title: Extranodal extension of lymph node metastasis is a marker of poor prognosis in oesophageal cancer: a systematic review with meta-analysis.
abstract: The extranodal extension (ENE) of nodal metastasis is the extension of neoplastic cells through the nodal capsule into the perinodal adipose tissue. This histological feature has recently been indicated as an important prognostic factor in different types of malignancies; in this manuscript, we aim at defining its role in the prognosis of oesophageal cancer with the tool of meta-analysis. Two independent authors searched SCOPUS and PubMed until 31 August 2015 without language restrictions. The studies with available data about prognostic parameters in subjects with oesophageal cancer, comparing patients with the presence of ENE (ENE+) versus only intranodal extension (ENE-), were considered as eligible. Data were summarised using risk ratios (RRs) for number of deaths/recurrences and HRs together with 95% CIs for time-dependent risk related to ENE+, adjusted for potential confounders. Fourteen studies were selected; they followed-up 1437 patients with oesophageal cancer for a median follow-up of 39.4 months. The presence of ENE was associated with a significantly increased risk of all-cause mortality (RR=1.33; 95% CI 1.18 to 1.50, p<0.0001, I2=49%; HR=2.72, 95% CI 2.03 to 3.64, p<0.0001, I2=0%), cancer-specific mortality (RR=1.35; 95% CI 1.14 to 1.59, p=0.001, I2=57%; HR=1.97, 95% CI 1.41 to 2.75, p<0.0001, I2=41%) and of risk of recurrence (RR=1.50, 95% CI 1.20 to 1.88, p<0.0001, I2=9%; HR=2.27, 95% CI 1.72 to 2.90, p<0.0001, I2=0%). On the basis of these results, in oesophageal cancer, ENE should be considered from the gross sampling to the pathology report, and in future oncological staging system.
authors.affiliation: Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Verona, Italy.|ARC-NET Research Center, University and Hospital Trust of Verona, Verona, Italy.|Department of Pathology, Santa Chiara Hospital, Trento, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Luchini
authors.affiliation: Department of Pathology, The Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Laura D
authors.initials: LD
authors.lastname: Wood
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Nottegar
authors.affiliation: Health Service and Population Research Department, King's College London, London, UK.
authors.forename: Brendon
authors.initials: B
authors.lastname: Stubbs
authors.affiliation: Department of Neuroscience, University of Padua, Padua, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Solmi
authors.affiliation: Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Capelli
authors.affiliation: Department of Surgery, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pea
authors.affiliation: Department of Medicine, DIMED, University of Padua, Padua, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sergi
authors.affiliation: Department of Medicine, DIMED, University of Padua, Padua, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Manzato
authors.affiliation: Department of Medicine, DIMED, University of Padua, Padua, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.affiliation: Department of Surgery, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Bagante
authors.affiliation: Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany.
authors.forename: Elfriede
authors.initials: E
authors.lastname: Bollschweiler
authors.affiliation: Upper G.I. Surgery Division, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Giacopuzzi
authors.affiliation: Department of Molecular Pathology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Kaneko
authors.affiliation: Upper G.I. Surgery Division, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: de Manzoni
authors.affiliation: Department of Pathology, Santa Chiara Hospital, Trento, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Barbareschi
authors.affiliation: Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Verona, Italy.|ARC-NET Research Center, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
authors.affiliation: Department of Medicine, DIMED, University of Padua, Padua, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Veronese
keywords: CANCER; METASTASIS; OESOPHAGUS