[Urological comorbidities in patients with rheumatoid arthritis : literature review]. / Urologische Begleiterkrankungen bei Patienten mit rheumatoider Arthritis : Literaturübersicht.

Patients with rheumatoid arthritis (RA) have an increased risk of urolithiasis which is further negatively impacted by a reduced bone density. Interstitial cystitis also tends to occur more often in patients with rheumatic diseases. The high incidence of bacterial urogenital infections is influenced by the use of immunomodulating drugs. Many RA patients have to undergo numerous tests until a diagnosis is reached and are then treated as outpatients on a tightly controlled schedule. Despite a closely controlled rheumatological follow-up, urological screening and determination of a baseline prostate-specific antigen (PSA) value (in men over 45 years old) should not be neglected. In patients with an increased risk of renal and bladder neoplasms or when such a diagnosis is known, the benefit of long-term use of high doses of non-steroidal anti-inflammatory drugs (NSAID, aspirin type) should be carefully weighed up with a risk profile and after specialist urological assessment. Patients who suffer from sexual dysfunction due to physical limitations and prolonged medical therapy should undergo urological and gynecological assessment to exclude contributing causes. The use of aphrodisiacs and erection-enhancing drugs (e.g. PDE5 inhibitors, local injection with prostaglandins and vacuum therapy) require prior approval by a medical specialist and also cardiovascular stability. Acute urinary retention is more common in chronic inflammatory musculoskeletal diseases.

[Synchronous bilateral renal cell cancer with a single ovarian metastasis and a fibromuscular dysplasia of the renal artery]. / Synchroner bilateraler Nierentumor mit singulärer Ovarialmetastase und fibromuskulärer Dysplasie der Nierenarterie.

INTRODUCTION: Ovarian metastases of renal cell cancer (RCC) are extremely rare with less than 20 cases reported to date. These metastases occur in the majority of cases metachronous (i. e. prior to or after identification of the primary tumour) or--such as in our case--synchronous. CASE REPORT: A 42-year-old women was diagnosed for synchronous bilateral renal and a left-sided ovarian mass. In a first surgical step, the ovarian metastasis was removed laparoscopically and the 20 cm tumour on the right kidney via a transperitoneal tumour nephrectomy (histology: clear cell RCC, pT3bN0V1R0M1). Prior to nephron-sparing surgery of the left kidney an angiography was performed revealing a massive fibromuscular dysplasia. Under cold ischaemic perfusion, the two RCCs (pT1aV0R0) on the left side were excised and the renal artery replaced by a Goretex graft. Twelve hours postoperatively the patient became anuric and two stents were placed endoradiologically because of a stenosis of the proximal anastomosis. Two years after surgery the patient is recurrence-free and her renal function is normal. CONCLUSION: Although extremely rare, the possibility of an ovarian metastasis should be considered in women with RCC. The presented case was unique because of synchronous bilateral RCC, an ovarian metastasis and a fibromuscular dysplasia of the renal artery requiring a sophisticated surgical approach.

Management of locally advanced prostate cancer: a European consensus.

This report summarises the findings of a European Consensus Group review of current standards of care in locally advanced prostate cancer defined as (a) untreated cancer extending clinically beyond the prostatic capsule in patients with no evidence of lymph node invasion or distant metastases, and (b) residual disease remaining after local treatment with positive surgical margins, seminal vesicle invasion, persistent prostate-specific antigen (PSA) and/or secondary PSA relapse. There was no overall consensus as to the standard of care in clinically apparent locally advanced prostate cancer. It was agreed, however, that hormonal therapy (e.g. with a gonadotrophin releasing hormone analogue [GnRHa]) represents a valid treatment in these patients. Treatment practices and regimens vary considerably between European countries, but GnRHa is widely used, either alone or in combination with antiandrogens. Hormonal therapy alone is a valid option, though the optimal modality, timing and duration of treatment remain to be defined. Adjuvant therapy with a GnRHa has been shown to improve survival in patients undergoing external beam radiotherapy. It is a viable option after prostatectomy in patients with persistent or secondary relapsing PSA. It was determined that optimal treatment will be different according to PSA, clinical staging and Gleason score, and the treatment of locally advanced disease should be individually tailored after discussion between physician and patient. In many instances, patients prefer and expect some form of treatment in preference to watchful waiting. Treatment nomograms such as the Kattan nomograms provide precise, comprehensive and invaluable tools for everyday use and may be used to predict outcomes and guide treatment decisions.

