Until then we have some old reports here:

1. Andrology
2. Endourology
3. Reconstruction
4. Calculus Disease
5. Incontinance
6. Oncology
7. Oncology Prostate
8. Prostate BPH
9. Equipment
10. Special Interest

Back home

Journal:	Cancer
Authors:	Buzio C, Andrulli S, santi R, Pavone L, Passalacqua R, Potenzoni D, Ferrozzi F, Vaglio A	Issue:	2001, 92: 2286-2296

Title:

Long term immunotherapy with low dose interleukin-2 and interferon a in the treatment of patients with advanced renal cell carinoma

Abstract:
In this study 50 patients with advanced renal cell carcinoma were evaluated in terms of response, toxicity, and immunologic effects following treatment with repeated cycles of recombinant interleukin-2 (rIL-2) and recombinant interferon a (rIFNa). This treatment was given for 4 consecutive weeks, with subcutaneous rIL-2 for 5 days per week, and twice weekly intramuscular rIFNa. Their results revealed that 1 patient had a complete response and 5 patients achieved a partial response, although the median follow up time for all 50 patients was only 13.4 months. They also found that 5 patients had stable disease and 30 patients had progressive disease. Treatment toxicity was assessed using the WHO grading system, and it was found that toxicity was limited to grades 1 and 2. The treatment doses were lower in this study compared to several other studies using this regimen and it was reported that, despite the lower dose, the anti-tumour effect was maintained, as the overall response rate was 12% (95% confidence interval, 3-21%) on the basis of intent to treat analysis. The 36-month survival probability for all 50 patients was 47%. The authors concluded that this low dose regimen produces comparable clinical response rates and survival probabilities to the higher dose regimens. If this were to be validated in a larger series, it would enable patients to receive the same immunological effects without the increased toxicity that would occur with a higher dose.

Reviewer: Jon-Paul Meyer

Journal:	BJU International
Authors:	Ueno M, Nakashima J, Ohigashi T, Deguchi N, Ban S, Akita M, Murai M	Issue:	2001, 88: 611-621

Title:

Establishment of a testicular carcinoma cell line producing alpha-fetoprotein

Abstract:
In this paper a newly established human cell line producing a-fetoprotein (AFP) is characterised. This cell line was taken from a 24 year old with a right testicular carcinoma, who underwent a radical orchidectomy. He also had 2 separate lung metastatic lesions, both of which were removed surgically. The cancer cells from one of these tumours were isolated and found to be composed of undifferentiated germ cells producing AFP, the authors termed this cell line KU-MT. This cell line was implanted into athymic mice, and it was possible to maintain it. This was also achieved in culture. This exciting newly established cell line, as well as providing a reproducible model system, should also offer a good insight into the differentiation of testicular carcinoma.

Reviewer: Jon-Paul Meyer

Journal:	BJU International
Authors:	Westenend PJ, Stoop JA, Hendriks JGM.	Issue:	2001; 88: 198-201

Title:

Human papillomaviruses 6/11, 16/18 and 31/33/51 are not associated with squamous cell carcinoma of the urinary bladder.

Abstract:
In this study the authors aim to assess the role of the human papillomavirus (HPV) - types 16,18,31 and 33 as an aetiological factor in squamous cell carcinoma (SCC) of the bladder. They examined 16 cases of SCC of the bladder using non-isotopic in situ hybridization with a suitably sensitive detector the presence of the above types of HPV. They reported that in this study of 16 cases there were no high risk HPV’s detected. Their results were similar to those previously reported. Previously, only 9 high risk HPV’s were detected in 105 cases, with 4 of this 9 being deemed to be a high risk in anogenital carcinomas. The authors therefore concluded that HPV does not have a major role in the pathogenesis of SCC of the bladder.

Reviewer: Jon-Paul Meyer

Journal:	BJU International
Authors:	Rotterud R, Berner A, Holm R, Skovlund E, Fossa SD.	Issue:	2001; 88: 202-208

Title:

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

Abstract:
This is a prospective study looking at possible molecular markers predictive of radioresponsiveness in patients with transitional cell carcinoma (TCC) of the bladder. The authors used patients with T2-T4a TCC treated with preoperative radiotherapy and cystectomy and from this group selected those with pT3b (42 patients) and pT0 (17 patients) to include in the study. These two groups were chosen as they represent separate categories thus removing the problem of stage reduction, so that only patients with no tumour (pT0) and patients with tumour extension through the bladder wall (pT3b) were included. It is stated that over the time period of this retrospective study radiotherapy schedules changed. The radiotherapy was given as either 2 Gy x23 over 4-5 weeks with cystectomy 4-5 weeks later (23 patients) or 4 Gy x5 over 1 week followed by a cystectomy in the week following radiotherapy (36 patients). In these cases, using the technique of immunohistochemistry the authors assessed the protein expression of p53, mdm2 and p21 in biopsy specimens taken before radiotherapy. Their results revealed that there was no difference in protein expression between patients with pT0 and pT3b disease. Interestingly, in the patients who received 46 Gy, increased p53 expression predicted the absence of residual tumour, in that, six of the seven patients with more than 50% expression of p53 had pT0 in their cystectomy specimen, whereas 10 of the 12 patients with less than 5% expression had pT3b in their cystectomy specimens – this was not the case with mdm2 and p21. The authors concluded reporting that the expression of mdm2 and p21 did not predict radioresponsiveness in patients with TCC. They also felt that despite their p53 figures, the role of p53 still remains unclear, as other studies previously conducted did not support their findings.

Reviewer: Jon-Paul Meyer

Journal:	BJU International
Authors:	Shelley MD, Kynaston H, Court J, Wilt TJ, coles B, Burgon K, Mason MD.	Issue:	2001; 88: 209-215

Title:

A systematic review of intravesical bacillus Calmette-Guerin plus transurethral resection vs transurethral resection alone in Ta and T1 bladder cancer.

Abstract:
In this article the authors set out to review the effectiveness of bacille Calmette Guerin (BCG) in patients with Ta and T1 bladder cancer in terms of reducing tumour recurrence. The authors performed an extensive database search to ascertain the number of randomised controlled trials comparing transurethral resection (TUR) alone with TUR and BCG for Ta or T1 disease. Six trials were identified giving 585 patients in total; 304 had TUR and BCG and 281 had TUR alone. The outcome measure was tumour recurrence. Their results revealed that across all six trials the Peto odds ratio for patients recurring at 1 year was 0.3 - significantly favouring BCG therapy. They concluded reporting that BCG provided a significantly better prophylaxis for tumour recurrence in Ta and T1 disease with respect to TUR alone. Unfortunately, the authors do not present data which compares the outcome of those with Ta disease to those with T1 disease, and a weakness in this study is that it takes six trials which did not use the same strain of BCG with the amount given varying between trials. Despite this an important conclusion is reached showing the benefit of BCG in Ta/T1 disease.

Reviewer: Jon-Paul Meyer

Journal:	Cancer
Authors:	Kankuri M, Pelliniemi TT, Pyhonen S, Nikkanen V, Helenius H, Salminen E	Issue:	2001; 15;92:761-7.

Title:

Feasibility of prolonged use of interferon alpha in metastatic kidney carcinoma

Abstract:
It is known that interferon alpha is effective in the treatment of metastatic renal cell carcinoma (RCC). In this paper the authors set out to determine the optimal schedule for its usage. They looked at 75 patients with metastatic renal cell carcinoma. Treatment dosage started at 4.5 million units and was increased to 18 million units during the first month; this was given 3 times per week. The authors continued this treatment until either progression or intolerable toxicity was reported or for a maximum of 2 years. Treatments were given each month with a one week pause. They reported a 17% overall response in their patients and a 43% rate of stable disease. The median survival time was 19.3 months and the median time to progression was 12.3 months. A treatment discontinuation rate of 8% - due to fatigue, cardiac dysrrhythmias and elevated liver enzymes – was reported. In this interesting paper the authors conclude that prolonged and intermittently administered alpha interferon, given three times per week in three weekly cycles for those with metastatic RCC, is an effective therapy. They felt treatment for more than 12 months for those patients who respond is tremendously beneficial and may improve their outcome. Clearly these promising conclusions need to be substantiated with a larger cohort of patients.

Reviewer: Jon-Paul Meyer

Journal:	Cancer
Authors:	Van Rhiijn BWG, Lurkin I, Kirkels WJ, Van der Kwsat TH, Zwarthoff EC.	Issue:	2001: 15, 92; 768-75

Title:

Microsatellite analysis - DNA test in urine competes with cystoscopy in follow up of superficial bladder cancer

Abstract:
A large number of patients undergo follow up cystoscopy per year following a transurethral resection of a superficial bladder tumour. In this paper the authors evaluate the use of microsatellite analysis (MA) – a DNA based method – in the follow up of these patients. They looked at a cohort of 109 patients following a transurethral resection (TUR) of a superficial bladder tumour. Prior to TUR the DNA for each patient was determined using urine and blood samples. The MA test was compared to the BTA stat test and cytology. Their results revealed that the MA test detected 18 of the 24 recurrent bladder tumours in 93 patients, with 16 patients of the original 109 having been excluded due to insufficient quality of the DNA. The 6 undetected tumours by the MA test were G1pTa lesions. The overall sensitivity of the MA test was 74% compared to 56% for the BTA stat test and 22% for urine cytology. Interestingly, 5 of the 9 patients who had positive MA tests yet negative cystoscopies went on to develop a tumour recurrence within 6 months. Of the 60 with both negative MA tests and negative cystoscopies only 7 developed a recurrence. The results that this paper has generated suggest that the MA test could potentially be an extremely useful diagnostic tool. This test warrants a randomised trial to substantiate or refute these initial results.

Reviewer: Jon-Paul Meyer

Journal:	Lancet
Authors:	Levi F, La Vecchia C, Boyle P, Lucchini F, Negri E.	Issue:	2001, 357:1853-4

Title:

Western and eastern European trends in testicular cancer mortality

Abstract:
This study compared mortality rates from testicular cancer in western and eastern Europe, the United States and Japan. In the wealthy western populations, incidence has been increasing, but mortality has fallen dramatically since the 1970s (probably due to the introduction of platinum-based chemotherapy). In Europe as a whole this is said to amount to 500 young men saved per year. Unfortunately, the mortality improvements in eastern Europe started later and have thus far been smaller. This presumably relates to socio-economic factors relating to the availability of expert oncology services, a suggestion supported by the fact that the USA appears always to have led the field. Similar findings have been found with childhood cancers that are now effectively treated with chemotherapy.

Reviewer: Kieran Jefferson

Journal:	Urology
Authors:	Chang BS, Kim HL, Yang XJ, Steinberg GD	Issue:	2001; 57:1063-1066

Title:

Correlation between biopsy and radical cystectomy in assessing grade and depth of invasion in bladder urothelial carcinoma.

Abstract:
In this paper the authors assess the degree of correlation between specimens obtained from bladder biopsy and radical cystoprostatectomy in terms of their pathological characteristics. Retrospectively they identified cases who underwent radical cystectomy at University of Chicago hospitals. Their pre-operative bladder biopsies and radical cystectomy specimens were reviewed by a single pathologist. For all cases the histological grade of the tumour was assessed using both the three-grade system, and the World Health Organisation and International Society of Urological Pathologists (WHO/ISUP) classification. Their results revealed that, using the WHO/ISUP classification, the histological grade was identical in the biopsy and in the cystectomy specimens when they were compared. Discrepancies arose when the traditional three grade system was used; the grade was increased by one grade in 19 (11%) of the 169 cases and decreased by one grade in 8 (5%) of cases. They also reported that patients with lamina propria invasion on biopsy had tumour extending outside the bladder in 15 (27%) of 55 cases, and those with muscularis propria invasion on biopsy had tumour extending outside the bladder in 47 (49%) of 96 cases. This included nodal metastasis in 22 (23%) of 96 cases. Overall, the authors reported that, in 78 (46%) of 169 cases, bladder biopsy understaged the true extent of the disease. In conclusion the authors felt that using the WHO/ISUP classification, the histological grade from the pre operative biopsy accurately predicts the true histological grade. However, the biopsy significantly under-represented the depth of tumour invasion. More accurate clinical staging is therefore required to identify those with organ-confined disease who are candidates for radical cystectomy.

Reviewer: Jon-Paul Meyer

Journal:	Molecular Research
Authors:	Wada Y, Gotoh A, Shirakawa T, Hamada K, Kamidono S	Issue:	2001;5:47-52

Title:

Gene therapy for bladder cancer using adenoviral vector

Abstract:
The authors in this paper set out to explore the use of modulating agents, which may act synergistically or additively with intravesical chemotherapeutic agents. Current treatments for superficial bladder cancer include transurethral resection followed by adjuvant BCG. BCG is reported to be effective in between 38% and 68% of cases. It is known that mutations in the p53 gene occur frequently in bladder cancer. In this study the authors examined the tumour suppressive function of the p53 gene in bladder cancer. To achieve this, recombinant adenovirus vectors containing wild type p53 (Ad5CMV-p53) or controls were constructed and delivered directly to human and murine bladder cancer cell lines. Their in vitro results revealed significant growth suppression of target cells by Ad5CMV-p53 in comparison with those receiving the control Ad5-CMV-PA vector or untreated control cells. In vivo studies using subcutaneous bladder tumour models in syngeneic mice revealed that the rate of tumour growth and volume was reduced to a greater extent by 14 days of intratumoural injection of Ad5CMV-p53 rather than Ad5CMV-PA. Also reported, was the fact that the survival time for those who were injected with Ad5CMV-p53 was significantly longer than the survival of the control groups, who were treated with Ad5CMV-PA. The results from this paper suggest that Ad5CMV-p53 is effective in suppressing bladder cancer growth and improving survival time, although further study is required to verify these exciting results.

Reviewer: Jon-Paul Meyer

Journal:	Urology
Authors:	Derogee M, Bevers RFM, Prins HJ, Jonges TGN, Elbers FH, Boon TA	Issue:	2001; 57:1133-1137

Title:

Testicular microlithiasis, a premalignant condition: prevalence, histologic findings, and relation to testicular tumour.

Abstract:
This is a retrospective analysis of the prevalence of testicular microlithiasis (TM). The authors studied TM patients and its association with testicular tumours, histopathological findings, and follow up. 1535 patients who had a testicular ultrasound (USS) in a 6 year period were included, their records were then retrospectively reviewed. In 63 of these patients, TM was diagnosed at USS and in 29 of these 63 patients a concomitant testicular tumour was also seen. The association between TM and testicular tumour was found to be statistically significant, although there was no statistically significant correlation found concerning the position of the TM within the testis and the tumour, the type of calcification, and histologic type of the tumour. In 34 patients, TM was found without malignancy at diagnosis. Of these 34 patients it was possible to follow up 31, and during a median follow up period of 61.8 months,1 patient developed a testicular tumour. In conclusion, the authors felt that TM should be regarded as a pre-malignant condition and suggested that patients with TM should be followed up with regular ultrasound scans and patients should be advised on testicular self examination. They also suggested the use of testicular biopsy in TM, although the usefulness of this has not been proven in a large series of patients with TM.

Reviewer: Jon-Paul Meyer

Journal:	Journal of Urology
Authors:	Saint F, Patard JJ, Irani J, Salomon L, Hoznek A, Legrand P, Debois H, Abbou H, and Chopin DK	Issue:	2001, 57: 617-621

Title:

Leukocyturia as a predictor of tolerance and efficacy of intravesical BCG maintenance therapy for superficial bladder cancer.

Abstract:
In this paper the authors set out to examine the significance of using leukocyturia as a predictor of tumour recurrence and occurrence of adverse events after treatment of superficial bladder cancer with bacille Calmette-Guerin (BCG). The authors prospectively enrolled 72 patients with a history of multifocal or recurrent papillary transitional cell carcinoma. They each received a course of weekly instillations over a period of 6 weeks, followed by maintenance therapy of 3 weekly instillations given at 3, 6, 12, 18, 24, 30, and 36 months. Three days after each BCG treatment urinary leukocytes were counted - each time by the same operator. Adverse events were also recorded; the authors used a 4 class scale that they defined to record the severity and duration of local and systemic adverse events. They also defined two subclasses (A and B). A was associated with systemic adverse events such as fever, flu-like symptoms or fatigue, and subclass B associated with local or regional adverse events such as frequency, haematuria or weak stream. For each patient, the authors calculated an adverse event score during the induction course and for the maintenance therapy - this was calculated as the sum of adverse events divided by the number of instillations given. The results reported were very interesting. The authors found that high leukocyturia during BCG treatment (cut-off value of 1.65 x 10 5 /ml urine) correlated with recurrence-free status. They also found that, during the induction and maintenance courses, the severity of adverse events after each instillation increased with the number of instillations and with leukocyturia. The median leukocyturia values associated with class I, II, and III adverse events were 4 x 10 4/ml, 1.5 x 10 5/ml and 3.5 x 10 5/ml, respectively. The authors, in their conclusion, felt that leukocyturia appeared to correlate with both efficacy and tolerability within the setting of their study. The results also suggested a link between adverse events and efficacy during BCG therapy. Obviously, this study only looked at 72 patients but, on the basis of these results, the use of leukocyturia as a possible predictor of adverse events and tumour response during treatment with BCG would seem to be an attractive option. In order to use leukocyturia as a basis on which to adapt an individual’s BCG therapy, a prospective randomised control study is required.

