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Biomedical subjects

S Siemer

Publications and source records attributed to S Siemer.

At least 19 recordsLinked to original sources
PubMed2006

Interleukin-2/interferon-alpha2a/13-retinoic acid-based chemoimmunotherapy in advanced renal cell carcinoma: results of a prospectively randomised trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN).

We performed a prospectively randomised clinical trial to compare the efficacy of four subcutaneous interleukin-2-(sc-IL-2) and sc interferon-alpha2a (sc-IFN-alpha2a)-based outpatient regimens in 379 patients with progressive metastatic renal cell carcinoma. Patients with lung metastases, an erythrocyte sedimentation rate < or =70 mm h(-1) and neutrophil counts < or =6000 microl(-1) (group I) were randomised to arm A: sc-IL-2, sc-IFN-alpha2a, peroral 13-cis-retinoic acid (po-13cRA) (n=78), or arm B: arm A plus inhaled-IL-2 (n=65). All others (group II) were randomised to arm C: arm A plus intravenous 5-fluorouracil (iv-5-FU) (n=116), or arm D: arm A plus po-Capecitabine (n=120). Median overall survival (OS) was 22 months (arm A; 3-year OS: 29.7%) and 18 months (arm B; 3-year OS: 29.2%) in group I, and 18 months (arm C; 3-year OS: 25.7%) and 16 months (arm D; 3-year OS: 32.6%) in group II. There were no statistically significant differences in OS, progression-free survival, and objective response between arms A and B, and between arms C and D, respectively. Given the known therapeutic efficacy of sc-IL-2/sc-INF-alpha2a/po-13cRA-based outpatient chemoimmunotherapies, our results did not establish survival advantages in favour of po-Capecitabine vs iv-5-FU, and in favour of short-term inhaled-IL-2 in patients with advanced renal cell carcinoma receiving systemic cytokines.

Adult↗
PubMed2006

[Expression of antimicrobial peptide MUC7 in kidneys with pyelonephritis].

BACKGROUND: Mucins are glycoproteins secreted by epithelial cells of various organ systems exerting multiple functions. MG2 as the protein transcript of the MUC7 gene has first been described as secreted by serous salivary glands in the oral cavity. We sought to explore changes of MUC7 expression in the kidney stimulated by bacterial infection of the upper urinary tract. METHODS: We investigated the gene expression of MUC7 by reverse transcriptase-polymerase chain reaction in voided urine specimens from 15 patients with acute pyelonephritis compared to 15 healthy volunteers. Furthermore, the gene and protein expression of MUC7 was studied in 15 renal tissue samples with chronic bacterial pyelonephritis versus 10 normal human kidney samples taken from tumor-bearing organs. RESULTS: MUC7 gene expression was detected in 5 of 15 voided urine samples of patients with pyelonephritis and in 2 samples from 15 healthy volunteers (Fisher's exact test p=0.39). MUC7 gene expression was detected in 7 of 15 tissue samples of kidneys with chronic pyelonephritis and in none of 10 normal renal tissue samples from tumor bearing organs (p=0.02). Immunohistochemical staining with the monoclonal antibody PANH3 revealed protein expression in 6 of the 15 tissue samples with chronic pyelonephritis, but not in normal tissue samples. CONCLUSION: Upregulated MUC7 expression in the urinary tract particularly in renal tubular epithelium can occur under inflammatory conditions. This indicates a putative role of MUC7 as an antimicrobial host defense molecule within the urogenital tract.

Adult↗
PubMed2006

Outcome of renal tumors in young adults.

PURPOSE: Sporadic RCC is rare in young adults. We retrospectively reviewed the outcomes of patients 20 to 40 years old at our institution. MATERIALS AND METHODS: Between 1975 and 2004, 2,710 patients were treated surgically for renal masses at our institution. We found 120 patients (4.4%) 20 to 40 years old. We analyzed the clinical presentation, pathological characteristics and outcome of these patients, and compared it to patients older than 40 years. RESULTS: The mean age of 120 young adults was 34.1 years (range 20.4 to 39.8). Symptomatic presentation was documented in 49.5% of patients. RCC was found in 87 (72.5%) young adults. Young patients generally had a higher rate of organ confined tumors than patients older than 40 years (73.6% vs 59.3%, p <0.05). Histopathological characteristics, tumor size, lymph node metastases and distant metastatic disease did not differ significantly in young and older patients. Women were significantly more likely to have benign lesions (41% vs 20%, p <0.05). Mean followup for 120 patients was 80.6 months and 15 of 87 patients with RCC (17.2%) died of tumor related causes (mean followup 27.5 months). The 10-year cancer specific survival rate was 78% in young adults and 68% in older patients (p = 0.22). Multivariate Cox regression analysis revealed lymph node metastases and tumor differentiation grade as independent prognostic parameters in young patients. CONCLUSIONS: Young patients are more likely to have symptomatic tumors at presentation. Nevertheless, they have more favorable pathological features and a definite trend to superior disease specific survival following surgical treatment. Organ sparing surgery should be considered in young women since benign lesions are frequent found in this population.

