Recurrence Of Superficial Bladder Cancer Research Articles

Disseminated Bacillus Calmette\u2013Gu\xe9rin (BCG) infection and acute exacerbation of interstitial pneumonitis: an autopsy case report and literature review

BackgroundIntravesical administration of Bacillus Calmette–Guérin (BCG) has proven useful for treatment and prevention of recurrence of superficial bladder cancer and in situ carcinoma. However, fatal side effects such as disseminated infections may occur. Early diagnosis and accurate therapy for interstitial pneumonitis (IP) are important because exacerbation of IP triggered by infections is the major cause of death. Although some fatality reports have suggested newly appeared IP after intravesical BCG treatment, to our knowledge, there are no reports which have demonstrated acute exacerbation of existing IP. Moreover, autopsy is lacking in previous reports. We report the case of a patient with fatal IP exacerbation after BCG instillation and the pathological findings of the autopsy.Case presentationA 77-year-old man with a medical history of IP was referred to our hospital because of fever and malaise. He had received an intravesical injection of BCG 1 day before the admission. His fever reduced after the use of antituberculosis drugs, so he was discharged home. He was referred to our hospital again because of a high fever 7 days after discharge. On hospitalisation, he showed high fever and systemic exanthema. Hepatosplenomegaly and myelosuppression were also observed. Biopsies revealed multiple epithelioid cell granulomas with Langhans giant cells of the liver and bone marrow. Biopsy DNA analyses of Mycobacterium bovis in the bone marrow, sputum, and blood were negative. His oxygen demand worsened drastically, and the ground-glass shadow expanded on the computed tomography scan. He was diagnosed with acute exacerbation of existing IP. We recommenced the antituberculosis drugs with steroid pulse therapy, but he died on day 35 because of respiratory failure. The autopsy revealed a diffuse appearance of multiple epithelioid cell granulomas with Langhans giant cells in multiple organs, although BCG was not evident.ConclusionsWe report the first case of acute exacerbation of chronic IP by BCG infection. This is also the first case of autopsy of a patient with acute exacerbation of existing IP induced by intravesical BCG treatment. Whether the trigger of acute IP exacerbation is infection or hypersensitivity to BCG is still controversial, because pathological evidence confirming BCG infection is lacking. Physicians who administer BCG against bladder cancer should be vigilant for acute exacerbation of IP.

Evaluation of miR-146a Urinary Level as a Marker for Recurrence of Superficial Bladder Cancer after Transurethral Resection of Bladder Tumor (TUR-BT)

Background: The most prevalent malignancy affect the urinary system is bladder cancer which exhibits a markedly high recurrence rate. The level of urinary microRNA-146a (miR-146a) was significantly higher in superficial bladder cancer patients, and were decreased to normal range after transurethral resection of the bladder tumor (TUR-BT). Its level was increased again if there is recurrence of the superficial bladder tumor diagnosed by follow up cystoscopy. miR-146 may be a clinically important marker for diagnosis and recurrence of superficial bladder cancer and is used instead of follow up operations as follow up cystoscopy for follow up of recurrence . Objective: our work aims to detect a simple, reliable and noninvasive diagnostic and surveillance methods for follow up of superficial bladder cancer. Methodology: The level of miR-146a in urine of 30 superficial bladder cancer patients was evaluated by quantitative reverse transcription polymerase chain reaction assay using voided urine samples before, after TUR-BT and after 3, 6,9,12 months of resection and compared with the result of follow up cystoscopy. Results: miR-146a was significantly increased in urine samples from patients with superficial cancer bladder than in those from the normal individuals (P <.000). Elevated urinary miR-146a levels in patients with bladder cancer were lowered to the normal level after TUR-BT and increased again in those who have tumor recurrence and remain in a normal level in those who have no recurrence after follow up for 3 ,6, 9,12 months after surgery(P=. 007, P=.000 respectively).Conclusion: Our study concluded that urinary miR-146a may be useful as a novel noninvasive diagnostic and follow up marker, anticancer agent or therapeutic target for superficial cancer bladder, also for increasing our knowledge of cancer biology.

