Showing papers by "Thomas N. Walsh published in 2017"

Predictors of overall and recurrence-free survival after neoadjuvant chemotherapy for gastroesophageal adenocarcinoma: Pooled analysis of individual patient data (IPD) from randomized controlled trials (RCTs)

Abstract: Background Neoadjuvant chemotherapy improves prognosis of patients with locally advanced gastroesophageal adenocarcinoma The aim of this study was to identify predictors for postoperative survival following neoadjuvant therapy These could be useful in deciding about postoperative continuation of chemotherapy Methods This meta-analysis used IPD from RCTs comparing neoadjuvant chemotherapy with surgery alone for gastroesophageal adenocarcinoma Trials providing IPD on age, sex, performance status, pT/N stage, resection status, overall and recurrence-free survival were included Survival was calculated in the entire study population and subgroups stratified by supposed predictors and compared using the log-rank test Multivariable Cox models were used to identify independent survival predictors Results Four RCTs providing IPD from 553 patients fulfilled the inclusion criteria (y)pT and (y)pN stage and resection status strongly predicted postoperative survival both after neoadjuvant therapy and surgery alone Patients with R1 resection after neoadjuvant therapy survived longer than those with R1 resection after surgery alone Patients with stage pN0 after surgery alone had better prognosis than those with ypN0 after neoadjuvant therapy Patients with stage ypT3/4 after neoadjuvant therapy survived longer than those with stage pT3/4 after surgery alone Multivariable regression identified resection status and (y)pN stage as predictors of survival in both groups (y)pT stage predicted survival only after surgery alone Conclusion After neoadjuvant therapy for gastroesophageal adenocarcinoma, survival is determined by the same factors as after surgery alone However, ypT stage is not an independent predictor These results can facilitate the decision about postoperative continuation of chemotherapy in pretreated patients

Gastroesophageal Mucosal Injury after Cholecystectomy: An Indication for Surveillance?

Abstract: Background Cholecystectomy alters bile release dynamics from pulsatile meal-stimulated to continuous, and results in retrograde duodeno-gastric bile reflux (DGR). Bile is implicated in mucosal injury after gastric surgery, but whether cholecystectomy causes esophagogastric mucosal inflammation, therefore increasing the risk of metaplasia, is unclear. Study Design This study examined whether cholecystectomy-induced DGR promotes chronic inflammatory mucosal changes of the stomach and/or the esophagogastric junction (EGJ). Four groups of patients were studied and compared with controls. A group of patients was studied before and 1 year after cholecystectomy; 2 further groups were studied long-term post-cholecystectomy (LTPC) at 5 to 10 years and 10 to 20 years. All underwent abdominal ultrasound and upper gastrointestinal endoscopy with gastric antral and EGJ biopsies, noting the presence of gastric bile pooling. Biopsy specimens were stained for Ki67 and p53 overexpression, and the bile reflux index (BRI) was calculated. Results At endoscopy, bile pooling was observed in 9 of 26 (34.6%) controls, in 8 of 25 (32%) patients pre-cholecystectomy, in 15 of 25 (60%) 1 year post-cholecystectomy patients (p = 0.047), and 23 of 29 (79.3%) LTPC patients (p = 0.001). Bile reflux index positivity at the EGJ increased from 19% of controls through 41% of LTPC patients (p = 0.032). Ki67 was overexpressed at the EGJ in 19% of controls, but in 62% of LTPC patients (p = 0.044); p53 was overexpressed at the EGJ in 19% of controls compared with 66% of LTPC patients (p = 0.001). Conclusions Duodeno-gastric bile reflux was more common in patients with gallstones than in controls, and its incidence doubled after cholecystectomy. This was associated with inflammatory changes in the gastric antrum and the EGJ, evident in most LTPC patients. Ki67 and p53 overexpression at the EGJ suggests cellular damage attributable to chronic bile exposure post-cholecystectomy, increasing the likelihood of dysplasia. Further studies are required to determine whether DGR-mediated esophageal mucosal injury is reversible or avoidable, and whether surveillance endoscopy is indicated after cholecystectomy.