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A Heidenreich

Publications and source records attributed to A Heidenreich.

At least 19 recordsLinked to original sources

Serum DNA and urine DNA alterations of urinary transitional cell bladder carcinoma detected by fluorescent microsatellite analysis.

There are no reliable serologic tumor markers for transitional cell carcinoma (TCC) of the urinary bladder and noninvasive urine investigations are inadequate. We used fluorescent microsatellite analysis (MSA) to detect serum DNA and urine-sediment DNA alterations in patients with bladder cancer and prospectively collected fresh tumor, peripheral blood, serum and spontaneous urine specimens from 39 consecutive patients treated for TCC of the bladder to obtain the corresponding DNA. Fluorescent MSA was performed with 17 polymorphic markers from the chromosomal regions 5q, 8p, 9p, 9q, 13q, 14q, 17p, 17q and 20q in the 39 cancer patients and in 10 healthy controls. Serum DNA alterations were identified in 84.5% (33 of 39 patients) and tumor-specific urine DNA alterations indicating the diagnosis were present in 72% (27 of 39 patients) of cases. None of the healthy controls displayed serum DNA alterations. The highest frequency of serum DNA aberrations (56%) was detected for chromosomal region 8p. The most frequent alterations in urine-sediment DNA, 36% and 26%, were detected in chromosomal regions 8p and 9p, respectively. Identification of serum DNA and urine-sediment DNA alterations was not related to stage of disease or grade of tumor (p > 0.05). Thus, MSA offers a highly sensitive and specific method for serum- and urine-bound diagnosis of bladder TCC.

Carcinoma, Transitional Cell↗

Organ sparing surgery for malignant germ cell tumor of the testis.

PURPOSE: We evaluate the indication, technique and long-term outcome of organ preserving tumor resection rather than standard orchiectomy in 73 patients with bilateral testicular germ cell tumors or tumors of a solitary testicle. MATERIALS AND METHODS: Tumor resection was performed in 73 patients with 52 and 17 metachronous and synchronous bilateral testicular germ cell tumors, respectively, and 4 testicular germ cell tumors of a solitary testicle. Histology of the enucleated germ cell tumor revealed seminoma in 42 (57.5%) patients, embryonal carcinoma in 14 (19.2%), mature teratoma in 11 (15.1%), and mixed and combined germ cell tumors in 6 (8.2%). Mean tumor diameter was 15 mm. (range 5 to 30). Associated testicular intraepithelial neoplasia was diagnosed in 82% of patients who underwent local radiation with 18 Gy. RESULTS: After a median followup of 91 months (range 3 to 191) 72 (98.6%) patients had no evidence of disease and 1 died of systemic tumor progression. No local relapse occurred in 46 patients with associated testicular intraepithelial neoplasia treated with local radiation. However, local recurrence did develop in 4 patients after 3, 6, 12 and 165 months without radiation but all survived after undergoing inguinal orchiectomy. Testosterone levels were normal in 62 (84.9%) patients, hypogonadism developed in 7 (9.6%) and preoperative levels remained low in 4 (5.5%). Of the 10 patients who postponed local radiation for paternity reasons 5 had successfully fathered a child after organ sparing surgery. CONCLUSIONS: After a long-term followup of greater than 7 years organ sparing surgery represents a viable therapeutic approach to bilateral testicular germ cell tumor with an excellent postoperative outcome. Tumor enucleation might be considered a standard approach if the guidelines are respected, including cold ischemia, organ confined tumor less than 20 mm., multiple biopsies of the tumor bed, adjuvant local irradiation postoperatively to avoid local recurrence, close followup and high compliance.

Adult↗

Microscopic and biochemical fertility characteristics of semen after shockwave lithotripsy of distal ureteral calculi.