Comparison of gemcitabine and anthracycline antibiotics in prevention of superficial bladder cancer recurrence

BackgroundBecause of the failure, shortage and related toxicities of Bacillus Calmette-Guérin (BCG), the other intravesical chemotherapy drugs are also widely used in clinical application. Gemcitabine and anthracycline antibiotics (epirubicin and pirarubicin) are widely used as first-line or salvage therapy, but which drug is better is less discussed.MethodsA total of 124 primary NMIBC patients administered intravesical therapy after transurethral resection of bladder tumor (TURBT) at Nanjing Drum Tower hospital from January 1996 to July 2018. After TURBT, all patients accepted standard intravesical chemotherapy. Recurrence was defined as the occurrence of a new tumor in the bladder. Progression was defined as confirmed tumor invading muscular layer. Treatment failure was defined as need for radical cystectomy (RC), systemic chemotherapy and radiation therapy.ResultsOf the 124 patients who underwent intravesical chemotherapy, 84 patients were given gemcitabine, 40 patients were given epirubicin or pirarubicin, with mean follow-up times (mean ± SD) of (34.8 ± 17.9) and (35.9 ± 22.1) months respectively. The clinical and pathological features of patients show no difference between two groups. Recurrence rate of patients given gemcitabine was 8.33% (7 out of 84), the recurrence rate was 45% (18 out of 40) for epirubicin or pirarubicin (P < 0.0001). The progression rates of gemcitabine, anthracycline antibiotics groups were 2.38% (2 out of 84) and 20% (8 out of 40), respectively (P < 0.001). The rate of treatment failure is 8.33% (7 out of 84) and 25% (10 out of 40), respectively (P = 0.012). Gemcitabine intravesical chemotherapy group was significantly related to a lower rate of recurrence (HR = 0.165, 95% CI 0.069–0.397, P = 0.000), progression (HR = 0.160, 95% CI 0.032–0.799, P = 0.026) and treatment failure (HR = 0.260, 95% CI 0.078–0.867, P = 0.028).ConclusionIn conclusion, gemcitabine intravesical chemotherapy group was significantly related to a lower rate of recurrence, progression and treatment failure. Gemcitabine could be considered as a choice for these patients who are not suitable for BCG.

Comparison of Recurrence of Low Risk Superficial Bladder Cancer in Patients with And Without Single Dose Intravesical Doxorubicin Instillation

Comparison of Recurrence of Low Risk Superficial Bladder Cancer in Patients with And Without Single Dose Intravesical Doxorubicin Instillation

Intravesical Bacillus Calmette-Guerin Cystitis

Intravesical BCG is known to significantly reduce superficial bladder cancer recurrence and progression rates, and as such has become a standard adjuvant treatment in medium and high-risk disease. It is however known that only 16% of patients are able to tolerate the full 36-month schedule, and the reasons for cessation are often due to local and systemic side effects. This review aims to look at ways to reduce local toxicity (and increase compliance) and the evidence base behind various strategies. The magnitude and level of evidence for all methods employed to try to reduce toxicity is scant. Reducing the amount of BCG in contact with the urothelium has been tried both by reducing dwell time and using lower (1/3) dose regimes. There is no oncological data to support or refute the use of a shorter dwell time, and furthermore, there is no evidence that reducing the dose has any effect on local side effect profiles. Good practice guidelines have been written to ensure BCG is administered in a way that reduces local side effects as much as possible; however, local toxicity is still common. Other approaches used to decrease BCG toxicity include oral anticholinergic use, anti-tuberculous chemotherapy, quinolone antibiotics, oral pentosan polysulphate as well as intravesical instillations. The oncological outcomes of using these adjuncts are largely unreported. Although it is usually self-limiting, BCG cystitis has important implications for patients, as it is the most common reason for cessation of BCG therapy. Despite the frequency with which it occurs, the treatment options for BCG cystitis are very limited and not backed up by high level evidence. More research is needed into the oncological outcomes of adjuvant therapies that appear to have good symptomatic benefit.

