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D Jocham

Publications and source records attributed to D Jocham.

At least 55 records · Page 3Linked to original sources
PubMed2001

Laparoscopic nephroureterectomy to exclude upper urinary tract malignancy associated with analgesic nephropathy.

BACKGROUND AND PURPOSE: Analgesic abuse is a potential cause of end-stage renal disease. Such patients bear an elevated risk of developing malignancies, predominantly transitional-cell carcinoma. We report our experience with laparoscopic nephroureterectomy carried out in patients with analgesic nephropathy to exclude upper urinary tract malignancy. All patients were scheduled to be put on the waiting list for cadaveric renal transplantation. PATIENTS AND METHODS: Since 1996, nine women and two men with a long-term history of analgesic abuse have undergone laparoscopic nephroureterectomy at our hospital. The median age was 63 years (range 51-70 years). All patients had developed end-stage renal failure secondary to heavy analgesic abuse with a median duration of 14 years (range 7-40 years). The median interval from the beginning of hemodialysis to laparoscopic nephroureterectomy was 36 months (range 6-76 months). RESULTS: The median operative time was 99 minutes (range 55-170 minutes). There were no conversions to open surgery. Two complications occurred, and three patients required blood transfusions. The median hospital stay lasted 5 days (range 2-12 days), and the median convalescence was 20 days (range 6-44 days). In seven patients, histopathologic examination of the kidney revealed changes attributable to analgesic abuse. None of the patients had a transitional-cell carcinoma, but in two patients, a renal-cell carcinoma stage pT1cN0cM0 grade 2 was detected. CONCLUSION: Patients with analgesic nephropathy bear an elevated risk for the development of transitional-cell or renal-cell carcinoma. In these patients, laparoscopic nephroureterectomy combines minimally operative invasiveness with a maximum of diagnostic safety.

Aged↗
PubMed2001

Laparoscopic nephrectomy in young-old, old-old, and oldest-old adults.

BACKGROUND: This study reports findings for laparoscopic nephrectomy in comparison with open nephrectomy in geriatric patients. METHODS: Since 1993, a total of 249 patients have undergone nephrectomy for benign disease at the Medical University of Lübeck, Germany. In 11 patients older than 65 years, a laparoscopic nephrectomy was performed (in the majority via a transperitoneal approach), and 42 patients older than 65 years underwent an open-flank nephrectomy. Clinical parameters were evaluated in comparison with both groups and stratified according to age groups. RESULTS: With respect to operative results (operative duration and pre- and postoperative hemoglobin levels), no relevant differences were observed between the laparoscopy group and the open-nephrectomy group, even when stratified according to patient age. However, patients in the laparoscopy group demonstrated a significant advantage concerning blood loss and the number of required blood transfusions, regardless of age. In addition, patients after laparoscopy showed advantages in the postoperative course. Benefits were proven for the analgesic consumption, hospital stay, and convalescence parameters. Although complication rates were comparable in both groups, an increase was observed in both groups for patients aged between 75 and 84 years. CONCLUSIONS: Laparoscopic nephrectomy offers comparable operative results (with reduced blood loss and less need for blood transfusions) when compared with open surgery. Significant advantages can be demonstrated in the postoperative course, and especially geriatric patients benefit from these aspects of the minimally invasive approach. Laparoscopy should be regarded as the primary therapeutic option for nephrectomy for benign disease in these patients.

Age Factors↗
PubMed2001

Nonrandomized comparison of open flank versus laparoscopic nephrectomy in 249 patients with benign renal disease.

