[Secondary malignancies in urinary diversions]. / Sekundärmalignome in Harnableitungen.

In contrast to ureterosigmoidostomy no reliable clinical data exist for tumor risk in different forms of urinary diversion using isolated intestinal segments.In 44 German urological departments, operation frequencies, indications, patient age, and operation dates of the different forms of urinary diversion, operated between 1970 and 2007, could be registered. The secondary tumors up to 2009 were registered as well and related to the numbers of the different forms of urinary diversions resulting in tumor prevalences.In 17,758 urinary diversions 32 secondary tumors occurred. The tumor risk in ureterosigmoidostomy (22-fold) and cystoplasty (13-fold) is significantly higher than in other continent forms of urinary diversion such as neobladders or pouches (p<0.0001). The difference between ureterosigmoidostomy and cystoplasty is not significant, nor is the difference between ileocecal pouches (0.14%) and ileal neobladders (0.05%) (p=0.46). The tumor risk in ileocecal (1.26%) and colonic neobladders (1.43%) is significantly higher (p=0.0001) than in ileal neobladders (0.5%). Of the 16 tumors that occurred following ureterosigmoidostomy, 16 (94%) developed directly at the ureterocolonic borderline in contrast to only 50% following urinary diversions via isolated intestinal segments.From postoperative year 5 regular endoscopic controls of ureterosigmoidostomies, cystoplasties, and orthotopic (ileo-)colonic neobladders are necessary. In ileocecal pouches, regular endoscopy is necessary at least in the presence of symptoms or should be performed routinely at greater intervals. Following neobladders or conduits, only urethroscopies for urethral recurrence are necessary.

[Sentinel node dissection in prostate cancer: current status]. / Sentinel-Lymphadenektomie beim Prostatakarzinom - Aktueller Stand.

Sentinel lymph node (SLN) dissection is an excellent staging procedure with high sensitivity (>95%) for detecting positive nodes. When the sentinel node is negative, there is high certainty that other lymph nodes are also negative. Limitations of this technique include the use of hormone therapy over several months and a preceding transurethral resection or suprapubic adenomectomy. When sentinel node dissection is performed in patients with intermediate and high-risk prostate cancer, it should be kept in mind that when the SLN is positive, other lymph nodes can be positive, too. The positive non-SLN can be located outside the SLN region. Therefore, both sentinel and extended lymph node dissection should be used in men with a higher risk of lymph node metastases.

[Sentinel lymph node dissection in prostate cancer. Experience after more than 800 interventions]. / Sentinel-Lymphadenektomie beim Prostatakarzinom. Erfahrungen nach über 800 Eingriffen.

There is no consensus on which prostate cancer patients should undergo lymph node removal and which lymph nodes should be included. Therefore, most clinicians rely on nomograms and dispense with lymph node dissection in patients with low-risk disease. Meanwhile, there are some studies which prove that there are also lymph node metastases in patients with low-risk prostate cancer and that lymph node metastases are predominantly localized outside the region of standard lymphadenectomy. In more than 800 men we could show that lymph node metastases were found more often than shown in the Partin tables. These lymph node metastases were detected by sentinel lymph node dissection outside the region of standard and extended lymphadenectomy. Because of insufficient preoperative diagnostics it is unclear which patients have positive lymph nodes. Therefore, it is useful to perform lymph node dissection in every patient. Men with positive nodes could have a better prognosis, when sentinel and extended lymph node dissection are performed.

[Pain therapy of urologic tumors -- prophylaxis and therapy of side effects]. / Schmerztherapie bei urologischen Tumoren -- Prophylaxe und Therapie der Nebenwirkungen.

