The complex structure of the smooth muscle layer of spermatic veins and its potential role in the development of varicocele testis.

OBJECTIVES: Varicocele, a dilatation of the pampiniform venous plexus, is considered to cause male infertility. The exact mechanism of varicocele development is not clarified yet. This study focused on the structure of varicocele veins, compared with normal spermatic veins, and its potential role in varicocele development. METHODS: Morphologic and immunohistochemical studies using antibodies against vWF and neurofilament-200 (NF-200) were performed on spermatic vein fragments of 20 varicocele patients and 40 normal spermatic cords. Casting preparation of veins was performed on five normal spermatic cords. RESULTS: Casting preparation frequently revealed circular constrictions of normal spermatic vein lumina. Histologic evaluation showed a strong longitudinal smooth muscle layer in the adventitia of large veins in addition to the circularly organised tunica media. Serial sections showed smooth muscle fibres branching from the outer longitudinal into the inner circular layer. Immunostaining for vWF revealed high vascularisation of this outer layer. Interestingly, the number of nerve fibres marked by NF-200 immunostaining was considerably higher in large veins compared to the testicular artery. The longitudinal smooth muscle layer was significantly degraded in the presence of varicocele grades I and II, and did not even exist in varicocele grade III. Correspondingly, the number of vasa vasorum and nerve fibres was reduced in varicocele veins. CONCLUSIONS: Our data show a complex smooth muscle organisation of spermatic veins, which serves the basis for a contractile mechanism, providing an effective blood transport through pampiniform plexus. This mechanism is obviously damaged in the varicocele. Molecular processes behind this impairment remain to be clarified.

Baseline follicle-stimulating hormone is a strong predictor for the outcome of the gonadotrophin-releasing hormone test in young men with unilateral medium- or high-grade varicocele.

OBJECTIVE: To investigate whether the gonadotrophin-releasing hormone (GnRH) test is an adequate diagnostic tool to identify testicular dysfunction in men with strictly unilateral varicocele and defined testicular volume; and to identify any peripheral venous variable which would predict the result of the GnRH test. PATIENTS AND METHODS: In all, 102 GnRH tests were done in men with a left-sided varicocele. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were determined. After intravenous administration of 100 microg GnRH, stimulated LH and FSH levels were measured. FSH levels of >8.2 U/L and LH levels of >51.7 U/L were considered exaggerated. RESULTS: In all, 50 men had an exaggerated GnRH test result; all had an exaggerated FSH response and six also had an elevated LH response. The baseline FSH levels were higher (P < 0.001) and the testicular volume was smaller (P < 0.01) in men with an exaggerated GnRH test response. All men with a baseline FSH level of >5.6 U/L had an exaggerated GnRH test response. CONCLUSION: A baseline FSH level of >5.6 U/L is a good predictor of the GnRH test outcome. Leydig cell function seems mainly undisturbed.

Lipid class distribution of fatty acids including conjugated linoleic acids in healthy and cancerous parts of human kidneys.

In this study the FA compositions of healthy and cancerous human renal tissues from the same patients are compared with special reference to the CLA and PUFA content. CLA was preferentially incorporated into neutral lipid compared with phospholipid classes. Its distribution profile was similar to that of monounsaturated FA, but unlike that found with 18:2n-6. Different incorporation patterns were found for individual CLA isomers. Comparing renal cell carcinoma (RCC) and healthy kidney, the total CLA content was significantly lower in the cholesterylester fraction and significantly higher in the PE and PS fractions from RCC. The most significant differences between healthy and cancerous renal tissue were in the content of t10,c12-CLA. Furthermore, the lipid class distributions of n-6 PUFA were determined, and several significant differences between RCC and healthy renal tissue were found. This is of interest, as it has been proposed that the anticarcinogenic properties of dietary CLA are associated with their interference in the metabolism of 20:4n-6. The involvement of CLA in preventing renal cancer cannot be definitively demonstrated from the design of this study, nor was it intended, but the complete determination of the FA composition of adjacent healthy and cancerous tissues may provide an insight if lipids are involved in this disease.

