Retrospective comparative analysis of choledochoscopic bile duct exploration versus ERCP for bile duct stones.

Debate still exists for the management of choledocholithiasis. The purpose of this study is to quantify the rate of recurrent choledocholithiasis post choledochoscopic bile duct exploration (CBDE) in comparison to ERCP and sphincterotomy, and to demonstrate the feasibility of this approach in a busy metropolitan hospital. Data of patients undergoing CBDE from 2009-2014 at the Northern Hospital, Victoria, Australia, was collected retrospectively. Primary outcomes were bile duct clearance rate and rate of recurrent stones post-clearance. Secondary outcomes measured were post-operative complications, laparoscopic to open conversion rate and operative time. Data of patients undergoing ERCP at the same institution was collected and compared. In total, there were 4,091 cholecystectomy cases performed from 2009-2014, of which 260 (6.3%) of patients had an intraoperative cholangiography (IOC) indicating a common bile duct (CBD) stone. Two hundred and forty-eight patients (95.3%) had a CBDE. The remaining 12 patients (4.6%) had radiological clearance, which were excluded from the study. The overall clearance rate for patients undergoing CBDE was 84% (209/248). The risk of recurrent stones up to 8 years post clearance was 2% (4/209). In the same institution, and between 1998-2012, a total of 1,148 patients underwent ERCP, of which 571 had endoscopic sphincterotomy (ES). Forty-three patients required a repeat ERCP for recurrent CBD stones with a complication rate of 7.5%. Time to recurrence ranged from 6 months to 10 years with a mean of 4.5 years. The rate of recurrence was lower in the CBDE group compared to the patients who had an ERCP (8.9% vs. 2%). CBDE is a feasible and effective method for clearance of CBD stones at the time of laparoscopic cholecystectomy. This approach, although not widely used, reduces the need for ERCP, which has inherent complications. In the longer term, this series showed a significant reduction in the rate of CBD stone recurrence.

Infection rates following hip and knee joint arthroplasty: large referral centre versus a small elective-only hospital.

PURPOSE: The aim of this study was to investigate deep infection rates following hip and knee arthroplasty at a large referral hospital and to compare these rates with a smaller hospital where only elective surgery was performed. Both hospitals were administered by the same public institution. METHODS: A search of the medical records was performed for all deep infections following elective primary hip and knee arthroplasty; revision procedures were excluded as were total hip replacement and hemiarthroplasty following trauma. To be considered, a deep infection cases must have had bacterial growth confirmed on deep tissue surgical specimens or on aspiration of the joint within 1 year of the index procedure. RESULTS: There were 14 infections confirmed following 1,160 arthroplasties at the larger hospital and 1 infection for the elective-only hospital following 466 arthroplasties. Statistical analysis showed there was a 7.06 greater chance of having an infection at the larger campus compared with the smaller campus CI (1.3, 130.7). Although there was a trend towards a greater number of infections at the larger hospital, the result was not statistically significant (P = 0.06). We acknowledge there were some differences between the two study populations. CONCLUSION: We found a trend towards, but not a statistically significant difference, between infection rates at the elective-only hospital compared to the larger institution. Given the low overall rate of infection, studies with improved statistical power are needed to determine whether there is a difference in infection rates at smaller elective-only hospitals versus larger hospitals providing elective and non-elective services. The reasons for the difference are likely to be multifactorial. We hypothesise that infection rates are increased in the larger hospital where there is more procedures, both clean and contaminated being performed in the operating theatres, as well as a greater number of inpatient beds and where the hospital admits non-elective cases via its emergency department. LEVEL OF EVIDENCE: Level-two cohort study.

Development of an eight gene expression profile implicating human breast tumours of all grade.

The goal of improving systemic treatment of breast cancers is to evolve from treating every patient with non-specific cytotoxic chemotherapy/hormonal therapy, to a more individually-tailored direct treatment. Although anatomic staging and histological grade are important prognostic factors, they often fail to predict the clinical course of this disease. This study aimed to develop a gene expression profile associated with breast cancers of differing grades. We extracted mRNA from FFPE archival breast IDC tissue samples (Grades I-III), including benign tumours. Affymetrix GeneChip(®) Human Genome U133 Plus 2.0 Arrays were used to determine gene expression profiles and validated by Q-PCR. IHC was used to detect the AXIN2 protein in all tissues. From the array data, an independent group t-test revealed that 178 genes were significantly (P ≤ 0.01) differentially expressed between three grades of malignant breast tumours when compared to benign tissues. From these results, eight genes were significantly differentially expressed in more than one comparison group and are involved in processes implicated in breast cancer development and/or progression. The two most implicated candidates genes were CLD10 and ESPTI1 as their gene expression profile from the microarray analysis was replicated in Q-PCR analyses of the original tumour samples as well as in an extended population. The IHC revealed a significant association between AXIN2 protein expression and ER status. It is readily acknowledged and established that significant differences exist in gene expression between different cancer grades. Expansion of this approach may lead to an improved ability to discriminate between cancer grade and other pathological factors.

