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The molecular events and transcriptional plasticity driving brain metastasis in clinically relevant breast tumor subtypes has not been determined. Here we comprehensively dissect genomic, transcriptomic and clinical data in patient-matched longitudinal tumor samples, and unravel distinct transcriptional programs enriched in brain metastasis. We report on subtype specific hub genes and functional processes, central to disease-affected networks in brain metastasis. Importantly, in luminal brain metastases we identify homologous recombination deficiency operative in transcriptomic and genomic data with recurrent breast mutational signatures A, F and K, associated with mismatch repair defects, TP53 mutations and homologous recombination deficiency (HRD) respectively. Utilizing PARP inhibition in patient-derived brain metastatic tumor explants we functionally validate HRD as a key vulnerability. Here, we demonstrate a functionally relevant HRD evident at genomic and transcriptomic levels pointing to genomic instability in breast cancer brain metastasis which is of potential translational significance., The molecular landscape of breast cancer brain metastases (BCBM) is still understudied, especially for different breast cancer subtypes. Here, the authors characterise subtype-specific BCBMs using genomics and transcriptomics and identify homologous recombination deficiency as a key therapeutic vulnerability.

Objective The vast majority of breast cancers are diagnosed via image-guided procedures yet despite significant advances, imaging does not identify all breast malignancies. Clinically suspicious breast lesions with normal breast imaging remain a cause for concern. The aim of this study is to determine the diagnostic value of clinical core and cutaneous punch biopsies in the diagnosis of breast malignancy in clinically suspicious lesions with normal breast imaging. Methods All patients with suspicious clinical breast findings and normal imaging who underwent a clinical core and/or cutaneous punch biopsy from 2012 to 2019 were reviewed retrospectively. Patients with subsequent breast malignant diagnosis were analysed. Results A total of 283 biopsies (166 clinical core, 117 cutaneous punch) performed over the 7-year period were included in the analysis. A total of 263/283 (93%) yielded a benign outcome. A total of 2/283 (0.7%) yielded B3 lesions (probably benign). These lesions were benign on final surgical excision. A total of 18/283 (6.3%) yielded a malignant histopathology. Sixteen out of 18 were cutaneous punch biopsies, and 2/18 were clinical core biopsies. A total of 14/18 patients presented with nipple changes, while 4/18 had a palpable area of concern. Histopathological analysis demonstrated Paget’s disease of the nipple in 8/18, invasive carcinoma in 9/18 out of which two represented a recurrence of breast malignancy. Cutaneous squamous cell carcinoma was diagnosed in 1/18. Conclusion Clinical core and cutaneous punch biopsies remain a valuable tool in the diagnosis of breast cancer particularly in the management of clinically suspicious radiographically occult malignancies.

Aim To assess the genders of lead authors and primary investigators in major surgical research meetings over a 10-year period in Ireland. Method We gathered data from the 3 main surgical conferences in Ireland. We looked at the abstracts of each of the plenary sessions over the last 10 year. We used the Irish Medical Council, previous published research from these authors and ResearchGate to help identify the gender of the author. We complied and analysed the data using Excel. Results We analysed 306 papers over the last 10 years. We found that the primary investigator was male in 78% of the papers and female in 20%. The primary author was male in 52% and was female in 46% of the papers. There has been little change over each 5-year interval for who was the primary investigator. In 2010–2015, it was 77% male and 23% female while from 2016–2020, it was 82% male and 18% female. Furthermore, in relation to the primary author, it has shifted from being relatively equal to becoming more male dominant. In 2010–2015, it was 52% female and 48% female while from 2016–2020, it was 57% male and 43% female. Conclusion The gender gap has appeared to have widened at the non-consultant hospital doctor level and it is very apparent that there is a large inequality at consultant level regarding surgical research in Ireland.

BackgroundSentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NACT) in patients with breast cancer who are initially node-positive but convert to clinically/radiologically node-negative remains controversial. The primary aim was to assess pooled 5-year disease-free (DFS) and overall (OS) survival for patients who are initially node-positive but have a negative SLNB after NACT, and do not proceed to axillary lymph node dissection (ALND).MethodsThe study was performed using PRISMA guidelines. A systematic literature search of relevant databases was conducted. The Der Simonian–Laird and Cochran–Mantel–Haenszel methods were used to calculate weighted pooled estimates for OS and DFS for this group compared with patients who had NACT and proceeded to ALND after a negative or positive SLNB.ResultsSeven studies involving 915 patients who had a negative SLNB after NACT were included. Pooled estimates of 5-year DFS and OS in patients with a negative SLNB after NACT were 86 (95 per cent c.i. 82.1 to 90.3) and 93.1 (87.8 to 97.0) per cent respectively. Patients with a positive SLNB who underwent ALND had reduced 5-year DFS (OR 0.49, 95 per cent c.i. 0.35 to 0.69; P < 0.001) and OS (OR 0.41, 0.16 to 1.02; P = 0.06) compared with those who had a negative SLNB after NACT. There were no differences in DFS for patients who had a negative SLNB only compared with those undergoing ALND with a pCR (OR 1.65, 0.71 to 3.79; P = 0.24).ConclusionPatients who are initially node-positive and who achieve a complete clinical/radiological axillary response after NACT with a subsequent negative SLNB have high rates of DFS and OS after 5 years. Patients with residual disease have significantly reduced DFS and further axillary treatment may still be warranted.

Breast ductal carcinoma in situ (DCIS) is clinically challenging, featuring high diagnosis rates and few targeted therapies. Expression/signaling from junctional adhesion molecule-A (JAM-A) has been linked to poor prognosis in invasive breast cancers, but its role in DCIS is unknown. Since progression from DCIS to invasive cancer has been linked with overexpression of the human epidermal growth factor receptor-2 (HER2), and JAM-A regulates HER2 expression, we evaluated JAM-A as a therapeutic target in DCIS. JAM-A expression was immunohistochemically assessed in patient DCIS tissues. A novel JAM-A antagonist (JBS2) was designed and tested alone/in combination with the HER2 kinase inhibitor lapatinib, using SUM-225 cells in vitro and in vivo as validated DCIS models. Murine tumors were proteomically analyzed. JAM-A expression was moderate/high in 96% of DCIS patient tissues, versus 23% of normal adjacent tissues. JBS2 bound to recombinant JAM-A, inhibiting cell viability in SUM-225 cells and a primary DCIS culture in vitro and in a chick embryo xenograft model. JBS2 reduced tumor progression in in vivo models of SUM-225 cells engrafted into mammary fat pads or directly injected into the mammary ducts of NOD-SCID mice. Preliminary proteomic analysis revealed alterations in angiogenic and apoptotic pathways. High JAM-A expression in aggressive DCIS lesions and their sensitivity to treatment by a novel JAM-A antagonist support the viability of testing JAM-A as a novel therapeutic target in DCIS.

