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Biomedical subjects

Georg Bartsch

Publications and source records attributed to Georg Bartsch.

At least 37 records · Page 2Linked to original sources

Two cycles of cisplatin-based chemotherapy for low-volume retroperitoneal stage II nonseminomatous germ cell tumours.

OBJECTIVE: To evaluate the oncological efficacy of reducing cisplatin-based chemotherapy to two cycles in patients with low-volume retroperitoneal stage II nonseminomatous germ cell tumours (NSGCTs). PATIENTS AND METHODS: From October 1988 until January 2004, two cycles of cisplatin-based chemotherapy were administered in 59 patients with low-volume retroperitoneal clinical stage II NSGCT (retroperitoneal mass of <5 cm in diameter). Regardless of remission detected on computed tomography, 6 weeks after chemotherapy the patients had a retroperitoneal lymph node dissection (RPLND) to assess residual active tumour or mature teratoma (open modified bilateral RPLND until 1992, then laparoscopic unilateral template RPLND). RESULTS: The chemotherapy was effective, as no active tumour was found in any of RPLND specimens. Mature teratoma was present in lymphatic tissue in 23 of 59 patients (39%). In one patient there was a pulmonary recurrence, successfully treated with cisplatin-based salvage chemotherapy. One patient died from an accident but with no evidence of tumour, and 56 patients remained free of disease at a mean follow-up of 98.6 months. No patient died from disease. All patients had antegrade ejaculation after laparoscopic RPLND, as did 89% after open RPLND. CONCLUSION: In this pilot study, the oncological efficacy of two cycles of cisplatin-based chemotherapy was favourable, but this approach still cannot be recommended as a standard treatment for patients with low-volume retroperitoneal stage II disease. RPLND after chemotherapy has diagnostic (detecting active tumour) and therapeutic (removing mature teratoma) value and can be done laparoscopically. Based on the present results a prospective randomized trial seems reasonable.

Adolescent↗

The androgen receptor pathway is by-passed in prostate cancer cells generated after prolonged treatment with bicalutamide.

BACKGROUND: Experimental work in various prostate cancer models revealed that the androgen receptor is frequently upregulated and implicated in tumor progression. However, little attention has been paid to the androgen receptor-signaling pathway in the development of therapy resistance in patients who receive chronic treatment with a non-steroidal anti-androgen. METHODS: We have generated a novel subline, LNCaP-Bic, after prolonged treatment with androgen and bicalutamide in vitro. Proliferation of LNCaP-Bic cells in the absence or presence of androgen, tocopherol succinate, and/or bicalutamide was assessed by cell counting. Androgen receptor expression was determined by Western blot. Luciferase activity was measured in cells transfected with an androgen-responsive reporter. RESULTS: In basal conditions, proliferation of LNCaP-Bic cells increased more than threefold over that of control LNCaP cells. Neither synthetic androgen R1881 nor bicalutamide showed any effect on LNCaP-Bic growth in vitro. Androgen receptor expression did not differ between the cell subline generated in the presence of bicalutamide and parental LNCaP cells. The ability of R1881 to induce reporter gene activity in LNCaP-Bic cells was reduced by 56%. Tocopherol succinate caused inhibition of proliferation only in the parental cell line although the androgen receptor and prostate-specific antigen were down regulated by the vitamin E derivative in both parental LNCaP and LNCaP-Bic cells. CONCLUSIONS: Androgen receptor-mediated signal transaction is not enhanced in cells selected in the presence of bicalutamide. Our data may suggest that a more differentiated approach in targeting the androgen receptor is needed in prostate cancers that become resistant to classic endocrine treatment.

Androgen Antagonists↗

Antitumor action and immune activation through cooperation of bee venom secretory phospholipase A2 and phosphatidylinositol-(3,4)-bisphosphate.