Organ sparing surgery for malignant germ cell tumor of the testis.

PURPOSE: We evaluate the indication, technique and long-term outcome of organ preserving tumor resection rather than standard orchiectomy in 73 patients with bilateral testicular germ cell tumors or tumors of a solitary testicle. MATERIALS AND METHODS: Tumor resection was performed in 73 patients with 52 and 17 metachronous and synchronous bilateral testicular germ cell tumors, respectively, and 4 testicular germ cell tumors of a solitary testicle. Histology of the enucleated germ cell tumor revealed seminoma in 42 (57.5%) patients, embryonal carcinoma in 14 (19.2%), mature teratoma in 11 (15.1%), and mixed and combined germ cell tumors in 6 (8.2%). Mean tumor diameter was 15 mm. (range 5 to 30). Associated testicular intraepithelial neoplasia was diagnosed in 82% of patients who underwent local radiation with 18 Gy. RESULTS: After a median followup of 91 months (range 3 to 191) 72 (98.6%) patients had no evidence of disease and 1 died of systemic tumor progression. No local relapse occurred in 46 patients with associated testicular intraepithelial neoplasia treated with local radiation. However, local recurrence did develop in 4 patients after 3, 6, 12 and 165 months without radiation but all survived after undergoing inguinal orchiectomy. Testosterone levels were normal in 62 (84.9%) patients, hypogonadism developed in 7 (9.6%) and preoperative levels remained low in 4 (5.5%). Of the 10 patients who postponed local radiation for paternity reasons 5 had successfully fathered a child after organ sparing surgery. CONCLUSIONS: After a long-term followup of greater than 7 years organ sparing surgery represents a viable therapeutic approach to bilateral testicular germ cell tumor with an excellent postoperative outcome. Tumor enucleation might be considered a standard approach if the guidelines are respected, including cold ischemia, organ confined tumor less than 20 mm., multiple biopsies of the tumor bed, adjuvant local irradiation postoperatively to avoid local recurrence, close followup and high compliance.

Intravesical BCG in patients with carcinoma in situ of the urinary bladder: long-term results of EORTC GU Group phase II protocol 30861.

OBJECTIVES: This phase II study was designed to assess the response rate, side effects and long-term efficacy of BCG in the treatment of carcinoma in situ (Cis) of the urinary bladder. METHODS: 103 eligible patients with Cis were treated with 6 consecutive weekly intravesical instillations of 120 mg BCG-Connaught. In case of no response, a second 6-week course was given. RESULTS: A complete response (CR) was observed in 77 of the 103 eligible patients (75%) and 93 evaluable patients (83%). In 6 of 10 patients the CR was induced by a second cycle of 6 weekly instillations. After a median follow-up of 7.6 years, 39 of the 77 CR patients (50%) are still alive and have retained their bladder, 31 (40%) without tumor recurrence. Another 7 patients underwent cystectomy and are still alive while 16 (20%) have died due to bladder cancer. Ten patients stopped treatment due to toxicity. In 2 patients, cystectomy was done because of severe cystitis and reduced bladder capacity. Drug cystitis, bacterial cystitis and fever occurred in 45, 15 and 15% of the patients, respectively. Severe drug cystitis was noted in 3 out of 10 patients receiving more than 6 instillations, necessitating cystectomy in 1 case. CONCLUSION: Intravesical short-term BCG is an effective treatment modality in Cis, yielding a high CR rate. This therapy may however be suboptimal in some patients as the 5-year disease-free rate in complete responders drops to 60%. Still, this is an acceptable result for patients in whom cystectomy would otherwise be performed in virtually all cases.

