The role of infiltrating lymphocytes in the neo-adjuvant treatment of women with HER2-positive breast cancer.

BACKGROUND: Pre-treatment tumour-associated lymphocytes (TILs) and stromal lymphocytes (SLs) are independent predictive markers of future pathological complete response (pCR) in HER2-positive breast cancer. Whilst studies have correlated baseline lymphocyte levels with subsequent pCR, few have studied the impact of neoadjuvant therapy on the immune environment. METHODS: We performed TIL analysis and T-cell analysis by IHC on the pretreatment and 'On-treatment' samples from patients recruited on the Phase-II TCHL (NCT01485926) clinical trial. Data were analysed using the Wilcoxon signed-rank test and the Spearman rank correlation. RESULTS: In our sample cohort (n = 66), patients who achieved a pCR at surgery, post-chemotherapy, had significantly higher counts of TILs (p = 0.05) but not SLs (p = 0.08) in their pre-treatment tumour samples. Patients who achieved a subsequent pCR after completing neo-adjuvant chemotherapy had significantly higher SLs (p = 9.09 × 10-3) but not TILs (p = 0.1) in their 'On-treatment' tumour biopsies. In a small cohort of samples (n = 16), infiltrating lymphocyte counts increased after 1 cycle of neo-adjuvant chemotherapy only in those tumours of patients who did not achieve a subsequent pCR. Finally, reduced CD3 + (p = 0.04, rho = 0.60) and CD4 + (p = 0.01, rho = 0.72) T-cell counts in 'On-treatment' biopsies were associated with decreased residual tumour content post-1 cycle of treatment; the latter being significantly associated with increased likelihood of subsequent pCR (p < 0.01). CONCLUSIONS: The immune system may be 'primed' prior to neoadjuvant treatment in those patients who subsequently achieve a pCR. In those patients who achieve a pCR, their immune response may return to baseline after only 1 cycle of treatment. However, in those who did not achieve a pCR, neo-adjuvant treatment may stimulate lymphocyte influx into the tumour.

Evaluation of medical student retention of clinical skills following simulation training.

BACKGROUND: Adequate clinical skills training is a challenge for present day medical education. Simulation Based Education (SBE) is playing an increasingly important role in healthcare education worldwide to teach invasive procedures. The impact of this teaching on students along with retention of what is taught is not fully understood. The purpose of this study was to evaluate the retention levels of practical skills taught and assessed by SBE and to explore the degree of re-training required to restore decayed performance. In exploring this aim, the study further investigates how skilled performance decays over time and which dimensions of clinical skills were more likely to decay. METHODS: Study participants were 51 final year medical students. They were provided with online pre-course videos and procedural guides asynchronously with repeatedly access. 7 of the skills taught over 2 years using task trainers were selected. Following demonstration from faculty, students practiced in small groups with faculty facilitated supervision and peer support prior to formal testing. Score sheets with itemised procedure checklists detailing the minimum passing standard (MPS) for each skill were designed. To test retention of skills, 18 months later, there was an unannounced test to demonstrate proficiency in the skills. Students were asked to complete a questionnaire indicating how many times and where they had practiced or performed the skills. RESULTS: 55% of the students were deficient in 3 or more skills and 4% were not competent in 5 or more skills. A significant number of students had never practiced some skills following the initial teaching session. A relationship was noted with the number of times students self-declared that they had practiced and their performance. Decay is evident in both psychomotor and cognitive domains of the skills. CONCLUSION: A curriculum with deliberate practice significantly increases the competence of students in defined clinical skills. Deliberate practice of clinical skills, under supervision of an engaged instructor, is a key component of the mastery model. Experiences and assessments in the clinical setting need to be augmented with focus on direct observation and focused feedback to reinforce the skills acquired in the simulated setting.

Long-term outcomes and healthcare utilization following critical illness--a population-based study.

