[Show abstract][Hide abstract] ABSTRACT: Background:We examined whether silencing of IGFBP7 was associated with survival in patients with oesophageal adenocarcinoma.Methods:Protein expression of IGFBP7 was determined using immunohistochemistry in a tissue microarray representing tumours from 65 patients with oesophageal adenocarcinoma who had not had neoadjuvant therapy. DNA methylation of the IGFBP7 promoter was determined with the melt curve analysis in cell lines and patient tissues.Results:Expression of IGFBP7 was observed in the oesophageal adenocarcinoma of 34 out of 65 (52%) patients and was associated with significantly reduced median (11 vs 92 months) and 5-year survival (25% vs 52%). Multivariate analysis identified expression as an independent prognostic indicator for survival (hazard ratio=3.24, 95% confidence interval=1.58-6.67, P-value=0.0014). Hypermethylation of IGFBP7 was associated with silencing of gene expression in cell lines and patient tissues (P-value=0.0225). Methylation was observed in the squamous mucosa of 2 out of 15 (13%) patients with Barrett's oesophagus and 3 out of 17 (18%) with oesophageal adenocarcinoma. Methylation was observed in 14 out of 18 (78%) of biopsies of Barrett's mucosa and 23 out of 34 (68%) patients with oesophageal adenocarcinoma.Conclusion:Reduced IGFBP7 protein expression was associated with longer survival in patients with oesophageal adenocarcinoma. Methylation of the IGFBP7 promoter was associated with silencing of gene expression and was frequent in Barrett's oesophagus and oesophageal adenocarcinoma.British Journal of Cancer advance online publication, 19 December 2013; doi:10.1038/bjc.2013.783 www.bjcancer.com.
British Journal of Cancer 12/2013; · 5.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Conventional measures of esophageal pressures or bolus transport fail to identify patients at risk of dysphagia after laparoscopic fundoplication.
Liquid and viscous swallows were evaluated with impedance/manometry in 19 patients with reflux disease before and after surgery. A new method of automated impedance manometry (AIM) analysis correlated esophageal pressure with impedance data and automatically calculated a range of pressure and bolus movement variables. An iterative analysis determined whether any variables were altered in relation to dysphagia. Standard measures of esophago-gastric junction pressure, bolus presence time, and total bolus transit time were also evaluated.
At 5 months postop, 15 patients reported some dysphagia, including 7 with new-onset dysphagia. For viscous boluses, three AIM-derived pressure-flow variables recorded preoperatively varied significantly in relation to postoperative dysphagia. These were: time from nadir esophageal impedance to peak esophageal pressure (TNadImp-PeakP), median intra-bolus pressure (IBP, mmHg), and the rate of bolus pressure rise (IBP slope, mmHgs(-1) ). These variables were combined to form a dysphagia risk index (DRI=IBP×IBP_slope/TNadImp-PeakP). DRI values derived from preoperative measurements were significantly elevated in those with postoperative dysphagia (DRI=58, IQR=21-408 vs no dysphagia DRI=9, IQR=2-19, P<0.02). A DRI >14 was optimally predictive of dysphagia (sensitivity 75% and specificity 93%).
Before surgery, a greater and faster compression of a swallowed viscous bolus with less bolus flow time relates to postoperative dysphagia. Thus, susceptibility to postfundoplication dysphagia is related to a pre-existing sub-clinical variation of esophageal function.
