Validation of sentinel lymph node dissection in prostate cancer: experience in more than 2,000 patients.

PURPOSE: Sentinel lymph node dissection (SLND) has replaced extended lymphadenectomy for nodal staging in several solid tumours. We present our results of SLND in prostate cancer in regard to detection and false-negative rate. METHODS: In a 2-day protocol about 300 MBq (99m)Tc-nanocolloid are injected into the prostate. Two hours later static scans of the pelvis are performed to get information about the number and location of radioactive lymph nodes. During surgery the radioactive nodes are excised with the help of a gamma probe and sent separately to the pathologist. The histological procedure includes haematoxylin and eosin staining, serial sections and immunohistochemistry. RESULTS: Since 1999, a total of 2,020 men underwent SLND alone or in combination with either standard or extended lymphadenectomy after radical retropubic prostatectomy. Lymph nodes positive for metastases were found in 16.7% of patients. The scintigraphic detection rate was 97.6% and the intraoperative detection rate 98%. For 187 lymph node-positive men who had either standard or extended lymphadenectomy in addition to SLND the false-negative rate could be calculated, resulting in false-negative findings in 11 of 187 patients (6%). CONCLUSION: Our results demonstrate that SLND in prostate cancer is a reliable procedure for nodal staging.

[How do residents in urology evaluate their daily routine at work-a survey analysis]. / Wie wird der Berufsalltag von Weiterbildungsassistenten in der Urologie in Deutschland bewertet ­ eine Fragebogenanalyse.

BACKGROUND: The changing conditions in German hospitals is causing a shortage of young people. In order to identify starting point for improvements, the Bavarian association of urologists in collaboration with the German Society of Residents in Urology (GeSRU) conducted an online survey among residents in urology in summer of 2017. MATERIALS AND METHODS: A standardised survey composed of 38 questions was distributed to participants through a mailing list of the GeSRU. Most questions were closed-ended; however, some did allow participants to respond by means of an open-ended answer. RESULTS: A total of 218 participants provided a total of 11,764 responses: 58% were female and 42% were male. Over 70% were aged between 31 and 35 years. In all, 29% of participants responded negatively to the question asking whether they feel like their medical studies at university prepared them well for the daily routine in their workplace. Participants particularly demanded a higher degree of practical experience during their studies, as well as more teaching of soft skills. In relation to choosing their specialisation, participants considered the intern year and their clinical traineeships as crucial factors. Participants did express appreciation of their field of specialization in relation to the broad range of available treatments, the opportunity of further specialising, the clientele of patients, the opportunity of working in a small team, innovations, and the high possibilities of opening their own medical practice. On a personal level, participants specifically wished for a more structured plan relating to their further internship, involving regular meetings. They also expressed the wish for more personalised career plans, more flexible work hours, and improved advanced training, both internally and externally. CONCLUSIONS: With the aim of making urology even more attractive, participants' wishes and suggestions should be taken into consideration. These, in general, involve a more structured training plan, better working conditions with part-time programmes, and improved surrounding conditions at the workplace, in particular for families.

[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.

[Non-muscle-invasive bladder cancer: Information transfer from the clinic to the doctor's office : Results of a questionnaire study and presentation of a software solution]. / Nicht muskelinvasives Harnblasenkarzinom: Risikostratifizierung und Befundweitergabe : Ergebnisse einer Fragebogenstudie und Vorstellung einer Softwarelösung.

BACKGROUND AND OBJECTIVES: The adjuvant treatment of non-muscle-invasive bladder cancer (NMIBC) is based on the individual risk profile (RP) and its sufficient transfer from the clinic to the doctor's office. The objectives of our study were to verify the importance and degree of transfer of RP and recommendation for risk-adapted adjuvant treatment (RAAT) in patients with NMIBC as well as to develop appropriate tools for this purpose, if necessary. MATERIALS AND METHODS: An email-based survey distributed to urologists in Brandenburg, Berlin, Bavaria and Lower Saxony explored the questions mentioned above. In addition, a tool for risk stratification and information transfer for patients with NMIBC was developed and validated. RESULTS: From a total of 134 questionnaires analyzed, 55 were from clinic urologists (CUs) and 79 were from ambulant urologists (AUs). Although 9 out of 10 urologists considered the RP of importance, only 29 % of CUs and 24 % of AUs (p = 0.553) confirmed that the RP was always mentioned in medical reports. The recommendation for RAAT was confirmed from 62 % of CUs and 20 % of AUs (p < 0.001). A recommendation for RAAT in the medical report was requested by 86 % of AUs. The risk calculator presented here - to our knowledge the first with integration of the 2004 WHO grading - is delivered in all mathematically possible constellations a RP, according to guideline recommendations. CONCLUSION: Urologists in the clinic and doctor's office both attach considerable importance to the determination and transfer of RP and the recommendation for RAAT. There was evidence to suggest an overestimation of the quality of medical reports by the CU. The risk calculator provides an easy and cost-neutral option to improve risk stratification and information transfer from the clinic to the doctor's office.

