MR imaging of the male pelvis

Prostate and urinary bladder cancer are the most frequently encountered malignancies of the urinary tract. Appropriate use of the different imaging techniques is crucial for accurate assessment of prognosis and for the development of appropriate treatment planning. Especially determination of local tumor extension and detection of nodal or bone metastases is extremely important. In this regard MR imaging is the most promising imaging technique. Therefore, in this review its role in staging these malignancies is evaluated and compared with clinical staging, and other imaging techniques. Finally, future developments, such as new sequences, new contrast agents, the role of surface coils and MR-guided biopsy, are considered. Also, the preferred radiological approach is discussed.     

Sprouting of bladder nerves into cystoplastic cecal segment in the rat

Incorporation of bowel into the bladder (enterocystoplasty) has been widely used to increase bladder capacity. It has been reported by others that the response of smooth muscle from the cystoplastic segment of the intestine shifts from that of the intestine (relaxation to α-agonists and ATP) to that of the bladder (contraction to α-agonists and ATP). This suggests a functional integration of the intestinal muscle into the bladder; the mechanisms are unknown. The aims of the present study were (1) to elucidate if there are signs of bladder nerves sprouting across the anastomosis into the intestinal segment, and (2) to study what happens with the intrinsic innervation of the intestinal segment. As a model, we used cecocystoplasty in rats. The bladder was opened and a patch of cecum with intact vascular supply was anastomosed to the bladder. After two to 11 months the rats were sacrificed and the bladders mounted as wholemounts and stained for acetylcholinesterase-containing nerves, or embedded in paraffin for histology. A pronounced degeneration of the myenteric plexus was found in the cecal segments. In some areas, this had proceeded to the extent that the ganglia were isolated ovoid lumps of cells with no apparent connection to other ganglia. Areas lacking ganglia and nerve trunks but still with muscle could be found in all specimens. Abundant axon bundles were demonstrated sprouting from the cut bladder nerves close to the anastomosis. The bundles spread out in a fan-like pattern or were organized as fewer thicker nerves. There were many nerve bundles entering the cecal segment where they branched and the diameter decreased till they no longer became visible. Some nerves reached surviving lumps of myenteric ganglion cells. The results show that the bladder nerves sprout into the anastomosed cecal segment. It is reasonable to assume that these nerves are responsible for the changes in receptor pharmacological properties of the cecal smooth muscle towards that of bladder muscle. Received: 30 October 1998 / Accepted: 18 May 1999     

Conservative treatment of neurogenic bladder dysfunction

Summary In neurogenic bladder dysfunction conservative treatment is preferred whenever possible and preservation of renal function remains the main topic. Additionally, a patient-related form of bladder management with decreased intravesical pressure and social dryness is needed. Therefore many strategies are available and after evaluation of the underlying neurogenic bladder dysfunction an individual kind of treatment can be used. Possible options are the clean intermittent catherization, anticholinergic drugs, detrusor triggering, electrical stimulation and bladder emptying by Valsalva's manouvre.      

同种异体大鼠胰腺移植膀胱引流术式模型的建立及分析

大鼠胰腺移植模型可用于解决临床移植中常见问题的初步探索性研究．采用目前临床胰腺移植常用的膀胱引流术式,建立大鼠的同种异体胰腺移植模型30例,其中12例存活超过5d,存活超过2周者6例,超过3个月者4例。尸检及病理结果表明,手术过程中血管吻合技术的熟练程度、吻合时间过长及移植胰腺冷缺血期间保存温度超过4℃而使之活力下降是移植后动物死亡的主要原因。     

Inhibition of cardiac inward-rectifier K current by terodiline

The antispasmodic agent terodiline has cardiotoxic effects that include QT lengthening. To determine whether inhibition of inwardly-rectifying K⁺ current (I_K1) might be a factor in the cardiotoxicity, we measured I_K1 in guinea pig ventricular myocytes. Terodiline reduced outward I_K1 with an IC₅₀ of 7 μM; maximal reduction was 60% with 100–300 μM concentration. Inhibition was independent of current direction, and persisted after removal of the drug. Terodiline (3–5 μM) lengthened action potentials in guinea pig papillary muscles by ca. 10%, primarily by slowing phase 3 repolarization; higher concentrations abbreviated the plateau and markedly slowed late repolarization. Terodiline washout provoked an extra lengthening, consistent with persistent inhibition of I_K1 and rapid recovery of net inward plateau current. The results suggest that inhibition of I_K1 is a likely factor in the cardiotoxicity of the drug.     

Different pH Dependency of Mitomycin C Activity in Monolayer and Three-Dimensional Cultures

