Laparoscopic surgery for gallbladder cancer: is skepticism still justified?

We’ve read with great interest the systematic review and meta-analysis by Li et al. recently published in HepatoBiliary Surgery and Nutrition, which compares open versus laparoscopic (LS) resection for gallbladder cancer (GBC) (1). This is a hot topic in the surgical community, especially for two major reasons: the growing tendency among the new generation of surgeons to adopt minimally invasive techniques, and the increasing proportion of potentially resectable GBC diagnoses, thanks to advances in imaging and diagnostics (2).

This systematic review aims to provide a comprehensive comparison of both short- and long-term outcomes of LS versus open surgery (OS) for GBC. The review confirms encouraging results for LS in terms of intraoperative blood loss, postoperative morbidity, and length of hospital stay, with a statistically significant advantage in overall survival at 2 years. Notably, the feared port-site metastasis did not emerge as a significant concern, showing a low incidence maybe after use of precautionary surgical techniques, en bloc resection of the gallbladder and liver parenchyma, and routinely use of plastic bags for specimen removal.

These findings challenge the skepticism still harbored by many surgeons—particularly those of earlier generations—who regard LS management of GBC as risky due to the complexity of liver resection and lymphadenectomy and the historical concerns over port-site recurrences (3).

Indeed, as with most minimally invasive procedures, intra- and post-operative results have improved along with technology, surgeon expertise, and patient selection have evolved. Still, several key considerations deserve further attention.

First, a major limitation of the included studies is the lack of detailed data on biliary duct resection. Due to its increased difficulty, it is common for centers to convert from laparoscopy to OS when resection of the common bile duct is needed after positive cystic duct margin. Unfortunately, the review does not report on conversion rates and numbers of biliary duct resection. This omission is relevant, since case selection may have biased the results if more complex cases were systematically managed with OS. In our opinion, robotic approach may decrease the difficulty of biliary duct resection and jejunal anastomosis in experienced centers.

Second, while the analysis suggests a shorter hospital stay with LS, this result should be interpreted with caution. Hospital length of stay often reflects institutional practices and healthcare systems rather than surgical efficacy. For instance, pressure to reduce inpatient stays is much greater in the United States than in many European or Asian countries. Hospital stay is important but not that relevant comparing different surgical approaches.

Third, and more importantly, disease-free survival (DFS)—which should be considered the most appropriate endpoint to assess oncological adequacy—was found to be similar between LS and OS. The observed improvement in overall survival in favor of LS may be influenced by post-recurrence treatment strategies rather than by the initial surgical radicality, which may vary a lot among different centres and countries. Given that the included studies were all retrospective and non-randomized, we advocate for a cautious interpretation of the better overall survival results favoring LS.

Fourth, the review reaffirms what previous studies have also shown: a lower number of lymph nodes (LNs) are typically retrieved during LS compared to OS (3,4). This reflects the current technical limitations of laparoscopy in liver hilum dissection where important inner vessels are placed. According to expert consensus, at least six LNs should be removed for accurate staging and treatment of GBC (5). In the present review, 3 out of 15 included studies failed to meet this threshold. This raise concerns over the true N0 staging in patients who had fewer nodes resected—a known prognostic factor, as false-negative N0 patients may show worse survival than true N0 cases. Therefore, real DFS and OS of different surgical approaches may be affected mainly by this aspect.

This issue was specifically addressed in our recently published IRON study, a large international multicenter retrospective cohort that directly compared open, LS, and robotic approaches for GBC resection (6). Our data confirmed that the robotic approach retrieved more LNs (median: 7) than both laparoscopy (median: 4) and OS (median: 5), and it was an independent predictor of adequate lymphadenectomy (≥6 nodes). We also found that experience with minimally invasive liver surgery (at least 20 resections/year) was a key factor to ensure proper nodal retrieval. These findings support the idea that technical limitations in LS lymphadenectomy could be overcome by robotic technology, thanks to enhanced dexterity and 3D visualization, especially useful for complex liver resections (7). It is regrettable that robotic surgery was not included in this systematic review, even if current series are still limited in size (8,9).

In conclusion, while minimally invasive surgery for GBC remains a matter of ongoing debate, mounting evidence—including this review—indicates that LS can be both safe and effective, at least in selected cases. However, some limitations persist, particularly regarding lymphadenectomy. These findings should prompt the surgical community to consider launching a prospective randomized controlled trial, which is still lacking in the field. Such a study would be essential to definitively establish the role of laparoscopy—and potentially robotics—in the oncologic management of GBC.

Supplementary

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Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.