Clinicopathological correlates, oncological impact, and validation of Oncotype DX™ in a European Tertiary Referral Centre.

Oncotype DX™ (ODX) score estimates prognosis and predicts breast cancer recurrence. It also individualizes patient adjuvant chemotherapy prescription in breast cancer. This assay relies on genetic and molecular markers; the clinicopathological phenotype of which are tested routinely. The aim of this study was determine whether clinicopathological and immunohistochemical information predicts ODX recurrence score (RS). Secondly, to assess the impact on adjuvant chemotherapy (AC) and oncological outcome of ODX testing in patients in a European tertiary referral center. Estrogen receptor positive (ER+), human epidermal growth factor receptor-2 negative (HER2-), lymph node negative (LN-), and female breast cancer patients with ODX testing performed between 2007 and 2015 were categorized into low- (<11), intermediate- (11-25), and high-risk (>25) groups. Clinicopathological and immunohistochemical correlates of RS were determined. Predictors of RS were assessed using binary logistic regression. Oncological outcome was assessed using Kaplan-Meier and Cox regression analyses. ODX was performed in 400 consecutive ER+LN- patients. Median follow-up was 74.1 months (3.0-144.4). Low grade (odds ratio [OR]:2.39; 95% confidence interval [CI]:1.04-5.51, p = 0.041) independently predicted low ODX, while high grade (OR:2.04; 95% CI: 1.19-3.49, p = 0.009) and reduced progesterone receptor (PgR) expression (OR: 2.57, 95% CI: 1.42-4.65, p = 0.002) independently predicted high ODX. Omission of AC in intermediate- (p = 0.159) and high-risk (p = 0.702) groups did not negatively impact survival. In conclusion, tumor grade independently predicts low and high RS, while PgR negativity predicts high RS. ODX reduced AC prescription without compromising oncological outcome.

The histopathological and molecular features of breast carcinoma with tumour budding-a systematic review and meta-analysis.

PURPOSE: Tumour budding (TB) is an adverse histological feature in many epithelial cancers. It is thought to represent epithelial-mesenchymal transition, a key step in the metastatic process. The significance of TB in breast carcinoma (BC) remains unclear. The aim of this study is to investigate the relationship between TB and other histological and molecular features of BC. METHODS: A systematic search was performed to identify studies that compared features of BC based on the presence or absence of high-grade TB. Dichotomous variables were pooled as odds ratios (OR) using the Der Simonian-Laird method. Quality assessment of the included studies was performed using the Newcastle-Ottawa scale (NOS). RESULTS: Seven studies with a total of 1040 patients (high-grade TB n = 519, 49.9%; low-grade/absent TB n = 521, 50.1%) were included. A moderate to high risk of bias was noted. The median NOS was 7 (range 6-8). High-grade TB was significantly associated with lymph node metastasis (OR 2.32, 95% c.i. 1.77 to 3.03, P < 0.001) and lymphovascular invasion (OR 3.08, 95% c.i. 2.13 to 4.47, P < 0.001). With regard to molecular subtypes, there was an increased likelihood of high-grade TB in oestrogen (OR 1.66, 95% c.i. 1.21 to 2.29, P = 0.002) and progesterone receptor-positive (OR 1.48, 95% c.i. 1.09 to 2.02, P = 0.01) tumours. In contrast, triple-negative breast cancer had a reduced incidence of high-grade TB (OR 0.46, 95% c.i. 0.30 to 0.72, P = 0.0006). CONCLUSION: High-grade TB is enriched in hormone receptor-positive BC and is associated with known adverse prognostic variables. TB may offer new insights into the metastatic process of BC.

Differential impact of hormone receptor status on survival and recurrence for HER2 receptor-positive breast cancers treated with Trastuzumab.

