Biomedical subjects

Jesco Pfitzenmaier

Publications and source records attributed to Jesco Pfitzenmaier.

13 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

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

Glucocorticoid use in prostate cancer and other solid tumours: implications for effectiveness of cytotoxic treatment and metastases.

Glucocorticoids have been used widely in conjunction with other treatment for patients with cancer because they have potent proapoptotic properties in lymphoid cells, can reduce nausea, and alleviate acute toxic effects in healthy tissue. However, glucocorticoids are used in a supportive-care role, even though to our knowledge no prospective clinical studies have assessed the effect of these steroids on the growth of solid tumours. Data from preclinical and, to some extent, clinical studies, suggest that glucocorticoids induce treatment resistance in solid tumours, including prostate cancer. Research has focussed on disseminated cells that have been shed by the tumour: the potential of glucocorticoids to render these cells resistant to apoptosis--and to downregulate the immune response--might contribute to tumour metastasis. Here, we review the benefits of glucocorticoids and their negative effects, such as induction of resistance in tumour cells and concomitant induction of apoptosis in immune cells, with particular emphasis on prostate cancer.

Antineoplastic Agents↗

PubMed2006

Telomerase activity in disseminated prostate cancer cells.

OBJECTIVE: To analyse telomerase activity in disseminated prostate cancer cells isolated from bone marrow aspirates taken from men with localized prostate cancer before radical prostatectomy (RP). PATIENTS AND METHODS: Disseminated epithelial prostate cancer cells were isolated from bone marrow aspirates from 69 men with localized prostate cancer before RP, by magnetic column-chromatography enrichment, followed by isolation of fluorescently labelled epithelial cells by micropipetting. We used pools of 10 non-epithelial bone marrow cells after tumour cell enrichment as control samples. These pure cell pools were tested for the presence of telomerase activity. RESULTS: In all, 49 of the patient samples contained disseminated prostate cancer cells. Homogeneous pools of 10 cells were obtained from 35 of these; 49% of the 35 specimens showed telomerase activity, whereas all five control samples did not. Telomerase activity in the 35 samples was not significantly associated with Gleason score, preoperative prostate-specific antigen level, tumour stage, or surgical margin status. Follow-up is continuing to assess an association with disease recurrence. CONCLUSION: This work shows the feasibility of isolating disseminated cancer cells for analysing individual or pooled cells. Compared to tissue staining, where telomerase is detected in 80-90% of samples, we found lower rates of telomerase activity in the disseminated tumour cells (49%). Telomerase-negative cells might provide information about cell dormancy, as telomerase is a marker of cell proliferation in immortal and cancer cells. Telomerase-positive cells might predict early disease recurrence, but a longer follow-up is needed to test this possibility.

Bone Marrow↗

PubMed2005

Lymph node metastases in non-muscle invasive bladder cancer are correlated with the number of transurethral resections and tumour upstaging at radical cystectomy.

UNLABELLED: The first paper in this section, from Mainz, attempts to identify the clinical variables associated with the prevalence of lymph node metastases in non-muscle invasive bladder cancer. The authors found that delay in cystectomy in this potentially dangerous type of tumour is to be avoided, with a higher incidence of lymph node metastases as the number of transurethral resections increases. A paper from Austria shows that in renal carcinoma the pT1 subdivision is associated with differences in conventional histopathology and expression of biomarkers. OBJECTIVE: To identify clinical variables associated with the prevalence of lymph node metastases (LNMs) in patients with non-muscle invasive transitional cell carcinoma (TCC) of the bladder treated with radical cystectomy. PATIENTS AND METHODS: Of 866 patients treated by radical cystectomy and pelvic lymphadenectomy between 1989 and 2002, 219 had non-muscle invasive TCC of the bladder. A retrospective evaluation of these patients included univariate and multivariate analyses of sex, age, number of transurethral resections of the bladder tumour (TURBTs), interval between first TURBT and cystectomy, adjuvant therapy, maximum histopathological tumour stage and grade at TURBT, and tumour upstaging in the cystectomy specimen. RESULTS: LNMs were diagnosed in 33 patients (15%). After multivariate analysis modelling, the number of TURBTs and tumour upstaging in the cystectomy specimen were correlated with the prevalence of LNMs at cystectomy. The number of TURBTs increased the prevalence of LNMs from 8% in patients with one TURBT to 24% in those with two to four TURBTs. Tumour upstaging in the cystectomy specimen increased the prevalence of LNMs from 4% to 36%. CONCLUSION: Inappropriate delay and inadequate staging of high-grade non-muscle invasive TCC of the bladder are to be avoided. The present multivariate analysis showed that the number of TURBTs and tumour upstaging in the cystectomy specimen correlated with an increased prevalence of LNMs.

