Biomedical subjects
Publications and source records attributed to D Zaak.
Painless swelling of the scrotum may be due either to an increase in bulk of the scrotal contents or to changes affecting the skin of the scrotum. The reliable and rapid differentiation of harmless from serious conditions such as cancer of the testicles, is essential.
Therapy of superficial bladder tumors is transurethral resection (TUR), and in cases of pT1 or high-grade tumors a re-TUR is indicated. Patients with carcinoma in situ receive intravesical chemotherapy or BCG for at least 3 months. Persistent carcinoma in situ may be treated by radical cystectomy. With the provision of a functionally adequate urinary diversion, cystectomy represents an effective treatment for patients with muscle-invasive bladder cancer without metastatic spread. Regional lymph node metastases can be found in up to 15% of stage T1 disease and are present in 33% of stage T3/4 lesions. Thus, lymphadenectomy gains diagnostic and possibly also therapeutic importance. For selected patients, who cannot be treated by radical cystectomy, multimodal concepts aiming to preserve the bladder are discussed. After or prior to cystectomy systemic chemotherapy may become necessary for some patients to positively affect the course of the disease in cases of locally advanced or metastatic lesions.
Even now, 60 years after the fundamental studies on oncological urinary cytology carried out by Papanicolaou and Marschall and the subsequent integration of the test they devised into the diagnostic investigations applied in the diagnosis of urothelial carcinoma, urinary cytology still maintains its place in the diagnosis of primary and recurrent tumours of the urinary tract. Newer diagnostic techniques involving urine-bound tumour markers have not so far achieved such high levels of acceptance as their method. It is possible, certainly, that a combination of these newer methods with cytological testing, or with other innovative diagnostic methods, such as photodynamic techniques, could prove very promising in the future and might overcome the limitations of urinary cytology.
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Urothelial carcinoma of the bladder is a frequent disease that can be identified timely by screening patients at high risk. Due to the high rate of disease recurrence, frequent follow-up procedures are necessary. For this purpose, cystoscopy is the standard procedure, and supplementary non-invasive procedures such as cytology or tumor marker tests are used. These tests have different advantages and disadvantages in terms of their sensitivities and specificities. Thus, they provide additional information, but are not able to replace cystoscopy as the standard instrument in the diagnosis of bladder cancer.
Increasing knowledge in molecular genetic research on urinary bladder carcinoma has allowed us to classify the morphological picture on the basis of a better understanding. But this new knowledge will only be ground-breaking if it can be correlated with the clinical outcome of urinary bladder tumours and with histopathological findings. The use of the new 2004 WHO classification results in a standardized diagnosis of urothelial tumours by means of an exact definition of the subgroups. In the future, trials can thus be compared worldwide and risk profiles can be stratified. Further research in molecular genetics and correlation with the current classification together with molecular biological techniques may allow refinement of this scheme, e.g. by immunohistochemical subclassifications, enabling identification of potentially genetically unstable tumours. In this paper we present the new 2004 WHO classification of urinary bladder tumours emphasizing the changes in relation to the former classifications focusing on histological typing, grading and molecular characterization. Until the new classification is finally validated, and those working in the field have become familiar with it, the WHO classification of 1973 should be mentioned additionally in the histopathological report.
In penile cancer there is still a diagnostic dilemma between over treatment of lymph node-negative patients and the missing of occult metastases by watchful waiting. In the current study the value of fluorescence diagnosis during radical inguinal lymph node dissection was evaluated. Five patients with penile cancer were elected to undergo groin dissection. All patients received 5-aminolevulinic acid (5-ALA) orally before the operation for fluorescence diagnosis. Intraoperatively, fluorescence detection of the lymph nodes was performed by visual detection and spectroscopy. Two of the five patients had positive inguinal lymph nodes. Fluorescence in tumor-bearing tissue was detectable in the exposed lymph nodes. Protoporphyrin IX (PPIX) is accumulated in tumor-positive lymph nodes, making fluorescence diagnosis in penile cancer possible. More studies with higher patient numbers are necessary to evaluate optimal dosage and excitation conditions to detect tumor-bearing nodes in vivo.
Every year, some 18,000 persons develop cancer of the bladder, making it one of the most common of the malignant diseases. Major underlying causal factors are exposure to aromatic amines, nicotine abuse, chronic infections and various medications. On the basis of the TMN system, a differentiation is made between superficial, invasive and metastasizing (lymphogeneous, hematogenous) carcinomas. A classical symptom is painless hematuria. The diagnosis is established primarily by white-light cystoscopy. Superficial urothelial lesions, which are often overlooked with this method, may be detected with the aid of the more sensitive method of fluorescence endoscopy. Depending upon local tumor spread and degree of differentiation, treatment includes transurethral electrocoagulation, laser coagulation, instillation of cytostatics and immunotherapeutic agents, as well as--in the case of muscle invasion--radical cystectomy.
