Biomedical subjects
Publications and source records attributed to T Otto.
In the last 10 years in Germany we have seen a lot of hernia repairs using mesh.Meta-analysis shows the advantages of using meshes in hernia surgery; recurrence rates in inguinal hernia surgery are less than 3% in studies. There is some discussion about minimally invasive surgery in Germany.In incisional hernia surgery there is no discussion about using meshes. The role of minimally invasive surgery has not yet been defined.
Bladder cancer has a high incidence; therefore, the prevention of bladder cancer is useful. Each year 15,000 patients suffer from bladder cancer in Germany. These tumors are chemically induced and the development of bladder cancer is determined by the carcinogen and the time of exposure i.e., exposition time. Development of bladder cancer also depends on the patient's age. In patients younger than 45 years bladder cancer is a rare disease. The incidence of bladder cancer is 3 of 100,000 in males at the age of 45-50 years and it increases in the cohort of males older than 80 years to 200 of 100,000. Bladder cancer is a serious disease. The annual loss of life related to bladder cancer is 64,700 life years in Germany alone! Identification of carcinogens makes a preventative approach possible and leads to the detection of occupationally endangered people. Bladder cancer carcinogens include aromatic amines, medicaments (chlornaphazin, phenacetin, and cyclophosphamide), cigarette consumption, chronic infection of the lower urinary tract, radiation therapy of the pelvis, bilharciosis, Balkan nephropathy, and chronic interstitial nephritis.
BACKGROUND: Purtscher's retinopathy is accompanied by a distinct loss of vision as a result of severe trauma to the chest or skull. Reports on visual prognosis in the literature are not uniform. PATIENTS: The data of 10 patients with Purtscher's retinopathy from the department of Ophthalmology in Freiburg, published data from 55 patients with Purtscher's retinopathy and 20 patients with traumatic retinal hemorrhages taken from the literature were evaluated. RESULTS: The average visual acuity of the 10 patients from Freiburg was 0.3 within a short period after the accident and the final average visual acuity was 0.46. The average visual acuity of the 55 patients with Purtscher's retinopathy was 0.21 within a short period after the accident with an average final visual acuity of 0.61. The average visual acuity of the 20 patients with traumatic retinal hemorrhages from the literature was 0.45 within a short period after the accident with an average final visual acuity of 0.74. Therefore the initial and the final visual acuity were better in patients with traumatic retinal hemorrhages compared to patients with Purtscher's retinopathy. CONCLUSION: In spite of severe initial retinal findings, the visual prognosis is usually not disappointing. Prognosis of visual acuity was better in patients with traumatic retinal hemorrhages compared to patients with Purtscher's retinopathy.
The techniques of DNA microarrays, protein arrays, and tissue microarrays complement one another and in the future the combination of these methods will possibly enable the detection of genes specific for bladder cancer. The SELDI technology (surface-enhanced laser desorption/ionization) will then be used to prove if the genes are translated into proteins and if those proteins have a relevant effect on the development and progression of the cancer disease. The consequence is the facilitation of the development of prognostic markers for this disease entity, which can then be easily tested in a large study population by tissue microarray. Beyond the gain of new insights into the biological understanding of the development and progression of bladder cancer, these techniques will hopefully enable the design of new therapeutic concepts, which apply to the individual biology of the tumor.
