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A Schlichter

Publications and source records attributed to A Schlichter.

At least 19 recordsLinked to original sources

New cut-off point between T1 and T2 renal cell carcinoma - necessary for a better discriminatory power of the TNM classification.

PURPOSE: We evaluated the pathological features of tumor size, lymph node and distant metastases, cell type, growth pattern, infiltration pattern, histological grade, local invasion and venous involvement of organ-confined renal carcinomas. The aim of this study was the re-evaluation of the TNM classification and the tumor cut-off point between T1 and T2 for renal cell carcinomas from the 1987 to the 1997 versions. MATERIALS AND METHODS: (1) Patients with renal cell carcinoma who had been operated between October 1992 and August 2001 were evaluated. 437 of 691 patients showed T1 and T2 tumors. These organ-confined tumors have been divided into five groups: group 1: tumor-size of 20 mm or less (n = 16), group 2: 21-30 mm (n = 79); group 3: 31-40 mm (n = 83; group 4: 41-70 mm (n = 184), and group 5: more than 70 mm in diameter (only T2, n = 75). Follow-up ranged from 0 to 100 months (average 28.63 months). (2) Of 15,347 autopsies performed in Jena between 1985 and 1996, 272 renal cell carcinomas were revealed. In 145 of these 272 cases renal cell carcinomas were limited to the kidney. These 145 tumors were divided accordingly into 5 groups: group 1: 20 mm or less (n = 33), group 2: 21- 30 mm (n = 31); group 3: 31-40 mm (n = 29); group 4: 41-70 mm (n = 42), and group 5: T2 (n = 10). Clinicopathological criteria examined were lymph node and distant metastases, cell type, growth pattern, infiltration pattern, histological grade, local invasion and venous involvement. To identify the optimal cut-off point between T1 and T2 disease the chi2 test was used. RESULTS: (1) In the clinical series only 1.8% (n = 8) of all cases showed lymph node metastases. Distant metastases were shown in 57 cases (13.04%); within group 1: 0%, group 2: 7.59%, group 3: 1.20%, group 4: 15.76%, group 5: 28%. The tumor grading was statistically correlated with tumor size. (2) In the pathological series 94 of the evaluated 145 patients were downstaged from T2(1987) to T1(1997). Lymph node and distant metastases were well correlated with tumor size. Lymph node metastases were seen in 0, 12.9, 31, 29.3 and 40% (group 1 to group 5) and distant metastases in 12.1, 25.8, 41.4, 47.7 and 60%. There were no statistically significant differences between T2(1997) and T1(3-7 cm). The tumor grading was statistically correlated with tumor size (grade 1: in 66.7, 25.8, 17.2, 9.5 and 0%). CONCLUSION: Our data suggest that the current cut-off diameter between T1 and T2 renal cell carcinomas (7 cm) is too high. Lowering the cut-off level will result in better discriminatory power of the TNM classification. From our data, we conclude that the cut-off diameter should be lowered to 3.5 cm (p < 0.001).

Adult↗

[Transesophageal echocardiography and intraoperative management of patients with renal cell carcinoma and rena cava extension].

OBJECTIVE: To evaluate the role of intraoperative real-time transesophageal echocardiography (TEE) for the anesthetic and surgical management of patients with renal cell carcinoma and vena cava extension. METHODS: Retrospective analysis of the intraoperative application of TEE in a series of 4 patients. RESULTS: Real-time TEE with a multiplane probe allowed visualization of inferior vena cava tumor extensions, accurate assessment of the distal extent of vena cava invasion into hepatic veins and right atrium, monitoring of embolism and evaluation of cardiac preload and function in all patients. CONCLUSION: Intraoperative TEE is a useful adjunct to the anesthetic and surgical management of patients with renal cell carcinoma and vena cava extension.

Carcinoma, Renal Cell↗

A Rsc3/Rsc30 zinc cluster dimer reveals novel roles for the chromatin remodeler RSC in gene expression and cell cycle control.

Chromatin remodeling complexes perform central roles in transcriptional regulation. Here, we identify Rsc3 and Rsc30 as novel components of the essential yeast remodeler RSC complex. Rsc3 and Rsc30 function requires their zinc cluster domain, a known site-specific DNA binding motif. RSC3 is essential, and rsc3 Ts- mutants display a G2/M cell cycle arrest involving the spindle assembly checkpoint pathway, whereas rsc30Delta mutants are viable and osmosensitive. Rsc3 and Rsc30 interact functionally and also physically as a stable Rsc3/Rsc30 heteromeric complex. However, DNA microarray analysis with rsc3 or rsc30 mutants reveals different effects on the expression levels of ribosomal protein genes and cell wall genes. We propose that Rsc3 and Rsc30 interact physically but have different roles in targeting or regulating RSC.