Bladder cancer and Th1 chemokines

Bladder cancer arises from the epithelial lining of the urinary bladder, and it is known as transitional cell carcinoma (TCC). Tobacco smoking is the main known contributor to urinary bladder cancer. However thirty percent of bladder tumors probably result from occupational exposure in the workplace to carcinogens. Immunotherapy by intravesicular delivery of Bacillus Calmette–Guérin (BCG) is used to treat and prevent the recurrence of superficial bladder cancer. Successful BCG immunotherapy for bladder cancer is associated with proper induction of T helper (Th)1 immunity. In bladder cancer patients after intravesicular BCG, urine was found to contain high levels of IP-10, and Interferon (IFN)-γ. TCC and endothelial cell lines were able to secrete IP-10 in response to BCG or IFN stimulation in vitro. Furthermore intravesicular BCG induces a cytokine-rich urinary microenvironment that is inhibitory to human endothelial cells and it is anti-angiogenetic by the induction of Th1 chemokines. Other studies suggest that therapeutic strategies involving Th1 induction and Th2 dampening may improve responses to immunotherapy. Further studies are needed to evaluate the IP-10 in circulation, and urine, as prognostic marker of bladder cancer patients, also in relation to BCG immunotherapy

Effect of bladder instillation of drugs on postoperative recurrence of superficial bladder cancer

Objective To compare and analyze the Brucea javanica oil emulsion, hydroxy camptothecin bladder perfusion of recurrence after operation of superficial bladder cancer. Methods 80 cases with superficial bladder cancer were randomly divided into group A and group B(n=40). Group A received intravesical instillation of Brucea javanica oil emulsion, group B received intravesical instillation of hydroxycamptothecin.The serum tumor marker levels were compared between two groups, and the recurrence rate and adverse reactions in the two groups were observed. Results At 1 day before operation, postoperative 7d, the serum Dickkopf-1(DKK-1), Dickkopf-2(DKK-2), Dickkopf-3(DKK-3), Dickkopf-4(DKK-4), vascular endothelial growth factor A(VEGFA), vascular endothelial growth factor B(VEGFB), vascular endothelial growth factor C(VEGFC) of the two groups had no statistically significant differences (P>0.05). Postoperative 6 months, the serum levels of DKK-1, DKK-2, DKK-3, DKK-4, VEGFA, VEGFB, VEGFC in group A were (20.62±2.84)g/L, (29.15±6.32)g/L, (18.66±4.53)g/L, (32.34±6.42)g/L, (80.72±9.16)g/L, (60.43±16.73)g/L, (70.31±8.41)g/L, respectively, which were lower than those of group B [(27.42±3.76)g/L, (38.16±4.34)g/L, (30.37±5.35)g/L, (47.26±7.72)g/L, (146.31±12.44)g/L, (83.14.14.07) g/L, (91.58±7.82)g/L, respectively, t=-2.92, -2.58, -2.82, -2.41, -2.80, -2.75, -2.70, all P<0.01]. The recurrence rate of group A was 7.5%(3/40), which was significantly lower than 15.0%(6/40) of group B(6/40)(χ2=6.11, P <0.05). The incidence rate of adverse reactions of group A was 12.5%, which was significantly lower than 27.5% of the control group(χ2=5.46, P<0.05). Conclusion Compared with hydroxyl camptothecine vesical perfusion, the effect of intravesical instillation of Brucea javanica oil emulsion in preventing the postoperative recurrence of superficial bladder cancer is more significant, can effectively reduce the levels of serum tumor marker, with less adverse reactions, it is worth application and promotion. Key words: Urinary bladder neoplasms; Brucea javanica; Hydroxycamptothecin; Chemotherapy, cancer, regional perfusion; Recurrence

MGMT hypermethylation and BCL-2 overexpression associated with superficial bladder cancer and recurrence.