INTRODUCTION: Hormone receptor status has major implications for treatment and survival of breast cancer. Yet the impact of hormone receptor status on outcome after Trastuzumab has received little attention. The objective here was to explore any differential effects of Trastuzumab treatment (Trast +ve) on Luminal B HER2 or HER2+(ER-) breast cancer subtypes. METHODS: A cohort of 469 HER2 receptor-positive breast cancers was categorised by molecular subtype and Trastuzumab treatment. Effects of Trastuzumab treatment on survival, locoregional recurrence and distant metastasis were investigated by subtype, using univariate and multivariate analysis. RESULTS: Trast +ve Luminal B HER2 patients had significant improvements in 5-year DFS (p < 0.001) and OS (p < 0.001), while Trast +ve HER2+(ER-) patients had significant improvements in 5-year DFS (p = 0.012) alone. Only Trast +ve Luminal B HER2 cancers displayed a significant reduction in LRR rates (p < 0.001). A significant reduction in distant metastasis rates was seen in Trast +ve Luminal B HER2 (p < 0.001) and HER2+(ER-) (p = 0.009) cancers. Interestingly, bone metastasis rates in Trast +ve Luminal B HER2 cancers demonstrated the greatest reduction (36.2-6.7%). Multivariate analysis of Trast +ve patients found no difference in distant metastasis rates (p = 0.96) between subtypes. Significantly, lower LRR rates were seen in Trast +ve Luminal B HER2 cancers, compared to Trast +ve HER2+(ER-) (p = 0.018). CONCLUSION: An enhanced response to Trastuzumab was seen in Luminal B HER2 cancers. We highlight how Trastuzumab treatment changed the natural history of the HER2 receptor-positive breast cancer, demonstrating improved efficacy in changing the outcome of hormone receptor-positive patients.

Association of clinical biomarkers and response to neoadjuvant therapy in breast cancer.

INTRODUCTION: Neoadjuvant therapy is an essential component of multimodality therapy for locally advanced breast adenocarcinoma (BC). Complete pathologic response (pCR) is a useful surrogate for long-term oncologic outcome. AIM: To assess the association between clinicopathologic, molecular and immunological markers and treatment response to neoadjuvant therapy in BC. METHODS: BC patients undergoing neoadjuvant therapy were identified from a prospectively maintained institutional database. Serum haematological/biochemical values, histopathologic, immunohistochemical data and TNM stage were obtained from electronic records. Patients were categorised into complete responders vs non-complete responders and responders vs non-responders. Statistical analysis was performed via SPSS. RESULTS: Overall, 299 BC patients were included. The average age was 49.8 ± 11.5 years. A pCR was evident in 22.6% (n = 69). pCR was associated with early T stage and non-luminal subtypes (HER2 enriched [HER2 +] and triple negative [TNBC]). The neutrophil-lymphocyte ratio (NLR) pre-operatively was lower in patients with a pCR (p = 0.02). The lymphocyte-CRP ratio (LCR) was also slightly reduced in responders (p = 0.049) at diagnosis. A pre-op NLR greater than 2 was not found to be a significant predictive factor (p = 0.071) on multivariable logistic regression analysis. T stage at diagnosis (p = 0.024), N stage (p = 0.001) and breast cancer subtype (p = 0.0001) were also determined to be significant predictive factors of complete response. CONCLUSION: pCR was more likely in patients with less advanced disease in BC. The presence of HER2 + or TNBC in BC also increases the likelihood of pCR. Neoadjuvant therapy stimulates the systemic inflammatory response; however, a reduced baseline NLR may be associated with increased pCR. Confirmation with larger datasets is required.

Evaluating the Necessity for Routine Sentinel Lymph Node Biopsy in Postmenopausal Patients Being Treated for Clinically Node Negative Breast Cancer the Era of RxPONDER.

INTRODUCTION: Traditionally, sentinel lymph node biopsy (SLNB) was performed to inform adjuvant chemotherapy prescription and prognosis in breast cancer. Following RxPONDER, the OncotypeDX Recurrence Score (RS) guides adjuvant chemotherapy prescription for all postmenopausal patients with estrogen receptor positive, human epidermal growth factor receptor-2 negative (ER+/HER2-) breast cancer with 0 to 3 positive lymph nodes (0-3 + LN). AIMS: To establish the oncological safety of omitting SLNB in postmenopausal patients with ER+/HER2- breast cancer indicated to undergo SLNB and to evaluate the primary determinants of chemotherapy prescription for these patients. PATIENTS AND METHODS: A retrospective cohort study was undertaken. Cox regression and Kaplan-Meier analyses were performed. Data analytics was performed using SPSS v26.0. RESULTS: Five hundred and seventy five consecutive patients were included (mean age: 66.5 years, range: 45-96). The median follow-up was 97.2 months (range: 3.0-181.6). Of the 575 patients, just 12 patients had positive SLNB (SLNB+) (2.1%). Using Kaplan-Meier analyses, SLNB+ failed to impact recurrence (P = .766) or mortality (P = .310). However, using Cox regression analyses, SLNB+ independently predicted poorer disease-free survival (hazard ratio: 1.001, 95% confidence interval (95% CI): 1.000-1.001, P = .029). Logistic regression analysis identified RS as the sole predictor of chemotherapy prescription (odds ratio: 1.171, 95% CI: 1.097-1.250, P < .001). CONCLUSION: Omitting SLNB may be safe and justifiable in postmenopausal patients with ER+/HER2- breast cancer with clinically negative axillae. Following RxPONDER, RS is the most important guide of chemotherapy use in these patients and SLNB may be less important than previously perceived. Prospective, randomized clinical trials are required to fully establish the oncological safety of omitting SLNB in this setting.

