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Biomedical subjects

L Höltl

Publications and source records attributed to L Höltl.

15 recordsLinked to original sources
PubMed2005

Late occurrence of bilateral tuberculous-like epididymo-orchitis after intravesical bacille Calmette-Guérin therapy for superficial bladder carcinoma.

We report a case of bilateral tuberculous-like epididymo-orchitis occurring 3 years after intravesical bacille Calmette-Guérin instillation therapy in an 83-year-old patient with proven superficial bladder carcinoma. The patient had no previous history of tuberculosis. Because of persistent inflammation and painful swelling of the epididymides and testes, the patient underwent bilateral orchiectomy. This case demonstrates the late adverse effects that can occur after intravesical BCG therapy, which in our patient ended in surgical removal of both gonads.

Adenocarcinoma↗
PubMed2002

Primary lymphatic metastatic spread in testicular cancer occurs ventral to the lumbar vessels.

OBJECTIVES: To analyze whether primary metastatic spread occurs behind the lumbar vessels and whether removal is necessary for accurate staging in diagnostic retroperitoneal lymph node dissection, because dissection of lymphatic tissue behind the lumbar vessels is a challenging maneuver. METHODS: One hundred thirty-nine patients were included in our study. Twenty-nine patients with clinical Stage I tumor underwent laparoscopic staging lymph node dissection, including removal of the lymph nodes behind the lumbar vessels. Sixty-four patients with Stage II testicular cancer were retrospectively examined by computed tomography to determine the localization of the enlarged lymph nodes in relation to the lumbar vessels. On the basis of these results, 49 patients with clinical Stage I underwent laparoscopic lymph node dissection within the same template but without dissection of the lymphatic tissue behind the lumbar vessels. RESULTS: In the first group, 10 of 29 patients had pathologic Stage IIA tumors, with positive nodes exclusively ventral to the lumbar vessels. In group 2, 39 patients with solitary metastatic lesions had enlarged lymph nodes, which were always ventral to the lumbar vessels. Only in 3 of 25 patients with multiple metastases was one enlarged node found behind the lumbar vessels. In group 3, no tumor recurrence either before or behind the lumbar vessels could be found in 46 patients after a mean follow-up of 27.8 months. CONCLUSIONS: On the basis of these data, we believe that primary lymphatic metastatic spread in testicular cancer always occurs ventral to the lumbar vessels. Therefore, the removal of lymphatic tissue behind the lumbar vessels for diagnostic procedures is not necessary.

Humans↗
PubMed2001

The disabled dendritic cell.

Dendritic cells are important antigen-presenting cells of the immune system that induce and modulate immune responses. They interact with T and B lymphocytes as well as with natural killer cells to promote activation and differentiation of these cells. Dendritic cells generated in vitro from monocytes by use of the cytokines GM-CSF and IL-4 are increasingly used clinically to enhance antitumor immunity in cancer patients. However, recent studies revealed that the functional repertoire of monocyte-derived dendritic cells may be incomplete. Important functions of monocyte-derived dendritic cells such as migration or the ability to induce natural killer cell activation or type 2 T helper cell differentiation appear to be impaired. We propose that all these deficiencies relate to a single biochemical deficiency of monocyte-derived dendritic cells. IL-4, which is used to generate monocyte-derived dendritic cells, suppresses phospholipase A2, the enzyme that liberates arachidonic acid from membrane phospholipids and contributes to the synthesis of platelet-activating factor. Monocyte-derived dendritic cells must therefore fail to generate platelet-activating factor as well as arachidonic acid derivatives such as prostaglandins, leukotrienes, and lipoxins, collectively referred to as eicosanoids. Since eicosanoids and platelet-activating factor are known to play an important role in processes such as leukocyte migration, natural killer cell activation, and type 2 T helper cell differentiation, the deficiency in eicosanoid and platelet-activating factor biosynthesis may be responsible for the observed handicaps of monocyte-derived dendritic cells.

Antigen-Presenting Cells↗
PubMed2001

Photodynamic diagnosis with 5-aminolevulinic acid in the treatment of secondary urethral tumors: first in vitro and in vivo results.

