R. McLaughlin

Effects of Age on the Detection and Management of Breast Cancer

Currently, breast cancer affects approximately 12% of women worldwide. While the incidence of breast cancer rises with age, a younger age at diagnosis is linked to increased mortality. We discuss age related factors affecting breast cancer diagnosis, management and treatment, exploring key concepts and identifying critical areas requiring further research. We examine age as a factor in breast cancer diagnosis and treatment relating it to factors such as genetic status, breast cancer subtype, hormone factors and nodal status. We examine the effects of age as seen through the adoption of population wide breast cancer screening programs. Assessing the incidence rates of each breast cancer subtype, in the context of age, we examine the observed correlations. We explore how age affects patient’s prognosis, exploring the effects of age on stage and subtype incidence. Finally we discuss the future of breast cancer diagnosis and treatment, examining the potential of emerging tests and technologies (such as microRNA) and how novel research findings are being translated into clinically relevant practices.

A pilot project of european working time directive compliant rosters in a university teaching hospital

BACKGROUND In response to the requirements of the European Working Time Directive (EWTD), a national implementation group was formed to liaise with local implementation groups at nine different pilot sites. As part of this process, a pilot EWTD compliant rota was run for six weeks amongst general surgical SHOs in University Hospital Galway. METHODS A rota was devised for nine general surgical SHOs, the aim being to achieve EWTD compliance. SHOs were asked to complete questionnaires to assess the effectiveness of the pilot. RESULT During the pilot SHOs were rostered for an average of 53.6 hours. Actual hours worked were 58.1 hours. Fifty-two point five per cent of working weeks were non-compliant with the provisions of the EWTD. Seventy per cent of the time SHOs felt that continuity of care was not achieved. Eighty-one per cent felt that patient care deteriorated during the pilot. SHOs spent an average of 2.5 days per week engaged in sessional commitments with their consultant. Fifty percent of SHOs missed elective operating sessions or outpatient clinics. SHOs attended an average of 1.3 emergency operations per week (range 0-8) and 5.5 elective procedures per week (range 0-12). All SHOs reported a deterioration in quantity or quality of training. However, 69% reported an improvement in their quality of life during the pilot. CONCLUSIONS With this tightly defined shift system, hours worked were in breach of the provisions of the EWTD. Sixty-nine per cent of SHOs reported an improvement in quality of life, but all reported a deterioration in training and 81% felt that patient care suffered.

The prognostic value of the tumor marker CA 15-3 at initial diagnosis of patients with breast cancer.

CA 15–3 has been most widely used as a serum tumor marker in follow-up and detection of breast cancer recurrence. In this study we have specifically focused upon the prognostic implications and utility of preoperative CA 15–3 levels. We have identified on our database 414 patients with breast cancer in whom serial levels of the serum tumor marker CA 15–3 had been determined at diagnosis and follow-up. We have analyzed the follow-up and clinical outcomes in these patients and from this data we have assessed the potential of CA 15–3 as a predictor of five-year overall and disease-free survival. Our results show that an initially elevated CA 15–3 level is associated with a very poor prognosis in both early and late stage disease. Elevated pre-biopsy CA 15–3 levels are associated with 14% five-year disease-free survival rates and 17% overall survival rates at five years. In contrast, normal CA 15–3 levels are associated with 47% five-year disease-free survival rates and 54% overall survival rates at five years (p<0.01). Comparison of five-year survival rates between patients with elevated and normal CA 15–3 levels in early breast cancer (stage I and II) also showed significant differences, with survival being 41% and 75%, respectively (p<0.01).

Are elevated levels of the tumour marker CA19-9 of any clinical significance?--an evaluation.