Radiotherapy of testicular intraepithelial neoplasia (TIN): a novel treatment regimen for a rare disease.

PURPOSE: Testicular intraepithelial neoplasia (TIN) is a consistent precursor of most invasive germ cell tumors, currently treated by radiotherapy with 20 Gy, which destroys TIN but preserves Leydig cells. Nevertheless, analysis has shown dose-dependent dysfunction even with low therapeutic doses of 20 Gy in some cases. Therefore, we tested a dose reduction regimen by delivering smaller fractional doses to enhance the tolerance of Leydig cells. METHODS AND MATERIALS: Between 1993 and 1999, 9 patients were treated for TIN in a prospective multicenter trial. A total dose of 13 Gy was administered in 10 fractions of 1.3 Gy. Hormonal levels of follicle-stimulating hormone, luteinizing hormone, and testosterone were assayed serially. RESULTS: During a median follow-up time of 36 months, no patient showed evidence of local disease. A first postradiation biopsy was obtained 3-12 months after radiotherapy; 5 patients underwent a second biopsy 2-3 years after treatment. All biopsies showed a Sertoli cell-only pattern. Follicle-stimulating hormone levels continued to increase 1 year after radiotherapy, signaling eradicated spermiogenesis. Luteinizing hormone and testosterone remained within the normal range 2 years after radiotherapy. CONCLUSIONS: In the treatment of TIN, there seems to be a dose reduction potential to 13 Gy by lowering single fractional doses, which enhances the therapeutic ratio in favor of the Leydig cells.

The ablative effect of quarter dose bacillus Calmette-Guerin on a papillary marker lesion of the bladder.

PURPOSE: Low dose bacillus Calmette-Guerin (BCG) for stage TaT1 transitional cell carcinoma of the bladder has been given in various studies with the aim of decreasing side effects while maintaining the same efficacy as full dose bacillus Calmette-Guerin. However, its application in clinical practice remains controversial. We examined the ablative activity and incidence of side effects of intravesical quarter dose BCG given for a papillary marker lesion of the bladder. MATERIALS AND METHODS: Included in our study were 44 patients with primary or recurrent, multiple but no more than 10 lesions of stage pTaT1, grades 1 to 2 transitional cell carcinoma of the bladder. Intravesical treatment begun 14 days after the complete transurethral resection of all visible tumors except 1 marker lesion no larger than 1 cm. consisted of instillations of 30 mg. Connaught strain BCG diluted in 50 ml. saline once weekly for 6 consecutive weeks. Two weeks after the last instillation any residual tumor was completely resected. In cases of complete disappearance of the marker lesion deep biopsy of the tumor area was done. Urine cytology was also performed. RESULTS: There was a complete response in 27 of the 44 patients (61%), no response in 12 (27%) and progression to carcinoma in situ in 1 (2%), while the response was not evaluable in 4. Local side effects included dysuria in 54% of cases and macroscopic hematuria in 39%. Neither BCG induced infection nor BCG sepsis was observed. CONCLUSIONS: Quarter dose BCG has a clear ablative effect on superficial bladder cancer with a 61% response rate. Phase III trials are now required to compare its efficacy and toxicity to those of full dose BCG.

[Interdisciplinary consensus on diagnosis and therapy of testicular tumors. Results of an update conference based on evidence-based medicine. German Testicular Cancer study Group (GTCSG)]. / Interdisziplinärer Konsensus zur Diagnostik und Therapie von Hodentumoren. Ergebnisse einer Update-Konferenz auf Grundlage evidenzbasierter Medizin (EBM). German Testicular Cancer Study Group (GTCSG).

