Expression of CD44 protein in bilharzial and non-bilharzial bladder cancers

OBJECTIVES: To investigate the expression of CD44 protein in bilharzial and non-bilharzial bladder carcinomas, and to relate the results of immunohistochemistry to the established prognostic factors, as studies clearly show that altered adhesive function of tumour cells is important in the metastatic process and CD44 is assumed to be critical in the malignant progression of many human tumours. PATIENTS AND METHODS: The study included 55 patients with bladder carcinoma confirmed by cystoscopy and biopsy. Of the 33 patients with transitional cell carcinoma (TCC), 19 were bilharzial and 14 non-bilharzial, and of 22 with squamous cell carcinoma (SCC), 12 were bilharzial and 10 non-bilharzial. CD44 expression was measured by immunohistochemical analysis of paraffin-embedded tissue obtained from these patients after appropriate treatment (transurethral resection, partial or radical cystectomy). RESULTS: There was significantly less CD44 expression in invasive TCC than in normal urothelium and pre-invasive TCC (P = 0.05). The expression of CD44 was inversely related to the tumour grade and depth of invasion (P = 0.05). However, there was no such relation for SCC; there was no significant difference between CD44 expression in metaplastic squamous epithelium, pre-invasive and invasive SCC. The presence or absence of bilharzial ova had no apparent effect on the expression of CD44, with no significant difference between CD44 expression in bilharzial and non-bilharzial bladder carcinomas. CONCLUSIONS: These data confirm that there is a reduction in CD44 expression with increasing tumour grade and stage of TCC, and may provide an additional aid in predicting the progression of this tumour. There was no such relationship with SCC, and no difference between CD44 expression in bilharzial and non-bilharzial bladder carcinomas.     

Comparison of microscopic (pT3a) and gross extravesical extension (pT3b) in pathological staging of bladder cancer: analysis of patient outcomes

Objective

To determine the prognostic value of pT3 bladder urothelial carcinoma substaging in patients without lymphatic involvement.

Patients and methods

Pathologic and clinical data were reviewed on patients who underwent radical cystectomy for urothelial carcinoma between 1991 and 2010. Of the 460 reviewed patients, 74 patients were diagnosed with pathologic T3No urothelial carcinoma of the bladder. The impact of pathologic substaging (pT3a vs. pT3b) was examined to determine the effect on overall and disease-specific survival.

Results

Five years disease-specific and overall survival rates were 46.9 % and 39.6 % for patients with pT3aNo tumor, whereas these ratios were 34.4 and 30.3 %, respectively, for patients with pT3bNo tumor (p > 0.05). Mean disease-specific survival time was 43.94 ± 6.50 months for pT3aNo, while it was 39.01 ± 7.19 months for pT3bNo (p = 0.539). In multivariate cox regression analysis, age (p = 0.459), gender (p = 0.710), urinary diversion type (p = 0.088), and pT3 substaging (p = 0.554) were not noticed as an independent predictive factor for survival.

Conclusion

Macroscopic extravesical extension (pT3b) is not associated with a worse outcome than pT3a disease in lymph node-negative cases of bladder urothelial carcinoma.     