Skin infiltration and locoregional lymph node extension in metastatic penile cancer leads to destruction in the inguinal and perineal region. Efficacy of systemic polychemotherapy based on cisplatin, methotrexate, and bleomycin (CMB scheme) is limited with an objective remission rate up to 30% only. The obligatorily superinfected defects require tension-free and extended coverage with immediate myocutaneous flaps after surgical resection. Pedicle flaps, consisting of skin, fascia, muscle, and the supplying vessels, are used to cover the post-resection defects. In the field of surgical uro-oncology the following myocutaneous flaps listed with the supplying vessels have proved themselves: M. tensor fasciae latae flap (A. circumflexa femoris lateralis), M. rectus abdominis flap (A. epigastrica inferior), M. gluteus maximus flap (A. glutea inferior). Data concerning a prospective study for neoadjuvant chemotherapy with CMB followed by surgical tumor resection with immediate myocutaneous flap reconstruction are presented. In 15 patients (median age: 69.7 years) suffering from squamous cell carcinoma of the penis (Tx, N3, M1 cutis), a surgical excision of the tumor was performed after neoadjuvant chemotherapy (median:2.4 cycles) and antibiotic pretreatment. All patients received coverage of the femoral vessels with a musculus sartorius transfer on both sides. An extended (up to 45x30 cm) tension-free coverage of groin defects was performed in two patients with a unilateral M. tensor fasciae latae flap (TFL) and in eight patients with a bilateral TFL. One patient received a M. gluteus maximus flap (GMFL) on both sides, three patients were treated with a combination of M. rectus abdominis flap (RFL) and TFL, and one patient received a combination of two TFL, one GMFL as well as one RFL. Of 31 myocutaneous pedicle flaps, 2 developed distant necrosis of the flap, in which one GMFL and one TFL were affected. No complete necrosis of the pedicle flap occurred. Primary wound healing was found in 29 of 31 myocutaneous flaps. The covering of groin defects by the use of myocutaneous flaps, such as the M. tensor fasciae latae, M. rectus abdominis, and M. gluteus maximus flap, is a method of first choice in the primary treatment of even bacterially contaminated wounds or after radiation therapy. The techniques of pedicle flaps are comparably applied in oncology and traumatology.
The great majority of phytotherapeutic, homeopathic and anthroposophical medicines are subject to the regulations in their respective field of application, implying a simple licensing process. In contrast with conventional medications in the area of oncology, some unconventional agents are given in observation studies without the prior testing of quality, side effects and efficacy that is normal in oncology. Unconventional therapeutics cannot be considered equivalent to placebo preparations. Since they may have an immunomodulatory action, one cannot exclude possible long-term adverse effects, including progression of tumors. To date there is no clear indication for routine use of unconventional therapeutic agents in urological oncology. A scientific evaluation according to the criteria of evidence-based medicine is required. This article presents proven results of treatment with unconventional medicines in urooncology against the background of the respective spectrum of methods.
Despite local tumor control, patients with locally advanced bladder cancer or lymphogenic metastasized urothelial carcinoma are at risk for systemic progress. Radical cystectomy is the gold standard treatment for muscle-invasive bladder tumors. Pelvic lymphadenectomy remains an integral part of the surgical treatment. However, the extent of the lymph node dissection depends on its diagnostic or curative intent and is more controversial. In addition, further treatment options such as systemic chemotherapy or combined radio-chemotherapy are needed to improve the outcome of locally advanced or metastasized disease. Therefore, administration of additional therapy to surgical treatment is intensively studied. The application of the neoadjuvant concept as well as the definite role of the adjuvant chemotherapy currently are contentious topics and subjects of meta-analyses and prospective randomized trials. In addition, bladder preservation as part of a multimodality treatment is still discussed as an option for selected patients unsuitable for radical cystectomy. This article gives an overview on the current concepts of the use of neoadjuvant systemic chemotherapy in the treatment of advanced urothelial cancer.
Despite radical cystectomy, 40% of the patients with locally advanced disease and more than 80% of the patients with lymphatic metastases die tumor related. This provides the rationale for additional effective systemic therapy following surgery. In addition, previous surgery and consecutive histopathological or cell-based evaluation offers the advantage to expose only those patients to adjuvant systemic chemotherapy, who belong to a defined high-risk group. Regional lymph node metastases range from less than 10% in T1 to nearly 33% in T3/T4 lesions. Therefore, the extend of the lymph node dissection as an integral part of the surgical treatment gains importance. As pathological assessment of an adequate number of lymph nodes increases the likelihood of proper staging and decisions on further therapy depend on accurate staging, a standardization of lymphadenectomy is desirable. This paper provides an overview on the current concepts of the use of adjuvant systemic chemotherapy in the treatment of advanced urothelial cancer.
Radical cystectomy is the treatment of choice for patients with muscle-invasive or locally advanced bladder carcinoma. Alternative treatment options are simultaneous radiochemotherapy following transurethral tumor resection or percutaneous definitive radiotherapy. To prevent early tumor progression, treatment decision should be made within 6 months after initial diagnosis. Extended lymphadenectomy seems to have an impact on progression-free survival, as determined in retrospective analyses. Excellent long-term results exist for urinary diversion using ileal neobladder or ureter bowel implantation into an augmented colon sigmoideum segment. Similarly good results are reported for female patients. Quality of life (QoL) in correlation to type of urinary diversion is under discussion. Ileal conduit seems to be of advantage for QoL especially in elderly patients. Surgical removal of metastases is controversially discussed, especially in those patients without tumor-related symptoms. An age of more than 70 years seems to be no exclusion criterion for radical cystectomy. Treatment morbidity and mortality are similar to those of younger patients. Long-term results confirm the excellent results of orthotopic bladder replacement.