Adult↗

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↗

PubMed2003

Elevation of cytokine levels in cachectic patients with prostate carcinoma.

BACKGROUND: Approximately 60-70% of patients with advanced prostate carcinoma (CaP) suffer from cachexia, one of the most devastating conditions associated with advanced malignant disease. The pathophysiology of cachexia is multifactorial, and several cytokines, such as tumor necrosis factor alpha (TNFalpha) and interleukin 1 (IL-1), IL-6, and IL-8, may be involved. The objective of the current study was to determine whether cachexia associated with advanced CaP is accompanied by increased serum levels of TNFalpha, IL-1beta, IL-6, and IL-8. METHODS: The levels of TNFalpha, IL-1beta, IL-6, IL-8, and prostate specific antigen (PSA) were examined in serum samples from normal donors (n = 10 donors), from patients with organ-confined CaP (n = 19 patients), from patients with advanced CaP without cachexia (n = 17 patients), and from patients with cachectic CaP (n = 26 patients). DPC Immulite and Abbott IMx Total-PSA assays were used to determine cytokine and PSA levels, respectively. RESULTS: Levels of TNFalpha, IL-6, and IL-8 were elevated significantly in the group of patients with advanced, cachectic CaP compared with patients who were without cachexia. In the cachectic patients, levels of TNFalpha were correlated positively with IL-8, and there was no correlation between PSA levels and any of the cytokine levels. IL-1beta levels were below the limit of detection in all samples. CONCLUSIONS: The current results show that levels of TNFalpha, IL-6, and IL-8 were increased in CaP patients with cachexia. Increased levels of these cytokines were not correlated with PSA levels, suggesting that they are regulated by a mechanism that is independent of PSA synthesis. Additional fundamental research is needed to determine the mechanisms involved and to identify potential therapeutic targets in patients with cachexia.

Aged↗

PubMed2003

Detection and isolation of prostate cancer cells from peripheral blood and bone marrow.

OBJECTIVES: To detect and isolate disseminated prostate cancer cells because significant effort has been directed toward defining the characteristics of the primary tumor that predict progression, but little progress has been made on evaluating the disseminated prostate cancer cell. Prostate-specific antigen (PSA) reverse transcriptase-polymerase chain reaction results in the bone marrow (BM) and peripheral blood (PB) of men with prostate cancer suggest many have disseminated cancer cells. METHODS: Disseminated epithelial cells were isolated from the BM and PB using Miltenyi antibody-coated paramagnetic microparticle technology. In the two-step selection process, anti-CD45 and anti-CD61 were used for negative selection, and anti-human epithelial antigen was used for positive selection. Cells were then stained for Ber-EP4 (a distinct epitope of the human epithelial antigen) and PSA. PSA reverse transcriptase-polymerase chain reaction was performed on an enriched aliquot. RESULTS: The normal controls were negative. Before prostatectomy, PSA-expressing epithelial cells were detected in 54% of BM and 24% of PB samples. At a median of 4 months after prostatectomy, PSA-expressing cells were detected in 33% of BM and 9% of PB specimens from men without evidence of disease. In men more than 5 years after prostatectomy, PSA-expressing cells were detected in the BM of 4 (29%) of 14, 2 of whom subsequently developed evidence of disease recurrence. CONCLUSIONS: The findings suggest that dissemination of cells is an early event in prostate cancer that is insufficient for the development of metastases. Isolation will allow interrogation of the phenotype and genotype of the cells.

