[Percutaneous nephrolithotomy - always effective and free of complications?]. / Perkutane Nephrolitholapaxie (PNL) - immer effektiv und komplikationslos?

PURPOSE: The purpose of this study was to evaluate the results and complications of percutaneous nephrolithotomies performed within 5 years in our patients. MATERIALS AND METHODS: From 2001 to 2005 in our department 158 percutaneous nephrolithotomies (PNL) in 131 patients and 138 renal units were performed. The indications for PNL were calculus greater than 2 cm, failed ESWL, and when there is additional urinary obstruction which was not caused by the stone itself. Data concerning past medical history, about the procedure including complications and the postoperative course were collected and evaluated. RESULTS: 87 (63 %) of the patients had a history of prior stones. The main symptoms were flank pain, recurrent renal colic and urinary tract infection. The stones treated had a size from 5 to 60 mm. In 40 patients (29 %) relief of urinary obstruction (double-J-ureteral stent or percutaneous nephrostomy) or ESWL was performed prior to PNL. Mean operating time was 83 (30 - 235) minutes including retrograde placement of a ureteral catheter and nephrostomy. Complications occurred in 26 (16.5 %) procedures. Severe complications were: one fatal pulmonary embolism, one septicaemia, three open revisions (including one nephrectomy) and four blood transfusions for blood loss. In 94 patients (68 %) there was no residual stone or gravel after the first PNL. No further therapy was necessary in 17 (39 %) of the 44 patients with incomplete stone removal. 19 patients underwent a secondary PNL. In these procedures the efficacy decreased. 102 of 131 patients (138 renal units = 73.9 %) were discharged without residual stone after 158 procedures. CONCLUSIONS: PNL is an efficient and rarely complicated procedure for larger stones of the upper urinary tract. Even so, the occurrence of severe complications must be considered. Complications can be minimised by the use of a standardised therapeutic pathway.

[Cystinuria - Cystine Stones: Recommendations for Diagnosis, Therapy and Follow-up]. / Zystinurie - Zystinsteinleiden: Aktuelle Empfehlungen zur Diagnostik, Therapie und Nachsorge.

Cystinuria, an autosomal-recessive disorder, is the cause of 1 - 2 % of all kidney stones observed in adults and about 10 % of those observed in infants. Despite increasing understanding of underlying pathomechanisms, patients still form recurrent stones and have to undergo repeated interventions with increasing risk of renal insufficiency. Dietary and medical metaphylaxis may lower the frequency of recurrent stones but are often not practiced. Regular follow-up examinations and optimal therapy significantly enlarge stone-free intervals. This review offers an overview of the underlying pathogenetic mechanisms as well as guidance for diagnosis, monitoring, metaphylaxis and therapy of cystinuria following the recommendations of the Deutsche Gesellschaft für Urologie (DGU) and the European Association of Urology (EAU).

Genetic alterations in metastatic renal cell carcinoma detected by comparative genomic hybridization: correlation with clinical and histological data.

In order to optimize the management of patients with renal cell carcinoma (RCC) it is important to define the genetic risk for metastatic disease. In this study we performed comparative genomic hybridization (CGH) on metastatic tumors aiming at the identification of genetic alterations associated with metastatic disease. We analyzed 46 renal tumors along with their metastases, and 15 non-metastatic renal tumors. Tumors were classified pathologically according to the Heidelberg classification of RCC, and staged according to the TNM-system. Standard CGH was performed using microdissected archival tissues and DOP-PCR. The average numbers of chromosomal aberrations per tumor were 3.0, 2.1 and 3.9 in patients without metastasis, in patients who developed metastases after a two-year latency period (late onset of metastatic disease) and in patients who developed metastases within two years after therapy of the primary tumor (early onset of metastatic disease). CGH revealed chromosomal aberrations in 91% of primary metastatic tumors. Deletions or losses of chromosomes 9 (26% vs 6%), 10 (21% vs 6%) and 18 (23% vs 0) and 17 (28% vs 7%) occurred more often in metastatic tumors than in non-metastatic tumors. Furthermore, these aberrations were more common in patients with early metastases. CGH analysis of 40 pairs of primary RCCs and their corresponding metastasis revealed similar aberrations in 70% of cases. In 30%, however, metastases showed additional chromosomal aberrations not detected in the corresponding primary tumors. In conclusion, we identified genetic alterations associated with metastatic disease in RCC which could be useful for predicting prognosis. Genetic changes leading to metastases occurred early in tumorigenesis of metastatic tumors.

