Retrospective Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2017; 23(8): 1412-1423
Published online Feb 28, 2017. doi: 10.3748/wjg.v23.i8.1412
Do pathological variables have prognostic significance in rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy and surgery?
Luca Reggiani Bonetti, Simona Lionti, Federica Domati, Valeria Barresi
Luca Reggiani Bonetti, Federica Domati, Department of Laboratory Integrated Activities, Anatomic Pathology and Legal Medicine, Section of Pathology, University of Modena and Reggio Emilia, 41124 Modena, Italy
Simona Lionti, Valeria Barresi, Department of Pathology in Evolutive Age and Adulthood, “Gaetano Barresi”, University of Messina, 98125 Messina, Italy
Author contributions: Reggiani Bonetti L designed the study, revised the histological slides, analyzed the results and wrote the paper; Lionti S designed the study, performed the statistical analyses and supervised the report; Domati F designed the study, collected the clinical data and supervised the report; Barresi V designed the study, revised the histological slides, analyzed the results and supervised the report.
Institutional review board statement: Ethical issues were discussed with the local ethics committee. Since the study was retrospective, no approval was needed to revise the histological slides.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: We have no financial relationships to disclose.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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:
Correspondence to: Dr. Valeria Barresi, Department of Pathology in Evolutive Age and Adulthood, “Gaetano Barresi”, University of Messina, Via Consolare Valeria, 98125 Messina, Italy.
Telephone: +39-90-2212537
Received: October 22, 2016
Peer-review started: October 25, 2016
First decision: December 19, 2016
Revised: December 29, 2016
Accepted: January 17, 2017
Article in press: January 17, 2017
Published online: February 28, 2017

To clarify which factors may influence pathological tumor response and affect clinical outcomes in patients with locally advanced rectal carcinoma treated with neo-adjuvant chemoradiotherapy and surgery.


Tumor regression grade (TRG) according to the Dworak system and yTNM stage were assessed and correlated with pre-treatment clinico-pathological variables in 215 clinically locally advanced (cTNM stage II and III) rectal carcinomas. Prognostic value of all pathological and clinical factors on disease free survival (DFS) and cancer specific survival (CSS) was analyzed by Kaplan Meier and Cox-regression analyses.


cN+ status, mucinous histotype or poor differentiation in the pre-treatment biopsy were significantly associated with lower pathological response (low Dworak grade and TNM remaining unchanged/upstaging). Cases showing acellular mucin pools in surgical specimens all had unremarkable clinical courses with no deaths or recurrences during follow-up. Dworak grade had prognostic significance for DFS and CSS. However, compared to the 5-tiered system, a simplified two-tiered grading system, in which grades 0, 1 and 2 were grouped as absent/partial regression and grades 3 and 4 were grouped as total/subtotal regression, was more reproducible and prognostically informative. The two-tiered Dworak system, yN stage, craniocaudal extension of the tumor and radial margin status were significant independent prognostic variables.


Our data suggest that caution should be applied in using a conservative approach in rectal carcinomas with cN+ status, extensive/lower involvement of the rectum and mucinous histotype or poor differentiation. Although Dworak TRG is prognostically significant, a simplified two-tiered system could be preferable. Finally, cases with acellular mucin pools should be carefully evaluated to definitely exclude residual mucinous carcinoma.

Keywords: Rectal carcinoma, Dworak, Acellular mucin pools, Downstaging, Mucinous

Core tip: This study evaluates the prognostic significance of clinico-pathological variables in patients with locally advanced rectal carcinoma treated with neo-adjuvant chemo-radiotherapy (CRT) and surgery. Our data show that tumors with cN+ status, extensive/lower involvement of the rectum, mucinous histotype and poor differentiation have a lower response to pre-operative CRT. Dworak tumor regression grade was prognostically informative; however, a simplified two-tiered system was more reproducible and prognostically significant. Acellular mucin pools were found in a percentage of cases with excellent outcomes. Although acellular mucin pools should be considered as complete pathological responses, careful histological examination is mandatory to exclude residual mucinous carcinoma.