Neurogastroenterology and Motility 05/2012; 24(9):812-e393. · 2.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Proximal gastric vagotomy (PGV) has little impact on the normal pattern of solid gastric emptying, despite denervation of the proximal two thirds of the stomach and loss of the proximal gastric pump. In four healthy volunteers and four patients with PGV, we investigated the possible compensatory mechanisms that may come into play after proximal denervation of the stomach. We measured antropyloroduodenal motility with a 10-lumen sleeve/side-hole catheter for 180 minutes after ingestion of a dual-isotope radiolabeled mixed liquid/solid meal. Patients with PGV exhibited faster liquid emptying, but the rate of solid emptying was similar to that in healthy volunteers. The frequency of propagated antropyloric pressure wave was similar between the two groups, but patients with PGV exhibited less isolated pressure waves in the proximal antrum. The amplitude and duration of pressure waves recorded in the distal antrum were significantly increased in the PGV patients as compared to healthy volunteers. Although the pattern of propagated antral contractions and solid gastric emptying remains unchanged after PGV, there is an increase in the amplitude and duration of distal antral contractions, which may compensate for loss of proximal gastric pumping mechanisms.
Journal of Gastrointestinal Surgery 04/2012; 4(5):526-30. · 2.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients may be unwilling to participate in clinical trials if they perceive risks. Outcomes were evaluated following surgery for gastro-oesophageal reflux in patients recruited to randomized trials compared with patients not in trials.
This study compared outcomes of patients who had surgery for reflux within or outside randomized trials between 1994 and 2009. The choice of procedure outside each trial was according to surgeon or patient preference. Clinical outcomes were determined 1 and 5 years after surgery using a standardized questionnaire, with analogue scales to assess heartburn, dysphagia and overall satisfaction. Subgroup analysis was undertaken for those aged less than 75 years undergoing laparoscopic Nissen fundoplication.
Some 417 patients entered six randomized trials evaluating surgery for reflux and 981 underwent surgery outside the trials. The trial group contained a higher proportion of men and younger patients, and patients in trials were more likely to have undergone Nissen fundoplication. At 1 year, patients in the trials had slightly lower heartburn scores and less abdominal bloating, but otherwise similar outcomes to those not in the trials. At 5 years there were no differences, except for a slightly higher dysphagia score for liquids in the trial group. For the subgroup analysis, demographic data were similar for both groups. There were no differences at 1 year, but at 5 years patients enrolled in the trials had higher scores for dysphagia for liquids and heartburn. All of the statistically significant differences were thought unlikely to be clinically relevant.
Participation in a randomized trial assessing surgery for reflux did not influence outcomes.
British Journal of Surgery 03/2012; 99(3):381-6. · 4.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Since the mid-1990s, laparoscopic fundoplication for gastro-oesophageal reflux disease has become the surgical procedure of choice. Several surgical groups perform routine post-operative contrast studies to exclude any (asymptomatic) anatomical abnormality and to expedite discharge from hospital. The purpose of this study was to determine the accuracy and interobserver reliability for surgeons and radiologists in contrast study interpretation.
11 surgeons and 13 radiologists (all blinded to outcome) retrospectively reviewed the contrast studies of 20 patients who had undergone a laparoscopic fundoplication. Each observer reported on fundal wrap position, leak or extravasation of contrast and contrast hold-up at the gastro-oesophageal junction (on a scale of 0-4). A κ coefficient was used to evaluate interobserver reliability.
Surgeons were more accurate than radiologists in identifying normal studies (specificity = 91.6% vs 78.9%), whereas both groups had similar accuracy in identifying abnormal studies (sensitivity = 82.3% vs 85.2%). There was higher agreement amongst surgeons than amongst radiologists when determining wrap position (κ = 0.65 vs 0.54). Both groups had low agreement when classifying a wrap migration as partial or total (κ = 0.33 vs 0.06). Radiologists were more likely to interpret the position of the wrap as abnormal (relative risk = 1.25) while surgeons reported a greater degree of hold-up of contrast at the gastro-oesophageal junction (mean score = 1.17 vs 0.86).
Radiologists would benefit from more information about the technical details of laparoscopic anti-reflux surgery. Standardised protocols for performing post-fundoplication contrast studies are needed.
The British journal of radiology 07/2011; 85(1014):792-9. · 2.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Laparoscopic 360° fundoplication is the most common operation for gastro-oesophageal reflux disease, but is associated with postoperative dysphagia in some patients. Patients with ineffective oesophageal motility may have a higher risk of developing postoperative dysphagia, but this remains unclear.
