Biomedical subjects

M Goepel

Publications and source records attributed to M Goepel.

At least 37 records · Page 2Linked to original sources

PubMed1999

[Detrusor myectomy (autoaugmentation) in the treatment of hyper-reflexive low compliance bladder].

After unsuccessful medical treatment of a neurogenic hyperreflexive bladder dysfunction further treatment options are the ileal bladder augmentation, the detrusor-myectomy (bladder auto-augmentation) and the sacral root deafferentation. All techniques lead to a low-pressure bladder with enlarged storage volume. The authors here report about their personal experience with the detrusor myectomy in 62 patients with hyperreflexive neurogenic bladder dysfunction from 1989 until 1998. Indication, surgical technique, and long-time results are presented.

Adult↗

PubMed1999

Characterization of alpha-adrenoceptor subtypes in the corpus cavernosum of patients undergoing sex change surgery.

PURPOSE: To characterize the subtypes of alpha1- and alpha2-adrenoceptors in the human corpus cavernosum from patients undergoing sex change surgery. MATERIALS AND METHODS: Saturation and competition radioligand binding studies were performed for characterization at the protein level. Alpha1-adrenoceptors were labeled with [3H]prazosin and [3H]tamsulosin, while alpha2-adrenoceptors were labeled with [3H]RX 821002. Alpha1-adrenoceptor subtype mRNA was additionally determined by reverse-transcriptase polymerase chain reaction and RNase protection assays. RESULTS: Human corpus cavernosum expressed approximately 32 and approximately 22 fmol./mg. protein alpha1- and alpha2-adrenoceptors, respectively. Competition studies with the alpha1A-selective antagonists 5-methylurapidil and (+)-niguldipine and the alpha1D-selective BMY 7378 revealed a mixed alpha1A/alpha1B-adrenoceptor population with no evidence for alpha1D-adrenoceptor protein. In contrast alpha1D-adrenoceptors were readily detected at the mRNA level. Competition binding studies with the alpha2A-selective oxymetazoline and the alpha2B-selective prazosin and ARC 239 revealed a homogeneous population of alpha2A-adrenoceptors. CONCLUSIONS: We conclude that human corpus cavernosum expresses predominantly alpha1A-, alpha1B- and alpha2A-adrenoceptor protein; additionally the alpha1D-adrenoceptor is present at the mRNA level.

Adrenergic alpha-Antagonists↗

PubMed1998

The importance of human glandular kallikrein and its correlation with different prostate specific antigen serum forms in the detection of prostate carcinoma.

BACKGROUND: Human glandular kallikrein (hK2), the prostate specific antigen (PSA) close homologue, possesses approximately 80% structure identity with PSA. The identification of PSA was an important step in the detection of prostate carcinoma (PCa). Thus, hK2 measurement in the serum has the potential to become another important diagnostic test for PCa. In the current study, the authors measured the serum concentrations of the hK2 with "in-house" immunofluorometric assays in different patient groups. The correlation between serum hK2 and different PSA forms was investigated. METHODS: The prospectively collected serum samples were obtained preoperatively on admission from 311 consecutive male patients. Sixteen patients did not fulfill inclusion criteria; the remaining patients were divided into four groups (Groups I-III confirmed histologically): Group I: patients with PCa (n = 56); Group II: patients with benign prostatic hyperplasia (BPH) (n = 163); Group III: patients with BPH with a chronic in-dwelling catheter (BPH cat) (n = 44); and Group IV-control group (n = 32). The patients in Group IV had urolithiasis, varicocele, or kidney or bladder tumors). An experimental immunofluorometric assay with an analytic sensitivity of 0.01 ng/mL and a functional sensitivity of 0.05 ng/mL was used to determine serum hK2 concentrations. Total PSA, free PSA, and PSA complexed to alpha-1-antichymotrypsin (PSA-ACT) also were measured. hK2 concentrations equal to or above the functional sensitivity limit were correlated with each of these PSA serum forms. Free to total PSA, hK2 to total PSA, and hK2 to free PSA ratios were calculated and compared in different patient groups. RESULTS: The hK2 concentrations were equal to or above the functional sensitivity limit in 179 of 311 samples (57.6%). In these samples, hK2 correlated best with free PSA (correlation coefficient [r] = 0.79) and correlated well with total PSA (r = 0.72) and PSA-ACT (r = 0.74). Similar correlations also could be observed when each clinical group was analyzed separately. The median proportion of hK2 in relation to total PSA was 2.1%, 1.8%, and 1.4%, respectively, for PCa, BPH, and BPH cat patients. Both the free to total PSA ratio and the hK2 to free PSA ratio discriminated well between PCa and BPH patients. Within the range of total PSA of 4-10 ng/mL (PCa [n = 11] and BPH [n = 41]) the hK2 to free PSA ratio had a specificity of 63.4% and 90.9% sensitivity (area under the receiver operating characteristic [ROC] curve = 0.85) whereas the free to total PSA ratio had a 34.1% specificity at the same sensitivity level (area under ROC curve = 0.74). CONCLUSIONS: The hK2 serum level correlates well with all PSA serum forms in all clearly defined clinical groups. The preliminary finding that the hK2 to free PSA ratio appeared to improve the detection of PCa compared with the free to total PSA ratio in patients with total PSA within a 4-10 ng/mL range is of clinical interest. Combining human serine proteases in the multivariate regression analysis will be a tool to improve cancer detection. Further investigations with more sensitive hK2 assays and in larger patient populations are needed to confirm this finding.

