[Show abstract][Hide abstract] ABSTRACT: The management of achalasia remains controversial, with little consensus on the optimal patient treatment pathway. In our own esophageal unit, we offer pneumatic dilatation as the initial therapy in most patients as first-line therapy. In this study, we aimed to examine the safety and efficacy of our own approach to the management of patients with a diagnosis of achalasia, examining symptomatic outcomes, patient satisfaction, and need for further intervention, as well as examining patient factors associated with treatment failure. Sixty-seven consecutive patients underwent pneumatic dilatation as first-line therapy (53% male, mean age 46 years). All attended regular outpatient follow-up (mean 37, range 3-132 months). Twenty-five percent of patients required a second intervention because of symptom recurrence, at a median period of 4.5 months. Symptomatic outcomes were excellent or good in 80%. Significant predictors of treatment failure and poor symptom score included a younger age at the time of diagnosis and increased esophageal diameter on barium swallow. This study suggests that pneumatic dilatation is a safe and effective approach as first-line therapy in patients with newly diagnosed achalasia.
Diseases of the Esophagus 03/2010; 23(6):465-72. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The transcription factor Nuclear factor kappa B (NF-kappaB) is central to the regulation of genes encoding for mediators of inflammation and carcinogenesis. In the esophagus, NF-kappaB is progressively activated from inflammation to Barrett's metaplasia and adenocarcinoma. Vitamin C, an antioxidant, can inhibit NF-kappaB in in vitro models, and the aim of this study was to prospectively assess the effect of supplemental vitamin C on NF-kappaB and associated cytokines in patients with Barrett's esophagus. Twenty-five patients with long-segment Barrett's and specialized intestinal metaplasia received dietary vitamin C (1000 mg/day) orally for four weeks, and had pre- and post-vitamin C endoscopic biopsies. NF-kappaB activity (activated p50 and p65 subunits) of nuclear extracts was assessed using the Active Motif NF-kappaB assay, and cytokines and growth factors were measured using the Evidence Investigator biochip array. NF-kappaB and related pro-inflammatory cytokines and growth factors (IL-8, VEGF, IL-10) were activated in all Barrett's tissue pre-treatment. Down-regulation in activated NF-kappaB and cytokines was observed in 8/25 (35%) patients. Dietary vitamin C supplementation may down-regulate pro-inflammatory markers in a subset of Barrett's patients. Further studies with larger numbers of endpoints will be needed to further evaluate this effect.
Diseases of the Esophagus 11/2009; 23(3):271-6. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Barrett's to adenocarcinoma sequence is characterized by molecular changes including activation of nuclear factor-kappaB (NF-kappaB) and related cytokines. In this observational nonrandomized study this molecular environment was compared in matched asymptomatic cohorts who had undergone either fundoplication or therapy with proton pump inhibitors (PPIs).
Asymptomatic patients with long-segment Barrett's esophagus had endoscopic biopsy specimens taken from 2 cm below the squamocolumnar junction for measurement of activated NF-kappaB and a panel of cytokines and growth factors.
Thirty-seven patients were recruited (surgical: n = 18, medical: n = 19). The mean patient age was 51 years, and the mean follow-up period was 5.6 years. There were no differences in the length of Barrett's segment and endoscopic and histopathologic features in both groups. Mean activated NF-kappaB p50 and p65 subunits, interleukin (IL)-1alpha, IL-1beta, and interleukin-8 levels, were significantly (P < .05) lower in the surgically treated group.
This study provides proxy support to the thesis that antireflux surgery may provide an environment that is less inflammatory and tumorigenic than that observed in medically treated patients.
American journal of surgery 04/2009; 199(2):137-43. · 2.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Laparoscopic fundoplication represents the gold standard in the surgical management of gastro-esophageal reflux disease (GERD). The achievement of long-lasting symptomatic and physiological control of reflux is the goal of therapy, as well as the minimization of troubling sequelae, in particular, dysphagia. On-table endoscopy after fundoplication was introduced in this Unit as a quality initiative in an attempt to minimize dysphagia and technical errors, and the aim of this study is to report the experience to date, and compare outcomes with the previous 100 cases performed by an experienced team.
