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.

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.

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.

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.

Mechanisms of columnar metaplasia and squamous regeneration in experimental Barrett's esophagus.

BACKGROUND: This study examined the effect of the lower esophageal milieu on the healing of a mucosal defect. METHODS: With a canine model a mucosal defect was created in the lower esophagus, and acid reflux was promoted by a cardioplasty and pentagastrin injection in 10 animals. At 3 months the regenerated mucosa was excised and underwent histologic examination. Six of these animals underwent an antireflux procedure, had their acid secretion suppressed, and were followed up for a further 3 months, at which time they were killed and the entire esophagus underwent histologic examination. RESULTS: When reflux was stimulated, healing of the mucosal defect was by columnar epithelium alone in seven of 10 animals. After reflux control in six animals healing was again by columnar epithelium, but in all six cases islands of squamous epithelium occurred. Histologic examination showed both types of regenerating epithelium to be in continuity with the ducts of the esophageal glands, lined in their proximal two thirds by columnar and in their distal one third by squamous cells. CONCLUSIONS: It is suggested that the type of regenerating epithelium is determined by the depth of injury to mucosa or gland ducts. If both cell types survive, a mixed pattern of regeneration may occur, but columnar repair will usually predominate because of its more rapid turnover. If the squamous cells of the mucosa and ducts are destroyed, however, repair will be by columnar epithelium alone.

Myocardial vagal stimulation impairs lower esophageal sphincter function.

BACKGROUND: Coronary artery disease and gastroesophageal reflux disease frequently coexist, but a direct pathophysiologic link has not been established. METHODS: This study examines the effect of myocardial vagal receptor stimulation on lower esophageal sphincter (LES) tone in eight adult mongrel dogs, each acting as its own control. Pharmacologic stimulation was carried out by the application of 1 cm gauze patches soaked in nicotine (200 micrograms/ml) to the epicardium. Epicardial vagal receptors were stimulated mechanically by digital friction. RESULTS: Pharmacologic stimulation produced a rapid fall in LES tone from a mean (SEM) of 12.6 (1.5) to 8.6 (0.9) sphinctometer units (p = 0.007). Mechanical stimulation also produced a rapid fall from 12.0 (1.5) sphinctometer units to 6.8 (0.7) (p = 0.007). Both were associated with a drop in mean arterial blood pressure and heart rate. Sham patches soaked in sterile water produced no effects. CONCLUSIONS: These data suggest a direct vagal reflex linking the myocardium and the LES that may explain the high incidence of gastroesophageal reflux in patients with heart disease.

DNA ploidy in squamous oesophageal carcinoma.

The role of DNA ploidy in the management of oesophageal carcinoma is unclear. Most studies have employed flow cytometry (FC) for DNA analysis but some have used image analysis (IA) of tissue sections. In this study aneuploidy rates in stage IIa squamous tumours were determined by both FC and IA of cell suspensions and results were compared with outcome in two patient subgroups. Group 1 (n = 15) were patients who died from tumour recurrence within 1 year of surgery while Group 2 (n = 21) were patients who survived tumour free for at least 1 year. Aneuploidy rates differed significantly between techniques; 29 of 36 tumours (81%) were aneuploid by IA compared with 19 of 34 (56%) by FC (P < 0.05). Aneuploidy rates differed significantly between groups 1 and 2 as determined by FC (79%) versus 40%) (P < 0.05) but not by IA (93% versus 71%) (P = ns). Euploid status was a good prognostic indicator; 6 of 7 (86%) patients with euploid tumours by IA and 12 of 15 (80%) by FC (P < 0.05) survived more than 1 year. The sensitivity and specificity of euploidy was 93% and 28.6% for IA compared with 78.6% and 60% for FC. Since 33 (92%) of these tumours exhibited a marked peritumoral desmoplastic or chronic inflammatory reaction IA, being more sensitive to subtle nuclear change, may be a more appropriate technique than FC for evaluation of the role of ploidy in such tumours.

Tumour micrometastases: the influence of angiogenesis.

INTRODUCTION: Many cancer patients have undetected micrometastatic disease at first presentation which ultimately progresses. Angiogenesis-the development of an independent blood supply-is a key event in the growth of metastases. Improved understanding of the influence of angiogenesis on micrometastatic growth may lead to new therapeutic intervention. METHODS: This study examines current concepts of the significance of micrometastases and the role of angiogenesis in their development and destruction. A comprehensive review of the literature on micrometastasis and angiogenesis was performed using the Medline database between 1966 and 1999. CONCLUSIONS: Advances in technology have improved our ability to diagnose metastatic disease, but micrometastases in loco-regional lymph nodes and at distant sites can only be detected by sophisticated histological techniques. While the significance of micrometastases remains controversial, there is increasing evidence that micrometastatic status provides useful prognostic information and should be part of standard staging techniques. Anti-angiogenic therapy has the potential to favourably influence management of certain cancers by manipulating a number of key events in the metastatic process.

Small cell carcinoma of the oesophagus.

Small cell carcinoma of the oesophagus is an uncommon malignancy. Only 272 cases have been reported to date. Inconsistency in therapeutic approaches reflects the paucity of individual experience and the unsatisfactory response to current management strategies. We report 11 cases drawn from a series of 1012 cases of oesophageal malignancy and perform a statistical analysis on treatment and survival data of 189 cases drawn from the world literature. Small cell carcinoma of the oesophagus was seen to have an incidence of 1%. Seven of 11 patients were female. A variety of therapeutic modalities were employed, and the median survival was 6.6 months. Statistical analysis of these and worldwide data showed a significant survival advantage for patients who received multimodality therapy.

