Immunonutrition in elective gastrointestinal surgery patients.

BACKGROUND: Previous trials have shown that perioperative immunonutrition could protect patients from infectious complications after gastrointestinal cancer operations. The purpose of this study was to determine whether perioperative immunonutrition decreases postoperative morbidity, especially infection complications, mortality and length of hospital stay in patients undergoing major gastrointestinal tract surgery. METHODS: One hundred patients with a planned elective operation for benign or malignant gastrointestinal illness were randomized into two groups: group 1) oral supplementation for five days before and five days after surgery with 900 mL/day of a formula enriched with arginine, gamma-3-fatty acid and RNA + liquid diet ad libitum on one and two postoperative day and then solid food (immunonutrition group; n = 50) or group 2) no artificial nutrition before and after surgery, on one and two postoperative day intravenous solution of 5% glucose and electrolytes and then normal diet (conventional group; n = 50). RESULTS: The groups were comparable for all key baseline and surgical characteristics. There were nine (18%) infectious complications in both groups. Overall complication rates were 28% (n = 14) in the immunonutrition group and 24% (n = 12) in the conventional group. No significant difference between the groups was found in complication rates, mortality or length of hospital stay. CONCLUSION: Routine perioperative immunonutrition to the patients undergoing major gastrointestinal surgery is not beneficial.

Suspicious urine cytology (class III) in patients with bladder cancer: should it be considered as negative or positive?

OBJECTIVES: Urine cytology is the gold standard in the diagnosis and follow-up of bladder cancer. Cytology, however, exhibits variable sensitivity depending on tumour grade and interpretation of urine specimens is highly dependent on the skill of the examiner. Positive cytology, classes IV and V by Papanicolaou classification, is a strong predictor for coexisting or subsequent malignancy, while the role of suspicious cytology, class III, is controversial. The objective of the study was to evaluate the role of the suspicious finding in cytological analysis, and whether it should be considered as a negative or positive sign for coexisting malignancy. MATERIAL AND METHODS: Six hundred and fifty-two consecutive patients with bladder cancer were studied in a prospective multicenter trial. One hundred and fifty-one of the patients were newly diagnosed, and the remaining 501 patients were under follow-up. A voided urine sample was obtained prior to TURB or prior to routine follow-up cystoscopy in those under the surveillance and split for culture and cytology. The cytopathological results were analyzed by a central review and only patients with samples available for review analysis were included. Sensitivity and specificity, as well as positive (PPV) and negative (NPV) predictive values of urine cytology were calculated by classifying the class III samples as negative or positive. RESULTS: A total of 570 patients were evaluable. One hundred and twenty nine (22.6%) were newly diagnosed and 441 were under follow-up, of whom 117 (26.5%) had recurrence. Cytology was classified as suspicious in 33/129 (25.6%) patients with primary tumour, and in 41/441 (9.3%) of those under the follow-up, of whom 20 (48.8%) had recurrence. Sensitivity increased from to 31.0% to 56.6% in primary tumours (p < 0.001) and from 17.8% to 34.7% in recurrent tumours (p < 0.001) if class III was determined as positive, whereas the specificity decreased from 96.6% to 90.1% (p < 0.001). Accordingly, the NPV increased from 76.3% to 79.1% and the PPV decreased from 65.6% to 56.2%. CONCLUSIONS: The poor sensitivity of voided urine cytology improved significantly when suspicious samples were determined as positive while the specificity remained high, a clear advantage compared with most of the new tumour marker tests. In addition, nearly half of the follow-up patients with suspicious class III cytology had recurrence implying that this patient category is at substantial risk for co-existing malignancy. Therefore, it is recommended that suspicious class III cytology together with class IV and V specimens should be considered positive.

Mutations of TP53 do not correlate with the sensitivity to paclitaxel--a study using 27 gynaecological cancer cell lines.

