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This is the case of an infant with a persistent dermatitis affecting the perioral, acral and napkin areas, in whom a simple oral therapy provided a rapid treatment response.

Oesophageal cancer has a reputation for poor survival, and a relatively high risk of major postoperative morbidity and mortality. Encouragingly, a recent international cancer registry study reports a doubling of survival outcomes in Ireland over the last 20 years. This study focused on both oncologic and operative outcomes in patients treated with curative intent requiring surgery at a high-volume center. All patients undergoing surgery or multimodal therapy with curative intent from 2009 to 2018 were studied. All data was recorded prospectively and maintained internally. The period 2009–2013 was compared with 2014–2018 to monitor any change in trends. Four hundred and seventy-five patients (adenocarcinoma 77%, mean age 65; 76% male; 64% neoadjuvant therapy) underwent open surgical resection, 54% via en bloc 2-stage, 19.8% en bloc 3-stage, and 26.5% by a transhiatal approach. New onset atrial fibrillation was the commonest index complication, in 108 (22.7%), 80 (18%) developed suspected pneumonia/respiratory tract infection, 20 (4.2%) an anastomotic leak, and 25 (5.2%) a chyle leak. The 90-day mortality rate was 1.2% and 0.8% at 30 days. The median survival was 77.17 months, with a 5-year survival of 56%. Consistent with registry data on population survival for oesophageal cancer, this study highlights markedly improved survival outcomes in patients treated curatively, reflecting international trends, as well as low mortality rates; however, cardiorespiratory complications remain significant.

Lymphoma diagnosis is complex, requiring a wide array of adjunctive tests to reach accurate diagnoses. We retrospectively examined the rates of concordance between referral and review lymphoma diagnoses on cases referred to St James’s Hospital, Dublin for multidisciplinary team review between 2013 and 2016. Frequency and cost of adjunctive diagnostic tests performed were also analysed. The overall discordance rate was 7.8% (14/179), compared with rates of 6%–48% in the published literature. 13 discordant cases required a change in clinical management following review of the referred diagnosis. Of all referred cases, 33.5% (60/179) required extra analyses to reach a final diagnosis, costing the reference laboratory €35463.40. We conclude that establishment of centralised haematopathology diagnostic networks would help reduce the rate of revision made to lymphoma diagnoses by providing specialist haematopathologist input and access to ancillary testing.

The first pillar of the End-TB Strategy is “early diagnosis and prompt treatment”. Nevertheless, long delays in starting tuberculosis (TB) treatment are reported. We aimed to describe the demographics and clinical features of TB in the west of Ireland and better understand the delays in treatment. We conducted a retrospective chart review of all patients diagnosed with active TB who attended the Galway University Hospital (GUH) TB clinic from 2014 to 2018. Eighty-five patients were diagnosed with TB and attended our clinic. Ten (12%) patients were receiving immunosuppressive therapy, 8 (9%) had drug resistance, and 41 (48%) had extra-pulmonary disease. Patients with extra-pulmonary disease had a longer length of stay before treatment (11 vs. 4 days; p = 0.006). Patients older than 55 had a longer length of stay before (16 vs. 5 days, p = 0.0001) and during (36 vs. 11 days, p = 0.004) treatment and were readmitted more frequently than younger patients. A total of 36% of patients were born outside Ireland. Non-Irish patients were younger (mean age 35 vs 48; p = 0.004) and more frequently had drug resistance (19% vs. 4%, p = 0.02). The median time from symptom onset to hospital presentation was 76 days (IQR 35–146 days) and the median time from first hospital presentation to TB treatment was 11 days (IQR 5–51 days). TB patients experienced long symptom durations in the community prior to presentation. Many TB patients experienced delays in diagnosis and treatment following presentation. Both pre-hospital and in-hospital delays need to be addressed in order to ‘End-TB’.

