Lorelle Smith - Academia.edu (original) (raw)

Papers by Lorelle Smith

Journal of the American College of Surgeons, 2015

Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, Jan 6, 2015

The poor prognosis and rising incidence of esophageal adenocarcinoma highlight the need for impro... more The poor prognosis and rising incidence of esophageal adenocarcinoma highlight the need for improved detection methods. The potential for circulating microRNAs (miRNAs) as biomarkers in other cancers has been shown, but circulating miRNAs have not been well characterized in esophageal adenocarcinoma. We investigated whether circulating exosomal miRNAs have potential to discriminate individuals with esophageal adenocarcinoma from healthy controls and non-dysplastic Barrett's esophagus. Seven hundred fifty-eight miRNAs were profiled in serum circulating exosomes from a cohort of 19 healthy controls, 10 individuals with Barrett's esophagus, and 18 individuals with locally advanced esophageal adenocarcinoma. MiRNA expression was assessed using all possible permutations of miRNA ratios per individual. Four hundred eight miRNA ratios were differentially expressed in individuals with cancer compared to controls and Barrett's esophagus (Mann-Whitney U test,…

Annals of surgery, 2015

Determine whether absorbable or nonabsorbable mesh in repair of large hiatus hernias reduces the ... more Determine whether absorbable or nonabsorbable mesh in repair of large hiatus hernias reduces the risk of recurrence, compared with suture repair. Repair of large hiatus hernia is associated with radiological recurrence rates of up to 30%, and to improve outcomes mesh repair has been recommended. Previous trials have shown less short-term recurrence with mesh, but adverse outcomes limit mesh use. Multicentre prospective double blind randomized controlled trial of 3 methods of repair: sutures versus absorbable mesh versus nonabsorbable mesh. Primary outcome-hernia recurrence assessed by barium meal radiology and endoscopy at 6 months. Secondary outcomes-clinical symptom scores at 1, 3, 6, and 12 months. A total of 126 patients enrolled: 43 sutures, 41 absorbable mesh, and 42 nonabsorbable mesh. Among them, 96.0% were followed up to 12 months, with objective follow-up data in 92.9%. A recurrent hernia (any size) was identified in 23.1% after suture repair, 30.8% after absorbable mesh, ...

World Journal of Surgery, 2014

Antireflux surgery is effective for the treatment of gastroesophageal reflux, but not all patient... more Antireflux surgery is effective for the treatment of gastroesophageal reflux, but not all patients benefit equally from it. The challenge is to identify the patients who will ultimately benefit from antireflux surgery. The aim of this study was to identify preoperative factors that predict clinical outcome after antireflux surgery, with special interest in the influence of socioeconomic factors. Preoperative clinical and socioeconomic data from 1,650 patients who were to undergo laparoscopic fundoplication were collected prospectively. Clinical outcome measures (persistent heartburn, dysphagia, satisfaction) were assessed at short-term (1 year) and longer-term (≥ 3 years) follow-up. At early follow-up, male gender (relative risk [RR] 1.091, p < 0.001) and the presence of a hiatus hernia (RR 1.065, p = 0.002) were independently associated with less heartburn. Male gender was also associated with higher overall satisfaction (RR 1.046, p = 0.034). An association was found between postoperative dysphagia and age (RR 0.988, p = 0.007) and the absence of a hiatus hernia (RR 0.767, p = 0.001). At longer-term follow-up, only male gender (RR 1.125, p < 0.001) was an independent prognostic factor for heartburn control. Male gender (RR 0.761, p = 0.001), the presence of a hiatus hernia (RR 0.823, p = 0.014), and cerebrovascular comorbidities (RR 1.306, p = 0.019) were independent prognosticators for dysphagia at longer-term follow-up. A hiatus hernia was the only factor associated with better overall satisfaction. Socioeconomic factors did not influence any clinical outcomes at short- and longer-term follow-up. Male gender and hiatus hernia are associated with a better clinical outcome following laparoscopic fundoplication, whereas socioeconomic status does not influence outcome.

World Journal of Surgery, 2010

Background Patients with gastroesophageal reflux referred for fundoplication present with differe... more Background Patients with gastroesophageal reflux referred for fundoplication present with different symptom patterns. Previous studies have not analyzed the clinical outcome after fundoplication in patients stratified according to symptom patterns. Methods Five hundred eighteen patients undergoing laparoscopic fundoplication were stratified according to reflux symptom patterns: group 1, regurgitation; group 2, poorly controlled reflux; group 3, regurgitation and poor reflux control (combination of 1 and 2); and group 4, symptoms well controlled but patient does not want to continue taking medication. Clinical outcomes (heartburn control, dysphagia, satisfaction) were assessed prospectively using a standardized questionnaire at early (6 months to 2 years) and late (3-5 years) follow-up intervals.