The correlation between inactivation of the TP53 gene through mutation or the presence of high-risk human papillomavirus (HPV) DNA and intrinsic paclitaxel sensitivity was studied in 27 gynaecological cancer cell lines. IC(50) values, as a measure of drug sensitivity, were determined using a 96-well clonogenic assay. TP53 mutations were investigated with polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct DNA sequencing. HPV status was studied with PCR using HPV consensus primers. TP53 mutations were found in 7/11 vulvar SCC cell lines. Only 2/9 endometrial and 1/7 ovarian cancer cell lines carried TP53 mutations. One vulvar and one endometrial cancer cell line were HPV-positive; both carrying HPV type-16 DNA. Thus, TP53 was functionally normal in 3/11 vulvar, 6/9 endometrial and 6/7 ovarian cancer cell lines. The IC(50) values for paclitaxel were 0.60-2.9, 0.49-2.3 and 0.40-3.4 nM in the vulvar, endometrial and ovarian cancer cell lines, respectively. No correlation could be demonstrated between inactivation of the TP53 gene and paclitaxel sensitivity in vitro; the cell lines were evaluated as one group or according to their anatomical origin or histology. Previous reports have given inconclusive results, partly due to the cell types used, i.e. normal, cancerous or transformed cells. Our results support the view that paclitaxel sensitivity of tumour-derived cancer cell lines is not related to the TP53 status.

Effect of intravesical instillations on the human complement factor H related protein (BTA stat) test.

OBJECTIVES: The BTA stat is a rapid, non-invasive, qualitative urine test that detects bladder tumor-associated antigen (human complement factor H related protein) in urine. The sensitivity of this test is superior to that of urine cytology in detecting primary and recurrent tumors of the urinary bladder. Intravesical instillations are widely used to avoid recurrences and even progression. The objective of this study was to evaluate the effect of intravesical treatments on the BTA stat Test. METHODS: 501 consecutive patients followed up for bladder cancer were studied, of which 490 were eligible for analysis. Three hundred and twenty-seven (66.7%) of the patients had no history of intravesical treatments, whereas the remaining 163 (33.3%) had received treatments: 66 (40.5%) at the time of evaluation. A voided urine sample was obtained prior to cystoscopy and split for culture and BTA stat testing. The overall sensitivity and specificity were calculated and compared to the patients with no, past and present instillations. RESULTS: The overall sensitivity for the BTA stat Test was 56.6%, and the specificity was 76.4%. The specificity of the BTA stat Test was 80.7, 70.7 and 65.3% in those with no, past or present intravesical instillation treatments, respectively. The difference in specificity between those with no and present instillations was significant (p = 0.023), whereas the notable difference between those with no and past instillations did not reach significance (p = 0.076), nor was the difference between patients with past and present instillations significant (p = 0.558). Present instillation of mitomycin C had the strongest adverse effect on the test as the specificity was only 25.0%, whereas past treatment did not interfere with testing. The adverse effect of BCG treatment on testing extended. CONCLUSION: The overall specificity of the test is decreased in patients receiving intravesical treatments, whereas past treatments did not interfere with testing in general. However, the adverse effect of BCG on testing seems to extend, and therefore it is suggested that the BTA stat Test should not be used in patients having received BCG, and in those with present instillation of any type.

Prognostic utility of human complement factor H related protein test (the BTA stat Test).

The purpose of the study was to determine, in addition to well-known prognostic factors, histological grade, stage, tumour size and multiplicity, the correlation of BTA stat Test on disease free interval (DFI) on primary superficial bladder cancer. A total of 116 patients with newly diagnosed bladder cancer were evaluated in a prospective multicentre study. A voided urine sample was obtained prior to TURB and split for culture, cytology and BTA stat testing. Follow-up data for the patients were collected until the first recurrence or the last visit and the DFI was analysed by Kaplan-Meier method and Cox analysis. Ninety-seven of the 116 (83.6%) patients were eligible for analysis. The BTA stat Test was positive in 73 (75.3%) patients, whereas cytology detected 20 (20.6%) cases. The DFI was found to be shorter among patients with a positive BTA stat Test, and also among those with intermediate or high-grade tumours. The BTA stat Test result divided patients with grade 2 tumours into two prognostic groups, in that those testing positive had 68.6% risk of recurrence during the first year compared to 42.9% risk of those with a negative test result (P = 0.041). Although the effect of tumour size on DFI was notable, the difference did not reach statistical significance (P = 0.064). Number of tumours was not related to DFI, nor was the difference between different stage of tumour of significance. BTA stat Test is not only sensitive in detection of primary bladder cancer, but also might have some independent prognostic significance.