OBJECTIVES: We report the results from a nonrandomized comparison of open flank versus laparoscopic nephrectomy in patients with benign renal disease. METHODS: From January 1993 to December 1997, 249 nephrectomies for benign renal disease were performed at our institution. There were 118 patients in the open flank nephrectomy group (median age 58.5, range 8-89 years) and 131 patients in the laparoscopic nephrectomy group (median age 40, range 16-73 years). Clinical parameters such as operative times, blood loss, transfusion rates, conversion and complication rates, start of oral intake, analgesic consumption, duration of hospitalization and convalescence and short-term mortality were compared among both groups. RESULTS: Median operative time in the open flank nephrectomy group was 90 (range 30-240) min and also 90 (range 41-210) min in the laparoscopic nephrectomy group. In the laparoscopy group 8 patients were converted to open surgery (6.1%). There were 27 complications (20.6%) in the laparoscopic nephrectomy group compared to 30 complications (25.4%) in the open flank nephrectomy group. Postoperatively, patients in the laparoscopic nephrectomy group required less morphine sulfate equivalent (12 vs. 20 mg) for pain control and they had a shorter hospital stay (4 vs. 10 days) and convalescence (24 vs. 36 days). The postoperative parameters are given as medians and reached statistically significant differences in favor of laparoscopic nephrectomy. CONCLUSIONS: Laparoscopic nephrectomy results in a significantly briefer postoperative course when compared to open flank nephrectomy. As a matter of fact laparoscopy in urology is still a center-related procedure and even in these centers only a minority of urologists practice laparoscopy. However, in experienced centers the laparoscopic technique should be offered to patients with benign renal disease who are scheduled for elective nephrectomy.

Adolescent↗
PubMed2001

Value of acute-phase proteins in the differential diagnosis of acute scrotum.

OBJECTIVES: The evaluation of patients with an acute scrotum is primarily based on physical examination, imaging studies, as well as blood and urine tests. However, the differential diagnosis may be difficult in some cases. In a retrospective study, we investigated the value of acutephase proteins in serum and plasma from patients with an acute scrotum. METHODS: A total of 104 patients (epididymitis n=52, testicular tumor n=17, testicular torsion n = 11, other conditions n = 24) with an acute scrotum were included in this study. In all patients the acute-phase proteins C-reactive protein (CRP), haptoglobin, alpha1-acid glycoprotein and transferrin in serum as well as fibrinogen in plasma were determined by turbidimetric analysis. The results were compared to the clinical findings, routine blood and urine tests and ultrasound. RESULTS: Patients with an epididymitis showed at least a 4-fold elevation of CRP except for 2 cases (median 63.2 mg/l). In these patients, the sensitivity of CRP was 96.2%, the specificity 94.2%, the negative predictive value 94.2% and the positive predictive value 94.3%. Patients with a testicular tumor had no significant elevation of CRP (median 9 mg/l) as well as those with a testicular torsion (median 5 mg/l) except for 1 patient. The difference between patients with epididymitis and those with noninflammatory conditions was statistically significant (p<0.001, Kruskal-Wallis test and Tukey-Kramer test). The remaining parameters (haptoglobin, fibrinogen, a1-acid glycoprotein, transferrin, white blood count, body temperature and ultrasound) were less sensitive and specific. CONCLUSIONS: Acute-phase proteins (especially C-reactive protein) are helpful in differentiating epididymitis from noninflammatory conditions like testicular torsion or tumor. Turbidimetric analysis of these proteins is rapid, easy and inexpensive.

Acute Disease↗
PubMed2001

Primary treatment of condylomata acuminata with viable bacillus Calmette-Guerin.

PURPOSE: Condylomata acuminata or genital warts are caused by human papillomavirus. Prevalence data show that infection rates are increasing. To our knowledge we report the first successful primary treatment of genital warts with topical bacillus Calmette-Guerin (BCG) and provide long-term followup in a group of adjuvant treated patients with recurrent condylomata acuminata. MATERIALS AND METHODS: In 10 consecutive men viable BCG was directly applied to the condylomata acuminata lesions once weekly for 6 weeks. In nonresponding patients another course of 9 applications was administered for 3 weeks. RESULTS: A complete response was achieved in 6 of the 10 men after 1 or 2 treatment cycles. All responding patients are disease-free at a median followup of 9.2 months (range 4 to 12). One patient achieved partial regression of the lesions and in 3 the condylomata did not disappear. Side effects were rare and mild. Long-term followup in 6 adjuvant treated patients with rapidly recurrent condylomata acuminata showed no further recurrence after topical BCG in 5 at a median of 30.8 months (range 29 to 50). CONCLUSIONS: Topical application of viable BCG has therapeutic activity as adjuvant and primary treatment for penile condylomata acuminata with negligible side effects. Long-term followup implies the prevention of recurrent disease.

