Prognostic Value of Intraoperative Bile Spillage in Gallbladder Adenocarcinoma

City of Hope researchers recently reported in Surgical Oncology that intraoperative bile spillage is associated with worse survival rates in patients with gallbladder adenocarcinoma.

Gallbladder adenocarcinoma is often discovered by chance, after a cholecystectomy procedure. In a majority of cases, patients are referred for general follow-up through tertiary care after a cholecystectomy, instead of proceeding with a more immediate oncologic resection. Timely surgery for patients with segment 4b/5 hepatectomy and portal lymph node dissection could provide a survival benefit related to the radical cholecystectomy, yet the usual time from cholecystectomy to referral has been inadequate, and has proved to be a negative prognostic factor. Many patients are considered unresectable when first evaluated, yet the optimal time span between the operations is likely 4‐8 weeks if disease progression is to be minimized.

In the past, research has found that the median time between cholecystectomy and reoperation is 2 months. This study has a median time between cholecystectomy and re‐resection of only 1 month; but only one third of referred patients had undergone a second operation.

The authors hypothesized that intraoperative bile spillage might serve as a prognostic tool with negative association. They conducted a retrospective study involving 66 cancer center patients who had a histologically confirmed gallbladder adenocarcinoma between 2009‐2017. The research reviewed the patient histories, disease manifestations, and treatments against both progression‐free survival (PFS) and overall survival (OS).

Tumor stage in the 66 patients was made up of T1 (n = 8, 12%), T2 (n = 23, 35%), and T3 (n = 35, 53%). Node stage was N0 (n = 22, 33%), N1+ (n = 26, 39%), Nx (n = 18, 27%). Patients had cholecystectomy alone (n = 27, 36%), cholecystectomy with partial hepatectomy (n = 30, 45%), or hepaticojejunostomy (n = 9, 14%). The Median PFS was 7 months (interquartile range [IQR], 2‐19), while median OS was 16 months (IQR, 10‐31).

The researchers noted decreased PFS in association with intraoperative spillage in a subset multivariate proportional hazards regression of 41 patients who underwent initial cholecystectomy (n = 12, 29%; hazard ratio [HR], 5.5; P = .0014). In patients who received drain placement, there was a decreased OS (n = 21, 51%; HR, 8.1; P = .006).

The authors concluded that “intraoperative bile spillage and surgical drain placement at initial
cholecystectomy are negatively associated with PFS and OS in gallbladder adenocarcinoma. Explicit documentation of spillage and drain placement rationale is critical, possibly indicating locally advanced disease and prompting stronger consideration of systemic therapy before definitive resection.”

The study supported other research strongly suggesting that for patients with gallbladder adenocarcinoma, intraoperative bile spillage during initial cholecystectomy is an independent predictor of decreased PFS. Drain placement at the time of cholecystectomy and a minimally invasive approach to treatment were also independently associated with decreased OS. The results support other findings that intraoperative bile spillage is a negative prognostic factor.

Intraoperative bile spillage should be considered a critical aspect of documentation and consideration of whether cholecystectomy is safe and effective.