Journal of Gastrointestinal Surgery, 2012

Introduction Nissen fundoplication can be followed by side effects, and this has driven modificat... more Introduction Nissen fundoplication can be followed by side effects, and this has driven modifications, including partial fundoplications. We previously reported early outcomes from a randomised trial of Nissen vs anterior 90°partial fundoplication. This paper reports 5-year follow-up outcomes to determine whether anterior 90°fundoplication achieves a satisfactory longer-term outcome. Methods From February 1999 to August 2003, 79 patients were randomised to Nissen vs anterior 90°fundoplication. Patients were followed yearly using a standardized clinical questionnaire which included symptom scores to assess heartburn, dysphagia, other post-fundoplication side effects and overall satisfaction with the outcome. Five-year clinical outcomes were analysed. Results Seventy-four patients were available for follow-up at 5 years. There were no significant differences for heartburn or satisfaction, although more patients used antisecretory medication after anterior 90°fundoplication (29.7 vs 8.1 %). Dysphagia was greater after Nissen fundoplication when measured by an analogue score for solid food and a composite dysphagia score. Symptoms of bloating were more common following Nissen fundoplication (80.0 vs 32.4 %), and less patients could eat a normal diet (78.4 vs 94.6 %). Re-operation was undertaken in four patients after Nissen fundoplication (dysphagia, three; hiatus hernia, one) vs three after anterior 90°fundoplication (recurrent reflux, three). Conclusions At 5 years, anterior 90°partial fundoplication was associated with less side effects, offset by greater use of antisecretory medication. Reflux symptoms and overall satisfaction were similar to Nissen fundoplication. Laparoscopic anterior 90°partial fundoplication is an effective treatment for gastro-esophageal reflux.

Journal of Gastrointestinal Surgery, 2013

There is a learning curve associated with laparoscopic antireflux surgery which has an impact on ... more There is a learning curve associated with laparoscopic antireflux surgery which has an impact on patient outcomes. It is unclear, however, whether this can be eliminated by supervision of early cases by experienced surgeons. The aim of this study was to evaluate the impact of training under supervision on outcomes for laparoscopic fundoplication. Patients undergoing primary laparoscopic antireflux surgery from 1995 to 2009 were identified from a prospective database. Patients were classified according to whether they were operated on by an experienced consultant or supervised trainee, and sub-categorised according to the presence of a very large hiatus hernia. A standardised questionnaire was used to assess outcomes for heartburn, dysphagia and satisfaction at 1 and 5 years follow-up. Outcomes for the study groups were compared. One thousand seven hundred and ten patients underwent surgery; 1,112 were operated on by consultants and 598 by trainees. The peri-operative complication rate was not different between the groups, although in patients operated on by trainees, there were increased rates of endoscopic dilatation (9 vs. 5 % p = 0.014) and re-operation (9 vs. 6 %, p = 0.031), and a lower satisfaction rate (76 vs. 82 %, p = 0.044) within 5 years of surgery. All other outcomes were similar for trainees vs. consultants. The learning curve for laparoscopic fundoplication had a small, but statistically significant, impact on patient outcomes, with slightly lesser outcomes when surgery was undertaken by trainees, even when supervised by experienced surgeons. Although the differences were not large, they raise questions about equipoise and highlight ethical dilemmas with teaching new generations of surgeons.

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, Jan 27, 2015

Esophageal cancer has a high mortality rate, and its multimodality treatment is often associated ... more Esophageal cancer has a high mortality rate, and its multimodality treatment is often associated with significant rates of severe toxicity. Effort is needed to uncover ways to maximize effectiveness of therapy through identification of predictive markers of response and toxicity. As such, the aim of this study was to identify genes predictive of chemoradiotherapy-induced gastrointestinal toxicity using an immune pathway-targeted approach. Adults with esophageal cancer treated with chemotherapy consisting of 5-fluorouracil and cisplatin and 45-50 Gy radiation were recruited to the study. Pre-therapy-collected whole blood was analyzed for relative expression of immune genes using real-time polymerase chain reaction (RT-PCR). Gene expression was compared between patients who experienced severe regimen-related gastrointestinal toxicity vs. those experiencing mild to moderate toxicity. Blood from 31 patients were analyzed by RT-PCR. Out of 84 immune genes investigated, TNF was significan...