A pilot study investigating feasibility of mainstreaming germline BRCA1 and BRCA2 testing in high-risk patients with breast and/or ovarian cancer in three tertiary Cancer Centres in Ireland.

In the Republic of Ireland (ROI), BRCA1/BRCA2 genetic testing has been traditionally undertaken in eligible individuals, after pre-test counselling by a Clinical Geneticist/Genetic Counsellor. Clinical Genetics services in ROI are poorly resourced, with routine waiting times for appointments at the time of this pilot often extending beyond a year. The consequent prolonged waiting times are unacceptable where therapeutic decision-making depends on the patient's BRCA status. "Mainstreaming" BRCA1/BRCA2 testing through routine oncology/surgical clinics has been implemented successfully in other centres in the UK and internationally. We aimed to pilot this pathway in three Irish tertiary centres. A service evaluation project was undertaken over a 6-month period between January and July 2017. Eligible patients, fulfilling pathology and age-based inclusion criteria defined by TGL clinical, were identified, and offered constitutional BRCA1/BRCA2 testing after pre-test counselling by treating clinicians. Tests were undertaken by TGL Clinical. Results were returned to clinicians by secure email. Onward referrals of patients with uncertain/pathogenic results, or suspicious family histories, to Clinical Genetics were made by the treating team. Surveys assessing patient and clinician satisfaction were sent to participating clinicians and a sample of participating patients. Data was collected with respect to diagnostic yield, turnaround time, onward referral rates, and patient and clinician feedback. A total of 101  patients underwent diagnostic germline BRCA1/BRCA2 tests through this pathway. Pathogenic variants were identified in 12 patients (12%). All patients in whom variants were identified were appropriately referred to Clinical Genetics. At least 12 additional patients with uninformative BRCA1/BRCA2 tests were also referred for formal assessment by Clinical Geneticist or Genetic Counsellor. Issues were noted in terms of time pressures and communication of results to patients. Results from a representative sample of participants completing the satisfaction survey indicated that the pathway was acceptable to patients and clinicians. Mainstreaming of constitutional BRCA1/BRCA2 testing guided by age- and pathology-based criteria is potentially feasible for patients with breast cancer as well as patients with ovarian cancer in Ireland.

A Novel Surrogate Nomogram Capable of Predicting OncotypeDX Recurrence Score©.

Background: OncotypeDX Recurrence Score© (RS) is a commercially available 21-gene expression assay which estimates prognosis and guides chemoendocrine prescription in early-stage estrogen-receptor positive, human epidermal growth factor receptor-2-negative (ER+/HER2−) breast cancer. Limitations of RS testing include the cost and turnaround time of several weeks. Aim: Our aim is to develop a user-friendly surrogate nomogram capable of predicting RS. Methods: Multivariable linear regression analyses were performed to determine predictors of RS and RS > 25. Receiver operating characteristic analysis produced an area under the curve (AUC) for each model, with training and test sets were composed of 70.3% (n = 315) and 29.7% (n = 133). A dynamic, user-friendly nomogram was built to predict RS using R (version 4.0.3). Results: 448 consecutive patients who underwent RS testing were included (median age: 58 years). Using multivariable regression analyses, postmenopausal status (ß-Coefficient: 0.25, 95% confidence intervals (CIs): 0.03−0.48, p = 0.028), grade 3 disease (ß-Coefficient: 0.28, 95% CIs: 0.03−0.52, p = 0.026), and estrogen receptor (ER) score (ß-Coefficient: −0.14, 95% CIs: −0.22−−0.06, p = 0.001) all independently predicted RS, with AUC of 0.719. Using multivariable regression analyses, grade 3 disease (odds ratio (OR): 5.67, 95% CIs: 1.32−40.00, p = 0.037), decreased ER score (OR: 1.33, 95% CIs: 1.02−1.66, p = 0.050) and decreased progesterone receptor score (OR: 1.16, 95% CIs: 1.06−1.25, p = 0.002) all independently predicted RS > 25, with AUC of 0.740 for the static and dynamic online nomogram model. Conclusions: This study designed and validated an online user-friendly nomogram from routinely available clinicopathological parameters capable of predicting outcomes of the 21-gene RS expression assay.

