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Markus Hohenfellner

Publications and source records attributed to Markus Hohenfellner.

12 recordsLinked to original sources
PubMed2007

Clinical and mechanistic aspects of glucocorticoid-induced chemotherapy resistance in the majority of solid tumors.

BACKGROUND: Glucocorticoids have been used widely in conjunction with cancer therapy due to their ability to induce apoptosis in hematological cells and to prevent nausea and emesis. However, recent data including ours, suggest induction of therapy-resistance by glucocorticoids in solid tumors, although it is unclear whether this happens only in few carcinomas or is a more common cell type specific phenomenon. MATERIAL AND METHODS: We performed an overall statistical analysis of our new and recent data with 157 tumor probes evaluated in vitro, ex vivo and in vivo. The effect of glucocorticoids on apoptosis, viability and cell cycle progression under diverse clinically important questions was examined. RESULTS: New in vivo results demonstrate glucocorticoid-induced chemotherapy resistance in xenografted prostate cancer. In an overall statistical analysis we found glucocorticoid-induced resistance in 89% of 157 analysed tumor samples. Resistance is common for several cytotoxic treatments and for several glucocorticoid-derivatives and due to an inhibition of apoptosis, promotion of viability and cell cycle progression. Resistance occurred at clinically achievable peak plasma levels of patients under anti-emetic glucocorticoid therapy and below, lasted for a long time, after one single dose, but was reversible upon removal of glucocorticoids. Two nonsteroidal alternative anti-emetic agents did not counteract anticancer treatment and may be sufficient to replace glucocorticoids in cotreatment of carcinoma patients. CONCLUSION: These data demonstrate the need for prospective clinical studies as well as for detailed mechanistic studies of GC-induced cell-type specific pro- and anti-apoptotic signalling.

Animals↗
PubMed2006

Design and validation of a new screening instrument for lower urinary tract dysfunction: the bladder control self-assessment questionnaire (B-SAQ).

OBJECTIVES: To develop and validate a short patient self-assessment screening questionnaire: bladder control self-assessment questionnaire (B-SAQ) for the evaluation of lower urinary tract symptoms. This first validation study was undertaken amongst women. PATIENTS AND METHODS: Three hundred twenty-nine women attending general gynaecology and urogynaecology clinics completed both the B-SAQ and Kings Health questionnaire prior to medical consultation, and independent physician assessment of the presence of lower urinary tract symptoms (LUTS) and need for treatment. The psychometric properties of the B-SAQ were subsequently analysed. RESULTS: The B-SAQ was quick and easy to complete, with 89% of respondents completing all items correctly in less than 5 min. The internal consistency (Cronbach's alpha score 0.90-0.91), criterion validity (Pearson's correlation values of 0.79 and 0.81, p<0.0001 with the incontinence impact domain of the Kings Health questionnaire), and test-retest reliability of the questionnaire were good. The sensitivity and specificity of the questionnaire to identify patients with bothersome LUTS was 98% and 79%, respectively. CONCLUSIONS: LUTS are commonly underreported. Empowering patients to self-assess their bladder symptoms and the need for treatment will improve treatment-seeking behaviour. The B-SAQ is a psychometrically robust, short screening questionnaire that offers patients the ability to assess their bladder symptoms and the bother they cause, and the potential benefit of seeking medical help.

Adolescent↗
PubMed2006

Ureteric replacement with Meckel's diverticulum.

OBJECTIVE: To report on four patients with obstruction of the upper urinary tract due to severe ureteric strictures at different levels, in whom a Meckel's diverticulum was used for ureteric replacement. PATIENTS AND METHODS: The patients were aged 3-64 years at the time of operation. In every patient, a Meckel's diverticulum was used to bridge a ureteric defect after recurrent reconstructive procedures. RESULTS: The mean (range) follow-up was 36 (12-69) months. There were no surgical complications, apart from mucus production in one case and renal function was normal in all patients after surgery. In one case, the invaginated Meckel's diverticulum was used for reflux protection. CONCLUSIONS: A Meckel's diverticulum, if present, appears to be an ideal intestinal substitute for a ureteric defect. The advantages of its use are its unique blood supply, its mobility, and its minimization of functional bowel length resection.