Urinary bladder carcinoma is one of the leading causes of death among men, and its high recurrence rates make it one of the most solid tumors to treat. The silencing of the tumor suppressor gene by hypermethylation of the CpG islands and overexpression of proto-oncogene proteins are the main mechanisms in cancers. Here, we investigate methylation status of O6-methylguanine-DNA-methyltransferase (MGMT), a tumor suppressor gene and expression level of BCL-2 a proto-oncogene protein that is frequently observed in bladder carcinoma and its recurrences. We analyzed the methylation of MGMT in 80 tissue samples of patients suffering from bladder cancer and 80 urine samples of cancer-free individuals by MS-PCR. Additionally, BCL-2 protein expression level was analyzed on these 80 tissue samples by immunohistochemistry. 45% of patients had MGMT methylation, of which this hypermethylation does not have significant association with an increase in grade, but there was significant association in cases with recurrence tumors and metastasis tumors. Among patients with recurrence tumor, 92.5% patients showed MGMT hypermethylation; 66% of these showed BCL-2 overexpression. Our data indicate that MGMT hypermethylation and BCL-2 overexpression may have an intense role in superficial bladder cancer recurrences.

LB-S&T-26 THE SAFETY AND EFFICACY OF LOW DOSE BCG INTRAVESICAL INSTILLATION FOR THE TREATMENT OF UREMIC OR KIDNEY TRANSPLANT PATIENTS WITH RECURRENT UROTHELIAL CARCINOMA OF THE BLADDER

You have accessJournal of UrologyLate-Breaking S&T Poster1 Apr 2016LB-S&T-26 THE SAFETY AND EFFICACY OF LOW DOSE BCG INTRAVESICAL INSTILLATION FOR THE TREATMENT OF UREMIC OR KIDNEY TRANSPLANT PATIENTS WITH RECURRENT UROTHELIAL CARCINOMA OF THE BLADDER Wei-Ting Kuo, Chia-Cheng Yu, and Tony T. Wu Wei-Ting KuoWei-Ting Kuo More articles by this author , Chia-Cheng YuChia-Cheng Yu More articles by this author , and Tony T. WuTony T. Wu More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.03.107AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Theoretically, immunosuppression is a relative contraindication for intravesical BCG trerapy because of the risk of severe morbidity and sepsis. We present our experience with intravesical BCG therapy in uremia/renal transplant patients with recurrent urothelial carcinoma of bladder. METHODS A total of 34 patients with recurrent superficial bladder cancer (pTa or pT1) were enrolled. Ten patients are uremic and the other 14 were renal transplantation patient. Intravesical instillation with low dose(1/2 or 1/3 of 81mg) of BCG was administered weekly for 6 weeks, postoperatively. Boost dose was given at 3 months interval and then every 6 months until 2 years postoperatively. Cystoscopic examination was performed every 3 months for the first year and semiannually for 2 years and then annually. RESULTS Low dose BCG intravesical instillation was completed in 30 patients. Tumor recurrence was recognized in 2 patients during followup, who restarted second BCG induction therapy without recurrence. BCG therapy was withdrawn in 4 patients due to BCG-related local toxicity. No major complication or systemic dissemination of TB bacili was noted. Transient dysuria and hematuria are the most common adverse events. CONCLUSIONS uremia/renal transplantation patients were traditionally considered as immuno-compromised and high risk for tumor recurrence. Low dose BCG intravesical instillation in such patients seems to be a safe prophylaxis with similar efficacy on tumor control. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e347 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Wei-Ting Kuo More articles by this author Chia-Cheng Yu More articles by this author Tony T. Wu More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Potential Effect of Liposomes and Liposome-Encapsulated Botulinum Toxin and Tacrolimus in the Treatment of Bladder Dysfunction.

Bladder drug delivery via catheter instillation is a widely used treatment for recurrence of superficial bladder cancer. Intravesical instillation of liposomal botulinum toxin has recently shown promise in the treatment of overactive bladder and interstitial cystitis/bladder pain syndrome, and studies of liposomal tacrolimus instillations show promise in the treatment of hemorrhagic cystitis. Liposomes are lipid vesicles composed of phospholipid bilayers surrounding an aqueous core that can encapsulate hydrophilic and hydrophobic drug molecules to be delivered to cells via endocytosis. This review will present new developments on instillations of liposomes and liposome-encapsulated drugs into the urinary bladder for treating lower urinary tract dysfunction.

