Tissue polypeptide-specific antigen in renal cell carcinoma.

OBJECTIVES: The usefulness of serum tissue polypeptide-specific antigen (TPS), a cytokeratin 18-associated marker, in renal cell carcinoma (RCC) was assessed in vitro and in vivo. METHODS: Indirect immunoperoxidase staining for TPS expression was performed on frozen sections of normal renal tissue and RCC specimens. By using a monoclonal TPS immunoradiometric assay, serum TPS concentrations were analyzed in 82 healthy controls, in 20 patients with locoregional RCC before and after surgery and in 18 patients with advanced disease following surgery receiving immunotherapy with interferon-gamma. RESULTS: Using immunohistochemistry, TPS was found to be expressed by both normal and cancerous renal epithelial cells. The mean TPS concentrations in 82 healthy controls was 56 +/- 49 U/1 with a 95% percentile of 78.5 U/1. Out of 20 patients with locoregional RCC, 8 presented with elevated values (mean 168 +/- 82 U/1) above the cut-off level (78.5 U/1, sensitivity 40%) which dropped to normal within 2 weeks after surgery. During a follow-up period of 1 year, none of the patients presented with tumor recurrence and TPS concentrations remained low (mean 52 +/- 36 U/1). In 18 patients receiving interferon-gamma therapy, serum TPS concentrations were monitored over a period of 12 months. In 5/18 patients, baseline levels were within the normal range (mean 37 +/- 21 U/1); interestingly, these at the same time were the only responders to immunotherapy (n = 2) or at least showed stable disease (n = 3). Response to therapy was reflected by low serum TPS levels (mean 28 +/- 23 U/1) over the entire observation period. Thirteen patients suffered progressive disease during therapy, all of them exhibiting significantly elevated (p < 0.005) pretherapeutic TPS concentrations (mean 186 +/- 124 U/1) that remained equally elevated throughout therapy (mean 192 +/- 102 U/1), reflecting tumor progression. CONCLUSIONS: TPS might have some clinical value as prognostic marker in RCC, possibly by reflecting the proliferative tendency of the tumor.

Primary metastatic carcinoma of the prostate in younger men: a plea to think over usual therapeutic strategies.

METHOD: The time from first diagnosis of primary multiple metastatic prostate carcinoma until progression and until death in patients less than 60 years old under two different therapeutic regimens was evaluated. RESULTS: In the group with pure androgen deprivation (n = 21), the mean time until progression was 11.3 (6-55) months, the mean survival time being 21.4 (11-75) months. In the group with androgen deprivation plus cytostatic therapy (n = 10), progression was noted after 26.7 (15-77) months with a medium survival time of 26.2 (16-82) months. CONCLUSION: The data argue in favor of changing the usual treatment strategy to combination therapy in "young' patients with primary metastatic prostatic cancer.

Circulating immune markers in advanced renal cell carcinoma during immunotherapy with interferon gamma.

Circulating immune markers sICAM-1, sELAM-1, sMHC-I, beta 2-MG, sCD4 and sCD8 were evaluated prior to and during immunotherapy with biologically active doses of interferon gamma (IFN-gamma) in 16 patients with advanced renal cell carcinoma (RCC) over a period of 12 months. Compared to 20 healthy controls, significantly (P < 0.01) elevated baseline levels of circulating adhesion molecules sICAM-1 (mean 1166 vs 230 ng/ml) and sELAM-1 (70 vs 17 ng/ml) were found in all patients. Compared to responders (n = 2) or patients with stable disease (n = 2), progressive disease during therapy (n = 12) was associated with significantly (P < 0.05) higher mean concentrations of sICAM-1 (1574 vs 962 ng/ml) and sELAM-1 (86 vs 46 ng/ml). Pretherapeutic and intratherapeutic levels of sMHC-I among the RCC patients were significantly (P < 0.05) lower than among the controls (0.41 vs 0.8 ng/ml). sCD4 levels clearly showed the same tendency (24 vs 33 U/l). sCD8 baseline levels, by contrast, were significantly (P < 0.05) elevated (564 vs 336 U/l), reflecting either activation of the NK-cell subset or increased synthesis of CD8+ T-suppressor cells. Again, significantly (P < 0.05) higher intratherapeutic sCD8 concentrations were observable with progressive disease than with response to therapy or stable disease (721 vs 355 U/l). Interestingly, although the biologically active dose of IFN-gamma was defined by an increase in beta 2-MG release of at least 30% within 48 h after injection, none of the other markers showed any significant alteration following IFN-gamma administration, suggesting that IFN-gamma in vivo does not produce changes in circulating markers of activation that might be expected on the basis of its effects in vitro. The finding of significantly elevated concentrations of sICAM-1, sELAM-1 and sCD8 in the presence of low sCD4 and sMHC-I levels might be of clinical significance for indicating ongoing tumor progression.