Outcome of the treatment of invasive non-transitional cell carcinoma

BACKGROUND: We evaluated the treatment outcomes of non-transitional cell carcinoma (non-TCC) cases after radical cystectomy. METHODS: Radical cystectomy was performed in 259 invasive bladder cancer patients in our department and of these, 59 (22.7%) were non-TCC. Primary squamous cell carcinomas (SCC), adenocarcinomas and undifferentiated cancers (UC) were grouped as non-TCC of the bladder. Of the 59 non-TCC; 32 SCC, 20 UC, five adenocarcinoma and two sarcomatoid tumor cases were demonstrated. RESULTS: The 5-year disease-specific survival rate of TCC and non-TCC cases were 48.9 and 28.2%, respectively (P = 0.0016). The 5-year disease-specific survival rates of SCC and UC were 25.1 and 23.4%, respectively. The median survival time of SCC, UC and adenocarcinoma cases were 19, 12 and 6 months, respectively (P = 0.4579). The disease-specific survival rates of TCC and non-TCC cases at stage pT2NoMo were 79.1 and 27.2%, respectively (P = 0.0000). The median survival time of SCC, UC and adenocarcinoma cases were 19, 12 and 13.3 months, respectively, for the same stage. The survival time of TCC, SCC and UC cases at stage pT3NoMo were 23, 26 and 45 months, respectively (P = 0.2307). The median survival time at stages pT2-3N1Mo for the same groups were 18, 16 and 11 months, respectively (P = 0.0939). CONCLUSION: The study presented here demonstrates that both TCC and non-TCC cases have poor survival rates in locally advanced disease and that at the pT2NoMo stage the prognosis of non-TCC cases is poor when compared with TCC cases.     

尿路复合性恶性肿瘤（附21例报告）

报告２１例尿路复合性恶性肿瘤，位于肾盂２例，膀胱１９例。主要临床表现为血尿，绝大多数病人伴有尿路刺激症状。低分化的移行细胞癌（ＴＣＣ）与继发性复合肿瘤有密切关系。２１例中１例为ＴＣＣ复合肉瘤，１１例为ＴＣＣ复合鳞癌，７例为ＴＣＣ复合腺癌，２例为腺癌复合鳞癌。本组２例肾盂肿瘤分别行肾输尿管全长加膀胱袖口状切除术和肾部分切除术，术后存活６个月和１年；膀胱肿瘤１４例行膀胱部分切除术，已生存３年４例，１年２例，未满１年２例，３例１～２年内死亡，失访３例；２例根治性膀胱全切术已生存５年和３年以上；３例行ＴＵＲＢｔ，已生存３年１例，１５年１例，未满１年１例。对尿路复合性恶性肿瘤的组织学、临床和病理特征进行了讨论。     

Numerical chromosomal aberrations in muscle invasive squamous cell and transitional cell cancer of the urinary bladder: an alternative to classic prognostic indicators?

OBJECTIVES: To evaluate the prognostic value of chromosomal aberrations in muscle invasive bladder cancer, because they are of diagnostic and prognostic significance in superficial bladder cancer. METHODS: One hundred ninety patients, who underwent radical cystectomy because of squamous cell carcinoma (SCC) of the urinary bladder in 94 cases and transitional cell carcinoma (TCC) in 96 cases, were studied retrospectively. Numerical aberrations of chromosomes 7, 9, and 17, p53 positivity, histologic stage and grade, histologic tumor type, lymph node status, and the presence of bilharzial eggs were investigated as possible prognostic factors. RESULTS: Univariate analysis demonstrated the prognostic significance of all parameters analyzed, excluding chromosome 9. Multivariate analysis revealed only T category (P = 0.01095266), lymph node involvement (P = 0.00054877), and p53 positivity (P = 0.0316974) to be independent prognostic factors in muscle invasive SCC and TCC. CONCLUSIONS: Although chromosomal aberrations are associated with progression-free survival, they are not independent prognostic factors and give the clinician no additional information on patients with muscle invasive bladder cancer.     

Adjuvant chemotherapy (MVP-CAB; methotrexate, vincristine, cisplatinum, cyclophosphamide, adriamycin, and bleomycin) for bladder cancer]

