Our sample size of patients who received re-resection for presumed incidental gallbladder cancer included a total of 701 patients, with most having T2 or T3 disease. Median overall survival was remarkably greater in patients show had received re-resection versus those who did not. Regardless of time frame after initial cholecystectomy [0-4, 5-8, 9-12 and >12 weeks] an improved overall survival was notable. However, amongst the four time frames listed above, early re-resection [0-4 weeks] showed worse overall survival in comparison to overall survival at 5-8, 9-12 weeks or >12 post initial cholecystectomy.
Papageorge el al also conducted a National Cancer Database analysis from 2004-2015 evaluating the benefit in overall survival in patients with gallbladder cancer undergoing re-resection. This study found that the median overall survival for patients who underwent resection (44 months) was significantly greater than those who did not (23 months) [5]. However, the study did not evaluate an optimal time for re-resection which remains to be a point of discussion based on prior studies. Our study sought to expand upon the data presented by Papageorge et al, compare re-resection rates in patients from 2004-2018 and to further describe potential benefit for early re-resection versus late re-resection.
Previous literature shows that re-resection provides a chance for curative therapy in a malignancy that traditionally presents with poor overall survival. However, some contest that the survival benefit of re-resection is limited to extent of disease/residual disease at the time of re-resection; as opposed to the time to re-resection [2; 6-8]. Few studies mention that despite stage of disease, median survival in patients with re-resection did not significantly differ from those who did not. The conflicting data with regards to improved overall survival is emphasized in the subset of patients with T1b disease [9-12]. In our sample size, only 53 patients with T1b disease underwent re-resection; therefore, making it difficult to draw conclusions regarding survival from this specific subset. However, other studies have provided evidence to show survival benefit associated with re-resection, regardless of disease burden at time of re-resection [13-17].
Barreto et al found that there was an increased risk of recurrence with delay in surgery by 1 month; however, when adjusted for stage of disease, the risk of recurrence was no longer significant [8]. While some literature supports the conclusion that timing of re-resection does not affect overall survival [18]; others that have shown that later re-resection is beneficial from a mortality standpoint [4]. There are a few proposed theories as to why early re-resection (within 0-4 weeks) is associated with poorer outcomes. One hypothesis remains that tumor staging may not be complete at that timepoint due to post-operative inflammation on cross sectional imaging. Time to allow for decrease in inflammation post initial cholecystectomy can allow for improved outcomes. Additionally, adhesions are commonly found in the early post- operative time period, which can lead to greater surgical complications [13].
As Papageorge emphasized, re-resection is underused; despite conflicting prior findings, NCCN guidelines continue to recommend re-resection in patients with T1b-T3 disease. Papageorge found a re-resection rate of 7.6%. Our study, showed a re-resection rate of 5.82%, indicating that with additional time and data, adherence to national guidelines for the treatment of incidental gallbladder cancer remains poor and emphasizes further education to implement recommendations.
Our study did present with limitations. Firstly, our sample size of patients who had undergone re-resection remained small, thus limiting the power of our study. Further, the retrospective nature of the study design may portend a concern for information bias or selection bias. Importantly, the NCDB is not able to differentiate the manner in which patients were diagnosed with malignancy; therefore, our sample size may include some patients that were not diagnosed incidentally. Further investigation is needed to delineate whether residual tumor at time of re-resection additionally impacts overall survival, as this remains to be a topic of discussion in recent literature.