Infrapyloric and gastroepiploic lymph node metastasis in right transverse colon cancer (InCLART study): multicentre, prospective, observational study

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The Japanese Research Society for Cancer of the Colon and Rectum (JSCCR) advocates D3 regional lymph node (LN) dissection during colectomy in patients with locally advanced tumors1. However, the concept of ‘complete mesocolic excision (CME) with central ligation’, introduced by Hohenberger et al., proposed routine infrapyloric and gastroepiploic LNs (IGLN) dissection rather than D3 lymphadenectomy for locally advanced right-sided transverse colon cancer (LARTCC) and hepatic flexure colon cancer (LAHFCC)2,3. The debate over routine or selective IGLN dissection reflects the lack of clinical relevance of IGLN metastasis in the literature as none of the previous studies provide solid evidence4. Neither the JSCCR1 nor the American Society of Colorectal Surgeons recommend routine IGLN dissection5. Thus, we conducted a standardized study to determine the prevalence of IGLN metastasis and to assess the feasibility, safety, and prognostic relevance of IGLN dissection for patients with LARTCC and LAHFCC. The InCLART observational study, conducted at 22 centres in 10 Chinese provinces (Table S1), enrolled consecutive patients with LARTCC or LAHFCC who underwent right hemi-colectomy according to CME principles. The IGLN were dissected routinely, marked intraoperatively, and then examined separately by pathologists. Ethical approval was granted by the Ruijin Hospital Ethics Committee (number: 2019-081). The study was approved by each collaborating centre’s research ethics board. Informed consent was obtained from each individual participant. This study was registered at ClinicalTrials.gov (NCT03936530); the protocol is available online6 (cf. Supplementary Materials for details). Between October 2019 and June 2023, 432 patients were enrolled (Table S2). The drop-out rate was 3.9% (17/432), leaving 415 patients were included into per-protocol analysis (Fig. S1). The baseline characteristics of per-protocol patients are shown in Table S3. The perioperative outcomes are summarized in Table S4. Intraoperative complications were observed in six patients (1.4%). Two deaths (0.5%) and 78 complications (18.8%) occurred within 30 days after surgery. Functional delayed gastric emptying (FDGE, 4.6%) was the most common complication. As seen in Table 1, the median number of IGLN was 5 (i.q.r. 3–8); the prevalence of IGLN metastasis was 3.4% (95% c.i. 1.9% to 5.7%). Metastatic main LNs were found in 53 (12.8%) specimens. Skip metastasis of IGLN was observed in only one patient (0.2%). Clinicopathological outcomes were compared between patients with and without metastatic IGLN (Table S5). Pathological results of the per-protocol patients LN, lymph node; IGLN, infrapyloric and gastroepiploic lymph node. The prognostic implications of IGLN have come into focus with the recent interest in CME3, although not yet widely adopted by all7. Clinicopathological outcomes of IGLN dissection diverge in reported clinical studies4. Variations in indications, inclusion of tumours located in the ascending colon or the caecum, stage IV cancers, and variable extent of IGLN dissection are possible reasons for the wide range of reported prevalence of IGLN metastasis (0.7–22.0%)4. This standardized series of patients strictly limited to LARTCC and LAHFCC highlights the reliability of our results. Of note, our study defined clear boundaries of IGLN dissection and indicated that both infrapyloric and gastroepiploic LN should be distinguished and marked intraoperatively. The median number of IGLN was higher than all previous studies (range 1.8–5)4. The median number of mesocolic LNs retrieved in our study (30, i.q.r. 21–41) was greater than that of the CME group (26, i.q.r. 19–35) according to a nationwide RCT in China (RELARC)8. From these results, it can be speculated that IGLN metastasis is not as common as previously reported. Whether the skip metastasis of IGLN truly existed or was related to erroneous grouping of IGLN and mesocolon during surgery remains unknown, given the extremely low rate of skip metastasis in previous studies as well as ours4. Previous studies reported postoperative morbidity ranging from 8.5% to 36.9% after routine IGLN dissection4. In our study, the morbidity was higher than that reported by a prospective, multicentre, snapshot study in China (11.7%)9. However, this study included patients undergoing D1 and D2 lymphadenectomy. Of note, the postoperative morbidity reported by two nationwide RCTs was 19.6%8 and 25.9%10 respectively. The 30-day mortality after surgery was 0.2%9 and 0.7%10 respectively, which was comparable to our study. Overall, routine IGLN dissection seems to be feasible and safe without increasing the total perioperative morbidity or mortality. Proximal ligation of the gastroepiploic vessels and decreased blood supply of distal stomach are theoretical reasons for FDGE after IGLN dissection. Neither of the two large-scale studies in China reported the incidence of FDGE after right hemi-colectomy8,9. One reason might be that some FDGEs were misdiagnosed as ileus because the clinical symptoms are similar. Our study had several limitations. The single-arm design made it impossible to investigate the safety and efficacy of IGLN dissection in a comparative method. The observed prevalence of IGLN metastasis was greater than the margin of permissible error. Finally, the prognostic value of IGLN metastasis is still unclear because of the temporary lack in survival data. In conclusion, the prevalence of IGLN metastasis in LARTCC and LAHFCC was low and skip metastasis was extremely rare. Considering the large sample size, prospective design, highly standardized technique, and the high-grade quality of lymphadenectomy, the results of InCLART study gives weight to the level of evidence, raising doubts as to the value of routine extended lymphadenectomy for LARTCC and LAHFCC. Moreover, although routine IGLN dissection was technically feasible and safe, it might increase the incidence of postoperative FDGE. However, these findings need to be further investigated by comparative studies once the long-term survival data are obtained. There is no involvement of the funder in study design, data collection, data analysis, manuscript preparation and publication decisions. The authors confirm that they had complete access to the study data that support the publication. Z.-H.C., Y.-C.G., and K.Y. contributed equally to this paper. All authors declare no conflict of interest in the submitted work. Supplementary material is available at BJS online. With reasonable requests, deidentified participant data are available from the corresponding author at [email protected].

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