Semaphorin-plexin signalling genes associated with human breast tumourigenesis.

INTRODUCTION: Gene expression profiling has enabled us to demonstrate the heterogeneity of breast cancers. The potential of a tumour to grow and metastasise is partly dependant on its ability to initiate angiogenesis or growth and remodelling of new blood vessels, usually from a pre-existing vascular network, to ensure delivery of oxygen, nutrients, and growth factors to rapidly dividing transformed cells along with access to the systemic circulation. Cell-cell signalling of semaphorin ligands through interaction with their plexin receptors is important for the homeostasis and morphogenesis of many tissues and has been widely studied for a role in neural connectivity, cancer, cell migration and immune responses. This study investigated the role of four semaphorin/plexin signalling genes in human breast cancers in vivo and in vitro. MATERIALS AND METHODS: mRNA was extracted from formalin fixed paraffin embedded archival breast invasive ductal carcinoma tissue samples of progressive grades (grades I-III) and compared to tissue from benign tumours. Gene expression profiles were determined by microarray using the Affymetrix GeneChip® Human Genome U133 Plus 2.0 Arrays and validated by Q-PCR using a Corbett RotorGene 6000. Following validation, the gene expression profile of the identified targets was correlated with those of the human breast cancer cell lines MCF-7 and MDA-MD-231. RESULTS: The array data revealed that 888 genes were found to be significantly (p≤0.05) differentially expressed between grades I and II tumours and 563 genes between grade III and benign tumours. From these genes, we identified four genes involved in semaphorin-plexin signalling including SEMA4D which has previously been identified as being involved in increased angiogenesis in breast cancers, and three other genes, SEMA4F, PLXNA2 and PLXNA3, which in the literature were associated with tumourigenesis, but not directly in breast tumourigenesis. The microarray analysis revealed that SEMA4D was significantly (P=0.0347) down-regulated in the grade III tumours compared to benign tumours; SEMA4F, was significantly (P=0.0159) down-regulated between grades I and II tumours; PLXNA2 was significantly (P=0.036) down-regulated between grade III and benign tumours and PLXNA3 significantly (P=0.042) up-regulated between grades I and II tumours. Gene expression of SEMA4D was validated using Q-PCR, demonstrating the same expression profile in both data sets. When the sample set was increased to incorporate more cases, SEMA4D continued to follow the same expression profile, including statistical significance for the differences observed and small standard deviations. In vitro the same pattern was present where expression for SEMA4D was significantly higher in MDA-MB-231 cells when compared to MCF-7 cells. The expression of SEMA4F, PLXNA2 and PLXNA3 could not be validated using Q-PCR, however in vitro analysis of these three genes revealed that both SEMA4F and PLXNA3 followed the microarray trend in expression, although they did not reach significance. In contrast, PLXNA2 demonstrated statistical significance and was in concordance with the literature. DISCUSSION: We, and others, have proposed SEMA4D to be a gene with a potentially protective effect in benign tumours that contributes to tumour growth and metastatic suppression. Previous data supports a role for SEMA4F as a tumour suppressor in the peripheral nervous system but our data seems to indicate that the gene is involved in tumour progression in breast cancer. Our in vitro analysis of PLXNA2 revealed that the gene has higher expression in more aggressive breast cancer cell types. Finally, our in vitro analysis on PLXNA3 also suggest that this gene may have some form of growth suppressive role in breast cancer, in addition to a similar role for the gene previously reported in ovarian cancer. From the data obtained in this study, SEMA4D may have a role in more aggressive and potentially metastatic breast tumours. CONCLUSIONS: Semaphorins and their receptors, the plexins, have been implicated in numerous aspects of neural development, however their expression in many other epithelial tissues suggests that the semaphorin-plexin signalling system also contributes to blood vessel growth and development. These findings warrant further investigation of the role of semaphorins and plexins and their role in normal and tumour-induced angiogenesis in vivo and in vitro. This may represent a new front of attack in anti-angiogenic therapies of breast and other cancers.