Analysis of point mutation in exon 2 of CYP2E1 gene in renal cell/urothelial cancer patients in comparison with control population.

OBJECTIVE: Genetic polymorphisms of human cytochrome P450s have been implicated to be of importance for susceptibility to different cancers. Recently, a point mutation was found in the exon 2 of the CYP2E1 gene (CYP2E1*2) [Hu et al. 1997]. In order to evaluate a possible link between the point mutation in exon 2 of the CYP2E1 gene and the susceptibility to renal cell/urothelial cancer, we developed a screening method based on the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). MATERIAL: DNA of peripheral white blood cells was isolated from 158 renal cell/urothelial cancer patients as well as from 150 controls. METHOD: Primers for PCR were designed by the Primer 3 release 0.1 program. The PCR yield a product of 215 base pairs (bp), which was digested with the restriction enzyme Hha I. The DNA fragments were separated on a 3% agarose gel stained with ethidium bromide. Restriction enzyme digestion of the PCR product obtained from the wild-type DNA resulted in the appearance of a 66 bp, a 43 bp, a 40 bp, a 39 bp and a 28 bp DNA fragment. In contrast to the wild-type, the digestion of the PCR product from DNA carrying the point mutation resulted in the loss of the 39 bp and 40 bp fragments and the appearance of an additional 79 bp fragment. Therefore, the loss of one Hha I restriction site caused by a single nucleotide exchange is suitable for the identification of the point mutation in exon 2 of CYP2E1 gene. RESULTS: However, we could not detect any point mutation in any of the 158 renal cell/urothelial cancer patients or the 150 controls. The distribution of the point mutation in exon 2 of CYP2E1 gene did not show any difference in renal cell/urothelial cancer patients and controls. CONCLUSION: This might indicate a lack of association between this CYP2E polymorphism (CYP2E1*2) and renal cell/urothelial cancer.

Effective analgesia for extracorporeal shock wave lithotripsy: transcutaneous electrical nerve stimulation.

OBJECTIVES: Extracorporeal shock wave lithotripsy (ESWL) has revolutionized the treatment of urinary stone disease. However, the most appropriate analgesia offering pain-free treatment, minimal side effects, and adequate cost effectiveness remains to be established. This prospective study was performed to evaluate the efficacy of transcutaneous electrical nerve stimulation (TENS) during ESWL using third-generation lithotripters. METHODS: Two pairs of stimulator electrodes were placed paravertebrally at L1 and near the lithotripter shock tube before ESWL. Treatment was carried out as follows: (a) shock wave administration was begun (no current = sham TENS); (b) in the case of severe pain, TENS was begun; and (c) if patients experienced no pain relief, analgesic drugs were given intravenously. RESULTS: Of 149 patients, 92 (62%) did not need any analgesia (neither TENS nor medication). In 42 (72%) of the remaining 57 patients, a TENS-related, pain-relieving response was observed. ESWL-induced pain could be reduced by 39.2%. The degree of fragmentation assessed by two urologists was found to be 90% for patients receiving TENS compared with a retrospectively analyzed control group (94%, n = 100). CONCLUSIONS: Two different theories explaining TENS-related analgesia are known: segmental (spinal) and supraspinal (central) inhibition. Since we did not observe any analgesic effect in patients having both pairs of electrodes attached around the shock tube (n = 30), supraspinal inhibition obviously accounts for the abovementioned pain relief. We conclude that TENS is a noninvasive, cost-effective method to achieve side-effect-free analgesia in ESWL using third-generation lithotripters.

[Increased incidence of renal cell carcinoma in central Europe. Does diagnostic increase reflect a true increase in incidence?]. / Inzidenzzunahme beim Nierenzellkarzinom in Mitteleuropa. Entspricht die diagnostische einer echten Inzidenzzunahme?