From 1991 to 2010, 2040 patients underwent primary laparoscopic fundoplication for gastro-oesophageal reflux disease and met the study inclusion criteria; 343 had a 90°, 498 a 180° and 1199 a 360° fundoplication. Primary peristalsis and distal contraction amplitude during oesophageal manometry were determined for 1354 patients. Postoperative dysphagia scores (range 0-45) were recorded at 3 and 12 months, then annually. Oesophageal dilatations and/or reoperations for dysphagia were recorded.
Preoperative oesophageal motility did not influence postoperative dysphagia scores, the need for dilatation and/or reoperation up to 6 years. Three-month dysphagia scores were lower after 90° and 180° compared with 360° fundoplication (mean(s.e.m.) 8·0(0·6) and 9·8(0·5) respectively versus 11·9(0·4); P < 0·001 and P = 0·003), but these differences diminished after 6 years of follow-up. The incidence of dilatation and reoperation for dysphagia was lower after 90° (2·6 and 0·6 per cent respectively) and 180° (4·4 and 1·0 per cent) fundoplications than with a 360° wrap (9·8 and 6·8 per cent; both P < 0·001 versus 90° and 180° groups).
Tailoring the degree of fundoplication according to preoperative oesophageal motility by standard manometric parameters has no long-term impact on postoperative dysphagia. There is, however, a proportionate increase in short-term dysphagia scores with increasing degree of wrap, and a corresponding proportionate increase in dilatations and reoperations for dysphagia. These differences in dysphagia scores diminish with time.
British Journal of Surgery 06/2011; 98(10):1414-21. · 4.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Randomized trials suggest that division of the short gastric vessels during Nissen fundoplication is unnecessary. Some trials report an increased risk of gas bloat symptoms following division of the short gastric vessels. In this study long-term follow-up data from the two largest randomized clinical trials of division versus no division of the short gastric vessels during laparoscopic Nissen fundoplication were combined to determine whether there were differences in late outcome.
Patients with gastro-oesophageal reflux disease who underwent primary laparoscopic antireflux surgery and were included in two previously reported randomized trials were studied. Of 99 patients enrolled in the Swedish study and 102 in the Australian study, the short gastric vessels were divided in 104 and left intact in 97. Data sets were combined and late clinical outcomes analysed.
At 10-12 years' follow-up (mean 11.5 years) clinical data were obtained from 170 patients (86 with vessels divided, 84 undivided). Statistical analysis of the combined data set showed no significant differences in symptoms of heartburn or dysphagia, ability to belch or vomit, and use of antisecretory medications. Division of the short gastric vessels was associated with a higher rate of bloating symptoms (72 versus 48 per cent; P = 0.002).
Division of the short gastric vessels is followed by a slightly poorer clinical outcome at late follow-up after Nissen fundoplication. Surgeons should avoid dividing these vessels when undertaking a laparoscopic Nissen fundoplication.
British Journal of Surgery 05/2011; 98(8):1063-7. · 4.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Reflux of duodeno-gastric fluid is a significant problem after esophagectomy with gastric conduit reconstruction. Symptoms may be severe and impact considerably upon the quality of life. Previous studies have suggested that a fundoplication type anastomosis may limit post-esophagectomy reflux.
The purpose of this study was to determine whether a modified fundoplication at the gastro-esophageal anastomosis prevents reflux after esophagectomy.
Prospective multicenter randomized controlled trial to compare a conventional end of esophagus to side of gastric conduit anastomosis with a modified fundoplication anastomosis in patients undergoing esophagectomy with intrathoracic anastomosis. Major outcomes were reflux symptoms, symptoms of dysphagia, and complications.