Analysis of false-positive BTA STAT test results in patients followed up for bladder cancer.

OBJECTIVES: To evaluate the role of a positive BTA stat Test result in patients with negative cystoscopic findings. METHODS: Five hundred one consecutive patients in follow-up for bladder cancer were studied. A voided urine sample was obtained before cystoscopy and split for culture, cytology, and BTA stat testing. In the case of a positive BTA stat Test, but negative cystoscopic findings, patients underwent additional investigations. RESULTS: Of 501 patients, 133 (26.5%) had bladder cancer recurrence at cystoscopy, of which the BTA stat Test detected 71 (53.4%); only 21 of the cases (17.9%) were detected by cytologic examination. Of the remaining 368 patients with no visible tumor at cystoscopy, 96 (26.1%) had a positive BTA stat Test result. Fifty-five of those (57.3%) underwent intravenous urography or renal ultrasound and random biopsies, and an additional 9 recurrences (16.4%) were detected. Of those 46 patients who had a true false-positive BTA stat Test, 3 (3 of 43, 7.0%) had recurrence at the next follow-up cystoscopy, 4 (8.7%) had a urine infection, and 8 (17.4%) had ongoing intravesical instillations; the latter two percentages were significantly higher than among those with true-negative BTA stat Test results (0% and 6.8%, respectively). CONCLUSIONS: Patients with a positive BTA stat Test result but negative cystoscopic findings have about a 16% risk of an undetected recurrence. False-positive results may be due to present instillation treatment and urine infection, and the predictive value of a BTA stat Test for subsequent recurrence seems relatively low.

Human complement factor H related protein test for monitoring bladder cancer.

PURPOSE: The BTA stat test is a rapid, noninvasive, qualitative urine test that detects bladder tumor associated antigen (human complement factor H related protein) in urine. We compared BTA stat test to voided urine cytology in patients monitored for bladder cancer in a prospective trial, and determined whether this test is effective in detection of recurrence not seen by regular cystoscopy. MATERIALS AND METHODS: A total of 445 consecutive patients with bladder cancer were studied. A voided urine sample was obtained before cystoscopy and divided for culture, cytology and BTA stat testing. In cases of a positive BTA stat test but negative cystoscopy, excretory urography or renal ultrasound, random biopsies and collected ureteral urine samples for ureteral cytology were obtained. The overall sensitivity and specificity as well as positive and negative predictive values for BTA stat test, cytology and their combination were calculated. RESULTS: Of the 445 patients 118 (26.5%) had bladder cancer recurrence on cystoscopy, which was detected by BTA stat test and cytology in 63 (53.4%) and 21 (17.8%), respectively. Of the remaining 327 patients not having recurrent tumor on cystoscopy 81 (24.8%) had a positive BTA stat test. Excretory urography or renal ultrasound and random biopsies in 48 (59.3%) of these patients revealed 7 recurrences, making the total number of recurrent tumors 125 of 412 (30.3%). The overall sensitivities and specificities for the BTA stat test, cytology and their combination were 56.0%, 19.2%, 60.0% and 85.7%, 98.3% and 85.0%, respectively. CONCLUSIONS: The sensitivity for detection of recurrent tumor on BTA stat test is superior to that of voided urine cytology in all bladder cancer categories, whereas the specificity of voided urine cytology is higher than that for BTA stat test. However, a sixth of the patients with apparent false-positive BTA stat test results chosen for further investigation had recurrent tumors that were not found on routine cystoscopy. Although the sensitivity and specificity were highest when both tests were used, the differences were not significant overall. Therefore, the BTA stat test could potentially replace urine cytology for followup of superficial bladder cancer.