We evaluated tumor cell growth modulation by bee venom secretory phospholipase A2 (bv-sPLA2) and phosphatidylinositol-(3,4)-bisphosphate as well as potential cooperative effects. In addition, the immunomodulatory impact of tumor cell treatment was examined by monitoring changes in phenotype and function of monocyte-derived dendritic cells (moDCs) cocultured with pretreated tumor cells. Bv-sPLA2 or phosphatidylinositol-(3,4)-bisphosphate alone displayed moderate effects on the proliferation of A498 renal cell carcinoma cells, T-47D breast cancer cells, DU145 prostate cancer cells and BEAS-2B transformed lung cells. However, when bv-sPLA2 was coadministered with phosphatidylinositol-(3,4)-bisphosphate a potent inhibition of [3H] thymidine incorporation into all tested cell lines occurred. This inhibition was due to massive cell lysis that reduced the number of cells with proliferative capacity. Importantly, tumor cell lysates generated with bv-sPLA2 plus phosphatidylinositol-(3,4)-bisphosphate induced maturation of human moDCs demonstrated by enhanced expression of CD83 and improved stimulation in allogeneic mixed leukocyte reactions. Our data demonstrate that bv-sPLA2 and phosphatidylinositol-(3,4)-bisphosphate synergistically generate tumor lysates which enhance the maturation of immunostimulatory human monocyte-derived dendritic cells. Such tumor lysates which represent complex mixtures of tumor antigens and simultaneously display potent adjuvant properties meet all requirements of a tumor vaccine.

Animals↗

IL-4 inhibits the TNF-alpha induced proliferation of renal cell carcinoma (RCC) and cooperates with TNF-alpha to induce apoptotic and cytokine responses by RCC: implications for antitumor immune responses.

OBJECTIVE: While previous reports clearly demonstrated antiproliferative effects of IL-4 on renal cell carcinoma (RCC) in vitro, the administration of IL-4 to patients with metastatic RCC in clinical trials could not recapitulate the promising preclinical results. In the present study we wanted to examine the context of IL-4 action and to establish conditions of enhanced IL-4 efficacy. METHODS: Primary and permanent human RCC cells were cultured in either serum-supplemented or chemically defined, serum-free culture medium in the presence or absence of cytokines. Cell proliferation was assessed as [(3)H]-thymidine incorporation. Cell apoptosis was measured using the fluorescent DNA intercalator 7-aminoactinomycin D and flow cytometry. In addition, culture media conditioned by RCC were subjected to cytokine antibody array and cytokine multiplex analysis. RESULTS: Our results indicate that the previously reported antiproliferative effects of IL-4 are serum-dependent. Under serum-free conditions, IL-4 failed to exhibit growth-inhibitory effects or was even growth-stimulatory. In a chemically defined, serum-free medium (AIM-V), however, IL-4 inhibited the TNF-alpha induced proliferation of RCC. IL-4 and TNF-alpha synergistically induced apoptosis of RCC as well as a complex cytokine response by RCC, which included the synergistic upregulation of RANTES and MCP-1. CONCLUSIONS: IL-4 alone has little effect on the spontaneous proliferation of RCC but can prevent the enhancement of proliferation induced by growth promoters like FBS and TNF-alpha. The concomitant growth inhibitory, apoptosis-inducing, and cytokine-enhancing effects of IL-4 in combination with TNF-alpha on RCC support the view that Th2 cytokines may be required for productive immune responses against RCC.

Apoptosis↗

What are the supportive structures of the female urethra?

AIMS: Female stress urinary incontinence is thought to result from impairment of the connective tissue "ligaments" of the urethra. Surgical repair of female incontinence mainly involves fixation of the urethra to the pubic bone or other surrounding structures. In the present anatomical-radiological study, the anatomy of the connective tissue structures around the female urethra was investigated to determine the anatomical structures that support the urethra and the rhabdosphincter. MATERIALS AND METHODS: The topography of the anterior compartment of the female pelvis was studied in serial sections and one anatomical preparation of 30 female fetuses and of six adult females. The pelves of 29 female fetuses were processed according to plastination histology technique. The pelves of the six adult specimens were processed according to sheet plastination technique. In addition, the anatomical findings were compared with MR images of 41 adult female volunteers. RESULTS: The ventro-lateral aspect of the urethra remains free of fixating ligaments throughout its pelvic course. Ventro-laterally the urethra is enclosed by the ventral parts of the levator ani, its fasciae and a ventral urethral connective tissue bridge connecting both sides. Dorsally, the urethra is intimately connected to the wall of the vagina. CONCLUSIONS: The female urethra has no direct ligamentous fixation to the pubic bone. Urethral continence after pregnancy and childbirth may be explained by a widening of the hiatus of the levator ani or the anterior vaginal wall, resulting in overstretching of the ventral urethral connective tissue bridge or the disruption of the fixation between urethra and vagina.

