Acupuncture for pain in extracorporeal shockwave lithotripsy.

BACKGROUND AND PURPOSE: In most cases, analgesia is required for extracorporeal shockwave lithotripsy (SWL) treatment. Commonly, a combination of a sedative and a synthetic opioid is used, with a wide range of undesirable side effects. To provide an alternative analgesic especially for outpatients, we performed a prospective trial investigating the usefulness of acupuncture. PATIENTS AND METHODS: A series of 90 patients were included in the study, 49% of whom presented with renal calculi and 10% with proximal-, 10% with middle-, and 31% with distal-ureteral stones. Pain control was performed by acupuncture in the traditional Asian method. The intensity of pain and patient satisfaction were assessed a visual analog scale (VAS). Patients with previous SWL under conventional analgesia also were asked about differences in pain and satisfaction. RESULTS: No significant side effects occurred. The median pain score on the VAS was 2/10 (interquartile range 1). Six patients (6.6%) specified a pain intensity of >4, and in 4 patients (4.4%), a conventional analgesic had to be given to finish SWL. The median satisfaction level was 2/5 (interquartile range 1). Nearly all (93.4%) of the patients would opt again for acupuncture in case of repeated SWL. CONCLUSION: In many patients, acupuncture achieves satisfactory pain control for SWL. Further randomized multi-institutional studies are needed to confirm this conclusion.

Do patients profit from 5-aminolevulinic acid-induced fluorescence diagnosis in transurethral resection of bladder carcinoma?

OBJECTIVES: To evaluate in a prospective study the influence of fluorescence diagnosis (FD) controlled transurethral resection of bladder tumors on therapeutic consequences. The aim was to determine in how many patients FD led to a change in treatment strategy compared with conventional white light (WL) cystoscopy. METHODS: A total of 279 patients with suspected bladder tumors underwent transurethral resection using FD in addition to WL cystoscopy. The number of additional tumor-positive patients, staging change, number of multilocular tumors exclusively detected by FD, and resulting therapeutic consequences compared with the results after WL cystoscopy were investigated. In addition a biopsy-based evaluation was performed. RESULTS: Tumor or dysplasia II degrees (moderate dysplasia) was detected in 177 patients. In 168 patients, tumor was detected by WL cystoscopy, and in 9 (5.1%) of the patients, tumor was completely overlooked by WL cystoscopy and diagnosed exclusively by FD (n = 3 TaG1-G2, n = 2 carcinoma in situ, n = 1 greater than T1, and n = 3 dysplasia II degrees ). Multilocular tumor involvement was detected in 10 cases using FD, and a change in the stage by detection of coexisting dysplasia II degrees and carcinoma in situ occurred in 8 patients. In 27 patients (15.3%), additional information was obtained by exclusive detection of tumors by FD. This resulted in a change in the treatment strategy for 16 patients (9%). CONCLUSIONS: FD leads to an improvement in the diagnosis of bladder carcinoma. It allows the early selection of the best treatment option and thus has a potentially positive effect on the prognosis of the affected patients.

Correlation of persistent stress urinary incontinence with quality of life after suspension procedures: is continence the only decisive postoperative criterion of success?

OBJECTIVES: To determine objective continence rates and to include in the evaluation subjective assessment of continence and quality of life by the affected patients and correlate these with the objective continence rates in a retrospective study. METHODS: One hundred thirty-three female patients in our clinic underwent suspension procedures for stress urinary incontinence, 68 undergoing a Burch colposuspension and 65 a Raz bladder neck suspension. The continence rate was evaluated by questionnaire and compared with patients' postoperative self-assessment of continence and pre- and postoperative quality of life assessments. RESULTS: For the 105 women returning evaluable questionnaires (57 Burch and 48 Raz procedure), the continence rate was 69.5% (75.4% in the Burch group, 60.4% in the Raz group). Mild incontinence requiring 1 to 2 sanitary pads daily was found in 19.3% of the Burch group and 31.3% of the Raz group. Moderate incontinence requiring 3 to 5 pads daily was found in 5.3% of the Burch and 8.3% of the Raz group. No patients had severe incontinence (more than 5 pads daily). Both groups showed statistically significant improvement in postoperative quality of life. Despite persistent incontinence, the satisfaction rate was comparable to that of continent patients. CONCLUSIONS: The results show that in addition to objective parameters, subjective assessment of quality of life is a factor that should be included in the postoperative evaluation of surgical results.

Clinical results of the transurethreal resection and evaluation of superficial bladder carcinomas by means of fluorescence diagnosis after intravesical instillation of 5-aminolevulinic acid.

