Molecular characterisation of the t(1;15)(p22;q22) translocation in the prostate cancer cell line LNCaP.

Although chromosome translocations are well-documented recurrent events in hematological malignancies and soft tissue sarcomas, their significance in carcinomas is less clear. We report here the molecular characterization of the reciprocal translocation t(1;15)(p22;q22) in the prostate carcinoma cell line, LNCaP. The chromosome 1 breakpoint was localized to a single BAC clone, RP11-290M5, by sequential FISH analysis of clones selected from the NCBI chromosome 1 map. This was further refined to a 580-bp region by Southern blot analysis. A 2.85-kb fragment spanning the der(1) breakpoint was amplified by long-range inverse PCR. The breakpoint on chromosome 1 was shown to lie between the CYR61 and the DDAH1 genes with the der(1) junctional sequence linking the CYR61 gene to the TSPAN3 (TM4SF8) gene on chromosome 15. Confirmatory PCR and FISH mapping of the der(15) showed loss of chromosome material proximal to the breakpoint on chromosome 15, containing the PSTPIP1 and RCN2 genes. On the available evidence we conclude that this translocation does not result in an in-frame gene fusion. Comparative expressed sequence hybridization (CESH) and comparative genomic hybridization (CGH) analysis, showed relative down-regulation of gene expression surrounding the breakpoint, but no gross change in genomic copy number. Real-time quantitative RT-PCR for genes around the breakpoint supported the CESH data. Therefore, here we may have revealed a gene down-regulation mechanism associated with a chromosome translocation, either through small deletion at the breakpoint or through another means of chromosome domain related gene regulation.

Long-term outcomes in patients with prostate cancer managed with intermittent androgen suppression.

OBJECTIVES: To assess the long-term outcomes of patients with prostate cancer managed with intermittent androgen suppression (IAS) following their enrollment in an open, non-randomised feasibility study initiated 10 years ago. PATIENTS AND METHODS: Patients with prostate cancer who developed marked side effects following androgen deprivation were considered for entry into the study. All patients were required to have been managed with androgen deprivation for a minimum of 9 months and to have achieved PSA remissions to levels <4 ng/ml or falls to greater than 90% of pre-treatment levels. Patients remained off treatment until PSA values rose to >20 ng/ml or individuals became symptomatic--at which stage a 9-month cycle of androgen suppression was repeated. Such on-off cycling continued until hormone-resistant disease developed and patients proceeded (off trial) to second-line therapies. RESULTS: 75 patients were recruited to the study following an initial referral with treatment-related side effects specifically associated with androgen deprivation. 86% of these remain alive at a median of 134 months (11 years) since initial histological diagnosis. Survival times and times to hormone resistance (from first cycle hormone deprivation) have also been calculated. Overall there is a median survival time of 95 months (8 years) from initial (first-cycle) androgen deprivation in those presenting with localised or locally advanced disease and a median survival time of 87 months (7 years) for those presenting with metastatic disease. There exists a median of 83 months to hormone resistance in the localised and locally advanced group and a median of 50 months in those presenting with metastatic disease. We have calculated a 100% 5-year actuarial survival rate for those presenting with localised or locally advanced disease (from time of first cycle hormone ablation) and a 70% 5-year actuarial survival rate for those presenting with metastatic. CONCLUSIONS: Long-term outcome figures and actuarial survival rates presented here provide further support for a pulsed or intermittent approach to androgen ablation in patients with prostate cancer. In addition, they serve as valuable extended outcome data for patients managed in this way. Likewise, data presented here suggests that apparent survival advantages appear related, at least in part, to a delay in the onset of androgen resistance and that such a management approach is both safe and effective in those presenting with both metastatic disease as well as those with more localised pathology.

Rectal strictures following abdominal aortic aneurysm surgery.

Rectal stricture formation is a rare complication of aortic aneurysm repair. Two case are described here. A combination of hypotension, a compromised internal iliac circulation and poor collateral supply following inferior mesenteric artery ligation can result in acute ischaemic proctitis--an infrequently described clinical entity. Ulceration and necrosis are the sequelae of prolonged ischaemia and fibrous stricture formation may result. One patient responded to dilatation and posterior mid-rectal myotomy; the other failed to respond to conservative measures and eventually had an end colostomy fashioned following intractable symptoms.

Lateral preputioplasty for phimosis.

There exists a lack of understanding of normal preputial development which is reflected in the large numbers of inappropriate referrals for circumcision. While the scarred prepuce invariably responds best to formal circumcision a more conservative approach is recommended in those symptomatic patients with non-retractile foreskins. In this study, patients referred to the out-patient department with a phimosis were assessed. Those with a phimosis and secondary preputial scarring were listed for circumcision. Those with a narrowed foreskin and a history of recurrent balanitis or local symptoms such as fissuration, thought suitable for a more conservative approach, were listed for preputioplasty. Those with a phimosis but without local symptoms were reassured and discharged. Thirty patients were referred for preputioplasty. One patient developed a post-operative wound infection which settled with oral antibiotics prescribed by his general practitioner. This left him with further preputial adhesions and he later underwent circumcision. The remaining patients reported no post-operative problems at follow-up. Cosmesis was good with high levels of patient satisfaction expressed. All had easily retractile foreskins at follow-up. Large numbers of patients might reasonably benefit from a lateral preputioplasty when presenting with a symptomatic phimosis in the absence of significant scarring of the prepuce. It avoids the needless loss of the foreskin, the importance of which is only now beginning to emerge.

Port-site metastasis after laparoscopic cholecystectomy for benign disease.

We describe the case history of a patient presenting with a port-site metastasis from an occult pancreatic malignancy after laparoscopy for benign gallbladder disease. While port-site recurrence is well recognized after laparoscopy for malignant disease, its presentation after laparoscopy for benign disease is rare, this being only the third such case to be reported in the literature. It emphasizes that all pathology localizing to port sites after surgery should be investigated, as it may represent the earliest sign of a hitherto occult intra-abdominal malignancy.

Family status, preference for sport aggressiveness, and sport fan motivation.

This study tested two hypotheses involving the use of sport spectating as an opportunity to spend time with one's family. First, it was hypothesized that scores on Family Motivation would be higher for fans who were married or had children than for unmarried fans without children. Second, it was predicted that among sport fans who were married or had children, those preferring a Nonaggressive sport would report higher scores on Family Motivation than those preferring an Aggressive sport. Analysis confirmed the first hypothesis while refuting the second.

Acute abdominal events and their impact on morbidity and mortality in a CAPD program.

A retrospective analysis was done to explore the impact of acute abdominal events other than peritonitis, on morbidity and mortality in a CAPD program over a span of 6 years. Subtlety of clinical manifestations and low yield from investigational attempts (except microbiologic) made decision-making as to whether or not to continue CAPD, hard. An increased prevalence of septicemic shock with its inevitable high risk of morbidity and mortality was striking. Timely termination of CAPD and change over to hemodialysis may help to prevent dissemination of infection in these patients. Among the vascular causes of death in CAPD patients, bowel infarction seemed to be the most common.