Fifty-six patients were enrolled. The fundoplication anastomosis was associated with significantly lower incidence of reflux (40% vs 70%), as well as a reduced incidence of severe reflux (8% vs 30%). Disturbance of sleep due to reflux was significantly reduced in the fundoplication group (18% vs 47%) as was the incidence of respiratory symptoms. The fundoplication anastomosis was not associated with an increase in dysphagia, and there was no difference in complications between the two groups.
Fundoplication anastomosis during esophagectomy is effective in protecting patients from reflux symptoms after esophagectomy and improves quality of life, particularly with regard to sleep disturbance.
Journal of Gastrointestinal Surgery 12/2009; 14(3):470-5. · 2.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Preoperative C-reactive protein (CRP) levels have been shown to be prognostic markers of survival in patients undergoing esophagectomy for cancer. No study has evaluated the predictive value for survival of CRP levels after neoadjuvant chemoradiotherapy.
Preoperative CRP levels were assessed in patients undergoing neoadjuvant therapy and esophagectomy for cancer. Groups were defined according to normal value cutoffs of the CRP measurements.
Seventy patients had normal CRP, and 20 patients had raised CRP. The groups did not differ in descriptives, comorbidities, white cell counts, pathological data, or morbidity. In-hospital death was higher in the raised CRP group (three versus one patient, p = 0.048). The Kaplan-Meier survival analysis showed a significant survival advantage of patients with normal CRP compared to patients with raised CRP levels (median survival, 65.4 versus 18.7 months; log rank test, p = 0.027). The Cox regression analysis identified three independent prognostic factors for survival: UICC stage (IIB/III versus I/IIA, HR 3.48, p = 0.007), completeness of resection (HR 6.33, p = 0.002), and CRP levels (raised versus normal, HR 5.07, p = 0.001).
Preoperative CRP levels are an independent prognostic marker for survival after neoadjuvant treatment in patients with esophageal cancer and may be of value in the re-staging process after neoadjuvant treatment.
Journal of Gastrointestinal Surgery 11/2009; 14(3):462-9. · 2.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It has been suggested that gender and age could be factors that influence the likelihood of success following antireflux surgery, and our anecdotal impression has been that the outcome following Nissen fundoplication in older women is often disappointing. If correct, characterization of the extent of any differences in outcome might help patient selection and, hence, surgical outcomes. Therefore, in this study we investigated the impact of gender and age on longer-term clinical outcomes following laparoscopic fundoplication.
Perioperative and follow-up data from patients undergoing laparoscopic fundoplication in our departments have been collected prospectively and stored in a database. From the database, patients who had undergone either an anterior 180 degrees partial or 360 degrees total laparoscopic fundoplication for gastroesophageal reflux and completed 5 years clinical follow-up were identified. Patients were classified according to gender and age, and outcome data were analyzed to determine differences. Analog scales of 0-10 were used to determine symptoms of heartburn and dysphagia and overall satisfaction.
Seven hundred three patients were studied (58% males). Females were less satisfied with the outcome (score = 7.8 +/- 2.8 vs. 8.4 +/- 2.5, P = 0.0036), and had higher scores for heartburn (2.0 +/- 2.7 vs. 1.2 +/- 2.2; P = 0.0001) and dysphagia for solid food (2.7 +/- 2.9 vs. 2.0 +/- 2.5, P = 0.0049) compared to males. Revisional procedures were undertaken more frequently in females (15.5% vs. 8.4%, P = 0.0038). Age had no impact on any clinical outcome.
While the outcome for laparoscopic fundoplication is not influenced by age, the outcome for women is poorer than in males.
World Journal of Surgery 09/2009; 33(12):2620-6. · 2.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The necessity for routine postoperative contrast studies following laparoscopic fundoplication for either gastroesophageal reflux disease or paraesophageal hernia is unclear.
To determine whether a routine contrast X-ray film influenced surgical decision making following laparoscopic fundoplication, we reviewed records from a prospective database of 1,894 patients who underwent a primary laparoscopic fundoplication for gastroesophageal reflux disease or paraesophageal hernia between October 1991 and June 2008, and identified those who underwent early reoperation. The value of early routine postoperative barium swallow examinations in the management of these patients was then determined.