Journal of the American College of Surgeons, 2015

Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, Jan 6, 2015

The poor prognosis and rising incidence of esophageal adenocarcinoma highlight the need for impro... more The poor prognosis and rising incidence of esophageal adenocarcinoma highlight the need for improved detection methods. The potential for circulating microRNAs (miRNAs) as biomarkers in other cancers has been shown, but circulating miRNAs have not been well characterized in esophageal adenocarcinoma. We investigated whether circulating exosomal miRNAs have potential to discriminate individuals with esophageal adenocarcinoma from healthy controls and non-dysplastic Barrett's esophagus. Seven hundred fifty-eight miRNAs were profiled in serum circulating exosomes from a cohort of 19 healthy controls, 10 individuals with Barrett's esophagus, and 18 individuals with locally advanced esophageal adenocarcinoma. MiRNA expression was assessed using all possible permutations of miRNA ratios per individual. Four hundred eight miRNA ratios were differentially expressed in individuals with cancer compared to controls and Barrett's esophagus (Mann-Whitney U test,…

Annals of surgery, 2015

Determine whether absorbable or nonabsorbable mesh in repair of large hiatus hernias reduces the ... more Determine whether absorbable or nonabsorbable mesh in repair of large hiatus hernias reduces the risk of recurrence, compared with suture repair. Repair of large hiatus hernia is associated with radiological recurrence rates of up to 30%, and to improve outcomes mesh repair has been recommended. Previous trials have shown less short-term recurrence with mesh, but adverse outcomes limit mesh use. Multicentre prospective double blind randomized controlled trial of 3 methods of repair: sutures versus absorbable mesh versus nonabsorbable mesh. Primary outcome-hernia recurrence assessed by barium meal radiology and endoscopy at 6 months. Secondary outcomes-clinical symptom scores at 1, 3, 6, and 12 months. A total of 126 patients enrolled: 43 sutures, 41 absorbable mesh, and 42 nonabsorbable mesh. Among them, 96.0% were followed up to 12 months, with objective follow-up data in 92.9%. A recurrent hernia (any size) was identified in 23.1% after suture repair, 30.8% after absorbable mesh, ...

World Journal of Surgery, 2014

Antireflux surgery is effective for the treatment of gastroesophageal reflux, but not all patient... more Antireflux surgery is effective for the treatment of gastroesophageal reflux, but not all patients benefit equally from it. The challenge is to identify the patients who will ultimately benefit from antireflux surgery. The aim of this study was to identify preoperative factors that predict clinical outcome after antireflux surgery, with special interest in the influence of socioeconomic factors. Preoperative clinical and socioeconomic data from 1,650 patients who were to undergo laparoscopic fundoplication were collected prospectively. Clinical outcome measures (persistent heartburn, dysphagia, satisfaction) were assessed at short-term (1 year) and longer-term (≥ 3 years) follow-up. At early follow-up, male gender (relative risk [RR] 1.091, p < 0.001) and the presence of a hiatus hernia (RR 1.065, p = 0.002) were independently associated with less heartburn. Male gender was also associated with higher overall satisfaction (RR 1.046, p = 0.034). An association was found between postoperative dysphagia and age (RR 0.988, p = 0.007) and the absence of a hiatus hernia (RR 0.767, p = 0.001). At longer-term follow-up, only male gender (RR 1.125, p < 0.001) was an independent prognostic factor for heartburn control. Male gender (RR 0.761, p = 0.001), the presence of a hiatus hernia (RR 0.823, p = 0.014), and cerebrovascular comorbidities (RR 1.306, p = 0.019) were independent prognosticators for dysphagia at longer-term follow-up. A hiatus hernia was the only factor associated with better overall satisfaction. Socioeconomic factors did not influence any clinical outcomes at short- and longer-term follow-up. Male gender and hiatus hernia are associated with a better clinical outcome following laparoscopic fundoplication, whereas socioeconomic status does not influence outcome.

World Journal of Surgery, 2010

Background Patients with gastroesophageal reflux referred for fundoplication present with differe... more Background Patients with gastroesophageal reflux referred for fundoplication present with different symptom patterns. Previous studies have not analyzed the clinical outcome after fundoplication in patients stratified according to symptom patterns. Methods Five hundred eighteen patients undergoing laparoscopic fundoplication were stratified according to reflux symptom patterns: group 1, regurgitation; group 2, poorly controlled reflux; group 3, regurgitation and poor reflux control (combination of 1 and 2); and group 4, symptoms well controlled but patient does not want to continue taking medication. Clinical outcomes (heartburn control, dysphagia, satisfaction) were assessed prospectively using a standardized questionnaire at early (6 months to 2 years) and late (3-5 years) follow-up intervals.