Pain is a cardinal symptom in 70 % of cancer patients. Even in developed countries, 30 to 80 % of these patients are inadequately treated. The main cause for this lack of care is not pain refractory to treatment but inadequate or incorrect use of analgesic drugs. A sufficient treatment of pain requires knowledge of the pathomechanism of pain and of the basics of pain management in cancer patients. The choice of analgesic drugs follows the WHO-recommended increase based on need. As long as possible, analgesic drugs should be given orally following a strict schedule and pre-emptively prior to renewed pain. The non-opioids are a heterogeneous group of drugs with different actions and side effects. Maximum doses exist for this group and weak opioids. A change to strong opioids is indicated when weak opioids fail to achieve sufficient pain control despite titration to the maximum dose. No upper limit exists for strong opioids and their use is limited by the side effects. The most frequent side effects are initial emesis and vomiting as well as long-lasting constipation. For this reason, most patients should be prescribed a temporary antiemetic and a laxative on a permanent basis.

[Renal neurilemoma--a rare differential diagnosis of renal tumors]. / Das Schwannom der Niere - Eine seltene Differenzialdiagnose renaler Raumforderungen.

Neurilemomas originate from the Schwann cells of nerve sheaths. They can occur ubiquitously as benign or malign variants. Renal neurilemomas are extremely rare. Imaging does not allow a certain diagnosis. Complete tumor resectioning is the only curative therapy. Effective conservative treatment is not known. Histological criteria of renal neurilemoma are: mesenchymal, spindle cell, capsulated tumor intensely positive to S-100 antiserum. Epithelial markers do not react.

[Value of sentinel node biopsy for urological tumors]. / Wertigkeit der Sentinel-Lymphknotenbiopsie bei urologischen Tumoren.

Gamma probe-guided lymphadenectomy of prostate cancer that is presumed to be localized furnishes evidence that lymphogenous spread of the disease is present considerably more often and earlier than previously assumed, even when the clinical stage is considered localized. Multiinstitutional trials have confirmed that in principle sentinel lymphadenectomy on its own is able to detect lymph node positive patients with minimal complications and a sufficient degree of certainty. Sentinel lymphadenectomy for penile cancer is an undemanding surgical procedure and in contrast to inguinal lymphadenectomy can be considered minimally invasive. Decisions on indication and necessity for an additional inguinal lymphadenectomy depending on tumor stage and local findings in the inguinal lymph nodes are handled quite differently in various centers and should be further standardized. The most recent studies on sentinel lymphadenectomy for urinary bladder and testicular cancer demonstrate that on principle the procedure is likely feasible also for these tumor entities. Whether it is possible to replace standard treatment methods with these procedures or at least have them serve an ancillary function remains to be determined in further investigations. Basically, the premise holds true that for all urological tumor entities before standard diagnostic techniques are abandoned, the value of exclusively performing sentinel lymphadenectomy must be adequately validated. It does not suffice to rely on the results from other working groups. It is in fact essential that the accuracy of the method - the feasibility of which can be influenced by numerous factors - be assessed by comparison with a standard lymphadenectomy performed in one's own center.

[Unenhanced spiral computerized tomography in acute diagnosis of flank pain. Examination in contraindications for contrast medium administration]. / Native Spiral-Computertomographie in der Akutdiagnostik von Flankenschmerzen. Untersuchung bei Kontraindikationen zur Kontrastmittelgabe.

The diagnostic value of unenhanced helical computed tomography was investigated in a prospective study. In 53 patients (aged 35 to 82 years) with acute flank pain tomography was performed in addition to abdominal plain film and ultrasound examination. All 53 patients had a contraindication for intravenous administration of contrast medium. Ureteral calculi were either confirmed or excluded by retrograde ureteropyelography in 44 cases, in 9 patients by asservation of calculi and clinical follow-up. Helical computed tomography was able to precisely identify all of the 34 ureteral calculi, whereas abdominal plain films led to 6 false positive and 17 false negative findings. In 1 patient with retroperitoneal lymphoma (diagnosed by CT) false positive findings occurred. Unenhanced helical computed tomography reaches a distinctively increased diagnostic value (sensitivity 100%, specificity 95%, accuracy 97%) in the evaluation of acute flank pain as compared to conventional radiologic imaging and ultrasound. This non-invasive procedure is to be considered method of choice for patients with contraindications for the application of radiopaque material.

Radioisotope guided pelvic lymph node dissection for prostate cancer.