PURPOSE: To elucidate the frequency and adversity of the effects of shockwave lithotripsy (SWL) on the male reproductive system. We investigated the possible alterations in the quality of semen in patients treated by SWL for pelvic ureteral stones. PATIENTS AND METHODS: The semen of 10 men was examined 1 day before and 5 and 90 days after SWL for distal ureteral stones, in accordance with the World Health Organisation guidelines. The results were compared with those from the semen samples of 10 healthy male volunteers undergoing SWL for calculi of the upper urinary tract. RESULTS: Microscopic analysis of the semen samples revealed a transient decline in sperm density (24.7%), sperm motility (10%), sperm vitality (8%), and seminal fructose (27.5%) after SWL for distal ureteral stones. A distinctly higher number of spermatozoa of pathological origin was detected after SWL in the same group. There was no trace of microscopic hemospermia before shockwave treatment, but it was detected in 90% of the patients with lower ureteral calculi after SWL. Macroscopic hemospermia was detected in two of these nine patients. No deterioration of the semen characteristics and no hemospermia was observed after treatment in the control group with upper urinary stones. CONCLUSIONS: Our investigations confirmed a transient deterioration in semen quality after SWL for distal ureteral calculi, whereas no deterioration was observed after SWL for upper ureteral stones. Impaired sperm quality values returned to normal within 12 weeks after SWL, clearly indicating a damaging effect of SWL on seminal vesicle or ejaculatory duct function. The initial procreative capacity was restored in all patients.

Adult↗

The use of bisphosphonate for the palliative treatment of painful bone metastasis due to hormone refractory prostate cancer.

PURPOSE: Hormone refractory prostate cancer is dominated by osseous metastases leading to bone pain and pathological fractures. We assessed the clinical efficacy of bisphosphonate in the management of symptomatic skeletal metastases due to prostate cancer. MATERIALS AND METHODS: A total of 85 patients with painful osseous metastases due to hormone refractory prostate cancer were treated with clodronate in an open prospective nonrandomized clinical study. Clodronate was started as an intravenous phase for 8 days at a dose of 300 mg. daily followed by an oral maintenance phase of 1,600 mg. daily. The primary study end point was decreased pain without an increase in analgesic medication for at least 2 consecutive measurements. Secondary end points were decreased analgesics, an improved Karnofsky index and mobility as well as the duration of bisphosphonate action. Decreased pain was documented by a 10-point visual analog scale and consumption of analgesics was documented in a diary. RESULTS: A palliative response with a significant decrease in mean pain score from 7.9 (range 6 to 10) to 2.5 (range 0 to 4) (p <0.001) was achieved in 64 of the 85 patients (75%), 19 (22%) were completely pain-free without further need of analgesics and 45 significantly decreased the daily consumption of analgesics. The mean duration of bisphosphonate action was 9 weeks (range 4 to 22) and mean survival was 12 weeks (range 6 to 22). Improvement in bone pain was paralleled by an improvement in the mean Karnofsky index of 45% (range 30% to 60%) to 70% (range 50% to 80%) at the end of the treatment period. CONCLUSIONS: Bisphosphonate treatment of painful osseous metastases due to hormone refractory prostate cancer results in a significant pain decrease and a significant decrease in the daily consumption of analgesics in 75% of patients. Each characteristic is paralleled by an increase in the Karnofsky index, mainly due to better mobility. Bisphosphonate should have a definite role in the palliative management of symptomatic hormone refractory prostate cancer.

Aged↗

Current status of cytotoxic chemotherapy in hormone refractory prostate cancer.

Adenocarcinoma of the prostate is the most prevalent neoplastic disease in men and continues to be a major cause of morbidity and mortality. Death from prostate cancer is associated with objective and biochemical progression following hormonal manipulations often described as hormone refractory prostate cancer (HRPCA). Therapy for HRPCA is primarily palliative and therapeutic efficacy has to be balanced against potential treatment-related side effects. Therapeutic efficacy may be assessed by evaluating the percentage of patients obtaining a PSA decline of > 50%, evaluating the response of bidimensionally measurable disease or by improvements in quality of life assessments. The most effective cytotoxic therapies at the present time seem to be combinations of estramustine phosphate with taxanes and etoposide. Regimes employing ketoconazole with estramustine, vinblastine or bisphosphonates seem to be worthy of further evaluation. Mitoxantrone has an impressive palliative effect in patients, particularly when combined with hydrocortisone. Oral chemotherapeutic regimens with a combination of estramustine phosphate, cyclophosphamide and prednisone appear to offer a less toxic alternative. For the future we need prospective randomized clinical phase-III studies, prognosticators identifying patients as being at high or low risk who might benefit from different therapeutic approaches and generally binding eligibility and response guidelines in order to be able to compare trials of different therapeutic approaches.

Anthracyclines↗

[Interdisciplinary consensus on diagnosis and therapy of testicular tumors. Results of an update conference based on evidence-based medicine. German Testicular Cancer study Group (GTCSG)].

