P. Olbert

Accuracy of frozen section examination of testicular tumors of uncertain origin.

INTRODUCTION A total of 80-90% of all testicular masses are malignant germ cell tumors. Benign testicular lesions are recognized in approximately 10-20% enabling a testis-preserving surgery on the findings of frozen section examination (FSE). However, there are only sparse information with regard to the reliability of FSE in testicular tumors of uncertain dignity. Therefore, we retrospectively reviewed our experience concerning the reliability of FSE in primary testicular tumors by comparing each FSE result to the final diagnosis. PATIENTS AND METHODS From 1974 to 2000, 354 patients were operated on a testicular tumor. During inguinal exploration and after clamping of the spermatic cord and appropriate dressing, a representative biopsy of the tumor was taken and sent for FSE. In case of malignancy radical orchiectomy was performed, in case of benign findings or in case of a germ cell tumor in a solitary testicle, the tumor was enucleated. Slides of FSE and the permanent sections were reviewed and compared with regard to the histological diagnosis and presence/absence of malignancy. RESULTS Based on FSE, 317 tumors (89.5%) were found to be malignant ((100 seminomas (38.5%), 217 nonseminomas (61.5%)) and 37 tumors (10.5%) were benign (17 epidermoid cysts, 14 Leydig cell tumors, two cystadenomas, two simple cysts, two hemangiomas). Comparing FSE and definitive diagnosis, FSE correctly identified all malignant and benign lesions. There was a failure rate of 10 and 8% to differentiate seminomatous from nonseminomatous tumors and vice versa based on FSE, which, however, was irrelevant for the surgical management. Complications of the enucleations (n = 37) were: testicular atrophy in three cases, testicular hematoma in three cases, orchitis/epididymitis in one case. Not a single case disclosed a local relapse after a mean follow-up of 105 (12-240) months. CONCLUSIONS Intraoperative FSE correctly identified all malignant and benign testicular masses including radical orchiectomy or organ-preserving surgery. Surgical management of testicular tumors based on FSE results is clinically practicable.

Serum DNA and urine DNA alterations of urinary transitional cell bladder carcinoma detected by fluorescent microsatellite analysis

There are no reliable serologic tumor markers for transitional cell carcinoma (TCC) of the urinary bladder and noninvasive urine investigations are inadequate. We used fluorescent microsatellite analysis (MSA) to detect serum DNA and urine‐sediment DNA alterations in patients with bladder cancer and prospectively collected fresh tumor, peripheral blood, serum and spontaneous urine specimens from 39 consecutive patients treated for TCC of the bladder to obtain the corresponding DNA. Fluorescent MSA was performed with 17 polymorphic markers from the chromosomal regions 5q, 8p, 9p, 9q, 13q, 14q, 17p, 17q and 20q in the 39 cancer patients and in 10 healthy controls. Serum DNA alterations were identified in 84.5% (33 of 39 patients) and tumor‐specific urine DNA alterations indicating the diagnosis were present in 72% (27 of 39 patients) of cases. None of the healthy controls displayed serum DNA alterations. The highest frequency of serum DNA aberrations (56%) was detected for chromosomal region 8p. The most frequent alterations in urine‐sediment DNA, 36% and 26%, were detected in chromosomal regions 8p and 9p, respectively. Identification of serum DNA and urine‐sediment DNA alterations was not related to stage of disease or grade of tumor (p > 0.05). Thus, MSA offers a highly sensitive and specific method for serum‐ and urine‐bound diagnosis of bladder TCC.

Management of chronic testalgia by microsurgical testicular denervation.

OBJECTIVES Chronic testicular pain (CTP) is defined as uni- or bilateral, intermittent or continuous testicular discomfort of at least 3 months duration that interferes with the patients daily activities and prompts him to seek medical advice is a rather common urological manifestation of chronic pain syndrome. Diagnosis and treatment of CTP has been a difficult and often unrewarding clinical situation. Success rates of conservative and surgical measures including epididymectomy and orchiectomy rarely exceed 55-73% and 10-40%, respectively. We report our experience on microsurgical testicular denervation as therapeutic option in CTP. PATIENTS AND METHODS Following an extensive preoperative work-up (urine/semen cultures, transrectal ultrasound, testicular sonography, pain and orthopedic consultation) not revealing any pathologic abnormalities and a positive response to spermatic cord block, 35 patients underwent microsurgical testicular denervation. In brief, spermatic cord was dissected, vas deferens, cremasteric muscle and testicular vessels were separated. After identification of the testicular artery by application of vasodilatating agents using magnifying loops or the operating microscope, all structures besides the testicular artery, vas deferens and 1-2 lymphatic vessels were coagulated and transsected using bipolar diathermy. RESULTS After a mean follow-up of 31.5 months 34/35 (96%) patients are completely pain-free; no intra- or postoperative complications were encountered. No case of testicular atrophy or hydrocele formation was observed during postoperative follow-up. CONCLUSIONS Microsurgical testicular denervation results in reliable and reproducible excellent therapeutic success rates of 96% and should be integrated in the management of CTP at an early stage. High success rates require adequate and meticulous diagnostic work-up of the patients by spermatic cord block using saline as placebo and different local anaesthetics as an initial therapeutic armentarium predicting postoperative outcome.