PURPOSE: The localization of lymph node metastases in prostate cancer varies enormously. Due to high morbidity complete pelvic lymphadenectomy is often decreased to modified staging lymphadenectomy, resulting in loss of sensitivity for detecting micrometastases. Based on the promising results of intraoperative gamma probe application for identifying sentinel lymph nodes in malignant melanoma, breast and penis cancer, we identified sentinel lymph nodes in prostate cancer using a comparable technique. MATERIALS AND METHODS: In 117 patients 99mtechnetium nanocolloid was transrectally injected directly into the prostate under ultrasound guidance 1 day before pelvic lymphadenectomy. Thereafter dynamic lymphoscintigraphy was done. Initially lymph nodes identified as sentinel lymph nodes by the gamma probe were removed and subsequently modified pelvic lymphadenectomy was performed. RESULTS: Lymphatic metastasis was detected in 28 cases. An average of 4 sentinel lymph nodes were identified per patient in 25 of 27 patients with micrometastasis, of which those in 24 contained micrometastasis for 96% sensitivity. In contrast, sensitivity of modified pelvic lymphadenectomy was 81.5%. In 16 patients only sentinel lymph nodes were positive. An average of 21.8 lymph nodes (range 10 to 51) was dissected per patient at pelvic lymphadenectomy. Lymph node metastasis was noted in 6 of the 46 patients with a prostate specific antigen between 4 and 10 ng./ml. and in 8 of the 64 with a stage pT2 tumor. CONCLUSIONS: Our study shows individual variability of lymphatic drainage of the prostate and limited sensitivity for detecting positive lymph nodes when the pelvic dissection area is limited. Furthermore, our experience implies that the identification of sentinel lymph nodes is feasible, not only in breast cancer and malignant melanoma, but also in prostate cancer using a comparable technique.

Disseminated cytokeratin positive tumor cells in the bone marrow of patients with prostate cancer: detection and prognostic value.

PURPOSE: Previous investigations have shown that cytokeratin 18 positive bone marrow cells in localized and lymphatically spread prostate cancer correlates with neither established prognostic factors nor with the biochemical and clinical course after radical prostatectomy. Since the well-known down-regulation of cytokeratin 18 in tumor cells may lead to false-negative results, we asked whether staining with a pan-cytokeratin antibody recognizing a common epitope of cytokeratins 8, 18 and 19 would result in different data. MATERIALS AND METHODS: Preoperative bone marrow aspirates of 82 patients with localized (N0) and lymphatically spread (N1) prostate cancer were examined using the monoclonal antibody cytokeratin 2 and the pan-cytokeratin antibody A 45-B/B3, called A 45. RESULTS: In contrast to findings with the cytokeratin 18 antibody, those with the pan-cytokeratin antibody correlated with the biochemical course. At a median followup of 1,477 days (4 years) patients with pan-cytokeratin positive cells in the preoperative bone marrow aspirate had biochemical progression significantly earlier than those with pan-cytokeratin negative results (mean time to prostate specific antigen relapse 886 versus 1,409 days, p < or =0.004). Compared with other parameters, such as prostate specific antigen, pathological stage and Gleason score, preoperative pan-cytokeratin findings proved to be an independent prognostic factor. CONCLUSIONS: Cytokeratin positive cells in the bone marrow also have prognostic relevance in prostate cancer. The comprehensive analysis of these cells, studies of the individual course of these findings and sufficiently long followup allow us to discuss whether and under what conditions metastasis may develop from 1 or several cytokeratin positive cells.

Biochemical course after radical retropubic prostatectomy: preliminary results.

OBJECTIVE: To investigate prognostic factors in localized and lymphatically spread prostate cancer. METHODS: The biochemical course after radical retropubic prostatectomy in 306 patients was subject to a retrospective analysis. RESULTS: Prostate-specific antigen (PSA), Gleason score (prostatectomy specimen) and pathological stage proved to be prognostically relevant (p < 0.0001). PSA, Gleason score and tumor stage also were to be considered as (independent) prognostic factors by means of a multivariate analysis (p < 0.001), whereas perineural invasion (prostatectomy specimen) and preoperative bone marrow findings (CK 2) had no impact on the course of the disease. After a median follow-up of 1,307 days (3.6 years), a biochemical relapse occurred in 41.8%. CONCLUSION: High preoperative PSA values and the resulting high portion of advanced tumor stages are a possible basis for the high biochemical relapse rate in our collective. The learning curves of several surgeons and the previously more restrictive pelvic lymphadenectomy (surgical understaging) may also be considered causes.