Electrohydraulic versus pneumatic disintegration in the treatment of ureteral stones: a randomized, prospective trial.

The efficacy and safety of electrohydraulic versus pneumatic lithotripsy in the treatment of ureteral stones were evaluated in a prospective, randomized study. A total of 72 patients with stones not capable of passing spontaneously and unsuitable for extracorporeal shock wave lithotripsy was randomized to either method (34 to electrohydraulic lithotripsy and 38 to pneumatic lithotripsy). While both techniques were equivalent in efficacy (85.3% for electrohydraulic and 89.5% for pneumatic lithotripsy), the perforation rates were significantly different (17.6 versus 2.6%, respectively). Although the long-term results revealed no significant differences, pneumatic lithotripsy, as the markedly safer and easier to handle technique, is currently the method of choice at our stone center for ureteral calculi requiring treatment but not suitable for extracorporeal shock wave lithotripsy.

Value of repeated analyses of 24-hour urine in recurrent calcium urolithiasis.

OBJECTIVES: The value of repeated analyses of 24-hour urine collections for daily excretion of calcium, uric acid, citrate, phosphorus, and creatinine and for volume and pH performed to detect and classify metabolic disorders in a selected group of calcium stone formers with striking recurrence rates was assessed in a retrospective study. METHODS: A total of 441 urinalyses made over a mean period of 80.4 months of samples obtained from 49 patients were reviewed. Fifty-nine percent of patients were initially found to have metabolic disorders (absorptive hypercalciuria types I and II, hyperuricuria, hypocitraturia) and therefore received specific drug therapy (allopurinol, thiazide, alkali citrate, orthophosphate) for a mean of 45.7 months (group I). The remaining patients were classified as metabolically inactive and were given general metaphylactic instructions (group II). RESULTS: In 73% of patients recurrent stones developed, with no statistically significant difference between the two groups (79% vs 65%). In 55% of group I patients, urinalyses continued to yield abnormal findings during follow-up; however, subsequent abnormal findings were also seen in 40% of the metabolically inactive group II patients. Overall, metabolic disorders were observed at some point in 75% of patients. Only 27% remained recurrence free, and 62% thereof also had pathologic urinary findings. CONCLUSIONS: It does not appear that drug treatment in recurrent calcium urolithiasis based on urinary findings is superior to simple general metaphylactic recommendations, nor that repeated analyses of 24-hour urine collections furnish additional information on the risk of recurrent stone formation or on the presence of risk factors leading to recurrence in the long-term course of disease.

Alkali citrate prophylaxis in idiopathic recurrent calcium oxalate urolithiasis--a prospective randomized study.

OBJECTIVE: To assess the efficacy of alkali citrate therapy in patients suffering from recurrent idiopathic calcium oxalate stone formation. PATIENTS AND METHODS: Fifty patients suffering from active stone formation who had had at least one stone annually over the previous 3 years were recruited and randomly divided into two groups. They were given either general prophylactic instructions, i.e. abundant liquid intake and dietary restrictions (group I, n = 25)--or were additionally treated with alkali citrate (group II, n = 25). RESULTS: In group I, the rate of stone formation was reduced from 1.8 to 0.7 stones per patient per year. Similar results were obtained for group II, the corresponding figures being 2.1 and 0.9. There was a statistically significant higher urinary citrate excretion in group II than in group I. No difference was seen between the two groups regarding recurrent stone formation (Student's t-test). Stone formation decreased in both groups (group I 27%, group II 31%). Subjectively, 56% of group II patients, all of whom had previously experienced severe colic, reported spontaneous stone elimination to be painless, whereas in group I all but one patient suffered pain. CONCLUSION: An objective benefit of alkali citrate could not be established.