OBJECTIVES: Photodynamic diagnosis (PDD) is able to detect dysplasia and transitional cell cancer of the bladder. We report our first experiences using PDD in the urethra. MATERIALS AND METHODS: Three patients with secondary transitional cell cancer of the urethra were treated by using PDD. 5-Aminolevulinic acid (ALA) was applied in a mixture with lubricant to achieve long enough contact with the urothelium. Negative effects were tested in vitro on three bladder cell lines. RESULTS: In vitro assays showed no enhanced negative effects on the viability of bladder cells using the combination of ALA/lubricant and medium in comparison to lubricant/medium alone. All patients showed markedly fluorescent areas, which were resected. The treatment was well tolerated without side effects attributable to the photosensitizer containing lubricant. CONCLUSION: Lubricant with ALA forms a viscous solution, which can successfully be used for PDD in the urethra. Thus marking tumors by fluorescence may improve transurethral resection and thus preserve the urethra.

Adult↗
PubMed2001

Life after cystectomy and orthotopic neobladder versus ileal conduit urinary diversion.

Patients frequently complain about changes in their everyday life after radical cystectomy and urinary diversion. The aim of this study was to compare subjective morbidity of ileal neobladder to the urethra versus ileal conduit urinary diversion and to elucidate its influence on quality of life. A total of 102 patients who underwent radical cystectomy due to a bladder malignancy were included in the study: 69 patients (67.6%) with an orthotopic neobladder and 33 patients (32.4%) with an ileal conduit. The compliance was 99% and mean follow-up was 37 months. All patients completed two retrospective quality-of-life questionnaires, namely the QLQ-C30 and a questionnaire developed at our institution to elucidate specific items regarding urinary diversion. The questioning was performed by a nonurologist. The results obtained from the validated (QLQ-C30) and our self-designed questionnaire clearly demonstrate that patients with an orthotopic neobladder better adapt to the new situation than patients with an ileal conduit. In addition, neobladder to the urethra improves quality of life due to a better self-confidence, better rehabilitation as well as restoration of leisure, professional, traveling, and social activities, and reduced risk of inadvertent loss of urine. For example, 74.6% of neobladder patients felt absolutely safe with the urinary diversion in contrast to 33.3% in the ileal conduit group. Only 1.5% of neobladder patients had wet clothes caused by urine leakage during day versus 48.5% of ileal conduit patients; 92.8% of neobladder patients felt not handicapped at all; and 87% felt not sickly or ill in contrast to 51.5% and 66.7% of ileal conduit patients, respectively. Moreover, 97% of our neobladder patients would recommend the same urinary diversion to a friend suffering from the same disease in contrast to only 36% of ileal conduit patients. The results obtained by this study demonstrate that quality of life is preserved in a higher degree after orthotopic neobladder than after ileal conduit urinary diversion.

Cystectomy↗
PubMed2001

Expression and immunogenicity of oncofetal antigen-immature laminin receptor in human renal cell carcinoma.

PURPOSE: The 32 to 44 kDa. oncofetal antigen-immature laminin receptor (OFA-iLR) is a multifunctional protein expressed by various tumors, including breast, lung, ovary and prostate carcinoma as well as lymphoma. OFA-iLR has been implicated in tumor invasiveness, metastasis and growth. Interferon-gamma producing effector T cells and interleukin (IL)-10 producing suppressor T cells specific for OFA-iLR have been described. MATERIALS AND METHODS: The 43515 IgG2a anti-OFA-iLR monoclonal antibody was used to detect OFA-iLR expression in human renal cell carcinoma tissue by flow cytometry and immunoblotting. Spontaneous or therapy induced immune responses against OFA-iLR were determined in patients with metastatic renal cell carcinoma. Proliferative and cytokine (interferon-gamma and IL-10) responses of peripheral blood mononuclear cells from patients with renal cell carcinoma against recombinant OFA-iLR were assessed. RESULTS: Using flow cytometry OFA-iLR was detected in all 13 tumors tested. Immunoblotting revealed differences in OFA-iLR expression in renal cell carcinoma and normal kidney tissue. OFA-iLR specific proliferative and cytokine responses of mononuclear cells were detected in all 6 patients tested. Importantly evidence was also obtained that treating metastatic renal cell carcinoma with tumor lysate pulsed dendritic cells would enhance OFA-iLR specific immunity. CONCLUSIONS: This study demonstrates that OFA-iLR is an immunogenic tumor associated antigen in human renal cell carcinoma. OFA-iLR specific effector T cells producing interferon-gamma may have a role in the control of tumor growth, whereas suppressor T cells producing IL-10 may promote tumor tolerance and, thus, tumor progression.

