Study protocol for an International Prospective Observational Cohort Study for Optimal Bowel Resection Extent and Central Radicality for Colon Cancer (T-REX study)

Abstract

This is a prospective observational cohort study aiming to include 4000 patients with stages I to III colon cancer treated at 35 specialist institutions in Japan, South Korea, Germany, Russia, Lithuania and Taiwan. The anatomical distribution of lymph nodes and feeding arteries are investigated using surgical specimens according to pre-specified categorizing methods using intraoperative anatomical markings. Primary analyses are performed to identify the general principles of metastatic lymph node distribution in terms of its relation to the location of the primary tumor and feeding arteries. Secondary analyses will be used to estimate prognostic outcomes according to bowel resection length and central radicality and will be used to evaluate the quality of resected surgical specimens. Through in-depth lymph node mapping, standardized criteria for the definite area of 'regional' lymph node resection in routine surgical procedures can be identified, which is expected to contribute to international standardization in colon cancer surgery (ClinicalTrials.gov NCT02938481).

Keywords: D3 dissection; bowel resection margin; complete mesocolic excision; lymph node mapping; lymphadenectomy.

© The Author(s) 2020. Published by Oxford University Press. The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

Figures

Figure 1.

Lymph node classification in colon cancer. According to the Japanese Classification of Colorectal Carcinoma (2nd English edition), lymph nodes were classified into pericolic, intermediate and main lymph nodes. Note that different anatomical landmarks are used to determine main lymph nodes depending on the primary tumor location (i.e. main lymph nodes are those along the superior mesenteric artery/vein for tumors in the right-sided colon or those located along the inferior mesenteric artery proximal to the origin of the left colic artery in the left-sided colon). (Reprinted with permission from ``Japanese D3 Dissection'' by Hideki Ueno and Kenichi Sugihara in Surgical Treatment of Colorectal Cancer (ISBN 978-981-10-5142-5; Springer Nature Singapore Pte Ltd. 2018))

Figure 2.

Schematic of the levels of central radicality in the T-REX study. Three categories of lymphadenectomy are provided for central radicality according to pre-specified anatomical landmarks. Subclassifications are provided for level C in tumors located in the ileocolic and right colic artery area and for level B in tumors located in the sigmoid artery area.

Figure 3.

Intraoperative markings and identification of feeding arteries in resected specimens. Intraoperative markings on the bowel at 5 cm intervals make 11 pericolic segments: i.e. primary tumor area; 0 D ≤ 5 cm (proximal/distal sides); 5 < D ≤ 10 cm (proximal/distal sides); 10 < D ≤ 15 cm (proximal/distal sides); 15 < D ≤ 20 cm (proximal/distal sides) and 20 cm < D (proximal/distal sides). The location of feeding arteries and pericolic lymph nodes are classified according to these segments.

Figure 4.

Patterns of feeding artery distribution. According to the Japanese Classification of Colorectal Carcinoma (2nd English edition), the pattern of feeding artery distribution is classified into four based on the distance of the first and second feeding arteries from the primary tumor.

Figure 5.

Groupings of retrieved lymph nodes in the T-REX study. Retrieved lymph nodes from the resected specimens were classified into pericolic, intermediate and main lymph nodes. The T-REX study provides subgroups of pericolic lymph nodes according to the pericolic segments determined by intraoperative markings at 5 cm intervals.

Figure 6.

Photography protocol for of colon cancer specimens. General principles. (1) Photographs should be taken with a high-resolution digital camera; (2) the camera should be mounted on a fixed stand to minimize movement artifacts; (3) images should not contain any direct patient identifiers but should be identified by the unique study number and preferably a second indirect identifier; (4) all images must include a metric scale to allow calibration when using image analysis software and (5) a white background is ideal, although any plain color is acceptable. Whole-specimen photographs: (1) ideally, the whole specimen should be photographed before it is opened; (2) the mesentery should be laid out flat but not under tension; (3) the site of the tumor and the site of the vascular ties must be clearly visible on the photographs; (4) the whole specimen should be visible in the image; (5) photographs should be taken from both the front and the back of the specimen; (6) ideally, the distal and proximal aspects should be labeled (mainly for left-sided and wedge excisions where orientation may be difficult); (7) photographs should be taken directly above the specimen to reduce distortion artifact and (8) additional close-up pictures if any mesocolic defects or perforations exist.