Therapeutic mammaplasty (TM) may be an alternative to mastectomy, but few well designed studies have evaluated the success of this approach or compared the short-term outcomes of TM with mastectomy with or without immediate breast reconstruction (IBR). Data from the national iBRA-2 and TeaM studies were combined to compare the safety and short-term outcomes of TM and mastectomy with or without IBR.The subgroup of patients in the TeaM study who underwent TM to avoid mastectomy were identified, and data on demographics, complications, oncology and adjuvant treatment were compared with those of patients undergoing mastectomy with or without IBR in the iBRA-2 study. The primary outcome was the percentage of successful breast-conserving procedures in the TM group. Secondary outcomes included postoperative complications and time to adjuvant therapy.A total of 2916 patients (TM 376; mastectomy 1532; mastectomy and IBR 1008) were included in the analysis. Patients undergoing TM were more likely to be obese and to have undergone bilateral surgery than those having IBR. However, patients undergoing mastectomy with or without IBR were more likely to experience complications than the TM group (TM: 79, 21·0 per cent; mastectomy: 570, 37·2 per cent; mastectomy and IBR: 359, 35·6 per cent; P 0·001). Breast conservation was possible in 87·0 per cent of patients who had TM, and TM did not delay adjuvant treatment.TM may allow high-risk patients who would not be candidates for IBR to avoid mastectomy safely. Further work is needed to explore the comparative patient-reported and cosmetic outcomes of the different approaches, and to establish long-term oncological safety.La mamoplastia terapéutica (therapeutic mammaplasty, TM) puede ser una alternativa a la mastectomía, pero hay pocos estudios bien diseñados que hayan evaluado el éxito de esta estrategia o hayan comparado los resultados a corto plazo de la TM con la mastectomía con o sin (+/-) reconstrucción mamaria inmediata (immediate breast reconstruction, IBR). Para comparar la seguridad y los resultados a corto plazo de la TM y la mastectomía +/- IBR se combinaron los datos de los estudios nacionales iBRA-2 y TeaM. MÉTODOS: En el estudio TeaM se identificó el subgrupo de pacientes al que se realizó una TM para evitar la mastectomía y se compararon los datos demográficos, las complicaciones, los resultados oncológicos y el tratamiento adyuvante con las pacientes sometidas a mastectomía +/- IBR del estudio iBRA-2. La variable principal fue el porcentaje de éxito de la cirugía conservadora de mama en el grupo TM. Las variables secundarias fueron las complicaciones postoperatorias y el intervalo de tiempo hasta el inicio del tratamiento adyuvante.Se incluyeron en el análisis 2.916 pacientes (TM n = 376; mastectomía n = 1.532; IBR n = 1.008). La TM era más frecuente en pacientes obesas o en las sometidas a cirugía bilateral en comparación con las pacientes con IBR. Sin embargo, las pacientes sometidas a una mastectomía +/- IBR tenían más probabilidades de desarrollar complicaciones que las del grupo TM (TM n = 79, 21,0%; mastectomía n = 570, 37,2%; mastectomía y IBR n = 359, 35,6%; P 0,001). La conservación de la mama fue posible en el 87% de las pacientes con TM y el procedimiento no retrasó el inicio del tratamiento adyuvante. CONCLUSIÓN: La TM puede permitir que pacientes de alto riesgo que no serían candidatas a IBR eviten la mastectomía de una forma segura. Se necesitan más trabajos para comparar los resultados percibidos por las pacientes y los estéticos de las diferentes estrategias terapéuticas y establecer la seguridad oncológica a largo plazo.

CD44 expression is elevated in basal-like breast cancer (BLBC) tissue, and correlates with increased efficiency of distant metastasis in patients and experimental models. We sought to characterize mechanisms underpinning CD44-promoted adhesion of BLBC cells to vascular endothelial monolayers and extracellular matrix (ECM) substrates. Stimulation with hyaluronan (HA), the native ligand for CD44, increased expression and activation of β1-integrin receptors, and increased α5-integrin subunit expression. Adhesion assays confirmed that CD44-signalling potentiated BLBC cell adhesion to endothelium and Fibronectin in an α5B1-integrin-dependent mechanism. Co-immunoprecipitation experiments confirmed HA-promoted association of CD44 with talin and the β1-integrin chain in BLBC cells. Knockdown of talin inhibited CD44 complexing with β1-integrin and repressed HA-induced, CD44-mediated activation of β1-integrin receptors. Immunoblotting confirmed that HA induced rapid phosphorylation of cortactin and paxillin, through a CD44-dependent and β1-integrin-dependent mechanism. Knockdown of CD44, cortactin or paxillin independently attenuated the adhesion of BL-BCa cells to endothelial monolayers and Fibronectin. Accordingly, we conclude that CD44 induced, integrin-mediated signaling not only underpins efficient adhesion of BLBC cells to BMECs to facilitate extravasation but initiates their adhesion to Fibronectin, enabling penetrant cancer cells to adhere more efficiently to underlying Fibronectin-enriched matrix present within the metastatic niche. Refereed/Peer-reviewed