Twenty-three patients with bladder cancer (TCC; 18 patients, SCC; 5 patients) were treated with adjuvant chemotherapy (day 1: methotrexate 20 mg/m2, vincristine 0.6 mg/m2, cyclophosphamide 500 mg/m2, adriamycin 20 mg/m2, bleomycin 30 mg, day 2: cisplatinum 50 mg/m2; MVP-CAB). A total of 3 cycles of MVP-CAB were given as preoperative or postoperative therapy. The following results were obtained. Group 1 (purpose to preserve the bladder, preoperative MVP-CAB): Four of 7 patients achieved a partial response. It was possible to perform bladder preservation surgery in 3 of these 4 patients. All 3 patients had pedunculated, solitary tumors, and there was no carcinoma in situ. Group 2 (purpose to improve the prognosis; preoperative MVP-CAB): Hydronephrosis did not resolve in the 4 patients with this complication. They received total cystectomy, and 2 patients died of cancer 23 months later. Group 3 (purpose to improve the prognosis; postoperative MVP-CAB): Ten of 12 patients (total cystectomy; 10 patients, partial cystectomy; 2 patients) survived disease-free for an average of 17 months (5-44 months), 1 patient developed recurrence 12 months later, and 1 patient died of cancer 6 months later. The 1-year survival rate in Group 3 was 86% for TCC, 100% for SCC, 80% for grade 3 TCC, and 89% for pT2 or more advanced cancer.     

Downstaging to non-invasive urothelial carcinoma is associated with improved outcome following radical cystectomy for patients with cT2 disease

Introduction

Pathologic stage is a critically important prognostic factor after radical cystectomy (RC) that is used to guide the use of secondary therapies. However, the risk of disease recurrence, for patients clinically diagnosed with muscle-invasive tumors who are found not to have muscle-invasive disease at RC are poorly defined. Therefore, we reviewed the long-term outcomes in patients who were downstaged to non-invasive urothelial carcinoma at time of RC.

Methods

We identified 1,177 consecutive patients with muscle-invasive urothelial carcinoma of the bladder who underwent radical cystectomy at our institution between 1980 and 1999 without neoadjuvant therapy. Postoperative disease recurrence and survival were estimated using the Kaplan?CMeier method and compared using the log rank test. Cox proportional hazard regression models were used to analyze the impact of pathologic stage on survival.

Results

Pathologic downstaging to non-muscle invasive disease was identified in 538 (45.7?%) patients. The 10-year cancer-specific survival was 84.1, 77.4, 71.1 and 58.5?% for those with pT0, pTis, pT1 and pT2 tumors, respectively. On multivariate analysis, the risk of cancer-specific mortality was significantly decreased for patients with non-muscle invasive disease than those with organ-confined muscle invasion (RR?0.39; p?=?0.002). There was no difference in disease-specific mortality among patients who had non-invasive (pT0, pTa, or pTis) disease (p?=?0.19).

Conclusions

Downstaging from clinical muscle-invasive bladder cancer to non-muscle invasive disease at RC is associated with a significant reduction in cancer-specific mortality. However, even patients with residual non-muscle invasive disease may suffer disease recurrence and require continued surveillance after surgery.     

The incidence and relevance of prostate cancer in radical cystoprostatectomy specimens

Purpose

To review the incidence, histopathological features and clinical outcomes of patients with incidental prostate cancer (CaP) found in cystoprostatectomy specimens (CP) excised for bladder cancer and to determine whether these prostate cancers could affect the follow-up strategy.

Patients and methods

We retrospectively reviewed the records of 110 patients who underwent CP for bladder cancer (1998?C2011) at our institution. CaP grade, stage, volume and surgical margin status were recorded. Prostatic involvement by bladder tumour or carcinoma in situ (CIS) was studied. Pre-operative prostate assessment and follow-up in those diagnosed with incidental CaP were analysed.

Results

Incidental CaP was identified in 35 patients (32.5?%), 4 with prostatic PIN alone and 2 patients with diagnoses of CaP prior to cystectomy were excluded from study. Of the CaP cases, 28.5?% had clinically significant disease: 5 with Gleason score 7, 2 with Gleason score 9, who also had extracapsular invasion of tumour, and three with positive surgical margins. All patients were pN0 for CaP. Of the 108 patients, 16.5?% had prostatic urethral involvement with CIS or TCC. In the subgroup of patients with the incidentally diagnosed CaP who developed local recurrence of bladder tumour and/or metastatic disease, none originated from their CaP.