Base Sequence↗

Computerized contrast angiosonography: a new diagnostic tool for the urologist?

OBJECTIVES: To evaluate the diagnostic potential of echo-enhanced ultrasonography (US) for depicting the vascularization pattern of renal cell carcinoma (RCC), and calculating the first-pass effect using harmonic imaging, against that obtained by triphasic helical computed tomography (CT). PATIENTS AND METHODS: Sixty patients with surgically confirmed RCC underwent US using B-mode and power Doppler methods with or without an intravenous microbubble echo-enhancing agent. After depicting and defining the tumour extent by B-mode US, the first-pass effect/enhancement by the echo-enhancing agent within the lesion, and that of a reference area of unaffected renal cortex, were recorded on-line by calculating the mean pixel intensity. Time-intensity curves, i.e. the rise time and gradient of both the suspected tumour and reference areas, were constructed. RESULTS: Using B-mode US, the extent of all tumours was delineated (mean tumour size 3.8 cm, SD 0.6). After applying the microbubble agent all tumours were enhanced, whereas the perfusion was decreased (in 48%), increased (in 16%) or similar (in 36%) compared with the cortical reference area. Using the Hounsfield classification, these results correlated well with the hypo/hypervascularity shown on CT. CONCLUSION: Ultrasonography has considerable potential in diagnosing RCC, if combined with echo-enhancing methods, harmonic imaging and computer-based calculation of tumour vascularization. Dynamic US studies should provide a diagnostic yield similar to that of CT.

Carcinoma, Renal Cell↗

Where are the limits of elective nephron- sparing surgery in renal cell carcinoma?

OBJECTIVES: The indication for elective nephron-sparing surgery (NSS) in renal cell carcinoma (RCC) is still controversial. The presented study was performed to determine limitations for NSS regarding to multifocality and to characterize the biological importance of these small tumor lesions. METHODS: In 372 patients who underwent radical nephrectomy for RCC consecutively, nephrectomy specimens were investigated by using 3-mm parenchyma sections regarding to local tumor spread and multifocality. To characterize multifocal tumors, we performed cytogenetic and molecular genetic investigations. RESULTS: Serial sections of 372 nephrectomy specimens revealed a total of 92 multifocal tumors in 61 specimens (16.4%). The correlation between tumor size and multifocality is shown as follows: tumor diameter 1-20 mm: 12.5%; 21-30 mm: 23.4%; 31-40 mm: 10.2%; >40 mm: 16.7%. The mean diameter of the multifocal tumors was 8.8x9.1x6.1 mm and the mean distance to the primary tumor was 26.4 mm (5-84 mm). Using cytogenetic and molecular genetic analysis, in nearly one third of all cases a concordance of chromosomal aberrations in primary and secondary tumors was found. CONCLUSIONS: Multifocality of renal cell carcinoma occurs independently from primary tumor size. The evidence of structural and/or numeric aberrations, found in additional tumor foci, obviously is an argument for their malignant potential. This findings have to be considered in preparation of nephron-sparing surgery for patients with renal cell carcinoma.

Carcinoma, Renal Cell↗

How accurate is diagnostic imaging in determination of size and multifocality of renal cell carcinoma as a prerequisite for nephron-sparing surgery?

BACKGROUND: The indication for elective nephron-sparing surgery (NSS) in renal cell carcinoma (RCC) is under discussion in the urological literature. The main problem of NSS is the multifocality of RCC. The presented study was performed to asses the accuracy of pre- and intraoperative ultrasound (US), and computerized tomography (CT) in determination of tumor size and detection of multifocal lesions. MATERIALS AND METHODS: Tumor size was measured by preoperative US and CT and compared with the tumor diameters in gross sections of the neoplastic kidneys. Multifocality was determined by 3-mm step sectioning of the nephrectomy specimen, and the results were correlated with preoperative US and CT on the one hand, and the ex situ sonography of the nephrectomized kidney on the other hand. RESULTS: US and CT show similar results in the determination of the tumor size. In only 22.9%, preoperative US and CT were able to detect multifocal tumors. Ex situ sonography had a sensitivity of 40.0% and a specificity of 87.2% in this regard. CONCLUSIONS: In preparation for nephron-sparing surgery of renal cell carcinoma, neither preoperative routine imaging, nor intraoperative ultrasound can safely predict multifocal lesions of renal cell carcinoma.