BACKGROUND: An "Interdisciplinary Consensus Statement on the Diagnosis and Therapy of Testicular Tumors" was prepared in 1996 by the "Interdisciplinary Testicular Tumor Working Group" (IAH) with input from representatives from diagnostic and therapeutic disciplines of various working groups of the German Cancer Society (Strahlenther Onkol 1997;173:397-406). In 1998 the IAH met again together with the "Testicular Tumor Working Party" of the Urooncology Working Group (AUO) and formed the "German Testicular Cancer Study Group" (GTCSG). Defined and accepted interdisciplinary standards from the initial meeting were revised based on current scientific developments and clinical results. This cooperating effort increased the quality of the initial recommendations and helped to put the recommendations for diagnosing and treating testicular tumor on a broader scientific basis. METHODS: According to the principles of "evidence-based medicine" (EBM), the Consensus from 1996 was modified, based on the current level of evidence from the published literature. The methodological process and evaluation criteria used were that of the "Cochrane Collaboration". RESULTS: An "Interdisciplinary Update Consensus Statement" summarizes and defines the diagnostic and therapeutic standards according to the current scientific practices in testicular cancer. For 21 separate areas scientifically based decision criteria are suggested. For treatment areas where more than one option exist without a consensus being reached for a preferred strategy, such as in seminoma in clinical Stage I or in non-seminoma Stages CS I or CS IIA/B, all acceptable alternative strategies with their respective advantages and disadvantages are presented. This "Interdisciplinary Update Consensus" was presented at the 24th National Congress of the German Cancer Society on March 21st and subsequently evaluated and approved by the various German scientific medical societies.

Impact of cytotoxic treatment on long-term fertility in patients with germ-cell cancer.

More than half of the patients with testicular germ-cell cancer show impaired spermatogenesis before undergoing cytotoxic treatment. The known pre-treatment infertility and the reversibility of the fertility problems observed in some after successful anti-cancer treatment have so far prevented an assessment of the true role of cytotoxic therapy in long-term fertility. The introduction of wait-and-see strategies (surveillance) for testicular cancer patients and recent prospective trials comparing patients with and without cytotoxic treatment have provided the means for estimating the extent to which treatment itself affects long-term fertility. Whether or not spermatogenesis is irreversibly impaired by chemotherapy is determined by the cumulative dose of cisplatin: at doses below 400 mg/m2, long-term effects on sperm production as well as on endocrine function are unlikely to occur. Higher doses should be expected to cause long-term losses of exocrine and endocrine gonadal function. In contrast, for adjuvant retroperitoneal radiotherapy in stage I seminoma patients, no data are available comparing long-term gonadal function with patients on surveillance. However, using modern radiation techniques, radiation doses to the para-aortic field (< 30 Gy) and testis shielding providing testis scatter radiation (< 30 cG), radiation-induced impairment of fertility is very unlikely.

Bladder neck strictures after radical retropubic prostatectomy: still an unsolved problem.

OBJECTIVE: To investigate the factors responsible for anastomotic strictures of the bladder neck after radical retropubic prostatectomy. PATIENTS AND METHODS: Of 239 consecutive patients who underwent radical retropubic prostatectomy between 1987 and 1996, 36 (15%) developed anastomotic strictures after surgery. The influence of tumour stage, previous prostatic surgery, urinary extravasation and postoperative bacteriuria were assessed. RESULTS: In 21 patients (58%), the bladder neck stricture occurred within 3 months of surgery, in 11 (30%) at 4-12 months after surgery and in four (11%) more than 12 months after surgery; three of these also had local recurrence. Advanced tumour stage and positive margins did not correlate with a higher stricture rate, nor was there a significant difference in stricture rates with three or four anastomotic sutures. However, extravasation at the time of catheter removal (16 of 36 patients (44%) with vs 34 of 183 patients without (19%) stricture, bacteriuria of > 10(6) c.f.u./mL at the time of catheter removal (stricture group 21 of 36 patients (58%) stricture with vs 71 of 203 (35%) without) and previous prostatic surgery (TURP or open surgery, stricture in 28% of those previously operated vs 13% with no previous surgery) were significant risk factors. CONCLUSION: There are three risk factors for anastomotic stricture after radical prostatectomy: previous operations on the prostate, extravasation and asymptomatic bacteriuria.