Reviewer: Jon-Paul Meyer

Journal:	Urology
Authors:	Gerhards S, Jung K, Koenig F, Daniltchenko D, Hauptmann S, Schorr D, and Loening SA	Issue:	2001, 57: 675-9

Title:

Excretion of matrix metalloproteiases 2 and 9 in urine is associated with a high stage and grade of bladder carcinoma

Abstract:
In this paper the authors examine the diagnostic clinical validity of the excretion of matrix metalloproteinases (MMP) 2 and 9 in the urine of patients with bladder cancer, according to the stage and grade of the tumour. MMPs are degradative enzymes that remodel extracellular components in healthy and diseased tissue. Prior studies have shown an association between tumour growth and metastasis and increased MMP expression. The authors studied a total of 129 people, consisting of a control group of 44 without malignancy, 14 with cystitis, 43 with stage Ta-T1 bladder cancer, 18 with stage T2 bladder cancer and 10 with stage T3-T4 bladder cancer. In each of these patients MMP-2 and MMP-9 excretion in urine samples was measured and related to urine creatinine concentration. Their results showed that the levels of MMP-2 and MMP-9 correlated with each other and with tumour stage and grade. Elevated excretions of the MMPs were mainly observed in the patients with muscle invasive disease (stage T2-T4). The diagnostic performance of the MMPs to differentiate between controls and patients with bladder cancer was determined by receiver operating characteristic analysis. The authors duly calculated the areas under the curves. These were shown to be significantly different for MMP-2 (P<0.01) and MMP-9 (P<0.001) in patients in the higher stage and grade groups. They also reported that considering the upper cut-off limits for MMP-2 of 277 microgram/g creatinine and for MMP-9 of 648 microgram/g creatinine, the overall sensitivity to detect bladder cancer was 0.51 for MMP-2 and 0.31 for MMP-9. These were for all patients with cancer combined. For patients with stage T2-T4 cancer it was 0.82 for MMP-2 and 0.61 for MMP-9. The authors also carried out cytological analysis of the urine for comparison, and they reported that the sensitivity of cytological analysis was 0.31. The results from logistic regression analysis revealed that MMP-2 showed the best results. This study has revealed that people with bladder cancer have significantly increased MMP-2 and 9 excretions, depending on their stage and grade. The authors concluded that, as this is an inexpensive technique, the use of MMP-2 in the urine may act as an additional tool in the prediction of advanced stage bladder cancer (T2 or greater), rather than just detect superficial tumours. These promising early results certainly justify further prospective study.

Reviewer: Jon-Paul Meyer

Journal:	International Journal of Impotence Research
Authors:	Haitel A, Posch B, El Baz M, Mokhtar A, Susani M, Ghoneim M, Marberger M	Issue:	2001, 165: 1481-7

Title:

Bilharzial related, organ confined, muscle invasive bladder cancer: prognostic value of apoptosis markers, proliferation markers, p53, e-cadherin, epidermal growth factor receptor and c-erbB-2

Abstract:
As its pithy title suggests, this paper analysed a cohort of bladder tumours for expression of a number of widely studied cell regulatory proteins and compared this to prognosis. Expression was determined by immunohistochemistry and was similar to many previous studies using tissue from western patients. The novelty of this study lies in its use of tissues from schistosome-infected patients from Egypt, including a predominance of squamous cell tumours. Tissues from 92 males and 17 females with organ-confined G2 disease were used. Samples were collected over a five-year period with follow up varying from 3 to 115 months. About 60% of patients were followed for more than two years. The layout of the paper is unfortunate and the hard facts are clouded by the sheer volume of data presented, most describing negative findings. Unfortunately, I was unable to glean from the paper which markers provided prognostic information independent of grade. This would appear to be the only indication for using expensive immunohistochemical techniques. The front-runner appears to be p53 overexpression which correlated with a poor prognosis in both tumour types (overexpression implies the presence of non-functional mutant p53). Other marker expression was rather confusing; for instance, expression of Bax and Bak, two proapoptotic members of the Bcl-2 family was highest in tumours of high grade, and differed between tumour types. The overall message appears to be that p53 status is one of the few reliable molecular predictors of prognosis, a situation which is similar to that in non-bilharzial TCC. The other markers seem unlikely to find widespread use in uro-oncological practice.

Reviewer: Kieran Jefferson

Journal:	Journal of Urology
Authors:	Yoshimura R, Sano H, Mitsuhashi M, Kohno M, Chargui J, Wada S.	Issue:	2001, 165: 1468-1472

Title:

Expression of cyclooxygenase-2 in patients with bladder carcinoma.

Abstract:
It is known that cyclooxygenase-2 has an important role in the development of metastasis in cancer due to angiogenesis function. The expression of cyclooxygenase-2 has been demonstrated to be up-regulated in colorectal cancer and also in several other cancers. In this paper the authors consider its expression in bladder cancer. They studied the expression of cyclooxygenase-1 and 2 in patients with bladder cancer, chronic cystitis and in those with a normal bladder. They looked at specimens taken from 79 male and 39 female patients at the same centre. The age range was 37 to 83 years old. This figure contained 10 patients with chronic cystitis and 8 patients with a normal bladder. The techniques used by the authors to study the expression of cyclooxygenase-1 and 2 were reverse transcriptase polymerase chain reactions and immunohistochemistry. Their results revealed that cyclooxygenase-1 was weakly expressed in tissues from chronic cystitis, but not expressed in the normal bladder or from any tissue taken from a cancer specimen. Cyclooxygenase-2 was shown to be strongly expressed in any tissue from a cancer specimen, with its expression being much higher in grade 3 than in grade 1 bladder cancer. Cyclooxygenase-2 was not expressed in tissue from a normal bladder, and only slightly seen in tissue specimen from bladders with chronic cystitis. These interesting results suggest that cyclooxygenase-2 is involved in the development and growth of bladder cancers. Clearly, further study is required to determine how they are involved in this process.

Reviewer: Jon-Paul Meyer

Journal:	Journal of Urology
Authors:	Palou J, Laguna P, Millan-Rodriguez F, Hall RR, Salvador-Bayarri J and Vicente-Rodriguez J.	Issue:	2001, 165: 1488-1491

Title:

Control group and maintenance treatment with bacillus Calmette-Guerin for carcinoma in situ and/or high grade bladder tumors.

Abstract:
Intravesical instillations of bacillus Calmette-Guerin (BCG) have been shown to give satisfactory results in the treatment of carcinoma in situ and in high grade superficial bladder cancers. In this paper the authors study the decrease in tumour recurrence in patients treated with maintenance therapy. The authors looked at patients who had received an initial course of 6 instillations of Connaught strain BCG for carcinoma in situ and/or high grade superficial bladder cancer. Six months following treatment 131 disease free patients were randomly assigned to either a control group (63 patients) or to a maintenance therapy group (65 patients) to receive 6 instillations every 6 months for a 2 year period. Patients were excluded if they had a history of invasive bladder cancer, previous radiotherapy, diagnosis of another primary tumour or had had adverse effects to BCG therapy. Of these 131 patients, 126 of them were evaluable. The author’s results revealed that in a mean follow up time of 79 months there were no significant differences between the groups in terms of recurrence or progression. 16 patients (26.2%) in the control group and 10 (15.1%) in the maintenance group had superficial relapses at a mean of 24 and 20 months respectively. In the control group, 9 patients had high grade superficial recurrence at a mean of 21 months with 2 of these undergoing a radical cystectomy. In the maintenance group, 8 patients had a high grade recurrence at a mean of 22 months, with 2 undergoing a radical cystectomy and 33.8% completed the 2 year planned treatment course. In the maintenance group, 32 discontinued due to reactions to the BCG, 1 had a contracted bladder, 3 progressed and 7 simply discontinued treatment. The authors concluded that 6 month maintenance BCG therapy in patients treated initially for carcinoma in situ and/or high grade superficial bladder tumours, who are disease free at 6 months, does not significantly decrease their chances of progression or recurrence. This needs to be verified in a study with much larger numbers, as should the authors conclusions be corroborated, then not giving patients maintenance BCG therapy would represent a significant cost saving and avoid unnecessary patient morbidity.

Reviewer: Jon-Paul Meyer

Journal:	Urology
Authors:	Schmitt B, Wilt TJ, Schellhammer PF, DeMasi V, Sartor O, Crawford ED, Bennett CL	Issue:	2001, 57: 727-732

Title:

Combined androgen blockade with non-steroidal anti-androgens for advanced prostatic cancer: a systematic review

Abstract:
This paper describes the results of a systematic review performed by the Cochrane Collaborative Review Group on Prostatic Diseases, based around a meta-analysis of 20 published randomised controlled trials (RCTs) comparing complete androgen blockade with castration. This analysis excludes trials using the steroidal anti-androgen cyproterone acetate and therefore differs from the recent analysis by the Prostate Cancer Triallists’ Collaborative Group (PCTCG) published in 2000. Also, the analysis was based on published data, whereas the PCTCG study obtained individual patient data for analysis. RCTs studying both metastatic and locally advanced prostate cancer were included and data analysed for overall survival, toxicity, progression-free survival, disease-specific survival and type of therapy. Twelve trials used flutamide, 8 used nilutamide and none used bicalutamide. A total of 5432 patients were analysable, but this figure fell dramatically for some end-points at late time-points (e.g. cancer-specific survival was based on two studies and 781 patients). Furthermore, many of the trials were unblinded. The results suggest a probable small survival advantage for combined androgen blockade (2-5%) at 5 years. This was gained at the expense of increased gastro-intestinal and ophthalmological symptoms and a single study showing a worsened quality of life. Patients therefore have to balance a potential small survival advantage against the risk of increased adverse events. These findings are remarkably similar to those of the PCTCG study when patients taking cyproterone acetate based CAB were excluded.

Reviewer: Kieran Jefferson

Journal:	International Journal of Epidemiology
Authors:	Zeegers MP, Tan FE, Goldbohm RA and van Den Brandt PA	Issue:	2001; 30:353-62.

Title:

Are coffee and tea consumption associated with urinary tract cancer risk? A systematic review and meta-analysis

Abstract:
It has long been suggested that bladder cancer is influenced by environmental factors, such as smoking and industrial chemical exposure, but the impact of coffee and tea consumption, on the risk of urinary tract cancer is less clear. This review sets out to summarise and quantify the associations between tea and coffee consumption with urinary tract cancer risk. The authors, in this review have both adjusted and unadjusted for age, smoking and sex. There are thirty-four case control and three follow up studies included in this review article. For these studies the authors calculated summary odds ratios (OR) by meta-regression analyses. Their results revealed that the unadjusted summary OR indicated a small increased risk of urinary tract cancer for coffee drinkers as compared to non-coffee drinkers. Neither adjusted nor unadjusted summary OR produced evidence for a positive association between tea consumption and urinary tract cancer. The authors noted that each of these thirty-four studies, although slightly different in their methodology, reached the same conclusions. In their conclusion, the authors in accordance with earlier reviews, felt that coffee consumption increased the risk of urinary tract cancer by approximately 20%. They also concluded that the consumption of tea does not appear to be associated with an increased risk of developing urinary tract cancer. Unfortunately, due to sparse data, the authors were unable to comment on the impact of the type and amount of coffee consumption on the risk of urinary tract cancer. Clearly this would be an area of further interesting study.

Reviewer: Jon-Paul Meyer

Journal:	European Urology
Authors:	Irani J, Humbert M, Lecocq B, Pires C, Lefebvre O, Dore B	Issue:	2001, 39:300-3

Title:

Renal tumour size: comparison between computed tomography and surgical measurements

Abstract:
This retrospective study analysed 100 radical nephrectomies, comparing measurements from pathological specimens with those from pre-operative CT scans. The authors' rationale for such a study relates to the potential for nephron-sparing surgery in patients with tumours of less than 40mm. Unsurprisingly, the correlation between CT and pathological measurements is very good, but became worse for small tumours. The authors go on to state that the potential for nephron-sparing surgery would have been lost in 3 of the 100 patients if CT criteria had been used. The findings are broadly similar to an earlier paper published by Herr and colleagues looking at specimens from patients who had undergone conservative surgery. Overall, this paper would appear to be of little impact. The benefits of partial nephrectomy in 'elective' patients are probably small, especially in patients with tumours at the upper end of the operable range. In patients with single kidneys, or other 'hard' indications for conservative surgery, these findings will make no difference. The real question is whether these findings matter and, if so, whether there is an alternative imaging modality which offers greater accuracy.

Reviewer: Kieran Jefferson

Journal:	European Urology
Authors:	Chahal R, Gogoi NK, Sundaram SK	Issue:	2001, 39:283-6

Title:

Is it necessary to perform urine cytology in screening patients with haematuria?

Abstract:
This paper describes a cohort of 285 patients presenting with haematuria who were evaluated using a standard assessment protocol. The authors examined the diagnostic utility of urine cytology in these patients. Within the study group there was a 19.2% incidence of tumours, of which the vast majority were bladder TCC. Only one upper tract TCC was found and no isolated bladder carcinoma in situ. Cytology was abnormal in 37 patients, 18 of which were frankly positive and 19 suspicious. All frankly positive patients had TCC while six of the 19 suspicious patients carried tumours. All patients' tumours were diagnosed radiologically or cystoscopically. The authors conclude that cytology is unnecessary in the investigation of haematuria and propose that savings in cost and manpower could be achieved by ceasing to use it. Unfortunately, the small size and limited (6-month) follow-up in this trial make this conclusion difficult to support. Cytology would be of most value in the early detection of upper tract TCC, which is fairly rare (only one case diagnosed in this cohort) and carcinoma in situ. Furthermore, extended follow-up might reveal subsequent progression to TCC in the 'false positive' group of cytological samples labelled suspicious.

Reviewer: Kieran Jefferson

Journal:	BJU International
Authors:	Koizumi M, Yonese J, Fukui I, Ogata E	Issue:	2001, 87: 348-51

Title:

The serum level of the amino-terminal propeptide of type 1 procollagen is a sensitive marker for prostate cancer metastasis to bone

Abstract:
This paper examines several biochemical markers of bone turnover as potential markers for metastasis in prostate cancer. Levels were compared in 40 patients with non-metastatic prostate cancer and 25 with bone metastases. Metastasis was determined by isotope bone scanning with calculation of disease extent using an algorithm developed by Soloway. The sensitivity and threshold level for each marker were determined for a specificity of 90%. The amino terminal propeptide of type 1 procollagen (P1NP) appeared the best marker, offering a sensitivity of 72% with a cut-off level of 47ng/ml; it also correlated best with calculated extent of disease. The study is interesting because it suggests that expensive radiological investigations could be replaced by cheaper and quicker biochemical assays. From this point of view, the choice of end-point appears misguided. The authors should perhaps have sought high sensitivity, so that in the presence of a negative PN1P test, isotope bone scanning could be avoided. Furthermore, it would have been interesting to know how the results varied for patients with differing levels of PSA which was a reasonable predictor in its own right.

Reviewer: Kieran Jefferson

Journal:	International Journal of Radiation Oncology
Authors:	Horwitz EM, Winter K, Hanks GE, Lawton CA, Russell AH, Machtay M.	Issue:	2001, 49:947-56

Title:

Subset analysis of RTOG 85-31 and 86-10 indicates an advantage for long-term vs short-term adjuvant hormones for patients with locally advanced nonmetastatic prostate cancer treated with radiation therapy

Abstract:
This paper uses subsets from two similarly constructed RTOG randomised controlled trials to test the results of short-term (essentially neoadjuvant) and long-term androgen ablation. Patients with positive nodes and post-prostatectomy patients were excluded, presumably to mimic the patient population in the EORTC study (Bolla NEJM, 1997), leaving 993 eligible patients. Long-term hormone treatment (goserelin) was commenced in the last week of radiotherapy and continued indefinitely, whereas short-term hormone ablation (goserelin and flutamide) was administered for two months pre- and during radiotherapy and stopped thereafter. Median follow-up was six years. Both hormone ablation groups showed delayed disease progression measured biochemically, radiologically and clinically. Long-term hormone therapy had a significantly greater effect. No significant improvement in overall or disease-specific survival was demonstrated. These data are consistent with other studies examining the effects of neoadjuvant hormone ablation which have not shown a survival advantage.

Reviewer: Kieran Jefferson

Journal:	International Journal of Radiation Oncology
Authors:	Lawton CA, Winter K, Murray K, Machtay M, Mesic JB, Hanks GE, Coughlin CT, Pilepich MV	Issue:	2001, 49:937-46

Title:

Updated results of the phase III Radiation Therapy Oncology Group (RTOG) trial 85-31 evaluating the potential benefit of androgen suppression following standard radiation therapy for unfavorable prognosis carcinoma of the prostate.

Abstract:
This paper describes the 6-year results of a large RCT comparing patients receiving and not receiving adjuvant goserelin post-radiotherapy for locally advanced prostatic carcinoma. Nine hundred and seventy-seven patients were randomised and more than 460 patients were analysed from each arm in this analysis. The results are very interesting in that they do not demonstrate a significant improvement in overall survival, but goserelin does appear to significantly delay the onset of distant metastasis and local extension, and to extend disease-free survival. However, patients with Gleason grading of 8-10 pre-treatment, do show a significant improvement in both disease-specific and absolute survival. One should remember when interpreting this data that it is essentially a comparison of immediate versus delayed hormone ablation in these patients and that this may explain the lack of survival effects, despite the short-term improvements in prognosis. It may be that the higher Gleason grade group represents a population which more rapidly develops hormone independence and can therefore not be restrained by delayed hormone ablation. It is interesting that the EORTC study data published by Bolla in 1997 demonstrated a survival advantage in the goserelin group. A major question, which must be addressed in the presence of such data, is whether the short term improvements in disease progression rate are outweighed by the side effects of the treatment. Unfortunately this is not an issue addressed by the published data.