Metastasis is the predominant cause of death from cancer yet we have few biomarkers to predict patients at increased risk of metastasis and are unable to effectively treat disseminated disease. Analysis of 448 primary breast tumors determined that expression of the hylauronan receptor CD44 associated with high grade (p = 0.046), ER-(p = 0.001) and PR-negative tumors (p = 0.029), and correlated with increased distant recurrence and reduced disease-free survival in patients with lymph-node positive or large tumors. To determine its functional role in distant metastasis, CD44 was knocked-down in MDA-MB-231 cells using two independent shRNA sequences. Loss of CD44 attenuated tumor cell adhesion to endothelial cells and reduced cell invasion but did not affect proliferation in vitro. To verify the importance of CD44 to post-intravasation events, tumor formation was assessed by quantitative in vivo imaging and post-mortem tissue analysis following an intra-cardiac injection of transfected cells. CD44 knock-down increased survival and decreased overall tumor burden at multiple sites, including the skeleton in vivo. We conclude that elevated CD44 expression on tumour cells within the systemic circulation increases the efficiency of post-intravasation events and distant metastasis in vivo, consistent with its association with increased distant recurrence and reduced disease-free survival in patients. Refereed/Peer-reviewed

Background The optimal timing of cholecystectomy for patients admitted with acute gallbladder pathology is unclear. Some studies have shown that emergency cholecystectomy during the index admission can reduce length of hospital stay with similar rates of conversion to open surgery, complications and mortality compared with a ‘delayed’ operation following discharge. Others have reported that cholecystectomy during the index acute admission results in higher morbidity, extended length of stay and increased costs. This study examined the cost-effectiveness of emergency versus delayed cholecystectomy for acute benign gallbladder disease. Methods Using data from a prospective population-based cohort study examining the outcomes of cholecystectomy in the UK and Ireland, a model-based cost–utility analysis was conducted from the perspective of the UK National Health Service, with a 1-year time horizon for costs and outcomes. Probabilistic sensitivity analysis was used to investigate the impact of parameter uncertainty on the results obtained from the model. Results Emergency cholecystectomy was found to be less costly (£4570 versus £4720; €5484 versus €5664) and more effective (0·8868 versus 0·8662 QALYs) than delayed cholecystectomy. Probabilistic sensitivity analysis showed that the emergency strategy is more than 60 per cent likely to be cost-effective across willingness-to-pay values for the QALY from £0 to £100 000 (€0–120 000). Conclusion Emergency cholecystectomy is less costly and more effective than delayed cholecystectomy. This approach is likely to be beneficial to patients in terms of improved health outcomes and to the healthcare provider owing to the reduced costs.

Background/Aims: Estrogen receptor (ER) is the prototype therapy predictive marker in oncology. The ER is now known to exist in two main forms with similar overall structure: ER-α and ER-β. Both forms may be expressed in breast cancer. The aim of this study was to examine breast cancer outcome in relation to expression of ER-β. Methods: In this investigation, we measured the expression of ER-α protein and ER-β mRNA in 121 extracts of invasive breast cancer. Association of expression with clinical outcome was examined using Kaplan-Meier and Cox regression analyses. Results: While ER-α expression was associated with good patient outcome [hazard ratio (HR) for death from breast cancer 0.37; 95% confidence interval (CI) 0.17–0.84; p = 0.017], ER-β predicted poor outcome (HR for death from breast cancer 2.49; 95% CI 1.10–5.63; p = 0.028). Conclusion: Based on these findings, we conclude that ER-β may have a different biological role from that of ER-α in breast cancer.

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.

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.

Differential signalling between the two oestrogen receptor (ER) isoforms in the presence of tamoxifen has been described. We hypothesise that differential recruitment of the steroid receptor co-activator, SRC-3 to ER-α and ER-β may in part explain associations between ER isoforms and response to endocrine treatment. SRC-3 was localised within epithelial cells of breast tumour tissue and was co-localised with ER-α and ER-β, (n = 112). Expression of SRC-3 was found to be positively associated with ER-α (P = 0.0021) and inversely with ER-β (P < 0.0001). Uniquely, this study utilises primary cell cultures derived from patient tumours, thus providing samples not readily available in most molecular model systems. These samples have enabled us to investigate the influence of growth factor pathways on steroid receptor-co-activator interactions. In HER2 (human epidermal growth factor receptor 2) positive primary tumour cell cultures 17β-estradiol induced a decrease in SRC-3, whereas upregulated SRC-3 expression. Furthermore, treatment with tamoxifen-induced SRC-3 recruitment to the ER-oestrogen response element and enhanced interaction between SRC-3 and ER-α, but not ER-β. Knockdown of SRC-3 results in a concomitant loss of expression of the oestrogen target gene pS2. Furthermore, silencing of SRC-3 resensitizes endocrine resistant, HER2 positive cells to the anti-proliferative effects of tamoxifen. The ability of ER-α, but not ER-β to recruit SRC-3 in the presence of tamoxifen may in part explain the differential ER isoform associations with recurrence in human breast cancer.