BACKGROUND AND OBJECTIVE: The high recurrence rate of superficial bladder carcinomas requires new approaches in diagnosis and therapy. Particularly, an improvement in detection, resulting in better resection of flat lesions, which are poorly or not detectable under white light, is necessary. The effectiveness of fluorescence diagnosis for detection and transurethral resection of bladder carcinomas was investigated in a prospective study. MATERIALS AND METHODS: From 120 patients, 347 biopsies were taken or tumors resected with the aid of fluorescence from 5-aminolevulinic acid. Urothelial carcinomas and dysplasias were detected in 124 cases. RESULTS: Of the lesions, 119 were fluorescence positive (N = 74 pTaG1/2; N = 9 pT1G1/2; N = 11 pT1G3; N = 7 carcinoma in situ; N = 6 p > T1; N = 12 dysplasia II), and 5 were falsely negative (N = 3 pTaG1/2; N = 1 pT1G1/2; N = 1 dysplasia II). The sensitivity of the fluorescence diagnosis (96.0%) was significantly higher than the 67.5% sensitivity of white-light cystoscopy (P < 0.0001). Taking the data for primary or recurrent tumor resection and secondary resection separately, the sensitivity was 100% and 80%, respectively, and was significantly higher than that of white-light cystoscopy, which was 80.8% and 20 %, respectively (P < 0.0001 and P < 0.0008). The lower sensitivity of fluorescence diagnosis in secondary transurethral resection is attributed to the higher rate of false-negative findings in areas of former resection. CONCLUSIONS: The high rate of false-positive findings limits the correct interpretation of fluorescence findings. In spite of this, fluorescence diagnosis is superior to white-light cystoscopy in every case. By means of better detection of urothelial neoplasias and dysplasias, as well as more thorough and extensive resection under fluorescence control, it should be possible to reduce the recurrence rate of superficial bladder carcinomas.

5-aminolevulinic acid-induced fluorescence endoscopy applied at secondary transurethral resection after conventional resection of primary superficial bladder tumors.

OBJECTIVES: A prospective investigation was carried out to evaluate the use of 5-aminolevulinic acid (5-ALA)-induced fluorescence diagnosis with secondary transurethral resection (TUR). METHODS: Fifty patients underwent secondary TUR of the former resection area 6 weeks after conventional TUR for superficial bladder carcinoma. 5-ALA-induced fluorescence diagnosis was used in addition to standard white light endoscopy. All former resection areas were biopsied regardless of fluorescence findings. In addition, specific red fluorescent areas were resected, as were suspicious areas seen at white light endoscopy. RESULTS: One hundred thirty areas or tumors were resected. The sensitivity of fluorescence cystoscopy was 77.8% (95% confidence interval 52.4% to 93.6%). Residual tumors were found in the area of the former resection in 7 (14%) of 50 patients; 4 of these 7 were fluorescence negative and 3 were fluorescence positive. In an additional 7 patients (14%), exclusively fluorescing tumors not visible under white light could be detected outside the areas of former resection (n = 5, Stage pTaG1/2; n = 1, Stage pT1G1/2; n = 1, carcinoma in situ). CONCLUSIONS: Despite high sensitivity, fluorescence diagnosis at this early stage of control does not allow us to evaluate sufficiently the granulation tissue of necrotic areas after TUR without biopsy. The main advantage of the 5-ALA-induced fluorescence endoscopy is in the evaluation of untreated urothelium because of the easier detection of tumors not visible by conventional endoscopy.

Benign ureteral tumors. Four case reports and a review of the literature.

The diagnosis of benign ureteral polyps should be considered especially in patients younger than 40 years with filling defects of the proximal ureter on the intravenous pyelogram (IVP). The excellent results of conservative organ-saving surgery (open resection, ureteroscopic resection, laser coagulation) require precise diagnostic management preoperatively in these patients.

Side effects of high-energy shockwaves in the human kidney: first experience with model comparing two shockwave sources.

The side effects of high-energy shockwaves (HESW) from two different sources on kidney parenchyma obtained from 10 patients treated by radical nephrectomy for renal cell carcinoma were examined. Immediately after nephrectomy, the kidneys were perfused with cold HTK solution and kept in hypothermia (8 degrees C) for a maximum of 4 hours. In five cases, the tumor-free parenchyma was treated at the upper or lower renal pole with 2000 shocks, energy output 21 kV, in an experimental electromagnetic shockwave system (Siemens Co., Erlangen). In the other five cases, the upper or lower poles were treated with 2000 shocks, energy output 24 kV, in an electrohydraulic spark gap system (MFL 5000; Dornier Medizintechnik, Germering). The resulting tissue defects were analyzed by histologic examinations. Changes after treatment with the electromagnetic system were found mainly in the tubules and midsized blood vessels in a well-defined focal area. Treatment with the electrohydraulic system was followed by tubular and glomerular lesions combined with vessel defects in a patchy pattern. The model is able to define the side effects of HESW in the human kidney and to test the side effects of different lithotripters.