Reviewer: Kieran Jefferson

Journal:	BJU International
Authors:	Onishi T, Oishi Y, Suzuki Y, Asano K	Issue:	2001, 87:312-5

Title:

Prognostic evaluation of transcatheter arterial embolisation for unresectable renal cell carcinoma with distant metastases

Abstract:
This paper describes a retrospective cohort study of 54 patients (24 treated, 30 not treated) examining the results of transcatheter arterial embolisation (TAE) with ethanol in patients with unresectable renal cell carcinoma. The groups were well-matched but were spread over an 18- year period. Half the treated patients showed a partial response to treatment in the primary tumour. No effect on metastases was evident. Symptoms such as haematuria resolved in 75% of the treated group. Short term symptoms of fever and back pain around the time of treatment were seen in all treated patients. Survival was significantly better in the treated group. This data is interesting but it is hard to overlook potential biases relating to the retrospective nature of the trial. For instance, was TAE used more often in the patients presenting most recently? Conversely, improvements in transarterial interventional radiology may mean that the current benefit is underestimated. Hopefully, the authors will commence a prospective RCT to address these issues.

Reviewer: Kieran Jefferson

Journal:	European Urology
Authors:	Irani J, Humbert M, Lecocq B, Pires C, Lefebvre O, Dore B	Issue:	2001, 39:300-3

Title:

Renal tumour size: comparison between computed tomography and surgical measurements

Abstract:
This retrospective study analysed 100 radical nephrectomies, comparing measurements from pathological specimens with those from pre-operative CT scans. The authors' rationale for such a study relates to the potential for nephron-sparing surgery in patients with tumours of less than 40mm. Unsurprisingly, the correlation between CT and pathological measurements is very good, but became worse for small tumours. The authors go on to state that the potential for nephron-sparing surgery would have been lost in 3 of the 100 patients if CT criteria had been used. The findings are broadly similar to an earlier paper published by Herr and colleagues looking at specimens from patients who had undergone conservative surgery. Overall, this paper would appear to be of little impact. The benefits of partial nephrectomy in 'elective' patients are probably small, especially in patients with tumours at the upper end of the operable range. In patients with single kidneys, or other 'hard' indications for conservative surgery, these findings will make no difference. The real question is whether these findings matter and, if so, whether there is an alternative imaging modality which offers greater accuracy.

Reviewer: Kieran Jefferson

Journal:	European Urology
Authors:	Chahal R, Gogoi NK, Sundaram SK	Issue:	2001, 39:283-6

Title:

Is it necessary to perform urine cytology in screening patients with haematuria?

Abstract:
This paper describes a cohort of 285 patients presenting with haematuria who were evaluated using a standard assessment protocol. The authors examined the diagnostic utility of urine cytology in these patients. Within the study group there was a 19.2% incidence of tumours, of which the vast majority were bladder TCC. Only one upper tract TCC was found and no isolated bladder carcinoma in situ. Cytology was abnormal in 37 patients, 18 of which were frankly positive and 19 suspicious. All frankly positive patients had TCC while six of the 19 suspicious patients carried tumours. All patients' tumours were diagnosed radiologically or cystoscopically. The authors conclude that cytology is unnecessary in the investigation of haematuria and propose that savings in cost and manpower could be achieved by ceasing to use it. Unfortunately, the small size and limited (6-month) follow-up in this trial make this conclusion difficult to support. Cytology would be of most value in the early detection of upper tract TCC, which is fairly rare (only one case diagnosed in this cohort) and carcinoma in situ. Furthermore, extended follow-up might reveal subsequent progression to TCC in the 'false positive' group of cytological samples labelled suspicious.

Reviewer: Kieran Jefferson

Journal:	BJU International
Authors:	Koizumi M, Yonese J, Fukui I, Ogata E	Issue:	2001, 87: 348-51

Title:

The serum level of the amino-terminal propeptide of type 1 procollagen is a sensitive marker for prostate cancer metastasis to bone

Abstract:
This paper examines several biochemical markers of bone turnover as potential markers for metastasis in prostate cancer. Levels were compared in 40 patients with non-metastatic prostate cancer and 25 with bone metastases. Metastasis was determined by isotope bone scanning with calculation of disease extent using an algorithm developed by Soloway. The sensitivity and threshold level for each marker were determined for a specificity of 90%. The amino terminal propeptide of type 1 procollagen (P1NP) appeared the best marker, offering a sensitivity of 72% with a cut-off level of 47ng/ml; it also correlated best with calculated extent of disease. The study is interesting because it suggests that expensive radiological investigations could be replaced by cheaper and quicker biochemical assays. From this point of view, the choice of end-point appears misguided. The authors should perhaps have sought high sensitivity, so that in the presence of a negative PN1P test, isotope bone scanning could be avoided. Furthermore, it would have been interesting to know how the results varied for patients with differing levels of PSA which was a reasonable predictor in its own right.

Reviewer: Kieran Jefferson

Journal:	International Journal of Radiation Oncology
Authors:	Horwitz EM, Winter K, Hanks GE, Lawton CA, Russell AH, Machtay M.	Issue:	2001, 49:947-56

Title:

Subset analysis of RTOG 85-31 and 86-10 indicates an advantage for long-term vs short-term adjuvant hormones for patients with locally advanced nonmetastatic prostate cancer treated with radiation therapy

Abstract:
This paper uses subsets from two similarly constructed RTOG randomised controlled trials to test the results of short-term (essentially neoadjuvant) and long-term androgen ablation. Patients with positive nodes and post-prostatectomy patients were excluded, presumably to mimic the patient population in the EORTC study (Bolla NEJM, 1997), leaving 993 eligible patients. Long-term hormone treatment (goserelin) was commenced in the last week of radiotherapy and continued indefinitely, whereas short-term hormone ablation (goserelin and flutamide) was administered for two months pre- and during radiotherapy and stopped thereafter. Median follow-up was six years. Both hormone ablation groups showed delayed disease progression measured biochemically, radiologically and clinically. Long-term hormone therapy had a significantly greater effect. No significant improvement in overall or disease-specific survival was demonstrated. These data are consistent with other studies examining the effects of neoadjuvant hormone ablation which have not shown a survival advantage.

Reviewer: Kieran Jefferson

Journal:	International Journal of Radiation Oncology
Authors:	Lawton CA, Winter K, Murray K, Machtay M, Mesic JB, Hanks GE, Coughlin CT, Pilepich MV	Issue:	2001, 49:937-46

Title:

Updated results of the phase III Radiation Therapy Oncology Group (RTOG) trial 85-31 evaluating the potential benefit of androgen suppression following standard radiation therapy for unfavorable prognosis carcinoma of the prostate.

Abstract:
This paper describes the 6-year results of a large RCT comparing patients receiving and not receiving adjuvant goserelin post-radiotherapy for locally advanced prostatic carcinoma. Nine hundred and seventy-seven patients were randomised and more than 460 patients were analysed from each arm in this analysis. The results are very interesting in that they do not demonstrate a significant improvement in overall survival, but goserelin does appear to significantly delay the onset of distant metastasis and local extension, and to extend disease-free survival. However, patients with Gleason grading of 8-10 pre-treatment, do show a significant improvement in both disease-specific and absolute survival. One should remember when interpreting this data that it is essentially a comparison of immediate versus delayed hormone ablation in these patients and that this may explain the lack of survival effects, despite the short-term improvements in prognosis. It may be that the higher Gleason grade group represents a population which more rapidly develops hormone independence and can therefore not be restrained by delayed hormone ablation. It is interesting that the EORTC study data published by Bolla in 1997 demonstrated a survival advantage in the goserelin group. A major question, which must be addressed in the presence of such data, is whether the short term improvements in disease progression rate are outweighed by the side effects of the treatment. Unfortunately this is not an issue addressed by the published data.

Reviewer: Kieran Jefferson

Journal:	BJU International
Authors:	Onishi T, Oishi Y, Suzuki Y, Asano K	Issue:	2001, 87:312-5

Title:

Prognostic evaluation of transcatheter arterial embolisation for unresectable renal cell carcinoma with distant metastases

Abstract:
This paper describes a retrospective cohort study of 54 patients (24 treated, 30 not treated) examining the results of transcatheter arterial embolisation (TAE) with ethanol in patients with unresectable renal cell carcinoma. The groups were well-matched but were spread over an 18- year period. Half the treated patients showed a partial response to treatment in the primary tumour. No effect on metastases was evident. Symptoms such as haematuria resolved in 75% of the treated group. Short term symptoms of fever and back pain around the time of treatment were seen in all treated patients. Survival was significantly better in the treated group. This data is interesting but it is hard to overlook potential biases relating to the retrospective nature of the trial. For instance, was TAE used more often in the patients presenting most recently? Conversely, improvements in transarterial interventional radiology may mean that the current benefit is underestimated. Hopefully, the authors will commence a prospective RCT to address these issues.

Reviewer: Kieran Jefferson

Journal:	Journal of Urology
Authors:	Raitanen MP, Marttila T, Nurmi M, Ala-Opas M, Nieminen P, Aine R, Tammela TL; Finnbladder Group.	Issue:	2001, 165: 374-7

Title:

Human complement factor H related protein test for monitoring bladder cancer

Abstract:
The human complement factor H related protein test will be better known to most urologists as the BTA stat test. This paper describes the use of this test in a large (445 patient) group of patients undergoing follow-up after a diagnosis of bladder cancer. The test is specifically compared with urine cytology, however the trial also raises some interesting points about the weaknesses of cystoscopic follow up since the protocol included extensive investigation of those patients with positive BTA test but negative cystoscopy. About 15% of patients with positive BTA test but negative cystoscopy were found to have a recurrence. Sensitivity and specificity for the BTA stat test were 56% and 86% respectively compared with 19.2% and 98.3% for voided urine cytology. The authors conclude that the BTA stat test outperforms urine cytology in follow-up of patients with bladder cancer. Their results may overestimate the accuracy of cytology as a single, experienced pathologist was used for the entire population of 445 patients. Of great interest also is their finding that BTA-positive patients were frequently found to have occult tumours when exposed to more rigorous investigation than a single cystoscopic examination. This paper may change a lot of urologists’ practice.

Reviewer: Kieran Jefferson

Journal:	Urological Research
Authors:	Uotila P, Valve E, Martikainen P, Nevalainen M, Nurmi M, Harkonen P.	Issue:	2001, 29: 25-28

Title:

Increased expression of cyclooxygenase-2 and nitric oxide synthase-2 in human prostate cancer.

Abstract:
It is known that cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase-2 (NOS-2) have important roles in the process of angiogenesis. In this paper the authors investigate the significance of these genes in human prostate cancer. The expression of these genes were investigated by immunohistochemistry, the expression of COX-1 and Cox-2 was confirmed by mRNA analysis. The authors used prostate cancer specimens taken from 12 patients who underwent a radical prostatectomy and compared them with control specimens, which they took from the prostates of 13 men who underwent cystoprostatectomy, operated upon for bladder cancer. They found that the staining of COX-2 and NOS-2 was significantly stronger in prostate cancer cells than in the non malignant control prostate specimens. The authors also reported that COX-2 was also detected in the non malignant glandular epithelium of the control prostates. Interestingly COX-2 and NOS-2 were also clearly expressed in the lesions of prostatic intraepithelial neoplasia (PIN) found in the control prostates. No significant differences were detected in the COX-1 expression between control and cancer patients. The results from this paper indicate that the expression of COX-2 and NOS-2 is elevated in prostatic adenocarcinoma and in PIN. Clearly, further study is required here with a larger number of patients, as these results may have significant therapeutic implications for future prostate cancer prevention and treatment, since inhibitors of COX-2 and NOS-2 are reported to have inhibited the growth of colon cancer cells.

Reviewer: Jon-Paul Meyer

Journal:	BJU International
Authors:	Hughes ODM, Perkins AC, Frier M, Wastie ML, Denton G, Price MR, Denley H and Bishop MC	Issue:	2001, 87: 39-46.

Title:

Imaging for staging bladder cancer: a clinical study of intravenous 111 indium labelled anti MUC1 mucin monoclonal antibody C595.

Abstract:
It is known that accurate tumour staging is important in determining the most appropriate management and prognosis in bladder cancer. All staging modalities have their limitations therefore the authors set out to evaluate an alternative method of staging. This paper investigates the clinical application of a 111 In labelled anti MUC1 mucin monoclonal antibody (mAb) imaging for the staging of invasive bladder cancer. 12 patients were included in this study, 2 had superficial disease and the remaining 10 had primary or recurrent tumours. All 12 patients received an intravenous bolus of 1mg C595 mAb labelled with 80 MBq of 111 In. A gamma camera was utilised to image the patient at 20 mins when the mAb was circulating in the blood and then again at 48 hours when the mAb was tissue bound. These patients were also staged, where the authors deemed appropriate with bone scans, CT, CXR and open or endoscopic surgery. The authors reported no adverse events following the injection with mAb. Their results showed that no bladder uptake was detected in the 2 patients with superficial disease. In 9 of the 10 patients with invasive disease there was positive tumour uptake of labelled C595. The authors felt that the false negative mAb scan was on a patient who was not an ideal candidate as they had recently received systemic chemotherapy. In 3 of the patients, the mAb imaging revealed distant metastatic disease prospectively, when it had not been detected by other methods, this information would have altered management. These patients were thus understaged, and their radical therapy was not curative. This study has shown that intravenous 111 In C595 can be used to detect primary invasive bladder cancer and metastasis, and in some cases metastasis not shown by more conventional methods. In order to fully evaluate this promising imaging technique a formal clinical trial is indicated.

Reviewer: Jon-Paul Meyer

Journal:	Lancet
Authors:	Wolk A, Andersson S, Mantzoros C, Trichopoulos D, Adami H	Issue:	2000, 356: 1902-3

Title:

Can measurements of IGF-1 and IGFBP-3 improve the sensitivity of prostate-cancer screening?

Abstract:
This paper examines an apparent paradox in results of previous epidemiological studies looking at elements of the insulin-like growth factor axis as predictors and markers of prostate cancer. Prospective studies have suggested that elevated levels of serum IGF-1 are a risk factor for subsequent development of prostate cancer, especially in the context of a reduced level of its major serum binding protein, IGFBP-3. However, in studies examining levels of these two elements at the time of a diagnosis of prostate cancer, no such pattern has been found. The investigators re-examined results from a cohort of patients diagnosed with prostate cancer and sub-divided patients by serum PSA level. In the group with the lowest PSA levels (PSA<3ng/ml) the IGFBP-3 level did appear to show an inverse correlation with prostate cancer diagnosis consistent with the previous data on prostate cancer risk. This correlation was lost at higher levels of serum PSA. The authors attempt to relate this to the serine protease activity of PSA; this seems unlikely as PSA is inactive in serum and one would logically expect higher PSA to correlate with lower IGFBP-3. While the proposed mechanisms for the observed results seem implausible, the idea of using this to refine diagnosis or potentially offer screening tests in the low PSA group is interesting. As usual there is the caveat regarding the risk of detecting clinically insignificant disease and clearly further studies are essential to confirm these findings, quantify the relative risks and assess the potential for clinical use.

Reviewer: Kieran Jefferson

Journal:	International Journal of Cancer
Authors:	F. Rae, S. Stephenson, D. Nicol, J. Clements	Issue:	2001, 88: 726-32.

Title:

Novel association of a diverse range of genes with renal cell carcinoma as identified by differential display

Abstract:
This paper describes the use of differential-display PCR (DD-PCR) to identify genes which are under or over-expressed in RCC relative to normal kidney from the same patient. Samples from 16 tumours were used and differential expression was concluded if four paired samples demonstrated the same difference in expression. Twenty-four loci were found to meet these criteria in this population of tumours; six were non-coding regions and the remainder were compared with sequence databases. From this, eight known genes were found to be over-expressed, including RGS-5 (a regulator of G-protein signalling); Notch-3 (a transmembrane receptor known to control embryological cell survival); Na-K-ATPase; HLA classII antigen; mitochondrial cytochrome C and adipophilin. The paper demonstrates how PCR technology can be used to identify large numbers of genes implicated in carcinogenesis and tumour progression, from which further work may identify the precise role of each of their protein products in the biology of cancer cells.

Reviewer: Kieran Jefferson

Journal:	Journal of the National Cancer Institute
Authors:	Chiang PW, Schneider A, Borgnat S, Gaub MP, Oudet P, Kurnit DM, Jacqmin D	Issue:	2000, 92: 1779-80

Title:

Molecular analysis of urine sediment for follow-up of urinary tract cancers

Abstract:
Genomic instability is one of the hallmarks of malignancy at the cellular level. This study describes the use of two techniques that can detect cellular aneuploidy (microsatellite analysis and quantitative PCR) to follow patients with bladder cancer using urine specimens. Forty-one patients with bladder cancer were studied, of whom 35 (85%) had detectable genomic aberrations using 17 microsatellite probes and examining 3 genes using QPCR. The changes were not, however stage or grade specific and appeared to be merely markers of general genomic instability. The six tumours which would not have been detected by the genomic analysis were all small superficial tumours. Subsequently, 19 patients were followed over a sequence of review cystoscopies and biopsies. In these patients the sediment analysis appeared to be more sensitive than cystoscopy for the detection of recurrent tumours. It appeared effective even after intravesical chemo- or immunotherapy. In summary, this paper describes an interesting non-invasive molecular adjunct to cystoscopy and conventional cytology. It would appear to offer particular promise for detection of carcinoma in situ in a cystoscopically normal bladder although this is not directly discussed by the authors.

