Timing of Gallbladder Cancer Reoperation Affects Survival

Pam Harrison

November 01, 2016

In patients whose gallbladder cancer is discovered incidentally, surgeons should aim to perform re-resection from 4 to 8 weeks after their initial surgery to optimize overall survival, a multi-institutional analysis suggests.

"Approximately 50% to 70% of gallbladder cancers are found incidentally during or after an elective cholecystectomy for presumed benign disease," write Cecilia Ethun, MD, a member of the US Extrahepatic Biliary Malignancy Consortium and a surgeon at Emory University in Atlanta, Georgia, and colleagues.

"[But] to our knowledge, no study has examined the effect of the timing of reoperation after the initial cholecystectomy on outcomes," they add.

"Based on data from the current study, it appears that reoperation between 4 and 8 weeks...is the optimal time interval for re-resection in patients with IGBC [incidentally discovered gallbladder cancer]."

The study was published online October 26 in JAMA Surgery.

The US Extrahepatic Biliary Malignancy Consortium consists of 10 high-volume academic institutions.

Among a cohort of 449 patients with gallbladder cancer reviewed by the consortium, 266 cases, or 59% overall, were discovered incidentally. Of those, 207 were included in the analysis.

The median time to reoperation was 7.4 weeks, the authors note.

However, 12% of the cohort underwent reoperation less than 4 weeks from the time of their initial cholecystectomy (group A). The remaining 44% underwent re-resection from 4 to 8 weeks after the initial procedure (group B).

The same percentage of patients underwent their second surgery longer than 8 weeks after their first (group C).

"A similar proportion of patients in each group had locoregional residual or distant disease at the time of reoperation and underwent completed resections," the authors write.

There was no difference in the extent of the resection performed. Most patients underwent the recommended partial hepatectomy (segments IVb and V), and portal lymph node dissection was performed in all groups.

Various tumor features and margin status were the same across the three groups.

The median follow-up was 13.9 months. Median overall survival (OS) was 40.4 months for patients who underwent their second operation between 4 and 8 weeks after their initial surgery (group B).

This compared to a median OS of 17.4 months for patients who underwent reoperation with the shortest time between the two procedures (<4 weeks). The median OS was 22.4 months for those with the longest interval between the two procedures (>8 weeks).

"Just as the timing of diagnosis of gallbladder cancer can translate to survival, so too may the timing of re-resection be an important, and heretofore underappreciated, determinant of outcomes in patients with IGBC," Dr Ethun and colleagues note.

The reasons for this are multiple. Among them may be the fact that performing the second surgery less than 4 weeks from the first may not allow surgeons enough time to completely evaluate and stage the tumor.

"Furthermore, inflammation in the operative field can make visualization of important structures on cross-sectional imaging near impossible in the early postoperative period," they write.

Several additional weeks may be needed for surgeons to adequately stage the tumor after the initial cholecystectomy.

On the other hand, reoperation after waiting longer than 8 weeks from the first surgery may allow the disease time to disseminate, leading to poorer outcomes.

Small Number of Patients

However, a pair of experts do not entirely agree with the authors' conclusions.

In an accompanying editorial, Vatche Agopian, MD, and Jonathan Hiatt, MD, of the David Geffen School of Medicine, University of California, Los Angeles, argue that "the relatively small number of patients in each group potentially limits the power to detect important differences that may explain the results."

As an example, they point out that fewer than one third of patients in the group with the longest median OS had a T3/4 tumor.

By comparison, between 44% and 46% of patients in the other two groups who had a T3/4 tumor.

"We agree with the authors that early reoperation risks considerable inflammation that may compromise reliable preoperative clinical staging and increase operative difficulty," Dr Agopian and Dr Hiatt note.

"[But] as with any retrospective study, the inherent bias regarding selection of patients for reoperation, as well as unknowable factors affecting the timing of reoperation, should lead to a softened conclusion that reoperation at 4 to 8 weeks was associated with better outcomes and not necessarily responsible for them."

Neither the study authors nor the editorialists have disclosed any relevant financial relationships.

JAMA Surg. Published online October 26, 2016. Full text, Editorial

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