Oesophageal cancer has a reputation for poor survival, and a relatively high risk of major postoperative morbidity and mortality. Encouragingly, a recent international cancer registry study reports a doubling of survival outcomes in Ireland over the last 20 years. This study focused on both oncologic and operative outcomes in patients treated with curative intent requiring surgery at a high-volume center.All patients undergoing surgery or multimodal therapy with curative intent from 2009 to 2018 were studied. All data was recorded prospectively and maintained internally. The period 2009-2013 was compared with 2014-2018 to monitor any change in trends.Four hundred and seventy-five patients (adenocarcinoma 77%, mean age 65; 76% male; 64% neoadjuvant therapy) underwent open surgical resection, 54% via en bloc 2-stage, 19.8% en bloc 3-stage, and 26.5% by a transhiatal approach. New onset atrial fibrillation was the commonest index complication, in 108 (22.7%), 80 (18%) developed suspected pneumonia/respiratory tract infection, 20 (4.2%) an anastomotic leak, and 25 (5.2%) a chyle leak. The 90-day mortality rate was 1.2% and 0.8% at 30 days. The median survival was 77.17 months, with a 5-year survival of 56%.Consistent with registry data on population survival for oesophageal cancer, this study highlights markedly improved survival outcomes in patients treated curatively, reflecting international trends, as well as low mortality rates; however, cardiorespiratory complications remain significant.

Globally, few precipitation records extend to the 18th century. The England Wales Precipitation (EWP) series is a notable exception with continuous monthly records from 1766. EWP has found widespread use across diverse fields of research including trend detection, evaluation of climate model simulations, as a proxy for mid‐latitude atmospheric circulation, a predictor in long‐term European gridded precipitation data sets, the assessment of drought and extremes, tree‐ring reconstructions and as a benchmark for other regional series. A key finding from EWP has been the multi‐centennial trends towards wetter winters and drier summers. We statistically reconstruct seasonal EWP using independent, quality‐assured temperature, pressure and circulation indices. Using a sleet and snow series for the UK derived by Profs. Gordon Manley and Elizabeth Shaw to examine winter reconstructions, we show that precipitation totals for pre‐1870 winters are likely biased low due to gauge under‐catch of snowfall and a higher incidence of snowfall during this period. When these factors are accounted for in our reconstructions, the observed trend to wetter winters in EWP is no longer evident. For summer, we find that pre‐1820 precipitation totals are too high, likely due to decreasing network density and less certain data at key stations. A significant trend to drier summers is not robustly present in our reconstructions of the EWP series. While our findings are more certain for winter than summer, we highlight (a) that extreme caution should be exercised when using EWP to make inferences about multi‐centennial trends, and; (b) that assessments of 18th and 19th Century winter precipitation should be aware of potential snow biases in early records. Our findings underline the importance of continual re‐appraisal of established long‐term climate data sets as new evidence becomes available. It is also likely that the identified biases in winter EWP have distorted many other long‐term European precipitation series., The trend towards wetter winters and drier summers in EWP can be explained by changes in measurement practice and data biases. For winter (Figure below), the timing of divergence aligns with the introduction of the Snowdon Pattern Rain Gauge in the UK around 1863. Given the widespread use of EWP across environmental and climate research, we expect that our findings will challenge understanding of multi‐centennial trends in precipitation in the UK. These changes in measurement practice are also likely to affect other long‐term precipitation records in north‐west Europe.

Over much of the globe, the temporal extent of meteorological records is limited, yet a wealth of data remains in paper or image form in numerous archives. To date, little attention has been given to the role that students might play in efforts to rescue these data. Here we summarize an ambitious research-led, accredited teaching experiment in which undergraduate students successfully transcribed more than 1,300 station years of daily precipitation data and associated metadata across Ireland over the period 1860–1939. We explore i) the potential for integrating data rescue activities into the classroom, ii) the ability of students to produce reliable transcriptions and, iii) the learning outcomes for students. Data previously transcribed by Met Éireann (Ireland’s National Meteorological Service) were used as a benchmark against which it was ascertained that students were as accurate as the professionals. Details on the assignment, its planning and execution, and student-aids used are provided. The experience highlights the benefits that can accrue for data rescue through innovative collaboration between national meteorological services and academic institutions. At the same time, students have gained valuable learning outcomes and firsthand understanding of the processes that underpin data rescue and analysis. The success of the project demonstrates the potential to extend data rescue in the classroom to other universities, thus providing both an enriched learning experience for the students and a lasting legacy to the scientific community.