Eighty patients who underwent laparoscopic Rosetti-Nissen fundoplication and on-table endoscopy (group 2) were compared with 100 consecutive prior cases (group 1). Patients were prospectively evaluated and had pre- and postoperative symptom scoring and analysis of complications (all patients), and manometry and 24-h pH testing in 120 patients (60 in each group).
Both groups were similar with respect to demographics, esophagitis, pH score, and dysmotility. No bougie was used in either group. On-table endoscopy resulted in technical modifications in 4 (5%) patients. Early grade 2 or 3 dysphagia was evident in 4 (5%) patients in group 2, compared with 15 (15%) in group 1 (p < 0.001). Late dysphagia was evident in one patient (1.5%) in group 2 compared with 7 (7%) in group 1 (p < 0.05). Dilatation was performed in four patients (5%) in group 2, compared with 11 (11%) in group 1 (p < 0.05).
These data suggest that on-table endoscopy may be a useful quality assurance adjunct in laparoscopic anti-reflux surgery, in particular, reducing the incidence of dysphagia and reinterventions.
Journal of Gastrointestinal Surgery 06/2008; 12(6):991-6. · 2.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obesity is a risk factor for esophageal adenocarcinoma, with a pathway through inflammation and metaplasia secondary to reflux the dominant hypothesis. The proinflammatory impact of adipocytokines associated with the metabolic syndrome of central adiposity may also be relevant. The objective of this study was to explore this profile in Barrett esophagus.
Patients with specialized intestinal metaplasia were invited to attend the metabolic syndrome screening where they underwent anthropometry, segmental bioelectrical impedance analysis, and blood pressure measurement, and had blood taken for quantification of fasting lipids, insulin, glucose, C-reactive protein, and adipocytokines.
One hundred two patients were studied. Forty-six percent of Barrett patients had metabolic syndrome and 78% were centrally obese. Patients with metabolic syndrome were significantly more obese by body mass index, had a 9.4 cm greater waistline, were more hypertensive, and were insulin resistant with 25% having fasting hyperinsulinemia compared with Barrett patients without metabolic syndrome. Metabolic syndrome was associated with elevated C-reactive protein, leptin, and a trend toward decreased adiponectin levels. Sixty percent of patients with long-segment Barrett had metabolic syndrome, and 92% were centrally obese compared with 23.8% and 62%, respectively (P = 0.007 and 0.005) in short-segment Barrett. Long-segment Barrett was associated with hyperinsulinemia and significantly increased levels of interleukin-6 compared with short-segment Barrett.
The prevalence of metabolic syndrome in Barrett far exceeds population norms, and the syndrome was significantly associated with the length of specialized intestinal metaplasia. The data do suggest that the metabolic syndrome may be relevant to the continuum of metaplasia within the Barrett cohort.
Annals of surgery 06/2008; 247(6):909-15. · 7.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Attempts to define the clinical significance of occult lymph node metastasis have yielded mixed results. We set out to quantify the influence on disease-free survival of occult lymph node metastasis in cases of esophageal or gastro-esophageal cancer previously staged as lymph node-negative by conventional H&E staining. We performed a systematic review and meta-analysis of observational studies published between 1966 and 2006 (identified through Medline and Embase). Twelve suitable cohort studies were identified. These studies suggest there is a significant (P < 0.001) association between occult lymph node metastasis and prognosis in cancer of the esophagus or esophago-gastric junction (pooled hazard ratio 3.16 with 95% confidence intervals of 2.25-4.42). We did not demonstrate study quality, number of nodes examined or number of lymph node sections examined to be significant sources of intertrial heterogeneity. Data from observational studies suggest that occult lymph node metastasis is an important prognostic factor in cancer of the esophagus or gastro-esophagus. Meta-analysis using individual patient data can now be justified.
