Dirk-Henrik Zermann

Perisphincteric Injection of Botulinum Toxin Type A

Background: Chronic prostatic pain is still a diagnostic and therapeutic problem. The clinical observation that prostatic and pelvic pain is accompanied by motoric and sensoric disorders of the pelvic floor muscles led to the hypothesis that prostatic pain roots in a changed processing of afferent and efferent information with the central nervous system (CNS).Methods: Neuro–urological work–up of 11 male patients with chronic prostatic pain was completed. This included a clinical evaluation of pelvic floor function, urodynamic investigation of bladder and urethra function and a cystoscopy to exclude morphological aberrations. A transurethral perisphincteric injection of 200 units botulinum toxin type A (BTX) was followed by a 2– to 4–week visit to evaluate their influence on the neuro–urological symptomatology.Results: All chronic prostatic pain patients suffered from a pathological pelvic floor tenderness, an inability of sufficient conscious pelvic floor control, a urethral hypersensitivity/hyperalgesia and a urethral muscle hyperactivity. Basic parameters of bladder function (capacity, sensitivity, compliance) were normal. The BTX injection was followed by a pelvic floor muscle weakening and a relief of prostatic pain and urethral hypersensitivity/hyperalgesia. A botulinum–related decrease of the functional urethral length, the urethral sphincter closure pressure, the postvoid residual volume and an increase of the peak and average uroflow were objectivated.Conclusion: A weakening of the urethral sphincter muscle via blocking acetylcholine release by BTX injection is followed by pain relief and symptom improvement. It can therefore be concluded that a barrage of nociceptive information from the dysfunctional pelvic floor overflood the CNS and induce a changed CNS processing. Interrupting the efferent branch of the disturbed central circle is one opportunity to treat chronic prostatic pain.

Neurourological insights into the etiology of genitourinary pain in men

PURPOSE Pelvic pain remains a challenging urological problem. Because antimicrobial therapy is often unsuccessful for relieving symptoms, it is reasonable to question whether pelvic pain is the result of microbiological versus functional pelvic disease. We analyzed clinical and urodynamic findings to evaluate the role of pelvic floor dysfunction in patients with pelvic pain. MATERIALS AND METHODS We retrospectively evaluated history, physical examination and urodynamic studies in 103 men with an average age of 47 years who presented with pelvic pain between August 1994 and August 1997. In all patients microbiological tests were negative before study entry. RESULTS The reported locations of pain were the prostate and/or perineal region in 45.6% of cases, scrotum and/or testis in 38.8%, penis in 5.8%, bladder in 5.8%, and lower abdomen and lower back in 1.9% each. Previous treatment consisted of 1 to 12 courses of antibiotics in the preceding 6 to 36 months. In 88.3% of the patients there was pathological tenderness of the striated muscle with poor to absent pelvic floor function. Urodynamics were performed in 84 cases. Cystometry was normal except for decreased compliance in 5 patients. Abnormal findings were mostly evident in the coordination of voiding and in dynamic sphincter-pelvic floor activity. Average sphincter pressure was increased to 104.9 cm. water in 72.6% of the patients, average peak urine flow was decreased to 9.9 ml. per second in 61.9% and functional urethral length was increased to greater than 35 mm. in 79.8%. Urethral profile pattern was dysfunctional, obstructed, and combined dysfunctional and obstructed in 52.4, 11.9 and 21.4% of the cases, respectively, while in 88.1% urethral sensitivity was minimally or markedly increased. CONCLUSIONS Since activity is a reflection of neural control, the apparent association of pelvic floor dysfunction with pelvic pain raises the probability of a primary or secondary central nervous system breakdown in the regulation of pelvic floor function. This hypothesis is supported by the improvement in symptoms caused by therapy aimed at modulating the pelvic floor, such as biofeedback, medication and sacral anterior root stimulation.