Antigens, Neoplasm↗
PubMed2000

Quality of life after cystectomy and orthotopic neobladder versus ileal conduit urinary diversion.

The impact of bladder removal and urinary diversion for patients' everyday life is largely unknown. The aims of this study were to compare subjective morbidity of ileal neobladder to the urethra versus ileal conduit urinary diversion and to elucidate its influence on quality of life. A total of 102 patients who underwent cystectomy due to a bladder malignancy were included in the study. In 69 patients (67.6%) an orthotopic neobladder and in 33 patients (32.4%) an ileal conduit was performed as urinary diversion. The compliance was 99% and mean follow-up was 37 months. All patients completed two retrospective quality of life questionnaires, namely the QLQ-C30 and a questionnaire developed at our institution to ask for urinary diversion specific items. The questioning and assessment was performed by non-urologists. The results obtained from the validated (QLQ-C30) and our own specially compiled questionnaire clearly demonstrate that patients with an orthotopic neobladder are more able to adapt to the new situation than patients with an ileal conduit. In addition, neobladder to the urethra improves the quality of life because it improves self-confidence, causes better rehabilitation as well as the restoration of leisure, professional, travelling, and social activities, and reduced risk of inadvertent loss of urine. For example, 92.8% of neobladder patients did not feel handicapped at all, and 87% did not feel sick or ill, in contrast to 51.5% and 66.7% of ileal conduit patients, respectively. Of the neobladder patients, 74.6% felt absolutely safe with the urinary diversion in contrast to 33.3% in the ileal conduit group. Only 1.5% of neobladder patients had wet clothes caused by urine leakage during the day, versus 48.5% of ileal conduit patients. Moreover, 97% of our neobladder patients would recommend the same urinary diversion to a friend suffering from the same disease, but only 36% of ileal conduit patients would do so. These results demonstrate that the quality of life is preserved to a higher degree after orthotopic neobladder than after ileal conduit urinary diversion.

Aged↗
PubMed1999

Mature dendritic cells induce T-helper type-1-dominant immune responses in patients with metastatic renal cell carcinoma.

We performed a pilot study on a dendritic cell (DC)-based vaccine in 4 patients with advanced renal cell carcinoma. The vaccine consisted of cultured blood DCs loaded with autologous tumor cell lysate plus keyhole limpet hemocyanin (KLH) and matured with a combination of tumor necrosis factor alpha and prostaglandin E(2). We describe the immune response against KLH induced by DC-based immunization in a patient undergoing an objective partial response and compare it with the responses observed in patients with either stable or progressive disease. The patient with the clinical response developed strong delayed-type hypersensitivity (DTH) against KLH after a single vaccination with antigen-loaded DCs, whereas the other patients failed to develop DTH reactivity even after repeated vaccinations. Antigenic stimulation of mononuclear cells (MNCs) induced proliferation and IFN-gamma but not IL-4 production as well as expression of the chemokine receptor CXCR3 consistent with a T-helper (Th) type-1 bias. Exogenous IL-12 enhanced and exogenous IL-4 diminished IFN-gamma production. In the 2 patients with stable disease two or more vaccinations were required to induce maximal MNC responses. In the patient with progressive disease MNC responses were hardly detectable. Anti-KLH antibodies appeared with different kinetics but could be detected in the serum of all patients. Isotype analysis revealed the presence of IgM, IgG(1), IgG(2) and IgG(3) as well as IgA and complete absence of IgE. The patient with progressive disease also developed IgG(4) antibodies indicative of a deviation towards Th2. Cultured blood DCs can be a potent vaccine for the antigen-specific immunization of patients with advanced kidney cancer. KLH serves as a tracer molecule which allows determination of the magnitude, kinetics and Th bias of the cellular and humoral immune response induced by DC-based immunization. The data also suggest that Th type-1-dominant immune responses involving DTH reaction are required for the induction of tumor regression.

Adjuvants, Immunologic↗
PubMed1999

Cellular and humoral immune responses in patients with metastatic renal cell carcinoma after vaccination with antigen pulsed dendritic cells.

