Hans Hedelin

FOUR BLADDER TUMOR MARKERS HAVE A DISAPPOINTINGLY LOW SENSITIVITY FOR SMALL SIZE AND LOW GRADE RECURRENCE

PURPOSE We determine the sensitivity and specificity of 3 bladder tumor markers in urine, including NMP22 assay (Matritech, Newton, Massachusetts), BTA stat test (Bion Diagnostic Sciences, Inc., Redmond, Washington) and UBC antigen (IDL Biotech, Sollentuna, Sweden), and bladder wash cytology for new and recurrent bladder cancer. We examine whether tumor size, grade, and stage influence sensitivity and specificity of the markers. MATERIALS AND METHODS A total of 304 samples in 250 patients were studied. There were 174 patients who had a history of bladder cancer, including 93 with and 81 without recurrent tumor at cystoscopy. The other group of patients consisted of 66 with newly diagnosed bladder tumor and 64 investigated for microscopic hematuria that was found to be idiopathic. BTA stat was assayed according to manufacturer instructions. NMP22 and UBC were measured in urine with an enzyme-linked immunosorbent assay. A cutoff level of 4 for NMP22 and 1 for UBC was chosen to get the same specificity for new tumors as BTA stat (75%) RESULTS There was a highly significant difference (p <0.001) in all markers between patients with new bladder tumors and those without. The difference was less pronounced for tumor recurrence for NMP22, UBC and BTA stat (p=0.002, 0.016 and 0.244, respectively). The difference between new and recurrent tumors disappeared when corrected for tumor size, grade and stage. The sensitivity for new tumors was 65%, 75% and 60% for NMP22, BTA stat and UBC, respectively. Cytology had a sensitivity of 41% for new tumors at a specificity of 94%. The specificity for recurrence was 64% for NMP22, 54% BTA stat and 72% UBC. The sensitivity was 45% for NMP22, 55% BTA stat and 40% UBC. CONCLUSIONS Tumor size, grade and stage have a strong impact on sensitivity, and specificity for all 3 tested tumor markers as well as bladder wash cytology. The tumor markers or any combination of them cannot replace followup cystoscopy, mainly because most recurrences are small. The role of the markers for screening high risk populations and as a complement to followup cystoscopy remains to be evaluated.

Combined treatment with temporary short-term high dose rate Iridium-192 brachytherapy and external beam radiotherapy for irradiation of localized prostatic carcinoma

PURPOSE To evaluate the treatment outcome after radical radiotherapy of localized prostate cancer in 50 patients (38 patients with stage T1-2 and 12 patients with stage T3) after a median follow-up time of 45 months (range 18-92 months). METHODS The treatment was given by combination of external beam radiotherapy (50 Gy) and brachytherapy (2 x 10 Gy). The brachytherapy was given using TRUS-guided percutaneously inserted temporary needles with a high dose rate remote afterloading technique with Ir-192 as the radionuclide source. Three target definitions and dose levels inside the prostate gland were used. Local control was evaluated by digital rectal examination, TRUS-guided biopsies and serum PSA evaluations. RESULTS Clinical and biopsy verified local control was achieved in 48 of the 50 (96%) patients; for stage T1-2 in 37 of 38 (97%) patients and for stage T3 in 11 of 12 (92%) patients. A posttreatment serum PSA level < or =1.0 ng/ml was seen in 42 (84%) patients, values from >1.0 to < or =2.0 ng/ml were seen in four (8%) patients and values exceeding 2.0 were seen in four (8%) patients. The late toxicity was minimal. CONCLUSION The local control results and the minimal toxicity after the combined radiotherapy treatment are promising. However, long term results are necessary before general use.

