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Biomedical subjects

T N Walsh

Publications and source records attributed to T N Walsh.

At least 19 recordsLinked to original sources
PubMed2005

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.

Adult↗
PubMed2004

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.

Angiogenesis Inhibitors↗
PubMed2004

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.

Adenocarcinoma↗
PubMed2003

Effect of neoadjuvant chemoradiotherapy on angiogenesis in oesophageal cancer.

BACKGROUND: Vascular endothelial growth factor (VEGF) levels are raised in the serum of patients with oesophageal carcinoma. The aim of this study was to evaluate the tumour microvasculature and the role of tumour-associated macrophages in VEGF production after neoadjuvant chemoradiotherapy and surgery for oesophageal cancer. METHODS: Sections from 92 consecutively resected oesophageal tumours were stained for VEGF, von Willebrand factor and CD68. Twenty-seven patients received preoperative chemoradiation and 65 underwent surgical excision alone. The cellular source of VEGF was determined by parallel-section staining. Microvessel density and macrophage count were determined for each tumour by means of image analysis software. RESULTS: There were no significant differences between the two groups in age, sex or tumour type. Local downstaging of disease was evident in most specimens of tumours that had received preoperative chemoradiation. All tumours stained positive for VEGF, including those demonstrating a complete pathological response. Staining of parallel sections confirmed macrophages as the principal source of VEGF. Mean microvessel density was 6.4 per high-power field (h.p.f.) in tumours that received preoperative chemoradiation compared with 5.3 per h.p.f. in those treated by surgery alone (P = 0.130). A significant increase in tumour-associated macrophage infiltration was noted in tumours treated with neoadjuvant chemoradiation (22.1 per h.p.f.) compared with those treated by surgery alone (14.3 per h.p.f.) (P = 0.042). CONCLUSION: Preoperative chemoradiation had little effect on the local angiogenic profile of the tumour in patients with oesophageal cancer. Tumour-infiltrating macrophages seem to be the source of persistent VEGF production after chemoradiotherapy and might explain the raised serum levels. Addition of an antiangiogenic agent to this regimen may be worthwhile in patients with oesophageal carcinoma.

Adenocarcinoma↗
PubMed2003

Neoadjuvant antiangiogenic therapy with tamoxifen does not impair gastrointestinal anastomotic repair in the rat.

INTRODUCTION: Antiangiogenic therapy has the potential to moderate tumour and micrometastatic growth. Its use in the perioperative period is attractive but its potential to compromise wound and anastomotic healing is a cause for concern. Tamoxifen is antiangiogenic but also favourably modifies some aspects of wound healing. We hypothesised that tamoxifen would not adversely affect skin wound and gut anastomotic healing. METHODS: A previously established model of tamoxifen, administered orally at antiangiogenic doses (20 mg/ml arachais oil/day), was used. Animals received two days pretreatment prior to laparotomy and small bowel anastomosis. Treatment was continued until completion of the study. The principal outcome measures are survival, macroscopic wound and anastomotic healing, anastomotic bursting pressure and PVA sponge granuloma hydroxyproline (OHP) content. RESULTS: Tamoxifen treated animals had fewer complications of skin wound healing than controls (4.5% vs. 19.5%; chi(2) 4.65, 1 d.f., P < 0.05). There was no significant difference in adhesion formation or macroscopic complications of anastomotic healing. Anastomotic bursting pressure was greater in tamoxifen treated animals at postoperative day 3 (39 +/- 4.4 vs. 22.5 +/- 3.5 mmHg; P < 0.01) and equal to that of controls on postoperative day 5 (144.4 +/- 9.4 vs. 127.3 +/- 10.9 mmHg; P = ns). Tamoxifen treated animals weighed significantly less than placebo controls from postoperative day 3 with no difference in mortality between groups (chi(2) = 0.06, 1 d.f., P = ns). PVA sponge granuloma OHP content on day 7 was higher in tamoxifen-treated animals (2.93 +/- 0.4 vs. 1.4 +/- 0.4 mg OHP/mg dry sponge weight; P = 0.03). CONCLUSION: Antiangiogenic therapy with tamoxifen has no demonstrable adverse effects on wound or anastomotic repair and its perioperative use is compatible with successful early surgical outcomes.