Adult↗
PubMed2006

Caudal regression sequence: vascular origin?

Caudal regression sequence (CRS) is a rare congenital defect of the lower spinal segments and the neural tube. Motor symptoms as well as neurological deficits and loss of bladder and bowel function are usually present. CRS is also associated with anomalies in other systems such as the gastrointestinal and genitourinary tract. Etiology and pathogenesis are poorly understood.A newborn presented with anomalies of the spinal column (lumbosacral) with absence/hypoplasia of the 12th thoracic and first lumbar vertebral anomaly body. Bladder and bowel initially were functional. MR-angiography exhibited an anomaly of the unpaired vessels originating from the aorta, a likely relict of a persisting vitelline artery. These findings indicate a potential vascular genesis of CRS, much as in sirenomelia.

Abnormalities, Multiple↗
PubMed2005

Elective nephron sparing surgery should become standard treatment for small unilateral renal cell carcinoma: Long-term survival data of 216 patients.

OBJECTIVES: Our experiences with elective nephron-sparing surgery (NSS) for renal cell carcinoma (RCC) in a consecutive series of 216 patients are presented. Clinicopathological features and long-term oncological outcome is compared to patients treated with radical nephrectomy (RN). METHODS: Between 1975 and 2002, NSS was performed in 488 patients; 311 of these patients had elective indications. Renal cell carcinoma was found in 241/311 patients (77.5%). Long-term follow up data could be obtained in 216/311 patients. Cancer-specific survival was estimated using the Kaplan-Meier method. Cox's regression analysis and log-rank tests were used to evaluate independent predictive values of different clinicopathological features. Survival data of the 216 patients after NSS surgery were compared to 369 patients with small RCC treated with RN. RESULTS: After a mean follow up of 66 months (median 64 months) 29 (13.4%) of 216 patients treated with NSS had died, 4 of them (1.8%) tumour-related. Tumour recurrence was detected in 12 patients (5.6%). 204 patients (94.4%) were free of tumour at last follow-up. Cancer specific survival rates at 5 and 10 years for patients treated with NSS (RN) were 97.8% (95.5%) and 95.8% (84.4%). CONCLUSIONS: Elective NSS surgery provides optimal long-term outcome in patients with small localized RCC. Compared to RN, renal parenchyma is preserved without any disadvantage in survival rates. Consequently elective NSS should be accepted as gold standard for small renal tumours.

Adult↗
PubMed2005

Current TNM classification of renal cell carcinoma evaluated: revising stage T3a.

PURPOSE: : Recent studies of rare cases of pT3a renal cell carcinoma extending directly into the adrenal gland showed worse survival than in other pT3a cases and recategorization as stage pT4 was suggested. We assessed the prognostic validity of a stage pT3a diagnosis based on perirenal fat infiltration. MATERIALS AND METHODS: : The records of 1,794 patients with renal cell carcinoma who underwent surgical resection between 1975 and 2000 at our institution were analyzed retrospectively. Focusing on pT3a tumors, as defined by perirenal fat infiltration, numerous clinical and histopathological parameters were investigated by univariate and multivariate statistical methods with cancer specific survival as the primary end point. RESULTS: : We identified 237 of 1,794 patients with perirenal fat infiltration, classified as having pT3a disease. In patients with pT3a tumors tumor size was a significant parameter predicting survival. The most significant cutoff value for tumor size in pT3a disease was 7 cm. Patients with distant metastasis had a worse prognosis independent of T classification. Therefore, to assess the prognostic value of the current T classification in regard to T3a tumors we excluded patients with tumor stage cM+ for further subgroup analysis. Survival comparison of pT1 pNall, cM0 (744 of 1,794 cases) and pT3a pNall, cM0 7 cm or less (100 of 237) as well as pT2 pNall, cM0 (265 of 1,794) and pT3a pNall, cM0 greater than 7 cm (93 of 237) yielded similar results. After splitting pT3a into a modified T1/T2 classification a significant difference in 5-year survival analysis for a modified T1/T2 stage was found (pT1 plus pT3a less than 7 cm 90% vs pT2 plus pT3a greater than 7 cm 73%, p <0.001). Subsequently multivariate analysis in all 1,794 patients showed that modified T stage was an independent significant predictor of cancer specific survival. CONCLUSIONS: : We suggest revising the current pT3a classification based on perirenal fat infiltration but rendering a modified pT1/pT2 classification, which resolves pT3a cases without the loss of prognostic validity. Perirenal fat infiltration should not be used to assign T category. Tumors directly infiltrating the adrenal gland should be reclassified as T4.