Neoadjuvant therapy (NAT) offers a unique opportunity to assess tumor response to systemic agents. However, a discrepancy may exist between the response of the primary tumor and involved nodes. We report on the frequency of response discordance after NAT in breast cancer.All consecutive node-positive patients receiving NAT in our department from 2009 to 2014 were identified. Patient demographics, and radiologic and pathologic features were tabulated. Tumor response was estimated by magnetic resonance imaging of the breast. Lymph node (LN) response was estimated from pathologic treatment response measurements. Statistical analysis was performed.A total of 108 node-positive patients treated with NAT were eligible for inclusion. Median age was 51.73 years (range, 20-87 years). All patients underwent axillary clearance, and 62% underwent mastectomy. A 40% mean reduction in tumor size was observed. Statistically, a positive correlation between tumor and LN response after NAT was observed (Spearman correlation coefficient, r = 0.46, P .001). Complete pathologic response was observed in 17 patients (15.7%). However, 21 patients experienced complete LN response, with only 81% of these patients (n = 17) experiencing a complete response in tumor also. A complete response was observed in tumor in 20 patients, and this predicted complete nodal response in 85% of cases (n = 17). Fifteen percent of primary tumors with complete pathologic response had persistently positive LNs.A significant discordance exists between the primary tumor and LN response, representing a concern for the lack of response of occult regional or systemic metastases due to potential biologic heterogeneity.

The pathological spectrum of lung tumours is broad; however it is dominated by primary lung carcinoma (cancer). The WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart, published in 2015, has significantly altered the landscape of lung cancer reporting, particularly with respect to lung adenocarcinoma. In this review article, the aim is to provide insight into lung pathology reporting and its implications. Lung tumours can be diagnosed on biopsy tissue, cytology material or resected specimens. Conservation of tissue for molecular characterization is paramount, particularly when small amounts of tissue are received. Histological and molecular diagnostics of lung cancer specimens guides personalized targeted therapy. A multidisciplinary approach to primary lung carcinoma management is imperative so as to achieve the best possible patient outcomes.

Summary Barrett’s esophagus (BE) is the main pathological precursor of esophageal adenocarcinoma (EAC). Progression to high-grade dysplasia (HGD) or EAC from nondysplastic BE (NDBE), low-grade dysplasia (LGD) and indefinite for dysplasia (IND) varies widely between population-based studies and specialized centers for many reasons, principally the rigor of the biopsy protocol and the accuracy of pathologic definition. In the Republic of Ireland, a multicenter prospective registry and bioresource (RIBBON) was established in 2011 involving six academic medical centers, and this paper represents the first report from this network. A detailed clinical, endoscopic and pathologic database registered 3,557 patients. BE was defined strictly by both endoscopic evidence of Barrett’s epithelium and the presence of specialized intestinal metaplasia (SIM). A prospective web-based database was used to gather information with initial and follow-up data abstracted by a data manager at each site. A total of 2,244 patients, 1,925 with no dysplasia, were included with complete follow-up. The median age at diagnosis was 60.5 with a 2.1:1 male to female ratio and a median follow-up time of 2.7 years (IQR 1.19–4.04), and 6609.25 person years. In this time period, 125 (5.57%) progressed to HGD/EAC, with 74 (3.3%) after 1 year of follow-up and 38 (1.69%) developed EAC, with 20 (0.89%) beyond 1 year. The overall incidence of HGD/EAC was 1.89% per year; 1.16% if the first year is excluded. The risk of progression to EAC alone overall was 0.57% per year, 0.31% excluding the first year, and 0.21% in the 1,925 patients who had SIM alone at diagnosis. Low-grade dysplasia (LGD) progressed to HGD/EAC in 31% of patients, a progression rate of 12.96% per year, 6.71% with the first year excluded. In a national collaboration of academic centers in Ireland, the progression rate for NDBE was similar to recent population studies. Almost one in two who progressed was evident within 1 year. Crucially, LGD diagnosed and confirmed by specialist gastrointestinal pathologists represents truly high-risk disease, highlighting the importance of expertise in diagnosis and management, and providing indirect support for ablative therapies in this context.