PURPOSE: Dendritic cells are the most potent stimulators of immune responses including antitumor responses. We performed a pilot study of cultured antigen loaded dendritic cells in patients with metastatic renal cell carcinoma. MATERIALS AND METHODS: Dendritic cells were obtained by culturing plastic adherent mononuclear cells from peripheral blood for 5 days in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4. Day 5 dendritic cells were loaded with cell lysate from cultured autologous tumor cells and with the immunogenic protein keyhole-limpet hemocyanin (KLH) which serves as a helper antigen and as a tracer molecule. During the antigen pulse dendritic cells were activated with a combination of tumor necrosis factor-alpha and prostaglandin E2. Dendritic cells were administered by 3 intravenous infusions at monthly intervals. Cellular and humoral immune responses to KLH and cell lysate were measured in vitro before and after the vaccinations. RESULTS: Preparation of 12 dendritic cell vaccines from patients with advanced renal cell carcinoma was successful. Treatment with fully activated CD83+ dendritic cells was well tolerated with moderate fever as the only side effect. Potent immunological responses to KLH and, most importantly, against cell lysate could be measured in vitro after the vaccinations. CONCLUSIONS: Our data demonstrate that a dendritic cell based vaccine can induce antigen specific immunity in patients with metastatic renal cell carcinoma. Dendritic cell based immunotherapy represents a feasible, well tolerated and promising new approach for the treatment of advanced renal cell carcinoma.

Aged↗
PubMed1999

Laparoscopic retroperitoneal lymphadenectomy after chemotherapy for stage IIB nonseminomatous testicular carcinoma.

PURPOSE: We investigated laparoscopic retroperitoneal lymphadenectomy after chemotherapy for stage IIB testicular carcinoma in terms of operative feasibility, overall morbidity and tumor control. MATERIALS AND METHODS: Between February 1995 and April 1998, 24 patients underwent laparoscopic retroperitoneal lymphadenectomy following initial chemotherapy for stage IIB (2 to 5 cm.) solitary or unilateral lymph node metastases. Mean tumor diameter was 2.4 cm. before and 1.1 cm. after chemotherapy. Laparoscopic retroperitoneal lymphadenectomy was performed in all patients, including those with complete remission. RESULTS: Laparoscopic retroperitoneal lymphadenectomy could be completed as planned in all patients and there was no need for conversion to open surgery. Operative time was 150 to 300 minutes (mean 240). Blood loss was minimal and no blood transfusions were required. The only postoperative complications were chylous ascites (5 patients) which resolved with conservative management (low fat diet) and a small asymptomatic lymphocele. Histological examination revealed necrosis in 71%, mature teratoma in 25% and active tumor in 4% of patients. Antegrade ejaculation was preserved in all patients. Mean postoperative hospital stay was 4 days, return to normal activities between 1 and 3 weeks, and time to complete recovery between 5 and 10 weeks. All patients were well without evidence of disease at a mean followup of 24.4 months. CONCLUSIONS: Laparoscopic retroperitoneal lymphadenectomy after chemotherapy proved feasible in select patients presenting with solitary or unilateral lymph node metastases and was associated with a low morbidity. Tumor control was not compromised by the laparoscopic approach.

Adolescent↗
PubMed1998

Human monocyte-derived dendritic cells produce macrophage colony-stimulating factor: enhancement of c-fms expression by interleukin-10.

Human monocyte-derived dendritic cells (DC) generated with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4 express c-fms (CD115), the receptor for macrophage-CSF (M-CSF). Expression of c-fms on monocyte-derived DC has been interpreted as the susceptibility of these cells to M-CSF-induced macrophage development. We show here that homogeneous cultures of CD14 DC constitutively produced large amounts of M-CSF. However, presence of M-CSF neither induced macrophage development nor did it prevent terminal maturation into CD83+ DC. M-CSF production by DC was driven by GM-CSF and inhibited by the specific phosphatidylinositol 3-kinase inhibitor wortmannin. M-CSF synthesis was rapidly induced during the first 24 h of DC culture and then declined during the 5-day culture period. Replating of the cells, which was associated by a transient adherence, always induced a strong up-regulation of M-CSF synthesis. Addition of recombinant IL-10 to DC cultures enhanced c-fms expression and induced macrophage development as measured by the strong up-regulation of CD14 expression as well as by enhanced expression of the Fcgamma receptors I, II, and III (CD64, CD32, CD16). Our data demonstrate that immature monocyte-derived DC produce M-CSF which does not induce macrophage development, despite the surface expression of c-fms on DC. IL-10 appears to induce macrophage development by up-regulating c-fms and, thereby, enhancing the sensitivity of the cells to endogenously produced M-CSF.