Reviewer: Kieran Jefferson

Journal:	BJU International
Authors:	Corman JM, Penson DF, Hur K, Khuri SF, Daley J, Henderson W, Krieger JN	Issue:	2000, 86: 782-9

Title:

Comparison of complications after radical and partial nephrectomy: results from the National Veterans Administration Surgical Quality Improvement Program

Abstract:
This paper examines the short-term complication rates of radical and partial nephrectomy using prospectively acquired data. This comes from a large database kept by Veterans Administration hospitals over a nine-year period, and includes 1373 radical and 512 partial nephrectomies performed for a number of pathologies. The database examines mortality and 20 complications occurring within 30 days of surgery and 45 pre-operative variables were stored to enable risk-adjustment. For both procedures, mortality is low at around 2%, and around 15% of patients in both groups suffered ‘morbidity’. There was no significant difference between groups. The authors conclude that partial nephrectomy is a safe procedure when compared with the radical operation but also discuss a number of weaknesses within the data which limit the value of these findings. Most of these weaknesses relate to the lack of a specific database for urology and the need to use rather non-specific, short-term morbidity data. Furthermore, there is no data on stage or grade of disease, which must be important when comparing these operations. Finally, it is interesting to hear that the authors perform radical rather than simple nephrectomy for benign renal disease. The data is however interesting because it describes results outside of ‘centres of excellence’; this is important if the ‘average’ urologist is considering offering partial nephrectomy to patients with low-volume, unilateral disease. The paper therefore offers a partial answer to the issue of partial versus radical nephrectomy. The best way to overcome the remaining quibbles would be to undertake a prospective randomised controlled trial for stage-matched disease.

Reviewer: Kieran Jefferson

Journal:	Journal of Urology
Authors:	Iversen P, Tyrrell CJ, Kaisary AV, Anderson JB, Van Poppel H, Tammela TL, Chamberlain M, Carroll K, Melezinek I	Issue:	2000, 164: 1579-82

Title:

Bicalutamide monotherapy compared with castration in patients with nonmetastatic locally advanced prostate cancer: 6.3 years of follow-up

Abstract:
This paper describes data from 2 studies comparing bicalutamide monotherapy with castration (either goserelin or orchidectomy) in patients with non-metastatic locally advanced disease. As candidates for androgen ablative therapy now include those with locally advanced, non-metastatic disease, the adverse effects associated with long-term castration become more significant. These include loss of sexual function and osteoporosis. Monotherapy with a non-steroidal anti-androgen such as bicalutamide 150mg od may reduce these effects since the serum testosterone level does not decline as it does with medical or surgical castration. The studies were randomised but not blinded and a total of 480 patients were included; end-points were timed to death and objective progression (evidence of metastases or >50% increase in prostate dimensions) and a quality of life (QoL) questionnaire was used. After 6.3 years, 56% of recruits had died but there was no statistical difference in the rate for those receiving monotherapy compared with the castrated group. Median survival estimates did suggest a small survival advantage for the castrated group. QoL scores were statistically better for monotherapy in respect of sexual function and physical capacity; interestingly, ‘overall health’ appeared to be worse on monotherapy, despite all other assessed variables being apparently better. This may say more about the accuracy of quality of life assessment then the treatments under study. The major adverse effect of bicalutamide is gynaecomastia and/or breast tenderness which affect the majority of patients to varying degrees. Overall, bicalutamide monotherapy appears to have a similar effect on patient survival to castration and preserves sexual function in a large number of patients. Patients opting for this therapy must, however, be prepared to trade sexual function for breast symptoms.

Reviewer: Kieran Jefferson

Journal:	International Journal of Cancer
Authors:	Wang DS, Rieger-Christ K, Latini JM, Moinzadeh A, Stoffel J, Pezza JA, Saini K, Libertino JA and Summerhayes IC	Issue:	2000, 88: 620-5

Title:

Molecular analysis of PTEN and MXI1 in primary bladder carcinoma.

Abstract:
The PTEN tumour suppressor gene encodes a dual specificity phosphatase which appears to be important in protection against a number of human malignancies; notably prostatic carcinoma. Similarly, the MXII gene is a tumour suppressor gene encoding a regulator of the myc oncogene. This study examines the frequency of PTEN and MXII mutations in invasive bladder carcinomas, the genes being neighbours on the long arm of chromosome 10. Twenty three per cent of the 35 bladder tumours analysed demonstrated PTEN mutations, none showed MXII mutations. The mutations identified all resulted in amino acid substitutions or truncation of the protein which would be expected to have functional implications. The main weakness of this paper is that there is no analysis of earlier stage tumours which might give information about the importance of PTEN mutation in stage progression of bladder cancer. Furthermore, the level of PTEN mutation is much higher than reported in previous studies which may stem from the relatively small number of tumours studied, or may represent differences in staging or inclusion criteria.

Reviewer: Kieran Jefferson

Journal:	BJU International
Authors:	McNeill S, Chrisofos M and Tolley D	Issue:	2000, 86: 619-623

Title:

The long-term outcome after laparoscopic nephroureterectomy: a comparison with open nephroureterectomy.

Abstract:
This paper describes a retrospective analysis of a series of 25 laparoscopic nephroureterectomies and compares the results with a series of 42 open nephroureterectomies. The aims were primarily to assess the adequacy of resection using the laparoscopic approach and therefore the primary end-point used was disease-specific death. As with all retrospective series, the comparison between the two groups is open to criticism. The open group contained a higher proportion of ureteric tumours (which might be prone to earlier local invasion) and were followed-up for a longer period on average. The average post-operative stay after open surgery (10.7 days) also appears unusually high. Notwithstanding these observations, the survival rates appear similar and the mean time to death was similar in both groups. It is also interesting to note that all deaths resulted from G3 disease. The data supports the contention that laparoscopic nephroureterectomy can be performed safely and does not appear to grossly compromise long-term survival. It is a shame that when introducing this procedure to their institution, the authors did not attempt a randomised prospective trial, which would have strengthened the findings.

Reviewer: Kieran Jefferson

Journal:	BJU International
Authors:	Cliff A, Heatherwick B, Scoble J and Parr N	Issue:	2000, 86: 644-647

Title:

The effect of fasting or desmopressin before treatment on the concentration of mitomycin C during intravesical administration.

Abstract:
This interesting study examines the amount of urine voided during intravesical chemotherapy and its potential effect on mitomycin concentration and efficacy. It is a nicely-designed crossover study where patients received 6 instillations of mitomycin, the first two without preparation, the second two after fasting for six hours and the final two an hour after ingestion of 200 mcg desmopressin (an analogue of AVP). Urine volume was measured as the sum of the volume voided post instillation and the residual volume calculated by ultrasound examination. Of 20 patients entered, 17 completed the study. There was a wide range of voided volumes when unprepared with a mean of 200 ml (diluting the 40 ml instillation by a factor of 6). After fasting, the mean fell to 143 ml and desmopressin reduced this further to 103 ml. The authors calculate that this increases the exposure to mitomycin by 20% in the fasted group and 38% in the desmopressin group. There were no side effects directly attributable to either fasting or desmopressin. The authors’ current practice is to fast patients prior to mitomycin instillations. The main question which needs to be answered following this study is whether the observed changes in urine output and estimated changes in drug exposure have any effect on outcome. This will obviously require a randomised controlled trial with a significantly larger study population and long-term follow-up.

Reviewer: Kieran Jefferson

Journal:	BJU International
Authors:	Elhilali M, Gleave M, Fradet Y, Davis I, Venner P, Saad F, Klotz L, Moore R, Ernst S, Paton V et al.	Issue:	2000, 86: 613-618

Title:

Placebo-associate remissions in a multicentre, randomised double-blind trial of interferon g-1b for the treatment of metastatic renal carcinoma.

Abstract:
Spontaneous regression is often mentioned in discussions of the treatment of renal cell carcinoma (RCC). About 70 cases have been reported in the literature and the spontaneous regression rate of RCC in large series is usually quoted in the order of 1%. This rate appears higher than in other tumours and has led to widespread attempts to induce a host response to RCC and the suggestion that nephrectomy in the presence of metastases may encourage such responses. This paper uses data from a large multi-centre blinded RCT and focuses on the response to placebo. One hundred and ninety seven patients were recruited across Canada. They had histologically confirmed RCC with metastases and had undergone nephrectomy or angioinfarction of the primary tumour. They were randomly and blindly assigned to receive interferon or placebo infusions and were given aetaminophen to minimise ifn side effects and preserve blinding. They were monitored clinically, biochemically and radiologically every 8 weeks. In this paper the authors report an unexpectedly high rate of spontaneous regression. Seven percent of the 90 evaluable patients in the placebo group underwent spontaneous RCC regression. Three were partial, lasting a maximum of 8 months, while 2 of the 3 complete radiological responses were maintained until the end of the study (31 and 10 months after recruitment). These response rates were no different to the interferon group. These rates are apparently higher than most previous reports but this may reflect closer monitoring - some of the short-term responses might not have been recorded by less rigorous protocols. The authors conclude that spontaneous regression is more common than previously thought and that this has major implications for interpretation of phase I and II data for RCC therapies.

Reviewer: Kieran Jefferson

Journal:	New England Journal of Medicine
Authors:	Childs R, Chernoff A, Contentin N, Bahceci E, Schrump D, Leitman S, Read EJ, Tisdale J, Dunbar C, Linehan WM, Young NS and Barrett AJ	Issue:	2000, 343: 750-759

Title:

Regression of metastatic renal cell carcinoma after nonmyeloablative allogeneic peripheral blood stem-cell transplantation.

Abstract:
This paper describes a further attempt to treat metastatic renal cell cancer immunologically using allogeneic cells. It describes a group of nineteen patients with advanced renal cell carcinoma who were given infusions of allogeneic peripheral blood stem cells (from HLA matched siblings). They were immunosuppressed for a short period to minimise graft versus host effects and then the immunosuppressive agents gradually withdrawn to unmask a graft versus tumour effect. Of the 19 patients, 10 responded to the treatment, 3 with complete responses (lasting for the duration of the trial period) and seven partial responses. However, 2 patients died of transplant-related complications and 8 others had varying degrees of graft versus host disease. The immunoresponsiveness of RCC provides potential for a number of immunological interventions, which may improve the dimal prognosis for metastatic RCC. This trial provides a further possible option, but one associated with significant side-effects and restricted to patients with HLA-matched siblings.

Reviewer: Kieran Jefferson

Journal:	Cancer
Authors:	Elias L, Lew D, Figlin RA, Flanigan RC, Thompson ME, Triozzi PL, Belt RJ, Wood DP Jr, Rivkin SE and David E	Issue:	2000, 89: 597-603

Title:

Infusional Interleukin-2 and 5-fluorouracil with subcutaneous interferon-a for the treatment of patients with advanced renal carcinoma.

Abstract:
This paper reports the results of a phase II trial performed under the auspices of the Southwest Oncology Group to determine the response rate to triple chemoimmunotherapy with 5-FU, IL-2 and IFN-a. The end point chosen was a response rate of at least 30% and 38 patients were entered. All these patients had metastatic or recurrent RCC, which could be measured using imaging techniques and good performance status. A 5-day combined treatment course was given for 4 weeks every 6 weeks and radiological assessment performed at least every 12 weeks. Median survival was 12 months and, of the 35 patients receiving treatment, 3 showed partial responses and one a complete response, failing to meet the pre-defined end-point. The authors also mention several patients with some evidence of responsiveness who had to withdraw from the trial; toxicity was a significant problem. The results are worse than other studies using similar regimens and do not seem to offer a significant advance in the management of metastatic renal cancer, especially given the cost and toxicity of the regimen.

Reviewer: Kieran Jefferson

Journal:	BJU International
Authors:	Symbas NP, Townsend MF, El-Galley R, Keane TE, Graham SD and Petros JA	Issue:	2000, 86: 203-207

Title:

Poor prognosis associated with thrombocytosis in patients with renal cell carcinoma.

Abstract:
This paper describes a retrospective study investigating the clinical significance of thrombocytosis in patients with advanced renal cell carcinoma (RCC). Three hundred and fifty patients with Robson Stage IV RCC had their records examined and 259 met the entry criteria (tissue diagnosis, at least one platelet count and follow-up until death). These patients were derived from two centres, spanned a period of 20 years and had been treated with a variety of different adjuvant therapies. No comparison of patients within or between adjuvant therapies is mentioned in the paper. On the basis of this limited data set, the authors constructed a Kaplan-Meier survival plot comparing those patients who had only normal platelet levels and those with thrombocytosis. Patients with thrombocytosis had a significantly worse prognosis until 6.5 years post-diagnosis. These findings were independent of a number of other prognostic indicators. This paper presents more questions than answers. It seems strange that the authors have made no attempt to control for adjuvant therapeutic regimen. Could it be that thrombocytosis is a marker of ineffective adjuvant therapy rather than a predictor of therapeutic failure? This would seem more likely than the mechanisms proposed by the authors. A prospective study with a standard investigative and therapeutic protocol would be the only means to resolve this. For the moment I suspect that few urologists will utilise platelet count as a discriminator by which to select therapies.

Reviewer: Kieran Jefferson

Journal:	Journal of Urology
Authors:	D'Hallewin MA, De Witte PA, Waelkens E, Merlevede W and Baert L	Issue:	2000, 164: 349-351

Title:

Fluorescence detection of flat bladder carcinoma in situ after intravesical instillation of hypericin.

Abstract:
This interesting paper investigated the use of hypericin, a potent photosensitiser derived from plants, as a tumour marker for transitional carcinoma in situ. Forty patients at high risk of cis were studied of whom 26 had macroscopic coexistent tumour, 9 had positive urine cytology in the absence of macroscopic tumour and 4 were post BCG therapy. Patients were given intravesical hypericin for two hours prior to cystoscopy and blue light fluorescence excitation used to visualise tumours. All macroscopic tumours showed red fluorescence, along with 134 flat areas of urothelium. These were compared with 281 bladder wall biopsies and showed a very high sensitivity (93%) and specificity (98.5%) for detection of cis. Post therapy inflammatory changes in those patients who had previously received radio-, chemo- or immunotherapy did not demonstrate fluorescence and did not, therefore result in false-positive findings. The drug was well tolerated by all patients. These results suggest great potential for hypericin in improving diagnosis of flat cis in the bladder and perhaps in photodynamic therapy of cis. The major disadvantage of this technique would appear to be the need for a lengthy intravesical administration pre-cystoscopy. This might limit its value in the initial diagnostic work-up for haematuria but would not be a great disadvantage if its use were limited to patients at moderate to high risk of cis.

Reviewer: Kieran Jefferson

Journal:	Urology
Authors:	Gill IS, Fergany A, Klein EA, Kaouk JH, Sung GT, Meraney AM, Savage SJ, Ulchaker JC and Novick AC	Issue:	2000, 56: 26-29

Title:

Laparosocpic radical cystoprostatectomy with ileal conduit performed completely intracorporeally: The initial 2 cases.

Abstract:
This paper reports an initial experience of laparoscopic radical cystoprostatectomy with ileal conduit formation in two patients. Both procedures took in excess of ten hours, with moderate blood loss and clear surgical margins. Post-operative course was impressive with oral intake commencing on day three and discharge on day six. No post-operative complications were reported in either case. The procedure has great potential if the long operative time can be reduced and if the results hold up over a larger series of patients. In the long term it may dramatically reduce the morbidity associated with radical surgery for bladder cancer. The main criticism of the paper is that it is a ‘series’ of only two patients; a larger series of patients would seem appropriate even for a report of technical feasibility.

Reviewer: Kieran Jefferson

Journal:	Urology
Authors:	Luciani LG, Cestari R and Tallarigo C	Issue:	2000, 56: 58-62

Title:

Incidental renal cell carcinoma – age and stage characterisation and clinical implications: study of 1092 patients (1982-1997).

Abstract:
This paper describes a retrospective analysis of the features of 1092 patients with renal cell carcinoma (RCC) treated in a single institution over a 16-year period. As expected from other published series, incidentally-discovered tumours formed a greater proportion of cases as time progressed and were, on average, of lower stage and grade than symptomatic tumours. One interesting finding was that incidentally-discovered tumours were found in older patients than were symptomatic tumours; the authors attribute this to a higher frequency of abdominal investigations in older persons. Otherwise, this paper adds little to the significant number of publications regarding incidental RCC. The authors claim that screening or case-finding of RCC would be desirable but cannot support this assertion from the data published here.

Reviewer: Kieran Jefferson

Journal:	Cancer
Authors:	Hayter CR, Paszat LF, Groome PA, Schulze K and MacKillop WJ	Issue:	2000, 89: 142-151

Title:

The management and outcome of bladder carcinoma in Ontario 1982-1984.

Abstract:
This population-based study examines the management and outcome of 20822 cases of invasive bladder carcinoma in Ontario, Canada between 1982 and 1994. Electronic records from the Ontario Cancer Registry were examined, from which the investigators were able to identify cases of invasive cancer (via ICD coding). From this information, it was possible to locate abstracts of the procedure and discharge information within other databases. Multivariate analyses were then performed to investigate death rates and bladder preservation. As might be expected, the average age of patients undergoing radical surgery was lower than those undergoing pelvic radiotherapy. Interestingly, there appeared to be an increase in conservative management with time - however no stage information was available from the registries used and this may reflect earlier diagnosis or more effective local therapies. There was also significant variation in rates of radical surgery and radiotherapy between regions of Ontario; these had no significant effect on survival but bladder preservation was affected. This study is of interest because it describes a large population of patients with bladder cancer without the exclusions necessitated by a formal trial protocol. While providing an interesting description of events, it is difficult to draw much useful information from the results, due largely to the paucity of data regarding stage and grade of tumour as mentioned above. It will be interesting to see whether the BAUS oncology database will enable a more accurate assessment of UK national practice and outcome data in a few years’ time.