Comparison of the Nottingham Prognostic Index and OncotypeDX© recurrence score in predicting outcome in estrogen receptor positive breast cancer.

INTRODUCTION: Traditionally, Nottingham prognostic index (NPI) informed prognosis in patients with estrogen receptor positive, human epidermal growth factor receptor-2 negative, node negative (ER+/HER2-/LN-) breast cancer. At present, OncotypeDX© Recurrence Score (RS) predicts prognosis and response to adjuvant chemotherapy (AC). AIMS: To compare NPI and RS for estimating prognosis in ER + breast cancer. METHODS: Consecutive patients with ER+/HER2-/LN- disease were included. Disease-free (DFS) and overall survival (OS) were determined using Kaplan-Meier and Cox regression analyses. RESULTS: 1471 patients met inclusion criteria. The mean follow-up was 110.7months. NPI was calculable for 1382 patients: 19.8% had NPI≤2.4 (291/1471), 33.0% had NPI 2.41-3.4 (486/1471), 30.0% had NPI 3.41-4.4 (441/1471), 10.9% had NPI 4.41-5.4 (160/1471), and 0.3% had NPI>5.4 (4/1471). In total, 329 patients underwent RS (mean RS: 18.7) and 82.1% had RS < 25 (270/329) and 17.9% had RS ≥ 25 (59/329). Using multivariable Cox regression analyses (n = 1382), NPI independently predicted DFS (Hazard ratio (HR): 1.357, 95% confidence interval (CI): 1.140-1.616, P < 0.001) and OS (HR: 1.003, 95% CI: 1.001-1.006, P = 0.024). When performing a focused analysis of those who underwent both NPI and RS (n = 329), neither biomarker predicted DFS or OS. Using Kaplan Meier analyses, NPI category predicted DFS (P = 0.008) and (P = 0.026) OS. Conversely, 21-gene RS group failed to predict DFS (P = 0.187) and OS (P = 0.296). CONCLUSION: In our focused analysis, neither NPI nor RS predicted survival outcomes. However, in the entire series, NPI independently predicted both DFS and OS. On the 40th anniversary since its derivation, NPI continues to provide accurate prognostication in breast cancer, outperforming RS in the current study.

Breast cancer recurrence: factors impacting occurrence and survival.

BACKGROUND: Breast cancer mortality has decreased due to improved screening and treatment options. Nevertheless, 25-30% of patients develop disease recurrence and die from the disease dissemination. Patients who develop metastatic disease represent a heterogeneous group and management plans are dependent on molecular subtype, disease burden and metastatic site. AIM: To determine predictive clinicopathological factors of disease recurrence and their impact on survival in the molecular era. METHODS: Consecutive patients who breast cancer developed recurrence at our tertiary referral centre between 2000 and 2015 were included. Clinicopathological and treatment data were assessed using descriptive statistics. Oncological outcome was assessed using Cox regression and Kaplan Meier analyses. RESULTS: Two hundred sixty-five consecutive patients who developed breast cancer recurrence were included; median age at metastasis was 59.3 years (range 27-87 years), and median time to recurrence (TTR) was 47.7 ± 38.5 months (range 3.0-194.3 months). Survival was 24.2% (64/265) 53.2% were luminal A (LABC) (141/265), 18.5% were luminal B (LBBC) (49/265), 18.5% were triple negative (TNBC) (49/265), and 9.8% were human epidermal growth factor receptor-2 overexpressing (HER2 +) (26/265). TTR for patients with LABC was 56.0 ± 41.3 months, LBBC was 48.4 ± 41.1 months, TNBC was 26.9 ± 28.5 months and HER2 + was 34.3 ± 21.8 months. Increased grade (P < 0.001), Nottingham Prognostic Indices (P < 0.001), TNBC (P < 0.001), HER2 + subtype (P < 0.001) and receiving targeted therapy (P = 0.006) predicted shorted TTR. Estrogen receptor positivity (P < 0.001), progesterone receptor positivity (P = 0.010), invasive lobular carcinoma (P = 0.009) and receiving endocrine therapy (P = 0.001) predicted longer TTR. CONCLUSION: Readily available clinicopathological factors predict risk of metastatic dissemination. Developing a tailored program to identify patients at risk of recurrence is crucial in controlling metastatic dissemination of breast cancer.

