Expression of integrin proteins in non‐muscle‐invasive bladder cancer: significance of intravesical recurrence after transurethral resection

Study Type – Aetiology (case control)
Level of Evidence 3b What’s known on the subject? and What does the study add? A number of studies have reported several clinicopathological factors closely associated with intravesical recurrence of non‐muscle invasive bladder cancer (NMIBC). In addition, various types of molecular markers have been shown to be useful for predicting intravesical recurrence of NMIBC following transurethral resection (TUR). Of six subunits of integrin proteins, including α2, α3, α5, α6, β1 and β4, the expression level of the β4 subunit in NMIBC, in addition to pathological T stage and concomitant carcinoma in situ appeared to be independently related to intravesical recurrence. Therefore, consideration of the expression levels of integrins, particularly that of the β4 subunit, in TUR specimens would contribute to further accurate prediction of intravesical recurrence of NMIBC.

OBJECTIVES

• ? To evaluate the expression of integrin proteins, a family of transmembrane heterodimers, in non‐muscle‐invasive bladder cancer (NMIBC).
• ? To assess the significance of these proteins as prognostic indicators in patients undergoing transurethral resection (TUR).

PATIENTS AND METHODS

• ? The present study comprised 161 patients diagnosed as having NMIBC after TUR.
• ? Expression levels of six subunits of integrin proteins, including α2, α3, α5, α6, β1 and β4, were measured in TUR specimens by immunohistochemical staining.

RESULTS

• ? Of the six proteins, expression levels of α2‐, α3‐, α6‐ and β4‐subunits were significantly associated with the incidence of intravesical recurrence. Univariate analysis identified expression levels of α3‐, α6‐ and β4‐subunits as important predictors of intravesical recurrence, while tumour size, pathological T stage and concomitant carcinoma in situ (CIS) were also important.
• ? Multivariate analysis showed that the expression level of the β4 subunit, pathological T stage and concomitant CIS are independently related to intravesical recurrence.
• ? There were significant differences in intravesical recurrence‐free survival for patients who were positive for the three independent risk factors; intravesical recurrence occurred in 10 of 49 (20.4%) patients who were negative for all risk factors, 31 of 68 who were positive for one risk factor (45.6%), and 30 of 44 who were positive for two or three risk factors (68.2%).

CONCLUSIONS

• ? Consideration of the expression levels of integrins, particularly those of the β4 subunit, in TUR specimens, in addition to conventional variables, would contribute to accurate prediction of intravesical recurrence after TUR for NMIBC patients.

     

Reduced bladder tumour recurrence rate associated with narrow‐band imaging surveillance cystoscopy

Study Type – Diagnostic (exploratory cohort)
Level of Evidence 2b What’s known on the subject? and What does the study add? Narrow‐band imaging cystoscopy is a new imaging modality developed to enhance conventional standard white‐light cystoscopy to evaluate bladder tumors. The current paper suggests that fulguration of low‐risk papillary bladder tumours using NBI cystoscopy results in fewer subsequent tumour recurrences than fulguration using standard cystoscopy. How, or if, NBI cystoscopy will become integrated into routine management of non‐invasive bladder tumours remains for further study.

OBJECTIVE

To evaluate frequency of recurrences among patients with papillary bladder tumours followed sequentially with conventional white‐light (WLI) cystoscopy and narrow‐band imaging (NBI) cystoscopy.

PATIENTS AND METHODS

A cohort of 126 patients with recurrent low‐grade papillary bladder tumours were followed every 6 months for 3 years by conventional WLI cystoscopy, and then over the next 3 consecutive years by NBI cystoscopy. Recurrent tumours detected were treated by outpatient fulguration or transurethral resection. We compared the tumour recurrence rate during follow‐up with WLI and NBI cystoscopy, using patients as their own controls.

RESULTS

Of the 126 patients, 94% had tumour recurrences during WLI cystoscopy vs 62% during NBI cystoscopy. The mean number of recurrent tumours was 5.2 with WLI cystoscopy vs 2.8 with NBI cystoscopy, and the median recurrence‐free survival time was 13 vs 29 months (P= 0.001).

CONCLUSION

Compared with follow‐up with WLI cystoscopy, NBI cystoscopy was associated with fewer patients having tumour recurrences, fewer numbers of recurrent tumours, and a longer recurrence‐free survival time.     