Mechanisms of shockwave action in the human kidney.

The effects on the human kidney parenchyma of high-energy shockwaves (HESW) with different energy densities were examined. Kidneys of patients treated by radical nephrectomy for renal cell carcinoma were perfused with cold HTK solution immediately after nephrectomy and kept in hypothermia (8 degrees C) for a maximum of 4 hours. The tumor-free parenchyma was treated with 2000 shocks at energy outputs of 15 kV (16 MPa, 0.15 mJ/mm2), 17 kV (32 MPa, 0.25 mJ/mm2), 19 kV (50 MPa, 0.4 mJ/mm2), and 21 kV (65 MPa, 0.6 mJ/mm2) in an experimental electromagnetic shockwave system (Siemens Co., Erlanger, Germany). Resulting tissue effects were analyzed by histologic and immunohistochemical examinations and confocal laser scanning microscopy. Different sensitivities of cell components, blood vessels, and tubules were found. Laser scanning microscopy revealed nuclear alterations in the vicinity of the focus up to a distance of approximately 10 mm. Severe histologic changes were found in a smaller zone, while immunohistochemistry studies revealed negative collagen IV staining in an area of approximately 4 x 4 mm (all distances measured within the plane perpendicular to the acoustic axis). From these results, it can be concluded that HESW directly damage the tubules and the vascular system, which might explain the clinical changes after extracorporeal shockwave lithotripsy in human patients. The extent of these effects seems to be dependent on the applied energy.

Treatment of human renal cell carcinoma with high-energy shock waves--a new in vivo/in vitro model.

The effects of high-energy shock waves (HESW) on the human renal cell carcinoma were examined. The kidneys were available from 32 patients treated by radical nephrectomy due to renal cell carcinoma. Immediately after nephrectomy the kidneys were perfused with cold HTK solution and stored for a maximum of 4 h in hypothermia at 8 degrees C. The tumors were treated with 4,000 shocks (65 mPa = 0.6 mJ/mm2) in an electromagnetic lithotriptor (Siemens Co., Erlangen, Germany). Microscopic and immunohistological examinations of the tumors were performed after treatment, and cell proliferation rates of treated and untreated specimens were analyzed by cell cultures in 10 cases. HESW induce severe microscopic damage in the tumor tissue as complete rupture of the vessel walls and destruction of the tubular-formed tumor masses in the focal area. Immunohistochemistry shows intact immune reactive endothelial cells by factor 8-associated antibodies until the border to histological damage. Around this region a zone of negative antibody reaction against collagen type 4 is found. In cell cultures the proliferation rates of treated specimens were significantly lower compared to untreated. The human renal cell carcinoma seems to be susceptible for treatment with shock waves. HESW induce direct damage of tumor cells and vascular damage in the tumor which may be the primary cause of tumor necrosis.

Experience in advanced prostatic cancer: orchiectomy and flutamide versus orchiectomy and estramustine phosphate.

OBJECTIVE: To compare pure hormonal treatment (orchiectomy plus flutamide) versus hormonal plus cytostatic treatment (orchiectomy plus estramustine phosphate [EMP]) as first-line therapy for advanced prostatic cancer. METHODS: From October 1985 to December 1991 a total of 99 patients were enrolled: 49 received orchiectomy plus EMP, 2 x 280 mg/day; 50 received orchiectomy plus flutamide, 3 x 250 mg/day. RESULTS: Of the 99 enrolled patients, 93 were evaluable for toxicity and 82 for efficacy. The median time to progression was 161 weeks for EMP versus 120 weeks for flutamide (p = 0.75, not significant). For distant metastases, bone pain, and poor performance status, treatment with EMP showed significantly better results than the flutamide group. The most frequent side effects were gastrointestinal for EMP and hot flushes for flutamide. CONCLUSIONS: For patients with advanced undifferentiated prostatic cancer and poor prognostic factors, treatment with EMP seems to show significant benefit.

Proliferation of tumor spheroids after shock-wave treatment.