Using a validated tetracycline (tet)-regulated MCF7-founder (MCF7F) expression system to modulate expression of CD44 standard form (CD44s), we report the functional importance of CD44s and that of a novel transcriptional target of hyaluronan (HA)/CD44s signaling, EMS1/cortactin, in underpinning breast cancer metastasis. In functional experiments, tet-regulated induction of CD44s potentiated the migration and invasion of MCF7F cells through HA-supplemented Matrigel. EMS1/cortactin was identified by expression profiling as a novel transcriptional target of HA/CD44 signaling, an association validated by quantitative PCR and immunoblotting experiments in a range of breast cancer cell lines. The mechanistic basis underpinning CD44-promoted transcription of EMS1/cortactin was shown to be dependent upon a NFkappaB mechanism, since pharmacological inhibition of IkappaKinase-2 or suppression of p65 Rel A expression attenuated CD44-induced increases in cortactin mRNA transcript levels. Overexpression of a c-myc tagged murine cortactin construct in the weakly invasive, CD44-deficient MCF7F and T47D cells potentiated their invasion. Furthermore, the functional importance of cortactin to CD44s-promoted metastasis was demonstrated by selective suppression of cortactin in CD44-expressing MCF7F-B5 and MDA-MB-231 breast cancer cells using RNAi, which was shown to result in attenuated CD44-promoted invasion and CD44-promoted adhesion to bone marrow endothelial cells (BMECs).

In human breast cancer, the growth factor receptor HER2 is associated with disease progression and resistance to endocrine treatment. Growth factor induced mitogen activated protein kinase activity can phosphorylate not only the oestrogen receptor, but also its coactivator proteins AIB1 and SRC-1.To determine whether insensitivity to endocrine treatment in HER2 positive patients is associated with enhanced expression of coactivator proteins, expression of the HER2 transcriptional regulator, PEA3, and coregulatory proteins, AIB1 and SRC-1, was assessed in a cohort of patients with breast cancer of known HER2 status.PEA3, AIB1, and SRC-1 protein expression in 70 primary breast tumours of known HER2 status (HER2 positive, n = 35) and six reduction mammoplasties was assessed using immunohistochemistry. Colocalisation of PEA3 with AIB1 and SRC-1 was determined using immunofluorescence. Expression of PEA3, AIB1, and SRC-1 was correlated with clinicopathological parameters.In primary breast tumours expression of PEA3, AIB1, and SRC-1 was associated with HER2 status (p = 0.0486, p = 0.0444, and p = 0.0012, respectively). In the HER2 positive population, PEA3 expression was associated with SRC-1 (p = 0.0354), and both PEA3 and SRC-1 were significantly associated with recurrence on univariate analysis (p = 0.0345; p0.0001). On multivariate analysis, SRC-1 was significantly associated with disease recurrence in HER2 positive patients (p = 0.0066).Patients with high expression of HER2 in combination with SRC-1 have a greater probability of recurrence on endocrine treatment compared with those who are HER2 positive but SRC-1 negative. SRC-1 may be an important predictive indicator and therapeutic target in breast cancer.

The aim of this current study was to examine the significance of CD44 expression in mediating cancer cell adhesion to human bone marrow endothelial cell(s) (hBMEC). Differential CD44 expression on two metastatic prostate cancer cell lines, PC3 (CD44 +ve) and DU145 (CD44 −ve) and four breast cancer cell lines was confirmed by immunoblotting and immunocytochemistry. In cell adhesion assays, PC3 but not DU145 cells demonstrated a rapid adhesion to hBMECs. Treatment of PC3 cells with a neutralizing antibody against CD44 standard (CD44s) and CD44 splice variants decreased PC3 cell adhesion to hBMECs. Similarly, depletion of CD44 expression using RNA interference decreased the ability of PC3 cells and two CD44 +ve breast cancer cell lines (MDA-MB-231 and MDA-MB-157) to bind FITC-conjugated hyaluronan (FITC-HA) and to adhere to hBMECs. In contrast, transfection of DU145 cells or the T47D and MCF-7 breast cancer cell lines to express CD44s increased cell surface binding of FITC-HA and cell adherence to hBMECs. Treatment of PC3 and MDA-MD-231 cells but not hBMECs with hyaluronidase attenuated cell adhesion, suggesting that cell surface expression of CD44 on prostate and breast cancer cells may promote the retention of a HA coat that facilitates their initial arrest on bone marrow endothelium.