Reviewer: Kieran Jefferson

Journal:	Journal of the National Cancer Institute
Authors:	Travis LB, Andersson M, Gospodarowicz M, van Leeuwen FE, Bergfeldt K, Lynch CF, Curtis RE, Kohler BA, Wiklund T, Storm H, Holowaty E, Hall P, Pukkala E, Sleijfer DT, Clarke EA, Boice JD Jr, Stovall M and Gilbert E	Issue:	2000, 92: 1165-1171

Title:

Treatment-associated leukaemia following testicular cancer.

Abstract:
This paper follows on from research by the same group, which demonstrated an increased risk of leukaemia in survivors of testicular cancer. In view of the excellent prognosis for most men with testicular cancer, an understanding of the long-term risks involved is important in treatment selection. The authors studied over 18,500 patients with testicular cancer treated over a 24 year period and case-matched those patients developing leukaemias. They then compared radiotherapy and chemotherapy doses in leukaemia cases and their matched controls, enabling relative risk values to be assigned to treatments by conditional logistic regression. They found a 3-fold increase in leukaemia risk following radiotherapy and slightly higher figures for radiotherapy in combination with cisplatin. These risks appear much lower using more modern radiotherapy techniques; indeed these were not statistically significant. Overall, the authors conclude that the risks are much smaller than many previous studies have suggested and that they are currently greatly outweighed by the improvements in testicular cancer cure rates.

Reviewer: Kieran Jefferson

Journal:	Urology
Authors:	Parekh D, Gilbert W, Koch M and Smith J	Issue:	2000, 55: 852-856

Title:

Continent urinary reconstruction versus ileal conduit: a contemporary single-institution comparison of perioperative morbidity and mortality.

Abstract:
This is a retrospective, single-institution analysis of 30-day patient morbidity and mortality in 198 patients undergoing radical cystectomy and orthotopic reconstruction (117 patients) or ileal conduit formation (81 patients). The authors suggest that they offer evidence for similar morbidity and mortality for both procedures. The results are impressive but there are significant difficulties in interpreting the data offered. Median figures are given with no information regarding means, standard errors, confidence intervals or statistical significance. Also, data regarding the two patient populations are absent; specifically, no information is given regarding the age of the patients in each group - although the authors acknowledge in their discussion that patients undergoing ileal conduit formation tended to be older. In order to obtain reliable information on the relative morbidities and mortalities of the two procedures, a randomised, controlled, prospective trial would be necessary, ideally multi-centred.

Reviewer: Kieran Jefferson

Journal:	Urology
Authors:	Giannopoulos A, Manousakas T, Mitropoulos D, Botsoli-Stergiou E, Constantinides C, Giannopoulou M and Choremi-Papadopoulou H	Issue:	2000, 55: 871-875

Title:

Comparative evaluation of the BTAstat test, NMP22 and voided urine cytology in the detection of primary and recurrent bladder tumours.

Abstract:
This prospective study compares the diagnostic efficacy of the BTAstat test, nuclear matrix protein 22 (NMP22) assay and voided urine cytology for detection of primary and secondary bladder tumours. Both the BTAstat test and NMP22 assay were found to be more sensitive than cytology in this study although cytology was much more specific. Interestingly, ‘suspicious’ cytology was not counted as a positive cytology result in this study - presumably reducing the sensitivity and increasing the specificity of this test. The conclusion of superior results with the two biochemical assays must therefore be treated with some caution. Furthermore, neither of the two biochemical tests offers sufficient sensitivity or specificity for the urologist to consider avoidance of a diagnostic flexible cystoscopy. At present, therefore these results are unlikely to alter practice.

Reviewer: Kieran Jefferson

Journal:	Journal of Urology
Authors:	Wolf JS JR, Seifman BD and Montie JE	Issue:	2000, 163: 1659-1664

Title:

Nephron sparing surgery for suspected malignancy: open surgery compared to laparoscopy with selective use of hand assistance.

Abstract:
This paper describes a series of ten laparoscopic nephron sparing nephrectomies, 8 with hand assistance, and attempts to compare them with a group of open nephron sparing procedures. The resultrs are, at first sight, impressive with a little change in operating time, a non-significant increase in blood loss and some evidence for improved post-operative course. The data on post-operative course, however, fails to reach statistical significance. No conversions to open surgery were required. The authors have been cautious in their conclusions, as is appropriate for non-randomised trial. This paper demonstrates the technical feasibility of nephron sparing laparoscopic surgery, but the ‘control’ group of open procedures is inadequate to draw any strong conclusions about its relative merits. It is unfortunate that the authors did not randomise patients to either open or laparoscopic surgery (as has been done with the better studies of laparoscopic cholecystectomy) as this would have provided more meaningful data. Furthermore, this is the work of only one surgeon; a good procedure needs to produce satisfactory results in the hands of most surgeons. These caveats aside, the paper is interesting and may herald a new era of laparoscopic cancer surgery.

Reviewer: Kieran Jefferson

Journal:	Journal of Urology
Authors:	Gill IS, Schweizer D, Hobart MG, Sung GT, Klein EA and Novick AC	Issue:	2000, 163: 1665-1670

Title:

Retroperitoneal laparoscopic radical nephrectomy: the Cleveland Clinic experience.

Abstract:
A large series of laparoscopic nephrectomies has been performed at the Cleveland Clinic using a retroperitoneoscopic approach. The authors describe the results of 53 procedures and compare data from the 34 most recent procedures with a group of open radical nephrectomies. The results are impressive with around 3-hour procedure time, minimal blood loss and a very short post-operative stay (1.6 days mean - 68% discharged within 23 hours). Only two laparoscopic procedures required conversion to open surgery for major complications and 8 patients experienced minor complications. The data is compared with 34 open radical nephrectomies and appears to compare very favourably with significant reductions in haemorrhage, hospital stay, analgesic requirements and convalescent period. The open surgical group were also reported to have a higher complication rate. The design of the study, however, appears poor with no properly randomised control group and a retrospective comparison with open surgery. The authors mention that they have performed 53 laparoscopic radical nephrectomies during a 3-year period but do not explain why data from only 34 cases was analysed comparatively. It is also interesting that the average surgical time was surprisingly similar with open nephrectomies averaging over three hours; could this reflect that the open procedures were performed on more complex cases or by less experienced surgeons? Given the large number of procedures in a relatively short period, a randomised controlled trial seems feasible to compare the techniques more reliably.

Reviewer: Kieran Jefferson

Journal:	New England Journal of Medicine
Authors:	Nortier JL, Martinez MC, Schmeiser HH, Arlt VM, Bieler CA, Petein M, Depierreux MF, De Pauw L, Abramowicz D, Vereerstraeten P and Vanherweghem JL	Issue:	2000, 342: 1686-1692

Title:

Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi).

Abstract:
This paper from a Belgian group adds another substance (aristolochic acid) to the long list of bladder carcinogens. This was discovered in a group of patients with Chinese-herb nephropathy, induced by the ingestion of a Chinese treatment for obesity. Of the 105 patients with end-stage nephropathy, 77 kidneys and 78 ureters had been excised from 39 patients who were advised to have nephrectomies after discovery of an index upper tract TCC. These were analysed for urothelial carcinoma and 18 urothelial carcinomas were found (46% prevalence) predominantly in the ureter and renal pelvis. A further 19 patients (49%) had urothelial dysplasia, with only two having a completely normal urothelium. The risk of frank carcinoma was related to the dose of aristolochic acid and DNA-damage relating to this chemical was universally seen. The authors conclude (with some degree of understatement) that ‘the prevalence of urothelial carcinoma among patients with end stage Chinese-herb nephropathy…is high’. While this observation is unlikely to lead to a massive change in the aetiology of most bladder cancers, it could induce interesting changes in the taking of social and occupational histories.

Reviewer: Kieran Jefferson

Journal:	Journal of Urology
Authors:	Guillonneau B, Vallancien G	Issue:	2000, 163: 418-22

Title:

Laparoscopic radical prostatectomy: The Montsouris experience

Abstract:
This paper describes a retrospective analysis of a series of 120 laparoscopic radical prostatectomies performed in a single institution and compares results in the first, second and third groups of 40 patients. Patient selection appears routine with one patient having a PSA as high as 35ng/ml. Results were assessed using standard histological and biochemical parameters of cancer clearance and a standardised classification of complications. The results appear excellent. Laparoscopic radical prostatectomy is a rather long operation with a duration of four hours even in the most recent group of forty patients but conversion to an open procedure is an infrequent event , as is transfusion of blood post-operatively. Blood loss figures are remarkably low and the authors attribute this to the excellent view afforded by the laparoscopic instrumentation. Interestingly, post-operative stay did not compare particularly favourably with the open procedure at a mean of 6 days (this is overlooked in the abstract). Cancer control rates did not compare unfavourably with the open procedure but follow-up is short – it seems likely that these results will extrapolate as with the open procedure. Continence and potency rates also appear comparable, however these are always contentious in view of the many assessment criteria that have been used by different authors. Finally, costs are not excessive. The paper is an excellent summary of the state of the art in laparoscopic radical prostatectomy; i.e. in expert hands it is an excellent procedure, notwithstanding the greater operative time and slightly increased expense. Whether these results could be extrapolated into the hands of the bulk of urological oncologists is another matter. A good procedure is one which the average surgeon can perform effectively – we will wait to see whether this proves to be true.

Reviewer: Kieran Jefferson

Journal:	BJU International
Authors:	Cooke P, James N, Ganesan R, Burton A, Young L and Wallace D	Issue:	2000, 85: 829-835

Title:

Bcl-2 expression identifies patients with advanced bladder cancer treated by radiotherapy who benefit from chemotherapy.

Abstract:
This study addresses the potential use of immunostaining for p53 and the anti-apoptotic molecule Bcl-2 for prognostication and treatment selection in muscle-invasive bladder cancer. It is a spin-off of a randomised clinical trial investigating the role of neoadjuvant cisplatin for bladder tumours treated by radical radiotherapy. Sections from 51 patients were stained for Bcl-2 and p53 and the result of staining was compared with patient survival and salvage cystectomy rate. No correlation was found between staining for either molecule and tumour stage, grade, overall survival and salvage cystectomy rate. However, Bcl-2 status did correlate with benefit from neoadjuvant chemotherapy; Bcl-2 negative patients receiving cisplatin had better outcomes than Bcl-2 positive patients. Several previous studies have looked at immunostaining for these molecules with similarly little prognostic information being found. More recent studies have looked at mRNA expression and particularly the expression ratio of Bcl-2 and other Bcl-2 family members. A better correlation with tumour stage, grade and prognosis has been found using these techniques.

Reviewer: Kieran Jefferson

Journal:	International Journal of Cancer
Authors:	Brennan P, Bogillot O, Cordier S, Greiser E, Schill W, Vineis P, Lopez-Abente G, Tzonou A, Chang-Claude J, Bolm-Audorff U, Jockel KH, Donato F, Serra C, Wahrendorf J, Hours M, T'Mannetje A, Kogevinas M and Boffetta P	Issue:	2000, 86: 289-294

Title:

Cigarette smoking and risk of bladder cancer in men: a pooled analysis of 11 case-control studies.

Abstract:
This paper describes the results of a meta-analysis of a number of large European case-control studies performed to assess the risk of bladder cancer associated with smoking. The results suggest a stronger association between smoking and subsequent development of bladder cancer than previously published and find an association between duration of smoking habit and risk. Interestingly, there was no observed increase in risk for patients smoking more than twenty cigarettes per day. Stopping smoking did reduce risk gradually, but never to the level of lifetime non-smokers. As with all meta-analyses, the results must be interpreted with caution, as discussed by the authors. There was some variation in protocols between the trials, the most notable being the use of patients with cardiovascular disease within one group of controls; smoking is a well-established risk factor for such diseases. Also, all the trials are retrospective case-control studies with obvious limitations on the reliability of the data regarding tobacco usage. Not-withstanding these caveats, the results highlight the very strong link between smoking and bladder cancer. It seems likely that the methodological flaws mean that the figures published here are still under-estimates.

Reviewer: Kieran Jefferson

Journal:	Nature Medicine
Authors:	Kugler A, Stuhler G, Walden P, Zoller G, Zobywalski A, Brossart P, Trefzer U, Ullrich S, Muller C, Becker V, Gross A, Hemmerlein B, Kanz L, Muller G and Ringert R-H	Issue:	2000, 6: 332-336

Title:

Regression of human metastatic renal cell carcinoma after vaccination with tumour cell-dendritic cell hybrids

Abstract:
This paper describes a very interesting and potentially useful approach to treatment of metastatic renal cell carcinoma (RCC). RCC is unusually resistant to adjuvant therapy and metastatic or unresectable disease is therefore associated with a dire prognosis. In rodent models, immunisation with cellular hybrids of tumour and antigen presenting cells has led to an immune response against tumours. Here, this work has been extended into humans. Tumour cells from seventeen patients were fused with allogeneic dendritic cells in order to encourage presentation of tumour antigens to patient immune cells; a cell-mediated immune response was evident. Seven patients showed a response to treatment. Four showed complete disease remission, one had a ‘mixed’ response (different responses between primary and secondary tumours) and two showed partial responses (tumour bulk fell by more than 50%). Reported side effects were trivial and responses were sustained over follow-up of several months. Clearly, this technique is some way from regular clinical use and would appear very costly. While it is unlikely to offer much for the current generation of RCC patients, it has the potential to significantly alter the prognosis for a number of metastatic malignancies.

Reviewer: Kieran Jefferson

Journal:	International Journal of Cancer
Authors:	Lein M, Jung K, Laube C, Hubner T, Winkelmann B, Stephan C, Hauptmann S, Rudolph B, Schnorr D and Loening SA	Issue:	2000, 85: 801-804

Title:

Matrix-metalloproteinases and their inhibitors in plasma and tumor tissue of patients with renal cell carcinoma.

Abstract:
Matrix metalloproteinases (MMPs) are thought to play an important role in tumour invasion and metastasis. They have been shown to be important in a number of tumour types and there is considerable commercial interest in MMP inhibitors as potential anticancer drugs. This study looks at expression of MMPs and TIMPs (tissue inhibitors of metalloproteinases) in renal cell carcinomas (RCC) and in plasma from patients with RCC. Statistically different levels of MMP-9 were seen in renal cell carcninomas and RCC plasma compared with normals. TIMP-1 was elevated in tumour tissue but not in patients’ plasma, whereas MMP-2 was altered in plasma but not in the tumour itself. As the authors note, there is considerable overlap between all groups studied and these tests will be of little value due to poor specificity/sensitivity. However, the results do suggest roles for MMPs in RCC progression and further study is clearly indicated.

Reviewer: Kieran Jefferson

Journal:	Journal of Urology
Authors:	Fergany AF, Hafez KS and Novick AC	Issue:	2000, 163: 442-445

Title:

Long- term results of nephron sparing surgery for localised renal cell carcinoma: 10-year follow up.

Abstract:
This paper addresses the safety of nephron-sparing surgery in both ‘imperative’ and ‘elective’ cases (imperative cases are those with associated contralateral renal disease necessitating renal preservation). It is a single-centre, retrospective case series including 107 patients with 10-year follow up. In this unit the procedure was associated with excellent cancer-specific survival and low local recurrence rates. Perhaps most interesting are the results of ‘elective’ surgery on small, incidentally-diagnosed tumours - all of these survived ten years. This would strongly suggest that such small tumours can be safely managed with nephron-sparing surgery. There are, however a few minor flaws in the paper. Most notable amongst these are the exclusion of four patients from the series because of ‘perioperative mortality’. If these four patients were all from the ‘elective’ group, this could potentially amount to about 15% of the 29 cases. Even if averaged among the 111 cases, mortality of 3.5% to 4% is very worrying to a surgeon considering a nephron-sparing approach to small isolated tumours. Furthermore, smaller centres performing the procedure less frequently might not achieve such excellent results. For the ‘elective’ group of patients, it would seem appropriate to perform a randomised controlled trial to assess outcomes.

Reviewer: Kieran Jefferson

Journal:	Journal of Urology
Authors:	Tsui KH, Shvarts O, Smith RB, Figlin R, de Kernion JB and Belldegrun A	Issue:	2000, 163: 426-430

Title:

Renal cell carcinoma: prognostic significance of incidentally detected tumours.

Abstract:
The title and abstract of this paper claim to offer data as to the prognostic significance of incidentally detected renal tumours. It therefore seemed reasonable to expect a randomised or carefully case-controlled prospective study of such tumours comparing observation with immediate treatment. It was disappointing then, to discover that this is merely a report of case series of renal tumours (admittedly a very large one). The authors looked retrospectively at 633 consecutive patients of whom only 95 (15%) had been detected incidentally (a figure attributed to the tertiary nature of much of their practice). Age and sex distribution were similar but incidentally detected tumours were of earlier stage and grade on average and 5-year survival significantly higher. The data might have been more informative had it excluded patients referred from other centres. It seems to offer nothing that has not been previously available in the literature. On the basis of their data the authors propose a screening programme for renal cell carcinoma , claiming that ‘…detection of renal cell carcinoma before symptom onset enables treatment of less aggressive tumours and provides a better prognosis for patients…’. They have failed adequately to demonstrate either point in this study and appear to be unfamiliar with the concept of lead-time bias. The only way to confirm their hypothesis would be a properly randomised, controlled trial of screened versus non-screened groups.