BACKGROUND: An "Interdisciplinary Consensus Statement on the Diagnosis and Therapy of Testicular Tumors" was prepared in 1996 by the "Interdisciplinary Testicular Tumor Working Group" (IAH) with input from representatives from diagnostic and therapeutic disciplines of various working groups of the German Cancer Society (Strahlenther Onkol 1997;173:397-406). In 1998 the IAH met again together with the "Testicular Tumor Working Party" of the Urooncology Working Group (AUO) and formed the "German Testicular Cancer Study Group" (GTCSG). Defined and accepted interdisciplinary standards from the initial meeting were revised based on current scientific developments and clinical results. This cooperating effort increased the quality of the initial recommendations and helped to put the recommendations for diagnosing and treating testicular tumor on a broader scientific basis. METHODS: According to the principles of "evidence-based medicine" (EBM), the Consensus from 1996 was modified, based on the current level of evidence from the published literature. The methodological process and evaluation criteria used were that of the "Cochrane Collaboration". RESULTS: An "Interdisciplinary Update Consensus Statement" summarizes and defines the diagnostic and therapeutic standards according to the current scientific practices in testicular cancer. For 21 separate areas scientifically based decision criteria are suggested. For treatment areas where more than one option exist without a consensus being reached for a preferred strategy, such as in seminoma in clinical Stage I or in non-seminoma Stages CS I or CS IIA/B, all acceptable alternative strategies with their respective advantages and disadvantages are presented. This "Interdisciplinary Update Consensus" was presented at the 24th National Congress of the German Cancer Society on March 21st and subsequently evaluated and approved by the various German scientific medical societies.

Evidence-Based Medicine↗

[Treatment outcomes in primary and secondary retroperitoneal fibrosis].

Retroperitoneal fibrosis (RPF) is an uncommon inflammatory disease of the retroperitoneum leading to extensive fibrosis with consecutive obstruction of adjacent organs, namely the ureters. Since no consensus on the standard therapy exists, aim of the current study was to evaluate the outcome of 39 patients with RPF. Between 1986 and 1997 39 cases of RPF were diagnosed: 21 cases had primary RPF and 18 patients had secondary RPF after aortofemoral graft (n = 13), radiation (n = 2), or prior retroperitoneal surgery (n = 2). 21 patients demonstrated unilateral and 16 cases had bilateral hydronephrosis, in 2 patients no dilatation was observed. In 28 cases (n = 12 primary RPF, n = 16 secondary RPF) initial management consisted of DJ-stent placement, whereas in 11 cases (n = 9 primary RPF, n = 2 secondary RPF) percutaneous nephrostomy had to be placed. All patients received oral immunosuppressive agents (prednisolone 1 mg/kg, azathioprine 1 mg/kg/day) for 3 months before reevaluation was performed. In case of complete remission, immunosuppressive medication was continued for another 3 months, in case of stable disease or progression surgery was performed. In 26 cases (n = 15 primary RPF, n = 11 secondary RPF) ureterolysis with intraperitoneal displacement and omental wrapping was performed. 3 patients demonstrated complete remission after oral prednisolone/azathioprine; in 2 cases RPF presented as pelvic mass and was resected followed by immunosuppressive therapy, in another 2 cases bilateral ileal replacement of the ureters had to be performed and 4 cases remained on DJ-stents and nephrostomy, resp. Postoperatively, all patients with primary RPF were continued on immunsuppressive medication for another 3 months. After a follow-up of 6 to 120 months only 3 patients developed a retroperitoneal recurrence and were treated by unilateral nephrectomy or DJ stent placement (n = 2). Our data suggest that the combination of both immunosuppressive medication and surgical management results in an excellent longterm outcome in idiopathic retroperitoneal fibrosis with a recurrence rate of only 8%. Combination therapy should be considered as therapeutic option early in the course of the disease. Primary reconstructive surgery appears to be the most promising approach in secondary retroperitoneal fibrosis with a recurrence rate of only 5%; short external compression of the ureter might be managed by endoluminal balloon dilatation.

Adult↗

[Microsurgical vasovasostomy in the age of modern reproduction medicine. A cost-benefit analysis].