Penile Prosthetic Surgery in Neurologically Impaired Patients: Long-Term Followup

PURPOSE Penile prosthetics are a viable option for erectile dysfunction in neurologically impaired patients. Penile implants can also be used to facilitate the management of urinary drainage when penile retraction has made this difficult. MATERIALS AND METHODS Between 1980 and 1996, 245 neurologically impaired patients with a mean age of 40.8 years (range 16 to 75), including 188 with paraplegia, 57 with quadriplegia and 197 with spinal cord injuries, were treated for erectile dysfunction and/or urinary incontinence with penile prosthesis implantation. The mean history of paralysis was 11.2 years (range 1 to 52). After neuro-urological evaluation all patients included in this study were considered candidates for penile prosthesis implantation. A followup program for treatment success, patient satisfaction, problems and complications was subsequently initiated. RESULTS During 17 years a total of 293 surgical procedures in 245 patients were done with the implantation of 147 semirigid (Jonas), 113 self-contained inflatable (Dynaflex) and 33 inflatable 3-piece (AMS 700) prostheses. There were 3 patient groups based on the indication for penile prosthetic surgery, namely group 1-134 patients with urinary management only, group 2-60 with erectile dysfunction only, and group 3-51 with urinary management and erectile dysfunction. At a mean followup of 7.2 years (maximum 17) 195 patients were reevaluated in clinic. In 122 patients (90.3%) urinary management problems were resolved. Erectile dysfunction treatment was successful in 76 patients (82.6%). There were 43 revisions for technical reasons and infections. The infection rate was 5% (12 patients). The perforation rate was different for different implant devices, that is 18.1% (15 of 83 cases) for semirigid devices, 2.4% (2 of 84) for self-contained inflatable devices and 0% (0 of 28) for inflatable 3-piece devices. CONCLUSIONS The implantation of a penile prosthesis is a safe procedure for erectile dysfunction and/or urinary incontinence in neurologically impaired patients. Based on technical advances the complication rates significantly decreased during the years. The implantation of an inflatable 3-piece penile prosthesis in a neurologically impaired patient is a safe and viable procedure. Indications include the management of erectile dysfunction and problematic urinary collection.

Real Indications for Adrenalectomy in Renal Cell Carcinoma

Objectives: Adrenalectomy is a part of radical nephrectomy because of the surgical oncology principle of a ‘wide margin beyond the malignancy’ and due to concern over possible metastases to the ipsilateral adrenal gland, especially in upper pole tumors. But, neither the frequency, predisposing factors of the renal cell carcinoma nor mechanisms of involvement of the adrenal gland are well defined. We assessed the ipsilateral adrenal involvement in renal cell carcinoma to determine whether ipsilateral adrenalectomy during radical nephrectomy is essential. Material and Method: In a series of 15,347 autopsies in Jena from 1985 through 1996, 272 renal cell carcinoma with 24 adrenal metastases were found. In the same period 9 adrenal metastases were found in 639 radical nephrectomies. Contralateral and bilateral metastases were seen in 15 cases of the autopsy series and in 2 cases of the operative series. Results: The risk of adrenal metastases correlated with multifocal tumors, pleomorphic cell type, anaplastic growth pattern and tumors that were larger than 2.5 cm. Of the 24 renal cell carcinomas with adrenal metastases in the autopsy series, 23 had evidence of widespread disease and 22 had lymph node metastases. A preoperative abdominal computerized tomography was performed in all 9 patients of the operative series with renal cell carcinoma and adrenal involvement. The adrenal gland was considered abnormal in 8 of the 9 cases (88.9%). Only in 1 patient was the computerized tomography incorrectly interpreted as negative. Conclusion: We think adrenalectomy should only be performed if there is radiographic evidence of metastases in the adrenal gland or adrenal infiltration by a large upper-pole tumor is possible. Macroscopically normal adrenal glands should not be removed during tumor nephrectomy because the need and benefit of routine adrenalectomy are extremely limited.