Introduction Paediatricians play a significant role in preventive healthcare1. There is a strong link between radiation exposure and the development of cancer2. The typical dose of radiation required for an abdominal x-ray (AXR) is 0.46 mSv, which is the equivalent approximate dose to 35 chest x-rays3. AXRs are frequently ordered for children in our hospital by staff in paediatric, surgical and Emergency Departments (ED) who may be unaware of the guidelines surrounding clinical indications for AXRs. Aims To review the indications for paediatric AXRs requested in our hospital and compare them to the Royal Children’s Hospital, Melbourne (RCHM) Guidelines4, which are considered the gold standard. Methods AXRs performed in University Hospital Galway from 1st June - 30th November 2018, on children ≤14 years old, were identified. Those ordered from the Neonatal Intensive Care Unit and those ordered directly by the patient’s General Practitioner were excluded. Details including patient age, clinical indication, requesting specialty, existing diagnoses and previous presentations with the same complaint were collected from the online radiology system. Results A total of 132 AXRs were identified, 83 of which were included in the analysis. In accordance with RCHM guidance, 49.4% (n=41) of requests were appropriate. Bowel obstruction and foreign body ingestion were the commonest indications for appropriate requests; constipation and non-specific abdominal pain were the commonest inappropriate requests. The paediatric department requested 55 AXRs, 49% (n=27) considered appropriate; the surgical department requested 9, zero considered appropriate. The ED requested 17 AXRs, 70.5% (n=12) considered appropriate. Conclusion During the 6-month period, over half of the AXR requests were deemed inappropriate and may have been avoided. Further education concerning AXR indications should be directed at paediatric and surgical teams primarily to minimise unnecessary investigations and limit radiation exposure. References Chang VY, Davidson TB ( 2015). Childhood Exposures and Risk of Malignancy in Adulthood. Pediatric Annals. 44(11), e270–e273. Willis CE, Slovis T L ( 2005). The ALARA concept in pediatric cr and dr: dose reduction in pediatric radiographic exams — a white paper conference. American Journal of Roentgenology, 184(2), 373–374. Linet M, Kim K, Rajaraman P ( 2008). Children’s exposure to diagnostic medical radiation and cancer risk: epidemiologic and dosimetric considerations. Pediatric Radiology, [online] 39(S1), pp.4–26. Available at: https://link.springer.com/article/10.1007/s00247–008–Z1026–3. The Royal Children’s Hospital Melbourne ( 2019). Clinical Practice Guidelines, Radiology - Acute Indications. [online] Available at: https://www.rch.org.au/clinicalguide/guideline_index/Radiology_Guidelines_Acute_indications/.

Breast implant–associated lymphoma has recently gained wide recognition. Anaplastic large cell lymphoma (ALCL) is the most frequently diagnosed subtype in this setting but the spectrum is broadening. A 66-year-old woman developed swelling and itch around her saline implant 6 years after its insertion. Imaging revealed a fluid collection surrounding the implant with an adjacent mass. Microscopy showed sclerotic tissue punctuated by discrete cellular nodules comprising small lymphocytes, eosinophils and interspersed large atypical Hodgkin Reed-Sternberg (HRS)-like cells. The HRS-like cells stained positively for CD30 and CD15 by immunohistochemistry. Small T-lymphocytes formed rosettes around HRS-like cells. Appearances were consistent with classical Hodgkin lymphoma (HL). Multiplex polymerase chain reaction demonstrated no clonal rearrangements of immunoglobulin or T-cell receptor genes, however, a t(14;18)(q32;q21)BCL2-JH translocation involving the major breakpoint region of the bcl2 gene was present. Staging positron emission tomography–computed tomography scan revealed FDG-avid masses in the right axilla and pelvis. Subsequent pathological examination identified low-grade follicular lymphoma (FL) with a t(14;18) translocation at these sites. To our knowledge, this is the first case of HL arising adjacent to a breast implant. An awareness of this diagnosis is important as classical HL, with its prominent mixed inflammatory background, may be overlooked as a reactive process when histologically assessing capsulectomy specimens. It is also important in the differential diagnosis for implant-associated ALCL as both contain large atypical CD30-positive cells highlighting the need for full immunohistochemical and molecular workup in such cases. This case also adds to the large body of literature regarding the association between HL and FL.

Perineural and intraneural infiltration is most often considered a diagnostic feature of malignancy but has been demonstrated in benign entities in a variety of organs. This brief report describes benign glands apparently infiltrating nerves around bile ducts in a resected extra-hepatic biliary tree performed on a background of recurrent cholangitis and prior cholecystectomy. To our knowledge, benign glands infiltrating nerves within bile ducts has not been reported outside of the setting of end stage primary sclerosing cholangitis where one example has been described. We identify several features which support the benign nature of this process including bland cytomorphology, identical appearance to adjacent glands and an exuberant neural rather than glandular proliferation supporting the probability of a reactive neural proliferation akin to traumatic neuroma. We propose a pathogenesis that is somewhat analogous to traumatic neuroma of the biliary tree which, despite its rarity, is a documented complication of cholecystectomy, comprising a reactive proliferation of nerve tissue in response to injury. This article is protected by copyright. All rights reserved.

