Identification of a recurrent t(4;6) chromosomal translocation in prostate cancer

PURPOSE: We developed and describe a practical method by which primary prostate cancer specimens can be screened for recurrent chromosomal translocations, which is a potential source of fusion genes, as well as a process by which identified translocations can be mapped to define the genes involved. MATERIALS AND METHODS: A series of 7 prostate cancer cell lines and 25 transiently established primary cell cultures, which were sourced from tissue harvested at 16 radical prostatectomies and 9 channel transurethral prostate resections, were screened for chromosomal translocations using multiplex-fluorescence in situ hybridization technology. A series of fluorescence in situ hybridization based breakpoint mapping experiments were performed to identify candidate genes involved in regions associated with recurrent translocation. RESULTS: Our analysis identified the repetition of 2 translocations in prostate cancer lines, that is t(1;15) and t(4;6), at a frequency of 28% and 57%, respectively. More significantly 4 of the 25 subsequently established primary cultures (16%) also revealed a t(4;6) translocation. Using the LNCaP cell line the breakpoints involved were mapped to the t(4;6)(q22;q15) region and a number of candidate genes were identified. CONCLUSIONS: We found that the t(4;6) translocation is also a repeat event in primary cell cultures from malignant prostate cancer. Breakpoint mapping showed that the gene UNC5C loses its promoter and first exon as a direct result of the translocation in the 4q22 region. As such, we identified it as a possible contributor to a putative fusion gene in prostate cancer.     

Validity evidence for the Simulated Colonoscopy Objective Performance Evaluation scoring system

Background

Low-cost, objective systems to assess and train endoscopy skills are needed. The aim of this study was to evaluate the ability of Simulated Colonoscopy Objective Performance Evaluation to assess the skills required to perform endoscopy.

Methods

Thirty-eight subjects were included in this study, all of whom performed 4 tasks. The scoring system measured performance by calculating precision and efficiency. Data analysis assessed the relationship between colonoscopy experience and performance on each task and the overall score.

Results

Endoscopic trainees' Simulated Colonoscopy Objective Performance Evaluation scores correlated significantly with total colonoscopy experience (r = .61, P = .003) and experience in the past 12 months (r = .63, P = .002). Significant differences were seen among practicing endoscopists, nonendoscopic surgeons, and trainees (P < .0001). When the 4 tasks were analyzed, each showed significant correlation with colonoscopy experience (scope manipulation, r = .44, P = .044; tool targeting, r = .45, P = .04; loop management, r = .47, P = .032; mucosal inspection, r = .65, P = .001) and significant differences in performance between the endoscopist groups, except for mucosal inspection (scope manipulation, P < .0001; tool targeting, P = .002; loop management, P = .0008; mucosal inspection, P = .27).

Conclusions

Simulated Colonoscopy Objective Performance Evaluation objectively assesses the technical skills required to perform endoscopy and shows promise as a platform for proficiency-based skills training.     

Anaemia management in patients with chronic kidney disease: Taiwan practice guidelines

The introduction of erythropoiesis‐stimulating agents (ESAs) markedly improved the lives of many anaemic patients with chronic kidney disease (CKD). In Taiwan, the strategy of management of anaemia in patients with CKD was different from many other parts of the world. In 1996, the National Health Insurance Administration of Taiwan applied a more restrictive reimbursement criteria for ESA use in patients with CKD. ESA is to be initiated when non‐dialysis CKD patients have a serum creatinine >6 mg/dL and a hematocrit <28% to maintain a hematocrit level not exceeding 30%. The maximal dose of epoetin‐α or β was 20 000 U per month. The target haemoglobin range and dose limitation for ESAs were the same for dialysis CKD patients. Thus, long before randomized controlled trials showing an increased risk for cardiovascular events at nearly normal haemoglobin concentrations and higher ESA doses in CKD, nephrologists in Taiwan had avoided the use of disproportionately high dosages of ESAs to achieve a haemoglobin level of 10–11 g/dL. Moreover, intravenous iron supplementation was encouraged earlier in Taiwan in 1996, when we reached consensus on the diagnostic criteria for iron deficiency (serum ferritin <300 ng/mL and/or transferrin saturation <30%). The experience of CKD anaemia management in Taiwan demonstrated that a reasonable haemoglobin target can be achieved by using the lowest possible ESA dose and intravenous iron supplementation.     

The effect of renal function on surgical outcomes of intracapsular hip fractures with osteosynthesis

Background

Chronic kidney disease (CKD) affects many physiologic systems, including bone quality, nutrition, and cardiovascular condition. Femoral neck fractures in patients on dialysis are associated with frequent complications and a high risk of mortality. However, the effect of CKD on clinical outcomes of patients with hip fractures treated with osteosynthesis remains unclear.