Adult↗
PubMed2006

Thoraco-abdominal approach to large retroperitoneal tumours.

OBJECTIVES: To evaluate the thoraco-abdominal approach for resection of retroperitoneal tumours, as this approach is rarely used because, although exposure is excellent, morbidity is presumed to be increased. PATIENTS AND METHODS: From October 2003 to September 2005, 21 patients (six female, 15 male), aged 14-76 years, underwent resection of very large and/or T4 retroperitoneal tumours through a thoraco-abdominal approach. RESULTS: In 16 (76%) patients tumour resection was complete. There were no significant complications during surgery. After surgery, there were complications in six patients (29%), in four of whom there was no long-term impairment. One patient died at 75 days after surgery from a complicated retroperitoneal haematoma. The mean (range) estimated blood loss was 2883 (50-20 000) mL, the intensive-care unit stay was 3.85 (0-30) days and the intermediate-care unit stay 2.6 (0-9) days. With a mean follow-up of 9.6 (1-19) months, 15 patients (72%) are recurrence-free, two (10%) have progressive disease, and four (19%) have died from malignancy. CONCLUSIONS: The thoraco-abdominal approach permits excellent exposure of the retroperitoneum for large and/or T4 tumours, allowing radical surgery in cases considered otherwise inoperable. Additional advantages are the possibilities of early vascular control and easy surgical extension of the procedure. These facts, combined with the reasonable morbidity found in our series, support the integration of the thoraco-abdominal approach in the regular options for urological surgery.

Abdomen↗
PubMed2006

Cytotoxic markers and frequency predict functional capacity of natural killer cells infiltrating renal cell carcinoma.

PURPOSE: Renal cell carcinoma harbors high numbers of infiltrating lymphocytes with apparent limited efficacy in tumor control. This study focused on the natural killer (NK) cells infiltrating renal cell carcinoma. EXPERIMENTAL DESIGN: Tumor-infiltrating lymphocytes (TIL) were isolated from renal cell carcinoma and analyzed for NK cell frequency and phenotype (n = 34). NK cells were enriched and tested for effector function. RESULTS: Two renal cell carcinoma subtypes were identified, one containing high (>20% of the lymphocyte population, n = 14), the other low (<20%, n = 20), NK cell numbers. NK cells of both groups were noncytolytic ex vivo but differed in CD16 and cytotoxic effector molecule expression as well as in their capacity to acquire cytotoxic activity: The majority of NK cells from tumors with high NK cell content (high NK-TIL) were CD16(bright), whereas few CD16bright NK cells were found in tumors with low NK cell frequencies (low NK-TIL). The CD16 dichotomy correlated with different capacities to develop cytotoxicity after short-term activation with interleukin-2 ex vivo: Low NK-TIL remained noncytolytic against K562 and unresponsive to signals via the activating receptor NKp46 despite expression of receptor and adaptor molecules. In contrast, high NK-TIL acquired cytotoxic function. As described for peripheral CD16bright NK cells, NK cells from high-NK tumors showed high per cell expression of granzyme A, granzyme B, and perforin. NK cells from low NK-TIL resembled CD16(neg/dim) peripheral NK cells with few cytotoxin+ cells and lower expression of perforin. CONCLUSION: The extent of NK cell infiltration and the expression of markers (CD16 and cytotoxins) predict the functional capacity of NK cells infiltrating renal cell carcinoma and can be used to characterize subgroups of renal cell carcinoma.

Adult↗
PubMed2006

Distribution of neuropeptide Y-containing nerves in the neurogenic and non-neurogenic detrusor.

