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Biomedical subjects

M Rhodes

Publications and source records attributed to M Rhodes.

At least 19 recordsLinked to original sources

Systematic review: Cyclo-oxygenase-2 in human oesophageal adenocarcinogenesis.

BACKGROUND: Published in vitro and animal in vivo studies have demonstrated that cyclo-oxygenase-2 plays an important role during oesophageal adenocarcinogenesis. However, the extent to which these studies are directly relevant to events in the human lower oesophagus is questionable. AIM: To perform a systematic review of all available human studies that have evaluated levels of cyclo-oxygenase-2 expression during the progression from Barrett's metaplasia to oesophageal adenocarcinoma. METHODS: A literature search was performed to identify all studies which qualitatively or quantitatively assessed cyclo-oxygenase-2 protein or gene expression in either Barrett's, dysplastic or adenocarcinoma tissue in humans. RESULTS: A total of 27 studies met the inclusion criteria. There was general agreement that cyclo-oxygenase-2 was either absent or very weakly expressed in normal oesophageal squamous mucosa, but considerable disagreement regarding the presence of cyclo-oxygenase-2 in Barrett's and low-grade dysplasia. All studies agreed that high-grade dysplasia and adenocarcinoma expressed cyclo-oxygenase-2 to some extent although levels varied considerably between tissue samples. CONCLUSIONS: There is conflicting evidence in the literature for cyclo-oxygenase-2 playing an important role in early oesophageal adenocarcinogenesis. Other non-cyclo-oxygenase-2 targets may account for the epidemiological data supporting the use of non-steroidal anti-inflammatory drugs in the chemoprevention of oesophageal adenocarcinoma.

Adenocarcinoma↗

Does open surgery continue to have a role in elective splenectomy?

BACKGROUND: Since it was first reported in 1991, laparoscopic splenectomy has become the procedure of choice for elective splenectomy. However, doubts have been raised regarding the suitability of patients with splenomegaly (>1 kg) for laparoscopic resection because there have been reports of greater morbidity and higher conversion rates in this group of patients. Since 2000, patients referred to the authors' center for splenectomy with an estimated spleen weight exceeding 1 kg have undergone splenectomy by the open approach. METHODS: Between September 1995 and April 2005, 95 elective splenectomies were performed by a single surgeon. Operative data were collected prospectively. RESULTS: A comparison between the operations that took place before 2001 (n = 47) and those performed after 2000 (n = 48) for all sizes of spleen showed significant reductions in conversion rate, operative time, and hospital stay in the later group. As compared with laparoscopic splenectomy (n = 11), open splenectomy (n = 18) for cases of splenomegaly resulted in a significantly shorter operative time, less operative blood loss, and no significant difference in hospital stay. CONCLUSION: Although laparoscopic splenectomy is the treatment of choice for the majority of patients requiring elective splenectomy, the procedure for patients with significant splenomegaly requires caution and common sense. This study shows that an open splenectomy for these patients significantly reduces operative time and blood loss without increasing morbidity or hospital stay.

Adolescent↗

Prospective randomized trial of laparoscopic gastrojejunostomy versus duodenal stenting for malignant gastric outflow obstruction.

BACKGROUND: We prospectively compared laparoscopic gastrojejunostomy with duodenal stenting as a means of palliating malignant gastric outflow obstruction. METHODS: A total of 27 patients with malignant gastric outflow obstruction were randomized to either laparoscopic gastrojejunostomy (LGJ) or duodenal stenting (DS) over a 3-year period. RESULTS: Thirteen patients underwent successful LGJ and 10 had successful DS. Eight patients had complications after LGJ, but none had complications after DS. Patients who underwent LGJ had a significant increase in visual analog pain score at day 1 (p = 0.05), and also had a longer hospital stay compared to those who underwent DS (11.4 vs. 5.2 days, p = 0.02). After DS, patients experienced an improvement in physical health at 1 month as measured using the Short Form-36 (SF-36) questionnaire (p < 0.01). There was no change following LGJ. CONCLUSION: Duodenal stenting is a safe means of palliating malignant gastric outflow obstruction. It offers significant advantages for patients compared with minimal-access surgery.

Aged↗

Systematic review: the chemoprevention of oesophageal adenocarcinoma.