Unenhanced helical computed tomography in the evaluation of acute flank pain.

OBJECTIVE: The diagnostic value of unenhanced helical computed tomography (CT) for the evaluation of acute flank pain is investigated in a prospective study. PATIENTS AND METHODS: In 125 patients aged 18-86 years, we performed unenhanced helical CT in addition to abdominal plain film, abdominal ultrasound and urinalysis as a diagnostic measure for acute flank pain. Ureteral calculi were confirmed or, respectively, excluded by retrograde ureteropyelography in 80 cases. In the other cases, diagnosis was verified by clinical course and/or stone asservation. RESULTS: In 91 of 125 patients the flank pain was caused by a ureteral calculus. In 67 of 91 patients with urolithiasis, stones could be collected for analysis. Helical CT was able to precisely identify 90 ureteral calculi. Abdominal plain films led to 8 false-positive and 48 false-negative findings. Thus, sensitivity of plain radiography, ultrasound and urinalysis was 47, 11 and 84% with a specificity 76, 97 and 32%, respectively. CONCLUSIONS: Unenhanced helical CT reaches a distinctively increased diagnostic value (sensitivity 99%, specificity 97%) in the evaluation of acute flank pain as compared to plain radiography, ultrasound and urinalysis.

First experience with gamma probe guided sentinel lymph node surgery in penile cancer.

Because of the curative approach, the detection of lymph node metastases in squamous cell carcinoma (SCC) of the penis is of significant clinical relevance. Sentinel lymph node (SLN) identification by means of lymphangiography has been proven to be insufficiently safe. However, the high morbidity of inguinal lymphadenectomy and the considerable individual variability regarding the location of lymph node metastases justify the necessity of a technique that enables the identification of SLNs. Since 1998, SLNs have been intraoperatively identified and selectively dissected, after peritumoral injection of technetium-99m nanocolloid and using lymphoscintigraphy, in three patients (one with malignant melanoma and two with SCC). At least one SLN could be detected in each patient. The maximum surgical time was 30 min. There were no severe complications. Lymph node metastases did not occur in any patient. Upon a mean follow-up of 10 months, all patients are currently free of tumor. Owing to the long-term results of sentinel lymphadenectomy in malignant melanoma of other locations and our preliminary results with respect to penile carcinoma. we consider the current method appropriate as the only primary operation for lymph node staging in early stages and, in combination with modified inguinal lymphadenectomy, in locally advanced stages.

The sentinel lymph node concept in prostate cancer - first results of gamma probe-guided sentinel lymph node identification.

OBJECTIVE: The goal of this study was to show lymphatic drainage and to verify the validity of lymphoscintigraphy for the identification of the sentinel lymph node (SLN) in prostate cancer. Furthermore, the question is to be raised whether the standardized pelvic lymphadenectomy is a sufficient means for also detecting solitary micrometastases. PATIENTS AND METHODS: Eleven patients with prostate cancer received a sonographically controlled, transrectal administration of a technetium-99m colloid injected directly into the prostate 1 day prior to pelvic lymphadenectomy. 20 min later the dynamic lymphoscintigraphy was carried out. During surgery, the SLNs were identified by using a gamma probe. The standard pelvic lymphadenectomy was performed after removal of the SLN. RESULTS: In 3 of 4 patients with micrometastasis the spread of the tumor could exclusively be found in those nodes which had been identified as SLNs by means of scintigraphy by combining preoperative lymphoscintigraphy and intraoperative gamma probe detection. In 2 cases, the pathologically proved SLNs were situated at the anteromedial region of the internal iliac artery, thus being located outside of the standard pelvic lymphadenectomy area. In 1 patient, however, the micrometastasis was found beyond those nodes which had been identified as SLN intraoperatively. CONCLUSIONS: In the future, we expect the restriction of pelvic staging lymphadenectomy to scintigraphically proved SLN. The perioperative morbidity may be reduced by increasing the sensitivity of the detection of micrometastases. Our data confirm earlier perceptions, according to which even modified standardized pelvic lymphadenectomy is considered insufficient in terms of the detection of micrometastases.

