Predictors of overall and recurrence-free survival after neoadjuvant chemotherapy for gastroesophageal adenocarcinoma: Pooled analysis of individual patient data (IPD) from randomized controlled trials (RCTs).

BACKGROUND: Neoadjuvant chemotherapy improves prognosis of patients with locally advanced gastroesophageal adenocarcinoma. The aim of this study was to identify predictors for postoperative survival following neoadjuvant therapy. These could be useful in deciding about postoperative continuation of chemotherapy. METHODS: This meta-analysis used IPD from RCTs comparing neoadjuvant chemotherapy with surgery alone for gastroesophageal adenocarcinoma. Trials providing IPD on age, sex, performance status, pT/N stage, resection status, overall and recurrence-free survival were included. Survival was calculated in the entire study population and subgroups stratified by supposed predictors and compared using the log-rank test. Multivariable Cox models were used to identify independent survival predictors. RESULTS: Four RCTs providing IPD from 553 patients fulfilled the inclusion criteria. (y)pT and (y)pN stage and resection status strongly predicted postoperative survival both after neoadjuvant therapy and surgery alone. Patients with R1 resection after neoadjuvant therapy survived longer than those with R1 resection after surgery alone. Patients with stage pN0 after surgery alone had better prognosis than those with ypN0 after neoadjuvant therapy. Patients with stage ypT3/4 after neoadjuvant therapy survived longer than those with stage pT3/4 after surgery alone. Multivariable regression identified resection status and (y)pN stage as predictors of survival in both groups. (y)pT stage predicted survival only after surgery alone. CONCLUSION: After neoadjuvant therapy for gastroesophageal adenocarcinoma, survival is determined by the same factors as after surgery alone. However, ypT stage is not an independent predictor. These results can facilitate the decision about postoperative continuation of chemotherapy in pretreated patients.

Penetrating stab injuries at a single urban unit: are we missing the point?

BACKGROUND: Penetrating trauma--the classical presentation of disorganised crime--can pose a challenge in their management due to their complexity and unpredictability. AIM: We examined the experience of one urban unit in the management of penetrating injuries to draw conclusions pertinent to other Irish centres. METHODS: A retrospective study was performed of all penetrating injuries presenting to the Emergency Department (ED) of Connolly Hospital, Dublin between January 2009 and December 2012. Information was collected from the Hospital Inpatient Enquiry database, theatre logbooks and ED records. RESULTS: One hundred and four patients presented with penetrating injuries in the given period. Four mortalities were recorded. Abdominal injury was recorded in 22% of patients; 26% had multiple injuries not involving the abdomen; 11% had an isolated thoracic injury. Fifty-seven percent required surgery, of which 40% required emergency or early surgical intervention. Laparotomy and laparoscopy were required in 14 and 7%, respectively; 5% required thoracotomy of which two had penetrating cardiac injuries, both of whom survived. CONCLUSIONS: Although many patients with penetrating trauma can be safely managed conservatively, our study shows that over half required surgical intervention. These data highlight the need for a trauma team in each Irish centre receiving trauma with a clear need for general surgeons on emergency on-call rotas to be experienced in trauma management. There is an urgent need to centralise the management of trauma to a limited number of designated trauma centres where expertise is available by surgeons with a special interest in trauma management.

Chemoradiotherapy, with adjuvant surgery for local control, confers a durable survival advantage in adenocarcinoma and squamous cell carcinoma of the oesophagus.

INTRODUCTION: Oesophageal cancer usually presents with systemic disease, necessitating systemic therapy. Neo-adjuvant chemoradiotherapy improves short-term survival, but its long-term impact is disputed because of limited accrual, treatment-protocol heterogeneity and a short follow-up of randomised trials. AIMS: Long-term results of two simultaneous randomised controlled trials (RCTs) comparing neo-adjuvant chemo-radiotherapy and surgery (MMT) with surgical monotherapy were examined, and the response of adenocarcinoma (AC) and squamous cell carcinoma (SCC) to identical regimens compared. METHODS: Between 1990 and 1997, two RCTs were undertaken on 211 patients. Patients with AC (n=113) or SCC (n=98) were separately-randomised to identical protocols of MMT or surgical monotherapy. RESULTS: 211 patients were followed to 206 months; 104 patients were randomised to MMT (58 AC and 46 SCC, respectively) and 107 to surgery. MMT provided a significant survival-advantage over surgical monotherapy for AC (P=0.004), SCC (P=0.01). There was a 54% relative risk-reduction in lymph-node metastasis following MMT, compared with surgery (64% versus 29%, P<0.001). MMT produced a pathologic complete response (pCR) in 25% and 31% of AC and SCC, respectively. Survival advantage accrued to MMT, pCR and node-negative patients: AC pCR versus surgical monotherapy (P=0.001); residual disease following MMT versus surgical monotherapy (P=0.008); SCC pCR versus surgical monotherapy (P=0.033). CONCLUSIONS: A survival advantage for MMT persisted long-term in AC and was replicated in SCC. MMT produced loco-regional tumour down-staging to extinction in 25-31% of patients, potentially permitting personalised treatment in this cohort that avoids the morbidity and mortality associated with resection. Node-negative patients with residual localised disease following MMT had a survival advantage over node-negative patients following surgery alone, supporting a systemic effect on micro-metastatic disease.