BACKGROUND: The purpose of this study was to examine hospital mortality, long-term mortality, and health service utilization among critically ill patients. We also determined whether these outcomes differed according to demographic and clinical characteristics. METHODS: We conducted a retrospective cohort study of adults (age ≥ 18 years) who survived admission to an intensive care unit (ICU) in Ontario, Canada, between 1 April 2002 and 31 March 2012, excluding isolated admissions to step-down or intermediate ICUs, coronary care ICUs, or cardiac surgery ICUs. Adults (age ≥ 18 years) who survived an acute hospitalization that did not include an ICU stay formed the comparator group. The primary outcome was mortality following hospital discharge. Secondary outcomes were healthcare utilization, including emergency room admissions and hospital readmissions during follow-up. RESULTS: Over the study interval, 500,124 patients were admitted to ICUs and 420,187 (84%) survived to hospital discharge. Median follow-up for survivors was 5.3 (interquartile range 2.5, 8.2) years. Patients admitted to an ICU were more likely to subsequently visit the emergency department, be readmitted to the hospital and ICU, receive home care support, require rehabilitation, and be admitted for long-term care. Those requiring more resources within the ICU required more resources after discharge. One-third of patients admitted to the ICU died during long-term follow-up, with overall probabilities of death of 11% and 29% at 1 year and 5 years, respectively. In the adjusted analysis, there was an increasing hazard of death with increasing age, reaching a hazard ratio of 18.08 (95 % confidence interval 16.60-19.68) for those ≥ 85 years of age compared with those aged 18-24 years. CONCLUSIONS: Healthcare utilization after hospital discharge was higher among ICU patients, and also among those requiring more healthcare resources during their ICU admission, than among all hospitalized patients as a group. One-third of ICU patients died within the 5 years following discharge, and age was the most influential determinant of outcome. These findings should help target post-ICU discharge services for high-risk groups and better inform goals-of-care discussions for elderly critically ill patients.

Meta-analysis to determine the clinical impact of axillary lymph node dissection in the treatment of invasive breast cancer.

There are divergent opinions regarding the optimum surgical management of the axilla in patients with invasive breast cancer. Guidelines mandate axillary lymph node dissection (ALND) in the setting of positive sentinel lymph nodes. However, recent studies have questioned the true benefits of this procedure. Therefore, a meta-analysis of relevant randomized trials was performed in order to clarify the oncological benefit of axillary lymph node dissection. A comprehensive search of published randomized trials that compared patients with primary operable breast cancer with/without ALND was performed using MEDLINE, and available data were cross-referenced. Reviews of each study were conducted, and data were extracted. Primary outcomes were overall survival and recurrent axillary disease. A total of 7347 patients with operable primary breast cancer were identified from 8 randomised controlled trials comparing axillary recurrence in patients with or without ALND. Six of these trials provided data on overall survival on 6895 patients. Overall survival favours patients having ALND (OR = 1.22 (95% CI 1.03-1.44, p = 0.02). Similarly, patients undergoing ALND had increased recurrence-free survival (OR = 2.25 (95% CI 1.28-3.94, p = 0.0047). ALND appears to positively impact on overall and recurrence-free survival from breast cancer. These data highlight the enduring benefits of ALND in an era where adjuvant therapies are being promoted to manage regionally advanced/metastatic disease.

An International Multicenter Review of the Malignancy Rate of Excised Papillomatous Breast Lesions.

BACKGROUND: Papillary lesions of the breast are a relatively rare, but heterogeneous group ranging from benign to atypical and malignant. Debate exists regarding the optimal management of these lesions. In the absence of more accurate risk-stratification models, traditional management guidelines recommend surgical excision, despite the majority of lesions proving benign. This study sought to determine the rate of malignancy in excised breast papillomas and to elucidate whether there exists a population in which surgical excision may be unnecessary. METHODS: A multicenter international retrospective review of core biopsy diagnosed breast papillomas and papillary lesions was performed between 2009 and 2013, following institutional ethical approval. Patient demographics, histopathological, and radiological findings were recorded. All data was tabulated, and statistical analysis performed using Stata. RESULTS: A total of 238 patients were included in the final analysis. The age profile of those with benign pathology was significantly younger than those with malignant pathology (p < 0.001). Atypia on core needle biopsy was significantly associated with a final pathological diagnosis of malignancy (OR = 2.73). The upgrade rate from benign core needle biopsy to malignancy on the final pathological sample was 14.4 %; however, only 3.7 % had invasive cancer. CONCLUSIONS: This international dataset is one of the largest in the published literature relating to breast papillomas. The overall risk of malignancy is significantly associated with older age and the presence of atypia on core needle biopsy. It may be possible to stratify higher-risk patients according to age and core needle biopsy findings, thereby avoiding surgery on low-risk patients.

Laminar airflow and the prevention of surgical site infection. More harm than good?