Serum neopterin as a parameter for monitoring the course of renal cell carcinoma during interferon-gamma therapy.

Serum analyses were performed regularly over 1 year of therapy with bioactive doses of recombinant interferon-gamma (mean 200 micrograms) in eight patients with advanced renal cell carcinoma in order to assess the usefulness of neopterin in monitoring the course of disease. The baseline level calculated from repeated measurements before treatment (2.87 + 0.59 nmol/liter) did not correlate with the extent of metastatic spread. All patients did show significant increases in serum neopterin concentrations 48 hr after IFN application (7.09 +/- 1.99 nmol/liter, P < 0.05, t test) in accordance with a temporary IFN-gamma-induced reinforcement of macrophage activity. However, no difference was observable when comparing the baseline values to those obtained 1 week after the last IFN application (3.05 +/- 1.16 nmol/liter). There was no correlation with the course of disease, i.e., neither with response (n = 1) nor with progression (n = 7). In contrast to previous studies, the present report shows that although serum neopterin is an appropriate marker for IFN-gamma-induced reinforcement of monocyte/macrophage activity, it is not suitable for monitoring the course of metastatic renal cell carcinoma.

The 'stone clinic effect': myth or reality?

Sixty-six active recurrent stone formers (RSF), i.e., with at least one stone annually over 3 years prior to the first examination at our stone clinic, were retrospectively evaluated. All received specific drug metaphylaxis which was discontinued after 5.5 +/- 2.1 years (period 1). They were reclassified according to the above definition into active and inactive RSF and were then left on a general metaphylactic regimen with regular urological follow-up every 6 months (period 2). 32 patients observed these recommendations for 5.7 +/- 2.6 years (group 1), 34 did not. 20 of these 34 could be reexamined after 6.3 +/- 2.2 years (group 2). Group 1 comprised 10 active and 22 inactive, group 2 comprised 1 active and 19 inactive RSF. While the recurrence rates among the inactive RSF of groups 1 and 2 decreased significantly during period 2, a statistically significant difference between them was not observed. Conversely, there was only a slight reduction of the recurrence rate in the active RSF. Both findings argue against a stone clinic effect. Interviews of the patients showed that stone formation was periodical for a mean of 12 +/- 8 years, after which it gradually faded out. This period is termed 'phase of regular stone formation' and appears to be an autonomous process that cannot usually be influenced by metaphylactic measures. This could explain the wide variability of reported success rates for the various metaphylactic regimens, as they would merely reflect the number of stone formers who are in their phase of regular stone formation.

Management of ureteric stones.

Based on experience with over 2,000 patients, the treatment of ureteric stones today relies on extracorporeal shock wave lithotripsy (ESWL) in situ and ureteroscopy with semirigid, ultrathin ureteroscopes combined with pneumatic or laser lithotripsy. All stones in the upper and larger stones in the distal third of the ureter are preferably treated by ESWL in situ, whereas smaller stones in the distal ureter are better treated by endoscopy. Midureteric stones continue to be the domain of primary ureteroscopy; in cases of moderate obstruction in asymptomatic patients, it may also be acceptable to wait for the stone to pass into the distal ureter spontaneously to be treated by ESWL in situ there. Manipulation of the stone back into the kidney and treating it by ESWL there (push back/ESWL) offers no advantage over ESWL in situ, as results are not better yet morbidity is higher. 'Blind' instrumentation has lost all justification, and incisional ureteric lithotomy is no longer indicated but in exceptional cases.

Incidence of antisperm antibodies in patients with carcinoma of the testis and in subfertile men with normogonadotropic oligoasthenoteratozoospermia.

