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T P Hennessy

Publications and source records attributed to T P Hennessy.

At least 19 recordsLinked to original sources
PubMed1998

Quantitative intracellular cytokine measurement: age-related changes in proinflammatory cytokine production.

The proinflammatory cytokines play a central role in mediating cellular and physiological responses, and levels may reflect immune system effectiveness. In this study, the effect of ageing on the inflammatory response was examined using a novel method to detect production of the proinflammatory cytokines, i.e. tumour necrosis factor-alpha (TNF-alpha), IL-6 and IL-1beta. Peripheral blood mononuclear cells (PBMC) obtained from healthy donors of different ages were incubated for 0, 24, 48 and 72 h with or without phorbol 12-myristate 13-acetate (PMA) stimulation. At each time point these cells were permeabilized and incubated with secondary conjugated FITC MoAbs specific for each cytokine. A flow cytometric system was developed to quantify specific intracellular fluorescence in T cells (CD3+) and monocytes (CD14+). TNF-alpha, IL-6 and IL-1beta production in cell culture supernatants was also measured using ELISAs. In older subjects, flow cytometry detected significant increases in intracellular T cell TNF-alpha and IL-6 (P < 0.05). IL-1beta was not detected in any of the T cell samples. Likewise, the monocytes of older subjects demonstrated increased intracellular levels of all three cytokines, but these increases were not significant (P > 0.05). These changes in intracellular proinflammatory cytokine levels may explain some of the exaggerated inflammatory responses seen in elderly patients.

Adult↗
PubMed1998

Barrett's esophagus and the presence of Helicobacter pylori.

OBJECTIVE: Although the role of Helicobacter pylori in the pathogenesis of peptic ulcer disease and antral gastritis has been well documented, the role of H. pylori in esophageal disease has not been clearly defined. To clarify this issue, we analyzed 141 patients with histologically confirmed esophageal disease. METHODS: The study group consisted of 82 patients with Barrett's esophagus, 19 with adenocarcinoma of the esophagus arising in columnar epithelium and 40 patients with reflux esophagitis without columnar metaplasia of the esophagus. In each of these cases the presence or absence of H. pylori was assessed histologically. RESULTS: H. pylori was present in 19 of 82 patients (23%) with Barrett's esophagus, but was absent in all patients with adenocarcinoma of the esophagus and in patients with reflux esophagitis without Barrett's metaplasia. H. pylori was found only in areas of gastric type metaplasia in the patients with Barrett's esophagus. All of the 19 Barrett's esophagus group with H. pylori had chronic inflammation, and in 16 the inflammation was severe. H. pylori was significantly associated with severity of inflammation in patients with Barrett's esophagus (p < 0.001). Members of the Barrett's group with evidence of moderate to severe dysplasia were negative for H. pylori. CONCLUSION: These data confirm that the presence of gastric type mucosa within the esophagus is a prerequisite for H. pylori colonization, and that H. pylori may contribute to the severity of inflammation in Barrett's epithelium.

Adenocarcinoma↗
PubMed1997

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.

Adult↗
PubMed1997

Acute food bolus impaction: aetiology and management.

A prospective study into the aetiology of acute food bolus obstruction (AFBO) was carried out on 17 consecutive patients who presented with this complaint. There were nine males and eight females. Twelve patients (71 per cent) had symptoms of oesophageal disease and 10 patients (59 per cent) had prior food bolus obstruction. Investigations included endoscopy, barium swallow, oesophageal pH and manometry studies. Evidence of oesophageal pathology was found in 12/14 (86 per cent) of patients investigated. No patients had malignancy and the most common abnormality, gastroesophageal reflux (GOR) was found in eight out of 14 (57 per cent) of cases. Oesophageal dysmotility was seen in five out of 12 (42 per cent) patients who had manometric studies. With such a high incidence of recurrence of AFBO, we suggest that patients with this condition be investigated to exclude malignancy and to identify benign oesophageal pathology using techniques such as oesophageal pH and manometry. Appropriate treatment of oesophageal disease may help prevent recurrence of this distressing condition.

Adult↗
PubMed1997

Delay in treatment for oesophageal cancer.