INTRODUCTION: Laminar airflow (LAF) systems are thought to minimise contamination of the surgical field with airborne microbes and thus to contribute to reducing surgical site infections (SSI). However recent publications have questioned whether LAF ventilation confers any significant benefit and may indeed be harmful. METHODS: A detailed literature review was undertaken through www.Pubmed.com and Google scholar (http://scholar.google.com). Search terms used included "laminar flow". "laminar airflow", "surgical site infection prevention", "theatre ventilation" and "operating room ventilation", "orthopaedic theatre" and "ultra-clean ventilation". Peer-reviewed publications in the English language over the last 50 years were included, up to and including March 2014. RESULTS: Laminar airflow systems are predominantly used in clean prosthetic implant surgery. Several studies have demonstrated decreased air bacterial contamination with LAF using bacterial sedimentation plates placed in key areas of the operating room. However, apart from the initial Medical Research Council study, there are few clinical studies demonstrating a convincing correlation between decreased SSI rates and LAF. Moreover, recent analyses suggest increased post-operative SSI rates. CONCLUSION: It is premature to dispense with LAF as a measure to improve air quality in operating rooms where prosthetic joint surgery is being carried out. However, new multi-centre trials to assess this or the use of national prospective surveillance systems to explore other variables that might explain these findings such as poor operating room discipline are needed, to resolve this important surgical issue.

Breaking Barriers to Successful Implementation of Day Case Laparoscopic Cholecystectomy.

Laparoscopic cholecystectomy is a common procedure performed in both emergency and elective settings. Our aim was to analyse the trends in laparoscopic surgery in Ireland in the public and private healthcare systems. In particular we studied the trend in day case laparoscopic cholecystectomy. National HIPE data for the years 2010-2012 was obtained. Similar datasets were obtained from the three main health insurers. 19,214 laparoscopic cholecystectomies were carried out in Ireland over the 3-year period. More procedures were performed in the public system than the private system from 2010-2012. There was a steady increase in surgeries performed in the public sector, while the private sector remained static. Although the ALOS was significantly higher in the public sector, there was an increase in the rate of day case procedures from 416 (13%) to 762 (21.9%). The day case rates in private hospitals increased only slightly from 29 (5.1%) in 2010 to 40 (5.9%) in 2012. Day case laparoscopic cholecystectomy has been shown to be a safe procedure, however significant barriers remain in place to the implementation of successful day case units nationwide.

Using Social Media to Increase Accessibility to Online Teaching Resources.

The key learning points of Surgical Grand Rounds (SGR) are often not accessible at times of exam revision for students. We sought to use Twitter as an online teaching repository. A SGR Twitter profile was created. 23 SGR presentations were made accessible on Twitter over a 3 month period. 93 students were invited to complete a questionnaire assessing usage of the repository. 84 (90%) in total responded, of these, 25 (80.6%) felt that the online provision of SGR through twitter was "useful". The majority (71%) felt that the online content was easily accessible. The novel use of social media is a useful adjunctive educational tool in accessing an online repository of SGR presentations.

Surgical attire, practices and their perception in the prevention of surgical site infection.

INTRODUCTION: Clean surgical scrubs, surgical gowns and headgear are worn by operative teams to decrease bacterial contamination and lower surgical site infection (SSI) rates. METHODS: A detailed review was undertaken of peer-reviewed publications and other sources of material in the English language over the last 50 years included. RESULTS: Surgical scrubs should be clean and made of tightly woven material. Studies investigating single-use gowns and drapes versus reusable gowns report conflicting evidence. Double gloving may reduce SSI rates in procedures where no antibiotic prophylaxis was administered. Bacterial contamination of the operative field has been shown to be decreased by the wearing of surgical headgear by the operating team. CONCLUSIONS: Further consideration and better trials are required to determine the impact of different theatre clothing on SSI rates.

Perspectives of educators and students on the efficacy of online teaching and learning strategies employed during COVID-19 in a health sciences institution.