Adipose Tissue↗

Reevaluation of the fetal muscle development of the vesical trigone.

PURPOSE: Fetal development of the interureteral muscle, a precondition of a sufficient opposite anchoring of the ureterovesical junction, and the muscle architecture of the bladder neck was investigated using immunohistochemical analysis. MATERIALS AND METHODS: We investigated the ureterotrigonal units in 38 fetal specimens (16 females, 22 males) and 7 newborns (2 females, 5 males) at 9 to 40 weeks of gestation. Histology was based on serial consecutive sections of the bladder base. Anti-human alpha-smooth muscle actin immunostaining was used to demonstrate the time course of muscle development and arrangement. RESULTS: A much earlier developmental stage of the trigone muscle configuration during fetal life was noted than has been reported to date. The condensation of myoblasts located mainly in the dorsal wall of the trigone and at the bladder outlet was present beginning at 12 weeks of gestation. The trigone develops continuously as a single circular muscular layer corresponding to the posterior part of the vesical sphincter muscle. Muscle fibers forming the interureteral junction were demonstrable beginning at 14 weeks of gestation. CONCLUSIONS: There is a close connection between the trigonal smooth muscle layer and the vesical sphincter muscle forming the main part of the trigone by 12 weeks of gestation. Fetal development of the trigone, in particular the muscle architecture of the bladder neck, which consists of only a ring-shaped muscular layer, and the transverse oriented interureteral muscle results in a functional entity representing the anatomical basis for a competent ureterovesical junction.

Female↗

Gender specific chronological and morphometric assessment of fetal bladder wall development.

PURPOSE: To enhance our understanding of sonographically visible alterations in bladder wall thickness, we delineated phenotypic changes occurring in developing smooth muscle cells of the fetal and postnatal bladder with respect to gender specific differences. MATERIALS AND METHODS: Bladders of 30 male and 18 female fetuses and 4 stillborn infants were immunostained with an alpha-smooth muscle actin antibody. Morphological and morphometric assessment was performed with the assistance of an image analysis system. RESULTS: Alpha-smooth muscle actin expression in fetal bladder wall was detectable at 9 weeks of gestation. Bladder wall thickness and mean profile area of smooth muscle bundles increased significantly with advancing gestation, mediated by linear growth patterns. Fetal bladder wall development occurred uniformly, unrelated to gender. CONCLUSIONS: Although the lower urinary tract emerges in a gender specific way, our results suggest that in normal fetal growth detrusor muscle formation proceeds independent of genital sex.

Actins↗

Treatment of severe bilateral nerve pain after Pfannenstiel incision.

The lower transverse abdominal incision, as described by Hermann Johannes Pfannenstiel, cutting both skin and fascia in a transverse fashion was popularized in 1900. Nerve pain syndromes included invalidating pain involving neuroma formation or scar encasement of the ilioinguinal or iliohypogastric nerves. We report a case of a female patient who developed severe pain at the lateral wound edges of a Pfannenstiel incision. The diagnosis of pain of nerve origin was made by infiltration of local anesthetic, after which the pain immediately vanished temporarily. Only complete excision of the scar and involved part of the nerve stopped the pain.

Abdomen↗

Optimizing the outcome of microsurgical subinguinal varicocelectomy using isosulfan blue: a prospective randomized trial.