Significance of muscularis mucosae on the risk of recurrence and progression in patients with superficial bladder cancer

Background. Due to the currently accepted operative technique of the transurethral resection (TUR) of bladder, during the surgery we obtain a histological material that is multiple pieces of the tissueof exophytic area of tumor, the bladder base and the bladder wall, in which a specialist histologist can be guided only with careful labeling, and the correct pathologic diagnosis is possible only in case of the presence of all layers of the bladder wall in the preparation. The performanceof TUR of bladderen blochas allowed visualizing an additional morphological feature in the preparation – its own muscularis mucosa. Objective. The evaluation of effectiveness of the transurethral surgical treatment of thepatients with superficial bladder cancer by comparing the immediate and long-term results of the standard TUR and the TUR of bladder wall tumor en bloc. The assessment of the role of the tumor invasion of propermuscularis mucosa in the prediction of recurrence and progression of superficial bladder cancer. Materials and methods. We analyzed the results of the examination and treatment of 270 patients with newly diagnosed «bladder cancer» who were treated between 2003 and 2012. All patients were divided into 2 groups: the main group (n = 94) who underwent the transurethral resection of the wall bladder tumor en bloc, and the compared group (n = 176) who underwent the standard transurethral resection. As a result wehave evaluated the role of the tumor invasion of propermuscularis mucosa in the prediction of recurrence and progression of superficial bladder cancer. Results and conclusions. The technique of the operation affects the recurrence rate by reducing it from 47.7 % in cases of the standard TUR to 34 % in cases of the TUR en bloc (p 0.05). The application of the TUR en bloc reduces the frequency of progressionby 4 times (p < 0.001) and increases the termsbeforethe progression by almost 2 times (p < 0.05). It allows to reduce the recurrences in the area of the resection to a minimum and to increase the periods before the occurrence of relapse. The presence of the damage ofproper muscularis mucosa (the in-growth or invasion, the categories T1b and T1c) increases the frequency of relapses for more than 2 times, and the way out of the tumor outside the layer of proper muscularis mucosareduces the term of relapse by 2.5 times, the progression rate increases from 2 % to 22.7 % and 18.5 %, and the average time before progression reduces from 41.5 to 26.0 and 17.1 with increase of the depth of tumor invasion with categories T1a, T1b and T1c respectively.

FGF2-mediated reciprocal tumor cell-endothelial cell interplay contributes to the growth of chemoresistant cells: a potential mechanism for superficial bladder cancer recurrence.

Patients with superficial bladder cancer can be definitively cured by one single transurethral resection (TUR) with additional intravesical chemotherapy; however, up to 75% of cases display frequent and multiple recurrences. One of the major causes of recurrence is that chemotherapeutic drugs used in intravesical regimens may induce chemoresistance. However, the mechanisms by which these chemoresistant cells develop into recurrent tumors remain unclear. Recent clinical evidence revealed that the expression of pro-angiogenic factor FGF2 was associated with early local relapse in patients with superficial bladder cancer. In this study, we conducted a preliminary investigation of the mechanisms of chemoresistant cells mediated bladder cancer recurrence, focusing on FGF2-initiated tumor cell-endothelial cell interaction on chemoresistant cancer cell growth. We found that the expression of FGF2 was increased in chemoresistant bladder cell lines and in bladder tissues after intravesical chemotherapy. Although chemoresistant bladder cells grow slower than parental cells, chemoresistant bladder cancer cells had stronger ability than parental cells to stimulate endothelial cell migration, growth, and tube formation by producing FGF2. Inversely, endothelial cells significantly promoted chemoresistant bladder cancer growth in vitro and in vivo. Thus, targeting chemotherapy-induced FGF2 upregulation may provide a promising approach to manage the recurrence of superficial bladder cancer.