Establishment of micrometastatic carcinoma cell lines: a novel source of tumor cell vaccines.

BACKGROUND: Cancer cells of microscopic metastases can be envisaged as ideal constituents for the development of a genetically modified, autologous tumor cell vaccine. However, their extremely low number has thus far blocked this approach. PURPOSE: The aim of this study was to culture micrometastatic tumor cells present in bone marrow of patients with various forms of epithelial cancer and to thereby establish immortalized cell lines. METHODS: Bone marrow aspirates from the upper iliac crest of 152 patients with cancer of the prostate, kidney, lung, breast, or colorectum were cultured at 1 x 10(7) to 6 x 10(7) mononuclear cells (MNC) per flask in fetal calf serum-containing RPMI-1640 medium supplemented with 10 ng/mL epidermal growth factor and 10 ng/mL basic fibroblast growth factor. The proliferation of epithelial cells on extracellular matrix-coated plates was monitored by sampling and staining aliquots with cytokeratin-specific antibodies. After 3-6 weeks in culture, the cells were transferred to Petri dishes, and 200-300 epithelial cells per plate were microinjected with DNA encoding for the simian virus 40 (SV40) large T antigen. Cells were screened at various time points for expression of large T antigen and epithelial markers, such as cytokeratins, prostate-specific antigen, prolactin-inducible protein, or intestinal-specific annexin; their bone marrow-seeking potential was tested in immunodeficient SCID (i.e., severe combined immunodeficiency) mice given subcutaneous transplants of the immortalized cells. RESULTS: Prior to culture, more than 90% of all samples presented with fewer than 10 tumor cells per 8 x 10(5) MNC. In 68 cases (44.7%), the established culture conditions allowed a two to four log transient expansion of these cells with rather small differences among the tumor types studied. Epidermal growth factor and basic fibroblast growth factor were found to be essential for this culture system. After microinjection of the propagated cells with T-antigen DNA, permanent cell lines were obtained; some of these cell lines (prostate and lung cancer cell lines) are now beyond culture passage 80. The cells showed no notable changes in the pattern of expressed epithelial antigens and were able to disseminate into bone marrow in SCID mice. CONCLUSIONS: This procedure allows the selective immortalization of micrometastatic carcinoma cells. Integration of SV40 DNA and expression of T antigen did not substantially change the epithelial phenotype of the propagated cells. IMPLICATIONS: The established system will allow an in-depth molecular analysis of human micrometastatic cancer cells and could become a useful source for the generation of autologous tumor cell vaccines.

[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.

Micrometastases of bone marrow in localized prostate cancer: correlation with established risk factors.

PURPOSE: The presence of cytokeratin 18-positive cells in bone marrow correlates with conventional risk factors in many tumors. We examined whether this was also valid for localized or lymphatically spread prostate cancer. PATIENTS AND METHODS: Immediately before radical prostatectomy, bone marrow aspirates from both sides of the iliac crest were taken from 287 patients. The presence of cells containing cytokeratin 18 was interpreted as micrometastasis. RESULTS: In patients with negative lymph nodes (n = 219), conventional risk factors (Gleason score, pathologic stage, ploidy, and preoperative prostate-specific antigen) did not correlate with the preoperative detection of cells containing cytokeratin 18. There was also no correlation with lymph node metastases. Furthermore, there was no interdependency between the preoperatively detected number of cells and the established risk factors. CONCLUSION: We assume the presence of epithelial cells in bone marrow to be an independent parameter, the clinical importance of which must be substantiated by further studies.

[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.

[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.

[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.

Detection of genetic alterations in micrometastatic cells in bone marrow of cancer patients by fluorescence in situ hybridization.