Adjuvants, Immunologic↗
PubMed2001

Technology evaluation: CV-787, Calydon Inc.

CV-787 is a recombinant adenovirus that replicates only in prostate-specific antigen (PSA)-producing cells, which is being developed by Calydon Inc for the treatment of prostate cancer [339621]. This attenuated replication-competent virus (ARCA) only replicates in and destroys PSA-producing cells. By engineering the prostate-specific enhancer (PSE) control element into the adenovirus, Calydon has established both a means for delivery and the mechanism for killing prostate cancer cells [339621]. In October 1999, Calydon began treating patients with biopsy-proven, prostate-confined cancer with CV-787 in a phase I/II multi-center, open-label, dose-finding study [362188], [344731]. In September 2000, Calydon initiated a a phase I/II multi-center, open-label, dose-finding trial of an intravenous formulation of CV-787 in men with metastatic prostate cancer [384039]. The trial was designed to enrol 48, and enrollment was continuing in April 2001. The study is being conducted at three medical centers: University of California at San Francisco; Johns Hopkins Oncology Center in Baltimore; and, University of Wisconsin at Madison. The primary objectives of this trial are to determine the safety, tolerability, and PSA efficacy of CV-787 administered intravenously to patients with end-stage prostate cancer [384039].

Adenoviruses, Human↗
PubMed2001

The fate of bacillus Calmette-Guerin after intravesical instillation.

PURPOSE: Long-term activation of immunocompetent cells of the bladder wall as well as case reports of systemic infections some months or years after intravesical bacillus Calmette-Guerin (BCG) therapy imply that mycobacteria may persist in the body. Therefore. we investigated the fate of BCG in patients after uncomplicated intravesical instillation therapy. MATERIAL AND METHODS: A total of 49 patients were included in the study, from whom various numbers of specimens were used for mycobacterial culture and molecular biological detection techniques. In 23 patients who received a total of 128 instillations urine, sputum, venous blood and bladder biopsies were screened for BCG by acid-fast staining and culture at different times before and after instillation. From 16 of the 23 patients and from an additional 26 a total of 180 bladder biopsies obtained at intervals 3 to 30 months after instillation were screened for mycobacterial 16S ribosomal DNA by a nested polymerase chain reaction protocol. RESULTS: No viable BCG was found in venous blood or in 127 of 128 sputum specimens before and 2 hours after instillation. Two of 56 bladder biopsies were culture positive. In urine BCG was detected in 96.4% of the specimens after 2 hours and in 67.9% after 24 hours after instillation. The number of positive specimens decreased and it was 27.1% on day 7 immediately before the next instillation. In 14 of 44 bladder biopsies (31.8%) mycobacterial ribosomal DNA was found within 1 week after the sixth instillation. A positive polymerase chain reaction was evident up to 24 months in between 4.2% and 37.5% of the investigated biopsies. After 30 months no ribosomal DNA was evident in the 6 samples available for testing. CONCLUSIONS: Nontraumatic intravesical instillation of BCG is not accompanied by systemic mycobacterial spread. Local persistence during the instillation course is evident since viable BCG is commonly found in the urine. Long lasting and persistent BCG DNA in the bladder wall may account for long-term immuno-activation. However, the remaining BCG may be a possible source of late systemic infections.

Adjuvants, Immunologic↗
PubMed2000

Killing of Fas ligand-resistant renal carcioma cells by interleukin-2- and BCG-activated effector cells.