The review showed that 53 patients (2.8%) underwent reoperative procedures within seven days of their original operation: 21 had originally undergone surgery for a paraesophageal hernia, and 32 for reflux. Of the 53 patients who underwent reoperation, 25 (47.2%) were treated for dysphagia, 17 (32.1%) for acute paraesophageal hernia, 6 (11.3%) for a gastrointestinal leak, and 5 (9.4%) for bleeding or peritonitis. Fifteen of the 17 patients who underwent repair of an acute hiatus hernia (0.8% of all patients) had no symptoms and underwent reoperative surgery because of radiological findings alone. Primary surgery for a large hiatus hernia was associated with a higher incidence of early reoperation (5.2 vs. 2.2%; P = 0.001).
Approximately 1 in 125 patients who underwent laparoscopic surgery for reflux or a large hiatus hernia had an important finding on an early postoperative contrast swallow, and benefited from this investigation by undergoing early reoperative intervention.
World Journal of Surgery 09/2009; 34(1):79-84. · 2.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Summary Disagreement exists about whether laparoscopy results in dispersal of tumour cells during laparoscopic cancer surgery and whether this results in the development of port-site metastases. Recent experimental work suggests that CO2, but not He, insufflation promotes the development of port-site metastases, suggesting that metabolic or immunological factors might also contribute to this problem. This study investigated whether insufflation results in an initial redistribution of tumour cells; and looked at the contribution of mechanical insufflation factors for the development of port-site metastases. A suspension of radio-labelled cancer cells was introduced into the left upper quadrant of the peritoneal cavity of 17 Dark Agouti rats, which underwent laparoscopy with CO2 pneumoperitoneum, gasless laparoscopy, or laparotomy. Surgery continued for a further 30 min, after which the rats were killed and the radioactivity present on the peritoneal surface of the anterior and lateral abdominal wall, and the laparoscopy port sites, was determined by scanning standardised samples of the abdominal wall with a y counter. There was less contamination of the abdominal wall from laparotomy than laparoscopy, irrespective of technique. No differences in contamination between the two laparoscopy groups could be demonstrated. Contamination of the port sites was similar except at the site through which the cells were originally introduced, where a greater radioactivity concentration was seen following gasless laparoscopy. This study suggests that it is not the use of gas insufflation during laparoscopy which is responsible for redistribution of tumour cells from a tumour site, but that redistribution is related to some other aspect of the laparoscopic environment. It is possible, when this finding is considered alongside previously reported studies, that a metabolic or immune disturbance, due to other properties of CO2 insufflation, could cause this problem. This possibility is being investigated further.
[Show abstract][Hide abstract] ABSTRACT: Summary Recent case reports of metastasis to laparoscopic trocar wounds suggest that laparoscopic surgery for malignancy could be associated with an increased incidence of wound metastases. Several experimental studies also support this hypothesis. This study sought to determine whether insufflation pressure could influence the development of port-site metastases, following laparoscopic surgery in an established animal model. 7–10 days after implantation of an adenocarcinoma in the left flank, 24 dark Agouti rats underwent laparoscopy with intraperitoneal tumour laceration, under either low (2 mmHg) or high (6 mmHg) insufflation pressure (12 rats in each group). All rats were killed 7 days after the procedure and the wounds examined for the presence of tumour metastasis. Three rats in the low pressure group and five rats in the high pressure group developed port-site tumours (p = 0.67). The number of port-site wounds which developed tumours was the same in both groups (eight per group). The development of laparoscopic port-site metastases is unlikely to be related to the insufflation pressure used during surgery.
[Show abstract][Hide abstract] ABSTRACT: A small proportion of patients who have laparoscopic antireflux procedures require revisional surgery. This study investigated long-term clinical outcomes.