Distribution of conjugated linoleic acid in total and subcellular fractions from normal and cancerous parts of human testes.

The objective of the present study was to examine differences in the fatty acid composition of subcellular fractions from normal and cancerous parts of human testes. The conjugated linoleic acid (CLA) content was significantly higher in total testicular carcinoma (TC), but significantly lower in the mitochondrial fraction of TC in comparison to normal testicular tissue. The subcellular distribution pattern of CLA was similar to that of monounsaturated fatty acids, but different to that of 18:2n-6 (linoleic acid), underlining the different physiological properties of CLA and 18 : 2n-6. Because polyunsaturated fatty acids (PUFAs) have been suggested to have an effect on cancer risk and previous research has found that CLA inhibits the metabolism of 18 : 2n-6 into 20 : 4n-6, the contents of n-6 and n-3 PUFAs were determined. Significant differences were observed for 18 : 2n-6, 18 : 3n-3, 20 : 5n-3, and 22 : 6n-3, with 18 : 2n-6, 18 : 3n-3, and 20 : 5n-3 contents being higher and 22 : 6n-3 content being lower in TC than in normal testicular tissue. These results indicate a changed availability of substrates for the cyclooxygenase (COX) or lipooxygenase (LOX) pathways generating eicosanoids. Although not statistically significant, the reduced content of 20 : 4n-6 shown in this study might be due to an increased metabolism of this fatty acid into eicosanoids.

Distribution of polyunsaturated fatty acids including conjugated linoleic acids in total and subcellular fractions from healthy and cancerous parts of human kidneys.

Differences in the FA composition of subcellular fractions from healthy and cancerous kidney tissues from the same patients were examined. Only minor differences in CLA content were found between the healthy and the cancerous tissue portions. Regarding the distribution pattern, CLA incorporation into nuclei and cytosol was significantly higher than incorporation into plasma membranes and mitochondria, which could be correlated to the neutral lipid content of these fractions. The subcellular distribution pattern of CLA was similar to that observed with monounsaturated FA but unlike that found with 18:2n-6, which underlines the different physiological properties of CLA and 18:2n-6. Because PUFA have been suggested to have an effect on cancer risk, the contents of n-3 and n-6 PUFA were determined in kidney and renal cell carcinoma (RCC). The 18:2n-6 content and delta5 desaturase activity were significantly lower, and the 18:3n-6, 20:3n-6, and 20:5n-3 contents and delta6 desaturase activity were significantly higher in RCC than in healthy renal tissue, indicating a changed PUFA metabolism in RCC. Previous research has suggested that CLA inhibits the elongation and desaturation of 18:2n-6 into 20:4n-6. In that case, one might speculate that a diet enriched in CLA would be a useful tool in preventing RCC. However, the involvement of CLA in preventing renal cancer could not be demonstrated definitively from the design of this experiment. Further understanding of the cause and/or consequence of the difference in FA metabolism may lead to a better understanding of RCC.

New application of a subcellular fractionation method to kidney and testis for the determination of conjugated linoleic acid in selected cell organelles of healthy and cancerous human tissues.

