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.

Emergency Aeromedical Services in Ireland: A Single-Centre Study in 2014.

This retrospective analysis includes patients requiring Emergency Aeromedical Services (EAS) in 2014. The aim of this paper is to evaluate the HEMS service in a single centre and to accurately assess whether certain internationally validated criteria can predict admission rates better than the currently used criteria. Using the American College of Surgeons (ACS) trauma-related dispatch criteria, each case was retrospectively evaluated. Results showed the mean total criteria met were 2.73 (?=0.88) and 1.45 (?=0.82) in admitted and discharged patients respectively. The total criteria met had a significant predictive value on admission rates (p<0.05). Increased admission rates were shown in patients with a high Mechanism of Injury (MOI) (p<0.05). False positive rates of HEMS transfer were higher when applying the current criteria compared to the ACS criteria. ACS total criteria can predict admission in HEMS patients with a higher specificity than currently used guidelines.

The prognostic value of tumour regression grade following neoadjuvant chemoradiation therapy for rectal cancer.

AIM: To date, there is no uniform consensus on whether tumour regression grade (TRG) is predictive of outcome in rectal cancer. Furthermore, the lack of standardization of TRG grading is a major source of variability in published studies. The aim of this study was to evaluate the prognostic impact of TRG in a cohort of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation therapy (CRT). In addition to the Mandard TRG, we utilized four TRG systems modified from the Mandard TRG system and applied them to the cohort to assess which TRG system is most informative. METHOD: One-hundred and fifty-three patients with a T3/T4 and/or a node-positive rectal cancer underwent neoadjuvant 5-fluorouracil-based CRT followed by surgical resection. RESULTS: Thirty-six (23.5%) patients achieving complete pathological response (ypCR) had a 5-year disease-free survival (DFS) rate of 100% compared with a DFS rate of 74% for 117 (76.5%) patients without ypCR (P = 0.003). The Royal College of Pathologists (RCPath) TRG best condenses the Mandard five-point TRG by stratifying patients into three groups with distinct 5-year DFS rates of 100%, 86% and 67%, respectively (P = 0.001). In multivariate analysis, pathological nodal status and circumferential resection margin (CRM) status, but not TRG, remained significant predictors of DFS (P = 0.002, P = 0.035 and P = 0.310, respectively). CONCLUSION: Our findings support the notion that ypCR status, nodal status after neoadjuvant CRT and CRM status, but not TRG, are predictors of long-term survival in patients with locally advanced rectal cancer.

Outcomes of patients presenting to a dedicated rapid access lung cancer clinic.

We examined the outcomes of the first 500 patients referred to a dedicated Rapid Access Lung Cancer Clinic. A total of 206 patients (41.2%) were diagnosed with a thoracic malignancy; 179 had primary lung cancer and 27 had secondary or other thoracic cancers. Pulmonary nodules requiring ongoing surveillance were found in a further 79 patients (15.8%). Of those patients found to have primary lung cancer, 24 (13.4%) had Small Cell and 145 (81%) had Non Small Cell Lung Cancer. In patients with Non small cell tumours, 26 (21.1%) were stage 1, 14 (11.4%) stage II, 37 (30.1%) stage III and 46 (37.4%) stage IV at diagnosis. For the 129 patients (72%) in whom the thoracic MDT recommended active treatment, primary therapy was surgical resection in 44 (24.6%), combined chemoradiation in 31 patients (17.3%), chemotherapy alone in 39 (21.8%) and radiation in 15 (8.4%).

An exploration of the impact of ethanol diluent on breath alcohol concentration in patients receiving paclitaxel chemotherapy.

PURPOSE: This study aimed to provide a better understanding of the impact of paclitaxel chemotherapy on breath alcohol in an Irish population. METHODS: Patients attending the Oncology Day Unit at Beaumont Hospital were invited to participate on the day of their treatment. The brand of paclitaxel used was Actavis Pharma Inc and contained 6 mg/mL paclitaxel in 50% Ethanol/ 50% Cremophor EL. Breath alcohol concentration was measured using the AlcoSense ™ Breathalyser on three separate visits. The primary end-point was the number of patients who were above the legal threshold for drink driving in Ireland. RESULTS: In total, 50 patients were recruited. 36 (68%) were female. The most common diagnosis was breast cancer (56%). Ten (20%) patients had metastatic disease and 4 (8%) had liver metastases. The mean paclitaxel dose administered was 118 mg. The mean amount of ethanol infused was 7.7 g. 27 patients had a detectable breath alcohol level on at least one visit. The mean breath alcohol concentration was 2 mcg/100 mL or 0.02 mg/L of breath. The maximum concentration of ethanol in exhaled breath was 11 mcg/100 mL or 0.11 mg/L which is 50% of the statutory limit for drink driving in Ireland. A weak correlation was observed between ethanol concentration in exhaled breath and the total amount of ethanol administered. Although no patient exceeded the general limit for drink driving in Ireland, three (6%) participants had a breath alcohol concentration above the threshold for professional, learner or novice drivers. CONCLUSION: Although definitive conclusions are limited by relatively small numbers, it seems unlikely that weekly paclitaxel infusions pose any significant risk to patients driving.

