Thomas N. Walsh

Preoperative chemo(radio)therapy versus primary surgery for gastroesophageal adenocarcinoma: Systematic review with meta-analysis combining individual patient and aggregate data

BACKGROUND The prognosis of patients with gastroesophageal adenocarcinoma is poor. There is conflicting evidence regarding effects of preoperative chemotherapy on survival and other outcomes. METHODS We conducted a meta-analysis with aggregate and individual patient data (IPD) to assess the effect of preoperative chemotherapy for gastroesophageal adenocarcinoma on survival and other outcomes. Two independent reviewers identified eligible randomised controlled trials (RCTs) comparing chemotherapy+/-radiotherapy followed by surgery with surgery alone for gastroesophageal adenocarcinoma. IPD was solicited from all trials. Meta-analyses were performed using the two stage method. RESULTS We identified 14 RCTs (2422 patients). For eight RCTs (1049 patients; 43.3%) we obtained IPD. Preoperative chemotherapy was associated with longer overall survival (hazard ratio [HR] 0.81; 95% confidence interval [CI] 0.73-0.89; p<0.0001). There were larger treatment effects in tumours of the gastroesophageal junction and for chemoradiotherapy compared to chemotherapy, but the tests for subgroup differences were not statistically significant. Preoperative chemotherapy was associated with longer disease-free survival, higher likelihood of R0 resection and more favourable post-treatment tumour stage, but not perioperative complications. CONCLUSION Preoperative chemotherapy for locoregional gastroesophageal adenocarcinoma increases survival compared to surgery alone. It should be offered to all eligible patients. There appear to be larger survival advantages in tumours of the gastroesophageal junction and for chemoradiotherapy, but these findings require prospective confirmation.

Validating the 5Fs mnemonic for cholelithiasis: time to include family history

Background The time-honoured mnemonic of ‘5Fs’ is a reminder to students that patients with upper abdominal pain and who conform to a profile of ‘fair, fat, female, fertile and forty’ are likely to have cholelithiasis. We feel, however, that a most important ‘F’—that for ‘family history’—is overlooked and should be introduced to enhance the value of a useful aide memoire. Methods To assess the usefulness of each of the existing factors of a popular mnemonic, 398 patients admitted with upper abdominal pain between March 2009 and April 2010 were studied. The clinical features expressed in the cholelithiasis mnemonic in patients with sonographic evidence of cholelithiasis were compared with those of patients without. Findings In the cholelithiasis group, significantly more patients were women (150/198 (75.8%) vs 111/200 (55.5%), p<0.001), fair (144/198 (62.9%) vs 54/200 (32.1%), (p<0.001)), fertile (135/198 (68.2%) vs 50/200 (25%) (p<0.001)) and had a body mass index >30 (56/198 (28.3%) vs 19/200 (9.5%) (p<0.001)) compared with controls; but age over 40 years did not predict cholelithiasis (82/198 (41.4%) vs 79/200 (39.5%) (p=0.697)). In the cholelithiasis group, 78/198 (39.4%) had a family history in at least one first-degree relative, compared with 27/200 (13.5%) of controls, (p<0.001). Where the phenotypic elements of the history existed in combination, that patient was found to be at an increased risk of cholelithiasis. Interpretation Our study found that the validated ‘students’ 5Fs’ mnemonic retains a role in clinical diagnosis of patients suspected of cholelithiasis but the factor ‘familial’ should be substituted for ‘forty’ in recognition of the role of inheritance and the changing demographics of gallstone incidence.

Cholecystogastric fistula: a brief report and review of the literature

Abstract Cholecystogastric fistula is a rare, life-threatening complication of cholelithiasis that presents a difficult challenge to the surgeon when it occurs in elderly and co-morbid patients. Following a case of a 68-year-old female who presented with a short history of epigastric pain and vomiting, and in whom a cholecystogastric fistula was identified on abdominal computed tomography and confirmed on upper gastrointestinal endoscopy, we performed a systematic review of the literature on the management of cholecystogastric fistula. Our patient underwent laparotomy without excision of the fistula nor cholecystectomy and had an uncomplicated post-operative course. Surgical management using an open approach remains the mainstay of treatment of cholecystogastric fistula although laparoscopic techniques are used with increasing success. Surgical closure of the fistula is not always necessary. Improved surgical techniques including the use of laparoscopic surgery have led to improved outcomes in the management of cholecystogastric fistula.

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)

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.