Does the immunocytochemical detection of epithelial cells in bone marrow (micrometastasis) influence the time to biochemical relapse after radical prostatectomy?

The detection of cytokeratin-positive bone marrow cells has been considered a prognostic factor in numerous malignant tumors. We investigated whether this was also valid for localized prostate cancer. Bone marrow aspirates were taken prior to radical prostatectomy from 169 consecutive patients with pT1/2 pN0 G1-3 adenocarcinoma of the prostate. The immunocytochemical detection of cytokeratin no. 18 (CK 18)-positive cells using monoclonal antibody CK 2 was interpreted as micrometastasis. Repeat marrow aspirations were performed at 6 months postoperatively and once a year thereafter. The patients were re-examined over a period of at least 10 and a maximum of 72 months (median 32 months). An increase in prostate specific antigen >/=0.5 ng/ml was considered a biochemical "relapse". One hundred and fifty-four patients had evaluable bone marrow aspirates, of which 74.7% were CK 18-negative and 25.3% positive. The latency period for biochemical relapse was 1481 days (median) in the CK 18-negative group and 1106 days (median) in the CK 18-positive group. This difference was not statistically significant. The CK 18-positive aspirates (n = 39) showed one positive cell in 20 cases, two positive cells in 8 and three or more positive cells in 11 cases. The preoperative number of cells had no statistically significant effect upon the onset of biochemical relapse. Only patients with three or more CK 18-positive cells tended to have a poorer prognosis. One hundred and thirteen patients had evaluable bone marrow aspirates pre- and postoperatively. Postoperative persistence or occurrence of CK 18-positive cells did not affect the outcome of the disease. The detection of CK 18-positive cells in bone marrow does not influence the prognosis of patients with localized prostate cancer within a period of 32 months (median). Solely a subgroup of patients showing a large preoperative number of CK 18-positive cells seems to tend to an unfavorable course of the disease. Thus, further studies are necessary aiming at a more detailed characterization of these cells.

Does the immunocytochemical detection of epithelial cells in bone marrow (micrometastasis) influence the time to biochemical relapse after radical prostatectomy?

The detection of cytokeratin-positive bone marrow cells has been considered a prognostic factor in numerous malignant tumors. We investigated whether this was also valid for localized prostate cancer. Bone marrow aspirates were taken prior to radical prostatectomy from 169 consecutive patients with pT1/2 pNO G1-3 adenocarcinoma of the prostate. The immunocytochemical detection of cytokeratin no. 18 (CK 18)-positive cells using monoclonal antibody CK 2 was interpreted as micrometastasis. Repeat marrow aspirations were performed at 6 months postoperatively and once a year thereafter. The patients were re-examined over a period of at least 10 and a maximum of 72 months (median 32 months). An increase in prostate specific antigen > or = 0.5 ng/ml was considered a biochemical "relapse". One hundred and fifty-four patients had evaluable bone marrow aspirates, of which 74.7% were CK 18-negative and 25.3% positive. The latency period for biochemical relapse was 1481 days (median) in the CK 18-negative group and 1106 days (median) in the CK 18-positive group. This difference was not statistically significant. The CK 18-positive aspirates (n = 39) showed one positive cell in 20 cases, two positive cells in 8 and three or more positive cells in 11 cases. The preoperative number of cells had no statistically significant effect upon the onset of biochemical relapse. Only patients with three or more CK 18-positive cells tended to have a poorer prognosis. One hundred and thirteen patients had evaluable bone marrow aspirates pre- and postoperatively. Postoperative persistence or occurrence of CK 18-positive cells did not affect the outcome of the disease. The detection of CK 18-positive cells in bone marrow does not influence the prognosis of patients with localized prostate cancer within a period fo 32 months (median). Solely a subgroup of patients showing a large preoperative number of CK 18-positive cells seems to tend to an unfavorable course of the disease. Thus, further studies are necessary aiming at a more detailed characterization of these cells.