BACKGROUND Immunohistochemical analysis of sentinel lymph nodes from patients with breast carcinoma and melanoma has been shown to increase the sensitivity for detecting lymph node metastases. To the authors' knowledge, this technique has not been described in patients with Merkel cell carcinoma. METHODS Lymphatic mapping and sentinel lymph node biopsy was performed on 26 patients with Merkel cell carcinoma between 1997 and 1999. All sentinel lymph nodes were analyzed with conventional hematoxylin and eosin (H&E) staining and then analyzed with immunohistochemical staining to evaluate whether this additional technique would increase the number of patients found to have lymph node metastasis. RESULTS The median age of the patients in the current study was 67 years and the median tumor size at the time of presentation was 2 cm. Lymph node metastases were identified in 5 of the 26 patients (19%). Three of these five lymph node positive patients were identified with H&E staining. The remaining two patients were identified only after immunohistochemical analysis. The median follow-up in this group of lymph node positive patients was 14 months, with 2 of the 5 lymph node positive patients developing a recurrence. The median follow-up in the 21 patients who were lymph node negative was 19 months, with only 1 patient having developed a recurrence at the time of last follow-up. CONCLUSIONS Immunohistochemical analysis of sentinel lymph nodes from patients with Merkel cell carcinoma appears to increase the sensitivity of detecting clinically occult lymph node metastases. Cancer 2001;92:1650–55. © 2001 American Cancer Society.

Genetic predisposition is responsible for 5–10% of all breast cancer, and a much larger percent of early-onset disease. Within the past few years, a number of genes associated with a high risk of breast cancer have been identified, including BRCA1, BRCA2, p53, and the Cowden disease gene PTEN/MMAC1. These genes appear to function as tumor suppressors, and although their mutation frequency in the general population is low, certain populations have a carrier frequency of up to 1% for particular BRCA1 and BRCA2 mutations. The isolation of these genes is likely to provide important insight into the pathogenesis of human cancer. The clinical application of these molecular discoveries raises controversial issues regarding presymptomatic testing for patients suspected of harboring cancer predisposing mutations.

Laparoscopic appendicectomy is a safe and feasible procedure. Its proposed benefits include reduced postoperative hospital stay, reduced postoperative pain and quicker return to full activity, as well as improved cosmetic results. Against this weighs the evidence of increased operative time, and it has been noted that the costs involved remain controversial and require further clarification. The procedure has not been greeted with the same enthusiasm as laparoscopic cholecystectomy – most likely because the benefits are not as apparent. This review article aims to bring together evidence available on these and other issues appropriate to laparoscopic appendicectomy to help evaluate the procedure in comparison with open appendicectomy.

Laparoscopic surgical techniques have recently entered the field of colorectal surgery. Because the laparoscopic approach has revolutionized biliary surgery, it is hoped that similar advances will be possible in the more elderly population with colorectal disease. Early experience suggests that such advances have not been achieved and there is concern about developing minimal access surgical techniques in the face of potentially curable cancer. This article reviews the current state of knowledge based on published series; however, the current lack of controlled data in patients with extended follow-up makes this area highly controversial. Suggestions regarding the future of laparoscopic surgery are made and include the establishment of a national register and the development of controlled randomized trials.