Conclusion

The majority of incidental CaP in CP specimens are organ confined and do not influence oncological outcome. The prognosis of such patients is primarily determined by bladder cancer. Our findings support previous reports and autopsy studies elsewhere.     

Microstaging of pT1 transitional cell carcinoma of the bladder: identification of subgroups with distinct risks of progression

Objectives. To evaluate microstaging by means of quantifying the depth of invasion of the subepithelial connective tissue in pT1 transitional cell carcinoma (TCC) of the bladder for its additional prognostic value with respect to disease recurrence and progression.Methods. We reviewed the pathologic findings of a consecutive series of 124 patients with pT1 tumors entered in a prospective randomized multicenter trial comparing mitomycin C and bacillus Calmette-Guérin treatment, with at least 3 years of follow-up and clinical outcome hidden from reviewers. The depth of invasion was established by identifying submucosal tumor invasion up to, in, or beyond the muscularis mucosae or vascular plexus and classified as pT1a, pT1b, or pT1c, respectively. In addition to tumor grade, the presence of carcinoma in situ (CIS) near the primary tumor or in biopsy specimens taken from abnormal looking mucosa was taken into account. The risks of recurrence and progression were calculated using Kaplan-Meier curves and modeled with proportional hazard models.Results. pT1 subclassification was possible in more than 90% of the specimens. The 3-year risk of recurrence was not different in any of the subgroups. By contrast, the Kaplan-Meier 3-year risk for progression was 6%, 33%, and 55% for pT1a, pT1b (hazard ratio [HR] 5.51), and pT1c (HR 12.35) tumors, respectively (log-rank test P < 0.001). The Kaplan-Meier 3-year risk of progression was 9% versus 39% (HR 5.62) for the absence or presence of CIS in the tumor (P = 0.001) and 8% versus 49% (HR 6.72) for CIS in biopsy specimens (P < 0.001). Tumor grade had no statistically significant prognostic value with respect to progression, nor had tumor volume or multifocality. The combination of the parameters (pT1c and CIS) increased the risk of progression by a factor of 27 (P < 0.0001) compared with the absence of pT1c and CIS.Conclusions. These data show that the extent of lamina propria invasion (pT1a, pT1b, pT1c) is a clinically relevant prognostic factor for progression of pT1 TCC of the bladder. With the combination of this pT1 subclassification and the presence of CIS subgroups, distinct risks of progression can be identified that may give additional information for follow-up and treatment policies.     

Inguinal lymph node metastasis of bladder carcinoma ten years after cystourethrectomy: a case report

A 79-year-old man had undergone radical cystourethrectomy for bladder carcinoma in January, 1989. Pathological report was Small cell carcinoma (SCC) > transitional cell carcinoma (TCC), G2 > G3, pT4 (prostate), ew (-). Ten years later, follow-up computed tomography (CT) revealed swollen left inguinal lymph node in October 1998 and lymph node dissection was performed in January, 2000. The pathological report showed TCC, G2. Left inguinal lymph node metastases appeared again in January, 2001. Chest X-ray films showed multiple lung metastases in March, 2001. Three couses of MVAC (methotrexate, vinblastine, doxorubicin cisplatinum) chemotherapy had been performed since September, 2001 but were in effective. Papillary tumor was observed at external urethral meatus in September, 2002 and the biopsied specimens showed TCC, G1 > G2, pathologically. Finally he died of respiratory insufficiency in January, 2003. It is suggested that the recurrent TCC tumor in the urethral remnants might metastasize into the inguinal lymph nodes.     