WS represents the standard procedure of choice for the treatment of obstructive azoospermia following vasectomy. However, recently, ICSI has been suggested by some to represent the solution for all cases of male factor infertility regardless of its etiology based on its success rates. Therefore, we compared VVS to MESA/TESE and ICSI in terms of pregnancy, complications, and costs. Between 1/93 and 6/98 157 VVS was performed microsurgically using the 2-layer technique in 157 patients following prior vasectomy. Between 9/94 and 9/97 69 couples underwent MESA/ICSI for epididymal obstruction not amenable to micro-surgical reconstruction such as post-inflammatory obstruction and congenital absence of the vas deferens; in the same time period 42 couples underwent TESE/ICSI for azoospermia of testicular origin due to cryptorchidism, testicular atrophy, obstruction of the rete testis. In most cases MESA or TESE and ICSI were performed metachronously. Mean intervall of vasal obstruction was 7.6 (0.5-18) years; patency after VVS was 77%, pregnancy rate was 52%. Local complication rate was 4.7%, no major complications were observed. Costs per life birth after VVS were as high as 5,447,-DM or 2,800 Euro. Pregnancy rates after MESA/TESE and ICSI were 22.5% and 19.5%, respectively with 16 singletons, 3 twins and 3 abortions; local complications occurred in 3.9% of the men. Multiple birth were noticed in 15.8% following ICSI, but only in 0.7% following VVS. 5.7% and 1.4% of the female partners experienced serious complications as a mild or severe ovarian hyperstimulation-syndrome, respectively. Costs per life birth after MESA/TESE cycle were as high as 28,804,-DM or 14,100 Euro. Even in the era of ICSI microsurgical vasovasostomy represents the standard approach for obstructive azoospermia following vasectomy. Based on a cost-benefit analysis VVS is more successful in terms of pregnancy rates (52% vs. 22.5%). We conclude that MESA/ICSI should be reserved for patients not amenable for microsurgical reconstruction.

Adult↗

Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours.

Testicular germ-cell tumours (TGCT) affect 1 in 500 men and are the most common cancer in males aged 15-40 in Western European populations. The incidence of TGCT has risen dramatically over the last century. Known risk factors for TGCT include a history of undescended testis (UDT), testicular dysgenesis, infertility, previously diagnosed TGCT (ref. 7) and a family history of the disease. Brothers of men with TGCT have an 8-10-fold risk of developing TGCT (refs 8,9), whereas the relative risk to fathers and sons is fourfold (ref. 9). This familial relative risk is much higher than that for most other types of cancer. We have collected samples from 134 families with two or more cases of TGCT, 87 of which are affected sibpairs. A genome-wide linkage search yielded a heterogeneity lod (hlod) score of 2.01 on chromosome Xq27 using all families compatible with X inheritance. We obtained a hlod score of 4.7 from families with at least one bilateral case, corresponding to a genome-wide significance level of P=0.034. The proportion of families with UDT linked to this locus was 73% compared with 26% of families without UDT (P=0.03). Our results provide evidence for a TGCT susceptibility gene on chromosome Xq27 that may also predispose to UDT.

Adolescent↗

Molecular genetic parameters in pathogenesis and prognosis of testicular germ cell tumors.

Aim of this review article was to critically analyze the recently described cytogenetic and molecular markers for testicular germ cell tumors with regard to their clinical utility. The isochromosme i(12p) represents the most common and characteristic cytogenetic finding which already appears in testicular carcinoma in situ. A number of proto-oncogenes (cyclin D and PTHLH) as well as putative tumor suppressor genes are localized on 12p; however, their role in pathogenesis and prognosis of testicular germ cell tumors has not been defined yet. Clinical characteristics of patients with familial testicular germ cell tumors indicate a genetic background for the development of testicular tumors. Although a number of chromosomal loci encoding potential testicular tumor susceptibility genes have been identified, the genetic basis of testicular cancer pathogenesis is still unknown. With regard to molecular prognostic risk factors most of the reported data on proliferation markers, tumor suppressor genes, proteases and adhesion molecules have to be confirmed in prospective randomized trials prior to their widespread clinical use. Based on the available data on prospective studies the percentage of embryonal carcinoma and vascular invasion appear to be the most significant prognosticators. Investigation and identification of those factors determining the aggressive biologic behavior of embryonal carcinoma compared to all other histological components appear to be most promising in the research for prgnosticators of metastatic disease. In conclusion, the increasing knowledge of molecular genetic events involved in pathogenesis and prognosis of testicular germ cell tumors will not only help to better understand development and progression of testicular cancer, but it will also define new approaches to classification and management of germ cell tumors

Carrier Proteins↗

Microsurgical vasovasostomy versus microsurgical epididymal sperm aspiration/testicular extraction of sperm combined with intracytoplasmic sperm injection. A cost-benefit analysis.