BACKGROUND: Healthcare education encountered unprecedented challenges during the COVID-19 pandemic, but the necessary responses have also provided learning opportunities for the future. AIMS: We aimed to evaluate the impact of COVID-19 on teaching and learning strategies and the perceptions of clinical educators and health sciences students on novel methods to improve online student engagement in Ireland's largest medical school. METHODS: Two separate online surveys designed to gain insights into the perceived efficacy of online teaching strategies were distributed to clinical educators and health sciences students (medical and pharmacy) over 7 months via email. RESULTS: A total of 86.4% of educators responded that rapport was more difficult to build online, and 90.5% reported less engagement from students online. The most popular methods that improved student engagement included using polls, a chat box function for questions, small group discussions and having student cameras turned on. Amongst educators surveyed, 81.8% felt a training course focused on teaching strategies at the start of every academic year would be beneficial. From the students' perspective, no difference was noted between the medicine and the pharmacy students. Seventy-five percent reported using quizzes/polls, and 63% reported using game-based platforms as techniques to improve online learning. Sixty-two percent of students described it as a positive outcome of learning during the pandemic. CONCLUSION: Any pandemic poses unique challenges to the delivery of healthcare education. These surveys report educators' and students' views on online teaching and learning strategies, highlighting novel mechanisms to improve student engagement and ultimately impact on graduate outcomes.

The surgical management of Spitz naevi and atypical spitzoid neoplasms: A review of the literature.

Melanocytic lesions with spitzoid differentiation represent a difficult management paradigm. Spitzoid lesions form a spectrum of distinct entities encompassing Spitz naevi, atypical Spitz naevi and spitzoid melanoma which range from benign to malignant. Differentiation between benign and malignant lesions can be challenging making surgical management difficult. In this article we highlight clinical conundrums regarding Spitz naevi. We review the literature in terms of the newer histological tools available to more explicitly classify these lesions which may have an impact on the clinical care that these patients receive. The article also examines the controversy which surrounds the role of sentinel lymph node biopsy (SLNB) and completion lymph node dissection in the management of melanocytic proliferations with Spitz differentiation.

Evaluating the clinical efficacy and cost effectiveness of direct access endoscopy.

INTRODUCTION: Direct access endoscopy (DAE) allows primary care physicians (PCPs) to refer patients with concerning symptoms for endoscopy in a timely manner. Guidelines are available to assist PCPs in appropriately selecting patients for DAE. The objective of this study was to evaluate both the clinical benefit and cost effectiveness of an upper gastrointestinal (UGI) DAE program. METHODS: The diagnostic yield of DAE patients attending for UGI studies was evaluated using a prospectively maintained database from 2004 to 2011. The diagnosis of UGI neoplasia, Barretts oesophagus, peptic ulcer disease or other conditions were recorded. In addition the age of the patient and the indication for the UGI endoscopy as per the PCP was compared with National Institute of Clinical Excellence (NICE) guidelines for UGI endoscopy. RESULTS: PCPs referred 4262 patients for UGI endoscopy. Oesophageal cancer was diagnosed in 7 and gastric cancer was identified in 27 patients. This represents a diagnostic yield overall of 0.8% for UGI cancers. Barretts oesophagus was identified in 148 (3.5%) and 185 patients (4.34%) were diagnosed with peptic ulcer disease. Interestingly, 3734 patients (87.6%) had a normal UGI endoscopy through our DAE program representing a cost of 2,296,410 Euro. In patients under 40 years of age the diagnostic yield for UGI cancer was 0.14%. More importantly, 92.2% of UGI endoscopies in patients less 40 years of age were normal. CONCLUSION: It is essential that PCPs adhere to published guidelines prior to referring patients to the DAE program. Furthermore, patients under 40 years of age may represent a subset of patients that may not benefit from immediate UGI endoscopy through a direct access program.

Patient and surgeon factors are associated with the use of laparoscopy in appendicitis.

AIM: The use of a minimally invasive approach to treat appendicitis has yet to be universally accepted. The objective of this study was to examine recent trends in Ireland in the surgical management of acute appendicitis. METHOD: Data were obtained from the Irish Hospital In-Patient Enquiry system for patients discharged with a diagnosis of appendicitis between 1999 and 2007. An anonymous postal survey was sent to all general surgeons of consultant and registrar level in Ireland to assess current attitudes to the use of laparoscopic appendectomy. RESULTS: The use of laparoscopic appendectomy increased throughout the study and was the most common approach for appendectomy in 2007. Multivariate analysis revealed age under 50 years (OR = 1.51), female sex (OR = 2.84) and residence in high-density population areas (OR = 4.15) as predictive factors for undergoing laparoscopic appendectomy in the most recent year of the study. While 97% of surgeons reported current use of laparoscopy in patients with acute right iliac fossa pain, in most cases it was selective. Surgeons in university teaching hospitals (42 of 77; 55%) were more likely to report using laparoscopic appendectomy for all cases of appendicitis than those in regional (six of 23; 26%) or general (13 of 53; 25%) hospitals (P = 0.048). CONCLUSION: This study has demonstrated a significant increase in laparoscopic appendectomy, yet a variety of patient and surgeon factors contribute to the choice of procedure. Differences in the perception of benefit of the laparoscopic approach amongst surgeons appears to be an important factor in determining the operative approach for appendectomy.