A continuous 305-year (1711–2016) monthly rainfall series is created for the Island of Ireland. Two overlapping data sources are employed: i) a previously unpublished UK Meteorological Office note containing annual rainfall anomalies and corresponding proportional monthly totals based on weather diaries and early observational records for the period 1711–1977 and; ii) a long-term, homogenised monthly rainfall series for the island of Ireland for the period 1850–2016. Using estimates of long-term average precipitation from the homogenised series to merge these sources, the new 305-year record is constructed and insights drawn about notable extremes, climate variability and change. The consistency of the resulting series was evaluated by comparison with independent long-term observations and reconstructions of precipitation, temperature and circulation indices from across the British-Irish Isles. Strong decadal consistency is evident throughout the record amongst all series in spring, summer and autumn. The winter series is probably too dry from the 1740s to the 1780s, but strong consistency with other records strengthens confidence from 1790 onwards. The new Island of Ireland series reveals remarkably wet winters during the 1730s, concurrent with a period of strong westerly airflow, glacial advance throughout Scandinavia and near unprecedented warmth in the Central England Temperature record – all consistent with the strong phase of the North Atlantic Oscillation. The driest winter decade in the series coincides with the Laki eruption of 1783–1784. Unusually wet summers occurred in the 1750s, consistent with proxy (tree-ring) reconstructions of summer precipitation in the region. In the annual series, the most recent decade (2006–2015) is found to be the wettest in over 300 years. The new series reveals statistically significant (0.05 level) multi-centennial trends in winter (increasing) and summer (decreasing) seasonal precipitation. However, given uncertainties in the early winter record, the former should be treated as tentative. Importantly, we show that the years 1940 to present – the period with the most widely available digitised records – is unrepresentative of long-term changes in all seasons. Although there are recognized uncertainties in the early record, the derived series offers valuable insights for understanding multi-decadal and centennial rainfall variability in Ireland, and provides a firm basis for benchmarking other long-term records and future reconstructions.

Background: The targets of bronchoscopic biopsy now include not only adequate tissue for histologic diagnosis but also tissue for further analysis. We prospectively compared standard and novel bronchoscopic endobronchial biopsy (EBB) retrieval methods attempting to increase tissue yield. Methods: EBB samples were retrieved using techniques A, B, and C using a standard forceps. Method A is routinely performed conventional method, where as in method B, biopsy forceps was left protruded from the bronchoscope and in method C, both valve and forceps were removed to prevent the loss of specimen. At least 6 EBB were retrieved per patient. Results were compared with gold standard composite of confirmatory pathological or clinic-radiologic follow up. Results: A total of 42 of 43 patients completed the study. The final gold standard diagnosis was cancer [non-small cell lung cancer, metastatic, carcinoid, carcinoma in situ (24)], benign disease [sarcoid, amyloid, hamartoma, and chondroid tumor (4)], and benign/nonspecific inflammation (14). EBB retrieved using standard method A were smaller than novel methods B and C (P=0.03). However, the percentage of cases where blood was the predominant component ( > 50%) was less by standard methods A (4/42) than B (16/42) and C (20/42) (P=0.001). There was no difference in mean viable tumor area (n=23, sensitivity for EBB for cancer 96%) between groups A compared with B and C (P 0.27) and adequacy in benign cases by subepithelial depth ( > 0.3 mm) (P=0.38). Conclusion: Standard retrieval of endobronchial biopsies through the bronchoscope and cap does not reduce the size of viable tissue and reduces contaminating blood and necrotic material.

T cell infiltration into colorectal tumors has been shown to correlate with improved patient outcomes. However, more detailed information on the makeup and relationships between the infiltrating T cell subsets is lacking. We therefore correlated the extent of immune infiltration into colorectal tumors with the frequencies of various T cell subsets. We prospectively recruited 22 patients at the time of surgical resection for colorectal cancer. The Klintrup-Mäkinen (KM) score was used to estimate the extent of immune infiltration into colorectal tumors. The frequencies of CD4 and CD8 T cells that produced cytokines or expressed the inhibitory molecule programed cell death 1 (PD-1) were determined by flow cytometry in colorectal tumor and matched uninvolved colonic tissue. In addition, the frequency of CD4 regulatory T cell (Treg) subsets was determined. An increased frequency of CD4 T cells producing IL-17 (Th17 cells) was observed in colorectal tumor tissue compared with adjacent uninvolved tissue. These Th17 cells mostly coproduced TNF-α, but not IFN-γ. IL-17 expression correlated positively with TNF-α and IL-10. Increased expression of the immune checkpoint molecule PD-1 was found in colorectal tumors compared with adjacent uninvolved tissue. There was a negative correlation between expression of PD-1 and IFN-γ, but not IL-17, for both CD4(+) and CD8(+) T cells. CD4(+)CD25(+)CD127(lo) and CD4(+)CD25(+)CD127(lo)FoxP3(+)CD39(+) Treg cells were enriched in colorectal tumors. A positive correlation between KM score and percentage CD4(+)CD25(+)CD127(lo) Treg cells was observed in tumors, suggesting that increased immune infiltration is associated with an increased proportion of Treg cells. In addition, there was a negative correlation between the frequency of CD4(+)CD25(+)CD127(lo) Treg cells and the expression of IFN-γ and IL-2, but not IL-17, in tumors. Taken together, these data suggest that both PD-1 expressing T cells and Treg cells within the tumor may have a suppressive effect on T cells secreting IFN-γ, IL-2, or TNF-α, but not Th17 cells.