A case report: small cell carcinoma transformed from transitional cell carcinoma of the urinary bladder

A 72-year-old man presented with gross hematuria. Cystoscopy showed a non-papillary tumor at the right side of the posterior wall. Transurethral resection of the bladder tumor (TURBT) was performed. Pathologic findings demonstrated superficial transitional cell carcinoma (TCC). However, recurrent tumors were detected at the same location after 69 months' follow up. TURBT was done for the biopsy and pathologic examination showed muscle-invasive TCC. After two courses of neoadjuvant chemotherapy (MVAC), we performed radical cystectomy with Hautmann's continent reservoir. Pathologic findings revealed small cell carcinoma without any TCC features. Immunohistochemical staining using chromogranin A and synaptophysin was positive in the latest TURBT and the radical cystectomy specimens. We report a case of primary small cell carcinoma transformed from TCC of the urinary bladder.     

Validierung von Präzystektomienomogrammen zur Vorhersage lokal fortgeschrittener Harnblasenkarzinome in einer multizentrischen Studie

Objective

Pre-cystectomy nomograms with a high predictive ability for locally advanced urothelial carcinomas of the bladder would enhance individual treatment tailoring and patient counselling. To date, there are two currently not externally validated nomograms for prediction of the tumour stages pT3–4 or lymph node involvement.

Materials and methods

Data from a German multicentre cystectomy series comprising 2,477 patients with urothelial carcinoma of the bladder were applied for the validation of two US nomograms, which were originally based on the data of 726 patients (nomogram 1: prediction of pT3-4 tumours, nomogram 2: prediction of lymph node involvement). Multivariate regression models assessed the value of clinical parameters integrated in both nomograms, i.e. age, gender, cT stage, TURB grade and associated Tis. Discriminative abilities of both nomograms were assessed by ROC analyses; calibration facilitated a comparison of the predicted probability and the actual incidence of locally advanced tumour stages.

Results

Of the patients, 44.5 and 25.8% demonstrated tumour stages pT3-4 and pN+, respectively. If only one case of a previously not known locally advanced carcinoma (pT3-4 and/or pN+) is considered as a staging error, the rate of understaging was 48.9% (n=1211). The predictive accuracies of the validated nomograms were 67.5 and 54.5%, respectively. The mean probabilities of pT3-4 tumours and lymph node involvement predicted by application of these nomograms were 36.7% (actual frequency 44.5%) and 20.2% (actual frequency 25.8%), respectively. Both nomograms underestimated the real incidence of locally advanced tumours.

Conclusions

The present study demonstrates that prediction of locally advanced urothelial carcinomas of the bladder by both validated nomograms is not conferrable to patients of the present German cystectomy series. Hence, there is still a need for statistical models with enhanced predictive accuracy.     

Recurrence and progression of stage T1, grade 3 transitional cell carcinoma of the bladder following intravesical immunotherapy with bacillus Calmette-Guerin

PURPOSE: We prospectively examined the incidence of recurrence and progression in patients with stage pT1, grade 3 carcinoma of the bladder following complete transurethral resection of the bladder tumor and adjuvant immunotherapy with bacillus Calmette-Guerin (BCG). MATERIALS AND METHODS: Between July 1987 and March 1999, 123 patients presenting to our clinic with superficial urothelial carcinoma (stage pT1, grades 1 to 3) received adjuvant intravesical immunotherapy with BCG after histologically confirmed complete transurethral tumor resection. Disease was stage pT1, grade 3 in 44 patients (36%). Median followup was 28 months (mean 43, range 5 to 141). RESULTS: Of the patients 36 (82%) with bladder preservation remained tumor-free during followup after 1 or 2 cycles of BCG. Superficial tumor recurred in 5 patients (11%) and muscle invasive progression was noted in 7 (16%). Radical cystectomy was performed in 4 cases (9%). Of the patients 5 (11%) died of cancer. Tumor-free survival for all patients was 89% (39 of 44). CONCLUSIONS: Adjuvant immunotherapy with BCG after complete transurethral resection of bladder tumor represents a highly effective primary treatment of stage pT1, grade 3 carcinoma of the bladder. Immediate radical cystectomy does not appear necessary.     