Metabolic changes and urodynamic findings after continent urinary diversion.

Methods of creating continent urinary diversions were developed in the mid-1980s (neobladder, pouch) providing patients with continence and anatomically appropriate voluntary urine discharge. In a follow-up investigation on 18 patients, the question to be clarified was whether continent urinary diversion meets the demands of an ideal bladder substitute. Follow-up examination showed normal clinical test values almost without exception. Only five out of 18 patients had discrete acidosis. Neither malabsorption syndrome nor any disorder of vitamin D3 metabolism was found. Ultrasonography and X-ray diagnostics showed normal conditions, without stones and reflux. Urodynamic investigations revealed that bladder emptying was almost free of residual urine, and continence was largely undisturbed. In accordance with these data, there is almost perfect patient acceptance. At present, there are still no sufficient data on the risk of tumour induction, since the latency period required (about 20 years) in most cases has not yet been reached. Since there are currently numerous publications on "urinary diversion carcinoma", consistent follow-up is necessary comprising not only the metabolic, but also the oncological risks of urinary diversion via intestinal segments.

Improved discrimination of prostate cancer and benign prostatic hyperplasia by means of the quotient of free and total PSA.

The value of t-PSA (total prostate specific antigen) and of the quotient of free and t-PSA (% f-PSA) for the discrimination of BPH (benign prostatic hyperplasia) and PC (prostate cancer) as well as possible influencing factors were subject to examination under study conditions. The sera of 210 patients (131 BPH, 79 PC patients) were examined by means of the Immulite test; thereof 76 male patients (47 BPH, 29 PC patients) were found to have a t-PSA-value between 4 and 10 ng/ml (grey area). Apart from the age and the findings of rectal digital examination, we recorded the prostate volume, indications of non-specific increases in PSA and for PC patients also the TNM-G stage. For patients with prostate cancer the quotient of f- and t-PSA was significantly lower (median: 0.08) than compared to patients with BPH (median: 0.22) (p<0.001). Also in the grey area the quotient was significantly lower in patients with malignant diagnosis (median: 0.12) than for patients with a non-malignant diagnosis (median: 0.21) (p<0.001). ROC curves were prepared in order to compare the capability of discrimination of the two parameters. At this point, the better discrimination potential of the quotient in the grey area became evident. Due to the fact that priority was given to the detection of carcinoma, the threshold value was defined at a level at which high sensitivity (90%) is existent in combination with an acceptable specificity (approx. 50%). The resultant values are for the total PSA area 0.21, for the grey area 0.19 as a cut-off. Neither the age, nor the prostate volume, nor urinary tract infections had any influence upon the quotient. There was also no correlation between the stage or the grading of the tumour and the percentage of the f-PSA. The quotient alleviates the discrimination between BPH and PC, in particular in the diagnostically problematic grey area. Thus, it can serve as an aid for the decision "biopsy or re-biopsy". As there is currently no standardized method for the application of % f-PSA, there is a requirement for further examination under homogeneous criteria.

[Treatment of benign prostatic hyperplasia]. / Behandlung der benignen Prostatahyperplasie.

Due to innovative pharmacological and endoscopic/interventional concepts of therapy, the strategies of facing the benign prostatic hyperplasia have undergone a significant diversification within the last ten years. In addition to phytotherapeutic drugs, which have been in clinical use for decades, alpha receptor blockers and blockers of DHT-synthesis have gained increasing importance. More or less convincing instrumental competing methods have been developed as an alternative to the transurethral resection of the prostate or the transvesical prostatectomy. Regarding the altered age pyramid structure and decreasing financial means, guidelines for the diagnosis and therapy of the BPH-syndrome are consequently being developed in order to support the establishment of an individual therapy of BPH, to increase the efficacy of therapy and to be able to get along with the existing financial barriers. The development of the International Prostate Symptoms Score (IPSS) is regarded essential for this effort.