Activated cytolytic effector cells like lymphokine-activated killer (LAK) and the recently described bacillus-Calmette-Guerin-activated killer (BAK) cells are thought to mediate antitumor effects against metastatic renal cell carcinoma (RCC) and superficial bladder cancer respectively. Perforin and Fas ligand (FasL) have been described as the major lytic principles in cellular cytotoxicity. Using a radioactive-release assay and specific inhibitors, we investigated the molecular mechanisms used by LAK and BAK cells in the lysis of renal carcinoma cells. In addition, we evaluated the susceptibility of RCC cells to FasL-mediated cytotoxicity. LAK and BAK cells effectively lysed the renal cancer cell line SK-RC-35 upon cell-cell contact. Both effector cell populations were shown to produce perforin and FasL as determined by reverse transcriptase/polymerase chain reaction (RT-PCR). Using fluorescence-activated cell sorting analyses and RT-PCR, we detected a marked Fas receptor (Fas, CD95) expression on RCC cells. However, RCC cells were shown to be resistant to killing by recombinant FasL and lysis by BAK and LAK cells was not inhibited in the presence of anti-FasL antibody. In contrast, the cytotoxicity exerted by LAK and BAK cells was drastically reduced in the presence of the Ca2+-chelating agent EGTA as well as concanamycin A, a specific inhibitor of perforin-mediated lysis. These results demonstrate that cytolysis of FasL-resistant RCC cells by activated immune cells is mediated via perforin. Our findings give further insights into the molecular mechanisms involved in the elimination of RCC by cytotoxic lymphocytes activated with biological response modifiers.

Adjuvants, Immunologic↗
PubMed2000

[Laparoscopic nephrectomy in geriatric patients: comparison with conventional nephrectomy].

INTRODUCTION: We report our experience with laparoscopic nephrectomy in comparison to open nephrectomy in geriatric patients. The laparoscopic technique is presented and the results are discussed with respect to the data from the current literature. MATERIAL AND METHODS: Since 1993, a total of 249 patient have undergone a nephrectomy for benign renal disease. In 131 patients a laparoscopic nephrectomy (in most cases via a transperitoneal approach) was performed and in 118 patients an open nephrectomy via a flank incision. Clinical parameters were compared between both groups as well as with respect to different age groups. RESULTS: There were no differences in terms of operative results (operative time, pre- and postoperative hemoglobin) between the laparoscopy group and open nephrectomy group as well as among the different age groups. Patients in the laparoscopy group demonstrated significant advantages with respect to blood loss, transfusion rate, analgesic consumption, hospital stay, and convalescence. These advantages were not related to patient age. The complication rate was comparable for both groups; however, both groups showed an elevation of the complication rate in the age groups 75 to 84 years. The mortality rate within the first 30 days after nephrectomy was 1.7% in the open nephrectomy group. CONCLUSIONS: The laparoscopic nephrectomy offers comparable operative results (with less blood loss and a lower transfusion rate) when compared to open nephrectomy. In terms of postoperative parameters, patients in the laparoscopy group have significant advantages. Especially geriatric patients benefit from these advantages and, therefore, the laparoscopic approach should be the preferred technique for a nephrectomy in these patients.

Aged↗
PubMed2000

The immunohistochemical assessment of occult regional lymph node metastases in patients with T3pN0M0 prostate cancer before definitive radiotherapy.

OBJECTIVE: To detect occult regional lymph node metastases in patients with T3pN0M0 prostate cancer not recognized by routine haematoxylin and eosin staining, and to evaluate the clinical relevance of this finding. PATIENTS AND METHODS: Formalin-fixed and paraffin-embedded pelvic lymph nodes (1118) from 92 patients were evaluated by immunohistochemistry using antibodies for prostate specific antigen (PSA) and pancytokeratin (AE1/AE3). Of the tumours, 14% were well, 69% moderately and 17% poorly differentiated. The extent of tumour was categorized as T3pN0M0 in all patients, who were referred for definitive radiotherapy after pelvic staging lymphadenectomy. The median (range) serum PSA value before treatment was 18.5 (0.4-342) microg/L. After radiotherapy, the patients were followed by assessing biochemical progression, pelvic recurrence and/or development of distant metastases. The median (range) observation time for all patients was 61 (16-136) months. RESULTS: Occult lymph node metastases were detected in four (4.4%) of the 92 patients. Patients with or without occult metastases had similar serum PSA levels and histological grades. None of the four patients with occult metastases progressed, compared with 37 of the 88 (42%) with no such metastases. CONCLUSION: Using immunohistochemistry the detection rate of occult lymph node metastases in patients with T3pN0M0 prostate cancer is low. The occurrence of such metastases is probably unrelated to the serum PSA value before treatment. The short-term outcome of patients subsequently treated with definitive radiotherapy does not seem to be associated with the finding of occult lymph node metastases, but long-term follow-up is needed. So far, the results do not justify the search for occult lymph node metastases as a routine procedure in these patients

Aged↗
PubMed2000

Reduction of side effects of intravesical therapy with bacille Calmette-Guérin by pentoxifylline?--an in vitro approach.