The incidence of oesophageal adenocarcinoma is increasing in the UK faster than any other malignancy. Despite its relatively poor prognosis and the limited success of existing treatments, there is enthusiasm that chemopreventive agents might be able to stem the transition from normal squamous epithelium to adenocarcinoma. We discuss gastro-oesophageal reflux as the main risk factor for the development of Barrett's metaplasia, the only known precursor of oesophageal adenocarcinoma. Treatment options for reflux disease are considered with regard to their effects on cancer risk. Recent advances in the molecular and cell biology of Barrett's are outlined, and potential targets for chemoprevention examined. Available treatments for reflux disease have not convincingly altered the likelihood of cancer development. Epidemiological and animal studies support the use of non-steroidal anti-inflammatory drugs as potential chemopreventive agents. Dietary agents, however, have a more favourable side-effect profile and may prove to be an attractive alternative, although more work is needed to fully explore this prospect.

Adenocarcinoma↗

Changes in functional gastrointestinal symptoms as a result of antireflux surgery.

BACKGROUND: This study identifies how functional symptoms are altered after antireflux surgery and whether there are any predictors of such change. METHODS: A total of 206 patients underwent successful laparoscopic Nissen fundoplication. A questionnaire was sent at a median of 4.3 years (range = 0.3-8.4) after fundoplication. Patients were asked to provide scores for reflux and functional symptoms that were experienced prior to surgery and at the time of the questionnaire. RESULTS: Eighty-one percent of patients responded. Scores for heartburn, regurgitation, and difficulty swallowing were felt to have significantly improved (p < 0.01). Flatulence was the only functional symptom to have significantly worsened (p < 0.01). A regression analysis incorporating prospectively collected data identified variables that were predictive of changes in functional symptoms following surgery. CONCLUSIONS: Flatulence was the only functional symptom to have worsened overall after surgery. Predictors of changes in functional symptoms may help clinicians when informing patients about gastrointestinal side effects following antireflux surgery.

Female↗

Laparoscopic resection of gastric gastrointestinal stromal tumors.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are neoplasms with low malignant potential. They occur most commonly in the stomach, where they are amenable to laparoscopic resection. METHODS: A case note review of all patients undergoing laparoscopic resection of a presumed gastric GIST at the Norfolk and Norwich University Hospital, United Kingdom, was conducted. RESULTS: Since September 1995, 30 patients have undergone this procedure. The patients had a mean age of 64.2 years (range, 31-87 years) and a mean weight of 74.1 kg (range, 44-104 kg). A presumptive diagnosis of GIST was made in all the cases based on the endoscopic and radiologic appearance of the lesion. Laparoscopic resection was completed successfully in 23 patients with a mean operating time of 73.8 min (range, 26-160 min). Seven procedures were converted to open surgery: three because the tumor was deemed too large for laparoscopic resection, two because the tumor could not be identified, one because of dense peritoneal adhesions, and one because of bleeding. The mean estimated blood loss was 196 ml (range, 0-1,000 ml), and the mean hospital stay was 5 days (ranges, 1-11 days). Pathologic analysis of the resected specimens showed 22 GISTs, 3 inflammatory fibroids, 2 submucosal lipomas, 1 submucosal varix, and 1 nest of heterotopic pancreatic tissue. D: uring a median follow-up period of 18 months (range, 2-101 months) there have been two cases of recurrence. In both cases, the tumor was catagorized as high risk for aggressive behavior after primary resection. CONCLUSION: Stapled laparoscopic resection is a safe and effective treatment option for nonmetastatic primary gastric GIST.

Adult↗

Short-term cost effectiveness and long-term cost analysis comparing laparoscopic Nissen fundoplication with proton-pump inhibitor maintenance for gastro-oesophageal reflux disease.