Flat urothelial hyperplasia, defined as markedly thickened urothelium without cytological atypia, is regarded in the new WHO classification as a urothelial lesion without malignant potential. Frequent deletions of chromosome 9 detected by fluorescence in situ hybridization (FISH) have been previously reported in flat urothelial hyperplasias found in patients with papillary bladder cancer. Using comparative genomic hybridization (CGH) and microsatellite analysis, these hyperplasias and concomitant papillary tumours of the same patients were screened for other genetic alterations to validate and extend the previous findings. Eleven flat hyperplasias detected by 5-ALA-induced fluorescence endoscopy and ten papillary urothelial carcinomas (pTaG1-G2) from ten patients were investigated. After microdissection, the DNA of the lesions was pre-amplified using whole genome amplification (I-PEP-PCR). Loss of heterozygosity (LOH) analyses were performed with five microsatellite markers at chromosomes 9p, 9q, and 17p. CGH was performed using standard protocols. In 6 of 11 hyperplasias and 7 of 10 papillary tumours, deletions at chromosome 9 were simultaneously shown by FISH, LOH, and CGH analyses. There was a good correlation between FISH, LOH, and CGH analyses, with identical results in 6 of 10 patients. In addition to deletions at chromosome 9, further genetic alterations were detected by CGH in 9 of 10 investigated hyperplasias, including changes frequently found in invasive papillary bladder cancer (loss of chromosomes 2q, 4, 8p, and 11p; gain of chromosome 17; and amplification at 11q12q13). There was considerable genetic heterogeneity between hyperplasias and papillary tumours, but a clonal relationship was suggested by LOH and/or CGH analyses in 5 of 10 cases. These data support the hypothesis that flat urothelial hyperplasias can display many genetic alterations commonly found in bladder cancer and could therefore be an early neoplastic lesion in the multistep development of invasive urothelial carcinoma.
Urological emergencies that require specialist treatment include testicular torsion, gross hematuria, urogenital injuries and acute flank pain. After initial symptoms-adapted therapy, patients should be transferred immediately to an urological department for imaging (e.g. ultrasound, IVP, CT) and further specific examinations (e.g.blood tests, urine analysis, microbiology). Acute lower abdominal and scrotal pain in young men may be symptomatic of testicular torsion, which requires immediate urological surgery. Gross hematuria is usually not a life-threatening emergency. Nevertheless, urogenital tumor has to be ruled out by an urologist. Patients with urogenital injuries are triaged into surgical and non-surgical treatments. Differential diagnosis of acute flank pain falls into several medical fields. After initial symptom-related therapy, further diagnostic procedures have to be performed. Septic presentation may be symptomatic of infectious hydronephrosis which requires immediate urological intervention.
Fluorescence diagnosis after application of 5-aminolevulinic acid (ALA) detects red-fluorescing preneoplastic and neoplastic lesions using light excitation. The principle of the method is the relative tumor-selective accumulation of the metabolite protoporphyrin IX (PPIX), which is built intracellularly out of exogenously applied ALA. The early detection of tumors and especially preneoplasias is an ideal prerequisite for genetic analysis of these lesions. With this approach, methods such as fluorescence in situ hybridization and loss of heterozygosity analysis for deletion mapping as well as gene sequencing data could be compared. New data are presented on deletions, numeric chromosomal aberrations, and oligoclonality of tumors found in about 30% of cases. The phenomenon of tumor-selective fluorescence was further investigated by parallel biochemical analysis, which showed marked differences in heme metabolism. The analysis of gene and protein expression may aid in identifying tumor-specific molecules associated with heme metabolism.
OBJECTIVES: To report our experience with conventional and fluorescence-controlled neodymium:yttrium-aluminum-garnet (Nd:YAG) laser therapy of urethral condylomata. Urethral condylomata can sometimes only be reached by endoscopy and are in general very susceptible to recurrence. They must therefore be considered as a therapeutic problem that has not yet been resolved. METHODS: One hundred sixty-eight patients with urethral condylomata were treated with the Nd:YAG laser (93 men using conventional white-light endoscopy and 75 men using fluorescence control after topical application of 5-aminolevulinic acid). The relapse characteristics were investigated according to the location and extent of the urethral lesions and with regard to the different endoscopy techniques. RESULTS: Of all patients, 35.7% developed recurrences of urethral condylomata after laser therapy. These were mainly located on the meatus and in the distal urethra. Only 4.8% of patients had proximal condylomata, and this was only seen in people with distal urethral involvement. Extensive, complete, or semicircularly arranged condylomata developed recurrence and complications (eg, strictures) more frequently after laser therapy. Significantly fewer recurrences (21.3% versus 47.3%) were observed in fluorescence-controlled laser therapy in a retrospective comparison with laser therapy under conventional conditions with a corresponding extent of human papillomavirus lesions. CONCLUSIONS: Nd:YAG laser therapy enables a specific topical clearance of human papillomavirus lesions at different locations in the urethra. 5-Aminolevulinic acid-induced fluorescence diagnostics enhances the effectiveness of Nd:YAG laser therapy of human papillomavirus lesions. Urethral instrumentation of any kind leads to viral contamination of the proximal urethra.