Immunotherapy with intravesical bacille Calmette-Guérin (BCG) is the treatment of choice against superficial bladder cancer recurrences. However, this therapy is associated with side effects that are considered to be the result of inflammatory cytokines. Since pentoxifylline is known to interfere with the production of cytokines, this drug was tested in vitro with regard to a later clinical application in BCG-treated patients. The cytokine release and the cytotoxicity of interleukin-2 or BCG-stimulated mononuclear cells were analyzed, and the growth of BCG under the influence of pentoxifylline was assayed. The results showed an inhibition of cytokine release of stimulated mononuclear cells. The cytotoxicity of BCG-stimulated mononuclear cells but not of lymphokine-stimulated mononuclear cells against bladder carcinoma cells was significantly inhibited. Restimulation with fresh BCG restored cytotoxicity. Direct coincubation of BCG and pentoxifylline resulted in a reduction of mycobacterial metabolism. From these data, we conclude that the use of pentoxifylline to reduce BCG-related side effects should be tested further in a clinical study.

Administration, Intravesical↗
PubMed2000

Why is urological laparoscopy minimally invasive?

OBJECTIVES: Laparoscopic procedures have been developed and established with the view that a similar operative effect can be achieved with less traumatization, especially as far as systemic stress response is concerned. We report a prospective, controlled, nonrandomized animal and patient study to determine the systemic response to laparoscopic and open surgical procedures. METHODS: In the animal study, 26 female pigs underwent either a laparoscopic bilateral varix ligation followed by bilateral nephrectomy (group I), sole introduction of trocars (group II) or sole establishment of an open surgical approach (group III). In the patient study, 145 patients underwent various laparoscopic procedures (nephrectomy, renal cyst marsupialization, varix ligation), open surgical procedures (nephrectomy, inguinal orchiectomy) or extracorporeal shockwave lithotripsy (ESWL). The serum parameters interleukin (IL)-6, IL-10 and C-reactive protein (CRP) were measured before, during and after the operative procedure. RESULTS: In animals and patients, laparoscopy resulted in significantly lower serum levels of CRP during and after the operative procedure. Animals in group I showed a 5-fold elevation, in group II a 3-fold elevation and in group III a 9-fold elevation of CRP. In patients, the increase of CRP was twice as high after open unilateral nephrectomy than after laparoscopic unilateral or bilateral nephrectomy. IL-6 showed less marked elevation during laparoscopy, ESWL and minor operative procedures like laparoscopic varix ligation or inguinal orchiectomy when compared to an open unilateral nephrectomy. The parameter IL-10 showed no significant differences among the patient groups. CONCLUSIONS: The extent of the acute phase reaction to the operative trauma correlates much more convincingly to the approach than to the extent of the procedure. Only larger operations like nephrectomy trigger a systemic acute phase reaction, which can be limited by the laparoscopic access. For minor operative procedures like varix ligation or exploration of cryptorchidism, laparoscopy offers technical advantages rather than minimal invasiveness.

Acute-Phase Reaction↗
PubMed2000

Sensitivity of BCG to modern antibiotics.