Routine follow-up cystoscopy in detection of recurrence in patients being monitored for bladder cancer.

BACKGROUND AND AIMS: Cystoscopy and urine cytology are the standard tools for monitoring superficial bladder cancer. The sensitivity of cystoscopy is, however, limited to the tumours that can be visualised, and the sensitivity of cytology is relatively low in low-stage/low-grade tumours. Therefore, new tumour markers have been developed. BTA stat has been reported to have high sensitivity in detecting both primary and recurrent bladder tumours, and may have the potential to detect tumours that cannot be visualised by routine cystoscopy including recurrences in upper tract. The objective of the study was to analyse the reliability of routine follow-up cystoscopy by further investigating patients with positive marker status, BTA stat Test and urine cytology, but negative cystoscopy. MATERIAL AND METHODS: 446 consecutive patients being followed for bladder cancer were analysed in a prospective multicenter study. A voided urine sample was obtained prior to cystoscopy and split for culture, cytology and BTA stat testing. In the case of positive marker status, BTA stat Test or urine cytology, but negative cystoscopy patients were further investigated by i.v. urography or renal ultrasound and random biopsies. The sensitivity of routine follow-up cystoscopy is reported. RESULTS: Of 446 patients 131 (29.4%) had a bladder cancer recurrence at routine cystoscopy. Of the remaining 315 patients not having recurrent tumour at cystoscopy, 56 patients (17.8%) had positive BTA stat Test result, 6 (1.9%) had positive cytology and 5 were positive by both tests. Nine recurrences that were missed at routine follow-up cystoscopy were detected by further investigations making the total number of bladder confined recurrent tumours 140 (140/446, 31.4%). Five of these 9 recurrences were high grade lesions (1 T1G3, 4 CIS), of which 4 were detected by positive cytology. The overall sensitivity of cystoscopy was 93.6%. CONCLUSIONS: We found that routine follow-up cystoscopy may miss over five percent of the recurrent tumours. Although cystoscopy remains the gold standard for bladder cancer follow-up, it is suggested that even with negative cystoscopy patients with positive marker status, BTA stat Test and especially urine cytology, should be considered at risk for coexisting, and in some case even high grade recurrence.

The dilemma of suspicious urine cytology in patients being followed for bladder cancer.

BACKGROUND AND AIMS: Urine cytology is gold standard for clinical tests used in the diagnosis and follow-up of bladder cancer. Cytology, however, exhibits variable sensitivity depending on tumour grade and interpretation of urine specimens is highly dependent on the skill of the examiner. Furthermore, a "suspicious" cytology report (class III) makes clinicians uncomfortable. In these cases, a more objective test, such as the BTA stat Test, may be useful in providing clarification. The aim of this study was to evaluate the dilemma of suspicious routine urine cytology and to determine whether the BTA stat Test provides diagnostic aid in this rare but controversial category. MATERIAL AND METHODS: 506 consecutive patients who were being followed for bladder cancer were included in the study. A voided urine sample was obtained prior to routine follow-up cystoscopy and split for culture and testing with the BTA stat Test. Clinical status of the disease was evaluated in patients with suspicious urine cytology, and the diagnostic aid of the BTA stat Test in these patients was determined. RESULTS: A total of 57 patients (11.3%) had urine cytology classified as suspicious. The BTA stat Test was positive in 29 (50.9%) and negative in 28 (49.1%) patients. Nineteen (33.3%) patients had recurrence at routine cystoscopy. Of the remaining 38 patients, 10 were further investigated due to a positive BTA stat Test. Two additional recurrences were detected bringing the total number of recurrences to 21 (36.8%), 48.3% (14/29) of the patients with positive and 25.0% (7/28) of the patients with negative BTA stat Test had recurrence (p = 0.069). Overall, 65.5% (19/29) of the patients with a positive BTA stat Test were found to have recurrence either at routine cystoscopy, at further investigations, or at the next cystoscopy compared to that of 35.7% (19/28) in those with negative testing (p = 0.024). The overall sensitivity of the BTA stat Test was 66.7%, and the specificity was 58.3%. CONCLUSIONS: At least a third of the patients under follow-up for bladder cancer with suspicious cytology had a recurrence, indicating that these patients are a risk group for recurrence. More importantly, a BTA stat Test result seems to provide some help in distinguishing those patients with very high risk for recurrence, for whom invasive further investigations should be conducted and a close follow-up policy maintained.

