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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. May 15, 2020; 12(5): 592-600
Published online May 15, 2020. doi: 10.4251/wjgo.v12.i5.592
Perineural invasion as a prognostic factor in patients with stage I-III rectal cancer – 5-year follow up
Milica Stojkovic Lalosevic, Tamara Milovanovic, Marjan Micev, Mirjana Stojkovic, Sanja Dragasevic, Milos Stulic, Ivan Rankovic, Vladimir Dugalic, Zoran Krivokapic, Aleksandra Pavlovic Markovic
Milica Stojkovic Lalosevic, Tamara Milovanovic, Mirjana Stojkovic, Sanja Dragasevic, Milos Stulic, Ivan Rankovic, Aleksandra Pavlovic Markovic, Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia, Belgrade 11000, Serbia
Milica Stojkovic Lalosevic, Tamara Milovanovic, Marjan Micev, Mirjana Stojkovic, Sanja Dragasevic, Milos Stulic, Ivan Rankovic, Vladimir Dugalic, Zoran Krivokapic, Aleksandra Pavlovic Markovic, School of Medicine, University of Belgrade, Belgrade 11000, Serbia
Marjan Micev, Vladimir Dugalic, Zoran Krivokapic, Clinic for Digestive Surgery - First Surgical Clinic, Clinical Center of Serbia, Belgrade 11000, Serbia
Author contributions: Stojkovic Lalosevic M and Milovanovic T reviewed the literature and contributed to manuscript drafting; Micev M contributed to study conception and design; Dugalic V and Krivokapic Z were the surgical team contributed to the review of the literature and final draft of the manuscript; Stulic M and Rankovic I contributed to manuscript drafting; Pavlovic Markovic A, Stojkovic M, Stojkovic Lalosevic M and were responsible for the revision of the manuscript for important intellectual content; all authors issued final approval for the version to be submitted.
Institutional review board statement: This study was approved by Institutional Ethical board (approval number 56-6, Clinical center of Serbia).
Informed consent statement: All study participants or their legal guardian gave informed consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement, and the manuscript was prepared and revised according to the STROBE Statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Milica Stojkovic Lalosevic, MD, PhD, Assistant Professor, Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia; School of Medicine, University of Belgrade, Koste Todorovica 2, Belgrade 11000, Serbia. drmilicastojkovic@gmail.com
Received: December 30, 2019
Peer-review started: December 30, 2019
First decision: February 21, 2020
Revised: March 23, 2020
Accepted: April 18, 2020
Article in press: April 18, 2020
Published online: May 15, 2020
ARTICLE HIGHLIGHTS
Research background
Rectal cancer (RC) accounts about one third of all diagnosed colorectal cancers. Although TNM staging has proven as applicable in very early and late disease stages, accuracy in the intermediary stages of the RC remains controversial. Precise pathological examination is needed in order to determine which patients would benefit from adjuvant therapy. Few previous investigations have focused on correlation of presence of perineural invasion (PNI) or/as well as lymphovascular invasion (LVI) with the cancer-related outcome in RC patients, therefore more studies in this field are needed.
Research motivation
Considering the rising incidence of RC, we have investigated easily applicable and reliable factors that can potentially predict potential outcomes in patients with RC.
Research objectives
We evaluated the clinical significance of PNI as well as LVI in patients with stage I-III RC and further investigated whether these two histopathological features alone and combined affect survival of RC patients.
Research methods
We have prospectively studied patients with early and intermediate RC. Using Kaplan-Meier method we have analyzed the median survival time, whereas Cox proportional hazards models were used to evaluate the influence of PNI and LVI as prognostic factors in RC patients.
Research results
Using Kaplan-Meier analysis for overall survival rate, we have found that both LVI and PNI were associated with lower overall survival rates as well as disease free survival rates (P < 0.01). Moreover when Cox multiple regression model was used, presence of LVI was associated with 3-fold higher risk of lethal outcome and 2-fold higher risk of disease recurrence (P < 0.05). Presence of PNI was associated with almost 4-fold higher risk of lethal outcome and 6-fold higher risk of disease recurrence (P < 0.05).
Research conclusions
This study supports the hypothesis that PNI as well as LVI should be carefully and thoroughly examined in the histopathological analysis of RC patients even in early and intermediate disease stages, bearing in mind that such findings could have a great impact on the prognosis. Also patients with both LVI and PNI involvement even in early stages of the disease should not be overlooked, and must be monitored carefully with more frequent and detailed check-ups.
Research perspectives
PNI and LVI should be included as obligatory analysis in histopathology reports of RC patients. Additional randomized prospective studies are necessary to confirm these results, and also to investigate other potential prognostic factors in RC patients.
