Circulating microRNAs predict biochemical recurrence in prostate cancer patients.

BACKGROUND: Circulating microRNAs (miRNAs) are emerging as promising biomarkers for prostate cancer. Here, we investigated the potential of these molecules to assist in prognosis and treatment decision-making. METHODS: MicroRNAs in the serum of patients who had experienced rapid biochemical recurrence (BCR) (n=8) or no recurrence (n=8) following radical prostatectomy (RP) were profiled using high-throughput qRT-PCR. Recurrence-associated miRNAs were subsequently quantitated by qRT-PCR in a validation cohort comprised of 70 patients with Gleason 7 cancers treated by RP, 31 of whom had undergone disease progression following surgery. The expression of recurrence-associated miRNAs was also examined in tumour tissue cohorts. RESULTS: Three miRNAs - miR-141, miR-146b-3p and miR-194 - were elevated in patients who subsequently experienced BCR in the screening study. MiR-146b-3p and miR-194 were also associated with disease progression in the validation cohort, as determined by log-rank tests and Cox proportional hazards regression. Multivariate analysis revealed that miR-146b-3p possessed prognostic information beyond standard clinicopathological parameters. Analysis of tissue cohorts revealed that miR-194 was robustly expressed in the prostate, elevated in metastases, and its expression in primary tumours was associated with a poor prognosis. CONCLUSION: Our study suggests that circulating miRNAs, measured at the time of RP, could be combined with current prognostic tools to predict future disease progression in men with intermediate risk prostate cancers.

Elevated levels of peritumoral chondroitin sulfate are predictive of poor prognosis in patients treated by radical prostatectomy for early-stage prostate cancer.

The disease course of localized prostate cancer is highly variable, and patients potentially curable by aggressive management are not readily identified by current clinical practice. Chondroitin sulfate (CS) glycosaminoglycan is a candidate biomarker as elevated levels of CS in peritumoral stroma of prostate cancer have been associated with prostate-specific antigen (PSA) failure. Immunoreactive CS was measured using image analysis of archived radical prostatectomy tissues, obtained from 157 men with a median of 47 months (range, 16-111 months) clinical follow-up. CS level, Gleason score, and preoperative serum PSA levels were independent predictors of PSA failure by Cox's multivariate analysis. Patients with low CS levels had significantly fewer PSA failures after radical prostatectomy than patients with high levels of CS (Kaplan-Meier plot; 32% PSA failures at 5 years for CS mean integrated absorbance cut point < 7.0 versus 50% for CS > or = 7.0, P = 0.0001). In the subgroup of patients with preoperative serum PSA levels < 10 ng/ml, CS was particularly useful in discriminating retrospectively those patients most suited for surgery (Kaplan-Meier plot; 14% PSA failures at 5 years for CS mean integrated absorbance cut point < 7.0 versus 47% for CS > or = 7.0, P = 0.0001). We conclude that measurements of CS level can assist in predicting patient outcome after surgery. Additionally, our data suggest that the combination of CS and PSA measurements may improve outcome prediction for patients with intermediate Gleason scores.

Laparoscopic exploration for a presumed intra-abdominal testicle.

Removal of intra-abdominal testes in patients over the age of 10 years is recommended because of the small risk of subsequent malignant change. We report an experience in a 35-year-old male with no testicle in his left scrotum in whom an ultrasound scan demonstrated a 3 x 4 cm mass at the left internal ring. At laparoscopy, by delineating the landmarks of the left vas and the left testicular vessels, it was possible to confirm the presence of a testicle at the internal ring; atrophic epididymal material was confirmed histologically. Laparoscopic exploration in this patient permitted a thorough examination of the abdominal cavity for an undescended left testicle and required admission for less than 24 hours. We conclude this procedure is the approach of choice in patients with suspected intra-abdominal testes.

A comparative treatment trial of endometriosis using the gonadotrophin-releasing hormone agonist, nafarelin, and the synthetic steroid, danazol.

A randomized and double-blind trial was carried out comparing intranasal nafarelin acetate (400 micrograms daily) and oral danazol (600 mg daily), given over 6 months, in the treatment of 49 patients with laparoscopically proven endometriosis. Both drugs produced a highly significant and similar reduction (of 60 to 70%) in objective American Fertility Society scoring, even in severe disease. No effect was seen on adhesions. Both drugs suppressed oestradiol levels to a similar extent, although nafarelin caused a substantial rise in the first 2 weeks after the initiation of therapy. Nafarelin suppressed LH substantially and FSH, testosterone and prolactin to a small degree, whereas FSH and LH increased slightly during danazol. Pregnancies occurred in 12 of 22 infertile women in the 12 months following nafarelin, and in 6 of 14 in the danazol group. Side-effects were reported at a similar rate with both drugs, but the pattern was different. Hot flushes were the predominant side effect with nafarelin, although oestradiol levels were not suppressed to the extent expected. Small amounts of spotting or light bleeding were experienced with both drugs, but these tended to decrease with time with nafarelin and increase with danazol.

Outpatient gamete intrafallopian transfer: a clinical analysis of 710 cases.

From February 1986 to June 1989 445 infertile couples were treated with a total of 710 treatment cycles involving laparoscopic gamete intrafallopian transfer (GIFT). The median age of the female partner was 33.5 years (range, 24 to 49 years) and the median duration of infertility was 4 years (range, 2 to 20 years). The final outcome of all 217 clinical pregnancies is known. There were 150 live births among which all but one baby survived, comprising 112 singleton births, 28 twin births, nine triplet births and one quadruplet birth. There were no still births, but there were two premature, multiple live births (one triplet, one quadruplet) among which no babies survived the neonatal period. Overall, 40 of the 152 potentially viable pregnancies were multiple (26.3%). Three of 206 potentially viable babies were born with congenital anomalies (1.5%). There were 50 clinical spontaneous abortions (24.8% of uterine pregnancies), one termination of pregnancy for Down's syndrome, and 14 ectopic pregnancies rate was 30.6% per laparoscopy and, among 740 initiated cycles, a live and surviving birth-per-initiated-cycle rate of 20.2%, or 33.7% to date per couple entering the programme. The 710 laparscopies resulted in two serious complications (0.3%), one of which required laparotomy. Eight other patients were admitted to hospital for rest and observation because of painful ovarian enlargement in the luteal phase. The total inpatient admission rate was 1.4%. Outpatient laparoscopic GIFT under general anaesthesia is a safe and effective procedure when conventional treatment for infertility has been unsuccessful.

Urethral stricture after cardiac surgery.

During January and February 1980 there was an epidemic of urethral strictures at the Royal Adelaide Hospital. These strictures all occurred in men undergoing coronary artery bypass surgery. The strictures were inflammatory in nature and the patients were assessed to determine if a common aetiological factor could be identified. Follow-up has reaffirmed that inflammatory strictures are difficult to treat. Only half of the patients responded to conservative treatment; the only factor which appeared to influence the outcome of treatment was the time taken for a patient to present because of his symptoms.