLRP) and transurethral resection (TURP) are presented. PATIENTS AND METHODS: The 120 patients were randomized to either TURP (N = 59) or HoLRP (N = 61). The patients were reviewed at 1, 3, 6, 12, 18, and 24 months postoperatively. Eighty six (72%) of the patients were available for review at the 2-year mark. RESULTS: At 2 years, there was no significant difference between the two groups in AUA Symptom Score, peak flow rate (Qmax) value, or quality of life score. Adverse events, including reoperations, incontinence, and loss of erectile potency, were also similar. CONCLUSIONS: The HoLRP and TURP procedures result in similar clinical outcomes at 2 years.

Prognostic significance of Ki-67 expression in transitional cell bladder carcinoma after radical cystectomy.

We evaluated the prognostic significance of the Ki-67 labeling index (Ki-67 LI) in 75 patients with transitional cell carcinoma of the bladder who underwent radical cystectomy. Immunohistochemical staining of archival material was performed by the streptavidin-biotin method. Univariate survival analysis showed that Ki-67 LI (p < 0.001), histologic grade (p < 0.05), tumor stage (p < 0.001) and the number of positive lymph nodes (p < 0.001) significantly correlated with prognosis. Multivariate survival analysis indicated that the Ki-67 LI (p < 0.05), histologic grade (p < 0.01), tumor stage (p < 0.01), presence of lymph node metastases (p < 0.05) and use of neo-adjuvant therapy (p < 0.05) had independent prognostic value. The Ki-67 LI is an independent prognostic factor for patients with transitional cell bladder cancer treated by radical cystectomy.

Superficial bladder cancer.

The majority of patients with bladder cancer have superficial disease. Occupational exposure to metabolites of aniline dyes and other aromatic amines has been associated with the development of bladder cancer. Latency periods can reach 50 years. Cigarette smoking has also been strongly linked to bladder cancer as an etiologic factor. The diagnosis of superficial bladder cancer can be elusive because its symptoms mimic those of other common urologic conditions such as urinary tract infection and prostatism. A high index of suspicion is required and a search for bladder cancer should be initiated in any adult (especially those over 50 years of age) who exhibits asymptomatic gross or microscopic hematuria, or irritative voiding symptoms. Cystoscopy is required for the screening and diagnosis of superficial bladder cancer, and resection of the lesion can be performed cystoscopically as well. Laser ablation of superficial lesions provides a treatment alternative that is less invasive and better tolerated by the patient, but it does not yield a tissue specimen for analysis. Urinary cytology has been invaluable in the screening, diagnosis, and follow-up of superficial bladder cancer patients, and now flow cytometry and image analysis techniques can complement it and may eventually supplant it. The key to the management of superficial bladder cancer is to identify those patients that may be at risk for recurrence and, more importantly, those who may progress to invasive or metastatic disease. Fortunately, most superficial bladder cancer remains superficial, and the overall prognosis is good, with 5-year survival rates for superficial disease of approximately 75%. As the natural history of superficial bladder cancer has become more evident through extensive research, risk factors such as tumor size, multiplicity, grade, depth of invasion, and condition of the surrounding mucosa have emerged. T1 lesions, those that invade the lamina propria, have a more ominous course than T0 and TA lesions. The mainstay of treatment for superficial disease is transurethral resection of the lesion or lesions. Intravesical therapy has been shown to have a definite effect in eradicating existing disease as well as reducing recurrences, but it has not been shown to prevent invasive disease.(ABSTRACT TRUNCATED AT 400 WORDS)