Metastatic non-clear cell renal cell carcinoma: current therapeutic options.

Non‐clear cell (ncc) renal cell carcinoma (RCC) accounts for ≈25% of all patients with metastatic RCC. It is refractory to standard immuno(chemo)therapy and, to date, no specific trials have been reported to evaluate the efficacy of novel targeted drugs in the different subtypes of metastatic nccRCC. We review all available data from subgroup analyses of the global sorafenib and sunitinib expanded access programmes, current phase‐III trials, and smaller multi‐ and single‐centre studies focusing on the activity of targeted agents in these specific and rare RCC subtypes. Both sorafenib and sunitinib have significant activity in metastatic nccRCC, but the efficacy of each agent seems to vary between different nccRCC forms. Preliminary clinical data for temsirolimus appear to be promising but more extensive and long‐term data are awaited. With the advent of novel therapeutic options, specific controlled multicentre trials are urgently needed to define their exact value and efficacy for treating the historically resistant nccRCC forms. The medium‐term aim should be to tailor the most advantageous therapy for each patient with respect to his/her individual RCC subtype and physical condition.

Biochemical markers of bone turnover in patients with localized and metastasized prostate cancer.

To evaluate and compare the value of several markers of bone turnover in different stages of prostate cancer, as bone metastases are a common feature in this disease, and for assessing bone metastases both bone formation and bone resorption markers are diagnostic.

Second-line strategies for metastatic renal cell carcinoma: classics and novel approaches

Objectives: Renal cell carcinoma is an aggressive malignancy with a high propensity for both early and metachronous regional and distant metastasis. While surgical resection is the mainstay of therapy for patients with localized disease, the prognosis for patients with distant metastasis is poor with a 5-year survival rate of less than 10%. Response rates to first-line immunotherapy or immunochemotherapy range from 10–35%; responses achieved are predominantly partial remissions of short duration. Until today, there is no standard therapeutic procedure for the growing number of patients who relapse following first-line therapy and desire further active treatment. Materials and Methods: This article reviews classic and recent publications about second- and third-line approaches, their potential efficacy and toxicity. Results: Several novel approaches have raised well-founded hope. Especially the application of monoclonal antibodies targeting VEGF signalling as well as different receptor tyrosine kinase inhibitors have the potential to change the face of second-line treatment of patients with metastatic RCC. Both groups of agents are focused in current phase III trials, either as mono- and/or combination therapy. Conclusions: Until today, second-line treatment of patients with metastatic RCC progressing under therapy with biological response modifiers remains an unresolved issue. The results of ongoing clinical trials evaluating novel targeted approaches can be expected with suspense.

Clinical experience with a new ultrasonic and LithoClast combination for percutaneous litholapaxy.

Objective  To assess a new lithotripter for intracorporal lithotripsy, which combines the mechanically driven pneumatic LithoClast™ (Electro‐Medical Systems, Nyon, Switzerland) and a new ultrasonic device (Electro‐Medical Systems), for use in percutaneous nephrolitholapaxy (PNL).

[Gender-specific characteristics and survival of renal cell carcinoma].

