Randomized phase III trial of 2nd line gemcitabine and paclitaxel chemotherapy in patients with advanced bladder cancer: short-term versus prolonged treatment [German Association of Urological Oncology (AUO) trial AB 20/99].

BACKGROUND: The second-line chemotherapeutic treatment for metastatic urothelial cancer (UC) after failure of cisplatin-based first-line therapy needs to be improved. Based on encouraging phase II data of gemcitabine and paclitaxel (Taxol) (GP), this trial was designed to compare a short-term (arm A) versus a prolonged (arm B) second-line combination chemotherapy of GP. PATIENTS AND METHODS: Of 102 randomized patients, 96 were eligible for analysis. Primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), objective response rates (ORR) and toxicity. RESULTS: Neither OS [arm A: 7.8 (95% CI: 4.2-11.4), arm B: 8.0 (95% CI: 4.9-11.1) months] and PFS [arm A: 4.0 (95% CI: 0-8.0), arm B: 3.1 (95% CI: 1.9-4.2) months] nor ORR (arm A: 37.5%, arm B: 41.5%) were significantly different. On prolonged treatment, more patients experienced severe anemia (arm A: 6.7% versus arm B: 26.7% grade III/IV anemia; P = 0.011). In six patients, treatment was stopped during the first cycle due to disease progression or toxicity. Two patients died due to treatment-related toxic effects. CONCLUSION: Due to rapid tumor progression and toxicity at this dosage and schedule in a multicenter setting, it was not feasible to deliver a prolonged regimen. However, a high response rate of ∼40% makes GP a promising second-line treatment option for patients with metastatic UC.

12-Year within-wound study of the effectiveness of custom pressure garment therapy.

Pressure garment therapy is standard of care for prevention and treatment of hypertrophic scarring after burn injury. Nevertheless there is little objective data that confirms effectiveness. The purpose of this study was to determine the effectiveness of pressure garment therapy with objective data obtained with a randomized within-wound comparison. We enrolled consecutive patients with forearm injuries over a 12-year period. The subjects wore custom garments with normal and low compression randomized to either the proximal or distal zones. Hardness, color and thickness of wounds were objectively measured using appropriate devices; clinical appearance was measured by a panel masked to the identity of the pressure treated area. Wounds treated with normal compression were significantly softer, thinner, and had improved clinical appearance. There was no interaction of any effect with patient ethnicity. However, these findings were clinically evident only with moderate to severe scarring. We conclude that pressure garment therapy is effective, but that the clinical benefit is restricted to those patients with moderate or severe scarring.

[Legal aspects of injuries due to positioning of the patient in urology]. / Juristische Aspekte bei Lagerungsschäden in der Urologie.

Each positioning of the patient has method specific risks and risk increasing factors which depend on the type of surgery carried out. The causes of damage during positioning are pressure and strain when the protective reflexes are out of action, as well as a reduction of the shielding muscle tone through anaesthesia. The surgeon is responsible for the positioning of the patient, and the anaesthetist for the "infusion arm". For this interdisciplinary cooperation, the principles of horizontal work division are required: strict role boundaries, trust without reciprocal direction, close coordination and reciprocal respect for the specialist requirements of the partner, resolution of conflicts taking these requirements into consideration and the final decision of the surgeon. Legally, the damage caused by the positioning of the patient is considered to be fully under control. It can only be reduced by medical care but can not be eliminated. For compensation, the medical practitioner must prove that the appropriate amount of care was taken in the positioning of the patient as well as in the medical cooperation.

The use of chemical treatments for improved comminution of artificial stones.

