Ian S. Bailey

Risk assessment using a novel score to predict anastomotic leak and major complications after oesophageal resection

BackgroundOesophagectomy is associated with significant morbidity and mortality. A simple score to define a patients risk of developing major complications would be beneficial.MethodsPatients who underwent upper gastrointestinal resections with an oesophageal anastomosis between 2005 and 2010 were reviewed and formed the development dataset with resections performed in 2011 forming a prospective validation dataset. The association between post-operative C-reactive protein (CRP), white cell count (WCC) and albumin levels with anastomotic leak (AL) or major complication including death using the Clavien–Dindo (CD) classification were analysed by receiver operating characteristic curves. After multivariate analysis, from the development dataset, these factors were combined to create a novel score which was subsequently tested on the validation dataset.ResultsTwo hundred fifty-eight patients were assessed to develop the score. Sixty-three patients (25%) developed a major complication, and there were seven (2.7%) in-patient deaths. Twenty-six (10%) patients were diagnosed with AL at median post-operative day 7 (range: 5–15). CRP (p = 0.002), WCC (p < 0.0001) and albumin (p = 0.001) were predictors of AL. Combining these markers improved prediction of AL (NUn score > 10: sensitivity 95%, specificity 49%, diagnostic accuracy 0.801 (95% confidence interval: 0.692–0.909, p < 0.0001)). The validation dataset confirmed these findings (NUn score > 10: sensitivity 100%, specificity 57%, diagnostic accuracy 0.879 (95% CI 0.763–0.994, p = 0.014)) and a major complication or death (NUn > 10: sensitivity 89%, specificity 63%, diagnostic accuracy 0.856 (95% CI 0.709–1, p = 0.001)).ConclusionsBlood-borne markers of the systemic inflammatory response are predictors of AL and major complications after oesophageal resection. When combined they may categorise a patients risk of developing a serious complication with higher sensitivity and specificity.

A prospective comparison of totally minimally invasive versus open Ivor Lewis esophagectomy.

The majority of esophagectomies in Western parts of the world are performed by a transthoracic approach reflecting the prevalence of adenocarcinoma of the lower esophagus or esophagogastric junction. Minimally invasive esophagectomy (MIE) has been reported in a variety of formats, but there are no series that directly compare totally minimally invasive thoracolaparoscopic 2 stage esophagectomy (MIE-2) with open Ivor Lewis (IVL). A prospective single-center cohort study of patients undergoing elective MIE-2 or IVL between January 2005 and November 2010 was performed. Short-term clinicopathologic outcomes were recorded using validated systems. One hundred and six patients (median age 66, range 36-85, 88 M : 18 F) underwent two-stage esophagectomy (53 MIE-2 and 53 IVL). Patient demographics (age, sex, body mass index, American Society of Anesthesiologists grade, tumor characteristics, neoadjuvant chemotherapy, and TNM stage) were comparable between the two groups. Outcomes for MIE-2 and IVL were comparable for anastomotic leak rates (5 [9%] vs. 2 [4%], P= 0.241), resection margin clearance (R0) (43 [81%] vs. 38 [72%], P= 0.253), median lymph node yield (19 vs. 18, P= 0.584), and median length of stay (12 [range 7-91] vs. 12 [range 7-101] days), respectively. Blood loss was significantly less for MIE-2 compared with IVL (median 300 [range 0-1250] mL vs. 400 [range 0-3000] mL, respectively, P= 0.021). MIE-2 in this series of selected patients supports its efficacy, when performed by an experienced minimally invasive surgical team. A well-designed multicenter trial addressing clinical effectiveness is now required.

Refining pathological evaluation of neoadjuvant therapy for adenocarcinoma of the esophagus