Evaluation of p21WAF1/CIP1 and cyclin D1 expression in the progression of superficial bladder cancer. Finbladder Group.

Immunoreactivity of p21WAF1/CIP1 and cyclin D1 proteins was assessed in a cohort of 207 patients with superficial (pTa-pT1) bladder cancer followed up for a mean of 4.9 years. The results of the immunostainings were compared with T category, WHO grade, tumor cell proliferation rate (MIB-1 score), the expressions of p53 and bcl-2 as well as survival. Sixty-eight percent and 75% of the tumors were p21WAF1/CIP1 positive (> or = 5% of cells positive) and cyclin D1 positive (> or = 10% of cells positive), respectively. The p21WAF1/CIP1 expression was related to cyclin D1 immunolabelling (P < 0.001) but not to the other variables studied. The expression of cyclin D1 was inversely associated with T category (P = 0.001), WHO grade (P = 0.006), MIB-1 score (P = 0.014), p53 expression (P = 0.001), and bcl-2 (P = 0.011) immunoreactivity. In univariate analysis, T category (P = 0.0001), WHO grade (P < 0.0001), MIB-1 score (P < 0.0001), bcl-2 (P = 0.0092), p53 (P = 0.0016) and p21WAF1/CIP1 (P = 0.009) expressions were significant prognostic factors with regard to tumor progression, whereas cyclin D1 was without any prognostic significance (P = 0.1). Out of 123 p21 positive tumors 21 progressed, whereas only 2 out of 58 p21 negative tumors progressed. In multivariate analysis, the MIB-1 score was the only independent predictor of cancer-specific survival (P = 0.03), whereas tumor grade (P = 0.002) and cyclin D1 expression (P = 0.04) were independent predictors of tumor recurrence. Only the WHO grade (P = 0.04) retained its prognostic value indicating the risk of progression. We suggest that in superficial bladder cancer p21WAF1/CIP1 and cyclin D1 immunohistochemistry provide no additional prognostic information compared with already established prognostic factors for predicting the risk of progressive disease.

Sensitivity of human complement factor H related protein (BTA stat) test and voided urine cytology in the diagnosis of bladder cancer.

PURPOSE: We compared the sensitivity of the BTA statdagger test, a rapid, noninvasive, qualitative urine test that detects bladder tumor associated antigen (human complement factor H related protein) in urine, to that of voided urine cytology in patients with primary bladder cancer. We also assessed the effect of tumor size, number, histological grade and stage on test sensitivity. MATERIALS AND METHODS: We evaluated 151 patients with newly diagnosed bladder cancer in a prospective multicenter study. A voided urine sample obtained before transurethral bladder tumor resection was divided for culture, cytology and BTA stat testing. RESULTS: Overall sensitivity of the BTA stat test and urine cytology for detecting primary bladder cancer was 81.5% and 30.3%, respectively (p <0.0001). The sensitivity of each test increased as tumor size, number, histological grade and stage increased. CONCLUSIONS: Sensitivity of the BTA stat test was superior to that of voided urine cytology in all tumor categories. This noninvasive, easy to perform, point of care test may have the potential to replace cytology for diagnosing bladder cancer.

Prognostic value of MIB-1 score, p53, EGFr, mitotic index and papillary status in primary superficial (Stage pTa/T1) bladder cancer: a prospective comparative study. The Finnbladder Group.

