Optimal Timing For Definitive Resection Of Incidental Gallbladder Cancer Determined

Overall survival is longer for gallbladder cancer patients who undergo resection in the 4–8 weeks following diagnosis than earlier or later

medwireNews: Definitive resection of incidentally discovered gallbladder cancer should be performed between 4 and 8 weeks after diagnosis, say US researchers.

They report in JAMA Surgery that overall survival (OS) was longer for patients who had surgery within this time period relative to those operated on before 4 weeks or after 8 weeks.

Researcher Shishir Maithel, from the Winship Cancer Institute in Atlanta, Georgia, and colleagues believe that this window “appears to be the optimal time interval for re-resection that balances both technical considerations and tumor biology” in this patient population.

The chart review comprised 207 patients with gallbladder cancer, discovered incidentally during or after an elective cholecystectomy, who underwent definitive resection at one of the 10 member institutions of the US Extrahepatic Biliary Malignancy Consortium. Twenty-five patients had the reoperation within 4 weeks of diagnosis, while for 91 patients each the wait time was 4–8 weeks and more than 8 weeks.

During a median follow-up of 13.9 months, OS was a median of 40.4 months for individuals in the 4–8 weeks group. This was significantly longer than the median OS times of 17.4 and 22.4 months for patients operated on earlier and later, respectively.

And in multivariable analysis adjusting for various clinicopathological parameters, definitive resection before 4 weeks or after 8 weeks was associated with a significant 2.63- and 2.07-fold increased risk of death, respectively, compared with resection during the 4–8 week period.

The investigators say that reoperating too early (before 4 weeks) may not allow for adequate evaluation of subclinical disease, whereas leaving the reoperation too late (after 8 weeks) could allow too much time for disease dissemination, thus explaining the inferior outcomes in these groups.

However, the authors of an invited commentary remark that “[w]hile it is undeniable that time allows for manifestation of subclinical disease, it is difficult to reconcile the authors’ contention that a few extra weeks of early observation allowed the identification of patients with initially advanced subclinical disease, while a similar number of weeks in the later period led to lower curability of disease without clinically detectable progression.”

Vatche Agopian and Jonathan Hiatt, both from the University of California–Los Angeles in the USA, commend the authors for providing the “largest analysis” to date of reoperation timing in patients with incidental gallbladder cancer.

But given the “relatively small number of patients in each group” and the selection bias inherent in any retrospective analysis, the commentators urge caution.

They add that these limitations “should lead to a softer conclusion that reoperation at 4 to 8 weeks was associated with better outcomes and not necessarily responsible for them.”


Ethun CG, Postlewait LM, Le N, et al. Association of optimal time interval to re-resection for incidental gallbladder cancer with overall survival. A multi-institution analysis from the US Extrahepatic Biliary Malignancy Consortium. JAMA Surg; Advance online publication 26 October 2016. doi:10.1001/jamasurg.2016.3642

Agopian VG, Hiatt JR. The timing of reoperation for incidental gallbladder cancer. Sooner or later? JAMA Surg; Advance online publication 26 October 2016. doi:10.1001/jamasurg.2016.3643

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