Basic surgical training in Ireland: the impact of operative experience, training program allocation and mentorship on trainee satisfaction.

BACKGROUND: Application to the Irish basic surgical training (BST) program in Ireland has decreased progressively over the past 5 years. We hypothesised that this decline was secondary to dissatisfaction with training correlated with reduced operative experience and lack of mentorship among BSTs. METHODS: An anonymous 15 question electronic survey was circulated to all BSTs appraising their impression of the operative experience available to them, their mentorship and their opinions of critical aspects of training. RESULTS: Fifty trainees responded to the survey. At the commencement of training 98 % (n = 43) intended to stay in surgery, decreasing to 79 % (n = 34) during the BST. Trainees who felt they had a mentor were three times more likely to be content in surgical training (OR 3.11; 95 % CI 0.94-10.25, P = 0.06). Trainees satisfied with their allocated rotation were more likely to be content in surgical training (OR 4.5; 95 % CI 1.03-19.6, P = 0.045). Individual trainee comments revealed dissatisfaction with operative exposure. CONCLUSION: Mentorship and satisfaction with allocated training rotation had a positive impact on trainee satisfaction and correlated with contentedness in surgical training. Operative experience is the main element that trainees report as lacking. This highlights the need for reform of the training system to improve current levels of mentorship and increase operative exposure to enhance its attractiveness to the best quality medical graduates.

Excision and primary closure of pilonidal sinus disease: worthwhile option with an acceptable recurrence rate.

BACKGROUND: Treatment of pilonidal sinus disease is controversial. Many claim policy of marsupialisation and healing by secondary intention. This is demanding in terms of nursing care and time lost from work. AIMS: To examine outcome of excision and primary closure of chronic pilonidal disease on recurrence rate and patient's daily activities. PATIENTS AND METHODS: One hundred and fourteen consecutive elective patients who had excision and primary closure of pilonidal sinus disease were reviewed. The demographic data and the post-operative outcome were studied. RESULTS: The recurrence of pilonidal sinus was noted in 9% of patients, wound breakdown occasioning delayed healing in 9%, patients able to drive by day 16 on average. The mean time to return to work was 20.5 days; duration of analgesia, 2.4 days; and duration of antibiotic treatment, 4.7 days. CONCLUSION: Excision and primary closure of chronic pilonidal sinus has low recurrence rate with early return to activities. Primary closure appears to be a cost-effective option for uncomplicated pilonidal sinus disease.

Taurine attenuates radiation-induced lung fibrosis in C57/Bl6 fibrosis prone mice.

INTRODUCTION: The amino acid taurine has an established role in attenuating lung fibrosis secondary to bleomycin-induced injury. This study evaluates taurine's effect on TGF-beta1 expression and the development of lung fibrosis after single-dose thoracic radiotherapy. METHODS: Four groups of C57/Bl6 mice received 14 Gy thoracic radiation. Mice were treated with taurine or saline supplementation by gavage. After 10 days and 14 weeks of treatment, TGF-beta1 levels were measured in serum and bronchoalveolar lavage fluid (BALF). Lung collagen content was determined using hydroxyproline analysis. RESULTS: Ten days post radiotherapy, serum TGF-beta1 levels were significantly lower after gavage with taurine rather than saline (P = 0.033). BALF TGF-beta1 at 10 days was also significantly lower in mice treated with taurine (P = 0.031). Hydroxyproline content was also significantly lower at 14 weeks in mice treated with taurine (P = 0.020). CONCLUSION: This study presents novel findings of taurine's role in protecting from TGF-beta1-associated development of lung fibrosis after thoracic radiation.

Collins' sign: validation of a clinical sign in cholelithiasis.

BACKGROUND: Cholelithiasis typically presents with right upper quadrant pain, as can pain from other right upper quadrant organs. Pain of cholelithiasis is often referred to tip of scapula. Professor Paddy Collins drew attention to fact that patients with gallstone pain would attempt to demonstrate this by placing their hand behind the back and thumb pointing upwards. This became known amongst his students as Collins' sign. AIM: To evaluate accuracy of Collins' sign as indicator of cholelithiasis. PATIENTS AND METHODS: Case-control study performed on 202 patients with symptomatic cholelithiasis and 200 control patients (with oesophagitis, gastritis or duodenal ulcer). Questionnaire examined pain pattern in both groups. The results analysed using t test and χ(2) test. RESULTS: Collins' sign was positive in 51.5% of gallstone patients and 7.5% of control group (P < 0.001). CONCLUSIONS: Collins' sign was positive in over half of all patients with cholelithiasis and was useful discriminator in diagnosis of gallstones.

Collagenous colitis as a possible cause of toxic megacolon.