Emerging therapies for thyroid carcinoma.

Thyroid carcinoma is the most commonly diagnosed endocrine malignancy. Its incidence is currently rising worldwide. The discovery of genetic mutations associated with the development of thyroid cancer, such as BRAF and RET, has lead to the development of new drugs which target the pathways which they influence. Despite recent advances, the prognosis of anaplastic thyroid carcinoma is still unfavourable. In this review we look at emerging novel therapies for the treatment of well-differentiated and medullary thyroid carcinoma, and advances and future directions in the management of anaplastic thyroid carcinoma.

Is there a requirement for axillary lymph node dissection following identification of micro-metastasis or isolated tumour cells at sentinel node biopsy for breast cancer?

INTRODUCTION: Recent decades have seen a significant shift towards conservative management of the axilla. Increasingly, immunohistochemical analysis of sentinel nodes leads to the detection of small tumour deposits, the significance of which remains uncertain. The aims of this study are to examine patients whose sentinel lymph nodes are positive for macro-metastasis, micro-metastasis or isolated tumour cells (ITCs) and to determine the rate of further nodal disease after axillary lymph node dissection (ALND). METHODS: A retrospective analysis of all patients undergoing a sentinel lymph node biopsy (SLNB) between January 2007 and December 2010 in a tertiary referral breast unit was performed. Patients who underwent an axillary lymph node dissection for macro-metastasis, micro-metastasis or ITCs were identified. Demographics, histological data and the rate of further axillary disease were examined. RESULTS: In total, 664 breast cancer patients attended the symptomatic breast unit during the study period, 360 of whom underwent a SLNB. Seventy patients had a SLNB positive for macro-metastasis. All of these patients underwent ALND. A positive SLNB with either micro-metastasis or ITCs was identified in 58 patients. Only 41 of the 58 patients went on to have an ALND, due primarily to variations in surgeons' preferences. Nineteen patients with micro-metastasis underwent an ALND. Four patients had further axillary disease (21%). Twenty-two patients had ITCs identified, of whom only one had further disease (4.5%). No statistically significant difference was found between the two groups in terms of tumour size, grade, lymphovascular invasion or oestrogen receptor status. CONCLUSION: ALND should be considered in patients with micro-metastasis at SLNB. It should rarely be employed in the setting of SLNB positive for ITCs.

Centralisation of rectal cancer care has improved patient survival in the republic of Ireland.

BACKGROUND: Centralisation of rectal cancer surgery to designated centres was a key objective of the Irish national cancer control program. A national audit of rectal cancer surgery indicated centralisation was associated with improved early surgical outcomes. This study aimed to determine the impact of implementation of the national cancer strategy on survival from rectal cancer. MATERIALS AND METHODS: Data were collected from the National Cancer Registry of Ireland to include all patients with Stage I-III rectal cancer undergoing rectal cancer surgery with curative intent between 2003 and 2012. Five-year overall survival and cancer-specific survival was compared between patients in the pre-centralisation (2003-2007) and post-centralisation period (2008-2012) and between patients receiving surgery in designated cancer centres and non-cancer centres. RESULTS: The proportion of rectal cancer surgery performed in a designated cancer centre increased from 42% during 2003-2007 to 58% during 2008-2012. Five-year overall survival increased from 66.1% in 2003-2007 to 73.5% in 2008-2012 (p < 0.001). Five-year cancer-specific survival increased from 75.3% in 2003-2007 to 81.9% in 2008-2012 (p < 0.001). Surgery in a cancer centre and surgery post-centralisation were significantly associated with overall and cancer specific survival using Cox proportional hazards regression. CONCLUSION: Survival following resection of rectal cancer was significantly improved following implementation of a national cancer strategy incorporating centralisation of rectal cancer surgery.

Acute complicated appendicitis caused by an ingested toothpick - A case report.