Multicellular tumor spheroids (MCTS) grown from the bladder cancer cell line RT112 and from the prostate cancer cell line PCA were exposed to 200 or 800 electromagnetically generated focused ultrasound shock waves. RT112 cells showed a distinct but transient decrease in proliferation whereas the effect of PCA cells was less pronounced. Flow-cytometric measurements of DNA content and Ki67 expression revealed no significant changes in the cell cycle distribution. The capacity of RT112 cells exposed to 800 shock waves to re-grow as MCTS was markedly decreased, indicating an alteration of intercellular adhesion.

Effects of high-energy shock waves on the viable human kidney.

Between September 1990 and July 1991, we treated 17 patients with renal-cell carcinoma by radical nephrectomy and two patients with urothelial carcinoma of the kidney pelvis by ureteronephrectomy. Immediately after nephrectomy, perfusion of the kidneys with cold HTK solution was performed and the organs were kept in hypothermia of 8 degrees C. The tumor-free parenchyma of the kidneys was treated 4 h later with shock waves of different energy levels in an experimental shock-wave system (Siemens Company, Erlangen). Light microscopy and examinations by scanning laser microscopy were performed after treatment. High-energy shock waves (HESW) produce significant changes in the tubulary and blood-vessel system of the viable human kidney, depending on the energy applied. Although our model is limited by hypothermia of the explanted kidneys, the effects of shock waves on the organs can be studied. Our model is suitable for testing the effects of different lithotriptors on the human kidney.

Determination of the energy-dependent extent of vascular damage caused by high-energy shock waves in an umbilical cord model.

To determine the spatial extent of shock-wave-induced vascular damage human umbilical cords were exposed to electromagnetically generated, focused ultrasound waves of different energy densities. During treatment macroscopically visible hematoma and superficial holes appeared. Following exposure specimens were fixed and examined histologically. In addition to vessel wall necrosis and rupture, complete detachment of endothelial cells in defined regions was observed. A correlation of the extent of the damage with the energy density distribution revealed that a local energy density of 0.3 mJ/mm2 is the lower threshold for the occurrence of severe vascular damage.

Radiation, Infection, and Macrophage Function IV. Effect of Radiation on the Proliferative Abilities of Mononuclear Phagocytes in Tuberculous Lesions of Rabbits.

Rabbits were irradiated with 400 to 600 rads 2 to 3 days before they were infected with BCG or with virulent tubercle bacilli. Biopsies were periodically removed from the resulting lesions and incubated for 1 hr with (3)H-thymidine in vitro under hyperbaric oxygen. Twelve to 16 days after radiation there was a reduction in the percentage of mononuclear cells (macrophages and some lymphocytes) that had incorporated (3)H-thymidine in the lesions. At this time, the lesions of the irradiated group were smaller than those of controls. These results can be explained by the reduction in the number of new mononuclear cells that entered the lesions of the irradiated group and support the tenet that local mononuclear cell division occurs mainly in cells that have recently emigrated from the blood stream. An alternate, but less likely, explanation of these results would be that radiation caused the bone marrow to release a higher percentage of "defective" mononuclear cells that were unable to divide, i.e., incorporate (3)H-thymidine, in the lesions. The reduction produced by radiation in both local cell infiltration and local cell division would decrease the number of macrophages available to control the tuberculous infection in the host.

Effect of formaldehyde on the immunogenicity of staphylococcal enterotoxin B for Macaca mulatta.

Monkeys were immunized with enterotoxin and enterotoxoid by intracutaneous injection or by feeding. Identical schedules were used to compare the effectiveness of the two antigens and the two routes. Enterotoxin administered intracutaneously was the most effective antigen, whereas oral administration of enterotoxoid was least effective. Intracutaneous injection of toxoid and oral feeding of toxin were intermediate and not too dissimilar in effectiveness. Antibody titers and protection persisted for at least 1 year at a relatively high level. Monkeys that had preimmunization hemagglutinins showed an anamnestic response after immunization. The development of protection and the appearance of antibodies subsequent to feeding toxin or toxoid suggest that ingestion of food contaminated by staphylococci or their metabolites may be one cause for the appearance of antitoxin in the serum of supposedly unexposed animals and man.

Permanent turbidity standards.

Permanent turbidity reference standards suitable for measurement of microbial suspensions were prepared by suspending finely divided titanium dioxide in aryl sulfonamide-formaldehyde or methylstyrene resins. Turbidities of these standards, adjusted to a useful range for microbiological and immunological studies, were compared with other reference standards in use today. Tube holders for a Coleman Photonephelometer and a Nepho-Colorimeter were modified to eliminate the water well and to allow use of optically standardized 10-, 16-, or 18-mm test tubes. The standards and the tube holders have been used satisfactorily for more than 12 years.