Association of tumor-associated trypsin inhibitor (TATI) expression with molecular markers, pathologic features and clinical outcomes of urothelial carcinoma of the urinary bladder

Purposes

To describe the differential tissue expression of tumor-associated trypsin inhibitor (TATI) in normal bladder urothelium, primary urothelial carcinoma of the bladder (UCB) and metastatic UCB and to assess the association of TATI expression with molecular markers commonly altered in UCB and clinical outcomes after radical cystectomy.

Methods

Slides from eight cystectomy patients without cancer, 191 radical cystectomy patients, 20 lymph nodes without metastasis and 40 lymph nodes with UCB were stained. Tissue expression of TATI, cyclin E1, cyclin D1, p53, p21, p27, pRB, Ki-67, Bcl-2, Caspase-3, Survivin and Cyclooxigenase-2 was measured in a tissue microarray. Cancer-specific and recurrence-free survival after radical cystectomy was recorded.

Results

TATI was expressed in 100% of patients without cancer, while 71% of radical cystectomy specimens and 90% of lymph node metastases exhibited decreased or no TATI expression. In radical cystectomy specimens, TATI expression decreased with advancing pathologic stage (P?P?=?0.055). In univariate analyses, but not in multivariable Cox proportional hazard regression analyses, decreased TATI expression was associated with increased probability of tumor recurrence and cancer-specific mortality. Decreased TATI expression was correlated with altered expression of Cyclooxigenase-2 (P?=?0.005), p21 (P?=?0.035) and Ki-67 (P?=?0.004).

Conclusions

We found that normal urothelium expresses TATI and that TATI expression decreases with advancing tumor stage. While there was no prognostic benefit to TATI when adjusted for standard clinicopathologic features, it seems to play an important biologic role in UCB pathogenesis and invasion. Its association with markers involved in the cell cycle, proliferation and inflammation serves as hypothesis for molecular interactions.     

Harnblasenkarzinompatienten im klinischen Tumorstadium T2

Background

Few and partially contradictory data are available regarding the prognostic signature of downstaging of muscle-invasive clinical tumour stages in patients treated with radical cystectomy.

Materials and methods

Clinicopathological parameters of 1,643 patients (study group, SG) treated with radical cystectomy due to muscle-invasive urothelial bladder cancer were summarized in a multi-institutional database. Patients of the SG fulfilled the following conditions: clinical tumour stage T2 N0 M0 and no administration of neoadjuvant radiation or chemotherapy. Cancer-specific survival (CSS) rates were calculated referring to pathological tumour stages in cystectomy specimens (pT2) (mean follow-up: 51 months). Furthermore, a multivariable model integrating clinical information was developed in order to predict the probability of downstaging.

Results

A total of 173 patients (10.5%) of the SG presented with downstaging in pathological tumour stages (pT0: 4.8%, pTa: 0.4%, pTis: 1.3%, pT1: 4.1%); 12 of these patients had positive lymph nodes (7%, in comparison with 21% pN+ of pT2 tumours and 43% of >pT2 tumours). Patients with tumour stages pT2 had CSS rates after 5 years of 89, 69 and 46%, respectively (p<0.001). In a multivariable Cox model the presence of pathological downstaging resulted in a significant reduction of cancer-specific mortality (HR 0.30; 95% CI 0.18–0.50). By logistic regression analysis the date of TURB (benefit for more recent operations) was identified as the only independent predictor for downstaging of muscle-invasive clinical tumour stages. Age, gender, grading and associated Tis in the TURB did not reveal any significant influence.

Conclusion

Patients with muscle-invasive clinical tumour stages and downstaging in cystectomy specimens represent a subgroup with significantly enhanced CSS rates. Further trials that integrate the parameters tumour size, stages cT2a vs cT2b and focality are required in order to define the independent prognostic signature of downstaging of tumour stages more precisely.     