PURPOSE: The acoustic and mechanical properties of various stone compositions are significantly different and thus result in varying degrees of fragility. Consequently, results to shock wave lithotripsy (SWL) are influenced accordingly. We report the results of a study of fragility of various stone compositions, and the influence on each stone's baseline physical properties and fragility when exposed to various chemolytic solutions. MATERIALS AND METHODS: Before SWL artificial stones of differing compositions were irrigated with various chemolytic solutions. Calcium oxalate monohydrate (COM) stones were treated with ethylenediaminetetraacetic acid (EDTA), stones composed of magnesium ammonium phosphate hydrogen were treated with hemiacidrin, and stones made of uric acid (UA) were treated with tromethamine. Synthetic urine served as a control for all stone groups. Using an ultrasound transmission technique, longitudinal wave propagation speed was measured in all groups of artificial stones. Stone density was also measured by using a pycnometer (based on Archimedes' principle). Based on these measurements transverse (shear) wave speed (assuming a constant Poisson's ratio), wave impedance and dynamic mechanical properties of the artificial stones were calculated. Moreover, the microhardness of these artificial stones was measured, and fragility testing using SWL with and without pretreatment with the previously mentioned chemolytic solutions, was performed. RESULTS: Wave speed, wave impedance, dynamic mechanical properties and microhardness of EDTA treated COM stones and tromethamine treated UA stones were found to decrease compared to untreated (synthetic urine) control groups. The suggestion that chemolytic pretreatment increases stone fragility was verified by the finding of increased stone comminution after SWL testing. Combining this medical pretreatment and SWL, the findings demonstrate a significant impact of various solvents on stone comminution, in particular EDTA treated COM stones, tromethamine treated UA stones and hemiacidrin treated magnesium ammonium phosphate hydrogen stones. These data suggest that by altering the chemical environment of the fluid surrounding the stones it is possible to increase the fragility of renal calculi in vitro. CONCLUSIONS: These results indicate that appropriate chemical treatments may provide a useful adjunctive modality for improving the efficacy of stone comminution during shock wave lithotripsy.

[A new method for the evaluation of stone fragmentation after ESWL]. / Eine neue Methode zur Evaluation der Steinfragmentation nach ESWL.

INTRODUCTION: Efficacy of ESWL treatment can be evaluated by determining the number and size of urinary stone fragments. However, the available methods for classification of stone fragments are inaccurate. Therefore, a method for semi-automatic determination of fragment size and number after ESWL was developed. METHODS: Artificial struvite stones (BON[N]-STONES) were disintegrated with a lithotriptor (Siemens, Lithostar plus) by application of 50 and 200 shock waves at 19 kV. The stone fragments were collected and pre-sorted on cascade sieves. Pictures taken of the fractions were digitalized and the images optimized in edge sharpness, contrast, and colour depth using an image processing software. Finally, the pixel number of each fragment was determined and the real area was calculated. Fragment size and volume were then depicted by frequency of occurrence in a histogram. RESULTS: Fragments with a diameter ranging from 0.3 - 5 mm could be determined by the system described. About 2,000 - 3,600 fragments were generated in this size range from the artificial struvite stones. With low shock-wave application, a considerable number of fragments larger than 2 mm could be observed. By increasing the impact to 200, more than 90 % of the stone volume was found in fragments smaller than 2 mm (previously 50 %). CONCLUSION: The system described enables a qualitative and quantitative description of stone fragmentation after ESWL not achieved thus far.

The methamphetamine burn patient.

Early aggressive fluid resuscitation has significantly decreased the morbidity and mortality associated with volume losses from large burns. Although most patients are adequately resuscitated using the Parkland formula, we noted increased fluid requirements for shock resuscitation in patients involved in methamphetamine laboratory explosions. Because predominant users are young healthy individuals in their 20s and 30s, we had not anticipated burn shock resuscitation failures in this patient group. We reviewed our experience with burn patients with documented methamphetamine use to determine whether this patient group presents new dilemmas to the burn surgeon. A 2-year retrospective study of 30 patients (15 methamphetamine users, 15 controls) revealed that the methamphetamine burn patient requires two to three times the standard Parkland formula resuscitation. In this study, methamphetamine burns larger than 40% TBSA had a 100% mortality.

Serial measurements increase the accuracy of laser Doppler assessment of burn wounds.

Traditional methods of judging burn depth by clinical evaluation of the wound based on appearance and sensation remain in wide use but are subject to individual variation by examiner. In addition to the clinical difficulties with burn wound management, observer dependency of wound assessment complicates clinical trials of burn wound therapy. A laser Doppler flowmeter with a multichannel probe was used to measure burn wound perfusion as a tool to predict wound outcome. Serial measurement with laser Doppler flowmetry had an 88% specificity and a positive predictive value of 81% for identifying nonhealing wounds. These results suggest that laser Doppler flowmetry is a potentially useful tool for burn wound assessment.

Current management of purpura fulminans: a multicenter study.