Stage Ta-T1 bladder cancer: the relationship between findings at first followup cystoscopy and subsequent recurrence and progression

PURPOSE: We studied the relationship of first cystoscopy findings with recurrence and progression rates in a large, population based series of patients with bladder cancer. MATERIALS AND METHODS: All 463 patients with an initial diagnosis of stage Ta-T1 bladder cancer in western Sweden in 1987 to 1988 were followed at least 5 years. The 355 patients who were treated with transurethral resection only until repeat cystoscopy or longer were selected for this report. RESULTS: Negative first cystoscopy findings were associated with significantly decreased recurrence and progression rates for all grades, and for stage Ta and T1 tumors. However, some patients with initial high grade carcinoma (WHO 2 to 3) had stage progression despite negative first cystoscopy. On multivariate analyses first cystoscopy findings and papillary urothelial neoplasm of low malignant potential versus grades 1 to 3 but not stage and the number of tumors had prognostic significance for time to recurrence. Only first cystoscopy findings and grade had prognostic significance for time to stage progression. CONCLUSIONS: Our data support other groups who recommend a less intense cystoscopy followup schedule in patients with negative cystoscopy findings 3 months after initial transurethral bladder resection. We recommend that patients with initial papillary urothelial neoplasm of low malignant potential and low grade carcinoma (WHO 1) with negative first cystoscopy findings undergo repeat cystoscopy at month 12. In our opinion followup should not be less intense in patients with high grade carcinoma (WHO 2-3), even in those with stage pTa disease.     

Cyclooxygenase-2 promotes angiogenesis in pTa/T1 urothelial bladder carcinoma but does not predict recurrence

OBJECTIVE: To investigate the effect of cyclooxygenase-2 (COX-2) on microvessel density (MVD) and on the clinical prognosis in patients with non-muscle invasive urothelial carcinoma of the bladder, as COX-2 expression is significantly greater in epithelial tumours and there is increasing evidence that COX-2 might contribute to tumour neovascularization. PATIENTS AND METHODS: We assessed tumour samples from 110 patients undergoing transurethral resection for primary pTa/pT1 bladder carcinoma (pTa, 84; pT1, 26; grade 1, 22; grade 2, 81; grade 3, seven). Paraffin sections were assessed immunohistochemically using antibodies against COX-2, CD34 (endothelial cells) and CD105 (proliferating vessels). COX-2 expression was quantified by the number of stained cells (negative, +, ++) and the MVD calculated as vessels per field. RESULTS: Of the 110 tumours, 45 (41%) had no immunostaining for COX-2, 40 had faint staining with at least isolated positive cells (+) and 25 stained ++. COX-2 positive tumours had significantly greater vascularization for proliferating vessels. In COX-2 negative tumours the MVD was 22.1, identified by CD34 immunostaining, and 3.4 for proliferating vessels (CD105), whereas COX-2 positive tumours had a MVD of 18.3 (CD34), and of 5.8, respectively (CD105). Complete follow-up data were available in 91 patients; after a mean follow-up of 25 months, 18 (20%) had tumour recurrences. There was no significant difference in the recurrence rates or disease-free survival between COX-2-positive (19%, 25.6 months) or -negative patients (21%, 25.2 months). CONCLUSION: These results confirm the involvement of COX-2 in angiogenesis in bladder cancer, as COX-2 promoted blood vessel proliferation in the tumour zone, and indicate the usefulness of COX-2-inhibiting drugs in preventing and treating superficial bladder cancer.     

Mild acute kidney injury is associated with increased mortality after cardiac surgery in patients with eGFR < 60 mL/min/1.73 m2

Background: A small increase in serum creatinine after cardiac surgery has been associated with increased mortality. However, it is unclear whether this association varies with baseline renal function. Methods: We retrospectively reviewed data on 1359 patients who underwent cardiac surgery over a 4-year period in two tertiary care hospitals including demographic data, comorbid conditions, and intra- and postoperative complications using a standardized form. We followed patients for 90 days postoperatively and death rates and length of hospital stay were noted. Results: The incidence of acute kidney injury (AKI) after cardiac surgery was 40.2%. Patients were grouped into terciles based on change in serum creatinine. Kaplan–Meier survival analysis and Cox regression analysis showed that the development of AKI with a small increase in serum creatinine of more than 0.3 mg/dL from baseline (tercile 3) was associated with a higher risk of mortality within 90 days and 7 days longer hospitalization following a cardiac surgery. Stratified analysis showed that only patients with baseline eGFR < 60 mL/min/1.73 m had fivefold higher mortality with rise of serum creatinine >0.3 mg/dL. Conclusions: Patients with baseline eGFR < 60 mL/min/1.73 m² had increased risk of mortality after cardiac surgery with a small increase in serum creatinine whereas a similar increase in serum creatinine in those with eGFR ≥ 60 mL/min/1.73 m² did not increase mortality.     