The incidence and the clinical relevance of sperm-reactive antibodies in subfertile men and in testicular cancer patients were assessed in a pilot study. The sera of 42 men with normogonadotropic oligoasthenoteratozoospermia (OAT syndrome, n = 20) or carcinoma of the testis after inguinal semicastration (n = 22) were analyzed for agglutinating antisperm antibodies using fluorescein-labeled antiglobulin. In the group with the OAT syndrome, the incidence of sperm-reactive antibodies was only 5%, which is comparable to that in normal fertile men. Although the incidence of 18% in the testicular cancer patients was markedly higher, only 2 of the patients in question had abnormal spermiograms, which in one case could, moreover, be explained by previous radiation therapy. In summary in this small group of patients, serum monitoring for sperm-reactive antibodies appeared to be of limited clinical relevance in patients with the OAT syndrome and in testicular cancer patients.

Color flow Doppler sonography for extracorporeal shock wave lithotripsy.

This report documents the usefulness of color Doppler sonography for early verification of urinary stone fragmentation during extracorporeal shock wave lithotripsy with ultrasonographic focusing. In the experimental study lithotripsy was performed on human urinary stones placed in pig kidneys. Increasing color flow within the stone mass created by movement of small fragments indicated fragmentation earlier than pixel movement on the standard gray scale sonogram. The success of treatment was demonstrated macroscopically. In the clinical study 25 patients with radiopaque kidney stones were treated by color Doppler guided shock wave lithotripsy and compared to a control group of 32 patients with similar stone characteristics in whom the end point of treatment was chosen based on B-mode sonography alone. The amount of color flow within the stone reflex determined the end point of treatment. The degree of fragmentation was confirmed by fluoroscopy immediately after treatment. Disintegration was successful in all cases and fragments passed spontaneously. Color Doppler imaging during shock wave lithotripsy provides reliable information on the spatial and temporal characteristics of stone fragmentation, and is superior to B-mode sonography by providing more immediate, objective information on stone fragmentation and allowing better evaluation of the focal zone. With the help of this technique, the number of applied shock waves could be reduced by 20% compared with the control group.

Plasma sialic acid in patients with prostate cancer.

Serum sialic acid (N-acetylneuraminic acid) was evaluated as a tumour marker for prostate cancer and compared with serum prostate specific antigen (PSA). The records of 35 patients suffering from prostate cancer (9 with bone metastases) were analysed and compared with those of 21 healthy individuals. Total serum sialic acid was significantly elevated among the cancer patients. Levels in patients with distant metastases were significantly higher than in those with locally restricted disease and normal individuals, whereas no such difference was seen between the latter 2 groups. A direct association between serum sialic acid and tumour T category and grade could not be established. The difference between the cancer and the control groups was reflected more significantly by PSA. As sialic acid lacks tumour specificity, it is not helpful in screening for prostate cancer, yet might contribute towards the early detection of tumour progression and metastases during both therapy and follow-up.

ESWL in situ or ureteroscopy for ureteric stones?

As documented by follow-up data on ureteric stones in 1259 ureteric units treated, ESWL in situ on advanced lithotriptors with stone location by ultrasonography and fluoroscopy was successful without any retrograde ureteric manipulation in 98% of stones in the upper, 71% in the iliac, and 84% in the distal ureter; 85% of the units were stone-free within 3 months: ancillary measures were needed in 11% and the stone-free state was reached after a median of 39 days. The results obtained with treatment after manipulation of the stone from the upper and mid-ureter by retrograde instrumentation were similar, but ancillary measures were needed in 20% of cases. Endoscopic management with rod-lens ureteroscopes was highly efficient in the distal and mid-ureter, but involved a complication rate of about 11% and required general anaesthesia. In the upper ureter it was abandoned in favour of the two former methods. Endoscopic stone removal has been greatly facilitated by the development of ultrathin, semirigid ureteroscopes 6.2-9 F in diameter, as well as by laser and pneumatic lithotriptors that operate through their minute working ports. Of the stones impacted in 127 ureteric units, 97% were successfully managed at the first attempt, involving an overall complication rate of 6%.(ABSTRACT TRUNCATED AT 250 WORDS)

Rare-earth elements in urinary calculi.