Carcinoma, Renal Cell↗

[Limits for organ-preserving surgery in renal cell carcinoma].

The indication for elective organ-preserving surgery in renal cell carcinoma is under discussion. The statements about the maximum tumor size, which could be considered for this surgical procedure, differ in the literature. In a series of 281 consecutive radical tumor nephrectomies we compared the results of preoperative ultrasound and computerized tomography regarding to tumor size and multifocality with the results of the postoperative systematically section of the removed kidneys. Further we analysed the results of 14.793 autopsies regarding to tumor size and multifocality. Serial section of the 281 nephrectomy specimens revealed a total of 64 multifocal tumors in 48 kidneys ( = 17,1 %). The correlation between tumor size and multifocality showed only in tumors up to 20 mm no additional lesions, whereas in the higher tumor categories the incidence was up to 23 %. These clinical investigations were confirmed by the results of the autopsies. In summery of the results we conclude, that the elective organ-preserving surgery of renal cell carcinoma is only indicated in tumors with a maximum diameter of 20 mm.

Carcinoma, Renal Cell↗

Two functionally distinct forms of the RSC nucleosome-remodeling complex, containing essential AT hook, BAH, and bromodomains.

RSC is an essential 15 protein nucleosome-remodeling complex from S. cerevisiae. We have identified two closely related RSC members, Rsc1 and Rsc2. Biochemical analysis revealed Rsc1 and Rsc2 in distinct complexes, defining two forms of RSC. Genetic analysis has shown that Rsc1 and Rsc2 possess shared and unique functions. Rsc1 and Rsc2 each contain two bromodomains, a bromo-adjacent homology (BAH) domain, and an AT hook. One of the bromodomains, the BAH domain, and the AT hook are each essential for Rsc1 and Rsc2 functions, although they are not required for assembly into RSC complexes. Therefore, these domains are required for RSC function. Additional genetic analysis provides further evidence that RSC function is related to transcriptional control.

Adenosine Triphosphatases↗

Telomerase activity and telomere lengths: alterations in renal cell carcinomas.

Detection of telomerase activity in renal cell carcinomas may be a key to understanding the loss of growth control in tumor cells. This enzyme forms the end of most chromosomal DNAs (that is, telomeres) found in renal tumors. When activated, the telomeres shorten with every cell cycle and then there is a compensatory lengthening of the cells, which then proliferate and eventually become immortal and metastasize. This complex multigenetic process may prove to be a useful marker of tumor progression and patient outcome.

Carcinoma, Renal Cell↗

Determination of telomerase activity for differential analysis of multifocal renal cell carcinomas.

Secondary tumors are found in approximately 12 to 22% of all renal cell carcinoma, and their origin is currently unknown. To determine their potential for malignancy, we examined the telomerase activity of primary tumors and secondary lesions, and found that 86% of the lesions had an identical telomerase status as the related primary tumors, and thus probably share their malignancy potential.

Adenocarcinoma, Clear Cell↗

Genetic characterization of multifocal tumor growth in renal cell carcinoma.

The primary cancer found in the kidney is renal cell carcinoma (RCC), which does not as yet have a delineation of the types of lesions that progress to tumor malignancy. We studied tissues from primary tumors and secondary lesions, and compared it with the surrounding normal kidney tissue using comparative genomic hybridization to determine their potential for malignancy. Although our sample size was small, we found that small multifocal tumors have the same potential as primary carcinoma to lead to RCC malignancy. Further genetic studies in a larger sample of patients is necessary before the risk of different lesions to remain benign or progress to RCC can be defined absolutely.

Carcinoma, Renal Cell↗

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.

Adrenal Gland Neoplasms↗

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 x 9.0 x 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.

Autopsy↗

Determination of telomerase activity in multifocal renal cell carcinoma.