Reviewer: Kieran Jefferson

Journal:	Journal of Urology
Authors:	Jacobsen J, Rasmuson T, Grankvist K and Ljungberg B	Issue:	2000, 163: 343-347

Title:

Vascular endothelial growth factor as a prognostic factor in renal cell carcinoma

Abstract:
Vascular endothelial growth factor (VEGF) has attracted great interest due to its central role in tumour angiogenesis, a process central to tumour growth and metastasis. Serum levels have been investigated in a number of tumour types as potential prognostic markers. This study attempts to correlate serum VEGF with clinicopathological findings and prognosis for renal cell carcinoma (RCC) in 164 patients. There is an increase in serum VEGF levels as tumour stage and grade rise, however there is considerable overlap between groups, suggesting that the clinical utility of serum VEGF as a staging test would be limited. Furthermore, VEGF was not a useful prognostic factor. Recent research into RCC has yielded information that further casts doubt on the findings. In their discussion, the authors postulate that the lower levels of VEGF seen in chromophobe tumours, when compared with clear cell tumours, relates to their better prognosis. However mutations in the VHL gene (a regulator of VEGF expression), which are very common in clear cell tumours, may explain this. The use of serum VEGF assay has also been challenged by studies which have shown considerable VEGF release from platelets during clotting. Fresh citrated plasma samples are now the recommended samples to prevent confounding platelet effects. A study using fresh citrated plasma samples could result in a clinically more useful assay.

Reviewer: Kieran Jefferson

Journal:	Journal of Urology
Authors:	Miyake H, Hara I, Yamanaka K, Arakawa S and Kamidono S	Issue:	1999, 162: 2176-2181

Title:

Synergistic enhancement of resistance to cisplatin in human bladder cancer cells by overexpression of mutant-type p53 and Bcl-2

Abstract:
Selective triggering of apoptotic (programmed cell death) pathways in cancer cells has become the ‘holy grail’ of contemporary cancer research. Currently, induction of apoptosis by treatments such as radiotherapy and chemotherapy is poorly targeted and, as tumours progress, resistance to apoptosis increases. Much recent research has demonstrated the importance of the p53 and Bcl-2 proteins to the regulation of apoptosis; p53 triggers apoptosis in addition to its role in regulating the cell cycle, while Bcl-2 prevents apoptosis. This paper describes the effects of transfection experiments leading to overexpression of Bcl-2 and mutant p53 in vitro and in vivo (when the cell line was implanted into nude mice). Cells from a transitional cell cancer line (with normal p53 and Bcl-2) showed reduced susceptibility to apoptotic induction by cisplatin when either transfection occurred. Cells transfected with both showed synergistic effects. The results might be expected given current knowledge of apoptosis. More interesting data might come from the next logical step – restoring the function of p53 and down-regulating Bcl-2 expression where these are mutated, to see whether a transfection technique might render tumours more susceptible to induction of apoptosis.

Reviewer: Kieran Jefferson

Journal:	European Urology
Authors:	van der Meijden A, Oosterlinck W, Brausi M, Kurth KH, Sylvester R and de Balincourt C	Issue:	1999, 35: 267-271

Title:

Significance of bladder biopsies in TA,T1 bladder tumours: a report from the EORTC genito-urinary tract cancer co-operative group

Abstract:
This study from the EORTC investigated the pathological findings from biopsies of normal looking urothelium and that around bladder tumours in patients with TA/1 transitional cell carcinomas of the bladder undergoing clinical trials evaluating intravesical chemotherapy or BCG. In patients with low risk tumours defined as solitary primary or recurrent TCCs, CIS in tissue adjacent to the primary tumour was found in 5% (n=100) of T1 tumours compared to 1% (n=272) of TA tumours. Random biopsies of normal looking epithelium detected CIS in 1% of patients with TA tumours and 4% of T1 tumours. In patients determined to be at higher risk of tumours (multiple or recurrent tumours), more tumour (10%) was found in random biopsies of normal looking tissue in TA disease, but these were almost all TA tumours and none was greater than T1. In patients with high risk T1 tumours, random biopsies detected cancer in 16% of cases, but only 1 of 29 was worse than T1. The additional tumour found on random biopsy seems low, but there are important differences between TA and T1 tumours.

Reviewer: Marc Laniado

Journal:	Cancer
Authors:	Hoffman MA, Renshaw AA and Loughlin KR	Issue:	1999, 85: 1565-1568

Title:

Squamous cell carcinoma of the penis and microscopic pathological margins: how much margin is needed for local cure?

Abstract:
Traditionally, at least a 2 cm surgical margin is necessary when performing a penectomy for cancer to provide adequate cancer control. Achieving this can make it more difficult to leave a penile stump that allows voiding whilst standing or adequate sexual function. This study from Harvard reports on the microscopic pathological margins found on review of specimens with T1 and T2 squamous cell carcinoma of the penis. None of 7 patients who had a partial penectomy had a local recurrence and the average microscopic margin was 14.4 mm (range 0 to 40 mm). The authors advocate that conventional surgical margins probably do not need to be as large as previously suggested. However, the degree of skin contraction that occurs with preparation of the surgical specimen was not definitively accounted for and it may still be wise to obtain 2 cm margins.

Reviewer: Marc Laniado

Journal:	Journal of Urology
Authors:	Mydlo JH, Weinstein R, Shah S, Solliday M and Macchia RJ	Issue:	1999, 161: 1128-1132

Title:

Long-term consequences from bladder perforation and/or violation in the presence of transitional cell carcinoma: results of a small series and a review of the literature.

Abstract:
The consequences of bladder perforation during surgery for transitional cell carcinoma are poorly described within the urological literature, as revealed by this literature review. The authors identified 16 cases from a review of patient databases from a number of institutions. Two patients died from sepsis and existing metastatic disease respectively. One patient with a pTa G2 tumour and who suffered an intraperitoneal perforation, developed metastasis at 4 months. It would appear that from both the experience of the authors and the review of the literature, extravesical tumour recurrence following perforation of the bladder is rare.

Reviewer: Andrew Elves

Journal:	Journal of Urology
Authors:	Clark PE, Streem SB and Geisinger MA	Issue:	1999, 161: 772-776

Title:

13-year experience with percutaneous management of upper tract transitional cell carcinoma

Abstract:
Upper tract transitional cell carcinoma represents 5% of all urothelial tumours. The low incidence of metachronous lesions in the contralateral upper tract (3%), supports the use of nephroureterectomy as the standard treatment for upper tract transitional cell carcinoma. However, there are some patients in whom a nephron sparing approach is required. The authors report the results of percutaneous management in 17 patients with 18 tumours. In 16 of the 18 treated renal units, definitive resection of the tumour was followed by 6 weekly percutaneous installations of BCG. Complete resection was achieved in 17 of 18 renal units. The stage and grade of tumours recorded (83% pTa, 11% pT1, 6% pT2) and mortality and recurrence rates over a mean follow-up of 20.5 months are given. Ipsilateral local recurrence developed in 6 renal units (33%). These results are comparable to other forms of conservative therapy.

Reviewer: Andrew Elves

Journal:	British Journal of Urology
Authors:	DJ Thomas, JT Roberts, RR Hall and J Reading	Issue:	1999, 83: 432-437

Title:

Radical transurethral resection and chemotherapy in the treatment of muscle-invasive bladder cancer: long-term follow-up.

Abstract:
The long-term follow-up of 50 patients with invasive bladder cancer (T2-T4a) treated by radical transurethral resection and cisplatin-methotrexate systemic chemotherapy is presented. At 3 months, 38 patients were tumour free, 8 had persistent muscle-invasive disease (treated with cystectomy or radiotherapy) and 4 had Ta, T1 or CIS disease. A further 10 patients relapsed with muscle invasive disease at a median of 15.6 months. Fifteen patients developed metastatic disease at a median of 20 months. Five-year disease specific survival for those with T2 tumours was 57% while for those with T3 and T4 the figure was 72%.

Reviewer: Andrew Elves

Journal:	Journal of Urology
Authors:	Figlin RA	Issue:	1999, 161: 381-387

Title:

Renal cell carcinoma: management of advanced disease

Abstract:
Following the recent publication in the Lancet of the MRC metastatic renal cell carcinoma study, this paper presents a timely review of the presentation, molecular biology, and treatment of advanced renal cell carcinoma and future prospects for the management of this disease.

Reviewer: Andrew Elves

Journal:	Journal of Urology
Authors:	Hautmann RE, de Petriconi R, Gottfried HW, Kleinschmidt K, Mattes R and Paiss T	Issue:	1999, 161: 422-428

Title:

Ileal neobladder: complications and functional results in 363 patients after 11 years of follow-up

Abstract:
Hautmann et al. present the complications and functional results of ileal neobladder in 363 patients. Perioperative death occurred in 11 patients (3%), while early neobladder related complications occurred in 56 patients (15.4%) and late complications in 85 patients (23.4%) with an early and late re-operation rate of 0.3 and 4.4% respectively. The re-operation rate for neobladder unrelated early and late complications was 12.1% and 12.4% respectively. A total of 3.9% of patients required intermittent self-catheterisation, while unacceptable day and night time incontinence (defined as more than one pad required per day or night) was 4.1% and 5% respectively.

Reviewer: Andrew Elves

Journal:	Urology
Authors:	Carter HB, Epstein JI and Partin AW.	Issue:	1999, 53(1): 126-130

Title:

Influence of age and prostate-specific antigen on the chance of curable prostate cancer among men with nonpalpable disease

Abstract:
By examining the pre-operative PSA and age of 492 men that underwent potentially curable radical prostatectomies for non-palpable (Stage T1c) disease, the authors aimed to determine predictors of probability of a cure. Following radical prostatectomy, a cancer was defined as curable if the tumour was confined or if capsular penetration was low grade with negative margins and seminal vesicles. They present results that report an indirect relationship between probability of cure and both age and PSA. Increasing age resulted in a lower probability of cure as did increasing PSA. They conclude that age is a stronger predictor of cure than PSA. Therefore, efforts aimed at early detection in young men are more likely to lead to a decrease in mortality than application of a lower threshold of normal PSA.

Reviewer: Jonathan Cartledge

Journal:	Urology
Authors:	Igarishi T, Marumo K, Onishi T, Kobayashi M, Aiba K, Tsushima T, Ozono S, Tomita Y, Terachi T, Satomi Y, Kawamura J and The Japanese Study Group Against Renal Cancer	Issue:	1999, 53(1): 53-59

Title:

Interferon-alpha and 5-fluoracil therapy in patients with metastatic renal cell cancer: an open multicenter trial

Abstract:
The authors report the treatment of 55 patients that had a previous nephrectomy for renal cell carcinoma and who presented for chemotherapy with metastatic disease either present at the time of surgery (21) or a late recurrence (34). Patients were given a 12 week course of combination chemotherapy, 5-fluoracil with human lymphoblastoid interferon and assessed for response and survival. An overall response rate of 20% was noted with median time to progression of 11 months and median survival of 33 months. The authors conclude that combination therapy does not confer a benefit over interferon therapy alone.

Reviewer: Jonathan Cartledge

Journal:	Journal of Urology
Authors:	Herr HW	Issue:	1999, 161: 33-35

Title:

Partial nephrectomy for unilateral renal carcinoma and a normal contralateral kidney: 10-year follow-up

Abstract:
Previous large studies have demonstrated a low risk of ipsilateral recurrence in patients undergoing partial nephrectomy for tumours 4 cm or less. However, concern remains regarding the efficacy of partial nephrectomy beyond 5 years. In an attempt to address this issue the author presents 10-year follow-up data on 70 patients undergoing partial nephrectomy with tumours of Fuhrman grade 1-2, ranging between 1.5 cm and 6.5 cm. Of the 70 patients, 98.5% had no local recurrence and 97% survived free of metastasis to 10 years. Interestingly, while ipsilateral multifocal disease was not observed in this series, 7% of patients developed contralateral disease in keeping with the findings of Dechet et al.

Reviewer: Andrew Elves

Journal:	Prostate Cancer and Prostatic Diseases
Authors:	Ravery V, Lamotte F, Hennequin CH, Toublanc M, Boccon-Gibod L, Hermieu JF, Delmas V and Boccon-Gibod L.	Issue:	1998, 1(6): 320-25

Title:

Adjuvant radiation therapy for recurrent PSA after radical prostatectomy in T1-T2 prostate cancer.

Abstract:
Twenty two patients, who were designated to have pT3 disease defined by biochemical failure (PSA > 0.1 ng/ml) after radical prostatectomy, underwent adjuvant radiotherapy (ART) at a mean 25 months. Patients who achieved an undetectable PSA had a lower preoperative mean PSA and a significantly lower mean PSA at time of ART (1.1 vs. 2.9 ng/ml, P<0.05). However, a longer follow up of these patients (mean 20.4 months) using ultra-sensitive PSA assays showed that unmeasurable levels persisted in only 36.4%. The authors conclude by recommending that patients with a low preoperative PSA and a serum PSA of less than 1 ng/ml prior to ART are the most likely to benefit from ART, as these were the only two parameters that statistically correlated with complete biochemical response to ART.

Reviewer: James Green

Journal:	Urology
Authors:	Smits G, Schaafsma E, Kiemeney L, Caris C, Debruyne F and Witjes JA.	Issue:	1998, 52(6): 1009-1014

Title:

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

Abstract:
The authors reviewed the pathological findings of 124 patients with pT1 TCC that were enrolled in an EORTC trial comparing BCG with MMC for treatment of superficial disease. They reclassified the depth of invasion up to, in or beyond muscularis mucosae or vascular plexus and labelled these pT1a, pT1b or pT1c respectively. Risk of recurrence by three years was the same for all subgroups. The progression risk however was 6%, 33% and 55% for pT1a, pT1b or pT1c respectively. Tumour grade was not related to risk of recurrence or progression, the presence of CIS increased the risk of progression from 8% to 39% if found in the tumour specimen. The authors conclude that recording the extent of lamina propria invasion is possible in standard histological preparations and provides further prognostic invasion of risk to progression.

Reviewer: Jonathan Cartledge

Journal:	Journal of Urology
Authors:	Haleblian GE, Skinner EC, Dickinson MG, Lieskovosky G, Boyd SD and Skinner DG.	Issue:	1998, 160: 2011-2014

Title:

Hydronephrosis as a prognostic indicator in bladder cancer patients.

Abstract:
Historically, the finding of hydronephrosis in patients presenting with bladder cancer has been regarded as a poor prognostic indicator. This study retrospectively reviewed 415 patients with carcinoma of the bladder treated with radical cystectomy, and investigated whether the presence of unilateral or bilateral upper tract obstruction could accurately predict advanced cancer stage (extravesical extension, stage greater than 3b or positive lymph nodes). The authors found a significant correlation between hydronephrosis and advanced cancer stage, and decreased patient survival. While 90% of patients with bilateral hydronephrosis had extravesical extension, a third of those patients with unilateral hydronephrosis had disease confined to the bladder (42% having non-invasive disease). The authors conclude that the presence of unilateral hydronephrosis or bilateral hydronephrosis is a readily available clinical datum that can help in clinical staging, and that the presence of bilateral hydronephrosis is a particularly ominous sign.

Reviewer: Andrew Elves

Journal:	Journal of Urology
Authors:	Poulsen AL, Horn T and Stevens K.	Issue:	1998, 160: 2015-2020

Title:

Radical cystectomy: extending the limits of pelvic lymph node dissection improves survival for patients with bladder cancer confined to the bladder wall.

Abstract:
The authors report the influence of the limits of pelvic lymph node dissection on survival following cystectomy for carcinoma of the bladder. At the time of cystectomy, either a limited lymph node dissection beginning at the bifurcation of the common iliac vessels, or an extended lymph node dissection beginning at the aortic bifurcation was performed. The 5-year recurrence free survival was higher in the extended lymph node dissection group than the limited dissection group (62% versus 56%) although this did not reach statistical significance. Among those patients with disease confined to the bladder (tumour stage pT3a or less), a significant improvement in 5-year recurrence free survival was achieved in those undergoing extended lymph node dissection compared to limited lymph node dissection (85% versus 64%). From this retrospective analysis, the authors conclude that an extended lymph node dissection, including nodes from the aortic to iliac bifurcations, improves recurrence free survival in patients undergoing radical cystectomy for carcinoma of the bladder.

Reviewer: Andrew Elves

Journal:	Urology
Authors:	Gill IS, Novick AC, Soble JJ, Tak Sung G, Remer EM, Hale J and O’Malley CM.	Issue:	1998, 52 (4): 543-551

Title:

Laparoscopic renal cryoablation: initial clinical series.

Abstract:
The authors report a series of 10 patients treated by renal cryoablation for renal lesions less than 4 cm diameter, peripheral, exophytic, enhancing on CT and away from the collecting system. Cryoablation is performed through retroperitoneal laparoscopic access and after complete renal mobilisation the 4.8 mm diameter probe inserted into the lesion under Doppler ultrasound guidance to produce a 2 cm or 4 cm ice ball. Average operative time was 2.4 hours with 9/10 patients discharged in 23 hours. The authors state that this technique is a feasible alternative to open partial nephrectomy in these patients but long term follow-up will be necessary.

Reviewer: Jonathan Cartledge

Journal:	Urology
Authors:	Gheiler EL, Tefelli MV, Tiguert R, de Olivera JG, Pontes JE and Wood DP.	Issue:	1998, 52 (3): 487-493

Title:

Management of primary urethral cancer

Abstract:
The authors retrospectively reviewed the records of 21 patients with primary urethral carcinoma. The tumours reported were adenocarcinoma (8), squamous cell carcinoma (11), transitional cell carcinoma (1) and malignant melanoma (1). They were distal in 9 and proximal in 12. Treatment included resection alone or resection +/- chemo/radiotherapy. The authors report an overall disease free survival rate of 62%. They describe survival rates by stage of disease and tumour type but the numbers in each group are small. They do, however, state that clinical-pathological stage was a strong predictor of survival and that, for Ta-2, local disease resection alone may be adequate treatment, confining chemo/radiotherapy for more advanced disease.