BACKGROUND: Dysphagia is the cardinal symptom of oesophageal cancer, yet many patients present late. This study examined prospectively the interval between onset of dysphagia and treatment and identified reasons for delay. METHODS: Patients with histologically confirmed oesophageal carcinoma were questioned about duration of symptoms and about each step of their diagnostic work-up. Delay was estimated from date of onset of symptoms to definitive treatment. RESULTS: Median delay was 15 weeks for 78 patients with dysphagia, and 17 weeks for 22 patients with other symptoms. The most frequent cause of delay was late presentation to the family doctor (44 per cent). For patients treated with surgery alone there was a trend towards more advanced stage of disease with longer delay to treatment, but no correlation with survival (P = 0.25). CONCLUSION: Lack of awareness of the sinister significance of dysphagia is the most important cause for delay in presentation of patients with oesophageal cancer.

Adult↗
PubMed1997

Cholecystectomy-induced gastroesophageal reflux: is it reduced by the laparoscopic approach?

OBJECTIVE: The incidence of gastroesophageal reflux and esophagitis increases significantly following cholecystectomy. Laparoscopic technique minimizes the metabolic and mechanical disturbances of cholecystectomy, but there has been no study of its effects on gastroesophageal reflux. The aim of this study was to examine the effect of laparoscopic cholecystectomy on the indices of gastroesophageal reflux. METHODS: A prospective study was carried out on patients scheduled for cholecystectomy. Informed consent was obtained. Preoperative 24-h pH studies and manometry were performed. Studies were repeated 3 months after surgery. Pathological acid reflux was defined in terms of the DeMeester acid score. RESULTS: Pre- and postoperative studies were carried out on 28 patients who had open cholecystectomy and on 22 patients who had laparoscopic cholecystectomy. The mean (SEM) DeMeester acid score increased from 14.8 (2.4) to 34.0 (6.7) following open cholecystectomy (p = 0.006) and from 13.9 (2.5) to 28.9 (4.3) following laparoscopic cholecystectomy (p = 0.002). Decrease in mean lower esophageal sphincter pressure in both groups was not significant. CONCLUSIONS: A significant increase in the incidence of gastroesophageal reflux occurred within 3 months after surgery in both study groups. Despite the less invasive nature of laparoscopic cholecystectomy, the type of surgery did not influence the degree of esophageal dysfunction.

Adult↗
PubMed1996

A comparison of multimodal therapy and surgery for esophageal adenocarcinoma.

BACKGROUND: Uncontrolled studies suggest that a combination of chemotherapy and radiotherapy improves the survival of patients with esophageal adenocarcinoma. We conducted a prospective, randomized trial comparing surgery alone with combined chemotherapy, radiotherapy, and surgery. METHODS: Patients assigned to multimodal therapy received two courses of chemotherapy in weeks 1 and 6 (fluorouracil, 15 mg per kilogram of body weight daily for five days, and cisplatin, 75 mg per square meter of body-surface area on day 7) and a course of radiotherapy (40 Gy, administered in 15 fractions over a three-week period, beginning concurrently with the first course of chemotherapy), followed by surgery. The patients assigned to surgery had no preoperative therapy. RESULTS: Of the 58 patients assigned to multimodal therapy and the 55 assigned to surgery, 10 and 1, respectively, were withdrawn for protocol violations. At the time of surgery, 23 of 55 patients (42 percent) treated with preoperative multimodal therapy who could be evaluated had positive nodes or metastases, as compared with 45 of the 55 patients (82 percent) who underwent surgery alone (P<0.001). Thirteen of the 52 patients (25 percent) who underwent surgery after multimodal therapy had complete responses as determined pathologically. The median survival of patients assigned to multimodal therapy was 16 months, as compared with 11 months for those assigned to surgery alone (P=0.01). At one, two, and three years, 52, 37, and 32 percent, respectively, of patients assigned to multimodal therapy were alive, as compared with 44, 26, and 6 percent of those assigned to surgery, with the survival advantage favoring multimodal therapy reaching significance at three years (P=0.01). CONCLUSIONS: Multimodal treatment is superior to surgery alone for patients with resectable adenocarcinoma of the esophagus.

Adenocarcinoma↗
PubMed1996

Tumour marker detection in oesophageal carcinoma.

Levels of the tumour markers CEA, CA 19-9, CA 125 and SCC were measured in 58 patients presenting with oesophageal carcinoma and compared with levels in patients with benign oesophageal disease and levels in normal volunteers. CEA and CA 19-9 were significantly increased in the patients with oesophageal cancer, however, individual sensitivity for CEA, CA 19-9, CA 125 and SCC was only 28, 34, 10, and 32%, respectively. The combined sensitivity of all markers was 64% and specificity was 80%. There was no difference in combined tumour marker sensitivity between squamous or adenocarcinomas of the oesophagus. No consistent change in marker levels occurred with treatment, and tumour marker levels could not be significantly correlated with stage of disease or short-term survival. These results indicate that tumour marker sensitivity is too low for oesophageal cancer screening and has poor prognostic significance in those undergoing treatment.

