Genetic instability in incidentally discovered and advanced prostate cancer.

OBJECTIVE: To investigate the frequency of microsatellite instability, a marker for genetic instability, in incidental and advanced prostate cancers, and to determine the role and prognostic importance of genetic instability in prostate carcinogenesis. PATIENTS AND METHODS: Microsatellite analysis was performed on 72 prostate cancers, of which 26 were incidentally discovered at transurethral prostatectomy (TURP) for benign disease. They were staged and graded 1-3 according to glandular differentiation. Fresh prostatic tissue was obtained at TURP performed for bladder outlet obstruction, from 43 patients (median age 73 years, range 55-88), with tissue from the remaining 29 (median age 75, range 53-83) patients obtained from pathology archives, having been originally collected at TURP between 1969 and 1986. RESULTS: Instability was detected in 14 (19%) cancers overall, in eight (31%) of 26 incidental tumours and in six (13%) of 46 clinically apparent tumours. These differences were not statistically different (2P=0.1). The time to progression and survival were similar between men with tumours showing instability and those with no instability. CONCLUSION: These data suggest that genetic instability is an early event in prostate carcinogenesis, but does not appear to influence prognosis.

Patients' tolerance of transrectal ultrasound-guided prostatic biopsy: an audit of 104 cases.

OBJECTIVE: To determine the frequency and severity of complications following transrectal ultrasonography (TRUS) guided prostatic biopsy, and of pain during the procedure. PATIENTS AND METHODS: The study included 129 men undergoing TRUS-guided prostatic biopsy who were asked to complete a questionnaire about pain and complications one week after biopsy. RESULTS: Of the 104 men who completed the questionnaire, 24% found the procedure moderately to extremely painful and 19% felt that they had had significant complications afterward, the commonest of these being painful or difficult voiding (13%) and haematuria (11%). Systemic symptoms of fever or 'sweats' occurred in 6%, with a diagnosis of septicaemia in three men, despite antibiotic prophylaxis. However, acute urinary retention occurred in only one man. Of all patients, 20% saw their general practitioner within a week, all of whom were prescribed antibiotics in addition to those given prophylactically in hospital. CONCLUSION: TRUS-guided biopsy is often a painful experience for patients and is commonly associated with complications, particularly voiding difficulties. Of particular concern were the three patients with septicaemia, and that one in five men felt sufficiently unwell to visit their doctor within a week of the procedure.

Two novel regions of interstitial deletion on chromosome 8p in colorectal cancer.

We have investigated interstitial deletions of chromosome 8 in 70 colorectal carcinomas and 11 colonic adenomas using 11 microsatellite markers, including eight spanning the centromeric region of chromosome 8p (p11.2-p12). Allelic loss or imbalance was observed in 38 (54%) cancers and four (36%) adenomas. Twenty-eight (40%) of the cancers had deletions of 8p11.2-p12. Two distinct and independent regions of interstitial loss were found within this region. Fluorescent in situ hybridization, using an alpha satellite repeat probe to the centromere of 8p and two probes to the P1 region, was performed in four tumours that demonstrated allelic imbalance. Localized heterozygous deletions were confirmed in all four tumours. Eleven (16%) cancers had localized deletion in the region ANK-1 to D8S255 (P1) and a further eleven (16%) cancers had a less well localized deletion in the region defined by the markers D8S87 to D8S259 (P2). Loss of both centromeric loci was identified in a further six (9%) tumours. A functional significance for these two deletion regions was sought by correlation with primary and secondary tumour characteristics. Isolated P2 deletion was associated with 'early' T1 cancers (2p=0.0002), and were also identified in 3/11 adenomas. Conversely, interstitial deletions of the P1 locus were more frequently seen in 'locally invasive' T3/4 cancers (2p=0.015), and isolated P1 deletions were also associated with the presence of liver metastases (2p=0.016). Our data provide evidence of at least two genes within the 8p11.2-p12 region, mutations in which may confer different and independent roles in the pathogenesis of colorectal cancer.

Genetic alterations in incidentally diagnosed, transitional zone prostate cancer: a seven year follow-up.

PURPOSE: To investigate the frequency and prognostic significance of genetic alterations in incidentally diagnosed, transitional zone prostate cancer. MATERIALS AND METHODS: Twenty-six incidentally diagnosed, transitional zone cancers were examined by the PCR for genetic alterations on chromosomes 8p and 13q and by immunohistochemistry for alterations of the expression of the cell-cycle regulatory proteins RB1 and p53 and of the cell adhesion molecules E-cadherin and alpha-catenin. RESULTS: All of the tumors had at least one molecular abnormality (median 2.0 range 1 to 4). Allelic loss on 8p occurred in 37% and on 13q in 50% of informative tumors. Abnormal expression of pRb was found in 67%, of p53 in 33%, of E-cadherin in 36% and of alpha-catenin in 43%. In addition microsatellite instability was found in 23% of tumors. Only loss of expression of alpha-catenin was found to have prognostic importance. CONCLUSIONS: Genetic alterations were common, but, apart from alpha-catenin, did not appear to be related to tumor progression. The lack of prognostic significance is likely to be due to the multifocal nature of prostate cancer, but may also relate to qualitative differences between transitional zone and peripheral zone prostate cancers.

Allelic loss on chromosomes 8p, 22q and 18q (DCC) in human prostate cancer.

Previous studies have suggested the involvement of tumour-suppressor genes on chromosomes 8p, 22q and 18q (DCC) in prostate cancer. The aim of this study was to further characterize these regions. We investigated 20 polymorphic regions on the 3 chromosome arms in 43 cancers and 10 cases of benign prostatic hyperplasia (BPH). Allelic loss was observed in 72% of cancers on 8p, 16% on 22q and 24% at DCC. For BPH, loss was observed in 20% on 8p and in 12% at DCC. The low incidence of LOH on 22q implies that this locus has no significant role in prostate carcinogenesis. At DCC, although the overall incidence was low, tumours with LOH were mostly of high grade or had metastases, suggesting a role for this gene in prostate cancer progression. On chromosome 8p, 29% of cancers had deletions at the LPL locus on 8p22 and 60% had deletions within a region flanked by the markers D8S339 and ANKI on 8p 11.1-p21.1. Within this region, 2 distinct areas of allelic loss were observed, at one or both ANKI and D8S255, and in the region defined by the markers D8S259-D8S505. For the regions 8p22 and ANKI-D8S255, tumours with metastases had a greater frequency of LOH compared to non-metastasizing tumours, suggesting the presence of putative metastasis-suppressor genes in these regions.

Monitoring the introduction of laparoscopic cholecystectomy in a district general hospital.

There has been recent concern regarding the widespread introduction of laparoscopic procedures without adequate training. We report a 2 year prospective series of 229 consecutive open and laparoscopic cholecystectomies, following the introduction of laparoscopic surgery at a district general hospital. All laparoscopic cholecystectomies were performed by surgeons without formal training in this procedure. The proportion of laparoscopic cholecystectomies rose from 27% in 1992 to 62% in 1993, with a conversion rate of 14%. An overall complication rate of 23% was recorded, 29% for open cholecystectomy and 16% for laparoscopic cholecystectomy. Procedure specific complication rates were 6% and 3% respectively. No major bile duct injuries occurred and the 30-day mortality was 0.9%. We conclude that laparoscopic cholecystectomy has been introduced as a safe procedure in this hospital, as compared to open cholecystectomy. It is recommended that new techniques should be introduced carefully and monitored by means of prospective audit.