Reviewer: Jonathan Cartledge

Journal:	Urology
Authors:	Landman J, Chang Y, Kavaler E, Droller MJ and Liu BC-S.	Issue:	1998, 52(3): 398-402

Title:

Sensitivity and specificity of NMP-22, telomerase, and BTA in the detection of human bladder cancer

Abstract:
The authors examined voided urine samples from patients with haematuria with and without a diagnosis of bladder cancer. Each sample was examined by cytology, BTA Assay, NMP-22 Assay and Telomerase Assay. Following cystoscopy, tumour grade and stage were recorded and sensitivity calculated. Specificity was calculated by subjecting urine from age matched controls without TCC. Despite only examining the urine from 47 patients with TCC and 30 control patients, the authors report sensitivity/specificity as follows: Cytology 40%/94%, BTA 40%/73%, NMP-22 81%/77% and Telomerase 80%/80%. They also report increasing sensitivity with increasing tumour grade.

Reviewer: Jonathan Cartledge

Journal:	Urology
Authors:	Witjes JA, Meijden APM, Collette L, Sylvester R, Debruyne FMJ, van Aubel A, Witjes WPJ, the EORTC GU Group and the Dutch South East Cooperative Urological Group.	Issue:	1998, 52(3): 403-410

Title:

Long-term follow-up of an EORTC randomized prospective trial comparing intravesical bacille Calmette-Guerin-RIVM and mitomycin C in superficial bladder cancer

Abstract:
This report from EORTC 30845 randomised 344 patients with primary or recurrent pTa and pT1 including CIS to receive either Mitomycin C (MMC) (30 mg/50 ml weekly for 4 weeks starting 7-15 days post resection, then monthly for 5 months) or BCG-RIVM (5 X 108 in 50 ml weekly for 6 weeks). Time to recurrence, progression and toxicity were assessed. After an average 7.2 year follow up, the authors report no significant difference in toxicity between groups and no significant difference in recurrence rate or time to progression. Overall recurrence rate per year was reported at BCG=0.164 and MMC=0.157. In patients with carcinoma in situ (CIS), 50% recurred on BCG and 56% on MMC. Progression was seen in 9.6% of patients, (27.5% with CIS vs. 7.2% without CIS). Overall 20 patients died of their disease. The authors conclude that intravesical MMC is an effective treatment option in high-risk patients. They were unable to confirm that BCG was more effective in preventing disease progression.

Reviewer: Jonathan Cartledge

Journal:	British Journal of Urology
Authors:	El-Mekresh MM, El-Baz MA, Abol-Enein H and Ghoneim MA.	Issue:	1998, 82: 206-212

Title:

Primary adenocarcinoma of the urinary bladder: a report of 185 cases.

Abstract:
The information obtained from retrospective reviews can be limited but, if the information is not available any other way, such reviews can be invaluable. Ghonheim, from Mansoura, Egypt, has once again collected another worthwhile series showing us that stage, grade and lymph node status are the most important prognostic indicators in patients with adenocarcinoma of the bladder. Schistosomiasis was present in 84% of the specimens. Five year survival was 55%.

Reviewer: Jonathan Glass

Journal:	Urology
Authors:	Campbell SC, Krishnamurthi V, Chow G, Hale J, Myles J and Novick AC.	Issue:	1998, 52 (1): 29-34

Title:

Renal cryosurgery: experimental evaluation of treatment parameters.

Abstract:
The authors tested an animal model for treating solid renal lesions with intra-renal cryosurgery. Nephrectomy was performed in 10 dogs. In the remaining kidney a 3.4 mm cryoprobe was inserted 10 mm into the lower pole with a thermometer probe 10 mm away. The probe was chilled to -195oC until the recorded temperature fell to -40oC. Ultrasound examination measured an ice ball of 16mm diameter formed after 10 minutes of freezing. After 28 days the animals were sacrificed. Histological examination revealed chronic inflammation and necrosis with no visible renal parenchyma for a mean diameter of 18.9 mm. The authors suggest a future role of cryosurgical ablation via laparoscopy for the conservative management of small renal lesions.

Reviewer: Jonathan Cartledge

Journal:	Urology
Authors:	Van der Poel HG, Van Balkan MR, Schamhart DHJ, Peelen P, de Reijke Th, Debrutne FMJ, Schalken JA and Witjes JA.	Issue:	1998, 51 (1): 44-49.

Title:

Bladder wash cytology, quantitative cytology, and the qualitative BTA test in patients with superficial bladder cancer.

Abstract:
Urine from 138 patients was with BTA test. Cystoscopy was performed and bladder wash analysed in all patients cytologically and using bladder wash karyometric (BWK) image analysis. All lesions seen at cystoscopy were resected and analysed histologically. Sensitivities for the tests are reported as 34.4% (BTA), 44.8% (cytology), and 69%(BWK). Specificity’s 81.3%(BTA), 92,5%(cytology) and 72.5%(BWK). Combination of tests did not improve outcomes. BTA missed 10 high grade pTa and 4 pT1 lesions. All CIS cases were BTA negative. The authors conclude may be useful in recurrent low-grade lesions. BWK was most sensitive for the recurrence of high grade lesions.

Reviewer: Mark Feneley

Journal:	British Journal of Urology
Authors:	Kelly JD, Hamilton PW, Williamson KE,Weir HP, McManus DT, Keane PF and Johnston SR.	Issue:	1997, 80: 927-932.

Title:

Validation of a rapid method to quantify apoptosis in superficial bladder cancer.

Abstract:
This paper attempts to find an index by which to assess the efficacy of chemotherapeutic agents in the treatment of superficial transitional cell carcinoma of the bladder. The authors of this paper have gone to some effort to show that this method is valid, efficient and reproducible.

Reviewer: Mark Feneley

Journal:	British Journal of Urology
Authors:	Herr HK	Issue:	1997, 80 (5): 762-765.

Title:

Tumour progression and survival in patients with T1G3 bladder tumours: 15-year outcome.

Abstract:
Further long term survival data are given on the relatively rare but highly problematic G3pT1 bladder tumour. Although most progression occurred within the first five years, progression was seen at any point over the 15 year period. A remarkable 24 out of 48 (50%) survived and 20 still had working bladders at 15 years.

Reviewer: Mark Feneley

Journal:	British Journal of Urology
Authors:	MV Hansen and A Zdanowski	Issue:	1997, 80 (5): 787-792.

Title:

The agreement among urological experts on the diagnostic management of patients with common urological problems.

Abstract:
Thirty three urologists were asked to investigate and treat 53 simulated urological conditions. The probability of the urologists using a certain test in a certain patient was recorded and the cost implications evaluated. Most consistency was seen treating stone patients, then bladder cancer, prostate cancer and lastly BPH. These were all university based consultants.

Reviewer: Mark Feneley

Journal:	Urology
Authors:	Buzzeo B, Heisey DM and Messing EM.	Issue:	1997, 50 (4): 525-528.

Title:

Bladder cancer in renal transplant recipients

Abstract:
Renal transplant patients appear to be at greater risk of developing bladder cancer. The authors used a complex statistical model that applied age and gender specific population risk rates for bladder cancer to 3130 renal transplant patients and calculated that they would expect 1.8 new cases of cancer in that group. On retrospectively reviewing the records of these transplant patients they found 6 cases of bladder cancer arising post transplant, giving a relative risk of 3.31. They conclude that because of this increased risk of cancer all cases of haematuria (common in renal transplant patients) should be appropriately investigated.

Reviewer: Mark Feneley

Journal:	British Journal of Urology
Authors:	Delahunt B, Bethwaite PB, and Thornton A.	Issue:	1997, 80 (3): 401-404.

Title:

Prognostic significance of microscopic vascularity for renal cell carcinoma.

Abstract:
Whilst the search continues for molecular prognostic markers in urological malignancy, pathologists still seek simple inexpensive histopathological indicators within tumours that might give clinicians prognostic information. This large study with reasonable follow up shows that patients whose tumours have a high mean microvascular density (MMD) have a prolonged survival over patients with tumours with a low MMD. MMD has previously shown to be inversely related to nuclear pleomorphism.

Reviewer: Mark Feneley

Journal:	Journal of Urology
Authors:	Figin RA, Pierce WC, and Kaboo R, Tso CL, Moldawer N, Gitlitz B, deKernion JB and Belldegrun A.	Issue:	1997, 158: 740-745.

Title:

Treatment of metastatic renal cell carcinoma with nephrectomy, Interleukin II and Cytokine-primed or Cd8(+) selected tumour infiltrating lymphocytes from primary tumour.

Abstract:
Thirty percent of renal cell carcinoma is metastatic at presentation and of those with apparently localised disease 30-50% may be expected to develop metastatic disease. The pronosis for those patients with metastatic disease is poor and has not been significantly improved by use of surgery, radiotherapy, hormone therapy, or chemotherapy. Immunotherapy using interleukin II has been associated with a significant response rate and durable remision in patients with good performance status.The authors present the results of a series of 62 patients enrolled to trials of interleukin II plus tumour infiltrating lymphocyte cell therapy. Five patients (9.1%) achieved a complete response and 14 (25.5%) achieved a partial response. Median duration of response was 14 months (0.8 - 64). Actuarial survival was 65% at 1 year and 43% at two years.

Reviewer: Mark Feneley

Journal:	Journal of Urology
Authors:	Maier U, Ehrenbock PM, and Hofbauer J.	Issue:	1997, 158: 814-817.

Title:

Late urological complications and malignancies after curative radiotherapy for gynaecological carcinomas: A retrospective analysis of 10,709 patients.

Abstract:
The authors report the long term complications of curative radiotherapy for primary gynaecological malignancy in a retrospective series of 10,709 patients. Severe late complications were seen in 1.24% of patients and included irradiated bladder, ureteral stenosis and urinary fistula. These complications required surgical intervention in approximately 80% of cases and were associated with significant mortality. The incidence of a second malignancy following radiotherapy was 1.24%, two thirds of which occured in the irradiated area. Relative risk for urothelial cancer was after radiotherapy was 4.46.

Reviewer: Mark Feneley

Journal:	Journal of Urology
Authors:	Silver DA, Stroumbakis N, Russo P, Fair RW and Herr HW.	Issue:	1997, 158: 768-771.

Title:

Ureteral carcinoma in situ at radical cystectomy: Does the margin matter?

Abstract:
Unexpected urothelial malignant change in the ureter at the time of cystectomy has been reported in between 1.5-8% of patients, and in one series up to 57% of patients with carcinoma of the bladder. Such findings have been regarded as an unfavourable prognostic factor. The authors’ report reviewed 401 radical cystectomy specimens identifying 31 patients with concominant ureteral carcinoma in situ, of whom 21 had positive margins. Of the 3 upper tract tumours observed only 1 recurred at the anastomosis. No significant association between positve urine cytology or ureteral recurrence was observed with respect to a positive ureteric margin. Over the follow-up period of 22.9 months, 7 of the 31 patients died, all from metastatic disease.

Reviewer: Mark Feneley

Journal:	Urology
Authors:	Michael Sarodsky, Hudson M, Ellis W, Soloway M, deVere White R, Sheinfeld J, Jarowenko M, Schellhammer P, Schervish E, Patel J, Chodak G, Lamm D, Johnson R, Henderson M, Adams G, Blumenstein B, Thoekle K, Pfalgraf R, Murchison H and Brunelle S.	Issue:	1997, 50 (3): 349-354.

Title:

Improved detection of recurrent bladder cancer using The Bard BTA stat Test.

Abstract:
The Bard BTA stat test identifies a bladder tumour associated antigen, a human complement factor H related protein which is produced by several human bladder cell lines but not epithelial cell lines. The authors tested frozen urine samples from 220 patients with histologically confirmed bladder cancer. BTA stat was positive in 67% (sensitivity). Previous cytological examination performed in 134/220 had demonstrated a sensitivity of 23% (BTA stat 58% for this group). To test specificity they assessed 555 urine samples from patients with no history of bladder cancer and reported an overall specificity of 93%, dropping to 88% in BPH, 76% in inflammatory disease, 50% in stone disease and 33% post invasive urological manipulation. They conclude that BTA stat is superior to urine cytology in detecting recurrent bladder cancer, with a specificity equal to cytology in healthy volunteers.

Reviewer: Mark Feneley

Journal:	British Journal of Urology
Authors:	Nemoto R, Nakamura I, Nishijima Y, et al.	Issue:	1997, 80 (2): 274-280.

Title:

Serum pyridinoline crosslinks as markers of tumour-induced bone resorption.

Abstract:
Pyridinoline (Py) is found in bone (and cartilage) where it acts as a crosslinking compound within collagen molecules. It is released into the circulation when bone is resorbed in bone metastasis. This study identifies that Py assay may have a role in identifying bone metastasis in renal cell carcinoma and prostate cancer, although in the latter it might miss identifying bone lesions in patients with sclerotic mets.

Reviewer: Mark Feneley

Journal:	British Journal of Urology
Authors:	Heyns CF, Van Vollenhoven P, Sttenkamp JW, Allen FJ, Van Velden DJJ.	Issue:	1997, 80 (2): 307-312.

Title:

Carcinoma of the penis - appraisal of a modified tumour-staging system

Abstract:
More accurate prognostic information can be obtained by combining histological differentiation and pathological extent of invasion than can be obtained from the current tumour grading system of the TNM system. All poorly differentiated tumours are classified as T4 regardless of invasion. Size of the tumour is not a factor in the new staging system. This modified system allows for avoiding lymphadenectomy and its associated complications in T1 tumours in the modified system.

Reviewer: Mark Feneley

Journal:	British Journal of Urology
Authors:	Fellin G, Graffer U, Bolner A, Ambrosini G, Caffo O, Luciani L.	Issue:	1997, 80: 44-49.

Title:

Combined chemotherapy and radiation with selective organ preservation for muscle invasive bladder carcinoma. A single institution phase II study.

Abstract:
This paper presents early data on results of a new protocol for the management of stage T2-4 bladder cancer with promising early results. Cystectomy was reserved for patients who had failed on this radiotherapy and chemotherapy regimen. The authors point out that bladder preservation must be a goal in treating invasive bladder cancer as long as survival is not compromised.

Reviewer: Mark Feneley

Journal:	British Journal of Urology
Authors:	Koren R, Paz A, Lask D, Kyzer S, Klein B, Schwartz A, Gal R.	Issue:	1997, 80: 40-43.

Title:

Lymph node revealing solution: a new method for detecting minute lymph nodes in cystectomy specimens.

Abstract:
A simple study showing how tiny lymph nodes from resected specimens that a histopathologist may miss can now be identified using a new solution containing ethanol, diethyl ether, glacial acetic acid and buffered formalin. Using this solution, patients were frequently upstaged.

Reviewer: Mark Feneley

Journal:	European Urology
Authors:	Weissbach L, Bussar-Maatz R, Mann K.	Issue:	1997, 32: 16-22.

Title:

The Value of Tumor Markers in Testicular Seminomas.

Abstract:
This study reports on the usefulness or otherwise of tumour markers in the management of seminomas. Placental alkaline phosphatase was most sensitive to detect metastatic disease (sensitivity 51%, specificity 91%) and was raised in 56% of patients prior to surgery. Nevertheless, a negative result meant that the odds of having metastatic diseased increase by less than twofold. Positive results for chorionic gonadotrophic hormone (sensitivity 42%, specificity 95%) or lactate dehydrogenase (sensitivity 46%, specificity 96%) increased the odds of having stage II or III disease by elevenfold, but negative results made little difference to the prior probability for this. These results indicate that positive results makes the chance of metastatic disease much more likely, but that negative results are not necessarily reliable and further investigations are required.

Reviewer: Mark Feneley

Journal:	Journal of Urology
Authors:	Pycha A, Mian C, Haitel A, Hofbauer J, Wiener H and Marberger M .	Issue:	1997, 157: 2116-2119.

Title:

Fluorescence in situ hybridization identifies more aggressive types of primarily noninvasive (stage pTa) bladder cancer.

Abstract:
While most bladder cancer is low grade and non-invasive, 70% of patients will have recurrent disease and 6-10% progression ultimately leading to death. This study evaluated genetic changes in chromosomes 7, 9, and 17 in cytological specimens of bladder cancer by in situ fluorescence hybridisation and related them to prognosis. The in situ hybridisation data obtained was also related to stage, grade, ploidy, p53 and Ki-67 expression. Patients with recurrent and progressive disease had a high incidence of trisomy 17 and 7, aneuploidy status and high positively for p53 and Ki-67 markers.

Reviewer: Mark Feneley

Journal:	Journal of Urology
Authors:	Hafez KS, Novick AC and Campbell SC.	Issue:	1997, 157: 2067-2070.

Title:

Patterns of tumor recurrence and guidelines for followup after nephron sparing surgery for sporadic renal cell carcinoma.

Abstract:
This paper reviews 327 patient who underwent nephron sparing surgery, describes patterns of tumor recurrence and proposes guidelines for the follow-up of patients after nephron sparing surgery for sporadic renal cell carcinoma. Employing biochemical assessments of renal and liver function, chest X-ray and abdominal CT every 6 months for 4 years and annually thereafter 38 (11.6%) patients were found to develop recurrence with a mean follow-up of 55.6 months. Thirteen patients (4%) had local recurrence with or without distant metastasis while 25 patients (8%) had distant metastasis without local recurrence. While chest X-ray or abdominal CT detected 13 recurrences, 25 were detected from clinical symptoms. The frequency of both local and distant recurrence increased with tumor stage. The authors propose that patients with T1 disease require annual follow-up by clinical and biochemical assessment with chest X-ray and abdominal CT being reserved for those patients withT2 stage disease or higher with the intervals for performing these investigations being determined by disease stage.