Bilateral breast cancer: analysis of incidence, outcome, survival and disease characteristics.

There has been conflicting evidence on the impact of bilateral breast cancer (BBC) on the survival and management of patients. The objectives of this study were to address the incidence of BBC and to investigate its characteristics and outcome compared to unilateral cancer. Data were acquired from the prospectively maintained NUIG breast cancer database between 1988 and 2008. BBC were then categorized as synchronous (within 12 months) or metachronous (after 12 months of first tumour). SPSS was used for data analysis. The incidence of BBC in our population was 4.4% (112 of 2,524). Of those 2.1% were synchronous while 2.3% were metachronous. Compared to unilateral cases, bilateral cancer patients were younger (P = 0.021) and had smaller size (P = 0.001) and earlier stage (P < 0.001) tumours at diagnosis. We identified the HER2/neu positivity as a risk factor for developing contralateral breast tumour and ER negativity as a risk factor for developing metachronous tumours. While there was no significant difference in survival for patients with bilateral compared to unilateral tumour (P > 0.05), the synchronous tumour was associated with poorer survival (P = 0.010) in comparison to metachronous tumour. This large single-institutional experience does not support the increasing practice of prophylactic mastectomy but does justify regular follow-up with mammography for early detection of contralateral tumour.

Neoadjuvant chemotherapy for luminal a breast cancer: Factors predictive of histopathologic response and oncologic outcome.

BACKGROUND: The benefit of chemotherapy (NAC) for patients with ER/PR positive, HER2 negative breast cancer is unclear. Our aim was to determine factors associated with histopathologic response and oncologic outcome following NAC in this group. METHODS: Consecutive female patients undergoing neoadjuvant therapy and surgery for locally advanced Luminal A breast cancer between 2010 and 2015 were studied. Multivariable linear, logistic, and Cox regression analysis was undertaken. RESULTS: 114 patients were studied. Pathological complete response (pCR) was achieved in 7.9% of patients, ypN0 in 25.5%, and downstaging in 33.6%. However, 43.9% exhibited a Sataloff C-D response. Tumor grade independently predicted pCR (P = 0.039), while PR score predicted ypN0 (P = 0.017) and downstaging (P=0.029). 5-year invasive disease-free (iDFS) and overall survival (OS) were 68.5 ± 4.7% and 77.7 ± 4.3%, respectively. CONCLUSION: After NAC for Luminal A breast cancer, pCR rates are low. Patients with high grade tumors with weak PR expression exhibit the most promising response rates.

Clinicopathological response to neoadjuvant therapies and pathological complete response as a biomarker of survival in human epidermal growth factor receptor-2 enriched breast cancer - A retrospective cohort study.

BACKGROUND: Human epidermal growth factor receptor-2 (HER2) is overexpressed in 20-25% of breast cancers. Complete eradication of disease following neoadjuvant therapies and chemotherapy has been referred to as pathological complete response (pCR). AIMS: To determine clinicopathological predictors of pCR to neoadjuvant therapies and to evaluate pCR as a surrogate to enhanced survival. METHODS: Consecutive female patients with HER2 positive (HER+) breast cancer managed surgically in a single institution between 2005 and 2015 were included. Descriptive statistics and binary logistic regression were used to determine predictors of pCR. Appraisal of pCR as a predictor of survival was performed using Kaplan-Meier curves and Cox regression analysis. RESULTS: 451 patients were included with a mean age of 56.6 ± 13.4 years (range 23-95). Disease-free (DFS) and overall survival (OS) was 82.3% (371/451) and 82.6% (376/451) respectively with a median follow-up of 108.0 months (range 3-184.0). 118 were treated in the neoadjuvant setting (26.2%): tumour size <50 mm (Odds Ratio (OR): 12.156, P = 0.023) and progesterone receptor negativity (OR: 2.762, P = 0.008) independently predicted breast pCR, while ductal carcinoma (OR: 3.203, P = 0.030) and grade 3 disease (OR: 2.788, P = 0.018) predicted axillary pCR. Both breast and axillary pCR predicted enhanced DFS (Hazard Ratio (HR): 0.470 & HR: 0.449) and OS (HR: 0.383 & HR: 0.307). Axillary pCR independently predicted improved OS (HR: 0.326). CONCLUSION: pCR is sensitive biomarker and surrogate to survival outcomes in HER2+ breast cancer. Patients likely to achieve pCR may be predicted from traditional clinicopathological characteristics and molecular parameters.