OBJECTIVE: To evaluate the role of neuropeptide Y in the detrusor of patients with neurogenic detrusor overactivity (NDO), as it has an important role in the neural regulation of the lower urinary tract by exerting differential effects on the release of cholinergic and adrenergic transmitters via autoinhibition and heterosynaptic interactions. MATERIALS AND METHODS: Detrusor biopsies were obtained from 38 patients; 31 had video-urodynamically verified NDO, caused by meningomyelocele in 17 or spinal cord injury in 14. Seven had stress urinary incontinence (SUI) and this group served as a control. All specimens were fixed, paraffin wax-embedded, sectioned and stained with a monoclonal antibody against neuropeptide Y and a general nerve marker protein-gene-product 9.5 (PGP 9.5). The number of PGP 9.5- and neuropeptide Y-containing nerves was quantified by a standardized evaluation using image-analysis software. RESULTS: The median (range) number of neuropeptide Y-containing nerves in the neurogenic detrusor, at 0.273 (0.126-0.639) per muscle cell nucleus (MCN), was significantly lower (P = 0.014) than that in patients with SUI, at 0.383 (0.267-0.728). In the neurogenic detrusor the number of PGP 9.5-positive nerves, at 0.278 (0.054-0.641)/MCN was also lower (P = 0.111) than in patients with SUI, at 0.368 (0.258-0.497). The ratio of neuropeptide Y to PGP 9.5 counts per biopsy did not differ between the groups (P = 0.628). CONCLUSIONS: The number of PGP 9.5-positive nerves was not significantly and the number of neuropeptide Y-containing nerves was significantly reduced in patients with NDO. This may have been caused by transynaptic nerve degeneration of the detrusor, as described by in patients with spinal cord injury. As neuropeptide Y inhibits the contractile response of the detrusor the reduction of neuropeptide Y-containing nerves may play a role in the development and persistence of DO.

Adolescent↗
PubMed2005

EAU guidelines on urological trauma.

PURPOSE: To determine the optimal evaluation and management of genitourinary (renal, ureteral, bladder, urethral and genital) injuries by review of the world's literature on the subject. METHODS: A consensus committee convened by the Health Care Office of the European Association of Urology (EAU) to summarize the literature concerning the diagnosis and treatment of genitourinary trauma. RESULTS: Findings of 350 citations are reviewed. CONCLUSIONS: The genitourinary trauma literature still relies heavily on expert opinion and single-institution retrospective series. Future prospective trials of the most significant issues, when possible, might improve the quality of evidence that dictates practitioner behavior.

Decision Trees↗
PubMed2005

Adherens junctions of the human detrusor.

OBJECTIVE: To immunohistochemically identify the protein composition of adherens junctions, which couple smooth muscle cells mechanically, and to confirm their decrease in different bladder dysfunctions, as studies in geriatric bladder dysfunction show fewer such junctions in patients with detrusor overactivity (DO) and bladder outlet obstruction (BOO). MATERIAL AND METHODS: Detrusor biopsies were obtained from video-urodynamically evaluated patients with neurogenic DO (NDO, 31 patients), BOO (six patients) and from six patients with stress urinary incontinence (SUI) with stable, unobstructed detrusors (serving as controls). Specimens were fixed, paraffin-embedded, sectioned, stained with a polyclonal pan-cadherin antibody, monoclonal alpha-, beta- and gamma-catenin antibodies, and a monoclonal integrin-beta1 antibody. All antibodies were known to react with proteins of adherens junctions. Two examiners unaware of sample origin evaluated the sections qualitatively and using a semiquantitative scale. The results were correlated with the patient groups. RESULTS: Specific immunohistochemical staining of pan-cadherin, alpha-, beta- and gamma-catenin could not be detected in any detrusor smooth muscle compartment, but was present in the urothelium. There was integrin-beta1 reactivity in the basement membranes of bladder smooth muscle cells in 38 of 43 detrusor biopsies. There were no differences among the three groups. CONCLUSION: The known proteins of cell-cell adherens junctions are not part of the cell-cell junctions of detrusor smooth muscle. The specific staining of integrin-beta1 indicates either the presence of cell-matrix junctions or of cell-cell junctions within the human detrusor. Further studies are needed to identify the complete protein composition of adherens junctions within smooth muscle cells.

Adherens Junctions↗
PubMed2004

Conversion from colonic or ileal conduit to continent cutaneous urinary diversion.