Diseases of the Esophagus 05/2008; 21(3):236-40. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Health-related quality of life (HR-QOL) assessment in esophageal cancer is increasingly performed. However, the association of baseline HR-QOL in predicting outcome is unclear. This study aimed to assess the impact of HR-QOL scores at diagnosis with major morbidity, mortality, failure to progress to surgery, recurrence within 1 year, and survival in patients with localized esophageal cancer. The European Organization for Research and Treatment of Cancer's quality of life questionnaire was completed at diagnosis. Univariate and multivariate logistic regression were used to investigate the relationship between baseline HR-QOL and outcomes adjusting for confounding variables. A total of 185 patients with localized esophageal cancer were included, 89 undergoing multimodal therapy and 96 surgery alone. Global QOL scores were significantly associated with in-hospital mortality (P = 0.020) but not with major morbidity (P = 0.709) or 1-year survival (P = 0.247). Symptoms of fatigue and dyspnea at baseline were significantly (P < 0.05) associated with major morbidity, in-hospital mortality, and survival in univariate analysis. After adjusting for known confounding variables in multivariate analysis, only worse dyspnea score remained predictive of in-hospital mortality and a worse fatigue score remained predictive of 1-year survival. HR-QOL was of no benefit in predicting survival in multivariate analysis that identified pathological nodal status as the most significant factor. HR-QOL questionnaires may be helpful in preoperative assessment of risk. It is possible that patients with unrecognized micrometastatic disease at the time of surgery may report worse systemic symptoms at diagnosis, in particular fatigue and dyspnea, and these and global QOL scores may also identify poorer reserves that may increase in-hospital morbidity and mortality postoperatively.
Diseases of the Esophagus 04/2008; 21(6):522-8. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Reflux-induced injury and oxidative stress result in esophageal inflammation and the potential for progression to intestinal metaplasia and adenocarcinoma. Proton-pump inhibitors represent the standard medical approach, but anti-inflammatories and antioxidants offer novel therapeutic possibilities.
Six weeks after an esophagojejunostomy reflux procedure, female Wistar rats (n = 100) were randomized to receive either an antioxidant (vitamin C, 8 mg or 28 mg/day), a cyclooxygenase-2 (COX-2) inhibitor (rofecoxib, 1 mg/day), or no therapy. After sacrifice 16 weeks later, esophageal injury was scored using pathologic and image analysis scoring.
Esophagitis was present in all 63 animals completing the study and was severe in 27 (43%). No animal developed metaplasia or tumor. The extent of inflammation and esophageal ulceration were not significantly different between experimental groups.
In this model of reflux injury, antioxidants and COX-2 inhibitors failed to ameliorate the severe inflammation induced. Further experimental designs should evaluate these novel approaches in less severe experimental models.
Journal of Surgical Research 04/2008; 145(1):33-40. · 2.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The report herein details a prospective audit of a unit's eight-year experience of the Rossetti-Nissen fundoplication using a predominantly laparoscopic technique, selective hiatal repair, no bougie and a standardised protocol of pre- and post-operative functional endoscopic and symptom assessment.
Three hundred and seventy-eight patients underwent the Rossetti-Nissen fundoplication. All patients had documented data on endoscopy, health related quality of life (HR-QoL), surgical details and complications pre-operatively and at six months post-operatively. Repeat physiological testing was performed at six months.
At a median follow-up of six (range 3-13) months there was improved symptom scoring and HR-QoL after fundoplication with an 89% patient satisfaction rate. Ninety-five patients (25%) reported some early dysphagia, and 91 of these reported the outcome of surgery to be excellent or good. Thirty-eight patients (10%) had recurrent heartburn and 28 (7%) were back on medication at six months post-operatively. At follow-up pH study at a median of six months, 89% of patients had normalised acid reflux scores.