Trauma assessment clinic: Virtually a safe and smarter way of managing trauma care in Ireland.

INTRODUCTION: The Trauma Assessment Clinic [TAC], also referred to as Virtual Fracture Clinic, offers a novel care pathway for patients and is being increasingly utilised across the Irish and UK health care systems. The provision of safe, patient centred, efficient and cost-effective treatment via a multidisciplinary team [MDT] approach is the primary focus of TAC. The Trauma and Orthopaedic unit at Tullamore Hospital was the first centre to introduce a TAC in Ireland and this overview outlines the experiences of this pilot. METHODS AND PATIENTS: Patients arriving to the Emergency Department with injuries that were TAC appropriate were treated as per a recognised protocol. They were given information regarding their injury and a removable splint or cast and told to expect a follow up phone call from the orthopaedic team. Within 24 h the patient's clinical notes and x-rays were assessed by the TAC MDT and patients were called immediately to be advised as to their planned treatment. RESULTS: To date the TAC pilot in Tullamore Hospital has reviewed 2704 patients. 35% of patients were discharged at the TAC review stage, 27% were referred to an appropriate clinic (e.g. Shoulder injuries referred to an upper limb specialist) or a general trauma follow-up clinic, and 38% were referred onto physiotherapy services local and community based for follow-up. A survey of patients reviewed in the TAC revealed that 97% of respondents agreed or strongly agreed that they were satisfied with their recovery. The cost of each TAC consultation was €28 versus €129 for a traditional fracture clinic appointment. CONCLUSION: Our experience of the TAC is that it provides a very safe, patient focused and cost-effective means of delivering trauma care. It provides a more streamlined and improved patient journey in select patients with certain fracture patterns, allowing for patient empowerment without compromising clinical care and marries current available technology with up to date best clinical practice.

Life-threatening gastrointestinal haemorrhage in Von Recklinghausen's disease.

Neurofibromatosis Type I (NF-1), also known as Von Recklinghausen's disease, is a common disorder, but gastrointestinal manifestations are rare and can be associated with severe complications and malignancy. We describe a case of multiple intestinal tumours, which presented as major per-rectal bleeding and was diagnosed by laparotomy. Presenting symptoms of this condition are usually non-specific, but the risk of malignancy and perforation should allow for a high index of suspicion in patients with NF-1 presenting with gastrointestinal symptoms. We present this case as a reminder that blood loss from the bowel in Von Recklinghausen's disease may be life-threatening, requiring immediate surgery to control haemorrhage.

Emergency aeromedical services in Ireland: a retrospective study for "MEDEVAC112".

AIM: This is a retrospective analysis of all consecutive patients requiring emergency aeromedical services (EAS) to a level II trauma centre. This analysis was performed to evaluate the new service to Tallaght Hospital in terms of: the criteria used for dispatch, an estimate of baseline efficiency of time critical management of patients, the cross-catchment transfer of patients. METHODS: Data were provided by the EAS with respect to the patients brought to Tallaght Hospital not including inter-facility transfers for the calendar year 2013. Using this information patient records were matched to the electronic database. Once patients were identified, their hospital journey was catalogued using chart review. Using Google Maps and the EAS data an estimated road-time was calculated. Specific dispatch criteria were unavailable, however, using five broad categories outlined by the American College of Surgeons (ACS) for trauma related dispatch criteria each case was evaluated. RESULTS: The EAS data had 52 cases which were reported to come to this unit. 48 patient records were accurately matched to this data. 25 % were discharged without speciality input. Seven patients died within 24 h only one of which was admitted under a speciality. 30 patients were admitted under specialist care with two requiring transfer to another centre. 80 % of admissions came under the primary management of the orthopaedic team. 11 patients required operative management, five required ICU management, three required chest drains and one patient required cardiac angiogram. Of the five dispatch criteria categories evaluated the mean number of criteria met was 3.1. CONCLUSION: 25 % of the patients were managed in the Emergency Department alone indicating an acceptable level of over-triage according to ACS guidelines. When comparing the dispatch criteria met for this 25 % there was no statistical difference compared with the other 75 %. Sensitivity and specificity analyses have looked at the question of dispatch criteria before and our data are comparable with international evidence. We suggest that further research be undertaken to develop this service to improve activation criteria and thereby the entire service delivered.