Aged↗

PubMed1998

Differential alpha1-adrenoceptor labeling by [3H]prazosin and [3H]tamsulosin.

The radioligand binding properties of [3H]prazosin and [3H]tamsulosin at alpha1-adrenoceptors of several rat tissues, human prostate and cloned rat and human alpha1-adrenoceptor subtypes were compared in Tris/EDTA buffer unless otherwise indicated. The affinity of [3H]tamsulosin at tissue and cloned alpha1A- and alpha1B-adrenoceptors was somewhat greater and smaller, respectively, than that of [3H]prazosin. In most rat tissues and at cloned rat alpha1A- and alpha1B-adrenoceptors, [3H]tamsulosin had a smaller Bmax than [3H]prazosin. Studies with rat liver showed that this was due to considerably poorer labeling of agonist low affinity sites, while both radioligands detected similar numbers of agonist high affinity sites. Statistically significant differences in the number of binding sites for both ligands were not detected in HEPES or glycylglycine buffer, as the detectable receptor number for [3H]prazosin and [3H]tamsulosin tended to be smaller and greater, respectively, in these than in Tris/EDTA buffer. Among human alpha1-adrenoceptor subtypes [3H]tamsulosin labeled fewer sites than [3H]prazosin for alpha1B- but more sites for alpha1A- and alpha1D-adrenoceptors. We conclude that [3H]prazosin and [3H]tamsulosin do not detect the same number of alpha1-adrenoceptors under a variety of conditions. This should be taken into account in the interpretation of data obtained with either radioligand.

Adrenergic alpha-Antagonists↗

PubMed1998

Comparison of human alpha1-adrenoceptor subtype coupling to protein kinase C activation and related signalling pathways.