IRRADIATION OF LOCALIZED PROSTATIC CARCINOMA WITH A COMBINATION OF HIGH DOSE RATE IRIDIUM-192 BRACHYTHERAPY AND EXTERNAL BEAM RADIOTHERAPY WITH THREE TARGET DEFINITIONS AND DOSE LEVELS INSIDE THE PROSTATE GLAND

PURPOSE Localized prostate cancer was treated with combined external beam radiotherapy and high dose rate Ir-192 brachytherapy with the purpose of a high dose. The technical aspects of a modified treatment are described. METHODS The brachytherapy was given in two sessions preceded and succeeded by external beam radiation. The radioactive source was temporarily implanted by a remote afterloading device through six to 15 needles inserted transperineally guided by transrectal ultrasound. The entire prostate gland was included in the clinical target volume. The urethra and the tumour volume could be defined and irradiated to different dose levels in more than 90% of the patients. RESULTS Fifty-four patients were treated. The total dose to the prostate was approximately 70 Gy and to the tumour volume 80 Gy. By calculating the corresponding dose given by 2.0 Gy fractions, considering the radiobiology by using the LQ formula and assuming an alpha/beta value for prostate tissue of 10, the dose to the prostate was approximately 84 Gy and to the tumour volume 112 Gy. For the late effects to the urethra an alpha/beta value of 3 was used, which corresponds to 85 Gy. The brachytherapy could be given with accuracy except when the dorsal border of the prostate was concave. The dose distribution then tended to be less satisfactory. Post-treatment calculations showed that the maximum dose to the rectum was 67 Gy (radiobiologically corrected to 88 Gy), given in a small volume. The early side effects from the brachytherapy were minimal. The treatment could not be performed as intended in four patients; three patients had a narrow pelvis and in one patient the prostate was unusually resilient, preventing the needles from being positioned properly. CONCLUSIONS This modification of a previously reported brachytherapy technique for prostate carcinoma permits a high radiation dose to the tumour and to the prostate gland, which ultimately may improve local control.

LONG-TERM FOLLOWUP OF A BLADDER CARCINOMA COHORT: ROUTINE FOLLOWUP UROGRAPHY IS NOT NECESSARY

PURPOSE We evaluate whether routine excretory urography is needed in the long-term followup of patients with bladder carcinoma. MATERIALS AND METHODS A total of 680 patients with an initial diagnosis of bladder carcinoma from 1987 to 1988 in western Sweden were prospectively registered and followed for at least 5 years. All carcinomas of the kidney, renal pelvis and ureter, and all surgically treated cases of ureteral stricture were registered. RESULTS During followup renal pelvic or ureteral carcinoma developed in 16 patients, renal cell carcinoma was diagnosed in 2 and 6 underwent surgery for benign obstruction of the distal ureter. CONCLUSIONS The low annual incidence of malignant upper urinary tract and renal tumors as well as ureteral strictures supports our opinion that routine imaging of the upper urinary tract is not indicated during followup of patients with bladder carcinoma. We recommend urography at initial diagnosis of bladder carcinoma, when tumor progression occurs and when symptoms or signs raise suspicion of upper urinary tract disease.

Newly diagnosed bladder cancer: The relationship of initial symptoms, degree of microhematuria and tumor marker status

PURPOSE We recorded initial symptoms and evaluated the frequency and intensity of hematuria in patients with newly diagnosed bladder cancer. We also evaluated and compared the sensitivity of bladder wash cytology, NMP22 (Matritech, Newton, Massachusetts), BTA Stat (Bion Diagnostic Sciences, Redmond, Washington) and UBC antigen (IDL Biotech, Sollentona, Sweden) with hematuria dipsticks and flow cytometry for determining the size of erythrocytes in urine. MATERIALS AND METHODS Urine samples were collected from 92 patients with newly diagnosed bladder cancer, 64 with idiopathic microhematuria and 42 with nephritis. Urine was analyzed for NMP22, BTA Stat, UBC and erythrocytes size using flow cytometry. Bladder wash cytology was done at cystoscopy. Urine was analyzed for microhematuria with hematuria dipsticks at home for 7 consecutive days immediately before the operation and in the hospital on the day of surgery. RESULTS Sensitivity was 75% for NMP22, 78% for BTA Stat, 64% for UBC and 61% for flow cytometry at 73% specificity. Cytology had 42% sensitivity at 97% specificity. Tumor size, grade and stage had a statistically significant influence on NMP22, BTA Stat, UBC and cytology. Of the patients 75% had microhematuria on the day of the operation and 75% had hematuria at least 1 of 7 days when tested at home the last week before transurethral bladder resection. The 70% of all patients with macroscopic hematuria as the initial symptom did not seem to differ from those without the condition in tumor size, grade, stage or tumor marker levels. CONCLUSIONS Flow cytometry was not well enough able to distinguish patients with bladder cancer from controls. The sensitivity of all tested markers, including hematuria dipsticks, was high for large and high grade, high stage tumors. Further studies are needed to evaluate whether a marker could be used to determine priority among patients referred due to microhematuria.