Tamoxifen inhibits endothelial cell proliferation and attenuates VEGF-mediated angiogenesis and migration in vivo.

INTRODUCTION: Angiogenesis is fundamental to tumour growth and vascular endothelial growth factor (VEGF) is one of the most potent proangiogenic cytokines known. We have previously demonstrated that tamoxifen reduces serum VEGF in certain cancer patients. We hypothesized that tamoxifen may attenuate the angiogenetic response to VEGF. METHODS: Human dermal microvessel endothelial primary cell cultures (HMEC) were incubated with tamoxifen (1.25-5.0 microg) or vehicle. Cell proliferation was quantified using 5-bromo-2'-deoxyuridine (BrdU) labelling endothelial cell proliferation assay. The effect of oral tamoxifen (20 mg/day) on VEGF-mediated angiogenesis in vivo was assessed using a Matrigel angiogenesis assay in the Sprague-Dawley rat. RESULTS: Tamoxifen (5.0 microg/ml) significantly reduced HMEC proliferation over 24 h when compared with cells treated with vehicle alone. Oral administration of tamoxifen in the rat (20 mg/day) significantly reduced endothelial cell proliferation and migration in response to VEGF. CONCLUSION: Tamoxifen (5.0 microg/ml) reduces proliferation of a VEGF-dependent endothelial cell line in vitro. In vivo, orally administered tamoxifen reduces VEGF-mediated angiogenesis in the rat. These findings indicate that tamoxifen may directly inhibit the effect of VEGF on the endothelial cell, in addition to its previously described effect of reducing serum VEGF levels. This data supports a role for tamoxifen in modulation of the VEGF-dependent angiogenic response to surgical trauma, particularly as an adjuvant therapy for VEGF-dependent tumours.

An ambulatory bile reflux monitoring system: an in vitro appraisal.

Assessment of duodenogastric bile reflux has hitherto been unsatisfactory. An ambulatory system which utilizes the optical properties of bilirubin is examined. Test readings are correlated with the laboratory values for bilirubin in each of a number of physiological solutions. For dilutions of pure bile there was a linear correlation between absorbance and bilirubin concentration (r = 0.93, p < 0.001). In the more acidic environment of gastric juice there was also a linear correlation between absorbance and bilirubin concentration (r = 0.65, p < 0.001), but absorbance values were significantly higher than those of pure bile solutions (F ratio = 130, p < 0.0001). Normal gastric secretions and saliva give low absorbance values (0.02-0.04). Common foodstuffs such as soups, tea and coffee give higher readings and may interfere with bile reflux assessment in a clinical setting. Bilitec 2000 has potential for use as an ambulatory bile reflux monitoring system but consideration should be given to a standard diet or attention must focus on the fasting period.

Audit of an oesophageal unit.

We report an audit of 786 oesophageal procedures, including 53 oesophagectomies, performed during 1990 in a specialist oesophageal unit. Apart from assessing morbidity and mortality, audit allows a review of cost efficiency and justification for certain practices with regard to patient management. The data reported here may provide a framework against which individual surgeons may assess their own results and compare costs of procedures with a similar outcome.

Laparoscopic repair of a strangulated Bochdalek hernia.

BACKGROUND: Bochdalek herniae are rare. They are usually repaired by open abdominal surgery or by a thoracic video-assisted approach. When strangulated and in a compromised patient the options are fewer. AIM: To describe a case treated by a laparoscopic approach. RESULTS: The procedure was technically difficult, but the patient recovered without recurrence. CONCLUSION: Laparoscopic repair is possible even with strangulation.

Cholecystectomy and oesophageal pathology: is there a link?

Symptoms persist in a significant proportion of patients following cholecystectomy, some of which may have an oesophageal aetiology. The oesophagus has not previously been studied in this patient group. In this study all patients who had undergone cholecystectomy over a four year period were invited for review and symptoms were documented. Oesophageal function was examined and compared with normal controls. Patients were subdivided into symptomatic and asymptomatic subgroups and their findings compared. Symptoms were present in 53 percent of the postcholecystectomy group. The mean (sem) DeMeester acid score was higher in the post-cholecystectomy group -20.6 (3.6) than in controls -6.7 (0.9) (p = 0.01). The incidence of oesophagitis and gastritis were also increased in this group. There was a trend towards increased reflux and oesophagitis in the symptomatic compared with the asymptomatic subgroup. Other findings confined to the post-cholecystectomy group included nutcracker oesophagus in 4 and irritable bowel syndrome in 3. It is suggested that cholecystectomy may be associated with changes in oesophageal function which, in turn, may be associated with persistent symptoms.

A new technique for measuring lower oesophageal sphincter competence in patients.

Oesophageal sphincter measurements were carried out on 80 patients using the stationary pull through technique; Normals (n = 21), Nutcracker (n = 12), Refluxers (n = 21), and Barrett's (n = 26). Sphincter pressure (LOSP), abdominal length of sphincter, and overall sphincter length were measured. The Sphincter Function Index (SFI) was calculated as the product of sphincter pressure and percentage sphincter length (AL) exposed to abdominal pressure. Patients also had routine endoscopy and 24 hour pHmetry. SFI values discriminated between all four groups. LOSP was significantly different for Barrett's (p < 0.01) and Nutcracker (p < 0.01) compared to normals. AL was significant for Refluxers (p < 0.001) and Barrett's (p < 0.001) compared to normals. SFI gives better discrimination than LOSP or AL alone and may be useful in evaluating the response to treatment.