In order to identify novel candidates associated with prostate cancer metastasis, we compared the proteomic profile of the poorly metastatic human prostate cancer cell line LNCaP, with its highly metastatic variant LNCaP-LN3, by two-dimensional gel electrophoresis. A major protein spot (pI of 5.9 and molecular weight of 37 kDa) was seen in LNCaP cells, but not in LNCaP-LN3 cells and was identified as lactate dehydrogenase-B (LDHB), by tandem mass spectrometry. Furthermore, enzyme kinetic assays and zymography showed a higher LDH enzyme activity in LNCaP cells compared with LNCaP-LN3. Bisulphite-modified DNA sequencing showed promoter hypermethylation in LNCaP-LN3 cells but not in LNCaP, Du145, PC3, CWR22 or BPH45 cells. Treatment of LNCaP-LN3 cells with 5 0 -azacytidine caused reexpression of LDHB transcripts. In tissues, LDHB promoter hypermethylation occurred at a higher frequency in prostate cancer, 14/ 31 (45%), compared to adjacent nonmalignant or benign tissue, 2/19 (11%) (Po0.025). Immunohistochemistry showed a higher frequency of LDHB expression in benign or nonmalignant tissues, 59/ 73 (81%), compared to cancer cases, 3/53 (6%) (Po0.001). Absent LDHB expression was also seen in 7/7 (100%) cases of metastatic cancer in bone. Our data are the first to show loss of LDHB expression in prostate cancer, the mechanism of which appears to involve promoter hypermethylation.

Early cholecystectomy for patients with acute cholecystitis is safe, cost effective, and leads to less time off work compared with delayed surgery. This study was designed to assess current practice in the management of acute cholecystitis in the UK. A postal questionnaire was sent to 440 consultant general surgeons to ascertain their current management of patients with acute cholecystitis. Replies were received from 308 consultants who were involved in treating patients with acute cholecystitis of whom 18 transferred these patients on to another team for further management the day after admission. Thirty two consultants (11%) routinely treated patients by early cholecystectomy, with limiting factors stated to be the availability of surgical staff, theatre space, and radiological investigations. The remaining consultants (n = 258) routinely manage their patients conservatively with intravenous antibiotics and allow the inflammation to resolve before undertaking cholecystectomy at a later date. Indications for undertaking early cholecystectomy during the first admission by this latter group included the presence of spreading peritonitis due to bile leak, empyema, and unexpected space on theatre list. The commonest method for both elective and early cholecystectomy is laparoscopic, but the percentage of consultants using an open method rises from 8% in the elective situation to 47% for urgent early cholecystectomy. Despite evidence which strongly advocates early cholecystectomy, this practice is routinely carried out by only 11% of consultants in the UK at present. O pinions among surgeons regarding the optimum management of acute cholecystitis remain divided. Some advocate early cholecystectomy during the initial admission, whereas others prefer to treat patients conservatively in the first instance with intravenous fluids and antibiotics and undertake delayed elective cholecystectomy. Two randomised controlled trials of early versus delayed laparoscopic cholecystectomy in the management of acute cholecystitis have both shown early laparoscopic cholecystectomy to be safe and associated with lower rates of conversion and reduced total hospital stay compared with delayed surgery.1 2 In addition, the hazards of conservative management of acute cholecystitis in the UK, especially with regard to patient readmissions, have recently been highlighted.3 4 The aim of this study therefore was to assess current practice in the management of acute cholecystitis by general surgeons in the UK. METHODSA postal questionnaire was sent to 440 consultant general surgeons. They were asked to provide details of their on-call commitments, subspecialist interests, and the management of patients under their care with acute cholecystitis. In particular they were asked whether they routinely opted for early cholecystectomy during the first admission or preferred initial conservative management and delayed interval cholecystectomy. Surgeons opting for early cholecystectomy were asked which factors limited this practice, with those opting fo...

Promoter hypermethylation of circulating cell DNA has been advocated as a diagnostic marker for prostate cancer, but its prognostic use is currently unclear. To assess this role, we compared hypermethylation of circulating cell DNA from prostate cancer patients with (Group 1, n = 20) and without (Group 2, n = 22) disease progression and age‐matched controls (benign prostatic hyperplasia, Group 3, n = 22). We measured hypermethylation of 10 gene promoters in 2 sequential venous samples, obtained at diagnosis and during disease progression (median time, 15 months later). Matched time samples were obtained in the nonprogressing patients. We found that more hypermethylation was detected in the diagnostic sample from the patients with cancer than in controls for GSTP1, RASSF1a, APC and RARβ (p < 0.0001). Patients undergoing disease progression had a significant increase in methylation levels of these 4 genes when compared to the other patients (p < 0.001). Patients at risk of disease progression have higher detectable concentrations of circulating cell hypermethylation, than those without progression. The extent of this hypermethylation increases during disease progression and can be used to identify the extent and duration of treatment response in prostate cancer. © 2007 Wiley‐Liss, Inc.

The use of screw fixation in the ilium as a means of spinopelvic anchorage is safe and effective in the treatment of neuromuscular scoliosis. The use of 2 screws in each iliac wing provides more stable fixation with fewer implant-related complications than using a single screw.