Journal of Gastrointestinal Surgery, 2012

Introduction Nissen fundoplication can be followed by side effects, and this has driven modificat... more Introduction Nissen fundoplication can be followed by side effects, and this has driven modifications, including partial fundoplications. We previously reported early outcomes from a randomised trial of Nissen vs anterior 90°partial fundoplication. This paper reports 5-year follow-up outcomes to determine whether anterior 90°fundoplication achieves a satisfactory longer-term outcome. Methods From February 1999 to August 2003, 79 patients were randomised to Nissen vs anterior 90°fundoplication. Patients were followed yearly using a standardized clinical questionnaire which included symptom scores to assess heartburn, dysphagia, other post-fundoplication side effects and overall satisfaction with the outcome. Five-year clinical outcomes were analysed. Results Seventy-four patients were available for follow-up at 5 years. There were no significant differences for heartburn or satisfaction, although more patients used antisecretory medication after anterior 90°fundoplication (29.7 vs 8.1 %). Dysphagia was greater after Nissen fundoplication when measured by an analogue score for solid food and a composite dysphagia score. Symptoms of bloating were more common following Nissen fundoplication (80.0 vs 32.4 %), and less patients could eat a normal diet (78.4 vs 94.6 %). Re-operation was undertaken in four patients after Nissen fundoplication (dysphagia, three; hiatus hernia, one) vs three after anterior 90°fundoplication (recurrent reflux, three). Conclusions At 5 years, anterior 90°partial fundoplication was associated with less side effects, offset by greater use of antisecretory medication. Reflux symptoms and overall satisfaction were similar to Nissen fundoplication. Laparoscopic anterior 90°partial fundoplication is an effective treatment for gastro-esophageal reflux.

Journal of Gastrointestinal Surgery, 2013

There is a learning curve associated with laparoscopic antireflux surgery which has an impact on ... more There is a learning curve associated with laparoscopic antireflux surgery which has an impact on patient outcomes. It is unclear, however, whether this can be eliminated by supervision of early cases by experienced surgeons. The aim of this study was to evaluate the impact of training under supervision on outcomes for laparoscopic fundoplication. Patients undergoing primary laparoscopic antireflux surgery from 1995 to 2009 were identified from a prospective database. Patients were classified according to whether they were operated on by an experienced consultant or supervised trainee, and sub-categorised according to the presence of a very large hiatus hernia. A standardised questionnaire was used to assess outcomes for heartburn, dysphagia and satisfaction at 1 and 5 years follow-up. Outcomes for the study groups were compared. One thousand seven hundred and ten patients underwent surgery; 1,112 were operated on by consultants and 598 by trainees. The peri-operative complication rate was not different between the groups, although in patients operated on by trainees, there were increased rates of endoscopic dilatation (9 vs. 5 % p = 0.014) and re-operation (9 vs. 6 %, p = 0.031), and a lower satisfaction rate (76 vs. 82 %, p = 0.044) within 5 years of surgery. All other outcomes were similar for trainees vs. consultants. The learning curve for laparoscopic fundoplication had a small, but statistically significant, impact on patient outcomes, with slightly lesser outcomes when surgery was undertaken by trainees, even when supervised by experienced surgeons. Although the differences were not large, they raise questions about equipoise and highlight ethical dilemmas with teaching new generations of surgeons.

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, Jan 27, 2015

Esophageal cancer has a high mortality rate, and its multimodality treatment is often associated ... more Esophageal cancer has a high mortality rate, and its multimodality treatment is often associated with significant rates of severe toxicity. Effort is needed to uncover ways to maximize effectiveness of therapy through identification of predictive markers of response and toxicity. As such, the aim of this study was to identify genes predictive of chemoradiotherapy-induced gastrointestinal toxicity using an immune pathway-targeted approach. Adults with esophageal cancer treated with chemotherapy consisting of 5-fluorouracil and cisplatin and 45-50 Gy radiation were recruited to the study. Pre-therapy-collected whole blood was analyzed for relative expression of immune genes using real-time polymerase chain reaction (RT-PCR). Gene expression was compared between patients who experienced severe regimen-related gastrointestinal toxicity vs. those experiencing mild to moderate toxicity. Blood from 31 patients were analyzed by RT-PCR. Out of 84 immune genes investigated, TNF was significan...