Introduction The role of sentinel lymph node biopsy (SLNB) in ductal carcinoma in situ (DCIS) is controversial. This study evaluates the risk of clinically relevant SLN metastasis following a core needle biopsy (CNB) diagnosis of pure DCIS. Materials and methods Cases that underwent SLNB following a CNB diagnosis of pure DCIS at our institution over a 4.5 year period were evaluated. Parameters including the DCIS characteristics on CNB, the rate of upstaging to invasive carcinoma at excision and the SLNB result were recorded. Results Of 296 patients with a CNB diagnosis DCIS, 181 had SLNB (62%). The rate of invasion at excision in those undergoing SLNB was 30% (54/181). SLN metastasis was detected in 7/181 cases (4%), including 6 cases with isolated tumour cells only (3.5%) and only 1 case with a macro-metastatic deposit (0.5%). Conclusion The risk of clinically significant SLN metastasis following a CNB diagnosis of DCIS is extremely low, despite a relatively high rate of upstaging to invasive carcinoma at excision. Our findings support the opinion that SLNB is not warranted following a CNB diagnosis of DCIS, particularly for those patients undergoing breast conservation surgery.

Eosinophilic disease of the gastrointestinal tract is rare and is characterized by the presence of gastrointestinal symptoms in association with eosinophilic infiltration of any part of the gastrointestinal tract. Clinical presentation of eosinophilic gastroenteritis (EGE) varies not only by the part of the gastrointestinal tract involved but also with the depth of eosinophilic infiltration of the gut wall. We describe the case of a 41-year-old woman with a history of atopy who presented with severe abdominal pain and diarrhoea. Investigations showed large-volume eosinophil-rich ascites and a markedly elevated peripheral blood eosinophil count and immunoglobulin E level. Bone marrow aspirate, trephine biopsy and T-cell studies showed no evidence of underlying haematological malignancy. Vasculitic disease and parasitic infection were systematically excluded. Colonic and upper gastrointestinal biopsies confirmed a diagnosis of EGE with eosinophilic ascites. The patient was treated with systemic corticosteroids and dietary allergen elimination with dramatic therapeutic response. The diagnostic and therapeutic challenges associated with EGE in its various forms are discussed.

There have been recent reports of a rare variant of renal cell carcinoma associated with upregulation of the anaplastic lymphoma kinase gene (ALK) arising as a consequence of chromosomal translocations. The tumours were described as having a characteristic morphology. Here, we describe a case with similar morphology characterised by eosinophilic cells, abundant intracytoplasmic lumina and scattered large ganglion-like tumour cells. There was focal staining for ALK demonstrated by immunohistochemistry. However, rather than exhibiting a chromosomal translocation involving ALK, the use of FISH and a break-apart probe demonstrated that there was increased copy number of intact 2p23, the chromosomal region containing the ALK gene. Furthermore, the use of comparative genomic hybridisation showed increase of the whole of chromosome 2 along with chromosomes 6 and 17. There was no evidence of loss of 3p nor of trisomy of 7 associated with clear cell and papillary carcinoma, respectively. We suggest that this demonstrates a novel mechanism of upregulation of ALK activity by increased copy number occurring during the development of a renal carcinoma with the characteristic ALK-associated morphology.