OBJECTIVE: A prospective randomized study was undertaken to determine whether cell proliferation indices (M/V index, MIB1), papillary status, the expression of p53 and epidermal growth factor receptor (EGFr) have prognostic value in superficial (pTa-pT1) bladder cancer (SBC). METHODS: 207 patients with primary SBC were followed up over a period of 4.9 (range 3.7-6.0) years. M/V index and papillary status were assessed by light microscopy, and expression of MIB1, p53 and EGFr was assessed by immunohistochemistry. The results of histopathological analyses were related to the survival data of the patients. RESULTS: Using univariate analysis, stage (p < 0.001), grade (p < 0.001), papillary status (p < 0.001), MIB1 (p < 0.001), M/V index (p < 0.001), EGFr (p < 0.001) and p53 (p = 0.002) were significant predictors of progression. Using multivariate analysis, MIB-1 score and papillary status were independent predictors of progressive disease and cancer-specific survival. Tumor grade was the only independent predictor of recurrence. CONCLUSION: Evaluation of tumor cell proliferation rate by M/V index or by MIB1 immunohistochemistry and assessment of papillary status by light microscopy are useful prognostic tools in tailoring treatment and follow-up schedule of patients with SBC.

Specificity of human complement factor H-related protein test (Bard BTA stat Test).

OBJECTIVE: The Bard BTA stat Test is a new, rapid, non-invasive qualitative test that detects bladder tumour-associated antigen (human Complement Factor H-related protein) in urine. The objective of this study was to evaluate the specificity of the Bard BTA start Test in a healthy population. MATERIALS AND METHODS: Voided urine samples from 100 healthy volunteers were collected and tested using the BTA stat Test. In the case of a positive BTA stat result, i.v. urography, cystoscopy, ultrasound and-re-testing were performed and the BTA stat Test was repeated three months later. RESULTS: Two subjects tested positive by the BTA stat Test, but no bladder cancer was found. The specificity of the BTA stat Test in the studied healthy population was 98%. CONCLUSIONS: The BTA stat Test has very high specificity with a true test-dependent false-positive rate occurring in only 2% of the healthy population. These results justify further studies with the BTA stat Test for bladder cancer diagnosis, monitoring, and screening.

Transurethral resection with perioperative instilation on interferon-alpha or epirubicin for the prophylaxis of recurrent primary superficial bladder cancer: a prospective randomized multicenter study--Finnbladder III.

PURPOSE: We evaluated the efficacy of single dose of interferon or epirubicin administered immediately after transurethral resection compared with transurethral resection only on the recurrence of primary (not recurrent) superficial bladder cancer. MATERIALS AND METHODS: A total of 283 patients with stages Ta to T1 primary superficial, grades 1 to 3 bladder cancer was randomized into study groups 1-transurethral resection only, 2-transurethral resection plus 50 million units interferon-a2b and 3-transurethral resection plus 100 mg. epirubicin. Eligible for final analysis were 200 patients, including 66 in group 1, 66 in group 2 and 68 in group 3. Patients were followed with cystoscopy every 3 months for 2 years or until the initial recurrence. RESULTS: Group 3 had the most favorable outcome, since 45 of the 68 patients (66%) were without recurrence after 2 years compared to 24 of the 66 (37%) in group 2 and 26 of the 66 (40%) in group 1 (log rank test p <0.001). Side effects were mostly mild and transient, and no differences were found among the groups. CONCLUSIONS: A single 100 mg. dose of epirubicin given intravesically immediately after transurethral resection is safe, and significantly decreases the recurrence of primary superficial bladder cancer. A 50 million unit dose of interferon-alpha2b is well tolerated but it has no effect on recurrence as a single dose. The long-term effect of this treatment remains to be studied.

p53 mutations and presence of HPV DNA do not correlate with radiosensitivity of gynecological cancer cell lines.