CA 19-9 is a tumour marker which has been used widely in patients with pancreatic adenocarcinoma. Elevated levels are associated with advanced disease at presentation and disease progression during follow-up. CA19-9 levels may also be elevated in a variety of other malignant and benign conditions. This study examined the significance and implications of elevated CA19-9 levels. An analysis of all CA19-9 measurements performed over a 4 yr period was undertaken and 204 patients with elevated CA19-9 levels were identified. One hundred and thirty patients (63.7 per cent) had malignant conditions and 74 (36.3 per cent) had benign conditions or no definite cause was found. There was a significant correlation between CA19-9 levels and CEA (r=0.3137; P<0.001) as well as alkaline phosphatase, ALT, AST, bilirubin, gamma glutamyl transpeptidase and lactate dehydrogenase. CA19-9 levels were significantly lower in patients with benign pathology than those with malignant pathology. Similar differences were observed for CEA. CA19-9 levels were in fact highest in patients with pancreatic carcinoma (P<0.05) while no significant differences were observed for CEA. In conclusion CA19-9 may be elevated in both benign as well as malignant conditions and interpretation of CA19-9 results must be made in light of the clinical condition of the patient.

Increasing Reporting of Adverse Events to Improve the Educational Value of the Morbidity and Mortality Conference

BACKGROUND The aim of this study was to investigate the impact of a validated complication proforma on surgical Morbidity and Mortality (M&M) conference reporting. STUDY DESIGN The ACS-NSQIP (American College of Surgeons-National Surgical Quality Improvement Program) 30-day complication proforma, when implemented, previously showed a 25% increase in morbidity and a 50% increase in mortality reporting. A pilot study introducing the paper-based proforma was undertaken, collecting prospective M&M data for 2,094 of 2,209 colorectal, upper gastrointestinal, breast, and vascular inpatients (94.7% compliance). A comparative analysis using the proforma vs traditional M&M data collection was used to compare accuracy of M&M data reporting. RESULTS There was a 73% increase in morbidities reported using the proforma as compared with M&M reporting (547 vs 316), and an increase of 10.81% (37 vs 41) in the reporting of mortalities. Of those patients with morbidities (n = 278), 70.24% (n = 203) had at least 1 surgical intervention. The median length of stay in patients with morbidities was 12 vs 3 days in those with no morbidities. CONCLUSIONS We demonstrated that prospective standardized incident recording provides significantly more accurate assessment of M&M data compared with current reporting methods. This increased accuracy should favorably affect surgical performance indicators and casemix funding.

Prognostic implications of p53 and bcl-2 expression in 108 women with stage two breast cancer.

BackgroundThe mortality and morbidity of patients with breast cancer can vary even between individuals with similar histological stage at diagnosis. Identification of those individuals with prognostically poorer tumours is an essential prerequisite in planning adjuvant therapies.Some prognostic indices of tumour size, grade, oestrogen receptor status and nodal status are well established.AimThe aim of this study was to examine the prognostic role of information relating to proto-oncogene and tumour suppressor gene expression.Methods108 women with stage II breast cancer were studied. Tumour expression of p53 and bcl-2 were scored and then correlated with recurrence and mortality.ResultsWe have shown that individuals poorly expressing bcl-2 in their tumours have a poorer disease-free and overall survival than those who express bcl-2. When p53 was strongly expressed, it was associated with poorer disease-free and overall survival.ConclusionThe profiling of individual tumour genetic expression of proto-oncogenes may allow for more specific identification of patients at higher risk’ of recurrence in breast cancer.

Influence of complications following immediate breast reconstruction on breast cancer recurrence rates

The rate of immediate breast reconstruction is rising. Postoperative infections are more frequent in patients who undergo reconstruction. The inflammatory response to a postoperative infection can increase the risk of tumour recurrence in other forms of cancer through the release of proinflammatory mediators. The aim of this study was to assess the relationship between complications and breast cancer recurrence in patients undergoing immediate reconstruction.