In vitro studies have demonstrated that trace elements have inhibitory as well as stimulatory effects on the crystallization of urinary stones. Little is known about the activities of rare-earth elements (REEs) in the human body. Although their physiological role is unclear, an effect on calcium transport mechanisms is discussed. In the present study, ten kidney stones (six oxalate and four phosphate stones) were analyzed by neutron-activation analysis for their REE patterns. Urinary stones are capable of concentrating these elements, and some fractionation into light and heavy REEs appears to take place during deposition. Significantly elevated concentrations of heavy REEs such as europium, terbium, and lutetium were detected in phosphate stones as compared with oxalate stones (P < 0.005).

Value of routine sonography in the diagnosis and conservative management of renal angiomyolipoma.

A prospective study was undertaken to assess the value of ultrasonography in the clinical monitoring of angiomyolipomas. 26 patients with angiomyolipomas as diagnosed by sonography and verified by computerized tomography (CT) were followed up by sonographic monitoring over a mean period of 45 months. One case was associated with tuberous sclerosis. Inclusion criteria for conservative management had been clinically asymptomatic angiomyolipomas smaller than 5 cm. Significant tumor growth and a change of the sonographic pattern during follow-up was seen in 2 patients. After renewed follow-up CT scanning failed to reveal negative density values, both patients were nephrectomized. Histologic examination showed hemorrhage in the tumor. The remaining 24 patients (92%) showed no changes in the sonographic patterns. Minor tumor growth of 0.5 cm on average was seen in 6 patients over a mean follow-up period of 52 months. Surgical intervention was refrained from in these 24 patients due to the consistent sonographic pattern and the absence of clinical symptoms. Once the angiomyolipoma is verified by CT, sonographic monitoring suffices if the sonostructure remains unchanged. Minor asymptomatic angiomyolipomas today no longer require surgical intervention as this benign tumor has a pathognomonic sonographic appearance.

Sonographic appearance of testicular microlithiasis.

Testicular microlithiasis was sonographically diagnosed in 16 patients. Using high-frequency transducers, the typical speckled pattern with multiple small bright echoes generated by intratubular calcifications appeared in the sonograms. The finding was bilateral in all but one patient who had previously undergone semicastration for testicular cancer and subsequent irradiation. In 6 cases a testicular tumor was present and visible in the sonogram. Sonography was performed in another 6 cases because of varicocele or epididymal cysts. The spermiograms and tumor marker levels of these patients were within the normal range, and there was no evidence of an extragonadal germinal tumor. Three patients presented with oligozoospermia, 1 thereof with hypogonadism. In 7 cases the sonographic diagnosis was histologically confirmed, i.e. multiple calcifications were found within the seminiferous tubules. The etiology and clinical significance of this rare phenomenon are unclear. Testicular microlithiasis is asymptomatic and also found in otherwise normal testes. However, in contrast to normal testes, a high percentage of testicular tumors is known to be associated with microcalcifications. In the presence of a definite sonographic diagnosis, exclusion of malignancy and sonographic follow-up are therefore indicated, as in the present series 44% of cases presented with testicular tumors.

Incidence of testicular microlithiasis.

In adults polytopic intratubular calcifications of the testes are rare. Known as testicular microlithiasis, they manifest themselves in a characteristic echo pattern on sonography with high-frequency transducers (5 to 10 MHz). This consists of multiple echogenic specks in an otherwise normal testicular parenchyma. In a retrospective analysis of 1,710 testicular sonograms of adults, bilateral intratesticular microliths were found in 11 cases (0.6%). In 5 of them, the microliths were associated with a testicular tumor. One patient with a tumor in the contralateral testis had undergone radiotherapy and another one presented with hypogonadism. Four patients with noncontributory histories presented with varicocele or epididymal cyst. Sonographic findings were confirmed histologically in 6 patients. Multiple intratubular calcifications were found in all of them. The pathogenesis of testicular microliths is still poorly understood. Their clinical relevance is unclear, but their incidence in adults appears to be higher than reported in the literature.

High resolution ultrasonography in the diagnosis of simple intratesticular cysts.

Simple intratesticular cysts are a rare condition. High resolution sonography permits unequivocal sonographic differentiation between intratesticular cysts and neoplastic lesions with a cystic appearance, so that conservative treatment seems justified. Seventeen patients with sonographically diagnosed intraparenchymal testicular cysts were followed up for an average of 29 months. No increase in size or change in echo pattern was found and surgical therefore not indicated.