BACKGROUND: This study examined the short-term cost-effectiveness and long-term cost of laparoscopic Nissen fundoplication (LNF) versus maintenance proton-pump inhibitor (PPI) medication for severe gastro-oesophageal reflux disease (GORD) based on a randomized clinical trial. METHODS: Costs and outcomes for 12 months were obtained from the first 100 patients in the trial. Detailed costing was performed using resource use data from hospital records and general practitioners' notes. Short-term incremental cost-effectiveness ratios, calculated as the cost difference divided by the effectiveness difference between LNF and PPI therapy, were analysed using net benefit and bootstrap approaches. Long-term cost was examined using sensitivity analyses incorporating published data from other large series. RESULTS: The incremental cost of LNF compared with PPI therapy per additional patient returned to a physiologically normal acid score (less than 13.9) at 3 months was pound5515 (95 per cent confidence interval (c.i.) pound3655 to pound13 400) and the incremental cost per point improvement in combined Gastro-Intestinal and Psychological Well-being score at 12 months was pound293 (90 per cent c.i. pound149 to pound5250). On average, LNF cost pound2247 (95 per cent c.i. pound2020 to pound2473) more than PPI therapy in year 1 and broke even in year 8. Break-even was highly sensitive to hospital unit costs but less sensitive to PPI ingestion rate after LNF, LNF reoperation rate, PPI relapse rate, future PPI price, PPI dose escalation and discount rate. CONCLUSION: From a National Health Service perspective, LNF may be cost-saving after 8 years compared with maintenance PPI therapy for the treatment of GORD.

Cost-Benefit Analysis↗

Randomized clinical trial of laparoscopic Nissen fundoplication compared with proton-pump inhibitors for treatment of chronic gastro-oesophageal reflux.

BACKGROUND: Both laparoscopic Nissen fundoplication (LNF) and proton-pump inhibitor (PPI) therapy are established in the treatment of gastro-oesophageal reflux disease (GORD). The aim of this study was to compare these two treatments in a randomized clinical trial. METHODS: Between July 1997 and August 2001, 340 patients with a history of GORD for at least 6 months were investigated by endoscopy, 24-h pH monitoring and manometry. Of these, 217 were randomized, 109 to LNF and 108 to PPI therapy. The two groups were well matched for age, sex, weight and severity of reflux. Twenty-four-hour pH monitoring and manometry were performed 3 months after treatment, and quality of life was assessed in both groups using the Psychological General Well-being Index and the Gastrointestinal Symptom Rating Scale at 3 and 12 months after treatment. RESULTS: At 3 months there was an improvement in lower oesophageal sphincter pressure from 6.3 to 17.2 mmHg in the LNF group but no change in the PPI group (8.1 and 7.9 mmHg before and after treatment respectively) (P < 0.001). The mean DeMeester acid exposure score improved from 42.7 to 8.6 (P < 0.001) in the LNF group and from 36.9 to 17.7 in the PPI group (P < 0.001). The mean gastrointestinal symptom and general well-being scores improved from 31.7 and 95.4 respectively before treatment to 37.0 and 106.2 at 12 months after LNF, compared with changes from 34.3 and 98.5 to 35.0 and 100.4 respectively in the PPI group. The differences in both of these scores were significant between the two groups at 12 months (P = 0.003). CONCLUSION: LNF leads to significantly less acid exposure of the lower oesophagus at 3 months and significantly greater improvements in both gastrointestinal and general well-being after 12 months compared with PPI treatment.

Adult↗

Pericardial effusion and cardiac tamponade in pediatric stem cell transplant recipients.

Pericardial effusion and cardiac tamponade is a rarely reported complication following stem cell transplant (SCT). The incidence among pediatric SCT recipients is not well defined. To assess the frequency of clinically significant pericardial effusions, we retrospectively examined clinically significant cardiac effusions at our center. Between January of 1993 and August 2004, clinically significant pericardial effusions were identified in nine of 205 patients (4.4%). The median age at the time of transplant was 9 years (range 0.6-18 years) and seven received an allogeneic transplant. All nine had normal cardiac function prior to transplant. The effusion developed at a median of 30 days (range 18-210 days). All allogeneic recipients had acute or clinically extensive graft-versus-host disease (GVHD) at the time the effusion was diagnosed. Seven patients (78%) required pericardiocentesis or surgical creation of a pericardial window. No patient died as a complication of the effusion or the therapeutic procedures. Clinically significant pericardial effusions are more common than previously reported in pediatric SCT recipients. Acute and chronic GVHD is an associated factor.

Adolescent↗

Endoscopy waiting times and impact of the two week wait scheme on diagnosis and outcome of upper gastrointestinal cancer.