PURPOSE: After ileal or colonic conduit diversion some patients, particularly adolescents, desire conversion to a continent diversion to improve quality of life. We report our long-term results on conversion from conduit diversion to continent cutaneous diversion. MATERIALS AND METHODS: Between 1986 and 2001, 39 patients (mean age 24 years, range 6 to 49) underwent conversion from a colonic (21) or ileal conduit (18) to an ileocecal pouch (Mainz pouch I) with a mean followup of 102 months (range 18 to 192). Conversion was performed after a mean of 11 years (range 1 to 36) of conduit urinary diversion by incorporating the preexisting colonic/ ileal conduit and the ileocecal pouch. RESULTS: A total of 21 patients (54%) experienced complications requiring surgical intervention including stoma stenosis (13%), pouch calculi (31%) and ureteral stenosis (6 of 75 renoureteral units, 8%). Continence was achieved in 95% of patients. Defecation was unchanged in 72% of patients without treatment. In 21% fecal frequency was medically controlled (cholestyramine, loperamide) and 8% of patients had fecal frequency. During followup early substitution of alkali was performed and in 19 patients (49%) the venous base excess was less than -2.5 mmol/l to prevent hyperchloremia and acidosis. CONCLUSIONS: The inclusion of a preexisting colonic or ileal conduit decreases resection length of bowel for continent cutaneous diversion. Acceptable complication rates, stable renal function and satisfaction of patient expectations support conversion from a conduit into a Mainz pouch I as a safe and viable option in the long run.

Adolescent↗
PubMed2002

Transposition of the left renal vein for treatment of the nutcracker phenomenon: long-term follow-up.

OBJECTIVES: To assess the therapeutic value of left renal vein transposition for treatment of the nutcracker phenomenon in long-term follow-up. METHODS: Eight patients (4 women and 4 men) between 23 and 58 years old (mean 39.1) underwent transposition of the left renal vein for treatment of the nutcracker phenomenon associated with recurrent gross hematuria and flank pain. The postoperative follow-up was 41 to 136 months (mean 66.4). RESULTS: No perioperative complications were encountered. The postoperative complications comprised deep vein thrombosis (n = 1), retroperitoneal hematoma necessitating surgical revision (n = 1), and paralytic ileus that resolved with conservative management (n = 1). One patient underwent laparotomy for treatment of mechanical ileus due to adhesions 4 years after the initial surgery. In 7 of 8 patients, transposition of the left renal vein efficiently relieved the symptoms related to the nutcracker phenomenon. In 1 patient, the hematuria persisted despite postoperative normalization of the pressure gradient between the left renal vein and the inferior vena cava. CONCLUSIONS: Transposition of the left renal vein is an efficient surgical approach for the treatment of the nutcracker phenomenon and is associated with an acceptable risk of complications. However, rare cases may be encountered in which the shunted connections between the renal veins and the collecting system are so matured that, despite removal of the obstruction of the renal venous backflow, gross hematuria may persist.

Adult↗
PubMedDate not supplied

Multislice computed tomography in planning nephron-sparing surgery in a prospective study with 76 patients: comparison of radiological and histopathological findings in the infiltration of renal structures.

OBJECTIVE: The aim of this prospective study is to determine the diagnostic accuracy of multidetector-row computed tomography (CT) compared to histopathologic findings in tumor staging of renal cell carcinoma, with the focus on tumor stage, vein and artery infiltration, and infiltration of the renal pelvis. MATERIALS AND METHODS: In a prospective study, a total of 76 consecutive patients with suspected renal cell carcinoma were preoperatively assessed for tumor staging using multidetector-row CT. Triphasic CT imaging (i.e., noncontrast, arterial, and parenchymal phase) was performed using multidetector-row CT with reconstructed slice thicknesses of 2 and 5 mm. Two blinded readers evaluated the CT scans independently; the results were then correlated with the histopathologic results. RESULTS: A total of 56 renal cell carcinomas were proven on histopathology. Readers 1 and 2 reached a sensitivity of 1.0 and 1.0 and a specificity of 0.41 and 0.42 for arterial infiltration, a sensitivity of 1.0 and 0.86 and a specificity of 0.58 and 0.5 for venous infiltration, and a sensitivity of 0.75 and 1.0 and a specificity of 0.5 and 0.44 for infiltration of the renal pelvis. The correlation between both readers was 0.7 for all modalities. CONCLUSIONS: The multiplanar reconstruction capability of multidetector-row CT allowed good sensitivity in predicting arterial infiltration. The lowest specificity was reached in excluding infiltration of the renal pelvis. Despite its high temporal and spatial resolution, the capacity of multidetector CT to predict intrarenal infiltrations is still limited.

Adult↗