PURPOSE: Varicoceles are the main cause of correctible male factor infertility. Loss of testicular volume and abnormal seminal parameters are indications for varicocelectomy. We assessed a prospective randomized trial comparing standard microsurgical varicocele repair with the microsurgical approach using isosulfan blue. We determined if the use of isosulfan blue reduces the incidence of postoperative hydroceles following microsurgical varicocele repair. MATERIALS AND METHODS: Two groups of 25 consecutive patients each were randomized. Indications for surgery included fertility problems as well as scrotal pain and difference in testicular size. All patients underwent microsurgical repair using the subinguinal approach. Patients in group 1 underwent standard microsurgery. Those in group 2 had additional isosulfan blue administration. All were investigated 3 and 6 months postoperatively regarding varicocele recurrence, hydrocele, atrophy, pain or other complications. RESULTS: There were no intraoperative complications. At 3 months postoperatively the incidence of hydrocele in group 1 was 20% decreasing to 16% at 6 months, whereas in group 2 no hydrocele was detectable. There were 2 patients in each group who reported ongoing pain, and 1 in each presented with recurrent varicocele. No atrophy was seen. In 1 patient blue pigmentation of the left hemiscrotum was seen at 3 months but vanished at 6 months. CONCLUSIONS: Microsurgical repair of varicoceles using isosulfan blue helps in identifying and preserving the lymphatic drainage. It prevents postoperative hydrocele, the most common postoperative complication, without any supplementary risk to the patient. Additionally, testicular edema causing impaired spermatogenesis can be avoided.

Adolescent↗

Tumor recurrence in the remnant urothelium of females undergoing radical cystectomy for transitional cell carcinoma of the bladder: long-term results from a single center.

PURPOSE: We analyzed the risk factors and incidence of secondary TCC of the remnant urothelium in women following radical cystectomy for TCC of the bladder. MATERIALS AND METHODS: A total of 85 women with a mean age of 64.5 years with clinically localized TCC of the bladder underwent radical cystectomy between 1992 and 2004. Orthotopic bladder substitution was performed in 46 females, while 39 underwent nonorthotopic urinary diversion. Of the entire cohort 22 (26%) patients underwent cystectomy for multifocal or recurrent TCC. Followup examinations were performed at 6-month intervals. RESULTS: Mean followup in the entire cohort was 49.8 months (median 42). Intraoperative frozen sections obtained from the urethra and distal ureters were negative for TCC and CIS in all patients. Four women (4.7%) had TCC in the remnant urothelium at a mean of 56 months postoperatively. These patients had undergone cystectomy for multifocal or recurrent TCC (4 of 22 or 18%). No secondary TCC was seen in the 63 patients with solitary invasive or nonrecurrent bladder cancer (p <0.05). Urethral recurrence was found in 2 patients (4.3%) 65 and 36 months after orthotopic neobladder surgery, respectively. In the orthotopic group 1 patient (2.1%) had an upper urinary tract tumor 76 months after surgery, while in the nonorthotopic group 1 (2.5%) was found to have an upper urinary tract tumor 48 months postoperatively. CONCLUSIONS: Recurrent or multifocal TCC may represent a risk factor for secondary TCC of the remnant urothelium after cystectomy. In our series all recurrent tumors were late recurrences (more than 36 months postoperatively). Because the rate of urethral recurrence in the current series corresponds to that reported in men (2% to 6%), urethra sparing cystectomy with orthotopic bladder replacement does not appear to compromise the oncological outcome in women.

Adult↗

The expression of transcription factor activating transcription factor 3 in the human prostate and its regulation by androgen in prostate cancer.