Checklists have been shown to improve patient outcomes. Checklist use is seen in the pre-operative to post-operative phases of the patient pathway. An adhesive checklist was developed for ward rounds due to the positive impact it could have on improving patient safety. Over an eight day period data were collected from five consultant-led teams that were randomly selected from the surgical department and divided into sticker groups and control groups. Across the board percentage adherence to the Good Surgical Practice Guidelines (GSPG) was markedly higher in the sticker study group, 1186 (91%) in comparison with the control group 718 (55%). There was significant improvement of documentation across all areas measured. An adhesive checklist for ward round note taking is a simple and cost-effective way to improve documentation, communication, hand-over, and patient safety. Successfully implemented in a tertiary level centre in Dublin, Ireland it is easily transferable to other surgical departments globally.

Introduction: Basal-like breast cancers (BL-BCa) have the worst prognosis of all subgroups of this disease. Hyaluronan (HA) and the HA receptor CD44 have a long-standing association with cell invasion and metastasis of breast cancer. The purpose of this study was to establish the relation of CD44 to BL-BCa and to characterize how HA/CD44 signaling promotes a protease-dependent invasion of breast cancer (BrCa) cells.Methods: CD44 expression was determined with immunohistochemistry (IHC) analysis of a breast cancer tissue microarray (TMA). In vitro experiments were performed on a panel of invasive BL-BCa cell lines, by using quantitative polymerase chain reaction (PCR), immunoblotting, protease activity assays, and invasion assays to characterize the basis of HA-induced, CD44-mediated invasion.Results: Expression of the hyaluronan (HA) receptor CD44 associated with the basal-like subgroup in a cohort of 141 breast tumor specimens (P = 0.018). Highly invasive cells of the representative BL-BCa cell line, MDA-MB-231 (MDA-MB-231Hi) exhibited increased invasion through a basement membrane matrix (Matrigel) and collagen. In further experiments, HA-induced promotion of CD44 signaling potentiated expression of urokinase plasminogen activator (uPA) and its receptor uPAR, and underpinned an increased cell-associated activity of this serine protease in MDA-MB-231Hi and a further BL-BCa cell line, Hs578T cells. Knockdown of CD44 attenuated both basal and HA-stimulated uPA and uPAR gene expression and uPA activity. Inhibition of uPA activity by using (a) a gene-targeted RNAi or (b) a small-molecule inhibitor of uPA attenuated HA-induced invasion of MDA-MB-231Hi cells through Matrigel. HA/CD44 signaling also was shown to increase invasion of MDA-MB-231 cells through collagen and to potentiate the collagen-degrading activity of MDA-MB-231Hi cells. CD44 signaling was subsequently shown to upregulate expression of two potent collagen-degrading enzymes, the cysteine protease cathepsin K and the matrix metalloprotease MT1-MMP. RNAi- or shRNA-mediated depletion of CD44 in MDA-MB-231Hi cells decreased basal and HA-induced cathepsin K and MT1-MMP expression, reduced the collagen-degrading activity of the cell, and attenuated cell invasion through collagen. Pharmacologic inhibition of cathepsin K or RNAi-mediated depletion of MT1-MMP also attenuated MDA-MB-231Hi cell invasion through collagen.Conclusion: HA-induced CD44 signaling increases a diverse spectrum of protease activity to facilitate the invasion associated with BL-BCa cells, providing new insights into the molecular basis of CD44-promoted invasion.

With the increasing incidence of breast cancer in patients over 70 years, there is interest in the best therapeutic approach.To review the management of breast cancer in elderly women and to identify the factors involved in the decision to treat patients with tamoxifen as first line therapy.Between 1986 and 1999, 302 female patients agedor = 70 years presented with primary breast cancer, of whom 219 underwent surgery, 79 received tamoxifen as first line treatment and four received primary radiotherapy. A retrospective review was performed on these 79 patients and the outcome recorded.Of these 79 patients, data was available on 68. Follow-up ranged from one to 63 months (median 17 months). Co-morbidity was the principal reason for choosing first line tamoxifen therapy in 61% and patient preference in 11%. Tumour size was less than 5cm in 51%. In 25% tumour size decreased, in 24% it remained stable and in 27% it increased in size following tamoxifen therapy. Additional treatment was prescribed for 33% of patients.In the authors' experience, for those elderly patients suffering considerable co-morbidity or who refuse surgical intervention, tamoxifen is an acceptable alternative.