Rossetti-Nissen fundoplication, with no use of an oesophageal bougie and no division of short gastric vessels, is an effective procedure giving 89% patient satisfaction and significant improvement in QoL parameters and physiological measurements.
The surgeon: journal of the Royal Colleges of Surgeons of Edinburgh and Ireland 03/2008; 6(1):19-24. · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Palliation of inoperable esophageal cancer with covered stents aims to relieve progressive dysphagia and improve health-related quality of life (HRQoL). Introducing a stent across the esophagogastric junction in lower third tumors may predispose to unchecked gastro-esophageal reflux (GER). Esophageal stents incorporating an anti-reflux valve have been introduced to address this problem. We prospectively compared an anti-reflux stent with a standard stent in the palliation of inoperable lower third esophageal tumors. Forty-nine consecutive patients with malignant dysphagia were randomized to receive a standard (n = 25, group 1) or an anti-reflux stent (n = 24, group 2). HRQoL was assessed before stenting, at 1 week and at 2 months, utilizing European Organization for Research and Treatment of Cancer questionnaires QLQ-C30, QLQ-OES24 and reflux questionnaires. Esophageal pH testing was performed within 1 week of the stent insertion. Detailed statistical analysis was employed to assess general QoL, symptoms and pH scores in both groups. Both groups reported significantly improved QoL, health and dysphagia scores at 1 week and 2 months after stenting. Group 2 patients reported significantly (P < 0.05) better DeMeester symptom, general reflux scores, and normal pH profile at 1 week. At 2 months DeMeester symptom scores were significantly (P < 0.05) better in group 2 compared with group 1. Standard and anti-reflux stents afford comparable relief from dysphagia and improved quality of life in patients with inoperable lower third esophageal cancer. Anti-reflux stents, however, controlled symptomatic and physiologically relevant reflux and should therefore be considered as optimal palliation in this cohort.
Diseases of the Esophagus 12/2007; 20(6):466-70. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obesity trends in the Western world parallel the increased incidence of adenocarcinoma of the esophagus and esophagogastric junction. The implications of obesity on standard outcomes in the management of localized adenocarcinoma, particularly operative risks, have not been systematically addressed.
This retrospective analysis of prospectively collected data included 150 consecutive patients (36 [24%] obese [body mass index > 30] and 114 nonobese), of whom 43 were normal weight (body mass index 20-25) and 71 were overweight (body mass index 25-30). Eighty-one patients underwent multimodal therapy. The primary end points were in-hospital mortality and morbidity, and median and overall survivals.
Thirty of 36 obese patients (84%) had a body mass index from 30 to 35. Compared with those of the nonobese cohort, obese patients had significantly increased respiratory complications (P = .037), perioperative blood transfusions (P = .021), anastomotic leaks (P = .009), and length of stay (P = .001), but no difference in mortality (P = .582) or major respiratory complications (P = .171). Median and overall survivals were equivalent (P = .348) in both groups.
Obesity was associated with increased respiratory complications and anastomotic leak rates but not with major respiratory complications, mortality, or survival. These outcomes suggest that the added risks of obesity on standard outcomes in esophageal cancer surgery are modest and should not independently have a significant impact on risk assessment in esophageal cancer management.
The Journal of thoracic and cardiovascular surgery 11/2007; 134(5):1284-91. · 3.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gastrointestinal stromal tumours (GISTs), although rare, are increasingly recognized, characterized immuno-phenotypically in most cases by a mutation in C-Kit. The advent of imatinib, a tyrosine kinase inhibitor, has presented a novel and effective therapy in advanced disease. The aim of this study was to present the experience and outcomes of a single centre.
Review of prospective GIST database at St James Hospital from 1997 to 2005. Survival data were analysed using Kaplan-Meier methods.