Investigating the Potential and Pitfalls of EV-Encapsulated MicroRNAs as Circulating Biomarkers of Breast Cancer.

Extracellular vesicles (EVs) shuttle microRNA (miRNA) throughout the circulation and are believed to represent a fingerprint of the releasing cell. We isolated and characterized serum EVs of breast tumour-bearing animals, breast cancer (BC) patients, and healthy controls. EVs were characterized using transmission electron microscopy (TEM), protein quantification, western blotting, and nanoparticle tracking analysis (NTA). Absolute quantitative (AQ)-PCR was employed to analyse EV-miR-451a expression. Isolated EVs had the appropriate morphology and size. Patient sera contained significantly more EVs than did healthy controls. In tumour-bearing animals, a correlation between serum EV number and tumour burden was observed. There was no significant relationship between EV protein yield and EV quantity determined by NTA, highlighting the requirement for direct quantification. Using AQ-PCR to relate miRNA copy number to EV yield, a significant increase in miRNA-451a copies/EV was detected in BC patient sera, suggesting potential as a novel biomarker of breast cancer.

A Review of the Impact of Neoadjuvant Chemotherapy on Breast Surgery Practice and Outcomes.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) is increasingly used in locally advanced breast cancer as it facilitates breast conserving surgery (BCS) and allows surgical treatment of patients considered inoperable at baseline. The aim of this study was to assess the trends in breast cancer management with regard to the administration of NAC and adjuvant chemotherapy and the effect this has on surgical practice, patient outcomes, and patterns of disease recurrence. PATIENTS AND METHODS: Patients treated with chemotherapy from 2005 to 2014 were identified from a prospectively maintained database. Clinicopathologic details, timing of chemotherapy delivery, and surgical procedures carried out were analyzed. RESULTS: A total of 1619 patients were included in the study. The NAC group (n = 383) had a higher T stage (P < .001) and higher grade disease than the adjuvant group (P = .017). Luminal A breast cancer was less likely to be treated by NAC. The proportion of patients treated with NAC has increased from 12.1% in 2005 to 48.3% in 2014 (P < .001). There was an increase in the BCS rate over time (P = .002); however, a higher proportion of the neoadjuvant group (55.5%) underwent mastectomy. Timing of chemotherapy influenced the type of reconstructive procedure carried out (P = .003). CONCLUSION: The number of patients with breast cancer being treated with NAC is increasing, which is influencing the increasing rate of BCS, though mastectomy is still central to the surgical management of those in receipt of NAC.

The changing cost of breast cancer care: lessons from a centralised modern cancer centre.

BACKGROUND: The cost of new cancer technologies has been the subject of intense debate in recent years. There have been significant advances in therapeutic techniques for breast cancer over the past 20 years. This has been accompanied by the concentration of services in designated cancer centres. The aim of this study was to examine the changing cost of breast cancer management over an 18-year period and identify factors underlying this. METHODS: We use breast cancer services data from Galway University Hospital in 1995-1996, 2005-2006 and 2011-2012 to examine the changing pattern of care costs and survival. RESULTS: The number of patients treated for breast cancer rose from 200 in 1995-1996, to 411 in 2005-2006 and 563 in 2011-2012. Two-year survival rose in line with national figures from 84 to 89.78 and 92.07%, in the three-time periods respectively. Adjusting for inflation, the average cost per patient rose from €14,710 (95% C.I., €13,398 to €16,022) in 1995-1996 to €30,405 (95% C.I., €38,620 to €32,189) in 2005-2006, before falling to €14,458 (C.I., €13,343 to €15,572) in 2011-2012. We found significant changes in the pattern of costs, with some rising in relative and absolute terms while others fell as new therapies became available and/or moved off patent. CONCLUSION: Within an evolving context where services are centralised, new therapies emerge and subsequently come off patent, our understanding of the value of cancer therapies continues to evolve. This has important implications for the evaluation of new therapies and broader policy initiatives in this area.