The coupling of human alpha1-adrenoceptor subtypes to protein kinase C (PKC) and PKC-related signalling events were investigated in rat-1 fibroblasts stably expressing alpha1A-, alpha1B- or alpha1D-adrenoceptors at densities of 1328+/-200, 5030+/-703 and 150+/-14 fmol/mg protein respectively. In functional assays the alpha1-adrenoceptor agonist phenylephrine significantly stimulated PKC (assessed as increased activity in the membrane fraction) in cells expressing alpha1A- or alpha1B- but not alpha1D-adrenoceptors. In immunoblot assays phorbol ester treatment enhanced membrane-associated immunoreactivity of PKCalpha, PKCdelta and PKCepsilon to a similar extent in all three cell lines. Stimulation of alpha1A- and alpha1B-adrenoceptors also increased immunoreactivity of PKCalpha, PKCdelta and PKCepsilon in the membrane fraction, while alpha1D-adrenoceptor stimulation yielded only very small and inconsistent alterations. Immunoreactivity of PKCzeta was not consistently affected by phorbol ester or phenylephrine in any of the cell lines. Stimulation of all three alpha1-adrenoceptors time- and concentration-dependently increased inositol phosphate formation. Maximum activation occurred with the order alpha1A approximately = alpha1B > alpha1D. Phenylephrine also concentration dependently elevated free intracellular [Ca2+] in all three cell lines with the order of efficacy alpha1A > alpha1B > alpha1D. In the presence of ethanol, phenylephrine stimulated phosphatidylethanol formation in alpha1A- and alpha1B-adrenoceptor-expressing cells time and concentration dependently but only weakly and inconsistently in alpha1D-adrenoceptor-expressing cells. The efficacy of phenylephrine (100 microM) relative to that of noradrenaline (100 microM) for stimulation of phosphatidylethanol formation was similar (> or = 75%) for all three subtypes. The alkylating agent phenoxybenzamine concentration dependently reduced alpha1A-adrenoceptor density and phenylephrine-stimulated Ca2+ elevations to levels seen with alpha1D-adrenoceptors but reductions of phenylephrine-stimulated phosphatidylethanol formation were weaker. We conclude that human alpha1A- and alpha1B-adrenoceptors expressed in rat-1 cells couple to activation of PKCalpha, PKCdelta and PKCepsilon but not PKCzeta; this may involve stimulation of phospholipases C and D and intracellular Ca2+ elevations. Activation of these pathways by alpha1D-adrenoceptors appears to be much weaker and was not detected consistently; this was not fully explained by weak partial agonism of phenylephrine at this subtype or by lower receptor densities. Overall the alpha1A-adrenoceptor may have the highest efficiency of stimulus-response coupling among human alpha1-adrenoceptor subtypes.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed1998

Muscarinic receptor subtypes in porcine detrusor: comparison with humans and regulation by bladder augmentation.

The properties of muscarinic acetylcholine receptors of porcine and human bladder detrusor were compared in radioligand binding studies using [3H]quinuclidinylbenzylate as the radioligand. The receptor affinity for the radioligand and the density of muscarinic receptors was similar in male and female pigs and in humans (Kd = 35 +/- 8 pM, Bmax = 153 +/- 30 fmol/mg protein). Atropine and subtype-selective antagonists had steep and monophasic competition curves in porcine and human detrusor with a rank order of potency of atropine >> hexahydro-sila-difenidol > or = AF-DX 116 > or = pirenzepine, indicating the presence of a homogeneous population of M2 muscarinic receptors. In female pigs bladder outflow obstruction generated by partial urethral ligation or its surgical treatment by ileum augmentation or autoaugmentation did not significantly alter expression of muscarinic receptors or of alpha2A-adrenoceptors, but the power was insufficient to exclude alterations of less than 60%. We conclude that porcine and human detrusor express muscarinic receptors of the M2 subtype; despite these qualitative similarities the use of the porcine model may be limited by large biological variance with regard to quantitative receptor expression.

Animals↗

PubMed1998

Tamsulosin treatment of 19,365 patients with lower urinary tract symptoms: does co-morbidity alter tolerability?

PURPOSE: We compare the tolerability and blood pressure effects of 0.4 mg. tamsulosin once daily in patients with lower urinary symptoms suggestive of benign prostatic obstruction with or without concomitant disease and/or antihypertensive medication. MATERIALS AND METHODS: Data from 2 open label, observational studies (study 1, 9,507 patients treated for 4 weeks and study 2, 9,858 patients treated for 12 weeks) were analyzed for global tolerability and effects on blood pressure stratifying for co-morbidity (none, diabetes, hypertension, other cardiovascular disease) and co-medication (diuretics, beta-blockers, calcium channel blockers, angiotensin converting enzyme inhibitors). RESULTS: Overall 90 and 95% of patients in studies 1 and 2, respectively, reported good or very good tolerability. While global tolerability was slightly reduced in patients with concomitant disease or some forms of medication (p < 0.05), it was rated as good or very good by more than 90 and 95% of patients even in those groups. In control patients, that is those with neither co-morbidity nor co-medication, the tamsulosin induced blood pressure reductions were similar to those previously reported for placebo treatment but were statistically significant (p < 0.05). Mean additional blood pressure reductions in patients with concomitant disease or medication were not more than 2 mm. Hg. CONCLUSIONS: Tamsulosin is well tolerated and has marginal effects on blood pressure in the majority of patients. It largely maintains its good global tolerability and minimal blood pressure effects in patients with cardiovascular co-morbidity or diabetes, or those on co-medication with antihypertensive agents.