Intravesical liposome drug delivery and IC/BPS.

Intravesical therapy has previously shown to be effective in delaying or preventing recurrence of superficial bladder cancer. This local route of drug administration is now demonstrating promise in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS) with the benefit of minimal systemic side effects. Liposomes (LPs) are lipid vesicles composed of phospholipid bilayers surrounding an aqueous core. They can incorporate drug molecules, both hydrophobic and hydrophilic, and vastly improve cellular uptake of these drug molecules via endocytosis. Intravesical LPs have therapeutic effects on IC/BPS patients, mainly due to their ability to form a protective lipid film on the urothelial surface and repair the damaged urothelium. This review considers the current status of intravesical LPs and LP mediated drug delivery for the treatment of IC/BPS.

Active specific immunotherapy: Using tumor heterogeneity to successfully fight cancer

Active specific immunotherapy: Using tumor heterogeneity to successfully fight cancer

The Inhibitory Effect of Intravesical Fisetin against Bladder Cancer by Induction of p53 and Down‐Regulation of NF‐kappa B Pathways in a Rat Bladder Carcinogenesis Model

Intravesical chemotherapy after transurethral resection has been widely used as an adjuvant therapy to prevent recurrence and progression of superficial bladder cancer. Due to the insufficiency of the current chemotherapeutics, there is an urgent need to search for more novel, effective and safe intravesical agents. Previously, we have proved the in vitro apoptotic effects of fisetin, a dietary flavonoid, on bladder carcinoma cells. In the present study, we have further explored its intravesical efficacy and investigated the underlying mechanisms of its inhibitory effect of bladder cancer through an autochthonous rat model of bladder cancer induced by intravesical N-methyl-N-nitrosourea (MNU). We found that fisetin-induced apoptosis in bladder cancer is mediated via modulation of two related pathways: up-regulation of p53 and down-regulation of NF-κB pathway activity, causing changes in the ratio of pro- and antiapoptotic proteins. Meanwhile, administration of fisetin significantly reduced the incidence of MNU-induced bladder tumours by suppressing NF-κB activation and modulating the expression of NF-κB target genes that regulate cell proliferation and cell apoptosis. Our study suggests that the activation of p53 and inhibition of the NF-κB pathway may play important roles in the fisetin-induced apoptosis in bladder cancer. Furthermore, intravesical fisetin effectively inhibited, without any toxicity, the carcinogenesis of bladder cancer in MNU-initiated rats. These findings identify the in vivo chemopreventive efficacy of fisetin and suggest that fisetin could be used as a novel, effective and safe intravesical agent for bladder cancer.

SUPERFICIAL BLADDER TUMOR;

Introduction: Bladder cancer is the second most common urologic cancer. Approximately 90% are transitional cellcarcinoma among which superficial bladder cancer constitutes about 50-70%. It is usually treated by transurethral resection withadjuvant intravesical instillations of chemotherapy or immunotherapy. Primary problems in superficial bladder cancers are its tendency torecur, about 50-80%, following surgical ablation alone, with progression to muscle invasive disease in 20-25% cases. Intravesicalchemotherapy appears to have major impact on decreasing chances of recurrence of superficial bladder cancer. Objective: To determinethe efficacy of single dose perioperative intravesical mitomycin C in reducing recurrence of superficial bladder tumor. Study Design:Comparative study. Settings: Department of Urology Shaikh Zayed Hospital Lahore. Duration of Study: One year.13-04-2009 to 13-04-2010. Methodology: Patients were divided into two groups randomly by using random numbers i.e. 40 patients in group A and 40 patientsin group B. Group A (40 patients) of bladder tumor received post TURBT single dose Mitomycin-C 40 mg/40ml N/Saline intravesically andGroup B (40 patients) was control group i.e. TURBT alone without Mitomycin-C. Results: The recurrence at first year follow up in bothgroups were showed a significant difference (p&lt;0.05) as shown in Table No V: There were only 10% recurrence in Group A i.e. patientswho had intravesical Mitomycin –C as compared to 55% recurrence in Group B, who did not received postoperative intravesicalMitomycin–C. Conclusions: It is concluded that one perioperative (within 6 hours of TURBT) intravesical instillation of chemotherapysignificantly decreases the risk of recurrence after TURBT in patients with stage Ta T1, single and multiple papillary bladder cancer in lowrisk as well as high risk tumors. One immediate instillation after TUR reduces the recurrence.