The NHS has introduced the two week wait scheme to detect upper gastrointestinal cancers at an early stage and improve survival rates The aim of this study was to assess the impact of this scheme and changes in endoscopy waiting times on tumour stage and resection rates over a four year period. Data were analysed prospectively for all patients diagnosed with oesophagogastric cancer between September 1998 and September 2002 and from those referred under the two week wait scheme since its introduction in 2000. Of those tumours diagnosed by this scheme (15%) only 5% were early disease (stage 1 or 2). Patients with early cancer, mainly diagnosed by routine gastroscopy, do not present with symptoms meeting the two week wait criteria. An increase in the resection rates for early disease will most probably be seen with a reduction in routine endoscopy waiting times.

Ambulatory Care↗

Stapled laparoscopic cystgastrostomy: a series with 15 cases.

BACKGROUND: The goal of this study was to assess the clinical outcome of patients undergoing laparoscopic stapled cystgastrostomy for pancreatic pseudocysts in contact with the posterior wall of the stomach. METHODS: We performed a case note review of all patients who have undergone stapled laparoscopic cystgastrostomy in Norwich, UK. The cystgastrostomy was fashioned through an anterior gastrotomy using a vascular ETS stapling device in all cases. RESULTS: Fifteen patients have undergone stapled laparoscopic cystgastrostomy. The procedure was completed successfully in 12 patients. Three procedures were converted to open surgery for technical reasons. There were no complications due to bleeding from the cystgastrostomy. Early complications included systemic sepsis (one), bleeding gastric ulcer (one) and pseudocyst recurrence due to partial closure of the cystgastrostomy (two). No late recurrences or other complications have been found at a median follow-up of 37 months. CONCLUSION: Stapled laparoscopic cystgastrostomy is a safe and effective procedure for draining pancreatic pseudocysts in contact with the posterior wall of the stomach. The use of a hemostatic stapling device to fashion the cystgastrostomy may reduce the risk of catastrophic hemorrhage from the pseudocyst wall.

Adult↗

Synthetic and naturally occurring COX-2 inhibitors suppress proliferation in a human oesophageal adenocarcinoma cell line (OE33) by inducing apoptosis and cell cycle arrest.

Epidemiological studies suggest that the use of NSAIDs and/or a high intake of fruit and vegetables reduce the risk of oesophageal adenocarcinoma. Since COX-2 is up-regulated in Barrett's oesophageal carcinogenesis, the protective effect of NSAIDs and natural food components might reflect COX-2 inhibition. We explored the effects of quercetin, a natural flavonoid with a potent COX-2 inhibitory activity, and two commercially available selective COX-2 inhibitors (NS-398 and nimesulide) on cell proliferation, apoptosis, PGE2 production and COX-2 mRNA expression in a human oesophageal adenocarcinoma cell line (OE33). Changes in the relative numbers of adherent and floating cells were quantified and apoptotic cells were identified using ethidium bromide and acridine orange staining under fluorescence microscopy. Flow cytometric analysis of adherent and floating cells was used to quantify apoptosis and to examine the effects of the agents on the cell cycle. After 48 h exposure at concentrations of > or =1 microM both COX-2 inhibitors and quercetin suppressed cell proliferation (P < 0.01) and increased the fraction of floating apoptotic cells. At higher concentrations (50 microM) and longer exposure (48 h) the effects of quercetin were significantly greater than those of the selective COX-2 inhibitors (P < 0.01). Cell cycle analyses showed that quercetin blocked cells in S phase, while the selective COX-2 inhibitors blocked cells in G1/S interphase. COX-2 mRNA expression was suppressed by quercetin and the synthetic COX-2 inhibitors in a time- and dose-dependent manner. Quercetin and the synthetic COX-2 inhibitors (10 microM) suppressed PGE2 production by approximately 70% after 24 h exposure (P < 0.001). We conclude that OE33 is a useful model for the study of COX-2 expression and associated phenomena in human adenocarcinoma cells. Synthetic COX-2 inhibitors and the food-borne flavonoid quercetin suppress proliferation, induce apoptosis and cell cycle block in human oesophageal adenocarcinoma cells in vitro, and future studies should assess their effects in vivo.

Adenocarcinoma↗

Endoscopic augmentation of the lower esophageal sphincter for the treatment of gastroesophageal reflux disease: multicenter study of the Gatekeeper Reflux Repair System.