Seven burn centers performed a 10-yr retrospective chart review of patients diagnosed with purpura fulminans. Patient demographics, etiology, presentation, medical and surgical treatment, and outcome were reviewed. A total of 70 patients were identified. Mean patient age was 13 yr. Neisseria meningitidis was the most common etiologic agent in infants and adolescents whereas Streptococcus commonly afflicted the adult population. Acute management consisted of antibiotic administration, volume resuscitation, ventilatory and inotropic support, with occasional use of corticosteroids (38%) and protein C replacement (9%). Full-thickness skin and soft-tissue necrosis was extensive, requiring skin grafting and amputations in 90% of the patients. One fourth of the patients required amputations of all extremities. Fasciotomies when performed early appeared to limit the level of amputation in 6 of 14 patients. Therefore, fasciotomies during the initial management of these patients may reduce the depth of soft-tissue involvement and the extent of amputations.

The 2002 Lindberg Award. PRN vs regularly scheduled opioid analgesics in pediatric burn patients.

Very little has been published on treating acute pain in children younger than the age of 3 for burns or any other trauma etiology. This study prospectively monitored the pain behavior and opioid analgesic intake of 31 pediatric burn patients (mean age = 23.71 months; SD = 15.75). Twelve of those children were randomized to conditions in which they either received opioid analgesics pro re nata (ie, as needed, pain contingent) or on a regular basis. The two groups did not show differences in demonstrable pain but, interestingly, they received equivalent does of opioid analgesics. As such, the pro re nata group was likely medicated largely on a regularly scheduled basis. For most of the remaining (nonrandomized) subjects, physicians ordered regularly scheduled opioid analgesics, suggesting that this practice has become largely institutionalized in the study setting. Information on pediatric opioid analgesic dosing and pain measurement strategies for nonverbal subjects can be derived from the findings.

Chemolitholysis and lithotripsy of infectious urinary stones - an in vitro study.

OBJECTIVES: This study was performed to look for an improvement of therapeutic strategies with regard to the treatment of infectious urinary stones using artificial stones made of struvite and apatite ('Bon(n) stones') which are comparable to their natural counterparts. MATERIALS AND METHODS: Using an experimental arrangement simulating the physiological conditions in the upper urinary tract, the efficacy of artificial urine (pH 5.7), Suby G solution (pH 3.6), mixtures of artificial urine with Suby G (pH 3.9 and pH 4.1) in dissolving artificial struvite and apatite stones (Bon(n) stones) was investigated. The dissolution of natural infectious urinary stones was also measured. Additionally, investigations on shock-wave lithotripsy (SWL) combined with initial chemolytic treatment of the stones were performed. RESULTS: The efficacy of Suby G solution in dissolving artificial stones was demonstrated. Direct comparison of chemolysis of natural and artificial stones showed no statistical difference between infectious urinary stones and Bon(n) stones of the same material. The investigations on SWL showed a significant improvement on stone comminution, especially of artificial apatite stones after initial chemolytic treatment with Suby G. CONCLUSION: New basics to improve dissolution of infectious urinary stones have been developed by performing standardized in vitro investigations. Local chemolysis with Suby G is an effective tool in the treatment of infectious stone disease. SWL can be improved by varying the physical properties of infectious stones through initial treatment with Suby G solution.

Dermatome setting for autografts to cover INTEGRA.

Using the INTEGRA Dermal Regeneration Template requires the outer silastic layer to be replaced with an autograft. We followed the manufacturer's directions for epidermal autografting and frequently obtained shredded, useless grafts, therefore, it seemed important to determine the proper dermatome setting. We evaluated dermatome settings from 0.002 to 0.012 inches. First, with feeler gauges, we verified the dermatome settings. Second, we harvested skin at various dermatome settings and measured the thickness histologically. We found that 1) the dermatome settings are reasonably accurate; 2) harvesting useful sheets at 0.002 and 0.004 inches is virtually impossible; 3) the variability of histologic graft thickness is enormous; and 4) a dermatome setting of 0.006 inches yields useful grafts. We no longer use the term epidermal autografting but rather ultrathin split-thickness grafting. To harvest these grafts, we now merely set the dermatome to 0.006 inches and make whatever midcourse corrections are necessary to obtain translucent grafts.

Sleep disturbance after burn injury.

This study describes sleep disturbance and related factors in a group of 74 patients at 1 week after discharge using a sleep problems questionnaire developed by the authors. Results indicated that a significant proportion of patients reported a problem with their sleep (73%). Several items were identified as highly prevalent, including frequent nighttime awakenings (87%), napping during the daytime (65%), sleeping alone (64%), experiencing pain during the night (62%), and difficulties with sleep onset (62%). Results suggest numerous possible interventions to improve patients' sleep quality. The usefulness of a more extensive questionnaire was also indicated.

Cones of skin occur where hypertrophic scar occurs.