Abdominal injuries in children: an analysis of 348 cases

Three hundred and forty-eight children from Skaraborg County, Sweden, admitted to hospital with abdominal injuries over a 30-year period (1951-1980), have been analysed and compared with all patients with abdominal injury (1407) admitted to hospital from the same area during the same period. The number of children admitted in the second half of the period was greater than during the first but the proportion of children compared with adults was considerably reduced. During the period abdominal injuries due to car accidents increased in adults but not in children. The most frequent cause of abdominal injury in children was a bicycle accident. Abdominal injury due to sport also increased over the period. Mortality decreased, with no deaths in the past 10 years, compared with 8.6 per cent mortality in the first 10 years of the period.

Adherence of urease-induced crystals to rat bladder epithelium.

SummaryApart from urine supersaturation with respect to struvite and calcium phosphate caused by urease-producing microorganisms, retention of formed crystals in the urinary tract is necessary for the formation of infection stones. This study was performed to investigate the role of the mucous coat lining the urothelium in the adhesion of urease-induced crystals. Removal of this glycosaminoglycan-containing layer from rat bladders increased the adherence of struvite and calcium phosphate crystals 5–6 times compared to that in intact rat bladders. Heparin completely restored the anti-adherence capacity while chondroitin sulphate had a very weak restorative effect and human urine had no restorative effect. These findings support the view that the mucous coat is of importance in preventing retention of urease-induced crystals.

The effects of urease in undiluted human urine.

Undiluted human urine and synthetic urine were inoculated with urease. No inhibitory activity against urease enzymatic activity could be detected in human urine. The urease-induced crystallization of both calcium phosphate and magnesium ammonium phosphate differed markedly, however, between the individuals studied, and it was less pronounced in human urine than in synthetic urine. This supports the observation made in experiments using diluted urine that human urine possesses an inhibitory activity against urease-induced crystallization and suggests that it has a large interindividual variation.

Abdominal injury from sporting activities

The frequency of abdominal injury is rising. In an analysis of 1,354 cases of closed abdominal trauma sustained during a 30-year period (1950-1979) in Skaraborg County, Sweden, a distinct increase was found in the numbers associated with sporting activities. The severity of the injuries caused by sports likewise showed an increase. The representation of injured organs was of the same order as in the total series of closed abdominal injuries. An analysis of the 136 cases of sports-associated injury is presented with regard to cause and type of the injuries, diagnosis and prognosis.

Analysis of Stone Fragility in Vitro and in Vivo With Piezoelectric Shock Waves Using the Edap LT-01

A total of 100 whole stones was fragmented in vitro at 3-minute intervals with piezoelectric shock waves using the EDAP LT-01 device until all fragments were less than 2 mm. Larger stones and stones with a high computerized tomography attenuation needed longer treatments for fragmentation. Smoothly bulging stones with an even structure according to plain x-ray films were also more resistant to the shock wave treatment. Calcium oxalate monohydrate stones were not more difficult to break than other types of calculi. Stone fragments from 100 patients after extracorporeal shock wave lithotripsy were also analyzed. The average size of the fragments collected was less than 1 mm. Larger stones produced larger fragments and required more treatment sessions.