BACKGROUND AND STUDY AIMS: The safety and effectiveness of the Gatekeeper Reflux Repair System (Medtronic Europe, Tolochenaz, Switzerland) in the treatment of gastroesophageal reflux disease (GERD) was evaluated. This new, reversible treatment modality involves the endoscopic introduction of expandable polyacrylonitrile-based hydrogel prostheses into the esophageal submucosa to augment the lower esophageal sphincter (LES). PATIENTS AND METHODS: For this study, data from two prospective, nonrandomized European multicenter trials were pooled. Sixty-nine GERD patients with heartburn and regurgitation and abnormal esophageal acid exposure (24-h pH < 4.0 for > 4 % of the total time) who had responded to proton-pump inhibitor (PPI) therapy were recruited, and 68 were treated with up to six prostheses placed at the gastroesophageal junction. Patients underwent esophageal manometry, endoscopy, 24-h pH-metry, and symptom scoring at intake and 1, 3, and 6 months after the procedure. RESULTS: A total of 77 procedures were performed in 67 patients, and a total of 270 prostheses were placed (mean 4.3 per procedure). At 1 and 6 months, 80.4 % and 70.4 % of the prostheses were retained, respectively. At 6 months, 24-h pH-metry outcomes with pH < 4.0 for > 4.0 % of the time decreased from 9.1 % to 6.1 % (n = 45; P < 0.05). Median LES pressure increased significantly from 8.8 mmHg at baseline to 13.8 mmHg at 6 months (n = 42, P < 0.01). Median GERD heartburn-related quality-of-life scores improved significantly from 24.0 to 5.0 (n = 53, P < 0.01) in patients no longer receiving PPI therapy. Two serious adverse events (3.0 %) occurred. Both patients recovered uneventfully. Prostheses were endoscopically removed from one patient without any adverse events. CONCLUSIONS: The Gatekeeper Reflux Repair System is a safe endoscopic treatment modality that significantly improves GERD symptoms and has objective effects on acid reflux.

Adult↗

Prospective randomized trial of laparoscopic (transabdominal preperitoneal) vs open (mesh) repair for bilateral and recurrent inguinal hernia.

BACKGROUND: Laparoscopic hernia repair excites controversy because its benefits are debatable and critics claim it is attended by serious complications. The one group of patients in whom benefits may outweigh the perceived disadvantages are those with bilateral or recurrent inguinal hernias. METHOD: One hundred twenty patients with bilateral or recurrent hernias were randomized to either laparoscopic transabdominal preperitoneal (TAPP) or open mesh repair. Patients completed a well-being questionnaire prior to and following surgery together with a visual analog pain score. Patients were followed up clinically at 1 and 3 months and thereafter by their general practitioner. RESULTS: Age and sex distribution was similar in the two groups. Laparoscopic TAPP hernia was quicker (40 vs 55 min; p < 0.001), less painful (visual analog pain score, 2.8 vs 4.3; p = 0.003) and allowed earlier return to work (11 vs 42 days; p < 0.001) compared to open mesh repair. CONCLUSION: This trial demonstrates that laparoscopic hernia repair via the TAPP route offers significant benefit to patients undergoing bilateral or recurrent inguinal hernia repair.

Adult↗

Attendance at a pain clinic with severe chronic pain after open and laparoscopic inguinal hernia repairs.

BACKGROUND: The aim was to compare the frequency of severe chronic pain that required attendance at a pain clinic after open and laparoscopic inguinal hernia repairs. METHODS: This was a retrospective analysis of 7999 patients who underwent inguinal hernia repair between January 1994 and December 2001. The definition of severe chronic pain was pain related to inguinal hernia surgery that was bad enough for the patient to seek further medical help and be referred to the specialist pain clinic after exclusion of surgically correctable pathology such as hernia recurrence. RESULTS: During the study there were 7153 open repairs and 846 laparoscopic repairs. Sixty-nine patients (1.0 per cent) were referred to the pain clinic a median of 16.9 (range 5.1-69.4) months after open hernia repair. Three patients (0.4 per cent) were referred a median of 16.5 (range 7.3-21.5) months after laparoscopic hernia repair (P = 0.045). CONCLUSION: Laparoscopic inguinal hernia repair was associated with a significantly lower frequency of attendance at the pain clinic with severe chronic pain.

Chronic Disease↗