Is TURBT able to cure high risk recurrent superficial or muscle invasive bladder cancer: Factors resulting in pT0 radical cystectomy specimens

In 76% of radical cystectomy patients there is discrepancy between the initial stage at transurethral resection and the final pathological stage of the cystectomy specimen. More specifically in contemporary series the absence of tumor at radical cystectomy specimens (stage pT0) is estimated at 5-25%. Our aim was to determine which factors contributed to the absence of tumor in our series of radical cystectomy patients. Fifty one patients were submitted to radical cystectomy in our department over the last 10 years (January 2002-January 2012). A thorough analysis of the patients' files with no residual tumor on the cystectomy specimen (pT0) was performed. Possible factors contributing to such a result were described and a systematic analysis of the relevant literature was performed. Five patients had a pT0 stage after radical cystectomy. Four of them had transitional cell carcinoma and one of them had squamous cell carcinoma of the bladder on the initial transurethral resection. None of the tumors presented lymphovascular invasion. Four patients are still alive and one died 45 months postoperatively from a cardiac cause. Four factors were identified in our study to contribute towards a pT0 cystectomy result. Those included the absence of lymphovascular invasion, the completeness of transurethral resection, the experience of the surgeon and the use of a standardized technique for the transurethral resection. The time to cystectomy in our series did not have a negative effect on pT0 final pathology result.

The Impact of Intravesical Gemcitabine and 1/3 Dose Bacillus Calmette-Guérin Instillation Therapy on the Quality of Life in Patients with Nonmuscle Invasive Bladder Cancer: Results of a Prospective, Randomized, Phase II Trial

Bacillus Calmette-Guérin and intravesical chemotherapy represent viable adjuvant options for intermediate risk nonmuscle invasive bladder cancer. Although bacillus Calmette-Guérin is perceived as less tolerable than intravesical chemotherapy, to our knowledge no comparative studies have addressed quality of life issues. We compared the quality of life of patients with nonmuscle invasive bladder cancer who received adjuvant intravesical gemcitabine or 1/3 dose bacillus Calmette-Guérin. Our multicenter, prospective, randomized, phase II study included 120 patients with intermediate risk nonmuscle invasive bladder cancer. Of these patients 88 remained assessable at 1-year followup. Only 1 patient was withdrawn because of adverse events. Overall 61 patients received 2,000 mg/50 cc gemcitabine weekly for 6 weeks (maintenance monthly for 1 year) while 59 received 1/3 dose bacillus Calmette-Guérin Connaught weekly for 6 weeks (maintenance 3 weekly instillations at 3, 6 and 12 months). Quality of life was measured by the EORTC QLQ-C30 (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 version 3.0) and QLQ-BLS24 (Quality of Life Superficial Bladder Cancer-Specific 24) questionnaires. Group differences were calculated using ANOVA (ANOVA/MANOVA). Treatment was well tolerated in both groups, although local and systemic side effects were more frequently reported in the bacillus Calmette-Guérin arm. Multivariate analyses showed no significant differences between the 2 groups in all quality of life dimensions. No significant changes over time in quality of life domains were detected for patients on bacillus Calmette-Guérin and gemcitabine except for physical functioning, which decreased significantly in both groups (p = 0.002). No significant differences were detected in terms of recurrence and progression between the 2 groups at 1-year followup. While a higher rate of side effects, albeit mild to moderate, was detected with 1/3 dose bacillus Calmette-Guérin compared to gemcitabine, our study failed to show significant differences between the 2 drugs in terms of quality of life.