Hypertrophic scarring is devastating for the patient, however the pathophysiology and treatment remain unknown after decades of research. The process follows deep dermal injury, occurs only on certain body parts, does not occur in the early fetus or in animals, and is a localized event. This suggests that an anatomic structure in human, deep dermis may be involved. The dermis is a matrix perforated by cones containing many structures including skin appendages and fat domes. We hypothesized that studying the cones might reveal a structure related to scarring. We examined tangential wounds from various body parts on human cadavers along with skin histology from various human body parts, the early fetus, partial thickness burns, hypertrophic scars, and two other species-rats and rabbits. We found that the cones may in fact be the structure. They exist where hypertrophic scar occurs-cheek, neck, chest, abdomen, back, buttock, arm, forearm, dorsal hand, thigh, leg, dorsal foot, helix and ear lobe. They do not exist where hypertrophic scar does not occur-scalp, forehead, concha, eyelid, palm, early fetus, and in rat, or rabbit. It also became apparent that the cones have been omitted from most considerations of skin histology. We suggest that the cones need to be studied in relation to hypertrophic scarring and restored to skin diagrams.

The utility of a burn specific measure of pain anxiety to prospectively predict pain and function: a comparative analysis.

Patients treated for burn injuries commonly experience high levels of acute pain and anxiety during hospitalization, particularly as it relates to their dressing changes and other medical procedures. A new instrument, the burn specific pain anxiety scale (BSPAS), was designed to characterize patient's anxiety in this setting, but its predictive validity in relation to other measures of anxiety has yet to be demonstrated. In this study, 27 patients with acute burn injuries completed three measures of anxiety upon admission to a major medical burn trauma center. Scores on the anxiety measures were compared with regard to their ability to predict subsequent ratings of procedural and background pain levels, pain medication usage, and physical and emotional functioning upon discharge. In support of criterion-related validity, the BSPAS was the best predictor of procedural pain levels as rated later the same day relative to the other global anxiety measures; moreover, the BSPAS did not predict later-day background pain levels as hypothesized. Both the BSPAS and the global anxiety measures were found to significantly predict total number of pain medications over a 24-h period. Finally, the BSPAS was the only significant predictor of decreased physical role functioning at discharge whereas the other more global measures of anxiety were better predictors of emotional functioning. These results provide preliminary evidence that the BSPAS is a unique and valid indicator of pain-related anxiety surrounding burn care in hospitalized patients and may be useful in identifying those patients at risk for decreased functional capacity at the time of discharge.

Toxic epidermal necrolysis (TEN) in elderly patients.

Toxic epidermal necrolysis (TEN) is a severe exfoliative disease of the skin and mucous membranes that results in high mortality. As the elderly population increases, the number of elderly patients with TEN can also be expected to increase. Elderly patients with comparably sized burn wounds usually have a poor prognosis. Our purpose was to determine whether elderly TEN patients exhibit similarly high mortality. A retrospective review was conducted of 52 patients treated for TEN from October 1991 through September 1998. Eleven patients were older than 65 years. All patients were treated according to our TEN protocol. Eight of 11 patients recovered, and 3 died. The mean total body surface area (TBSA) involvement for the patients who recovered was 24%, compared with 66% for the nonsurvivors. The survival rate for elderly patients (73%) compares well with that for those younger than 65 years (89%). Therefore, we propose that we should be aggressive in treating elderly patients with TEN.

Prospective trial of thick vs standard split-thickness skin grafts in burns of the hand.

For best function and appearance, thick skin grafts for hands are generally preferred to thinner grafts. But how thick is thick enough? This prospective randomized trial was designed to compare 0.015-inch skin grafts for burned hands to hand grafts that are 0.025 inches thick. Consecutive patients receiving skin grafts to hands were randomized to have sheet grafts using donor sites of 0.015-inch or 0.025-inch thickness. To prevent delayed healing and potential hypertrophic scarring, the thick graft donor sites were grafted with 0.008-inch grafts. There were no significant differences in range of motion, final appearance, or patient satisfaction between the two groups at 1 year. There were problems with donor site healing in both groups. We recommend that hand grafts for adults be at least 0.015 inches thick but do not see an advantage to the use of very thick (0.025-inch) grafts, even with thin split-thickness skin grafts to the donor site.

Rates, trends, and severity of depression after burn injuries.