In a consecutive series of 245 patients with renal cell carcinoma (RCC) all nephrectomy specimens were examined regarding the presence of additional multifocal lesions. Therefore, 3-mm step sections were performed and investigated by macroscopical and histopathological examination. Twenty-six multifocal tumors were found in 19 specimens by this procedure. In order to characterize the biological activity of these multifocal lesions in more detail, their telomerase activity was analyzed. Fourteen of the 23 investigated multifocal tumors (60.9%) displayed telomerase activity. In three cases the tissue probes were too small for further investigations. Telomerase activity was also detected in 10 out of 15 (66.7%) matched primary renal cell carcinomas. In contrast, all corresponding normal kidney cortex tissues used as control were telomerase negative. From our results we conclude, that small tumor lesions of RCC must be expected to have a malignant potential similar to that of primary carcinomas. Hence, nephron-sparing surgery cannot be routinely carried out even in patients with small tumors.

Carcinoma, Renal Cell↗

[Lymphocyte transformation test (LTT) as a model for evaluating cytokine-induced immunomodulation in renal cell carcinoma].

We investigated the immunomodulatory capacity of cytokines produced by renal cell carcinoma in vitro by analyzing their effects on mitogen-induced T-lymphocyte blast cell transformation. All of the tested 70 cell cultures, derived from 70 tumor areas in 33 patients, had immunomodulatory capacity. In addition to suppression in the lymphocyte transformation test (max. 44/70; 63%) there was also superinduction (max. 37/70; 53%). We found no significant correlation with the stage and grade of primary tumors. However, the suppression of mitogen-induced T-lymphocyte blast cell transformation was significant in multifocal tumors (0.08% TCM, P < 0.001) and non-significant in metastatic tumors. The production of the assayed cytokines IL-6, IL-10, IL-11, and TGF beta 1 was variable and there was no significant correlation to the immunomodulatory capacity of the tumors.

Carcinoma, Renal Cell↗

Nephron sparing surgery for renal cell carcinoma 4 cm. or less in diameter: indicated or under treated?

PURPOSE: Although radical nephrectomy is the standard treatment for localized unilateral renal cell carcinoma with a normal contralateral kidney, there is ongoing interest in the use of nephron sparing surgery or partial nephrectomy in such cases. The extent of radical surgery in such cases has also been reconsidered in view of the uncertainty regarding the malignant or benign nature. MATERIALS AND METHODS: Of 14,793 autopsies in Jena from 1985 until 1995 there were 260 renal cell carcinomas. Of the 260 renal cell carcinomas the diameter was 40 mm. or less in 104. These 104 tumors were divided into group 1-20 mm. or less (33 cases), group 2-21 to 30 mm. (28) and group 3-31 to 40 mm. (43). RESULTS: Grade 1 renal cell carcinomas decreased in frequency with increasing tumor diameter, while an opposite result was noted for grade 3. Lymph node and distant metastases were well correlated with tumor size. With an increase in tumor size the frequency of venous involvement increased as well. Significantly more multifocal malignant renal cell carcinomas were seen in tumors between 21 and 40 mm. compared to those 20 mm. or less in diameter. CONCLUSIONS: The metastatic potential and biology of these small nodules are not yet known. To lower the risk of local recurrence the results of our study suggest that nephron sparing surgery might be advisable in patients with renal cell carcinoma 20 mm. or less in diameter.

Adult↗

Cytogenetic, histopathologic, and immunologic studies of multifocal renal cell carcinoma.

BACKGROUND: Multifocal tumor areas occurred in 12-22% of patients with renal cell carcinoma. It is unknown whether these tumors have malignant potential and characterize a higher risk for metastases. The performance of nephron-sparing surgery in patients with low grade or low stage tumors is controversial. METHODS: Primary and secondary tumors were analyzed by conventional cytogenetics and fluorescence in situ hybridization. Production of interleukin (IL)-6, IL-10, IL-11, and transforming growth factor (TGF)-beta1 were determined using standard enzyme-linked immunosorbent assay and bioassays. RESULTS: In 15.2% of the renal cell carcinoma cases evaluated, multifocal tumors were detected. Cytogenetics revealed a concordance of primary and secondary tumors in 9 of 14 cases (64%). In 11 of 12 multifocal tumors (94%), the same immunologic activity status was observed in both primary and secondary tumors. CONCLUSIONS: Secondary tumors must be expected to have malignant potential similar to that of the primary tumors. This was underscored by the high concordance of cytogenetic, histopathologic, and immunologic data in this study.

Carcinoma, Renal Cell↗