INTRODUCTION AND IMPORTANCE: Acute appendicitis is one of the most common presentations to the emergency department, particularly in young adults. A combination of clinical suspicion, inflammatory blood markers and imaging modalities such as ultrasound and CT are used for its definitive diagnosis. Early detection and intervention are paramount to reduce morbidity and mortality. Laparoscopic appendicectomy is the current gold standard in the management of appendicitis, especially if complicated according to EAES guidelines. There are few documented cases in the literature of acute appendicitis secondary to foreign body ingestion. On account of this, there are currently no guidelines for its management. Our literature review highlights the importance of surgical management of foreign body acute appendicitis. CASE PRESENTATION: This case report describes the rare presentation of acute complicated appendicitis caused by an ingested toothpick in a 64 year old woman. The patient was admitted with a 3 day history of lower abdominal pain, localizing to the right iliac fossa with raised inflammatory markers. CT imaging reported acute complicated appendicitis. Laparoscopic appendicectomy was performed during which a toothpick was seen protruding through the appendiceal wall. Post operatively the patient was treated with IV antibiotics for 5 days prior to discharge. CLINICAL DISCUSSION: Due to the rare nature of foreign body appendicitis there are no specific guidelines on the respective surgical approach. A literature review showed that in the setting of foreign body appendicitis, surgical intervention is paramount with no scope for conservative management. CONCLUSION: Surgical approach is based on the clinical judgement and skillset of the operating surgeon.

Cytosolic phospholipase A2-α expression in breast cancer is associated with EGFR expression and correlates with an adverse prognosis in luminal tumours.

BACKGROUND: The eicosanoid signalling pathway promotes the progression of malignancies through the production of proliferative prostaglandins (PGs). Cytosolic phospholipase A(2)α (cPLA(2)α) activity provides the substrate for cyclooxygenase-dependent PG release, and we have previously found that cPLA(2)α expression correlated with EGFR/HER2 over-expression in a small number of breast cancer cell lines. METHODS: The importance of differential cPLA(2)α activity in clinical breast cancer was established by relating the expression of cPLA(2)α in tissue samples from breast cancer patients, and two microarray-based gene expression datasets to different clinicopathological and therapeutic parameters. RESULTS: High cPLA(2)α mRNA expression correlated with clinical parameters of poor prognosis, which are characteristic of highly invasive tumours of the HER2-positive and basal-like subtype, including low oestrogen receptor expression and high EGFR expression. High cPLA(2)α expression decreased overall survival in patients with luminal cancers, and correlated with a reduced effect of tamoxifen treatment. The cPLA(2)α expression was an independent predictive parameter of poor response to endocrine therapy in the first 5 years of follow-up. CONCLUSION: This study shows a role of cPLA(2)α in luminal breast cancer progression, in which the enzyme could represent a novel therapeutic target and a predictive marker.

HOXC11-SRC-1 regulation of S100beta in cutaneous melanoma: new targets for the kinase inhibitor dasatinib.

BACKGROUND: Cutaneous melanoma is an aggressive disease. S100beta is an established biomarker of disease progression; however, the mechanism of its regulation in melanoma is undefined. METHODS: Expression of HOXC11 and SRC-1 was examined by immunohistochemistry and immunofluorescence. Molecular and cellular techniques were used to investigate regulation of S100beta, including, western blot, qPCR, ChIP and migration assays. RESULTS: Expression levels of the transcription factor HOXC11 and its coactivator SRC-1 were significantly elevated in malignant melanoma in comparison with benign nevi (P<0.001 and P=0.017, respectively, n=80), and expression of HOXC11 and SRC-1 in the malignant tissue associated with each other (P<0.001). HOXC11 recruitment to the promoter of S100beta was observed in the primary melanoma cell line SKMel28. S100beta expression was found to be dependant on both HOXC11 and SRC-1. Treatment with the Src/Abl inhibitor, dasatinib, reduced HOXC11-SRC-1 interaction and prevented recruitment of HOXC11 to the S100beta promoter. Dasatinib inhibited both mRNA and protein levels of S100beta and reduced migration of the metastatic cell line MeWo. CONCLUSION: We have defined a signalling mechanism regulating S100beta in melanoma, which can be modulated by dasatinib. Profiling patients for expression of key markers of this network has the potential to increase the efficacy of dasatinib treatment.