Carcinoma, Renal Cell↗
PubMed2004

[Interventional radiologic management for early post-transplant perfusion failure of renal allografts].

PURPOSE: Open surgery for correction of early vascular complications in allogenic kidney transplantation carries the risk for increased morbidity and graft loss. The question was raised whether modern interventional radiologic techniques, especially the use of vascular stents, could play an alternative therapeutic role in those complicated cases. MATERIAL AND METHODS: 3 patients with early postoperative perfusion failure of their renal grafts were referred to the radiologist after Doppler sonography. Immediate digital subtraction angiography was initiated and during the same session percutaneous transluminal angiography and placement of a vascular stent were performed to treat the vascular lesion. Anticoagulation was started with low-dose aspirin 100 mg/day. RESULTS: In all 3 patients an intimal dissection of the renal artery with formation of a relevant stenosis was found. Stenosis was corrected by angioplasty and stenting. In one case an accidentally found renal vein thrombosis was additionally treated by transcatheter thrombo-aspiration. No complications related to the interventions occurred. In 2 patients diuresis returned immediately and renal function remained stable in the longterm (follow-up 6 month). In one case massive peripheral arterial thrombosis had to be diagnosed in spite of successful recanalization of the renal artery. After explantation of the organ histology revealed extended parenchymal necrosis. CONCLUSIONS: The timely use of angiography after Doppler sonographic diagnosis for renal transplant perfusion failure is of help not only for exact diagnosis but also for immediate treatment. Radiologic interventional techniques should be regarded as potentially effective and safe for the treatment of early vascular complications after renal transplantation.

Aged↗
PubMed2004

Adrenal metastases in 1635 patients with renal cell carcinoma: outcome and indication for adrenalectomy.

PURPOSE: Routine removal of the ipsilateral adrenal gland in patients with renal cell carcinoma who undergo nephrectomy has been a matter of dispute. In a retrospective study we screened for subgroups of patients with renal cell carcinoma from a large single center patient population who may have benefited from ipsilateral adrenalectomy. MATERIALS AND METHODS: Radical nephrectomy was performed in 1635 patients at a single institution between 1980 and 2000. A total of 1010 patients underwent radical nephrectomy plus ipsilateral adrenalectomy, whereas in 625 no simultaneous adrenalectomy was performed. Numerous clinical and histopathological parameters were investigated by univariate and multivariate statistical methods for their predictive value in regard to cancer specific survival. RESULTS: Metastases in the adrenal gland were found in 5.5% of patients (56 of 1010) undergoing nephrectomy with adrenalectomy. Of 30 patients with adrenal metastasis and preoperative computerized tomography/magnetic resonance imaging 23 were found to have histological evidence of cancer, approaching a false-negative rate of 23.3%. All patients with false-negative computerized tomography/magnetic resonance imaging had a primary tumor of greater than 4 cm. Patients with adrenal metastases predominately had pT3 or greater tumor stage (82%). Cancer specific survival rates (75% vs 73% for adrenalectomy vs no adrenalectomy) and postoperative complications rates (7% vs 8%) did not differ significantly between the 2 groups. The prognosis in patients with a solitary adrenal metastasis (18 of 56) was more favorable than in patients with additional metastatic sites (38 of 56). CONCLUSIONS: Adrenal metastases from primary renal cell carcinoma were found significantly more often in patients with advanced tumor stages. Ipsilateral adrenalectomy should be recommended for all resectable renal cell carcinoma with a primary tumor of greater than 4 cm or with nonorgan confined tumor stages (T3 or greater) since a false-negative rate of about 20% can be expected with current imaging techniques.

Adrenal Gland Neoplasms↗
PubMed2003

[Systemic chemotherapy for transitional cell carcinoma of the urothelium].