Adrenergic alpha-Antagonists↗

PubMed1998

Comparison of tamsulosin efficacy in subgroups of patients with lower urinary tract symptoms.

We have compared the results of treatment with tamsulosin (0.4 mg once daily) in subgroups of patients with lower urinary tract symptoms suggestive of benign prostatic obstruction, based on two large-scale, open-label, observational studies. Improvements of IPSS or Q(max) were largely unaffected by patient age. Patients with severe symptoms benefited at least as much from treatment as those with mild or moderate symptoms, and the majority of patients with severe symptoms were shifted to the moderate or even mild symptoms group. We conclude that tamsulosin is effective in patients of all age groups, and should be considered as an alternative to surgery even in patients with severe symptoms.

Journal Article↗

PubMed1998

Free-to-total prostate-specific antigen (PSA) ratio improves the specificity for detecting prostate cancer in patients with prostatism and intermediate PSA levels.

OBJECTIVE: To investigate the clinical significance of the free-to-total prostate-specific antigen (PSA) ratio in improving the specificity of PSA measurement for detecting prostate cancer within the diagnostic intermediate range (4-10 ng/mL total PSA) in patients referred for the treatment of urinary symptoms. PATIENTS AND METHODS: Serum samples were obtained from 333 consecutive patients with obstructive and irritative urinary symptoms. Of these men, 114 had total PSA levels of 4-10 ng/mL; 22 had prostate cancer (group 1) and 71 had benign prostatic hyperplasia (BPH, group 2). Group 3 consisted of 21 patients with BPH and a chronic indwelling catheter. The concentrations of free and total PSA (ProStatus, Wallac Oy, Turku, Finland) and PSA complexed to alpha-1-antichymotrypsin were measured and the free-to-total PSA ratio calculated. All patients under 70 years of age or with suspicious findings on digital rectal examination or transrectal ultrasonography underwent ultrasound-guided sextant prostate biopsies. Of the 114 patients, 105 (92%) underwent transurethral resection of the prostate and six (5%) radical retropubic prostatectomy. RESULTS: Patients in group 1 had significantly lower median free PSA concentrations (0.78 ng/mL vs 1.13 ng/mL, P < 0.001) and a lower free-to-total PSA ratio (12.1% vs 19.9%, P < 0.001) than those in group 2. The differences were similar between group 1 and group 3 (median free PSA in group 3, 1.06 ng/mL, P = 0.03, and free-to-total PSA ratio 18.7%, P = 0.007). There were no significant differences between patients in groups 2 and 3. The free-to-total PSA ratio had a higher specificity than total PSA at all sensitivity levels, e.g. a threshold free-to-total PSA ratio of 0.20 detected 91% of cancers and spared 48% (group 2) or 46% (group 3) from unnecessary biopsies. The area under the receiver operating characteristic curve for group 1 vs group 2 was 0.56 (total PSA) and 0.78 (free-to-total PSA ratio) and for group 1 vs group 3 was 0.56 (total PSA) and 0.81 (free-to-total PSA ratio). CONCLUSION: In those patients with extensive symptoms from BPH and requiring surgical treatment, the free-to-total PSA ratio improves the specificity for detecting prostate cancer in the diagnostic 'grey zone' of 4-10 ng/mL total PSA. This improvement occurred in patients with or without a chronic indwelling catheter for urinary retention.

Aged↗

PubMed1998

Stimulation of alpha1A-adrenoceptors in Rat-1 cells inhibits extracellular signal-regulated kinase by activating p38 mitogen-activated protein kinase.