Adult↗
PubMed1996

Upper oesophageal sphincter function during general anaesthesia.

The effect of anaesthesia on the upper oesophageal sphincter response to acid in the distal oesophagus and hypopharynx, and the effect of atracurium besylate on acid migration into the hypopharynx, was studied in 102 patients undergoing elective varicose vein surgery. Group 1 (n = 48) received a general anaesthetic and the muscle relaxant atracurium besylate whereas group 2 (n = 54) received a general anaesthetic without relaxation. Upper oesophageal sphincter tone was significantly lower in patients receiving muscle relaxants ('sphinctometer output', eight versus 14, P < 0.05). Sixteen patients (16 per cent) had reflux into the distal oesophagus during anaesthesia (nine in group 1 and seven in group 2, P not significant), of whom seven had reflux to the hypopharynx. There was no difference in incidence of hypopharyngeal acid exposure between groups. Upper oesophageal sphincter tone did not alter in response to reflux into the distal oesophagus or hypopharynx in either group. The upper oesophageal sphincter fails to protect the hypopharynx under general anaesthesia even if patients do not receive a muscle relaxant.

Adult↗
PubMed1996

Cancer of the oesophagus.

Oesophageal cancer is the fourth most common tumour in developing countries, comprising mainly squamous cell tumours, although the incidence of adenocarcinoma has increased enormously over the last decades. Surgical resection has long been acknowledged as the mainstay of treatment, and developments in surgical technique are reviewed. The roles of radiotherapy and chemotherapy in the management of oesophageal cancer remain unclear, especially as the majority of studies to date have been uncontrolled trials. We present an analysis of 601 patients who underwent resection for carcinoma of the oesophagus between 1970 and 1994 in the Department of Clinical Surgery, St James's Hospital, Dublin. The analysis shows clearly that, while peri-operative mortality continues to improve, conventional surgery offers little prospect of cure in the majority of cases. We have therefore embarked upon a prospective controlled trial of neoadjuvant chemoradiotherapy followed by surgery versus surgery alone in patients with adenocarcinoma or squamous cell tumours of the oesophagus. Preliminary results indicate that multi-modality treatment may have a valuable role to play in the treatment of carcinoma of the oesophagus.

Adenocarcinoma↗
PubMed1995

Gastric motility following oesophagectomy.

The motility of the vagally denervated transposed stomach after oesophagectomy was examined by ambulatory gastric manometry and videofluoroscopy. Two groups of subjects were studied. Group 1 comprised ten patients who had undergone oesophagectomy 6-12 months previously and group 2 consisted of six normal control subjects. Studies were performed on fasting and fed subjects, and following injection of erythromycin 8 mg/kg. No distinguishable manometric wave activity was seen in either group while fasting. Feeding generated a measurable wave pattern in the patient group only. A significant increase in the mean (s.e.m.) distal wave amplitude was identified after infusion of erythromycin in both patients (34.0(15.1) versus 12.2(3.1) mmHg, P < 0.05) and controls (15.1(3.4) versus 5.0(0.0) mmHg, P = 0.05). The response to erythromycin was more rapid in patients than in controls (mean(s.e.m.) 113(16) versus 377(133) s, P < 0.05) and the effect persisted for longer (more than 1 h) in those who had undergone oesophagectomy. Videofluoroscopy confirmed purposeful motility in both the normal and vagally denervated stomach. It is concluded that the transposed stomach is a dynamic conduit. Enhancement of motility was greatest in the denervated stomach, indicative of denervation supersensitivity.

Erythromycin↗
PubMed1995

Ambulatory oesophageal bile reflux monitoring in Barrett's oesophagus.

Bile reflux has been implicated in the pathogenesis of Barrett's oesophagus but evaluation remains difficult. Bilitec 2000 is an ambulatory system that detects bilirubin based on its spectrophotometric properties. Oesophageal bile exposure was evaluated in three groups of patients. Group 1 (n = 11) were normal controls, group 2 (n = 13) were patients with uncomplicated gastro-oesophageal reflux and group 3 (n = 12) were patients with Barrett's oesophagus. Bile reflux was greater in patients with Barrett's mucosa than in controls or those with uncomplicated reflux. This difference was seen in the supine and interdigestive periods. The percentage of time at which gastric pH was greater than 4 and oesophageal pH was above 7 did not differ between the groups. Bilitec 2000 detects greater bile reflux in patients with Barrett's oesophagus. No corresponding gastric or oesophageal alkaline shift is found. This ambulatory bile reflux monitoring system may be a useful tool in clinical practice.