A total of 32 patients (19 males/13 females) with a median age of 61 years (10-84) were treated. The stomach (n = 20) was the dominant site. Surgery was the first line of treatment for all these tumours, and in seven cases this was performed laparoscopically. C-Kit was positive in 81% of cases. The median survival was 78 months with a 5-year survival of 71%.
GISTs are rare and surgical resection, increasingly with minimally invasive approaches, is associated with high cure rates, particularly in gastric tumours.
Irish Journal of Medical Science 10/2007; 176(3):157-60. · 0.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Node-positive esophageal cancer is associated with a dismal prognosis. The impact of a solitary involved node, however, is unclear, and this study examined the implications of a solitary node compared with greater nodal involvement and node-negative disease. The clinical and pathologic details of 604 patients were entered prospectively into a database from1993 and 2005. Four pathologic groups were analyzed: node-negative, one lymph node positive, two or three lymph nodes positive, and greater than three lymph nodes positive. Three hundred and fifteen patients (52%) were node-positive and 289 were node-negative. The median survival was 26 months in the node-negative group. Patients (n=84) who had one node positive had a median survival of 16 months (p=0.03 vs node-negative). Eighty-four patients who had two or three nodes positive had a median survival of 11 months compared with a median survival of 8 months in the 146 patients who had greater than three nodes positive (p=0.01). The survival of patients with one node positive [number of nodes (N)=1] was also significantly greater than the survival of patients with 2-3 nodes positive (N=2-3) (p=0.049) and greater than three nodes positive (p<0001). The presence of a solitary involved lymph node has a negative impact on survival compared with node-negative disease, but it is associated with significantly improved overall survival compared with all other nodal groups.
Journal of Gastrointestinal Surgery 04/2007; 11(4):493-9. · 2.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Health-related quality of life (HRQL) outcomes are important in assessing new approaches to the treatment of cancer. Neoadjuvant therapy is being used increasingly before surgery in patients with localized oesophageal cancer. This prospective non-randomized study evaluated HRQL in patients treated by preoperative chemotherapy and radiation therapy followed by surgery (multimodal therapy) or by surgery alone.
Data from European Organization for Research and Treatment of Cancer quality of life questionnaires QLQ-30 and QLQ-OES24 were collected prospectively. Questionnaires were completed at diagnosis, after chemoradiotherapy where applicable, and at 3, 6 and 12 months after surgery.
The study included 202 consecutive patients with oesophageal cancer considered suitable for curative (R0) resection at the time of staging. Eighty-seven patients received chemotherapy combined with external-beam radiotherapy before surgery. At baseline, 75 (86 percent) of 87 patients in the multimodal group completed questionnaires, compared with 72 (62.6 percent) of 115 in the surgery-alone group. There were no significant differences in baseline global HRQL scores between groups. Preoperative chemoradiotherapy significantly reduced physical (P=0.004) and role (P=0.007) functioning before surgery, despite a significant (P=0.043) improvement in the dysphagia score. Oesophageal resection had a negative impact on global, functional and symptom HRQL scores at 3 months in both groups. Most variables had recovered by 6 months in the two groups, but at 12 months physical and role functioning remained impaired in the surgery-alone group, and social functioning and financial worries in the multimodal group.
Although the multimodal regimen had a negative impact on HRQL before surgery, postoperative quality of life in patients who had multimodal therapy was similar to that in those who had surgery alone.
British Journal of Surgery 10/2006; 93(9):1084-90. · 5.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The role of neoadjuvant chemotherapy and radiation therapy before resection in esophageal cancer remains controversial. Operative risks may be increased, but this has not been systematically addressed in published trials or reports.
This was a prospective, nonrandomized, restricted cohort design of patients (n = 200) from 1997 to 2003 with resectable cancer of the esophagus or esophagogastric junction. A total of 102 patients underwent multimodal therapy with 5-fluorouracil, cisplatin, and radiation therapy before surgery, and 98 patients opted for surgery alone. In-hospital mortality and morbidity were the primary end points, and cancer survival was a secondary end point.