Moderate activity of systemic chemotherapy for advanced urothelial cancer has been reported for more than 30 years. Only with the advent of potent combination therapy in the mid eighties of the past century clinically significant response rates as well as prolonged survival has been documented. This review summarizes seven Phase-III trials of systemic chemotherapy for advanced urothelial carcinoma as well as results from adjuvant and neoadjuvant Phase-III trials for muscle-invasive bladder cancer including the most recent reports.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

[Long-term outcome of conservative surgery for kidney cancer: survival, blood pressure, and renal function].

PURPOSE: Nephron-sparing surgery (NSS) for renal cell carcinoma (RCC) remains controversial for elective indications (low stage RCC in the presence of a normal contralateral kidney). In this single center study survival rate and, as novel aspects, the frequency of postoperative arterial hypertension and renal function parameters were investigated to evaluate safety and efficacy of NSS. PATIENTS AND METHODS: The complete data of 248 patients operated nephron-sparing for RCC between 1975 and 1995 were evaluated. One hundred and seventy-five patients were treated for elective indication (95% with tumor stage T1 or T2), 73 patients for mandatory indication (bilateral tumors, solitary kidney, renal insufficiency). The mean follow-up was 75 months (maximum 23 years). RESULTS: Mean tumor-size was lower under elective (3.8 cm) than under mandatory (4.7 cm) indication. Overall tumor-specific survival after 5 years for both indications was 88%. Comparing preoperative vs. follow-up values, arterial blood pressure and serum-creatinine values remained unchanged for both indications. The incidence of postoperative proteinuria (19% imperative, 11% elective indication) was strongly related to hypertension. CONCLUSIONS: NSS for RCC under elective indication achieves patient survival comparable to the results of radical nephrectomy. The presented data do not indicate significant longterm complications such as arterial hypertension, proteinuria or deterioration of renal function as a result of glomerulosclerosis or hyperfiltration. This gives further argument for the concept of NSS in RCC as an alternative to radical nephrectomy in the presence of a healthy contralateral kidney.

Blood Pressure↗
PubMed2001

[Bilateral kidney tumor. Therapy management and histopathological results with long-term follow-up of 66 patients].

Bilateral renal cell carcinoma is detected at an incidence rate of 1.6-6% of all renal tumors. The management, histopathological results and the long-term follow-up of 66 patients with bilateral renal cell carcinoma (29 synchronous, 37 asynchronous tumors) are presented in this issue. The incidence rate of bilateral renal cell carcinoma (RCC) at our hospital was 3.5%. Nephron-sparing surgery should be used first for the smaller and favourably located tumor when radical nephrectomy of the contralateral tumor is necessary. Thus, the patients can be spared dialysis. The histopathological results showed a significantly higher incidence rate of chromophil RCCs in cases of synchronous bilateral renal tumors (36%). The 5-year survival rate was 82%. Patients with asynchronous renal cell carcinomas were significantly younger than those with synchronous RCCs (median age: 60.2 years). The histopathological results were similar to unilateral renal cell carcinomas. Clear cell carcinoma was detected in 70% of cases. The 5-year survival rate was 61% and lower than that of synchronous tumors (82%). There was no significant difference because of the small number of cases. Current standardised techniques of nephron-sparing surgery achieve good survival rates, therefore making bilateral nephrectomy only necessary in very poor cases. In cases of chromophil renal cell carcinomas, the contralateral kidney should always be carefully examined, because these tumors were significantly more often detected to be bilateral. The risk of also developing a tumor in the contralateral kidney increases with decreasing age at first manifestation (< 55 years, 6%). Especially in those younger than 55 years, partial nephrectomy seems to be recommended for unilateral renal tumors in patients with a normal contralateral kidney (tumor size < 4 cm in diameter).

Adenocarcinoma, Clear Cell↗
PubMed2000

[Value of ultrasound in early diagnosis of renal cell carcinoma].

The importance of ultrasonography in early detection of renal cell carcinoma was analyzed for 1854 patients, who were operated from 1975 to 1997. The 5-year survival rate of all patients amounts to 75%, the 10- and 20-year survival rate was 68% and 64%. While from 1975 to 1986 tumor symptoms like hematuria (30%), abdominal pain (19%) and palpable mass (3%) lead to diagnosis of renal cell carcinoma in 56% of all cases, there were only 26% from 1987 to 1997. 83% of asymptomatical tumors from 1987 to 1997 were accidentally detected by means of ultrasonography in a kidney independent examination. These tumors are significantly smaller (5.5 cm) than the tumors of symptomatical patients (7.8 cm) and show often a significantly lower local tumor stage, a better tumor grade, frequently lymph nodes, which are free of tumor infiltration and more rarely distant metastasis. The 5-year survival rate of patients with incidental tumors, detected by ultrasonography (82%) was significantly better (log rank < 0.001) in comparison with the symptomatical patients (72%). These results verify 1. The effectivity of ultrasonography in early diagnosis of renal cell carcinoma and 2. The advantage of survival on patients with early tumor detection. That's why asymptomatic patients, who selected under risk factors should be examinated by ultrasonography consistently too.