Single-dose antibiotic prophylaxis in transurethral resection of the prostate: a prospective randomized trial.

OBJECTIVE: To evaluate the efficacy of single-dose antibiotic prophylaxis in transurethral resection of the prostate (TURP). PATIENTS AND METHODS: A total of 139 patients were entered into a prospective randomized trial comparing single-dose antibiotic prophylaxis with no antibiotic before surgery. Twelve patients were excluded because they had significant bacteriuria before surgery (defined as > or = 10(5) bacteria/mL). Of the remaining 127 patients, 62 were allocated to the single-dose group (A) and 65 to the no-antibiotic group (B). All 62 patients in group A received 1 g of ceftriaxone intravenously 1-2 h before surgery with the anaesthetic premedication, the 65 in group B receiving none. Urine cultures were collected post-operatively as the catheter was removed and again 4 weeks after hospitalization. RESULTS: The incidence of post-operative bacteriuria was statistically significantly different, occurring in five patients (9%) in group A and 16 patients (26%) in group B (Fisher's exact test, one-tail P = 0.009). There was no significant difference between the groups 4 weeks after hospitalization. The overall incidence of bacteriuria post-operatively and 4 weeks after hospitalization was 11 patients (18%) in group A and 22 patients (34%) in group B (P = 0.03). CONCLUSION: Single-dose antibiotic prophylaxis with 1 g of ceftriaxone intravenously is effective in patients undergoing TURP and is recommended for such surgery.

[Publications: good or bad? Critical appraisal of scientific publications]. / Publikationen: Gut oder Schlecht? Kritische Betrachtung wissenschaftlicher Publikationen.

Doctors interested in medical research are flooded by publications in numerous scientific journals. Scientific manuscripts manifest, however, a wide range in terms of quality and conclusiveness, irrespective of their scientific context and the reader ought to be able to assess the value of the presented data and information. We have thus compiled a checklist in an attempt to provide the doctor with a relatively simple means of distinguishing between "good" and "bad" publications, even if he/she is not concerned with scientific methodology issues on a routine basis. Some aspects of "publication bias" are also touched upon in order to point out certain problems from the opposite perspective, namely that of the physician concerned with active scientific work.

[An interdisciplinary consensus conference on the diagnosis and therapy of testicular tumors]. / Interdisziplinäre Konsensus-Konferenz zur "Diagnostik und Therapie von Hodentumoren".

In 1988 the German testicular working group was set up by leading experts in the fields of urology, medical and radio-oncology. Since then, the working group has initiated several clinical studies and conferences with the aim of defining current standards in the treatment of testicular germ cell tumours. After a series of preliminary joint meetings with representatives from the AUO, AIO and ARO of the "Deutsche Krebsgesellschaft", a conference was held in May 1996 to agree on a consensus in diagnosis and treatment of testicular germ cell tumours. The standards which have been agreed on at the conference refer to the current international literature and provide recommendations for the majority of clinical situations. Treatment strategies differing from these standards should not be chosen except for well argued individual settings or patients treated in clinical trials. No consensus could be reached for nonseminomatous stage I, IIA and IIB tumours. As a consequence, the differing treatment strategies for these stages are summarized in this paper. A subsequent conference in later years is needed to possibly find an agreement for these tumour stages and to update the current standards according to new clinical experience and knowledge.

Does isoniazid reduce side effects of intravesical bacillus Calmette-Guerin therapy in superficial bladder cancer? Interim results of European Organization for Research and Treatment of Cancer Protocol 30911.