PURPOSE: ATF3 is a member of the basic leucine zipper/cyclic adenosine monophosphate responsive element binding protein family of transcription factors. There is overwhelming evidence that it is a stress inducible factor acting in a signal-type and cell-type dependent manner, and it is involved in cell proliferation and survival. We found that ATF3 was differently expressed in an in vitro prostate cancer tumor progression model and we investigated the possible role of ATF3 in prostate cancer. MATERIALS AND METHODS: ATF3 up-regulation in vivo/in vitro and androgen regulation were assessed by immunohistochemistry and immunoblot analysis. Results after forced ATF3 transfection were evaluated by proliferation assay and cell cycle analysis. RESULTS: Immunohistochemistry and immunoblot analysis revealed ATF3 up-regulation in prostate cancer in vitro and in vivo, and stimulation of expression by androgens. Antiandrogen treatment decreased ATF3 expression in androgen sensitive cells but acted as a stimulator in long-term androgen ablated cells representing a model for therapy refractory disease. Expression in tumors increased with higher Gleason scores and highest expression was observed in samples of therapy refractory tumor tissue. Forced ATF3 over expression in a prostate cancer cell line induced cell proliferation and accelerated cell cycle progression from G1 to S-phase. CONCLUSIONS: These data provide new insight into the role of ATF3 in prostate cancer development and/or progression. They indicate that ATF3 is an androgen regulated gene that is highly expressed in prostate tumors and stimulating cell proliferation. It represents a possible target for prostate cancer therapy.

Activating Transcription Factor 3↗

Amniotic fluid and placental stem cells.

Human amniotic fluid has been used in prenatal diagnosis for more than 70 years. It has proven to be a safe, reliable, and simple screening tool for a wide variety of developmental and genetic diseases. However, there is now evidence that amniotic fluid may have more use than only as a diagnostic tool and may be the source of a powerful therapy for a multitude of congenital and adult disorders. A subset of cells found in amniotic fluid and placenta has been isolated and found to be capable of maintaining prolonged undifferentiated proliferation as well as able to differentiate into multiple tissue types encompassing the three germ layers. It is possible that in the near future, we will see the development of therapies using progenitor cells isolated from amniotic fluid and placenta for the treatment of newborns with congenital malformations as well as of adults, using cryopreserved amniotic fluid and placental stem cells. In this chapter, we describe a number of experiments that have isolated and characterized pluripotent progenitor cells from amniotic fluid and placenta. We also discuss various cell lines derived from amniotic fluid and placenta and future directions for this area of research.

Adult Stem Cells↗

Treatment of adult female epispadias without exstrophy in the presence of rhabdosphincter function.

Female epispadias without exstrophy is a very rare entity. Symptoms of female epispadias are primary urinary incontinence and anatomical abnormal features. A 24-year-old married women with two children presented with primary urinary incontinence. Due to previous failure of correct diagnosis and ineffective medical treatment, the patient developed psychological problems (anxiety and depression). In the presence of minimal rhabdosphincter function we could achieve socially acceptable urinary continence by bladder neck plication and a Burch colposuspension. The patient did not consent to a major reconstruction.

Adult↗

Assessment of aberrations on chromosome 8 in prostatic atrophy.

OBJECTIVE: To systematically examine the genetic alterations on chromosome 8 in prostate epithelia deriving from atrophic areas, and to compare these alterations with those of cells derived from prostatic intraepithelial neoplasia (PIN) and prostate cancer in the same organ. MATERIAL AND METHODS: Tissue microarrays were constructed from 50 patients with histologically different tissues, including normal, PIN, atrophy and cancer lesions. Control samples were obtained from 10 patients who died from causes other than prostate cancer. Multicolour DNA probes for 8p22, centromere 8 and 8q24 were used to detect genetic alterations by fluorescence in situ hybridisation analysis. RESULTS: Chromosomal alterations were detected on chromosome 8 in all analysed tissues. Including all observed signal patterns, a gradual increase of nuclei with loss of 8p22 was detected in normal (16%), in atrophy (21%), in PIN (25%) and in cancer tissue (31%), and there was gain in 8q24 in normal tissue (10%), in atrophy lesions (19%), in PIN (21%) and in cancer (27%). Generally, in all three lesion types the percentage of cells with 8q24 gain was significantly lower than the percentage of cells with loss of 8p22. CONCLUSION: This investigation confirms the presence of severe chromosomal aberrations in the epithelium of the atrophic glands of the prostate. The aberrations are the same those that can be found in PIN and in prostate cancer. These findings confirm the genetic instability of the cells in the atrophic areas of the prostate, which can be a target for further injuries, leading to prostate cancer.