Thermal preconditioning prevents peritendinous adhesions and inflammation

Adhesion formation is one of the foremost obstacles to a reliably good outcome in tendon and joint surgery. Thermal preconditioning has been found to reduce the inflammatory response through the induction of molecular chaperone expression, a recently described family of cytoprotective intracellular proteins. The authors analyzed the effect of thermal preconditioning on the inflammatory response to surgery, on tendon healing, and on the formation of peritendinous adhesions in 16 New Zealand White rabbits. Very significant decreases in adhesion formation and in the gliding and dimensions of tendons in animals that had thermal preconditioning were found. Tendons from these animals also showed a decreased level of adhesion formation and a significantly diminished inflammatory response on histologic examination with no biomechanically significant deleterious effect on the strength of tendon healing on testing load to failure. These findings are consistent with induction of heat shock proteins by hyperthermic pretreatment. Such prevention of peritendinous adhesions and the inflammatory response to injury and surgery without compromising healing are findings that have significant implications for tendon surgery and all surgery involving joints and soft tissues.

Emergency surgery pre-operative delays - realities and economic impacts.

BACKGROUND A key principle of acute surgical service provision is the establishment of a distinct patient flow process and an emergency theatre. Time-to-theatre (TTT) is a key performance indicator of theatre efficiency. The combined impacts of an aging population, increasing demands and complexity associated with centralisation of emergency and oncology services has placed pressure on emergency theatre access. We examined our institutions experience with running a designated emergency theatre for acute surgical patients. METHODS A retrospective review of an electronic prospectively maintained database was performed between 1/1/12 and 31/12/13. A cost analysis was conducted to assess the economic impact of delayed TTT, with every 24hr delay incurring the cost of an additional overnight bed. Delays and the economic effects were assessed only after the first 24 h as an in-patient had elapsed. RESULTS In total, 7041 procedures were performed. Overall mean TTT was 26 h, 2 min. There were significant differences between different age groups, with those aged under 16 year and over 65 having mean TTT at 6 h, 34 min (95% C.I. 0.51-2.15, p < 0.001) and 23 h, 41 min (95% C.I. 19.6-23.9, p < 0.001) respectively. 2421 (34%) waited greater than 24 h for emergency procedures. The >65 years age group had a mean TTT of 23 h, 41 min which was significantly longer than the overall mean TTT Vascular and urological emergencies are significantly disadvantaged in competition with other services for a shared emergency theatre. The economic impact of delayed TTT was calculated at €7,116,000, or €9880/day of additional costs generated from delayed TTT over a 24 month period. CONCLUSION One third of patients waited longer than 24 h for emergency surgery, with the elderly disproportionately represented in this group. Aside from the clinical risks of delayed and out of hours surgery, such practices incur significant additional costs. New strategies must be devised to ensure efficient access to emergency theatres, investment in such services is likely to be financially and clinically beneficial.

An Appraisal of Inflammatory Markers in Distinguishing Acute Uncomplicated and Complicated Appendicitis

Background: It remains difficult to distinguish between complicated appendicitis (CAP) and uncomplicated appendicitis (UAP). There is a paucity of studies utilizing inflammatory markers to stratify the severity of acute appendicitis. This study aimed to evaluate and demonstrate the potential clinical utility of inflammatory markers as adjuncts in distinguishing CAP and UAP. Methods: A comparative observational study was performed. Patients diagnosed with acute appendicitis were categorized as (a) complicated (necrosis, perforation, abscess) and (b) uncomplicated (inflamed, edematous). Hematological indices were combined to generate the following ratios: white cell lymphocyte ratio (WLR), white cell neutrophil ratio (WNR) and neutrophil lymphocyte ratio (NLR). Parameter accuracy was assessed using summary receiver operating characteristic (sROC) curves, classification and regression tree analysis and confusion matrix generation. Results: On sROC analysis, neutrophils (area under the curve (AUC) 0.79, p < 0.001), WLR (AUC 0.79, p < 0.001) and NLR (AUC 0.79, p < 0.001) were the most accurate parameters in distinguishing CAP and UAP. White cell count (WCC; AUC 0.76, p < 0.001) and C-reactive protein (AUC 0.75, p < 0.001) were less accurate. WCC >12.25 (sensitivity 70%, specificity 68%) and NLR >5.47 (sensitivity 78%, specificity 70%) were the most accurate in identifying CAP. Conclusion: Inflammatory marker cutoff points can be generated and utilized to differentiate between UAP and CAP. This may be useful when deciding between conservative and operative management.