The impact of outpatient systemic anti-cancer treatment on patient costs and work practices.

BACKGROUND: There is extensive focus on the rising costs of healthcare. However, for patients undergoing cancer treatment, there are additional personal costs, which are poorly characterised. AIM: To qualify indirect costs during anti-cancer therapy in a designated Irish cancer centre. METHODS: An anonymous questionnaire collected demographic data, current work practice, and personal expenditure on regular and non-regular indirect costs during treatment. Differences between groups of interest were compared using the Mann-Whitney U test. RESULTS: In total, there were 151 responders of median age 58 years; 60 % were female and 74 % were not working. Breast cancer (29 %) was the most frequent diagnosis. Indirect costs totalled a median of €1138 (range €21.60-€7089.84) per patient, with median monthly outgoings of €354. The greatest median monthly costs were hair accessories (€400), transportation (€65), and complementary therapies (€55). The majority (74 %) of patients used a car and median monthly fuel expenditure was €31 (range €1.44-€463.32). Women spent more money during treatment (€1617) than men (€974, p = 0.00128). In addition, median monthly expenditure was greater for those less than 50 years old (€1621 vs €1105; p = 0.04236), those who lived greater than 25 km away (€2015 vs €1078; p = 0.00008) and those without a medical card (€2023 vs €961; p = 0.00024). CONCLUSION: This study highlights the need for greater awareness of indirect expenditures associated with systemic anti-cancer therapy in Ireland.

Taxane-resistant lymphoepithelial-like carcinoma: excellent response to VIP chemotherapy.

BACKGROUND: Lymphoepithelial-like carcinoma is a rare tumour type. The optimal treatment for this disease is not known. No effective therapies are described in the literature. AIMS: This report describes a case of lymphoepithelial-like carcinoma and documents a therapeutic strategy which has proved effective. RESULTS: The patient was initially treated with a common platinum-based chemotherapy regimen incorporating a taxane (Carbplatin and Docetaxel). Disease stabilization initially occurred but the patient soon progressed. The patient was then treated with VIP chemotherapy and had a complete response. CONCLUSION: VIP chemotherapy appears to be an effective therapeutic strategy in lymphoepithelial-like carcinoma.

Twenty-two years of phase III trials for patients with advanced non-small-cell lung cancer: sobering results.

PURPOSE: To determine the changes in clinical trials and outcomes of patients with advanced-stage non-small-cell lung cancer (NSCLC) treated on phase III randomized trials initiated in North America from 1973 to 1994. PATIENTS AND METHODS: Phase III trials for patients with advanced-stage NSCLC were identified through a search of the National Cancer Institute's Cancer Therapy Evaluation Program database from 1973 to 1994, contact with Cooperative Groups, and by literature search of MEDLINE. Patients with advanced NSCLC treated during a similar time interval were also examined in the SEER database. Trends were tested in the number of trials, in the number and sex of patients entered on the trials, and in survival over time. RESULTS: Thirty-three phase III trials were initiated between 1973 and 1994. Twenty-four trials (73%) were initiated within the first half of this period (1973 to 1983) and accounted for 5,359 (64%) of the 8,434 eligible patients. The median number of patients treated per arm of the trials rose from 77 (1973 to 1983) to 121 (1984 to 1994) (P <.001). Five trials (15%) showed a statistically significant difference in survival between treatment arms, with a median prolongation of the median survival of 2 months (range, 0.7 to 2.7 months). CONCLUSION: Analysis of past trials in North America shows that the prolongation in median survival between two arms of a randomized study was rarely in excess of 2 months. Techniques for improved use of patient resources and appropriate trial design for phase III randomized therapeutic trials with patients with advanced NSCLC need to be developed.

Phase II trial of paclitaxel by 96-hour continuous infusion in combination with cisplatin for patients with advanced non-small cell lung cancer.