This is a prospective randomized multicenter trial for evaluation of the biological response modifier Factor AF2 in advanced urothelial cancer treated with chemotherapy. Main aim of the study was the analysis of supportive effects. Additionally patients were examined with regard to tumor response, time to progression and survival. 106 patients with advanced urothelial cancer received chemotherapy with cisplatin and methotrexate. They were randomized for additional Factor AF2 (500 mg i.v., given at days 0-3, 7-10 and 11-14). Myelotoxicity was more common and severe in the group without Factor AF2 reaching statistical significance. Gastrointestinal side effects occurred in both groups, though grade III to IV toxicity was more common without Factor AF2. Overall remission rate was 38%, median survival 33 weeks, mean time to progression 20 weeks. There was no significant difference between the two groups with or without Factor AF2.
To develop new therapeutic strategies we examined the expression and signaltransduction of G protein-coupled receptors in a human transitional cell carcinoma cell line. The receptors for lysophosphatidic acid (LPA) and thrombin potently stimulate cell migration. Pretreatment with PTX completely inhibited cell motility induced by LPA. In the model of chemically induced bladder carcinoma in rats the effects of intravesical instillation of PTX or phosphate buffered saline was examined. The incidence of G2-G3 cells in cytology was significantly reduced in rats treated with PTX. To ascertain the side effects of intravesical instillation of PTX a Phase I study was initiated. 15 patients were instilled with PTX at 5 dose levels (14-72 micrograms/100 ml) 3 times a week. Instillation of PTX up to 72 micrograms was without local or systemic side effects. PTX is a substance which potently inhibits tumor cell motility and progression. Intravesical treatment was well tolerated and therefore, the influence of PTX on local tumor should be evaluated in a Phase II study.
Although replacement of olfactory receptor neurons (ORNs) and subsequent reinnervation of the olfactory bulb occur following ORN injury, the intrinsic and extrinsic factors that contribute to the regulation of this dynamic process have not yet been fully identified. Recent research indicates that several growth factors have neurogenic effects on ORNs in vitro, and that chronic in vivo administration of either basic fibroblast growth factor, epidermal growth factor, or transforming growth factor-alpha (TGF-alpha) following chemical lesion can enhance the normal rate of ORN reinnervation of the olfactory bulb. The primary goal of the present experiments was to further assess the extent to which growth factor-related enhancements in the rate of anatomical recovery during ORN reconstitution and subsequent reinnervation of olfactory bulb are accompanied by enhancements in the rate of recovery of odor-guided behavior.A series of experiments in rats was conducted to initially characterize the time course of the anatomical and behavioral recovery normally observed following ORN reconstitution as a consequence of olfactory nerve transection, and to subsequently characterize the anatomical and behavioral effects of TGF-alpha administration on this normal rate of recovery. Consistent with a host of prior studies, olfactory nerve transection produced consistent and substantial deafferentation of olfactory bulb followed by a time-dependent anatomical recovery which was significantly enhanced by administration of TGF-alpha. The effect of TGF-alpha on functional recovery following olfactory nerve transection was also assessed using an odor-guided fear conditioning task. ORN lesioned animals receiving injections of TGF-alpha during recovery were found to display enhanced conditioned responding to an olfactory stimulus compared to untreated subjects. Further behavioral analyses suggested that this enhanced functional recovery was likely not due to non-specific effects of TGF-alpha on cognition or motor activity, but rather to enhanced olfactory input to the CNS. Future studies will likely reveal the exact mechanism of action mediating the anatomical and concomitant behavioral effects of this growth factor. Since ORNs are one of only a few populations of neurons capable of regeneration or replacement, the continued study of the cellular and molecular factors that coordinate this regenerative process may ultimately lead to the development of therapeutic strategies to promote an enhanced functional recovery following injury to other neuronal populations.