SIMILARITY OF DISTRIBUTIONS OF SPINAL C-FOS AND PLASMA EXTRAVASATION AFTER ACUTE CHEMICAL IRRITATION OF THE BLADDER AND THE PROSTATE

PURPOSE Persistent pain in referred areas and voiding dysfunction are characteristic symptoms of chronic abacterial prostatitis. Since referred pain from visceral organs is considered a neurological event, it appeared reasonable to hypothesize that the persistent pain associated with prostatitis might also be explained by neural mechanisms. Neurogenic plasma extravasation and c-fos expression in the spinal cord, after chemical irritation of the rat prostate, was identified as a method to investigate the neurogenic aspect of prostatic inflammation. MATERIALS AND METHODS The distribution of plasma extravasation using Evans blue dye was determined after chemical irritation of the prostate and bladder of the rat, and the distribution of dye extravasation was analyzed. c-fos expression within the spinal cord was determined immunocytochemically after chemical irritation of the prostate, bladder and superficial somatic region determined by the dye extravasation as a referred pain area (tail root). RESULTS Chemical irritation of the prostate resulted in plasma extravasation in L5 to S2 dermatomes (primarily in L6 and S1). In rats receiving bladder irritation, the distribution of plasma extravasation showed a similar pattern to that observed in animals receiving prostatic irritation. Chemical irritation of the 3 structures resulted in expression of c-fos positive cells within the lumbosacral spinal cord. With each treatment the majority of c-fos positive cells were in the L6 and S1 segments. In all 3 groups the highest percentages of c-fos positive cells were observed in deeper laminae, including the dorsal commissure and sacral parasympathetic nucleus. CONCLUSIONS Our results strongly suggest that referred pain status in inflammation of the bladder and prostate is neurogenically mediated. Based on these studies, there should be significant overlaps of nociceptive neurons within the spinal cord, which receive nociceptive inputs from pelvic soma and viscera.

Preoperative simulation of partial nephrectomy with three-dimensional computed tomography

Objective To evaluate prospectively the accuracy of computer‐aided three‐dimensional (3D) volume‐rendered computed tomography (CT) in determining the appropriate anatomical limits (tumour size, tumour location, multifocality and vascular supply) and as a potential tool in the preoperative simulation of nephron‐sparing surgery (NSS) in patients with small‐volume renal cell carcinoma (RCC).

Spinal NK1 receptor is upregulated after chronic bladder irritation

&NA; It has been suggested that there is a significant upregulation of the NK1 receptor (NK1R) on neurons in the dorsal spinal cord after long‐term somatic inflammation. This upregulation appears to play a significant role in central sensitization in chronic pain states. However, it is not clear whether such a change is also observed after chronic visceral (bladder) inflammation. Changes in NK1R immunoreactivity after chronic bladder irritation were investigated in order to evaluate the existence of hypersensitive states in the spinal cord after chronic bladder irritation. Experiments were performed on a total of 12 adult female Sprague–Dawley rats. In six animals, cyclophosphamide (CPA) was administered intraperitoneally for 2 weeks. Another six animals were given intraperitoneal saline injections and served as the control group. After these treatments, immunohistochemical staining for NK1Rs and substance P in rat lumbosacral spinal cord was performed. In CPA‐treated animals, NK1R‐positive areas and staining intensity within the dorsal spinal cord were significantly increased in the L5 to S2 spinal cord areas, especially in the L6 and S1 segments. In the L6 spinal segment, CPA‐treatment enhanced NK1R immunostaining in the medial and the lateral dorsal horn, as well as in the lateral laminae including the sacral parasympathetic nucleus to a lesser extent. In CPA‐treated animals, substance P staining intensity increased in the same regions in which NK1R immunoreactivity was increased. This finding probably implies the upregulation of spinal NK1R and the occurrence of central sensitization within the spinal cord after chronic visceral inflammation.

Multifocality in Renal Cell Carcinoma: A Bilateral Event?

