Expression of MAGE-A3, NY-ESO-1, LAGE-1 and PRAME in urothelial carcinoma.

BACKGROUND: The potential for cancer-testis (CT) antigens as targets for immunotherapy in cancer patients has been heavily investigated, and currently cancer vaccine trials based on the CT antigens, MAGE-A3 and NY-ESO-1, are being carried out. METHODS: We used specific q-RT-PCR assays to analyse the expression of the CT genes MAGE-A3, NY-ESO-1 (CTAG1B), LAGE-1 (CTAG2) and PRAME in a panel of bladder tumours from 350 patients with long-term follow-up and detailed treatment information. RESULTS: Overall, 43% of the tumours expressed MAGE-A3, 35% expressed NY-ESO-1, 27% expressed LAGE-1 and 20% expressed PRAME. In all, 56% of the tumours expressed at least one of the CT genes analysed. Univariate Cox regression analysis of CT gene expression in non-muscle-invasive tumours showed that expression of MAGE-A3 (P=0.026), LAGE-1 (P=0.001) and NY-ESO-1 (P=0.040) was significantly associated with a shorter progression-free survival. In addition, we found that patients with tumours expressing PRAME responded poorly to chemotherapy (P=0.02, χ(2)-test). CONCLUSION: Cancer-testis genes are frequently expressed in bladder cancer and especially in tumours of high stage and grade. In addition, the CT gene expression may have both prognostic and predictive value. Development of specific immunotherapy against the CT antigens in bladder cancer may ultimately increase patient survival.

Long term follow-up of superficial invasive bladder carcinoma with or without concomitant epithelial atypia--recurrence and progression.

OBJECTIVE: To examine the significance of concomitant epithelial atypia on late recurrence and progression by long-term follow-up of superficial invasive bladder tumours (stage T1). MATERIAL AND METHODS: Seventy consecutive, unselected patients with newly diagnosed transurethral resection (TURB)-treated stage T1 bladder tumour, and at least 1 year progression-free survival. Preselected site biopsies (PSB) were obtained prospectively to evaluate the significance of concomitant urothelial atypia. Followed for up to 17.6 years. RESULTS: The cumulative probability of recurrence (overall) was 85%, and for new stage T1 tumour 70% after 10 years. Forty per cent of those who survived 5 years without recurrence, were readmitted with often invasive recurrence later. Positive PSB significantly (p < 0.0001) predicted new T1 tumour. Progression (T2+ or metastases) occurred in 27 cases (39%) after the first year. The cumulative probability was 60% (15 years), with a mean progression-free interval of 64 months. Positive PSB, size >3 cm and early recurrence were significant predictive factors in multivariate analysis. CONCLUSION: T1-tumours are at high risk for late invasive recurrence and progression, especially if associated with urothelial atypia elsewhere in the bladder.

Long-term follow-up of noninvasive bladder tumours (stage Ta): recurrence and progression.

OBJECTIVE: To evaluate long-term recurrence-free and progression-free survival of noninvasive bladder tumours (stage Ta), and the significance of simple risk factors, including concomitant epithelial dysplasia. PATIENTS AND METHODS: The study included 217 patients with primary noninvasive bladder tumour (stage Ta) who were followed routinely for up to 20 years. Voided urine cytology (VUC) and preselected site biopsies (PSB) were obtained prospectively to evaluate the significance of concomitant epithelial dysplasia. RESULTS: The mean follow-up was 84 months (maximum 238). Of all tumours, 39% did not relapse, a further 20% recurred infrequently (less than once a year) and 41% recurred frequently, amongst which the most frequent were multiple and early recurrent tumours; 42 (19%) tumours progressed to stage T1+ and 23 (11%) progressed further (stage T2+ or metastases). No grade 1 tumours became invasive. Positive VUC or PSB, a short recurrence-free period or multiplicity, and size > 3 cm were significant predictive factors. The treatment and surveillance of epithelium-confined bladder tumours are discussed. CONCLUSION: Concomitant dysplasia and early recurrence are associated with considerable risk of progression in the long-term follow-up in a group of otherwise low-risk superficial bladder tumours (stage Ta).