Our purpose was to determine the antitumor efficacy and safety profile of the combination of paclitaxel administered by 96-h continuous i.v. infusion followed by bolus cisplatin in patients with untreated advanced non-small cell lung cancer (NSCLC). Fifty-eight patients with untreated advanced or recurrent NSCLC were enrolled between October 1995 and December 1998. The median patient age was 60 years (age range, 34-75 years). Twenty-four patients were female. The majority of patients (n = 52) had an Eastern Cooperative Oncology Group performance status of 0/1. Twelve patients had stage IIIB NSCLC, 43 had stage IV disease, and 3 had recurrent disease after prior resection. Seven patients had received cranial irradiation for brain metastases, and 5 patients had received bone irradiation before enrollment. Patients were treated with paclitaxel (120 mg/m2/96 h) by continuous i.v. infusion followed by cisplatin (80 mg/m2) on day 5. Therapy was administered every 3 weeks as tolerated until disease progression or a maximum of six cycles. A total of 264 cycles of therapy were administered. Twenty-nine patients received all six cycles. Forty-six patients had measurable disease, with 20 patients achieving a partial response, and no complete responses were seen (overall response rate, 43%; 95% confidence interval, 29-60%). The median progression-free survival was 5.5 months. At a median potential follow-up of 27.2 months, the median survival for all 58 enrolled patients was 8.5 months, and the actuarial 1-year survival was 37% (95% confidence interval, 25.9-50.5%). This is the most extensive evaluation of prolonged continuous infusional paclitaxel in patients with advanced-stage cancer. In contrast to predictions from in vitro cytotoxicity models, the regimen does not appear to be obviously superior to shorter infusion times in the clinical setting. Additional trials of this regimen in patients with NSCLC are therefore of low priority.

Advanced Merkel cell cancer and the elderly.

BACKGROUND: Merkel cell cancer (MCC) is an uncommon neuroendocrine skin cancer occurring predominantly in elderly Caucasians. It tends to metastasize to regional lymph nodes and viscera and is sensitive to chemotherapy but recurs rapidly. AIM: To report one such case, its response to chemotherapy and briefly review the literature. METHODS: A 73-year-old male with a fungating primary lesion on his left knee and ulcerated inguinal lymph nodes was diagnosed with MCC and treated with chemotherapy. The two largest case series and reviews of case reports were summarised. RESULTS: His ulcer healed after two cycles of carboplatin and etoposide with improvement in quality of life. Overall response rates of nearly 60% to chemotherapy are reported but median survival is only nine months with metastatic disease. CONCLUSIONS: Chemotherapy should be considered for fit elderly patients with MCC who have recurrent or advanced disease.

Lung carcinoma metastasis at the site of central venous access.

Tumor metastases rarely are reported in association with central venous catheters. The case reported herein is that of a solid tumor metastasis at the site of a previous indwelling line ipsilateral to a pleural effusion in a patient with non-small cell lung cancer. A review of the literature reveals a single case of intrathoracic malignancy seeding at the site of a central venous catheter. Other investigators are urged to collect information about the development of tumor implants at the site of catheter insertion in patients with cancer and pleural effusions to further define the extent of the problem.

Bronchioloalveolar carcinoma of the lung: recurrences and survival in patients with stage I disease.

OBJECTIVES: The aim of our study was to retrospectively compare the patient characteristics, the frequency and pattern of recurrent disease, and survival in patients with stage I bronchioloalveolar carcinoma and adenocarcinoma of the lung. METHODS: Patients with stage I bronchioloalveolar carcinoma or adenocarcinoma other than bronchioloalveolar carcinoma resected between 1984 and 1992 with adequate clinical follow-up were studied. The clinical characteristics of the patients, extent of initial surgical resection, sites of recurrent disease, and overall survival were examined and compared between the 2 groups. The median follow-up for patients with bronchioloalveolar carcinoma and adenocarcinoma was 6.2 years and 5.9 years, respectively. RESULTS: A total of 138 patients were identified. Thirty-three patients had bronchioloalveolar carcinoma and 105 patients had adenocarcinoma. Eleven (33%) of the patients with bronchioloalveolar carcinoma had never smoked cigarettes versus 9 (9%) of the patients with adenocarcinoma (P =.0036). There were no significant differences between patients with bronchioloalveolar carcinoma and adenocarcinoma in sex distribution and overall recurrence rate. Of the 12 patients with recurrent bronchioloalveolar carcinoma, 1 patient (8%) had extrathoracic disease develop at the site of first recurrence compared with 49% of patients with recurrent adenocarcinoma (P <.001). The 5-year survival in patients with bronchioloalveolar carcinoma and in those with adenocarcinoma was 83% and 63%, respectively (P =.04). CONCLUSIONS: Stage I bronchioloalveolar carcinoma is more likely to occur in nonsmokers. Survival is longer in patients with bronchioloalveolar carcinoma. Further research is warranted to define the etiology, clinical course, and molecular abnormalities in patients with bronchioloalveolar carcinoma to generate more effective therapeutic approaches.