OBJECTIVE: To report a prospective phase II study of patients with disseminated peritoneal carcinomatosis and symptomatic disease, in whom the peritoneal metastases were resected. PATIENTS AND METHODS: From 1995 to 1999, 32 patients (20 men and 12 women, median age 56 years, range 32-75) with peritoneal carcinomatosis were enrolled in the trial. Pain and ascites were determined according to the National Cancer Institute score/criteria, and performance scored according to the World Health Organisation criteria. RESULTS: All patients had intraperitoneal disseminated malignancies with clinically evident ascites, and presented with abdominal pain. The median (range) operative duration was 2.9 (1-5.5) h and the hospital stay 25 (10-44) days, with no deaths at 30 days. The ascites was completely cured in 25 of the 32 patients, pain relieved in 28 and the performance score improved in 25. The median survival time was 1 year; the 1- and 2-year survival rates were 45% and 38%, respectively. Patients with residual metastases after incomplete resection had a significantly worse prognosis, but the prognosis was significantly better in those with a low tumour burden. CONCLUSIONS: Peritoneal carcinomatosis is treatable; radical peritonectomy improves the performance score in selected patients with cancer-related ascites and/or pain, and is now the standard approach in the authors' Cancer Centre.
BACKGROUND: Surgery, chemotherapy and radiotherapy are the mainstay of tumor management. However, in systemic disease cure can be achieved in yet a few tumor entities. Based on cell biological research we have characterized the process of tumor progression and metastasis and disclosed that the loss of cell-cell adhesion in association with an increased tumor cell motility is an essential feature of the malignant potential of a tumor. METHODS: According to this principle we derived therapeutical methods differing from hitherto existing treatments by being exclusively focused on tumor cell motility. Characterization of so-called anti-motility factors was performed biochemically as well as with motility assays by in vitro studies in established bladder carcinoma cell lines. RESULTS: We evaluated the potential therapeutic benefit in a model of chemically induced bladder carcinoma followed by a phase I/II trial applying antimotility factors in patients with advanced bladder cancer. CONCLUSION: Both basic research as well as the results of first clinical trials confirm, that advanced carcinomas can be influenced by inhibition of tumor cell motility.
BACKGROUND: To assess the efficacy and toxicity of repeated single 24-hour infusion of low-dose 5-fluorouracil for symptomatic hormone-refractory prostate cancer using relevant endpoints of palliation and biological response. PATIENTS AND METHODS: 25 patients with histologically confirmed prostatic adenocarcinoma and symptomatic progressive disease despite one or several hormonal treatments and chemotherapy were included in the study. Treatment consisted of a single 24-hour infusion of 500 mg/m(2) 5-fluorouracil (5-FU) to be repeated on day 21. This regimen was continued until either progression or serious toxicity occurred. Response was assessed by serial measurements of serum prostate-specific antigen (PSA) as well as by health-related quality-of-life instruments (EORTC QLQ-C30 and McGill-Melzack Present Pain Intensity Scale) every 3 weeks. In 10 patients with bidimensionally measurable metastases, objective responses were assessed every 3 months. RESULTS: A mean number of four courses of repeated single 24-hour infusion of 5-FU was administered (range 2-6). Toxicity was absent or mild, and no patient had to be withdrawn from therapy. All patients required analgesics prior to treatment and only 3 patients experienced a significant reduction in pain for 9 weeks, the remaining patients experienced no deterioration for a mean duration of 12 weeks (6-18 weeks). Five patients (20%) demonstrated a biological response of a 50% or greater decrease in PSA from baseline, including 2 (12%) with a 75% or greater decline for 10 weeks (range 6-16 weeks). One partial remission was observed among 10 patients with measurable lesions lasting 12 weeks; 4 patients had stable disease with a mean duration of 12 weeks. Mean survival time from the onset of treatment with 5-FU was 7 months (2-12 months). CONCLUSIONS: Though less toxic than other 5-FU regimens, repeated single low-dose 24-hour infusion is of no significant benefit in patients with symptomatic hormone-refractory prostate cancer.