Long-term results of intravesical bacillus Calmette-Guérin therapy for stage T1 superficial bladder cancer

OBJECTIVES: To examine in a prospective study the incidence of recurrence and progression in patients with Stage T1 bladder carcinoma after complete transurethral resection of the bladder tumor and adjuvant immunotherapy with bacillus Calmette-Guérin (BCG). METHODS: Between July 1987 and April 1999, 126 patients presenting to our clinic with a superficial urothelial carcinoma of the bladder (Stage pT1, grade 1-3) received adjuvant intravesical immunotherapy with BCG after complete transurethral resection of the bladder tumor. In the case of recurrence of superficial tumor (pTa, pT1, or carcinoma in situ), patients received a second cycle of BCG. For muscle-invasive tumor progression (pT2, pT3, or pT4), radical cystectomy was recommended. Six of the patients (5%) presented with Stage pT1,G1 tumor, 74 (59%) with Stage pT1,G2 tumor, and 46 patients (36%) with Stage pT1,G3 tumor. Median follow-up was 53 months (range 3 to 144). RESULTS: One hundred eight patients (86%) remained tumor-free with a retained bladder during the follow-up after one or two 6-week cycles of BCG. Twenty-four patients (19%) had a recurrence of superficial tumor, 13 (10%) had muscle-invasive progression after the first BCG cycle, and an additional 4 (3%) had progression after the second BCG cycle. Six patients (5%) underwent radical cystectomy, and 9 patients (7%) died as a result of tumor progression. The tumor-free survival rate of all patients was 89% (112 of 126). CONCLUSIONS: Adjuvant immunotherapy with BCG after complete transurethral resection of the bladder tumor represents a highly effective primary treatment for Stage T1 carcinoma of the bladder. Even in Stage pT1,G3 tumor, immediate radical cystectomy does not appear necessary.     

p53, p21 and mdm2 expression vs the response to radiotherapy in transitional cell carcinoma of the bladder

OBJECTIVE: To identify, in a retrospective study, possible molecular markers predictive of radioresponsiveness in patients with transitional cell carcinoma (TCC) of the bladder. PATIENTS AND METHODS: Patients with T2-T4a TCC treated with preoperative radiotherapy and cystectomy were included in the study if their cystectomy specimen was pT3b (in 42) or pT0 (in 17). Because treatment schedules changed over time, radiotherapy was given either as 2 Gy x 23 over 4-5 weeks with cystectomy 4-5 weeks later (in 23), or as 4 Gy x 5 during 1 week with cystectomy in the following week (in 36 patients). Protein expression of p53, mdm2 and p21 (CDKN1 A/WAF1/CIP1/SDI1) was assessed immunohistochemically in biopsies taken before radiotherapy. RESULTS: There was no difference in protein expression when comparing all patients with pT0 and pT3b. However, for patients receiving 46 Gy, increased p53 expression (but not p21 or mdm2) predicted the absence of residual tumour (P = 0.005): six of seven patients with > 50% p53 expression had pT0 in the cystectomy specimen, whereas 10 of 12 patients with < or = 5% expression had pT3b. Over-expression of p53 correlated with longer overall (P = 0.045) and cancer-specific survival (P = 0.020). CONCLUSION: The expression of mdm2 or p21 did not predict radioresponsiveness in patients with TCC of the bladder. The role of p53 remains unclear; the view that p53 over-expression confers radioresistance in bladder cancer is not supported.     