In Rat-1 fibroblasts, endothelin-1 and a protein kinase C-stimulating phorbol ester stimulated extracellular signal-regulated kinase (ERK), whereas phenylephrine, acting at stably transfected human alpha1A-adrenoceptors, inhibited basal and endothelin-1- and phorbol ester-stimulated ERK. On the other hand, phenylephrine stimulated p38 mitogen-activated protein kinase (MAPK). Anisomycin caused p38 activation and ERK inhibition quantitatively similar to those produced by phenylephrine. SB 203,580, an inhibitor of p38, significantly attenuated phenylephrine- and anisomycin-induced ERK inhibition. The ERK inhibition by phenylephrine was not affected by the cytosolic phospholipase A2 inhibitor arachidonyltrifluoromethyl ketone or the cyclooxygenase inhibitor indomethacin but was significantly attenuated by a combination of the phosphatase inhibitors Na3VO4 and okadaic acid. Neither SB 203,580 nor the phosphatase inhibitors significantly affected ERK inhibition by the adenylyl cyclase activator forskolin. We conclude that there is a previously unrecognized interaction between ERK and p38 MAPK, in which activation of p38 causes inhibition of ERK; this may at least partly involve MAPK phosphatases that inactivate ERK.

Animals↗

PubMed1998

Tamsulosin: real life clinical experience in 19,365 patients.

OBJECTIVE: To compare the efficacy, global tolerability and blood pressure effects of tamsulosin (0.4 mg once daily) in subgroups of patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO). METHODS: Data from two open-label, observational studies (Study I: 9,507 patients treated for 4 weeks, Study II: 9,858 patients treated for 12 weeks) were analyzed to compare efficacy, global tolerability and effects on blood pressure in subgroups of patients. RESULTS: The efficacy of tamsulosin was largely unaffected by age or previous phytotherapy; in patients with severe symptoms, the efficacy was at least as large as in those with mild or moderate symptoms. More than 90% of patients reported a good or very good tolerability; in a multivariate analysis, this was slightly reduced in patients with concomitant disease but not affected by antihypertensive co-medication or baseline blood pressure. In patients without co-morbidity or co-medication, the tamsulosin-induced blood pressure reductions were similar to those previously reported for placebo treatment; mean additional blood pressure reductions in patients with concomitant disease or medication was not more than 2 mm Hg. Patients who had previously been treated with beta-sitosterol, other plant extracts or finasteride reported tamsulosin to be more effective than their previous treatment. Patients who had previously received beta-sitosterol or other plant extracts rated the global tolerability of tamsulosin to be similar to that of their previous treatment, while those who had previously received finasteride or other alpha 1-adrenoceptor antagonists rated the global tolerability of tamsulosin to be significantly better than that of their previous treatment. CONCLUSIONS: We conclude that tamsulosin is efficacious in all types of patients with LUTS suggestive of BPO. It is globally well tolerated and has marginal effects on blood pressure, including the vast majority of patients with cardiovascular comorbidity, diabetes or on antihypertensive comedication.

Adrenergic alpha-Antagonists↗

PubMed1997

Comparison of adrenoceptor subtype expression in porcine and human bladder and prostate.

We have quantified and characterized alpha 1-, alpha 2- and beta-adrenoceptor subtypes in porcine bladder detrusor and bladder neck, human bladder detrusor, and porcine and human prostate. alpha 1-, alpha 2- and beta-adrenoceptor were identified in radioligand binding studies using [3H]prazosin, [3H]RX 821002 and [125I]iodocyanopindolol, respectively, as the radioligands. In porcine male and female detrusor and bladder neck and male prostate, adrenoceptors were detected in the order of abundance beta > alpha 2 >> alpha 1 (not detectable), with no major difference between the sexes or between detrusor and bladder neck. In human detrusor and prostate the order of abundance was beta > alpha 2 >> alpha 1 (not detectable) and beta >> alpha 1 > alpha 2, respectively. The alpha 2-adrenoceptors in all tissues were homogeneously of the alpha 2A-subtype as evidenced by competition binding studies with yohimbine, prazosin, ARC 239 and oxymetazoline. The beta-adrenoceptors represented a mixed population with a dominance of the beta 2-subtype in all tissues as demonstrated by competition binding with ICI 118,551 and CGP 20,712A. We conclude that pigs may be a suitable model for studies of detrusor function with respect to adrenoceptor expression. They may be less suitable for studies of bladder neck or prostate function.

Adrenergic alpha-1 Receptor Agonists↗

PubMed1997

Detection of vital germ cell tumor cells in short-term cell cultures of primary tumors and of retroperitoneal metastasis--clinical implications.