Androstadienes↗
PubMed1998

Dendritic cell-based immunotherapy of renal cell carcinoma.

Dendritic cells potently stimulate antigen-specific immune responses and recent data indicate that they are also capable of eliciting antitumor immune responses. We are performing a pilot study which tests the safety and efficacy of antigen-loaded, cultured blood dendritic cells in patients with metastatic renal cell carcinoma. Dendritic cells are simultaneously pulsed with lysate from autologous tumor cells and with the immunogenic protein keyhole limpet hemocyanin. During the pulse, the cells are activated with a combination of tumor necrosis factor-alpha and prostaglandin E2. Patients receive 5-10 X 10(6) dendritic cells per intravenous infusion and up to six infusions at monthly intervals. The first results demonstrate that this treatment modality is very well tolerated and can be associated with strong immunological and clinical responses. The present article discusses the importance of dendritic cell maturation and the role of helper antigens in dendritic cell-based immunotherapy.

Animals↗
PubMed1996

Retroperitoneal lymphadenectomy for clinical stage I nonseminomatous testicular tumor: laparoscopy versus open surgery and impact of learning curve.

PURPOSE: Laparoscopic retroperitoneal lymphadenectomy for clinical stage I nonseminomatous testicular tumors was compared to open surgery, taking into account the impact of the learning curve. MATERIALS AND METHODS: Between August 1992 and September 1995, 29 consecutive patients underwent laparoscopic retroperitoneal lymphadenectomy. Open surgical retroperitoneal lymphadenectomy was performed on 30 patients between January 1988 and July 1992. RESULTS: A comparison of the 14 initial and 15 subsequent laparoscopies showed a steep learning curve (operative time shorter by 36%, blood loss decreased by 50% and postoperative hospital stay shorter by 27%). When comparing the last 15 laparoscopic procedures to the open operations, the latter were superior only in terms of operative time (shorter by 18%). With regard to all other parameters open surgery was inferior (increased blood loss by 38%, longer postoperative hospital stay by 166%, more serious complications and a greater complication rate). Antegrade ejaculation was preserved after all laparoscopic and after 28 of the 30 open operations. There were no retroperitoneal recurrences in either group (mean followup 16 months after laparoscopy and 54 months after open surgery). CONCLUSIONS: Laparoscopic retroperitoneal lymphadenectomy is a demanding operation that is superior to open surgery once the learning curve has been overcome. However, this is possible only if laparoscopic retroperitoneal lymphadenectomy is performed on a regular basis.

Adult↗
PubMed1996

Usefulness of the ratio free/total prostate-specific antigen in addition to total PSA levels in prostate cancer screening.

OBJECTIVES: Two different studies were performed. The aim of the first study was to define whether the measurement of the ratio between free and total prostate-specific antigen (f/t PSA) in serum may enhance the ability of PSA-based screening for early detection of prostate cancer in men with elevated serum PSA levels. A second study was undertaken to investigate the value of f/t PSA ratio in serum to improve the specificity of prostate cancer screening in men with serum PSA levels between 2.5 and 10.0 ng/mL. METHODS: In a retrospective study of 266 men with elevated PSA levels and proven biopsy results, f/t PSA levels were measured using deep frozen serum samples. In a second study we enrolled 158 men with elevated PSA levels according to age reference ranges apparent from our current PSA screening study with additional measurement of the f/t PSA ratio. All study volunteers with a free f/t PSA ratio cutoff point of < or = 22% underwent digital rectal examination, transrectal ultrasonography, and biopsy of the prostate. Free and total PSA levels were measured with the Delfia PSA dual label f/t PSA kit (Wallac Oy Turku, Finland). RESULTS: 106 of 158 men with elevated total PSA values between 2.5 and 10.0 ng/mL (group 1) have been further evaluated and 37 prostate cancers were detected. Mean percentage of free PSA was 10% in men with cancer and 22% in men with benign prostatic hyperplasia. Using a f/t PSA ratio of < or = 22% as a biopsy criterion 30% of the negative biopsies could be eliminated while still detecting 98% carcinomas. CONCLUSIONS: Measurement of f/t PSA reduces the number of unnecessary biopsies in PSA screening without missing many cancers.

Aged↗