OBJECTIVE: The correlation between p53 tumor suppressor gene mutations and the presence of high-risk human papillomavirus (HPV) DNA with the in vitro radiosensitivity of gynecological malignancies was studied in 26 cell lines derived from gynecological cancers of 23 patients. METHODS: Comparison of the intrinsic radiosensitivity was performed with mean inactivation dose (D) determined with the 96-well plate clonogenic assay. p53 mutations were investigated with polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) analysis and direct DNA sequencing, and the presence of HPV DNA was studied with PCR using HPV consensus primers. RESULTS: p53 mutations were found in 6 of 10 vulvar squamous cell carcinoma (SCC) lines. Nine vulvar and 1 vaginal SCC cell lines were HPV DNA negative and 1 vulvar cell line was HPV 16 positive. All 4 cervical SCC lines were HPV positive and possessed the wild-type p53. Three cell lines expressed HPV 16 and 1 HPV 68. Among 10 endometrial cancer cell lines, 2 cell lines with mutant p53 and 1 HPV 16 positive cell line were found. No correlation could be demonstrated between inactivation of the p53 gene and radiosensitivity in vitro; the cell lines were evaluated as one group or according to their anatomical origin or histology. CONCLUSION: Our results indicate that inactivation of the p53 gene through mutation or binding with HPV DNA does not increase the resistance of gynecological malignancies to ionizing radiation in vitro.

P53 accumulation, deoxyribonucleic acid ploidy and progression of bladder cancer.

PURPOSE: The alterations in deoxyribonucleic acid (DNA) ploidy and p53 expression during progression of bladder cancer were determined. MATERIALS AND METHODS: p53 Expression and DNA ploidy were studied in 51 patients with transitional cell carcinoma of the bladder (mean followup 5 years). Of 29 primarily superficial tumors (stages Ta and T1) 17 became subsequently invasive (greater than stage T2) within an average of 4 years (group 2) and 12 recurred superficially with no sign of progression during a mean followup of 10.8 years (group 1). Of the patients 22 had metastatic disease (group 3). Samples of tumors at diagnosis and recurrence or progression were analyzed by immunohistochemistry and flow cytometry. RESULTS: p53 Accumulation was detected at diagnosis in 29 of the 51 patients (57%), including 3 of 12 (25%) in group 1, 5 of 17 (29%) in group 2 and 14 of 22 (64%) in group 3. The p values for the differences between groups 1 and 3, and 2 and 3 were 0.07 and 0.054, respectively. Abnormal DNA contents were noted in 3 of 12 (25%), 11 of 17 (65%) and 16 of 22 (73%) patients in groups 1 to 3, respectively, and the differences between groups 1 and 2, and 1 and 3 were statistically significant. Using these 2 genetic markers, we found genetic progression to be uncommon in groups 1 and 3, whereas in group 2 an initially negative p53 staining became positive at invasion into the muscle in 5 of 12 patients (42%). CONCLUSIONS: The tumors in patients with superficial recurrences are mostly diploid and negative for p53, and those with metastasis are nondiploid and positive for p53 from the beginning, while further genetic progression is uncommon. However, p53 tends to accumulate frequently when the tumor begins to invade the muscle. There seems to be a need for caution against under staging an apparent stage T1 tumor that is positive for p53.

A controlled study of intravesical epirubicin with or without alpha 2b-interferon as prophylaxis for recurrent superficial transitional cell carcinoma of the bladder. Finnish Multicentre Study Group.