Adolescent↗
PubMed2000

Diagnosis of nonpalpable testes in childhood: comparison of magnetic resonance imaging and laparoscopy in a prospective study.

In a prospective study, the accuracy of magnetic resonance imaging (MRI) and laparoscopy in the diagnosis of nonpalpable testes was evaluated. Advantages and disadvantages of the two procedures were compared. 29 boys with unilateral nonpalpable testis underwent MRI. When MRI failed to demonstrate a testis, laparoscopy with a 1.9 mm mini-laparoscope was performed. All cases were verified by operative exploration of the inguinal region. MRI demonstrated 10 inguinal and 7 abdominal testes. MRI revealed no testis in 12 boys. The false positive rate was 32%, correct negative findings were confirmed in four patients. When laparoscopy was performed, preservable testis could be demonstrated in 8 of 12 patients (1 abdominal, 7 inguinal) which otherwise were not visible on MRI. The correct positive rate was 100%. We encountered no complications with laparoscopy. In summary, laparoscopic evaluation is recommended as the preferable method in pediatric cases of nonpalpable testes.

Adolescent↗
PubMed1999

Protein kinase CK2: evidence for a protein kinase CK2beta subunit fraction, devoid of the catalytic CK2alpha subunit, in mouse brain and testicles.

The highest CK2 activity was found in mouse testicles and brain, followed by spleen, liver, lung, kidney and heart. The activity values were directly correlated with the protein expression level of the CK2 subunits alpha (catalytic) and beta (regulatory). The alpha' subunit was only detected in brain and testicles. By contrast, Northern blot analyses of the CK2alpha mRNA revealed a somewhat different picture. Here, the strongest signals were obtained for brain, liver, heart and lung. In kidney, spleen and testicles mRNAs were only weakly detectable. For CK2alpha' mRNA distribution strong signals were observed for lung, liver and testicles. In the case of CK2beta mRNA the highest signals were found for testicles, kidney, brain and liver. The amount of CK2beta mRNA in testicles was estimated to be about 6-fold higher than in brain. The strongest CK2beta signals in the Western blot were found for testicles and brain. The amount of CK2beta protein in brain in comparison to the other organs (except testicles) was estimated to be ca. 2-3-fold higher whereas the ratio of CK2beta between testicles and brain was estimated to be 3-4-fold. Results from the immunoprecipitation experiments support the notion for the existence of free CK2beta population and/or CK2beta in complex with other protein(s) present in brain and testicles. In all other mouse organs investigated, i.e. heart, lung, liver, kidney and spleen, no comparable amount of free CK2beta was observed. This is the first physiological evidence for the existence of a 'free CK2beta' (or in complex with proteins other than CK2a) in normal animal tissue apart from the hitherto dogmatic association with CK2alpha in a tetrameric holoenzyme complex.

Animals↗
PubMed1999

Determination of mRNA, and protein levels of p53, MDM2 and protein kinase CK2 subunits in F9 cells after treatment with the apoptosis-inducing drugs cisplatin and carboplatin.

Protein kinase CK2 is a pleiotropic serine/threonine kinase which has been shown to phosphorylate numerous substrates. Evidence is accumulating that CK2 may exist complexed to a variety of cellular proteins, e.g. p53, MDM2, and A-Raf. Here, we explored the effects of the chemotherapeutic drugs cisplatin and carboplatin on the mRNA and protein levels of p53, MDM2 and CK2 in a murine teratocarcinoma cell line F9. Northern and Western blot analyses were performed and the CK2 activity was determined. The degree of apoptosis after drug treatment was assessed using the TUNEL test. Six hours after cisplatin and carboplatin treatment, the RNA level of p53 dropped by 59% +/- 9% and 86% +/- 8% respectively, whereas the observed level of p53 protein rose to 7 and 10 times over the untreated control, respectively. Treatment with 33 microM cisplatin prompted apoptosis as early as 4 h after drug treatment. More than 50% apoptotic cells were seen after 6 h. We conclude that cisplatin and its second generation drug carboplatin act similarly i.e. both drugs cause a concomitant decrease in p53 mRNA and an increase in p53 protein level. After 4 h treatment with either of the two drugs, p53 levels reach a threshold which leads to the initiation of apoptosis.

Animals↗