The viability of bacillus Calmette-Guérin (BCG) in intravesical instillation therapy has been demonstrated to be crucial for the prevention of bladder tumour recurrence. The aim of the present study was to determine the effects of modern antibacterial chemotherapeutics on BCG viability, particularly cycloserine, which has been recommended in the treatment of BCG-induced sepsis. The minimal inhibitory concentrations (MICs) of 32 antibacterial drugs potentially effective against the Connaught BCG strain were measured in vitro by the radiometric BACTEC 460TB method. The MICs were compared with the drug concentrations achievable in blood and urine. Susceptibility testing of cycloserine was performed with three different strains (Connaught, Tice and RIVM), using the modified proportion method, as defined in the German guidelines for anti-tuberculosis drug testing. The Connaught BCG strain was highly susceptible to fluoroquinolones, but was resistant to beta-lactams, macrolides (except clarithromycin), and some aminoglycosides. It was also sensitive to doxycycline and gentamicin at dosages that typically occur in the urine of patients after a normal dose. Connaught BCG was susceptible to all the tuberculostatic drugs tested, except for pyrazinamide. All the BCG strains analysed were resistant to cycloserine. During intravesical BCG instillation therapy, simultaneous administration of fluoroquinolones, doxycycline or gentamicin should be avoided. In cases of severe systemic complications, or if one of the antituberculosis drugs is not tolerated, fluoroquinolones may be used. Cycloserine is no longer recommended for the early treatment of BCG sepsis.

Administration, Intravesical↗
PubMed2000

Fatal basilar artery thrombosis after chemotherapy for testicular cancer.

We report a 31-year-old patient with a pT3N2M1 seminoma who received cisplatin-based chemotherapy. During the second course of chemotherapy, the patient suffered a thrombosis of the basilar artery. He died 14 h after hospital admission. Cerebrovascular events related to cisplatin-based chemotherapy are rare, however, these potentially fatal events should be kept in mind when treating patients with testicular cancer.

Adult↗
PubMed2000

Perforin-mediated lysis of tumor cells by Mycobacterium bovis Bacillus Calmette-Guérin-activated killer cells.

Immunotherapy with Bacillus Calmette-Guérin (BCG) is clinically established in the treatment of superficial bladder cancer. In our attempt to clarify the underlying immunological mechanism, we could previously show that stimulation of PBMC with BCG leads to the generation of cytotoxic BCG-activated killer (BAK) cells. Among others, these BAK cells as well as lymphokine-activated killer (LAK) cells have been suggested as possible effector cells during BCG therapy. To understand BCG-induced activation of effector lymphocytes more precisely, we investigated the lytic pathways of human BAK cells and compared BAK cell cytotoxicity with LAK cell cytotoxicity. Perforin and Fas ligand (FasL) are the major cytolytic molecules of cytotoxic lymphocytes. Our results demonstrate that BAK and LAK cells showed an increased expression of perforin and FasL as compared with unstimulated controls. Killing of T-24 bladder tumor as well as Jurkat cells by BAK and LAK cells was predominantly mediated via perforin as demonstrated by a drastically reduced lysis in the presence of concanamycin A and EGTA/MgCl2, respectively. In contrast, lysis (radioactive release assay) and membrane disintegration (Annexin V binding) of both targets by BAK and LAK cells could not be blocked with an inhibitory anti-FasL monoclonal antibody (NOK-1). Nevertheless, T-24 and Jurkat were susceptible to killing by recombinant soluble FasL and by Chinese hamster ovary cells expressing membrane-bound FasL. We conclude that cellular mediators of BCG effector mechanisms, such as BAK and LAK cells, kill their targets via perforin and independent of the FasL pathway. Because we also found increased numbers of perforin-expressing lymphocytes in patients after BCG therapy, our findings have potential clinical relevance because BCG therapy would not be impaired by FasL resistance of target cells, which recently has been described for some tumors.

Adjuvants, Immunologic↗
PubMed2000

Technology evaluation: TG-1031, Transgene SA.

Tumor-associated antigens have considerable promise not only as diagnostic or prognostic markers but also as targets for active or passive immunotherapy. The epithelial mucin MUC1 is a transmembrane molecule which is expressed by most glandular epithelial cells. Transgene has developed VV-MUC1-IL-2 (TG-1031), an antigen-specific therapy, involving the tumor antigen MUC1 and the cytokine IL-2 combined with a vaccinia virus vector. Vaccinia virus vectors have been shown to stimulate a strong immune response to encoded antigens in vivo. This therapy has potential for the treatment of breast cancer, prostate cancer and other adenocarcinomas and is currently under investigation in phase I and II trials.

Animals↗