[Complications after surgery for pilonidal cyst. An introduction to a new debate on a "costly" disease]. / Komplikationer efter operation for cystis pilonidalis. Oplaeg til ny debat om en "kostbar" sygdom.

The frequency of wound complications following operation for pilonidal disease in our department was compared with results from the literature. The case-records of 88 consecutive patients operated for 100 sinuses (12 recurrences), were evaluated retrospectively, supplemented by a questionnaire. Wound healing problems occurred in 69% of the sutured sinuses. Length of hospitalization was two days in uncomplicated, five days in complicated, and eight days in open treated cases. Convalescence (days off work) took 25 days, 41 days and 26 days, respectively. There was no correlation between previous history of pilonidal disease, wound healing complications, and outcome (recurrence frequency). Relapses occurred in 18%. In conclusion, the closure of pilonidal sinuses had a high frequency of wound healing complications and recurrences.

Long-term survival of patients with bladder tumours: the significance of risk factors.

OBJECTIVE: To evaluate the significance of known risk factors, accessible by simple endoscopic and histological/cytological examination, on the clinical course and long-term survival of patients with superficial urinary bladder tumours. PATIENTS AND METHODS: The study included 584 consecutive unselected patients, primarily admitted between 1976 and 1984 for newly diagnosed bladder tumour, which was superficial (Ta, T1, Tis) in 362. The patients were followed routinely in a control programme; causes of death were obtained by autopsy (44%), from hospital files (33%) or from death certificates (8%), the remaining patients being alive at the end of the study, up to 20 years after initial diagnosis. Known risk factors, e.g. tumour size, histological grade, multiplicity and positive urine cytology, and dysplasia as assessed by random or pre-selected site biopsies, were evaluated as predetermining factors for new occurrences and survival. RESULTS: Invasion of the lamina propria was the most significant prognostic factor detected in the multivariate analysis. While 14% of patients with Ta tumours had died from cancer after 15 years, 63% of the T1 tumours were eventually fatal, reaching the mortality of those with T2 disease. Other independent significant factors were tumour size and, to a lesser extent, histological grade. Multiplicity and concomitant epithelial changes, as assayed by voided urine cytology and pre-selected site biopsies, were relevant prognostic factors for Ta but not for T1 tumours. CONCLUSION: In the therapy and surveillance of superficial urinary bladder tumours, the presence of lamina propria invasion is very important.

[Fractures following accidental falls among the elderly in the county of Aarhus]. / Frakturer efter faldulykker hos aeldre i Arhus Amt.

The incidence rates of common fall-related fractures were investigated in a Danish population of elderly people (> 64 years). One thousand one hundred and eighty fractures in 1016 patients were observed. About 26/1000 suffered a fracture per year, 47% being hip fractures, and 33% fractures of the wrist. Incidence rates increased with age, most markedly for fractures in the weight-bearing skeleton (hip, pelvis and vertebral column). Patients with a fall-related fracture had a four times higher risk of getting a new fracture. Increased mortality, adjusted for age and sex, ranged from 10 to 30 percent in the first year; except for fractures of the wrist, which were not associated with increased mortality.

[Cepstrum analysis in voice disorders]. / Cepstrumanalyse bei Stimmerkrankungen.

Objective data and reproducible procedures are increasingly demanded for assessment and long-term comparison in voice disturbances. Well-known electroacoustic methods like formant analysis, autocorrelation and inverse filtering have been applied for this purpose, though without leaving experimental stage. The cepstrum analysis presented here permits an easy and distinct separation of glottal pitch and filter function of the vocal tract. In this study, 112 normal and hoarse voices were analyzed. The sum of amplitudes of the first cepstral pitch peaks differed significantly between the different degrees of hoarseness (0-3). Disturbances producing hoarseness, however, could not be sufficiently differentiated by the method in its present state.