Purpose. Previous studies by other investigators have shown an enhancement of mitomycin C (MMC) activity at acidic extracellular pH (pH_e) in monolayer cultures of human cells. The goal of the present study was to determine if the efficacy of intravesical MMC therapy in patients treated for superficial bladder cancer can be enhanced by using acidified dosing solutions. We evaluated (a) the effect of pH_e on MMC activity in patient bladder tumors in vitro, and (b) the pH dependency of MMC activity in 2-dimensional monolayer and 3-dimensional multilayer cultures of human bladder RT4 tumor cells. Methods. Patient bladder tumors were maintained as 3-dimensional histocultures. RT4 cells were harvested and maintained as monolayer cultures or as 3-dimensional cell pellets on a collagen gel matrix. The cell pellets were 300–450 cell layers and 4,000–5,000 µm in diameter. Tumors or cells were incubated for 2 hr with MMC-containing media at pH_eof 5, 6, and 7.4. The drug effect was measured by the inhibition of DNA precursor (thymidine) incorporation. The stability of MMC as a function of pH_e was determined. About 24% of MMC was degraded following 2 hr exposure at pH_e 5 and 2% at pH_e 6 and 7.4. Results. The drug concentrations required to inhibit thymidine incorporation by 50% (IC₅₀) were corrected for the degraded MMC at acidic pH_e. The results showed no pH-dependent MMC activity in human patient bladder tumors nor in RT4 multilayer cultures; the IC₅₀ values were about 10 µg/ml at all three pH_e. In contrast, the monolayer RT4 cultures showed a pH-dependent MMC cytotoxicity; the IC₅₀ were 0.1, 0.8 and 1.2 µg/ ml at pH_e 5,6 and 7.4, respectively (p < 0.05). Pre-incubation of multi-layered RT4 cultures in acidic pH medium for 8 hr enhanced the MMC activity; the IC₅₀ was reduced by about 5 fold at pH_e 5 and about 3 fold at pH_e 6. Similar pH-dependent MMC activity was found when multilayers were pre-treated for 1 hr with 0.5 µml nigericin, a proton ionophore known to cause the intracellular pH (pH_i) to equilibrate with pH_e. Conclusions. These data suggest that the difference in the pH dependency of MMC activity in the monolayer and multilayer systems was due to the different experimental conditions. The time lag for pH_i to equilibrate with pH_e in the multilayer systems and the instability of MMC at low pH_e imply that the efficacy of intravesical MMC therapy is unlikely to be enhanced by using acidic dosing solution.     

Contractile and cytoskeletal proteins in urinary bladder smooth muscle from rats treated with epidermal growth factor

Systemic treatment with epidermal growth factor (EGF) induces growth of all wall layers in the urinary tract of pigs and rats. The present study was initiated to describe morphological and biochemical changes in the bladder smooth muscle from rats treated with EGF for 4 weeks. Eight-week-old female Wistar rats were treated with subcutaneous injections of vehicle (n=16) or EGF (n=8, 150 g/kg per day) for 4 weeks. After EGF treatment the bladders were increased in weight [74.4±0.4 vs 122.1±0.5 mg, P<0.001 (mean ± SEM)]. Sodium dedecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) analyses of six bladders from each group revealed that the total amounts of actin, myosin and desmin were statistically significantly increased by 62%, 61% and 154%, respectively. The relative amounts of actin and myosin were unchanged whereas the desmin to actin ratio was significantly increased — as previously described in rat bladder smooth muscle hypertrophy. Light and electron microscopy of two bladders from each group revealed increased wall thickness involving all wall layers. The smooth muscle fibres at a midventral bladder location seemed only slightly hypertrophic — some degree of hyperplasia was therefore suspected. In conclusion, EGF treatment for 4 weeks induced a net synthesis of contractile and cytoskeletal proteins in the urinary bladder smooth muscle.     

Denervation supersensitivity of the urethra to α-adrenergics in the chronic neurogenic bladder

Summary The response of the urethral pressure profile to the administration of various autonomic drugs was compared between a group of eight patients with chronic neurogenic bladder as evidenced by denervation supersensitivity to besacholine^R and a group of 10 control subjects. A supersensitive response to the administration of an -stimulant with a rise of maximum urethral pressure of 10 mmHg or more above the control urethral pressure was uniformly observed in the urethra of patients with chronically denervated bladders. Mechanisms of supersensitivity are postulated and the significance of -adrenergic innervation of the urethra are stressed. These results appear to add pharmacological evidence of -adrenergic predominance in the urethra which is now believed to be dually innervated.     

Tumors of the urinary bladder in painters: a case-control study

In a case-control study, 403 male patients with a diagnosis of "bladder tumor" and (as controls) 426 patients suffering from prostate disease were investigated. The results of this study indicate that past employment as a painter was associated with an excess risk of bladder tumor. The relative risk of bladder tumor estimated for painters was 2.76. The possible role of benzidine-based azodyes (or azodyes based on substituted benzidines) as a carcinogenic risk factor for painters is discussed.     

Detection of a rare point mutation in Ki-ras of a human bladder cancer xenograft by polymerase chain reaction and direct sequencing

Summary This paper represents the first report of a codon 59 mutation in Ki-ras from a spontaneous human transitional cell carcinoma of the bladder. Point mutations have the potential to activate the ras genes if they occur in critical coding regions. These include the sequences of codons 12, 13, 59, 61 and 63. Mutations in codons 12, 13 and 61 have been reported in a wide variety of human cancers, including transitional cell carcinoma of the bladder. However mutations in codon 59 have been reported only in retroviral Ki-ras and as a result of in vitro mutagenesis experiments. We have used the polymerase chain reaction and direct sequencing to detect mutations of Ki-ras, and allele-specific restriction analysis to detect mutations of N-ras in xenografts and continuous cell lines established from bladder cancer biopsies of ten different patients as well as in direct biopsy specimens from five human bladder tumours. For studies of Ki-ras, a 139 bp fragment which spanned the critical codons 12 and 13 and a 128 bp fragment that spanned the sequences of codon 59, 61 and 63 were enzymatically amplified and then sequenced. No N-ras mutations were detected. A heterozygous mutation of Ki-ras at codon 59 GCA G/ACA was detected in one line. This mutation is being expressed and appears stable as it was detected over several xenograft passages and was present in paraffin-embedded tissue from the primary tumour of the patient. The biological significance of the mutation in bladder cancer is currently under study.