Paraphrases on postoperative outcomes in gallbladder cancer: Fundus and body vs. neck and cystic duct, a retrospective multicenter study

Dear Editor,

Gall bladder and choledoch pathologies maintain their cruciality today in the hepatobiliary discipline. It is with considerable interest that we have perused the forthcoming article entitled “Impact of longitudinal tumor location on postoperative outcomes in gallbladder cancer: Fundus and body vs. neck and cystic duct, a retrospective multicenter study” published in volume 28, Ann Hepatobiliary Pancreat Surg regarding the prognostic impact of longitudinal tumor location on gallbladder cancer (GBC). This multicenter retrospective study incorporated propensity score matching (PSM) and provided valuable data confirming that GBCs located in the neck and cystic duct (NC-GBC) demonstrated significantly worse clinicopathological features and postoperative outcomes compared to those in the fundus and body (FB-GBC) [1]. Kim et al. [1] have shown that NC-GBC is associated with more frequent elevated preoperative CA19-9 levels, more advanced histologic grade and tumor stages, more frequent lymphovascular and perineural invasion, lower R0 resection rates, higher recurrence rates, and poorer 5-year overall and disease-free survival rates in both the overall cohort and after PSM. Their PSM analysis explicitly highlights the persistence of lower R0 resection rates, higher recurrence rates, and worse survival in the NC-GBC group even when matched for pT-stage, pN-stage, and histologic grade. While their multivariate analysis identified elevated preoperative CA19-9 levels, lymph node metastasis, and non-R0 resection as independent prognostic factors, all of these factors were significantly more frequent in the NC-GBC group in univariate and PSM analyses. While their results are statistically accurate within the multivariate model presented, we contend that this interpretation might have underestimated the fundamental role of tumor location. The anatomical proximity of the neck and cystic duct to major hepatic vascular structures, the extrahepatic bile duct, neural systems, and lymphatic pathways could inherently drive higher rates of R1 resection and lymph node metastasis observed in NC-GBC. Aggressive features noted in NC-GBC (e.g., higher histologic grade, more advanced stages, increased invasion) might reflect an intrinsic difference in tumor biology based on the origin site, compounded by anatomical constraints. Nevertheless, upon closer inspection, their study’s retrospective nature and the heterogeneity in surgical approaches and adjuvant treatments across multiple centers are acknowledged limitations. These factors might have potentially influenced their results of a multivariate analysis, making it challenging to definitively separate an “independent” effect of location from effects of factors strongly influenced by location and varied clinical management. Given consistently worse outcomes and aggressive features associated with NC-GBC across univariate and PSM analyses with a clear anatomical rationale provided by the authors, we believe that the longitudinal tumor location in the neck/cystic duct should still be considered a critical prognostic indicator, which signifies a tumor that might not only anatomically challenging, but also likely to exhibit a more aggressive phenotype, inherently increasing the risk of incomplete resection and metastatic spread, which subsequently can manifest as independent prognostic factors. Further prospective studies, potentially focusing on standardized surgical approaches for NC-GBC, are needed to fully elucidate the interplay between location, resectability, biological aggressiveness, and long-term outcomes. This issue merits further investigation. We extend our thanks to Kim et al. [1] for their valuable study in Ann Hepatobiliary Pancreat Surg on longitudinal tumor location of GBC and its postoperative outcomes.

Funding Statement

FUNDING None.