Improved preoperative localizing studies have facilitated minimally invasive approaches in the treatment of primary hyperparathyroidism (PHPT). Success depends on the ability to reliably select patients who have PHPT due to single-gland disease. We propose a model encompassing preoperative clinical, biochemical, and imaging studies to predict a patient's suitability for minimally invasive surgery.For the purposes of the present study, 180 consecutive patients were included for analysis. A 5-variable model based on preoperative ionized serum calcium (1.4 mmol/l), intact parathyroid hormone level (≥ 2 times the upper limit of normal), positive sestamibi scan for a single affected gland, positive ultrasound scan for a single gland, and concordance between the two imaging modalities for single-gland disease at a similar location was employed, where a score of 1 was allocated for each variable present.Of the 180 patients, 62 (34%) underwent bilateral exploration, 63 (36%) underwent unilateral exploration, and 55 (30%) underwent minimally invasive parathyroidectomy. The results showed that 92% had single-gland disease, 3% had double adenomas, and 5% had hyperplasia. Biochemical cure was achieved in 98.9%. Mean follow-up was 153 days (range: 80-342 days). With the predictive scoring model, a score of ≥ 3 had a positive predictive value of 100% for single-gland disease.A scoring model encompassing preoperative biochemical and imaging data can be successfully employed to predict suitability for minimally invasive surgery in the majority of patients with single-gland disease.

It is an integral component of doctor's duty of care to understand the significant impact laboratory testing has on the expense an ultimate quality of healthcare patients receive, yet the costs of these tests are poorly perceived. Utilising semi-structured interviews and questionnaires, we assessed surgeon's perceived costs of two commonly encountered clinical scenarios requiring out of hours laboratory testing. Of the 35 participants only 23.3% (n = 7) accurately estimated the overall cost. The most expensive test was "Type and Screen" at Euro 83, with 77.3% (n = 17) underestimating the cost. Non-consultant hospital doctors qualified for 3 years were more likely to underestimate on-call costs (p = 0.042). It is of utmost importance to improve the knowledge of all surgeons of the financial implications of investigations. Through education we can potentially reduce un-warranted costs and fulfill our duty of care in the most cost efficient manner.

Following the implementation of the Fottrell report, entry to medical school in Ireland has undergone significant change. Medical school studentship is now awarded based on a combination of points obtained from the final examination of Irish secondary schools (the leaving certificate) combined with HPAT scores (Health Professions Admissions Test). The HPAT is designed to test a candidate's knowledge in several different fields including problem solving skills, logical and non verbal reasoning. A sample HPAT was administered to a test group composed of consultant surgeons, non consultant hospital doctors, and medical students. Statistical analysis was performed and no significant difference was found between the performances of the groups. This is surprising as it was expected that groups with greater experience at medical problem solving would have translated to higher scores. This exposes a flaw within the HPAT system and a potential weakness in the process of doctor selection.

Background: The incidence of ductal carcinoma in situ (DCIS) has increased markedly with the introduction of population based mammographic screening. DCIS is usually diagnosed non-operatively. Although sentinel lymph node biopsy (SNB) has become standard of care in patients with invasive breast carcinoma the use of SNB in patients with DCIS is controversial. Aims: This study examines the justification for offering SNB at the time of primary surgery to patients with a needle core biopsy (NCB) diagnosis of DCIS. Methods: A retrospective analysis of 145 patients, diagnosed with DCIS by NCB and who had SNB performed at the time of primary surgery, was performed. The study focussed on rates of SNB positivity and underestimation of invasive carcinoma by NCB, and sought to identify factors that might predict the presence of invasive carcinoma in the excision specimen. Results: 7/145 patients (4.8%) had a positive sentinel lymph node (SN), 4 macrometastases and 3 micrometastases. 6/7 patients had invasive carcinoma in the final excision specimen. 55/145 patients (37.9%) with NCB diagnosis of DCIS had invasive carcinoma in the excision specimen. The median invasive tumour size was 6mm. A radiological mass and areas of invasion less than 1mm, amounting to “at least microinvasion” on NCB were predictive of invasive carcinoma in the excision specimen. Conclusions: SNB positivity in pure DCIS is rare. In view of the high rate of underestimation of invasive carcinoma in patients with NCB diagnosis of DCIS in this study, SNB appears justified in this group of patients in our centres.