OBJECTIVE: To compare the haemostatic properties of standard transurethral resection of the prostate (TURP) and transurethral vaporization resection of the prostate (TUVRP), as perioperative bleeding is still regarded as the major complication of prostate resection. MATERIALS AND METHODS: Isolated blood-perfused porcine kidneys were used to determine the haemostatic efficacy of TURP and TUVRP (using two different electrodes). Bleeding was quantified precisely in relation to tissue ablation for the two techniques, and specimens were evaluated histologically. RESULTS: Both TUVRP groups had significantly less bleeding (P = 0.005) than the TURP group for a standardized ablation volume of perfused kidney tissue (18.9, 19.5 and 24.1 mL/min, respectively). The different TUVRP electrodes had no significant haemostatic differences. The histology showed significantly (P = 0.03) larger coagulation zones for the TUVRP groups than for standard TURP. CONCLUSIONS: TUVRP ex-vivo was associated with significantly better haemostasis than TURP. The haemostatic properties of different active electrodes for TUVRP seem to be equivalent.
5-aminolevulinic acid-induced fluorescence endoscopy (AFE) has enormously increased the effectiveness of early cancer detection. This was first shown for cancer of the bladder. After application of 5-aminolevulinic acid (5-ALA) endogenous protoporphyrin IX (PP IX) accumulates in tumor tissue. When such tissue is then irradiated with blue light, the neoplastic areas can be identified by red fluorescence and, in the case of the bladder, can be removed by transurethral resection (TUR) or laser coagulation in the same endoscopic session. The great advantage of this highly sensitive technique (95%) is to be seen in particular in the detection of flat urothelial neoplastic lesions--until recently a deficit in conventional white-light endoscopy. Initial investigations show that improved early detection and the reduction in the residual tumor rate lead to longer recurrence-free intervals.
Brain metastases (BM) indicate an advanced stage of renal cell cancer (RCC). They pose an increasing challenge to urologists as a result of improved survival due to modern therapy. Median survival of untreated patients with BM who often suffer from neurological deficits is 3 months. Radiosurgery with the Gamma Knife (GK) has increased in use as an alternative to whole brain radiation therapy (WBRT) and/or surgery. This study reports the results of a consecutive series of RCC patients treated for BM by GK radiosurgery during a 5-year period. Between 1994 and 1999, 58 patients with a total of 277 BM and 3.0 (1-19) BM/patient were treated. Because of recurrent BM, 23 (40%) patients received repeated (multiple) GK sessions. The median tumor volume was 3.4 cm3 (0.1-19.1). The median interval between diagnosis of RCC and GK treatment was 2.2 years (0.1-17.2). Symptomatic side effects were detected in 9 (16%) of 58 patients. The median actuarial survival time was 9.9 months. Local tumor control could be achieved in 95% of patients. The GK therapy induced a significant tumor remission accompanied by rapid neurological improvement in 70% of patients. Compared to standard radiotherapy, GK radiosurgery is more effective, less time consuming, and can be repeated. Compared to surgery, radiosurgery is less invasive and better suited to treat multiple metastases in one single session. Surgery and radiosurgery, however, are supplementary methods that are highly effective to control intracerebral metastasizing RCC.
The rapid development of laparoscopy in urology necessitates the training of specialists to guarantee the high standard of patient care. The real-time data communication of medical information between physicians in different locations is known as telemedicine. Telementoring describes the assistance of an experienced surgeon, while telerobotics requires the use of robots. Two robots, the established AESOP and the PAKY + RCM developed at the Johns Hopkins Hospital (JHH), were used to perform a telerobotic laparoscopic renal cyst ablation in cooperation between Baltimore and Munich. The telementor maneuvered the robots over a distance of 8000 km using eight ISDN lines and a PC. AESOP moved the camera, while PAKY allowed the use of a fan retractor in the abdomen. The telerobotic operation was performed without complications or system and communication failures. Telementoring can be used for training purposes but also for consultation between specialists in emergency settings.
PURPOSE: Penile carcinoma is a difficult disease to treat due to its aggressive nature and the psychological effects of amputation, which is often the recommended therapy. Outcome data from the last 13 years on patients with penile carcinoma treated with Nd:YAG laser coagulation were evaluated and compared with outcome data on conventional organ sparing techniques. MATERIALS AND METHODS: For the last 13 years 29 patients were treated with Nd:YAG laser coagulation, including 17 with carcinoma in situ, and 10 with stage T1 and 2 with T2 cancer. Mean patient age was 55.1 years and mean followup was 46.7 months. RESULTS: All patients are alive. Disease recurred in 1 patient with T1 tumor and 1 with carcinoma in situ. All patients were satisfied with the cosmetic and functional result. CONCLUSIONS: Recurrence rates after Nd:YAG laser treatment for T1 tumors are comparable to those after partial amputation. Excellent cosmetic and functional results can be achieved without compromising oncological principles. For patients with metastasis prognosis is limited by the distant disease and, therefore, amputation is only necessary to achieve local control.
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