AIM To assess tumour regression grade (TRG) and lymph node downstaging to help define patients who benefit from neoadjuvant chemotherapy. METHODS Two hundred and eighteen consecutive patients with adenocarcinoma of the esophagus or gastro-esophageal junction treated with surgery alone or neoadjuvant chemotherapy and surgery between 2005 and 2011 at a single institution were reviewed. Triplet neoadjuvant chemotherapy consisting of platinum, fluoropyrimidine and anthracycline was considered for operable patients (World Health Organization performance status ≤ 2) with clinical stage T2-4 N0-1. Response to neoadjuvant chemotherapy (NAC) was assessed using TRG, as described by Mandard et al. In addition lymph node downstaging was also assessed. Lymph node downstaging was defined by cN1 at diagnosis: assessed radiologically (computed tomography, positron emission tomography, endoscopic ultrasonography), then pathologically recorded as N0 after surgery; ypN0 if NAC given prior to surgery, or pN0 if surgery alone. Patients were followed up for 5 years post surgery. Recurrence was defined radiologically, with or without pathological confirmation. An association was examined between t TRG and lymph node downstaging with disease free survival (DFS) and a comprehensive range of clinicopathological characteristics. RESULTS Two hundred and eighteen patients underwent esophageal resection during the study interval with a mean follow up of 3 years (median follow up: 2.552, 95%CI: 2.022-3.081). There was a 1.8% (n = 4) inpatient mortality rate. One hundred and thirty-six (62.4%) patients received NAC, with 74.3% (n = 101) of patients demonstrating some signs of pathological tumour regression (TRG 1-4) and 5.9% (n = 8) having a complete pathological response. Forty four point one percent (n = 60) had downstaging of their nodal disease (cN1 to ypN0), compared to only 15.9% (n = 13) that underwent surgery alone (pre-operatively overstaged: cN1 to pN0), (P < 0.0001). Response to NAC was associated with significantly increased DFS (mean DFS; TRG 1-2: 5.1 years, 95%CI: 4.6-5.6 vs TRG 3-5: 2.8 years, 95%CI: 2.2-3.3, P < 0.0001). Nodal down-staging conferred a significant DFS advantage for those patients with a poor primary tumour response to NAC (median DFS; TRG 3-5 and nodal down-staging: 5.533 years, 95%CI: 3.558-7.531 vs TRG 3-5 and no nodal down-staging: 1.114 years, 95%CI: 0.961-1.267, P < 0.0001). CONCLUSION Response to NAC in the primary tumour and in the lymph nodes are both independently associated with improved DFS.

The relevance of the Siewert classification in the era of multimodal therapy for adenocarcinoma of the gastro‐oesophageal junction

The Siewert classification has been used to plan treatment for tumours of the gastro‐oesophageal junction since its proposal in the 1980s. The purpose of this study was to assess its continued relevance by evaluating whether there were differences in the biology and clinical characteristics of adenocarcinomas by Siewert type, in a contemporary cohort of patients, in whom the majority had received neoadjuvant chemotherapy.

The relevance of the Siewert classification in the era of multimodal therapy for adenocarcinoma of the gastro-oesophageal junction

Introduction Since the early 1980s the Siewert classification has been used to plan treatment for tumours of the gastro-oesophageal junction. However, the relationship between tumour site and survival has not been conclusively demonstrated, with conflicting outcomes in the largest series, before the widespread application of neoadjuvant chemotherapy. The aim of this study was to evaluate whether there were differences in the biology and clinical characteristics of adenocarcinomas by Siewert type, in a contemporary cohort of patients, in whom the majority had received neoadjuvant chemotherapy. The relationship of the surgical approach and tumour site with patient survival was also assessed. Methods A prospective database was reviewed for all patients who underwent resection for adenocarcinoma of the distal oesophagus and gastro-oesophageal junction from 2005 to 2011. In our unit, based on pre-operative assessment, distal oesophageal, type I and II tumours are treated as oesophageal cancer, with transthoracic procedures. Type III tumours are treated as gastric cancer with an abdominal approach. Classification systems used for analysis included TNM 7 for staging, Clavien-Dindo for grading complications and Siewert with final tumour site determined from the pathological specimen. Survival was estimated by Kaplan–Meier analysis excluding inpatient deaths (n=4) and R1 resections (n=42). Results 216 patients underwent oesophagogastric resection: 133 for type I, 51 for type II and 33 for type III tumours. Median follow-up was 2.94 years. 62.5% of patients received neoadjuvant chemotherapy with no difference between groups. There were no significant differences in age, sex, pT stage, pN stage, pM stage, ASA, or inpatient complications between patients with adenocarcinoma based on their Siewert classification. Type I tumours were significantly associated with coexisting Barretts metaplasia (presence of Barretts: Type I 58.3%, Type II 21.6%, Type III 9.1%; pType II > Type I). Median overall survival was significantly shorter for more distal tumours (Type I: 4.96 years vs Type II: 3.3 years vs Type III: 2.64 years; p=0.04). The surgical approach did not influence survival for all tumour types and had no impact on the rate or severity of complications. Conclusion This study demonstrates significant differences in the biological characteristics of adenocarcinomas of the gastro-oesophageal junction based on their anatomical topographical sub-classification. In the era of multimodal therapy overall survival is worse for tumours arising at or below the gastro-oesophageal junction compared with oesophageal tumours. Competing interests None declared.