Lower cyclooxygenase-2 expression is associated with recurrence of solitary non-muscle invasive bladder carcinoma.

BackgroundA new modality is necessary to prevent recurrence of superficial bladder cancer after complete transurethral resection because of the high recurrence rate even with current prophylaxis protocols.MethodsIn order to analyze the predictive value of cyclooxygenase-2 (COX-2) expression and tumor infiltrating lymphocytes (TILs) in recurrence of this disease tumor specimens from 127 patients with solitary papillary non-muscle invasive bladder cancer (NMIBC), 78 with recurrent disease and 49 without recurrence during follow up of minimum 5 years, were retrieved for tissue microarrays construction and immunohistochemical analysis. COX-2 expression was scored according to Allred’s scoring protocol, while presence of TILs was categorized as absent (no) or present (yes) on whole tissue sections.ResultsCOX-2 immunoreactivity was presented in 70 (71%), weak in 16% and strong in 55% of cases, while 29 (29%) tumors were negative. TILs were present in 64 (58%) NMIBC, while 44 cases (41%) did not reveal mononuclear infiltration in tumoral stroma. Statistical analysis demonstrated a higher proportion of patients with recurrence in the group with the COX-2 score 0, and lower in the group with score 2 (p=0.0001, p=0.0101, respectively). In addition, a higher proportion of recurrent patients in the group with no TILs, and lower proportion in the group with TILs were found (p=0.009, p=0.009, respectively). Univariate and multivariate analysis revealed overexpression of COX-2 and presence of TILs as negative predictors.ConclusionPatients with lower COX-2 expression and absence of TILs in NMIBC need to be followed up more vigorously and probably selected for adjuvant therapy.Virtual slideThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1411318819790406

Activity of intravesical CG0070 in Rb-inactive superficial bladder cancer after BCG failure: Updated results of a phase I/II trial.

4593 Background: Loss of retinoblastoma (Rb) tumor suppressor activity occurs commonly in bladder cancer and leads to upregulation of the E2F-1 transcription factor. CG0070 is a replication-competent oncolytic adenovirus genetically modified to express GMCSF under control of the human E2F-1 promoter. Updated results from a phase I study of CG0070 in patients with recurrent superficial bladder cancer (T1, Ta, Tcis) after BCG treatment are presented here. Methods: The V-0046 phase I/II study previously reported the safety and evidence of efficacy of single and multiple doses of intravesical CG0070. Efficacy was determined using quarterly cystoscopy, biopsy, and/or urine cytology. Tumor Rb status was assessed immunohistochemically in 18 tumors. Results: 35 patients were treated with either a single dose (n=13) of CG0070 ranging from 1x1012 to 3x1013 viral particles (vp) or with weekly x 6 (n=9) or every 4 week x 3-6 doses (n=13) ranging from 1x1012 to 1x1013 vp per dose. The most common adverse events regardless of schedule were flu-like illness, dysuria, hematuria, bladder spasm, and nocturia. No maximum tolerated dose was reached. Urine GMCSF and CG0070 levels were detectable in almost all patients suggesting in-vivo viral replication. The CR rate in the single dose cohort was 23% (3/13), and 64% (14/22) in the multi-dose cohorts. The CR rate for patients with either CIS or Ta tumors was 65% (15/23). Of all responders, 11 recurred with a remission duration ranging from 3.0 - 33.4 months and 6 patients, all in the multiple dose cohorts, remain in remission as of last follow-up with a remission duration ranging from 3.3 – 38.2 months. Phosphorylated (inactive) Rb was detected in 13 of the 18 (72%) patients evaluated. Nine of these 13 patients (70%) had a complete response. All patients (5/5, 100%) with known phosphorylated Rb treated in the weekly cohort experienced a CR. Conclusions: CG0070 was well tolerated with minimal toxicities. Complete responses were more frequently observed in the multiple-dose cohorts, including durable CRs in patients with inactive Rb and in patients with CIS. Further study in Rb-inactive superficial tumors is warranted.