Detection of micrometastatic tumor cells in bone marrow of cancer patients has been shown to be of prognostic significance. To further characterize these cells, we combined antibody labeling and fluorescence in situ hybridization (FISH). For detection of numerical changes of chromosome 17, nine patients with proven breast cancer whose bone marrow contained epithelial tumor cells were evaluated. Epithelial cells were stained by anticytokeratin antibody. Afterwards FISH was performed using an alpha-satellite probe specific for chromosome 17. In a second series bone marrow epithelial cells of eight patients with breast cancer and of six with prostatic cancer were evaluated for the amplification of HER-2/neu by using a gene-specific DNA probe. In the first series four patients had only single epithelial cells in their bone marrow. Only one single cell showed five hybridization signals, whereas all other single cells showed two or less. Five patients had clusters of epithelial cells in bone marrow with or without additional single cells. One hundred four cells had three or more hybridization signals and 103 of these polysomic cells were located in tumor cell clusters. In the second series we could detect HER-2/neu amplification in bone marrow epithelial tumor cells in two of eight patients with breast cancer but in none of the prostatic cancer patients. These results show that it is possible to detect numerical chromosomal changes and oncogene amplification in bone marrow micrometastatic epithelial cells of cancer patients by combining immunophenotyping and FISH.

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.

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.

[Evaluation of new technical alternative procedures for therapy of symptomatic benign prostatic hyperplasia]. / Bewertung neuer technischer Alternativverfahren zur Therapie der symptomatischen BPH.

Transurethral resection of the prostate is still the gold standard in the treatment of symptomatic benign prostatic hyperplasia. It has proved possible to reduce the mortality of this treatment almost to zero, while the morbidity has remained unchanged at 18% for decades. Therefore, understandably, procedures are being looked for that will be similarly effective but have lower morbidity. Current developments in this field are transurethral implants (spiral, intraurethral catheter, Wall-Stent), the balloon dilatation, transurethral incision (TUIP), laser therapy (TULIP, ITK), ultrasound-induced aspiration of tissue and heat treatment (hyperthermia, thermotherapy). Chances and risks inherent in these different technical procedures and the amount of investment they involve are reviewed. Potential for the future can at best be attributed to the Wall-Stent, TUIP, the application of laser and the thermotherapy.

[Pain therapy and quality of life]. / Schmerztherapie und Lebensqualität.

In the treatment of advanced hormone-resistant prostate cancer, the aim is an improvement in quality of life since treatment strategies are merely palliative and life cannot be prolonged. Therapy is based on medical pain relief for different aspects of pain without seriously affecting activity and quality of life. With respect to therapy of chronic pain, Germany can be regarded as a developing country. It is definitely in the interest of urological cancer patients that this situation will be finished.

[Stage-adapted pain therapy in advanced malignant urologic diseases]. / Stadienadaptierte Schmerztherapie bei fortgeschrittenen urologischen Malignomerkrankungen.

In advanced urological malignant diseases pain therapy is frequently of prime importance. Considerable progress in this area has led to the treatment of pain being taken on increasingly by specialized groups, in some cases without feedback to the urologist. In this situation it seems expedient for a urologist working in the field of oncology to be thoroughly informed of the present status of knowledge in modern pain treatment. The opportunities opened up by interdisciplinary team work directed by a urologist are pointed out, as are the requirements this imposes. The current chances of medicamentous cancer pain therapy and the treatment options in the fields of anaesthesiology, neurology and neurosurgery are touched upon with reference to the pathophysiology of chronic painful conditions.

[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.

[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.

[Pelvic lymph node dissection. Complication management]. / Pelvine Lymphadenektomie. Komplikationsmanagement.

Extended pelvic lymph node dissection allows exact lymph node staging and has the potential to improve prognosis. In addition to these advantages, there are some perioperative and postoperative complications. In case of transection of the obturator nerve, a microsurgical end-to-end anastomosis should be performed. The most frequent postoperative complication is (symptomatic) lymphocele which is predominantly diagnosed after extraperitoneal surgery. Meticulous lymph node dissection with clipping of lymphatic vessels, sparing the lateral wall of the external iliac artery from dissection, sufficient postoperative drainage, and application of low molecular weight heparin in the upper arm may reduce their incidence. Instillation of sclerosing agents and sufficient drainage are normally successful. If not, laparoscopic fenestration of lymphocele should be performed. Regular ultrasound examinations are necessary to diagnose and treat postoperative lymphocele in a timely manner.

[Prostate and bladder cancer: detection of disseminated tumor cells in bone marrow]. / Prostata- und Harnblasenkarzinom: Detektion von disseminierten Tumorzellen im Knochenmark.

The prognosis of prostate and bladder cancer patients is predominantly determined by the detection of distant sites of metastasis. In clinical routine, virtually only lymph node staging is of relevance to determine metastasis. Detection and characterization of disseminated tumor cells in peripheral blood or bone marrow is an additional parameter of prognostic significance. In this article, we will summarize recent progress on the prognostic value of disseminated tumor cells in bone marrow and its translation into routine clinical analysis.