Anastomosis, Surgical↗
PubMed2002

Neoadjuvant treatment of advanced stage esophageal adenocarcinoma increases survival.

Sophisticated surgical approaches have a definite but limited role in esophageal cancer. The majority have systemic disease at presentation, minimal residual disease following resection or co-morbid conditions that preclude extensive surgery. This paper examines whether neoadjuvant therapy is effective in advanced-stage disease. A randomized trial, closing September 1995, was followed up to determine results at 5 years. All patients were followed up for more than 5 years. Median survival, based on intention-to-treat, was 17 months for multimodal therapy vs. 12 months for surgery alone (P=0.002). Survival based on treatment received was 27 months vs. 14 months (P=0.0006). Multimodal therapy enhances survival for patients with minimal residual disease. This is consistent with the literature. Under-powered trials cannot prove a real difference to be significant. Future trials should target patients with minimal residual disease.

Adenocarcinoma↗
PubMed2001

Effect of multimodality therapy on circulating vascular endothelial growth factor levels in patients with oesophageal cancer.

BACKGROUND: Angiogenesis is critical for tumour growth and metastasis. The switch to the angiogenic phenotype depends on the net balance between positive and negative angiogenic factors released by the tumour. It was hypothesized that patients with oesophageal cancer would express raised serum levels of vascular endothelial growth factor (VEGF) which would return to normal values with neoadjuvant chemoradiotherapy. METHODS: Forty-four patients with oesophageal cancer who were selected for treatment with neoadjuvant chemoradiotherapy had blood samples taken before treatment, during chemoradiotherapy, before operation, on days 1, 3 and 5 after surgery, and 3 months after resection. Serum levels of VEGF were measured. Values were correlated with response to treatment. Controls were patients who were undergoing surgery for non-malignant conditions. RESULTS: Serum VEGF levels were raised in patients with oesophageal cancer compared with age-matched controls (mean 247 versus 1157 pg/ml; P < 0.01). VEGF levels were unaffected by neoadjuvant treatment but fell significantly on the first day after operation (652 versus 1057 pg/ml before operation; P < 0.05). No decrease occurred in control patients. VEGF levels had returned to preoperative levels by day 5. A similar postoperative rise in VEGF levels was seen in the control subjects (1194 pg/ml on day 5 versus 71 pg/ml before operation; P = 0.001). There was no correlation between VEGF level and response to treatment or tumour stage. VEGF levels had decreased significantly at 3 months following tumour resection (594 versus 1558 pg/ml on day 5; P = 0.03). CONCLUSION: VEGF levels are raised in patients with oesophageal cancer and are unaltered by neoadjuvant treatment, suggesting an additional source other than tumour cells for this proangiogenic agent.

Adenocarcinoma↗
PubMed2001

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.

Administration, Oral↗
PubMed2000

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.

Bone Marrow Neoplasms↗
PubMed1998

Significance of angiogenesis in cancer therapy.

BACKGROUND: For most solid tumours, surgery remains the most effective primary treatment. Despite apparently curative resection, significant numbers of patients develop secondary disease due to growth of undetected micrometastases. The ability of a tumour to metastasize is related to the degree of angiogenesis it induces. In addition, micrometastases rely on new vessel formation to provide the nutrients necessary for growth. A better understanding of how tumours acquire their blood supply may lead to more effective adjuvant therapies and improve survival following surgery. METHODS: A systematic review of the literature on angiogenesis between 1971 and 1997 was performed using the Medline database to ascertain current thinking on angiogenesis and its relevance in oncological surgery. RESULTS: Angiogenesis is a physiological process subject to autocrine and paracrine regulation which has the potential to become abnormal and play a part in a number of pathological states, including cancer. Increased angiogenic stimuli in the perioperative period, associated with concomitant reduction in tumour-derived antiangiogenic factors following resection of a primary tumour, result in a permissive environment which allows micrometastases to grow. CONCLUSION: Recognition of the role of angiogenesis in metastatic tumour growth represents a significant development in our understanding of tumour biology. The development of antiangiogenic agents offers new promise in the treatment of malignancy. Such agents may prevent or control the development and growth of primary and metastatic tumours.

Growth Substances↗
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

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↗