In the last years the incidence of renal cell carcinoma diagnosis increased about 15-20%. The main aim of this study was to analyse the reason of the increase of incidence. In the present autopsy series comprising 23,801 autopsies the percentage of patients who died of renal cell carcinoma is 1.77% in Jena and 1.55% in Königgrätz (200,000 inhabitants each). Over this time the incidence of renal cell carcinoma in autopsies has increased. In spite of the increased amount of incidentally found renal cell carcinomas since beginning widespread use of ultrasonography the percentage of clinically recognized renal cell carcinomas on the total of all found renal cell carcinomas in autopsies is nearly constant about the 12-year period in Jena and 10-year period in Königgrätz. Thus, the increased number of radical nephrectomies is not only caused by widespread use of ultrasonography. The increasing trend of the incidence of renal cell carcinoma seems to be real.

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.

CYP2E1 genotyping in renal cell/urothelial cancer patients in comparison with control populations.

OBJECTIVE: Genetic polymorphisms in enzymes involved in carcinogen metabolism have been found to influence susceptibility to cancer. Ethanol-inducible CYP2E1 is an enzyme of major toxicological interest because it metabolizes several drugs, precarcinogens, and solvents to reactive metabolites. In the present investigation, we studied the cytochrome P450 2E1 genetic polymorphism in renal cell/urothelial cancer patients in comparison with healthy control populations in the regions of Jena and Halle in Germany. PATIENTS AND MATERIAL: DNA of peripheral white blood cells was isolated both from 273 renal cell/urothelial cancer patients and 298 controls from the regions of Jena and Halle. METHOD: We focused on polymorphisms in the promoter region and intron 6 of the CYP2E1 gene. The polymorphims were identified as restriction fragment length polymorphisms (RFLPs) by polymerase chain reaction (PCR) and subsequently applying the restriction enzymes PstI/RsaI and DraI. RESULTS: In the region of Jena as well as of Halle, the frequency distributions of the PstI/RsaI, DraI, and combined DraI + PstI/RsaI genotypes showed no significant differences between controls and renal cell/urothelial cancer patients. We did not find significant differences between Jena and Halle. 86.7% of all subjects with a homozygote PstI/RsaI genotype also carried a homozygote DraI genotype, whereas 5.2% of all subjects with a heterozygote PstI/RsaI genotype also carried a heterozygote DraI genotype. The heterozygote genotype of PstI/RsaI polymorphism always determines the heterozygote genotype of DraI polymorphism. Our results failed to demonstrate any differences in the distribution of CYP2E1 polymorphisms between renal cell/urothelial cancer patients and controls. CONCLUSION: Summing up, our results show that CYP2E1 genotype cannot predict risk for renal cell/urothelial cancer in the population from 2 different regions in Germany. The results demonstrate a lack of association between CYP2E1 genetic polymorphism and renal cell cancer/urothelial cancer.

Impact of CYP2E1 genotype in renal cell and urothelial cancer patients.

Genetic polymorphisms of enzymes involved in carcinogen metabolism have been found to influence susceptibility to cancer. Ethanol-inducible CYP2E1 is an enzyme of major toxicological interest because it metabolizes several drugs, precarcinogens and solvents to reactive metabolites. In the present study, we investigated the cytochrome P450 2E1 genetic polymorphism in renal cell/urothelial cancer patients from two German regions, Jena and Halle, different with respect to their environmental pollution degree in comparison with healthy controls from the same regions. DNA of peripheral white blood cells was isolated both from 224 renal cell/urothelial cancer patients and 304 controls. We focussed on polymorphisms in the promoter region and intron 6 of the CYP2E1 gene. The polymorphisms were identified as RFLP's by amplification of the appropriate DNA fragment and subsequent digestion with the restriction enzymes PstI, RsaI and DraI. In Jena as well as in Halle, the frequency distributions of the PstI/RsaI, DraI and combined DraI + PstI/RsaI genotypes showed no significant differences between controls and renal cell/urothelial cancer patients. We did not find significant differences between Jena and Halle. 86.2% of all subjects with a homozygote PstI/RsaI genotype also carried a heterozygote DraI genotype, whereas 5.1% of the subjects with a heterozygote PstI/RsaI genotype also carried a heterozygote DraI genotype. Renal cell cancer as well as urothelial cancer risk was not elevated in patients with heterozygote DraI, PstI/RsaI and combined DraI + PstI/RsaI genotypes (odds ratios slightly insignificantly increased). Interestingly enough, an association between these polymorphisms and renal cell cancer risk was found in the female subgroup but not in the male subgroup. The basis of these sex-specifically increased risks are different frequencies concerning heterozygote and homozygote genotypes in controls and cancer patients. In controls, the heterozygote genotype frequency was lower in females than in males. In renal cell cancer patients, the results were quite the contrary. Summing up, our results demonstrate an lack between CYP2E1 genetic polymorphism and renal cell/urothelial cancer risk.