Patients requiring late revisional surgery following laparoscopic fundoplication for gastro-oesophageal reflux were identified from a prospective database. Long-term outcomes were determined using a questionnaire evaluating symptom scores for heartburn, dysphagia and satisfaction.
The database search found 109 patients, including 98 (5.6 per cent) of 1751 patients who had primary surgery in the authors' unit. Indications for surgical revision were dysphagia (52 patients), recurrent reflux (36), mechanical symptoms related to paraoesophageal herniation (16) and atypical symptoms (five). The median time to revision was 26 months. Outcome data were available for 104 patients (median follow-up 66 months) and satisfaction data for 102, 88 of whom were highly satisfied (62.7 per cent) or satisfied (23.5 per cent) with the outcome. Patients who had revision for dysphagia had a higher incidence of poorly controlled heartburn (20 versus 2 per cent; P = 0.004), troublesome dysphagia (16 versus 6 per cent; P = 0.118) and a lower satisfaction score (P = 0.023) than those with recurrent reflux or paraoesophageal herniation.
Revisional surgery following laparoscopic fundoplication can produce good long-term results, but revision for dysphagia has less satisfactory outcomes.
British Journal of Surgery 05/2009; 96(4):391-7. · 4.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We examined the effect of aspirin on survival following resection for squamous cell carcinoma (SCC) of the esophagus or adenocarcinoma of the gastric cardia.
Patients who underwent esophagectomy for these cancers between May 2000 and December 2002 were allocated to one of three groups and given daily either a low dose of aspirin, placebo, or no tablets.
The 5-year survival for all patients on aspirin (445) was 51.2%, placebo (658) 41%, and no tablet (495) 42.3% (P = 0.04 for difference between treatments). The 5-year survival for all SCC patients on aspirin (267) was 49.8%, placebo (433) 42.2%, and no tablet (343) 41.2% (P = 0.26). There was a significant improvement in survival for patients with adenocarcinoma of the cardia on aspirin compared with the two control groups combined (P = 0.029). Survival for T2N0M0 SCC patients was significantly improved with aspirin (71) compared with placebo (167) or no tablet (134) (P = 0.0004). However, there was no significant difference between the survival curves for T2N0M0 adenocarcinoma patients on aspirin (21) and the two control groups combined (65) (P = 0.29).
The results of this preliminary study support further investigation of aspirin as adjuvant therapy to improve survival in subsets of postesophagectomy patients.
Annals of Surgical Oncology 03/2009; 16(5):1397-402. · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obesity has long been considered to be a predisposing factor for gastroesophageal reflux. It is also thought to predispose patients to a poorer clinical outcome following antireflux surgery. This study examined the effect of body mass index (BMI) on clinical outcomes following laparoscopic antireflux surgery.
Patients were included if they had undergone a laparoscopic fundoplication, their presurgical BMI was known, and they had been followed for at least 12 months after surgery. The clinical outcome was determined using a structured questionnaire, and this was applied yearly after surgery. Patients were divided into four groups according to BMI: normal weight (BMI < 25), overweight (BMI 25-29.9), obese (BMI 30-34.9), and morbidly obese (BMI > or = 35). The most recent clinical outcome data was analyzed for each BMI group.
Patients, 481, were studied. One hundred three (21%) had a normal BMI, 208 (43%) were overweight, 115 (24%) were obese, and 55 (12%) were morbidly obese. Mean follow-up was 7.5 years. Conversion to an open operation and requirement for revision surgery were not influenced by preoperative weight. Operating time was longer in obese patients (mean 86 vs 75 min). Clinical outcomes improved following surgery regardless of BMI.
Preoperative BMI does not influence the clinical outcome following laparoscopic antireflux surgery. Obesity is not a contraindication for laparoscopic fundoplication.
Journal of Gastrointestinal Surgery 03/2009; 13(6):1064-70. · 2.36 Impact Factor