Methods

One hundred and thirty patients with 130 femoral neck fractures treated with internal fixation were divided into two groups and the data were then analyzed. Group 1 consisted of 98 patients (98 hip fractures) with normal renal function (estimated glomerular filtration rate, or eGFR, ≥60 ml/min/1.73 m²). Group 2 was composed of 32 patients (32 hip fractures) with CKD (eGFR <60 ml/min/1.73 m²) without dialysis. Clinical outcomes as well as early and late complications were recorded for each group. Survivorship analysis was performed, and the mortality and complication rates for the groups were then compared.

Results

In Group 1, 32 complications (32.6 %) occurred in 98 hips, including 5 cases of nonunion and 16 cases of osteonecrosis. In Group 2, 24 complications (75 %) developed in 32 hips; these included 8 cases of nonunion and 3 cases of osteonecrosis. The mean duration of follow-up was 32 months. The overall mortality rate was 11.5 %. No difference was noted in early, late, or overall mortality rate between two groups. Patient with CKD had a higher nonunion rate (OR = 5.9, P = 0.023). Meanwhile, CKD and displaced fracture pattern were independent predictors for revision surgery (OR = 3.0, P = 0.032; OR = 6.9, P = 0.001, respectively).

Conclusions

Osteosynthesis is a safe and effective treatment for femoral neck fractures; however, patients with femoral neck fracture and CKD have a higher risk of nonunion and subsequent surgical revision.

Level of relevance

Prognostic studies, Level III.     

Bone mineral density changes after parathyroidectomy are dependent on biochemical profile

Background

Bone mineral density (BMD) has been found to improve after parathyroidectomy (PTX) in patients with primary hyperparathyroidism. There are few data on the effect of PTX on BMD in normocalcemic and normohormonal primary hyperparathyroidism.

One-stage reconstruction of large midline abdominal wall defects using a composite free anterolateral thigh flap with vascularized fascia lata

OBJECTIVE: Large midline abdominal wall defects are continuously a challenge for reconstructive surgeons. Adequate skin coverage and fascia repair of the abdominal wall is necessary for achieving acceptable results. The purpose of this paper is to present a new approach to abdominal wall reconstruction using a free vascularized composite anterolateral thigh (ALT) flap with fascia lata. METHODS: Seven patients with large full-thickness abdominal wall defects were successfully reconstructed by means of a composite ALT flap combined with vascularized fascia lata. The size of the skin islands ranged from 20 to 32 cm in length and 10 to 22 cm in width, and the vascularized fascia lata sheath measured 14 to 28 cm and 8 to 18 cm, respectively. Functional outcome of the abdominal wall strength and donor thigh morbidity were investigated by using a Cybex kinetic dynamometer. RESULTS: All flaps survived. No postoperative ventral hernia occurred except for one mild inguinal incision hernia. Subjectively there were no significant donor site problems. Objective assessment was performed in 4 patients 2 years postoperatively. In the reconstructed abdomen, isokinetic concentric and eccentric measurements of extension/flexion ratios of the abdominal wall strength showed no apparent decrease compared with other references. Functional evaluation of quadriceps femoris muscle contraction forces after free ALT composite flap harvest showed an averaged deficit of 30% as compared with the contralateral legs. However, no difficulties in daily ambulating were reported by the patients. CONCLUSION: The free composite ALT myocutaneous flap with vascularized fascia lata provides an alternative option for a stable repair in complex abdominal wall defects.     

Immunotyping of Chlamydia trachomatis with monoclonal antibodies

Rapid and precise immunotyping of Chlamydia trachomatis was achieved by testing whole organisms (elementary bodies) in the microimmunofluorescence test with monoclonal antibodies. Monoclonal antibodies were produced with standard techniques by using an immunization schedule that encouraged the development of immunotype-specific antibodies. Fifteen monotypic or multitypic (subspecies) monoclonal antibodies were chosen for use in a two-step typing system that required strains of C. trachomatis to be tested against six to eight monoclonal antibodies for classification. Immunotyping with monoclonal antibodies was studied by testing 313 strains, typed with the previous method that utilized immunized mouse antisera, that represented each of the 15 established serovars. The two-step monoclonal antibody method resulted in a classification similar to the current one. Only one strain typed differently with the two methods. With the monoclonal antibody method, available lymphogranuloma venereum (LGV) serovars L1 and L3 could not be differentiated from trachoma serovars E and G, respectively, unless the strains had been identified as LGV. Monoclonal antibody typing was simpler to perform and more precise; it allowed easy differentiation between closely related serovars. Three new types were discovered among the strains previously classified as serovars D, I, and L2. These are tentatively being considered subtypes and are labeled D', I', and L2'.     

Anti-PF4/heparin antibodies are associated with arteriovenous fistula thrombosis in non-diabetic hemodialysis patients

Aim  

Anti-platelet factor 4/heparin complex antibodies (anti-PF4/heparin Ab) have been found to cause heparin-induced thrombocytopenia (HIT), a clinical syndrome thrombocytopenia and thrombosis. There is still controversy as to whether the presence of anti-PF4/heparin antibodies in hemodialysis patients augments clot formation in access fistula thrombosis, peripheral artery disease (PAD), and coronary heart disease (CHD).