A case of transitional cell carcinoma with squamous differentiation which developed squamous cell carcinoma in situ in the clinical course

In August 2000, a 62-year-old woman presented to another municipal hospital with macroscopic Transurethral resection of bladder tumor (TUR-Bt) was performed. The pathological hematuria. diagnosis was transitional cell carcinoma (TCC), G2 > squamous cell carcinoma (SCC). TUR-Bt repeated in July 2003 indicated recurrence. The pathological diagnosis was TCC, G2. She was referred to our hospital in August 2003 because she desired bladder preservation. After cystoscopy and random biopsy, pathological diagnosis was TCC with squamous differentiation, G1-G2, pTis. She received 7 weekly intravesical bacillus Calmette-Guerin (BCG) instillations. In April 2004, TUR-Bt was repeated and multiple recurrences were found. The pathological diagnosis was TCC with squamous differentiation, G1-G2, pTa. She received 10 weekly intravesical Pirarubicin hydrochroride instillations. In August cystoscopy and random biopsy were performed for evaluation of the intavesical instillation treatment. Pathological diagnosis was atypical squamous cells. In November, cystoscopy revealed recurrence of a bladder tumor. After admission, a small papillary tumor and multiple flat lesion biopsies demonstrated SCC without obvious invasion. The patient underwent cystectomy. There were widespread areas of full thickness squamous atypia. Most of the bladder did not show appearance of typical TCC, but the final pathological diagnosis was TCC because the case developed from TCC and could not be diagnosed as pure SCC. The diagnosis of SCC in situ of bladder is difficult, and this may contribute to its rarity.     

Tm:YAG laser en bloc mucosectomy for accurate staging of primary bladder cancer: early experience

Introduction

Exact pathological staging of bladder cancer is crucial for determination of further treatment. One limiting factor is the surgical ??incise and scatter?? technique that might contribute to tumour recurrence. En bloc resection techniques are en emerging issue. We present initial results with Thulium:YAG (Tm:YAG) en bloc resection of bladder tumours for treatment and accurate staging of solitary transitional cell carcinoma of the bladder.

Materials and methods

From June through October 2010, six patients were treated by TmLRBT (Thulium laser resection of bladder tumour). Inclusion criteria were solitary lesions, treatment naive patients and tumour localisation of the lower bladder wall and trigonum. En bloc resection was applied on all of the tumours. Two cold-cut biopsies from the tumour base were extracted. On five of the six patients, a re-resection was performed after 6?weeks.

Results

Pathological evaluation revealed 1 patient with pTa G1, 2 patients with pTa G2 and 3 patients with pT1 G3. All of the resected specimens provided detrusor muscle, and all biopsies were positive for muscle cells. No intra-, peri- or post-operative complications were observed. Bladder irrigation was mandatory in only 50% of the patients. All patients were negative for residual TCC in re-resection 6?weeks after initial treatment.

Conclusion

TmLRBT has been proven safe and effective for both, treatment and pathological staging of primary TCC of the bladder. Tm:YAG en bloc resection therefore could be an appropriate tool for accurate staging with possibly lower scattering potential for the assessment and treatment of patients with TCC.     

A stage-dependent follow-up strategy after radical cystectomy for bladder carcinoma

With the aim of developing stage-dependent follow-up strategy after radical cystectomy for bladder carcinoma, the records of 111 patients with bladder carcinoma who underwent radical cystectomy during the period between 1986 and 2003, were reviewed for the date and site of recurrence. Intrapelvic recurrence developed in 3 out of 56 patients with pT1> or =, 1 of 22 with pT2 and 6 out of 33 with pT3< or = at a median of 34 (range 32-58), 28, 8 (4-51) months, respectively. Extrapelvic recurrence developed in 20 patients with pT1> or =, 4 with pT2 and 14 with pT3< or = at a median of 43 (20-66), 15.5 (13-20), 8 (2-46) months, respectively. Recurrence developed earlier and more frequently in patients with pT3< or = and pT2 than those with pT1> or =. A stage-specific approach to tumor surveillance after radical cystectomy for bladder carcinoma, taking into consideration the risk of recurrence, represents a new approach for efficiently detecting recurrence and reducing medical costs. Our results offer the possibility of a new stage-specific approach to tumor surveillance after radical cystectomy for bladder carcinoma, for efficiently detecting recurrence and reducing medical costs, taking into consideration the risk of recurrence.