PURPOSE: We analyzed the influence of the tuberculostatic agent isoniazid on the incidence and severity of adverse effects of intravesical bacillus Calmette-Guerin (BCG) therapy in patients with superficial bladder cancer. MATERIALS AND METHODS: In a prospective randomized multicenter study the side effects of intravesical instillations with Tice strain BCG with and without isoniazid were compared in patients with stages pTa and pT1 bladder tumors. Isoniazid was given orally at a dose of 300 mg. daily at every instillation in an attempt to decrease the side effects of BCG. RESULTS: No differences in local or systemic adverse reactions after intravesical immune therapy with BCG could be observed between patients treated with or without prophylactic isoniazid therapy. However, analysis of liver function tests after BCG with isoniazid showed slightly more liver toxicity compared to BCG alone. CONCLUSIONS: Prophylactic administration of isoniazid during BCG instillations provides no decrease in any known side effect of BCG. In contrast, transient liver function disturbances are encountered slightly more frequently when isoniazid is administered. The use of prophylactic isoniazid in patients treated with BCG is not recommended.

Testis-preserving surgery in bilateral testicular germ cell tumours.

OBJECTIVE: To evaluate the indications, techniques and outcome of organ-preserving tumour enucleation in patients with bilateral testicular germ cell tumours (BTGCT) rather than standard bilateral radical orchidectomy which results in loss of fertility and a lifelong requirement for androgen replacement. PATIENTS AND METHODS: In 13 patients with BTGCT of 6-30 mm in diameter, the tumours were enucleated under cold ischaemia after inguinal testicular exploration, and biopsies of the tumour bed and the peripheral parenchyma were taken. Histology of the orchidectomy specimen revealed a seminoma in four cases, an embryonal carcinoma in three, a teratocarcinoma and a mixed-germ cell tumour in two each, and a mature teratoma in one. Histology of the enucleated tumours showed a seminoma in seven cases, an embryonal carcinoma in five and a mature teratoma in one. Six of the 13 patients underwent testicular radiation (20 Gy) for carcinoma in situ (CIS) and five patients had adjuvant local therapy. Six months postoperatively a testicular biopsy was taken to determine the success of therapy. RESULTS: The median follow-up was 62 months (range 14-163) and the 13 patients are currently free of disease; one patient had local recurrence 9 months after tumour enucleation but after orchidectomy the patient is free of disease after a follow-up of 156 months. Serum concentrations of luteinizing hormone and testosterone were within the normal range in all patients and no androgen substitution was necessary. A testicular biopsy taken 6 months post-operatively revealed Sertoli cells only in all patients who had received radiation therapy. CONCLUSIONS: These results suggest that organ-sparing surgery in patients with BTGCT represents a new therapeutic approach with endocrinological and psychological advantages. In our experience, enucleation resection of testicular tumours is possible with certain prerequisites, i.e. the tumour is organ-confined with no infiltration of the rete testis, multiple biopsies of the tumour bed and peripheral parenchyma should be taken, any associated CIS treated by radiation therapy, and patients must be followed closely.

Clinical usefulness of percentage of free serum prostate specific antigen.

Serum concentrations of total and free prostate specific antigen were measured retrospectively in 268 patients, in order to test the usefulness of percentage of free prostate specific antigen in distinguishing between cancer and benign hyperplasia of the prostate and to improve the specificity of cancer screening. Four groups were investigated: 94 urologic patients without prostate disease (controls), 98 patients with a histologically confirmed benign hyperplasia, 76 with histologically established prostatic adenocarcinoma, 18 of them after radical prostatectomy. Total and free prostate specific antigen concentrations were measured in frozen serum, in a retrospective mode, by using an equimolar monoclonal antibody immunoassay. Median percentage of free prostate specific antigen was 20.48% in controls, 17.75% in patients with hyperplasia, 10.52% in patients with cancer and 33.03% in patients after prostatectomy. Median percentage of free prostate specific antigen was significantly lower in men with cancer than in patients with benign hyperplasia (P < 0.0001). The percentage of free prostate specific antigen increased the specificity of cancer screening: a cut-off of 23.6% detected at least 90% of cancers and would have eliminated 34.7% of biopsies in benign hyperplasias. A prospective study is ongoing to confirm these results.