In patient cohorts matched for operative risk factors, the odds ratio for postoperative sepsis (P = .007), respiratory failure (P = .009), and acute respiratory distress syndrome (P = .02) was increased in the multimodal group. There was no significant difference between groups comparing median and 1-, 2-, and 3-year survivals.
Multimodal therapy was associated with increased respiratory and septic complications compared with a surgery-only cohort undergoing the equivalent surgery. Respiratory failure was in most cases idiopathic. The data suggest that efforts should be made to limit radiation lung exposure in multimodal regimens, and to understand and modulate the local and systemic effects of preoperative chemoradiation.
The Journal of thoracic and cardiovascular surgery 10/2006; 132(3):549-55. · 3.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Multimodal therapy comprising neoadjuvant chemotherapy and radiation therapy prior to radical resection is increasingly utilized in gastroesophageal cancer. The achievement of a complete pathological response (pCR) or a major response is associated with an improved survival. However, up to 70% of patients show an incomplete or no response to the neoadjuvant regimen, and the identification of factors which predict a response would be of considerable clinical benefit. A retrospective analysis of a prospectively updated esophageal cancer database was performed. The predictive values of the following clinicopathological factors were investigated: age, sex, tobacco, alcohol, weight, clinical history, tumor type, site, length, width, morphology and differentiation. Statistical analysis was performed using Chi-square test with Pearson's test or Kruskal-Wallis test. One hundred and seventy-six patients were identified who had undergone neo-adjuvant chemoradiotherapy at St James's Hospital Dublin, between January 1990 and June 2003. A complete pathological response was seen in 40 cases (23%). There was a significant (P < 0.05) relationship between response to chemoradiotherapy and pretreatment tumor length. The median tumor length in the pCR group was 2 cm (1-5 cm) compared with 3 cm (2-7 cm) in non-responders (P < 0.05). Body weight, sex, tobacco or alcohol usage, tumor site, or differentiation were not predictive of response, although a trend (P = 0.08) was observed for squamous cell cancer compared with adenocarcinoma. Smaller tumor length was predictive of a greater response to chemotherapy and radiation therapy. This may reflect different tumor biology, perhaps with acquired resistance to treatment-induced apoptosis in the larger tumors. A simpler explanation is that the existing dose and treatment schedule for combination chemoradiotherapy is suboptimal in patients with larger tumors.
Diseases of the Esophagus 08/2006; 19(4):273-6. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Transesophageal endoscopic plication (TEP) is a novel endotherapeutic approach in the management of gastroesophageal reflux disease (GERD). This non-randomized prospective study compares TEP with laparoscopic Nissen fundoplication (LNF).
Twenty-four consecutive patients treated with LNF, and 27 managed by TEP were studied. Symptom severity scores, endoscopy, 24 h esophageal pH and esophageal manometry and quality-of-life assessments were obtained pre- and posttreatment.
In the LNF group the mean age was 36 yr (17-68) compared with 39 yr (22-62) in the TEP group. Symptom scoring, acid regurgitation score, reduction in the requirements of proton pump inhibitors (PPIs), and quality of life remained significantly improved in both groups at a median of 1 yr [10-18 months] follow-up post procedure. However, the improvement was significantly better in symptom score (p= 0.0383) and the control of acid reflux in the LNF group (p= 0.0007). Post-procedure dysphagia was more common in the LNF group.
Both techniques improved symptom score, acid regurgitation, quality of life, and reduced the requirements for PPIs. The control of heartburn and acid reflux was better for LNF. TEP, like LNF, is a safe and effective method of management of symptomatic GERD but further developments are necessary to ensure control of esophageal acid reflux.
The American Journal of Gastroenterology 04/2006; 101(3):431-6. · 9.21 Impact Factor