It is commonly assumed that patients hospitalized for burn treatment will experience some level of depression. However, little is known about the trends in severity of depression over time. The purpose of this study was to determine the rates and severity of depression over a 2-year period. The Beck Depression Inventory was administered at 1 month (N = 151), 1 year (N = 130), and 2 years (N = 125) after discharge. At 1 month, 54% of patients showed symptoms of moderate to severe depression, and at 2 years, 43% of the patients responding still reported moderate to severe depression. The average correlation between scores over time was high. Women had higher depression scores than men at each time period. An interaction between gender and having a head or neck injury was also observed at 1 month and 1 year after discharge. Results suggest that routine outpatient screening for depression is warranted.

Chemolysis of struvite stones by acidification of artificial urine--an in vitro study.

OBJECTIVE: The aim of the study was to look for strategies that improve the clinical outcome of struvite stones. An in vitro experimental set up with artificial stones made of struvite (BON(N)-STONES) was chosen to perform standardized and reproducible analyses on various artificial urines with pH-values that may be reached by acidification with oral methionine treatment. MATERIALS AND METHODS: Artificial ball-shaped stones made of struvite (BON(N)-STONES) with a diameter of 0.8 cm were used. The investigations on chemolysis were performed using a dissolution device which simulates the physiological conditions in the upper urinary tract with computer-assisted on line measurement of data. For chemolysis of struvite BON(N)-STONES artificial urines according to Griffith at four different pH-values (pH 5.75, pH 6.0, pH 6.25, pH 6.5) were used. Furthermore natural and struvite BON(N)-STONES were treated with Suby G-solution (pH = 4.0). RESULTS: Comparing natural and artificial struvite stones after treatment with Suby G there was no significant difference regarding their dissolution rate. The dissolution rate of struvite stones in artificial urine rose with a decreasing pH-value. The diminution of the pH-value from 6.5 to 5.75 lead to an increase of the dissolution rate of more than 35%. This increase in the dissolution rate decreased with falling pH-value. CONCLUSIONS: The acidification of urine accelerated the dissolution rate of struvite stones in vitro. Considering in vivo conditions the intake of 1,500-3,000 mg L-methionine may lead to a sufficient acidification for a good dissolution of struvite stones.

A new type of artificial urinary calculi: in vitro study by spiral CT.

RATIONALE AND OBJECTIVES: Artificial urinary calculi similar to natural stones have long been sought in urologic research. In an experimental study, the authors assessed the CT characteristics of a new type of artificially produced urinary calculus [BON(N)-STONE]. METHODS: Six different types of urinary calculi (uric acid, struvite, cystine, calcium oxalate, brushite, and apatite) were produced by a coating technique in which several layers of a suspension of pure substance were applied around a core and dried. A total of 60 stones (10 per group) were studied by spiral CT at two energy levels (100 and 120 kV, 250 mA) with 1-mm slice thickness. RESULTS: All calculi showed a small hyperdense core surrounded by a homogeneous matrix and a slightly hyperdense outer rim. From the least to the most dense, the stone types were uric acid, struvite, cystine, calcium oxalate, brushite, and apatite. Absolute CT values at 100 and 120 kV could differentiate between all groups of stones at a significance level of P < 0.001 or better. Attenuation values were in a comparable range to reported values for natural stones, with the exception of uric acid and struvite, which were notably lower. CONCLUSION: These artificially produced urinary calculi showed properties similar to those of natural stones. Thus, this seems to be a promising stone model for further investigations.

Influence of alkaline solutions on chemolitholysis and lithotripsy of uric acid stones. An in vitro study.

OBJECTIVES: This study was performed to look for an improvement of therapeutic strategies with regard to the treatment of uric acid stones using artificial stones made of uric acid (BON(N)-STONES) which are comparable to their natural counterparts. MATERIALS AND METHODS: Using an experimental arrangement simulating the physiological conditions in the upper urinary tract the efficacy of different alkaline solutions and artificial urine in dissolving artificial uric acid stones (BON(N)-STONES) was investigated. The dissolution of natural uric acid stones was measured and investigations on shock wave lithotripsy (SWL) combined with initial chemolytic treatment of the stones were performed. RESULTS: The efficacy of alkaline solutions, especially THAM at a pH of 10, in dissolving artificial uric acid stones was demonstrated. The investigations on SWL showed a significant improvement on stone comminution of artificial uric acid stones after initial chemolytic treatment with THAM. CONCLUSIONS: New basics to improve dissolution of uric acid stones have been developed by performing standardized in vitro investigations. The suggestion was confirmed that stone fragility and thus SWL can be improved by varying the physical properties of uric acid stones through initial treatment with THAM solution.