Bone Marrow Cells↗

PubMed2003

Metabolic evaluation of 94 patients 5 to 16 years after ileocecal pouch (Mainz pouch 1) continent urinary diversion.

UNLABELLED: PURPOSE In continent urinary diversion metabolic disturbances may be encountered in long-term followup. We evaluated metabolic consequences in patients with a minimum followup of 5 years after Mainz pouch 1 urinary diversion. MATERIALS AND METHODS: At our institution continent urinary diversion using the ileocecal segment was performed between 1983 and 1995 in 458 patients. A total of 94 patients with an ileocecal pouch for a minimum of 5 years were reevaluated for metabolic changes. Median followup was 9.0 years. Routine laboratory parameters, blood gas analysis, vitamin B12, vitamin D25, cross-laps, bone specific alkaline phosphatase, osteocalcin and propeptide of type I collagen were obtained. Bone density was measured in 18 patients. Vitamin B12 changes could be followed longitudinally in 24 patients. RESULTS: Medians of all parameters were in normal ranges. Clinical examinations revealed no signs of megaloblastic anemia, funicular myelosis or osteoporosis. There was no significant decrease of vitamin B12 in the long run. After followup examination we recommended vitamin B12 supplementation in 32% of patients because levels were in the lower normal range or below. A total of 37% of patients continue to take Na+/K+-citrate for prevention of metabolic acidosis. CONCLUSIONS: Patients with an ileocecal pouch and a followup of more than 5 years did not present with clinical symptoms caused by metabolic disturbances. Nevertheless, systematic followup of blood gases in particular and alkali supplementation may have prevented bone demineralization. Followup of vitamin B12 is of concern because about a third of these patients need supplementation.

Acidosis↗

PubMed2003

Characterization of C4-2 prostate cancer bone metastases and their response to castration.

UNLABELLED: New well-characterized preclinical models of prostate cancer (CaP) bone metastases are needed to improve our understanding of the development of CaP-related bone disease in patients. Here we describe characterization of a model consisting of direct injection of C4-2 cells into tibias. INTRODUCTION: Prostate cancer (CaP) has a high proclivity to metastasize to bone. Development and characterization of preclinical models of CaP bone metastases are of high interest. The objective of this study was to characterize C4-2 bone metastases and their response to castration. MATERIALS AND METHODS: Cell suspensions of C4-2, a subline of LNCaP, were injected directly into the tibias of intact male mice. In groups A (n = 7) and B (n = 5), animals were killed 3 and 8 weeks after injection of C4-2 cells, respectively. In group C (n = 7), animals were castrated 3 weeks after injection and killed 5 weeks after castration. Serum prostate-specific antigen (PSA) levels and bone mineral density (BMD) were measured, and bone histomorphometric analysis was performed. RESULTS: C4-2 cells decreased BMD of the injected tibias by 36.1% and bone volume by 74.1% versus normal tibias. Castration caused a 32.3% drop in serum PSA (p = 0.0438), with a nadir at day 14, after which it began to rise again. Bone destruction in the tumorous tibias of castrated animals was decreased by 15.9% versus tumorous tibias of intact animals (p = 0.0392). However, BMD in the tumorous tibias of castrated mice was still lower than in normal tibias of intact animals. Castration also decreased BMD and bone volume in nontumorous tibias (p = 0.0406 and 0.0232, respectively). CONCLUSIONS: The C4-2 model of bone metastasis recapitulates the response to androgen deprivation observed in CaP patients with bone metastases and is suitable for study of interactions between tumor and bone cells and evaluation of new therapeutic modalities.

Animals↗

PubMed2002

Transitional cell carcinoma of the renal pelvis presenting as a renal abscess.

We report on a 76-year-old woman who was diagnosed with a primary renal abscess of the left kidney. After percutaneous drainage, no clinical improvement was observed. Surgical exploration and nephrectomy were performed. The histologic evaluation revealed an unsuspected transitional cell carcinoma of the renal pelvis, which had been misinterpreted as a primary renal abscess. Malignancy must be considered as an underlying cause for the formation of a renal abscess, especially if no other predisposing factors such as diabetes mellitus or urinary stones are present.

Abscess↗

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↗