The Saint James's Hospital Biobank was established in 2008, to develop a high-quality breast tissue BioResource, as a part of the breast cancer clinical care pathway. The aims of this work were: (1) to ascertain the quality of RNA, DNA, and protein in biobanked carcinomas and normal breast tissues, (2) to assess the efficacy of AllPrep (R) (Qiagen) in isolating RNA, DNA, and protein simultaneously, (3) to compare AllPrep with RNEasy (R) and QIAamp (R) (both Qiagen), and (4) to examine the effectiveness of Allprotect (R) (Qiagen), a new tissue stabilization medium in preserving DNA, RNA, and proteins. One hundred eleven frozen samples of carcinoma and normal breast tissue were analyzed. Tumor and normal tissue morphology were confirmed by frozen sections. Tissue type, tissue treatment (Allprotect vs. no Allprotect), extraction kit, and nucleic acid quantification were analyzed by utilizing a 4 factorial design (SPSS PASW 18 Statistics Software (R)). QIAamp (DNA isolation), AllPrep (DNA, RNA, and Protein isolation), and RNeasy (RNA isolation) kits were assessed and compared. Mean DNA yield and A(260/280) values using QIAamp were 33.2 ng/mu L and 1.86, respectively, and using AllPrep were 23.2 ng/mu L and 1.94. Mean RNA yield and RNA Integrity Number (RIN) values with RNeasy were 73.4 ng/mu L and 8.16, respectively, and with AllPrep were 74.8 ng/mu L and 7.92. Allprotect-treated tissues produced higher RIN values of borderline significance (P = 0.055). No discernible loss of RNA stability was detected after 6 h incubation of stabilized or nonstabilized tissues at room temperature or 4 degrees C or in 9 freeze-thaw cycles. Allprotect requires further detailed evaluation, but we consider AllPrep to be an excellent option for the simultaneous extraction of RNA, DNA, and protein from tumor and normal breast tissues. The essential presampling procedures that maintain the diagnostic integrity of pathology specimens do not appear to compromise the quality of molecular isolates.

Setting: The Southwest of Ireland (Counties Cork and Kerry) 1987–2000, average population 549 500. Objective: Nontuberculous mycobacteria (NTM) cause significant morbidity worldwide and the study of epidemiology and characteristics helps in their prevention and treatment. This study was performed to determine the incidence of NTM disease in comparison to Mycobacterium tuberculosis ( M. tuberculosis ) and Mycobacterium bovis ( M. bovis ) in Southwest Ireland, over the above time period. Design: A retrospective study was carried out in all human isolates of NTM, M. tuberculosis and M. bovis between 1987 and 2000, in the Southwest Region of Ireland. Results: The mean incidence of NTM (0.4/100 000 population) has risen since 1995, principally of pulmonary Mycobacterium avium intracellulare complex (MAC). The annual incidence of M. tuberculosis in humans over 14 years in the same region was 9.71/100 000 population with a significant reduction since 1994 and M. bovis remained constant at 0.5/100 000 population. Conclusion: The increasing incidence of disease causing NTM noted in Southwest Ireland reflects global data and is surmised to be due to an ageing population, increased incidence related to chronic fibrotic lung disease, and environmental mycobacterial factors.

386 Background: Xenograft tumours are validated models using either patient samples (primary xenografts) or cell lines (secondary xenografts) grown in a murine host. Repeated culturing of cancer cell lines results in epigenetic changes and subsequent behaviour changes distinct from primary human cancers. The aim of this study is to form both models and compare their responses to chemotherapy agents. Methods: Fresh primary colorectal adenocarcinoma tissue or colorectal cell lines (SW480 non metastatic line / SW620 metastatic line) were inoculated subcutaneously into immunodeficient mice to form primary and secondary xenografts respectively. Both models were subjected to either a 5-fluorouracil (5-FU) or irinotecan trial. The clinical response and biological features were evaluated. Results: Secondary xenografts were more aggressive with a shorter time to tumour formation, higher uptake rate and more aggressive histological features. The mice were randomised to either the control group (saline) or to the treatment group [60mg/kg of 5FU (SW620 / primary xenografts) or 60 mg/kg of Irinotecan (SW480 / primary xenografts)] via intraperitoneal injection. In the 5FU group, the primary xenografts began regressing after Day 2 but the secondary xenografts continued to grow until Day 8. The decrease from the maximal tumor volume to the study end point (Day 12 in primary xenograft group and Day 10 in secondary xenograft group) was evaluated with primary xenografts showing a greater decrease compared to secondary xenografts (56.6% vs. 10.4%; p =0.002). Conclusions: We demonstrated the ability to grow tumours in mice from fresh human colonic adenocarcinomas. Tumours formed in mice from patient derived adenocarcinomas produce more clinically accurate testing than tumours formed from cell line and may allow for drug screening in order to personalise an individual’s chemotherapy regime.