Phase II neoadjuvant trial of paclitaxel by 96-hour continuous infusion (CIVI) in combination with cisplatin followed by chest radiotherapy for patients with stage III non-small-cell lung cancer.

Sixteen patients with untreated locally advanced (n = 15) or recurrent (n = 1) non-small-cell lung cancer (NSCLC) were enrolled in this study between July 1996 and March 1999. Eight patients had stage IIIA NSCLC, seven had stage IIIB disease, and one had recurrent disease after prior resection of stage I disease. Patients were treated with paclitaxel 30 mg/m2/d for 4 days by continuous intravenous infusion followed by cisplatin 80 mg/m2 on day 5. Therapy was administered every 3 weeks until disease progression or a maximum of four cycles. Thoracic radiation was started within 3 to 4 weeks of day 1 of the last cycle of paclitaxel and cisplatin. Fourteen patients (87.5%) received all four cycles of chemotherapy and subsequent radiation therapy. Forty-four percent of patients achieved a partial response, and 1 patient complete response (overall response rate, 50%). The median progression-free survival was 8.8 months. At a median potential follow-up of 3.7 years, the median survival for all 16 enrolled patients was 13.2 months, and the actuarial 1-, 2-, and 3-year survivals were 62.5%, 43.8%, and 21.9%. In contrast to predictions from in vitro cytotoxicity models, the sequential use of prolonged infusional paclitaxel and bolus cisplatin followed by thoracic radiation does not appear to have a greater impact over shorter chemotherapy

Chemotherapy induced peripheral neuropathy: the modified total neuropathy score in clinical practice.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, potentially reversible side effect of some chemotherapeutic agents. CIPN is associated with decreased balance, function and quality of life (QoL). This association has to date been under-investigated. AIMS: To profile patients presenting with CIPN using the modified Total Neuropathy Score (mTNS) in this cross-sectional study and to examine the relationship between CIPN (measured by mTNS) and indices of balance, quality of life (QoL) and function. METHODS: Patients receiving neurotoxic chemotherapy regimens were identified using hospital databases. Those who did not have a pre-existing neuropathy were invited to complete mTNS, Berg Balance Scale (BBS), timed up and go (TUG), and FACT-G QoL questionnaire. mTNS scores were profiled and also correlated with BBS, TUG and FACT-G using Spearmans correlation coefficient. RESULTS: A total of 29 patients undergoing neurotoxic chemotherapy regimens were tested. The patients mTNS scores ranged between 1 and 12 (median = 5), indicating that all patients had clinical evidence of neuropathy on mTNS. No significant correlations were found between mTNS and BERG (r = -0.29), TUG (r = 0.14), or FACT-G (r = 0.05). CONCLUSIONS: This study found a high prevalence of CIPN in patients treated with neurotoxic chemotherapy regimens. The mTNS provided a clinically applicable, sensitive screening tool for CIPN which could prove useful in clinical practice. mTNS did not correlate with BBS, TUG or FACT-G in this sample, possibly due to relatively mild levels of CIPN and consequent subtle impairments which were not adequately captured by gross functional assessments.

The effect of inclement weather on ankle fracture management in an Irish trauma unit.

INTRODUCTION: Ireland is unfamiliar with extreme weather conditions. Such conditions occurred in winter 2009-2010 and 2010-2011, with much of the country being affected by snow and ice. We reviewed the effect that these conditions had on the treatment of ankle fractures in our trauma unit. MATERIALS AND METHODS: The study period was from November until February for four consecutive years from 2008-2009 until 2011-2012. We compared two winters with extreme weather with two winters with regular weather conditions. Information from Met Eireann was compared with demographics from patient records to differentiate ice-related injuries from non-ice-related injuries. Ankle fractures were classified using the Lauge-Hansen classification. We compared waiting times in A&E, waiting times for theatre, delays relating to injury severity, and overall length of stay for both groups. RESULTS: We identified 44 ice-related injuries and 67 non-ice-related injuries. Ice-related injuries trended towards more severe fracture configurations using the Lauge-Hansen classification. Patients sustaining ankle injuries during inclement weather were significantly younger than patients sustaining injuries during regular weather conditions. There were no other significant differences between the two groups. DISCUSSION: Ice-related injuries trended towards a greater severity of fracture configuration. We identified no significant increase in the time to treatment or overall length of stay of patients sustaining ankle fractures during these times. Ice-related injuries did not have greater rates of complications. These results are a testament to the trauma staff in this unit who absorbed the increased workload without compromising patient care.