To clarify the mechanism of the anticarcinogenic effect of conjugated linoleic acid (CLA), its intracellular distribution needs to be determined. Subcellular fractionation using centrifugation techniques is a method that is frequently used for isolation of cell organelles from different tissues. But as the size and density of the organelles differ, the method needs to be optimised for every type of tissue. The novelty of this study is the application of a subcellular fractionation method to human healthy and cancerous renal and testicular tissue. Separation of total tissue homogenate into nuclei, cytosol, and a mixture of mitochondria and plasma membranes was achieved by differential centrifugation. As mitochondria and plasma membranes seemed to be too similar in size and weight to be separated by differential centrifugation, discontinuous density-gradient centrifugation was carried out successfully. The purity of the subcellular fractions was checked by measuring the activity of marker enzymes. All fractions were highly enriched in their corresponding marker enzyme. However, the nuclear fractions of kidney and renal cell carcinoma were slightly contaminated with mitochondria and plasma membrane fractions of all tissues with lysosomes. The fraction designated the cytosolic fraction contained not only cytosol, but also microsomes and lysosomes. The CLA contents of the subcellular fractions were in the range 0.13-0.37% of total fatty acids and were lowest in the plasma membrane fractions of all types of tissue studied. C16:0, C18:0, C18:1 c9, C18:2 n-6, and C20:4 n-6 were found to be the major fatty acids in all the subcellular fractions studied. However, marked variations in fatty acid content between subcellular fractions and between types of tissue were detectable. Because of these differences between tissues, no general statement on characteristic fatty acid profiles of single subcellular fractions is possible.

Phlebography: why it is important to study radiological imaging of spermatic veins.

OBJECTIVES: We delineate the role of phlebography which is a standard procedure during antegrade and retrograde sclerotherapy of idiopathic varicoceles. MATERIAL AND METHODS: Based on our experience with antegrade sclerotherapy in 5,254 adults and adolescents we present typical phlebographies of the internal spermatic vein and radiological images after irregular cannulation of different arteries and veins on the scrotal floor. The sequalae of misinjections and paravascular application of the sclerosing agent polidocanol are discussed. A radiological classification of venous drainage roots of the pampiniform plexus is introduced on the basis of 236 consecutive antegrade phlebographies. The findings are compared with the results of retrograde phlebography previously given in literature. RESULTS: Phlebography helps to ascertain that sclerotherapy is performed in an anatomically appropriate manner. Thus, misinjections and paravascular applications of polidocanol can be ruled out. Antegrade phlebography enables to visualize a high rate of side veins and collaterals of the internal spermatic vein and thus seems to be equivalent to the retrograde imaging in tracing the additional drainage roots of the pampiniform plexus. These additional roots are considered to be the source of persisting varicoceles after surgical treatment. CONCLUSIONS: Phlebography is needed to achieve good results after sclerotherapy of varicoceles and to minimize the toxic side effects of polidocanol. Finally it is a prove that the treatment has been performed accurately for forensic reasons.

Transurethral resection for bladder cancer using 5-aminolevulinic acid induced fluorescence endoscopy versus white light endoscopy.

PURPOSE: Endoscopy done under fluorescence induced by 5-aminolevulinic acid has proved to be a procedure with high sensitivity for detecting transitional cell carcinoma of the bladder. In this multicenter, parallel group, phase III study we compared 5-aminolevulinic acid fluorescence endoscopy guided transurethral bladder resection with transurethral bladder resection done using only white light endoscopy. The proportion of tumor-free resected cases in the 2 groups was evaluated. MATERIALS AND METHODS: After patient stratification according to participating centers and European Organization for the Research and Treatment of Cancer risk score 65 and 64 were randomized to the 5-aminolevulinic acid fluorescence and white light endoscopy groups, respectively. Residual tumor was evaluated in the 2 groups by repeat transurethral resection 10 to 14 days later. Analysis was performed according to the intent to treat principle with all patients randomized, followed by per protocol analysis. RESULTS: Intent to treat analysis revealed that in the white light endoscopy group 40.6% of cases were resected tumor-free at primary resection, whereas with 5-aminolevulinic acid fluorescence endoscopy guided transurethral resection 61.5% were resected tumor-free (p <0014). On protocol analysis 46.9% patients in the white light and 67.3% in the 5-aminolevulinic acid fluorescence endoscopy groups were resected tumor-free (p <0.031). No difference was noted in the 2 groups in regard to side effects or laboratory findings. CONCLUSIONS: The risk of residual tumor after transurethral resection of transitional cell carcinoma is significantly decreased by 5-aminolevulinic acid fluorescence endoscopy.