By establishing short-term cell cultures derived from retroperitoneal metastasis after neoadjuvant chemotherapy, our aim was to improve the diagnosis and prognosis in patients with advanced testicular germ cell tumors. The histological evaluation of surgically removed metastatic tissue by retroperitoneal lymphadenectomy (RLA) is extremely complicated after previous chemotherapy, but knowledge of persistence of vital tumor cells in residual lesions is of great prognostic value and therapeutic consequence in patients with testicular germ cell tumors. We therefore investigated whether vital tumor tissue could be detected in short-term cell cultures derived from such metastatic lesions by measuring the concentration of the tumor markers beta human chorionic gonadotropin (beta HCG) and alpha-1 fetoprotein (AFP) in cell culture supernatants. We initially demonstrated the specificity of the determination in cell cultures of human transitional-cell carcinoma cell lines, human foreskin fibroblasts and normal testicular tissue. In a group of 20 patients with untreated primary testicular germ cell tumors, detection of beta HCG and AFP was increased about threefold in cell culture supernatants in comparison to the serum concentration. Finally, we prepared primary cell cultures from surgically removed retroperitoneal metastasis of 12 patients with testicular germ cell tumors after chemotherapy. The serum concentrations of beta HCG and AFP of all patients were at normal values when RLA was performed. However, pathologically increased concentrations of beta HCG (3/3) and AFP (2/3) in cell culture supernatants were found in 3 of 12 cell cultures. Interestingly, these three patients with a pathological increase in beta HCG and AFP as determined in the supernatant of the short-term cell cultures had tumor progression within a mean follow-up of 3 +/- 1 months (P < 0.01), whereas 9 of 12 patients who had no pathological increase in beta HCG and AFP as determined in the supernatant of the short-term cell culture were in complete remission (CR) after a mean follow-up of 40 +/- 11.6 months.

Adult↗

PubMed1997

[Long-term results of wall stent implantation in benign prostatic hyperplasia and high risk status].

The implantation of a Wallstent prosthesis is a minimally invasive alternative to conventional TUR-P for the treatment of infravesical obstruction owing to benign prostatic hyperplasia. We report on the long-term follow-up of 37 patients with a high-risk status for TUR-P who have been implanted since May 1990. The ASA status was: ASA I: 0, ASA II: 2, ASA III: 17 and ASA IV: 18 patients. The median follow-up is now 38.5 months. Directly after implantation, a medium increase in the maximum flow-rate from 7.5 ml/s to 16.9 ml/s was documented. Residual urine was reduced from 120 to 24.2 ml on average. After 12, 18, 24 and 36 months, average maximum flow rates of 16.1, 16.7, 12.0 and 11.6 ml/s were evaluated. The corresponding residual urine was 50.3, 121.1, 56.8 and 65 ml, respectively. Also, micturition frequency decreased from 12.4 preoperatively to 8.3, 7.6, 8.0, and 8.4 per day on average. Nearly all patients reported perineal discomfort in the 1st weeks after implantation. For this reason, the stent had to be removed in 1 patient on the 45th postoperative day. In addition, a dislocated stent had to be replaced in 2 patients. Six of 15 retention patients presented with persisting detrusor dysfunction after implantation and were therefore discharged with a suprapubic tube. Endoscopic controls showed complete urothelial coverage in 78% of our patients after 6 months. After 18 months all stents were completely covered. Long-term follow-up showed reobstruction in 6 of 37 patients (16.7%) and signs of incontinence in 4 of 37 (10.8%). The late complication rate is therefore calculated at 27.5%. Stent-related deaths could not be found. We conclude that Wallstent implantation into the prostatic urethra is an alternative to TUR-P for patients at high risk from surgery. The good postoperative results also remain stable during long-term follow-up.

Aged↗

PubMed1997

[Post-traumatic priapism in a 10-year-old boy].

The case of a 10-year-old boy with post-traumatic priapism after perineal trauma is presented. Interdisciplinary treatment using angiography and selective catheter embolization for juvenile high-flow priapism is demonstrated. The literature and the diagnostic possibilities resulting from color duplex sonography are discussed.

Arteriovenous Fistula↗

PubMed1997

[Therapy with mitomycin C, folic acid and 5-fluorouracil in treatment of metastatic, refractory urinary bladder carcinoma--phase II study].