[Laparoscopic management of a ureteral lesions in Schauta-Stoeckel radical vaginal hysterectomy]. / Laparoskopische Versorgung einer Ureterläsion bei radikaler vaginaler Hysterektomie nach Schauta-Stoeckel.

We report on the laparoscopic repair of an ureteral injury during radical vaginal hysterectomy according to Schauta-Stoeckel combined with laparoscopic paraaortic and pelvic lymphadenectomy. A 0.5 cm long oval incision of the left ureter 4 cm from the bladder was noticed during laparoscopic inspection at the final stage of the operation. The injury was repaired through a transvesical ureteral stent under laparoscopic guidance with laparoscopic intracorporeal suturing. On postoperative day 10 the ureteral stent was removed. An intravenous urogram taken 4 weeks after the operation showed normal conditions. Therefore primary laparoscopic repair of an ureteral injury is possible and effective.

Glycose aminoglycane excretion and concentration in the urine of patients with frequently recurrent calcium-oxalate lithiasis prior to and following Diclofenac-Na therapy.

Excretion and concentration of glycose aminoglycans were measured in 19 patients with frequent relapses of calcium-oxalate lithiasis, prior to and two weeks after onset of Diclofenac-Na therapy. In most patients, markedly enhanced glycose aminoglycan concentration and excretion could be demonstrated. Elevation of the high-molecular inhibitor potential in the urine results in reduced risk of calcium-oxalate lithogenesis, which may explain the therapeutic success of nonsteroidal anti-inflammatory drugs in the treatment of therapy resistant calcium-oxalate lithiasis.

[The prognosis of patients with struvite calculi with remaining/recurrent calculi and treatment refractory urinary tract infections]. / Zur Prognose von Struvitsteinpatienten mit Rest-/Rezidivsteinen und therapieresistenten Harnwegsinfekten.

29 patients suffering from recurrent struvite stones and/or persistent urinary tract infection were analyzed retrospectively with a follow-up time of 10 +/- 6 years. A sanitation of the urease-positive urinary tract infection was possible in 12 patients (41%). After 10 out of 53 operations (19%) rest stones were found. An unilateral nephrectomy was done in 3 cases. Despite rest calculi and persistent urinary tract infection no further calculus growth or deterioration of renal function was found in most patients.

[Non-medicamentous prevention of calcium oxalate urinary calculi]. / Nichtmedikamentöse Prophylaxe beim Calcium-Oxalat-Harnsteinleiden.

In a prospective study the efficacy and actual outcome of non-medicamentous preventive measures with metabolically unremarkable calcium-oxalate urolithiasis were investigated in 49 idiopathic calcium-oxalate stone formers. Overnight urine excretion was not increased. The mean concentration and excretion of essential parameters in terms of lithogenesis were hardly influenced. The obvious reduction of the pelvi-calyceal area in both lithogenous and non-lithogenous kidneys after one year of calculus prophylaxis was striking. By means of a discriminant function including morphological parameters and high-molecular urine components some developments may be verified in the discriminant space suggesting a good prophylactic result in many patients.

Influence of magnesium on the absorption and excretion of calcium and oxalate ions.

In two test series additional oxalic acid excretion in urine was induced in healthy test persons by administering a spinach diet. This additional excretion could be markedly reduced by magnesium administration. Calcium and citrate excretions are largely unaffected by magnesium administration. Magnesium excretions, however, are clearly increased. The calcium oxalate crystallization rates in the 5-or 7-hour urines reveal a behavior parallel to that of the oxalic acid excretion profile. In the control urines, the crystal picture is characterized by numerous medium-sized whewellite crystals. In contrast, in the test series weddellite crystals are reduced in size and frequency after magnesium administration. New aspects of magnesium effects must be discussed; above all the possible absorption changes resulting from gastrointestinal diseases.