Good quality white-light transurethral resection of bladder tumours (GQ-WLTURBT) with experienced surgeons performing complete resections and obtaining detrusor muscle reduces early recurrence in new non-muscle-invasive bladder cancer: validation across time and place and recommendation for benchmarking

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Staging of patients with prostate cancer is the cornerstone of treatment. However, after curative intended therapy a high portion of patients relapse with local and/or distant recurrence. Therefore, one may question whether surgical lymph node dissection (LND) is sufficiently reliable for staging of these patients. Several imaging methods for primary LN staging of patients with prostate cancer have been tested. Acceptable detection rates have not been achieved by CT or MRI or for that matter with PET/CT using the most common tracer fluoromethylcholine (FCH). Other more recent metabolic tracers like acetate and choline seem to be more sensitive for assessment of LNs in both primary staging and re‐staging. However, previous studies were small. Therefore, we assessed the value of [¹⁸F]FCH PET/CT for primary LN staging in a prospective study of a larger sample and with a ‘blinded’ review. After a study period of 3 years and >200 included patients, we concluded that [¹⁸F]FCH PET/CT did not reach an optimal detection rate compared with LND, and, therefore, it cannot replace this procedure. However, we did detect several bone metastases with [¹⁸F]FCH PET/CT that the normal bone scans had missed, and this might be worth pursuing.

OBJECTIVES

• ? To assess the value of [¹⁸F]fluoromethylcholine (FCH) positron emission tomography/computed tomography (PET/CT) for lymph node (LN) staging of prostate cancer.
• ? To evaluate if FCH PET/CT can replace LN dissection (LND) for LN staging of prostate cancer, as about one‐third of patients with prostate cancer who receive intended curative therapy will have recurrence, one reason being undetected LN involvement.

PATIENTS AND METHODS

• ? From January 2008 to December 2010, 210 intermediate‐ or high‐risk patients had a FCH PET/CT scan before regional LND.
• ? After dissection, the result of histological examination of the LNs (gold standard) was compared with the result of FCH PET/CT obtained by ‘blinded review’.
• ? Sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of FCH PET/CT were measured for detection of LNe metastases.

RESULTS

• ? Of the 210 patients, 76 (36.2%) were in the intermediate‐risk group and 134 (63.8%) were in the high‐risk group. A medium (range) of 5 (1–28) LNs were removed per patient.
• ? Histological examination of removed LNs showed metastases in 41 patients. Sensitivity, specificity, PPV, and NPV of FCH PET/CT for patient‐based LN staging were 73.2%, 87.6%, 58.8% and 93.1%, respectively.
• ? Corresponding values for LN‐based analyses were 56.2%, 94.0%, 40.2%, and 96.8%, respectively.
• ? The mean diameter of the true positive LN metastases was significantly larger than that of the false negative LNs (10.3 vs 4.6 mm; P < 0.001).
• ? In addition, FCH PET/CT detected a high focal bone uptake, consistent with bone metastases, in 18 patients, 12 of which had histologically benign LNs.

CONCLUSIONS

• ? Due to a relatively low sensitivity and a correspondingly rather low PPV, FCH PET/CT is not ideal for primary LN staging in patients with prostate cancer.
• ? However, FCH PET/CT does convey important additional information otherwise not recognised, especially for bone metastases.

     

5-aminolaevulinic acid-induced fluorescence cystoscopy during transurethral resection reduces the risk of recurrence in stage Ta/T1 bladder cancer

OBJECTIVE: To assess the influence of 5-aminolaevulinic acid-induced fluorescence cystoscopy (FC) during transurethral resection (TUR) on the recurrence rate and the length of tumour-free interval in stage Ta/T1 transitional cell carcinoma (TCC) of the urinary bladder. PATIENTS AND METHODS: In all, 122 patients with primary or recurrent stage Ta/T1 bladder TCC treated with TUR were enrolled in a prospective randomized study. In group A the TUR was performed with standard white-light endoscopy, and in group B with FC. The patients were followed using standard cystoscopy and urinary cytology. The recurrence-free interval was evaluated in whole groups, for single and multiple, and for primary and recurrent tumours separately. RESULTS: At the time of the first cystoscopy (10-15 weeks after TUR) tumour recurrence was detected in 23 of 62 patients (37%) in group A, but only in five of 60 patients (8%) in group B. The recurrence-free survival rates in group A were 39% and 28% after 12 and 24 months, compared to 66% and 40% respectively in group B (P = 0.008, log-rank test). In separate analyses, the recurrence-free survival rates were significantly higher using FC in multiple (P = 0.001) and in recurrent (P = 0.02) tumours. In solitary and primary tumours the median time to recurrence was also longer in group B, but the difference was not statistically significant. CONCLUSION: 5-aminolaevulinic acid-induced FC during TUR reduces the recurrence rate in stage Ta/T1 bladder TCC. The most significant benefit is in patients with multiple and recurrent tumours.