We performed a phase II trial with second-line chemotherapy in patients with refractory, metastatic cancer of the bladder. Second-line therapy consists of 2.6 cycles of mitomycin-C, 5-fluorouracil and folic acid. Two patients suffered from WHO grade III side effects (nephrotoxicity, leukocytopenia). We did not find any complete or partial remission. Four patients had a stable disease; 3.3 months after therapy, patients developed tumor progression with a median survival of 9 months. Four patients reported an improvement in quality of life. Since all patients received supportive care, improvement in quality of life cannot be related to chemotherapy alone. In conclusion, second-line chemotherapy with mitomycin-C, 5-fluorouracil and folic acid has no effect on refractory, metastatic cancer of the bladder and is no alternative for cisplatin and methotrexate-based chemotherapy.

Aged↗

PubMed1997

[Long-term outcome of surgical therapy of metastatic non-seminomatous germ cell tumor in advanced tumor stages].

We present long-term results (minimum follow-up 5 years) in 145 patients with advanced non-seminomatous germ cell tumours, who underwent radical retroperitoneal lymphadenectomy (RPLA) after chemotherapy. We correlated patients' outcomes (death of disease) to different kinds of chemotherapy and to intraoperative findings. We found that patients who were treated by a modified Einhorn scheme with cisplatin, etoposide and bleomycin have a good prognosis. In all, 90% showed no evidence of disease (NED). The NED rate was significantly lower in patients who were treated by sequential alternative chemotherapy (DOD = 37%). We determined the following prognostic factors which predict a poor outcome: salvage RPLA in the case of progressive disease or tumour marker increase during chemotherapy (DOD = 89%, P < 0.0001) residual tumour in multiple-organ systems (DOD = 41%, P = 0.0006) vital tumour in RPLA specimen (DOD = 53%, P < 0.0001) residual tumour mass > 5 cm (DOD = 41%, P = 0.0188). We found that histopathological findings of the primary tumour and tumour stage IIc-IIIc according to the Lugano classification have no prognostic significance for death of disease.

Adult↗

PubMed1997

Management of neurogenic fecal incontinence in myelodysplastic children by a modified continent appendiceal stoma and antegrade colonic enema.

OBJECTIVES: Antegrade colonic enemas for neurogenic fecal incontinence via reverse reimplanted appendices (Mitrofanoff principle) have been primarily reported by Malone and coworkers in 1990. We used a modification of the described surgical technique and treated the first 10 patients with neurogenic fecal incontinence due to spina bifida. The surgical procedure and the results are reported. METHODS: Since November 1991, we have used a surgical procedure similar to the appendiceal continence mechanism in urinary diversion to establish a continent colonic cutaneous stoma for antegrade enemas in 10 myelodysplastic patients (4 females, 6 males; median age 13.2 years [range 6 to 26]) with severe neurogenic fecal incontinence. The average follow-up is now 26.4 months (range 12.5 to 50). All patients had neurogenic bladder dysfunction successfully managed by clean intermittent catheterization, anticholinergic drugs, or artificial sphincter implantation. The surgical technique for fecal incontinence included the partial orthotopic submucosal imbedding of the appendix into a cecal tenia and the fixation of the ileocecal region at the inner side of the abdominal wall after creation of an appendicocutaneous catheterizable stoma. RESULTS: All patients reached fecal continence for at least 38 hours (median 45.3) by using antegrade colonic enemas with 1.5% saline solution (n = 9) or GoLYTELY solution (n = 1), 0.5 to 1.5 L every 2 to 3 days. All other therapies (diet, oral medication, rectal purgative, or enema) to reach fecal continence had previously failed. There were only two complications seen at the follow-up. One boy with an artificial urinary sphincter presented with infection of the sphincter system, which led to explantation. Another boy presented 15 months after creation of the colonic appendiceal stoma with saline intoxication possibly due to a homemade saline solution. CONCLUSIONS: We conclude that the antegrade colonic enema via an orthotopic continent appendiceal stoma is a safe and highly effective treatment modality for fecal incontinence in patients with neurogenic bowel dysfunction if nonsurgical management has failed.

Adolescent↗