Collagenous colitis is a microscopic colitis characterized by normal appearing colonic mucosa on endoscopy. It is regarded as a clinically benign disease which rarely results in serious complications. We report a case of toxic megacolon occurring in a patient with collagenous colitis. This is the first reported case of toxic megacolon occurring in this subset of patients.

Intra-operative examination of the sentinel node in breast cancer.

Intra-operative sentinel node analysis allows immediate progression to axillary clearance in patients with node positive breast cancer and reduces the need for re-operation. Despite this, intra-operative sentinel node analysis is infrequently performed in Ireland. We report our experience using this technique. Sentinel node biopsy was performed in 47 consecutive patients with symptomatic T1-T2 clinically node negative breast cancer. Sentinel nodes were examined intra-operatively by frozen section and imprint cytology and definitive histological assessment was performed on paraffin-embedded tissue. The sentinel node was identified in 46 (98%) patients. Twelve patients had axillary metastases. The sensitivity of intra-operative analysis in identifying nodal metastases was 92%. False negative rate was 8%, negative predictive value 97%, and specificity 100%. Intra-operative analysis of the sentinel node allowed re-operation to be avoided in 92% of patients with axillary node metastases. In our experience this technique can be readily introduced with reliable outcomes.

Lack of awareness of oesophageal carcinoma among the public in Ireland.

BACKGROUND: Oesophageal cancer is advanced in the majority at presentation and its symptoms are usually present for many months suggesting poor awareness of its symptoms. Few studies have examined awareness of oesophageal cancer amongst the public. AIMS: This study aimed to identify the level of awareness among the general public of oesophageal cancer, of its symptoms, of its awareness campaigns and to compare it with other common cancers. METHODS: Face-to-face interviews were conducted with 279 members of the public. People were asked about their awareness of a range of cancers, and their knowledge of cancer symptoms and cancer awareness campaigns. RESULTS: Awareness of oesophageal cancer was low and knowledge of its symptoms was even lower. Despite the efforts of awareness campaigns, knowledge of these campaigns was poor amongst the public. CONCLUSION: Awareness of oesophageal cancer and its symptoms is low amongst the public. This needs to be addressed if disease is to be detected at an earlier and curable stage.

Lipoma of the cord and round ligament: an overlooked diagnosis?

Lipoma of the cord, once considered rare and insignificant, has been cast in a new light by laparoscopic pre-peritoneal surgery, with diagnostic and therapeutic implications. This study aimed to determine the incidence, significance and association of spermatic cord lipomas to inguinal hernias. A retrospective review was performed for all hernia operations carried out between January 1999 and November 2002. The incidence of cord lipomas and their relation to inguinal hernias were evaluated. There were 123 repairs performed on 111 patients, 90 of which were laparoscopic via the pre-peritoneal approach, 29 were open and 4 converted from laparoscopic to open in the early part of the series. All but two cases were male (neither female had associated lipoma of the round ligament). Twenty-six lipomas of the cord were identified with an incidence of 21%. Sixteen were associated with hernia and only 10 were pure cord lipoma, an incidence of 8%. Thirteen repairs represented recurrent hernias, two of which had pure cord lipoma, one had an associated sac. Only two lipomas were suspected clinically prior to surgery. Lipoma of the cord is a poorly recognised entity that can be present with groin symptoms and clinical findings indistinguishable from inguinal hernia. Its incidence was poorly appreciated prior to the laparoscopic era.

Neoadjuvant treatment of oesophageal adenocarcinoma.

Oesophageal adenocarcinoma is an enigma. It has emerged, seemingly from nowhere, in the late 20th century to dominate the oesophageal oncological landscape. This review will examine whether the current outcome for adenocarcinoma is as good as it gets or whether additional treatment is necessary and if so whether neoadjuvant therapy is effective.

Improvement in efficacy of chemoradiotherapy by addition of an antiangiogenic agent in a murine tumor model.

BACKGROUND: Chemoradiotherapy improves survival for some cancer patients. Methods of enhancing treatment response would further enhance survival rates. The effect of the addition of an antiangiogenic agent to a chemoradiotherapy regime has not previously been examined. MATERIALS AND METHODS: C57B16 mice were inoculated with 1 x 10(6) Lewis lung carcinoma cells into the flank and randomized to 1 of 10 treatment groups when tumor volume approached 1000 mm(3). Animals received combinations of standard doses of intraperitoneal cisplatin, 5-fluorouracil, and the antiangiogenic agent genistein, together with 10 or 20 Gy of external beam radiotherapy. Animals were sacrificed at day 6 when tumor volume, microvessel density, and serum VEGF were determined. RESULTS: Mean (SEM) tumor volume in the chemoradiotherapy group was 762 (212) mm(3) versus 565 (79) mm(3) in the chemoradiotherapy plus genistein group (P = 0.04, unpaired t-test). The addition of genistein produced a significant reduction in tumor microvessel density (P = 0.01) as well as serum VEGF levels (P < 0.05) compared to those animals receiving chemoradiation alone. CONCLUSIONS: This study provides proof of principle that chemoradiation can be enhanced by the addition of an antiangiogenic agent to the regime and suggests that further examination of such regimes is warranted.