28 Background: Gastroesophageal cancer is a major cause of cancer-related mortality. The ToGA study, established the benefit of trastuzumab in combination with chemotherapy in HER2 positive metastatic gastroesophageal tumors. We report a multi-centre Irish experience of examining HER2 status by IHC and FISH amongst gastroesophageal adenocarcinomas. Methods: HER2 testing was performed on biopsy or resection specimens of patients with early stage and metastatic gastroesophageal tumors between 2010 and 2012. We defined HER2 positive(+) as IHC3+ or FISH(+) {HER2:17ch ≥2}. All specimens which were IHC2+ or IHC3+, where treatment with trastuzumab was under consideration, went on to have FISH testing. Results: Between 2010 and 2012 HER2 status was established in all patients presenting with biopsy proven gastroesophageal cancers, this amounted to 88 patients (53 gastric, 35 esophageal). Within the population examined 64% of patients had metastatic disease. The majority (51%) had intestinal type adenocarcinomas, the remainder having diffuse type (16%), mixed type (3%) or undetermined (18%). Nineteen patients (21%) were defined as being HER2+ (14 male, 5 female). Four were FISH (+) IHC3+, five were FISH (+) IHC2+ and in ten patients HER2 status was defined by IHC3+ alone as FISH testing was indeterminate (1 patient) or not tested (9 patients). In the subset of HER2+ patients (19 patients), the majority had gastric cancer (63%). Intestinal type adenocarcinoma occurred in 12 patients (63%), the remainder being diffuse type (2 patients), mixed (1 patient) or undetermined (4 patients). Seven patients (36%) had localized disease. In the metastatic cases the distribution of metastases was as follows: 9(47%) liver, 3(15%) lung, 3(15%) peritoneal, 1(5%) adrenal, 1(5%) brain and 1(5%) ovarian. Five patients are receiving trastuzumab for HER2+ disease in combination with cisplatin and fluorouracil based chemotherapy. Conclusions: In a cohort of Irish patients we found similar levels of HER2+ gastroesophageal cancers (21%) as that demonstrated in the ToGA trial (22%). Clinicopathologic characteristics were broadly similar also. Outcome of our experience with HER2 directed therapy will be reported.

Background: There is an urgent need to measure phosphorylated cell signaling proteins in cancer tissue for the individualization of molecular targeted kinase inhibitor therapy. However, phosphoproteins fluctuate rapidly following tissue procurement. Snap-freezing preserves phosphoproteins, but is unavailable in most clinics and compromises diagnostic morphology. Formalin fixation preserves tissue histomorphology, but penetrates tissue slowly, and is unsuitable for stabilizing phosphoproteins. We originated and evaluated a novel one-step biomarker and histology preservative (BHP) chemistry that stabilizes signaling protein phosphorylation and retains formalin-like tissue histomorphology with equivalent immunohistochemistry in a single paraffin block. Results: Total protein yield extracted from BHP-fixed, routine paraffin-embedded mouse liver was 100% compared to snapfrozen tissue. The abundance of 14 phosphorylated proteins was found to be stable over extended fixation times in BHP fixed paraffin embedded human colon mucosa. Compared to matched snap-frozen tissue, 8 phosphoproteins were equally preserved in mouse liver, while AMPKb1 Ser108 was slightly elevated after BHP fixation. More than 25 tissues from mouse, cat and human specimens were evaluated for preservation of histomorphology. Selected tissues were evaluated in a multisite, independent pathology review. Tissue fixed with BHP showed equivalent preservation of cytoplasmic and membrane cytomorphology, with significantly better nuclear chromatin preservation by BHP compared to formalin. Immunohistochemical staining of 13 non-phosphorylated proteins, including estrogen receptor alpha, progesterone receptor, Ki-67 and Her2, was equal to or stronger in BHP compared to formalin. BHP demonstrated significantly improved immunohistochemical detection of phosphorylated proteins ERK Thr202/Tyr204, GSK3-a/b Ser21/Ser9, p38-MAPK Thr180/Tyr182, eIF4G Ser1108 and Acetyl-CoA Carboxylase Ser79. Conclusion: In a single paraffin block BHP preserved the phosphorylation state of several signaling proteins at a level comparable to snap-freezing, while maintaining the full diagnostic immunohistochemical and histomorphologic detail of formalin fixation. This new tissue fixative has the potential to greatly facilitate personalized medicine, biobanking, and phospho-proteomic research.