Adolescent↗

The proximal neurovascular plate and the tri-zonal neural architecture around the prostate gland: importance in the athermal robotic technique of nerve-sparing prostatectomy.

OBJECTIVE: To review the neural architecture around the prostate gland, as it is relevant for nerve-sparing robotic prostatectomy, including in particular the anatomy of the proximal neurovascular tissue, the neurovascular bundle (NVB), and accessory neural pathways (ANPs). MATERIALS AND METHODS: The aims of this study were achieved in collaboration between the Cornell Institute of Robotic Surgery, New York, NY, USA and the Institute of Urology at the University of Innsbruck, Austria. The broad steps were: (i) anatomical studies of 10 fresh and two fixed male cadavers; and (ii) collection of videotape and still image data from 200 men undergoing radical prostatectomy by the athermal robotic technique at the Cornell Institute. RESULTS: From a surgical standpoint there was a tri-zonal neural architecture including the proximal neurovascular plate (PNP), the predominant NVB (PNB) and ANPs. The PNP was a mean (range) of 5 (3-10) mm lateral to the seminal vesicles, was 3 (2-7) mm thick, 7 (5-25) mm wide and 9 (4-30) mm long. It was within 6 (4-15) mm of the bladder neck, 5 (2-7) mm of the endopelvic fascia and overlapped 5 (0-7) mm of the proximal prostate. The PNB varied in shape and size from the proximal to distal end, was thickest at the base and most variable near the apex. In eight of 12 cases, there was a medial extension behind the prostate, which converged medially at the apex in four cases. ANPs were noted within the layers of levator fascia and/or lateral pelvic fascia on the anterolateral aspect in five cases and in three on the posterior aspect of the prostate. In nine cadavers, the proximal third of the prostate was covered by the PNP where these ANPs were most prominent. The ANPs formed a plexus on the posterolateral aspect of the apex in four cases. CONCLUSION: We have created an anatomical map of neurovascular tissue relevant to robotic prostatectomy. A tri-zonal neural architecture is described which has helped in standardizing the steps of robotic prostatectomy.

Adult↗

Laparoscopic varicocele ligation in children and adolescents using isosulphan blue: a prospective randomized trial.

OBJECTIVES: To evaluate, in a randomized prospective trial in children and adolescents, the feasibility of isosulphan blue-based lymphatic vessel preservation during laparoscopic varicocelectomy and its impact on the complication rate, as the operative management of varicoceles remains controversial. PATIENTS AND METHODS: In all, 50 consecutive patients were randomly assigned to two laparoscopic varicocelectomy groups. The indications for surgery included scrotal pain and a difference in testicular size, as well as severe cosmetic impairment. All the patients had a laparoscopic varicocelectomy using three ports. Patients in group A had standard laparoscopy, while those in group B had additional isosulphan blue administered. After surgery, the patients were assessed at 3, 6 and 12 months for varicocele recurrence, hydrocele formation, atrophy, pain or other complications. RESULTS: There were no intraoperative complications or conversions to open surgery. There were no adverse reactions, scrotal haematomas or atrophy. At 3 months after surgery, the incidence of hydrocele in group A was 20% whereas in group B no hydroceles were detected (P = 0.025); at 6 months the 20% still had hydroceles. One patient in each group had varicocele recurrence associated with persistent pain. In two patients in group B, blue pigmentation of the left hemiscrotum persisted at the 3-month follow-up but resolved by 6 months. CONCLUSIONS: Laparoscopic repair of varicoceles using isosulphan blue helps to identify and preserve the lymphatic drainage. It prevents secondary hydrocele formation, the most common complication, with no supplementary risk to the patient. Also, testicular oedema causing impaired spermatogenesis can be avoided.

Adolescent↗