Reviewer: Mark Feneley

Journal:	Journal of Urology
Authors:	Kuettel MR, Parda DS, Harter WK, Rodgers JE and Lynch JH.	Issue:	1997, 157: 1669-1671.

Title:

Treatment of female urethral carcinoma in medically inoperable patients using external beam irradiation and high dose rate intracavitary brachytherapy.

Abstract:
The authors describe their experience with combination high dose rate brachytherapy and external beam irradiation for treatment of locally advanced carcinoma of the urethra in 4 medically inoperable women. Treatment was well tolerated; all patients maintained voluntary bladder function with good local control as defined by negative physical examination at 12 to 55 months after therapy.

Reviewer: Mark Feneley

Journal:	Journal of Urology
Authors:	Ovesen H, Horn T and Steven K.	Issue:	1997, 157: 1655-1659.

Title:

Long-term efficacy of intravesical bacillus Calmette-Guerin for carcinoma in situ: relationship of progression to histological response and p53 nuclear accumulation.

Abstract:
Fifty to 90% of patients presenting with carcinoma in situ of the bladder treated by transurethral resection alone will have progression to invasive disease within 5 years. Intravesical bacillus Calmette-Guerin (BCG) will eradicate carcinoma in situ in 53-93% of patients, yet progression may still be anticipated in 21-43%. Recurrence within the first two years is associated with a particularly high progression rate. The authors evaluate the influence of histological response to intravesical BCG and nuclear accumulation of p53 upon the clinical behaviour in a group of 60 patients with Berquist grade 3 carcinoma in situ. Complete histological response rate was 64% after 1 or 2 courses of BCG although this decreased to 52% at 4 years. Progression was related to the initial histological response being higher in those patients showing a partial or no response as well as whether carcinoma in situ was primary or secondary. Progression rate was also related to the nuclear p53 reactivity after but not before treatment. Interestingly, all three patients with complete histological response but post treatment p53 nuclear reactivity after BCG had progression. The authors conclude that those patients with a complete histological response and without p53 nuclear activity after BCG may be followed conservatively, advising cystectomy in all other patients.

Reviewer: Mark Feneley

Journal:	Cancer
Authors:	Riggs DR, DeHaven JI and Lamm DL.	Issue:	1997, 79: 1987-1994.

Title:

Allium sativum (garlic) treatment for murine transitional cell carcinoma.

Abstract:
Popular opinion is that garlic is healthy. This study evaluated whether garlic may be of benefit in the treatment of transitional cell carcinoma (TCC) on the basis that garlic stimulates the immune system. Mice were injected with murine bladder cancer cells and randomised to receive either saline injection or garlic into the inoculation site. Injections of garlic led to a large number of animal deaths, but in another arm of the study mice were given garlic by mouth. These mice did better with greater reductions in tumour size and less mortality. The role of garlic in the treatment of bladder cancer is worthy of further exploration.

Reviewer: Mark Feneley

Journal:	Journal of Urology
Authors:	Wunderlich H, Steiner T, and Junker U, Schlichter A and Schubert J.	Issue:	1997, 157: 1602-1603.

Title:

Serum transforming growth factor-b1 in patients with renal cell carcinoma.

Abstract:
The use of tumour markers to identify patients with metastases from renal cell carcinoma has remained difficult. This study examined the utility of serum transforming growth factor-b1 (TGF-b1), which is produced by renal cell carcinoma, as a staging marker for renal cell carcinoma. Serum TGF-b1 was measured by enzyme-linked immunoabsorbent assay in 21 patients prior to radical nephrectomy and 21 healthy controls. Mean transforming growth factor-b1 levels in patients with renal cell carcinoma were177 ± 54.1 as opposed to 65.5 ± 15.8 ng/ml in healthy controls. This difference was statistically significant. While no statistically significant difference was found with regard to tumour stage or grade, transforming growth factor-b1 remained elevated 4 weeks post-operatively in those patients with node positive disease or distant metastasis. However, it also remained significantly raised in patients who did not have metastatic disease. It would appear from this preliminary study that transforming growth factor-b1 offers limited means for identifying patients with a poor prognosis although larger quantitative studies are required with longer follow-up.

Reviewer: Mark Feneley

Journal:	Journal of Urology
Authors:	Keeley FX Jr, Bibbo M and Bagley DH.	Issue:	1997, 157: 1560-1565.

Title:

Ureteroscopic treatment and surveillance of upper tract transitional cell carcinoma.

Abstract:
Standard treatment for transitional cell carcinoma of the upper urinary tract is nephroureterectomy with a cuff of bladder. These account for 2-5% of all urothelial tumours. Increasing interest is developing in nephron-sparing treatment for upper tract tumours since the advent of improved endoscopic instruments and techniques for tissue ablation. This paper reports the authors' experience in 41 kidneys with upper tract tumours managed by semi-rigid or flexible ureteroscopy. Tumours were biopsied, and treated with either (1) fulguration (2) the neodymium: YAG laser (3) and/or holmium:YAG laser. Patients were treated every 6-12 weeks until tumour free. They were followed up by cystoscopy and cytology at 3-month intervals, retrograde ureteropyelography and ureteroscopy at 6-month intervals and imaging of the contralateral kidney at 12 months. Median follow-up reported was 26 months (range 3-116 months). Twenty-eight renal units (68%) were tumour free after a mean of 1.57 ureteroscopic treatments (range 1-6), including 8 (29%) that had recurrences. Twenty-four patients (86%) remain tumour free at the most recent follow-up. High grade, size and mulitfocality were all associated tumour persistence and recurrence. Seventy five percent of recurrences were not identified radiologically. It would appear that for single, small, low-grade tumours endoscopic management might offer an alternative to nephroureterectomy in patients where a nephron-sparing procedure is desirable.

Reviewer: Mark Feneley

Journal:	Cancer
Authors:	Neugut AI, Ahsan H, Robinson E and Ennis RD.	Issue:	1997, 79:1600-1604.

Title:

Bladder carcinoma and other second malignancies after radiotherapy for prostate carcinoma.

Abstract:
This study from the Surveillance, Epidemiology and End Results Program (SEER) group shows that the risk of bladder cancer after radiotherapy for prostate cancer increases by a factor 1.5 (95% confidence interval 1.1 to 2.0) after 8 years. As the risk per person-year of a bladder cancer is 0.19% and it increases to only 0.26%, it is probably not clinically relevant.

Reviewer: Mark Feneley

Journal:	British Journal of Urology
Authors:	Maiche AG and Pyrhonen S.	Issue:	1997, 79: 481-483.

Title:

Verrucous carcinoma of the penis: three cases treated with interferon-alpha.

Abstract:
The authors report three cases of locally recurrent verrucous carcinoma where interferon alpha was used in addition to non-radical surgical excision. The results of radiotherapy and chemotherapy are known to be poor. The good outcome in these cases suggests that immunotherapy should be considered for difficult case of verrucous carcinoma, particularly in patients who refuse partial/complete amputation.

Reviewer: Mark Feneley

Journal:	Journal of Urology
Authors:	Smith JA, Jr., Crawford ED, Paradelo JC, Blumenstein B, Herschman BR, Grossman HB and Christie DW.	Issue:	1997, 157: 805-7; 807-8.

Title:

Treatment of advanced bladder cancer with combined pre-operative irradiation and radical cystectomy versus radical cystectomy alone: a phase III intergroup study.

Abstract:
Despite its title, this study evaluated the combination of pre-operative irradiation (2000 rad) with radical cystectomy against radical cystectomy alone in 140 patients with either invasive bladder cancer, rapidly recurring high-grade superficial bladder cancer or carcinoma in situ. The study was randomised but the required number of patients to reach adequate statistical was not reached. The five-year survival was 53% for cystectomy alone verses 43% for those receiving both irradiation and surgery. This was not a significant difference though several flaws in the study design, namely recruitment and pre-operative staging, are discussed and the way they impact upon the value of the study.

Reviewer: Mark Feneley

Journal:	Cancer
Authors:	Mizutani Y, Okada Y and Yoshida O.	Issue:	1997, 79: 1190-94.

Title:

Expression of platelet-derived endothelial cell growth factor in bladder carcinoma.

Abstract:
This study showed that patients with pTa tumours likely to present with additional tumours may be distinguished by the level of platelet-derived endothelial cell growth factor (PDECGF) in the tissue resection. High levels were associated with multiple new tumours. Levels of PDECGF were higher in patients with invasive or poorly differentiated cancer. It would be useful to know if this can predict which patients will progress.

Reviewer: Mark Feneley

Journal:	Cancer
Authors:	Mizutani Y, Okada Y, Yoshida O, Fukumoto M and Bonavida B.	Issue:	1997, 79: 1180-1189.

Title:

Doxorubicin sensitizes human bladder carcinoma cells to Fas-mediated cytotoxicity.

Abstract:
This study on cell lines attempts to address the relative chemoresistance of bladder cancer and strategies to overcome it. Fas antigen when present on bladder tumour cells participates in cytotoxicity mediated by T lymphocytes and natural killer cells. Anti-Fas monoclonal antibodies induce apoptosis of cells expressing Fas. Treatment of bladder tumour cells with a combination of anti-Fas monoclonal antibodies and doxorubicin resulted in a synergistic cytotoxic effect by lymphocytes even in cells that were doxorubicin resistant. This was true for freshly isolated bladder carcinoma cells also. Combinations of chemotherapy and immunotherapy may be a promising way forward in the treatment of bladder cancer.

Reviewer: Mark Feneley

Journal:	British Journal of Urology
Authors:	The United Kingdom and Eire Bladder Tumour Antigen Study group.	Issue:	1997, 79: 362-366.

Title:

The use of the bladder-tumour associated analyte test to determine the type of cystoscopy in the follow-up of patients with bladder cancer.

Abstract:
This was a prospective multicentre study in which a bladder-tumour associated analyte (BTA) urine test was performed on patients scheduled for follow-up rigid cystoscopy. Those with a negative test were then examined by flexible cystoscopy. The sensitivity of the test was 58% and the specificity was 86%. This gives a likelihood ratio for a positive result of 4.1 and for a negative result of 2.1. The prior probability of a tumour is made greater when the test result is positive (ie the odds increase 4.1 fold) whereas the odds of a tumour being absent changes by only 2.1 fold when the test result is negative. The negative predictive value is not changed by much therefore. False negatives included six patients with high-grade tumours. The authors conclude that the test cannot replace cystoscopy as follow-up for TCC. Cost savings could be made, as patients with a negative BTA test may be able to avoid cystoscopy with a general anaesthetic. The role of the BTA test may therefore be quite small since the majority of check cystoscopies are already performed using a flexible cystoscope.

Reviewer: Mark Feneley

Journal:	British Journal of Urology
Authors:	Hrouda D, Muir GH and Dalgleish AG.	Issue:	1997, 79: 307-316.

Title:

The role of immunotherapy for urological tumours

Abstract:
This paper reviews the use and potential of immunotherapy in bladder, renal and prostate cancers. BCG is the only intravesical therapy which has been shown to reduce disease progression in patients with superficial bladder cancer and remains the most effective example of immunotherapy to date. Interleukin-2 is the current gold standard for advanced renal cell carcinoma, however only 7% of patients having complete regression with this treatment. A number of new immunotherapy approaches such as tumour vaccines are entering clinical trials.

Reviewer: Mark Feneley

Journal:	Journal of Urology
Authors:	Sandock DS, Seftel AD and Resnick MI.	Issue:	1997, 157: 798-799.

Title:

The role of gamma-glutamyl transpeptidase in the pre-operative metastatic evaluation of renal cell carcinoma.

Abstract:
Gamma-glutamyl transpeptidase (GGT) is found predominantly in hepatocyte smooth endoplasmic reticulum and elevated in a number of hepatic diseases or in the presence of microsomal induction. However GGT has also been found in the proximal convoluted tubule of the kidney. This study evaluated the utility of GGT as a marker of metastatic renal cell carcinoma by comparing the serum GGT and alkaline phosphatase in 53 patients with metastatic renal cell carcinoma against 27 with clinically localised disease. Gamma-glutamyl transpeptidase was more commonly elevated in patients with metastatic disease than those with clinically localised disease, and appeared to be more sensitive than alkaline phosphatase. The authors conclude that GGT is a better predictor of metastatic disease than alkaline phosphatase and the finding of elevated GGT should prompt a search for metastasis.

Reviewer: Mark Feneley

Journal:	European Urology
Authors:	Schwaibold H, Pichlmeier U, Klingenberger HJ and Huland H.	Issue:	1997, 31: 153-159.

Title:

Long-term follow-up of cytostatic intravesical instillation in patients with superficial bladder carcinoma. Is short-term, intensive instillation better than maintenance therapy?

Abstract:
This was a prospective, randomised multicenter trial with 419 patients evaluated after a median follow-up of 57 months. New transitional cell tumours were found in 22.7% of patients and there was an overall progression rate of 9.8%. Patients who received short-term intensive weekly doses of mitomycin in combination with long-term maintenance had substantially fewer new tumours. The advantage was especially clear in patients entering the study with a history of new tumours following resection in whom the relative risk of a new tumour was 0.06 (95% confidence interval 0.008 to 0.506).

Reviewer: Mark Feneley

Journal:	Cancer Research
Authors:	Pham HT, Block NL, Lokeshwar VB.	Issue:	1997, 57: 778-783.

Title:

Tumor-derived hyaluronidase: a diagnostic urine marker for high-grade bladder cancer.

Abstract:
This fascinating study indicates a new test on urine that may help identify patients with high-grade bladder tumours. The presence of hyaluronidase in the urine of patients was able to identify patients with grade 2 or 3 bladder tumours with a sensitivity of 100% and specificity of 88.8%. Hyaluronidase breaks down hyaluronic acid to angiogenic products, both of which are elevated in urine and the tissue specimen. The negative predictive value approaches 100% and the use of this test will be to identify which patients do not need cystoscopy to detect new tumours.

Reviewer: Mark Feneley

Journal:	Cancer Research
Authors:	Lokeshwar VB, Obek C, Soloway MS, Block NL.	Issue:	1997, 57: 773-777.

Title:

Tumor-associated hyaluronic acid: a new sensitive and specific urine marker for bladder cancer.

Abstract:
Levels of hyaluronic acid measured by ELISA in the urine were able to identify patients with all grades of bladder cancer with a sensitivity of 91.9% and specificity of 92.8%. This corresponds to a positive likelihood ratio of 12.8 and a negative likelihood ratio of 11.5. These likelihood ratios indicate that the prior probability of a bladder tumour being present is changed substantially. These tests will need further evaluation, but they appear extremely promising.

Reviewer: Mark Feneley

Journal:	Cancer
Authors:	Lee CCR, Yamamoto S, Morimura K, Wanibuchi H, Nishisaka N, Ikemoto S, Nakatani T, Wada S, Kishimoto T, Fukushima S.	Issue:	1997, 79: 780-9.

Title:

Significance of cyclin D1 overexpression in transitional cell carcinomas of the urinary bladder and its correlation with histopathologic features.

Abstract:
There is a need to identify new biological markers that can distinguish bladder tumours which have the potential to invade and those that do not. Cyclin D1 is a cell cycle protein that advances the cell through the G1/S-transition phase. It was expressed in low stage and well differentiated tumours and inversely in relation to p53. The ratio between the two may eventually prove clinically useful, but this has yet to be determined.

Reviewer: Mark Feneley

Journal:	British Journal of Urology
Authors:	Heidenreich A, Holtl W, Albrecht W, Pont J and Engelmann UH.	Issue:	1997, 79: 253-257.

Title:

Testis-preserving surgery in bilateral testicular germ cell tumours.

Abstract:
Thirteen patients with bilateral germ cell tumours of the testis underwent organ-preserving tumour enucleation of one side rather than bilateral orchiectomy. Patients with carcinoma in situ (CIS) underwent testicular irradiation. The tumours were seminoma in about half the cases and the rest were teratomas. Testicular biopsy was performed at 6 months. One patient developed local recurrence of a embryonal/choriocarcinoma in the testis at 9 months which required orchiectomy. None of the patients required androgen replacement. Patients with CIS who had irradiation had biopsies showing Sertoli cells only. The authors recommend this approach for bilateral tumours provided the tumour is organ-confined, the rete testis is not involved, multiple biopsies of tumour bed and peripheral parenchyma are taken and CIS is treated by radiotherapy.

Reviewer: Mark Feneley

Journal:	British Journal of Urology
Authors:	Doherty AP, Bower M and Christmas TJ.	Issue:	1997, 79: 247-252.

Title:

The role of tumour markers in the diagnosis and treatment of testicular germ cell cancers.

Abstract:
This interesting review concludes that the present tumour markers aFP, bHCG and LDH1 are insufficiently accurate to replace the necessity for histological diagnosis. New markers are being evaluated of which the most promising are placental alkaline phosphatase and neuron specific enolase in seminoma.

Reviewer: Mark Feneley

Journal:	Cancer Research
Authors:	O'Brien T, Cranston D, Fuggle S, Bicknell R, Harris AL.	Issue:	1997, 57: 136-140.

Title:

Two mechanisms of basic fibroblast growth factor-induced angiogenesis in bladder cancer.

Abstract:
Angiogenesis is important to the continued growth of a tumour when it outstrips its ability to be viable by diffusion of waste and nutrition. Previously, bFGF (FGF-2) levels have been shown to be elevated in the urine of patients with bladder cancer. This study shows that elevated tissue levels of immunoreactive bFGF do not appear to distinguish normal from invasive bladder tumours, although levels are much higher in invasive compared to superficial tumours. The tumour cells do not appear to be the source of the elevated bFGF which probably originates from the epithelial basement membranes and detrusor muscle.

Reviewer: Mark Feneley