OBJECTIVES: To evaluate the efficacy of intravesical epirubicin with or without alpha 2b-interferon (alpha 2b-IFN) as a prophylactic treatment for recurrent superficial transitional cell carcinoma (TCC) of the urinary bladder. PATIENTS AND METHODS: A total of 81 patients with superficial (stage Ta and T1), well or moderately differentiated (grades 1 and 2) TCC were treated between June 1988 and December 1993. The patients were randomized into three groups: Group 1 was treated by transurethral resection (TUR) alone; Group 2 received 50 mg epirubicin and Group 3 received 50 mg epirubicin combined with 10 MU alpha 2b-IFN, intravesically in 50 mL sterile buffer solution. The instillations were started 1 week after TUR and were performed weekly during the first month and then once a month for one year. The patients were followed for a total of 2 years. Recurrence rate and tumour rate were calculated to assess the behaviour of the disease. RESULTS: The patients were followed for a mean of 20 months. Patients receiving intravesical chemoimmunotherapy (Group 3) had the most favourable outcome; they had comparatively lower recurrence and tumour rates, fewer patients with recurrences and, most importantly, the longest disease-free interval. Side-effects were mostly mild and transient, and no differences were found among the groups. CONCLUSIONS: In reducing the number of patients having recurrences and extending the recurrence-free interval, intravesical chemoimmunotherapy with epirubicin and alpha 2b-IFN had a promising effect on the natural course of superficial bladder cancer, particularly in patients with a history of prior recurrences.

Impact of tumour grade, stage, number and size, and smoking and sex, on survival in patients with transitional cell carcinoma of the bladder.

OBJECTIVE: To evaluate the impact of the grade, stage number and size of the tumour and of smoking and sex of patient on survival, and the relationship between smoking and tumour grade, stage, number and size, and sex of patient in patients with transitional cell carcinoma (TCC) of the urinary bladder. PATIENTS AND METHODS: The study comprised 252 consecutive patients with histologically verified TCC of the bladder reporting to Oulu University Central Hospital between 1978 and 1986. The average duration of follow-up was 6.7 years. The association between smoking and other covariates was analysed by cross-tabulation and standard chi-squared analyses. The Kaplan-Meier method was used to obtain estimated survival curves and significant differences determined using log rank statistics. RESULTS: Smoking had no impact on tumour grade, stage, size and number or aggressiveness of metastases. Prognosis was noticeably better if the patient did not smoke, as 27% of the non-smokers and 40% of the smokers had died during the first 10 years after diagnosis. Survival was also better in patients with low grade (I, II), non-invasive (Ta/T1) and small (< or = 3 cm) tumours. CONCLUSION: In addition to the well-known prognostic factors (histological grade and stage of the tumour), smoking is a risk factor for bladder cancer and also has an impact on prognosis, leading to higher mortality from the disease in the longer term.

Impact of tumour grade, stage, number and size, smoking habits and sex on the recurrence rate and disease-free interval in patients with transitional cell carcinoma of the bladder.

The recurrence rate and the time interval until the first recurrence were analysed in 169 consecutive conservatively treated patients with transitional cell carcinoma of the urinary bladder, in relation to initial tumour grade, number, size and stage, sex and smoking habits, at least five years after the diagnosis of the disease. The recurrence rate was higher among patients with more than three tumours and among patients with an invasive disease, while tumour size, histological grade and sex had no effect on the recurrence rate. The time until the first recurrence was found to be shorter among patients with an invasive disease and those with more than three tumours, and also among females. Smoking did not have any impact on the disease-free interval or on recurrence. We suggest that patients with multiple tumours are at great risk of recurrent disease. If invasion into muscle is found, the risk of recurrences will be high, and transurethral electroresection might not be an adequate form of therapy.

Relationship between blood groups and tumour grade, number, size, stage, recurrence and survival in patients with transitional cell carcinoma of the bladder.

Blood group was correlated with the tumour grade, number, size, stage and recurrence rate and with survival in 261 consecutive patients with bladder cancer analyzed at least five years after diagnosis of the disease. The distribution of blood groups did not differ from that in the general population. There were no significant differences in the incidence of invasion at the time of diagnosis or later, in the number of the tumours or in the recurrence rate. A tendency for high-grade and large-sized tumours was observed in the blood groups O(H) and B. Differences in mortality were not observed until eight years after diagnosis, so that 28% of the patients with blood group A and 40% of those with blood group O had died of bladder cancer by ten years after diagnosis. Since the differences are small, the clinical significance of blood groups as a prognostic factor in bladder cancer patients is minimal. However, there seems to be a need for further research of the significance of genetic background in the natural history of bladder cancer.