Adolescent↗
PubMed1995

Cardiac ischaemia induces vagally mediated lower oesophageal sphincter relaxation.

Gastro-oesophageal reflux and coronary artery disease frequently coexist. Direct stimulation of myocardial vagal receptors impairs lower oesophageal sphincter (LOS) function but the effect of cardiac ischaemia has not been examined. Eight adult mongrel dogs were studied under general anaesthesia. Each underwent occlusion of the left circumflex coronary artery before and after bilateral cervical vagotomy. Blood pressure, heart rate and LOS responses were measured. Median (range) LOS tone was significantly reduced by coronary artery occlusion, from 9 (6-14) to 6 (3-8) sphinctometer units (P < 0.01). This was accompanied by a reduction in heart rate (P < 0.05) and blood pressure (P < 0.01). After bilateral cervical vagotomy the same ischaemic insult produced no significant alteration in LOS tone or heart rate. These data suggest a direct vagal reflex to explain the high incidence of gastro-oesophageal reflux in patients with coronary artery disease.

Animals↗
PubMed1995

Helicobacter pylori infection increases following cholecystectomy.

Cholecystectomy is frequently linked with duodenogastric reflux and gastritis but its effect on Helicobacter Pylori (H pylori) infection has not been examined. In a prospective study, twenty two patients with documented cholelithiasis underwent upper gastrointestinal endoscopy and biopsy and 24hr dual channel pH monitoring prior to cholecystectomy and again at 3-6 months post-operatively. The antral biopsies were histologically assessed for H pylori and gastritis and awarded an alkaline reflux score. The number of patients with H pylori infection increased from 7 (32%) preoperatively to 15 (68%) post-cholecystectomy (p < 0.05). Cholecystectomy was also associated with an increase in the incidence of gastritis from 7 to 15 (p < 0.05). The increase in H pylori infection rate occurred in association with an increase in the percentage time gastric pH > 4 in the supine position, from 9.6 (2.2) to 22.2 (4.8) percent, (p < 0.01). The median chemical gastritis score, however, did not change significantly following surgery [8(3-11) vs 7(3-11)]. Seven patients remained symptomatic following cholecystectomy all of whom were H pylori positive and had gastritis. H pylori can survive in the alkaline environment which follows cholecystectomy and may contribute to the post-cholecystectomy syndrome.

Adult↗
PubMed1994

Expression of epidermal growth factor receptor and proliferating cell nuclear antigen predicts response of esophageal squamous cell carcinoma to chemoradiotherapy.

BACKGROUND: Multimodality therapy with chemotherapy and radiotherapy followed by surgery may improve survival in patients with esophageal squamous cell carcinoma compared with each of the individual treatment options. Histologic assessment of resected tumors after chemoradiotherapy shows that some patients have a complete response with no residual tumor, whereas other patients derive no benefit. The ability to predict response to chemoradiotherapy would allow treatment to be planned accordingly. METHODS: Expression of the tumor growth and proliferation proteins epidermal growth factor receptor (EGFR) and proliferating cell nuclear antigen (PCNA) was determined using immunohistochemical staining of pretreatment endoscopic biopsies from patients with esophageal squamous cell carcinoma who were randomized to chemoradiotherapy before surgery. Response to chemoradiotherapy was assessed by histologic examination of the resected specimens. Response to chemoradiotherapy and survival were correlated with EGFR and PCNA expression individually and with both markers combined as EGFR/PCNA: RESULTS: Of 14 patients available for study, 6 had a complete histologic response (CR) to chemoradiotherapy with no residual tumor in the resected specimen, 3 had a partial response (PR) to chemoradiotherapy, and the remaining 5 had minimal response (MR). Of the nine patients with a CR or PR, tumors of eight patients were negative for one or both markers. Of the five patients with an MR, four tumors were positive for both EGFR and PCNA (P < 0.05, Fisher's exact test). Comparison of survival from the date of randomization shows that patients with tumors negative for one or both markers had a significant survival advantage (P = 0.0003, log-rank test). CONCLUSIONS: Evaluation of PCNA and EGFR status of pretreatment biopsies may identify a group of patients likely to derive the greatest benefit from chemoradiotherapy before surgery in terms of histologic response and long term survival.

Adult↗