Objectives: The major disadvantage of nephron-sparing surgery for renal cell carcinoma is the risk of local recurrence. This is most likely a manifestation of undetected small additional tumors in the renal remnant. To define more clearly the incidence and nature of unilateral and bilateral multifocal tumors, an autopsy study was undertaken. Materials and Methods: In a series of 14,793 autopsies from 1985 to 1995, 260 renal cell carcinomas were found. In all cases of renal cell carcinoma a search for small renal lesions was performed in the apparently normal-appearing portion of the kidneys. Every kidney was serially and systematically cut (5 mm) to probe for intraparenchymal lesions. Results: Of the 260 renal cell carcinomas 36 cases (13.85%) had multifocal malignant and/or benign nodules. The number of the additional nodules ranged from 2 to 18. 12% of the malignant multifocal carcinomas were limited to the ipsilateral kidney and 88% were bilateral. The average size of the multifocal renal lesions was 8.7 × 9.0 × 9.5 (range 3–23) mm. Renal cell carcinomas with low stage and good grading have a higher incidence of multifocal nodules. No significant difference was found with regard to metastasized and nonmetastasized renal cell carcinomas. In 38.1% of all chromophilic renal cell carcinomas additional nodules were found. Conclusions: Multifocality in renal cell carcinomas cannot be predicted reliably, although the papillary histological pattern, good grading and low staging seems to be associated with a higher incidence of multifocality. Nearly 90% of the multifocal nodules were bilateral.

Increased Transforming Growth Factor β1 Plasma Level in Patients with Renal Cell Carcinoma:A Tumor-Specific Marker?

Purpose: The most worrying problem with renal cell carcinoma (RCC) seems to be the prediction of metastases by means of tumor-specific markers. Therefore, much effort is committed to the development of new markers. Materials and Methods: The level of latent transforming growth factor β1 (TGF-β1) was measured in plasma samples by ELISA. These samples were collected from patients with RCC before they underwent radical nephrectomy, from patients 1 h after extracorporeal lithotripsy, from patients with pyelonephritis, and from healthy controls. Results: In all cases of RCC the levels of latent TGF-β1 in plasma were much higher (n = 20, 41.0 ± 13.9 ng/ml, range 19.3–78.1 ng/ml) than in healthy controls (n = 20, 3.8 ± 2.9 ng/ml, range 0.6–9.9 ng/ml, p < 0.0001). The TGF-β1 levels in plasma after extracorporeal lithotripsy (n = 20, 7.4 ± 4.64 ng/ml, range 2.9–21.7 ng/ml, p < 0.01) and in patients suffering from pyelonephritis (n = 20, 18.93 ± 14.2 ng/ml, range 4.2–46.7 ng/ml, p < 0.001) were also higher than in healthy controls. Conclusion: We conclude that increased levels of latent TGF-β1 are common in the plasma of RCC patients. The TGF-β1 plasma level in RCC was found to be significantly higher than in cases of inflammation. Thus, TGF-β1 is a possible tumor-prognostic marker in RCC.

Effects of estrogen and progesterone on urinary bladder in female rabbit: evaluation by quantitative morphometric analysis.

OBJECTIVES To investigate possible effects of estrogen and/or progesterone on the histologic characteristics of female rabbit urinary bladders, we carried out quantitative morphometric analysis of the rabbit bladders. METHODS Mature female rabbits were treated by ovariectomy with and without successive estrogen and/or progesterone administration. Area densities of the connective tissue (CT) and smooth muscle (SM) cells, the area of single SM cells, and the thickness of the bladder wall were determined by computer-assisted quantitative morphometric analysis. RESULTS Six weeks after each treatment, ovariectomy alone resulted in a decrease in CT density of the bladder. Successive estrogen treatment increased the bladder wet weight and SM cell density within the bladder wall. Progesterone treatment reduced CT degradation in ovariectomized rabbits. Sex steroids did not significantly influence the area of each SM cell. There was no significant difference in histologic characteristics between the rabbits treated by estrogen alone and those treated by combination (estrogen and progesterone) therapy. CONCLUSIONS Ovariectomy and successive hormonal replacement therapy resulted in morphologic changes within the rabbit urinary bladder. Cotreatment with progesterone did not significantly change the morphologic findings produced by estrogen treatment alone.