To investigate the potential genetic changes underlying the progression of human hormone-resistant prostate cancer, we related chromosomal alterations of the DU 145 cell line and a subline isolated form a metastasis in an orthotopic model to tumorigenicity, metastasis and chemoresistance. In 15 mice 1 x 10(5) DU 145 cells were injected into the dorsal prostate. From a resulting paraaortic lymphnode metastasis, we isolated a subline (DU 145 MN1), which was injected into 15 nude mice. The sulforhodamine B (SRB) assay was used to analyze cell doubling time and the IC(50) of cisplatin and 5-fluorouracil for both cell lines. Cytogenetic characterization was performed with conventional karyotype analysis and fluorescence in situ hybridization (FISH). After orthotopic implantation of DU 145 cells tumorigenicity was 100% whereas only 2 mice revealed lymphnode metastases. In contrast, the take rate after implantation of DU 145 MN1 was 100%, with lymphnode metastases in 7 mice. The SRB assay revealed a 8-fold increased IC(50) for cisplatin and a 2.5-fold increase for 5-FU in DU 145 MN1 as compared to DU 145 cells. There was gain of a chromosome 8 and only two copies of chromosome 17 in the DU 145 MN1 cells as compared to the parental cell line. The emergence of an i(9)(q10) in addition to two normal chromosome 9 homologues in the DU 145 MN1 cell line was confirmed by FISH using a chromosome 9-specific painting probe. In summary, clonal evolution of the chromosomal changes following repeated orthotopic implantation, may assist in locating the genes involved in the progression and chemoresistance of human hormone-resistant prostate cancer.
BACKGROUND: Electroretinograms (ERG) or pattern-electroretinograms (PERG) could be valuable for the quantification of potential damage to the pig retina by experimental erbium:YAG laser treatment. We therefore performed a normative study of ERGs and PERGs in pigs. METHODS: We recorded ERGs and PERGs under general anaesthesia in two experiments. In experiment 1 we examined eight eyes from six pigs of 20-25 kg body weight; in experiment 2 we examined four eyes from four pigs of 40-45 kg body weight. We used flash and checkerboard stimuli. In experiment 1, the stimulus parameters were mean luminance 48.3 cd/m2 for checkerboard stimuli, 96.6 cd/m2 for ERG, check sizes of 4 degrees, 8 degrees, and 16 degrees, temporal frequencies were 16 Hz for ERG and 8 rev/s for PERG. Three measurements were repeated after two weeks. Stimulus parameters for experiment 2 were luminance 175 (350) cd/m2, check sizes 1.6 degrees, 3.2 degrees, 6.7 degrees, and 16 degrees, temporal frequencies 6.3 Hz for ERG and 8 rev/s for PERG. Recordings were subjected to Fourier analysis. RESULTS: In experiment 1 the mean ERG amplitude was 1.02 +/- 0.89 microV with a coefficient of variation of 42% for repeat sessions. The mean PERG amplitudes were 0.53 +/- 0.25 microV for 16 degrees checks, 0.36 +/- 0.21 microV for 8 degrees, and 0.25 +/- 0.17 microV for 4 degrees. The mean coefficient of variation between two measurements was 103% for 16 degrees checks, 24% for 8 degrees, and 116% for 4 degrees. In experiment 2 the mean ERG amplitude was 9.72 +/- 3.96 microV. The mean PERG amplitudes were 0.77 +/- 0.50 microV for 16 degrees checks, 0.09 +/- 0.16 microV for 6.7 degrees, 0.07 +/- 0.13 microV for 3.2 degrees, and 0.08 +/- 0.09 microV for 1.6 degrees. CONCLUSIONS: It was possible to record ERGs and PERGs in pigs. However, the ERG amplitudes were small; PERG amplitudes were even smaller in both groups and cannot be reliably recorded. A problem for both ERG and PERG was the high intra-individual and interindividual variability. Therefore, only very extensive damage to the retina by vitrectomy or Er:YAG laser treatment might lead to a significant change in the ERG or PERG amplitudes.
The prognostic factors for infiltrating tumors established by the TNM system in 1997 include: Depth of infiltration, degree of differentiation, status of lymph nodes distant metastases. Of the additional factors investigated, only tumor size and hydronephrosis appear to be of prognostic significance. In the scope of molecular markers, the loss of expression of the epithelial cell-cell adhesion molecule E-cadherin signals an unfavorable clinical course. In cases of carcinoma of the urinary bladder without metastases (T2-4,N0,M0), radical cystectomy is the therapy of choice. A preceding neoadjuvant systemic regimen of chemotherapy with three cycles of M-VAC (methotrexate, vinblastine, adriamycin, cisplatin) significantly improves the survival rate. In patients with locally advanced urinary bladder carcinoma, however, adjuvant systemic chemotherapy with M-VAC after cystectomy and lymphadenectomy offers no advantages for survival. Quality of life in patients with metastatic bladder cancer disease is improved by new cytotoxic drugs, i.e. gemcitabine or taxanes.