PURPOSE: Vasovasostomy (VVS) represents the standard therapy of choice for the treatment of obstructive azoospermia following vasectomy. However, recently, intracytoplasmic sperm injection (ICSI) has been suggested by some to represent the solution for all cases of malefactor infertility regardless of its etiology based on its success rates. Therefore, we compared VVS to microsurgical epididymal sperm aspiration (MESA)/testicular extraction of sperm (TESE) and ICSI in terms of pregnancy, complications, and costs. PATIENTS AND METHODS: Between 1/93 and 6/98, 157 VVS were performed microsurgically using the double-layer technique. Between 9/94 and 9/97, 69 and 42 couples underwent MESA/ICSI and TESE/ICSI, respectively, for epididymal obstruction and azoospermia of testicular origin. RESULTS: The mean interval of vasal obstruction was 7.6 (0.5-18) years; patency after VVS was 77%, pregnancy rate was 52%. Local complication rate was 4.7%, no major complications were observed. Costs per life birth after VVS were 5,447 DM or 2,793 Euro. Pregnancy rates after MESA/TESE and ICSI were 22.5 and 19.5%, respectively, with 16 singletons, 3 twins and 3 abortions; local complications occurred in 3.9% of the men. Multiple births were noticed in 15.8% following ICSI, but in only 0.7% following VVS. 5.7 and 1.4% of the female partners experienced serious complications (mild or severe ovarian hyperstimulation syndrome, respectively). Costs per life birth after a MESA/TESE cycle amounted to 28,804 DM or 14,547 Euro. CONCLUSIONS: Even in the era of ICSI, microsurgical VVS represents the standard approach for obstructive azoospermia following vasectomy. Based on a cost-benefit analysis, VVS is more successful in terms of pregnancy rates (52 vs. 22.5%). VVS does not expose the female partners to complications following treatment of male infertility. In contrast to ICSI, multiple birth rates do not increase after VVS. We conclude that MESA/ICSI should be reversed for patients who are not amenable for microsurgical reconstruction.

Adult↗

Aneuploidy of chromosome 9 and the tumor suppressor genes p16(INK4) and p15(INK4B) detected by in situ hybridization in locally advanced prostate cancer.

INTRODUCTION AND OBJECTIVES: The linked p16(INK4)/MTS1 and p15(INK4B)/MTS2 genes on chromosome 9p21 encode proteins that inhibit the cyclinD dependent kinases CDK4/6. Biallelic homozygous deletions involving this locus have been identified in a wide range of tumor cell lines, but in a lower frequency of primary tumors. As PCR based approaches analyzing for homozygous deletions could be confounded by unavoidable contributions of normal cells in microdissected tissue, we performed in situ hybridization (ISH) on primary prostate carcinomas to accurately evaluate p16 and p15 copy numbers on a cell-by-cell basis. MATERIAL AND METHODS: p16 and p15 loci were evaluated in 28 pT3N0M0 prostate cancer specimens. Of 28 patients, 15 (53%) were ascertained showing no recurrence (mean follow-up 61+/-17 months), 13 (47%) developed recurrences within 27+/-19 months. Tissues were provided for ISH analysis in a blinded fashion. Isolated DNA derived from P1 clone 1063 compromising p16 and p15 as well as a centromeric probe for chromosome 9 were used for hybridization. Signals were enumerated within 300 interphase nuclei per tumor specimen, and in 100 nuclei derived from 18 benign prostate tissues and 7 adjacent PIN regions. RESULTS: ISH detected aneuploid tumors in 12/13 (92%) patients with recurrence and in 5/15 (33%) without recurrence (p<0.0014). Whereas 3/7 PIN specimens associated with nonrecurrent PCA demonstrated euploidy, all 4/7 PIN associated with recurrent disease demonstrated the same aneuploidy for chr9 as the primary tumor. All benign tissues evaluated exhibited euploidy for chr9, p16 and p15. None of the PCA and PIN samples revealed homozygous deletions for p16(INK4)/MTS1/p15(INK4B)/MTS2; 2/28 (7.1%) PCA exhibited partial deletion for p16(INK4)/MTS1/p15(INK4B)/MTS2 and aneuploidy for chr9; both PCA derived from the recurrent group. CONCLUSIONS: Deletion of 9p21 was rare and therefore such genetic alterations may not play an important role in the pathogenesis of PCA. Analysis of the limited number of PCA examined suggest a strong association between chr9 aneuploidy and recurrenct disease. Aneuploidy in both PIN and PCA suggests that the clinical outcome of PCA might already be determined in the preinvasive PIN.

Aneuploidy↗