BACKGROUND Renal cell carcinoma (RCC) occurs twice as often in men as in women; however, the influence of gender on stage, grade, subtype and prognosis has not been studied in detail. METHODS This study included 780 patients treated by (partial) nephrectomy at our institution in Marburg between 1990 and 2005. The mean follow-up was 5.44 years. RESULTS Of the 780 patients, 486 (62%) were men and 294 (38%) were women. Women were significantly older (mean, 65.3 vs. 62.2 years; p<0.001, t-test), presented at lower T stages (p=0.046, chi(2)) and suffered metastasis less frequently at diagnosis (p=0.026, chi(2)). In addition, women more frequently had clear cell tumours (85.2% vs. 78.3%) and less frequently papillary tumours (11.0% vs. 18.8%) than men (p=0.026, chi(2)). In contrast, men had an increased risk of death from RCC (HR 1.23, CI 0.92-1.63); Kaplan-Meier curves revealed a significant difference in tumour-specific survival between men and women (p=0.033, log rank; 5-year survival 74% vs. 83%). However, unlike tumour stage and tumour grade, gender could not be retained as a significant independent prognostic marker in multivariate analysis. CONCLUSION In general, RCC in men is characterized by higher tumour stages and more frequent metastasis at diagnosis along with inferior tumour-specific survival. However, as gender failed to qualify as an independent prognostic marker for tumour-specific survival, delayed diagnosis due to insufficient routine medical check-up and/or a more aggressive tumour biology might be be a concurrent cause. Thorough regular medical check-ups for men, also with regard to RCC, are thus mandatory.

Experimental studies and first clinical experience with a new Lithoclast and ultrasound combination for lithotripsy.

OBJECTIVES A new lithotriptor for intracorporeal lithotripsy was developed combining the two most effective lithotriptors. A combination of the mechanically driven Lithoclast Master and a new ultrasonic device was constructed. Efficacy was tested in standardized model stones and in patient treatment. MATERIAL The new lithotriptor is composed of a Lithoclast Master and an ultrasonic device (EMS, Nyon, Switzerland). The 1.0 mm Lithoclast probe is advanced off-center through the hollow 3.3 mm ultrasonic probe and protrudes about 1 mm. Five different artificial stones of defined hardness and density were used as model stones for disintegration. Time until first fragmentation and complete fragmentation (particles smaller than 2.2 mm to fit through the ultrasonic probe), percent disintegration after 1 min and time until 50% disintegration were determined for the new device as well as lithoclast and ultrasound alone. A total of 68 patients were treated by percutaneous nephrolitholapaxy (PNL) with the new device from February 1999 to August 2001. Lithotripsy was performed after fluoroscopically guided puncture of the lower calix and dilatation of the nephrostomy tract with coaxial bougies. Thirty-five patients had complete and 33 patients partial staghorn calculi. RESULTS First fragmentation was reached 25-200 times faster with the combination as with either mode alone. Disintegrated stone mass after 1 min was 1.5-4 times larger in combined lithotripsy and 50% disintegration time 30-50% shorter. Clinically, complete stone free rate (KUB and ultrasound) was 66% after the first PNL. Sixteen out of 68 patients had a second look PNL with an overall stone free rate of 89.7% by dismission. Stone composition was calcium-oxalate-monohydrate in 13%, Ca-ox-monohydrate/uric acid in 35%, apatite in 20% and cystine in 11%. CONCLUSION In in vitro experiments and clinically the new lithotriptor provides easy handling and high effectivity in fragmentation of all stones regardless of their composition.

CD34+ fibrocytes in chronic cystitis and noninvasive and invasive urothelial carcinomas of the urinary bladder

CD34+ fibrocytes are constitutive elements of the connective tissue where they play a role in matrix synthesis and tumor-associated stromal remodeling. Secreted protein, acidic, and rich in cysteine (SPARC) is a pivotal mediator of stromal remodeling precipitated by invasive carcinomas. The present study was undertaken to investigate CD34+ fibrocytes in the stroma of the tumor-free urinary bladder, chronic cystitis, and urothelial carcinomas together with stromal expression of α-smooth muscle actin (α-SMA), CD117, and SPARC. In tumor-free urinary bladder and chronic cystitis, CD34+ fibrocytes were found in the deep lamina propria and tunica muscularis, whereas the superficial lamina propria disclosed a CD34-negative and α-SMA-positive fibrocyte-like cell. Invasive urothelial carcinomas revealed a complete loss of CD34+ fibrocytes and concomitant appearance of α-SMA-reactive myofibroblasts which showed strong expression of SPARC. CD117 expression of tumor-free and tumor-associated stroma revealed no differences. We in this study for the first time describe CD34+ fibrocytes in the urinary bladder and an up-to-now unknown population of α-SMA-positive fibrocytes exclusively occurring in the superficial lamina propria. Stromal remodeling associated with invasive carcinomas in the urinary bladder is characterized by a loss of CD34+ fibrocytes paralleled by a gain of α-SMA-positive myofibroblasts and increased expression of SPARC.