Colonic perforation in Behcet's syndrome.

A 17-year-old gentleman was admitted to our hospital for headache, the differential diagnosis of which included Behcet's syndrome (BS). He developed an acute abdomen and was found to have air under the diaphragm on erect chest X-ray. Subsequent laparotomy revealed multiple perforations throughout the colon. This report describes an unusual complication of Behcets syndrome occurring at the time of presentation and a review of the current literature of reported cases.

Aesthetic journeys: a review of cosmetic surgery tourism.

Background: Medical tourism has witnessed significant growth in recent years. The emerging trend towards international travel for cosmetic surgical interventions has not previously been reviewed. The current review aims to critically address the scale and impact of cosmetic surgical tourism and to delineate the complication profile of this form of medical tourism. Methods: Articles published in the English language on the PubMed database that were relevant to surgical tourism and the complications of elective surgical procedures abroad were examined. Reference lists of articles identified were further scrutinized. The search terms used included combinations of 'surgery abroad', 'cosmetic surgery abroad', 'cosmetic surgery tourism', 'cosmetic surgery complications' and 'aesthetic tourism'. Results: This article critically reviews the epidemiology of cosmetic surgical tourism and its associated economic factors. Surgical complications of selected procedures, including perioperative complications, are described. The implications for travel medicine practice are considered and recommendations for further research are proposed. Conclusion: This narrative literature review focuses on the issues affecting travellers who obtain cosmetic surgical treatment overseas. There is a lack of focus in the travel medicine literature on the non-surgery-related morbidity of this special group of travellers. Original research exploring the motivation and pre-travel preparation, including the psychological counselling, of cosmetic surgical tourists is indicated.

The role of liver resection in patients with metastatic breast cancer: a systematic review examining the survival impact.

INTRODUCTION: Approximately 10% of breast cancer patients will present with solid organ metastases, while up to 30% will develop metastatic disease during their treatment course. Liver metastases are usually treated with systemic chemotherapy. Although colorectal liver metastases are routinely resected, this is not yet the standard of care for breast cancer-related liver metastases. This review examines the evidence for resection of breast cancer-related liver metastases. METHODS: A systematic review identified 25 articles for inclusion, 12 papers concerning patients with isolated liver metastases, and 13 papers concerning patients with extrahepatic metastases. Data from 1080 patients were included. RESULTS: Two hundred eighty patients underwent hepatic resections for breast cancer-associated metastases with no extrahepatic metastases. Reported 5-year survival ranged from 24.6 to 78%. Median overall survival ranged from 29.5 to 116 months. For patients with oligometastatic disease undergoing resection, 5-year survival ranged from 21 to 57%, with median overall survival ranging from 32 to 58 months. Reported 30-day morbidity ranged from 14 to 42% for isolated and multiple metastases. CONCLUSION: Hepatic resection can be considered in the management of breast cancer patients with isolated liver metastases as well as those with oligometastatic disease.

Disappearing portal venous gas in acute pancreatitis and small bowel ischemia.

We report an usual case of hepatic portal venous gas (HPVG) in the setting of acute pancreatitis and small bowel ischemia. Interestingly, the HPVG disappeared within 2 hours of the original computed tomography scan, despite the patient having small bowel ischemia. The patient had a complicated clinical course, dying 62 days postadmission. This case highlights that HPVG in setting of acute pancreatitis and small bowel ischemia has a very high morbidity and mortality, requiring early detection and aggressive surgical management.

Circulating MicroRNAs in Cancer.

It is believed that microRNAs have potential as circulating biomarkers of disease; however, successful clinical implementation remains a challenge. This chapter highlights broad variations in approaches to microRNA analysis where whole blood, serum and plasma have each been employed as viable sources. Further discrepancies in approaches are seen in endogenous controls and extraction methods utilized. This has resulted in contradictory publications, even when the same microRNA is targeted in the same disease setting.Analysis of blood samples highlighted the impact of both collection method and storage, on the microRNA profile. Analysis of a panel of microRNAs across whole blood, serum, and plasma originating from the same individual emphasized the impact of starting material on microRNA profile. This is a highly topical field of research with immense potential for translation into the clinical setting. Standardization of sample harvesting, processing and analysis will be key to this translation. Methods of sample harvesting, preservation, and analysis are outlined, with important mitigating factors highlighted.